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Medical treatment of neuroendocrine tumours (NETs) has drawn a lot of attention due to the recent demonstration of efficacy of several drugs on progression-free survival, including somatostatin analogs, small tyrosine kinase inhibitors and mTOR inhibitors (or rapalogs). The latter are approved as therapeutic agents in advanced pancreatic NETs and have been demonstrated to be effective in different types of NETs, with variable efficacy due to the development of resistance to treatment. Early detection of patients that may benefit from rapalogs treatment is of paramount importance in order to select the better treatment and avoid ineffective and expensive treatments. Predictive markers for therapeutic response are under intensive investigation, aiming at a tailored patient management and more appropriate resource utilization. This review summarizes the available data on the tissue, circulating and imaging markers that are potentially predictive of rapalog efficacy in NETs.

Context Cystic dystrophy in heterotopic pancreas is a rare and serious condition. Diagnosis is difficult because of non-specific clinical manifestations and radiologic and endoscopic imaging are pivotal. Therapeutic management is still under debate. Case report We describe a case of cystic dystrophy of the duodenal wall in heterotopic pancreas complicated with chronic pancreatitis and pancreatic cystadenoma. Discussion Computed tomography and magnetic resonance are very useful in demonstrating the presence of cysts in a thickened duodenal wall but, for the most part, endoscopic ultrasonography is the most useful imaging examination. The choice of different therapeutic options is still under debate; although some authors have proposed a medical approach using octreotide or endoscopic treatment for selected patients, a pancreaticoduodenectomy is usually proposed for symptomatic patients. Conclusion When surgery is needed, a pancreaticoduodenectomy is preferred, reserving by-pass procedures for high risk patients. Because of the non-specific clinical manifestation and the very difficult diagnosis and therapeutic management, these patients should be studied and treated in specialized and dedicated centers.

Digestive and Liver Disease

Digestive and Livers Disease

The outcome of endoscopic biliary stent insertion for postoperative bile duct stenosis was retrospectively evaluated.Fifty-seven patients with biliary stenosis from laparoscopic cholecystectomy were included from February 1992 to January 2000. One to three stents were inserted for an average of 12.4 months, with stent exchange every three months to avoid cholangitis caused by obstruction.Successful stent insertion was achieved in 43/57 (75.4%) patients. Stent insertion failed in 10 patients with complete and four patients with incomplete biliary obstruction. Early complications occurred in four patients. Late complications occurred in 5/43 patients. Five patients experienced recurrence of stenosis.Endoscopic treatment should be the initial management of choice for postoperative bile duct stetiosis.

Thymomas are relatively slow-growing neoplasms that should be considered malignant tumours. When treated in the early stages, however, they have an excellent prognosis for long-term survival. Surgery, radiation therapy and chemotherapy all play a role in the management of these neoplasms. Surgery is the treatment of choice in thymoma patients and has become an increasingly accepted procedure in the treatment of myasthenia gravis (MG) since 1936, when thymectomy was performed for this disease for the first time. Improvement in myasthenic symptoms is nearly always observed following thymectomy, but the rates of complete remission vary from 7% to 63%. We have studied the potential preoperative factors predicting the evolution of MG.

Natural orifice transluminal endoscopic surgery (NOTES) is a new reality that is progressively gaining popularity in the scientific community. The aim of this study was to report the authors' experience with various peroral transgastric procedures performed on the porcine model. The technical difficulties and challenges that arose were also analyzed.Ten anesthetized pigs, divided into an acute (3) and a survival group (7) underwent the following procedures using a double channel endoscope: peritoneoscopy (10), cholecystectomy (6),splenectomy (3), and gastrojejunostomy (3).All the procedures were completed successfully. There was one complication related to the gastric wall incision. In the survival experiment group all pigs (4) submitted to biliare procedures made an uncomplicated recovery after a follow-up period of 2 weeks. Gastrojejunostomies (3) were instead graved by one technical failure (anastomosis disruption at post-mortem examination) and one case of mortality (premature euthanasia for evidences of sepsis). Complete gastric cleansing was impossible to achieve and overinflation was a common problem. The creation of gastro-enteric anastomoses was technically difficult with the current available devices.Transgastric endoscopic surgery is technically feasible in a porcine model. A new instrumentation is needed and could strongly help to overcome the technical difficulties highlighted. More extensive animal studies are mandatory in order to evaluate the benefits and the limitations of this new technique.

The outcome of endoscopic biliary stent insertion for postoperative bile duct stenosis was retrospectively evaluated.Fifty-seven patients with biliary stenosis from laparoscopic cholecystectomy were included from February 1992 to January 2000. One to three stents were inserted for an average of 12.4 months, with stent exchange every 3 months to avoid cholangitis caused by clogging.Successful stent insertion was achieved in 43/57 (75.4%) patients. Stent insertion failed in 10 patients with complete and in 4 patients with incomplete biliary obstruction. Early complications occurred in 4 patients. Late complications occurred in 5/43 patients. Five patients experienced recurrence of stenosis.Endoscopic treatment should be the initial management of choice for postoperative bile duct stenosis.

