IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer.

BACKGROUND: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. METHODS: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry. RESULTS: In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor-infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively). CONCLUSIONS: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.

IMMUNOREACT 6: weak immune surveillance characterizes early-onset rectal cancer.

BACKGROUND: Colon cancer in young patients is often associated with hereditary syndromes; however, in early-onset rectal cancer, mutations of these genes are rarely observed. The aim of this study was to analyse the features of the local immune microenvironment and the mutational pattern in early-onset rectal cancer. METHODS: Commonly mutated genes were analysed within a rectal cancer series from the University Hospital of Padova. Mutation frequency and immune gene expression in a cohort from The Cancer Genome Atlas ('TCGA') were compared and immune-cell infiltration levels in the healthy rectal mucosa adjacent to rectal cancers were evaluated in the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 ('IMMUNOREACT') series. RESULTS: In the authors' series, the mutation frequency of BRAF, KRAS, and NRAS, as well as microsatellite instability frequency, were not different between early- and late-onset rectal cancer. In The Cancer Genome Atlas series, among the genes with the most considerable difference in mutation frequency between young and older patients, seven genes are involved in the immune response and CD69, CD3, and CD8ß expression was lower in early-onset rectal cancer. In the IMMUNOlogical microenvironment in REctal AdenoCarcinoma Treatment 1 and 2 series, young patients had a lower rate of CD4+ T cells, but higher T regulator infiltration in the rectal mucosa. CONCLUSION: Early-onset rectal cancer is rarely associated with common hereditary syndromes. The tumour microenvironment is characterized by a high frequency of mutations impairing the local immune surveillance mechanisms and low expression of immune editing-related genes. A constitutively low number of CD4 T cells associated with a high number of T regulators indicates an imbalance in the immune surveillance mechanisms.

A modified Nissen fundoplication: subjective and objective midterm results.

PURPOSE: The failure rate of laparoscopic anti-reflux surgery is approximately 10-20%. The aim of our prospective study was to investigate whether a modified Nissen fundoplication (MNF) can improve reflux symptoms and prevent surgical treatment failure in the midterm. METHODS: The MNF consisted of (1) suturing the esophagus to the diaphragmatic crura on each side using four non-absorbable stitches, (2) reinforcing clearly weak crura with a tailored Ultrapro mesh, and (3) fixing the upper stitch of the valve to the diaphragm. Forty-eight consecutive patients experiencing typical gastroesophageal reflux disease (GERD) symptoms at least three times per week for 6 months or longer were assessed before and after surgery using validated symptom and quality of life (GERD-HRQL) questionnaires, high-resolution manometry, 24-h impedance-pH monitoring, endoscopy, and barium swallow. RESULTS: Mortality and perioperative complications were nil. At median follow-up of 46.7 months, the patients experienced significant improvements in symptom and GERD-HRQL scores. One patient presented with severe dyspepsia and another complained of dysphagia requiring a repeat surgery 12 months after the first operation. Esophageal acid exposure (8.8 vs 0.1; p < 0.0001), reflux number (62 vs 8.5; p < 0.0001), and symptom-reflux association (19 vs 0; p < 0.0001) significantly decreased postoperatively. The median esophagogastric junction contractile integral (EGJ-CI) from 31 cases (8.2 vs 21.2 mmHg cm; p = 0.0003) and the abdominal length of the lower esophageal sphincter (LES) (0 vs 16 mm; p = 0.01) increased postoperatively. CONCLUSIONS: Our data demonstrate that the MNF is a safe and effective procedure both in the short term and midterm.

Outcome and quality of life of patients with augmented bladder or urinary diversion after kidney transplantation.

