Role of STAT3 in In Vitro Transformation Triggered by TRK Oncogenes

TRK oncoproteins are chimeric versions of the NTRK1/NGF receptor and display constitutive tyrosine kinase activity leading to transformation of NIH3T3 cells and neuronal differentiation of PC12 cells. Signal Transducer and Activator of Transcription (STAT) 3 is activated in response to cytokines and growth factors and it has been recently identified as a novel signal transducer for TrkA, mediating the functions of NGF in nervous system. In this paper we have investigated STAT3 involvement in signalling induced by TRK oncogenes. We showed that TRK oncogenes trigger STAT3 phosphorylation both on Y705 and S727 residues and STAT3 transcriptional activity. MAPK pathway was involved in the induction of STAT3 phosphorylation. Interestingly, we have shown reduced STAT3 protein level in NIH3T3 transformed foci expressing TRK oncogenes. Overall, we have unveiled a dual role for STAT3 in TRK oncogenes-induced NIH3T3 transformation: i) decreased STAT3 protein levels, driven by TRK oncoproteins activity, are associated to morphological transformation; ii) residual STAT3 transcriptional activity is required for cell growth

Ilioinguinal nerve neurectomy is better than preservation in lichtenstein hernia repair. A systematic literature review and meta-analysis

Objective This study aimed to evaluate the incidence of chronic groin pain (primary outcome) and alterations of sensitivity (secondary outcome) after Lichtenstein inguinal hernia repair, comparing neurectomy with ilioinguinal nerve preservation surgery. Summary background data The exact cause of chronic groin postoperative pain after mesh inguinal hernia repair is usually unclear. Section of the ilioinguinal nerve (neurectomy) may reduce postoperative chronic pain. Methods We followed PRISMA guidelines to identify randomized studies reporting comparative outcomes of neurectomy versus ilioinguinal nerve preservation surgery during Lichtenstein hernia repairs. Studies were identified by searching in PubMed, Scopus, and Web of Science from April 2020. The protocol for this systematic review and meta-analysis was submitted and accepted from PROSPERO: CRD420201610. Results In this systematic review and meta-analysis, 16 RCTs were included and 1550 patients were evaluated: 756 patients underwent neurectomy (neurectomy group) vs 794 patients underwent ilioinguinal nerve preservation surgery (nerve preser- vation group). All included studies analyzed Lichtenstein hernia repair. The majority of the new studies and data comes from a relatively narrow geographic region; other bias of this meta-analysis is the suitability of pooling data for many of these studies. A statistically significant percentage of patients with prosthetic inguinal hernia repair had reduced groin pain a 6 months after surgery at 8.94% (38/425) in the neurectomy group versus 25.11% (113/450) in the nerve preservatio group [relative risk (RR) 0.39, 95% confidence interval (CI) 0.28–0.54; Z = 5.60 (P 0.00001)]. Neurectomy did no significantly increase the groin paresthesia 6 months after surgery at 8.5% (30/353) in the neurectomy group versu 4.5% (17/373) in the nerve preservation group [RR 1.62, 95% CI 0.94–2.80; Z = 1.74 (P = 0.08)]. At 12 months afte surgery, there is no advantage of neurectomy over chronic groin pain; no significant differences were found in th 12-month postoperative groin pain rate at 9% (9/100) in the neurectomy group versus 17.85% (20/112) in the inguina nerve preservation group [RR 0.50, 95% CI 0.24–1.05; Z = 1.83 (P = 0.07)]. One study (115 patients) reported dat about paresthesia at 12 months after surgery (7.27%, 4/55 in neurectomy group vs. 5%, 3/60 in nerve preservatio group) and results were not significantly different between the two groups [RR 1.45, 95% CI 0.34, 6.21;Z = 0.5 (P = 0.61)]. The subgroup analysis of the studies that identified the IIN showed a significant reduction of the 6th mont evaluation of pain in both groups and confirmed the same trend in favor of neurectomy reported in the previous overal analysis: statistically significant reduction of pain 6 months after surgery at 3.79% (6/158) in the neurectomy grou versus 14.6% (26/178) in the nerve preservation group [RR 0.28, 95% CI 0.13–0.63; Z = 3.10 (P = 0.002)]. Conclusion Ilioinguinal nerve identification in Lichtenstein inguinal hernia repair is the fundamental step to reduce or avoid postoperative pain. Prophylactic ilioinguinal nerve neurectomy seems to offer some advantages concerning pain in the first 6th month postoperative period, although it might be possible that the small number of cases contributed to the insignificancy regarding paresthesia and hypoesthesia. Nowadays, prudent surgeons should discuss with patients and their families the uncertain benefits and the potential risk of neurectomy before performing the hernioplasty