Carotid endarterectomy (CEA) has a positive effect on stroke free survival in patients with either symptomatic or asymptomatic severe carotid bifurcation stenosis. However, most trials have excluded elder patients. In addition, concerns have arisen regarding the benefits of CEA in the elderly population, especially in women. In this study, we performed an outcome analysis in patients undergoing CEA comparing those eighty and older to their younger counterparts. A total of 262 carotid operations were performed under local anaesthesia between 1998 and 2004; 76 (34%) were carotid reconstructions in 70 patients over 75 yr of age. Twenty patients (26%) presented with asymptomatic critical stenosis. Transient ischemic symptoms were the reason for presentation in 35 patients (46%). Progressive stroke was documented in two patients (3%) and a stroke with persisting neurological deficit was demonstrated in 19 cases (25%). Coronary artery disease was present in 47 patients (38%) and arterial hypertension in 55 (72%). Fifty-nine patients (84%) were classified as ASA group 3. Seventy-one thromboendarterectomies of the carotid bifurcation with direct closure were performed. Five patients had other types of reconstruction. Postoperative complications occurred in three patients. One had a transient neurological deficit and another a lethal stroke; the third patient died from myocardial infarction. The in-hospital mortality was 2.9%, which was not significantly higher than the results of the reconstructions in younger patients (1.5%). Surgery for carotid artery occlusive disease under local anaesthesia can be safely performed in selected patients of more than 75 yr of age.

A cDNA clone (p422) containing about 200 bp of coding sequences for steroid sulphatase (STS) has been isolated from a λgt11 expression library by antibody screening and has been assigned by mapping with a somatic cell hybrid panel and by in situ hybridization to Xp22.3; a localization coincident with the previously identified locus for STS expression. Although no significant hybridization of this clone to the Y chromosome was observed, p422 has been used to isolate a longer cDNA clone and genomic sequences which do recognize Y-specific restriction fragments. An abbreviated STS gene has been localized to Yqll.2. The coding sequences for the human enzyme shows little homology to sequences in mice.

Recently the NOTES approach has been extended to mediastinum by a transesophageal access and to the thorax by a transvescical endoscopic approach. The aim of this study was to assess the feasibility and the safety of transgastric endoscopic approach to the thoracic cavity, with lung biopsy, in a survival porcine model.The study was performed on four 20-30 kg female pigs (Sus scrofus domesticus). Following gastric wall incision, the muscular pars of the left diaphragmatic dome was incised along with the parietal pleura and the endoscope advanced into the thoracic cavity. In all animals, a thoracoscopy was performed as well as peripheral lung biopsy. At the end of the operation the endoscope was withdrawn from the thoracic cavity after pleural sac decompression and the diaphragmatic incision closed by endoscopic clips under maximal expansion of lungs. The gastric incision was finally closed by endoscopic clips. Chest-tube placement was not utilized. Animals were sacrificed by day 15 postoperatively.The gastroscope was easily introduced into the thoracic cavity that allowed to visualize the pleural cavity and to perform simple surgical procedures such as lung biopsies without complications. There were neither respiratory distress episodes nor surgical complications to report. No adverse event occurred during the survival period. The postmortem examination 15 days after surgery revealed a good closure of the diaphragmatic incision. At necropsy, the lung biopsies were completely healed. There were no signs of infection in both thoracic and peritoneal cavities. The length of follow-up and number of animals studied might have not been sufficient.This study demonstrates the feasibility of transgastric thoracoscopy in porcine model. Long-term follow-up of much larger series will be necessary for provision of more reliable answers if this approach should be adopted in the future and eventually translated for humans with advantages for patients.

A 58-year old man was admitted to the hospital because of melena. He had a 1-year history of mechanical aortic valve replacement and coronary stent placement because of myocardial infarction and he was taking warfarin and clopidogrel. Esophagogastroduodenoscopy and colonoscopy were negative for bleeding. Capsule endoscopy showed bleeding diffuse angiodysplasia of the small bowel. The patient was treated with octreotide 20 mg, at monthly interval. After 25 months there had been no recurrence of gastrointestinal bleeding. The case suggests that mechanical valve replacement may not prevent gastrointestinal bleeding in Heyde syndrome and that octreotide treatment should be considered in these cases.

Significant postoperative bile leaks occur in approximately 1% of patients. The goal of endoscopic therapy is to eliminate the transpapillary pressure gradient, thereby permitting preferential transpapillary bile flow rather than extravasation at the site of leak.Sixty-four patients were retrospectively evaluated. Endoscopic treatment comprised endoscopic sphincterotomy followed by insertion of a naso-biliary drainage or a stent. Retained stones were extracted by standard procedures.The site of bile extravasation was the cystic duct in 50 cases, ducts of Luschka in 4 cases, common bile duct in 6 cases and common hepatic duct in 4 cases. Retained bile duct stones were detected in 21 cases and papillary stenosis in 4 cases. Endoscopic sphincterotomy was performed in 25 cases, with stones extraction and nasobiliary drainage in 21 cases, and placement of stent in the remainder. Bile leaks resolved in 96.9% of patients, after endoscopic procedure. Two cases of mild pancreatitis were evidenced from endoscopic treatment.Endoscopic management is the treatment of choice of postcholecystectomy bile leaks.