Metaverse and Telementoring: From Surgery to Workshop.

BACKGROUND: The Coronavirus 2019 (COVID-19) pandemic has favored the growth of telemedicine systems and in this context the idea of Metaverse was born and developed. A 3D reality in which people can interact with each other through digital reproductions of themselves. Metaverse has already been tested in numerous medical fields due to its ability to combine visual and auditory information with tactile sensations. The purpose of this study is to highlight its potential also in its ability to be used as a telementoring place where the skills and knowledge of surgeons from all over the world can be combined. MATERIAL AND METHODS: The first HPB Surgery Workshop was held at the "Metaverse Surgical Hospital, USA". During the workshop, surgeons located in various parts of the world reported on hepatic, pancreatic and biliary tract surgery and remotely supported the execution of a robotic liver resection. RESULTS: The Metaverse gave the opportunity for surgeons to meet and discuss HPB pathologies and its surgical strategies and for surgeons in training to interface with experts by participating in a moment of advanced training. CONCLUSION: In the Metaverse, telementoring can be used at very low cost to improve clinical and surgical practice.

A Systematic Review of Varying Definitions and the Clinical Significance of Fredet's Fascia in the Era of Complete Mesocolic Excision.

BACKGROUND: Fredet's fascia represents a crucial landmark for vascular surgical anatomy, especially in minimally invasive complete mesocolic excision (CME) for right-sided colon adenocarcinoma. Fredet's fascia allows access to the gastrocolic trunk of Henle (GCTH), the most critical step in both open and minimally invasive right-sided CME techniques. Despite this, a recent workshop of expert surgeons on the standardization of the laparoscopic right hemicolectomy with CME did not recognize or include the term of Fredet's fascia or area. Hence, we undertook a systematic review of articles that include the terms "Fredet's fascia or area", or synonyms thereof, with special emphasis on the types of articles published, the nationality, and the relevance of this area to surgical treatments. METHODS: We conducted a systematic review up to 15 July 2022 on PubMed, WOS, SCOPUS, and Google Scholar. RESULTS: The results of the study revealed that the term "Fredet's fascia" is poorly used in the English language medical literature. In addition, the study found controversial and conflicting data among authors regarding the definition of "Fredet's fascia" and its topographical limits. CONCLUSIONS: Knowledge of Fredet's fascia's surgical relevance is essential for colorectal surgeons to avoid accidental injuries to the superior mesenteric vascular pedicle during minimally invasive right hemicolectomies with CME. In order to avoid confusion and clarify this fascia for future use, we suggest moving beyond the use of the eponymous term by using a "descriptive term" instead, based on the fascia's anatomic structure. Fredet's fascia could, therefore, be more appropriately renamed "sub-mesocolic pre-duodenopancreatic fascia".

Multi-visceral resection for left-sided pancreatic ductal adenocarcinoma: a multicenter retrospective analysis from European countries.

BACKGROUND: Due to delayed diagnosis and a lower surgical indication rate, left-sided pancreatic ductal adenocarcinoma (PDAC) is often associated with a poor prognosis in comparison to pancreatic head tumors. Multi-visceral resections (MVR) associated with distal pancreatectomy could be proposed for patients presenting with locally infiltrating disease. METHODS: We retrospectively analyzed a multi-centric cohort of left-sided PDAC patients operated on from 2009 to 2020. Thirteen European high-volume HPB centers participated in this study. We analyzed patients who underwent distal pancreatectomy (DP) associated with MVR and compared them to standard DP patients. RESULTS: Among 258 patients treated curatively for PDAC of the body and tail, 28 patients successfully underwent MVR. A longer operative time was observed in the MVR group (295 min +/- 74 vs. 250 min +/- 96, p= 0.248). The post-operative complication rate was comparable between the two groups (46.4% in the MVR group vs. 62.2% in the control group, p= 0.108). The incidence of positive margin (R1) was similar between the two groups (28.6% vs. 26.6%; p=0.827). After a median follow-up of 25 (9-111) months, overall survival was comparable between the two groups (p= 0.519). CONCLUSIONS: Multi-visceral resection in left-sided pancreatic ductal adenocarcinoma is safe and feasible and should be considered in selected cases as it seems to provide acceptable surgical and oncological outcomes.

