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Background
Small bowel (intestine) adenocarcinomas are much rarer than their large bowel cousins. Histopathologically, the majority of tumors are similar if not identical to colon cancers. Overall, there is a poor prognosis which may be a result of a frequent late diagnosis.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Rare
Primary small bowel malignancies: single-center results of three decades.Ojha A, Zacherl J, Scheuba C, Jakesz R, Wenzl E.
University Clinic of Surgery, University of Vienna, Austria.
J Clin Gastroenterol 2000 Apr;30(3):289-93 Abstract quote. We highlight one medical center's experiences with primary malignancies of the small bowel. During a 27-year period, 79 patients were treated for small bowel tumors. Of these, 15 (20%) were lost to follow-up; thus, 64 patients were reviewed retrospectively with emphasis on histological distribution and their topography, perioperative complications, overall survival, and prognostic factors.
In our 64-patient series, 33 (51.6%) presented with adenocarcinoma; 10 (15.5%), lymphoma; 8 (12.1%), leiomyosarcoma; 5 (7.6%), neurogenic tumor; 2 (3%), unclassified carcinoma; 5 (7.6%), other types of sarcoma; and 1 patient presented with synchronous adenocarcinoma and lymphoma. Of all patients, 30 (46.9%) were curatively treated, whereas 34 (53.1%) underwent palliative procedures. Hospital lethality was 9.4% and mainly occurred in patients operated on under emergency circumstances. Reoperation rate was 29.7%. The observation period lasted at least five years or until death; three patients were alive less than five years postoperatively.
Cumulative five-year survival rate was 22.5% in the adenocarcinoma group, 33.3% in the lymphoma group, 33.3% in the leiomyosarcoma group, and 22.2% in patients with other tumors. The uncharacteristic symptoms presented by patients suffering from small intestinal malignancies make early diagnosis difficult.
Therefore, especially in patients with long-standing bowel diseases, malignancy should be considered. Early diagnosis and surgical treatment lead to a good prognosis as shown by our study.
DISEASE ASSOCIATIONS CHARACTERIZATION CROHN'S DISEASE
Adenocarcinoma complicating Crohn's disease.Michelassi F, Testa G, Pomidor WJ, Lashner BA, Block GE.
Department of Surgery, University of Chicago Medical School, Illinois.
Dis Colon Rectum 1993 Jul;36(7):654-61 Abstract quote We report on 14 cases of intestinal adenocarcinoma complicating Crohn's disease, seven occurring in the small bowel and seven in the large bowel. In both locations, two-thirds of patients were male.
The average ages at the time of diagnosis of Crohn's disease and of cancer were similar between the two groups of patients: 28 and 48 years, respectively. The diagnosis of cancer was suspected or obtained preoperatively in only four cases of large bowel cancer; in two patients with large bowel cancer and five with small bowel cancer, the diagnosis was made at laparotomy. In the remaining cases, only careful histologic examination revealed the carcinoma. Six small bowel cancers were located in the ileum, and five colonic cancers were distal to the splenic flexure. Two small bowel and one large bowel cancer were multifocal and had surrounding mucosal dysplasia. All tumors, except one small bowel cancer, underwent resection.
Survival correlated with stage of tumor at resection; no patient with regional or distant metastasis survived five years, in comparison with an 83 percent five-year actuarial survival rate of patients with tumor confined to the intestinal wall. Mean survival was six months for patients with small bowel cancer in comparison with 65 months for patients with large bowel cancer, reflecting a tendency toward more advanced lesions in the small bowel cancer group.
PATHOGENESIS CHARACTERIZATION ACYL-CoA SYNTHETASE
Impaired expression of Acyl-CoA-synthetase 5 in epithelial tumors of the small intestine.
Gassler N, Schneider A, Kopitz J, Schnolzer M, Obermuller N, Kartenbeck J, Otto HF, Autschbach F.
Hum Pathol. 2003 Oct;34(10):1048-52 Abstract quote.
Fatty acids are implicated in tumorigenesis, but data are limited concerning endogenous fatty acid metabolism of tumor cells in adenomas and adenocarcinomas of the small intestine. The recently cloned human acyl-CoA-synthetase 5 (ACS5) is predominantly found in the small intestine and represents a key enzyme in providing cytosolic acyl-CoA thioesters.
Protein synthesis and mRNA expression of ACS5 were studied in human intestinal tissues using different methods, including a newly established monoclonal antibody. In the healthy small intestine, expression of ACS5 was restricted to the villus surface epithelium but was not detectable in enterocytes lining crypts. ACS5 protein and mRNA were progressively diminished in epithelial cells of adenomas and adenocarcinomas of the small intestine.
In conclusion, altered expression of ACS5 is probably related to the adenoma-carcinoma sequence of small intestinal epithelial tumors due to an impaired acyl-CoA thioester synthesis.COX-2
COX-2, Inflammatory Secreted PLA2, and Cytoplasmic PLA2 Protein Expression in Small Bowel Adenocarcinomas Compared with Colorectal Adenocarcinomas.Wendum D, Svrcek M, Rigau V, Boelle PY, Sebbagh N, Parc R, Masliah J, Trugnan G, Flejou JF.
