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.

Post-Irradiation Bladder Syndrome After Radiotherapy of Malignant Neoplasm of Small Pelvis Organs: An Observational, Non-Interventional Clinical Study Assessing VESIcare®/Solifenacin Treatment Results.

BACKGROUND Radiotherapy is explicitly indicated as one of the excluding factors in diagnosing overactive bladder syndrome (OAB). Nevertheless, symptoms of OAB such as urgent episodes, incontinence, pollakiuria, and nocturia, which are consequences of irradiation, led us to test the effectiveness of VESIcare®/Solifenacin in patients demonstrating these symptoms after radiation therapy of small pelvis organs due to malignant neoplasm. MATERIAL AND METHODS We conducted an observatory clinical study including 300 consecutive patients with symptoms of post-irradiation bladder; 271 of those patients completed the study. The observation time was 6 months and consisted of 3 consecutive visits taking place at 12-week intervals. We used VESIcare® at a dose of 5 mg a day. Every sixth patient was examined urodynamically at the beginning and at the end of the observation period, with an inflow speed of 50 ml/s. RESULTS We noticed improvement and decline in the average number of episodes a day in the following parameters: number of micturitions a day (-36%, P<0.01), nocturia (-50%, P<0.01), urgent episodes (-41%, P<0.03), and episodes of incontinence (-43%, P<0.01). The patients' quality of life improved. The average maximal cystometric volume increased by 34 ml (21%, p<0.01), average bladder volume of "first desire" increased by 42 ml (49%, P<0.01), and average detrusor muscle pressure at maximal cystometric volume diminished by 9 cmH2O (-36%, P<0.03). CONCLUSIONS The substance is well-tolerated. Solifenacin administered long-term to patients with symptoms of OAB after radiotherapy of a malignant neoplasm of the small pelvis organs has a daily impact in decreasing number of urgent episodes, incontinence, pollakiuria, and nocturia.

Histopathological assessment of residual retroperitoneal mass removed in patients after chemotherapy for non-seminomatous germ cell tumours of the testis.

Between 1990 and 1999, 182 men were treated for non-seminomatous germ cell testicular tumours. In 24 of them after chemotherapy a residual retroperitoneal mass was removed. In 14 of them additional immunohistochemical (IHC) examinations using antibodies against cytokeratins, vimentin, PLAP, CD30, AFP, ßhCG, p53, and MIB-1 were performed. We compared the results of those additional studies with the results of routine histopathological examination. Histological assessment revealed most frequently (ca. 54% of cases) non-neoplastic lesions, i.e. fibro-cystic, necrotic or inflammatory tumours and lymphatic tissue. In about 33% of cases, surviving live neoplastic cells were found.

Multifocal colorectal adenocarcinoma with a synchronous multifocal carcinoid of the small intestine--case report and literature review.

The paper presents a case report of coexisting multifocal colorectal cancer and multifocal carcinoid of the small intestine. Our literature review did not demonstrate any report of such case. We emphasize necessity of careful inspection of abdominal cavity during any surgical procedure since small lesions, in particular in the small intestine, may be omitted--as was the case during the initial colectomy in our case. Current epidemiological data are also presented and standards of management for diagnosis and treatment of gastrointestinal carcinoid.