Treatment of chronic HCV genotype 1 infection with telaprevir: a Bayesian mixed treatment comparison of fixed-length and response-guided treatment regimens in treatment-naïve and –experienced patients

BACKGROUND: Telaprevir (TVR) has been approved for response-guided-therapy (RGT) of chronic hepatitis C (HCV) genotype-1-infection in treatment-naïve and –experienced patients. In RGT-regimens patients that did not achieve extended rapid-virological-response (eRVR) within the first 4–12 weeks undergo treatment for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a fixed-duration regardless of their RVR. METHODS: This systematic review and Bayesian mixed-treatment-comparison (MTC) aimed to compare the efficacy and safety of standard-therapy with pegylated-interferon-α/ribavirin (Peg-IFN-α/RBV (48 weeks), group A), FLT with TVR, Peg-IFN-α/RBV for 12 weeks with a long (+36 weeks, group B) or short (+12 weeks, group C) tail of Peg-IFN-α/RBV treatment, and RGT with 12 weeks of TVR, Peg-IFN-α/RBV followed by 12 weeks of Peg-IFN-α/RBV (group D) or no therapy (group E). RESULTS: We identified seven randomized controlled trials including 3505 patients. Compared to standard-treatment (group A), treatment-naïve patients allocated to groups B, C, and D were significantly more likely to achieve sustained-virological-response (SVR, odds ratios (OR): B vs. A 3.5 (credibility interval [CrI] 2.2-5.4), C vs. A 3.0 (CrI 1.8-4.9), D vs. A 3.4 (CrI 2.5-4.6)). Treatment-experienced patients achieved increased SVR rates when they were treated in group B (OR: 8.2 (CrI 5.0-13.5)), C (OR 7.0 (CrI 3.9-12.8)), or simulated group D (OR 8.2 (CrI 4.3-15.3)). Patients treated with short RGT (simulated group E) did also have a significant improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6-8.2)), whereas the effect was not significant in treatment-naïve patients (OR E vs. A 1.6 (CrI 0.9-2.7)). CONCLUSION: Long FLT and RGT regimens are useful treatment options for HCV-genotype-1 in both treatment-naïve and -experienced patients. A short 24-weeks FLT regimen does not seem to be inferior and should further be evaluated in clinical trials to reduce side effects and costs of treatment

Ten Years of Treatment with 400 mg Imatinib per Day in a Case of Advanced Gastrointestinal Stromal Tumor

Imatinib mesylate, as treatment for gastrointestinal stromal tumors (GIST), has dramatically changed the prognosis for survival – not only because it is efficacious, but also because it attracted attention to this malignant disease. GIST is now a well-known disease entity and a paradigm for targeted therapies in malignant diseases. A now 74-year-old patient presented with recurrence of a primary duodenal GIST (initial diagnosis and primary resection in 1998; diameter 10 cm, KIT exon 11 mutation, PM V559D) and liver metastasis after a second surgical resection was performed in 2000. Conventional chemotherapy with adriamycin and ifosfamide failed to control growth of the relapsed tumor and liver metastasis. In July 2001, compassionate use of imatinib was started. Tumor regression was observed at continuous follow-ups (every 2 months for the first 6 months, and 6 months thereafter) and persisted until now. The patient's physical performance has remained in good condition. Side effects consisted of periorbital edema and sudden muscle cramps of toes and fingers, pain of bones and joints, an intentional tremor, a paler color of the skin, as well as a slight anemia. Imatinib is the first orally administered anticancer drug. Our case shows that a sustained response is possible with continuous therapy over a long time, if the drug is well tolerated. This implies a high compliance of the patient and suggests that resistance to imatinib does not have to develop. Exon 11 (point) mutation might not only represent a positive predictor for imatinib response in general, but especially for imatinib response on long-term

Needle biopsy through the abdominal wall for the diagnosis of gastrointestinal stromal tumour - Does it increase the risk for tumour cell seeding and recurrence?

Purpose: Preoperative percutaneous transabdominal wall biopsy may be considered to diagnose gastrointestinal stromal tumour (GIST) and plan preoperative treatment with tyrosine kinase inhibitors when an endoscopic biopsy is not possible. Hypothetically, a transabdominal wall biopsy might lead to cell seeding and conversion of a local GIST to a disseminated one. We investigated the influence of preoperative needle biopsy on survival outcomes. Methods: We collected the clinical data from hospital case records of the 397 patients who participated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) randomised trial and who had a transabdominal fine needle and/or core needle biopsy carried out prior to study entry. The SSG XVIII/AIO trial compared 1 and 3 years of adjuvant imatinib in a patient population with a high risk of GIST recurrence after macroscopically radical surgery. The primary end-point was recurrence-free survival (RFS), and the secondary end-points included overall survival (OS). Results: A total of 47 (12.0%) out of the 393 patients with data available underwent a percutaneous biopsy. No significant difference in RFS or OS was found between the patients who underwent or did not undergo a percutaneous biopsy either in the entire series or in subpopulation analyses, except for a statistically significant RFS advantage for patients who had a percutaneous biopsy and a tumour >= 10 cm in diameter. Conclusion: A preoperative diagnostic percutaneous biopsy of a suspected GIST may not increase the risk for GIST recurrence in a patient population who receive adjuvant imatinib after the biopsy. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