High adherence to enhanced recovery pathway independently reduces major morbidity and mortality rates after colorectal surgery: a reappraisal of the iCral2 and iCral3 multicenter prospective studies

Background: Enhanced recovery after surgery (ERAS) offers lower overall morbidity rates and shorter hospital stay after colorectal surgery (CRS); high adherence rates to ERAS may significantly reduce major morbidity (MM), anastomotic leakage (AL), and mortality (M) rates as well. Methods: Prospective enrollment of patients submitted to elective CRS with anastomosis in two separate 18- and 12-month periods among 78 surgical centers in Italy from 2019 to 2021. Adherence to ERAS pathway items was measured upon explicit criteria in every case. After univariate analysis, independent predictors of primary endpoints (MM, AL, and M rates) were identified through logistic regression analyses, presenting odds ratios (OR) and 95% confidence intervals. Results: An institutional ERAS status was declared by 48 out of 78 (61.5%) participating centers. The median overall adherence to ERAS was 75%. Among 8,359 patients included in both studies, MM, AL, and M rates were 6.3%, 4.4%, and 1.0%, respectively. Several patient-related and treatment-related variables showed independently higher rates for primary endpoints: male gender, American Society of Anesthesiologists class III, neoadjuvant treatment, perioperative steroids, intra- and/or postoperative blood transfusions, length of the operation >180’, surgery for malignancy. On the other hand, ERAS adherence >85% independently reduced MM (OR, 0.91) and M (OR, 0.25) rates, whereas no mechanical bowel preparation independently reduced AL (OR, 0.68) rates. Conclusions: Among other patient- or treatment-related variables, ERAS adherence >85% independently reduced MM and M rates, whereas no mechanical bowel preparation independently reduced AL rates after CRS

Targeting COPZ1 non-oncogene addiction counteracts the viability of thyroid tumor cells

Thyroid carcinoma is generally associated with good prognosis, but no effective treatments are currently available for aggressive forms not cured by standard therapy. To find novel therapeutic targets for this tumor type, we had previously performed a siRNA-based functional screening to identify genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same extent for the viability of normal cells (non-oncogene addiction paradigm). Among those, we found the coatomer protein complex ζ1 (COPZ1) gene, which is involved in intracellular traffic, autophagy and lipid homeostasis. In this paper, we investigated the mechanisms through which COPZ1 depletion leads to thyroid tumor cell death. We showed that siRNA-mediated COPZ1 depletion causes abortive autophagy, endoplasmic reticulum stress, unfolded protein response and apoptosis. Interestingly, we observed that mouse tumor xenografts, locally treated with siRNA targeting COPZ1, showed a significant reduction of tumor growth. On the whole, we demonstrated for the first time the crucial role of COPZ1 in the viability of thyroid tumor cells, suggesting that it may be considered an attractive target for novel therapeutic approaches for thyroid cancer

Operational experience on the generation and control of high brightness electron bunch trains at SPARC-LAB

Sub-picosecond, high-brightness electron bunch trains are routinely produced at SPARC-LAB via the velocity bunching technique. Such bunch trains can be used to drive multi-color Free Electron Lasers (FELs) and plasma wake field accelerators. In this paper we present recent results at SPARC-LAB on the generation of such beams, highlighting the key points of our scheme. We will discuss also the on-going machine upgrades to allow driving FELs with plasma accelerated beams or with short electron pulses at an increased energy

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN)

Background Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. Methods This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed >= 12, and proximal and distal free resection margins length >= 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. Results A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to infinity). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to infinity). Conclusions Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection

Segmental transverse colectomy. Minimally invasive versus open approach: results from a multicenter collaborative study

