FULL TEXT - Libyan Journal of Medicine
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FULL TEXT - Libyan Journal of Medicine
Libyan Journal of Medicine, volume 2, Supplement 1 Third African Oncology Conference, 19-21 Jan 2007, Sabratha, Libya Libyan J Med: AOP: 070520 THIRD AFRICAN ONCOLOGY CONFERNCE, 19-21 JAN. 2007 AFRICAN ONCOLOGY INSTITUTE SABRATHA, LIBYA Edited by Abougeala Abussa1, MD & Riyad Bendardaf2, MD, PhD African Oncology Institute, Sabratha, Libya and 2Department of Oncology and Radiotherapy,Turku University Hospital, TURKU-Finland - - - - - 1 1 ABSTRACT BOOK CONTENT 1. RESPONSE TO CHEMOTHERAPY (IRINOTECAN PLUS 5FLUOROURACIL) IN COLORECTAL CARCINOMA CAN BE PREDICTED BY TUMOUR DNA CONTENT. R. Bendardaf, H. Lamlum , R. Ristamäki, A. Ålgars , Y.Collan , S. Pyrhönen. 2. SURVIVAL OF BREAST CANCER PATIENTS TREATED IN TRIPOLI/LIBYA 2000-2005. Manal El-Habbash, Abukris Alwindi. 3. PCR BASED IN HOUSE METHOD OF HLA GENOTYPING FOR BONE MARROW TRANSPLANTATION. Rajesh Singh. J, S. Mudasir Ahmad, Awatif Altrablsi, Abugeala Aboussa. 4. OPERATIVE GUIDELINES AND STRATEGIES IN STANDARDIZING CLINICAL MANAGEMENT OF COLORECTAL CARCINOMA. V.Roetzscher, Rishi M., Elhousieni M., El Hanash A. 5. CAN ENDOSCOPIC ABLATION UND SURVEILLANCE BE RECOMMENDED AS PRIMARY TREATMENT OF SUPERFICIAL TRANSITIONAL CELL CARCINOMA (TCC) OF THE UPPER URINARY TRACT (UUT ) ? Erfai Emtair, R. Kuntz. 6. GASTROINTESTINAL STROMAL TUMORS (GIST). Abdulsalam Lalli. Mustafa Eljadal. 7. TUMOUR ASSOCIATED ANGIOGENESIS IN HUMAN COLORECTAL CANCER. Khaled A Rmali, Malcolm C A Puntis and Wen G Jiang. 8. THE EXPRESSION OF VHL (VON-HIPPEL LINDAU) GENE IN BREAST PANTIES AND ITS IMPACT ON INVASIVENESS OF HUMAN BREAST CANCER CELLS. Khaled A Rmali , Mohammad K Zia, Robert E Mansel, Wen G Jiang. 9. LOW COLLAGENASE-1 (MMP-1) AND MT1-MMP EXPRESSION LEVELS ARE FAVOURABLE SURVIVAL MARKERS IN ADVANCED COLORECTAL CARCINOMA. R. Bendardaf , H. Lamlum a, P. Vihinen , R. Ristamäki, J. Laine, S. Pyrhönen . 10. TREATMENT OUT-COME IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA AT AL JAMAHIYRIA HOSPITAL BENGAZI. Rabia O. Nafo, Soad S. Kardash, Mohamed El Mangosh, Mohamed Latiwish, Farag Bodabous. 11. CARDIOVASCULAR SURGERY IN THE MANAGEMENT OF MALIGNANT RENAL NEOPLASMS: A REPORT OF TWO RARE CASES DONE IN THE AFRICAN INSTITUTE OF ONCOLOGY. Ali Saleh Nas. 12. Prognostic significane of Ezrin in advanced colorectal cancer patients. A. Elzagheid, R.Bendardaf, A. Buhmeida, K. Syrjanen , S. Pyrhonen , O. Carpen. 13. BIOCHEMICAL AND CYTOLOGICAL MARKERS IN TUBERCOULOUS AND LUNG CANCER PLEURAL EFFUSIONS. Mabrouk Bashir, Amina Alziadi. - - - - - A- FREE PAPERS 2 14. OVER VIEW OF CANCER PAIN MANAGEMENT IN AFRICAN ONCOLOGY INSTITUTE. Muftah-S-AL shibani, Ammar Mohi , Lamia. 15. EVALUATION OF THE EFFICACY OF THE SURGICAL TREATMENT OF PULMONARY METASTASES. Ali Saleh Nasr. 16. SURVIVAL OF THE BREAST CANCER PATIENTS WITH BONE METASTASES. Manal El-Habbash, Abukris Alwindi. 17. REASONS FOR DELAY IN DIAGNOSIS IN BREAST CANCER PATIENTS – A PROSPECTIVE STUDY. Alramah Alarbi Alrmieh*, Abukhrais Alwandi, Vijay Ahuja. 18. THE BENEFITS OF PHYSIOTHERAPY TO THE BREAST CANCER PATIENT. Sami Elmahgoub* and Riyad Bendardaf 19. BONE AND SOFT TISSUE METASTASIS OF HEPATOCELLULAR CARCINOMA : A CASE REPORT. Walid masuad Abdullah. 20. BREAST CANCER DURING PREGNANCY IN BENGHAZI. Salah Salem El Taktuk MD, Tawfik Ali Abouzalout MD, Hamed R Bosrewill MD, Hussein O El-Bernawi FRCSI. 21. EVALUATION OR CERVICAL CANCER BY MRI: DETECTION STAGING AND FOLLOW UP. Fariha.Buzghia. 22. INVASIVE LOBULAR CARCINOMA BREAST – A CASE REPORT. R.K.Bhatnagar, A. Fitori, Ismail Faisal,A.Mubarka. 23. OVARIAN CANCER PROFILE IN EASTERN LIBYA. M. El Mistiri , R. Shembesh,S El Brki, A Attia. 24. LUNG CANCER PROFILE IN EASTERN LIBYA. Mufid El Mistiri , Mabruka Khalid, Faiz El Sadawya, A. Wahab Gadir, Awad Bendardaf. 25. EPIDEMIOLOGY OF CLINICAL FEMALE GENITAL TRACT MALIGNANCY IN BENGHAZI. Fatma essa, Ali EL-Rrabti, Faraj Ben Ali. 26. A rare thyroglossal cyst with formation of papillary thyroid carcinoma. M.A. Darwish, A. Abussa, H. Hashmi 27. GASTRIC LYMPHOMA TRIPOLI MEDICAL CENTER’S EXPERIENCE. Afaf Abu Shaala, Abukris Alwindi. 28 Pediatric acute lymphoblastic leukemia:Biology, diagnosis and prognosis. Dina A Yassin. 29 Current potentials for cancer pain management. Ahmed Helmy A. Abouel Soud. 28. MANAGEMENT OF CHRONIC MYELOID LEUKAEMIA. John M Goldman. Haematology Department, Imperial College London. 29. CANCER REGISTRATION. Paola Pisani. Oxford University. 30. SCREENING AND EARLY DETECTION. Dr. Lawrence von Karsa. 31. CANCER INCIDENCE IN EASTERN LIBYA: PRELIMINARY RESULTS OF THE YEAR 2004. Mufid El Mistiri, et al. Benghazi Cancer Registry. Research Centre Garyounis Uninersity. www.cancerlibya.com. 32. ANNUAL REPORT OF THE AOI CANCER REGISTRY FOR 2006. Abougeila Abussa, Dr. Hussein El Hashmi, Dr. Vijay Ahuja. Waled m Ab Massoud, Hussam Al Ganga. 33. SURGICAL MANAGEMENT AND TREATMENT OF BREAST CANCER. Stephen J. Kirk. 34. RADIOTHERAPY IN BREAST CANCER. Paul Henry. - - - - - B- PLENARY LECTURE. 3 35. ENDOCRINE MANAGEMENT OF BREAST CANCER. ABUKRIS ALWINDI. 36. MULTIVISCERAL RESECTION IN ADVANCED COLONIC CANCER: IT IS A PALLIATIVE OR A CURATIVE THERAPY? Sacco R, Gervasi R, Rizzuto A, Pata F. 37. CHEMOTHERAPY FOR COLO-RECTAL CANCER. Jamal Zekri. 38. RADIOTHERAPY IN RECTAL CANCER. Dr. Paul Henry. 39. MINIMALLY INVASIVE CANCER SURGERY. Ali M. Ghellai . 40. BREAST RECONSTRUCTION IN THE MANAGEMENT AND TREATMENT OF BREAST CANCER. Stephen J. Kirk. 41. HEPATIC RESECTION FOR METASTATIC COLO-RECTAL CANCER. 20 Years of experience. Aroldo Fianchini, Walter Siquini, Asselhab Salem. 42. TARGETED THERAPY IN NON-HODGKIN’S LYMPHOMA WITH MONOCLONAL ANTIBODIES. Abdul Shlebak. 43. UPDATE ON MULTIPLE MYELOMA. Moulod El-Agnaf. 44. CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA. Salem Zarrouk. 45. THE ROLE OF MULTI-DISCIPLINARY TEAMS (MDT) IN OPTIMISING THE PROVISION OF HAEMATO-ONCOLOGY CARE. Abdul Shlebak. 46. CURRENT RESULTS OF ALLOGENEIC HEMOPOIETIC STEM CELL TRANSPLANTATION. Andrea Bacigalupo. 47. CURRENT PROBLEMS OF VOLUNTARY BLOOD DONATION AND CLINICAL TRANSFUSION PRACTICE IN EUROPE. Umberto Rossi. 48. PALLIATIVE CARE IN ONCOLOGY. Filbet M. 49. ESTABLISHMENT OF PAIN CLINICS IN ARAB, AFRICAN AND DEVELOPING COUNTRIES. M. S. El-Ansary. 50. VENOUS THROMBOEMBOLISM AND CANCER. Abdul Razzak Shlebak. 51. ESTABLISHMENT OF PAIN CLINICS IN ARAB, AFRICAN AND DEVELOPING COUNTRIES. M. S. El-Ansary A) FREE PAPERS 1. RESPONSE TO CHEMOTHERAPY (IRINOTECAN PLUS 5FLUOROURACIL) IN COLORECTAL CARCINOMA CAN BE PREDICTED BY TUMOUR DNA CONTENT R. Bendardaf a*, H. Lamlum a, R. Ristamäki a, A. Ålgars a, Y.Collan b, S. Pyrhönen a Department of Oncology and Radiotherapy, b Department of Pathology, Turku University Hospital, Turku, Finland Abstract Background: The aim of this study was to identify markers that might predict response to chemotherapy. Postoperative chemotherapy improves the outcome in stage III colon cancer and is widely accepted as a standard therapy, but there are currently no reliable predictors to identify and select patients that will benefit. Patients and methods: - - - - - a 4 Using DNA image cytometry the DNA content was determined from the isolated nuclei of 56 primary colorectal carcinomas of patients who received chemotherapy (either irinotecan or irinotecan plus 5-fluorouracil and folinic acid) for advanced disease. Response to chemotherapy could be reliably evaluated in 53 patients. Results: The modal DNA content (ploidy status) of the tumour correlated with the observed response to chemotherapy (p=0.01). An objective response was observed in 56% of patients whose tumour histograms displayed tetraploid, peri-tetraploid or multiploid pattern of peaks, compared with 19% in patients with diploid, peri-diploid or aneuploid peaks. Notably, 86% (6/7) of patients whose tumour displayed a multiploid peak pattern showed an objective response and one patient had stable disease. Conclusion: This study suggests that modal DNA content can be used to predict a patient's response to chemotherapy in advanced colorectal carcinoma. This may help in identifying patients who will benefit most from therapy for advanced colorectal cancer. Key words: 5-FU, colorectal carcinoma, image DNA cytometry, irinotecan, ploidy, response. 2. Survival of Breast Cancer Patients Treated in Tripoli/Libya 2000-2005 Manal El-Habbash, Abukris Alwindi. Oncology Department, Tripoli Medical Center Department of medicine, Alfateh University . To study survival of breast cancer over the 2000-2005. To compare this cohort survival to a previous cohort presented at St Gallen 2003 abstract No.p5 To relate recurrence rate and survival to risk factor as menopausal status, lymph node involvement, and Estrogen and progesterone status Design and Setting: Non-randomized retrospective study in patients with breast cancer confirmed by biopsy in Oncology department in Tripoli medical center. Patients: Five hundred fifty two patients were included in this study in the period between January 2000, and December 2005. Results: The age ranged between 20-70 years with mean =45.1years.1.8% were male. 56% are premenopausal women. The commonest stage, was stage II (43.3 %%) and stage I, III, and IV were (9.6%, 33.5%, 10.5% respectively.60% have lymph node involvement. Most patients were treated by mastectomy and axillary clearance (76%). 65% are known estrogen and progesterone receptor status, where 53.8% are estrogen and progesterone positive and 46.2% are negative. 70% received Chemotherapy as CAF. 28.6% had recurrence, most common site of recurrence was as visceral metastases in 36%, 31.6% with bone metastases, and local recurrence in 17%. Overall recurrence rate at 1,2and 5 years was 14.8%, 25.4%and 38.4% respectively. - - - - - Study objective: 5 Overall survival rate at 1,2and 5 years was 95%, 87.4%and 78.6% respectively. Overall recurrence rate at 1,2and 5 years and survival rate was better in node negative patients p=0.0001. Overall recurrence rate at 1,2and 5 years and survival rate was better in estrogen positive patients than in estrogen negative patients p=0.0001 Conclusion: Marked improvement in survival has occurred compared to the previous cohort .this probably reflect better staging, more availability of estrogen and progesterone receptors, more uses of radiotherapy, and more uses of Anthracyclines. 3. PCR BASED IN HOUSE METHOD OF HLA GENOTYPING FOR BONE MARROW TRANSPLANTATION. Rajesh Singh.J, S. Mudasir Ahmad*, Awatif Altrablsi, Abugeala Aboussa. Department of Molecular Diagnostics, African Oncology Institute, Sabratha, Libya ABSTRACT Introduction: The aim of the study was to develop the In house PCR protocol of HLA genotyping for Bone marrow transplantation (BMT). HLA molecules are diverse group of cell surface glycoprotein involved in the regulation of immune response. They play an important role in intracellular recognition and in the discrimination between self and nonself. The major role is in determining whether transplanted tissue is accepted as self ( histocompatible) or rejected as foreign (histoincompatible). Materials and methods: Twenty siblings from three families are selected as donors for molecular HLA typing. DNA isolation and purification was done using Genomic DNA purification Kit ( Promega, USA). Amplification was carried in a thermal cycler (Master Cycler TECHNE-GENIUS, England) by using SSP primer sequences (Dynal). After amplification, the reaction products were fractionated by gel electrophoresis in 2 % agarose gels. All the PCR results were tested for reproducibility by at least three times. Bands that did not show fidelity were eliminated. Results and conclusions: Results based on this study showed by HLA-A, HLA-B and HLA- DR markers are efficient among siblings when compared with non familial donors. For confirmation the results were compared with commercially available Kits. The method is fast, sensitive and cheap to select immediate donors for BMT. The method can be used for our continuous study of Bone Marrow transplantation (BMT). AND STRATEGIES MANAGEMENT IN OF Introduction - - V.Roetzscher , Rishi M., Elhousieni M., El Hanash A. Department of General Surgery , University of Al Fatah, Tripoli Central Hospital, Tripoli, Libya Arab Jamahiriya Abstract - - 4. OPERATIVE GUIDELINES STANDARDIZING CLINICAL COLORECTAL CARCINOMA 6 Locoregional recurrence and distant metastases decide on the clinical course of colorectal carcinoma in terms of prognosis .The assessment of risk of locoregional recurrence can be derived from histopathological evaluation of residual disease (R0-2) and systematic lymphadenectomy , which are responsible for the extent of large bowel resection .Where as tumour stage and tumour grade reflect independent oncological factors , local recurrence rates are proved to be related to surgical application of oncological principles following no-touch – isolation technique and systematic lymphadenectomy . Increasing knowledge of tumour biology , metabolic behaviour of tumour cells , updated operative methods and multidisciplinary approach in treatment of colorectal carcinoma has changed thoroughly the clinical understanding . As long as reliable documentation , clinical analysis , and statistical comparison is not available in terms of primary and secondary prevention on a national level , standardized treatment following international recommendation is necessary . This will guarantee satisfying clinical outcome , which can be assumed to be comparable with international results . Material and methods A retrospective study of 45 cases of colorectal cancer was analyzed between January 2004 and December 2005 concerning the mode of treatment in terms of operative methods applied , completeness of primary tumour removal and management of relevant lymphatic drainage .Tumour pathology was considered using Dukes tumour classification, and clinical data were drawn from individual medical files , and compared with up–to–date standards in operative treatment.The individual procedures were examined in detail to derive future clinical practice. 5. CAN ENDOSCOPIC ABLATION UND SURVEILLANCE BE RECOMMENDED AS PRIMARY TREATMENT OF SUPERFICIAL TRANSITIONAL CELL CARCINOMA (TCC) OF THE UPPER URINARY TRACT (UUT ) ? Introduction & Objectives This prospective study to evaluate whether ureterorenoscopy (URS) combined with holmium laser resection (HOLR) and endoscopic surveillance could be recommended as primary treatment of superficial TCC of the UUT, in the same way as endoscopic resection and surveillance is recommended as primary treatment for superficial TCC of the urinary Bladder. Material & Methods 27 patients with 29 renal units (RU) underwent a total of 140 URS, 81 with HOLR for superficial ureteral and/or pelvicalyceal tumors, and 59 for surveillance. 2 patients had bilateral disease, 9 patients had solitary kidneys and 2 patients renal insufficiency. 16 patients (59.2 % ) had associated bladder tumor HOLR was performed with 7.5 F semirigid and 8.5 F flexible ureteroscopes, a holmium: YAG-Laser at 5-15 W. (0.5-1.0 J., 10-15 Hz.) and 220 nm flexible laser fibers. Postoperative surveillance included cystoscopy and URS with retrograde pyelography, UTT cytology and biopsies of suspicious areas. - - - - - Erfai Emtair, R. Kuntz. Urological department, Iben Senna Hospital, Tahdi university-Sirte, Libya. Auguste-Viktoria-Hospital, Berlin, Germany 7 Results 17 of 29 RU (58.6 %) showed solitary and 12 (41.4 %)multifokal lesions (pTa-1, G1G2). 12 of 29 RU (41.4%) remained tumor-free after initial URS with HOLR (mean follow up 19 , range 3-40 mo), and 7 of 29 RU (24.1 %) remained tumor-free after 1 HOLR for tumor recurrence (mean follow up 13.4, range 3-30 mo). 1 patient with bilateral disease and 2 patients with solitary kidneys underwent a total of 22 HOLR for persistent tumor growth without tumor progression (mean follow up 21.3, range 3-42 mo). 5 patients with unilateral disease and a total of 18 HOLR. had to be treated with nephrectomy for various reasons, 1-14 mo.after initial HOLR. None of the 27 patients has required dialysis Conclusions Endoscopic holmium laser ablation and careful endoscopic surveillance seems to be safe and effective and can be recommended as primary treatment of superficial TCC of the UUT, even in patients with normal renal function. However, the patients should be able to completely understand the risks of this approach and be fully cooperative. 6. GASTROINTESTINAL STROMAL TUMORS (GIST) Abdulsalam Lalli, Mustafa Eljadal. Surgery Department, Agelat Hospital and Oncology center ABSTRACT Background: Gastrointestinal stromal tumors (GISTS) belong to a group of cancers called soft tissue sarcoma. GISTS may occur anywhere along the length of the digestive tract. Aim: Patients with upper or lower GIT bleeding with a mass lesion or obstruction with negative endoscopies finding we have to put in mind the gist affection. Material and Methods: We studied 14 cases of GISTS collected for 3 years, 4 males and 10 females, the mean age of patients (22-79 years). Results: The most common anatomic locations are stomach 60%, small bowel 30%,rectum,colon and esophagus each 3% Because of there is no general screening test to detect the tumor early, so the earlier any tumor is discovered and treated the better is the chance of survival. - - - - - Conclusions: 8 7. TUMOUR ASSOCIATED ANGIOGENESIS IN HUMAN COLORECTAL CANCER Khaled A Rmali, Malcolm C A Puntis and Wen G Jiang. Department of Surgery, Wales College of Medicine, University of Cardiff, United Kingdom. ABSTRACT Tumour angiogenesis is a critical step in the growth, metastatic spread, and re-growth of colorectal cancer. Angiogenesis specific to tumour is a complicated process, the mechanisms of which remain unclear. Metastasis of colorectal cancer may result from passive entry into the circulation secondary to angiogenic factors effect. The survival and growth of colorectal tumour and thus their metastases are dependent on the balance of endogenous angiogenic and anti-angiogenic factors such that the outcome favours increased angiogenesis. Angiogenesis has become an attractive target for anticancer drug development, based on its important roles in tumour growth, invasion, and metastasis. Several growth factors have been identified that regulate angiogenesis in colorectal cancer; the most important of these is vascular endothelial growth factors, and of the several angiogenic factors, VEGF expression at the deepest invasive site of tumour was the most statistically significant indicator of prognosis in advanced colorectal carcinoma. In this review paper we provide an overview on angiogenic factors and their receptors. More over we will showing the role of newly identified tumour endothelial markers (TEMs) that are involved in tumour-associated angiogenic process in colorectal cancer, and its therapeutic value. 8. THE EXPRESSION OF VHL (VON-HIPPEL LINDAU) GENE IN BREAST PANTIES AND ITS IMPACT ON INVASIVENESS OF HUMAN BREAST CANCER CELLS. ABSTRACT Background The von Hippel-Lindau (VHL) gene is located on the short arm of chromosome 3, its mutation leading to the development of the von Hippel-Lindau disease. VHL gene is a putative tumour suppressor gene in VHL and a few other conditions, possibly by negative regulation of hypoxia inducible factor-1 (HIF-1) and the stromal derived factor-1 (SDF-1) receptor, CXCR4, via which exerts inhibition of angiogenesis and tumour cell migration. The current study investigated the role of VHL in the invasion of human breast cancer cells, in vitro, and in clinical breast tumours. Methods Primary Breast cancer samples (n=124), adjacent non-cancerous breast tissues obtained from patients in cohort (n= 33) and a panel of human breast cancer cells (n=12) were used. Tissue distribution of VHL protein in human breast cancer tissues - - - - - Khaled A Rmali , Mohammad K Zia, Robert E Mansel, Wen G Jiang. Department of Surgery, Wales College of Medicine, Cardiff University, Cadrdiff, United Kingdom.. 