Inferior mesenteric artery ligation level in rectal cancer surgery: still no answer-a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis is to summarize the current scientific evidence regarding the impact of the level of inferior mesenteric artery (IMA) ligation on post-operative and oncological outcomes in rectal cancer surgery. METHODS: We conducted a systematic review of the literature up to 06 September 2022. Included were RCTs that compared patients who underwent high (HL) vs. anterior (LL) IMA ligation for resection of rectal cancer. The literature search was performed on Medline/PubMed, Scopus, and the Web of Science without any language restrictions. The primary endpoint was overall anastomotic leakage (AL). Secondary endpoints were oncological outcomes, intraoperative complications, urogenital functional outcomes, and length of hospital stay. RESULTS: Eleven RCTs (1331 patients) were included. The overall rate of AL was lower in the LL group, but the difference was not statistically significant (RR 1.43, 95% CI 0.95 to 2.96). The overall number of harvested lymph nodes was higher in the LL group, but the difference was not statistically significant (MD 0.93, 95% CI - 2.21 to 0.34). The number of lymph nodes harvested was assessed in 256 patients, and all had a laparoscopic procedure. The number of lymph nodes was higher when LL was associated with lymphadenectomy of the vascular root than when IMA was ligated at its origin, but there the difference was not statistically significant (MD - 0.37, 95% CI - 1.00 to 0.26). Overall survival at 5 years was slightly better in the LL group, but the difference was not statistically significant (RR 0.98, 95% CI 0.93 to 1.05). Disease-free survival at 5 years was higher in the LL group, but the difference was not statistically significant (RR 0.97, 95% CI 0.89 to 1.04). CONCLUSIONS: There is no evidence to support HL or LL according to results in terms of AL or oncologic outcome. Moreover, there is not enough evidence to determine the impact of the level of IMA ligation on functional outcomes. The level of IMA ligation should be chosen case by case based on expected functional and oncological outcomes.

Robotic versus laparoscopic left colectomy: a propensity score matched analysis from a bi-centric experience.

The advantages of using the robotic platform may not be clearly evident in left colectomies, where the surgeon operates in an "open field" and does not routinely require intraoperative suturing. Current evidences are based on limited cohorts reporting conflicting outcomes regarding robotic left colectomies (RLC). The aim of this study is to report a bi-centric experience with robotic left colectomy in order to help in defining the role of the robotic approach for these procedures. This is a bi-centric propensity score matched study including patients who underwent RLC or laparoscopic left colectomy (LLC) between January 1, 2012 and May 1, 2022. RLC patients were matched to LLC patients in a 1:1 ratio. Main outcomes were conversion to open surgery and 30-day morbidity. In total, 300 patients were included. Of 143 (47.7%) RLC patients, 119 could be matched. After matching, conversion rate (4.2 vs. 7.6%, p = 0.265), 30-day morbidity (16.1 vs. 13.7%, p = 0.736), Clavien-Dindo grade ≥ 3 complications (2.4 vs 3.2%, p = 0.572), transfusions (0.8 vs. 4.0%, p = 0.219), and 30-day mortality (0.8 vs 0.8%, p = 1.000) were comparable for RLC and LLC, respectively. Median operative time was longer for RLC (296 min 260-340 vs. 245, 195-296, p < 0.0001). Early oral feeding, time to first flatus, and hospital stay were similar between groups. RLC has safety parameters as well as conversion to open surgery comparable with standard laparoscopy. Operative time is longer with the robotic approach.

Systemic Inflammatory Indices in Second-Line Soft Tissue Sarcoma Patients: Focus on Lymphocyte/Monocyte Ratio and Trabectedin.

