Primary small bowel adenocarcinoma: current view on clinical features, risk and prognostic factors, treatment and outcome.

Small bowel adenocarcinoma (SBA) is a rare but increasing cause of gastrointestinal malignancy, being both a diagnostic and therapeutic challenge. The goal of treatment is margin negative resection of a lesion and local lymphadenectomy, followed by modern adjuvant chemotherapy combinations in selected cases. Improved outcomes in patients with SBA are encouraging, but elucidation of mechanisms of carcinogenesis and risk factors as well as improved treatment for this malignancy is very needed.

Small Bowel Intussusception Caused by Multiple Intestinal Metastases from a Giant Cell Carcinoma of the Lung: a Case Report.

Small bowel obstruction (SBO) due to intussusception in adults is a rare condition. Diagnosis at the time of admission is usually challenging. More often than not, a bowel intussusception in adults is secondary to an organic condition, frequently malignancies. Therefore, a surgical approach is indicated most of the times. We report the case of a forty-nine years old lady presenting with a SBO secondary to small bowel metastases with two ileo-ileal intussusceptions, one of which was missed at initial surgical exploration. A giant cell carcinoma of the lung (GCCL) with small bowel metastases was diagnosed subsequently. The case is presented as well as a brief review of literature.

MALT lymphoma of the small bowel with protein-losing enteropathy.

Mucosa-associated lymphoid tissue (MALT) lymphoma usually arises from chronic inflammation. We herein report a case of small intestinal MALT lymphoma with protein-losing enteropathy (PLE). A 73-year-old woman presented with lower leg edema and severe hypoalbuminemia. She had a medical history of pylorus-preserving pancreaticoduodenectomy with Billroth II reconstruction. Oral and anal route double-balloon enteroscopies revealed irregular nodular mucosal lesions with erosion extending from the jejunum to terminal ileum. Histopathological evaluation of the biopsied mucosa showed proliferation of small-to-medium-sized lambda light chain-restricted B cells. Plasmacytic differentiation and lymphoepithelial lesions were present, leading to the diagnosis of MALT lymphoma. Tc-99m albumin scintigraphy indicated tracer exudation in the small bowel, suggesting the presence of PLE. Combination immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen improved both MALT lymphoma and PLE, whereas rituximab monotherapy was not successful. This case is considered to be common type of MALT lymphoma at an uncommon site and is distinct from immunoproliferative small intestinal disease (IPSID). To our knowledge, this is the first case of non-IPSID-type small intestinal MALT lymphoma complicated by PLE. Gastrointestinal reconstruction may be responsible for underlying chronic inflammation via small intestinal bacterial overgrowth.

Vascular endothelial growth factors, angiogenesis, and survival in human ileal enterochromaffin cell carcinoids.

BACKGROUND AND AIMS: Well-differentiated neuro-endocrine ileal carcinoids are composed of serotonin-producing enterochromaffin (EC) cells. Life expectancy is determined by metastatic spread to the liver because medical treatment options are still very limited. Selective inhibition of angiogenesis or lymphangiogenesis might prevent tumour growth and metastatic spread. We examined the role of the vascular endothelial growth factors (VEGFs) A, B, C, D, and their receptors (VEGFRs) 1, 2, 3 in angiogenesis and lymphangiogenesis of ileal EC cell carcinoids with and without liver metastases. METHODS: The expression of various VEGFs and VEGFRs was determined by quantitative real-time RT-PCR in healthy mucosa, primary tumour, lymph node metastases and liver metastases of 25 patients with ileal EC cell carcinoids. Microvessel density (MVD) was determined by CD-31 staining in primary tumours and lymphatic vessel density (LVD) by LYVE-1 staining. VEGF expression levels, MVD, LVD, and patients' survival time were correlated using logistic regression and Kaplan-Meier survival analysis. RESULTS: VEGF-A was highly expressed with no difference between normal mucosa and tumours. VEGF-B and -D as well as VEGFR-1 and -2 expression levels were significantly increased in the tumours when compared to normal mucosa. Patients with liver metastasis, however, had a significantly lower expression of the factors A, B, and C and the receptors 2 and 3. MVD in primary tumours positively correlated with the expression of VEGF ligands and their receptors, except for VEGF-D. LVD did not correlate with any VEGF ligand or receptor. Interestingly, low expression levels of VEGF-B were associated with poor survival. CONCLUSION: Patients with more aggressive metastatic spreading had relatively decreased expression levels of VEGF ligands and receptors. Thus, anti-angiogenic therapy may not be a suitable target in metastatic ileal EC cell carcinoids.

