Small-Bowel Tumors Detected by Wireless Capsule Endoscopy

Small bowel tumors are difficult to diagnose because of their endoscopic inaccessibility. This has been overcome by the use of the Pillcam™ SB capsule (Given Imaging, Yoqneam, Israel). The purpose of this report is to describe the largest series of patients with small bowel tumors detected by capsule endoscopy. Eighty six patients were derived from the Given Imaging clinical database on a survey of Pillcam™ SB capsule users who were diagnosed with 87 small bowel tumors, 1 cecal tumor, and 1 gastric tumor. The population consisted of 55 males and 31 females. 69% of patients were referred for capsule endoscopy for obscure gastrointestinal bleeding (59/86 patients) and 31% (27/86 patients) were referred for other indications including anemia, polyposis, and abdominal pain. All patients have histologically confirmed tumors. Eighty six patients reported 395 previous negative procedures (average of 4.6 per patient). Malignant tumors comprised 61% (54/89) and benign 39% (35/89). Of the 87 reported small bowel tumors, 4 were identified in the duodenum, 43 tumors were identified in the jejunum, 18 tumors were identified in the ileum, and 22 tumors were located in the mid to distal small bowel. The most common malignant tumors were adenocarcinoma, carcinoids, melanomas, lymphomas, and sarcomas. The most common benign tumors were GIST, hemangiomas, hamartomas, adenomas, and granulation tissue polyps. Capsule endoscopy is the diagnostic procedure of choice in patients with suspected small bowel tumors.     

Double-Balloon Enteroscopy and Small Bowel Tumors: A South-European Single-Center Experience

Small bowel tumors are rare, accounting for 1–2% of all gastrointestinal neoplasms. We sought to determine the diagnostic and therapeutic impact of double-balloon enteroscopy (DBE) in patients with small bowel tumors. Between January 2005 and March 2008, 78 patients underwent 96 DBE. All nine patients (seven males; mean age 68 ± 11.3 years) with small bowel tumors were retrospectively reviewed. Clinical presentation was: mid-gastrointestinal bleeding or iron-deficient anemia (55.6%); abdominal pain (22.2%); nausea/vomiting and abdominal distension (22.2%). Five patients had abnormal findings in previous capsule endoscopy and four in previous radiologic examinations. Route of insertion was exclusively oral and abnormal lesions were detected in all patients (jejunum 8; ileum 1). Biopsies were taken in seven patients and provided definitive histological diagnosis in all except one. There were no complications of DBE. Surgical resection took place in eight patients. Final histologic diagnosis were: primary carcinoma (33.3%), gastrointestinal stromal tumor (GIST) (33.3%), malignant lymphoma (22.2%), and carcinoid tumor (11.1%). Mean follow-up time was 15.4 ± 12.7 months (range 2–34 months). Six patients were submitted to chemotherapy. Two patients died. Small bowel tumors are common in patients submitted to DBE. Given its safety and diagnostic capabilities, DBE should be considered the gold-standard method in the study of these neoplasms.     

Small bowel tumors detected and missed during capsule endoscopy: Single center experience

AIM:To characterize small bowel(SB)tumors detected by capsule endoscopy(CE),and identify missed tumors.METHODS:The study included 145 consecutive patients in whom 150 CEs were performed.Following CE,the medical records of the study population were reviewed.Results of double-or single-balloon enteroscopy performed after CE and the results of surgery in all patients operated on were retrieved.The patients were contacted through telephone interviews or postal mail.In addition,the national cancer registry and the polish clinical gastrointestinal stromal tumor(GIST)Registry were searched to identify missed neoplasms.RESULTS:Indications for CE included overt and occult obscure gastrointestinal bleeding(n=81,53.7%),anemia(n=19,12.7%),malabsorption(n=18,12%),abnormal CB follow through(n=9,6%),abdominal pain(n=7,5%),celiac disease(n=5,3%),neuroendocrine tumor(n=3,2%),Crohn’s disease(n=2,<2%),Peutz-Jeghers syndrome(n=2,<2%),other polyposes(n=2,<2%),and diarrhea(n=2,<2%).The capsule reached the colon in 115(76.6%)examinations.In 150 investigations,CE identified 15SB tumors(10%),14 of which were operated on or treated endoscopically.Malignancies included metastatic melanoma(n=1),adenocarcinoma(n=2),and GIST(n=3).Benign neoplasms included dysplastic Peutz-Jeghers polyps(n=4).Non-neoplastic masses included venous malformation(n=1),inflammatory tumors(n=2),and a mass of unknown histology(n=1).During the follow-up period,three additional SB tumors were found(2 GISTs and one mesenteric tumor of undefined nature).The National Cancer Registry and Polish Clinical GIST Registry revealed no additional SB neoplasms in the post-examination period(follow-up:range 4.2-102.5 mo,median 39 mo).The sensitivity of CE for tumor detection was 83.3%,and the negative predictive value was 97.6%.The specificity and positive predictive value were both 100%.CONCLUSION:Neoplasms may be missed by CE,especially in the proximal SB.In overt obscure gastrointestinal bleeding,complementary endoscopic and/or radiologic diagnostic tests are indi     

