A coordinate deregulation of microRNAs expressed in mucosa adjacent to tumor predicts relapse after resection in localized colon cancer

Up to 20% of colorectal cancer (CRC) node-negative patients develop loco-regional or distant recurrences within 5 years from surgery. No predictive biomarker able to identify the node-negative subjects at high risk of relapse after curative treatment is presently available.Forty-eight localized (i.e. stage I-II) colon cancer patients who underwent radical tumor resection were considered. The expression of five miRNAs, involved in CRC progression, was investigated by qRT-PCR in both tumor tissue and matched normal colon mucosa.Interestingly, we found that the coordinate deregulation of four miRNAs (i.e. miR-18a, miR-21, miR-182 and miR-183), evaluated in the normal mucosa adjacent to tumor, is predictive of relapse within 55 months from curative surgery.Our results, if confirmed in independent studies, may help to identify high-risk patients who could benefit most from adjuvant therapy. Moreover, this work highlights the importance of extending the search for tissue biomarkers also to the tumor-adjacent mucosa

A new multianodic large area photomultiplier to be used in underwater neutrino detectors

In this article we describe the properties of a new 10-in. hemispherical photomultiplier manufactured by Hamamatsu. The prototype has a segmented photocathode and four independent amplification stages. The photomultiplier is one of the main components of a newly designed direction-sensitive optical module to be employed in large-scale underwater neutrino telescopes. The R&D activity has been co-funded by the INFN and the KM3NeT Consortium. The prototype performance fully meets with the design specifications

Delphi initiative for early-onset colorectal cancer (DIRECt). International Management Guidelines.

BACKGROUND AND AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), comprised of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was employed to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. Based on current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors.The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC

High Risk of Rectal Cancer and of Metachronous Colorectal Cancer in Probands of Families Fulfilling the Amsterdam Criteria.

Abstract OBJECTIVE: To investigate the risk of metachronous colorectal cancer (CRC), its impact on survival, and the risk of rectal cancer in a cohort of probands meeting the Amsterdam criteria. BACKGROUND: Several determinants of decision-making for the management of CRC in patients with a putative diagnosis of Lynch syndrome are scarcely defined, and many of them undergo segmental bowel resection instead of the advised total colectomy. METHODS: A retrospective cohort study was conducted on 65 probands of the Amsterdam-positive families who had surgery for primary CRC and at least 5-year surveillance thereafter. The rates of metachronous CRC and of rectal cancer were evaluated, together with their association with preoperatively available clinical predictors. Differences in overall survival between patients with and without metachronous CRC were evaluated using a time-dependent Cox model. RESULTS: Seventeen patients (26.2%) had metachronous CRC. No clinical feature was associated with an increased risk of its development. The risk of death in patients with metachronous CRC was 6-fold increased. Neither a 2-year interval endoscopic surveillance after surgery, nor total colectomy was associated with a significant reduction in metachronous CRC. Eighteen patients (23.7%) had rectal cancer at first presentation, 5 patients of the remainder (10.6%) developed rectal cancer after primary colon resection. Two patients undergoing total colectomy developed a metachronous rectal cancer (18.2%). A first-degree family history of rectal cancer was associated with an increased risk of rectal cancer. CONCLUSIONS: Probands of families fulfilling the Amsterdam criteria carry a high risk of rectal cancer and of metachronous CRC. Total proctocolectomy, or total colectomy and a 1-year interval of proctoscopic surveillance should be advised when a high risk of rectal cancer can be predicted

18F-FDG PET/MRI for Rectal Cancer TNM Restaging After Preoperative Chemoradiotherapy: Initial Experience

OBJECTIVE: F-18-FDG-PET/MRI is a novel hybrid techinque that has been recently introduced in oncological imaging, showing promising results. The aim of this study is to assess the value of whole-body F-18-FDG-PET/MRI for predicting the pathological stage of locally advanced rectal cancer after preoperative chemoradiotherapy. DESIGN: This was a prospective observational study. SETTINGS: The study was conducted at a tertiary care hospital. PATIENTS: Thirty-six patients with locally advanced rectal cancer (25 male, median age 68.5 years) were prospectively assessed with PET/MRI and thoracoabdominal CT before and after preoperative chemoradiotherapy. Twenty-seven patients underwent low anterior or abdominoperineal resection. Nine patients with a complete clinical response underwent organ-preserving treatment (8 local excision and 1 watch-and-wait approach) with > 1-year follow-up. MAIN OUTCOME MEASURES: One radiologist evaluated pelvic MRI and CT. A second radiologist and a nuclear medicine physician jointly assessed PET/MRI. The imaging was compared with histology or follow-up (ypT0 vs T >= 1 and ypN0 vs ypN+ categories). Metastases were confirmed with biopsy or a follow-up CT scan at least at 1 year after preoperative chemoradiotherapy. The sensitivity, specificity, and accuracy values of the imaging techniques were calculated using standard formulas. RESULTS: The accuracy for ypT staging was 89% and 92%, and the accuracy for ypN was 86% and 92% for MRI and PET/MRI. Compared with CT, PET/MRI correctly diagnosed 4 of 5 metastases, but it did not detect a lung metastatic nodule. In 11% of the patients, the PET/MRI changed the treatment strategy. LIMITATIONS: This study is limited by its small sample size. CONCLUSIONS: Although the whole-body PET/MRI was more accurate than the pelvic MRI alone for the prediction of tumor and node response to preoperative chemoradiotherapy, the technique performed worse than CT in detecting small lung metastasis

Programmed cell death-ligand 1 (PD-L1) overexpression in ampulla of Vater carcinoma and its pre-invasive lesions

PD-1/PD-L1 checkpoint immunotherapy has recently been proposed as a promising treatment in relapsed/refractory disease, eventually used in combination with the traditional chemotherapy in different cancer settings. No data are still now available about PD-L1 expression in ampulla of Vater carcinoma and its preinvasive lesions