9 were assessed using immunohistochemical analysis, and VHL transcript using quantitative reverse transcription PCR . Invasiveness and migration of cancer cells were assessed using the Matrigel invasion and Cytodex-2 migration assays.Statistical analysis was student t test. Results MCF-7 and ZR-751 expressed very high levels of VHL transcripts, but the highly aggressive MDA 231, MDA MB 435 and MDA MB 453 expressed either non-or low level. The levels of VHL transcripts were significantly lower in grade 2 and grade 3 tumours ( M±SD 1.36+0.55 and 0.9+0.37), compared with grade 1 tumours (M±SD 12.3+7.6, p<0.002). Node positive tumours had lower levels of VHL than node negative tumours. Although tumours from patients with metastasis and from those who died of breast cancer had low levels of VHL, the most significant reduction of VHL was seen in tumours which developed local recurrence (p=0.03). The staining of VHL protein was most abundant in mammary epithelial cells and moderate in endothelial cells. Tumour cells in breast tissues had low to moderate VHL staining. Full-length human VHL cDNA, isolated from normal human tissues were cloned into pCR-GFT-NT expression vector (pCR3-GFP/VHL). pCR3-GFP/VHL transfected MDA MB 231 (MDA 231VHL+) exhibited a reduce spontaneous in vitro invasiveness (M±SD 14.8+2.7) compared with control cells (M±SD 18.4+1.4). MDA 231VHL+ cells also lost their invasion response to HGF/SF, an invasion inducing cytokine. The MDA 231VHL+ cells had substantially reduce motility compared with that of controls (M±SD 14.8+0.7 for MDA 231VHL+ and 20.7+1.2 for control, p<0.001. Conclusion VHL exerts inhibitory effects on the invasive and migratory capacity of breast cancer cells in vitro. Low levels of VHL occur in most aggressive breast tumours. Taken together, VHL is a powerful putative tumour suppressor gene in human breast cancer. 9. LOW COLLAGENASE-1 (MMP-1) AND MT1-MMP EXPRESSION LEVELS ARE FAVOURABLE SURVIVAL MARKERS IN ADVANCED COLORECTAL CARCINOMA R. Bendardaf a*, H. Lamlum a, P. Vihinen a, R. Ristamäki a, J. Laine b, S. Pyrhönen a, Department of Oncology and Radiotherapy, b Department of Pathology, Turku University Hospital, Turku, Finland a Objective: Extracellular matrix degradation is required for invasive growth and metastasis formation in colorectal carcinoma, therefore we have examined matrix metalloproteinases expression (MMP-1, MMP-13 and MT1-MMP) and apoptosis in tumours from 49 patients with advanced colorectal disease. Methods: MMP expression was determined immunohistochemically and apoptotic index (AI) was ascertained using the Tunel assay. - - - - - Abstract 10 Results: Low levels of MT1-MMP, MMP-1 and AI were found to be favourable markers significantly associated with longer survival. MT1-MMP expression levels below the median (≤14.0% of tumour cells) were associated with better overall survival (median 26.2 vs. 15.6 months, p=0.02) and MMP-1 expression levels below the median (≤ 28.7% of tumour cells) correlated with longer survival following metastasis (median 21.5 vs. 13.3 months, p=0.05). MT1-MMP, MMP-1 and AI were all found to have significant independent effects on survival. Interestingly, MMP-1 expression levels above the median were associated with distal disease of the colon (p=0.02) Conclusions: These findings reveal that MT1-MMP and MMP-1 expression levels and AI are useful prognostic indicators in advanced colorectal carcinoma and suggest that markers of MMP expression might be used in identifying patients who would benefit from new treatment modalities involving MMP inhibitors. Key words: MMP-1, MMP-13, MT1-MMP, AI, colorectal carcinoma, survival. 10. TREATMENT OUT-COME IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIAAT AL JAMAHIYRIA HOSPITAL BENGAZI Rabia O. Nafo, Soad S. Kardash, Mohamed El Mangosh, Mohamed Latiwish, Farag Bodabous. Department of Medicine, Hematology unit Faculty of Medicine, Gar Younis University Benghazi- Libya. Abstract: Acute lymphoblastic leukemia (ALL) is a malignant disease of the lymphoid system. It affects all age groups with peak incidences in children and elderly. We conducted this study to determine the clinical characteristics and management outcome among the adult Libyan patients who were treated in Al Jamahiyria Hospital – Benghazi. Key words: Malignancy, Leukemia, Acute lymphoblastic leukemia, chemotherapy. Ali Saleh Nasr MD, PhD, FETCS. Thoracic & Cardiovascular Surgery Consultant, Tajoura Cardiac Centre, Tripoli- Libya. Thoracic & Cardiovascular Surgery Consultant, African Institute of Oncology, Sabrata, Libya Either Transmural or endovascular invasion of regional veins is peculiar to various retroperitoneal and pelvic tumors. Such venous extension (VE) is principally a trait of malignant renal neoplasm (MRN). The mass ordinarily remains localized within the ipsilateral renal vein as a tumor thrombus (TT). Regardless of whether this is at the - - - - - CARDIOVASCULAR SURGERY IN THE MANAGEMENT OF MALIGNANT RENAL NEOPLASMS: A REPORT OF TWO RARE CASES DONE IN THE AFRICAN INSTITUTE OF ONCOLOGY. 11 outset of endovenous origin or from actual penetration across the vessel wall, once inside the vein it manifests little or no tendency to infiltrate intima. Consequently, in many instances, TT continues as a non-adherent isthmus into the inferior vena cava (IVC), sometimes propagating from there into the right heart chambers, and on rare occasions even into the pulmonary artery. Invasion of regional arteries invaded directly. I reported two cases of malignant renal neoplasm (MRN) with invasion of great vessels. CASE 1 A 77-year-old man admitted in our institute. Patient transferred from Sabrata Teaching Hospital as a case of right renal mass, USG, C-T scan and MRI suggestive of extension of tumor beyond renal capsule and into the inferior vena cava. Aim and Plan of Surgery In this case, the patient underwent laporatomy with the aim of complete resection of the MRN with tumor thrombus (TT) into the inferior vena cava (IVC). For that, a new procedure used to extract the tumor thrombus as proved by a review of the literature, which reveals my case to be the first case done by this procedure. After a complete mobilization of the colon, dissection of the IVC had done proximal and distal control of the IVC and its tributaries done using vascular sling. The left renal artery and vein encircled by one sling and this will not allow the blood to supply the kidney during venous clamping and this will prevent any congestion. Two purse string stitches applied on the IVC at the level of renal hilum, fogorty catheter passed up to the level of the diaphragm, which work as intravascular clamp. Cavotomy done where the fogorty catheter inflated and the assistants close the slings by just bulling it up the tumor thrombus (TT) extracted and detached from the renal vein and the Cavotomy closed by partial clamp after removal of the fogorty catheter. All the slings released except the right renal sling. Cavotomy closed using non-absorbable monofilament continuous stitches and the partial clamp removed. Right nephrectomy with complete resection of the right renal vein with a stump of tissue from the IVC (Partial side cavectomy). The defect closed by simple one layer of non-absorbable monofilament continuous stitches. Histopathological examination shows renal cell carcinoma of clear type, grade III, stage III and the patient referred to the oncology committee where Interferon therapy recommended. A 29-year-old patient admitted in our institute with complain of pain in the left lumbar and left gluteal region, which is radiating to the left leg since 8 months associated with loss of appetite and weight. Physical examination reveals a huge abdominal mass; C-T scan done showed left hypochondrial mass with extensive Para aortic lymphadenopathy invading the abdominal aorta. Aim and Plan of Surgery: Our aim was to complete resection the MRN with the aortic part, which invaded by the tumor and replace it with Dacron prosthesis. The patient underwent laporatomy where Complete resection of the MRN done. The abdominal aorta where found compressed by the enlarged Para aortic lymph nodes which completely dissected. - - - - - CASE 2 12 There was no direct invasion of the aorta. The weight of this malignant renal neoplasm (MRN) was 9 kilograms. Histopathological examination shows renal cell carcinoma of clear type, grade II, stage III and the postoperative staging was T3 N1 M0. Patient referred to the oncology committee where Interferon therapy recommended. 11. Prognostic significane of Ezrin in advanced colorectal cancer patients A. Elzagheid, R.Bendardaf, A. Buhmeida , K. Syrjanen , S. Pyrhonen , O. Carpen. Department of Oncology and Radiotherapy , Turku University Hospital , Savitehtaankatu 1 P B 52 , FIN – 20521 , Turku , Finland , Department of Pathology , University of Turku Kiinamyllynkatu 10 , FIN – 20520 , Turku Finland . Abstract Background and Objective : To test the ezrin expression in colorectal cancer (CRC) Patients and correlate its expression with clinico pathological outcome . Material and Methods : We examined Ezrin expression in 66 formalin – fixed , paraffin – embedded CRC samples using immunohistochemistry (IHC). Results : Ezrin expression was significantly ( p = 0.001) related to localization of the primary tumor , being more intense in colon as compared with rectal carcinoma . Conclusion : Taken together , these tentative data ( based on a limited sample size ) implicate that analyzing Ezrin expression in CRC might provide clinically valuable information in predicting DSS as well as survival with metastases . If confirmed in larger studies , such information would have a significant impact on our decisions concerning the therapy and management of these patients . Key Words : Ezrin , colorectal cancer , immunohistochemistry , disease – specific survival , survival with metastases. - - - - - Furthermore , tumors in the descending colon had the highest level of ezrin expression , as compared with all the other localizations ( p = 0.018). In univariate analysis , ezrin was an almost significant predictor of disease specific survival ( DSS) , which decreased linearly along with the up- regulation of ezrin from 44 months down to 28 months ( p = 0.056 ; ANOVA) . Importantly , Ezrin was a significant predictor of survival with metastases ( WMS ) , which decreased from 36.6 to 20.5 months from negative – weak to intense expression ( p = 0.022 ; ANOVA ) . In univariate (Kaplan – Meier ) survival analysis , the 3- grade system was not a significant predictor of DFS , DSS or WMS , but using the 2- grade system (negative – weak vs. moderate – strong ) , ezrin expression significantly predicted 5- year DSS and also WMS with borderline significance . 13 BIOCHEMICAL AND CYTOLOGICAL MARKERS IN TUBERCOULOUS AND LUNG CANCER PLEURAL EFFUSIONS 12. DR. Mabrouk Bashir, *Dr. Amina Alziadi, Respiratory Department TMC. Abstract The objective is to find out if biochemical and cytological analysis of pleural effusion can be taken as helpful markers to differentiate between malignant and non malignant causes. Methods and materials: Prospective designed study was conducted in TMC for a period of two years and half ( March 2004 to Oct. 2006 ) including all patients admitted with exudative pleural effusion due to TB or lung cancer. At admission pleural effusion was assisted clinically and radiologically, aspiration and pleural biopsy was done for each patient and samples were sent for biochemical, cytological and histopathological studies. Results: In this study 174 adult patients (142 M) & (32 F) have the biochemical criteria of exudative plural effusion, histopathologically (91) have effusion associated with lung cancer and (83) have tuberculous pleural effusion. The effusion cytological analysis for the lymphocytes percentage showed no statistically significant difference between TB and malignant effusions (P= 0.444). Biochemically high LDH levels were associated with effusions due to lung cancer, and expressed in significant statistical value (P< 0.0001). Whereas Protein and Sugar contents, doesn't show any significant difference between the two examined groups (P = 0.8485) and (P = 0.0890) respectively. Conclusion: - - - - - Tuberculosis and Lung Cancer are common causes of exudative pleural effusion, and in the absence of histological prove, it is difficult to differentiate between the two pathologies in most of the cases. From this study we can conclude that the histology is necessary to establish the cause of exudative pleural effusion, and among the biochemical markers LDH is the most helpful to differentiate between malignant and tuberculous effusions 14 13. OVER VIEW OF CANCER PAIN MANAGEMENT IN AFRICAN ONCOLOGY INSTITUTE. Muftah-S-AL shibani, Ammar Mohi , Lamia, Departments of anaesthesiology ,ICU and pain care unit, AOI, Sabratha Objective; To demonstrate the activities of pain care unit in African cancer institute in a period of one year duration since starting of this unit. Introduction: It has been established by the WHO that every day four million people through out the world are suffering from cancer pain and the prevalence is rising. About 30% to 50% of cancer patients have pain at the time of diagnosis and by time the disease advances this proportion rises up to 80% and all terminal cases have pain. In the late 80s WHO introduced 3 step ladder treatment of cancer pain. It has been proved that 80% to 90% of cancer pain can be controlled by following this step ladder system. With the help of our government and help of the scientific and supportive administration in the African oncology institute a pain clinic was estsablished. Materials and methods:The activities undertaken by the pain clinic at AOI since its inception in Jan 2006 are presented. The organization of the department , allocation of resources and the clinical work undertaken was reviewed. A total of 123 patients were referred to the pain clinic since 1 Jan 2006 . An analysis was done based on the following criteria : clinical presentation, primary malignancy, prior and current anticancer treatment, pain treatment and response. The basic treatment approach is that on the first visit patients are assessed generally and measurement of their pain regarding site ,severity and type is done. Any associated symptoms or signs are also recorded.For measurement of severity the VRS & VAS score is used. In addition to assessment of sleep, activity and psychological assessment which is vital in cancer patients management.The treatment is given according to the WHO step ladder guide lines and the patients are supplied with medicines and a follow up chart containing all data Results : Most of the patients are referred to the pain clinic from the other clinical departments of the institute. Most of them have completed their initial treatment with surgery, CT , RT or a combination of these. Some of them still on active anti cancer treatment. Majority of patients presented with mild to moderate pain and were started on step 2 in WHO step ladder. Nearly 50% of these had to be shifted to step 3 because of unsatisfactory control of pain. Some coming in terminal stages were directly put on step 3. The common sites of primary cancers in these patients were prostate (16.5%), lung (15.4%), colon (14.6%) and breast (5.6%) Response to treatment was satisfactory in most cases and they are on regular followup. Conclusion´: Caner pain management programme is very essential and vital factor in management of cancer patients in order to provide them with better quality of life with the stress on “ not just to add days to what is left of life but to add life to what is left of days “ Key words; cancer pain , CNS plasticity , hyperalgesia , WHO step ladder ,adjuvant therapy - - - - - Abstract 15 14. EVALUATION OF THE EFFICACY OF THE SURGICAL TREATMENT OF PULMONARY METASTASES. Ali Saleh Nasr, MD, PhD, FETCS. Thoracic & Cardiovascular Surgery Consultant, Tajoura Cardiac Centre, Tripoli- Libya. Thoracic & Cardiovascular Surgery Consultant, African Institute of Oncology, Sabrata, Libya The lungs are the organ system that acquires the most metastases of any system in the entire body by several routes. Nowadays, the surgical treatment is an established technique in the treatment of PM & it is not a precondition that the primary tumor radically resected, but it must be under control. PATIENTS AND METHODS: In a period of 10 yrs, 43 pts underwent surgery for PM. In this group of pts 23 male (53.5 %) and 20 female pts (46.5 %). In this study we had recommended that the pt must be able to withstand the operation planned, it must be possible to remove all of the PM at operation, the primary site and extra PM, must be controlled or controllable,& there must no be better treatment available offering the same chance of cure or of superior palliation. RESULTS: The main surgical procedure was Thoracotomy & Sternotomy where only in 1 pt (2.3%) The main types of resections were wedge resection (60.7%), Segmentectomy (4.6%), Metastectomy (6.9 %), Lobectomy (16.2%), Pneumonectomy (2.3%) & Explorative Thoracotomy (9.3%). At time of this study, pts were involved in the estimations of 3 yrs and 5 yrs survival rates were 25 and 16 pts respectively .1 yr survival rate were 69.8 %. 3yrs survival rates were 40.0 %. 5 yrs survival rates were 31.2 % - - - - - CONCLUSION: Surgical treatment of PM is safe and effective method. PM should resected with minimal amount of healthy surrounding tissue. Thoracotomy considered as the best surgical approach and median Sternotomy must be limited to the bilateral lesions. The best survival rates seen in pts with primary tumor in suprarenal glands and lungs followed by bones and breasts, in pts with carcinomas followed by pts with malignant melanoma and sarcomas, in pts average interval more than 49 months & in pts without lymph nodes metastases seen at time of operations. 16 15. SURVIVAL OF THE BREAST CANCER PATIENTS WITH BONE METASTASES . Manal El-Habbash, Abukris Alwindi , Oncology department -Tripoli medical center, Department of medicine -Alfateh University. Study objective: To study relation of survival in the breast cancer and bone metastases in the period 2000-2005. Design and Setting: Non-randomized retrospective study in patients with breast cancer confirmed by biopsy in Oncology department in Tripoli medical center. Patients: Five hundred fifty two patients were seen, 79 patients representing 14.3% were included in this study in the period between January 2000, and December 2005, who presented with bone metastases as initial presentation, or who developed recurrence as bone metastases on follow up. Results: The age ranged between 20-70 years with mean =49.6years. 5% were male. 48 % are premenopausal women. 62% are known estrogen and progesterone receptor status, where 57.2% are estrogen and progesterone positive and 42.8% are negative. 46.8% they received chemotherapy as second line in relapse cases where Taxane based chemotherapy were given in 83.7% of them.36.7% received radiotherapy to chest wall and axilla. All of them received radiotherapy as palliative intent to bone metastases. Bisphosphonates was given in form of zoledronate or pamidronate 4weekly injection. 