Three-year survival and distribution of lymph node metastases in gastric cancer following neoadjuvant chemotherapy: results from a European randomized clinical trial.

BACKGROUND: Adequate lymphadenectomy is an important step in gastrectomy for cancer, with a modified D2 lymphadenectomy being recommended for advanced gastric cancers. When assessing a novel technique for the treatment of gastric cancer, lymphadenectomy should be non-inferior. The aim of this study was to assess completeness of lymphadenectomy and distribution patterns between open total gastrectomy (OTG) and minimally invasive total gastrectomy (MITG) in the era of peri-operative chemotherapy. METHODS: This is a retrospective analysis of the STOMACH trial, a randomized clinical trial in thirteen hospitals in Europe. Patients were randomized between OTG and MITG for advanced gastric cancer after neoadjuvant chemotherapy. Three-year survival, number of resected lymph nodes, completeness of lymphadenectomy, and distribution patterns were examined. RESULTS: A total of 96 patients were included in this trial and randomized between OTG (49 patients) and MITG (47 patients). No difference in 3-year survival was observed, this was 57.1% in OTG group versus 46.8% in MITG group (P = 0.186). The mean number of examined lymph nodes per patient was 44.3 ± 16.7 in the OTG group and 40.7 ± 16.3 in the MITG group (P = 0.209). D2 lymphadenectomy of 71.4% in the OTG group and 74.5% in the MITG group was performed according to the surgeons; according to the pathologist compliance to D2 lymphadenectomy was 30% in the OTG group and 36% in the MITG group. Tier 2 lymph node metastases (stations 7-12) were observed in 19.6% in the OTG group versus 43.5% in the MITG group (P = 0.024). CONCLUSION: No difference in 3-year survival was observed between open and minimally invasive gastrectomy. No differences were observed for lymph node yield and type of lymphadenectomy. Adherence to D2 lymphadenectomy reported by the pathologist was markedly low.

Health related quality of life following open versus minimally invasive total gastrectomy for cancer: Results from a randomized clinical trial.

INTRODUCTION: Minimally invasive techniques show improved short-term and comparable long-term outcomes compared to open techniques in the treatment of gastric cancer and improved survival has been seen with the implementation of multimodality treatment. Therefore, focus of research has shifted towards optimizing treatment regimens and improving quality of life. MATERIALS AND METHODS: A randomized trial was performed in thirteen hospitals in Europe. Patients were randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG) after neoadjuvant chemotherapy. This study investigated patient reported outcome measures (PROMs) on health-related quality of life (HRQoL) following OTG or MITG, using the Euro-Qol-5D (EQ-5D) and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires, modules C30 and STO22. Due to multiple testing a p-value < 0.001 was deemed statistically significant. RESULTS: Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. A response compliance of 80% was achieved for all PROMs. The EQ5D overall health score one year after surgery was 85 (60-90) in the open group and 68 (50-83.8) in the minimally invasive group (P = 0.049). The median EORTC-QLQ-C30 overall health score one year postoperatively was 83,3 (66,7-83,3) in the open group and 58,3 (35,4-66,7) in the minimally invasive group (P = 0.002). This was not statistically significant. CONCLUSION: No differences were observed between open total gastrectomy and minimally invasive total gastrectomy regarding HRQoL data, collected using the EQ-5D, EORTC QLQ-C30 and EORTC-QLQ-STO22 questionnaires.

Open versus minimally invasive total gastrectomy after neoadjuvant chemotherapy: results of a European randomized trial.

BACKGROUND: Surgical resection with adequate lymphadenectomy is regarded the only curative option for gastric cancer. Regarding minimally invasive techniques, mainly Asian studies showed comparable oncological and short-term postoperative outcomes. The incidence of gastric cancer is lower in the Western population and patients often present with more advanced stages of disease. Therefore, the reproducibility of these Asian results in the Western population remains to be investigated. METHODS: A randomized trial was performed in thirteen hospitals in Europe. Patients with an indication for total gastrectomy who received neoadjuvant chemotherapy were eligible for inclusion and randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG). Primary outcome was oncological safety, measured as the number of resected lymph nodes and radicality. Secondary outcomes were postoperative complications, recovery and 1-year survival. RESULTS: Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. The mean number of resected lymph nodes was 43.4 ± 17.3 in OTG and 41.7 ± 16.1 in MITG (p = 0.612). Forty-eight patients in the OTG group had a R0 resection and 44 patients in the MITG group (p = 0.617). One-year survival was 90.4% in OTG and 85.5% in MITG (p = 0.701). No significant differences were found regarding postoperative complications and recovery. CONCLUSION: These findings provide evidence that MITG after neoadjuvant therapy is not inferior regarding oncological quality of resection in comparison to OTG in Western patients with resectable gastric cancer. In addition, no differences in postoperative complications and recovery were seen.

Adipose-derived mesenchymal stem cells slow disease progression of acute-on-chronic liver failure.

