Impact of dose escalation on colostomy-free survival and treatment outcome in squamous cell anal carcinoma.

PURPOSE: Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer. METHODS: Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0). RESULTS: The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3­year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3­year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3­year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3­year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067). CONCLUSION: Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.

The effect of oral pancreatic enzyme supplementation on the course and outcome of acute pancreatitis: a randomized, double-blind parallel-group study.

CONTEXT: Pancreatic exocrine insufficiency is a significant problem after acute pancreatitis. OBJECTIVE: To evaluate whether oral pancreatic enzyme supplementation improves the recovery of pancreatic exocrine function and to explore the efficacy, safety and tolerability of pancreatic enzyme supplementation in patients during the refeeding period after acute pancreatitis. DESIGN: Prospective double-blind, placebo controlled, randomized study. PATIENTS: The sudy included 56 patients with acute pancreatitis. MAIN OUTCOME MEASURES: Primary efficacy variable was recovery from pancreatic exocrine insufficiency. Secondary objectives were body weight, abdominal pain, course of APACHE II score, patient's symptoms and quality of life. RESULTS: Twenty of the 56 patients showed low fecal elastase values indicating pancreatic exocrine insufficiency after acute pancreatitis. Median time to recovery from exocrine pancreatic insufficiency was 14 days in the enzyme supplementation group and 23 days in the placebo group but overall differences for primary and all but one secondary endpoint did not reach statistical significance. However, a positive tendency in favour of enzyme supplementation was found for quality of life parameters (FACT-Pa) in all subscores. There were no relevant differences between placebo and oral pancreatic enzyme supplementation detected with respect to safety and tolerability. CONCLUSION: Enzyme supplementation positively effects the course of acute pancreatitis if administered during the early refeeding phase after acute pancreatitis. There is evidence that oral pancreatic enzyme supplementation has a positive impact on the course of the disease and the global health status (less weight loss, less flatulence, improved quality of life). Oral pancreatic enzyme supplementation was safely administered and can be added to the treatment regimen of patients in a refeeding status after severe acute pancreatitis.

[Gastrointestinal stromal tumors (GIST). Clinical characteristics, diagnosis, and therapy in five cases]. / Gastrointestinale Stromatumoren (GIST) Klinische Charakteristika, Diagnostik und Therapie anhand von fünf Fallberichten.

Gastrointestinal stromal tumors (GIST) are rare causes of gastrointestinal bleeding. In most cases these tumors are localized in the stomach and small intestine, more rarely in the esophagus and colon.Pluripotent mesenchymal cells are the suspected origin of GIST. The pathogenesis is obviously initiated by gene mutations, leading to an overexpression and activation of tyrosine kinase proteins. This activation is followed by uncontrolled proliferation and loss of apoptosis. The immunohistochemical detection of the protein CD 117 (c-kit) is an important diagnostic tool. Activating c-kit mutations are observed in most cases of GIST. Grading of GIST remains a problem. Size and mitotic rate are the most powerful predictive factors associated with malignant behavior. The most common symptoms of GIST are pain and gastrointestinal bleeding. Endoscopy, sonography, scintigraphy or radiology -- enteroclysma, computed tomography (CT) and magnetic resonance imaging (MRI) -- are possible methods to detect a GIST. Surgical resection is the standard therapy of GIST. In cases of metastatic GIST, systemic therapy with imatinib, a tyrosine kinase inhibitor, frequently leads to partial remission and clinical improvement. Only few side effects are described. Five patients with GIST are reported. In all cases gastrointestinal bleeding was the main symptom. All tumors were surgically resected, and no signs of recurrence or metastasis have been observed in any of the patients so far (19-51 months postoperatively).

Modern diagnostics of chronic pancreatitis.

Chronic pancreatitis is a well-defined disease on histopathological grounds, but for clinical purposes diagnosis is generally not based on histological specimens. Imaging procedures, non-invasive or with different degrees of invasiveness, and pancreatic function tests are therefore the diagnostic mainstay in patients with suggestive clinical history. The correct diagnosis of chronic pancreatitis is easy in late stages but difficult in an early stage of the disease. A particular challenge is the differentiation between acute or recurrent acute and early chronic pancreatitis. Earlier classifications (Cambridge and Marseille) did not consider the complex interrelationship between (especially alcoholic) acute and chronic pancreatitis. A possible solution is to separate the entities into probable and definite alcoholic chronic pancreatitis, with the assignment into the latter category achieved by follow-up investigations. Up to now the best diagnostic accuracy at an early stage is achieved by the detection of abnormalities of the ductal system in endoscopic retrograde pancreatography or by assessing exocrine function with the secretin-ceruletide test. The endoscopic ultrasound may substitute the endoscopic retrograde pancreatography as superior imaging modality that detects both parenchymal and ductal changes of chronic pancreatitis at an early stage. Magnetic resonance pancreatography is a further promising diagnostic tool without the risk of pancreatitis after endoscopic retrograde pancreatography, but imaging of the side branches, which is crucial for detection of early chronic pancreatitis, is not yet sufficient. Faecal elastase is a progress in non-invasive testing of exocrine pancreatic function, but its value for the diagnosis of chronic pancreatitis under conditions of clinical practice is limited. Several (13)C breath tests have been developed, but their availability and their diagnostic accuracy in chronic pancreatitis is still limited. Light to moderate exocrine pancreatic insufficiency is not detectable with adequate accuracy by tubeless function tests. A specific serum marker of pancreatic fibrosis which would reliably indicate the presence of chronic pancreatitis or its progression to is not available.

Influence of Helicobacter pylori infection and omeprazole treatment on gastric regional CO2.

