Stapled Anastomosis Versus Hand-Sewn Anastomosis With Mucosectomy for Ileal Pouch-Anal Anastomosis: A Systematic Review and Meta-analysis of Postoperative Outcomes, Functional Outcomes, and Oncological Safety.

PURPOSE: This systematic review and meta-analysis aimed to compare outcomes between stapled ileal pouch-anal anastomosis (IPAA) and hand-sewn IPAA with mucosectomy in cases of ulcerative colitis and familial adenomatous polyposis. METHODS: This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines 2020 and AMSTAR 2 (Assessing the methodological quality of systematic reviews) guidelines. We included randomized clinical trials (RCTs) and controlled clinical trials (CCTs). Subgroup analysis was performed according to the indication for surgery. RESULTS: The bibliographic research yielded 31 trials: 3 RCTs, 5 prospective clinical trials, and 24 CCTs including 8872 patients: 4871 patients in the stapled group and 4038 in the hand-sewn group. Regarding postoperative outcomes, the stapled group had a lower rate of anastomotic stricture, small bowel obstruction, and ileal pouch failure. There were no differences between the 2 groups in terms of operative time, anastomotic leak, pelvic sepsis, pouchitis, or hospital stay. For functional outcomes, the stapled group was associated with greater outcomes in terms of seepage per day and by night, pad use, night incontinence, resting pressure, and squeeze pressure. There were no differences in stool Frequency per 24h, stool frequency at night, antidiarrheal medication, sexual impotence, or length of the high-pressure zone. There was no difference between the 2 groups in terms of dysplasia and neoplasia. CONCLUSIONS: Compared to hand-sewn anastomosis, stapled ileoanal anastomosis leads to a large reduction in anastomotic stricture, small bowel obstruction, ileal pouch failure, seepage by day and night, pad use, and night incontinence. This may ensure a higher resting pressure and squeeze pressure in manometry evaluation. PROTOCOL REGISTRATION: The protocol was registered at PROSPERO under CRD 42022379880.

A systematic review and meta-analysis of hernia sac management in laparoscopic groin hernia mesh repair: reduction or transection?

BACKGROUND: There is no consensus regarding hernia sac management during laparoscopic hernia repair, and this systematic review and meta-analysis aimed to compare the postoperative outcomes of sac reduction (RS) and sac transection (TS) during laparoscopic mesh hernia repair. METHODS: We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 and AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews) guidelines. We used the RevMan 5.4 statistical package from the Cochrane collaboration for meta-analysis. A random effects model was used. RESULTS: The literature search yielded six eligible studies including 2941 patients: 821 patients in the TS group and 2120 patients in the RS group. In the pooled analysis, the TS group was associated with a lower incidence of seroma (OR = 1.71; 95% CI [1.22, 2.39], p = 0.002) and shorter hospital stay (MD = -0.07; 95% CI [-0.12, -0.02], p = 0.008). There was no significant difference between the two groups in terms of morbidity (OR = 0.87; 95% CI [0.34, 2.19], p = 0.76), operative time (MD = -4.39; 95% CI [-13.62, 4.84], p = 0.35), recurrence (OR = 2.70; 95% CI [0.50, 14.50], p = 0.25), and Postoperative pain. CONCLUSIONS: This meta-analysis showed that hernia sac transection is associated with a lower seroma rate and shorter hospital stay with similar morbidity, operative time, recurrence, and postoperative pain compared to the reduction of the hernia sac. PROTOCOL: The protocol was registered in PROSPERO with ID CRD42023391730.

Using a Reinforced Stapler Decreases the Incidence of Postoperative Pancreatic Fistula After Distal Pancreatectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: There is no consensus on the pancreatic transection during distal pancreatectomy (DP) to reduce postoperative pancreatic fistula (POPF). This meta-analysis aimed to evaluate the effects of a reinforced stapler on the postoperative outcomes of DP. METHODS: We systematically searched electronic databases and bibliographic reference lists in The PubMed/MEDLINE, Google Scholar, Cochrane Library's Controlled Trials Registry and Database of Systematic Reviews, Embase, and Scopus. Review Manager Software was used for pooled estimates. RESULTS: Seven eligible studies published between 2007 and 2021 were included with 553 patients (267 patients in the reinforced stapler group and 286 patients in the standard stapler group). The reinforced stapler reduced the POPF grade B and C (OR = 0.33; 95% CI [0.19, 0.57], p < 0.01). There was no difference between the reinforced stapler group and standard stapler group in terms of mortality rate (OR = 0.39; 95% CI [0.04, 3.57], p = 0.40), postoperative haemorrhage (OR = 0.53; 95% CI [0.20, 1.43], p = 0.21), and reoperation rate (OR = 0.91; 95% CI [0.40, 2.06], p = 0.82). CONCLUSIONS: Reinforced stapling in DP is safe and seems to reduce POPF grade B/C with similar mortality rates, postoperative bleeding, and reoperation rate. The protocol of this systematic review with meta-analysis was registered in PROSPERO (ID: CRD42021286849).