A serious complication of chronic hepatic insufficiency is acute-on-chronic liver failure, a recognized syndrome characterized by acute decompensation of cirrhosis and organ/system failure. We investigated the use of adipose-derived mesenchymal stem cells (AD-MSCs) in an experimental model of acute-on-chronic liver failure, developed by microsurgical extrahepatic cholestasis in rats. Rats undergoing microsurgical extrahepatic cholestasis were treated by intraparenchymal liver injection of human or rat AD-MSCs, undifferentiated or previously differentiated in vitro toward the hepatocyte lineage. The groups treated with rat AD-MSCs showed less ascites, lower hepato- and splenomegaly, less testicular atrophy, and an improvement in serum biochemical hepatic parameters. There was also an improvement in histological liver changes, in which the area of fibrosis and bile duct proliferation were significantly decreased in the group treated with predifferentiated rat AD-MSCs. In conclusion, an isograft of hepatocyte-predifferentiated AD-MSCs injected intraparenchymally 2 weeks after microsurgery in extrahepatic cholestatic rats prevents secondary complications of acute-on-chronic hepatic failure. These data support the potential use of autologous AD-MSCs in the treatment of human cholestasis, and specifically of newborn biliary atresia, which could be beneficial for patients awaiting transplant.

Role of laryngeal mask airway in laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is one of the most commonly performed surgical procedures and the laryngeal mask airway (LMA) is the most common supraglottic airway device used by the anesthesiologists to manage airway during general anesthesia. Use of LMA has some advantages when compared to endotracheal intubation, such as quick and ease of placement, a lesser requirement for neuromuscular blockade and a lower incidence of postoperative morbididy. However, the use of the LMA in laparoscopy is controversial, based on a concern about increased risk of regurgitation and pulmonary aspiration. The ability of these devices to provide optimal ventilation during laparoscopic procedures has been also questioned. The most important parameter to secure an adequate ventilation and oxygenation for the LMA under pneumoperitoneum condition is its seal pressure of airway. A good sealing pressure, not only state correct patient ventilation, but it reduces the potential risk of aspiration due to the better seal of airway. In addition, the LMAs incorporating a gastric access, permitting a safe anesthesia based on these commented points. We did a literature search to clarify if the use of LMA in preference to intubation provides inadequate ventilation or increase the risk of aspiration in patients undergoing laparoscopic cholecystectomy. We found evidence stating that LMA with drain channel achieves adequate ventilation for these procedures. Limited evidence was found to consider these devices completely safe against aspiration. However, we observed that the incidence of regurgitation and aspiration associated with the use of the LMA in laparoscopic surgery is very low.

Wound healing reaction: A switch from gestation to senescence.

The repair of wounded tissue during postnatal life could be associated with the upregulation of some functions characteristic of the initial phases of embryonic development. The focusing of these recapitulated systemic functions in the interstitial space of the injured tissue is established through a heterogeneous endothelial barrier which has excretory-secretory abilities which in turn, would induce a gastrulation-like process. The repair of adult tissues using upregulated embryonic mechanisms could explain the universality of the inflammatory response against injury, regardless of its etiology. However, the early activation after the injury of embryonic mechanisms does not always guarantee tissue regeneration since their long-term execution is mediated by the host organism.

Surgical inflammatory stress: the embryo takes hold of the reins again.

The surgical inflammatory response can be a type of high-grade acute stress response associated with an increasingly complex trophic functional system for using oxygen. This systemic neuro-immune-endocrine response seems to induce the re-expression of 2 extraembryonic-like functional axes, i.e. coelomic-amniotic and trophoblastic-yolk-sac-related, within injured tissues and organs, thus favoring their re-development. Accordingly, through the up-regulation of two systemic inflammatory phenotypes, i.e. neurogenic and immune-related, a gestational-like response using embryonic functions would be induced in the patient's injured tissues and organs, which would therefore result in their repair. Here we establish a comparison between the pathophysiological mechanisms that are produced during the inflammatory response and the physiological mechanisms that are expressed during early embryonic development. In this way, surgical inflammation could be a high-grade stress response whose pathophysiological mechanisms would be based on the recapitulation of ontogenic and phylogenetic-related functions. Thus, the ultimate objective of surgical inflammation, as a gestational process, is creating new tissues/organs for repairing the injured ones. Since surgical inflammation and early embryonic development share common production mechanisms, the factors that hamper the wound healing reaction in surgical patients could be similar to those that impair the gestational process.

A half century (1961-2011) of applying microsurgery to experimental liver research.

The development of microsurgery has been dependent on experimental animals. Microsurgery could be a very valuable technique to improve experimental models of liver diseases. Microdissection and microsutures are the two main microsurgical techniques that can be considered for classifying the experimental models developed for liver research in the rat. Partial portal vein ligation, extrahepatic cholestasis and hepatectomies are all models based on microdissection. On the other hand, in portacaval shunts, orthotopic liver transplantation and partial heterotopic liver transplantation, the microsuture techniques stand out. By reducing surgical complications, these microsurgical techniques allow for improving the resulting experimental models. If good experimental models for liver research are successfully developed, the results obtained from their study might be particularly useful in patients with liver disease. Therefore experimental liver microsurgery could be an invaluable way to translate laboratory data on liver research into new clinical diagnostic and therapeutic strategies.