38% of patients received Aromatase inhibitor. Recurrence rate at 1year was 37.7%, at 2year was 28.3%, and at 5years was 43%. Overall survival rate with bone metastases at 1,2and 5 years was assessed which were 92 %, 83%and 63.4% respectively. - - - - - Conclusion: We conclude that isolated bone metastases are compatible with prolonged survival and good quality of life. 17 16. REASONS FOR DELAY IN DIAGNOSIS IN BREAST CANCER PATIENTS – A PROSPECTIVE STUDY Alramah Alarbi Alrmieh*, Abukhrais Alwandi**, Vijay Ahuja*. *African Oncology Institute, Sabratha. ** Tripoli Medical Centre Abstract Breast cancer is one of the common cancers in Libyan women. Most of the patients present with locally advanced disease, resulting in poor survival rates. This prospective study was planned, to get a baseline data on the reasons for the delay in the diagnosis of breast cancer in Libyan women, as well as to get information about their knowledge in relation to breast cancer. Sixty one women with a diagnosis of breast cancer, attending the hospital (AOI & TMC) between 1st Jan and 30th June 2006 were included in the study. A questionnaire that covered the objectives of the study was offered to them and the response was tabulated. In addition, details of stage at presentation and histological diagnosis were collected from the case records. It was observed that the first manifestation of breast cancer was a palpable lump in 90.2% cases and it was detected accidentally in 59%. Majority (54%) of the women present in advanced stages of disease (stage III or IV) at diagnosis. Most of the cases (63%) were not aware of breast self-examination (BSE) and there was a delay of more than 1 month in seeking medical advice in 44.3% of cases. It was also found that most of the women have no knowledge of breast cancer, its presentation and methods of early detection and also have a fear of cancer. This study stresses the need for Health education for women regarding breast cancer highlighting the early signs and symptoms, importance of prompt treatment and curability of early stage disease. 17. THE BENEFITS OF PHYSIOTHERAPY TO THE BREAST CANCER PATIENT. Abstract The incidence of breast cancer is continuously increasing worldwide. The number of cured patients is also increasing and those with chronic disease, even if not cured, survive longer. Surgery and radiotherapy treatments have developed during the past decades causing less damage to the structures. However, patients are still left with varying degrees of impairment of arm function, in particular those receiving both surgery and radiotherapy to the axilla. Physical activity is of benefit for cancer patients in general including reduced fatigue, nausea, body fat, anxiety and depression and increased muscle strength, lean body mass, aerobic capacity, enhanced immune function, and improved quality of life ratings Thus, due to these benefits, it is of great importance that these patients do not experience physical restrictions in their daily work or in sports or other spare time activities, but should continue with such activities postoperatively as soon as possible. - - - - - Sami Elmahgoub,* Osama Husomi, Riyad Bendardaf**. Departement of Physiotherapy, Faculty of Medical Technology, Alfateh University,Tripoli, Libya, Department of Oncology and Radiotherapy, Turku University Central Hospital, Savitehtaankatu 1, PB 52, FIN 20521, Turku, Finland. 18 Indeed, physical restriction is associated with arm lymphoedema, reduced shoulder mobility and muscle strength, which are well known late symptoms of breast cancer treatment. This presentation discusses and describes in detail the different physiotherapy approaches that can help to avoid these complications and significantly improve quality of life for the breast cancer patient. 18. BONE AND SOFT TISSUE METASTASIS OF HEPATOCELLULAR CARCINOMA : A CASE REPORT Walid masuad Abdullah, Medical oncology department. AOI sabratha Abstract Soft tissue metastasis of HCC is rarely reported in literature. Hence this case is presented. A 49yrs old Libyan male a known case of hebatitis c virus infection on ribavirin and interferon therapy , presented on march 2006 with Rt hypochondrial pain, anorexia and liver enlargement CT scan showed : multiple liver lesions which were not resectable, liver biopsy revealed low differentiated hepatocellular carcinoma , the pt was advised for chemotherapy / chemo-embolization , but he refused treatment and so was put on supportive therapy . The pt developed pathological fracture of the Rt humerus , bone scan revealed multiple bone lesions involving long bones, pelvis, and vertebrae. He was put on pain management and I/V bisphosphonate. During the subsequent months he developed 3 soft tissue masses on the Lt chest wall, Rt shoulder, and neck , biopsy was planned to confirm metastasis but the Pt refused , and it was presumed soft tissue metastasis from HCC. 19. BREAST CANCER DURING PREGNANCY IN BENGHAZI Salah Salem El Taktuk MD, Tawfik Ali Abouzalout MD, Hamed R Bosrewill MD, Hussein O El-Bernawi FRCSI, University of Garyounis, General surgery department. Aim and objective: Breast cancer is one of the most common malignancies in women, physiological changes that occur in pregnancy imposes difficulties in assessment and management. We aim here to highlight the Incidence and assessment difficulties of breast cancer in pregnant ladies in Benghazi Method: All pregnant women who attended the breast clinic in 7th October hospital and diagnosed with breast cancer in the period of June 1990 till June 2005 (15 years) were included. Records were retrospectively analyzed .Age, period of pregnancy, cancer stage, and treatment modalities. - - - - - Abstract 19 Results The result showed that there were 34 cases of breast carcinoma in pregnancy out of 748 breast cancer women (4.7%) most of the patients came with stage II and III. Conclusion Careful breast examination should be performed at initial obstetrics visit and at least in each trimester of pregnancy to improve prognosis. 20. EVALUATION OR CERVICAL CANCER BY MRI: DETECTION STAGING AND FOLLOW UP Dr Fariha.Buzghia, Obstetric &Gynecology Department ,Garyoun University Abstract Objective: This study is performed to evaluated the role of MRI imaging in cervical carcinoma, detection of the lesions, staging and its value in follow up of previously treated cases. Methods: Forty four women(classified into 2 groups) presented by either positive cervical smear for cervical carcinoma or cervical mass associated with vaginal discharge or postcoital bleeding were included in this study. Their ages ranged from35 to69 years with mean age of 52, 32 years. Not all patients were subjected to MRI(according to availability) All had examination under anesthesia EUA and 30 had MRI evaluation . Results : MRI detected all cases within or above stage IB ,either the primary tumor or tumor recurrence(40 cases out of41 patients)MRI was accurate in detection of tumor invasion of the upper or lower thirds of vagina ,extension to the pelvic wall and invasion of the bladder and rectum MRI was able to clearly identify lymph node enlargement . Sensitivity of MRI in the first group was 97% and in the second group was 100% Conclusion : MRI is considered very helpful in detection, staging and follow up patients with cervical carcinoma. Key words :MRI ,cervical carcinoma INVASIVE LOBULAR CARCINOMA BREAST – A CASE REPORT R. K. Bhatnagar*, A. Fitori Ismail**, Faisal*, A.Mubarka* Dept of Histopathology, AOI, Sabratha,** Dept of Surgery, Sabratha Teaching Hospital, Sabratha. Abstract: - - - - - 21. 20 Lobular carcinoma comprises 3-5% of all breast carcinomas and breast carcinomas comprise 19.9% - 24% of all carcinomas in female. though incidance of breast carcinoma in females remains same as per globally, where it ranks second or third (after carcinomas of git and pancreas and uterine cervix) carcinoma, this variety of carcinoma is not so common(incidance of overall malignancies in libya is approximately 20% of all surgical specimens sent for histopathology, in one study) We report a case of invasive lobular carcinoma, breast in a 41 year female. her hematological, biochemical and tumor marker – studies were within normal limits except for low t3 and high tsh (hypothyroid state), her chest x-ray was normal, mammography done one year back was suspicious for rt. breast and lymphnodes, family history was insignificant as was other history and physical parameters. she underwent modified radical mastectomy at surgical wards, sabratha teaching hospital, after biopsy proved it to be invasive lobular carcinoma, breast. her post-operative course was uneventful and she was discharged. her histopathological findings will be discussed here 22. OVARIAN CANCER PROFILE IN EASTERN LIBYA M. El Mistiri , R. Shembesh,S El Brki, A Attia, Al Jamahiriya Hospital, Medical Oncology Unit, Faculty of Medicine, Garyounis University, Benghazi, Libya Abstract Ovarian cancer is the fifth most common cancer among women, and it causes more deaths than any other type of female reproductive cancer.The cause is unknown. The risk for developing ovarian cancer appears to be affected by several factors. The more children a woman has and the earlier in life she gives birth, the lower her risk of ovarian cancer. Certain genes (BRCA1 and BRCA2) are responsible for a small number of ovarian cancer cases. Result :ovarian cancer represent 4% of all cancer patients attending oncology clinic at Al Jamahiriya Hospital (118 cases out of 3074 ) . The median age was 50 years, Stage distribution was: Stage I 15 %, Stage II 6 %, Stage III 38 %, Stage IV 38 %. Conclusion: Ovarian cancer symptoms are often vague and non-specific, By the time the cancer is diagnosed it is usually quite advanced i.e. cancer is rarely diagnosed in its early stages. The outcome is often poor. The age-distribution shows a peak between 40-60 years, while other age groups had analogous frequency. Older women are at highest risk. About 25% of ovarian cancer deaths occur in women between 35 and 54 years of age. - - - - - Method: Retrospective review of cancer patients attending Oncology Clinic at Al Jamahiriya Hospital in Benghazi ( the only referral clinic in Eastern Libya) over a nine year period ( from 01/01/1998 to 15/12/2006). All cases of ovarian cancer were analyzed according to age, sex, place of residence, stage and histological type. 21 23. LUNG CANCER PROFILE IN EASTERN LIBYA Mufid El Mistiri , Mabruka Khalid, Faiz El Sadawya, A. Wahab Gadir, Awad Bendardaf, Oncology unit Jamhuria Hospital, Quefia Chest Hospital Faculty of Medicine, Garyounis University Benghazi Libya Abstract Lung cancer is the leading cause of cancer death among Libyan males. Despite the remarkable improvement in diagnostic, staging, and therapeutic modalities overall survival has not changed significantly over the past 20 years. Methods: Retrospective review of cancer patients attending oncology clinic at Aljamahiria Hospital in Benghazi (the only referral clinic in eastern Libya) from 01/01/2002 to 15/12/2006, cases of Lung cancer were analyzed for tobacco history age, sex, place of residence, stage and histological types Results: Lung cancer accounts for 11, 4% of all cancer patients attending oncology clinic at Aljamahiria Hospital (228 cases out of 2065), the median age was 45 years. 60% of patients were below the age of fifty. Stage distribution were, stage I 3.5%, stage II 7%, stage III 31% and stage IV 59%. The commonest histological type was squames cell carcinoma 25.4% followed by adenocarcinoma 23%, large cell carcinoma 12% and small cell carcinoma 10%. 97.5% of male patients were smoker while 20.8% of lung cancer were in women with smoking habit Conclusion: Lung cancer is the most common cancer among Libyan men. Early detection to achieve bitter prognosis remain very difficult. Cigarette smoking is by far the most important single causing factor for lung cancer in Libya. The result of this study focus the urgent needs to promote a strong and well organized national educational campaign against smoking. 24. EPIDEMIOLOGY OF CLINICAL FEMALE GENITAL TRACT MALIGNANCY IN BENGHAZI ABSTRACT The objective of this study was to detrmine the risk factors of genital tract malignancy,common clinical presentation and clinical staging at time of admission. - - - - - Fatma essa, Ali EL-Rrabti, Faraj Ben Ali, Department of obs&gynae-faculty of medicine-Garyounis university-Benghazy-Libya 22 The study was designed as a retrospective study of gynaecological malignancy who admitted to-el-jamahiriya hospital-Bengazy from first of jan.2000 to first of jan.2001. The percentage of patients who diagnosed with genital malignancy 1.4%. The commenest age group in cervical&ovarian malignancy are 40-60years while in uterine malignancy65-70years oldand theres no cases of vulval or vaginal malignancy was admitted to hospital in this period.Most of patients of uterine and cervical malignancy are diabetic and hypertensive.THE common clinical presentation was bleeding in cervical and uterine malignancy while in ovarian cancer pain was the commonest presenting symptom THE study was concluded that age and parity not protective factors and diabetes, hypertensive carries high risk of developing endometrial cancer in women more than 60 years old. KEY WORDS: genital tract malignancy-clinical presentation-clinical staging-risk factors A rare thyroglossal cyst with formation of papillary thyroid carcinoma. - - - - - 25. 23 A rare thyroglossal cyst with formation of papillary thyroid carcinoma CASE REPORT Dr.med. M.A. Darwish Dr. Hussein Elhashmi Dr. Salah Rodwan Dr. Abougeala Abussa ENT and general surgery department, AOI, Sabratha, Libya ABSTRACT: A case of a rare thyroglossal cyst with formation of papillary thyroid carcinoma in a patient. 40 years old male Head and neck Examination, ultrasound and Neck CT scan gives a suspicion of a huge central neck cyst. FNAC was inconclusive, complete Surgical excision of the cyst with the body of the attached hyoid bone was done (preoperative and intra operative suspicion of a benign Thyroglossal cyst), The local Histopathological work up of the specimen suspected a papillary malignant thyroid tissue in a neck cyst and requested consultation, which was done abroad, (Prof. Essen Germany),the final diagnosis of papillary thyroid carcinoma in a thyroglossal cyst was made, the patient underwent total thyroidectomy and he received radioactive Iodine twice, he is now disease free one year postoperative on Thyroxine therapy and regular follow up. These rare tumors make clinical and histopathological difficulties in the diagnosis. - - - - - Key Words: Thyroglossal cysts, papillary thyroid carcinoma, postoperative followup. 24 26. GASTRIC EXPERIENCE LYMPHOMA TRIPOLI MEDICAL CENTER’S Afaf Abu Shaala, Abukris Alwindi, Department of hematology-oncology, T.M.C Introduction: Gastric lymphomas are uncommon tumors constituting less than 2% of primary stomach malignancy. Stomach is the most frequent site of extra-nodal non Hodgkin's lymphoma The diagnosis is difficult and may be complicated by several factors like ¾ Vague symptoms. ¾ Problems in pathological diagnosis. ¾ Difficulty in staging with radio-imaging and endoscopic biopsy. Purpose: this is a retrospective study in which we analyzed the clinical characteristics and treatment and survival of 20 patients with gastric lymphoma in our oncology center in Tripoli medical center between February 1991up to February 2004. Patients and methods: 20 Pts of gastric lymphoma 9 females and 11 males. Between February 1991-febraury 2004 Main age is (55.5years) (23-79 years) of age Medium of follow up of 50monthes(17-155m) They are classified as high grade (7) 35% intermediate grade (4) 20% low grade (9) 45% All are phenotype B 20/20 CD 20 positive only 3 Pts Helicobacter pylori positive 2& negative 1 Stage IE (5) 25% Stage IIE (10) 50% Stage IIIE (5) 25% Stage IV (0) 0% 4 Pts was treated with chemotherapy 20%. 15 Pts was treated with chemo +surgery 75% 1 Pt was treated with chemo+surg+radio 5% No pt was treated with surgery only Chemotherapy 18 PTS received CHOP 90% 1 Pt received CVP 5% 1PTs received COPP 5% - 9 9 9 9 9 (6.7cycle /PT) - Total No; of cycles 135/20 2 PTS was relapsed 10% 1 after 1 year of CR 1 after 7 years of CR - - - 9 25 27. Pediatric acute lymphoblastic leukemia: Biology, diagnosis and prognosis Dina A Yassin, Prof. of Clinical Pathology National Cancer Institute, Cairo University Acute leukemias (AL) are a heterogenous group of neoplasms arising from transformation of uncommitted or partially committed hematopoietic stem cells. The retained partial capacity of differentiation was the basis for phenotypic classification. ALL is the most common malignant disease affecting children accounting for 30% of childhood cancer. The highest incidence in children aged 1-5 years with a peak at 3-4 years. ALL is divided into B-lineage ALL accounting for 70%-80% and T-lineage ALL 15%. In Egypt, the corresponding figures are 60%-70% and 30%. Biology of ALL: Initial mutations may occur anywhere across a particular gene. The consequence of a mutation in a gene is determined by its location with respect to the two functional parts of the gene. Known risk factors include: ionizing radiation, genetic conditions mainly Down syndrome, race and birth weight. Diagnosis: Clinically, symptoms and signs that result from either bone marrow failure or involvement of extramedullary sites by leukemia cells. Laboratory investigations: complete blood picture, bone marrow (BM) aspiration, BM biopsy in certain cases, cytochemistry, immunophenotyping, cytogenetic analysis and molecular characterization. Prognosis: A subset of prognostic factors at diagnosis is used for the initial stratification of children with ALL for treatment assignment. They include: age, total leucocytic count, CNS status, immunophenotype subtype, chromosome number and the type of chromosomal translocation. The early responses to treatment as well as minimal residual disease after induction therapy are also included. More than 95% of children attain remission and 75%-85% survive free of leukemia recurrence at least 5 years. Despite the treatment advances and patient stratification according to prognostic factors numerous biologic and therapeutic questions remain to be answered to achieve the goal of curing every child with ALL. 28. Current potentials for cancer pain management Ahmed Helmy A. Abouel Soud, Board member of the World Society of Pain Clinicians WSPC, Pain relief unit, National Cancer Institute, Cairo University Nowadays palliative care is a very important item in the agenda of cancer management and by far pain relief is one of the most important goals in palliative care.Cancer pain represents a great challenge for pain clinicians as we are managing patients with poor general condition, mostly with organ dysfunction either single or multiple which can influence the type and dosage of different analgesic medications, beside the dynamic process of cancer pain which requires continuous evaluation and - - - - - Abstract 26 changing the pain therapy accordingly, and finally anxiety, depression and insomnia which make things worse. Our main task as pain clinicians is to achieve the best quality of pain relief with the least possible hazards and side effects. This goal can be achieved by proper selection of our weapons for pain relief according to the patienťs pain presentation after adequate assessement. Patients with advanced and / or metastatic cancer may complain of pain of any type and at any site of the body due to either local spread of the tumor or its distant metastases or the effect of cancer therapy. Our tools for pain relief are used separately or in combination in the form of pharmacotherapy (the art of analgesic usage by proper selection of analgesic drugs in their optimal dosage and at the proper time) and the interventional pain therapy which can offer a good quality of pain relief in a high percentage of patients, in which we can interrupt permanantely the pain pathway by selectively destroying the pain transmitting fibers percutaneously i.e. without open surgery (e.g. posterior root destruction for localized rib pain metastases, cordotomy for unilateral pain below the level of the shoulder originating from either bone or soft tissues and celiac plexus destruction for upper abdominal cancer or superior hypogastric plexus destruction for pelvic cancer). The use of spinal opioids can offer pain relief in certain situations for patients with generalized pain. So, by following a proper pain management algorithm, we can offer our patients a good quality of pain relief and a better quality of life. B) PLENARY LECTURE CML is now defined by the presence of a BCR-ABL fusion gene usually located on the der(22q-) or Philadelphia chromosome but occasionally found on a normal appearing no. 22 chromosome and more rarely on a ‘normal’ no. 9 chromosome. The fusion gene expresses an oncoprotein with greatly enhanced protein tyrosine kinase activity, which is believed to be the initiating event in CML. In the early 1990s Brian Druker, then working at the Dana Farber Cancer Institute in Boston, conceived the notion that a small molecule could been designed to specifically block the kinase activity of the oncoprotein and thereby reverse the clinical and haematological features of CML. Working with scientists from Ciba- - - - - - 29. MANAGEMENT OF CHRONIC MYELOID LEUKAEMIA. 