Interaction analysis of subgroup effects in randomized trials: the essential methodological points.

Subgroup analysis aims to identify subgroups (usually defined by baseline/demographic characteristics), who would (or not) benefit from an intervention under specific conditions. Often performed post hoc (not pre-specified in the protocol), subgroup analyses are prone to elevated type I error due to multiple testing, inadequate power, and inappropriate statistical interpretation. Aside from the well-known Bonferroni correction, subgroup treatment interaction tests can provide useful information to support the hypothesis. Using data from a previously published randomized trial where a p value of 0.015 was found for the comparison between standard and Hemopatch® groups in (the subgroup of) 135 patients who had hand-sewn pancreatic stump closure we first sought to determine whether there was interaction between the number and proportion of the dependent event of interest (POPF) among the subgroup population (patients with hand-sewn stump closure and use of Hemopatch®), Next, we calculated the relative excess risk due to interaction (RERI) and the "attributable proportion" (AP). The p value of the interaction was p = 0.034, the RERI was - 0.77 (p = 0.0204) (the probability of POPF was 0.77 because of the interaction), the RERI was 13% (patients are 13% less likely to sustain POPF because of the interaction), and the AP was - 0.616 (61.6% of patients who did not develop POPF did so because of the interaction). Although no causality can be implied, Hemopatch® may potentially decrease the POPF after distal pancreatectomy when the stump is closed hand-sewn. The hypothesis generated by our subgroup analysis requires confirmation by a specific, randomized trial, including only patients undergoing hand-sewn closure of the pancreatic stump after distal pancreatectomy.Trial registration: INS-621000-0760.

Pancreatic stump closure after distal pancreatectomy: Systematic review and meta-analysis of randomized clinical trials comparing non-autologous versus no reinforcement: Value of prediction intervals.

BACKGROUND: This meta-analysis of randomized trials aimed to assess the benefits and harms of non-autologous versus no reinforcement of the pancreatic stump following distal pancreatectomy (DP). METHODS: It was performed in accordance with PRISMA 2020 and AMSTAR 2 Guidelines. (registered in PROSPERO ID: EROCRD42021286863). RESULTS: Nine relevant articles (between 2009 and 2021) were retrieved, comparing non-autologous reinforcement (757 patients) with non-reinforcement (740 patients) after PD. Pooled analysis showed a statistically significant lower rate of postoperative pancreatic fistula (POPF) in the reinforcement group (RR â€‹= â€‹0.677; 95 â€‹% CI [0.479, 0.956], p â€‹= â€‹0.027). The 95 â€‹% predictive interval (0.267-1.718) showed heterogeneity. Non-autologous reinforcement other than with "Tachosil®" was effective (subgroup analysis). No statistically significant differences were found between the two groups with regard to secondary outcomes. CONCLUSIONS: This meta-analysis showed that covering the stump with non-autologous reinforcement other than Tachosil® had a preventive effect on the onset of POPF.

Effectiveness of Hemopatch® versus Surgicel® Original to control mild and moderate liver bleeding.

BACKGROUND: Adjunct hemostats can be of use in certain surgical settings. We compared the effectiveness of two hemostats, Hemopatch® and Surgicel® Original in controlling bleeding from liver lesions in an experimental model. METHODS: Control of grades 1 (mild) and 2 (moderate) bleeding (according to the Validated Intraoperative Bleeding [VIBe] SCALE) was assessed for 10 min after Hemopatch® (n = 198) or Surgicel® Original (n = 199) application on 397 liver surface lesions. The primary endpoint was hemostatic success (reaching VIBe SCALE grade 0 at 10 min). The secondary endpoint was time to hemostasis (time to reach and maintain grade 0). A generalized linear mixed model and an accelerated failure time model were used to assess the primary and secondary endpoints, respectively. RESULTS: The overall hemostatic success rate of Hemopatch® was statistically significantly superior to that of Surgicel® Original (83.8% versus 73.4%; p = 0.0036; odds ratio [OR] 2.38, 95% confidence interval [CI] 1.33-4.27) and time to hemostasis was reduced by 15.9% (p = 0.0032; 95% CI 0.749-0.944). Grade 2 bleeds treated with Hemopatch® had statistically significantly higher hemostatic success (71.7% versus 48.5%; p = 0.0007; OR 2.97, 95% CI 1.58-5.58) and shorter time to hemostasis (49.6% reduction, p = 3.6 × 10-8); differences for grade 1 bleeds (hemostatic success rate or time to hemostasis) were not statistically significant. CONCLUSIONS: Hemopatch® provided better control of VIBe SCALE bleeding compared to Surgicel® Original for Grade 2 bleeds in this porcine model, highlighting the importance of choosing a suitable hemostat to optimize control of bleeding during surgery.

