Transabdominal pre-peritoneal (TAPP) versus totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair.

BACKGROUND: An inguinal hernia occurs when part of the intestine protrudes through the abdominal muscles. In adults, this common condition is much more likely in men than in women. Inguinal hernia can be monitored by 'watchful waiting', but if symptoms persist or worsen, surgery is usually required, which can be open or laparoscopic. Laparoscopic (keyhole) repair of inguinal hernias in adults is generally performed using either the transabdominal preperitoneal (TAPP) or the totally extraperitoneal (TEP) method. Both methods include the use of mesh placed in front of the peritoneal lining of the abdominal wall, but for the TAPP technique, the abdominal cavity needs to be entered to place the mesh, and for the TEP technique, the whole procedure is done on the outside of the peritoneal lining of the abdominall wall. Whether one method is superior to the other has not been established, and there is debate about their relative benefits and harms. An advantage of TEP is its avoidance of the abdominal cavity; the downside is that it requires a steeper learning curve for clinicians. TAPP is considered simpler and makes it possible to inspect the contralateral side, but TAPP may have a higher risk of visceral injury compared to TEP. This is an update of a Cochrane review first published in 2005. OBJECTIVES: To compare the benefits and harms of laparoscopic TAPP technique versus laparoscopic TEP technique for inguinal hernia repair in adults. SEARCH METHODS: On 25 October 2022, the authors searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); and Ovid Embase, for published randomised controlled trials. To identify studies in progress, we searched ClinicalTrials.gov and the WHO International Clinical Trial Registry Platform (ICTRP). SELECTION CRITERIA: All prospective randomised, quasi-randomised, and cluster-randomised trials that compared the laparoscopic TAPP technique with the laparoscopic TEP technique for inguinal hernia repair in adults were eligible for inclusion. We included studies that involved a mix of different types of groin hernia if we could extract data for the inguinal hernias. Studies may have also included a group of participants receiving hernia repair by open surgery, but these groups were not included in our review. DATA COLLECTION AND ANALYSIS: Both review authors independently evaluated trial eligibility, extracted data from included studies, and assessed the risk of bias in the included studies. The review's primary outcomes were serious adverse events, chronic pain (persisting for at least six months after surgery), and hernia recurrence. We also assessed a variety of secondary outcomes at perioperative, early postoperative, and late postoperative time points. We performed statistical analyses using the random-effects model, and expressed the results as odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with their respective 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for key outcomes as high, moderate, low or very low. MAIN RESULTS: We included 23 studies in this review update, which randomised 1156 people to TAPP and 1110 people to TEP, all requiring repair of inguinal hernias. Study sample sizes varied from 40 to 316 participants. The vast majority of study participants were male. We judged most studies to be at 'high' or 'unclear' risk of bias. Our judgements of the certainty of the evidence were low or very low for all outcomes we assessed. There may be little to no difference between TAPP and TEP laparoscopic techniques for serious adverse events (0.4% versus 0.7%; OR 0.58, 95% CI 0.15 to 2.32, P = 0.45, I2 = 0%; 19 studies, 1735 participants; low certainty of evidence); and hernia recurrence (1.2% versus 1.1%; OR 1.14, 95% CI 0.49 to 2.62, P = 0.97, I2 = 0%; 17 studies, 1712 participants; low certainty of evidence). The evidence is very uncertain about the effects of TAPP versus TEP techniques on chronic pain (OR 0.62, 95% CI 0.20 to 1.97, P = 0.68, I2 = 0%; 6 studies, 860 participants; very low certainty of evidence). In terms of secondary outcomes, the evidence is very uncertain for TAPP versus TEP techniques for perioperative visceral and vascular injury (15 studies, 1523 participants; very low certainty of evidence), and for haematoma or seroma during the early (≤ 30 days) postoperative phase (OR 0.86, 95% CI 0.54 to 1.37, P = 0.3861, I2 = 0%; 15 studies, 1423 participants; very low certainty of evidence). TEP technique may carry a higher risk of conversion to another hernia repair method (either TAPP technique or open surgery) when compared to TAPP (2.5% versus 0.7%; OR 0.28, 95% CI 0.09 to 0.84, P = 0.02, I2 = 0%; 13 studies, 1178 participants; low certainty of evidence). Only two studies (474 participants) reported quality of life in the late (> 30 days) postoperative phase; overall, there was an improvement in quality of life from the pre- to post-operative assessment, but the evidence suggests little to no difference between the techniques (low certainty of evidence). AUTHORS' CONCLUSIONS: This review update found that there may be little to no difference between the TAPP and TEP techniques for serious adverse events, hernia recurrence, or chronic pain (low- to very-low-certainty evidence). Decisions about which method to use will most likely reflect surgeon and patient preference until high-certainty evidence becomes available. There may be a higher risk of needing to convert from TEP to TAPP or open surgery when compared to the risk of needing to convert from TAPP to open surgery (low-certainty evidence). If surgeons opt for TEP as their standard laparoscopic method, they could consider having a strategy for how to handle the potential need for conversion. This might include proficiency in the TAPP approach or having informed the patient about the risk of conversion to open surgery. For surgeons or surgical departments, the choice of a laparoscopic technique should involve shared decision-making with patients and their families or carers. Future research could focus on patient-reported outcomes, such as quality of life.