30. John M Goldman, Haematology Department, Imperial College London 27 Geigy (now Novartis) a 2-phenylaminopyrimidine derivative originally named CGP57148B was developed and entered clinical trials in 1998. Initial results looked so promising that a phase III study, termed the IRIS study, was launched in 2000, as a result of which the drug, now named imatinib mesylate (IM) (Glivec, Novartis Pharmaceuticals), has become the standard initial treatment for new patients with CML in chronic phase. Most of the patients who would have been offered allogeneic stem cell transplant in the 1990s now receive imatinib as initial treatment instead. IM should also be considered as part of the initial treatment of patients who present with CML in advanced phase (accelerated phase or blastic transformation) but it should unquestionably be supplemented by use of additional cytotoxic drugs. Stem cell transplantation should also be considered for eligible patients whose advanced phase disease can be controlled by initial therapy. Results of the IRIS study The IRIS study, which recruited patients over a 6-month period in 2000, is a prospective study whereby newly diagnosed chronic phase CML patients were randomly allocated to start treatment with IM or with the combination of interferonalfa and cytarabine (IFN/Ara-C). In the event the majority of patients allocated to the IFN/Ara-C arm crossed over to the IM arm within the first two years of the study and so as a comparison of the two arms the study collapsed. However, the investigators continued to monitor carefully the patients in IM arm, and the results after a median follow-up of 5-years have just been published. Of 553 patients in the IM arm, 98% achieved a complete haematological response, 92% achieved a major cytogenetic response (<35% Ph-positive marrow metaphases) and 87% achieved a complete cytogenetic response (CCyR). The overall survival at 5 years was 89% and the survival without progression to advanced phase was 92%. Of great interest was the observation that patients who achieved CCyR appeared to have a low risk of progression to advanced phase and this risk appeared to diminish with the passage of each year on IM. Survival for this cohort of patients was significantly better than survival of historical control patients treated with IFN or IFN-containing combinations on both sides of the Atlantic. - - - - - In general the drug is well tolerated at 400 mg daily and some patients have been treated successfully with 600 or even 800 mg daily. Side-effects have included myelosuppression, bone pains, fluid retention, weight gain, nausea, rashes, and disturbances of liver function but in general these could be controlled by dose adjustment. Rare cases of cardiac failure possibly attributable to myocardial damage have been reported. A small number of patients have had to abandon the drug on account of toxicity. 28 31. CANCER REGISTRATION Paola Pisani, Oxford University Cancer registration is the basis of the rational planning of cancer control activities. Measures of the size of the problem permit a justified allocation of resources for diagnosis and treatment, the implementation of interventions of primary prevention and the evaluation of their performance. Cancer registries provide the evidence to support bidding for improvements in health services and for investments in research. WHO is calling for greater investments to face the increasing problem of chronic diseases in low- and middle-income countries and promotes the establishment of surveillance systems able to support evidence-based policies. Active good quality cancer registries (CR) are currently unevenly distributed in the world. Most developed countries have systems covering 50% to 100% of their populations and can rely on regular statistics on mortality at the national level. Cancer registries cover only 1% and 3% of Africa and Asia respectively, where they are the only source of information on cancer occurrence and survival. The dramatic increase in size and aging of populations in developing countries is producing a continuing increase of the number of cases referring to health services largely inadequate to cope with demand. The demand for statistics and therefore for monitoring systems that permit objective knowledge of the situation is a consequence of current trends. In order to produce reliable good quality statistics a cancer registry requires access to all possible sources of information on the cases and regular estimates on the demographic composition of the population. The latter are fundamental in order to compute rates of incidence which measure the risk of developing the disease in the population. The registry needs trained staff devoted to that activity, a minimum of computing equipment and a budget for running costs. The amount of resources required to run successfully a registry depend on the size of the population covered and accessibility of the information. This depends by local geographic and structural conditions; in the absence of a high level of computerization of the health system the registry staff will have to actively search and abstract the data, moving around the area covered and visiting regularly relevant health facilities. In order to be successful registration must be a continuing and systematic activity performed by staff with - - - - - The minimum requirement for a cancer registry is to produce accurate statistics on the incidence of malignant diseases in the population covered. Accurate figures include all newly diagnosed cases in both sexes and of every age; characteristics of the tumour in terms of organ site, morphology, degree of malignancy and stage at presentation. The distribution of cancer cases needs to be examined at least by sex, age, geography, time and socio-economic status, in order to identify subgroups of the population at different level of risk. Cancer registries can be a powerful source of information also in the evaluation of clinical practice by measuring the outcome of case management at the population level as compared to the expected outcome based on recommended guidelines of best practice. The extent to which the registry can satisfy the need of knowledge of the different sectors involved in cancer care depends on the extent of its database and of the amount of information recorded on each case. 29 specific competence and supervised by motivated leaders. It also requires the cooperation of all bodies involved in the delivery of cancer care. 32. SCREENING AND EARLY DETECTION Lawrence von Karsa, Head, Screening Quality Control Group (ECN), International Agency for Research on Cancer, Lyon, France Abstract The present lecture will present the underlying principles and current status of European guidelines for quality assurance of breast, cervical and colorectal cancer screening. Cancer screening aims to reduce the burden of the disease in the population by early detection of asymptomatic lesions at a time at which treatment can be more effective and generally less detrimental for quality of life than treatment at a later stage. In a number of studies, systematic early detection of breast, cervical and colorectal cancer has been shown to be a viable option for cancer control. However, evaluation of interventions in trials is only one very important step in a process leading to improvement in the health of a population. The conditions under which a cancer screening method is routinely applied may differ considerably from the conditions in a controlled study. In such cases, the expected benefit to the target population and the persons attending screening may be substantially reduced or even lacking. This is the rationale for quality assurance in cancer screening. Quality assurance refers to the efforts and activities undertaken to guarantee that a product, service or enterprise fulfils the purpose for which it is intended. Routine implementation of cancer screening programmes of requisite high quality has the potential to substantially increase the overall effectiveness and efficiency of the delivery of cancer care in any country because quality assurance of the screening process not only addresses performance of the screening test and communication to and invitation of the target population. Diagnosis and treatment of screen-detected lesions must also be optimized; and cost-effective delivery of high-quality diagnosis and treatment must be assured for screening participants anywhere in the country or region being served by screening. Patients, the cancer of which is diagnosed outside the screening programme, generally also benefit from these efforts because the same professionals or services providing health care to them are frequently also involved in diagnosis and treatment of persons with screen-detected lesions. Moreover, not only the screening process but also the process by which a screening programme is set up must be well managed in order to avoid inappropriate fluctuations in quality over time or in different places. The experience in many countries in Europe which have implemented nationwide cancer screening programmes has shown that international cooperation and collaboration in developing and implementing standards and guidelines for cancer screening is the key to translating advances in knowledge into programmes which actually reach the millions of persons who may benefit from such services. Due to the increasing availability of resources, and the advent of less costly screening - - - - - On return, the registry provides a service to the medical community, to public health operators, policy makers and governments by disseminating information, being the source of recruitment of cases for clinical and epidemiological studies and by providing evidence for all rational decisions. 30 tests, particularly for cervical cancer, population screening is becoming an option for public health policy across the globe. In light of the approaching global epidemic of cancer, particularly in low and medium resource countries, international collaboation in developing and implementing quality assurance of cancer screening programmes once widely considered to be a luxury – may soon become one of the most powerful ways to effectively meet this challenge. 33. CANCER INCIDENCE IN EASTERN LIBYA: PRELIMINARY RESULTS OF THE YEAR 2004 Mufid El Mistiri, Nadia El Sahli, , Mohamed El Mangush, Salah Habil, Faraj El Hamri, Saeed Hammad, Salem El Gauarsha, Adel Attia, Rehab Shembesh, A.H Hawil, Ramadan Sahnon, Muftah Sahati, Faraj El Orfi, Sanad Swissi Research Centre Garyounis Uninersity Abstract Background Cancer registration in northern Africa is still limited, and until 2003 there have been no population based data for Libya. Benghazi Cancer Registry (BCR) was founded in 2002 and it covers the whole region of Eastern Libya (1,6 million population). Actually BCR is the only population-based cancer registry in Libya and has recently published his first report on cancer incidence Methodology All malignant cases diagnosed during 2004 were collected from different sources of information, including death certificates. Data were checked through IARCcrgTools software, developed by IARC. Cases were coded using the third edition of the International Classification of Diseases for Oncology (ICD-O-3). The most valid basis of diagnosis for a given cancer case was coded using the recommendations of the European Network of Cancer Registries (ENCR). World standard population was used to calculate age-standardized rates (ASR). Results: A total of 1053 new cancer cases (including non-melanomatous skin cancer) were diagnosed in 2004 (last updated Nov 2006). The incidence rates for all cancers were 66 per 100,000 (crude) and 120 (C.I. 95%: 94.9- 114.4) per 100,000 (ASR) for males and 56 (crude) and 102 (C.I. 95%: 76.1-93.9) per 100,000 (ASR) for females. The most common cancers in males were lung (19%), colon and rectum (10%) and bladder cancer (9%). The most common cancers in females were breast (26%), colon and rectum (9%) and endometrium (8%). The percentage of cases diagnosed on the basis of histology or cytology was 75% in males and 85% in females whereas the proportion of cases registered on the basis of death certificate only (DCO) was 6%. Childhood cancers represent 5% of all cases diagnosed in 2004. Conclusion: These preliminary results of the year 2004 show that cancer incidence rates in Eastern Libya are similar to those reported in 2003. The reduction of cases reported by DCO is sign of improvement in data quality while some slightly increased incidence rates may be due to a better data collection. Cancer registry is an essential tool to provide policy makers with reliable data on cancer epidemiology in order to contribute towards the formulation of cancer treatment strategies. The co-operation of - - - - - Benghazi Cancer Registry www.cancerlibya.com 31 the medical community should be encouraged to ensure the provision of high-quality information. Key Words: Benghazi, cancer, incidence, Libya, population-based registry 34. ANNUAL REPORT OF THE AOI CANCER REGISTRY FOR 2006 Dr. Abougeila Abussa, Dr. Hussein El Hashmi, Dr. Vijay Ahuja, Waled m Ab Massoud, Hussam Al Ganga African Oncology Institute, Sabratha, Libya. Abstract The African Oncology Institute revamped its hospital cancer registry in 2006. A new patient information form was introduced and data collection commenced in a prospective fashion from 1st Jan 2006. The registry maintains data on all patients diagnosed with cancer registered at the institute. The aim of this hospital based registry is to collect data on all cancer patients with emphasis on mode of diagnosis, prior treatment, histopathology, stage or clinical extent of disease at presentation, intention to treat, type of treatment offered and outcome of treatment. The goals of this registry are to improve patient care by evaluation of outcomes, to assess the utilization of facilities of the hospital and to provide data for physician education and research. This report presents the data for the year 2006. A total of 504 patients diagnosed with cancer were registered at the hospital from 1-1-2006 to 31-10-2006. Males constituted 52.4% and females 47.6%. The peak incidence for males was in the 60-70 years age group and in 41-50 years age group for females. Fifty four percent had received cancer directed treatment at another centre prior to registration. Presentation with advanced disease was observed in 26.3% and only 15.6 % had localized disease at start of treatment. The leading sites of cancer in males were lung (17.4%), prostate(12.5%) and colorectal(10.2%) whereas in females, breast (35%) was the most common followed by colorectal(12%) and ovarian cancer(7%). Radical treatment was offered to 59.1% and 27.5% received palliative treatment. Symptomatic treatment was offered to 10.3% cases. The treatment modalities employed included surgery (20.2%), radiotherapy (27.8%) and chemotherapy (74.1%). At the time of analysis 36.5% cases were on treatment, 7.9 % had completed treatment, 28.9% were non compliant and 12.3% died during the period. Updated data for the full year will be presented at the conference. 35. SURGICAL MANAGEMENT AND TREATMENT OF BREAST CANCER Stephen J. Kirk MD, FRCSI, FRCS (Glas), Consultant Surgeon The Ulster Hospital, Belfast, Honorary Senior Lecturer The Queens University, Belfast Surgery remains the primary treatment of choice following a diagnosis of breast cancer. By the early nineteenth century the procedure of radical mastectomy, described by Halstead, had become the “Gold Standard” surgical procedure in the management of breast cancer. This treatment the prime treatment for almost 75 years. During the last 30 years several large clinical trials, have shown that breast conserving surgery combined with other modalities of treatment is as effective as the radical - - - - - Abstract 32 surgery proposed by Halstead. Mastectomy when required is now much less radical that before. Now the procedures of modified radical mastectomy, quadrantectomy, segmentectomy and wide local excision have all gained acceptance. This paper will discuss the indications (tumour, size, location, type, patient choice etc) for each of these procedures and place in context the disadvantages and advantages of each. The management of the axilla in breast cancer has always attracted controversy. However, surgery to the axilla remains an integral part of the management of breast cancer. The paper will discus the indications for axillary sampling, axillary clearance and will address sentinel node biopsy. 36. RADIOTHERAPY IN BREAST CANCER Paul Henry, Consultant Oncologist, Ulster Hospital, Belfast Abstract DCIS is increasingly important in the screening era and indications for radiotherapy will be discussed. Dose fractionation schedules for invasive breast cancer will be discussed with reference to the Start trial. Other trials (DRIME, SUPREMO) will be mentioned. Technique of radiotherapy delivery will be outlined. Radiotherapy is routine after breast conserving surgery but may possibly be omitted in certain subgroups. The indications for post mastectomy radiotherapy will also be discussed. Increasingly there is concern about the long term side effects of radiotherapy ie breast cosmetic impairment especially after reconstructive surgery but also cardiac complications and radiation induced malignancy. Finally the issue of breast cancer as a consequence of radiotherapy used to treat Hodgkin’s disease will be discussed and it’s current management. 