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Enteroscopic identification of an adenocarcinoma of the small bowel in a patient with previously unrecognized hereditary nonpolyposis colorectal cancer syndrome
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 1999 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 94, No. 7, 1999 ISSN 0002-9270/99/$20.00 PII S0002-9270(99)00296-8
Enteroscopic Identification of an Adenocarcinoma of the Small Bowel in a Patient With Previously Unrecognized Hereditary Nonpolyposis Colorectal Cancer Syndrome M. Pennazio, M.D., A. Arrigoni, M.D., and F. P. Rossini, M.D. Gastroenterology-Gastrointestinal Endoscopy Service, Department of Oncology, S. Giovanni A.S. Hospital, Turin, Italy
ABSTRACT Tumors of the small bowel are uncommon and seldom suspected on a clinical basis. Together with the relative inaccessibility of the small bowel to endoscopic investigation, the rarity of these tumors undoubtedly delays their diagnosis. The case reported is of a patient with an adenocarcinoma of the jejunum presenting as gastrointestinal bleeding of obscure origin. Diagnosis was by push enteroscopy, after several years of unsuccessful radiological and upper and lower endoscopic evaluation. The patient’s family fulfilled the Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome, which was previously unrecognized. This report emphasizes the value of push enteroscopy and the limits of radiography of the small bowel when investigating patients with obscure GI bleeding. It also underlines the importance of a careful evaluation of the pedigree (concerning history of colorectal and extracolonic cancer) of all patients, including those who present with adenocarcinoma of the small bowel; it is similarly important to consider the possibility of small bowel cancer in members of families with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. (Am J Gastroenterol 1999;94: 1962–1966. © 1999 by Am. Coll. of Gastroenterology)
INTRODUCTION Obscure gastrointestinal (GI) bleeding is most commonly defined as acute or chronic blood loss, either intermittent or continuous, with iron-deficiency anemia and heme-positive stool. After careful upper and lower endoscopy, the source of bleeding is still undetected in 3–5% of patients (1–3), in whom bleeding is more likely to continue and the site of bleeding may be in the small bowel. Unless bleeding is massive, the cause is often difficult to diagnose if it is located within the small bowel. The small bowel’s length and tortuosity makes it less accessible than the stomach and colon, therefore limiting the diagnostic accuracy of conventional procedures, and especially of barium studies (4, 5).
A case is reported in which an adenocarcinoma of the jejunum was diagnosed by push enteroscopy, after lengthy and inconclusive radiological and endoscopic evaluation, in a patient presenting with obscure GI bleeding who had previously been unrecognized as belonging to a family with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.
CASE REPORT A 58-yr-old woman was sent to our unit suffering from sideropenic anaemia due to gastrointestinal bleeding of unknown origin, after a series of inconclusive investigations carried out elsewhere. Family history showed a marked aggregation of colonic and extracolonic cancers (Fig. 1). In detail, the kindred fulfilled the standard criteria clinically defining HNPCC syndrome, known as the “Amsterdam criteria” (6): a) at least three relatives with histologically verified colorectal cancer, b) one of them a first degree relative of the other two, c) at least two generations affected, and d) colorectal cancer diagnosed ⬍50 yr of age in at least one of the relatives. Seven relatives were affected by colorectal cancer, three of them ⬍50 yr, and three generations were involved; moreover, it is noteworthy that two cases of endometrial cancer, which is typical of the Lynch II variant of HNPCC (7, 8), and two cases of colorectal adenomas were recorded in the kindred. When the patient was 50 yr of age, endometrial carcinoma had been diagnosed; hysteroadnessiectomy with lymphadenectomy (pT1,N0,M0, stage IB) and subsequent radiotherapy were performed. Follow-up controls were negative until the age of 55 yr, when she complained of asthenia, and investigations revealed an iron-deficiency anaemia. As sole investigation, she underwent colonoscopy, which was negative. Cyclic oral and intravenous iron therapy was prescribed, but a tendency toward iron-deficiency and anemization persisted at repeated controls. At the age of 57 yr, the patient was again hospitalized: hemoglobin level was 6.2 g/dl and serum ferritin 11 ng/ml, whereas folates and vita-
AJG – July, 1999
Enteroscopic Identification of Small Bowel Adenocarcinoma
1963
Figure 1. Extended pedigree concerning cancer occurrence in the family of B.C. The arrow indicates the patient. Age of onset and cancer site are reported in affected subjects. The age at the present time is reported in unaffected subjects. Cancer site: CO ⫽ colon and rectum; ST ⫽ stomach; SB ⫽ small bowel; UT ⫽ uterus; LI ⫽ liver; LEU ⫽ lymphoma; AD ⫽ colonic adenoma.