OBJECTIVE: The aim of the study was to assess results and quality of life after kidney transplant in adult patients with previously bladder augmentation or urinary diversion due to significant lower urinary tract dysfunction. MATERIALS AND METHODS: This cross-sectional study examines the outcome of 19 renal allografts transplanted in patients with augmented bladder or urinary diversion over a ten years period; moreover we submitted SF36 questionnaire to evaluate quality of life of these patients and compared the results with the general population. RESULT: Between January 1, 2005 and 31 December 2015 we performed 19/1093 renal transplantations in patients with abnormal lower urinary tract previously treated with bladder augmentation or bladder recycling. Current post-transplant follow-up was 47 months (range 18-188). No patient developed any episode of acute or chronic rejection. Mean serum creatinine after one year from transplant was 102 umol/L. Overall survival is 94.8% at the end of follow-up and graft survival is 89.6%. No significant differences emerged between patients undergoing transplant with lower urinary tract dysfunction and patients without, regarding to recurrent urinary tract infection. There was not statistically significant difference for vitality (p = 0.8088) and mental health (p = 0.8668). CONCLUSIONS: Presence of a previously augmented bladder or other lower urinary tract dysfunction treated in kidney transplant patients doesn't worsen the final outcome. Mental health and the vitality of these patients are similar to the general population.

Minimally invasive surgery for colorectal cancer: quality of life, body image, cosmesis, and functional results.

BACKGROUND: The aims of this cross-sectional study were to assess the long-term quality of life, the body image, and the cosmetic and functional results in patients who had laparoscopic-assisted for colorectal cancer. METHODS: Forty-two patients were enrolled in this study: 21 consecutive patients who had undergone laparoscopic-assisted colonic resection and 21 patients who had open colonic resection, selected according to stage, gender, age, cancer site, and type of resection. The patients answered four questionnaires about their quality of life, body image, functional, and cosmetic results. Nonparametric tests were used for statistical analysis. RESULTS: Postoperative hospital stay was shorter in patients who had laparoscopic-assisted resection. The cosmetic score was significantly better in the laparoscopic-assisted group than in the open group (p < 0.01). In spite of similar overall body image score, patients who had a laparoscopic-assisted resection reported a significantly better satisfaction with their own body (p = 0.05). Quality-of-life and functional results were similar in both groups. CONCLUSIONS: The cosmetic results and the consequent satisfaction with the body were significantly better after laparoscopic assisted resection compared to equivalent open procedure. These effects seemed to be temporary but they could help patients to accept the burden of surgery.

Combined RET and Ki-67 assessment in sporadic medullary thyroid carcinoma: a useful tool for patient risk stratification.

OBJECTIVE: Medullary thyroid carcinoma (MTC) derives from the parafollicular C cells, being sporadic in 75% of cases and familial in 25%, due to RET proto-oncogene germinal mutations. In sporadic forms, stage at diagnosis is the most important negative prognostic factor. The aim of this study was to evaluate the prognostic impact of molecular and immunohistochemical markers in sporadic MTC. DESIGN AND METHODS: We studied 60 patients with sporadic MTC. For each case, we sought RET somatic mutations in the primary cancer and in lymph node metastases. The primary cancer also underwent immunohistochemical examination for Ki-67. RESULTS: A somatic RET mutation was found in 38% of patients, being M918T in 52% of them. We observed a statistically significant association between RET mutations and male gender (P<0.01), tumor size (P<0.05), lymph nodes (P<0.05) and distant metastases (P<0.001), advanced stage (P<0.05), increased risk of persistent disease (P=0.01), and low overall survival (P<0.01). High Ki-67 levels were similarly associated with extra-thyroid spread (P<0.05), lymph nodes (P<0.05) and distant metastases (P<0.001), advanced stage (P=0.01), and low overall survival (P=0.01). Combining somatic RET analysis with Ki-67 assessment seems to be useful for increasing the specificity of Ki-67 assessment alone and identifying patients with a more aggressive cancer: in our series, only the patients who died during the follow-up had both a somatic RET mutation and a Ki-67 expression level >50 cells/mm(2). CONCLUSIONS: The combined evaluation of RET and Ki-67 could act as an adjuvant prognostic marker useful for ameliorating the initial risk stratification of patients with sporadic MTC.