Jejunitis and brown bowel syndrome with multifocal carcinogenesis of the small bowel.

This is the first report describing a case where prolonged, severe malabsorption from brown bowel syndrome progressed to multifocally spread small bowel adenocarcinoma. This case involves a female patient who was initially diagnosed with chronic jejunitis associated with primary diffuse lymphangiectasia at the age of 26 years. The course of the disease was clinically, endoscopically, and histologically followed for 21 years until her death at the age 47 due to multifocal, metastasizing adenocarcinoma of the small bowel. Multiple lipofuscin deposits (so-called brown bowel syndrome) and severe jejunitis were observed microscopically, and sections of the small bowel showed dense lymphoplasmacytic infiltration of the lamina propria as well as blocked lymphatic vessels. After several decades, multifocal nests of adenocarcinoma cells and extensive, flat, neoplastic mucosal proliferations were found only in the small bowel, along with a loss of the mismatch repair protein MLH1 as a long-term consequence of chronic jejunitis with malabsorption. No evidence was found for hereditary nonpolyposis colon carcinoma syndrome. This article demonstrates for the first time multifocal carcinogenesis in the small bowel in a malabsorption syndrome in an enteritis-dysplasia-carcinoma sequence.

Brown bowel syndrome: a rare complication in diseases associated with long-standing malabsorption.

BACKGROUND/AIMS: Longtime chronic malabsorption may among other things cause a lack of liposoluble vitamins. Vitamin E deficiency can lead to formation of lipofuscin aggregates. Its deficiency is also associated with an increased lipofuscinosis of the bowel, i.e. brown bowel syndrome. METHODS: Systematic research via Medline on brown bowel syndrome, lipofuscinosis, and vitamin E deficiency was performed. We combined our own clinical experience and a review of the literature for this paper. Its goal is to inform about the possible consequences of severe malabsorption and brown bowel syndrome. RESULTS: Systematic data about the occurrence of severe malabsorption and brown bowel syndrome are rare. Only about 27 scientific reports can be found on this subject. Brown bowel syndrome is found mostly in conjunction with vitamin E deficiency and lipofuscinosis of the bowel. The clinical findings are caused by both malabsorption and lipofuscinosis. Case reports show a therapeutic effect of vitamin E. CONCLUSION: Vitamin deficiency caused by longtime chronic malabsorption can lead to the development of brown bowel syndrome, which is seen as the expression of lipofuscinosis of the bowel, and can cause further clinical disorders. Patients with malabsorption should therefore be monitored regarding their vitamin E levels.

Colon capsule endoscopy: detection of colonic polyps compared with conventional colonoscopy and visualization of extracolonic pathologies.

BACKGROUND: Conventional colonoscopy (CC) is the gold standard for diagnostic examination of the colon. However, the overall acceptance of this procedure is low due to patient fears of complications or embarrassment. Colon capsule endoscopy (CCE) represents a minimally invasive, patient-friendly procedure that offers complete visualization of the entire intestine. OBJECTIVE: To assess the PillCam Colon 2 (Given Imaging Ltd, Israel) capsule with regard to feasibility, sensitivity and specificity for the detection of colonic pathologies and additional recorded extracolonic findings. METHODS: CCE was performed before CC in patients indicated for CC for known or suspected colonic disease. The results of both techniques were compared with regard to polyp detection. Additionally, bowel preparation and extracolonic pathologies were analyzed. RESULTS: Twenty-four patients (mean age 51.1 years) were included in the analysis. Visualization of the colon was complete in 23 CCs and 17 CCEs. No adverse events or major technical failures occurred. CC detected 47 polyps and CCE detected 43 polyps of any size (per-finding sensitivity 90.9%, specificity 67.6%). The accuracy of CCE in detecting polyp carriers was 81.5% (per-patient analysis). On average, the colon was adequately cleansed in 90.1% of patients. CCE identified esophageal, gastric and small bowel pathologies in seven (24%), nine (38%) and 14 (58%) patients, respectively. CONCLUSIONS: CCE proved to be technically feasible and safe. Acceptable sensitivity and moderate specificity levels in polyp detection were recorded. Bowel preparation was adequate in most patients. Because extracolonic pathologies were effectively visualized, new indications for the PillCam Colon 2 may be defined.

Capsule endoscopy in patients with cardiac pacemakers and implantable cardioverter-defibrillators - a retrospective multicenter investigation.