Academic surgery amid the COVID-19 pandemic: A perspective of the present and future challenges.

This narrative review describes the trials and tribulations of academic surgeons in four major cities of their respective countries and the solutions they retained to keep academia alive in their practice. The four pillars of an "academic surgeon" _teaching, producing scientific works presented in meetings, publications and research_ are dealt with bearing in mind the modifications brought about by the pandemic and the solutions to keep academia active. Throughout the pandemic, the ultimate goal has been and will be to improve care and train the next generation of surgeons and encourage and monitor researchers, guide the mentees through the tasks of leadership, and foster good sound presentations at scientific meetings and encourage innovative and fruitful publications. The pros and cons of the alternatives imposed by the pandemic for the above-mentioned academic components, based on the literature, are reviewed and analyzed as they are taking place today in Shanghai, Milan, Graz, TaiChung and Hsinchu. Our perspective for the future is that teaching will take a new aspect and make wide use of electronic platforms, but also, the face-to-face modality will surface again. According to local needs and funding, many will most likely choose the hybrid solution (electronic and presential). Production of scientific works in meetings has gained momentum, again with the hybrid solution being preferred. Scientific publications have already increased on topics that are no longer related to COVID-19, and both clinical and experimental research are flourishing. This review can provide insight to guide young and accomplished academic surgeons through these difficult times and beyond, promoting a renaissance of clinical research and relevant publications, teaching of surgery and scientific meetings with a hybrid approach, and, finally, contribute to the training and formation of a new generation of surgeons for the future post-COVID-19 era.

Clinical Impact of Stump Closure Reinforced With Hemopatch on the Prevention of Clinically Relevant Pancreatic Fistula After Distal Pancreatectomy: A Multicenter Randomized Trial.

Introduction: Postoperative pancreatic fistula (POPF) is the most dreaded complication after distal pancreatectomy (DP). This multicenter randomized trial evaluated the efficacy, safety, and tolerance of Hemopatch in preventing clinically relevant (grades B/C according to the ISGPS classification) POPF after DP. Material and methods: After stump closure, patients were randomized to affix Hemopatch to the stump or not. Statistical significance was set at 0.025. Clinical significance was defined as the number of patients needed to treat (NNT) to avoid 1 B/C POPF. Results: Of 631 eligible patients, 360 were randomized and 315 analyzed per protocol (155 in the standard closure group; 160 in the Hemopatch group). The rates of B/C POPF (the primary endpoint) were 23.2% and 16.3% (P = 0.120), while the number of patients with 1 or more complications (including patients with B/C POPF) was 34.8% and 24.4% (P = 0.049) in the standard and Hemopatch groups, respectively. In patients with hand-sewn stump and main duct closure, the rates were 26.2% versus 10.0% (P = 0.014) and 23.3% versus 7.7% (P = 0.015) in the standard and Hemopatch groups, respectively. The NNT in these 2 subgroups was 6 and 6.4, respectively. Conclusion: The results of the first randomized trial evaluating Hemopatch-reinforced pancreatic stump after DP to prevent type B/C POPF do not allow us to conclude that the risk of B/C POPF was lower. Based on the NNT, however, routine use of Hemopatch after DP may result in fewer complications (including POPF) overall, especially in cases with hand-sewn closure of the pancreatic stump or main pancreatic duct.

Enhancing safety of laparoscopic surgery in COVID-19 era: clinical experience with low-cost filtration devices.