High peritoneal incision approach in endoscopic transabdominal preperitoneal patch plasty (TAPP) for inguinal hernia after radical prostatectomy.

BACKGROUND: Inguinal hernia develops as one of the common complications after robotic or laparoscopic radical prostatectomy (RP). Transabdominal preperitoneal patch plasty (TAPP) for an inguinal hernia after RP is difficult to perform due to postoperative severe adhesions in the preperitoneal cavity. We have introduced a high peritoneal incision approach (HPIA) in TAPP for inguinal hernia patients in whom peritoneal dissection is difficult due to severe adhesions after RP. We evaluate the safety and efficacy of TAPP with a HPIA for patients with an inguinal hernia after robot-assisted RP (RARP). METHODS: Patients characteristics and surgical outcome were evaluated by a retrospective analysis. RESULTS: From January 2014 to December 2017, 21 consecutive patients underwent TAPP for an inguinal hernia after RARP. Twenty-four lesions were the type 3b and three were type 3a according to the Nyhus classification. A circular incision TAPP was performed for 10 hernia lesions in eight patients and TAPP with HPIA was utilized for 17 lesions in 13 patients. The mean operation time for the unilateral hernia in the HPIA (137.8 ± 20.7 min) was significantly shorter than that (182.2 ± 42.0 min) in the circular incision TAPP (p = .038). The HPIA was complete in all patients, while the circular incision TAPP was converted to intraperitoneal onlay mesh (IPOM)intraperitoneal onlay mesh in five patients (55.6%, p = .008) due to dense adhesions with difficult dissection. No recurrent was observed after follow-up period of 48 months in both groups. CONCLUSIONS: The TAPP with HPIA is feasible and a safe and reliable treatment of choice in patients with an inguinal hernia after RARP.

Protective effect of Cyclo(His-Pro) on peritoneal fibrosis through regulation of HDAC3 expression.

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.

Surgical outcomes of novel retroperitoneal low anterior vs posterior and transperitoneal access in single-port partial nephrectomy.

