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Table 1 Summary of Five Cases of Recurrent Colorectal Cancer Involving the Duodenum and Pancreas
Overall
Age Primary Initial Time to
Case Pathology Mode of Other Sites Survival
(Years) Location Stage Recurrence Symptoms Treatment
Recurrence of Disease* Status
(Months)
(Months)
Moderately None
Neoadjuvant 5-FU/Xrt and Hematogenous (previous lung
1 61 Rectal T3 N0 115 Bleeding differentiated 70 (Dead)
pancreaticoduodenectomy adenocarcinoma metastasis metastasis)
Nausea, Neoadjuvant capecitabine/Xrt Well-differentiated Local None
2 67 Cecum T3 N2 103 48 (Alive)
vomiting and pancreaticoduodenectomy adenocarcinoma recurrence
Poorly None
Pain, nausea, Neoadjuvant capecitabine/Xrt Local
3 51 Cecum T3 N2 42 differentiated (previous lung 50 (Dead)
vomiting and pancreaticoduodenectomy recurrence
adenocarcinoma metastases)
Moderately
Pain, nausea, Local
4 59 Right colon T4 N1 10 Capecitabine/Xrt differentiated None 14 (Dead)
vomiting adenocarcinoma recurrence
Poorly
Lymphatic Liver and
5 66 Right colon T3 N1 46 Pain Capecitabine/oxaliplatin differentiated 6 (Dead)
adenocarcinoma metastasis lung
In May 2003, the patient reported weight loss and vague abdominal only 1 case. The surgical margins from the initial CRC resection were
pain. Computed tomography revealed a 6-cm peripancreatic mass negative in each case except case 4, in which the margin status could
with invasion into the pancreas and duodenum. The patient also had not be determined.
retroperitoneal and mesenteric lymphadenopathy, liver metastases, The mechanism of recurrence was thought to be by direct exten-
and lung metastases. Esophagogastroduodenoscopy revealed a duode- sion in 3 patients, hematogenous spread in 1 patient, and lymphatic
nal mass, which pathology confirmed was adenocarcinoma. Review of spread in 1 patient (Table 1). Three patients underwent aggressive
his duodenal pathology specimen at MDACC showed that the tumor trimodality treatment, with a resulting mean survival of 56 months.
was a poorly differentiated CK20-positive and CK7-negative adeno- Of these 3 cases, patient 2 remains alive without evidence of disease
carcinoma. The patient was presented to a multidisciplinary confer- recurrence at last follow-up (48 months after recurrence), while
ence, and considering his cytokeratin staining pattern and extensive patients 1 and 3 died of disease at 70 and 50 months, respectively,
ileocolic mesenteric adenopathy, the patient was determined to have after their duodenal recurrence. These impressive survival results
recurrent colon cancer, with the peripancreatic mass representing a were observed despite both patients having a history of previous
large nodal mass. pulmonary metastases. All 3 patients who underwent pancreati-
Despite treatment with capecitabine and oxaliplatin, the patient coduodenectomy experienced durable relief from their presenting
died in December 2003, 7 months after the recurrence. symptoms of bleeding, as in patient 1, or duodenal obstruction,
as in patients 2 and 3. The 2 patients who did not have surgical
Results resection of their duodenal recurrence survived for 6 months and
The time from initial diagnosis of colon or rectal cancer to recurrence 14 months, respectively, after the diagnosis of recurrence.