Departments of Pathology (DW, MS, VR, NS, J-FF) and Digestive Surgery (RP), Hopital Saint-Antoine.
Mod Pathol 2003 Feb;16(2):130-6 Abstract quote Cyclooxygenase-2 (COX-2), human synovial inflammatory secreted phospholipase A2 (sPLA2) and cytoplasmic phospholipase A2 (cPLA2) are involved in eicosanoid production and also seem to participate in colorectal tumorigenesis. As there are no data regarding these enzymes in human small bowel tumors, we wanted to determine whether they were involved in human small bowel tumorigenesis, and whether their expression was different in small bowel compared to colorectal adenocarcinomas, as suggested by animal studies.
We studied their protein expression by immunohistochemistry in 25 small bowel adenocarcinomas and compared it to 48 colorectal adenocarcinomas. Seventy-six percent of the small bowel and 88% of the colorectal adenocarcinomas had a moderate or strong COX-2 expression. Sixty-eight percent of the small bowel and 67% of the colorectal adenocarcinomas had a moderate or strong sPLA2 expression. Forty-eight percent of the small bowel and 35% of the colorectal adenocarcinomas had a moderate or strong cPLA2 expression.
In conclusion, the increased expression of COX-2, sPLA2, and sometimes cPLA2 in both small bowel and colorectal adenocarcinomas is in accordance with the likely eicosanoid involvement in tumor development. The same pattern of protein expression found in both types of adenocarcinoma contradicts experimental results in mice. Moreover, our results strengthen the similarities between these two types of human cancer.
CYTOGENETIC ABNORMALITIES
- Immunohistochemical investigation of tumorigenic pathways in small intestinal adenocarcinoma: a comparison with colorectal adenocarcinoma.
Zhang MQ, Chen ZM, Wang HL.
1Lauren V Ackerman Laboratory of Surgical Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Mod Pathol. 2006 Apr;19(4):573-80. Abstract quote
Small intestinal adenocarcinoma is an uncommon neoplasm morphologically similar to or indistinguishable from colorectal adenocarcinoma. Although much has been learned about genetic pathways critical to colorectal tumorigenesis, little is known about molecular alterations involved in the development of small intestinal adenocarcinoma.
In this study, we immunohistochemically compared non-ampullary small intestinal adenocarcinomas with sporadic colorectal adenocarcinomas for the expression of several proteins known to serve pivotal roles in colorectal tumorigenesis. These included adenomatous polyposis coli and beta-catenin involved in the Wnt signaling pathway, and DNA mismatch repair enzymes hMLH1, hMSH2 and hMSH6 involved in the microsatellite instability pathway. The expression of two important tumor suppressors, p53 and RB, was also examined. The results show that complete loss of adenomatous polyposis coli immunoreactivity, presumably resulting from its gene mutations, was observed in eight of 26 (31%) small intestinal adenocarcinomas and 36 of 51 (71%) colorectal adenocarcinomas (P=0.0008). Nuclear localization of beta-catenin, an indirect evidence of deregulated Wnt signaling pathway, was observed in 5 (19%) small intestinal adenocarcinomas and 36 (71%) colorectal adenocarcinomas (P<0.0001). Total lack of nuclear staining for one or more of the DNA mismatch repair enzymes occurred in a similar low frequency in both small intestinal and colorectal adenocarcinomas, seen in two of 25 (8%) and 10 of 47 (21%) cases, respectively (P=0.1958). The frequencies of aberrant p53 and RB expression were also similar between small intestinal and colorectal adenocarcinomas.
These observations indicate that defects in the Wnt and microsatellite instability pathways occur in over 90% of colorectal adenocarcinomas, but in only 40% of small intestinal adenocarcinomas. Small intestinal tumorigenesis appears to follow a distinct, yet unidentified, molecular pathway(s) from its colorectal counterpart despite their morphologic similarity.
Involvement of 1p36 region in two cases of adenocarcinoma of the ampulla of Vater.Bernasconi B, Dossena B, Billo PR, Tibiletti MG, Sessa F.
Department of Pathology, Ospedale di Circolo, University of Insubria, Varese, Italy
Cancer Genet Cytogenet 2002 Oct 15;138(2):133-8 Abstract quote Cancer of the ampulla of Vater is an uncommon disease that leads to death in 60% of affected patients. There is general agreement that local spread of the tumour (T stage) is the only significant and independent prognostic factor for this cancer.
Although the genetic mechanisms underlying the development of ampullary tumors are still mostly unknown because of their rarity, the genetic anomalies involved in tumor development might serve as additional prognostic markers. Cytogenetic studies may be helpful in identifying specific chromosome regions involved in these cancers.
We studied two cases of poorly differentiated ampullary adenocarcinomas using conventional and molecular cytogenetics on direct preparations. The cytogenetic analysis revealed complex chromosome complements in both cases with different cell lines, rearrangements, chromosome markers, and aneuploidies. Interestingly, the involvement of the 1p36 region was a feature of both cases. The molecular studies showed an absence of high microsatellite instability (MSI) and the morphologic and immunohistochemical pattern did not suggest MSI.