A second-line standard of treatment has not yet been identified in patients with soft tissue sarcomas (STS), so identifying predictive markers could be a valuable tool. Recent studies have shown that the intratumoral and inflammatory systems significantly influence tumor aggressiveness. We aimed to investigate prognostic values of pre-therapy neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory index (SII), progression-free survival (PFS), and overall survival (OS) of STS patients receiving second-line treatment. In this single-center retrospective analysis, ninety-nine patients with STS were enrolled. All patients received second-line treatment after progressing to anthracycline. PFS and OS curves were calculated using the Kaplan-Meier method of RNA sequencing, and CIBERSORT analysis was performed on six surgical specimens of liposarcoma patients. A high NLR, PLR, and SII were significantly associated with worse PFS (p = 0.019; p = 0.004; p = 0.006). Low LMR was significantly associated with worse OS (p = 0.006). Patients treated with Trabectedin showed a better PFS when the LMR was low, while patients treated with other regimens showed a worse PFS when the LMR was low (p = 0.0154). The intratumoral immune infiltrates analysis seems to show a correlation between intratumoral macrophages and LMR. PS ECOG. The metastatic onset and tumor burden showed prognostic significance for PFS (p = 0.004; p = 0.041; p = 0.0086). According to the histologies, PFS was: 5.7 mo in liposarcoma patients vs. 3.8 mo in leiomyosarcoma patients vs. 3.1 months in patients with other histologies (p = 0.053). Our results confirm the prognostic role of systemic inflammatory markers in patients with STS. Moreover, we demonstrated that LMR is a specific predictor of Trabectedin efficacy and could be useful in daily clinical practice. We also highlighted a possible correlation between LMR levels and the percentage of intratumoral macrophages.

Inframesocolic Approach for Robotic Enucleation of Branch-Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas.

BACKGROUND: The inframesocolic approach to the uncinate process of the pancreas has been rarely described in literature. To the best of our knowledge, no robotic cases have been reported. METHODS: The case of a 74-year-old woman, with a 43-mm branch-duct intraductal papillary mucinous neoplasm with worrisome features within the uncinate process of the pancreas, is described. RESULTS: After diagnostic work-up, due to the uncertain potential of malignancy and the strong motivation of the patient to undergo surgery, we performed a robotic enucleation through an inframesocolic approach. The neoplasm was more than 1 cm from the main pancreatic duct. Final pathological diagnosis revealed a low-grade dysplasia branch-duct intraductal papillary mucinous neoplasm. CONCLUSIONS: The inframesocolic approach could represent an easy way to access the uncinate process of the pancreas, allowing safe limited resection in selected cases such as small branch-duct IPMN or pancreatic neuroendocrine tumors.

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 ∞). 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 ∞). 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.

Hyperthermic intraperitoneal chemotherapy and colorectal cancer: From physiology to surgery.

The pursuit of this paper is to collect principal reviews and systematic reviews about hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) used in colorectal cancer (CRC). We focus on principal biological aspects of CRC, hyperthermia effects, and surgical procedures. We searched PubMed/MEDLINE for the principal reviews and systematic reviews published from 2010 to 2021 regarding the bimodal treatment (CRS + HIPEC) against local and advanced CRC. In the literature, from several studies, it seems that the efficacy of bimodal treatment with an accurate CRS can extend overall survival. Despite these studies, there are not still any straight guidelines more detailed and scheduled about the use of combined treatment in patients with CRC. Even if the concept is still not very clear and shared, after a careful evaluation of the published data, and after some technical and pathophysiological descriptions, we concluded that it is possible to improve the overall survival and quality of life and to reduce the tumor relapse in patients affected by locally advanced (pT4) CRC with peritoneal metastases.

Dysbiosis and Gastrointestinal Surgery: Current Insights and Future Research.

Surgery of the gastrointestinal tract can result in deep changes among the gut commensals in terms of abundance, function and health consequences. Elective colorectal surgery can occur for neoplastic or inflammatory bowel disease; in these settings, microbiota imbalance is described as a preoperative condition, and it is linked to post-operative complications, as well. The study of bariatric patients led to several insights into the role of gut microbiota in obesity and after major surgical injuries. Preoperative dysbiosis and post-surgical microbiota reassessment are still poorly understood, and they could become a key part of preventing post-surgical complications. In the current review, we outline the most recent literature regarding agents and molecular pathways involved in pre- and post-operative dysbiosis in patients undergoing gastrointestinal surgery. Defining the standard method for microbiota assessment in these patients could set up the future approach and clinical practice.