The relationship between MIB-1 proliferative activity and mitotic index in gastrointestinal stromal tumors

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GIST) are mesenchymal tumors originating from the gastrointestinal canal wall. Although a number of studies are performed concerning prognostic factors, no indicators of recurrence or metastasis could be established. In this study we assessed the prognostic value of MIB-1 proliferative index (PI) in GIST, and whether there was a relationship to any other clinicopathological findings. METHODOLOGY: In the study 37 patients with GIST diagnosis were included. The cases were classified as low, intermediate, and high risk groups according to tumor size and mitotic activity. The average PI of 10% in high risk group was set as the cut-off value. RESULTS: Of all the cases, those with a MIB-1 PI over the cut-off value had a significantly shorter survival (Log-rank test, p < 0.05). Likewise cases with small bowel tumors with a MIB-1 PI over the cut-off value had a significantly shorter survival (Log-rank test, p < 0.05). A statistically significant negative correlation was found between presence of necrosis and survival using McPearson correlation test (p < 0.01). CONCLUSIONS: MIB-1 PI and presence of necrosis are possible indicators of prognosis especially in GIST cases of the small bowel.     

New aspects of prognostic factors in adenocarcinomas of the small bowel.

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.     

Diagnosis and outcome of small bowel tumors found by capsule endoscopy: a three-center Australian experience

OBJECTIVE: The objective of the study was to examine diagnosis and outcome in a series of patients with small bowel tumors detected by capsule endoscopy (CE) in three Australian centers. METHODS: Review of prospectively collected data from 416 CEs identified 27 tumors in 26 patients. Clinical parameters, tumor histology, and follow-up are reported. RESULTS: Twenty-seven tumors were identified in 26 patients (mean age 61 +/- 13.7 yr). Indications for CE were obscure gastrointestinal (GI) bleeding (21), suspected tumor (3), abdominal pain (1), diarrhea (1). Prior radiology found a possible lesion in 8 of 23 (35%). Nine tumors were proven benign: hamartoma (4), cystic lymphangioma (1), primary amyloid (1), lipoma (1). Two lesions were non-neoplastic: heterotopic gastric mucosa and inflammatory fibroid polyp. Seventeen tumors were malignant: five adenocarcinomas, six carcinoids, two melanoma metastases, two gastrointestinal stromal tumors (GIST), one colon carcinoma metastasis, one non-Hodgkin's lymphoma. Tumors were surgically resected in 23 patients. Resection was considered curative in 12 (52%). Mean duration of follow-up was 26 +/- 13.7 months. Of the five patients with primary adenocarcinoma only one remains disease free. Three of the six with carcinoid tumors have had no recurrence up to 51 months postresection. Both patients with GIST are disease free. Anemia resolved after surgery in the patients with melanoma. CONCLUSIONS: Small bowel tumors are a significant finding at CE and are often missed by other methods of investigation. In many patients, detection of a tumor alters management and improves outcome. Even in malignant lesions, treatment is potentially curative in the absence of metastatic disease.     

