Angelo Iossa

Evidence for multipotent endodermal stem/progenitor cell populations in human gallbladder

BACKGROUND & AIMS Multipotent stem/progenitor cells are found in peribiliary glands throughout human biliary trees and are able to generate mature cells of hepato-biliary and pancreatic endocrine lineages. The presence of endodermal stem/progenitors in human gallbladder was explored. METHODS Gallbladders were obtained from organ donors and laparoscopic surgery for symptomatic cholelithiasis. Tissues or isolated cells were characterized by immunohistochemistry and flow cytometry. EpCAM+ (Epithelial Cell Adhesion Molecule) cells were immunoselected by magnetic microbeads, plated onto plastic in self-replication conditions and subsequently transferred to distinct serum-free, hormonally defined media tailored for differentiation to specific adult fates. In vivo studies were conducted in an experimental model of liver cirrhosis. RESULTS The gallbladder does not have peribiliary glands, but it has stem/progenitors organized instead in mucosal crypts. Most of these can be isolated by immune-selection for EpCAM. Approximately 10% of EpCAM+ cells in situ and of immunoselected EpCAM+ cells co-expressed multiple pluripotency genes and various stem cell markers; other EpCAM+ cells qualified as progenitors. Single EpCAM+ cells demonstrated clonogenic expansion ex vivo with maintenance of stemness in self-replication conditions. Freshly isolated or cultured EpCAM+ cells could be differentiated to multiple, distinct adult fates: cords of albumin-secreting hepatocytes, branching ducts of secretin receptor+ cholangiocytes, or glucose-responsive, insulin/glucagon-secreting neoislets. EpCAM+ cells transplanted in vivo in immune-compromised hosts gave rise to human albumin-producing hepatocytes and to human Cytokeratin7+ cholangiocytes occurring in higher numbers when transplanted in cirrhotic mice. CONCLUSIONS Human gallbladders contain easily isolatable cells with phenotypic and biological properties of multipotent, endodermal stem cells.

Helicobacter pylori infection in obesity and its clinical outcome after bariatric surgery

The present review summarizes the prevalence and active clinical problems in obese patients with Helicobacter pylori (H. pylori) infection, as well as the outcomes after bariatric surgery in this patient population. The involvement of H. pylori in the pathophysiology of obesity is still debated. It may be that the infection is protective against obesity, because of the gastritis-induced decrease in production and secretion of the orexigenic hormone ghrelin. However, recent epidemiological studies have failed to show an association between H. pylori infection and reduced body mass index. H. pylori infection might represent a limiting factor in the access to bariatric bypass surgery, even if high-quality evidence indicating the advantages of preoperative H. pylori screening and eradication is lacking. The clinical management of infection is complicated by the lower eradication rates with standard therapeutic regimens reported in obese patients than in the normal-weight population. Prospective clinical studies to ameliorate both H. pylori eradication rates and control the clinical outcomes of H. pylori infection after different bariatric procedures are warranted.

Gastroesophageal Reflux Disease and Sleeve Gastrectomy

Gastroesophageal reflux disease (GERD) and/or hiatus hernia (HH) are one of the most common disorders of the upper gastrointestinal tract. Despite the positive effect of sleeve gastrectomy (SG) regarding weight loss and improvement in obesity co-morbidities, there are concerns about the development of de novo gastroesophageal reflux disease or worsening the existing GERD after this bariatric operation. Furthermore, controversy exists on the consequences of SG in lower esophageal sphincter function and about the ideal procedure when a hiatus hernia is preoperatively diagnosed or discovered during the laparoscopic SG. This review systematically investigates the incidence, the pathophysiology of GERD and/or HH in morbidly obese individuals before and after SG, and the treatment options for concomitant HH repair during laparoscopic sleeve gastrectomy.

Lightweight polypropylene mesh fixation in laparoscopic incisional hernia repair

Abstract Introduction: The choice of the mesh and fixation methods in laparoscopic incisional hernia repair is a crucial issue in preventing complications and recurrence. The authors report a series of 40 consecutive laparoscopic incisional hernia repairs, focusing on the use of lightweight polypropylene mesh and on the way of mesh fixation. Material and methods: Forty laparoscopic incisional hernia repairs performed consecutively in 38 patients (16 males, 22 females) were retrospectively evaluated. Patients were divided into two groups depending on tacks used: Titanium tacks vs absorbable tacks. Results: All patients received totally laparoscopic incisional hernia repair by the use of lightweight polypropylene mesh. No major post-operative complications were reported. Post-operative pain (evaluated by VNS) was higher in Group A (titanium tacks, p < 0.05). No differences in follow-up as well as in recurrence incidence (one case in both groups, <6 months time interval) were reported. Conclusions: Securestrap™ absorbable tacks are safe and effective and easy to use and did not increase the risk of mesh dislocation compared with non-absorbable tacks. The specific design well fits the lightweight polypropylene mesh Physiomesh™. Further evaluations in larger randomized studies are needed to confirm these preliminary data.

Reinforcement of hiatal defect repair with absorbable mesh fixed with non-permanent devices.