Prognostic and Predictive Role of Body Composition in Metastatic Neuroendocrine Tumor Patients Treated with Everolimus: A Real-World Data Analysis.

Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an upregulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression. The aim of this study is to investigate the role of body composition indexes in patients with metastatic NETs treated with everolimus. The study population included 30 patients with well-differentiated (G1-G2), metastatic NETs treated with everolimus at the IRCCS Romagnolo Institute for the Study of Tumors (IRST) "Dino Amadori", Meldola (FC), Italy. The body composition indexes (skeletal muscle index [SMI] and adipose tissue indexes) were assessed by measuring on a computed tomography (CT) scan the cross-sectional area at L3 at baseline and at the first radiological assessment after the start of treatment. The body mass index (BMI) was assessed at baseline. The median progression-free survival (PFS) was 8.9 months (95% confidence interval [CI]: 3.4-13.7 months). The PFS stratified by tertiles was 3.2 months (95% CI: 0.9-10.1 months) in patients with low SMI (tertile 1), 14.2 months (95% CI: 2.3 months-not estimable [NE]) in patients with intermediate SMI (tertile 2), and 9.1 months (95% CI: 2.7 months-NE) in patients with high SMI (tertile 3) (p = 0.039). Similarly, the other body composition indexes also showed a statistically significant difference in the three groups on the basis of tertiles. The median PFS was 3.2 months (95% CI: 0.9-6.7 months) in underweight patients (BMI ≤ 18.49 kg/m2) and 10.1 months (95% CI: 3.7-28.4 months) in normal-weight patients (p = 0.011). There were no significant differences in terms of overall survival. The study showed a correlation between PFS and the body composition indexes in patients with NETs treated with everolimus, underlining the role of adipose and muscle tissue in these patients.

Robotic versus laparoscopic left colectomy: a systematic review and meta-analysis.

BACKGROUND: This study aimed to review the new evidence to understand whether the robotic approach could find some clear indication also in left colectomy. METHODS: A systematic review of studies published from 2004 to 2022 in the Web of Science, PubMed, and Scopus databases and comparing laparoscopic (LLC) and robotic left colectomy (RLC) was performed. All comparative studies evaluating robotic left colectomy (RLC) versus laparoscopic (LLC) left colectomy with at least 20 patients in the robotic arm were included. Abstract, editorials, and reviews were excluded. The Newcastle-Ottawa Scale for cohort studies was used to assess the methodological quality. The random-effect model was used to calculate pooled effect estimates. RESULTS: Among the 139 articles identified, 11 were eligible, with a total of 52,589 patients (RLC, n = 13,506 versus LLC, n = 39,083). The rate of conversion to open surgery was lower for robotic procedures (RR 0.5, 0.5-0.6; p < 0.001). Operative time was longer for the robotic procedures in the pooled analysis (WMD 39.1, 17.3-60.9, p = 0.002). Overall complications (RR 0.9, 0.8-0.9, p < 0.001), anastomotic leaks (RR 0.7, 0.7-0.8; p < 0.001), and superficial wound infection (RR 3.1, 2.8-3.4; p < 0.001) were less common after RLC. There were no significant differences in mortality (RR 1.1; 0.8-1.6, p = 0.124). There were no differences between RLC and LLC with regards to postoperative variables in the subgroup analysis on malignancies. CONCLUSIONS: Robotic left colectomy requires less conversion to open surgery than the standard laparoscopic approach. Postoperative morbidity rates seemed to be lower during RLC, but this was not confirmed in the procedures performed for malignancies.

Numerical and experimental analysis of Lagrangian dispersion in two-dimensional chaotic flows.