min B12 were normal. A bone marrow aspirate showed only a slight erythroid hyperplasia. Fecal occult blood test was positive. Esophagogastroduodenoscopy and total colonoscopy were repeated but did not reveal the source of gastrointestinal bleeding. Colorectal polyps, 0.6 –1 cm in diameter, were removed during colonoscopy, and histological examination demonstrated tubular and tubulovillous adenomas, one with high grade dysplasia. Enteroclysis was normal. A small bowel vascular lesion and/or a radiation injury were hypothesized. The patient was therefore referred to our unit for enteroscopy. On entry, routine laboratory investigations confirmed iron deficiency anemia (hemoglobin level 8.8 g/dl, ferritin 7.5 ng/ml). Push enteroscopy was carried out under deep sedation using small boluses of propofol. An Olympus SIF100 videoenteroscope (Olympus Optical Co., Hamburg, GmBh, Europe) was used. Immediately beyond the angle of Treitz, enteroscopy revealed a vegetating, ulcerated lesion, that was oozing blood; the lesion caused a narrow stenosis of the lumen (Figure 2). Biopsies were taken and selective endoscopic contrastography (S.E.C.) confirmed the pres-
ence of a short, stenotic tract with rigid walls at the level of the first jejunal loop (Figure 3). Histological examination revealed a small bowel adenocarcinoma. A CT scan confirmed the mass, without involvement of contiguous organs or liver metastases. Subsequent laparotomy revealed a tumor mass involving the angle of Treitz and the first jejunal loop, which reached the serosa and formed an adherence to the transverse mesocolon. No peritoneal or liver metastases were found. The section was carried out proximally, at the level of the IV duodenal portion, and distally, 20 cm beyond the tumor. The transverse mesocolon was resected “en bloc”. A duodenojejunal terminoterminal anastomosis was performed. Pathological examination of the resected tissue confirmed a moderately differentiated adenocarcinoma, infiltrating the serosa and the mesocolic connective tissue. None of the 15 lymph nodes removed was involved by the tumor (pT4,N0,M0). Postoperative recovery was normal and the patient was discharged 12 days after surgery. She subsequently felt well and hemoglobin had increased to normal values. Four months after surgery, she underwent a follow-up enteros-
1964
Pennazio et al.
AJG – Vol. 94, No. 7, 1999
DISCUSSION
Figure 2. Push enteroscopy, demonstrating a vegetating, ulcerated lesion immediately beyond the angle of Treitz, with a narrow stenosis of the lumen.
copy that showed a normal anastomotic appearance without signs of recurrence. Abdominal ultrasonography and x-ray of the chest did not show metastases.
Figure 3. Selective endoscopic contrastography (S.E.C.): A Teflon probe is passed through the biopsy channel of the enteroscope and placed exactly under visual and fluoroscopic control. The contrast medium is then injected and its distribution is observed fluoroscopically; radiograms may be taken at the right moment. Selective endoscopic contrastography visualized a narrow, short, stenotic tract with rigid walls at the level of the first jejunal loop.