37. ENDOCRINE MANAGEMENT OF BREAST CANCER Five years of adjuvant tamoxifen has been the standard treatment for post menopausal women with hormone positive breast cancer. Five years of tamoxifen resulted in significant reduction in recurrence and mortality as 5, 10, and 15 years. Significant reduction in contralateral breast cancer has also been observed. Thromboembolism and endometrial cancer are the major side effects. More recently the third generation aromatase inhibitors (AIs) were shown to be superior to Tamoxifen in the treatment of post menopausal women with hormone positive metastatic breast cancer They prolong time to progression but no significant effect on overall survival has been demonstrated. The AIs have a favorable toxicity profile compared with Tamoxifen .This led to their use in the adjuvant setting in treating postmenopausal women with hormone positive breast cancer where large clinical trials have shown their superiority The AIs have shown superiority over Tamoxifen in prolonging time to distant recurrence and disease free survival. Contralateral breast cancer was also significantly reduced The - - - - - ABUKRIS ALWINDI, DEPARTMENT OF ONCOLOGY AND HAEMATOLOGY TRIPOLI MEDICAL CENTER, TRIPOLI, LIBYA 33 AIs are also effective given after Tamoxifen however the Sequencing of AIs with Tamoxifen remains controversial Osteopaenia and fractures are more common with AIs . They are also more expensive. In premenopausal women with hormone positive breast cancer ovarian ablation usually with LHRH analogue is a valuable option Tamoxifen is commonly used AIs combined with LHRH analogue are not supported by large clinical trials 38. MULTIVISCERAL RESECTION IN ADVANCED CANCER: IS it A PALLIATIVE OR A CURATIVE THERAPY? COLONIC Sacco R, Gervasi R, Rizzuto A, Pata F, General Surgery, “Magna Graecia” University, Catanzaro, Italy 1. Jemal A, Tiwari RC, Murray T, et al., Cancer Statistics, 2004, CA Cancer Journal Clin 54 : 8-29, 2004 2. Sugarbaker PH, Corlew S, Influence of surgical tecniques on survival in patients with colorectal cancer, Diseases of the Colon & Rectum 1982; 25:545-557 3. Nakafusa Y, Tanaka T, Tanaka M, Kitajima Y, Sato S, Miyazaki K, Comparison of multivisceral resection and standard operation for locally advanced colorectal cancer: analysis of prognostic factors for short-term and long-term outcome. Disesases of Colon & Rectum, 2004 Dec;47(12):2055-63 4. Izbicki JR, Hosch SB, Knoefel WT, Passlick B, Bloechle C, Broelsch CE., Extended resections are beneficial for patients with locally advanced colorectal cancer, Diseases of Colon & Rectum 1995 Dec;38(12):1251-6 - - - - - Colonic carcinoma is, in western countries, the second most common cause of death due to cancer, with peak of incidence between 60 and 70 of age and a rate male/female of 2:11. At the moment of diagnosis ¼ patients shows a locally advanced neoplasm which involves nearby organs and structures2. Frozen section histology is not reliable and the differentiation between neoplastic invasion and inflammatory adhesions can be performed on the definite postoperative histology. In these cases, the excision of the primitive tumor and involved organs may be performed in order to achieve a curative effect3. The removal “en bloc" of the tumor and organs involved is necessary in view of the radical (R0) resection. The prognosis is not necessary poor and, actually, some of those tumors show a mainly local aggressivity, without involving lymph nodes and with chances of disease free survival4. Advanced age is not an independent risk factor, and multivisceral resection can be safely performed even at an advanced age (>70). From January 1998 to June 2006, 13 patients (8 males and 5 females) with locally advanced adenocarcinoma of the Colorectum (T4) underwent extended resection. Median age was 62,5 years. Only one patient (7,7%) died in postoperative time with survival rate of 92,3%. Multivisceral resections are not a palliative procedures and they can be considered, in selected patients, as curative therapy in treatment of Colorectal cancer5. 34 5. Lehnert T, Methner M, Pollok A, Schaible A, Hinz U, Herfarth C, Multivisceral resection for locally advanced primary colon and rectal cancer: an analysis of prognostic factors in 201 patients, Annals of Surgery 2002 Feb;235(2):217-25 39. CHEMOTHERAPY FOR COLO-RECTAL CANCER Dr Jamal Zekri, Consultant Medical Oncologist, Clatterbridge Centre for Oncology, UK Abstract World wide it has been estimated there are at least half a million new cases of colorectal cancer (CRC) each year. Historically and for many years, CRC was considered to be chemo-resistant. However, randomized controlled trials demonstrated improvement in quality of life and over all survival (OS) when 5FU based chemotherapy was compared to best supportive care in the metastatic setting. A number of studies addressed the role of infusion vs. bolus, oral vs. IV and continuous vs. intermittent chemotherapy. Over the last 5 years, trials confirmed that the addition of oxaliplatin or irinotecan to 5FU significantly improve response rates (RR), progression free survival (PFS) and in some trials OS. Cetuximab, an EGFR monoclonal antibody in combination with irinotecan improves RR and OS in irinotecan resistant population. The addition of bevacizumab, a VEGF monoclonal antibody to irinotecan improves RR, PFS and OS in the first line setting. In the adjuvant setting, early evidence demonstrated that 5FU produced an improvement in disease free survival (DFS) and OS. Based on this evidence, patients with Stage III received 6 months of 5FU based chemotherapy as the gold standard adjuvant regimen. Newer chemotherapy agents were investigated in the adjuvant setting. Oxaliplatin+5FU+LV (FOLFOX) produced significant improvement in DFS at 3 years when compared to 5FU+LV in the MOSAIC study (78.2% vs. 72.9%, p=0.002). This was confirmed by the results of the NSABP C-07 trial. FOLFOX now is the standard adjuvant chemotherapy for CRC. Current adjuvant trials are investigating the role of adding targeted biological agents (Cetuximab and Bevacizumab). Dr. Paul Henry, Consultant Oncologist, Ulster Hospital, Belfast Abstract Critical to the management of rectal cancer is the availability of radiology expertise in the imaging of this disease specifically MRI and endo-anal ultrasound. Landmark trials to be discussed will be the Swedish rectal cancer trials, the Dutch TME trial and - - - - RADIOTHERAPY IN RECTAL CANCER - 40. 35 the MRC CRO7 trial. All this provides guidance for the selection of appropriate neoadjuvant therapy ie short course pre-operative radiotherapy and long course preoperative chemo-radiotherapy. Current management is based on gold standard TME surgery and advances in pathology assessment of surgical specimens. The further role for capecitabine in pre-operative treatment will be discussed and other developments/ongoing trials will be mentioned. 41. MINIMALLY INVASIVE CANCER SURGERY Ali M. Ghellai , MD , FACS, Clinical Assistant Professor of Surgery , State University Of New York , Upstate, Medical University , USA Abstract Despite the widespread use and proliferation of laparoscopy in most general surgical procedures , it has faced resistance in tha field of surgical oncology . Several oncological concerns were raised and centered on the fear of inadequacy of resection , port – site recurrence , changes in dissemination patterns and the unknown long term outcome , this lecture focuses on clarifying these concerns and issues involving laparoscopic cancer management to include cancer biology in relation to minimal access surgery , effect preumoperitoneum on tumor biology , abdominal wall reecurence , organ specific management and future prospects in this field . Despite the availability of modem diagnostic imaging modalities , assessment of intrabdominal malignancies is often inadequate , especially in patient considered for curative resection 30-40% of patients with hepatobiliary and pancreatic malignancies harbor occult metastases that were deened respectable by radiological imaging . Underestimation of tumor stage has resulted in many unnccessary diagnostic laparotomies . Staging laparoscopy is gaining wide acceptance worldwide as a minimally invasive alternative to diagnostic laparotomies . This presentation will highlight the importance , principles , and the technical steps of staging laparoscopy and will set guidelines for its use. 42. BREAST RECONSTRUCTION TREATMENT OF BREAST CANCER IN THE MANAGEMENT AND Stephen J. Kirk MD, FRCSI, FRCS (Glas), Consultant Surgeon The Ulster Hospital, Belfast, Honorary Senior Lecturer The Queens University, Belfast For some patients breast conserving surgery is not an option, these patients therefore require treatment with mastectomy. Such patients are candidates for breast reconstruction, which may be performed as an immediate or delayed procedure. Despite concerns that it may be the - - - - - Abstract 36 case there is no evidence that immediate reconstruction delays detection of recurrence or contributes to a worse outcome. Several options are available for breast reconstruction, using either prosthetic materials or autologous tissue. The preferred autologous tissue techniques are Tram flap and Latissimus Dorsi technique. The Tram flap is now the most commonly used flap. Recently interest has developed in Oncoplastic tissue reconstruction (improving the cosmetic outcome) for women undergoing conservation surgery. This provides further surgical options for both the surgeon and the patient. This paper will discuss the indications disadvantages for each of the procedures 43. HEPATIC RESECTION CANCER: 20 Years of experience FOR METASTATIC COLO-RECTAL Aroldo Fianchini, Walter Siquini, Asselhab Salem, Department of General Surgery, Surgical Clinic, Ancona University, Italy Hepatic resection is presently the only potentially curative therapy for patients with hepatic metastases from colorectal cancer, five years survival rates of 25% to 60% are currently reported for this patients. At present no equally effective therapeutic alternative exists and surgical resection represents the treatment of choice and the standard for assessment of any competitive therapeutic approach. The mortality rate of liver resection has considerably decreased and are uniformly less than 5% in modern series. Hepatic resection is now contraindicated if all detectable tumor cannot be removed ( no Re resection ), if remnant liver is insufficient and if distant extra hepatic inoperable disease is present. From July1985 to September 2004, hepatic resection for metastatic colorectal cancer was performed in 138 patients (77 men and 61 women). Average age was 62 (range 18-79) years. In all patients, the primary tumor had been resected for cure, 41(29.7%) patients synchronously and 97 (70.3%) metachronously, intraoperative Ultrasonography (IOUS) changed surgical treatment in 16 cases. A Pringle maneuver was made on 126 cases with mean time of hilar clamp of 31 minutes (range 10-59), Mean time of hepatic resection was 210 minutes (range 85-370). The operative mortality and morbidity was respectively 1.45% (2 patients) and 32.6% (45 patients). The median survival was 35 moths with 5 years and 10 years survival rates of 36.2% and 18.2% respectively. The following clinical and pathological factors were studied, age , size and number of metastases, operative time, interval between diagnosis and resection, serum preoperative CEA and CA19-9, perioperative transfusion and complications. Univariate analysis revealed that solitary versus multiple metastases (5-years survival 38.2% vs 23.3% p0.034), size of metastases <3cm versus >3cm (5-years survival 66.2% vs 26.5% p0.001) and interval between diagnosis and resection <3 months versus >3 months (5 years survival 38.3% vs 21.3% p0.037) were significant factors to overall survival. The mean survival time after resection of metachronous vs synchronous colorectal metastases was 35 months vs 34 months and 5 years survival 35.5% vs 26.3% respectively (p0.57) age serum CEA and CA 19-9, transfusion - - - - - Abstract 37 complication and stage of primary tumor has not statistic meaning About 7-10% of patients with colorectal cancer may become candidates for curative resection of liver metastases. The use of neoadjuvant systemic chemotherapy for “ unresectable” colorectal metastases converts a proportion (16%) of patients to resectability. The biggest future challenge is to increase the resectability rates to 15%- 20%. preoperative percutaneous portal vein embolization and two- staged hepatectomy with portal vein ligation are two different techniques which have been performed to induce remnant liver hypertrophy in order to decrease the risk of postoperative hepatic failure. 44. TARGETED THERAPY IN NON-HODGKIN’S LYMPHOMA WITH MONOCLONAL ANTIBODIES Abdul Shlebak MD FRCP Edin FRCP Lond FRCPath, St Mary’s Hospital, London, UK Introduction: Anti-CD20 mAbs is among the most extensively investigated and have shown definitive clinical efficacy. Rituximab (Mabthera) is a genetically engineered chimeric anti-CD20 mAb, with mouse variable and human constant regions. Consecutive trials in America, Europe and Japan have shown Mabthera to be highly effective agent with acceptable safety profile against aggressive and indolent B cell NHL as a single agent and in combination with cytotoxic drugs. Indications: 1) First-line treatment of diffuse large B-cell, CD20 positive, NHL in combination with CHOP chemotherapy or other anthracycline-based chemotherapy. 2) Relapsed or refractory, low grade or follicular CD20 positive NHL 3) First-line treatment of follicular, CD20 positive, NHL in combination with CVP chemotherapy (7) Overview of efficacy and safety: Relapsed or refractory, low-grade or follicular CD20 positive NHL: Regimens tested include treatment weekly for 4 doses and treatment weekly for 8 doses. Results are summarised below (1): Weekly x 4 n=166 Weekly x 8 n=37 48% 6% 57% 14% ORR CR - - - - - Rituximab was the first mAb approved in the USA for cancer therapy in 1997 (1). Rituximab, today, has had experience in more than 960, 000 patient exposures and has been of numerous completed trials (2, 3). 38 Bulky disease Weekly x 4 n=39 36% 3% Retreatment, Weekly x 4 n=60 38% 10% 13.4 Median 15.0 (2.5-36.5+) 6.9 Duration of 11.2 response (3.0-25.1) (1.9-42.1+) (2.8-25.0+) (months) + ongoing response Duration of response: interval from the onset of response to disease progression Impressive single-agent response rates (1) with durable responses achieved on retreatment (1, 3) similar to initial exposure (1). Diffuse large B-cell NHL: The CR rates were increased by adding Rituximab to standard CHOP chemotherapy in a recent French GELA study. The study also prolongs event-free and overall survival (OS). The safety and effectiveness were evaluated in further, randomized, multicentre studies with a collective enrollment of nearly 2000 patients (1, 6). Adverse reactions: Rituximab targets CD20+ B cells, while it generally spares other cells and tissues. Within the first 3 doses, CD20+ B cells are rapidly depleted with a general return to pre-treatment levels within 6-12 months after completion of therapy. Despite profound B cell depletion, no apparent increase in infection was observed (5). The incidence of grade 3 or 4 adverse events was similar in patients retreated compared with initial treatment 58% v 57% respectively (1). The following serious adverse reactions, some with fatal outcomes, have been reported in patients treated with Rituximab. Severe or fatal infusion reactions, tumor lysis syndrome, severe mucocutaneous reactions, hepatitis B reactivation with fulminant hepatitis, hypersensitivity reactions, cardiac arrhythmias, renal toxicity, bowel obstruction and perforation. The most common adverse reactions were infusion reactions. Other emerging mAbs therapies for NHL: References: 1. Rituxan (Rituximab) full prescribing information, Genentech, Inc, 2006. 2. Piro LD, White CA, Grillo-Lopez AJ et al. Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular nonHodgkin’s lymphoma. Ann Oncol. 1999; 10:655-661. - - - - - The recent approval of Gemtuzumab, Ozogamicin, Alemtuzumab and Ibritumomab tiuxetan by the FDA in America revealed clear evidence that mAbs have significant roles in the current treatment of haematological malignancies. Lymphoma cells are inherently sensitive to radiation. The aim of radioimmunotherapy is to target and therefore focus radiation to lymphoma tissues whilst minimizing toxicity to normal cells. A recent study showed 90Y Ibritumomab tiuxetan produced higher response rates than Rituximab. In addition, a recombinant anti-CD22 (BL22) immunotoxin showed significant efficacy in chemotherapy-resistant hairy cell leukaemia patients. 39 3. Davis TA, Grillo-Lopez AJ, White CA et al. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin’s lymphoma: safety and efficacy of retreatment. J Clin Oncol. 2000; 18:3135-3143. 4. Kunkel L, Wong A, Maneatis T et al. Optimizing the use of rituximab for the treatment of B-cell non-Hodgkin’s lymphoma: a benefit-risk update. Semin Oncol. 2000; 27(suppl):53-61. 5. McLaughlin P, Grillo-Lopez AJ, Link BK et al. Rituximab chimeric antiCD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998; 16:2823-2833. 6. Bertrand Coiffier, M.D., Eric Lepage, M.D., Ph.D., Josette Brière, M.D., Raoul Herbrecht, M.D., Hervé Tilly, M.D., Reda Bouabdallah, M.D., Pierre Morel, M.D., Eric Van Den Neste, M.D., Gilles Salles, M.D., Ph.D., Philippe Gaulard, M.D., Felix Reyes, M.D., Pierre Lederlin, Pierre Lederlin, Ph.D., and Christian Gisselbrecht, M.D. CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma. 2002; 346: 235-242. 7. Robert Marcus, Kevin Imrie, Andrew Belch, David Cunningham, Eduardo Flores, John Catalano, Philippe Solal-Celigny, Fritz Offner, Jan Walewski, Joäo Raposo, Andrew Jack, and Paul Smith. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. 2005; 105: 14171423. 45. UPDATE ON MULTIPLE MYELOMA Dr. Moulod El-Agnaf. Abstract Multiple Myeloma remains largely incurable despite conventional and HDT. Novel biological agents are urgently required. Recent studies demonstrate that various growth factors, including Interleukin (IL6) insulin like growth factors (IGF)-1, vascular endothehial growth factors (VEGF). The tumour necrosis factor (TNF) play an important part in the pathogenesis of the disease and mediate tumour growth, drug resistance and migration in the bone marrow. Targeting these factors represents an important future strategy in Multiple Myeloma treatment. Novel agents such as Thalidomide and its analogues and Bortezomib (Velcade) have shown promise even in refractory Myeloma and their role will be discussed. - - - - - Myeloma is a plasma cell tumour with an annual incidence of approximately 50 cases/million. Median age at presentation is 70 years. Most cases present de novo, some evolve from Monoclonal Gammopathy of Unknown Significance (MGUS). Approximately 30% of myeloma patients are below the age of 65 years and 2% are below the age of 40 years. This age distribution has implications for those patients eligible for high dose treatment (HDT) and stem cell transplantation. The majority of patients, however, are still treated with oral chemotherapy. This update will focus on the presentation, diagnostic investigations, prognostic factors and staging of Multiple Myeloma, general supportive management of the disease and its complications. 