PURPOSE: Single-Port Robot-Assisted Partial Nephrectomy (SP-RAPN) can be performed by transperitoneal and retroperitoneal approaches. However, there is a lack of surgical outcomes for novel Retroperitoneal Low Anterior Access (LAA) in SP-RAPN. The study compared outcomes of the standard approach (SA), considering transperitoneal (TP) and posterior retroperitoneal (RP) access vs LAA in SP-RAPN series. METHODS: 102 consecutive patients underwent SP-RAPN between 2019 and 2023 at a tertiary referral robotic center were identified. Baseline characteristics, peri- and post-operative outcomes were collected. Patients were stratified according to surgical approach into standard (RP or TP) vs LAA and, subsequently, RP vs LAA. Multivariable logistic regression analysis was used to test the probability of the same-day discharge adjusting for comorbidity indexes. RESULTS: Overall, 102 consecutive patients were included in this study (68 SA - 26 TP and 42 posterior RP vs 34 LAA). Median age was 60 (IQR 51.5-66) years and median BMI was 31 (IQR 26.3-37.6). No baseline differences were observed. LAA exhibited significantly shorter length of stay (LOS) (median 10 [IQR 8-12] vs 24 [IQR 12-30.2.] hours, p < .0001), reduced post-operative pain (p < .0001) and decreased narcotic use on 0-1 PO Day (p < .001) compared to SA and RP only. Multivariate analysis, adjusting for comorbidities, identified LAA as a strong predictor for Same-Day Discharge. CONCLUSION: LAA is an effective approach as well as RP and TP, regardless of the renal mass location, whether it is anterior or posterior, upper/mid or lower pole, yielding favorable outcomes in LOS, post-operative pain and decreased narcotics use compared to SA in SP-RAPN.

Modifications of surgical techniques in laparoscopic percutaneous extraperitoneal closure of inguinal ring for childhood inguinal hernia to achieve zero recurrence and zero subcutaneous stitch granuloma.

PURPOSE: To present our technical modifications of single incision laparoscopic percutaneous extraperitoneal closure (SILPEC) of the internal inguinal ring (IIR) for pediatric inguinal hernia (PIH). METHODS: The prospectively collected data of all children diagnosed with PIH undergoing SILPEC at our center from 2016 to 2023 were reviewed and divided into two groups for result comparison: Group A: before and Group B: after the implementation of full modifications. Our modifications included using a nonabsorbable monofilament suture, creating a peritoneal thermal injury at the internal inguinal ring (IIR), employing a cannula to ensure the suture at the IIR ligates only the peritoneum, and double ligation of the IIR in selected cases. RESULTS: 1755 patients in group A and in group B (1 month to 14 years old) were enrolled. There were no significant differences regarding baseline patient characteristics between the two groups. At a median follow-up of 40 months, the rate of recurrent CIH and subcutaneous stitch granuloma (SSG) was 2.3% and 1.5% in group A vs. 0% and 0% in group B (p < 0.001). There were no hydroceles, no ascended or atrophic testis. CONCLUSIONS: Our SILPEC technical modifications can achieve zero recurrence and zero SSG for PIH.

[Influence of neoadjuvant chemoradiotherapy on peritoneal wound healing after abdominoperineal resection].

Objective: To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR). Methods: This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded. Results: None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0-300.0) minutes, 240.0 (225.0-270.0) minutes and 270.0 (240.0-356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7-12.7; OR=2.6, 95%CI: 1.0-6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0-12.0) days, 10.0 (8.0-17.0) days and 11.5 (9.0-19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively (H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (ß [95% CI]: 4.4 [0.5-8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ2=4.133, P=0.023). Conclusions: In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

Selective therapeutic efficacy of tyrosine kinase inhibitor sorafenib on the restoration of methylglyoxal-induced peritoneal fibrosis.

Peritoneal fibrosis, a common complication observed in long-term peritoneal dialysis patients, can gradually lead to ultrafiltration failure and the development of encapsulating peritoneal sclerosis. Although mechanisms of peritoneal fibrosis have been proposed, effective therapeutic options are unsatisfactory. Recently, several tyrosine kinase inhibitors have proven to be anti-fibrosis in rodent models. To assess the potential therapeutic effects of tyrosine kinase inhibitors on peritoneal fibrosis in the larger animal model, a novel porcine model of peritoneal fibrosis induced by 40 mM methylglyoxal in 2.5 % dialysate was established, and two different doses (20 mg/kg and 30 mg/kg) of sorafenib were given orally to evaluate their therapeutic efficacy in this study. Our results showed that sorafenib effectively reduced adhesions between peritoneal organs and significantly diminished the thickening of both the parietal and visceral peritoneum. Angiogenesis, vascular endothelial growth factor A production, myofibroblast infiltration, and decreased endothelial glycocalyx resulting from dialysate and methylglyoxal stimulations were also alleviated with sorafenib. However, therapeutic efficacy in ameliorating loss of mesothelial cells, restoring decreased ultrafiltration volume, and improving elevated small solutes transport rates was limited. In conclusion, this study demonstrated that sorafenib could potentially be used for peritoneal fibrosis treatment, but applying sorafenib alone might not be sufficient to fully rescue methylglyoxal-induced peritoneal defects.

