Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and is currently the main cause of death in patients with cirrhosis.¹ Liver resection is the first therapeutic option in patients with early tumors and well-preserved liver function.^2-4 In the past 2 decades, a significant improvement in the perioperative management of HCC has occurred, with a parallel reduction of resection-related mortality from 10% and 20% to a near-zero rate in referral centers.^3,5,6 Despite this reduction, liver resection for HCC is still burdened by potentially life-threatening complications, among which liver decompensation (LD) remains the most fearsome and least effectively treated.

The role of laparoscopic techniques in pancreatic surgery is still controversial especially regarding to exocrine malignancies. Operative time, conversion rate, adequacy of dissection, and morbidity do represent factors of major concern. Whereas laparoscopic resection of left sided pancreatic lesions requires no anastomosis and therefore has gained worldwide acceptance over the last years, excision of cephalic lesions by mimimal access has little place in surgeons' practice because of its technical complexity and duration of surgery. This study was designed to assess the feasibility and results of laparoscopic pancreaticoduodenectomy for neoplasms of the pancreatic head, analyzing steps of learning curve, conversion rate, and short-term outcomes. From August 2002 to December 2006, 19 patients affected by pancreatic neoplasm of the head were approached by minimally invasive technique. A video-assisted procedure with pancreaticoduodenal resection and anastomoses fashioned through a midline minilaparotomy of 7 cm was achieved in 7 patients. Conversion to laparotomy was required in 6 patients, in 3 for bleeding and in 3 for difficulties in dissection. Cephalic pancreatoduodenectomy was achieved by thorough intracorporeal technique in 6 patients. Mortality was nil. Oncologic principles with adequate lymphadenectomy and resection margins were respected and short-term outcomes and mean survival were quite acceptable and equal to those of conventional surgery.

Introduction: The exciting concept of performing surgery in the peritoneal cavity without abdominal incisions by means of flexible endoscopes introduced through natural orifices—natural orifice transluminal endoscopic surgery (NOTES) has been widely investigated in recent years in experimental settings. However, experience with this procedure in human beings is still lacking. In this paper, we report the preliminary results of a small consecutive series of transvaginal endoscopic cholecystectomies. Methods: A standard double-channel gastroscope introduced into the abdominal cavity through a posterior colpotomy was used to perform the cholecystectomy. The introduction of a 5-mm trocar in the left-upper abdominal quadrant was mandatory to create and monitor the pneumoperitoneum and allow the application of the standard laparoscopic clips. This port was also used to introduce a grasper that assisted in the exposure of the gallbladder. The gallbladder was removed through the vagina and was protected in a plastic bag. Results: Since July 2007, 3 patients were successfully operated on by this approach, including 1 morbidly obese woman with a body mass index (BMI) of 45. The mean operative time was 136 minutes (range, 110–190). No postoperative complications occurred, and the patients did not complain of pain at both access sites. At the 1-month follow-up, none of the patients complained of dyspareunia. Conclusions: The transvaginal cholecystectomy is feasible, safe, and reproducible in women within a wide range of BMI. NOTES might dramatically change the way surgery will be conceived and performed in the future, as it holds the potential to abolish the historic association of surgery with pain and scars.

Interfering with tumor metabolism is an emerging strategy for treating cancers that are resistant to standard therapies. Featuring a rapid proliferation rate and exacerbated glycolysis, hepatocellular carcinoma (HCC) creates a highly hypoxic microenvironment with excessive production of lactic and carbonic acids. These metabolic conditions promote disease aggressiveness and cancer-related immunosuppression. The pH regulatory molecules work as a bridge between tumor cells and their surrounding milieu. Herein, we show that the pH regulatory molecules CAIX, CAXII and V-ATPase are overexpressed in the HCC microenvironment and that interfering with their pathways exerts antitumor activity. Importantly, the V-ATPase complex was expressed by M2-like tumor-associated macrophages. Blocking ex vivo V-ATPase activity established a less immune-suppressive tumor microenvironment and reversed the mesenchymal features of HCC. Thus, targeting the unique cross-talk between tumor cells and the tumor microenvironment played by pH regulatory molecules holds promise as a strategy to control HCC progression and to reduce the immunosuppressive pressure mediated by the hypoxic/acidic metabolism, particularly considering the potential combination of this strategy with emerging immune checkpoint-based immunotherapies.