Creating an Innovative Artificial Intelligence-Based Technology (TCRact) for Designing and Optimizing T Cell Receptors for Use in Cancer Immunotherapies: Protocol for an Observational Trial.

BACKGROUND: Cancer continues to be the leading cause of mortality in high-income countries, necessitating the development of more precise and effective treatment modalities. Immunotherapy, specifically adoptive cell transfer of T cell receptor (TCR)-engineered T cells (TCR-T therapy), has shown promise in engaging the immune system for cancer treatment. One of the biggest challenges in the development of TCR-T therapies is the proper prediction of the pairing between TCRs and peptide-human leukocyte antigen (pHLAs). Modern computational immunology, using artificial intelligence (AI)-based platforms, provides the means to optimize the speed and accuracy of TCR screening and discovery. OBJECTIVE: This study proposes an observational clinical trial protocol to collect patient samples and generate a database of pHLA:TCR sequences to aid the development of an AI-based platform for efficient selection of specific TCRs. METHODS: The multicenter observational study, involving 8 participating hospitals, aims to enroll patients diagnosed with stage II, III, or IV colorectal cancer adenocarcinoma. RESULTS: Patient recruitment has recently been completed, with 100 participants enrolled. Primary tumor tissue and peripheral blood samples have been obtained, and peripheral blood mononuclear cells have been isolated and cryopreserved. Nucleic acid extraction (DNA and RNA) has been performed in 86 cases. Additionally, 57 samples underwent whole exome sequencing to determine the presence of somatic mutations and RNA sequencing for gene expression profiling. CONCLUSIONS: The results of this study may have a significant impact on the treatment of patients with colorectal cancer. The comprehensive database of pHLA:TCR sequences generated through this observational clinical trial will facilitate the development of the AI-based platform for TCR selection. The results obtained thus far demonstrate successful patient recruitment and sample collection, laying the foundation for further analysis and the development of an innovative tool to expedite and enhance TCR selection for precision cancer treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04994093; https://clinicaltrials.gov/ct2/show/NCT04994093. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45872.

A Rare Case of Dedifferentiated Liposarcoma with Osteosarcomatous Differentiation-Diagnostic and Therapeutic Challenges.

INTRODUCTION: Liposarcomas are the most common of all sarcomas. A well-differentiated liposarcoma can transform into a dedifferentiated liposarcoma with myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of MDM2 gene is then characteristic. Treatment usually involves surgical resection to radically remove the tumor. Other treatments such as chemotherapy and radiotherapy may also be used. CASE REPORT: A 60-year-old patient was admitted to the hospital for surgical treatment of a left renal mass. The true location of the tumor was discovered only intraoperatively. The lesion was completely removed laparoscopically with preservation of the capsule. Genomic amplification of MDM2 gene was confirmed. One and a half years after surgery, despite the removal of the tumor without the surrounding margin of healthy tissue, the patient remains without recurrence. CONCLUSION: Dedifferentiated liposarcoma with osteosarcomatous differentiation is a sporadic case and may occur in various locations of the retroperitoneal space, also mimicking a renal tumor. The laparoscopic technique is a safe surgical treatment for tumors of unclear origin. Removal of dedifferentiated liposarcoma with osteosarcomatous differentiation tumor with preservation of the lesion capsule without maintaining a margin of healthy tissue also allows for long-term cure. Precise immunohistochemical and molecular studies may have an impact on the effectiveness of further treatment and the prognosis of the patient. A patient after surgical treatment of liposarcoma requires constant outpatient follow-up for the reason of the high risk of local and distant recurrence.

Angiogenic Role of Mesothelium-Derived Chemokine CXCL1 During Unfavorable Peritoneal Tissue Remodeling in Patients Receiving Peritoneal Dialysis as Renal Replacement Therapy.

