Laparoscopic Versus Open Incisional Hernia Repair: Long-Term Follow-up Results of a Randomized Clinical Trial.

PURPOSE: Long-term extension of a previous randomized controlled clinical trial comparing open (OVHR) vs. laparoscopic (LVHR) ventral hernia repair, assessing recurrence, reoperation, mesh-related complications and self-reported quality of life with 10 years of follow-up. METHODS: Eighty-five patients were followed up to assess recurrence (main endpoint), reoperation, mesh complications and death, from the date of index until recurrence, death or study completion, whichever was first. Recurrence, reoperation rates and death were estimated by intention to treat. Mesh-related complications were only assessed in the LVHR group, excluding conversions (intraperitoneal onlay; n = 40). Quality of life, using the European Hernia Society Quality of Life score, was assessed in surviving non-reoperated patients (n = 47). RESULTS: The incidence rates with 10 person-years of follow-up were 21.01% (CI 13.24-33.36) for recurrence, 11.92% (CI: 6.60-21.53) for reoperation and 24.88% (CI 16.81-36.82) for death. Sixty-two percent of recurrences occurred within the first 2 years of follow-up. No significant differences between arms were found in any of the outcomes analyzed. Incidence rate of intraperitoneal mesh complications with 10 person-years of follow-up was 6.15% (CI 1.99-19.09). The mean EuraHS-QoL score with 13.8 years of mean follow-up for living non-reoperated patients was 6.63 (CI 4.50-8.78) over 90 possible points with no significant differences between arms. CONCLUSION: In incisional ventral hernias with wall defects up to 15 cm wide, laparoscopic repair seems to be as safe and effective as open techniques, with no long-term differences in recurrence and reoperation rates or global quality of life, although lack of statistical power does not allow definitive conclusions on equivalence between alternatives. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov (NCT04192838).

Initial results of the oesophageal and gastric cancer registry from the Comunidad Valenciana. / Resultados iniciales del registro de carcinomas esófago-gástricos de la Comunidad Valenciana.

AIMS: To evaluate the initial results of the oesophagogastric cancer registry developed for the Sociedad Valenciana de Cirugía and the Health Department of the Comunidad Valenciana (Spain). METHODS: Fourteen of the 24 public hospitals belonging to the Comunidad Valenciana participated. All patients with diagnosis of oesophageal or gastric carcinomas operated from January 2013 to December 2014 were evaluated. Demographic, clinical and pathological data were analysed. RESULTS: Four hundred and thirty-four patients (120 oesophageal carcinomas and 314 gastric carcinomas) were included. Only two hospitals operated more than 10 patients with oesophageal cancer per year. Transthoracic oesophaguectomy was the most frequent approach (84.2%) in tumours localized within the oesophagus. A total gastrectomy was performed in 50.9% patients with gastroesophageal junction (GOJ) carcinomas. Postoperative 30-day and 90-day mortality were 8% and 11.6% in oesophageal carcinoma and 5.9 and 8.6% in gastric carcinoma. Before surgery, middle oesophagus carcinomas were treated mostly (76,5%) with chemoradiotherapy. On the contrary, lower oesophagus and GOJ carcinomas were treated preferably with chemotherapy alone (45.5 and 53.4%). Any neoadjuvant treatment was administered to 73.6% of gastric cancer patients. Half patients with oesophageal carcinoma or gastric carcinoma received no adjuvant treatment. CONCLUSIONS: This registry revealed that half patients with oesophageal cancer were operated in hospitals with less than 10 cases per year at the Comunidad Valenciana. Also, it detected capacity improvement for some clinical outcomes of oesophageal and gastric carcinomas.

Searching for Antipneumococcal Targets: Choline-Binding Modules as Phagocytosis Enhancers.

Choline-binding proteins (CBPs) from Streptococcus pneumoniae comprise a family of modular polypeptides involved in essential events of this pathogen. They recognize the choline residues present in the teichoic and lipoteichoic acids of the cell wall using the so-called choline-binding modules (CBMs). The importance of CBPs in pneumococcal physiology points to them as novel targets to combat antimicrobial resistances shown by this organism. In this work we have tested the ability of exogenously added CBMs to act as CBP inhibitors by competing with the latter for the binding to the choline molecules in the bacterial surface. First, we carried out a thorough physicochemical characterization of three native CBMs, namely C-LytA, C-Cpl1, and C-CbpD, and assessed their affinity for choline and macromolecular, pneumococcal cell-wall mimics. The interaction with these substrates was evaluated by molecular modeling, analytical ultracentrifugation, surface plasmon resonance, and fluorescence and circular dichroism spectroscopies. Van't Hoff thermal analyses unveiled the existence of one noncanonical choline binding site in each of the C-Cpl1 and C-CbpD proteins, leading in total to 5 ligand-binding sites per dimer and 4 sites per monomer, respectively. Remarkably, the binding affinities of the CBMs do not directly correlate with their native oligomeric state or with the number of choline-binding sites, suggesting that choline recognition by these modules is a complex phenomenon. On the other hand, the exogenous addition of CBMs to pneumococcal planktonic cultures caused extensive cell-chaining probably as a consequence of the inhibition of CBP attachment to the cell wall. This was accompanied by bacterial aggregation and sedimentation, causing an enhancement of bacterial phagocytosis by peritoneal macrophages. In addition, the rational design of an oligomeric variant of a native CBM led to a substantial increase in its antibacterial activity by multivalency effects. These results suggest that CBMs might constitute promising nonlytic antimicrobial candidates based on the natural induction of the host defense system.