Outcomes of non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms treated with surgery: a real-world population-based study.

OBJECTIVE: To assess the outcomes of non-metastatic poorly differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) treated with radical surgery. METHODS: Surveillance, Epidemiology, and End Results (SEER) database (1998-2015) was accessed, and patients with non-metastatic poorly differentiated/undifferentiated GEP-NENs were reviewed. Multivariable Cox regression analysis was used to evaluate factors affecting overall survival (OS) and cancer-specific survival (CSS). Patients treated with radical surgery were matched to those who did not undergo surgery through propensity score matching and Kaplan-Meier survival estimates were used to evaluate the impact of surgery in the post-propensity cohort. RESULTS: A total of 1517 patients were included. Within multivariable Cox regression models and compared to no surgery, radical surgery was associated with improved OS (HR: 0.41; 95% CI: 0.34-0.50) and CSS (HR: 0.37; 95% CI: 0.29-0.47). A total of 233 patients who underwent no surgery were then matched to 233 patients who underwent radical surgery. Within the post-propensity cohort, radical surgery was associated with improved OS (P < 0.001). CONCLUSIONS: Radical surgery is associated with improved survival outcomes in patients with non-metastatic poorly differentiated GEP-NENs. Further studies are required to better identify the best timing of radical surgery within the context of multimodal management.

Early salvage total mesorectal excision (sTME) after organ preservation failure in rectal cancer does not worsen postoperative outcomes compared to primary TME: systematic review and meta-analysis.

IMPORTANCE: While oncological outcomes of early salvage total mesorectal excision (sTME) after local excision (LE) have been well studied, the impact of LE before TME on postoperative outcomes remains unclear. We aimed to compare early sTME with a primary TME for rectal cancer. METHODS: Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines with the random-effects model were adopted using Review Manager Version 5.3 for pooled estimates. RESULTS: We retrieved eleven relevant articles including 1728 patients (350 patients in the sTME group and 1438 patients in the TME group). There was no significant difference between the two groups in terms of mortality (OR = 0.90, 95%CI [0.21 to 3.77], p = 0.88), morbidity (OR = 1.19, 95%CI [0.59 to 2.38], p = 0.63), conversion to open surgery (OR = 1.34, 95%CI [0.61 to 2.94], p = 0.47), anastomotic leak (OR = 1.38, 95%CI [0.50 to 3.83], p = 0.53), hospital stay (MD = 0.23 day, 95%CI [- 1.63 to 2.10], p < 0.81), diverting stoma rate (OR = 0.69, 95%CI [0.44 to 1.09], p = 0.11), abdominoperineal resection rate (OR = 1.47, 95%CI [0.91 to 2.37], p = 0.11), local recurrence (OR = 0.94, 95%CI [0.44 to 2.04], p = 0.88), and distant recurrence (OR = 0.88, 95%CI [0.52 to 1.48], p = 0.62). sTME was associated with significantly longer operative time (MD = 25.62 min, 95%CI[11.92 to 39.32], p < 0.001) lower number of harvested lymph nodes (MD = - 2.25 lymph node, 95%CI [- 3.86 to - 0.65], p = 0.006), and higher proportion of incomplete TME (OR = 0.25, 95%CI [0.11 to 0.61], p = 0.002). CONCLUSIONS: sTME is not associated with increased postoperative morbidity, mortality, or local recurrence. However, the operative times are longer and yield a poor specimen quality.

A Real-World, Population-Based Analysis of the Outcomes of Colorectal Cancer Patients with Isolated Synchronous Liver or Lung Metastases Treated with Metastasectomy.