Peritoneal dialysis (PD) is a valuable 'home treatment' option, even more so during the ongoing Coronavirus pandemic. However, the long-term use of PD is limited by unfavourable tissue remodelling in the peritoneal membrane, which is associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while the involvement of other angiogenic signaling pathways is still poorly understood. Here, we have identified the crucial contribution of mesothelial cell-derived angiogenic CXC chemokine ligand 1 (CXCL1) to peritoneal angiogenesis in PD. CXCL1 expression and peritoneal microvessel density were analysed in biopsies obtained by the International Peritoneal Biobank (NCT01893710 at www.clinicaltrials.gov), comparing 13 children with end-stage kidney disease before initiating PD to 43 children on chronic PD. The angiogenic potential of mesothelial cell-derived CXCL1 was assessed in vitro by measuring endothelial tube formation of human microvascular endothelial cells (HMECs) treated with conditioned medium from human peritoneal mesothelial cells (HPMCs) stimulated to release CXCL1 by treatment with either recombinant IL-17 or PD effluent. We found that the capillary density in the human peritoneum correlated with local CXCL1 expression. Both CXCL1 expression and microvessel density were higher in PD patients than in the age-matched patients prior to initiation of PD. Exposure of HMECs to recombinant CXCL1 or conditioned medium from IL-17-stimulated HPMCs resulted in increased endothelial tube formation, while selective inhibition of mesothelial CXCL1 production by specific antibodies or through silencing of relevant transcription factors abolished the proangiogenic effect of HPMC-conditioned medium. In conclusion, peritoneal mesothelium-derived CXCL1 promotes endothelial tube formation in vitro and associates with peritoneal microvessel density in uremic patients undergoing PD, thus providing novel targets for therapeutic intervention to prolong PD therapy.

Introducing of the First DCD Kidney Transplantation Program in Poland.

In many countries, including Poland, the main problem with transplantation is the insufficiency of organ donors in relation to the demand for organs. Hence, the common aim globally is to increase the pool of donors. The prolonged survival of patients after transplantation, with respect to the survival time of patients on dialysis, makes the search much more intense. After the recourse of expanded criteria donors (ECD), the next step was obtaining kidneys from donors after irreversible cardiac death (DCD). Therefore, based on Dutch, British, and Spanish experience, it can be hypothesized that the introduction of DCD procedures in countries that have not launched these programs and the improvement of DCD procedures may shorten the waiting time for organ transplantation globally. The legal basis for the procurement of organs after irreversible cardiac arrest came into existence in Poland in 2010. Previously, such organ procurements were not in practice. Since 1984, when Poland published irreversible cardiac arrest as a criterion of brain death, it became the only way to determine death prior to the procurement of organs. The aim of this report was to evaluate the results of the first 19 transplantation cases involving harvested kidneys from donors after cardiac arrest, which was irreversible and clinically confirmed, without any doubt as per the ethical protocol of DCD. Understanding, support, and public perception are essential for this program's initiation and maintenance.

Long-term survival in a patient with unresectable liver metastases from uveal melanoma treated with transarterial chemoembolization with irinotecan eluting beads - case report and review of literature.

INTRODUCTION: Treatment of unresectable liver metastases (LM) from uveal melanoma (UM) remains a major clinical challenge. Systemic chemotherapy and chemoimmunotherapy regimens extrapolated from cutaneous melanoma are considered to be ineffective in therapy of metastases from uveal melanoma. Studies suggest that the progression of hepatic metastases rather than the primary tumor or metastases in other organs determines survival. CASE REPORT: We report a case of transarterial chemoembolization of 57-year-old man diagnosed with unresectable liver metastases from uveal melanoma with irinotecan eluting beads. Therapy resulted in long progression free survival and overall survival, 41 months and 45 months after diagnosis of metastatic disease respectively. Patient did not experience any major side effects of the therapy. Follow-up CTs indicate stable disease in mRECIST criteria and partial response in CHOI criteria. CONCLUSIONS: Transarterial chemoembolization with drug eluting beads loaded with irinotecan may be an effective treatment of unresectable liver metastases from uveal melanoma.

Prosthetic materials for treating posterior vaginal wall prolapse and rectocele - own experience.

