A. Bloomenthal

Oncologic Efficacy Is Not Compromised, and May Be Improved with Minimally Invasive Esophagectomy

BACKGROUND Major morbidity and mortality rates continue to be high in large series of transthoracic esophagectomies. Minimally invasive approaches are being increasingly used. We compare our growing series of minimally invasive (combined thoracoscopic and laparoscopic) esophagectomies (MIEs) with a series of open transthoracic esophagectomies. STUDY DESIGN We identified 65 patients who underwent an MIE with thoracoscopy/laparotomy (n = 11), Ivor Lewis (n = 2), or 3-hole approach (n = 52). These patients were compared with 53 patients who underwent open Ivor-Lewis esophagectomy (n = 15) or 3-hole esophagectomy (n = 38) over the past 10 years. RESULTS The MIE and open groups were similar regarding gender and average age. The majority of patients in the open group underwent neoadjuvant chemoradiation therapy (81%); a significantly smaller (43%) number of patients in the MIE group underwent neoadjuvant therapy (p < 0.0001). Regarding oncologic efficacy, 97% and 94% of patients in both groups underwent R0 resections. Patients undergoing MIE had a significant increase in the number of harvested lymph nodes (median 20 vs 9; p < 0.0001). Length of stay was significantly decreased in patients who underwent MIE (8.5 days vs 16 days; p = 0.002). Finally, there were significantly fewer serious complications (grades 3-5) in the MIE group (19% vs 48%; p = 0.0008). CONCLUSIONS In this initial report of a single-institution series of MIE, we demonstrate that oncologic efficacy is not compromised and may actually be improved with a significantly increased number of harvested LNs. We also demonstrate that this approach is associated with fewer serious complications and a significant decrease in the length of postoperative hospital stay.

Gene silencing in the endocrine pancreas mediated by short-interfering RNA

Objectives: RNA interference as mediated by short-interfering RNA (siRNA) offers a nonviral means to silence genes in tissue; however, few data exist about gene therapy using siRNA in pancreas tissue. To determine if siRNA treatment could silence an endogenous gene in pancreatic islets, we developed a murine model using the endocrine pancreas. Methods: The insulin 2 (Ins2) gene was targeted with siRNA, and quantitative RT-PCR, fluorescent microscopy, and FACS were used to measure transcript levels and siRNA cellular uptake and transfection efficiency. Isolated pancreatic islets were transfected with siRNA in vitro using a liposomal delivery method in a dose titration (50-400 nM) or pooled from BALB/c mice having received siRNA (100 μg) via hydrodynamic tail vein injection. Results: The Ins2 transcript level was significantly reduced by 55% in vitro with FACS data showing a transfection efficiency over 45% with the 400 nM concentration. In vivo delivery of siRNA to pancreatic islets revealed a 33% reduction in Ins2 mRNA levels, although siRNA was able to be detected in 19% of isolated islet cells. Conclusion: We have successfully used RNA interference to silence an endogenous tissue-specific gene (Ins2) in pancreatic islets when transfected in vitro or administered in vivo.

Prevalence and treatment of bleeding complications in chronic pancreatitis

ObjectivesAs spontaneous major haemorrhage in patients with chronic pancreatitis is rare, limited data have been reported, and no evidence-based guidelines are currently available regarding the optimal treatment modality.Patients and methodsWe report our experience with 36 patients with severe bleeding complications from a series of 541 patients presenting with chronic pancreatitis (representing a prevalence of 6.7% of admitted patients), treated in one surgical department over a period of 9.5 years, with a median follow-up of 4.1 years.ResultsHaemorrhage was indirectly related to chronic pancreatitis in eight patients (22.2%) with ulcer or variceal bleeding. Three patients (8.4%) demonstrated spleen infarction or rupture. The most common causes of major haemorrhage were pseudoaneurysms in 25 patients (69.4%). Nine of them were treated with primary embolization. Sixteen patients with pseudoaneurysms underwent surgery. The only mortalities (8.3%) observed were from bleeding-associated complications of pseudoaneurysms. Two patients died after surgery, and one after primary embolization. We observed a higher re-bleeding rate after surgery (25% vs 11% after embolization). The presence of haemorrhagic shock, and the amount of blood transfused, were significant determinants of hospital mortality. Patient age, pseudoaneurysm location, and treatment modality had no significant influence on mortality.ConclusionsAny haemodynamically stable patient with haemorrhage due to arterial pseudoaneurysms should undergo angiography with embolization when technically possible. If there are no other pancreas-related indications for surgery, embolization remains the definitive treatment. If embolization is not available or has failed, surgery is indicated, although perioperative morbidity will be higher.