OBJECTIVE: To assess the survival outcomes among a contemporary cohort of colorectal cancer patients with isolated synchronous liver or lung metastases treated with or without surgical resection of the metastases. METHODS: Surveillance, epidemiology and end results database has been accessed and cases with isolated liver or lung metastases diagnosed 2010-2015 have been accessed. Kaplan-Meier survival estimates were used to compare overall survival among patients who had or had not undergone metastasectomy. Multivariable Cox regression analysis was then used to assess the impact of metastasectomy on colorectal cancer-specific survival. RESULTS: A total of 16,372 patients with colorectal cancer with isolated liver or lung metastases (M1a disease) were included in the current analysis (including 14,832 patients with isolated liver metastases and 1540 patients with isolated lung metastases). Patients who had undergone surgical resection of liver metastases have better overall survival compared to patients who had not undergone surgical resection of liver metastases (median overall survival: 38.0 months vs. 13.0 months; P < 0.001). Likewise, patients who had undergone surgical resection of lung metastases have better overall survival compared to patients who had not undergone surgical resection of lung metastases (median overall survival: 45.0 months vs. 19.0 months; P < 0.001). In a multivariable Cox regression analysis and among patients with isolated liver metastases, surgery to the metastases was associated with a reduced hazard of death (hazard ratio (HR) 0.567; 95% CI 0.529-0.609; P < 0.001). Likewise, and among patients with isolated lung metastases, surgery to the metastases was associated with a reduced hazard of death (HR 0.482; 95% CI 0.349-0.665; P < 0.001). CONCLUSION: In a contemporary cohort, metastasectomy seems to be associated with improvement in overall and cancer-specific survival among patients with isolated synchronous liver or lung metastases from colorectal cancer. Whether this survival difference is totally ascribed to the effect of metastasectomy or it is the fact that patients who were eligible for surgical resection have limited disease extent and better medical profile (thus, leading to better survival) is unclear from such a population-based study.

Comparison of three prognostic models for predicting cancer-specific survival among patients with gastrointestinal stromal tumors.

AIM: To evaluate the predictive value for cancer-specific survival of the models of the American Joint Committee on Cancer (AJCC) stage, NIH and Armed Forces Institute of Pathology (AFIP) among patients with gastrointestinal stromal tumors (GISTs). METHODS: Surveillance, Epidemiology and End Results database (2010-2014) was accessed. Overall survival analysis and adjusted cancer-specific Cox regression hazard was calculated. RESULTS: For gastric GISTs, concordance-index according to AJCC was 0.834; according to NIH was 0.833; according to AFIP was 0.836. Concordance-index for nongastric GISTs according to AJCC was 0.800, according to NIH was 0.801 and according to AFIP was 0.799. CONCLUSION: The performance of the three models is comparable with regards to cancer-specific survival prediction.

Validation of the eighth clinical American Joint Committee on Cancer stage grouping for esophageal cancer.

AIM: To validate the American Joint Committee on Cancer (AJCC) clinical staging system for esophageal cancer using Surveillance, Epidemiology and End Results database. METHODS: Cancer-specific survival analyses for clinically-staged patients with esophageal cancer according to both seventh and eighth editions were conducted through Kaplan-Meier analysis. RESULTS: For cancer-specific survival according to both seventh and eighth clinical systems, p-values for pairwise comparisons were nonsignificant in many comparisons. C-index for adenocarcinoma was: 0.671 according to the seventh AJCC and 0.671 according to the clinical eighth AJCC. C-index for squamous cell carcinoma according to the seventh AJCC was: 0.634 and 0.643 according to clinical eighth AJCC. CONCLUSION: Minimal improvement was achieved by the eighth clinical AJCC staging system for esophageal cancer.

Analysis of the hemostatic potential of modern topical sealants on arterial and venous anastomoses: an experimental porcine study.