We present a review and a new assessment of the Lagrangian dispersion properties of a 2D model of chaotic advection and diffusion in a regular lattice of non stationary kinematic eddies. This model represents an ideal case for which it is possible to analyze the same system from three different perspectives: theory, modelling and experiments. At this regard, we examine absolute and relative Lagrangian dispersion for a kinematic flow, a hydrodynamic model (Delft3D), and a laboratory experiment, in terms of established dynamical system techniques, such as the measure of (Lagrangian) finite-scale Lyapunov exponents (FSLE). The new main results concern: (i) an experimental verification of the scale-dependent dispersion properties of the chaotic advection and diffusion model here considered; (ii) a qualitative and quantitative assessment of the hydro-dynamical Lagrangian simulations. The latter, even though obtained for an idealized open flow configuration, contributes to the overall validation of the computational features of the Delft3D model.

Robotic versus laparoscopic inguinal hernia repair: an updated systematic review and meta-analysis.

The aim of this study was to review the latest evidence on the robotic approach (RHR) for inguinal hernia repair comparing the pooled outcome of this technique with those of the standard laparoscopic procedure (LHR). A systematic literature search was performed in PubMed, Web of Science and Scopus for studies published between 2010 and 2021 concerning the comparison between RHR versus LHR. After screening 582 articles, 9 articles with a total of 64,426 patients (7589 RHRs) were eligible for inclusion. Among preoperative variables, a pooled higher ratio of ASA > 2 patients was found in the robotic group (12.4 vs 8.6%, p < 0.001). Unilateral hernia repair was more common in the laparoscopic group (79.9 vs 68.1, p < 0.001). Overall, operative time was longer in the robotic group (160 vs 90 min, p < 0.001); this was confirmed also in the sub-analysis on unilateral procedures (88 vs 68 min, p = 0.040). The operative time for robotic bilateral repair was similar to the laparoscopic one (111 vs 100, p = 0.797). Conversion to open surgery was 0% in the robotic group. The pooled rate of chronic pain and postoperative complications was similar between the groups. The standardized mean difference MD of the costs between LHR versus RHR was - 3270$ (95% CI - 4757 to - 1782, p < 0.001). In conclusion, laparoscopic and robotic inguinal hernia repair have similar safety parameters and postoperative outcomes. Robotic approach may require longer operative time if the unilateral repair is performed. Costs are higher in the robotic group.

Risk factors for anastomotic leakage after anterior resection for rectal cancer (RALAR study): A nationwide retrospective study of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group.

AIM: Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage. METHODS: The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient-, disease-, treatment- and postoperative outcome-related factors on anastomotic leak after univariable and multivariable analysis was measured. RESULTS: A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30-day leak-related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection. CONCLUSIONS: While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high-risk patients eligible for protective stoma construction.

HRAS overexpression predicts response to Lenvatinib treatment in gastroenteropancreatic neuroendocrine tumors.

Introduction: Neuroendocrine neoplasms (NENs) are a rare group of tumors exceptionally heterogeneous, with clinical presentation ranging from well differentiated more indolent tumors to poorly differentiated very aggressive forms. Both are often diagnosed after the metastatic spread and require appropriate medical treatment. A high priority need in the management of this disease is the identification of effective therapeutic strategies for advanced and metastatic patients. The recent TALENT trial demonstrated the efficacy of lenvatinib, a multi-tyrosine kinase inhibitor, in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with no other treatment indication. Further development of this drug in advanced NETs is warranted. Methods: We investigated potential clinical and molecular determinants of lenvatinib response in human primary cultures derived from patients with GEP-NET of different grades and sites of origin. We correlated response to treatment with patient clinical characteristics, with the mutational status of 161-cancer associated genes and with the expression levels of MKI-related genes. Results: Lenvatinib exerted a significant antitumor activity in primary GEP-NET cells, with median survival inhibitions similar or higher than those of standard frontline treatments. Of the 11 primary cultures analyzed in our case series, 6 were classified as responder showing a significant survival inhibition, and 5 as non-responder. We observed that the overexpression of HRAS in the original tumor tissue compared to the matched healthy tissue significantly correlated with responsiveness of primary cells to lenvatinib (p=.048). All 5 non-responder cultures showed normal HRAS expression, while of the 6 responder cultures, 4 had HRAS overexpression. Overexpression of HRAS was not associated with gene mutation. None of the other evaluated clinical variables (grade, Ki67, site of origin and syndromic disease) or molecular markers correlated with response. Discussion: Lenvatinib appears to be a highly effective drug for the treatment of NETs. The evaluation of HRAS expression in the tumor tissue might improve patient selection and optimize therapeutic outcome.