Effect of cellular senescence on the response of human peritoneal mesothelial cells to TGF-ß.

Transforming growth factor ß (TGF-ß) is implicated in both mesothelial-to-mesenchymal transition (MMT) and cellular senescence of human peritoneal mesothelial cells (HPMCs). We previously showed that senescent HPMCs could spontaneously acquire some phenotypic features of MMT, which in young HPMCs were induced by TGF-ß. Here, we used electron microscopy, as well as global gene and protein profiling to assess in detail how exposure to TGF-ß impacts on young and senescent HPMCs in vitro. We found that TGF-ß induced structural changes consistent with MMT in young, but not in senescent HPMCs. Of all genes and proteins identified reliably in HPMCs across all treatments and states, 4,656 targets represented overlapping genes and proteins. Following exposure to TGF-ß, 137 proteins and 46 transcripts were significantly changed in young cells, compared to 225 proteins and only 2 transcripts in senescent cells. Identified differences between young and senescent HPMCs were related predominantly to wound healing, integrin-mediated signalling, production of proteases and extracellular matrix components, and cytoskeleton structure. Thus, the response of senescent HPMCs to TGF-ß differs or is less pronounced compared to young cells. As a result, the character and magnitude of the postulated contribution of HPMCs to TGF-ß-induced peritoneal remodelling may change with cell senescence.

Survival and its relationship with the type of peritoneal solute transfer rate, in patients with chronic kidney disease incident on peritoneal dialysis therapy in RTS Colombia between the years 2007-2017.

INTRODUCTION: In some studies, the peritoneal solute transfer rate (PSTR) through the peritoneal membrane has been related to an increased risk of mortality. It has been observed in the literature that those patients with rapid diffusion of solutes through the peritoneal membrane (high/fast transfer) and probably those with high average transfer characterized by the Peritoneal Equilibrium Test (PET) are associated with higher mortality compared to those patients who have a slow transfer rate. However, some authors have not documented this fact. In the present study, we want to evaluate the (etiological) relationship between the characteristics of peritoneal membrane transfer and mortality and survival of the technique in an incident population on peritoneal dialysis in RTS Colombia during the years 2007-2017 using a competing risk model. MATERIALS AND METHODS: A retrospective cohort study was carried out at RTS Colombia in the period between 2007 and 2017. In total, there were 8170 incident patients older than 18 years, who had a Peritoneal Equilibration Test (PET) between 28 and 180 days from the start of therapy. Demographic, clinical, and laboratory variables were evaluated. The (etiological) relationship between the type of peritoneal solute transfer rate at the start of therapy and overall mortality and technique survival were analyzed using a competing risk model (cause-specific proportional hazard model described by Royston-Lambert). RESULTS: Patients were classified into four categories based on the PET result: Slow/Low transfer (16.0%), low average (35.4%), high average (32.9%), and High/Fast transfer (15.7%). During follow-up, with a median of 730 days, 3025 (37.02%) patients died, 1079 (13.2%) were transferred to hemodialysis and 661 (8.1%) were transplanted. In the analysis of competing risks, adjusted for age, sex, presence of DM, HTA, body mass index, residual function, albumin, hemoglobin, phosphorus, and modality of PD at the start of therapy, we found cause-specific HR (HRce) for high/fast transfer was 1.13 (95% CI 0.98-1.30) p = 0.078, high average 1.08 (95% CI 0.96-1.22) p = 0.195, low average 1.09 (95% CI 0.96-1.22) p = 0.156 compared to the low/slow transfer rate. For technique survival, cause-specific HR for high/rapid transfer of 1.22 (95% CI 0.98-1.52) p = 0.66, high average HR was 1.10 (95% CI 0.91-1.33) p = 0.296, low average HR of 1.03 (95% CI 0.85-1.24) p = 0.733 compared with the low/slow transfer rate, adjusted for age, sex, DM, HTA, BMI, residual renal function, albumin, phosphorus, hemoglobin, and PD modality at start of therapy. Non-significant differences. CONCLUSIONS: When evaluating the etiological relationship between the type of peritoneal solute transfer rate and overall mortality and survival of the technique using a competing risk model, we found no etiological relationship between the characteristics of peritoneal membrane transfer according to the classification given by Twardowski assessed at the start of peritoneal dialysis therapy and overall mortality or technique survival in adjusted models. The analysis will then be made from the prognostic model with the purpose of predicting the risk of mortality and survival of the technique using the risk subdistribution model (Fine & Gray).