One of the widely accepted adjunctive agents in the variety of surgical modalities are sealants. Our study aim was to compare four commonly used modern sealants in a standardized experimental setting to assess their feasibility, and hemostatic efficacy in vascular anastomosis. Forty landrace pigs (weight: 24.7 ± 3.8 kg) were randomized into the control (n = 8) and four sealant groups; TachoSil® (n = 8), Tissucol Duo® (n = 8), Coseal® (n = 8), and FloSeal® (n = 8). After doing a portal vein end-to-end anastomosis as well as stitches of aortic incision, the sealants were applied on anastomotic site. The control group was left intact. In portal vein anastomosis, the sealants led to a complete hemostasis significantly better than control group. The mean of blood loss was also significantly reduced. In successful subgroups, there was a difference in the mean-time to reach complete hemostasis ranging from 15 s in Coseal® to 76 s in FloSeal® group (p < 0.05). In aortotomy experiments, except Tissucol Due®, which had insufficient hemostasis, other sealants led to a complete hemostasis. The mean blood loss was significantly reduced in sealants groups as well. The four sealants are effective in reducing the suture-hole bleeding in portal vein anastomosis. However, the hemostatic potential is heterogeneous among sealants. This means that "one-size-fits-all" approach is not appropriate for application of sealants in diversity of vascular surgery and it should be based on the type and the severity of injury and the structure of tissue. Comparison of hemostasis efficacy of four modern sealants (TachoSil®, Tissucol Duo®, Coseal®, and FloSeal®) in vascular anastomosis in porcine model. The figures below show the total blood loss (g) in the control and sealant groups after aortotomy (left) and portal vein anastomosis (right). The mean of blood loss decreased significantly by the usage of sealants in both experiment groups as compared to control group (*: p < 0.05; sealant groups vs. control group). 1. The right column shows the mean of blood loss (g) in all experiments in each group. 2. The middle column presents the subgroup with unsuccessful hemostasis at the end of observation time (Tmax = 20 sec. for aortotmy and 300 sec. for portal vein anastomosis). 3. The left column shows mean of total blood loss in subgroups with successful hemostasis during observation time (20 sec for aortotomy and 300 sec for portal vein).

Efficacy and safety of intraperitoneal ropivacaine in pain management following laparoscopic digestive surgery: A systematic review and meta-analysis of RCTs.

BACKGROUND: Managing postoperative pain effectively with an opioid-free regimen following laparoscopic surgery (LS) remains a significant challenge. Intraperitoneal instillation of ropivacaine has been explored for its potential to reduce acute postoperative pain, but its efficacy and safety are still under debate. This study aimed to evaluate the efficacy and safety of intraperitoneal instillation of ropivacaine for acute pain management following laparoscopic digestive surgery. METHODS: We used PRISMA 2020 and a measurement tool to assess systematic reviews 2 guidelines to conduct this review. The random-effects model was adopted using Review Manager Version 5.4 for pooled estimates. RESULTS: We retained 24 eligible RCTs involving 1705 patients (862 patients in the intraperitoneal instillation group and 843 patients in the control group). The intraperitoneal instillation group reduced total opioid consumption during the first 24 hours postoperatively (MD = -21.93 95% CI [-27.64, -16.23], P < .01), decreased pain scores at different time (4 hours, 8 hours, 12 hours and 24 hours), shorter the hospital stay (MD = -0.20 95% CI [-0.36, -0.05], P < .01), reduced the postoperative shoulder pain (MD = 0.18 95% CI [0.07, 0.44], P < .01), and decreased postoperative nausea and vomiting (MD = 0.47 95% CI [0.29, 0.77], P < .01). CONCLUSION: Intraperitoneal instillation of ropivacaine appears to be an effective component of multimodal pain management strategies following laparoscopic digestive surgery, significantly reducing opioid consumption and improving postoperative recovery markers. Despite these promising results, additional high-quality trials are needed to confirm the efficacy and safety of this approach. REGISTRATION: The registration number at PROSPERO was CRD42021279238.

Robotic versus laparoscopic total mesorectal excision with lateral lymph node dissection for advanced rectal cancer: A systematic review and meta-analysis.