Diagnosis of obscure GI bleeding is one of the most vexing problems confronting physicians. The most common cause for GI bleeding of small bowel origin is angiodysplasia, followed by tumors (9). Small bowel neoplasms account for 5–10% of all cases of chronic blood loss of obscure origin (10, 11). They are rare entities, comprising ⬍5% of all GI tumors, despite the fact that the small intestine makes up 80 –90% of the luminal surface area of the entire alimentary tract (12). Adenocarcinomas, carcinoids, lymphomas, and leiomyosarcomas are the most common small bowel cancers, although overall annual incidence is ⬍1/100,000 (11, 13). Malignant tumors present most frequently in the fifth to seventh decade of life, with a slight male predominance (11, 14). Adenocarcinomas are the most common malignant small bowel tumors, representing approximately 45% of all small intestinal carcinomas, with a frequency of 0.35% in large autopsy series (15). They most commonly occur proximal to the mid-jejunum (in 90% of cases) and are circumferential lesions that slowly occlude the lumen (15, 16). Typically, patients present with vague, nonspecific abdominal pain, weight loss, and occult or acute GI bleeding (16). The nonspecific nature of the symptoms and the rarity of these tumors explain why diagnosis is often delayed, contributing to the poor prognosis of patients with these tumors (17). Diagnosis of small bowel tumors relies on radiological and endoscopic investigations. The yield of small bowel follow-through is usually low, except in cases of large tumors with ulcerations and strictures; the test is not diagnostic of adenocarcinoma (9, 18). Arteriography of adenocarcinomas may also reveal indicative vascular lesions within a mass; echography and CT scan do not seem very helpful with regard to diagnosis (19). In general, the yield of small bowel follow-through performed to evaluate patients with obscure GI bleeding is 0 –5.6% overall and 2–3% for small bowel tumors (20). The use of enteroclysis may increase the yield to 21% (5, 21); in this patient, enteroclysis had failed to detect a lesion as the likely source of bleeding. An adenocarcinoma of the proximal jejunum near the ligament of Treitz was easily found at push enteroscopy, after about 3 yr of unsuccessful (and costly) examination procedures. Even in retrospect, the diagnostic lesion was not discernible on any of the radiograms. This indicates the importance of modifying the technique of enteroclysis in patients with obscure GI bleeding to evaluate the duodeno-jejunal flexure, which may be inadequately shown by “conventionally-performed” enteroclysis (21). It must be emphasized that a false-negative enteroclysis may deflect the workup away from the small bowel, wasting time and money in making the diagnosis. Delay in diagnosis may alter the outcome and should be minimized whenever possible. As mentioned by Lewis et al. (9), enteroscopy may be diagnostic of small bowel tumors even when all previous diagnostic procedures are negative. Our
AJG – July, 1999
findings corroborate these conclusions. Diagnostic yields of push enteroscopy have been reported to be as high as 50% overall, and 5–21% for small bowel tumors (22–29). Thus, in patients with obscure GI bleeding, push enteroscopy could well be proposed as the first step toward diagnosis, particularly when esophagogastroduodenoscopy and total colonoscopy give negative results (29). However, physicians should take into account that exploration of the small bowel is, at present, restricted to the jejunum, for up to 120 –150 cm beyond the ligament of Treitz. Even in this tract, a negative finding requires careful evaluation, particularly in patients with radiological suspicion of jejunal neoplasm (28, 30). In selected patients, fluoroscopy may be useful to ensure the reliability of negative endoscopic findings (31). Moreover, if push enteroscopy is used as an early procedure in the investigation of obscure GI bleeding and gives negative result, other diagnostic procedures (such as enteroclysis or sonde enteroscopy in patients with slow blood loss, and angiography or intraoperative enteroscopy in patients with occult transfusion dependent bleeding) must subsequently be performed because of the possibility of distal lesions (32). Selective endoscopic contrastography was performed during enteroscopy (Figure 3). A Teflon probe was passed through the biopsy channel of the enteroscope and placed exactly under visual and fluoroscopic control. The contrast medium was then injected and its distribution was observed fluoroscopically. This technique was employed on the analogy of the technique we use in the large bowel and terminal ileum (33), to better define the lesion and to give the surgeon useful information concerning the length of the stenosis. A similar, although more accurate, method has recently been reported (34). Although it is part of the tumor spectrum of HNPCC (7, 8), small bowel carcinoma is not considered to be a main tumor of the syndrome. In a recent series of 110 Italian HNPCC families, no cases of small bowel carcinoma were recorded (35). In other series, a nonnegligible incidence of small bowel carcinomas was reported in HNPCC. In a study of 1317 high risk members of HNPCC families, 10 small bowel cancers were observed, which is 25 times the expected number (36). Moreover, the occurrence of cancers of the small bowel, as well as of the stomach and the hepatobiliary tract, were distributed among families in a way consistent with a uniform risk across families and not necessarily linked to a Lynch syndrome II variant of HNPCC (36). The reason for such discrepancies is probably that the real frequency of these tumors is underevaluated because of diagnostic difficulty. In the case reported, the family history suggesting an HNPCC syndrome had not been adequately evaluated before the patient entered our unit. A careful evaluation of the pedigree should be part of the medical history. The high family risk might have induced the physician to hypothesize a cancer even when the more obvious locations of cancer, such as the colon-rectum, had been excluded. All persons at high risk for HNPCC should be regarded as having an
Enteroscopic Identification of Small Bowel Adenocarcinoma
1965
elevated risk for stomach, small bowel, or hepatobiliary cancer, whatever the family history of extracolonic cancer (37). Unlike endometrial and ovarian cancer (38), systematic screening of small bowel cancer has never been proposed in surveillance of HNPCC families. Large series are required to assess whether screening for this type of tumor should be added to the current surveillance strategy, and which screening modalities, in terms of techniques, frequency, and age of beginning, could be applied. In conclusion, this report emphasizes the value of push enteroscopy when investigating patients with obscure GI bleeding. A high index of suspicion in patients from HNPCC families and early enteroscopic evaluation are necessary to diagnose early stage tumors. Whether this approach will affect prognosis remains to be seen. Reprint requests and correspondence: M. Pennazio, M.D., Gastroenterology-Gastrointestinal Endoscopy Service, Department of Oncology, S. Giovanni A.S. Hospital, Via Cavour 31, 10123 Turin, Italy. Received Oct. 17, 1997; accepted Sep. 18, 1998.
