Based on several case-control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit-model and the Kaplan-Meier method. Twenty-three of 479 (prevalence 4.8%, 95% CI 3.1-7.1) patients reported at least 1 first-degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3-2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9 -3.5) and by standardized interviews of first-degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1-5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1-3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer.

The vast majority of colorectal cancer-related deaths can be attributed to metastatic spreading of the disease. Therefore, deciphering molecular mechanisms of metastatic dissemination is a key prerequisite to improve future treatment options. With this aim, we took advantage of different colorectal cancer cell lines and recently established primary cultures enriched in colon cancer stem cells, also known as tumor-initiating cells (TIC), to identify genes and miRNAs with regulatory functions in colorectal cancer progression. We show here that metastasis-derived TICs display increased capacity for self-renewal, TGFβ signaling activity, and reduced expression of the miR-371∼373 cluster compared with nonmetastatic cultures. TGFβ receptor 2 () and aldehyde dehydrogenase A1 () were identified as important target genes of the miR-371∼373 cluster. In addition, TGFBR2 repression, either by direct knockdown or indirectly via overexpression of the entire miR-371∼373 cluster, decreased tumor-initiating potential of TICs. We observed significantly reduced self-renewal activity as well as lowered tumor initiation and metastatic outgrowth capacity following stable overexpression of the miR-371∼373 cluster in different colon TIC cultures. Inhibitor of DNA binding 1 (ID1) was affected by both TGFBR2 and miR-371∼373 cluster alterations. Functional sphere and tumor formation as well as metastatic dissemination assays validated the link between miR-371∼373 and ID1. Altogether, our results establish the miR-371∼373/TGFBR2/ID1 signaling axis as a novel regulatory mechanism of TIC self-renewal and metastatic colonization. These findings establish the miR-371∼373/TGFBR2/ID1 signaling axis as a novel mechanism regulating self-renewal of tumor-initiating cell and metastatic colonization, potentially opening new concepts for therapeutic targeting of cancer metastasis. http://cancerres.aacrjournals.org/content/canres/78/14/3793/F1.large.jpg .

Laparoscopic treatment of type 4 hiatal hernia is safe. With respect to the quality of life, anterior hemifundoplication is highly effective.

In view of the described complication, there is still considerable controversy regarding the routine use of mesh. To increase safety, a composite mesh should be preferred.

Laparoscopic sleeve gastrectomy (LSG) was initially introduced for super-obese patients in a two-step concept in order to reduce the perioperative risk. Many years before a very similar technique - the Magenstrasse and Mill (M & M) operation - was developed by Johnston in Leeds / UK as a "more physiological" bariatric procedure with acceptable weight loss, while preserving gastric emptying mechanisms and thus minimising possible side-effects such as vomiting, dumping and diarrhoea, which are common complications of gastric bypass procedures. The following manuscript analyses the current literature and our own preliminary results and parallels publications of the M & M procedure. Until now numerous modifications (e. g., bougie size and residual volume, stapler technique, use of buttress mate-rial) have been reported. However, reported -morbidity and mortality rates were equal to those of gastric banding and gastric bypass (RYGB). In conclusion, laparoscopic sleeve gastrectomy (LSG) has now proven to be as effective as the RYGB for weight loss over a three-year period. Control of hunger and feeling of fullness are -reported to be superior compared to gastric band-ing. Laparoscopic sleeve gastrectomy is no longer an experimental procedure. It should be accepted as one of the effective standard procedures for surgical treatment of morbid obesity.