Open randomized clinical trial of laparoscopic versus open incisional hernia repair.

BACKGROUND: Incisional hernia is a common complication following abdominal surgery. Although the use of prosthetics has decreased recurrence rates, the standard open approach is still unsatisfactory. Laparoscopic techniques are an attempt to provide similar outcomes with the advantages of minimally invasive surgery. METHODS: Open randomized controlled clinical trial with follow-up at 1, 2, 3, 7, and 15 days, and 1, 3, and 12 months from hernia repair. The study was carried out in the surgery departments of three general hospitals of the Valencia Health Agency. OBJECTIVES: To compare laparoscopic with anterior open repair using health-related quality of life outcomes as main endpoints. RESULTS: Eighty-four patients with incisional hernia were randomly allocated to an open group (OG) (n = 39) or to a laparoscopic group (LG) (n = 45). Seventy-four patients completed 1-year follow up. Mean length of stay and time to oral intake were similar between groups. Operative time was 32 min longer in the LG (p < 0.001). Conversion rate was 11%. The local complication rate was superior in the LG (33.3% versus 5.2%) (p < 0.001). Recurrence rate at 1 year (7.9% versus 9.7%) was similar in the two groups. There were no significant differences in the pain scores or the EQ5D tariffs between the two groups during follow-up. CONCLUSIONS: Laparoscopic incisional hernia repair does not seem to be a better procedure than the open anterior technique in terms of operative time, hospitalization, complications, pain or quality of life.

MicroRNAs Establish the Right-Handed Dominance of the Heart Laterality Pathway in Vertebrates.

Despite their external bilateral symmetry, vertebrates have internal left/right (L/R) asymmetries required for optimal organ function. BMP-induced epithelial to mesenchymal transition (EMT) in the lateral plate mesoderm (LPM) triggers L/R asymmetric cell movements toward the midline, higher from the right, which are crucial for heart laterality in vertebrates. However, how the L/R asymmetric levels of EMT factors are achieved is not known. Here, we show that the posterior-to-anterior Nodal wave upregulates several microRNAs (miRNAs) to transiently attenuate the levels of EMT factors (Prrx1a and Snail1) on the left LPM in a Pitx2-independent manner in the fish and mouse. These data clarify the role of Nodal in heart laterality and explain how Nodal and BMP exert their respective dominance on the left and right sides through the mutual inhibition of their respective targets, ensuring the proper balance of L/R information required for heart laterality and morphogenesis.

A gene regulatory network to control EMT programs in development and disease.

The Epithelial to Mesenchymal Transition (EMT) regulates cell plasticity during embryonic development and in disease. It is dynamically orchestrated by transcription factors (EMT-TFs), including Snail, Zeb, Twist and Prrx, all activated by TGF-ß among other signals. Here we find that Snail1 and Prrx1, which respectively associate with gain or loss of stem-like properties and with bad or good prognosis in cancer patients, are expressed in complementary patterns during vertebrate development and in cancer. We show that this complementarity is established through a feedback loop in which Snail1 directly represses Prrx1, and Prrx1, through direct activation of the miR-15 family, attenuates the expression of Snail1. We also describe how this gene regulatory network can establish a hierarchical temporal expression of Snail1 and Prrx1 during EMT and validate its existence in vitro and in vivo, providing a mechanism to switch and select different EMT programs with important implications in development and disease.

Clinical and manometric results of endorectal advancement flaps for complex anal fistula.

BACKGROUNDS AND AIM: Endorectal advancement flap repair is a well-recognized method for the treatment of complex anorectal fistula. The purpose of this study was to prospectively assess the clinical and functional results of endorectal advancement flaps for complex anorectal fistula and to identify factors that affect outcome. MATERIALS AND METHODS: A prospective study of 56 patients was performed. Clinical and functional results were studied using the Wexner continence scale and anal manometry before and after surgery. Factors associated with recurrence and incontinence were analyzed by univariate and multivariate regression analysis. RESULTS: Sixty endorectal flaps were constructed in 56 patients. Mean age was 49 years (range 24-74). The fistula was of cryptoglandular origin in 91.1% cases. Mean follow-up was 43.8 months. The technique was repeated in four patients because of recurrence (7.1%), with subsequent healing in all cases. There were significant reductions in maximum resting pressure 3 months after surgery (83.6+/-33.2 vs 45.6+/-18.3, p<0.001) and maximum squeeze pressure (208.8+/-91.5 vs 169.5+/-75, p<0.001). Before surgery, five patients (8.9%) reported incontinence symptoms. After surgery, 78.6% patients had normal continence, seven patients (12.5%) complained of minor incontinence, and five (9%) had major continence disturbances. None of the variables studied (age, sex, previous fistula surgery, rectovaginal fistula, and Crohn's disease) affected the outcome of the procedure in multivariate analysis. CONCLUSIONS: Endorectal advancement flap repair is an effective technique for complex anal fistula, with a low recurrence rate (7.1%). Patients (21.4%) reported disturbed anal continence. It is still not possible to identify factors that are predictive of failure or incontinence.