Andrea Gianatti

Background: Liver transplantation (LT) for Hepatocellular carcinoma (HCC) is still burdened by a significant risk of tumor recurrence. The aim of this study was to apply the Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score for prediction of HCC recurrence and survival. Methods: This retrospective study included all adult patients who consecutively underwent LT for HCC from January 2000 to July 2022 at a single institution. Results: During a median follow-up of 64 months, 56 (19%) out of 298 patients [54%, 36% and 10% with a RETREAT score equal to 0/1 (low), 2/3 (medium) and 4–6 (high), respectively] experienced HCC recurrence after a median of 31 months. The HCC recurrence rates at 1, 5 and 10 years were respectively 4%, 16% and 23%. The 5-year RFS for low-, medium- and high-risk groups were 93%, 78% and 58% (p < 0.001), respectively. In the competitive risk analysis, the medium- and high-risk RETREAT groups had respectively a 2.3 HR (p = 0.017) and 6.4 HR (p < 0.001) of HCC recurrence compared with the low-risk group. Overall, 119 patients died [32 (27%) due to HCC recurrence], and the 5-year survival was 74% (95%, 86% and 61% for low-, medium- and high-risk groups, respectively). In the multivariate analysis, the RETREAT score was associated with the overall survival only for the highest risk class, which yielded a 2.5 HR of death compared with the lowest risk categories (p < 0.001). Conclusions: This study validates the RETREAT score and confirms its ability to predict the risk of HCC recurrence.

Background/Objectives: Melanoma is an aggressive cutaneous malignancy with a rising incidence. While most cases are sporadic, 5–10% are hereditary, especially in patients with multiple or familial melanomas. The aim of this study is to explore the epidemiological, clinical, histological, and genetic features of this class of patients to identify risk factors for better management and surveillance. Methods: Between 2021 and 2024, patients with multiple melanomas or a familial history of melanoma were recruited. Collected data included demographic, clinic-pathologic features, and genetic analyses. Results: Patients >60 years had a higher prevalence of multiple melanomas (>50%, p = 0.0002), while familial melanoma was more common in those p = 0.0004). Younger patients showed the highest nevi counts (mean: 139.6) and density (p < 0.0001). Dermatologists more frequently detected subsequent melanomas in older patients (>60 years) (p = 0.001). Genetic testing and melanoma subtypes showed no significant age-related differences. Conclusions: melanoma can develop at any age, and early detection through regular screening is crucial. Older patients (>60 years) have a higher prevalence of multiple melanomas, influenced by UV exposure and genetics. Indeed, in our cohort, a history of sun exposure, sunburns, and tanning bed use emerged as key risk factors, particularly among older individuals. Genetic testing showed a 4.3% rate of pathogenic/likely pathogenic variants, mainly in CDKN2A. Family history and nevus burden are significant risk factors, highlighting the need for targeted surveillance in high-risk populations.

