Limited nutrient availability in the tumor microenvironment renders pancreatic tumors sensitive to allosteric IDH1 inhibitors.

Nutrient-deprived conditions in the tumor microenvironment (TME) restrain cancer cell viability due to increased free radicals and reduced energy production. In pancreatic cancer cells a cytosolic metabolic enzyme, wild-type isocitrate dehydrogenase 1 (wtIDH1), enables adaptation to these conditions. Under nutrient starvation, wtIDH1 oxidizes isocitrate to generate α-ketoglutarate (αKG) for anaplerosis and NADPH to support antioxidant defense. In this study, we show that allosteric inhibitors of mutant IDH1 (mIDH1) are potent wtIDH1 inhibitors under conditions present in the TME. We demonstrate that low magnesium levels facilitate allosteric inhibition of wtIDH1, which is lethal to cancer cells when nutrients are limited. Furthermore, the Food & Drug Administration (FDA)-approved mIDH1 inhibitor ivosidenib (AG-120) dramatically inhibited tumor growth in preclinical models of pancreatic cancer, highlighting this approach as a potential therapeutic strategy against wild-type IDH1 cancers.

Mirizzi Syndrome: A Case Report and Review of the Literature.

Mirizzi syndrome (MS) is a rare complication of chronic gallstones. Mirizzi syndrome is characterized by a set of symptoms that results from obstruction of the common hepatic or common bile duct (CBD). This may be due to extrinsic compression from an impacted gallstone in the gallbladder neck or cystic duct because of inflammatory changes secondary to chronic gallstone cholecystitis. We present a case of an 86-year-old patient with chronic gallstones who presented with abdominal pain and jaundice. The patient was diagnosed with MS type V after endoscopic retrograde cholangiopancreatography (ERCP). CBD stone fragments/debris were removed, and the patient was referred for surgical intervention for the repair of cholecystoduodenal fistula. MS must be in the differential diagnosis in elderly patients with chronic gallstone cholecystitis presenting with obstructive jaundice. Multiple diagnostic and therapeutic approaches are required to diagnose and manage the different types of MS. We aim to present the case to highlight and raise awareness of MS, particularly in patients with chronic gallstones.

Clinical Practice Guidelines For The Management Of Colorectal Cancer, A Consensus Statement By The Society Of Surgeons® And Surgical Oncology Society Of Pakistan®.

A joint effort by the Society of Surgeons Pakistan and Society of Surgical Oncology Pakistan, these guidelines provide a framework for the practicing surgeons involved in care and management of patients with colorectal cancer. The guidelines take into account the issues related to our local circumstances and provide a minimum standard of care that must be given to these patients. The Guideline Committee had members from all disciplines, including surgery, surgical oncology, medical oncology and radiation oncology. The guidelines have attempted to simplify things to understand and follow for the practicing surgeons. With these guidelines we wish to eliminate disparities in treatment among institutions and prevent any under treatment of patients.

Outcome of purse-string versus linear skin closure after ileostomy stoma reversal in terms of stoma sites infection and cosmesis.

OBJECTIVE: To evaluate the incidence of infection and patient satisfaction in terms of cosmesis between purse-string closure and the usual linear closure of stoma wound. METHODS: The experimental randomised clinical trial was conducted from December 2017 to December 2018 at the Surgical Unit 1, Lahore General Hospital, Lahore, Pakistan, and comprised patients undergoing ileostomy stoma reversal. The patients were randomised into 2 groups using computer-generated random numbers. Group A underwent purse-string closure, while group B received linear closure. Both groups were followed post-operatively at 1 and 3 months for wound infection. Patient satisfaction was ascertained using standard tools. Data was analysed using SPSS version 20. RESULTS: Of the 72 patients, there were 37(51.4%) in group A and 35(48.6%) in group B. Overall, there were 50(69.4%) males and 22(30.5%) females. Infection occurred in 2(5.4%) group A patients and in 8(22.8%) group B patients (p=0.023). Patients in group A were more satisfied at 3 months post-surgery than patients in group B (p=0.001). CONCLUSIONS: Purse-string closure was found to be associated with a lower incidence of wound infection and higher patient satisfaction compared to linear closure.