Isolated Splenic Metastasis In Locally Advanced Colorectal Cancer

World Journal of Colorectal Surgery
Volume 4, Issue 2
2014
Article 2
Isolated Splenic Metastasis In Locally
Advanced Colorectal Cancer With Suspicious
Liver Lesions: Combined Multi-Organ
Resection Is Safe And Feasible. A Case
Report And Review Of Literature
Caroline C H Siew∗
Kon Voi Tay†
Surendra Kumar Mantoo‡
∗
National Healthcare Group, Singapore, [email protected]
National University Hospital, Singapore
‡
Khoo Teck Puat Hospital, Singapore
†
c
Copyright 2014
The Berkeley Electronic Press. All rights reserved.
Isolated Splenic Metastasis In Locally
Advanced Colorectal Cancer With Suspicious
Liver Lesions: Combined Multi-Organ
Resection Is Safe And Feasible. A Case
Report And Review Of Literature
Caroline C H Siew, Kon Voi Tay, and Surendra Kumar Mantoo
Abstract
Isolated splenic metastases are rare, with only 26 cases reported in English literature to date.
We describe a case of locally advanced sigmoid colon mucinous adenocarcinoma with suspicious
liver and splenic lesions seen on preoperative imaging. Resection of liver and extrahepatic disease
has been shown to improve survival in metastatic colorectal cancer, with combined resection recently demonstrated to be a feasible and safe option. Combined multi-organ resection involving
resection of primary colonic tumor with enbloc resection of the involved cuff of bladder, wedge resection of the liver lesion and splenectomy was performed uneventfully in our patient. Histology
revealed splenic metastasis but benign liver lesions. She was discharged home well on postoperative day 7 and subsequently received adjuvant chemotherapy. Current literature is reviewed
and discussed. Definite conclusions regarding the management of synchronous splenic metastasis
from colorectal carcinoma are not available due to paucity of evidence. Therapeutic options of
splenectomy and possibly adjuvant chemotherapy appear to have a positive impact on long term
survival. Simultaneous multiorgan resection for metastatic colorectal carcinoma is a reasonable
option in selected cases with multidisciplinary support.
KEYWORDS: Colorectal cancer, Splenic metastasis, Multi-organ resection
Siew et al.: Isolated Splenic Metastasis In Locally Advanced Colorectal Cancer
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Isolated Splenic Metastasis In Locally Advanced Colorectal Cancer With
Suspicious Liver Lesions: Combined Multi-Organ Resection Is Safe And
Feasible. A Case Report And Review Of Literature
Introduction:
Isolated splenic metastases remain a rare entity in colorectal cancer. The presence of
splenic metastases usually represents widely disseminated disease. Autopsy studies
reveal a 2% incidence of splenic metastases in colorectal cancer [1, 2]. Anatomical,
histological, functional and immunological features of the spleen may explain the low
prevalence of splenic metastases [3-6]. Synchronous splenic metastases are
infrequent, with most studies describing metachronous lesions [7]. All reported
patients underwent splenectomy, although the role of resection on long term survival
is not yet well defined for synchronous isolated splenic metastasis.
We present a case of locally advanced colorectal cancer with possible liver and
splenic metastases at presentation. The patient underwent open simultaneous major
resection uneventfully - resection of the sigmoid colon, en-bloc resection of a cuff of
bladder involved, wedge resection of the liver lesion and a splenectomy. The final
histology revealed benign liver lesions and isolated splenic metastasis. The final
pathologic stage was T4aN0M1a, Stage IVa.
Case Presentation:
A 67-year-old woman presented in November 2013 with painless per rectal bleeding
associated with symptomatic anemia. Haemoglobin was 8.6 g/dL on admission with a
deranged coagulation profile (INR 3.1) due to warfarin treatment for atrial fibrillation.