Synchronous incidental gastrointestinal stromal and epithelial malignant tumors

AIM： To investigate the incidence of incidental gastrointestinal stromal tumor （GIST） and its etiopathogenesis. METHODS： From January 1, 2000 to December 31, 2007, 13804 cases of gastrointestinal epithelial malignant tumor （EMT） and 521 cases of pancreatic adenocarcinoma （PAC） were successfully treated with surgery at the Department of General Surgery and the Department of Thoracic Surgery, West China Hospital, Sichuan University, China. The clinical and pathologic data of 311 cases of primary GIST, including 257 cases with clinical GIST and 54 cases of incidental GIST were analyzed. RESULTS： Of the 311 patients, 54 had incidental GIST, accounting for 17.4%. Of these tumors, 27 were found in 1.13% patients with esophageal squamous cell carcinoma （ESCC）, 22 in 0.53% patients with gastric adenocarcinoma （GAC）, 2 in 0.38% patients with PAC, 2 in 0.03% patients with colorectal adenocarcinoma, and 1 in one patient with GAC accompanying ESCC, respectively. Patients with incidental GIST presented symptoms indistinguishable from those with EMT. All incidental GIST lesions were small in size, and the majority had a low mitotic activity while only 1.9% （5/257） of clinical GIST lesions had a high risk.CONCLUSION： Incidental GIST may occur synchronously with other tumors and has a high prevalence in males. Surgery is its best treatment modality.     

Double-balloon enteroscopy in small bowel tumors: A Chinese single-center study

AIM: To analyze the clinical characteristics of small bowel tumors detected by double-balloon enteroscopy (DBE) and to evaluate the diagnostic value of DBE in tumors. METHODS: Four hundred and forty consecutive DBE examinations were performed in 400 patients (250 males and 150 females, mean age 46.9 ± 16.3 years, range 14-86 years) between January 2007 and April 2012. Of these, 252 patients underwent the antegrade approach, and 188 patients underwent the retrograde approach. All the patients enrolled in our study were suspected of having small bowel diseases with a negative etiological diagnosis following other routine examinations, such as upper and lower gastrointestinal endoscopy and radiography tests. Data on tumors, such as clinical information, endoscopic findings and opera-tion results, were retrospectively collected. RESULTS: Small bowel tumors were diagnosed in 78 patients, of whom 67 were diagnosed using DBE, resulting in a diagnostic yield of 16.8% (67/400); the other 11 patients had negative DBE findings and were diagnosed through surgery or capsule endoscopy. Adenocarcinoma (29.5%, 23/78), gastrointestinal stromal tumor (24.4%, 19/78) and lymphoma (15.4%, 12/78) were the most common tumors. Among the 78 tumors, 60.3% (47/78) were located in the jejunum, and the overall number of malignant tumors was 74.4% (58/78). DBE examinations were frequently performed in patients with obscure gastrointestinal bleeding (47.4%) and abdominal pain (24.4%). The positive detection rate for DBE in the 78 patients with small bowel tumors was 85.9% (67/78), which was higher than that of a computed tomography scan (72.9%, 51/70). Based on the operation results, the accuracy rates of DBE for locating small bowel neoplasms, such as adenocarcinoma, gastrointestinal stromal tumor and lymphoma, were 94.4%, 100% and 100%, respectively. The positive biopsy rates for adenocarcinoma and lymphoma were 71.4% and 60%, respectively. CONCLUSION: DBE is a useful diagnostic tool with high clinical practice value and should be consider     

Treatment of patients with advanced gastrointestinal stromal tumor of small bowel： Implications of imatinib mesylate

AIM: To examine the impact of imatinib mesylate (Glivec) on patient survival and response and its safety,and the correlation of the response rate with the kit gene mutation status. METHODS: Thirty-three of 74 (44.6%) small bowel gastrointestinal stromal tumor (GIST) patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients. Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients. Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha (PDGFRA). The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed. RESULTS: Advanced small bowel GIST patients treated with Glivec had substantially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response (PR) (67.8%). Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate (PR) was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate (ORR) of 66.7% (not significant). CONCLUSION: Glivec significantly prolongs the post-recurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients with advanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs. There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.     

Elevated (> or = 10%) MIB-1 proliferative index correlates with poor outcome in gastric stromal tumor patients: a study of 35 cases

Mitotic activity and tumor size are currently regarded as the most powerful prognostic indicators for patients with gastrointestinal stromal tumor (GIST). This retrospective study evaluated the prognostic accuracy of MIB-1 proliferative index (PI) in combination with these two indicators in 35 GIST patients. Within a high-risk group, determined initially by tumor size and mitotic count, overall survival was significantly shorter for patients whose tumors had PI 10% MIB-1 positive cells. When tumor location (gastric versus small intestine) was taken into account, a combination of tumor size, mitotic count, and PI 10% identified a subgroup of patients with significantly shorter survival for gastric (but not small intestinal) GIST. Based on our results, MIB-1 immunostaining, when used in combination with tumor size and mitotic count, appears to be a powerful tool for identifying patients, especially those with gastric tumors, at high risk of recurrence and early tumor-related death.     