Malignant ileocaecal serotonin-producing carcinoid tumours: the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis.

Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index >/=1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p/=1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, p/=1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.

Primary jejunoileal neoplasmas: a review of 60 cases.

AIM: Primary neoplasmas of the jejunum and ileum are infrequent and lack specific manifestations and inaccessibility of conventional endoscopy, so the diagnosis of these tumors are usually delayed. So far the data of primary jejunoileal neoplasmas is still scarce, especially in Chinese medical literature in English. There may be some differences among the Chinese and the westerners in jejunoileal neoplasmas. METHODS: A retrospective analysis was made on clinical findings and pathological types. RESULTS: Of the 60 patients with jejunal or ileal neoplasmas, the most frequent symptom was abdominal pain (57 %), followed by tarry stool (43 %) and hematochezia (10 %). Abdominal mass (40 %) was the most common finding on physical examination, followed by anemia and weight loss (35 %). 67 % of the jejunoileal neoplasms were located in the jejunum. Among the malignant neoplasmas (68 %), malignant stroma (47 %) was most common, while the benign stromoma (20 %) was the most common benign neoplasmas. Preoperatively, 40 patients (67 %) were diagnosed as small bowel neoplasmas, of which 34 were found by enteroclysis. Abdominal mass was shown by CT in 18 cases and by ultrasonography in 13. The mean duration of symptoms before diagnosis was 7 months. In 41 patients with malignant tumors, the duration of symptoms before diagnosis exceeded 12 months in 21 cases, lymphatic or distant metastases were found in 26 (63 %)cases during operation. An emergency laparotomy was performed in 4 patients (7 %) owing to intestinal obstruction or perforation. CONCLUSION: Primary jejunoileal neoplasmas in Chinese present some difference from Westerners on clinical features and histopathologic types. Enteroclysis remains the major relevant diagnostic procedure in this study, the misdiagnotic rate is high preoperatively due to failure of detection by conventional imaging procedures such as CT and inaccessibility of routine endoscopy. For the suspected patients, combined application of aforementioned procedures may facilitate early diagnosis. The wireless capsule endoscopy may improve the diagnostic rate of jejunoileal neoplasmas in the future.

Malignancy risk prediction for primary jejunun-ilear tumors

This work is aimed at identifying factors associated with primary jejunum-ileal tumors malignancy, defining a prediction model with sensitivity, specificity and accuracy to distinguish malign from benign neoplasms. These tumors are rare, have highly unspecific presentation and, frequently, are diagnosed late. We reviewed the charts of 42 patients with primary jejunum-ileal tumors treated in the Department of General Surgery of Rio de Janeiro State University Hospital, Rio de Janeiro, RJ, Brazil, from 1969 to 1998. We performed bivariate analyses, based on chi 2 test, searching associations between tumors malignancy and demographic and clinical variables. Then logistic regression was employed to consider the independent effect of variables previously identified on malignancy risk. The malign tumors included 11 adenocarcinomas, 7 leiomyosarcomas, 5 carcinoids and 4 lymphomas; the benign tumors included 10 leiomyomas, 2 hamartomas, and single cases of adenoma, multiple neurilemoma and choristoma. The bivariate analyses indicated the association between malignancy and palpable abdominal mass (P = 0.003), period from signs and symptoms onset to diagnosis (P = 0.016), anemia (P = 0.020), anorexia (P = 0.003), abdominal pain (P = 0.031), weight loss (P = 0.001), nausea and vomit (P = 0.094), and intestinal obstruction (P = 0.066); no association with patients demographic characteristics were found. In the final logistic regression model, weight loss, anemia and intestinal obstruction were statistically associated with the dependent variable of interest. Based only on three variables--weight loss, anemia and intestinal obstruction-the model defined was able to predict primary jejunum-ileal tumors malignancy with sensitivity of 85.2 per cent, specificity of 80.0 per cent, and accuracy of 83.3 per cent

Increased intestinal non-substance P tachykinin concentrations in malignant midgut carcinoid disease.