40 46. CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA Salem Zarrouk, Pediatric Hematology and Oncology Dept , Tripoli Medical Center Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer in children , and with current therapy almost 80% of them can be cured . Most current chemotherapy protocols usedtailored treatment according to risk groups based on known prognostic features , which include clinical , biological , genetic and molecular feature . Patient with favorable features (standard risk): (Age 1 to 99.9 years , WBC count < 50,000 /ul B- cell precureor type , hyperdeploidy , TEL – AML 1 fusion , and early good response to treatment ) can be treated with conventional standard therapy to minimize late side effects . Patient with unfavorable features (high risk ) : (Age <1 yearor > 9.99 years WBC count > 50,000/ul , T-cell type , hypodeploidy , MLL gene re-arrangement , BCR – ABL fusion , and poor early response to treatment ) usually require more intensive therapy , and some may need allergenic hematopoietic stem cell transplantation . In this presentation will focus on some of the advances in diagnsis and treatment of childhood ALL 47. THE ROLE OF MULTI-DISCIPLINARY TEAMS (MDT) IN OPTIMISING THE PROVISION OF HAEMATO-ONCOLOGY CARE Dr Abdul Shlebak MD FRCP Lond FRCP Edin FRCPath,, St Mary’s Hospital, London, UK. The haematological malignancies are a complex group of neoplastic diseases, linked by their bone marrow origin. The growing understanding of molecular and cytogenetic abnormalities is challenging and has transformed both diagnosis and management of patients. The immunophenotypic characterisation of tumour cells as well as by molecular methods is now regarded as being as important as the traditional morphological diagnostic approach. This trend has been accelerated by the introduction of monoclonal antibody therapy and by novel drugs designed to specifically target the molecular abnormalities responsible for the development of the tumour. Such developments are of fundamental clinical importance as they increasingly define not just the diseases themselves, but how an individual patient should best be treated. Building these advances into the routine care of patients represents a demanding agenda for the clinicians and hospitals involved. Just as the diseases are distinctive and show many differences from solid tumours, so too is the organisation of services. There is a degree of separation between the clinical services for haematological malignancies and those for solid tumours, perhaps reflecting their particular development pathways and the nature of the specialities involved. Despite these differences, there are compelling reasons for regarding all - - - - - Background 41 - - cancer services as a logical whole, in which the diagnosis and treatment of the various disease types has an immense amount in common. Operationally the reality is that local hospital services for common solid tumours in cancer units rely heavily on haematology services. The active support of haematology services ‘round the clock’ underpins the safe delivery of chemotherapy for all tumour types, particularly the diagnosis and management of life-threatening complications. Services for patients with haematological malignancies do have distinctive features. The management of haematological malignancies involves a range of clinical and laboratory skills, the processes of diagnosis and subsequent clinical management are dominated by one medical discipline, clinical haematology. Indeed it remains perfectly possible for a patient’s diagnosis to be made by a single clinician who then goes on to initiate treatment and subsequently determines further treatment as the patient’s clinical course progresses. The same individual may also determine the point at which active therapy may no longer be appropriate for that patient. Thus for many patients, particularly those with leukaemia, it is not unusual for decisions on their management to involve only one or possibly two individual consultants, probably colleagues in the same discipline and hospital. It has been observed in some areas that less use is made of palliative services in haemato-oncology than is the case for patients with many solid tumours. Other features of haemato-oncology services are equally characteristic. The main form of therapy for these diseases is chemotherapy (including immunotherapy). Other modalities such as radiotherapy have their roles, but these are more limited. Many national trials in these diseases have been extremely well supported by haematologists in all types and sizes of hospital, with high rates of trial entry. This has led to the widespread and routine adoption of evidence based protocols to help guide care in the various malignancies. Collaboration in research has frequently been extended in other ways. In some places, but by no means all, there is professional networking between clinicians in district hospitals and between them and colleagues in more specialised units. In some places this collaboration can be very close, in others relatively token. It is a paradox that despite the mass of trial evidence about chemotherapy regimens for the various clinical types and sub-types of disease, there is no well-established Cochrane Group and less research evidence than we would have wished to guide recommendations in some areas. The management of individual patients should, as always, be based on sound and comprehensive diagnostic information. This is crucial in these diseases as the precise diagnosis does, in many situations, define the most appropriate treatment. Decisions on management should involve a range of knowledgeable professionals in the disease areas concerned, meeting together. They need to determine the management of individual patients as well as agreeing more general policies and operational procedures. Those managing patients with these diseases face difficult diagnostic and clinical decisions - such as defining the point at which further cycles of chemotherapy are not appropriate and change to a more palliative approach may be preferred. It is essential that this collective involvement in decision-making is adopted for haematological malignancies, as for other cancer types, even though for some disease types most of those involved will be from one discipline. These arrangements should cover all patients and are likely to improve decisions about their care. The number of patients with each discrete type of haematological malignancy presenting each year to cancer units is, by the standards of those who manage many solid tumours, often low. Whilst the use of protocols derived from clinical trials evidence may be a partial 42 response to low throughput, issues remain about expertise and specialisation which cannot be easily evaded. Thus the challenge of preparing service guidance for haematological malignancies is set against a very distinctive backcloth. The recommendations are designed to offer considerable flexibility in implementation. However, consistency in the quality of care should be the primary goal. The British Committee for Standardisation in Haematology (BCSH) definition of Haemato-oncology levels of service; Level 1 Hospitals providing conventional chemotherapy and other forms of outpatient treatment, using dose levels that would not be expected to produce prolonged Neutrogena. Level 2 Facilities for remission induction in patients with acute leukaemia, using standard intensive chemotherapy regimes. This level of facility is also required to treat patients with aggressive lymphoma. Level 3 Facilities for autologous transplantation, using either bone marrow or peripheral blood stem cells. Level 4 Centres with expertise in both autologous and allogeneic transplantation. • All patients with haematological cancer should be managed by multi-disciplinary haemato-oncology teams. • In order to reduce errors, every diagnosis of possible haematological malignancy should be reviewed by specialists in diagnosis of haematological malignancy. Results of tests should be integrated and interpreted by experts who work with local haematooncology multi-disciplinary teams (MDTs) and provide a specialised service at network level. This is most easily achieved by locating all specialist haemato pathology diagnostic services in a single laboratory. • There should be rapid-access diagnostic services for patients with lymphadenopathy (chronically swollen lymph nodes or neck lumps). • Clinical nurse and palliative care specialists are to have central roles in haematooncology teams, working closely with their medical colleagues. Clinical nurse specialists will arrange for patients and carers to receive multi-faceted support, coordinated care, and all the information they want, throughout the course of the illness. • MDTs which manage patients with acute leukaemia should provide treatment intended to induce remission for sufficient new patients for the units concerned to develop and maintain expertise. This treatment should be provided at a single facility within any one hospital site, in designated wards with continuous access to specialist nurses and haematologists. • High dose therapy with progenitor cell transplantation is to be carried out only in centres which meet approved accreditation standards, including the minimum caseload criterion of 10 procedures per annum. - - - - - Key recommendations: 43 References: Cartwright, RA, McNally RJQ, Rowland J et al. The descriptive epidemiology of leukaemia and related conditions in parts of the United Kingdom 1984-1993. London: Leukaemia Research Fund, 1997 Quinn M, Babb P, Brock A, et al. Cancer trends in England and Wales 1950-1999. London: The Stationery Office, 2001 Improving Outcomes in Haematological Cancers, The Research Evidence. Available on the NICE website (www.nice.org.uk). National Institute for Clinical Excellence. Guidance on the use of imatinib for chronic myeloid leukaemia. Technology Appraisal Guidance No. 50. London: NICE, 2002, 18 National Institute for Clinical Excellence, Guidance on the use of rituximab for recurrent or refractory Stage III or IV follicular non-Hodgkin’s lymphoma. Technology Appraisal Guidance No. 37. London: NICE, 2002 UK Department of the Environment, The effects of benzene on human health. Available at www.defra.gov.uk/environment/airquality/aqs/benzene/6.htm 48. CURRENT RESULTS OF ALLOGENEIC HEMOPOIETIC STEM CELL TRANSPLANTATION Andrea Bacigalupo, for the Genova BMT Unit, Divisione di Ematologia e Trapianto di Midollo Osseo, Ospedale San Martino, Genova, ITALY. Transplant related mortality (TRM) is a major draw back for allogeneic hemopoietic stem cell transplantation (HSCT). In the present study we analyze the reduction of TRM in our Unit in 4 time periods: <=1985, 86-1990, 91-95, 96-2000. We included a total of 1033 consecutive allogeneic HSCT for hematologic malignancies, 865 with leukemia and 278 with a diagnosis other thank leukemia; the latter included lymphoma, myeloma, myelofibrosis, myelodisplasia. Minimum follow up for survivors is 2 years. There were several major modifications during the four eras: increasing patient age (from a median age of 23 to 38 years), increasing use of alternative donors (from 5% to 42%), and less patients receiving total body irradiation (TBI) (from 97% to 52%). Also graft versus host disease (GvHD) prophylaxis has changed and is now almost exclusively combined cyclosporin and methotrexate Acute GvHD grade III-IV significantly decreased (from 22% to 12% p=0.001), whereas overall chronic GvHD increased (from 16% to 38% ,p=0.002). TRM has declined significantly from 46% to 25% overall (p<0.00001); major reduction was seen in acute GvHD as a cause of death (from 17% to 7%) and hepatitis/VOD (from 7% to 1.4%), whereas death due to chronic GvHD has remained stable at 3%. In the period 1996-2000 TRM for HLA identical siblings is 17%, for family mismatched donors it is 52% and for unrelated donors 40%. Relapse has remained stable at 30% (p=0.4) and survival has improved from 32% to 53% (p<0.0001). For first remission /first chronic phase patients receiving a graft from a matched siblings the current TRM is 16%, the relapse rate 34% and survival 72%. For unrelated donor transplants these figures are 36%, 11%, 60%. We confirm that transplant mortality has been significantly reduced over the past two decades, despite increasing age, and increasing donor/recipient disparities. Relapse has remained unchanged, and consequently survival is improved>. - - - - - Abstract 44 49. CURRENT PROBLEMS OF VOLUNTARY BLOOD DONATION AND CLINICAL TRANSFUSION PRACTICE IN EUROPE Umberto Rossi, ESTM President, Milano, Italy The following is a report on current problems of voluntary blood donation and clinical transfusion practice in Europe, seen from a point of view of professional development, through my experience of President of the ESTM (European School of Transfusion Medicine). The establishment of the ESTM has been the result of a series of study documents and discussions on the teaching of Transfusion Medicine, originated by the Council of Europe (in 1963 and 1985) and developed by the ISBT within its European Regional Congresses and by the Italian Society of Transfusion Medicine (SIMTI) through its "Symposia for European Cooperation" (from 1990 to 1994) (Table I), following the recommendation issued, in 1989, at the end of the ISBT 1st European Regional Congress in Lugano. Table I - Symposia for European Cooperation (1990-1995) published by ISBT and SIMTI - Teaching of Transfusion Medicine (U. Rossi, J.D. Cash: editors) First SIITS-AICT Symposium for European Cooperation - Cernobbio (Italy), 1st October 1990 - Voluntary blood donors Associations: present and future (U. Rossi, V. Fresia, B. Genetet: editors) Second SIITS-AICT Symposium for European Cooperation - Cernobbio (Italy), 6th October 1990 - Teaching and education in Transfusion Medicine (U. Rossi, J.D. Cash: editors) Main session of the 3rd ISBT Regional (2nd European) Congress - Prague (Czechia), 15th October 1991 - Therapy with plasma and albumin: production and clinical use (U. Rossi, W.G. Van Aken, M. Orlando: editors) Third SIITS-AICT Symposium for European Cooperation - Rome (Italy), 6th June 1992 - Mass media and blood donation (U. Rossi, I. Cipriani, V. Fresia: editors) Fourth SIITS-AICT Symposium for European Cooperation - Rome (Italy), 6th June 1992 - Teaching of Transfusion Medicine to undergraduate medical students (U. Rossi, H. Seyfried: editors) Symposium of the 4th ISBT Regional (3rd European) Congress - Barcelona (Spain), 15th June 1993 - Therapeutic haemapheresis (U. Rossi, A. Bussel, M. Valbonesi: editors) Fifth SIMTI Symposium for European Cooperation - Genova (Italy), 9th June 1994 In May 1991, the consequences of the new political situation of Europe on Transfusion Medicine were discussed in the Board of SIMTI (the Italian Society of Transfusion Medicine). Most of the Board members, having benefited in earlier years from the scientific and professional help received by more advanced European countries, felt the time had come to try and give help, in turn, to Colleagues of countries who started facing problems we had more or less recently overcome: a sort of deep gratitude to Europe and faith in the future. On 30th March 1992, the ESTM was born in Milano, through the signatures of the Board members and the previous Presidents of SIMTI. The birth and the rapid growth of the ESTM are a clear witness of the profound need for increasing harmonisation of the teaching of Transfusion Medicine within a geographical Europe wider than the "political" definitions, given by the European Union and the Council of Europe. - - Common features of these European Symposia have been the recognition of the present situation possibly in all countries of the new "broader" Europe, the trial of "transfusing" all the scientific data and documentation work gathered by the Council of Europe and by National Societies into the European Community, and the elaboration of some concrete proposals and guidelines for further harmonisation within Europe. The ESTM courses have been performed, at varying degrees of complexity, dealing with many aspects of Transfusion Medicine, including promotion of voluntary blood donation, detection and prevention of transfusion transmissible infections, blood safety and transfusion risks, emergency Transfusion - - - Past activities of the ESTM 45 Medicine, autotransfusion, haemapheresis, quality assurance and quality management, immunohaematology and immunogenetics, transplant immunology, laboratory haematology, diagnostics of haemostasis, haemotherapy, clinical transfusion practice, transfusion in Obstetrics, Neonatology and Paediatrics, blood-sparing medicine and surgery, haemovigilance, prospects of Transfusion Medicine. 74 courses have so far been organised (Table II) in 27 European countries (Russia, Spain, Italy, Greece, Switzerland, Norway, France, Belgium, Czechia, The Netherlands, Portugal, Great Britain, Slovenia, Germany, Austria, Croatia, Estonia, Poland, Romania, Slovakia, Bosnia-Herzegovina, Ukraine, Bulgaria, Serbia, Turkey, Latvia and Albania), in Israel and in Argentina and Brazil (Table III). So far, 108 coordinators and more than 530 teachers have been involved, from 32 European countries (and some from Israel, UAE, Latin America, Australia and USA). Participants have been so far more than 2.800, from 40 European countries (and some from Canada, Argentina, Cuba, Guatemala, Peru, Uruguay, Brazil, Kazakhstan, Hong-Kong, Israel, Jordan, Egypt, Angola and Gambia). A course, in January 1999, has been co-organised in Senegal. Transfusion Medicine in Paediatric Haematology (Coordinators: U. Rossi, A.A.M. Todd) Moscow (Russia), 7 September 1992 (in collaboration with the ESH) Transfusion Medicine in clinical practice in the year 2000 (Coordinators: U. Rossi, W.G. Van Aken, C. Martín-Vega) Barcelona (Spain), 12 June 1993 (before the ISBT European Regional Congress) Current problems of Transfusion Medicine in clinical practice (Coordinators: A.A.M. Todd, U. Rossi) St. Petersburg (Russia), 6-8 September 1993 Basic methods and criteria for paternity investigation (Coordinators: W.R. Mayr, U. Rossi) Venezia (Italy), 16-17 October 1993 (after the ISFH Congress) Optimal use of blood and blood components - Immunohaematology in Transfusion Medicine (Coordinators: T. Mandalaki, N. Renieri, U. Rossi) Athens (Greece), 25-26 February 1994 Current problems in Transfusion Medicine (Coordinator: G.F. Riedler) Luzern (Switzerland), 5 May 1994 (in collaboration with the Swiss Society of Transfusion Medicine) Haemotherapy (Coordinators: B. Solheim, H.E. Heier) Oslo (Norway), 4-7 October 1994 (Scandinavian regional residential course) Haemorrhagic disorders and Transfusion Medicine (Coordinators: S. Machin, L. Drouet, P.M. Mannucci) Belgirate (Italy), 21-24 October 1994 (in collaboration with the ESH) Diagnostic application of cytofluorimetric methods using monoclonal antibodies (Coordinators: B. Brando, J.-E. O’Connor) Valencia (Spain), 18-20 November 1994 Immunoematologia e Medicina Trasfusionale (Coordinators: P. Zucchelli, D. Rossi, U. Rossi) Belgirate (Italy), 12-16 December 1994 (in Italian) Il Laboratorio di Ematologia (Coordinators: S. Biagiotti, D. Banfi) Belgirate (Italy), 12-16 December 1994 (in Italian) Biochemistry and molecular genetic basis of major human blood group markers (Coordinators: J.-P. Cartron, P. Rouger) Paris (France), 26-29 April 1995 (in collaboration with the INTS) Red cell immunohaematology (Coordinators: P. Tippett, G. Daniels) Belgirate (Italy), 20-23 May 1995 Biological, clinical and technical problems of platelet transfusions (Coordinators: E.A.E. Robinson, C. Martín-Vega) Venezia (Italy), 2 July 1995 (before the ISBT European Regional Congress) Technical problems of red cell immunohaematology (Coordinators: M.-J. Stelling-Auderset, G.-L. Molaro) Genève (Switzerland), 31 August-2 September 1995 Immunological problems of organ and bone marrow transplantation (Coordinators: W.R. Mayr, G. Reali) Belgirate (Italy), 22-25 September 1995 Production and clinical use of plasma fractions (Coordinators: W.G. Van Aken, T. Burnouf) Tours (France), 15-18 November 1995 Supportive transfusion therapy in oncological patients (Coordinators: A. Brand, M. Peetermans) Bruxelles (Belgium), 1-4 February 1996 (in collaboration with the ESO and the EORTC) Immune haemolytic anaemias (Coordinators: G. Garratty, C. Martín-Vega) Sitges (Spain), 15-17 March 1996 Transfusion Medicine, Haematology and Clinical Pathology (Coordinators: U. Rossi, L. Walterová) Prague (Czechia), 25-28 April 1996 Detection and prevention of transfusion-transmissible infections (Coordinators: J.A.J. Barbara, G. De Stasio) The Hague (The Netherlands), 8-11 May 1996 Platelet immunohaematology (Coordinators: C. Mueller-Eckhardt, A.H. Waters) Taormina (Italy), 23-25 May 1996 Promotion and maintenance of voluntary, non-remunerated blood donation (Coordinators: E. Sandborg, J. Koistinen, J.-M. Cárdenas) Santiago (Spain), 9-12 June 1996 (in collaboration with the IFRCRCS) Effective use of blood and blood components in medicine and surgery (Coordinators: N. Drouet, A. Maniatis) Grenoble (France), 16-18 June 1996 Medicina Trasfusional en/em Pediatria - Transfusión/Transfusâo autóloga (Coordinators: C. Martín-Vega, G. De Sousa) Lisboa (Portugal), 3-5 October 1996 (1st “Iberic” course, in Spanish and Portuguese) - - - - - Table II - ESTM courses, 1992-2005 46 Quality assurance in Transfusion Medicine (Coordinators: J. Chapman, D. Grgičević) Dubrovnik (Croatia), 23-26 April 1998 Transfusion Medicine in disasters and hospital emergencies (Coordinators: M.J.G. Thomas, U. Rossi) Pescara (Italy), 11-14 June 1998 Detection and prevention of transfusion-transmitted infections (Coordinators: J. Barbara, M.