The significance of CD44 expression in gastrointestinal neuroendocrine tumors

BACKGROUND/AIMS: Expression of CD44 and its isoforms has been demonstrated to be a prognostic marker in many neoplasms. Gastrointestinal neuroendocrine tumor is a slow-growing neoplasm, whose behavior is determined by site of occurrence, size or specific histologic growth pattern. In this study, the feasibility of using CD44 as a prognostic marker in gastrointestinal neuroendocrine tumor is evaluated. METHODOLOGY: Representative paraffin-embedded sections of gastrointestinal neuroendocrine tumor from 22 patients were studied by immunohistochemical staining using monoclonal antibodies against CD44, Ki-67, and p53 retrospectively. The correlation between these markers and clinical behavior of the tumors was analyzed. RESULTS: Positive expression of CD44 was observed in 15 cases (68%) of gastrointestinal neuroendocrine tumor. Expression of CD44 showed significant inverse correlation with lymph node status (P=0.049), distant metastasis (p<0.001) and mortality (p=0.002). Neither p53 nor Ki-67 correlated with lymph node status, distant metastasis and overall survival. Both lymph node status and distant metastasis showed strong correlation to survival after multivariate analysis. Patients with the tumor growing from the hindgut had better survival (p=0.024). The patients with stronger CD44 immunoreactivity (> or = 2+) tumors had significantly favorable survival (p=0.004) compared with those with weaker immunoreactivity (< or = 1+) tumors. CONCLUSIONS: Expression of CD44 in gastrointestinal neuroendocrine tumor inversely correlates with tumor metastasis, associates with a favorable outcome and may serve as one of the prognostic indicators.     

Small bowel metastases from primary carcinoma of the lung: clinical findings and outcome

OBJECTIVE: Symptomatic small bowel metastases from primary carcinoma of the lung have been rarely reported. The aim of this study was to describe clinical presentation and outcome in a series of patients. METHODS: Between 1984 and 1996, 1544 patients with lung cancer were referred to our institution for surgery and 1399 were operated on. Seven of them developed a symptomatic small bowel metastasis. Clinical, radiological, and pathology records were reviewed. RESULTS: In 6 of 7 patients, the lung cancer was previously operated on from 0.5 to 24 months before the diagnosis of small bowel metastasis. In 1 patient, the primary tumor was diagnosed after small bowel metastasis resection. Clinical symptoms at presentation were acute peritonitis in 2 patients, progressive digestive obstruction in 3, and gastrointestinal bleeding in 2. The diagnosis was suspected on abdominal ultrasonography in 2 cases, and small bowel radiography in 3 cases. It was confirmed either by computed tomographic scan or by push enteroscopy. All patients underwent operation (intestinal resection in 6 and bypass in 1) with no postoperative death. Small bowel metastases were located in the jejunum in 2 patients, in the ileum in 3, and in both sites in 2. Histological features of the metastases were identical to the primary tumor: squamous cell carcinoma (n = 3), undifferentiated large cell carcinoma (n = 2), adenosquamous carcinoma (n = 1), and adenocarcinoma (n = 1). In 6 patients, small bowel metastases were associated with other metastatic sites. Six patients died within 8 months after metastasis resection. One patient was alive 22 months after bowel resection. CONCLUSIONS: Symptomatic small bowel metastases can occur early in the course of lung cancer. Resection should be considered as the best palliative treatment to prevent bowel obstruction or peritonitis.     