Exploring the Role of Cell-Free Nucleic Acids and Peritoneal Dialysis: A Narrative Review.

INTRODUCTION: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation. CONCLUSIONS: This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.

Caffeic acid phenethyl ester restores mitochondrial homeostasis against peritoneal fibrosis induced by peritoneal dialysis through the AMPK/SIRT1 pathway.

Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective interventions for peritoneal fibrosis. In the present study, we explored whether adding caffeic acid phenethyl ester (CAPE) to peritoneal dialysis fluid (PDF) improved peritoneal fibrosis caused by PD and explored the molecular mechanism. We established a peritoneal fibrosis model in Sprague-Dawley rats through intraperitoneal injection of PDF and lipopolysaccharide (LPS). Rats in the PD group showed increased peritoneal thickness, submesothelial collagen deposition, and the expression of TGFß1 and α-SMA. Adding CAPE to PDF significantly inhibited PD-induced submesothelial thickening, reduced TGFß1 and α-SMA expression, alleviated peritoneal fibrosis, and improved the peritoneal ultrafiltration function. In vitro, peritoneal mesothelial cells (PMCs) treated with PDF showed inhibition of the AMPK/SIRT1 pathway, mitochondrial membrane potential depolarization, overproduction of mitochondrial reactive oxygen species (ROS), decreased ATP synthesis, and induction of mesothelial-mesenchymal transition (MMT). CAPE activated the AMPK/SIRT1 pathway, thereby inhibiting mitochondrial membrane potential depolarization, reducing mitochondrial ROS generation, and maintaining ATP synthesis. However, the beneficial effects of CAPE were counteracted by an AMPK inhibitor and siSIRT1. Our results suggest that CAPE maintains mitochondrial homeostasis by upregulating the AMPK/SIRT1 pathway, which alleviates oxidative stress and MMT, thereby mitigating the damage to the peritoneal structure and function caused by PD. These findings suggest that adding CAPE to PDF may prevent and treat peritoneal fibrosis.

Autophagy caused by oxidative stress promotes TGF-ß1-induced epithelial-to-mesenchymal transition in human peritoneal mesothelial cells.

Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-ß1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-ß1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-ß1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 µM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-ß1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 µM) downregulated TGF-ß1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-ß1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-ß1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.

LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis.

Peritoneal dialysis (PD), hemodialysis and kidney transplantation are the three therapies to treat uremia. However, PD is discontinued for peritoneal membrane fibrosis (PMF) and loss of peritoneal transport function (PTF) due to damage from high concentrations of glucose in PD fluids (PDFs). The mechanism behind PMF is unclear, and there are no available biomarkers for the evaluation of PMF and PTF. Using microarray screening, we found that a new long noncoding RNA (lncRNA), RPL29P2, was upregulated in the PM (peritoneal membrane) of long-term PD patients, and its expression level was correlated with PMF severity and the PTF loss. In vitro and rat model assays suggested that lncRNA RPL29P2 targets miR-1184 and induces the expression of collagen type I alpha 1 chain (COL1A1). Silencing RPL29P2 in the PD rat model might suppress the HG-induced phenotypic transition of Human peritoneal mesothelial cells (HPMCs), alleviate HG-induced fibrosis and prevent the loss of PTF. Overall, our findings revealed that lncRNA RPL29P2, which targets miR-1184 and collagen, may represent a useful marker and therapeutic target of PMF in PD patients.