BACKGROUND: Surgery in the era of the current COVID-19 pandemic has been curtailed and restricted to emergency and certain oncological indications, and requires special attention concerning the safety of patients and health care personnel. Desufflation during or after laparoscopic surgery has been reported to entail a potential risk of contamination from 2019-nCoV through the aerosol generated during dissection and/or use of energy-driven devices. In order to protect the operating room staff, it is vital to filter the released aerosol. METHODS: The assemblage of two easily available and low-cost filter systems to prevent potential dissemination of Coronavirus via the aerosol is described. RESULTS: Forty-nine patients underwent laparoscopic surgeries with the use of one of the two described tools, both of which proved to be effective in smoke evacuation, without affecting laparoscopic visualization. CONCLUSION: The proposed systems are cost-effective, easily assembled and reproducible, and provide complete viral filtration during intra- and postoperative release of CO2.

A New Synthetic Conduit for the Treatment of Peripheral Nerve Injuries.

BACKGROUND: Peripheral nerve defects (PND) often cause lifelong physical disability, and the available treatment options are often not satisfactory. PND are usually bridged with an autologous nerve transplant or a nerve guidance conduit (NGC), when coaptation as preferred technique is not possible. The aim of this experimental study was to determine the effectiveness of a novel NGC for regeneration in the treatment of PND. MATERIALS AND METHODS: A conduit made of gelatin with an innovative interior structure was tested for the repair of a 6-mm gap versus direct microsurgical suture repair without gap. RESULTS: We found that bridging the defect with this conduit was as effective as direct microsurgical coaptation without a defect. CONCLUSIONS: This nerve conduit, effective in bridging neural defects, appears as an alternative to autologous nerve grafts, avoiding the problems related to nerve graft harvesting, host-donor differences in diameter, mismatches in number and pattern of fascicles, cross-sectional shape and area, and morbidity of the donor area.

Quality of life in uncomplicated recurrent diverticulitis: surgical vs. conservative treatment.

Elective sigmoid colectomy for recurrent uncomplicated diverticulitis remains controversial and is decided on an individual basis. Eighty patients treated conservatively (44 patients) or by elective surgery (36 patients) for recurrent uncomplicated diverticulitis were contacted and assessed for quality of life. The mean difference in quality of life scores was greater after surgery (overall + 2.14%, laparoscopic resection +4.95%, p = 0.36 and p = 0.11, respectively) as compared to conservative management. Female patients undergoing laparoscopic resection had statistically significantly higher quality of life scores than women treated conservatively (+8.98%; p = 0.049). Twenty-eight of 29 responding patients stated that they were highly satisfied and would have the operation done again. Elective sigmoidectomy is a valid treatment option for recurrent uncomplicated diverticulitis in terms of quality of life. Quality of life improved most if surgery was performed laparoscopically, especially in women.

Laparoscopic Cholecystectomy in the Cirrhotic: Review of Literature on Indications and Technique.

Cholelithiasis is twice more common in patients suffering from liver cirrhosis compared to overall population and in those patients, acute cholecystitis occurs significantly more often. Our goal was to review the literature and to overview the indications, contra-indications, and alternatives in the cirrhotic with biliary stones. We conducted a systematic review of the literature using the key words "Cirrhosis", "cholecystectomy", "laparoscopy"and "indications". Selected articles were reviewed for information specific to indications, contra-indications, and alternatives to laparoscopic cholecystectomy in cirrhotics. Results showed that laparoscopic cholecystectomy might offer several advantages in cirrhotic population, however cholecystectomy can be challenging: specific indications and alternatives to surgery must be discussed case by case. Laparoscopic cholecystectomy can be performed safely in selected patients with cirrhosis; special precautions are warranted regarding pneumoperitoneum pressure, trocar placement and increased safety with Indocyanine-green (ICG) fluorescence cholangiography. Nevertheless, in high-risk cirrhotic patients (Child C) and/or in common bile duct lithiasis endoscopic and non-surgical conservative treatments are preferable.

The risk of COVID-19 transmission by laparoscopic smoke may be lower than for laparotomy: a narrative review.