This study may help to characterized ampullary adenocarcinomas showing complex karyotypes, poor differentiation and poor prognosis. In these tumors, the 1p36 region may play a relevant role in the progression towards a high grade of anaplasia.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC
The accuracy of CT staging of small bowel adenocarcinoma: CT/pathologic correlation.Buckley JA, Siegelman SS, Jones B, Fishman EK.
Department of Radiology, Stanford University Medical Center, CA, USA.
J Comput Assist Tomogr 1997 Nov-Dec;21(6):986-91 Abstract quote PURPOSE: Several studies have documented the use of CT in the evaluation of small bowel neoplasms, but few have addressed the CT staging of adenocarcinoma. We retrospectively correlated CT and pathologic staging to evaluate the accuracy of CT for staging small bowel adenocarcinoma using American Joint Committee on Cancer criteria.
METHOD: The preoperative CT scans of 15 patients with pathologically proven small bowel adenocarcinoma were analyzed. Two blinded readers separately interpreted extent of invasion, presence of lymphadenopathy, and distant metastases. Pathologic and CT staging were compared.
RESULTS: The overall accuracy of CT staging was 47% (14/30). The sensitivity of detection of mesenteric infiltration was 88%. The sensitivity and specificity for detection of distant metastases were 58 and 63% and for lymphadenopathy 75 and 20%, respectively. Errors occurred in patients with Crohn disease, adenomas, Peutz-Jegher syndrome, small bowel obstruction, and perforation and on suboptimal studies.
CONCLUSION: The accuracy of CT staging of small bowel adenocarcinoma is 47%. CT is highly sensitive but not specific for the detection of mesenteric infiltration and regional lymphadenopathy. Since spiral CT may offer improved detection of distant metastases and increased accuracy in the evaluation of patients with concomitant bowel disease, further research is needed to determine the maximal utility of CT in the staging of adenocarcinoma of the small bowel.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL
Small bowel cancer: a 30-year review.Frost DB, Mercado PD, Tyrell JS.
Division of Surgical Oncology, Southern California Permanente Medical Group, Los Angeles Medical Center.
Ann Surg Oncol 1994 Jul;1(4):290-5 Abstract quote BACKGROUND: Small bowel cancer is a relatively rare tumor with an incidence of 2,700 new cases and 900 deaths per year. The influence of stage on survival has been reported only once previously. Patterns of recurrence are unreported.
METHODS: All cases of small bowel cancer treated at our hospital over a 30-year period (1960-1989) were reviewed.
RESULTS: The site of most cancers was the duodenum (46%), followed in frequency by the jejunum (33%) and the ileum (21%). Adenocarcinoma was the most common histology (63%), followed in frequency by lymphoma (15%), leiomyosarcoma (13%), carcinoid tumors (6%), and miscellaneous (3%). Analysis of stage distribution by site showed a decrease in stages I and II with more distal locations. Associated cancers occurred in 11%, but none were seen in the group with carcinoid tumors. Actuarial 10-year survival rates were 24% for those with adenocarcinoma (all stages) 75% for stage I, 25% for those with stage II, and 0% for stage III. A subgroup of 10 patients who underwent a pancreaticoduodenectomy (one stage I, seven stage II, two stage III) had a 30% 10-year survival rate. Those patients with lymphoma had a 12% 10-year survival rate, and those with leiomyosarcoma had a 20% 10-year survival rate. A 100% 10-year survival rate was observed in those with carcinoid tumors. Peritoneal carcinomatosis was the most common failure pattern (33%), followed in frequency by local recurrence in 23% and abdominal wall recurrence in 15%.
CONCLUSIONS: A correlation exists between the pathologic stage and the survival rate for adenocarcinoma. The most common recurrence pattern for adenocarcinoma was carcinomatosis, followed in frequency by abdominal wall recurrence. Leiomyosarcoma preferentially metastasizes to the liver.
Primary adenocarcinoma of the jejunum and ileum. A clinicopathologic study.Bridge MF, Perzin KH.
Cancer 1975 Nov;36(5):1876-87 Abstract quote The clinical and pathologic features of 43 primary adenacarcinomas of the small intestine (32 jejunal and 11 ileal) are reported. Seventy-four percent of the patients presented with partial or complete small bowel obstruction, 56% complained of abdominal pain, 37% had symptoms of anemia (weakness, easy fatigability), and 35% had lost weight.
Anemic hemoglobin levels occurred in 69%, and a palpable abdominal mass in 25%. Treatment consisted of a "curative" or "palliative" resection, or a bypass procedure. Seventy-nine percent of the tumors showed an annular, constricting pattern, while the remaining 21% had a predominantly fungating or polypoid appearance. Three individuals currently free of clinical recurrence have been followed less than 5 years. Of the remaining 40 patients, a 5-year cure was achieved in 11 (28%), including 6 (15%) who at present have no recurrence and 5 (13%) who subsequently died of other causes.
Within 5 years, 28 of these 40 patients (70%) were known or presumed dead tumor, and 1 had succumbed to other causes (2%). Various pathologic features were correlated with the clinical course. Documented lymph node metastasis proved to be the most valuable prognostic finding, 88% of these individuals dying of tumor, as contrasted to 45% of those with tumor-free nodes.