Warfarin was withheld and she received a blood transfusion. Colonoscopy revealed a
circumferential tumour at the sigmoid colon with impending obstruction (Figure 1) and
biopsies confirmed adenocarcinoma. Further preoperative investigations showed a
locally advanced sigmoid tumour with bladder involvement, liver lesions suspicious
for metastases at segment 4B and 7, and a splenic lesion on abdominal computed
tomography (CT). No lung lesions were identified (Figure 2). Preoperative
carcinoembryonic antigen (CEA) was high at 88 ug/L.
Intraoperative findings at the time of laparotomy were that of a bulky sigmoid tumour
invading into the dome of the bladder. Intraoperative liver ultrasound showed a 1cm
solid lesion in segment 6 and cystic lesion in segment 7 (Figure 3). Intraoperative
ultrasound of the spleen showed a solid component located peripherally, close to the
left hemidiaphragm (Figure 4). There was no obvious peritoneal disease. We
proceeded to perform a sigmoid colectomy with enbloc resection of the cuff of bladder
involved, wedge resection of the segment 6 liver lesion and a splenectomy. A cuff of
diaphragm was resected during splenectomy due to local involvement (Figure 5).
Surgical duration was 5 hours with total blood loss of 500mls. Postoperative recovery
was uneventful, warfarin was restarted inpatient and the patient was discharged
th
home on the 7 postoperative day.
Histopathological examination of the specimen showed a poorly differentiated
mucinous adenocarcinoma of the sigmoid colon with serosal invasion (T4a). Zero of
the twelve regional lymph nodes were positive for metastatic carcinoma (N0).
Resection margins were clear and there was no tumour invasion into the resected
cuff of bladder. Histology of the spleen revealed metastatic mucinous
adenocarcinoma, but the splenic hilum and resected cuff of diaphragm were not
involved by tumour. The final pathologic stage was T4aN0M1a, Stage IVa. The
resected segment 6 lesion in liver was a biliary hamartoma, with no malignancy
identified. Reduction of CEA levels to normal range was noted postoperatively and
the patient completed adjuvant chemotherapy uneventfully.
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Vol. 4, Iss. 2 [2014], Art. 2
Discussion:
Splenic metastases from colorectal cancer are rare and usually occur in disseminated
disease. The common sites of colorectal cancer metastases are the liver, lung and
peritoneum [8]. A study by Berge et al on splenic metastases involved a series of
7165 autopsies and reported the incidence of splenic metastasis in colon and rectal
cancer patients to be 4.4% and 1.6% respectively. None of these cases were isolated
metastases [1]. Another autopsy study by Warren and Davis found that only 2.2% of
colon and rectal carcinomas had splenic metastases, none of which were solitary
metastatic disease [2].
Since the first case report of isolated solitary splenic metastasis in colorectal cancer
by Dunbar et al. in 1969 [9], there are only 26 cases reported in English-language
medical literature. Twenty two cases are metachronous metastases and the
remaining four cases are synchronous [7]. In all cases, primary tumor was at least T3
and above with variable lymph node involvement. Two cases of mucinous
adenocarcinoma have been reported prior to our patient [10, 11].
The prognostic significance of mucinous adenocarcinoma is controversial. Patients
with mucinous adenocarcinoma have been shown to present with larger tumors,
deeper invasion and higher rates of nodal and distal metastases [12]. Mucinous
adenocarcinoma is also known to spread preferentially to the peritoneum, possibly
related to the production of mucus under pressure, which allows the tumor cells to
gain access to the peritoneal cavity [13].
Splenic metastases are usually diagnosed on imaging done for staging in the workup
of colorectal cancer or during oncological follow up. Patients are usually
asymptomatic and may present solely with a rising (CEA) level. Symptomatic patients
may present with splenomegaly, left hypochrondrial pain and non-specific symptoms
of weight loss. Few patients presented with splenic abscess [10] or spontaneous
rupture [14, 15].
