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Background: Genetic alterations within the epidermal growth factor receptor (EGFR) pathway, including KRAS mutations, have been demonstrated to be associated with response to EGFR inhibitors like cetuximab in colorectal cancers. Mutations in the KRAS gene have been found in 70-90% of pancreatic cancers. Unfortunately, the addition of cetuximab to chemotherapy did not increase response or survival in patients with advanced pancreatic cancer in phase II and phase III studies. The aim of this study was to evaluate the relationship between KRAS mutations and response or survival in patients with metastatic pancreatic cancer treated with cetuximab plus chemotherapy. Methods: Within a multicenter phase II trial, 64 patients with metastatic pancreatic cancer were treated with cetuximab in combination with gemcitabine and oxaliplatin until disease progression. Analyses of the EGFR pathway, including KRAS mutations, could be performed in 25 patients. Analyses were carried out following microdissection of the tumor. Results: Fourteen (56%) of the 25 patients examined harbored a point mutation in codon 12 of the KRAS gene. No differences between the groups were noted in median progression-free survival (104 days in KRAS wild-type patients vs. 118 days in patients with KRAS mutations). Overall survival was longer in wild-type patients compared to patients with KRAS mutations (263 vs. 162 days), but the difference did not reach statistical significance. A further analysis of our clinical phase II trial showed that the presence of a rash was significantly correlated with overall survival. Conclusions: KRAS mutation in codon 12 may be associated with reduced survival compared to KRAS wild type. The role of KRAS mutations for cetuximab therapy in pancreatic cancer warrants further investigation in larger trials to exclude an epiphenomenon. Furthermore, the development of a rash is indicative of clinical benefit. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: The aim of the present study was to evaluate the 6-month survival rate of patients with inoperable or metastatic pancreatic cancer treated with irinotecan and gemcitabine plus 5-fluorouracil. Secondary efficacy end points included response rate, time to progression (TTP), overall survival (OS) and toxicity. Patients and Methods: 30 patients with histologically proven pancreatic carcinoma and at least one bidimensionally measurable lesion were enrolled. Of the patients, 83% had metastatic and 17% locally advanced disease. One cycle, lasting 21 days, comprised treatment on days 1 and 8 consisting of 75 mg/m2 irinotecan i.v. for 90 min, 1,000 mg/m2 gemcitabine i.v. for 30 min and 2,000 mg/m2 fluorouracil (5-FU) for 24 h. A total of six cycles was planned for each patient. Results: 28 patients competed at least one treatment cycle and were therefore assessable for efficacy, and 75% of them achieved the primary end point of the study (survival after 6 months). One-year survival was 25%. Stabilization (partial response and stable disease) was observed in 35.7% (10/28) and partial remission in 7.1% (2/28). The objective response rate was 7.1% (2/28) after completion of the six cycles. Median TTP was 3.4 months (1.2–11.5), and median OS was 8.3 months (2.1–36.2). Regarding severe hematological toxicities, only neutropenia was observed (grade 3 20.7%, 6/29, and grade 4 3.5%, 1/29). In spite of anti-emetic supportive care, nausea affected most of the patients: 79.3% (23/29). Grade 3 vomiting was observed in 4 of the 29 patients (13.8%) and grade 4 in 1 patient (3.5%). Only 1 patient experienced diarrhea grade 3 (3.5%) and 1 patient (3.5%) suffered from a grade 3 peroneal nerve enervation. Conclusions: A combination of irinotecan, gemcitabine and 5-FU is feasible and shows considerable efficacy in patients with inoperable or metastatic pancreatic cancer. Due to its low toxicity, this combination might be an interesting cytotoxic regimen in addition to targeted therapies. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract Introduction Progressive multifocal leukoencephalopathy is an opportunistic infection occurring in patients with severe cellular immunodeficiency. This case highlights the role of cellular immunodeficiency in the reactivation of John Cunningham virus in a case of an early stage plasmacytoma. Case presentation A 76-year-old Caucasian woman presented with progressive left-sided hemiparesis, accompanied by hypoesthesia, hypoalgesia and neuropsychological symptoms. Magnetic resonance imaging demonstrated new hyperattenuating lesions in the right thalamus and left-sided subcortically. A polymerase chain reaction test revealed 4500 copies of John Cunningham virus-deoxyribonucleic acid/ml in cerebrospinal fluid. Human immunodeficiency virus infection was ruled out. A bone marrow biopsy showed an early stage immunoglobulin G-kappa plasmacytoma. Cidofovir (5mg/kg) weekly for three weeks was started. A significant improvement of her neuropsychological symptoms was achieved, but motor system and sensory symptoms did not change. Conclusions This case shows a rapid course of progressive multifocal leukoencephalopathy with severe residual deficits. In the diagnostic workup of all patients with atypical neurologic symptoms or immunodeficiency, progressive multifocal leukoencephalopathy should be included as a differential diagnosis.