The potential role of the extracellular matrix in the activity of trabectedin in UPS and L-sarcoma: evidences from a patient-derived primary culture case series in tridimensional and zebrafish models.

BACKGROUND: Soft tissue sarcomas (STS) are a rare group of solid neoplasm including among others liposarcoma, leiomyosarcoma (L-sarcoma) and undifferentiated pleomorphic sarcoma (UPS) entities. The current first-line treatment is represented by anthracycline based- regimens, second-line may include trabectedin. Currently the activity of trabectedin and its mechanism of action is not completely elucidated. METHODS: Taking the advantages of our 3D patient-derived primary culture translational model we performed genomic-, chemobiogram, proteomic- and in vivo analysis in a UPS culture (S1). Furthermore pharmacological profiling of a UPS and L-sarcoma patient-derived case series and in silico analysis were carried out. RESULTS: Trabectedin exhibited an increased activity in 3D respect to 2D cultures suggesting an extracellular matrix (ECM) and timp1 involvement in its mechanism of action. Moreover 3D S1 xenotranspanted zebrafish model showed an increased sensitivity to trabectedin. Finally the results were further validated in a UPS and L-sarcoma case series. CONCLUSIONS: Taken together these results confirmed the activity of trabectedin in these STS histotypes. Moreover the data underline the ECM involvement in the cytotoxic effect mediated by trabectedin and could open the door for researches aimed to focus on the patient setting that could benefit from this agent.

Current Status of the Self-Expandable Metal Stent as a Bridge to Surgery Versus Emergency Surgery in Colorectal Cancer: Results from an Updated Systematic Review and Meta-Analysis of the Literature.

Background: The current use of endoscopic stenting as a bridge to surgery is not always accepted in standard clinical practice to treat neoplastic colonic obstructions. Objectives: The role of colonic self-expandable metal stent (SEMS) positioning as a bridge to resective surgery versus emergency surgery (ES) for malignant obstruction, using all new data and available variables, was studied and we focused on short- and long-term results. Materials and Methods: A systematic review with meta-analysis was performed. PubMed, SCOPUS and Web of Science databases were included. The search comprised only randomized controlled trials (RCTs) investigating the interventions that included SEMS positioning versus ES. The primary outcomes were the rates of overall postoperative mortality, clinical and technical success. The secondary outcomes were the short- and long-term results. Results: A total of 12 studies were eligible for further analyses. A laparoscopic colectomy was the most common operation performed in the SEMS group, whereas the traditional open approach was commonly used in the ES group. Intraoperative colonic lavage was seldomly performed during ES. There were no differences in mortality rates between the two groups (RR 1.06, 95% CI 0.55 to 2.04; I2 = 0%). In the SEMS group, the rate of successful primary anastomosis was significantly higher in of SEMS (69.75%) than in the ES (55.07%) (RR 1.26, 95% 245 CI 1.01 to 1.57; I2 = 86%). Conversely, the upfront Hartmann procedure was performed more frequently in the ES (39.1%) as compared to the SEMS group (23.4%) (RR 0.61, 95% CI 0.45 to 0.85; I2 = 23%). The overall postoperative complications rate was significantly lower in the SEMS group (32.74%) than in the ES group (48.25%) (RR 0.61, 95% CI 0.41 to 0.91; I2 = 65%). Conclusions: In the presence of malignant colorectal obstruction, SEMS is safe and associated with the same mortality and significantly lower morbidity than the ES group. The rate of successful primary anastomosis was significantly higher than the ES group. Nevertheless, recurrence and survival outcomes are not significantly different between the two groups. The analysis of short- and long-term results can suggest the use of SEMS as a bridge to resective surgery when it is performed by an endoscopist with adequate expertise in both colonoscopy and fluoroscopic techniques and who performed commonly colonic stenting.