OBJECTIVES: This report describes results of posterior vaginal wall prolapse and rectocele treatment performing tension free reconstruction method with polypropylene mesh implantation. MATERIAL AND METHODS: In years 2001 to 20015, 71 female patients in age of 42-82 years were surgically treated. Besides difficult emptying they complained of feeling of heaviness in the pelvis (38%) and dyspareunia (16.9%). Defecography and magnetic resonance proved the presence of rectocele in 84.5%, enterocele in 38%, descending perineum in 28.2%, genital organ prolapse in 23.9%, and rectal prolapse in 22.5% cases. 37 patients with defects of low location have undergone implantation of prosthetic material from vaginal approach. In cases of high location and genital organ prolapse abdominal approach was done. RESULTS: Permanent reconstruction of the rectovaginal septum has been achieved in 70 patients (98%). Symptoms of dyschesia, pelvic plain, heavy straining were persisted in 4 patients (10.3%). 3 cases of mash erosions were diagnosed. One patient was reoperated. Among 6 other patients who needed futher surgical treatment only one was reoperated because of vaginal prolapse. 81.7% of patients was satisfied with their treatment. CONCLUSION: Using prosthetic materials in pelvic floor defects treatment is characterized by high efficacy and low complication percentage.

Anatomical and functional results of a modified sacral perineocolporectopexy for extreme forms of complex pelvic organs prolapse--own experience.

OBJECTIVES: Anatomical and functional results of a modified sacral perineocolporectopexy for extreme forms of complex pelvic organs prolapse. MATERIAL AND METHODS: Between 2005 and 2010, 10 women aged 47-75 years were treated by abdomino-perineal implantation of polypropylene mesh for modified sacral perineocolporectopexy and subsequently followed-up. They were suffering from enterocele (9 pts), genital prolapse (8 pts), descending perineum (5 pts), rectal prolapse (4 pts), rectocele (3 pts). Five women were incontinent (mean Wexner: 9) and six had incomplete rectal evacuation. Defecography revealed enterocele III°(5 pts) and II°(4 pts). MR designed descending perineum in 5 pts (mean: 3.8 cm). RESULTS: Permanent reconstruction of the pelvic floor and remission of organs prolapse was achieved at 12-months follow-up in all except 1 patient. There were 2 small vaginal erosions of the mesh and 1 haematoma within the pelvic floor Improvement at rectal emptying was found in 4 patients, feeling of pelvic heaviness in 6 patients, dyspareunia in 3 patients. Mean incontinence score decreased from 9 to 4. CONCLUSIONS: 1. Modified sacral perineocolporectopexy is effective in the treatment of complex pelvic floor anatomical defects and organ prolapse. 2. Improvements in rectal emptying, pelvic feeling of heaviness and dyspareunia have been achieved. 3. The implant tolerance was good and the complications rate was law.

Abdominal rectopexy with absorbable and non-absorbable materials in the treatment for rectal prolapse.

UNLABELLED: THE AIM OF THE STUDY was to present and compare own results of abdominal rectopexy performed with absorbable and nonabsorbable materials used in surgical repair of rectal prolapse. MATERIAL AND METHODS: In the years 1991-2009, 50 patients were operated on for rectal prolapse. The first 8 patients (group I) were operated using absorbale polyglycolic acid mesh. The next 42 patients were operated using non-absorbable polypropylene mesh (group II). 12 patients with chronic, incurable constipation had sigmoidectomy and rectopexy performed at the same operation. Rectopexy was performed with the mesh and fixed to the pelvic fascia and periosteum and mesorectum, leaving the anterior one third of the rectum free. 6 months after surgery functional outcomes were evaluated. Statistic analysis with the level of statistical significance p < 0.005 was applied to obtained functional results. RESULTS: On the follow up visits, there were no symptoms of the recurrence of rectal prolapse in 5 patients (62.5%) from group I and in 25 patients (92.6%) from group II. Patients relapsing were reoperated 24 to 98 months after primary surgery. In all patients from group I (absorbable mesh), prosthetic material was not found at reoperation. In redo surgery only non-absorbable mesh was used. CONCLUSIONS: The effectiveness of rectal fixation depends on the on the durability of the prosthetic material. In the studied group polypropylene mesh was superior in rectopexy to absorbable mesh.