Colonoscopy-associated perforation: a 7-year survey of in-hospital frequency, treatment and outcome in a German university hospital.

AIM: Perforation occurs rarely after colonoscopy, but is associated with high morbidity and mortality. In this study, we assessed the perforation rate in our hospital, its clinical diagnosis and the long-term outcome. METHOD: During the study period, 7535 examinations were performed, of which 4830 were diagnostic and 2705 therapeutic. The latter included polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), dilatation and argon plasma coagulation (APC). RESULTS: Overall, 25 (0.33%) perforations occurred with two (0.026%) procedure-related deaths. Seven (0.14%) perforations occurred during a diagnostic procedure and 18 (0.67%) occurred during a therapeutic procedure. Dilation, submusous resection (SMR) and APC accounted for more perforations than polypectomy or diagnostic colonoscopy. Pre-existing gastrointestinal disease was present in 24 (96%) perforations. Three (12%) patients were treated conservatively and 22 (88%) underwent surgery. The site of perforation was closed by suture in four (18%) patients and resected with colonic anastomosis in five (23%) patients. Two patients underwent endoscopic clipping. A stoma was created after resection in 13 (59%) patients. CONCLUSION: Death from perforation after colonoscopy is rare, occurring in 1/3500 examinations. The risk is increased in therapeutic colonoscopy and in the presence of previous gastrointestinal disease. Dilatation, SMR and APC appeared to confer a higher risk of perforation than polypectomy or diagnostic colonoscopy.

[CA 19-9 in the differential diagnosis of pancreatic lesions]. / 80-jähriger Patient mit Pankreasraumforderung. Diagnostische Wertigkeit des Tumormarkers CA 19-9.

CA 19-9 is still used in the differential diagnosis of pancreatic lesions. As it has been shown to be elevated in many other non-pancreatic diseases--sometimes even extraordinarily--this marker should not be used to set the diagnosis of a pancreas carcinoma anymore. Especially if there is a concomitant cholestasis there is no diagnostic value to perform the measurement of CA 19-9. As the histological confirmation is the only way to get the exact diagnosis endoscopic ultrasound guided fine-needle aspiration biopsy should be considered in lesions of the pancreatic head.

Butyrate and propionate downregulate ERK phosphorylation in HT-29 colon carcinoma cells prior to differentiation.

We have characterized the effects of different short-chain fatty acids (SCFAs) on cell growth and differentiation as well as the phosphorylation state of ERK1 and 2 in the human colon adenocarcinoma cell line HT-29. Of the five SCFAs tested, only butyrate and propionate impaired cellular proliferation. Moreover, butyrate and propionate specifically resulted in a decrease in ERK1 and 2 phosphorylation at 3 and 6 hours post-treatment, suggesting a correlation between the ability of these SCFAs to inhibit cellular proliferation and decrease ERK phosphorylation. Notably, the decrease in ERK phosphorylation was observed prior to the induction of the differentiation markers alkaline phosphatase (AP) and carcinoembryonic antigen (CEA) by butyrate and propionate from days 6 to 18 post-treatment. In the case of butyrate- and propionate-induced differentiation, ERK phosphorylation is a marker and may play a role in the proliferation and/or differentiation states of this cell line.

Relationship between microsatellite instability, response and survival in palliative patients with colorectal cancer undergoing first-line chemotherapy.

BACKGROUND AND AIMS: The aim of this work was to investigate the relationship between microsatellite instability (MSI), treatment response and survival in palliative patients with colorectal cancer (CRC) undergoing first-line treatment with weekly 24-hour infusion (24-h inf.) of high-dose 5-fluorouracil (5-FU) and folinic acid (FA). PATIENTS AND METHODS: Tumour material from the colorectal primary carcinomas was analysed for 43 patients. MSI analysis was carried out and immunohistochemistry was performed with hMLH1 and hMSH2. RESULTS: Tumours of 7 patients (16%) were highly instable (MSI-H). These patients had a better response rate (72% vs. 41%; p = 0.072) and a significantly better median survival (33 months, [95% CI 20-46] vs. 19 months, [95% CI 10-28]; p = 0.021) than microsatellite stable (MSS) patients (n = 36). Furthermore, MSI status was shown to be an independent predictive marker for survival (p = 0.037). CONCLUSION: These data provide further support for the hypothesis that MSI-H CRC might have a better response and survival than (MSS) CRC in palliative first-line treatment.

Histological changes in the colonic mucosa following irrigation with short-chain fatty acids.

OBJECTIVES: Short-chain fatty acids (SCFAs) derived from bacterial fermentation of complex carbohydrates are preferred luminal nutrients of the colonic mucosa. Starvation of colonocytes through lack or impaired metabolism of luminal SCFAs may be a cofactor in the pathogenesis of ulcerative colitis. DESIGN: A detailed histological evaluation of colonic biopsy specimens was performed in patients with active distal ulcerative colitis who were treated with rectal enemas containing a mixture of SCFAs, n-butyrate alone or saline placebo. Together with light microscopic parameters of mucosal inflammation, the pattern of crypt cell proliferation (proliferating cell nuclear antigen) and the mucosal activity of factor XIII were assessed. RESULTS: Butyrate reduced the density of polymorphonuclear leucocytes in the lamina propria (4 weeks: P = 0.063; 8 weeks: P = 0.091); other inflammatory parameters remained unchanged. Both butyrate and the SCFA mixture reduced significantly the number of proliferating cells in the upper 40% of crypts. Tissue factor XIII activity in active ulcerative colitis was significantly lower than in mucosa from normal colons; however, it was not affected by SCFA or butyrate irrigation. CONCLUSION: SCFAs and butyrate have a more marked effect on crypt cell proliferation than on parameters of inflammation in patients with active ulcerative colitis.