REFERENCES 1. Peterson WL. Obscure gastrointestinal bleeding. Med Clin North Am 1988;72:1169 –76. 2. Netaville R, Nardy J, Marton R. Small bowel hemorrhage. Ann Surg 1968;167:949 –57. 3. Thompson JN, Slaeim RR, Hemingway AP, et al. Specialist investigation of obscure gastrointestinal bleeding. Gut 1987; 28:47–51. 4. Thompson JN, Hemingway AP, McPherson GA, et al. Obscure gastrointestinal hemorrhage of small bowel origin. Br Med J 1984;288:1663–5. 5. Rex DK, Lappas JC, Maglinte DDT, et al. Enteroclysis in the evaluation of suspected small intestinal bleeding. Gastroenterology 1989;97:58 – 64. 6. Vasen HFA, Mecklin JP, Meera Khan P, et al. The International Collaborative Group on hereditary non-polyposis colorectal cancer (ICG-HNPCC). Dis Colon Rectum 1991;34: 424 –5. 7. Vasen HFA, Offerhaus GJA, den Hartog Jager FCA, et al. The tumor spectrum in hereditary non polyposis colorectal cancer. Int J Cancer 1990;46:31– 4. 8. Lynch HT, Watson P, Kriegler M. Differential diagnosis of hereditary non polyposis colorectal cancer (Lynch syndrome I and Lynch syndrome II). Dis Colon Rectum 1988;31:372–7. 9. Lewis BS, Kornbluth A, Wayne JD. Small bowel tumours: Yield of enteroscopy. Gut 1991;32:763–5. 10. Ashley S, Wells S. Tumors of the small intestine. Semin Oncol 1988;15:116 –28. 11. Martin RG. Malignant tumors of the small intestine. Surg Clin North Am 1986;66:779 – 85. 12. Williamson RCM, Welch CE, Malt RA. Adenocarcinomas and lymphomas of the small intestine. Distribution and etiologic associations. Ann Surg 1983;197:172– 8. 13. Brophy C, Cahow CE. Primary small bowel malignant tumors. Unrecognized until emergent laparotomy. Am Surg 1989;55: 408 –12. 14. Laws H, Han S, Aldrete J. Malignant tumors of the small bowel. South Med J 1984;77:1087–96.