A few cases of superficially invasive carcinoma found in an otherwise benign adenomatous lesion had a good prognosis when symptoms were produced mainly by the adenoma, the carcinoma being a relatively minor component.
DUODENUM
Primary duodenal adenocarcinoma: a 40-year experience.Ryder NM, Ko CY, Hines OJ, Gloor B, Reber HA.
UCLA School of Medicine, Division of General Surgery, PO Box 956904, 10833 Le Conte Ave, CHS 72-231, Los Angeles, CA 90095-6904, USA.
Arch Surg 2000 Sep;135(9):1070-4 Abstract quote HYPOTHESIS: In patients with duodenal adenocarcinoma, certain pathologic features of the tumor will have prognostic significance.
DESIGN: Retrospective case series.
PATIENTS: Forty-nine patients diagnosed with duodenal adenocarcinoma between 1957 and 1998.
RESULTS: The tumors of 31 (63%) of the 49 patients underwent resection, 18 (37%) had surgical palliation or underwent biopsy. Mean (+/- SEM) survival for all patients was 49 +/- 9 months. The patients whose tumors were resected had longer survival than those who underwent palliation (mean +/- SEM, 66 +/- 13 months vs 18 +/- 6 months, P =.02). Multivariate analysis revealed large tumor size (P =.01), transmural invasion (P =.004), and moderate to poor tumor grade (P =.03) were negatively correlated with survival. Lymph node status did not influence survival.
CONCLUSIONS: Our 40-year experience with duodenal adenocarcinoma demonstrates that large tumor size, advanced histological grade, and transmural invasion are associated with decreased survival. These results underscore the importance of early diagnosis, and suggest the presence of nodal spread is not a contraindication to resection.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Generally, identical to large bowel adenocarcinomas VARIANTS GENERAL
Primary duodenal carcinoma showing divergent growth patterns as determined by microdissection-based mutational genotyping.Cheung O, Kandil H, Moser AJ, Swalsky PA, Sasatomi E, Finkelstein SD.
Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pa 15213, USA.
Arch Pathol Lab Med. 2003 Jul;127(7):861-4 Abstract quote Primary duodenal adenocarcinoma accounts for less than 0.5% of all gastrointestinal cancers.
We report a case of duodenal adenocarcinoma with highly divergent growth patterns consisting of poorly differentiated adenocarcinoma and neuroendocrine carcinoma proven to arise as a single neoplasm of monoclonal origin, as demonstrated by microdissection-based mutational profiling.
Multicomponent growth patterns, as seen in this case, can occasionally be encountered in gastrointestinal malignancies and have led to speculation about the pathogenesis. The methods used to clearly establish monoclonal origin based on the unique profiling of mutational damage can address fundamental issues related to tumor development and progression, while providing cogent clinical information.
Our findings confirm the great potential for intestinal epithelial cells to differentiate along different histogenetic lines during tumor progression.
SPECIAL STAINS/
IMMUNOHISTO-
CHEMISTRYCHARACTERIZATION AMACR
- Differential expression of alpha-methylacyl coenzyme A racemase in adenocarcinomas of the small and large intestines.
Chen ZM, Ritter JH, Wang HL.
Lauren V. Ackerman Laboratory of Surgical Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Am J Surg Pathol. 2005 Jul;29(7):890-6. Abstract quote
Alpha-methylacyl coenzyme A racemase (AMACR), a novel immunomarker for prostatic adenocarcinoma, has recently been shown to be expressed in a number of malignancies including colorectal adenocarcinoma.
In the current study, 59 surgically resected primary small intestinal adenocarcinomas (34 ampullary and 25 non-ampullary) were immunohistochemically examined for AMACR expression and compared with 66 colorectal adenocarcinomas (including 24 secondary tumors involving the small intestine by direct extension or metastasis).
The results show that no AMACR immunoreactivity was detected in normal-appearing small and large intestinal mucosa. While 41 of 66 (62%) colorectal adenocarcinomas exhibited a variable degree of cytoplasmic staining, only 1 of 25 (4%) non-ampullary and 2 of 34 (6%) ampullary small intestinal adenocarcinomas showed positive AMACR immunoreactivity (P < 0.0001). Interestingly, AMACR appeared to be less frequently expressed in mucinous or poorly differentiated colorectal adenocarcinomas when compared with non-mucinous or better-differentiated counterparts, suggesting an association with microsatellite instability status.
These results extend our previous observations that small intestinal adenocarcinomas differ markedly from colorectal adenocarcinomas despite their morphologic similarity. The different AMACR expression patterns may not only provide an additional diagnostic tool in the distinction between adenocarcinomas of the small and large intestinal origins but may also shed light on further understanding of intestinal tumorigenesis.CYTOKERATIN
- Alteration of cytokeratin 7 and cytokeratin 20 expression profile is uniquely associated with tumorigenesis of primary adenocarcinoma of the small intestine.
Chen ZM, Wang HL.
Lauren V. Ackerman Laboratory of Surgical Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
Am J Surg Pathol. 2004 Oct;28(10):1352-9. Abstract quote
Twenty-four cases of primary nonampullary small intestinal adenocarcinoma were immunohistochemically examined for the expression of cytokeratin (CK) 7 and CK20 and compared with 23 colorectal adenocarcinomas secondarily involving the small intestine by direct extension or metastasis.