INTRODUCTION: Lateral pelvic node dissection (LPND) poses significant technical challenges. Despite the advent of robotic surgery, determining the optimal minimally invasive approach remains a topic of debate. This study aimed to compare postoperative outcomes between robotic total mesorectal excision with LPND (R-LPND) and laparoscopic total mesorectal excision with LPND (L-LPND). METHODS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 and AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews) guidelines. Utilizing the RevMan 5.3.5 statistical package from the Cochrane Collaboration, a random-effects model was employed. RESULTS: Six eligible studies involving 652 patients (316 and 336 in the R-LPND and L-LPND groups, respectively) were retrieved. The robotic approach demonstrated favourable outcomes compared with the laparoscopic approach, manifesting in lower morbidity rates, reduced urinary complications, shorter hospital stays, and a higher number of harvested lateral pelvic lymph nodes. However, longer operative time was associated with the robotic approach. No significant differences were observed between the two groups regarding major complications, anastomotic leak, intra-abdominal infection, neurological complications, LPND time, overall recurrence, and local recurrence. CONCLUSIONS: In summary, the robotic approach is a safe and feasible alternative for Total Mesorectal Excision (TME) with LPND in advanced rectal cancer. Notably, it is associated with lower morbidity, particularly a reduction in urinary complications, a shorter hospital stay and increased number of harvested lateral pelvic nodes. The trade-off for these benefits is a longer operative time.

Correction: Oweira et al. Kynurenine Is the Main Metabolite of Tryptophan Degradation by Tryptophan 2,3-Dioxygenase in HepaRG Tumor Cells. J. Clin. Med. 2022, 11, 4794.

There was an error in the original publication [...].

Robotic versus open total pancreatectomy: a systematic review and meta-analysis.

Limited data are available on postoperative outcomes in patients undergoing robotic total pancreatectomy (RTP). This systematic review and meta-analysis aimed to compare the postoperative outcomes of RTP and open total pancreatectomy (OTP). We performed a systematic review with meta-analysis according to the PRISMA 2020 and AMSTAR 2 guidelines. We included studies conducted through August 10, 2022, that systematically searched electronic databases and compared RTP with OTP. We retained four controlled clinical trials in the literature search, including 156 patients: 65 in the RTP group and 91 in the OTP group. There was no difference between the RTP group and OTP group in terms of mortality, severe complications, morbidity, bleeding, biliary leak, delayed gastric emptying, reoperation, operative time, length of stay, harvested lymph nodes, and positive resection margin. The RTP reduces the delay of the first liquid diet, first oral diet, and out of bed. RTP is feasible and safe in selected patients. Robotic surgery allows for a quicker recovery. In cases of major vessel invasion, conversion to laparotomy should be preoperatively considered.

Banded versus non-banded sleeve gastrectomy: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic banded sleeve gastrectomy (LBSG) has been compared to laparoscopic sleeve gastrectomy (LSG) in terms of anthropometric results and postoperative complications, which are controversial. This systematic review and meta-analysis aimed to compare the safety and efficacy of LBSG and LSG. METHODS: We performed a systematic review with meta-analysis according to preferred reporting items for systematic review and meta-analysis 2020 and assessing the methodological quality of systematic review 2 guidelines. We included studies that systematically searched electronic databases and compared LBSG with LSG conducted until August 10, 2021. RESULTS: The literature search yielded 8 comparative studies. Seven hundred forty-three patients were included: 352 in the LBSG group and 391 in the LSG group. LBSG group allowed greater anthropometric parameters (body mass index [BMI] after 1 year (mean difference [MD] = -3.18; 95% CI [-5.45, -0.92], P = .006), %EWL after 1 year (MD = 8.02; 95% CI [1.22, 14.81], P = .02), and %EWL after 3 years (MD = 10.60; 95% CI [5.60, 15.69], P < .001) and similar results with LSG group in terms of operative time (MD = 1.23; 95% CI [-4.71, 7.17], P = .69), food intolerance (OR = 1.72; 95% CI [0.84, 3.49], P = .14), postoperative vomiting (OR = 2.10; 95% CI [0.69, 6.35], P = .19), and De novo GERD (OR = 0.65; 95% CI [0.34, 1.26], P = .2). Nevertheless, major postoperative complications did not differ between the 2 groups. CONCLUSIONS: This systematic review and meta-analysis comparing LBSG and LSG concluded that banding sleeve gastrectomy (SG) may ensure a lower BMI and %EWL after 1 year of follow-up, and a significant reduction in %EWL after 3 years of follow-up. There is no evidence to support LBSG in vomiting, de novo GERD, food intolerance, or operative time.

How to prevent postoperative ileus in colorectal surgery? a systematic review.

