Purpose The purpose of this study was to establish the influence of time interval between preoperative hyperfractionated radiotherapy (5 × 5 Gy) and surgery on long-term overall survival (5 years) and recurrence rate in patients with locally advanced rectal cancer operated on according to total mesorectal excision technique. Methods The treatment group comprised 154 patients with locally advanced rectal cancer who were operated on between 1999 and 2006 in the 1st Department of General Surgery, Jagiellonian University, Cracow, Poland. The data on survival has been systematically collected until 31st of December 2010. In addition, the following aspects were analyzed: the significance of time interval between the end of radiotherapy and surgical treatment and its influence on downsizing, downstaging, rate of curative resections, and sphincter-sparing procedures. Patients were qualified to preoperative radiotherapy 5 × 5 Gy and then randomly assigned to subgroups with different time intervals between radiotherapy and surgery: one subgroup consisted of 77 patients operated on 7–10 days after the end of irradiation, and the second subgroup consisted of 77 patients operated on after 4–5 weeks. Both groups were homogenous in sex, age, cancer stage and localization, distal and circumferential resection margins, and number of resected lymph nodes. Results The 5-year survival rate in patients operated on 7–10 days after irradiation was 63%, whereas in those operated on after 4–5 weeks, it was 73%—the difference was not statistically significant (log rank, p = 0.24). A statistically significant increase in 5-year survival rate was observed only in patients with downstaging after radiotherapy—90% in comparison with 60% in patients without response to neoadjuvant treatment (log rank, p = 0.004). Recurrence was diagnosed in 13.2% of patients. A lower rate of systemic recurrence was observed in patients operated on 4–5 weeks after the end of irradiation (2.8% vs. 12.3% in the subgroup with a shorter interval, p = 0.035). No differences in local recurrence rates were observed in both subgroups of irradiated patients (p = 0.119). The longer time interval between radiotherapy and surgery resulted in higher downstaging rate (44.2% vs. 13% in patients with a shorter interval, p = 0.0001) although it did not increase the rate of sphincter-saving procedures (p = 0.627) and curative resections (p = 0.132). Conclusions 1. Improved 5-year survival rate is observed only in patients with downstaging after preoperative irradiation dose of 25 Gy. 2. Longer time interval after preoperative radiotherapy 25 Gy does not improve the rate of sphincter-saving procedures and curative resections (R0) despite higher downstaging rate observed in this regimen.

This paper reviews the distribution of interstitial cells of Cajal (ICC) in the human gastro-intestinal (GI) tract, based on ultrastructural and immunohistochemical evidence. The distribution and morphology of ICC at each level of the normal GI tracts is addressed from the perspective of their functional significance. Alterations of ICC reported in as well as in GI stromal tumours are reviewed, with emphasis on the place of ICC in the pathophysiology of disease.

Upper non-variceal gastrointestinal bleeding is a condition that requires immediate medical intervention and has a high associated mortality rate (exceeding 10%). The vast majority of upper gastrointestinal bleeding cases are due to peptic ulcers. Helicobacter pylori infection, non-steroidal anti-inflammatory drugs and aspirin are the main risk factors for peptic ulcer disease. Endoscopic therapy has generally been recommended as the first-line treatment for upper gastrointestinal bleeding as it has been shown to reduce recurrent bleeding, the need for surgery and mortality. Early endoscopy (within 24 h of hospital admission) has a greater impact than delayed endoscopy on the length of hospital stay and requirement for blood transfusion. This paper aims to review and compare the efficacy of the types of endoscopic hemostasis most commonly used to control non-variceal gastrointestinal bleeding by pooling data from the literature.

It has been reported that intake of ω-3 polyunsaturated fatty acids (PUFAs) reduces the risk of coronary heart disease. It also influences bile composition, decreasing biliary cholesterol saturation in the bile of patients with gallstones. In addition to bile composition disturbances, gallbladder hypomotility must be a cofactor in the pathogenesis of cholelithiasis, as it leads to the prolonged nucleation phase. Our current knowledge about gallbladder motility has been enhanced by the study of a population of newly described interstitial (stromal) cells—telocytes (TCs). The purpose of this study was to determine whether TC loss, reported by our team recently, might be related to bile lithogenicity, expressed as cholesterol saturation index or the difference in biliary PUFA profiles in patients who suffer from cholecystolithiasis and those not affected by this disease. We determined biliary lipid composition including the fatty acid composition of the phospholipid species in bile. Thus, we investigated whether differences in biliary fatty acid profiles (ω-3 PUFA and ω-6 PUFA) in gallbladder bile may influence its lithogenicity and the quantity of TCs within the gallbladder wall. We conclude that the altered PUFA concentrations in the gallbladder bile, with elevation of ω-6 PUFA, constitute important factors influencing TC density in the gallbladder wall, being one of the possible pathophysiological components for the gallstone disease development. This study established that altered bile composition in patients with cholelithiasis may influence TC quantity within the gallbladder muscle, and we concluded that reduction in TC number may be a consequence of the supersaturated bile toxicity, while some other bile components (ω-3 PUFA, glycocholic, and taurocholic acids) may exert protective effects on TC and thus possibly influence the mechanisms regulating gallbladder and extrahepatic bile duct motility. Thus, ω-3 PUFA may represent a possible option to prevent formation of cholesterol gallstones.

Introduction: Gastric cancer is one of the most common cancer-related causes of death. This is mainly due to the lack of good noninvasive method/biomarkers suitable for early-tumour diagnosis and planning of further therapy modalities. Chemokines play an important role in cancer progression and metastasis formation. In gastric cancer patients, clinical relevance of CXCL12 and CCL5 level has been postulated. Aim of the study: Efforts were undertaken to examine whether expanded chemokine range may be relevant for evaluation of preoperative staging of gastric cancer patients. Material and methods: Plasma from 66 gastric cancer patients and 11 healthy controls was obtained, and CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL9, and CXCL10 levels were determined by flow cytometry FlexSet system. Results: In gastric cancer patients’ plasma an increased level of CCL2, CCL4, CCL5, CXCL8, CXCL9, and CXCL10 was observed. In the case of CCL2, CXCL9, and CXCL10, the chemokine levels correlated with advanced (III and IV in TNM classification) disease stage. In the case of CCL4, CCL5, and CXCL8, elevated levels were observed in all cancer patients in comparison to healthy donors. Conclusions: The accuracy of preoperative diagnosis in gastric cancer may include the monitoring of a wide range of chemokines in patients’ plasma. Increased levels of chemokines may warn that the disease is more advanced than conventional diagnostic procedures suggest.

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