While normal small intestinal mucosa was diffusely positive for CK20 and completely negative for CK7 expression, all small intestinal adenocarcinomas (24 of 24) showed a variable degree of CK7 expression. Specifically, the CK7 staining pattern was diffuse in 13 cases (54%) and focal in the remaining cases. Sixteen small intestinal adenocarcinomas (67%) coexpressed CK7 and CK20, and 8 (33%) completely lost CK20 immunoreactivity when compared with adjacent non-neoplastic small intestinal mucosa. In the latter cases, the loss of CK20 immunoreactivity with a reciprocal emergence of CK7 expression was evident. This was in contrast to secondary colorectal adenocarcinomas where 22 cases (96%) expressed CK20, among which only 1 case showed focal CK7 expression. The remaining 1 case was negative for both CK7 and CK20. Interestingly, adenomatous epithelium associated with small intestinal adenocarcinomas identified in 18 cases also exhibited CK7 positivity with a sharp transition from CK7-negative normal-appearing epithelium. Taken together, these observations delineate an alteration of CK7 and CK20 expression profile that occurs early in small intestinal tumorigenesis.
This unique pattern may be of diagnostic value in distinguishing primary small intestinal adenocarcinoma from secondary colorectal adenocarcinoma.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES BRUNNER GLAND HYPERPLASIA
- Gastric Foveolar Metaplasia With Dysplastic Changes in Brunner Gland Hyperplasia: Possible Precursor Lesions for Brunner Gland Adenocarcinoma.
Sakurai T, Sakashita H, Honjo G, Kasyu I, Manabe T.
From the *Laboratory of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan; daggerDepartment of Pathology, Tenri Hospital, Nara, Japan; and double daggerDepartment of Pathology, Kyoto Katsura Hospital, Kyoto, Japan.
Am J Surg Pathol. 2005 Nov;29(11):1442-1448. Abstract quote
Cases of adenocarcinomas developed in Brunner gland hyperplasia (BGH) have been sporadically reported.
Herein, we report the morphologic spectrum of hyperplastic changes culminating into dysplasia and carcinoma in 722 cases of BGH listed in our files. Fifteen of these cases showed dysplastic changes, with 8 graded as low-grade dysplasia, 5 as high-grade dysplasia, 11 as atypical hyperplasia, and 2 as invasive carcinoma, although each frequently coexisted in the same tumor. In two carcinomas, one had high-grade dysplasia in the mucosa, and another had only atypical hyperplasia. Interestingly, hyperplastic glands around dysplastic foci were associated with gastric foveolar metaplasia and papillary configuration in 13 cases, 11 of which showed a gradual increase in nuclear atypism in the transition from metaplastic to dysplastic glands.
All of the metaplastic gastric glands showed diffuse and strong immunopositivity for gastric foveolar mucin (MUC5AC). Immunohistochemical profiles also supported the concept of a continuous spectrum in carcinogenesis from gastric foveolar hyperplasia through atypical hyperplasia or dysplasia and eventually to frank adenocarcinoma.
The results of our study suggest, therefore, that dysplastic and/or carcinomatous change does occur in BGH, that they form the continuous morphologic spectrum, and that papillary foveolar metaplasia may be a precursor lesion in the process of carcinogenesis with a background of BGH.
PROGNOSIS CHARACTERIZATION
Adenocarcinoma of the small bowel: a study of 37 cases with emphasis on histologic prognostic factors.Abrahams NA, Halverson A, Fazio VW, Rybicki LA, Goldblum JR.
Department of Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Avenue L25, Cleveland, OH 44195, USA.
Dis Colon Rectum 2002 Nov;45(11):1496-502 Abstract quote PURPOSE: Primary small-bowel adenocarcinoma is uncommon. There are few large studies that have evaluated the prognostic impact of clinical and pathologic parameters. The purpose of this study was to perform a comprehensive analysis of the Cleveland Clinic experience with small-bowel adenocarcinoma, with emphasis on histopathologic parameters as prognostic indicators.
METHODS: Thirty-seven cases of primary small-bowel adenocarcinomas resected at the Cleveland Clinic between 1978 and 1999 were retrospectively studied. Metastatic tumors and those arising from the biliary system were excluded from analysis. Clinical and pathologic data were recorded and their impact on prognosis was evaluated by either Kaplan-Meier or Cox proportional hazards analysis.
RESULTS: The cohort included 25 males, and the age range was 24 to 82 (mean, 56) years. Tumor location was duodenum (18), jejunum (10), ileum (2), and site not specified (7). Patients most frequently presented with abdominal pain (48 percent), anemia (39 percent) and small-bowel obstruction (33 percent). Underlying conditions included Crohn's disease (4) and familial adenomatous polyposis (2). Overall survival was 52 and 47 percent at 5 and 10 years, respectively, with a mean follow-up of 50.5 (range, 0.5-184) months for all patients. Features found to be negative prognostic factors for survival were positive surgical margins (P < 0.001), extramural venous spread (P < 0.001), lymph node metastases (P = 0.038), poor tumor differentiation (P = 0.015), depth of tumor invasion (P = 0.023), and history of Crohn's disease (P < 0.001). Age, gender, tumor size, growth pattern, lymphocytic host response, and adjuvant therapy did not affect survival.
