Targeting Lysyl Oxidase as a Potential Therapeutic Approach to Reducing Fibrotic Scars Post-operatively: Its Biological Role in Post-Surgical Scar Development.

Abdominal and pelvic surgery, or any surgical injury of the peritoneum, often leads to chronic abdominal adhesions that may lead to bowel obstruction, infertility, and pain. Current therapeutic strategies are usually ineffective, and the pathological mechanisms of the disease are unclear. Excess collagen cross-linking is a key mediator for extra-cellular matrix deposition and fibrogenesis. Lysyl oxidase is a key enzyme that catalyzes the formation of stabilizing cross-links in collagen. Dysregulation of Lysyl oxidase (Lox) expressing upregulates collagen cross-linking, leading ECM deposition. Tissue hypoxia during surgery induces molecular mechanisms and active transcription factors to promote the expression of several genes related to inflammation, oxidative stress, and fibrosis, such as transforming growth factor beta, and Lox. Studies have shown that targeting Lox improves clinical outcomes and fibrotic parameters in liver, lung, and myocardial fibrosis, therefore, Lox may be a potential drug target in the prevention of postsurgical adhesion.

Review the Role of Metabolism Reprogramming in the Pathogenesis of Post-surgical Adhesion: A New Therapeutic Strategy.

Metabolic reprogramming is defined as the skill of cells to change their metabolism to support the induced energy demand due to continuous growth. Metabolic reprogramming is a well- known occurrence in the progression of neoplastic cells, although, evidence has shown that it is present in fibrotic disorders. Post-surgical adhesion as a fibrotic disorder is a medical challenge and is defined by fibrotic bands connected between organs with the abdominal wall. Despite many investigations carried out about the pathogenesis of the disorder but there are many unknowns, therefore, targeting special pathways may have the potential to prevent the formation of fibrotic bands post-operative. Glycolysis is a necessary metabolic pathway in living cells. In hypoxic conditions, it is the dominant pathway in the production of energy for different types of cells such as fibroblasts, immune cells, and endothelial cells. Also, glycolysis is a main downstream target for transforming growth factor ß (TGF-ß) and upregulates during fibrotic conditions. Furthermore, this is noteworthy that hypoxia induces factor 1 alpha (HIF-1α) as a transcription factor, elevated during the hypoxia condition stimulates different signaling pathways such as TGF-ß/SMAD, nuclear factor kappa B (NF-kB), and mTOR pathway to control glycolytic metabolism and T-cell trafficking for immune cell migration. Different evidence has indicated that the administration of glycolytic inhibitors has the potential to prevent the development of fibrotic markers. In this review, we pointed out the role of the glycolysis pathway and its connection to profibrotic cytokines to promote inflammatory and fibrotic pathways. Based on the results of studies related to fibrotic disorders we hypothesized that targeting glycolysis may have therapeutic potential in the prevention of postoperative adhesions.

Novel technique for arterial reconstruction in simultaneous pancreas-kidney transplantation, a randomized clinical trial.

INTRODUCTION: Simultaneous pancreas kidney (SPK) transplantation is an invaluable procedure to enhance the quality of life of insulin-dependent patients with advanced renal disease. The creation of vascular anastomoses of the donor's pancreas vessels to the recipient's, is of utmost importance to predict the graft outcome and surgical complications. In the study we introduce a novel technique for arterial reconstruction during SPK transplantation. METHODS: Conventionally, during the SPK transplantation, a so-called Y-graft is anastomosed between donor's superior mesenteric and splenic artery to the recipient's right iliac artery. In the study we adopted a new technique by preparing an extra extension using the donor's carotid artery, to be anastomosed to the Y-graft and the iliac artery. In this non-blinded randomized clinical trial we compared the surgical complications and early outcomes between the 2 groups of patients with the traditional and new arterial reconstruction techniques during 3 months after transplantation. RESULTS: Thirty adult patients were included in the study. The incidence of pancreatitis, vascular thrombosis and surgical site infection was lower in the new Y-graft and extension technique, which was not statistically significant. However, the calculated Cohen's d index showed the medium effect of new Y-graft and extension technique on complication after SPK transplantations. CONCLUSION: The post-operative complications tend to be lower in the novel arterial reconstruction technique, however a study on a larger patient group is encouraged to confirm our primary results. TRIAL REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials on 12/05/2022; IRCT 20210625051701N2; ( http://www.irct.ir/ ).

Serial transverse enteroplasty and nipple valve construction, two life saving techniques for patients with short bowel syndrome, a report of 5 cases.

BACKGROUND: Various abdominal pathologies end up with surgical resection of small intestine. When the small intestine remnant is too short for adequate fluid and micronutrients absorption, short bowel syndrome is diagnosed. The disabling condition needs a multidisciplinary approach to design parenteral nutrition, care for thrombotic, hepatic and infectious complications and gradually wean the patient from parenteral nutrition. Various surgical techniques have been introduced to increase absorptive mucosa and enhance the intestinal adaptation process. Serial transverse enteroplasty and nipple valve reconstruction are among the procedures, which will be discussed in the current article. CASE PRESENTATION: Herein, we presented 5 cases of short bowel syndrome as a consequence of abdominal laparotomies, patients were referred to our center to receive parenteral nutrition and to be prepared for the final autologous gastrointestinal reconstruction or intestinal transplantation, if indicated. CONCLUSION: Patient's age, performance status and bowel remnant length determines the appropriate technique for autologous gastrointestinal reconstruction. Serial transverse enteroplasty is designed to increase bowel's length by creating zigzag patterns through dilated bowel loops. Presence of ileocecal valve is crucial to delay intestinal transit time and to prevent colonic bacterial transfer to ileum. Patient's with ileocecal valve loss benefit from creating an artificial valve, namely, nipple valve.

Lessons learned from successful autologous gastrointestinal reconstruction in patients with intestinal failure: a case series.

BACKGROUND: Intestinal failure (IF) is a rare but severe form of organ failure. The condition is defined as body's inability to absorb adequate fluids, macronutrients and minerals for growth and development, so that intravenous supplementation is necessary. A broad spectrum of diseases, trauma and complications of surgery might eventually end up with intestinal failure. Nowadays, intestinal failure patients are preferably cared for in intestinal rehabilitation units (IRU). Autologous gastrointestinal reconstruction (AGIR) refers to non-transplant operative management of IF patients designed to improve enteral tolerance and gut absorptive capacity. CASE PRESENTATION: Herein we present five cases with complications of surgeries due to peptic ulcer bleeding, blunt abdominal trauma, obesity and gastric tumor. The surgeries were complicated by anastomotic leak, peritonitis and fistula formation. By adopting multidisciplinary decisions and special care for each complication, all the five patients were successfully managed and discharged. DISCUSSION AND CONCLUSIONS: As presented, re-anastomosis in presence of abdominal contamination will probably fail. In patients with intestinal failure, PN should start as soon as possible to increase the success rate of future surgeries and prevent potential need for intestinal transplantation. We suggest referring patients with complicated outcomes of gastrointestinal surgeries to the IRUs to reduce morbidity and mortality.