High chromosomal instability in adenocarcinoma of the ileum arising from multifocal gastric heterotopia with gastritis cystica profunda

Adenocarcinoma of the small intestine arising from heterotopic gastric mucosa is extremely rare. In this report, we present the case of a 68-year-old woman who complained of abdominal pain, weight loss and subileus. Gross examination of resected small bowel revealed multiple flat polypous lesions with cysts in the ileal submucosa, one of which containing an ulcerated, stenosing tumour. On microscopic examination, an adenocarcinoma of the ileum arising from multifocal gastric heterotopia with secondary gastritis cystica profunda was diagnosed. Comparative genomic hybridization of the adenocarcinoma revealed chromosomal gains at 1q, 3q, 5p, 8q, 11p, 12p, 13q and losses at Xp, 4q, 8p, 10p, 14q, 17p, 20p, compatible with a high degree of genomic instability

Gelungene Versöhnung - unsichere Zukunft? Zur Raison d'être der deutsch-französischen Beziehungen in der neuen Europäischen Union

"Die Frage nach der Notwendigkeit und Legitimität der deutsch-französischen Sonderbeziehung im Europa der 25 stellt sich nach der Ablehnung der Europäischen Verfassung in Frankreich und den Niederlanden sowie dem vorläufigen Scheitern der EU-Finanzverhandlungen umso dringlicher. Mit der Rolle und Perzeption der deutsch-französischen Zusammenarbeit in der erweiterten Europäischen Union setzte sich im Juni ein internationales Kolloquium mit dem Titel 'Gelungene Versöhnung – unsichere Zukunft?' in Erinnerung an Joseph Rovan auseinander, dessen Tagungsergebnisse das Dossier dokumentiert. Neben Beiträgen zur Bewertung der aktuellen Krise und den Herausforderungen an Deutschland und Frankreich, analysieren (weitere Beiträge) den Blick der anderen Mitgliedstaaten auf das 'couple'." (Autorenreferat

Religion, Identity and Radicalisation

The current rise in the numbers of young British Muslims travelling from the UK to Syria has raised a number of questions about the UK Government’s counter-terrorism strategy and policy. Within the current discourse on radicalisation and Syria, listening to the voices of young British Muslims is crucial, if the UK Government, the police and other key stakeholders are serious about preventing the escalation of young people going out to fight in Syria. This article makes an important contribution to helping us better understand young British Muslims’ perceptions of the crisis in Syria and offers policy makers some thoughts on how best to engage young people in the debate on Syria without demonising them or stereotyping them as ‘suspects’

Effect of KIT and PDGFRA Mutations on Survival in Patients With Gastrointestinal Stromal Tumors Treated With Adjuvant Imatinib An Exploratory Analysis of a Randomized Clinical Trial

IMPORTANCE Little is known about whether the duration of adjuvant imatinib influences the prognostic significance of KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations. OBJECTIVE To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in patients with gastrointestinal stromal tumors (GISTs) treated with surgery and adjuvant imatinib. DESIGN, SETTING, AND PARTICIPANTS This exploratory study is based on the Scandinavian Sarcoma Group VIII/Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) multicenter clinical trial. Between February 4, 2004, and September 29, 2008, 400 patients who had undergone surgery for GISTs with a high risk of recurrence were randomized to receive adjuvant imatinib for 1 or 3 years. Of the 397 patients who provided consent, 341 (85.9%) had centrally confirmed, localized GISTs with mutation analysis for KIT and PDGFRA performed centrally using conventional sequencing. During a median follow-up of 88 months (completed December 31, 2013), 142 patients had GIST recurrence. Data of the evaluable population were analyzed February 4, 2004, through December 31, 2013. MAIN OUTCOMES AND MEASURES The main outcome was RFS. Mutations were grouped by the gene and exon. KIT exon 11 mutations were further grouped as deletion or insertion-deletion mutations, substitution mutations, insertion or duplication mutations, and mutations that involved codons 557 and/or 558. RESULTS Of the 341 patients (175 men and 166women; median age at study entry, 62 years) in the 1-year group and 60 years in the 3-year group), 274 (80.4%) had GISTs with a KIT mutation, 43 (12.6%) had GISTs that harbored a PDGFRA mutation, and 24 (7.0%) had GISTs thatwere wild type for these genes. PDGFRA mutations and KIT exon 11 insertion or duplication mutations were associated with favorable RFS, whereas KIT exon 9 mutations were associated with unfavorable outcome. Patients with KIT exon 11 deletion or insertion-deletion mutation had better RFS when allocated to the 3-year group compared with the 1-year group (5-year RFS, 71.0% vs 41.3%; P CONCLUSIONS AND RELEVANCE Patients with KIT exon 11 deletion mutations benefit most from the longer duration of adjuvant imatinib. The duration of adjuvant imatinib modifies the risk of GIST recurrence associated with some KIT mutations, including deletions that affect exon 11 codons 557 and/or 558.Peer reviewe