CONCLUSIONS: Pathologic features, including positive surgical margins, extramural venous spread, positive lymph nodes, poor tumor differentiation, depth of tumor invasion, and history of Crohn's disease, are of major prognostic significance in small-bowel adenocarcinoma. Although many of these prognostic features are similar to the ones used for colorectal adenocarcinoma, they are easily applicable and reproducible for small-bowel adenocarcinomas. This is important considering the often dismal prognosis of small-bowel adenocarcinoma.
Primary cancers of the small bowel: analysis of prognostic factors and results of surgical management.Talamonti MS, Goetz LH, Rao S, Joehl RJ.
Department of Surgery, Northwestern University Medical School, Chicago, IL USA.
Arch Surg 2002 May;137(5):564-70 Abstract quote HYPOTHESIS: This study was done to review the clinical presentation, surgical management, pathologic features, and prognostic factors for primary small-bowel cancers.
DESIGN: Retrospective case series.
SETTING: Tertiary care, university hospital.
PATIENTS: One hundred twenty-nine patients were surgically treated between January 1, 1977, and December 31, 2000. There were 73 men and 56 women, with a median age of 55 years (age range, 19-82 years). Median follow-up was 36 months.
MAIN OUTCOME MEASURES: Presenting symptoms and signs, operations performed, and surgical pathologic features were analyzed and survival curves were generated.
RESULTS: Clinical findings included abdominal pain (63%), vomiting (48%), weight loss (44%), and gastrointestinal tract bleeding (23%). The distribution of tumors by histological features was as follows: adenocarcinoma (33%), carcinoid tumor (29%), lymphoma (19%), and sarcoma (19%). Cumulative 5-year survival rate was 37% in the adenocarcinoma group, 64% in the carcinoid tumor group, 29% in the lymphoma group, and 22% in the sarcoma group. Significant prognostic predictors of overall survival for the entire cohort and for each tumor subtype included complete resection and American Joint Committee on Cancer tumor stage (P<.05). Patient age, tumor location, histological grade, and use of chemotherapy and radiation therapy did not significantly influence survival. Curative resections were accomplished in 83 patients (64%) with a median survival of 37 months compared with 46 patients undergoing incomplete or palliative resections with a median survival of 10 months (P<.05). Adjacent organ resection was required in 18 (22%) of the 83 patients undergoing potentially curative resections. The median time to recurrence was 16 months. Twenty-one patients (16%) developed associated primary cancers.
CONCLUSIONS: Aggressive surgical resection in an attempt to achieve complete tumor removal seems warranted. Despite complete resections, patients with high-stage tumors remain at risk for recurrence.
New aspects of prognostic factors in adenocarcinomas of the small bowel.Brucher BL, Stein HJ, Roder JD, Busch R, Fink U, Werner M, Siewert JR.
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar der TU Munchen, Ismaninger Strasse 22, D-81675 Munchen, Germany.
Hepatogastroenterology 2001 May-Jun;48(39):727-32 Abstract quote BACKGROUND/AIMS: Primary small bowel tumors are rare and the prognosis is generally considered to be poor. Histologically chiefly adenocarcinomas are reported. The surgeon is challenged in their treatment, because of the infrequency, unspecific symptoms and delay in diagnosis. Retrospectively we investigated the surgical therapy, combined morbidity, survival rates and prognostic factors in a large series of primary adenocarcinomas of the small bowel at a single surgical center.
METHODOLOGY: Between 1985 and 1998, 94 patients with a primary tumors of the small bowel (malignant n = 62 [65.9%], benign n = 32 [34.1%]) were operated on. The subgroup of the adenocarcinomas (n = 22) were considered for this study.
RESULTS: The median follow-up is 8.4 years (range: 0.9-14.2 years). Sixteen patients had a follow-up more than 5 years. The main surgical procedure was a small bowel segment resection. Morbidity was 13.6% (only in patients with a duodenal tumors) and the 30-day mortality 5.6%. The estimated 2-year-survival rate was 66%, the 5-year-survival rate 45%. Univariate analysis identified the presence of the residual tumor (R-status) (P = 0.004), tumor stage according to the UICC (P = 0.01), lymph node metastasis (P = 0.007), distant metastasis (P = 0.001), lymphangiosis carcinomatosa (P = 0.001) and vascular invasion (P = 0.0008) as prognostic factors.
CONCLUSIONS: A complete macroscopic and microscopic tumor resection including a systemic lymph node dissection has to be the aim of any curative surgical approach in patients with adenocarcinoma of the small bowel.
Prognostic value of the TNM-classification for small bowel cancer.Contant CM, Damhuis RA, van Geel AN, van Eijck CH, Wiggers T.
Department of Surgical Oncology, Academic Hospital Rotterdam, Dr. Daniel den Hoed Cancer Center, The Netherlands.