-K. Sultsmann, U. Rossi) Pärnu (Estonia), 12-15 September 1998 Red cell immunohaematology (Coordinators: G.L. Daniels, B. Zupanska) Warsaw (Poland), 20-29 September 1998 Therapeutic haemapheresis - Diagnosis and treatment of emergencies in haemostatic disorders (Coordinators: P. Höcker, L. Walterová) Prague (Czechia), 12-15 November 1998 Inmunohematología/immunohematología de eritrocitos, leucocitos y/e plaquetas (Coordinators: C. Martín-Vega, G. De Sousa) Barcelona (Spain), 27-29 November 1998 (2nd “Iberic” course, in Spanish and Portuguese) Red cell immunohaematology towards its second century: old and new methods in transfusion practice (Coordinators: C. Levene, D. Blanchard, D.J. A Shefayim, Tel Aviv (Israel), 6-9 May 1999 (before the ISBT European Regional Congress) Immunogenetic aspects of blood transfusion and bone marrow transplantation (Coordinator: M. Bohinječ) Ljubljana (Slovenia), 27-29 May 1999 (in collaboration with the Centre for Transfusion Medicine of the Republic of Slovenia) Promotion and maintenance of voluntary, non-remunerated blood donation (Coordinators: E. Sandborg, V. Hafner, U. Rossi) Bucharest (Romania), 23-26 September 1999 (in collaboration with the IFRCRCS and the Council of Europe) Autotransfusion (Coordinators: V. Brubnjak-Jevtič, U. Rossi) Portorož (Slovenia), 9-11 December 1999 (in collaboration with the University Medical Centre of Ljubljana and the Blood Transfusion Centre of Slovenia) Risk perception and risk assessment in Transfusion Medicine: how to achieve a sound transfusion practice based on scientific truth Bruxelles (Belgium), 26-29 February 2000 (Coordinators: J. Barbara, J. Leikola, U. Ro Laboratory Haematology and Transfusion Medicine in the year 2000: reality and prospects (Coordinators: L. Luzzatto, A. Brand, U. Rossi) Castellanza (Italy), 22-25 June 2000 Use and abuse of blood and blood products (Coordinators: V. Kretschmer, E. Fehérvízyová, L. Walterová) Bratislava (Slovakia), 6-9 July 2000 Haemotherapy (Coordinators: H.E. Heier, B.G. Solheim) Oslo (Norway), 7-10 November 2000 (Scandinavian regional residential course) Safety assurance in blood therapy (Coordinators: V. Brubnjak-Jevtič, U. Rossi) Portorož (Slovenia), 14-16 December 2000 (in collaboration with the University Medical Centre of Ljubljana and the Blood Transfusion Centre of Slovenia Calidad/Qualidade en/em Medicina Transfusional (Coordinators: C. Martín-Vega, G. De Sousa) Lisboa (Portugal), 17-19 March 2001 (3rd “Iberic” course, in Spanish and Portuguese) La terapia trasfusionale in età neonatale e pediatrica (Coordinators: G. Isacchi, P.G. Mori) Genova (Italy), 4-5 May 2001 (in Italian, in collaboration with SIMTI) Seguridad en Medicina Trasfusional (Coordinators: S. Wendel, O. Torres) Buenos Aires (Argentina), 4 September 2001 (1st “Latin-American” course, in Spanish and Portuguese, in collaboration with the Asociación Argentina de Hemoterapia e Inmunohematología – AAHI) Molecular and cellular basis of immunity and alloimmunity (Coordinator: M. Bohinječ) Ljubljana (Slovenia), 23 -26 September 2001 (in collaboration with the Centre for Transfusion Medicine of the Republic of Slovenia) The future of blood safety, a challenge for the whole Europe: how can international regulations be implemented all over Sarajevo (Bosnia-Herzegovina), 25-28 October 2001 (1st “Balkan-European” course) (Coordinators: J. Barbara, M. Blagoevska, M. Haračíć, U. R Transfusion Medicine and intensive care in surgery (Coordinators: L. Lukič, B. Kremžar, V. Brubnjak-Jevtič, U. Rossi) - - - - - Practical aspects of blood transfusion (Coordinators: M. Contreras, M. De Silva) London (Great Britain), 6-7 November 1996 Therapeutic haemapheresis (Coordinators: M. Valbonesi, P. Höcker) Genova (Italy), 16-18 November 1996 Paediatric Transfusion (Coordinators: J.K.M. Duguid, R. Stathopoulou, T. Mandalaki) Athens (Greece), 28 February-2 March 1997 Autosufficienza del sangue e dei suoi prodotti: promozione della donazione volontaria; gestione di qualità dei Servizi Trasfusionali Roma (Italy), 17-20 April 1997 (in Italian) (Coordinators: A.L. Massaro, U. Rossi) Problems of autologous blood donation and transfusion (Coordinators: W. Mempel, F. Mercuriali) Bled (Slovenia), 8-11 May 1997 Organisation and quality management of Blood Transfusion Services (Coordinators: J. Emmanuel, A.L. Massaro, M.A. Vesga, A. Padilla) Sevilla (Spain), 1-3 June 1997 (in collaboration with the WHO) Sicurezza del sangue e dei suoi prodotti: emovigilanza; indicazioni cliniche alla trasfusione (Coordinators: G. De Stasio, U. Rossi) Roma (Italy), 26-29 June 1997 (in Italian) Practical workshop on techniques in haemapheresis (Coordinators: A.. Bussel, P. Höcker, V. Kretschmer, A. Robinson) Paris (France), 10-13 September 1997 (in collaboration with the ESH, ESFH and FSH) Haemorrhagic disorders and Transfusion Medicine (Coordinators: S. Machin, E. Seifried) Frankfurt (Germany), 29 September-1 October 1997 (before the ISBT European Regional Congress, in collaboration with the ESH) Haemoterapi/Haemotherapy (Coordinators: B.G. Solheim, H.E. Heier) Oslo (Norway), 4-7 November 1997 (Scandinavian regional residential course) Transfusion Medicine and intensive care (Coordinators: B. Blauhut, J. Skodlar) Linz (Austria), 7-9 November 1997 Progressi scientifici e tecnologici in Medicina Trasfusionale (Coordinators: A. Iacone, U. Rossi) Roma (Italy), 20-23 November 1997 (in Italian) 47 Portorož (Slovenia), 13-15 December 2001 (in collaboration with the University Medical Centre of Ljubljana and the Blood Transfusion Centre of Slovenia) Segurança transfusional no século XXI: desafios para a América Latina (Coordinators: L. Amorim, J. Rosenblit, O. Torres, M.C. de Samaniego) Itaparica-Bahia, (Brazil), 30 May -1 June 2002 (2nd“Latin-American” course, in Spanish and Portuguese, in collaboration with the Sociedad Brasileira de Hematologia e Hemoterapia - SBHH) Present and future problems of Transfusion Medicine in South-Eastern Europe (coordinators: U.Rossi, G.Aprili) Lecce, 5-6 June 2002 (“Balkan-European” work meeting) Blood-sparing medicine and surgery: the absolute need of safe autologous and homologous blood donation Lviv (Ukraine), 19-21 September 2002 (Coordinators: V. Kretschmer, L. Walterová, V. L.Novak, U. Ro Basic clinical and organisational requirements for an effective haemovigilance (Coordinators: P. Strengers, E. Love, C. Politis, T. Lissitchkov) Sofia (Bulgaria), 28 November-1 December 2002 (2nd “Balkan-European” course) Blood therapy in Neonatology and Paediatrics (Coordinators: L.Lukič, V.Brubnjak-Jevtič, J.Primožič, M.Benedik-Dolničar, U.Rossi) Portorož (Slovenia), 12-14 December 2002 (in collaboration with the University Medical Centre of Ljubljana and the Blood Transfusion Centre of Slovenia Haemovigilance (Coordinators: P.F.W. Strengers, J.-C. Faber, U. Rossi) Piacenza (Italy), 20-21 June 2003 (in collaboration with SIMTI) The contribution of clinical medicine to blood safety (Coordinators: L. Walterová, V. Kretschmer, G. Bogdanović, U. Rossi) Belgrade (Serbia), 9-12 October 2003 (3rd “Balkan-European” course) Paediatric Transfusion Medicine (Coordinators: A. Brand, E.F. van Leeuwen, U. Rossi) Napoli (Italy), 28-29 November 2003 (in collaboration with SIMTI) Hemovigilancia/Hemovigilância (Coordinators: C. Martín-Vega G. de Sousa E. Muñiz-Díaz) Barcelona (Spain), 19-21 March 2004 (4th “Iberic course”, in Spanish and Portuguese, in collaboration with AEHH, SETS, APIH) Transfusion treatment of thalassaemia and other chronic anaemias (Coordinators: M. Bayik, D. Canatan, C. Politis, U. Rossi) Antalya (Turkey), 20-25 April 2004 (4th "Balkan-European" course, in collaboration with ITSS / BBTST) Clinical Immunogenetics and cell therapy (coordinator: Mateja Bohinječ) Ljubljana (Slovenia), 6-9 June 2004 (in collaboration with the Centre of Transfusion Medicine of the Republic of Slovenia) Blood-sparing medicine and surgery: an essential aspect of a safe and well-organised Transfusion Service Riga (Latvia), 5-9 July 2004 (Coordinators: V. Kretschmer, L. Shapiro, G. Nemceva, U. Ro Transfusion Medicine in Obstetrics (Coordinators: S.Beljanski-Rogan, T.Blejec, I.Bricl, V.Brubnjak-Jevtič, U.Rossi) Portorož (Slovenia), 3-4 December 2004 (in collaboration with the University Medical Centre of Ljubljana and the Blood Transfusion Centre of Slovenia) The essential contribution of Clinical Medicine to blood safety (Coordinators: J. Koistinen, V Hafner, A. Gjata, U. Rossi) Tirana (Albania), 1-5 October 2005. Contribuição da Medicina Clínica a segurança transfusional (Coordinators: L. Amorim, U. Rossi). Rio de Janeiro (Brazil), 6 November 2005 (3rd “Latin-American” course, in Spanish and Portuguese, in collaboration with the Sociedad Brasileira de Hematologia e Hemoterapia - SBHH) Clinical Transfusion Medicine (Coordinators: H.E. Heier, P. Turek, L. Walterová) Liberec (Czechia), 29 March - 2 April 2006. Table III, 30 countries where 72 ESTM courses have taken place (+ courses locally organised, with ESTM collaboration) 18 (6 in Italian) 7 (2 “Iberic”) 2 (+ 2) 2 3 2 2 2 (2 “Iberic”) 1 (+ 8) 1 (+ 1) 1 1 1 1 1 1 Germany Great Britain Latvia Netherlands Poland Romania Serbia Slovakia Turkey Ukraine Norway 1 1 1 1 1 1 1 1 1 1 Israel 1 Argentina Brazil (+ 3) (+ 1) (+ 2) Regional professional development in Europe The initiatives taken in the last twelve years, in the whole of Europe, by the ISBT, by some National Scientific Societies and by the ESTM have considerably helped to clarify the theory and practice of Transfusion Medicine in most European countries and to establish some network of scientific and professional communication: acting - - - - - Italy Spain France Belgium Czechia Greece Russia Portugal Slovenia Switzerland Albania Austria Bosnia-Herz. Bulgaria Croatia Estonia 48 - - somehow also as a stimulus for countries of other continents (Africa and Asia) bordering the Mediterranean Sea. Some relevant national differences still exist in different countries or areas of Europe, waiting for proper recognition, study and common European solution. Issues and problems such as the organisation of truly voluntary non-remunerated blood donation, the establishment of a regularly donating donor population, the optimal index of donation, the contribution of autotransfusion, the development of bloodless surgery, the organization and responsibility of Blood Transfusion Services and plasma fractionation plants, the economic conditions of the supply of plasma related to the need of plasma fractions, the definition of the real clinical need of albumin, the extent of genome testing, the implementation of leucodepletion and of pathogen inactivation, all are of paramount importance for the future of Transfusion Medicine in Europe. Within this frame, the activities of the ESTM in the last few years have been oriented towards a more full appreciation of the critical relevance of the contribution of clinical medicine to blood safety. More generally, the ESTM experience has allowed to fully appreciate that teaching and training should extend beyond academic schemes and continuously reach all Transfusion Medicine specialists and clinicians, and that “transfusing medical science into medical practice” is the real present challenge of Transfusion Medicine all over Europe, and should be felt as a common responsibility for anyone involved in European Transfusion Medicine. Moreover, training must respect local situations in which trainees are working, satisfy local operational needs and involve local professional and scientific associations. Several aspects of Transfusion Medicine have been currently discussed in Europe along the last few years: education to voluntary blood donation, common effort to phase out paid donation converting replacement donors into periodic voluntary donors, European or at least regional policy concerning migrant blood donors, antiHBV donor vaccination, acceptance as donors of thalassaemia trait-carriers, reliable and user-friendly electronic data-processing system in any Blood Transfusion Service, unified labelling to be introduced throughout the region, adoption of the ISBT 128 to assure an internationally usable system, regional blood component exchange with minimum standards for emergency conditions, common attitudes for the generalised establishment of good clinical transfusion practice, hospitals' responsibility for basic haemovigilance, implementation of a regional network for haemovigilance, diffusion of WHO's learning materials. Agreement was reached on a series of basic requirements, essential to build an acceptable safety of blood donation and Transfusion Medicine in all European countries: 1) A clear definition of what is meant by the medical specialization in "Transfusion Medicine" and the existence in the country of a sufficient number of dedicated Transfusion Medicine specialists. 2) The presence of a minimum core of Transfusion Medicine competence in the cultural background of general doctors and other specialists, of nurses and technicians. 3) A well functioning organisation of voluntary donation, within the national system of public health and hospital assistance, with adequate consideration of donors' medical care. 49 4) A general feeling of belonging to a national, but also to a European medical and transfusional community. 5) A proper cultural approach to blood safety and risk management. 6) A widespread application of "quality" principles, in the frame of quality management, to the national organisation (central and peripheral) of Transfusion Medicine. Which are the perspectives of further regional professional development? This "European approach" has become now even more important, since 10 new countries have recently joined the European Union and other countries (Croatia, Romania, Bulgaria, Turkey) are next future candidates. The European Union Directive of 2002 has reinforced the importance of adequate training to assure quality and safety in blood transfusion. Education in "quality management", being fairly independent from financial resources and mainly addressed to human behaviour, can be considered an adequate common way to overcome national differences in Transfusion Medicine in Europe. Measures should be taken (at political, scientific and professional levels) to ensure that countries with limited resources develop faster, to reduce the "educational gap" as soon as possible. No decision on Transfusion Medicine education in any country should anymore be taken without a clear understanding of its impact on the whole of Europe. All European countries need a professional approach based on a "non-profit" attitude of persons and institutions, whereby help could be given "from the bottom" and "from aside", and not from above. One should avoid causing hidden resentment, in "receivers”, against the kind of initiatives often taken by Western and International Organisations, when money is given more generously to real or so-called experts rather than being kept for the real needs of the country. It is essential that, in any team, both "experts" from "high-income" and "receivers" from "low-income" countries should feel equally engaged and responsible for common success. Money and expertise alone do not automatically guarantee any positive outcome, unless long-lasting human commitment is present. One has to underline that, although basic financial resources are a pre-requisite for constructing any Transfusion Service, what makes blood transfusion safe and effective is certainly not wealth by itself, but rather political maturity, moral solidarity, cultural development and medical competency: all factors dependent much more on human dedication than financial prosperity. While actively continuing regional educational activity in Europe, encouragement can be given to the development of Transfusion Medicine education in other regions of the world. The long-standing attention of the ISBT and the more recent interest of the - - - - - It became clear that nearly all the medical and transfusion problems in Europe need to be addressed not only by individual national measures, but also (and mainly) by a common "transversal", European approach for the whole region. Although the heterogeneity of languages, of ethnical origins, and of cultural and religious traditions might make this approach sometimes very difficult, the very same reasons make it even more necessary and urgent. 50 WHO on the implementation of “regional schools of Transfusion Medicine” may offer opportunities for an optimal development of the “educational fermentation” presently observed e.g. in Latin-America, in Asia, in the Arabic countries, in Africa. Always keeping in mind the absolute need to adjust any experiences to the different situations of any particular region, I shall be glad if also the ESTM experience could help finding the best solutions for the sound organisation of voluntary blood donation and Transfusion Medicine educational activities in any other non-European part of the world 50. PALLIATIVE CARE IN ONCOLOGY The palliative care movement is born in the 1967 in UK when Cicely Saunders founds the St Christophers Hospice near to London for patients with advanced cancer. From there the palliative care are developed now all around the world. Palliative care definition ( EAPC) Palliative care is the active, total care of the patients whose disease is not responsive to curative treatment. Control of pain, of other symptoms, and of social, psychological and spiritual problems is paramount. Palliative care is interdisciplinary in its approach and encompasses the patient, the family and the community in its scope. In a sense, palliative care is to offer the most basic concept of care – that of providing for the needs of the patient wherever he or she is cared for, either at home or in the hospital. Palliative care affirms life and regards dying as a normal process; it neither hastens nor postpones death. It sets out to preserve the best possible quality of life until death. Cancer is a public health problem worldwide Over 20 millions of people live with cancer. The estimated number of new cancer cases each year could rise from nearly 11 million in 2002 to 19 million by 2030 if the current rates remain the same. The majority of these new cases will occur in low and middle income countries. (IARC, 2006) Pain relief and palliative care is an urgent humanitarian need for millions of patients worldwide The majority of cases occur in the developing world where very few people get the proper treatment and 80% of cases present in very late stages When to start palliative care in oncology? Beside the specific treatment of the cancer as chemotherapy , surgery, radiotherapy… palliative care should be provided if needed to the patient and his family ,even at the early stage of the disease . How palliative care can help patients and family? Relieving pain and suffering, control of the burdening symptoms, helping the family to cope with the patient improve the quality of life of the patients.The team work is a very essential component for palliative care. Conclusion The WHO On May 2005 the World Health Assembly adopted a Cancer Prevention & Control Resolution (WHA58.22) which:emphasizes the need for reinforcing comprehensive cancer control programmes worldwide recognizes the provision of - - - - - Dr Filbet M, Centre hospitalier Lyon sud, CHU DE LYON,Hospices Civils de Lyon, France. Abstract 51 - - - - - palliative care as an urgent humanitarian responsibility stresses the need for improving opioid availability 52 51. CANCER PAIN MANAGEMENT Dr Filbet M, Centre hospitalier Lyon sud, CHU DE LYON,Hospices Civils de Lyon, France Abstract Pain can be managed effectively in most patients with cancer or with a history of cancer. An accurate diagnosis of the cause and type of pain is key to finding the most effective treatment. - - - - - Approximately 25% of newly diagnosed cancer patients have some degree of pain, as do one third of patients undergoing cancer treatment and 75 % of patients with advanced disease. Patients with cancer can have pain from the tumor itself, as a side effect of treatment, or completely independent of the disease or its treatment. Whether in the hospital, at home, or in a long-term care facility, effective pain management is an essential part of comprehensive cancer care. A whole cancer pain assessment should be necessary to know th epain intensity,the localisation, the type and the effects for teh quality of life of the patient. The Cancer pain treatment follow the WHO recommendations and the 3 steps ladder : -step one non oipoides -step 2 mild opioides -steps 3 strong opoides The teatment should be given by the mouth , by the clock and adapted to the patient. A each step the adjuvants drug can be added The sides effects should be prevented Treatment of breakthrought pain Complexes pain situations will be discussed as bones pain metastasis neuropathic pain.. Conclusions : The pain cancer can be relief for most of the patients easily following teh who recommendations.Complexes situations need to be seen by experts. 