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15. Kleinerman J, Yardumian K, Tamaki HT. Primary carcinoma of the duodenum. Ann Intern Med 1950;32:451– 8. 16. Aghazarian SG, Birely BC. Adenocarcinoma of the small intestine: A plea for early diagnosis. South J Med 1993;86: 1067–9. 17. Coutsoftides T, Shibata HR. Primary malignant tumors of the small intestine. Dis Colon Rectum 1979;22:24 – 6. 18. Kawamoto K, Motooka M, Hirata N, et al. Early primary carcinoma of the duodenal bulb arising from Brunner’s glands. Gastrointest Endosc 1994;40:232– 4. 19. Nolan DJ. Radiology of the small intestine. In: Nelson RL, Nyhus LM, eds. Surgery of the small intestine. Norwalk: Appleton & Lange, 1987:59. 20. Rabe F, Becker G, Begozzi M. Efficacy study of the small bowel examination. Radiology 1981;140:47–50. 21. Moch A, Herlinger H, Kochman ML, et al. Enteroclysis in the evaluation of obscure gastrointestinal bleeding. Am J Roentgenol 1994;163:1381– 4. 22. Foutch PG, Sawyer R, Sanowsky RA. Push enteroscopy for diagnosis of patients with gastrointestinal bleeding. Gastrointest Endosc 1990;36:337– 41. 23. Foutch PG, Sanowski R, Kelly S. Enteroscopy, a method for detection of small bowel tumors. Am J Gastroenterol 1985; 80:887–90. 24. Barkin JS, Lewis BS, Reiner DK, et al. Diagnostic and therapeutic jejunoscopy with a new, longer enteroscope. Gastrointest Endosc 1992;38:55– 8. 25. Barkin JS, Chong J, Reiner DK. First generation video enteroscope: Fourth generation push-type small bowel enteroscopy utilizing an overtube. Gastrointest Endosc 1994;40:743–7. 26. Chong J, Tangle M, Barkin JS, et al. Small bowel push-type fiberoptic enteroscopy for patients with occult gastrointestinal bleeding or suspected small bowel pathology. Am J Gastroenterol 1994;89:2143– 6.
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27. Davies GR, Benson MJ, Gertner DJ, et al. Diagnostic and therapeutic push type enteroscopy in clinical use. Gut 1995; 37:346 –52. 28. Pennazio M, Arrigoni A, Risio M, et al. Clinical evaluation of push type enteroscopy. Endoscopy 1995;27:164 –70. 29. Rossini FP, Arrigoni A, Pennazio M. Clinical enteroscopy. J Clin Gastroenterol 1996;22:231– 6. 30. Arrigoni A, Pennazio M, Rossini FP. Enteroscopy in small bowel neoplastic pathology. Acta Endoscopica 1996:26:255– 61. 31. Pennazio M, Arrigoni A, Rossini FP. Push enteroscopy for small bowel tumors. Gastrointest Endosc 1995;41:524 –5 (letter). 32. Pennazio M, Rossini FP. Main issues in push enteroscopy. Ital J Gastroenterol Hepatol 1998;30:96 –101. 33. Rossini FP, Ferrari A, Mezzedimi R, et al. Selective endoscopic contrastography (S.E.C.): An original association of radiology and endoscopy of the small and large intestine. Endoscopy 1979;3:207–11. 34. Willis JR, Chokshi HR, Zuckerman GR, et al. Enteroscopyenteroclysis: Experience with a combined endoscopic-radiographic technique. Gastrointest Endosc 1997;45:163–7. 35. Arrigoni A, Bargiacchi S, Benatti P, et al. Collection of Italian hereditary non-polyposis colorectal cancer (HNPCC) pedigrees. Tumori 1996;82:151–79. 36. Watson P, Lynch HT. Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 1993;71:677– 85. 37. Watson P, Lynch HT. The tumor spectrum in HNPCC. Anticancer Research 1994;14:1635– 40. 38. Lynch HT, Smyrk T, Fitzgibbons R, et al. Update on the differential diagnosis, surveillance and management of hereditary non-polyposis colorectal cancer. Eur J Cancer 1995;31: 1039 – 46.
