Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: Epidemiological changes in Germany

AIM:To study the epidemiologic changes of gastroenteropancreatic neuroendocrine tumors(GEP-NET)in Germany,we analyzed two time periods 1976-1988 and1998-2006.METHODS:We evaluated epidemiological data of GEP-NET from the former East German National Cancer Registry(DDR Krebsregister,1976-1988)and its successor,the Joint Cancer Registry(GKR,1998-2006),which was founded after German reunification.Due to a particularly substantial database the epidemiological data from the federal states of Mecklenburg-Western Pomerania,Saxony,Brandenburg and Thuringia,covering a population of more than 10.8 million people,were analyzed.Survival probabilities were calculated using life table analysis.In addition,GEP-NET patients were evaluated for one or more second(non-GEP-NET)primary malignancies.RESULTS:A total of 2821 GEP neuroendocrine neoplasms were identified in the two registries.The overall incidence increased significantly between 1976 and2006 from 0.31(per 100.000 inhabitants per year)to2.27 for men and from 0.57 to 2.38 for women.In the later period studied(2004-2006),the small intestine was the most common site.Neuroendocrine(NE)neoplasms of the small intestine showed the largest absolute increase in incidence,while rectal NE neoplasms exhibited the greatest relative increase.Only the incidence of appendiceal NET in women showed little change between 1976 and 2006.Overall survival of patients varied for sex,tumor site and the two periods studied but improved significantly over time.Interestingly,about 20%of the GEP-NET patients developed one or more second malignancies.Their most common location was the gastrointestinal tract.GEP-NET patients without second malignancies fared better than those with one or more of them.CONCLUSION:The number of detected GEP-NET increased about 5-fold in Germany between 1976 and2006.At the same time,their anatomic distribution changed,and the survival of GEP-NET patients improved significantly.Second malignancies are common and influence the overall survival of GEP-NET patients.Thus,GEP-NET warrant our attention as well as intensive research on their tumorigenesis.

Management of early gastrointestinal neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) of the stomach, duo- denum, appendix or rectum that are small (≤ 1 cm) and well differentiated can be considered "early" tumors, since they generally have a (very) good prognosis. In the new WHO classification of 2010, these neoplasms are called neuroendocrine tumors/ carcinoids (NETs), grade (G) 1 or 2, and distinguished from poorly differentiated neuroendocrine carcinomas (NECs), G3. NETs are increasing, with a rise in the age-adjusted incidence in the U.S.A. by about 700 % in the last 35 years. Improved early detection seems to be the main reason for these epidemiological changes. Both the better generalavailability of endoscopy, and imaging techniques, have led to a shift in the discovery of smaller-sized (≤ 10-20 mm) intestinal NETs/carcinoids and earlier tumor stages at diagnosis. Endoscopic screening is therefore effective in the early diagnosis, not only of colorectal adenocarcinomas, but also of NETs/carcinoids. Endoscopic removal, followed up with endoscopic surveillance is the treatment of choice in NETs/carcinoids of the stomach, duodenum and rectum that are ≤ 10 mm in size, have a low proliferative activity (G1), do not infiltrate the muscular layer and show no angioinvasion. In all the other intestinal NENs, optimal treatment generally needs surgery and/or medical therapy depending on type, biology and stage of the tumor, as well as the individual situation of the patient.

Neuroendocrine tumors of the small bowels are on the rise:Early aspects and management

Neuroendocrine tumors of the small bowel are on the rise. In the US they have increased by 300%-500% in the last 35 years. At the same time their prognosis is much improved. Today,most neuroendocrine tumors (NETs) of the duodenum are detected "incidentally" and therefore recognized at an early stage. Duodenal NETs which are well differentiated,not larger than 10 mm and limited to the mucosa/submucosa can be endoscopically resected. The management of duodenal NETs ranging between 10 and 20 mm needs an interdisciplinary discussion. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is recommended for well-differentiated duodenal NET tumors greater than 20 mm,for localized sporadic gastrinomas (of any size) and for localized poorly differentiated NE cancers. Surgery is recommended for any ileal NET. Advanced ileal NETs with a carcinoid syndrome are treated with longacting somatostatin analogs. This treatment significantly improves (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management,tumor biology,type,localization and stage of the neoplasm,as well as the patient's individual circumstances have to be taken into account.