Postoperative ileus (PI) after colorectal surgery is a common surgical problem. This systematic review aimed to investigate the available data in the literature to reduce the PI in the area of colorectal surgery out of the enhanced recovery after surgery principles, referring to published randomized controlled trials (RCTs) and meta-analyses, and to provide recommendations according to the Oxford Centre for Evidence-Based Medicine. The authors conducted bibliographic research on 1 December 2022. The authors retained meta-analyses and RCTs. The authors concluded that when we combined colonic mechanical preparation with oral antibiotic decontamination, the authors found a significant reduction in PI. The open approach was associated with a higher PI rate. The robotic and laparoscopic approaches had similar PI rates. Low ligation of the inferior mesenteric artery presented a PI similar to that of high ligation of the inferior mesenteric artery. There was no difference between the isoperistaltic and antiperistaltic anastomoses or between the intracorporeal and extracorporeal anastomoses. This study summarized the available data in the literature, including meta-analyses and RCTs. For a higher level of evidence, additional multicenter RCTs and meta-analyses of RCTs remain necessary.

A systematic review and meta-analysis of liver venous deprivation versus portal vein embolization before hepatectomy: future liver volume, postoperative outcomes, and oncological safety.

Introduction: This systematic review aimed to compare liver venous deprivation (LVD) with portal vein embolization (PVE) in terms of future liver volume, postoperative outcomes, and oncological safety before major hepatectomy. Methods: We conducted this systematic review and meta-analysis following the PRISMA guidelines 2020 and AMSTAR 2 guidelines. Comparative articles published before November 2022 were retained. Results: The literature search identified nine eligible comparative studies. They included 557 patients, 207 in the LVD group and 350 in the PVE group. This systematic review and meta-analysis concluded that LVD was associated with higher future liver remnant (FLR) volume after embolization, percentage of FLR hypertrophy, lower failure of resection due to low FLR, faster kinetic growth, higher day 5 prothrombin time, and higher 3 years' disease-free survival. This study did not find any difference between the LVD and PVE groups in terms of complications related to embolization, FLR percentage of hypertrophy after embolization, failure of resection, 3-month mortality, overall morbidity, major complications, operative time, blood loss, bile leak, ascites, post hepatectomy liver failure, day 5 bilirubin level, hospital stay, and three years' overall survival. Conclusion: LVD is as feasible and safe as PVE with encouraging results making some selected patients more suitable for surgery, even with a small FLR. Systematic review registration: The review protocol was registered in PROSPERO before conducting the study (CRD42021287628).

Risk Factors of Rejection in Renal Transplant Recipients: A Narrative Review.

Multiple factors influence graft rejection after kidney transplantation. Pre-operative factors affecting graft function and survival include donor and recipient characteristics such as age, gender, race, and immunologic compatibility. In addition, several peri- and post-operative parameters affect graft function and rejection, such as cold and warm ischemia times, and post-operative immunosuppressive treatment. Exposure to non-self-human leucocyte antigens (HLAs) prior to transplantation up-regulates the recipient's immune system. A higher rate of acute rejection is observed in transplant recipients with a history of pregnancies or significant exposure to blood products because these patients have higher panel reactive antibody (PRA) levels. Identifying these risk factors will help physicians to reduce the risk of allograft rejection, thereby promoting graft survival. In the current review, we summarize the existing literature on donor- and recipient-related risk factors of graft rejection and graft loss following kidney transplantation.

Kynurenine Is the Main Metabolite of Tryptophan Degradation by Tryptophan 2,3-Dioxygenase in HepG2 Tumor Cells.

There are two main enzymes that convert tryptophan (Trp) to kynurenine (Kyn): tryptophan-2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO). Kyn accumulation can promote immunosuppression in certain cancers. In this study, we investigated Trp degradation to Kyn by IDO and TDO in primary human hepatocytes (PHH) and tumoral HepG2 cells. To quantify Trp-degradation and Kyn-accumulation, using reversed-phase high-pressure liquid chromatography, the levels of Trp and Kyn were determined in the culture media of PHH and HepG2 cells. The role of IDO in Trp metabolism was investigated by activating IDO with IFN-γ and inhibiting IDO with 1-methyl-tryptophan (1-DL-MT). The role of TDO was investigated using one of two TDO inhibitors: 680C91 or LM10. Real-time PCR was used to measure TDO and IDO expression. Trp was degraded in both PHH and HepG2 cells, but degradation was higher in PHH cells. However, Kyn accumulation was higher in the supernatants of HepG2 cells. Stimulating IDO with IFN-γ did not significantly affect Trp degradation and Kyn accumulation, even though it strongly upregulated IDO expression. Inhibiting IDO with 1-DL-MT also had no effect on Trp degradation. In contrast, inhibiting TDO with 680C91 or LM10 significantly reduced Trp degradation. The expression of TDO but not of IDO correlated positively with Kyn accumulation in the HepG2 cell culture media. Furthermore, TDO degraded L-Trp but not D-Trp in HepG2 cells. Kyn is the main metabolite of Trp degradation by TDO in HepG2 cells. The accumulation of Kyn in HepG2 cells could be a key mechanism for tumor immune resistance. Two TDO inhibitors, 680C91 and LM10, could be useful in immunotherapy for liver cancers.