BACKGROUND: Surgical smoke is a well-recognized hazard in the operating room. At the beginning of the COVID-19 pandemic, surgical societies quickly published guidelines recommending avoiding laparoscopy or to consider open surgery because of the fear of transmission of SARS-CoV-2 through surgical smoke or aerosol. This narrative review of the literature aimed to determine whether there are any differences in the creation of surgical smoke/aerosol between laparoscopy and laparotomy and if laparoscopy may be safer than laparotomy. METHODS: A literature search was performed using the Pubmed, Embase and Google scholar search engines, as well as manual search of the major journals with specific COVID-19 sections for ahead-of-print publications. RESULTS: Of 1098 identified articles, we critically appraised 50. Surgical smoke created by electrosurgical and ultrasonic devices has the same composition both in laparoscopy and laparotomy. SARS-CoV-2 has never been found in surgical smoke and there is currently no data to support its virulence if ever it could be transmitted through surgical smoke/aerosol. CONCLUSION: If laparoscopy is performed in a closed cavity enabling containment of surgical smoke/aerosol, and proper evacuation of smoke with simple measures is respected, and as long as laparoscopy is not contraindicated, we believe that this surgical approach may be safer for the operating team while the patient has the benefits of minimally invasive surgery. Evidence-based research in this field is needed for definitive determination of safety.

The Bucharest ESTES consensus statement on peritonitis.

INTRODUCTION: Peritonitis is still an important health problem associated with high morbidity and mortality. A multidisciplinary approach to the management of patients with peritonitis may be an important factor to reduce the risks for patients and improve efficiency, outcome, and the cost of care. METHODS: Expert panel discussion on Peritonitis was held in Bucharest on May 2017, during the 17th ECTES Congress, involving surgeons, infectious disease specialists, radiologists and intensivists with the goal of defining recommendations for the optimal management of peritonitis. CONCLUSION: This document is an updated presentation of management of peritonitis and represents the summary of the final recommendations approved by a panel of experts.

Complete mesocolic excision for colonic cancer.

INTRODUCTION: Complete mesocolic excision for colonic cancer is similar in concept to total mesorectal excision for rectal cancer. This review aims to provide the embryological and anatomical rationale behind CME, and to review the current literature on CME, relative to the feasibility via laparoscopy, the oncological adequacy and outcomes. EVIDENCE ACQUISITION: A literature search was performed at the end of 2017 according the PRISMA guidelines for systematic reviews. Of 3980 articles found, we analyzed 96 articles. Of note, many case series had overlapping populations; there were five review articles, two consensus conference proceedings, six comparative but only one randomized trial. EVIDENCE SYNTHESIS: The embryonic and anatomical rationale is well described. CME is feasible via laparoscopy, which may facilitate dissection and anatomic precision: no statistically significant differences were found when compared to open CME regarding overall survival. However, morbidity may be higher in the hands of non-expert laparoscopic surgeons. CONCLUSIONS: Oncological adequacy can be obtained with laparoscopic CME, with increased lymph node retrieval. However, until now, there is no formal proof that CME improves local recurrence or survival.

Splenic Flexure Mobilization in Sigmoid and Rectal Resections: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: There is no consensus regarding whether splenic flexure mobilization (SFM) should be performed selectively or routinely for sigmoid and rectal resections. The aim of this study was to evaluate the impact of SFM on anastomotic leak and surgical site infection rates in sigmoid and rectal resections. METHODS: PubMed, MEDLINE, EMBASE, Cochrane Library, and Scopus databases were searched by two independent researchers. Anastomotic leak was the primary endpoint. Inclusion criteria were clinical studies comparing SFM to non-SFM during sigmoid and rectal resections. The Mantel-Haenszel method with a random-effects model was used. The odds ratio (OR) was used for dichotomous variables, whereas the mean difference (MD) was used for continuous variables. RESULTS: Six of 74 potentially eligible studies totaling 12,398 patients (4,356 with SFM and 8,042 without SFM) were selected for further examination. The overall bias risk was found to be high. There was no significant difference in anastomotic leak rates when SFM patients were compared to their non-SFM counterparts [OR (95%CI) = 2.00 (0.95, 4.18); p=0.07]. SFM patients had a longer operating time [MD (95%CI) = 31.62 (24.51, 38.72); p<0.001] and increased incisional SSI rates compared to their non-SFM counterparts [11.1% vs. 9.1%; OR (95%CI) = 1.23 (1.09, 1.40); p=0.0008]. A subgroup analysis of rectal cancer cases found significantly higher anastomotic leak rates with SFM [5.4% vs. 1.5%; OR (95%CI) = 2.37 (1.09, 5.16); p=0.03]. CONCLUSION: This systematic review found that SFM was not associated with significantly decreased anastomotic leak rates. SSI rates were significantly increased in patients undergoing SFM.