Vol. 94, No. 7, 1999 ISSN 0002-9270/99/$20.00 PII S0002-9270(99)00296-8
Enteroscopic Identification of an Adenocarcinoma of the Small Bowel in a Patient With Previously Unrecognized Hereditary Nonpolyposis Colorectal Cancer Syndrome M. Pennazio, M.D., A. Arrigoni, M.D., and F. P. Rossini, M.D. Gastroenterology-Gastrointestinal Endoscopy Service, Department of Oncology, S. Giovanni A.S. Hospital, Turin, Italy
ABSTRACT Tumors of the small bowel are uncommon and seldom suspected on a clinical basis. Together with the relative inaccessibility of the small bowel to endoscopic investigation, the rarity of these tumors undoubtedly delays their diagnosis. The case reported is of a patient with an adenocarcinoma of the jejunum presenting as gastrointestinal bleeding of obscure origin. Diagnosis was by push enteroscopy, after several years of unsuccessful radiological and upper and lower endoscopic evaluation. The patient’s family fulfilled the Amsterdam criteria for hereditary nonpolyposis colorectal cancer syndrome, which was previously unrecognized. This report emphasizes the value of push enteroscopy and the limits of radiography of the small bowel when investigating patients with obscure GI bleeding. It also underlines the importance of a careful evaluation of the pedigree (concerning history of colorectal and extracolonic cancer) of all patients, including those who present with adenocarcinoma of the small bowel; it is similarly important to consider the possibility of small bowel cancer in members of families with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. (Am J Gastroenterol 1999;94: 1962–1966. © 1999 by Am. Coll. of Gastroenterology)
INTRODUCTION Obscure gastrointestinal (GI) bleeding is most commonly defined as acute or chronic blood loss, either intermittent or continuous, with iron-deficiency anemia and heme-positive stool. After careful upper and lower endoscopy, the source of bleeding is still undetected in 3–5% of patients (1–3), in whom bleeding is more likely to continue and the site of bleeding may be in the small bowel. Unless bleeding is massive, the cause is often difficult to diagnose if it is located within the small bowel. The small bowel’s length and tortuosity makes it less accessible than the stomach and colon, therefore limiting the diagnostic accuracy of conventional procedures, and especially of barium studies (4, 5).
A case is reported in which an adenocarcinoma of the jejunum was diagnosed by push enteroscopy, after lengthy and inconclusive radiological and endoscopic evaluation, in a patient presenting with obscure GI bleeding who had previously been unrecognized as belonging to a family with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.
CASE REPORT A 58-yr-old woman was sent to our unit suffering from sideropenic anaemia due to gastrointestinal bleeding of unknown origin, after a series of inconclusive investigations carried out elsewhere. Family history showed a marked aggregation of colonic and extracolonic cancers (Fig. 1). In detail, the kindred fulfilled the standard criteria clinically defining HNPCC syndrome, known as the “Amsterdam criteria” (6): a) at least three relatives with histologically verified colorectal cancer, b) one of them a first degree relative of the other two, c) at least two generations affected, and d) colorectal cancer diagnosed ⬍50 yr of age in at least one of the relatives. Seven relatives were affected by colorectal cancer, three of them ⬍50 yr, and three generations were involved; moreover, it is noteworthy that two cases of endometrial cancer, which is typical of the Lynch II variant of HNPCC (7, 8), and two cases of colorectal adenomas were recorded in the kindred. When the patient was 50 yr of age, endometrial carcinoma had been diagnosed; hysteroadnessiectomy with lymphadenectomy (pT1,N0,M0, stage IB) and subsequent radiotherapy were performed. Follow-up controls were negative until the age of 55 yr, when she complained of asthenia, and investigations revealed an iron-deficiency anaemia. As sole investigation, she underwent colonoscopy, which was negative. Cyclic oral and intravenous iron therapy was prescribed, but a tendency toward iron-deficiency and anemization persisted at repeated controls. At the age of 57 yr, the patient was again hospitalized: hemoglobin level was 6.2 g/dl and serum ferritin 11 ng/ml, whereas folates and vita-
AJG – July, 1999
Enteroscopic Identification of Small Bowel Adenocarcinoma
1963
Figure 1. Extended pedigree concerning cancer occurrence in the family of B.C. The arrow indicates the patient. Age of onset and cancer site are reported in affected subjects. The age at the present time is reported in unaffected subjects. Cancer site: CO ⫽ colon and rectum; ST ⫽ stomach; SB ⫽ small bowel; UT ⫽ uterus; LI ⫽ liver; LEU ⫽ lymphoma; AD ⫽ colonic adenoma.
