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Transplantation of an organ from a donor carries an unavoidable risk of tumor transmission. The need to extend the donor pool increases the use of organs from donors with malignancies and potential disease transmission is a constant tension influencing donor suitability decisions. Current classification systems for the assessment of donor malignancy transmission risk have evolved from reports of potential transmission events in recipients to national donation and transplant surveillance agencies. Although the risk of malignancy transmission is very low in the general transplant setting it must constantly be balanced with the transplant benefits. Guidelines are mainly based on large registries and sparse case reports of transmission, so they cannot cover all the possible situations. For this reason, in 2004 in Italy, the National Transplant Center gave rise to the Second Opinion Service, charged by the Ministry of Health, by structuring expertise in diagnostic oncology and risk transmission and making it available to the Italian Transplant Centers. In this paper the registry of the Italian Oncological Second Opinion was reviewed, from 2016 to 2018, to detail the most frequent and problematic neoplastic topics addressed, those are separately reported and discussed. Furthermore, a review of the most recent strategies and risk stratification is provided, according to the most recent literature evidence and to the European Guidelines.

The number of patients awaiting a kidney transplant is constantly rising but lack of organs leads kidneys from extended criteria donors (ECD) to be used to increase the donor pool. Pre-transplant biopsies are routinely evaluated through the Karpinski-Remuzzi score but consensus on its correlation with graft survival is controversial. This study aims to test a new diagnostic model relying on digital pathology to evaluate pre-transplant biopsies and to correlate it with graft outcomes. Pre-transplant biopsies from 78 ECD utilized as single kidney transplantation were scanned, converted to whole-slide images (WSIs), and reassessed by two expert nephropathologists using the Remuzzi-Karpinski score. The correlation between graft survival at 36 months median follow-up and parameters assigned by either WSI or glass slide score (GSL) by on-call pathologists was evaluated, as well as the agreement between the GSL and the WSIs score. No relation was found between the GSL assessed by on-call pathologists and graft survival (P = 0.413). Conversely, the WSI score assigned by the two nephropathologists strongly correlated with graft loss probability, as confirmed by the ROC curves analysis (DeLong test P = 0.046). Digital pathology allows to share expertise in the transplant urgent setting, ensuring higher accuracy and favoring standardization of the process. Its employment may significantly increase the predictive capability of the pre-transplant biopsy evaluation for ECD, improving the quality of allocation and patient safety.

Aim To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment. Methods A systematic literature search was performed using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT. Results A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post-treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51-0.79; p < 0.001) as well as of post-treatment mortality (OR: 0.54; 95%CI = 0.35-0.83; p = 0.006). Conclusions Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment.

Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described.

Background: In the setting of kidney transplantation, histopathology of kidney biopsies is a key element in the organ assessment and allocation. Despite the broad diffusion of the Remuzzi-Karpinski score on preimplantation kidney biopsies, scientific evidence of its correlation to the transplantation outcome is controversial. The main issues affecting the prognostic value of histopathology are the referral to general on-call pathologists and the semiquantitative feature of the score, which can raise issues of interpretation. Digital pathology has shown very reliable and effective in the oncological diagnosis and treatment; however, the spread of such technologies is lagging behind in the field of transplantation. The aim of our study was to create a digital online platform where whole-slide images (WSI) of preimplantation kidney biopsies could be uploaded and stored. Methods: We included 210 kidney biopsies collected between January 2015 and December 2019 from the joint collaboration of the transplantation centers of Padua and Verona. The selected slides, stained with hematoxylin and eosin, were digitized and uploaded on a shared web platform. For each case, the on-call pathologists' Remuzzi grades were obtained from the original report, together with the clinical data and the posttransplantation follow-up. Results: The storage of WSI of preimplantation kidney biopsies would have several clinical, scientific, and educational advantages. The clinical utility relies on the possibility to consult online expert pathologists and real-time quality checks of diagnosis. From the perspective of follow-up, the archived digitized biopsies can offer a useful comparison to posttransplantation biopsies. In addition, the digital online platform is a precious tool for multidisciplinary meetings aimed both at the clinical discussion and at the design of research projects. Furthermore, this archive of readily available WSI is an important educational resource for the training of prof