Laparoscopic distal pancreatectomy: better than open?

Distal pancreatectomy is well suited to the laparoscopic approach. Laparoscopic distal pancreatectomy (LDP) provides the same postoperative recovery advantages reputed to minimal access surgery. However, there have been fears as to the safety of LDP in terms of life-threatening intra-operative events and post-operative complications, adequate carcinological outcomes as compared to traditional (open) distal pancreatectomy (ODP) when performed for cancer, as well as to whether the laparoscopic approach is well adapted to the variety of diseases that may affect the pancreas (ranging from trauma to benign or malignant disease) and whether the minimal access approach is well adapted to perform pancreatic surgery safely in the obese, the elderly or the frail. In this review of the literature, we sought to determine whether LDP was as safe, provided the same oncological outcomes and was applicable to all diseases involving the body and tail of the pancreas, and to particular patient characteristics, compared to the traditional open approach. Last we looked at cost issues. We concluded that this review of the literature allowed to state that laparoscopic distal pancreatectomy is feasible and safe for a wide range of diseases, both benign and malignant. Morbidity, mortality, and probably, also, carcinological outcomes are comparable to open surgery. The overall costs are similar but the advantages of minimal access surgery make it the preferred approach, once the surgical expertise is acquired and present.

Laparoscopy in Blunt Abdominal Trauma: for Whom? When?and Why?

The management of blunt abdominal trauma has evolved over time. While laparotomy is the standard of care in hemodynamically unstable patients, stable patients are usually treated by non-operative management (NOM), incorporating adjuncts such as interventional radiology. However, although NOM has shown good results in solid organ injuries, other lesions, namely those involving the hollow viscus, diaphragm, and mesentery, do not qualify for this approach and need surgical exploration. Laparoscopy can substantially reduce additional surgical aggression. It has both diagnostic and therapeutic potential and, when negative, may reduce the number of unnecessary laparotomies. Although some studies have shown promising results on the use of laparoscopy in blunt abdominal trauma, randomized controlled studies are lacking. Laparoscopy requires adequate training and experience as well as sufficient staffing and equipment.

Multi-port versus single-port cholecystectomy: results of a multi-centre, randomised controlled trial (MUSIC trial).

BACKGROUND: Single-port laparoscopic surgery as an alternative to conventional laparoscopic cholecystectomy for benign disease has not yet been accepted as a standard procedure. The aim of the multi-port versus single-port cholecystectomy trial was to compare morbidity rates after single-access (SPC) and standard laparoscopy (MPC). METHODS: This non-inferiority phase 3 trial was conducted at 20 hospital surgical departments in six countries. At each centre, patients were randomly assigned to undergo either SPC or MPC. The primary outcome was overall morbidity within 60 days after surgery. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov (NCT01104727). RESULTS: The study was conducted between April 2011 and May 2015. A total of 600 patients were randomly assigned to receive either SPC (n = 297) or MPC (n = 303) and were eligible for data analysis. Postsurgical complications within 60 days were recorded in 13 patients (4.7 %) in the SPC group and in 16 (6.1 %) in the MPC group (P = 0.468); however, single-access procedures took longer [70 min (range 25-265) vs. 55 min (range 22-185); P < 0.001]. There were no significant differences in hospital length of stay or pain VAS scores between the two groups. An incisional hernia developed within 1 year in six patients in the SPC group and in three in the MPC group (P = 0.331). Patients were more satisfied with aesthetic results after SPC, whereas surgeons rated the aesthetic results higher after MPC. No difference in quality of life scores, as measured by the gastrointestinal quality of life index at 60 days after surgery, was observed between the two groups. CONCLUSIONS: In selected patients undergoing cholecystectomy for benign gallbladder disease, SPC is non-inferior to MPC in terms of safety but it entails a longer operative time. Possible concerns about a higher risk of incisional hernia following SPC do not appear to be justified. Patient satisfaction with aesthetic results was greater after SPC than after MPC.