Common imaging techniques include ultrasound, computed tomography (CT) scan of
the abdomen or magnetic resonance imaging (MRI). These typically reveal
hypodense splenic lesions which may be subcapsular or intraparenchymal in
locations [16]. Gasent Blesa et al described a case where 2-fluorodeoxyglucose
positron emission tomography (PET) scan was utilized to demonstrate an isolated
splenic metastasis in a patient with rising CEA levels but negative radiological studies
[17]. Gencosmanoglu et al describe a case where FDG PET-CT was used to further
evaluate a splenic lesion identified on CT scan. They suggest that FDG-PET
scanning allows better detection of metastatic deposits, especially if lesions are too
small to be seen on other imaging techniques. In addition, FDG-PET scanning can
assess if a lesion seen on CT is indeed tumor and also assess for involvement of
other sites by metastatic disease [18].
Metastases from colorectal cancer may reach the spleen via the splenic artery, the
splenic vein or lymphatics. A review of the literature found that the primary tumour
was located in the left colon or rectum in 70%. [7] This suggests a possible retrograde
spread of tumour deposits to the spleen via the inferior mesenteric vein to the splenic
vein [19]. The spleen parenchyma lacks afferent lymphatics but these are present in
the capsular, subcapsular and trabecular regions. The lymphatic distribution would
explain the subcapsular location of isolated splenic metastases, while
haematogenous metastases would be expected to be intraparenchymal.
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Siew et al.: Isolated Splenic Metastasis In Locally Advanced Colorectal Cancer
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In our patient, the peripheral location of the splenic metastasis and lack of splenic
hilar involvement would suggest lymphatic rather than haematogeneous route of
spread. However, the patient had T4 local disease of the left colon with no regional
lymph node involvement. We postulate that lymphatic spread of tumour to the spleen
was unlikely in our patient and would like to consider transcoelomic spread instead.
Peritoneal seeding typically results in metastases outside the splenic capsule rather
than involving the parenchyma. In our patient, the adherence of the diaphragm to the
splenic lesion further represents its outer location.
Some explanations have been proposed regarding the low incidence of splenic
metastasis. The sharp angle made by the splenic artery with the celiac axis and
rhythmic contractions of the sinusoidal splenic architecture prevent tumor emboli from
lodging in the spleen [3]. As the second largest organ of the reticuloendothelial
system, good immune surveillance provided by the rich supply of immunocompetent
cells within the spleen appears to inhibit tumor cell proliferation [3]. Experimental
studies also suggest that the development of splenic metastases is limited by the
destruction of malignant cells within the spleen [4]. Another experimental study by
Miller and Milton demonstrated a much lower growth rate of adenocarcinoma cells
after injection into the spleen as compared to the liver [5]. The absence of afferent
splenic lymphatics is another possible reason [6].
Splenectomy is the treatment of choice for splenic metastasis and was performed in
all reported cases of isolated splenic metastasis. Results appear optimistic but there
is no long-term survival data to indicate the efficacy and benefit of splenectomy for
isolated colorectal splenic metastasis. Current data indicate that long-term survival
after splenectomy in patients with isolated metachronous splenic metastasis varies
from 0.5 to 7 years and varies from 1 month to 6 years in patients with synchronous
splenic metastases [7]. Laparoscopic approach for splenectomy has been described
[17], but its use is controversial due to the risk of peritoneal dissemination during the
procedure.
To our knowledge, there are no previously described cases involving combined
resection of the primary colorectal tumour, en bloc bladder resection, liver
metastectomy, and splenectomy. A recent systematic review of outcomes of patients
undergoing resection for colorectal liver metastases in the setting of extrahepatic
disease suggests a benefit of resection of metastases despite multifocal disease.