BACKGROUND & AIMS: Capsule endoscopy (CE) is an established tool for the investigation of the small intestine. The Food and Drug Administration, Given Imaging and Olympus have not recommended the use of capsule endoscopy in patients with cardiac pacemakers and implantable cardioverter defibrillators (ICDs). The aim of this retrospective study was to investigate the safety of capsule endoscopy systems (Given Imaging and Olympus) when applied in patients with different types of pacemakers/ICDs in vivo. METHODS: A standardized questionnaire was sent to high volume centers in Germany and in Austria. The questionnaire covered the age and gender of the examined patients, indication of CE, brand and type of CE, brand and model of pacemaker/ICD, check of the devices before and after CE, monitoring during CE, possible interference between CE and cardiac pacemakers/ICDs and possible adverse events during CE. RESULTS: Data from 62 patients were retrieved for this study. Capsules used were Given Imaging (n=58; M2A, M2Aplus, PillCam SB2), Olympus EndoCapsule (n=3), Given PillCam Colon (n=1). The collective included patients with pacemakers/ICDS from seven brands (Biotronik, Medtronic, St. Jude Medical, Guidant, Boston Scientific, Ela Sorin, Vitatron) with a total of 19/8 (pacemaker/ICD) different types. In two patients interference between capsule endoscopy and telemetry (loss of images/gaps in video) was recorded. None of the cardiac pacemakers or ICDs was impaired in function. No clinically evident event was observed in any of these patients. CONCLUSIONS: Clinical use of these CE types is safe in patients with cardiac pacemakers and ICDs. Interference can occur between CE and ECG-telemetry leading to loss of images or impaired quality of video.

Mast cell tryptase in sera of patients with Crohn's disease and mastocytosis.

INTRODUCTION: The pathogenesis of Crohn's disease is unclear, but an abnormal immune response seems to play an important role. This study investigated whether serum tryptase could be shown in Crohn's disease as a marker of disease. MATERIALS AND METHODS: Mast cell tryptase was detected in sera of 48 patients with active Crohn's disease, 31 patients with inactive Crohn's disease, 17 patients with mastocytosis, and 50 controls. Tryptase detection was carried out by UniCap System. Tryptase levels are given as U/l x m2 body surface area to overcome variations of body weight, height, etc. between malnourished and normal persons. RESULTS: Serum tryptase levels (U/l x m2 body surface area) of controls were 2.4+/-1.0, of patients with Crohn's disease 2.5+/-2.0. In contrast, serum tryptase values were significantly increased in untreated patients with mastocytosis (21.19+/-18.55). DISCUSSION: Mast cell tryptase is not elevated in sera of Crohn's disease. It might thus be speculated that this highly mast cell associated mediator might only contribute to local symptoms of Crohn's disease such as diarrhea, abdominal pain, etc., but not to its systemic inflammatory effects (Th 1 cytokine pattern). Tryptase may be well used for the screening of patients with mastocytosis.

Long-term partial remission of autoimmune thrombocytopenia in a patient treated with the anti-tumor necrosis factor-alpha antibody infliximab for refractory fistulizing Crohn's disease.

BACKGROUND: Up to the present date, the treatment of recurrent chronic fistulas occurring with Crohn's disease represents a challenging task for both internists and surgeons alike. METHODS: Conservative methods of treatment using steroids, dietotherapy, antibiotics or immunosuppressive agents are not particularly effective in treating fistulas. Treatment with anti-tumor necrosis factor-alpha (TNFalpha) antibodies results in more remissions of fistulas. However, its use requires appropriate medical experience and causes substantial costs. Surgical procedures such as fistula sanitation or protective ileostomy are often obfuscated by the recurrence of the condition. The efficiency of anti-TNFalpha antibodies for the treatment of active Crohn's disease has been evidenced through several multicenter, double-blind, placebo-controlled studies. RESULTS: Here we report the successful anti-TNFalpha treatment of a patient suffering from chronic, fistulizing, therapy-resistant Crohn's disease and a concomitant chronic autoimmune thrombocytopenia. The chimeric anti-TNFalpha antibody infliximab markedly reduced the disease activity of Crohn's disease, and, in addition, substantially increased the platelet counts. After infliximab application, no other treatment of autoimmune thrombocytopenia was required. After infliximab therapy, autoantibodies to dsDNS could be observed. However, there were no signs of a lupus-like disease. CONCLUSION: This report indicates a favorable therapeutic response of autoimmune thrombocytopenia associated to Crohn's disease.

Serum levels of hepatocyte growth factor/scatter factor in patients with liver metastases from breast cancer.