Perioperative outcomes and platinum resistant recurrence in patients undergoing systematic, protocol-based, total parietal peritonectomy during interval cytoreductive surgery for advanced ovarian cancer: results of the TORPEDO study.

OBJECTIVE: The TORPEDO (CTRI/2018/12/016789) is the single-arm, prospective, interventional study evaluating the role of a total parietal peritonectomy (TPP) in patients undergoing interval cytoreductive surgery (iCRS). In this manuscript, we report the perioperative outcomes and platinum resistant recurrence (PRR) in 218 patients enrolled in the study. METHODS: A TPP was performed in all patients undergoing iCRS irrespective of the residual disease extent. hyperthermic intraperitoneal chemotherapy (HIPEC) was performed as per the clinician's discretion with 75 mg/m² of cisplatin. Maintenance therapy was also used at the discretion of the treating clinicians. RESULTS: From 9th December 2018 to 31st July 2022 (recruitment complete), 218 patients were enrolled at 4 medical centers in India. The median surgical peritoneal cancer index was 14 and a complete gross resection was achieved in 95.8%. HIPEC was performed in 130 (59.6%) patients. The 90-day major morbidity was 17.4% and 2.7% patients died within 90 days of surgery. Adjuvant chemotherapy was delayed beyond 6 weeks in 7.3%. At a median follow-up of 19 months (95% confidence interval [CI]=15.9-35 months), 101 (46.3%) recurrences and 19 (8.7%) deaths had occurred. The median progression-free survival was 22 months (95% CI=17-35 months) and the median overall survival (OS) not reached. Platinum resistant recurrence was observed in 6.4%. The projected 3-year OS was 81.5% and in 80 patients treated before may 2020, it was 77.5%. CONCLUSION: The morbidity and mortality of TPP with or without HIPEC performed during iCRS is acceptable. The incidence was of PRR is low. Early survival results are encouraging and warrant conduction of a randomized controlled trial comparing TPP with conventional surgery.

Extra-peritoneal vs. Trans-peritoneal Radical Cystectomy pros and cons.

One of the most common cancers of the urinary tract is bladder tumors. Bladder cancers are divided into two groups: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer. (1)  Trans-Peritoneal  Radical Cystectomy (RC) with  pelvic lymphadenectomy is the standard technique in muscle invasive and high risk non-muscle invasive bladder cancer (2). and Urologist around the world are more familiar with trans-peritoneal technique. In some articles extra-peritoneal Radical Cystectomy (RC) implied as an decreased  postoperative  complications techniques. In this letter we want to compare these two techniques and find out the pros and cons of these techniques.

Faster both in operative time and functional recovery by the extraperitoneal daVinci SP-based robot-assisted radical prostatectomy: a propensity score matching analysis compared to transperitoneal multiport counterpart.

We aim to investigate the peri-operative outcomes after extraperitoneal single-port based robot-assisted radical prostatectomy (eSP-RARP) utilizing the da Vinci SP system compared to conventional transperitoneal multi-port counterparts (tMP-RARP), in an era when pelvic lymph node dissection (PNLD) was omitted for the node-negative case. With exclusion criteria of volume + 50 g, suspicious rectal invasion, and node-positive disease given relatively weak grasping power and limited range of motion from the current SP system, 50 consecutive patients (Since December 2021) with localized prostate cancer underwent eSP-RARP by a single urologist maintaining identical surgical technique for 100 consecutive tMP-RARP cases (Since December 2020). Given initial selection criteria, each group was matched to a 1:1 ratio based on the risk-stratification parameters and the prostate volume. The operative time, which was maintained in each group during the study period, was significantly faster in eSP-RARP groups than in tMP-RARP (149.2 vs. 163.2 min, p = 0.025), while the weight of the removed specimen (27.1 vs. 29.0 g, p = 0.420) and margin positivity (14.7% vs. 11.7% in pT2, p = 0.812) were similar. The gas-out (1.5 vs. 1.88 days, p = 0.003) and solid diet dates (2.26 vs. 3.22 days, p < 0.001) were faster in the eSP-RARP group. The single-pad continence dates (30.5 vs. 51.9 days, p = 0.145) and zero-pad continence dates (105.5 vs. 146.2 days, p = 0.210) were identical. 90-day single-pad continence rate was 92% vs. 82% (p = 0.142, 52% vs. 56% in zero-pad continence). Based on these, daVinci SP-based RARP restored bowel function faster with shorter operative time through an extraperitoneal approach than the conventional transperitoneal multi-port counterpart while maintaining similar incontinence outcomes in cases without a routine PNLD.