[Effect of nutrition factors on the pathogenesis of colorectal carcinoma]. / Einfluss von Ernährungsfaktoren auf die Entstehung kolorektaler Karzinome.

There is convincing evidence that nutrition affects colorectal carcinogenesis in a complex fashion. Dietary components either promote or inhibit the carcinogenic process. The composition of dietary fats seems to be less important as a promoting factor than a positive energy balance, especially in combination with low physical activity. Excessive consumption of red meat is associated with increased risk, which may be due to the heme contained in myoglobin. Alcohol stimulates cell proliferation in the rectum and may thus increase cancer risk. Complex carbohydrates (e.g., dietary fiber) are degraded in the colon to short-chain fatty acids which exhibit protective effects in experimental models of carcinogenesis. The putative protection from vitamins and trace elements merits further attention.

Butyrate inhibits interleukin-1-mediated nuclear factor-kappa B activation in human epithelial cells.

Nuclear factor-kappa B (NF-kappaB) is a critical transcription factor for the inducible expression of multiple genes involved in inflammation. NF-kappaB is sequestered in the cytoplasm by inhibitory IkappaB proteins. Extracellular stimuli, notably interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) activate NF-kappaB nuclear translocation via IkappaB phosphorylation and degradation. Since previous reports suggest that the short chain fatty acid butyrate has antiinflammatory properties, the effects of butyrate on NF-kappaB nuclear translocation in human epithelial cells (HeLa229) were tested. In cells pretreated with butyrate, a time- and dose-dependent inhibition of IL-1beta-mediated NF-kappaB nuclear translocation was observed. However, IkappaB alpha phosphorylation and degradation occurred rapidly in both butyrate pretreated and nonpretreated cells, respectively. These data indicate that inhibition of IL-1beta-induced NF-kappaB activation by butyrate does not require an intact IkappaB alpha protein.

[Palliative second-line treatment with oxaliplatin, gemcitabine and weekly high-dose 5-fluorouracil as 24-h infusion in patients with metastatic pancreatic adenocarcinoma]. / Palliative Zweitbehandlung mit Oxaliplatin, Gemcitabin und wochentlich hochdosiert 5-Fluorouracil als 24-h-Infusion beim metastasierten Adenokarzinom des Pankreas.

The most commonly used treatment in the palliative first-line therapy of metastatic pancreatic adenocarcinoma is the Gemcitabine (Gem) monotherapy, while several combination therapies are currently being tested in clinical trials. With regard to pancreatic cancer, a palliative second-line therapy has not been established, yet. The four patients presented in this paper received a palliative second-line therapy with Oxaliplatin (L-OHP), Gem and high-dose 5-Fluorouracil (5-FU) as a 24-h infusion after a first-line therapy with Gem and weekly high-dose 5-FU as a 24-h infusion. During second-line therapy, four patients received 67 chemotherapy applications, which were well tolerated. As severe symptom of toxicity, thrombocytopenia (CTC toxicity grade 4) was observed in one patient. As a result of second-line therapy, stable disease (SD) with a significant decrease of CA 19 - 9 was achieved in three patients and partial remission (PR) in one patient. After palliative first- and second-line treatment the survival time of the patients was 9, 9, 15 and 20 months. Currently, a multicentre phase I study has been started aiming at an optimisation of the three-drug combination dosage.

Complete remission with long-term survival in a patient with esophageal carcinoma and a tracheoesophageal fistula after treatment with the AIO regimen and bi-weekly cisplatin.

INTRODUCTION: To date, only few reports are available on patients with esophageal carcinoma containing a tracheoesophageal fistula under chemotherapy. CASE REPORT: A 56-year-old patient presented to the hospital with a stenosing squamous cell carcinoma of the esophagus containing a tracheoesophageal fistula 3 cm above the carina. After placement of a Port-a-Cath and adequate hydration he received weekly 500 mg/m (2) i. v. folinic acid (FA) as a 1 - 2-hour infusion and 2000 mg/m (2) 5-fluorouracil (5-FU) as a 24-hour infusion (24-h inf.) (AIO regimen) with prior application of bi-weekly 50 mg/m (2) i. v. cisplatin. A tracheal Y-Dumont metallic stent was inserted prior to initiating systemic treatment. The patient's alimentation was completely parenteral. After three cycles of chemotherapy (six months) the patient revealed complete remission (CR) with closure of the tracheoesophageal fistula. The tracheal Y-Dumont stent could be removed and the patient had oral alimentation restored. 29 months after initiating treatment he is without evidence of disease. CONCLUSION: Patients with esophageal carcinoma containing a tracheoesophageal fistula might benefit from chemotherapy and should not be generally excluded from systemic treatment.