BACKGROUND: Gastric regional CO(2) accumulation indicates gastric mucosal hypoperfusion in critically ill patients. CO(2) is also a reaction product of urea degradation, and we therefore tested the hypothesis if regional pCO(2) is influenced by Helicobacter pylori infection. MATERIAL: Seven H. pylori-positive and 7 H. pylori-negative volunteers (age range 21-30 years) were investigated. During a 6- to 7-hour observation period, we obtained every 30 min arterial blood gases, gastric juice pH from a glass pH electrode and regional pCO2 from a gastric tonometer. The study protocol included subsequent periods of baseline measurements, pentagastrin stimulation (0.6 microg/kg/h/i.v.) and application of omeprazole (40 mg i.v.). RESULTS: Gastric regional pCO(2) was increased in H. pylori-positive versus H. pylori-negative subjects before (64.4 +/- 3.1 vs. 50.0 +/- 2.9 mm Hg, p < 0.005) but not after application of omeprazole. The effect of omeprazole on gastric juice pH was increased in H. pylori-positive subjects (mean pH during 4 h 6.1 +/- 0.3 in H. pylori-positive vs. 2.5 +/- 0.2 in H. pylori-negative subjects; p < 0.0001). There was a difference in arterial pCO(2) between H. pylori-positive and H. pylori- negative subjects (43.1 +/- 0.3 versus 38.9 +/- 0.3 mm Hg; p < 0.0001). CONCLUSION: H. pylori infection has a significant effect on gastric regional CO(2) that is suppressed by application of a proton pump inhibitor.

Identification of enterohepatic Helicobacter species in patients suffering from inflammatory bowel disease.

Using a group-specific PCR assay, we investigated the presence of enterohepatic Helicobacter species in gut specimens from patients with inflammatory bowel disease. Enterohepatic Helicobacter species were detected in 12% (3 of 25) of the patients with Crohn's disease, in 17% (3 of 18) of the ulcerative colitis samples, and in 4% (1 of 23) of the controls.

EUS in the diagnosis of early chronic pancreatitis: a prospective follow-up study.

BACKGROUND: The aim of this prospective, follow-up study was to investigate the value of EUS in the diagnosis of alcohol-induced chronic pancreatitis. METHODS: One hundred thirty patients with known (n = 51) or clinically suspected (n = 79) chronic pancreatitis were included. Patients with a history of chronic use of alcohol and recurrent abdominal pain underwent endoscopic retrograde pancreatography and EUS. The 38 patients with normal endoscopic retrograde pancreatography but signs of chronic pancreatitis on EUS were included in a follow-up program. RESULTS: All patients with chronic pancreatitis confirmed by retrograde pancreatography (n = 92; 70.8%) had ductal or parenchymal changes detectable with EUS. Among 38 patients (29.2%) with normal retrograde pancreatography, 32 (84.2%) presented with morphologic features consistent with chronic pancreatitis by EUS. During follow-up (median 18 months, range 6-25 months) chronic pancreatitis was confirmed by repeat endoscopic retrograde pancreatography in 22 of these 32 patients (68.8%). On the basis of these follow-up data, the sensitivities of EUS and endoscopic retrograde pancreatography at the time of the first examination were, respectively, 100% and 80.7% (p < 0.001). CONCLUSION: EUS detects chronic pancreatitis in all cases if endoscopic retrograde pancreatography was suggestive for chronic pancreatitis. However, EUS is more sensitive than endoscopic retrograde pancreatography in the detection of early morphologic changes of chronic pancreatitis in patients with abdominal pain and a history of chronic and continued ingestion of alcohol.

Treatment of benign biliary strictures in chronic pancreatitis by self-expandable metal stents.

AIM: To determine the efficacy the value of self-expandable metal stents in patients with benign biliary strictures caused by chronic pancreatitis. METHOD: 61 patients with symptomatic common bile duct strictures caused by alcoholic chronic pancreatitis were treated by interventional endoscopy. RESULTS: Initial endoscopic drainage was successful in all cases, with complete resolution of obstructive jaundice. Of 45 patients who needed definitive therapy after a 12-months interval of interventional endoscopy, 12 patients were treated with repeated plastic stent insertion (19.7%) or by surgery (n = 30; 49.2%). In 3 patients a self-expandable metal stent was inserted into the common bile duct (4.9%). In patients treated with metal stents, no symptoms of biliary obstruction occurred during a mean follow-up period of 37 (range 18-53) months. The long-term success rate of treatment with metal stents was 100%. CONCLUSIONS: Endoscopic drainage of biliary obstruction by self-expandable metal stents provides excellent long-term results. To identify patients who benefit most from self-expandable metal stent insertion, further, prospective randomized studies are necessary.

F-18 Fluorodeoxyglucose (FDG) and C-Reactive Protein (CRP).

This study was done to evaluate if the accuracy of FDG-PET concerning the differentiation of benign and malignant pancreatic masses differs for patients with and without elevated C-Reactive Protein (CRP). Three hundred-four patients (165 neoplasms, 98 chronic pancreatitis, and 41 benign lesions) received FDG-PET of the abdomen prior to planned resective surgery. CRP was unknown, normal, and elevated with 211, 71, and 22 patients, respectively. For differentiation of benign and malignant lesions, specificity was 87% for patients with unknown or normal CRP, and it was 40% for patients with elevated CRP (P < 0.01). Thirty-five percent of those patients with both a positive PET and elevated CRP were false positive. On the contrary, sensitivity was slightly higher in the group with elevated CRP (92% vs. 80%, NS). FDG-PET is a sensitive and specific test for patients with normal CRP, however, FDG-PET may be false positive if CRP is elevated. Proper patient selection is therefore important. CRP or other parameters indicative of active inflammation appear useful adjuncts for the interpretation of increased FDG-accumulation.