53 52. VENOUS THROMBOEMBOLISM AND CANCER Abdul Razzak Shlebak MD FRCP (Lond) FRCP (Edin) FRCPath The impact of thrombosis in cancer patients: The association between malignancy and clinical thrombosis has been recognized since 1865, when it was first reported by Armand Trousseau (1). The annual estimated frequency of venous thromboembolism (VTE), including both deep vein thrombosis (DVT) and pulmonary embolism (PE), in cancer patients in the U.S. is approximately 1 in 200 (2). An estimated 1,372,910 new cancer cases in 2005 in the U.S (3), includes almost 7,000 cases of cancer-associated thrombosis per year. If left untreated, cancerassociated thrombosis can result in significant morbidity and mortality. Epidemiology data indicate that thrombosis is the second leading cause of mortality in cancer patients, second only to the cancer itself (4). Additionally, one in seven hospitalized cancer patients die as a result of PE (5). Results from several studies have suggested that patients with cancer have a higher risk of VTE and death than non-cancer patients. In a prospective cohort study of 355 patients by Prandoni and colleagues, patients with cancer were found to have an increased risk of recurrent VTE (hazard ratio = 1.72) compared to non-cancer patients (6). Likewise, an analysis of Medicare data by Levitan and colleagues found that patients with concurrent VTE and malignancy have a more than three-fold higher risk of recurrent VTE and death than patients with VTE but without malignancy (7). Epidemiology The tumour type, stage and location, may impact the risk for thrombosis. Cancers associated with the highest frequency of VTE include brain, pancreatic, and ovarian (7). Cancers associated with the highest prevalence of VTE include breast, colorectal, and lung (7), which is consistent with the high frequency of these tumour types in the general population (8). Other factors such as cancer therapy (chemotherapy, hormonal therapy, investigative procedures, surgical interventions, and immobility may also increase the risk for cancer-associated thrombosis. The mechanisms of clotting activation in cancer patients are not fully understood. However, there are probably both non-specific and specific mechanisms involved. Non-specific mechanisms may include tissue damage and inflammatory responses caused by the tumour that may ultimately lead to tissue factor (TF) expression and coagulation activation. Specific mechanisms could include the production of cytokines by the tumour resulting in TF expression by monocytes. In addition, tumour cells may produce procoagulant factors causing direct activation of coagulation. In patients with idiopathic VTE without known risk factors for thrombosis, occult malignancy should be sought with full clinical examination, plain chest radiography and abdominal/pelvic ultrasonongraphy. One recent study indicated that patients with symptomatic idiopathic VTE have an approximate 10% incidence of subsequent cancer (9). In addition, patients with a recurrent, idiopathic DVT have an almost 10fold increased incidence of cancer (10). The Fundamental Research in Oncology and Thrombosis (FRONTLINE) study was the first comprehensive global survey of thrombosis in cancer (11). A total of 3,891 physicians responded to the survey, which included questions related to oncologists’ perceptions of the risk of VTE in cancer patients undergoing surgical and medical management. Physicians reported that brain and pancreatic cancers were associated with an increased risk of VTE, consistent with earlier reports. The use of central venous lines was associated with a high risk of VTE by 80% of respondents. Surgical - - - - - Evidence-based practice: 54 and medical management differed significantly, with over 50% of surgeons reporting that they routinely use thromboprophylaxis in cancer patients undergoing surgery whereas medical oncologists reported using prophylaxis in less than 5% of their patients. A LMWH was the most popular method for prevention of VTE, especially in Europe. Twenty percent of respondents used aspirin for thromboprophylaxis despite the lack of published literature for this use. Secondary prophylaxis, for those patients who had an episode of DVT, was typically continued for three to six months. Concluding remarks: Haemostatic activation is common in cancer patients, although the causal mechanisms remain to be fully demonstrated. Cancer patients with VTE have an increased risk of recurrent VTE and death compared to cancer patients without VTE. Given the prevalence of thrombosis in cancer patients and its potential negative impact on patient care and clinical outcomes, health care professionals must be made aware of this condition to allow the appropriate risk assessment and stratification for such cohort in order to be able to provide the prevention strategies and instigate therapy as early as possible in order to prevent fatalities. References - - - - - 1. Trousseau A. Phlegmatia alba dolens. Clinique Medicale De L’Hotel-Dieu de Paris. 1865; 3:654–712. 2. Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation. 2003; 107(23 suppl 1):I17–21. 3. Jemal A, Murray T, Ward E et al. Cancer statistics, 2005. CA Cancer J Clin. 2005; 55:10–30. 4. Donati MB. Cancer and thrombosis. Haemostasis. 1994; 24:128–31. 5. Shen VS, Pollak EW. Fatal pulmonary embolism in cancer patients: is heparin prophylaxis justified? South Med J. 1980; 73:841–3. 6. Prandoni P, Lensing AW, Cogo A et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996; 125:1–7. 7. Levitan N, Dowlati A, Remick SC et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore). 1999; 78:285–91. 8. Rickles FR, Levine MN, Dvorak HF. Abnormalities of Haemostasis in Malignancy. In: Colman RW, Hirsh J, Marder VJ et al., eds. Haemostasis and Thrombosis. Philadelphia: Lippincott Williams & Wilkins; 2001:1131–52. 9. Piccioli A, Lensing AW, Prins MH et al. Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial. J Thromb Haemost. 2004; 2:884–9. 10. Piccioli A, Prandoni P. Idiopathic venous thromboembolism as a first manifestation of cancer. Haemostasis. 2001; 31 (suppl 1):37–9. 11. Kakkar AK, Levine M, Pinedo HM et al. Venous thrombosis in cancer patients: insights from the FRONTLINE survey. Oncologist. 2003; 8:381–8. 55 53. ESTABLISHMENT OF PAIN CLINICS IN ARAB, AFRICAN AND DEVELOPING COUNTRIES. To start pain clinic in Arab, African and developing countries is a real challenge. The pain physician will face the following problems. [i] 1. Other specialties (surgery, orthopedics, oncology and neurology) are not convinced that pain should be treated as a separate entity. a. This belief resulted from the early medical education that you have to treat the cause but not the symptom. This is a real word of truth that is used to serve a false meaning or evil end. It is well known that so many diseases are accompanied with pain but the cause of pain could not be treated such as (cancer, nerve trauma, post herpetic neuralgia and failed back surgery). This medical idol resulted in under estimating the importance of relief of acute and chronic pain with under treatment of all types of pain. b. In other consideration a great number of surgeons will consider the anesthesiologist as an assistant for their work. So how come to refer a patient to an assistant? . In early days during the year 1982 and with the establishment of Avicenna Pain Relief Unit, Al-Azhar University, most of my colleagues from other specialties were making fun and sarcasm of the pain clinic. They said what service the anesthesiologist can do to relief pain? They also said the anesthesiologist is like a pickpocket he just picking up pain. It is known that the word pain in Arabic is pronounced as (Al-Alam). This word (Al-Alam) means also in Arabic Egyptian dialect a Pen. So this means that the anesthesiologist is nothing but a pickpocket or a thief. [ii] 2. Most of the official health authorities will not permit to start the pain relief service as they have the concept mentioned above or they have more hectic health problems such as to control epidemic diseases, nutrition of school age children, high birth rate and control of over population. a. On 1982 there were no room for the pain clinic in the outpatient building except a storeroom for dirty utilities of the clinic. I started to clean it in collaboration with some porters in the hospital after the end of the official working hours. These over time working hours were paid from my own pocket. The administration office refused to supply me with a nurse, secretary, desk or chairs. Later on the general manager of Al-Azhar University Hospitals issued two official documents to close Avicenna Pain Relief Unit (1985 and 1988). This was done on assumption that the pain clinic is just doing symptomatic treatment. The end result that during 1982 the pain clinic received 43 patients only. 3. The official pharmacy authorities were afraid from inefficient control on narcotic prescriptions. So the best way to control narcotics is not to prescribe them what so ever. The patients with cancer suffered from pain till 1987. With the start of the WHO program awareness about narcotics wake up. 4. Other problems will be present from one country to another. Some colleagues will not refer the patient with pain problems to the pain clinic not to loose the patient as a private practice. For example patients with failed back surgery are permanent customers to orthopedic or neurosurgery clinics. They will attend those clinics monthly for follow up and to pay a consultation fees. One of my intimate orthopedic surgeons told me that such patients are a source of fixed income to his - - - - - M. S. El-Ansary, Avicenna Pain Relief Unit, Al-Azhar Univ. Cairo, Egypt 56 - clinic. If he is going to refer them to the pain clinic how he can cover his monthly fixed expenses. 5. The perseverance of the pain doctors to continue their work in such circumstances. For the anesthesiologist to start a pain relief clinic in developing countries it is very difficult. So many pain clinics closed after short time as the pain doctors in charge of those clinics rapidly give up. To solve such problems you have to try to do the following: 1. Repeated public awareness by lectures and mass media to attract the attention of other specialties that pain management is and integral part of the treatment and not alternative. [iii] a. The Egyptian Society for the Management of Pain (ESMP) was established on 1982 and accepted as a Middle East Chapter of the International Association for the Study of Pain (IASP) on 1988. The ESMP arranged an annual congress for management of pain starting 1982 till now. Invitation of guest speakers from the developed countries in these congresses increased the awareness about the importance of management of pain. b. Since then repeated public talks in the mass media (Radio and TV) were done to increase the awareness of the layman by the importance of the pain clinics. This formulated an increased demand within the public opinion for the pain relief service. c. In the mean time attendance of so many lectures and congresses of related specialties (orthopedic, neurosurgery, neurology, and oncology) to explain to them what the pain clinic could do for the chronic pain patients. d. Personal contact was done with the junior staff from other specialties to convince them to refer pain problems to the pain clinic. Senior staff has no time to refer patients or will consider that referral of the patient to the pain clinic will be on expense of his medical skill, efficiency or dignity. e. Repeated and regular training courses for all branches of medicine were done every three-month. Clinical training was also prepared for junior staff from other specialties to work in the pain clinic. Later on those trainee started to be a base for referral of the patients to the pain clinic.[iv] f. The strong doctor – patient relationship could consider some of the patients who achieved good pain relief to be volunteers working in the pain clinic. Those volunteers could visit the patients at home (cancer pain patients). They also have very strong word of mouth to advise the patients to attend the pain clinic even without referral from other specialties. 2. You have to assure the doctors dealing with the patient in the private practice that you are going to help but not to pick up the patient. You should not treat the patient without a report from the treating doctor. The patient should know that the pain clinic is an integral part from his treatment plan. In the mean time after the method for pain relief was done, the patient is referred back to the treating doctor. For example in case a patient attend the private pain clinic with acute Herpes Zoster, immediate therapy for pain should be done and in the same time advise the patient to visit the dermatology clinic. The pain clinic working under supervision of anesthesiologist is not a rheumatology clinic. Rheumatoid arthritis should be treated in the rheumatology clinics but not in the pain clinic. 3. On 1982 I have no financial support from the hospital administration office. a. Treatment of some patients with intractable pain opened the door to receive some financial support from the patient or his relatives (Al-Zakah). [v] Official regulations would not permit to receive liquid money at hand. So I asked the donors to 57 - buy the instruments or equipments and to be officially offered them to the administration office. Then these instruments or equipments are to be delivered to the pain clinic. b. Acute postoperative pain management resulted in rapid ambulation of the patients and less complications. The official health authorities should know that good pain control would shorten the duration of hospital stay. This will save much money for the governmental health care. c. Although the general manager of Al-Azhar University Hospitals issued two official documents to close Avicenna Pain Relief Unit (1985 and 1988), but the patients and volunteers raised a petition to the hospital medical council against the General Manager. In a meeting with the hospital medical council I told them I am grateful to the General Manager as I am going to treat all the patients in my private clinic. The hospital medical council reopened the pain clinic. 4. By 1987 Confrontation with pharmacy authorities to put a clear agreement about firm and flexible system to control narcotic prescription. Following a meeting between the ESMP and the minister of public health he issued an official and legal order to control narcotic prescriptions for cancer pain patients (Slow Release Morphine 30mg Tabs). This resulted in the availability of Narcotics in the governmental outpatient pain relief and oncology clinics. In the mean time the pharmacy authorities were still against narcotic prescription in the outpatient pain clinics for fear of legal responsibility. In another meeting with security and pharmacy authorities, the later announced that they have the logic to differentiate between medical handling of narcotics and criminal narcotic delivery for street addicts. So the pharmacy authorities gave up and there are a regular supply of slow release morphine 30 mg. This is recently and smoothly followed by the use of fentanyl patch. 5. To start a pain clinic in the developing Arab and African nations is a great effort. But more difficult to continue and to develop this clinic. The newly borne pain clinic should start as [vi]: a. Class I. In which simple nerve and epidural blocks are to be done. Acute postoperative pain service could be also included. In addition to prescription of Slow release Morphine. b. In class II clinics management of cancer pain by itrathecal phenol, epidural and intrathecal narcotics would be available. Performance of major nerve blocks like celiac plexus block is also listed. c. Class III clinics or Units will permit the use of spinal cord stimulation and other electronic and computerized neuro axial pumps. A pain research unit will be also available. The following spotlights may be of value for any one starting the pain clinic. d. One should know how to deal with the patient in the outpatient clinic but not in the theater. The patient with chronic pain is a human being and a part of his society. Chronic pain is not just transmitted into anatomical pathways but a multifactorial syndrome. The pain clinician should do a break through in the patient personality to end by friendship before suggesting any type of therapy. In the western world the psychiatrist is available all the time but in the Arab and African nations he is absent all the time. e. One should be ready to tolerate the sarcasm of his colleagues. Any new idea will be faced by many objections. The nature of the human behavior is to reject things he does not know about. f. The pain doctor starting a pain clinic should sacrifice some of his private work and holydays to stay in the pain clinic. The newborn clinic needs an 58 extra care. One should behave like a mother. She will sacrifice every thing for the survival of her baby. Most of the doctors in Arab, African and developing countries will seek for another job in rich or developed countries to increase their income. This well ends by discontinuation of the efforts done to establish the pain clinic. g. Not to give up if you has no patients attending the clinic. With points mentioned above the clinic will be overcrowded. h. This opened the door for further problems to deal with over crowded clinic. 6. On 1984 the pain clinic received (5639 Patients). Another problems started to appear like: a. Limited number of medical staff to examine and treat the patients. b. No time for medical records. c. Limited number of nursing staff. d. The patients were obliged to wait for 3-4 hours before attending the clinic. Some of them tried to bypass their turn. e. The doctors, nurses and secretary were exhausted, and no body was happy. 7. On 1985 the total number of patients reduced to (3840 Patients). Reorganization of the pain clinic was done as follows: a. More number of doctors, nurses and qualified secretary. b. Only referred cases should be treated in the pain clinic. c. There was enough time to examine and treat the patients. d. Most of the patient could wait for their turn on the bases of first come first serve. e. The end result every body was happy. References: i . M. S. El-Ansary, Some Problems of Pain Relief in Egypt. Pain Journal of the ESMP.P 65-72, Vol. 5, N.2, Oct. (1987). ii . M. S. El-Ansary, Some Problems of Pain Relief in Egypt. Pain Journal of the ESMP.P 65-72, Vol. 5, N.2, Oct. (1987). iii . Lipton . S. Therapy of Pain , Ch 3 , Current View on the Management of pain Relief Center. 1St. Edit. M.T.P. Press. P 64, (1981). iv . Lipton . S. Therapy of Pain , Ch 3 , Current View on the Management of pain Relief Center. 1St. Edit. M.T.P. Press. P 64, (1981). v M. S. El-Ansary, Some Problems of Pain Relief in Egypt. Pain Journal of the ESMP.P 65-72, Vol. 5, N.2, Oct. (1987). vi . Lipton. S and Wells C., The pain Clinic Starting and Organization. Persistent Pain, Vol. 4, Grune and Statton. P. Ch. 10, P. 160, (1983). vii. vi. Lloyd. J. W., Equipment For Setting Up a pain Clinic, Brit. Journal of Hospital Medicine, P. 179, (1980). - - - - - On conclusion, to establish pain clinic in the Arab, African and developing countries is very difficult. Increased awareness about the pain clinics, good contact with the mass media, proper control of narcotics, training programs for junior staff and perseverance of the pain doctors will pave the way for the establishment and progress of the pain clinics. All what is mentioned above are just guidelines but every one can find other ways to establish the pain clinic. [vii] 59