Background: Since 2010, combination therapy with gemcitabine and cisplatin is the standard treatment for patients with biliary tract cancer (BTC) based on the ABC-02 trial. However, treatment after first-line progression is less clearly defined. We therefore retrospectively analyzed the efficacy of a 3-drug chemotherapy regimen in patients with advanced BTC., Methods: Patients with advanced BTC treated with palliative chemotherapy between April 2000 and October 2005 at Regensburg University Hospital were reviewed retrospectively. We analyzed the efficacy and safety of an institutional standard 3-drug regimen consisting of irinotecan, gemcitabine and 5-FU (IGF). One cycle, lasting 21 days, included applications on days 1 and 8 consisting of 75 mg/m2 irinotecan i.v. for 90 min, 1,000 mg/m2 gemcitabine i.v. for 30 min and 2,000 mg/m2 fluorouracil (5-FU) for 24 h., Results: A total of 12 histologically confirmed cases with gallbladder cancer and intrahepatic BTC were reviewed. Fifty percent of the patients (6/12) had been pretreated with other chemotherapies. Median progression-free survival was 9.4 months (1.5-21.5) and median overall survival was 17.2 months (2.5-24.3). Only neutropenia (8%) was observed as an NCI-CTC grade 3 toxicity. Anemia and leucopenia grades 1 and 2 were the most common side effects., Conclusions: The combination of IGF shows a promising survival benefit with manageable toxicity in patients with advanced BTC. Therefore, this regimen seems to be a feasible second-line treatment option for patients with rapid progression under first-line therapy with gemcitabine and cisplatin and with a good performance status., (© 2016 S. Karger AG, Basel.)

Purpose: Clinical relevance of colonic bowel wall thickening seen on abdominal CT scans is unknown. Recommendations for further diagnostic procedures are lacking. The aim of this retrospective study was to evaluate detecting of bowel wall thickening on CT scan and findings that were seen in case of endoscopical evaluation., Methods: The radiological database was retrospectively reviewed for all reports of CT scans from 2003 to 2009 at the University Hospital Regensburg, Germany. Patients with underlying diseases for suspected bowel wall thickening were excluded., Results: Sixty-two patients with bowel wall thickening were detected. Twenty-one percent (13/62) had generalized bowel wall thickening. In 58%, bowel wall thickening was limited to one segment of the colon (36/62), mostly left sided (25/62). Forty-four percent of patients (27/62) were sent to endoscopy. In 15% (4/27), malignancy was suspected, and it could be histologically confirmed in two patients. Nineteen percent (5/27) had normal endoscopy, and 67% (18/62) showed benign findings., Conclusion: Colonic bowel wall thickening is not a common finding on CT scan in this study. Consequential endoscopic evaluation was performed in less than 50% of patients. Pathological findings were detected in 80% of these patients. We recommend endoscopical evaluation if bowel wall thickening is reported on CT scan.