Usefulness of Ultrasonography for Diagnosis of Small Bowel Tumors: A Comparison Between Ultrasonography and Endoscopic Modalities

Ultrasonography is a standard, noninvasive modality used to evaluate patients with gastrointestinal diseases. This study assessed the usefulness of ultrasonography in the detection of small bowel tumors.This study enrolled 558 consecutive patients (295 males, 263 females; mean age 71.1 years) who underwent ultrasonography before capsule endoscopy and/or balloon-assisted endoscopy. Ultrasonographic detection of small bowel tumors was compared with detection by capsule endoscopy and/or balloon-assisted endoscopy. In addition, factors affecting small bowel tumor detection by ultrasonography and clinical characteristics of patients with small bowel tumors undetected by ultrasonography were evaluated.Ninety-seven tumors (52 benign, 45 malignant) detected by capsule endoscopy and/or balloon-assisted endoscopy were retrospectively analyzed. The sensitivity and specificity of ultrasonography in the detection of small bowel tumors were 50.5% (47/93) and 100% (465/465), respectively. If we restricted patients to those with a tumor >20 mm in size, its detection ratio would become higher (91.7%): the ratio of submucosal tumor >20 mm in size was 85.7% (6/7) and that of partial and circumferential ulcerative tumors >20 mm in size was 96.9% (31/32), respectively. Small bowel tumors detected by ultrasonography (mean 33.2 mm) were significantly larger than those undetected by ultrasonography (mean 8.7 mm). The percentage of small bowel tumors located in the ileum detected by ultrasonography (70.6%) was significantly higher than those undetected by ultrasonography (29.4%). Of the 46 small bowel tumors undetected by ultrasonography, 42 (91.3%) were benign tumors with good clinical prognosis.Ultrasonography is a useful modality for detecting larger small bowel tumors and ulcerative lesions. Ultrasonography should be considered a first-line modality for patients suspected of having small bowel tumors, because most small bowel tumors undetected by ultrasonography were benign tumors with good clinical prognosis.     

Interventional digital subtraction angiography for small bowel gastrointestinal stromal tumors with bleeding

AIM: To retrospectively evaluate the diagnostic efficacy of interventional digital subtraction angiography (DSA) for bleeding small bowel gastrointestinal stromal tumors (GISTs).METHODS: Between January 2006 and December 2013, small bowel tumors in 25 consecutive patients undergoing emergency interventional DSA were histopathologically confirmed as GIST after surgical resection. The medical records of these patients and the effects of interventional DSA and the presentation and management of the condition were retrospectively reviewed.RESULTS: Of the 25 patients with an age range from 34- to 70-year-old (mean: 54 ± 12 years), 8 were male and 17 were female. Obscure gastrointestinal bleeding, including tarry or bloody stool and intermittent melena, was observed in all cases, and one case also involved hematemesis. Nineteen patients required acute blood transfusion. There were a total of 28 small bowel tumors detected by DSA. Among these, 20 were located in the jejunum and 8 were located in the ileum. The DSA characteristics of the GISTs included a hypervascular mass of well-defined, homogeneous enhancement and early developed draining veins. One case involved a complication of intussusception of the small intestine that was discovered during surgery. No pseudoaneurysms, arteriovenous malformations or fistulae, or arterial rupture were observed. The completely excised size was approximately 1.20 to 5.50 cm (mean: 3.05 ± 1.25 cm) in maximum diameter based on measurements after the resection. There were ulcerations (n = 8), erosions (n = 10), hyperemia and edema (n = 10) on the intra-luminal side of the tumors. Eight tumors in patients with a large amount of blood loss were treated with transcatheter arterial embolization with gelfoam particles during interventional DSA.CONCLUSION: Emergency interventional DSA is a useful imaging option for locating and diagnosing small bowel GISTs in patients with bleeding, and is an effective treatment modality.     

"起源胃壁强化征"辅助CT诊断胃外生型胃肠间质瘤

目的探讨肿瘤起源胃壁强化特征及坏死囊变成分的极性分布情况在胃外生型胃肠间质瘤（GIST）鉴别诊断中的意义。 方法回顾分析经手术病理证实的胃外生型（Ⅲ型）GIST病例18例，对照组设置与胃壁脂肪间隙消失的邻近脏器起源肿瘤16例（胰腺神经内分泌肿瘤6例，胰腺实性假乳头状瘤8例，肝癌2例），观察记录与肿瘤贴邻的胃壁是否存在CT"起源胃壁强化征"及"坏死囊变极性"分布的情况。同时测量肿瘤长径及动静脉期CT值。 结果GIST肿块相邻胃壁局限高强化比例（9/15）高于其他脏器来源肿瘤（0/16），差异具有统计学意义（χ²=12.857，P=0.007）。肿瘤坏死囊变极性分布情况，GIST较其他脏器来源肿瘤更多偏离胃壁侧分布，但差异无统计学意义（χ²=5.947，P=0.051）。两组肿瘤的长径（Z=-0.587，P=0.570）、动脉期（Z=-0.829，P=0.412）及静脉期平均CT值（Z=-1.450，P=0.147）差异均无统计学意义。 结论起源胃壁强化征可辅助CT鉴别诊断胃外生型胃肠间质瘤。     