Abstract Aim: To report the results of an open label prospective study on a new technique for laparoscopic hiatal hernia (HH) repair with absorbable mesh fixed with absorbable materials Methods: From January 2011 to May 2013, 43 patients were treated; group A, 20 patients submitted to laparoscopic sleeve gastrectomy (LSG); group B, 13 patients submitted to revisional surgery for the diagnosis of HH and symptomatic GERD post-LSG; and group C, ten patients submitted to 360° fundoplication. All patients underwent cruroplasty reinforced with bio-absorbable mesh fixed with absorbable tacks and/or fibrin glue. Conversion rate, intra-operative complications, operative time (tacks vs tacks plus fibrin glue), perioperative complications, perioperative symptoms and radiological control set the criteria for clinical/surgical evaluation. Results: Conversion and mortality rate was 0%. The mean time for mesh fixation with the tacks vs tacks plus fibrin glue was 6.2 ± 2 vs 7.3 ± 3 min. The remission of GERD symptoms was observed in 39 patients, and we did not observe any cases of mesh-related complications at a mean follow-up of 17.4 months. Recurrence rate was 2.3% (one asymptomatic patient of group B). Conclusions: Reinforcement with absorbable mesh-cancel bio mesh is a safe and effective option for laparoscopic HH repair in normal weight and obese patients.

Complications of staple line and anastomoses following laparoscopic bariatric surgery

With over 600 million people being obese, and given the scientific demonstration of the advantages of surgical treatment, bariatric surgery is on the rise. The promising long-term results in terms of weight loss, and particularly in relation to comorbidities and the control/cure rate, mean that the number of procedures performed in all countries remains high. However, the risk of potentially complex or fatal complications, though small, is present and is related to the procedures per se. This review is a guide for bariatric and/or general surgeons, offering a complete overview of the pathogenesis of anastomosis and staple line following the most common laparoscopic bariatric procedures: sleeve gastrectomy, gastric bypass, and mini-gastric bypass. The review is divided according to the procedure and the complications (leak, bleeding and stenosis), and evaluates all the factors that can potentially improve or worsen the complication rate, representing a “unicum” in the present literature on bariatric surgery.

Severe Events Related to Use of Stents in Bariatric Surgical Complications

Introduction: Endoscopic self-expandable stents are emerging as safe and effective options for the treatment of bariatric surgery complications. Our aim is to report 3 cases of severe complications after self-expandable stent implantation. Case Description: A retrospective database analysis showed 14 major complications over the past 400 bariatric procedures (3.5%); 8 of them were managed conservatively. Three cases of unusual severe complications after self-expandable stent implantation were observed. In case 1 (leak after resleeving), the self-expandable stent migrated twice and caused an esophageal stenosis, which was treated by endoscopic dilation. Three months later, the stenosis recurred and the patient was a candidate for distal esophagectomy. In case 2 (gastrojejunal stricture after Roux-en-Y gastric bypass), the endoscopic dilation was complicated by perforation and treated with a self-expandable stent. The patient required an emergency laparoscopy to remove the stent that had migrated into the ileum. After 1 month, gastrojejunal stenosis recurred and the patient underwent laparoscopic revision of the anastomosis. In case 3 (leak after vertical banded gastroplasty [VBG]–Roux-en-Y gastric bypass conversion), the self-expandable stent migrated twice and caused an esophageal-pleural fistula managed with a new stent. Discussion: Bariatric surgeons have to balance the possible advantages of self-expandable stents on a case-by-case basis. Complications of endoscopic stents can be life-threatening and are underestimated and under-reported in the literature.

Gallbladder is a highly available source of multipotent progenitor/stem cells with hepatocyte, cholangiocyte and pancreatic potentialities

Biliary tree stem/progenitor cells (BTSCs) have been identified in glands of normal human extrahepatic bile ducts (Mancino M et al., 2007; Gaudio et al., 2009) and are able to generate in vitro and in vivo mature cells of the hepato-biliary and pancreatic endocrine lineages (Carpino et al., 2012). The aims of the present study have been to investigate in normal and pathological gallbladders: i) the presence and location of BTSCs and ii) the possibility to isolate, culture and differentiate BTSCs. Our results showed that, in normal and pathological gallbladders, the surface epithelium contained cells with the phenotype of BTSCs. Tissue digestion resulted in the isolation of 15±3.7 and 13.3±3.6 million viable cells from normal and pathological gallbladder, respectively. In vitro, single EpCAM sorted cells showed a clonogenic capacity maintaining an endodermal-like phenotype for more than a month. When transferred into differentiation conditions, cells differentiated to a distinct fate resulting in cords of albumin-secreting hepatocytes, branching ducts of secretin receptor+ cholangiocytes or functional pancreatic islets. In vivo, EpCAM+ cells injected into fibrotic livers of SCID mice resulted in repopulation of mice livers by albumin-producing human hepatocytes. In conclusion, normal and pathological gallbladders contain easily isolable cells with the phenotype and the biological properties of BTSCs.