BACKGROUND: Diarrhoea is an important feature of the carcinoid syndrome, and various agents which may be released from carcinoid tumours have been considered to contribute pathophysiologically. The aim of the present study was to determine luminal concentrations of possible chemical mediators in an uninvolved small intestinal segment using a two-balloon six-channel tube in nine patients with malignant midgut carcinoid disease. METHODS: All patients were treated with interferon and/or octreotide to alleviate the most severe flush. Ion transport was measured during luminal perfusion and luminal perfusate concentrations of calcitonin gene-related peptide, neurotensin, prostaglandin E (PGE)2, neuropeptide Y, somatostatin, vasoactive intestinal polypeptide, substance P and other tachykinins (neurokinin A, neurokinin B, neuropeptide K, eledoisin) were determined by separate assays. RESULTS: Carcinoid patients showed decreased absorption of Cl-, Na+, K+ and water and increased luminal content of non-substance P tachykinins to 424.5 fmol/cm per h, compared with 255.5 fmol/cm per h in control subjects. There were also increased luminal concentrations of PGE2, commonly claimed as a more general mediator of diarrhoea. CONCLUSIONS: The observed increase in intestinal tachykinins may involve extended activity from tachykinin-containing intrinsic neurones in the enteric nervous system, contributing to enhanced intestinal motility and secretory diarrhoea in patients with carcinoid syndrome.

Electrophysiological properties of human carcinoid cells of the gut.

BACKGROUND & AIMS: Because of their diffuse distribution, neuroendocrine cells of the gut have not been isolated successfully for electrophysiological characterization. We therefore established primary cell cultures from surgically resected human carcinoids and investigated them electrophysiologically. METHODS: The neuroendocrine identity of the isolated gut tumor cells was determined immunocytochemically. The electrophysiological properties of the cells were studied by the patch-clamp technique. RESULTS: The primary cell cultures expressed neurofilament proteins, cytokeratins, and key proteins of the secretion machinery. Spontaneous action potentials were observed in most cells. Using the whole-cell mode of the patch-clamp technique, tetrodotoxin-sensitive voltage-gated sodium currents as well as voltage-gated calcium currents were identified. Calcium channel currents were carried mainly by dihydropyridine-sensitive, L-type calcium channels. The L-type calcium channel currents were also partially blocked by the omega-conotoxins GVIA and MVIIC. Moreover, omega-agatoxin IVA reversibly reduced a component of the calcium channel currents, indicating that neuroendocrine gut tumor cells express different types of voltage-gated calcium channels. In addition, somatostatin was found to inhibit partially the voltage-dependent calcium channel currents and thus calcium-dependent hormone release. CONCLUSIONS: Carcinoid cells of the human gut are electrically excitable cells. They express voltage-dependent sodium and calcium channels as well as somatostatin receptors.

Abnormalities of the interdigestive migrating motor complex in a patient with carcinoid syndrome

As pressöes intraluminais do antro gástrico, duodeno e jejuno foram registradas durante 206 minutos após jejum de 12 horas em uma paciente com síndrome carcinóide devida a neoplasia de células enterocromafins do ileo e com metástasis hepáticas. A alteraçäo mais conspícua foi a presença de taquirritmia de 16-17 ondas de pressäo/minuto, predominando nos "fronts" de atividade tanto no duodeno como no jejuno. Períodos com 11-12 ondas/minutos apareceram irregularmente e a ocorrência simultânea de 12 ondas/minuto no duodeno e 16 ondas/minuto no jenuno foi registrada. O antro gástrico permaneceu em quiescência motora durante todo o transcurso do estudo manométrico. Presume-se que as alteraçöes sejam produzidas pelas substâncias secretadas pelo tumor carcinóide

Abnormalities of the interdigestive migrating motor complex in a patient with carcinoid syndrome.

Intraluminal pressures of the gastric antrum, duodenum and jejunum were recorded for 206 min after a 12 h fast in a patient with carcinoid syndrome due to neoplasia of enterochromaffin cells of the ileum and with hepatic metastases. The most conspicuous alteration was a tachyrrhythmia of 16 waves/min predominating in the activity fronts of both duodenum and jejunum. Periods of 11-12 waves/min frequency appeared irregularly and the simultaneous occurrence of frequencies of 11 waves/min and 16 waves/min was also recorded. The gastric antrum was fully quiescent throughout the study. The alterations observed are presumed to be produced by substances secreted by the carcinoid tumor.