Clinicopathologic characteristics of colorectal neuroendocrine tumor]

BACKGROUND/AIMS: Colorectal neuroendocrine carcinoma is a rare neoplasm exhibiting fulminant progression and having poor prognosis. The purpose of this study is to verify the clinicopathologic characteristics of colorectal neuroendocrine carcinoma. METHODS: From June 1997 to December 2004 at Asan Medical Center, ten patients were originally identified as colorectal neuroendocrine carcinoma on the basis of H&E and immunohistochemical staining (IHC). Carcinoid tumors were excluded in this study. Medical records of thirteen patients were reviewed retrospectively. RESULTS: Ten patients (0.2%) with colorectal neuroendocrine tumors were identified from 4,512 patients with colorectal cancer; ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation. Their median age was 60 (41-83) years. The subjects consisted of six males and seven females. Nine tumors were located in the rectum, two in the sigmoid, and each one in the transverse colon and cecum, respectively. Nine of ten neuroendocrine carcinomas expressed synaptophysin, but chromogranin A were expressed in four. All patients were advanced at the time of diagnosis, with AJCC TNM staging: stage IIIB (n=2), stage IIIC (n=3), and stage IV (n=8). The median survival for ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation were 16.4 months and 30 months, respectively. Five patients who received chemotherapy showed median survival of 32 months (stage III) and 17.5 months (stage IV), whereas other five patients without chemotherapy died with a median survival of 6.2 months. CONCLUSIONS: Colorectal neuroendocrine tumors are extremely rare showing aggressive behavior biologically, i.e fulminant early distant metastasis. Nevertheless, improved survival may be achieved by aggressive multimodality therapy.     

Neuroendocrine Carcinomas of the Colon and Rectum

PURPOSE: This study was designed to review experience with neuroendocrine carcinomas of the colon and rectum at a single institution, with emphasis on the pathology and clinical characteristics of this uncommon malignancy. METHODS: A study group of patients was identified from a prospective colorectal service database. Pathology was reviewed and neuroendocrine tumors were classified by a single pathologist. Medical records were retrospectively reviewed. RESULTS: From March 1975 to September 1998, 38 patients with neuroendocrine carcinomas were identified from the colorectal service database comprising 6495 patients (0.6 percent). These neuroendocrine carcinomas did not include carcinoid tumors. Average patient age was 57 years (range, 29–86 years). There were 17 males (44.7 percent) and 21 females (55.3 percent). Tumors were located as follows: 17 colon, 14 rectum, 6 anal canal, and 1 appendix. The diagnosis of neuroendocrine carcinoma was suggested preoperatively from tissue biopsy in 59.3 percent (16/27) of patients evaluable. Pathology was reviewed and tumors were categorized as small cell carcinoma (n = 22) or large cell neuroendocrine carcinoma (n = 16). Most tumors (20/25 evaluable, 80 percent) stained positive by means of immunohistochemistry for neuroendocrine markers, including chromogranin (18/19), synaptophysin (10/15), and/or neuron-specific enolase (14/15). Metastatic disease was detected at the time of diagnosis in 69.4 percent of the patients (25/36). Tumors were advanced at the time of diagnosis, with American Joint Committee on Cancer (AJCC) Stage I (n = 6), Stage III (n = 7), and Stage IV (n = 25) tumors. As a group, these tumors had a poor prognosis, with a median survival of 10.4 months. One-year, two-year, and three-year survival was 46 percent, 26 percent, and 13 percent, respectively. There was no significant difference in survival based on pathologic subtypes. Median follow-up time was 9.4 months (range, 0.6–263.7 months). CONCLUSIONS: Neuroendocrine carcinomas of the colon and rectum are uncommon, comprising less than 1 percent of colon and rectal cancers. Pathologically, these tumors are poorly differentiated carcinomas with distinctive cytoarchitectural features and are often immunoreactive for markers of neuroendocrine differentiation. The prognosis for highgrade neuroendocrine carcinomas is poor, as most patients have metastatic disease at the time of diagnosis.