Evaluation of the combined laparoscopic and mediastinoscopic esophagectomy technique.

BACKGROUND: Laparoscopic esophagectomy is technically difficult especially during dissection in the upper mediastinum. This limitation may be surpassed with the help of mediastinoscopy or of the recently introduced robotic surgical systems. The aim of the present study was to evaluate in an experimental porcine model the feasibility of the combined laparoscopic and mediastinoscopic transhiatal esophagectomy technique and to compare it with the robotic-assisted transhiatal and conventional approaches. MATERIALS AND METHODS: Transhiatal esophagectomy was performed in Landrace pigs under general anesthesia using three different techniques: Group A (n = 9): combined laparoscopic and mediastinoscopic, group B (n = 4): robotic-assisted and group C (n = 8): conventional "open". The feasibility, difficulty and accuracy of the procedure along with operative time, blood loss, intraoperative incidents and overall satisfaction of the surgical team were assessed for each technique. RESULTS: Operations in group A were feasible and reproducible. Although the procedure was technically difficult, the constant view on the operative field was highly appreciated by the operative team and facilitated an accurate and safe dissection. The main intraoperative complications were related to the side-effects of tension pneumothorax accompanying pleural injuries. In group B the features of the robotic system reduced the difficulty of dissection and obviated the need for mediastinoscopy. Operations in group C were quick and almost incident-free, facilitated also by the particularities of the animal model that could not reproduce identically the clinical situation. CONCLUSIONS: The combined laparoscopic and mediastinoscopic esophagectomy technique is feasible and offers certain advantages over the open approach while the robotic-assisted approach is an emerging less difficult alternative. Further studies are required to establish whether the advantages of minimally-invasive approach compensate for the increased technical difficulty and prolonged operative time.

Primary and locally recurrent retroperitoneal soft-tissue sarcoma: local control and survival.

AIM: To evaluate local control for long-term prognosis in retroperitoneal soft-tissue sarcoma (primary tumors (PT) and local recurrence (LR)). METHODS: A total of 110 patients underwent surgery between 1988 and 2002. Prospectively gathered clinicopathological data were analyzed. Kaplan-Meier estimations and Cox regression analyses were performed. RESULTS: Resectability was 90%, being comparable for PT (n=71) and LR (n=39). Morbidity, mortality, blood loss, and operation time did not differ for PT or LR (24% vs. 31%, p=0.41; 7.0% vs. 5.1%, p=1.0; 1000 ml vs. 1500 ml, p=0.17; 240 min vs. 255 min, p=0.13). Hospitalization was comparable in both groups (median, 12 days (PT) and 13 days (LR)). Follow-up was 89 months (median, IQR 37-112 months). Local 3- and 5-year control rates after complete resection of PT were 66% and 59% (19% and 9% for LR, p<0.001). The mean number of operations were 1.4 for PT and 2.4 for LR (p=0.0047). The 5-year survival rates after complete resection were 51% for PT and 43% for LR (p=0.39). The 5-year survival rates were 65%, 4%, and 0% for complete resection, incomplete resection, and exploration, respectively (p<0.001). Multivariate analysis showed high-grade and blood loss with a poor prognosis. CONCLUSIONS: Comparable resectability rates and perioperative outcome were observed for surgery of PT and LR. Consequent reoperation leads to respectable long-term survival rates after resection of LR. The prognosis in retroperitoneal sarcomas varies significantly according to resectability, grade and blood loss.

Immune-compromised state in the rat pancreas after chronic alcohol exposure: the role of peroxisome proliferator-activated receptor gamma.

Alcohol exposure is known to sensitize acinar cells to various insults but the pathophysiological mechanisms of alcoholic pancreatitis remain unknown. Alcohol abuse has been shown to mediate an anti-inflammatory response and periods of immune suppression seem to be associated with organ injury and mortality. The purpose of this study was to determine the mechanisms by which alcohol exerts transcriptional activities in the rat pancreas and how alcohol alters the inflammatory response. Using the Lieber-DeCarli alcohol/control diet, rats that were fed with alcohol over 14 weeks demonstrated a decrease of inflammatory cells in pancreatic tissue compared to controls. The anti-inflammatory effects of alcohol were confirmed by decreased expression of pro-inflammatory cytokines including TNFalpha, IL-1beta, IL-18, TGFbeta, and MCP-1. In addition, alcohol significantly increased the activity of PPARgamma, which is a known anti-inflammatory transcription factor, while pro-inflammatory factors including AP-2 and EGR-1 were significantly suppressed. NFkappaB binding showed a tendency towards a reduction. Electron microscopy studies revealed enlarged and injured mitochondria and lysosomes, accompanied by peri-cellular fibrosis. Furthermore, alcohol exposure increased the activities of trypsin and cathepsin B, both known to be critical in initiating acinar cell injury and pancreatitis. Despite the known alcohol-mediated acinar cell and mitochondrial injury, the mitochondrial-mediated apoptotic pathway was attenuated. These data demonstrate that the pancreas exposed to alcohol maintains an anti-inflammatory state by activating PPARgamma. Intracellular mitochondrial and lysosomal damage after chronic alcohol exposure induces premature activation of digestive enzymes and establishment of peri-cellular fibrosis in the absence of inflammation.

Bombesin receptors in distinct tissue compartments of human pancreatic diseases.

Overexpression of receptors for regulatory peptides in various human diseases is reportedly of clinical interest. Among these peptides, bombesin and gastrin-releasing peptide (GRP) have been shown to play a physiological and pathophysiological role in pancreatic tissues. Our aim has been to localize bombesin receptors in the human diseased pancreas to identify potential clinical applications of bombesin analogs in this tissue. The presence of bombesin receptor subtypes has been evaluated in specimens of human pancreatic tissues with chronic pancreatitis (n = 23) and ductal pancreatic carcinoma (n = 29) with in vitro receptor autoradiography on tissue sections incubated with 125I-[Tyr4]-bombesin or the universal ligand 125I-[D-Tyr6, beta-Ala11, Phe13, Nle14]-bombesin(6-14) as radioligands and displaced by subtype-selective bombesin receptor agonists and antagonists. GRP receptors were identified in the pancreatic exocrine parenchyma in 17 of 20 cases with chronic pancreatitis. No measurable bombesin receptors were found in the tumor tissue of ductal pancreatic carcinomas, however, GRP receptors were detected in a subset of peritumoral small veins in 19 of 29 samples. Moreover, residual pancreatic islets in these tissues were shown to express the BB3 receptor subtype. These data demonstrate the presence of bombesin receptors in three distinct tissue compartments of the pancreas, namely GRP receptors in the exocrine parenchyma in chronic pancreatitis and in peritumoral vessels around ductal pancreatic carcinomas, and BB3 receptors in residual pancreatic islets. Such a selective expression of bombesin receptor subtypes in pancreatic tissues may not only be of pathophysiological significance but may represent the basis for potential diagnostic and therapeutic clinical applications of bombesin analogs, including GRP receptor scintigraphy to differentiate chronic pancreatitis from ductal pancreatic carcinoma.