none65noThe role of minimally invasive surgery in the treatment of transverse colon cancer is still controversial. The aim of this study is to investigate the advantages of a totally laparoscopic technique comparing open versus laparoscopic/robotic approach. Three hundred and eighty-eight patients with transverse colon cancer, treated with a segmental colon resection, were retrospectively analyzed. Demographic data, tumor stage, operative time, intraoperative complications, number of harvested lymph nodes and recovery outcomes were recorded. Recurrences and death were also evaluated during the follow-up. No differences were found between conventional and minimally invasive surgery, both for oncological long-term outcomes (recurrence rate p = 0.28; mortality p = 0.62) and postoperative complications (overall rate p = 0.43; anemia p = 0.78; nausea p = 0.68; infections p = 0.91; bleeding p = 0.62; anastomotic leak p = 0.55; ileus p = 0.75). Nevertheless, recovery outcomes showed statistically significant differences in favor of minimally invasive surgery in terms of time to first flatus (p = 0.001), tolerance to solid diet (p = 0.017), time to first mobilization (p = 0.001) and hospital stay (p = 0.004). Compared with laparoscopic approach, robotic surgery showed significantly better results for time to first flatus (p = 0.001), to first mobilization (p = 0.005) and tolerance to solid diet (p = 0.001). Finally, anastomosis evaluation confirmed the superiority of intracorporeal approach which showed significantly better results for time to first flatus (p = 0.001), to first mobilization (p = 0.003) and tolerance to solid diet (p = 0.001); moreover, we recorded a statistical difference in favor of intracorporeal approach for infection rate (p = 0.04), bleeding (p = 0.001) and anastomotic leak (p = 0.03). Minimally invasive approach is safe and effective as the conventional open surgery, with comparable oncological results but not negligible advantages in terms of recovery outcomes. Moreover, we demonstrated that robotic approach may be considered a valid option and an intracorporeal anastomosis should always be preferred.noneMilone, Marco; Degiuli, Maurizio; Velotti, Nunzio; Manigrasso, Michele; Vertaldi, Sara; D'Ugo, Domenico; De Palma, Giovanni Domenico; Dario Bruzzese, Giuseppe Servillo, Giuseppe De Simone, Katia Di Lauro, Silvia Sofia, Marco Ettore Allaix, Mario Morino, Rossella Reddavid, Carlo Alberto Ammirati, Stefano Scabini, Gabriele Anania, Cristina Bombardini, Andrea Barberis, Roberta Longhin, Andrea Belli, Francesco Bianco, Giampaolo Formisano, Giuseppe Giuliani, Paolo Pietro Bianchi, Davide Cavaliere, Leonardo Solaini, Claudio Coco, Gianluca Rizzo, Andrea Coratti, Raffaele De Luca, Michele Simone, Alberto Di Leo, Giovanni De Manzoni, Paola De Nardi, Ugo Elmore, Riccardo Rosati, Andrea Vignali, Paolo Delrio, Ugo Pace, Daniela Rega, Antonio Di Cataldo, Giovanni Li Destri, Annibale Donini, Luigina Graziosi, Andrea Fontana, Michela Mineccia, Sergio Gentilli, Manuela Monni, Mario Guerrieri, Monica Ortenzi, Francesca Pecchini, Micaela Piccoli, Italy. Corrado Pedrazzani, Giulia Turri, Sara Pollesel, Franco Roviello, Marco Rigamonti, Michele Zuolo, Mauro Santarelli, Federica Saraceno, Pierpaolo Sileri Giuseppe Sigismondo Sica, Luigi Siragusa Salvatore Pucciarelli, Matteo ZuinMilone, Marco; Degiuli, Maurizio; Velotti, Nunzio; Manigrasso, Michele; Vertaldi, Sara; D'Ugo, Domenico; De Palma, Giovanni Domenico; Dario Bruzzese, Giuseppe Servillo, Giuseppe De Simone, Katia Di Lauro, Silvia Sofia, Marco Ettore Allaix, Mario Morino, Rossella Reddavid, Carlo Alberto Ammirati, Stefano Scabini, Gabriele Anania, Cristina Bombardini, Andrea Barberis, Roberta Longhin, Andrea Belli, Francesco Bianco, Giampaolo Formisano, Giuseppe Giuliani, Paolo Pietro Bianchi, Davide Cavaliere, Leonardo Solaini, Claudio Coco, Gianluca Rizzo, Andrea Coratti, Raffaele De Luca, Michele Simone, Alberto Di Leo, Giovanni De Manzoni, Paola De Nardi, Ugo Elmore, Riccardo Rosati, Andrea Vignali, Paolo Delrio, Ugo Pace, Daniela Rega, Antonio Di Cataldo, Giovanni Li Destri, Annibale Donini, Luigina Graziosi, Andrea Fontana, Michela Mineccia, Sergio Gentilli, Manuela Monni, Mario Guerrieri, Monica Ortenzi, Francesca Pecchini, Micaela Piccoli, Italy. Corrado Pedrazzani, Giulia Turri, Sara Pollesel, Franco Roviello, Marco Rigamonti, Michele Zuolo, Mauro Santarelli, Federica Saraceno, Pierpaolo Sileri Giuseppe Sigismondo Sica, Luigi Siragusa Salvatore Pucciarelli, Matteo Zui

Appendectomy during the COVID-19 pandemic in Italy: a multicenter ambispective cohort study by the Italian Society of Endoscopic Surgery and new technologies (the CRAC study)

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March-April 2019 vs March-April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p < 0.001). The following determinants increased the likelihood of complication occurrence: undergoing surgery during 2020 (+ 67%), the increase of a unit in the AAST score (+ 26%), surgery performed > 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 202