in our series ranged from 6 months to 10 years. All patients initially
had localized disease treated with surgery and adjuvant chemotherapy Discussion
with or without radiation therapy. The most common presenting Adenocarcinoma involving the duodenum and pancreas can result
symptoms of recurrence at the duodenal-pancreatic interface were pain, from primary duodenal adenocarcinoma, primary pancreatic adeno-
nausea, and vomiting. In all cases, pathologic evaluation conducted carcinoma, metastatic disease, or local invasion by adenocarcinoma
at MDACC determined that the recurrence was an adenocarcinoma originating in neighboring organs. Differentiating between these
consistent with a colorectal primary tumor. Comparison with the various situations requires thorough pathologic analysis and high-qual-
patients primary tumor was performed in 3 cases (cases 1, 3, and 4). ity radiologic imaging. In particular, making a distinction between
No coexisting adenoma or dysplasia was present to suggest a duodenal adenocarcinomas of the small bowel and colon is often difficult. A
primary tumor in any case. study examining the use of CK7 and CK20 to distinguish small
In these 5 cases, evaluation with EGD or CT (and usually both) bowel adenocarcinoma from colorectal adenocarcinoma found that, of
demonstrated the presence of recurrent disease. Pathologic diagnosis of 24 small-intestine adenocarcinomas, CK7 and CK20 were expressed
recurrence was made by endoscopic duodenal biopsy in all patients. All in 100% and 67%, respectively.10 Of the 23 CRC cases in the study,
cases presented with involvement of the pancreas and second portion of CK7 was expressed in 4%, and CK20 was expressed in 95%. However,
the duodenum. Lymph node involvement at the initial CRC diagnosis a recent study examining 486 carcinomas of the digestive system found
was present in 4 cases, whereas direct duodenal invasion was present in far fewer discernable differences in CK7 and CK20 expression levels.11
Table 2 Reported Cases of Relapsed Colorectal Cancer Involving the Duodenum and Pancreas
Primary Time to Recurrence Other Sites Overall Survival
Study Year Treatment Survival Status
Location (Months) of Disease* (Months)
Kamal et al6 2003 Rectum 48 None Duodenal resection 10 Alive
Right colon 48 None Pancreaticoduodenectomy 31 Alive
Sperti et al28 2003 Colon Synchronous Colon Pancreaticoduodenectomy 28 Alive
Right colon 10 None Pancreaticoduodenectomy 17 Dead
Ascending colon 42 None Pancreaticoduodenectomy 20 Alive
Wagle et al29 2001
Hepatic flexure 18 None Pancreaticoduodenectomy 4 Alive
Le Borgne et al30 2000 Colon 6 None Pancreaticoduodenectomy 12 Dead
Yoshimi et al31 1999 Ascending colon 36 None Pancreaticoduodenectomy 24 Dead
Right colon 15 NR Pancreaticoduodenectomy 41 Dead
Harrison et al27 1997
Right colon 15 NR Pancreaticoduodenectomy 21 Dead
Colon 34 None Pancreaticoduodenectomy 43 Alive
Nakeeb et al32 1995
Colon 14 None Pancreaticoduodenectomy 24 Dead
Alfonso et al5 1979 Hepatic flexure 17 None Pancreaticoduodenectomy 12 Alive
Of the 23 small intestine adenocarcinomas and 68 colorectal adeno- carcinomatosis and direct extension were excluded, the rate of CRC
carcinomas, CK7 was expressed in 34% and 10%, respectively, while involvement of the small intestine was 2%-3%.21 Hematogenous
CK20 was expressed in 47% and 76%, respectively. Case 4, which spread was the modality of recurrence for the patient in case 1, who
demonstrated a CK20-negative and focal CK7-positive expression initially presented with a primary tumor in the rectum.
pattern, reflects the CK pattern frequently observed in patients with The use of pancreaticoduodenectomy for patients with colon
microsatellite-unstable colon adenocarcinomas.12 cancer who initially present with pancreatic and duodenal involve-
Involvement of the duodenum and pancreas by locally recurrent ment has been described in case series from MDACC and
CRC is most commonly associated with a right-sided colon cancer, Memorial Sloan-Kettering Cancer Center (MSKCC).22,23 In the
as seen in cases 2, 3, and 4. This is because the hepatic flexure of the MDACC series, 7 patients with duodenum or pancreatic head
colon is tightly affixed to the infra-ampullary portion of the descend- invasion by colon cancer underwent a pancreaticoduodenectomy.
ing duodenum by the transverse mesocolon.13 In addition, invasion The median overall survival (OS) was 32 months, with no opera-
from the periduodenal and peripancreatic lymph nodes can result in tive or postoperative deaths. In the series from MSKCC, 8 patients
involvement of the duodenum and pancreas, as seen in case 5. The with right-sided colon cancer involving the duodenum or pancreas
lymphatic drainage from the cecum and ascending colon follows the underwent pancreaticoduodenectomy or duodenectomy. No post-
ileocolic vessels toward the root of the superior mesenteric artery and operative deaths occurred, and 6 patients were alive without disease
vein, adjacent to the duodenum and pancreas. A previous study has recurrence at a median follow-up time of 26 months.