Hwang et al demonstrated an improved 5-year survival compared with patients
excluded from resection – 42% vs 0% 5-year survival [20]. Improved median overall
survival has also been demonstrated in metastatic colorectal cancer patients who had
combined liver and extrahepatic disease resection (32-40 months) compared to those
treated with only systemic chemotherapy (16-24 months) [21,22]. It is currently
unclear whether primary colorectal cancer and synchronous liver metastases should
be resected simultaneously or as a staged procedure. Simultaneous colon and liver
resection is considered a high risk procedure, with quoted mortality rate of 7-12%
[23,24]. However, recent studies have shown that simultaneous resection can be
performed safely, with associated benefits of reduced total hospitalization stay by
reducing the need for a second procedure and hence better cost effectiveness [2527]. Current opinion suggests that combined resection is safe and feasible in selected
patients [28]. Our patient underwent resection of the primary sigmoid tumour with
enbloc resection of the involved bladder, wedge resection of the segment 6 liver
lesion, and a splenectomy uneventfully. The surgery was a concerted effort between
the colorectal, hepatobiliary and urology surgical teams. Intraoperative ultrasound
provided the additional benefit of allowing us to further evaluate as well as accurately
delineate the liver and splenic lesions during surgery.
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Vol. 4, Iss. 2 [2014], Art. 2
The role of adjuvant therapy in colorectal cancer patients with splenic metastases is
not clear. Of the 26 cases described prior in the literature, 12 patients are known to
have received adjuvant chemotherapy [7]. Survival benefit of adjuvant therapy cannot
be determined based on these case reports due to small patient numbers and lack of
long term follow-up.
Conclusion:
Isolated splenic metastasis from colorectal carcinoma is rare, and synchronous
metastases are infrequent. Therapeutic options are currently limited to splenectomy
and possibly adjuvant chemotherapy due to paucity of evidence. Simultaneous
multiorgan resection is feasible and safe in selected cases with multidisciplinary
support.
Figure 1: Colonoscopy showed a stenotic circumferential sigmoid tumour
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Siew et al.: Isolated Splenic Metastasis In Locally Advanced Colorectal Cancer
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Figure 2: Suspicious liver and splenic lesions with locally advanced sigmoid tumour
Figure 3: Intraoperative ultrasound of liver showing 1cm solid lesion in segment 6
and cystic lesion in segment 7
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Figure 4: Intraoperative ultrasound of spleen showing peripherally located solid
lesion
Figure 5: Splenectomy specimen with cuff of diaphragm and tumour (circled)
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References:
1. Berge T (1974) Splenic metastases. Frequencies and patterns. Acta Pathol
Microbiol Scand A 82:499–506
2. Warren S, Davis AH (1934) Studies on tumor metastasis: the metastases of
carcinoma to the spleen. Am J Cancer 21:517–533
3. Kim JC, Jeong CS, Kim HC et al (2000) Isolated splenic metastasis from colorectal
carcinoma: a case report. J Korean Med Sci 15:355–358
4. Eichner ER (1979) Splenic function, normal, too much and too little. Am J Med
66:311-320.
5. Miller JN, Milton GW (1965) An experimental comparison between tumor growth in
spleen and liver. J Pathol Bacteriol 90:515–21.
6. Waller RM 3rd, Fajman WA (1982) An unusual cause of an isolated, focal splenic
defect demonstrated by liver–spleen scintigraphy. Clin Nucl Med 7:5–7
7. Saad GSA, Hussein M, El-Saghir NS, Termos S, Sharara AI, Shamseddine A
(2011) Isolated splenic metastasis from colorectal cancer. Int J Clin Oncol 16:306–
313
8. Feig BW, Ching CD (2012) Cancer of the Colon, Rectum, and Anus. The MD
Anderson Surgical Oncology Handbook. 11:396-397
9. Dunbar WH, Beahrs OH, Morlock CG (1969) Solitary splenic metastasis incidental
to rectal carcinoma: report of a case. Mayo Clin Proc 44:40–45
10. Pisanu A, Ravarino A, Nieddu R et al (2007) Synchronous isolated splenic
metastasis from colon carcinoma and concomitant splenic abscess: a case report and
review of the literature. World J Gastroenterol 13:5516–5520
11. Mainprize KS, Berry AR (1997) Solitary splenic metastasis from colorectal
carcinoma. Br J Surg 84: 70
12. Numata M, Shiozawa M, Watanabe T, Tamagawa H, Yamamoto N, Morinaga S,
Watanabe K, Godai T, Oshima T, Fujii S, Kunisaki C, Rino Y, Masuda M, Akaike M
(2012) The clinicopathological features of colorectal mucinous adenocarcinoma and a
therapeutic strategy for the Disease. World J Surgical Oncology 10:109
13. Sugarbaker P (2001) Mucinous colorectal carcinoma. J Surg Oncol 77:282-283
14. Achuthan R, Joseph A, Haray PN (1999) Splenic metastasis from a rectal tumour:
an unusual presentation. Ann R Coll Surg Engl 81: 139
15. Al-Obaidi SM (1989) Spontaneous rupture of the spleen due to metastatic
carcinoma. Br J Clin Pract 43: 385-386
16. Imada H, Nataka H, Horie A (1991) Radiological diagnosis of splenic metastasis
and its prevalence at autopsy. Nippon Igaku Hoshasen Gakkai Zasshi 51(5):498-503.
