Background: Although as many as 10% of pancreatic cancer cases may have an inherited component, familial pancreatic cancer has not been linked to defects in any specific gene. Some studies have shown ...that families with germline mutations in the breast cancer susceptibility gene BRCA2 have an increased risk of breast and ovarian cancers, as well as a modestly increased risk of pancreatic cancer. To study these relationships in more detail, we examined whether BRCA2 germline mutations are associated with familial pancreatic cancer. Methods: We identified 26 European families in which at least two first-degree relatives had a histologically confirmed diagnosis of pancreatic ductal adenocarcinoma. We sequenced genomic DNA isolated from peripheral blood lymphocytes obtained from participating family members to identify germline mutations in BRCA2. Results: Three (12%, exact 95% confidence interval CI = 2% to 30%) families carried germline frameshift mutations in the BRCA2 gene that are predicted to result in a truncated BRCA2 protein. Two additional families harbored mutations previously designated as unclassified variants of BRCA2. Thus, 19% (exact 95% CI = 7% to 39%) of the families in our study had either a frameshift mutation or an unclassified variant of BRCA2. None of the families in our study met the criteria for familial breast or ovarian cancer. Conclusions: Our data support an important role for BRCA2 germline mutations in a subpopulation of families with familial pancreatic cancer. BRCA2 mutation analysis should be included in molecular genetic testing and counseling strategies in families with at least two first-degree relatives affected with ductal adenocarcinoma of the pancreas.
The prevalence of cervical heterotopic gastric mucosa (HGM) of the proximal oesophagus differs widely between studies, perhaps due to examination conditions during endoscopy. In this study we aimed ...to determine whether narrow band imaging (NBI) or high definition (HD) imaging improves detection of HGM. Possible factors of influence for HGM detection, in particular setting (position, timing, in-/out-patient), examination time and sedation parameters, were analysed.
Retrospective analysis of 641 consecutive patients who underwent an oesophagogastroduodenoscopy (EGD) by the same, substantially experienced endoscopist between June 2011 and August 2013. The type of endoscope was randomly assigned to patients.
A total of 85 patients showed HGM with an overall prevalence of 13.3 %. The detection rate in the HD-NBI group was 18/127 (14.2 %) and in the HD white light (HDWL) group, 15/104 (14.4 %, p = 0.957). The detection rate between standard definition white light (SDWL) endoscopy (52/410, 12.7 %) and HD endoscopy did not differ significantly (33/231, 14.3 %, p = 0.566). Setting, sedation dosage and examination times were equally distributed between study groups. The indication of dysphagia (11.8 % vs. 2.4 % with p = 0.000, respectively) and dyspepsia (19.1 % vs. 10.8 %, p = 0.047, respectively) occurred significantly more often in HGM patients than in the control group. There was no difference in the detection rate depending on HGM size.
The prevalence of HGM in the upper EGD is high and does not differ significantly between the study groups of SDWL, HDWL and HD-NBI under equivalent conditions.
This randomized phase II trial investigated the efficacy and safety of capecitabine/oxaliplatin (CapOx) plus bevacizumab and dose-modified capecitabine/irinotecan (mCapIri) plus bevacizumab as ...first-line therapy in patients with metastatic colorectal cancer (mCRC).
Patients received bevacizumab 7.5 mg/kg with oxaliplatin 130 mg/m2/day 1 plus capecitabine 1000 mg/m2 bid/days 1–14 or with irinotecan 200 mg/m2/day 1 plus capecitabine 800 mg/m2 bid/days 1–14 both every 21 days. The primary end point was 6 months progression-free survival (PFS).
A total of 255 patients were enrolled. The intent-to-treat population comprised 247 patients (CapOx–bevacizumab: n = 127; mCapIri–bevacizumab: n = 120). The six-month PFS rates were 76% (95% CI, 69%–84%) and 84% (95% CI, 77%–90%). Median PFS and OS were 10.4 months (95% CI, 9.0–12.0) and 24.4 months (95% CI, 19.3–30.7) with CapOx–bevacizumab, and 12.1 months (95% CI, 10.8–13.2) and 25.5 months (95% CI, 21.0–31.0) with mCapIri–bevacizumab. Grade 3/4 diarrhea as predominant toxic effect occurred in 22% of patients with CapOx–bevacizumab and in 16% with mCapIri–bevacizumab.
Both, CapOx–bevacizumab and mCapIri–bevacizumab, show promising activity and an excellent toxic effect profile. Efficacy is in the range of other bevacizumab-containing combination regimen although lower doses of irinotecan and capecitabine were selected for mCapIri.
Purpose
To identify key factors for the best practice of knowledge transfer from high-income settings to low- and middle-income settings.
Results
Interactive sessions led to the identification of ...European learnings that can and should be shared beyond Europe. Furthermore, methods were characterised which may lead to successful knowledge transfer with subsequent quality improvement.
Conclusion
To ensure successful implementation of knowledge and new methods, political support is extremely important. A strong focus should be an improvement of collaboration and network development. Rehabilitation, early and late pallative care, cost effectiveness and long-term follow-up are priorities. Limitations are budget constraints which limit the execution of NCCPs.
The olfactory receptor (OR) family was found to be expressed mainly in the nasal epithelium. In the last two decades members of the OR family were detected to be functional expressed in different ...parts of the human body such as in liver, prostate or intestine cancer cells. Here, we detected the expression of several ORs in the human chronic myelogenous leukemia (CML) cell line K562 and in white blood cells of clinically diagnosed acute myeloid leukemia (AML) patients by RT-PCR and next-generation sequencing. With calcium-imaging, we characterized in greater detail the cell biological role of one OR (OR2AT4) in leukemia. In both cell systems, the OR2AT4 agonist Sandalore-evoked strong Ca(2+) influx via the adenylate cyclase-cAMP-mediated pathway. The OR2AT4 antagonist Phenirat prevented the Sandalore-induced intracellular Ca(2+) increase. Western blot and flow cytometric experiments revealed that stimulation of OR2AT4 reduced the proliferation by decreasing p38-MAPK phosphorylation and induced apoptosis via phosphorylation of p44/42-MAPK. Furthermore, Sandalore increased the number of hemoglobin-containing cells in culture. We described for the first time an OR-mediated pathway in CML and AML that can regulate proliferation, apoptosis and differentiation after activation. This mechanism offers novel therapeutic options for the treatment of AML.
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