The Impact of Positive Peritoneal Cytology on the Survival Rates of Early-Stage-Disease Endometrial Cancer Patients: Systematic Review and Meta-Analysis.

Background and Objectives: The impact of positive peritoneal cytology has been a matter of controversy in early-stage endometrial cancer for several years. The latest staging systems do not take into consideration its presence; however, emerging evidence about its potential harmful effect on patient survival outcomes suggests otherwise. In the present systematic review and meta-analysis, we sought to accumulate current evidence. Materials and Methods: Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar and Clinicaltrials.gov databases were searched for relevant articles. Effect sizes were calculated in Rstudio using the meta function. A sensitivity analysis was carried out to evaluate the possibility of small-study effects and p-hacking. Trial sequential analysis was used to evaluate the adequacy of the sample size. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale. Results: Fifteen articles were finally included in the present systematic review that involved 19,255 women with early-stage endometrial cancer. The Newcastle-Ottawa scale indicated that the majority of included studies had a moderate risk of bias in their selection of participants, a moderate risk of bias in terms of the comparability of groups (positive peritoneal cytology vs. negative peritoneal cytology) and a low risk of bias concerning the assessment of the outcome. The results of the meta-analysis indicated that women with early-stage endometrial cancer and positive peritoneal cytology had significantly lower 5-year recurrence-free survival (RFS) (hazards ratio (HR) 0.26, 95% CI 0.09, 0.71). As a result of the decreased recurrence-free survival, patients with positive peritoneal cytology also exhibited reduced 5-year overall survival outcomes (HR 0.50, 95% CI 0.27, 0.92). The overall survival of the included patients was considerably higher among those that did not have positive peritoneal cytology (HR 12.76, 95% CI 2.78, 58.51). Conclusions: Positive peritoneal cytology seems to be a negative prognostic indicator of survival outcomes of patients with endometrial cancer. Considering the absence of data related to the molecular profile of patients, further research is needed to evaluate if this factor should be reinstituted in future staging systems.

Glued suture-less peritoneum closure in laparoscopic inguinal hernia repair reduces acute postoperative pain.

Inguinal hernia repair is performed more than 20 million times per annum, representing a significant health and economic burden. Over the last three decades, significant technical advances have started to reduce the invasiveness of these surgeries, which translated to better recovery and reduced costs. Here we bring forward an innovative surgical technique using a biodegradable cyanoacrylate glue instead of a traumatic suture to close the peritoneum, which is a highly innervated tissue layer, at the end of endoscopy hernia surgery. To test how this affects the invasiveness of hernia surgery, we conducted a cohort study. A total of 183 patients that underwent minimally invasive hernia repair, and the peritoneum was closed with either a conventional traumatic suture (n = 126, 68.9%) or our innovative approach using glue (n = 57, 31.1%). The proportion of patients experiencing acute pain after surgery was significantly reduced (36.8 vs. 54.0%, p = 0.032) by using glue instead of a suture. In accordance, the mean pain level was higher in the suture group (VAS = 1.5 vs. 1.3, p = 0.029) and more patients were still using painkillers (77.9 vs. 52.4%, p = 0.023). Furthermore, the rate of complications was not increased in the glue group. Using multivariate regressions, we identified that using a traumatic suture was an independent predictor of acute postoperative pain (OR 2.0, 95% CI 1.1-3.9, p = 0.042). In conclusion, suture-less glue closure of the peritoneum is innovative, safe, less painful, and possibly leads to enhanced recovery and decreased health costs.

Inhibition of STAT3 by S3I-201 suppress peritoneal fibroblast phenotype conversion and alleviate peritoneal fibrosis.

Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis.