Explore the vast range of titles available.

Postoperative adhesions remain one of the more challenging issues in surgical practice. Although peritoneal adhesions occur after every abdominal operation, the density, time interval to develop symptoms, and clinical presentation are highly variable with no predictable patterns. Numerous studies have investigated the pathophysiology of postoperative adhesions both in vitro and in vivo. Factors such as type and location of adhesions, as well as timing and recurrence of adhesive obstruction remain unpredictable and poorly understood. Although the majority of postoperative adhesions are clinically silent, the consequences of adhesion formation can represent a lifelong problem including chronic abdominal pain, recurrent intestinal obstruction requiring multiple hospitalizations, and infertility. Moreover, adhesive disease can become a chronic medical condition with significant morbidity and no effective therapy. Despite recent advances in surgical techniques, there is no reliable strategy to manage postoperative adhesions. We herein review the pathophysiology and clinical significance of postoperative adhesions while highlighting current techniques of prevention and treatment.

Regulatory T (Treg) cells and T-helper-17 (Th17) cells may be involved in endometriosis. Information on the pattern of change in the percentages of Treg and Th17 cells in the peripheral blood (PB) and peritoneal fluid (PF) of women with early and advanced endometriosis is unclear. To investigate the pattern of change in the percentages of Treg and Th17 cells in the PB and PF of women with early and advanced endometriosis. We recruited 31 women with laparoscopically and histologically confirmed, revised American Society of Reproductive Medicine stage I-II endometriosis, 39 women with stage III-IV endometriosis, and 36 control subjects without visible endometriosis. PB and PF samples were collected and T-cell subpopulations analyzed by flow cytometry using specific monoclonal antibodies recognizing CD4+, CD25+, FOXP3+, and IL-17A+ markers. PF concentrations of TGF-β and IL-17 were measured by ELISA. The percentages of CD25+FOXP3+ Treg cells within the CD4+ T-cell population were significantly higher in the PF of women with advanced endometriosis than in either early endometriosis or in control subjects (P < 0.05 for both). A persistently lower percentage of CD4+IL-17A+ Th17 cells was found in both PB and PF of women with early and advanced endometriosis. Compared with IL-17 levels, PF levels of TGF-β were significantly higher in women with endometriosis (P = 0.01). Our findings reconfirmed the current speculation that endometriosis is related to alteration of Treg and Th17 cells in the pelvis causing survival and implantation of ectopic endometrial lesions.

In chronic peritoneal diseases, mesothelial-mesenchymal transition is determined by cues from the extracellular environment rather than just the cellular genome. The transformation of peritoneal mesothelial cells and other host cells into myofibroblasts is mediated by cell membrane receptors, Transforming Growth Factor β1 (TGF-β1), Src and Hypoxia-inducible factor (HIF). This article provides a narrative review of the reprogramming of mesothelial mesenchymal transition in chronic peritoneal diseases, drawing on the similarities in pathophysiology between encapsulating peritoneal sclerosis and peritoneal metastasis, with a particular focus on TGF-β1 signaling and estrogen receptor modulators. Estrogen receptors act at the cell membrane/cytosol as tyrosine kinases that can phosphorylate Src, in a similar way to other receptor tyrosine kinases; or can activate the estrogen response element via nuclear translocation. Tamoxifen can modulate estrogen membrane receptors, and has been shown to be a potent inhibitor of mesothelial-mesenchymal transition (MMT), peritoneal mesothelial cell migration, stromal fibrosis, and neoangiogenesis in the treatment of encapsulating peritoneal sclerosis, with a known side effect and safety profile. The ability of tamoxifen to inhibit the transduction pathways of TGF-β1 and HIF and achieve a quiescent peritoneal stroma makes it a potential candidate for use in cancer treatments. This is relevant to tumors that spread to the peritoneum, particularly those with mesenchymal phenotypes, such as colorectal CMS4 and MSS/EMT gastric cancers, and pancreatic cancer with its desmoplastic stroma. Morphological changes observed during mesothelial mesenchymal transition can be treated with estrogen receptor modulation and TGF-β1 inhibition, which may enable the regression of encapsulating peritoneal sclerosis and peritoneal metastasis.

Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime.

Background Adhesive small bowel obstruction (ASBO) is an important cause of hospital admission, is associated with significant morbidity and mortality, and therefore is a substantial burden for healthcare systems worldwide. Icodextrin 4% solution (Adept, Shire Pharmaceuticals, UK) is a high-molecular-weight a-1,4 glucose polymer approved in Europe for use as intraoperative lavage and postoperative instillation to reduce the occurrence of post-surgery intra-abdominal adhesions. The present clinical study aimed to evaluate the safety and effectiveness of icodextrin 4% in decreasing the incidence, extent, and severity of adhesions in patients after abdominal surgery for ASBO. Methods The study was a single-center prospective, randomized investigation. The study is designed and conducted in compliance with the principles of Good Clinical Practice regulations. Safety and efficacy of icodextrin 4% in the study group are compared to no anti-adhesion treatment in a parallel control group with blinded evaluation of primary endpoints. Primary endpoints are the evaluation of the therapeutic role of icodextrin 4% in reducing ASBO recurrence incidence and the need of laparotomies for ASBO recurrence, as well as adhesion formation (with evaluation of their incidence, extent, and severity). A sum of 181 patients with ASBO and surgical indication to laparotomy were enrolled and randomized in two groups. Patients were submitted to adhesiolysis with bowel resection if required with or without anastomosis. The first group received traditional treatment (control group), whereas the second group was treated with the addition of icodextrin 4% solution before the abdominal closure. Results Ninety-one patients were randomized to have icodextrin 4% solution administered intraperitoneally, and 90 patients were randomized to have the traditional treatment. The two study groups were homogeneous regarding their baseline characteristics. The ASBO recurrence rate was 2.19% (2/91) in the icodextrin groups vs 11.11% (10/90) in the control group after a mean follow-up period of 41.4 months ( p  < 0.05). No differences were found in the need of laparotomies for ASBO recurrence in the studied groups. The adhesion severity score seems lower in the group treated with the addition of icodextrin ( p  = n.s.). Conclusions The data resulting from this RCT showed that the use of icodextrin 4% solution in ASBO is safe and reduces intra-abdominal adhesion formation and the risk of re-obstruction.

Background SMARCA4 -deficient undifferentiated tumor ( SMARCA4 -UT) is a rare and highly malignant primary tumor characterized by the loss of SMARCA4 expression. Despite advancements in oncology, diagnosing and treating SMARCA4-UT remain significant clinical challenges. Case demonstration A 67-year-old male with a history of smoking presented to the hospital with complaints of abdominal distention and pain lasting for more than four days. Abdominal computed tomography (CT) revealed a high-density mass measuring approximately 41 × 37 mm in the right lower quadrant. Additionally, chest CT identified a high-density mass measuring 63 × 48 mm in the upper lobe of the right lung. The patient underwent partial small bowel resection, and postoperative pathological examination confirmed a diagnosis of SMARCA4 -UT originating in the small mesentery. Unfortunately, the patient succumbed to respiratory failure 21 days after the diagnosis. Conclusion SMARCA4 -UT is an exceedingly rare and aggressive undifferentiated tumor. This case highlights a presentation of SMARCA4 -UT with abdominal pain and distention as initial symptoms. Clinicians should consider SMARCA4 -UT in middle-aged or elderly male patients with a history of smoking who present with large masses. Comprehensive chest imaging is essential to exclude the thoracic primary disease in such cases.

This study aimed to compare the differences between rat and mouse models of peritoneal adhesions (PAs). The cecum-abdominal wall ischemic injury suture method was used to establish postoperative PA models in Sprague–Dawley rats and BALB/c mice. Adhesion progression was systematically evaluated via a multimodal system comprising imaging (micro-computed tomography [CT]), macroscopic scoring (Degree of Adhesion and Separation Index [DASI]), and histopathology/immunohistochemistry. Scanning electron microscopy (SEM) of human and rodent peritonea provided a supplementary morphological reference. Imaging and macroscopic evaluations revealed that rats developed more severe and persistent adhesions than mice. This was evidenced by denser CT shadows on day 14 and significantly higher DASI scores on days 7 and 14 ( p  < 0.01). Histological analysis confirmed more robust collagen deposition and higher expression of profibrotic proteins (TGF-β1 and fibronectin) in rats. SEM findings indicated that the rat peritoneum has more abundant microvilli and a more regular texture, providing a morphological substrate that more closely resembles the human peritoneal surface than that of mice. The rat model exhibits more robust and persistent peritoneal adhesion features than the mouse model, making it a more suitable platform for clinical phenotype studies and translational evaluation. Its morphological similarity to the human peritoneum provides a supplementary structural reference for these interspecies differences.

Postoperative peritoneal adhesion (PA), a prevalent complication of abdominal surgery, arises from aberrant healing of the injured peritoneum. This process involves mesothelial cell trans-differentiation into myofibroblast-like cells, driving peritoneal matrix remodeling and pathological fibrous band formation between organs. Existing therapeutic strategies to prevent PA exhibit limited efficacy, underscoring the need for previously unrecognized mechanistic insights into PA pathogenesis. Here, we elucidate the role of autophagy in mesothelial cell transition and PA development. Utilizing a murine PA model coupled with comprehensive in vitro analyses, we demonstrate that HMGB1-mediated autophagy facilitates TGF-β mediated mesothelial cell trans-differentiation. Specifically, autophagic degradation of E-cadherin counteracts TGF-β-driven mesothelial transition. Pharmacological activation of autophagy via rapamycin or recombinant HMGB1 potentiated this transition, whereas HMGB1 inhibitor (glycyrrhizin) or autophagy suppressor (spautin-1) markedly attenuated it. Crucially, early postoperative administration of glycyrrhizin or spautin-1 significantly reduced PA severity. Our findings unveil autophagy and HMGB1 as pivotal regulator targets of mesothelial plasticity during PA formation, provide mechanistic insights into peritoneum repair, and propose novel therapeutic avenues for PA prevention.

Abstract Context NOTCH signaling is activated in endometriotic lesions, but the exact mechanisms remains unclear. IL-6, which is increased in the peritoneal fluid of women with endometriosis, induces NOTCH1 through E-proteins including E2A and HEB in cancer. Objective To study the role of E-proteins in inducing NOTCH1 expression under the regulation of IL-6 in endometriosis. Setting and Design The expression of E-proteins and NOTCH1 was first investigated in endometrium of women with endometriosis and the baboon model of endometriosis. Regulation of E-proteins and NOTCH1 expression was examined after IL-6 stimulation and siRNA mediated inhibition of E2A or/and HEB in human endometriotic epithelial cells (12Z) in vitro, and subsequently following IL-6 treatment in the mouse model of endometriosis in vivo. Results E2A, HEB, and NOTCH1 were significantly upregulated in glandular epithelium (GE) of ectopic endometrium compared to eutopic endometrium in both women and the baboon model. IL-6 treatment upregulated the expression of NOTCH1 together with E2A and HEB in 12Z cells. Small interfering RNA inhibition of E2A and HEB or HEB alone decreased NOTCH1 expression. Binding efficiency of both E2A and HEB was significantly higher at the binding sites on the human NOTCH1 promoter after IL-6 treatment. Finally, IL-6 treatment resulted in a significantly increased number of endometriotic lesions along with increased expression of E2A, HEB, and NOTCH1 in GE of the lesions compared with the vehicle group in an endometriosis mouse model. Conclusions IL-6 induced NOTCH1 expression is mediated by E-proteins in the ectopic GE cells, which may promote endometriotic lesion development.

Postoperative adhesions are most common issues for almost any types of abdominal and pelvic surgery, leading to adverse consequences. Pharmacological treatments and physical barrier devices are two main approaches to address postoperative adhesions but can only alleviate or reduce adhesions to some extent. There is an urgent need for a reliable approach to completely prevent postoperative adhesions and to significantly improve the clinical outcomes, which, however, is unmet with current technologies. Here we report that by applying a viscous, cream-like yet injectable zwitterionic polymer solution to the traumatized surface, postoperative adhesion was completely and reliably prevented in three clinically relevant but increasingly challenging models in rats. The success rate of full prevention is over 93% among 42 animals tested, which is a major leap in antiadhesion performance. Clinically used Interceed film can hardly prevent the adhesion in any of these models. Unlike current antiadhesion materials serving solely as physical barriers, the “nonfouling” zwitterionic polymer functioned as a protective layer for antiadhesion applications with the inherent benefit of resisting protein/cell adhesions. The nonfouling nature of the polymer prevented the absorption of fibronectins and fibroblasts, which contribute to the initial and late-stage development of the adhesion, respectively. This is the key working mechanism that differentiated our “complete prevention” approach from current underperforming antiadhesion materials. This work implies a safe, effective, and convenient way to fully prevent postoperative adhesions suffered by current surgical patients.