Ketamine as a component of multimodal analgesia for pain management in bariatric surgery: A systematic review and meta-analysis of randomized controlled trials.

Introduction: Anaesthesia in morbidly obese people is challenging with a high dose of opioid consumption. This systematic review and meta-analysis of randomised controlled trials (RCTs) summaries evidence comparing ketamine to placebo for pain management after bariatric surgery. Methods: We used PRISMA 2020 and AMSTAR 2 guidelines to conduct this study. The random-effects model was adopted using Review Manager Version 5.3 for pooled estimates. Results: Seven RCTs published between 2009 and 2021 were eligible, including a total of 412 patients (202 patients in the ketamine group and 210 patients in the control group). In the ketamine group total opioid consumption during the first 24 h postoperatively was reduced (mean difference, MD = -5.89; 95% CI [-10.39, -1.38], p = 0.01), lower pain score at 4 h (MD = -0.81; 95% CI [-1.52, -0.10], p = 0.03), pain score at 8 h (MD = -1.00; 95% CI [-1.21, -0.79], p < 0.01), and shorter hospital stay (MD = -0.10; 95% CI [-0.20, -0.01], p = 0.03). There was no significant difference between the two groups regarding duration of anaesthesia (MD = -3.42; 95% CI [-8.62, 1.82], p = 0.20), or sedation score (MD = -0.02; 95% CI [-0.21, 0.17], p = 0.84). As concern the postoperative complications, risks of postoperative nausea and vomiting(OR = 0.75; 95% CI [0.27, 2.04], p = 0.56), hallucinations (OR = 5.47; 95% CI [0.26, 117.23], p = 0.28), dizziness (OR = 1.05; 95% CI [0.14, 7.78], p = 0.96), and euphoria (OR = 5.77; 95% CI [0.65, 51.52], p = 0.12) were not different between the two groups either. Conclusion: Ketamine could be an effective and safe technique for pain management following bariatric surgery. It reduces opioid consumption, postoperative pain, and hospital stay.RegistrationThis review was registered in PROSPERO (CRD42022296484).

Irrigation during laparoscopic appendectomy for complicated appendicitis increases the operative time and reoperation rate: a meta-analysis of randomized clinical trials.

This meta-analysis of randomized clinical trials (RCT) aimed to compare peritoneal irrigation followed by suction with aspiration only during laparoscopic surgery for complicated appendicitis (LA). PRISMA guidelines with the random-effects model were adopted using Review Manager Version 5.3 for pooled estimates. We retained six eligible RCT published between 2012 and 2019. They involved a total of 1019 patients (541 patients in the aspiration group and 478 patients in the irrigation group). Aspiration only during LA is associated with shorter operative time (MD = 8.50 min, 95% CI [- 12.97 to - 4.02], p = 0.0002) and lower reoperation rate (OR = 0.37 95% CI [0.14-0.96], p = 0.04). There was no difference between aspiration group and irrigation group in terms of Intraperitoneal abscess (IPA) (OR = 0.99 95% CI [0.54-1.81], p = 0.95), morbidity rate (OR = 1.14 95% CI [0.44-2.98], p = 0.79), wound infection (OR = 0.94 95% CI [0.20-4.40], p = 0.94), and hospital stay (MD = 0.65 day, 95% CI [- 0.52 to 1.82], p = 0.27). Irrigation during LA prevents post-appendectomy IPA in neither adults nor pediatric patients. However, it lengthens the operative time and involves a higher reoperation rate.