Produced by The Berkeley Electronic Press, 2014
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World Journal of Colorectal Surgery
Vol. 4, Iss. 2 [2014], Art. 2
17. Gasent Blesa JM, de la Morena E, Laforga Canales JB et al (2008) Clinical case
report and literature review: metachronous colorectal splenic metastases. Clin Transl
Oncol 10:445–457
18. Gencosmanoglu R, Aker F, Kir G, Tozun N (2006) Isolated metachronous splenic
metastasis from synchronous colon cancer. World Journal of Surgical Oncology 4:42
19. Indudhara R, Vogt D, Levin HS et al (1997) Isolated splenic metastases from
colon cancer. South Med J 90:633–636
20. Hwang M et al (2014) Systematic review of outcomes of patients undergoing
resection for colorectal liver metastases in the setting of extra hepatic disease. Eur J
Cancer (Article in press)
21. Kawano D, Takeo S, Tsukamoto S, Katsura M, Masuyama E, Nakaji Y (2012)
Prediction of the prognosis and surgical indications for pulmonary metastectomy from
colorectal carcinoma in patients with combined hepatic metastases. Lung Cancer
75(2): 209–12
22. Kornprat P, Jarnagin WR, Gonen M, DeMatteo RP, Fong Y, Blumgart LH, et al
(2007) Outcome after hepatectomy for multiple (four or more) colorectal metastases
in the era of effective chemotherapy. Ann Surg Oncol 4(3):1151–60
23. Nordlinger B, Guiguet M, Vaillant JC, Balladur P, Boudjema K, Bachellier P, et al
(1996) Surgical resection of colorectal carcinoma metastases to the liver. A
prognostic scoring system to improve case selection, based on 1568 patients.
Association Francaise de Chirurgie. Cancer 77:1254-62
24. Bolton JS, Fuhrman GM (2000) Survival after resection of multiple bilobar hepatic
metastases from colorectal carcinoma. Ann Surg 231:743-51
25. Martin R, Paty P, Fong Y et al (2003) Simultaneous liver and colorectal resections
are safe for synchronous colorectal liver metastasis. J Am Coll Surg 197:233–242
26. Martin R, Augenstein V, Reuter N, Scoggins C, McMasters K (2009)
Simultaneous versus staged resection for synchronous colorectal cancer liver
metastases. J Am Coll Surg 208:842–852
27. Abbott DE, Cantor SB, Hu CY, Aloia TA, You YN, Nouyen S, Chang GJ (2012)
Optimizing clinical and economic outcomes of surgical therapy for patients with
colorectal cancer and synchronous liver metastases. J Am Coll Surg 215:262–70
28. McKenzie SP, Vargas HD, Evers BM, Davenport DL (2014) Selection criteria for
combined resection of synchronous colorectal cancer hepatic metastases: a
cautionary note. Int J Colorectal Dis (Online publication)
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