min B12 were normal. A bone marrow aspirate showed only a slight erythroid hyperplasia. Fecal occult blood test was positive. Esophagogastroduodenoscopy and total colonoscopy were repeated but did not reveal the source of gastrointestinal bleeding. Colorectal polyps, 0.6 –1 cm in diameter, were removed during colonoscopy, and histological examination demonstrated tubular and tubulovillous adenomas, one with high grade dysplasia. Enteroclysis was normal. A small bowel vascular lesion and/or a radiation injury were hypothesized. The patient was therefore referred to our unit for enteroscopy. On entry, routine laboratory investigations confirmed iron deficiency anemia (hemoglobin level 8.8 g/dl, ferritin 7.5 ng/ml). Push enteroscopy was carried out under deep sedation using small boluses of propofol. An Olympus SIF100 videoenteroscope (Olympus Optical Co., Hamburg, GmBh, Europe) was used. Immediately beyond the angle of Treitz, enteroscopy revealed a vegetating, ulcerated lesion, that was oozing blood; the lesion caused a narrow stenosis of the lumen (Figure 2). Biopsies were taken and selective endoscopic contrastography (S.E.C.) confirmed the pres-
ence of a short, stenotic tract with rigid walls at the level of the first jejunal loop (Figure 3). Histological examination revealed a small bowel adenocarcinoma. A CT scan confirmed the mass, without involvement of contiguous organs or liver metastases. Subsequent laparotomy revealed a tumor mass involving the angle of Treitz and the first jejunal loop, which reached the serosa and formed an adherence to the transverse mesocolon. No peritoneal or liver metastases were found. The section was carried out proximally, at the level of the IV duodenal portion, and distally, 20 cm beyond the tumor. The transverse mesocolon was resected “en bloc”. A duodenojejunal terminoterminal anastomosis was performed. Pathological examination of the resected tissue confirmed a moderately differentiated adenocarcinoma, infiltrating the serosa and the mesocolic connective tissue. None of the 15 lymph nodes removed was involved by the tumor (pT4,N0,M0). Postoperative recovery was normal and the patient was discharged 12 days after surgery. She subsequently felt well and hemoglobin had increased to normal values. Four months after surgery, she underwent a follow-up enteros-
1964
Pennazio et al.
AJG – Vol. 94, No. 7, 1999
DISCUSSION
Figure 2. Push enteroscopy, demonstrating a vegetating, ulcerated lesion immediately beyond the angle of Treitz, with a narrow stenosis of the lumen.
copy that showed a normal anastomotic appearance without signs of recurrence. Abdominal ultrasonography and x-ray of the chest did not show metastases.
Figure 3. Selective endoscopic contrastography (S.E.C.): A Teflon probe is passed through the biopsy channel of the enteroscope and placed exactly under visual and fluoroscopic control. The contrast medium is then injected and its distribution is observed fluoroscopically; radiograms may be taken at the right moment. Selective endoscopic contrastography visualized a narrow, short, stenotic tract with rigid walls at the level of the first jejunal loop.
Diagnosis of obscure GI bleeding is one of the most vexing problems confronting physicians. The most common cause for GI bleeding of small bowel origin is angiodysplasia, followed by tumors (9). Small bowel neoplasms account for 5–10% of all cases of chronic blood loss of obscure origin (10, 11). They are rare entities, comprising ⬍5% of all GI tumors, despite the fact that the small intestine makes up 80 –90% of the luminal surface area of the entire alimentary tract (12). Adenocarcinomas, carcinoids, lymphomas, and leiomyosarcomas are the most common small bowel cancers, although overall annual incidence is ⬍1/100,000 (11, 13). Malignant tumors present most frequently in the fifth to seventh decade of life, with a slight male predominance (11, 14). Adenocarcinomas are the most common malignant small bowel tumors, representing approximately 45% of all small intestinal carcinomas, with a frequency of 0.35% in large autopsy series (15). They most commonly occur proximal to the mid-jejunum (in 90% of cases) and are circumferential lesions that slowly occlude the lumen (15, 16). Typically, patients present with vague, nonspecific abdominal pain, weight loss, and occult or acute GI bleeding (16). The nonspecific nature of the symptoms and the rarity of these tumors explain why diagnosis is often delayed, contributing to the poor prognosis of patients with these tumors (17). Diagnosis of small bowel tumors relies on radiological and endoscopic investigations. The yield of small bowel follow-through is usually low, except in cases of large tumors with ulcerations and strictures; the test is not diagnostic of adenocarcinoma (9, 18). Arteriography of adenocarcinomas may also reveal indicative vascular lesions within a mass; echography and CT scan do not seem very helpful with regard to diagnosis (19). In general, the yield of small bowel follow-through performed to evaluate patients with obscure GI bleeding is 0 –5.6% overall and 2–3% for small bowel tumors (20). The use of enteroclysis may increase the yield to 21% (5, 21); in this patient, enteroclysis had failed to detect a lesion as the likely source of bleeding. An adenocarcinoma of the proximal jejunum near the ligament of Treitz was easily found at push enteroscopy, after about 3 yr of unsuccessful (and costly) examination procedures. Even in retrospect, the diagnostic lesion was not discernible on any of the radiograms. This indicates the importance of modifying the technique of enteroclysis in patients with obscure GI bleeding to evaluate the duodeno-jejunal flexure, which may be inadequately shown by “conventionally-performed” enteroclysis (21). It must be emphasized that a false-negative enteroclysis may deflect the workup away from the small bowel, wasting time and money in making the diagnosis. Delay in diagnosis may alter the outcome and should be minimized whenever possible. As mentioned by Lewis et al. (9), enteroscopy may be diagnostic of small bowel tumors even when all previous diagnostic procedures are negative. Our
AJG – July, 1999
findings corroborate these conclusions. Diagnostic yields of push enteroscopy have been reported to be as high as 50% overall, and 5–21% for small bowel tumors (22–29). Thus, in patients with obscure GI bleeding, push enteroscopy could well be proposed as the first step toward diagnosis, particularly when esophagogastroduodenoscopy and total colonoscopy give negative results (29). However, physicians should take into account that exploration of the small bowel is, at present, restricted to the jejunum, for up to 120 –150 cm beyond the ligament of Treitz. Even in this tract, a negative finding requires careful evaluation, particularly in patients with radiological suspicion of jejunal neoplasm (28, 30). In selected patients, fluoroscopy may be useful to ensure the reliability of negative endoscopic findings (31). Moreover, if push enteroscopy is used as an early procedure in the investigation of obscure GI bleeding and gives negative result, other diagnostic procedures (such as enteroclysis or sonde enteroscopy in patients with slow blood loss, and angiography or intraoperative enteroscopy in patients with occult transfusion dependent bleeding) must subsequently be performed because of the possibility of distal lesions (32). Selective endoscopic contrastography was performed during enteroscopy (Figure 3). A Teflon probe was passed through the biopsy channel of the enteroscope and placed exactly under visual and fluoroscopic control. The contrast medium was then injected and its distribution was observed fluoroscopically. This technique was employed on the analogy of the technique we use in the large bowel and terminal ileum (33), to better define the lesion and to give the surgeon useful information concerning the length of the stenosis. A similar, although more accurate, method has recently been reported (34). Although it is part of the tumor spectrum of HNPCC (7, 8), small bowel carcinoma is not considered to be a main tumor of the syndrome. In a recent series of 110 Italian HNPCC families, no cases of small bowel carcinoma were recorded (35). In other series, a nonnegligible incidence of small bowel carcinomas was reported in HNPCC. In a study of 1317 high risk members of HNPCC families, 10 small bowel cancers were observed, which is 25 times the expected number (36). Moreover, the occurrence of cancers of the small bowel, as well as of the stomach and the hepatobiliary tract, were distributed among families in a way consistent with a uniform risk across families and not necessarily linked to a Lynch syndrome II variant of HNPCC (36). The reason for such discrepancies is probably that the real frequency of these tumors is underevaluated because of diagnostic difficulty. In the case reported, the family history suggesting an HNPCC syndrome had not been adequately evaluated before the patient entered our unit. A careful evaluation of the pedigree should be part of the medical history. The high family risk might have induced the physician to hypothesize a cancer even when the more obvious locations of cancer, such as the colon-rectum, had been excluded. All persons at high risk for HNPCC should be regarded as having an
Enteroscopic Identification of Small Bowel Adenocarcinoma
1965
elevated risk for stomach, small bowel, or hepatobiliary cancer, whatever the family history of extracolonic cancer (37). Unlike endometrial and ovarian cancer (38), systematic screening of small bowel cancer has never been proposed in surveillance of HNPCC families. Large series are required to assess whether screening for this type of tumor should be added to the current surveillance strategy, and which screening modalities, in terms of techniques, frequency, and age of beginning, could be applied. In conclusion, this report emphasizes the value of push enteroscopy when investigating patients with obscure GI bleeding. A high index of suspicion in patients from HNPCC families and early enteroscopic evaluation are necessary to diagnose early stage tumors. Whether this approach will affect prognosis remains to be seen. Reprint requests and correspondence: M. Pennazio, M.D., Gastroenterology-Gastrointestinal Endoscopy Service, Department of Oncology, S. Giovanni A.S. Hospital, Via Cavour 31, 10123 Turin, Italy. Received Oct. 17, 1997; accepted Sep. 18, 1998.
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