Hepatogastroenterology 1997 Mar-Apr;44(14):430-4 Abstract quote BACKGROUND/AIMS: To examine the relationship between the pathological stage and survival for adenocarcinoma of the small bowel.
MATERIALS AND METHODS: The medical records of 99 patients with small bowel cancer, diagnosed between January 1984 and December 1993, were reviewed retrospectively. Lymphomas and carcinomas of the ampulla of Vater were excluded from this study. All operated patients with adenocarcinomas were staged by the TNM-classification using pathological and surgical reports.
RESULTS: Sixty-four adenocarcinomas, 24 carcinoid tumours and 11 sarcomas were analysed. The cancer-specific 5-year survival rate for patients with adenocarcinoma, carcinoid tumours and sarcomas was 22%, 39% and 55%, respectively. Twenty-eight patients with adenocarcinoma underwent radical tumor resection: segmental resection in 20, pancreaticoduodenectomy in 7 and ileocoecal resection in one patient. In the remaining 34 patients "curative" resection was not feasible and none of them survived for more than 3 years. The 5-year survival rate of the curatively resected patients was 46%. Actuarial 3-year survival rate for stage I was 38%, 70% for stage II and 0% for stage III.
CONCLUSION: Our results demonstrate that survival is poor for patients with lymph node metastasis, despite apparently curative surgery.
Factors influencing long-term survival in 100 cases of small intestine primary adenocarcinoma.Veyrieres M, Baillet P, Hay JM, Fingerhut A, Bouillot JL, Julien M.
French Associations for Surgical Research, Bois-Colombes.
Am J Surg 1997 Mar;173(3):237-9 Abstract quote BACKGROUND: Factors influencing long-term survival in patients undergoing operation for adenocarcinoma of the small intestine are poorly recognized.
METHODS: Retrospective study of 100 cases culled within a 10-year period by questionnaire, including 59 males and 41 females, median age 61 years (range 30 to 86). No patients were lost to follow-up (median 27 months). All patients underwent operation: curative in 65% and palliative in 35%.
RESULTS: Overall actuarial 5-year survival was 38%, 0% after palliative treatment and 54% after curative resection. In patients undergoing curative resection, 5-year survival was 63% when the lymph nodes were not involved, and 52% when they were; 57% when the serosa was not involved, and 53% when it was; 56% when the tumor was well or moderately well differentiated and 40% when it was undifferentiated. Other factors influencing long-term survival were the emergency setting, the site, the multiplicity, and the size of tumor (none with statistically significant differences). Five and 10-year survival was 78% and 69%, respectively, when the patient was anemic compared with 35% and 17%, respectively when the patient was not (P <0.01). There were 14 patients with previous carcinoma, 2 with Crohn's disease, and 1 each with celiac disease and ileal tuberculosis. There were also 8 patients with associated duodenal and proximal jejunal polyps. Thirteen patients sustained a total of 14 further cancers.
CONCLUSIONS: Patients should be followed up closely because the possibility of sustaining another abdominal carcinoma is high (16%). As associated polyps are nearly always duodenal or jejunal, preoperative or intraoperative endoscopy of the upper gastrointestinal tract including the initial portion of the jejunum should be able to detect their presence and reduce the risk of early recurrence.
Adenocarcinoma of the small intestine: 21-year review of diagnosis, treatment, and prognosis.Bauer RL, Palmer ML, Bauer AM, Nava HR, Douglass HO Jr.
Roswell Park Cancer Institute, Department of Surgical Oncology, Buffalo, NY 14263.
Ann Surg Oncol 1994 May;1(3):183-8 Abstract quote BACKGROUND: The purpose of this study was to evaluate the tumor characteristics and treatment associated with an improved overall survival in patients with adenocarcinoma of the small intestine.
METHODS: The records of all patients with primary adenocarcinoma of the small bowel seen between January 1971 and December 1991 were reviewed retrospectively. The study comprised 38 patients, 22 (58%) with duodenal tumors, 11 (29%) with jejunal tumors, and five (13%) with ileal tumors.
RESULTS: Although not statistically significant, the patients with duodenal adenocarcinoma lived longer than the patients with jejunal or ileal lesions (p = 0.77). The overall survival was 23% and seemed to correlate best with absence of lymph node metastases (p = 0.04) and pancreaticoduodenectomy for localized duodenal tumors (p = 0.04). The patient's age, duration of symptoms, disease-free interval, tumor location, type of recurrence, and histologic grade did not significantly influence survival.
CONCLUSIONS: The lethality of small-intestinal adenocarcinoma appears to be related to a delay in diagnosis and treatment. When a definitive surgical procedure is performed before lymph node metastases appear, the patient's chance for long-term survival is greatly improved.
DUODENUM
Extent of resection in the management of duodenal adenocarcinoma.
Kaklamanos IG, Bathe OF, Franceschi D, Camarda C, Levi J, Livingstone AS.
Department of Surgery, University of Miami, Florida 33136, USA.
Am J Surg. 2000 Jan;179(1):37-41. Abstract quote
BACKGROUND: It has been postulated that segmental duodenal resection (SR) is not an adequate operation for patients with adenocarcinoma of the duodenum and that pancreaticoduodenectomy (PD) is the procedure of choice, regardless of the tumor site. However, data from previous studies do not clearly support this position.