Single-port versus multi-port cholecystectomy for patients with acute cholecystitis: a retrospective comparative analysis

BACKGROUND: Trans-umbilical single-port laparoscopic cholecystectomy for chronic gallbladder disease is becoming increasingly accepted worldwide. But so far, no reports exist about the challenging single-port surgery for acute cholecystitis. The objective of this study was to describe our experience with single-port cholecystectomy in comparison to the conventional laparoscopic technique. METHODS: Between August 2008 and March 2010, 73 patients with symptomatic gallbladder disease and histopathological signs of acute cholecystitis underwent laparoscopic cholecystec- tomy at our institution. Thirty-six patients were operated on with the single-port technique (SP group) and the data were compared with a control group of 37 patients who were treated with the multi-port technique (MP group). RESULTS: The mean age in the SP group was 61.5 (range 21-81) years and in the MP group was 60 (range 21-94) (P=0.712). Gender, ASA status and BMI were not significantly different. The number of white blood cells was different before [SP: 9.2 (range 2.8-78.4); MP: 13.2 (range 4.4-28.6); P=0.001] and after the operation [SP: 7.8 (range 3.5-184.8); MP: 11.1 (range 5-20.8); P=0.002]. Mean operating time was 88 (range 34-174) minutes in the SP group vs 94 (range 39-209) minutes in the MP group (P=0.147). Four patients (5%) required conversion to an open procedure (SP: 1; MP: 3; P=0.320). During the follow- up period of 332 (range 29-570) days in the SP group and 428 (range 111-619) days in the MP group (P=0.044), eleven (15%) patients developed postoperative complications (P=0.745) and two patients in the SP group required reoperation (P=0.154). CONCLUSIONS: Trans-umbilical single-port cholecystectomy for beginning acute cholecystitis is feasible and the complicationrate is comparable with the standard multi-port operation. In spite of our good results, these operations are difficult to perform and should only be done in high-volume centers for laparoscopic surgery with experience in single-port surgery.

Managementofearlyasymptomaticgastrointestinalstromaltumorsofthe stomach

Gastrointestinal stromal tumors(GIST) are the most common mesenchymal tumors of the digestive tract. Approximately two thirds of clinically manifest tumors occur in the stomach, nearly one third in the small bowel, and the rest in the colorectal region with a few cas-es in the esophagus. GIST originate within the smooth muscle layer in the wall of the tubular gastrointestinal tract and grow mostly toward the serosa, far less often toward the mucosa. In the latter case, ulceration may develop and can cause gastrointestinal bleeding as the cardinal symptom. However, most GIST of the stomach are asymptomatic. They are increasingly detected incidentally as small intramural or submucosal tumors during endoscopy and particularly during endoscopic ultra-sound. Epidemiological and molecular genetic findings suggest that early asymptomatic GIST of the stomach(< 1 cm) show self-limiting tumorigenesis. Thus, early(< 1 cm) asymptomatic gastric GIST(synonym: micro-GIST) are found in 20%-30% of the elderly. The mostlyelderly people with early gastric GIST have an excellent GIST-specific prognosis. Patients with early GIST of the stomach can therefore be managed by endoscopic sur-veillance.

Human iPSC-derived iMSCs improve bone regeneration in mini-pigs

Autologous bone marrow concentrate(BMC)and mesenchymal stem cells(MSCs)have beneficial effects on the healing of bone defects.To address the shortcomings associated with the use of primary MSCs,induced pluripotent stem cell(iPSC)-derived MSCs(iMSCs)have been proposed as an alternative.The aim of this study was to investigate the bone regeneration potential of human iMSCs combined with calcium phosphate granules(CPG)in critical-size defects in the proximal tibias of mini-pigs in the early phase of bone healing compared to that of a previously reported autograft treatment and treatment with a composite made of either a combination of autologous BMC and CPG or CPG alone.iMSCs were derived from iPSCs originating from human fetal foreskin fibroblasts(HFFs).They were able to differentiate into osteoblasts in vitro,express a plethora of bone morphogenic proteins(BMPs)and secrete paracrine signaling-associated cytokines such as PDGF-AA and osteopontin.Radiologically and histomorphometrically,HFF-iMSC+CPG transplantation resulted in significantly better osseous consolidation than the transplantation of CPG alone and produced no significantly different outcomes compared to the transplantation of autologous BMC+CPG after 6 weeks.The results of this translational study imply that iMSCs represent a valuable future treatment option for load-bearing bone defects in humans.