OBJECTIVE: Recent studies have shown that the pleiotropic cytokine hepatocyte growth factor/scatter factor (HGF/SF) and its receptor c-Met play major roles in the malignant progression of numerous tumors. For patients with breast cancer liver metastases, increased serum levels of HGF/SF have been reported. We studied the relationship between the clinical course of the disease and the serum levels of HGF/SF in such patients. METHODS: We examined 51 patients treated for breast cancer liver metastases. Serum concentrations of HGF/SF were measured before each therapy cycle and compared to the corresponding tumor marker levels. RESULTS: Mean serum levels of HGF/SF in patients with liver metastases were increased above the reported reference levels of primary breast cancer patients. Serum levels of HGF/SF were correlated with tumor marker levels in a logarithmic relation (r = 0.47, p < 0.001). In some cases serum concentrations of HGF/SF changed similarly to the course of the corresponding tumor markers. CONCLUSIONS: Serum levels of HGF/SF are associated with the clinical course of metastatic breast cancer patients with liver metastases. Further studies are required to clarify the potential value of the HGF/SF serum concentration as a tumor marker. HGF/SF and its receptor c-Met should be further evaluated as therapeutic targets.

Prognostic factors for patients with liver metastases from breast cancer.

BACKGROUND: The prognosis of patients with liver metastases from breast cancer is commonly poor. After initial diagnosis of hepatic metastases, a median survival time of 1-20 months can be expected. The definition of prognostic factors for such patients may influence therapeutic decisions. In particular, the characterization of patients who can expect long-term survival could assist in optimizing treatment. METHODS: We retrospectively studied n = 350 patients with liver metastases from breast cancer. All patients were stratified following their survival after occurrence of liver metastases. Kaplan-Meier studies were performed, as well as univariate and multivariate analyses of several clinical, histopathological and therapeutic factors. RESULTS: Median survival time was 14 months. N = 66 (18.9%) patients survived longer than 36 months after the primary diagnosis. Multivariate analysis showed prognostic relevance for the time interval between the primary diagnosis of breast cancer and the initial diagnosis of hepatic metastases (p < 0.05). Furthermore, prognostic relevance was found for the pattern of metastasization (p < 0.05) and for signs of hepatic dysfunction (ascites, jaundice, p < 0.005). Univariate analysis showed a prognostic benefit for patients with an expression of Ki-67 < 20%, p53 < 50% and a positive hormonal receptor status. Patients who received a regional therapy survived on average longer than patients who were only treated systemically (33 versus 11 months, p < 0.001). CONCLUSIONS: Consideration of prognostic implications of the described parameters may help to find the most appropriate treatment for patients with liver metastases from breast cancer. The possibility of local therapeutic interventions should be considered in a defined subgroup.

Endoscopic stenting of the common bile duct allows successful treatment of a breast cancer patient with excessive liver metastases.

The treatment of a jaundiced patient with hyperbilirubinaemia due to breast cancer liver metastases is still a challenging problem. The associated hepatic dysfunction often represents a limiting factor for delivering standard dose chemotherapy. We report on the successful treatment of a jaundiced patient with excessive, recurrent liver metastases from breast cancer, using a combined chemotherapy of mitomycin and 5-fluorouracil after endoscopic stenting of the common bile duct.

Serum levels of soluble E-selectin are associated with the clinical course of metastatic disease in patients with liver metastases from breast cancer.

Increasing evidence indicates that the expression of the endothelial adhesion molecule E-selectin is associated with progression and metastasis of breast cancer. Patients with liver metastases also show increased serum levels of the soluble form of E-selectin. It was our aim to compare serum levels of soluble E-selectin (sES) in such patients with the biology of the primary tumor and the course of the metastatic disease under therapy. We examined 69 patients with liver metastases from breast cancer who were selected to receive systemic tumor therapy because of progressive disease (n = 44) or newly detected liver metastases (n = 25). Serum concentrations of sES were measured before each therapy cycle using a specific ELISA. Serum concentrations of sES before the start of therapy were compared to clinical parameters and histopathological findings referring to the primary tumor. Secondly, serum levels of sES were compared to serum concentrations of the corresponding tumor markers. We observed a possible trend for certain unfavorable prognostic parameters (e.g., young women, low-graded tumors, human epidermal growth factor receptor 2 overexpression) to be related to higher serum levels of sES. Serum levels of sES were correlated with tumor marker levels in a logarithmical relation (r = 0.44, P < 0.0005). In some cases it could be demonstrated that serum levels of sES changed similarly to the course of tumor marker levels. We conclude that serum levels of sES are associated with the clinical course of liver metastases from breast cancer. Further investigations are needed to clarify if serum levels of sES may serve as tumor marker in certain clinical situations. E-selectin should be evaluated as a possible target for antimetastatic therapy studies.