Purpose: BRAF mutations are grouped in activating RASindependent signaling as monomers (class 1-V600E) or as dimers (class 2-codons 597/601), and RAS-dependent with impaired kinase activity (class 3-codons 594/596). Although clinical, pathologic, and molecular features of V600EBRAFmutated metastatic colorectal cancer (mCRC) are well known, limited data are available from the two other classes. Experimental Design: Data from 117 patients with BRAF (92 class 1, 12 class 2, and 13 class 3)-mutated mCRC were collected. A total of 540 BRAF wt mCRCs were included as control. IHC profiling was performed to determine the consensus molecular subtypes (CMS), cytokeratin 7/20 profiles, tumor-infiltrating lymphocyte infiltration, and BM1/BM2 categorization. Overall survival (OS) and progression-free survival were evaluated by Kaplan-Meier and log-rank test. Results: Class 3 BRAF-mutated mCRC was more frequently left sided (P = 0.0028), pN0 (P = 0.0159), and without peritoneal metastases (P = 0.0176) compared with class 1, whereas class 2 cases were similar to class 1. Hazard ratio for OS, as compared with BRAF wt, was 2.38 [95% confidence interval (CI), 1.61-3.54] for class 1, 1.90 (95% CI, 0.85-4.26) for class 2, and 0.93 (95% CI, 0.51-1.69) for class 3 (P < 0.0001). Class 2 and 3 tumors were all assigned to CMS2-3. A higher median CD3/CD8-positive lymphocyte infiltration was observed in BRAF-mutated class 2 (P = 0.033) compared with class 3 cases. Conclusions: For the first time, different clinical and pathologic features and outcome data were reported according to the three BRAF mutation classes in mCRC. Specific targeted treatment strategies should be identified in the near future for such patients.

IMPORTANCE The combination of a triple-drug chemotherapy regimen with an anti–epidermal growth factor receptor (EGFR) agent as a first-line treatment of metastatic colorectal cancer (mCRC) showed promising activity along with safety concerns in single-arm phase 2 trials. The role of maintenance following chemotherapy and anti-EGFR and the optimal regimen to be adopted are not established. OBJECTIVES To evaluate the activity and safety of cetuximab plus modified FOLFOXIRI (mFOLFOXIRI) and explore the role of maintenance with cetuximab or bevacizumab in RAS and BRAF wild-type mCRC. DESIGN, SETTING, AND PARTICIPANTS In a prospective, noncomparative, open-label, multicenter, randomized phase 2 trial, patients aged 18 to 75 years with unresectable, previously untreated RAS and BRAF wild-type (before amendment, KRAS wild-type) mCRC were recruited from 21 oncology units in Italy from October 19, 2011, to March 1, 2015 (followed up through May 31, 2017). In total, 323 patients were screened and 143 were randomized to 2 treatment arms to receive as a first-line induction a regimen of mFOLFOXIRI plus cetuximab followed by cetuximab (arm A) or bevacizumab (arm B) until disease progression. Primary analyses were conducted in a modified intention-to-treat population. INTERVENTIONS mFOLFOXIRI plus cetuximab repeated every 2 weeks for up to 8 cycles, followed by maintenance with cetuximab or bevacizumab until disease progression. MAIN OUTCOMES AND MEASURES The primary end point was the 10-month progression-free rate (PFR); secondary end points included progression-free and overall survival, response rate, rate of metastases resection, and adverse events. RESULTS Of 143 patients randomized, 116 (81.1%) (median [interquartile range (IQR)] age, 59.5 [53-67] years; 34 [29.3%] women) had RAS and BRAF wild-type mCRC. At a median (IQR) follow-up of 44.0 (30.5-52.1) months, 10-month PFRs were 50.8% (90% CI, 39.5%-62.2%) in arm A and 40.4% (90% CI, 29.4%-52.1%) in arm B. The overall respon