reported 8 cases in which pancreatic involvement from right-side colon Numerous small case series also describe the use of pancre-
cancer were localized to the pancreatic head.14 This involvement was aticoduodenectomy for the treatment of patients with metastatic
believed to result from local peripancreatic nodal invasion in 3 cases, disease involving the pancreas. However, the vast majority of these
from invasion by a paraduodenal mass in 1 case, and from metastatic studies report outcomes for patients with multiple primary tumor
disease in 4 cases. types, with the predominant tumor being renal cell carcinoma.24,25
Metastases to the duodenum and pancreas are rare, with autop- The Fox Chase Cancer Center has reported the outcomes for
sy series reporting small-intestinal metastases in approximately 18 patients, 8 with colon cancer, who had locally recurrent upper
2%-4% of all cancer cases and pancreatic metastases in approximately abdominal cancers that involved the pancreas.26 All patients under-
4%-15%.8,9,15-17 Involvement of the pancreas by primary CRCs has went a pancreatic resection, with all 8 patients with colon cancer
been reported in 2%-7% of cases described in autopsy series.16,17 In requiring a pancreaticoduodenectomy. The median OS for all
general, these metastases are components of widespread metastatic dis- 18 patients was 46 months. In addition, investigators from MSKCC
ease, and the frequency of solitary metastases to these sites is unknown. reported a series of 18 patients who underwent pancreaticoduode-
Tumors that most commonly metastasize to the pancreas are those nectomy for isolated metastatic or locally advanced nonperiampullary
of the lung, stomach, and kidney. For small-intestinal metastases, the cancers.27 The median OS was 40 months. There was no significant
most common primary tumors are melanoma, lung cancers, and breast difference in survival between the subgroup of patients with direct
cancers.8,18-20 In 2 autopsy series in which involvement by peritoneal invasion (8 cases) and the subgroup of patients with metastatic or
locally recurrent disease (10 cases). The primary tumor types in these resection of colorectal liver metastases: FFCD ACHBTH AURC 9002
18 patients comprised 7 colon cancers, 4 gastric cancers, 3 renal cell trial. J Clin Oncol 2006; 24:4976-82.
5. Alfonso A, Morehouse H, Dallemand S, et al. Local duodenal metastasis
cancers, 2 lung cancers, 1 bladder cancer, and 1 melanoma. from colonic carcinoma. J Clin Gastroenterol 1979; 1:149-52.
From the literature, individual patient data are available for 6. Kamal HS, Farah RE, Hamzi HA, et al. Unusual presentation of rectal
13 patients who underwent surgical resection of recurrent or metastat- adenocarcinoma. Rom J Gastroenterol 2003; 12:47-50.
7. Sebastian JJ, Zaragozano R, Vicente J, et al. Duodenal obstruction
ic CRC involving the pancreas and duodenum (Table 2).5,6,27-32 The secondary to a metastasis from an adenocarcinoma of the cecum: a case
majority of these recurrences were from adenocarcinomas of the right report. Am J Gastroenterol 1997; 92:1051-2.
colon (12 of 13). The mean OS for these 12 cases was 24 months. 8. Willis RA. The Spread of Tumours in the Human Body. London:
Butterworth & Co; 1973.
In our series, the mean OS for all 5 patients was 38 months. For 9. Telerman A, Gerard B, Van den Heule B, et al. Gastrointestinal metas-
the 3 patients who underwent aggressive multimodality treatment tases from extra-abdominal tumors. Endoscopy 1985; 17:99-101.
with resection, chemotherapy, and radiation therapy, the OS was 10. Chen ZM, Wang HL. Alteration of cytokeratin 7 and cytokeratin 20
expression profile is uniquely associated with tumorigenesis of primary
48 months, 50 months, and 70 months, respectively. These 3 patients adenocarcinoma of the small intestine. Am J Surg Pathol 2004; 28:1352-9.
represent a highly selected group, with 2 patients demonstrating pro- 11. Lee MJ, Lee HS, Kim WH, et al. Expression of mucins and cytokera-
longed DFIs from initial diagnosis of > 8 years. tins in primary carcinomas of the digestive system. Mod Pathol 2003;
16:403-10.
At MDACC, we often favor the delivery of chemoradiation before 12. McGregor DK, Wu TT, Rashid A, et al. Reduced expression of cyto-
surgical resection in patients with localized recurrences. This approach keratin 20 in colorectal carcinomas with high levels of microsatellite
allows for a reduction in the tumor burden before a planned surgi- instability. Am J Surg Pathol 2004; 28:712-8.