METHODS: We reviewed the records of 63 patients treated for duodenal adenocarcinoma from 1979 through 1998. Perioperative outcome, patient survival, and extent of lymphadenectomy were compared in patients who underwent PD and SR.
RESULTS: The overall morbidity for PD and SR was 27% and 18%, respectively (not significant [NS]). Patients who underwent SR had a 5-year survival of 60% versus 30% for patients who underwent PD (NS). Lymph node status was a prognostic factor for survival (P = 0.014). The mean number of lymph nodes in the specimens was 9.9 +/- 2.1 for PD and 8.3 +/- 4.4 for SR (NS).
CONCLUSIONS: Segmental duodenal resection for patients with duodenal adenocarcinoma is associated with acceptable postoperative morbidity and long-term survival. The procedure is especially well suited for distal duodenal tumors. Clearance of lymph nodes and outcome are comparable to PD.
Adenocarcinoma of the duodenum: factors influencing long-term survival.
Sohn TA, Lillemoe KD, Cameron JL, Pitt HA, Kaufman HS, Hruban RH, Yeo CJ.
Departments of Surgery and Pathology, The John Hopkins Medical Insitutions, Baltimore, MD, USA.
J Gastrointest Surg. 1998 Jan-Feb;2(1):79-87. Abstract quote
This single-institution retrospective analysis reviews the management and outcome of patients with surgically treated adenocarcinoma of the duodenum. Between February 1984 and August 1996, fifty-five patients with adenocarcinoma of the duodenum underwent surgery at The Johns Hopkins Hospital.
Univariate analysis was performed to identify possible prognostic indicators. Curative resection was performed in 48 patients (87%): 35 of these patients (73%) underwent a pancreaticoduodenectomy (PD), whereas 27% (n = 13) underwent a pancreas-sparing duodenectomy (PSD). Patients undergoing PD were comparable to those undergoing PSD with respect to demographic factors, presenting symptoms, and tumor pathology. The remaining 13% of patients (n = 7) were deemed unresectable at the time of surgery and underwent biopsy and/or palliative bypass. PD was associated with an increase in postoperative complications when compared to PSD (57% vs. 30%), but this difference was not statistically significant. One perioperative death occurred following PD (mortality 2.9%).
The overall 5-year survival rate for the 48 patients undergoing potentially curative resection was 53%. Negative resection margins (P <0.001), PD (P <0.005), and tumors in the first and second portions of the duodenum (P <0.05) were favorable predictors of long-term survival by univariate analysis. Nodal status, tumor diameter, degree of differentiation, and the use of adjuvant chemoradiation therapy did not influence survival.
These data support an aggressive role for resection in patients with adenocarcinoma of the dueodenum
TREATMENT CHARACTERIZATION GENERAL Surgical resection and lymph node removal DUODENUM
Adenocarcinoma of the third and fourth portions of the duodenum: results of surgical treatment.
Tocchi A, Mazzoni G, Puma F, Miccini M, Cassini D, Bettelli E, Tagliacozzo S.
First Department of Surgery of the University of Rome La Sapienza Medical School, Rome, Italy.
Arch Surg. 2003 Jan;138(1):80-5. Abstract quote
HYPOTHESIS: To verify the adequacy of duodenal segmentectomy after intestinal derotation in the treatment of primary adenocarcinoma of the third and fourth portions of the duodenum.
DESIGN: A retrospective review of the surgical management of patients who underwent derotation of the third and fourth portions of the duodenum was undertaken to determine long-term outcome.
SETTING: Departments of surgery in 3 university hospitals.
PATIENTS: Between January 1, 1980, and December 31, 2000, 47 patients with primary adenocarcinoma of the third and fourth portions of the duodenum were surgically treated at 3 different institutions.
MAIN OUTCOME MEASURES: Details of primary surgery were abstracted from clinical records of the original hospital referral. Postoperative clinical course and long-term outcome were evaluated by a review of the hospital records and follow-up.
RESULTS: The results of a barium swallow test series was positive in 38 cases (80.8%) and esophagogastroduodenoscopy was primarily diagnostic in 30 patients (63.8%). In all cases duodenal segmentectomy was attempted. Twenty-two patients underwent palliative gastrojejunal bypass and in 9 patients pancreaticoduodenectomy was performed. In 16 cases duodenal segmentectomy was performed after intestinal derotation. Anastomoses were performed manually in all cases. Fifteen of the resected patients died of recurrent disease. A median (SD) disease-free survival of 36 (23.6) months (range, 6-85 months) was observed. The median (SD) overall survival was 37.5 (23.9) months (range, 11-85 months), the overall 5-year survival rate was 23% (11 patients), and the actuarial 5-year survival rate was 51% (24 patients).
CONCLUSIONS: Duodenal segmentectomy associated with intestinal derotation was shown to be a straightforward, safe procedure for the treatment of the primary adenocarcinoma of the third and fourth portions of the duodenum. This surgical procedure should be preferred to pancreaticoduodenectomy because it is associated with negligible rates of morbidity and mortality, while allowing for satisfactory margin clearance and adequate lymphadenectomy.Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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