BACKGROUND Cancer is recognized as the most common cause of death in high-income countries. Compared to the traditionally used chemo and/or radiotherapies, recent advances in medical research allowed for the implementation of more precise and effective treatment modalities actively engaging the immune system. One of the examples of immunotherapy involves the adoptive cell transfer (ACT) of modified cells, such as T cells, expressing either chimeric antigen receptors (CAR) or T cell receptors (TCR) that specifically recognize tumor antigens. To date, several studies have demonstrated the outstanding efficacy of TCR-engineered T (TCR-T) cells in the eradication of cancer cells, paving the way for the development of successful therapies. Nevertheless, predicting the pairing between TCR and peptide-Human Leukocyte Antigen (pHLA) is one of the biggest challenges of modern computational immunology. Until now, TCR screening has been time-consuming, labor-intensive and required large financial outlays. In order to meet the growing need for precision medicine and the development of TCR-T therapies, we propose an Artificial Intelligence (AI) based platform to optimize the speed and accuracy in TCR screening and discovery. OBJECTIVE The aim of this study is to propose an observational clinical trial protocol for the collection of patient samples needed to generate a database of pHLA:TCR sequences to aid the development of an AI-based platform for the selection of specific TCRs. METHODS The multicenter observational study is currently in progress in 8 participating hospitals. All selected patients with diagnosed stage II, III or IV colorectal cancer (CRC) adenocarcinoma will be evaluated for the eligibility for the study. RESULTS The patient recruitment has been recently completed (December 2022). A hundred participants have been enrolled into the study from whom primary tumor tissue and peripheral blood samples have been obtained. Peripheral blood mononuclear cells (PBMCs) from peripheral blood samples have been isolated and cryopreserved. Nucleic acid extraction (DNA and RNA) has been performed in 86 cases. 57 samples have undergone Whole Exome Sequencing (WES) to determine the presence of somatic mutations and RNAseq for gene expression profiling. CONCLUSIONS The results of this study may have a significant influence on the treatment of CRC patients. The proposed protocol provides the basic information for the development of an innovative AI platform that allows fast and safe in silico prediction of TCRs, which may be utilized in cancer immunotherapy. CLINICALTRIAL Trial Registration: ClinicalTrials.gov NCT04994093
Introduction Laparoscopic sleeve gastrectomy (SG) is currently the most commonly performed bariatric operation, but re-do surgery may be necessary in up to half of the patients. Single anastomosis duodeno-ileal bypass (SADI-S) is quickly gaining recognition as a revisional procedure after failed SG. Aim To discuss the surgical technique and analyze initial outcomes after introduction of SADI-S after SG with 1-year follow-up. Material and methods This is a retrospective cohort study of consecutive patients who underwent re-do bariatric surgery – revisional SADI-S – in 2021 at a secondary referral public hospital. All patients’ follow-up was completed 1 year after. Results 14 consecutive patients, 6 (43%) males and 8 females, were included. Median maximal body mass index (BMI) was 52.29 (47.96–77.16) kg/m 2 , BMI before SADI-S was 43.09 (41.64–48.99) kg/m 2 . No perioperative morbidity was recorded. Four (28%) patients reported recurrent abdominal crampy pain and diarrhea that required dietary advisement and pharmacological therapy in the postoperative period. No reoperations, mortality or readmissions were recorded during 1-year follow-up. SADI-S was associated with further weight loss, resulting in median BMI of 37.55 (36.29–39.43) kg/m 2 1 year after SADI-S. Observed additional percentage total weight loss (%TWL) 1 year after SADI-S was 18.65% (17.25–21.89%), while additional percentage excess body mass index loss (%EBMIL) was 35.88% (29.18–41.92%). There was 1 case of diabetes mellitus type 2 remission and improvement in glycemic control in 1 patient. 4/6 patients (66.67%) had improvement in control of hypertension. Conclusions SADI-S is promising re-do surgery after SG with low postoperative morbidity. Additional %TWL 1 year after SADI-S is ~19%, while additional %EBMIL is ~36%, with significant improvement of obesity-related comorbidities.
Introduction: Resection of the portal vein or superior mesenteric vein infiltrated by the pancreatic cancer is currently a standard during open pancreatic surgery for cancer. When found intraoperatively it often leads to conversion. Nowadays, research data for laparoscopic pancreatectomies with major venous resections and reconstructions are scarce. Aim: To present our own results of laparoscopic total pancreatectomies, pancreaticoduodenectomy and distal pancreatectomies (RAMPS) performed for cancer with major venous resection and reconstructions of the portal system. Material and methods: This is a retrospective study of our own clinical material of consecutive patients treated for adenocarcinoma of pancreas who underwent laparoscopic pancreatectomies with major venous resection and reconstruction in 2020 and 2021. Results: The study included 6 females and 2 males in median age of 68 years . 6 tumors were located in the pancreatic head, 1 in the pancreatic neck and 1 in the pancreatic body. Surgical procedures included 5 total pancreatectomies, 2 RAMPS and 1 Whipple pancreaticoduodenectomy. There were no conversions. Median time of vascular closure was 55.5 (41-70) min. Median blood loss was 500 (250-900) ml. Median length of hospital stay (LOS) was 18.5 (11-34) days. We observed no complications related directly to vascular resection. Conclusions: Laparoscopic approach for pancreatectomies with portal or superior mesenteric vein resections could be a safe and feasible approach in the hands of an experienced surgeon.
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