13. Treitel H, Meyers MA, Maza V. Changes in the duodenal loop second-
cal intervention. In addition, preoperative radiation therapy, which ary to carcinoma of the hepatic flexure of the colon. Br J Radiol 1970;
is delivered when blood flow and oxygenation are unimpaired by 43:209-13.
postsurgical changes, might have an improved benefit-to-risk ratio 14. Charnsangavej C, Whitley NO. Metastases to the pancreas and peri-
pancreatic lymph nodes from carcinoma of the right side of the colon:
compared with postoperative radiation therapy. An important benefit CT findings in 12 patients. AJR Am J Roentgenol 1993; 160:49-52.
of this approach is improved patient selection for an aggressive surgical 15. Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma; analysis of
intervention. If, during neoadjuvant therapy, local tumor progression 1000 autopsied cases. Cancer 1950; 3:74-85.
16. Adsay NV, Andea A, Basturk O, et al. Secondary tumors of the pan-
or new metastatic disease develops, inappropriate surgical intervention creas: an analysis of a surgical and autopsy database and review of the
might then be avoided, as in case 4. In the 3 patients who ultimately literature. Virchows Arch 2004; 444:527-35.
underwent pancreaticoduodenectomy, the intervals between initial 17. Nakamura E, Shimizu M, Itoh T, et al. Secondary tumors of the
pancreas: clinicopathologic study of 103 autopsy cases of Japanese
diagnosis of duodenal relapse and surgical resection were 4, 5, and 7 patients. Pathol Int 2001; 51:686-90.
months, respectively. 18. Richie RE, Reynolds VH, Sawyers JL. Tumor metastases to the small
There are limitations to the interpretation of our findings. As a ret- bowel from extra-abdominal sites. South Med J 1973; 66:1383-7.
19. Kadakia SC, Parker A, Canales L. Metastatic tumors to the upper
rospective case series, there is the potential for selection and interpreta- gastrointestinal tract: endoscopic experience. Am J Gastroenterol 1992;
tion bias. Because of the aggressive nature of the treatment discussed in 87:1418-23.
this report, patients who underwent multimodality therapy represent 20. Brady LW, ONeill EA, Farber SH. Unusual sites of metastases. Semin
Oncol 1977; 4:59-64.
a heavily selected group. The selection of such patients for aggressive 21. Farmer RG, Hawk WA. Metastatic tumors of the small bowel.
therapy, as represented in our report, should be made by an integrated Gastroenterology 1964; 47:496-504.
multidisciplinary team, and the applicability of our treatment approach 22. Curley SA, Evans DB, Ames FC. Resection for cure of carcinoma of
the colon directly invading the duodenum or pancreatic head. J Am
to other medical settings without multidisciplinary cancer care might Coll Surg 1994; 179:587-92.
not be appropriate. 23. Koea JB, Conlon K, Paty PB, et al. Pancreatic or duodenal resection
or both for advanced carcinoma of the right colon: is it justified? Dis
Colon Rectum 2000; 43:460-5.
Conclusion 24. Eidt S, Jergas M, Schmidt R, et al. Metastasis to the pancreas-an indica-
This case series and literature review suggests that selected patients tion for pancreatic resection? Langenbecks Arch Surg 2007; 392:539-42.
with CRC with relapsed disease involving the duodenum and pan- 25. Hiotis SP, Klimstra DS, Conlon KC, et al. Results after pancreatic
resection for metastatic lesions. Ann Surg Oncol 2002; 9:675-9.
creas can achieve long-term palliation of symptoms and prolonged 26. Pingpank JF Jr, Hoffman JP, Sigurdson ER, et al. Pancreatic resection
survival with a pancreaticoduodenectomy. Our experience suggests for locally advanced primary and metastatic nonpancreatic neoplasms.
that the best outcomes appear to be obtained through a multimodal- Am Surg 2002; 68:337-40; discussion 340-1.
27. Harrison LE, Merchant N, Cohen AM, et al. Pancreaticoduodenectomy
ity therapy approach. for nonperiampullary primary tumors. Am J Surg 1997; 174:393-5.
28. Sperti C, Pasquali C, Liessi G, et al. Pancreatic resection for metastatic
tumors to the pancreas. J Surg Oncol 2003; 83:161-6; discussion 166.
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