It has been shown that vertical transmission of the SARS-CoV-2 strain is relatively rare, and there is still limited information on the specific impact of maternal SARS-CoV-2 infection on vertical transmission. The current study focuses on a transcriptomics analysis aimed at examining differences in gene expression between placentas from mother–newborn pairs affected by COVID-19 and those from unaffected controls. Additionally, it investigates the in situ expression of molecules involved in placental inflammation. The Papa Giovanni XXIII Hospital in Bergamo, Italy, has recorded three instances of intrauterine transmission of SARS-CoV-2. The first two cases occurred early in the pandemic and involved pregnant women in their third trimester who were diagnosed with SARS-CoV-2. The third case involved an asymptomatic woman in her second trimester with a twin pregnancy, who unfortunately delivered two stillborn fetuses due to the premature rupture of membranes. Transcriptomic analysis revealed significant differences in gene expression between the placentae of COVID-19-affected mother/newborn pairs and two matched controls. The infected and control placentae were matched for gestational age. According to the Benjamani–Hochberg method, 305 genes met the criterion of an adjusted p-value of less than 0.05, and 219 genes met the criterion of less than 0.01. Up-regulated genes involved in cell signaling (e.g., CCL20, C3, MARCO) and immune response (e.g., LILRA3, CXCL10, CD48, CD86, IL1RN, IL-18R1) suggest their potential role in the inflammatory response to SARS-CoV-2. RNAscope^® technology, coupled with image analysis, was utilized to quantify the surface area covered by SARS-CoV-2, ACE2, IL-1β, IL-6, IL-8, IL-10, and TNF-α on both the maternal and fetal sides of the placenta. A non-statistically significant gradient for SARS-CoV-2 was observed, with a higher surface coverage on the fetal side (2.42 ± 3.71%) compared to the maternal side (0.74 ± 1.19%) of the placenta. Although not statistically significant, the surface area covered by ACE2 mRNA was higher on the maternal side (0.02 ± 0.04%) compared to the fetal side (0.01 ± 0.01%) of the placenta. IL-6 and IL-8 were more prevalent on the fetal side (0.03 ± 0.04% and 0.06 ± 0.08%, respectively) compared to the maternal side (0.02 ± 0.01% and 0.02 ± 0.02%, respectively). The mean surface areas of IL-1β and IL-10 were found to be equal on both the fetal (0.04 ± 0.04% and 0.01 ± 0.01%, respectively) and maternal sides of the placenta (0.04 ± 0.05% and 0.01 ± 0.01%, respectively). The mean surface area of TNF-α was found to be equal on both the fetal and maternal sides of the placenta (0.02 ± 0.02% and 0.02 ± 0.02%, respectively). On the maternal side, ACE-2 and all examined interleukins, but not TNF-α, exhibited an inverse mRNA amount compared to SARS-CoV-2. On the fetal side, ACE-2, IL-6 and IL-8 were inversely correlated with SARS-CoV-2 (r = −0.3, r = −0.1 and r = −0.4, respectively), while IL-1β and IL-10 showed positive correlations (r = 0.9, p = 0.005 and r = 0.5, respectively). TNF-α exhibited a positive correlation with SARS-CoV-2 on both maternal (r = 0.4) and fetal sides (r = 0.9) of the placenta. Further research is needed to evaluate the correlation between cell signaling and immune response genes in the placenta and the vertical transmission of SARS-CoV-2. Nonetheless, the current study extends our comprehension of the molecular and immunological factors involved in SARS-CoV-2 placental infection underlying maternal–fetal transmission.

Introduction Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. Methods Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. Results Overall, a median DNA concentration of 3.3 ng/µL (range 0.1–10.0 ng/µL) and 13.4 ng/µL (range 2.0–45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2–11.9 ng/µL) and 9.3 ng/µL (range 0.5–18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. Conclusions Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

Background: Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. Methods: A systematic search was carried out in electronic databases Pubmed-MEDLINE and Embase to retrieve studies on the comparison of PD-L1 expression before and after conventional therapy. Data were extracted and a quantitative analysis with pooled odds ratios (ORs) was performed when applicable. Results: Of 5688 items, 15 were finally included. Only a minority of studies assessed PD-L1 with the recommended combined positive score (CPS). The results are highly heterogeneous, with some studies reporting an increase in PD-L1 expression and others reporting a decrease. Three studies allowed for quantitative analysis and showed a pooled OR of 0.49 (CI 0.27–0.90). Conclusions: From the present evidence, a clear conclusion towards an increase or decrease in PD-L1 expression after combined therapy cannot be drawn, but even with few studies available, a trend towards an increase in expression in tumor cells at a cutoff of 1% can be noted in patients undergoing platinum-based therapy. Future studies will provide more robust data on the effect of combined therapy on PD-L1 expression.

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Objectives: to investigate the accuracy of transurethral resection of bladder tumours (TURBT) in detecting histological variants (BHV) at radical cystectomy (RC) and to evaluate the impact of TURBT before cystectomy on oncological outcomes. Methods: Data of 410 consecutive RCs were assessed. Positive and negative predictive values were used to assess the accuracy of TURBT in detecting BHV. Cohen’s Kappa coefficient was used to calculate the agreement grade. Logistic regression analysis predicted features based on the presence of BHV at TURBT. Multivariable backward conditional Cox regression analysis was used to estimate oncological outcomes. Results: A total of 73 patients (17.8%) showed BHV at TURBT as compared to 108 (26.3%) at RC. A moderate agreement in histological diagnosis was found between TURBT and RC (0.58). However, sensitivity and specificity in detecting BHV were 56% and 96%, respectively. Furthermore, positive predictive value (PPV) was 84.7% and negative predictive value (NPV) was 84.6%. Presence of BHV at TURBT was an independent predictor for pathologic upstage, albeit not a predictor for positive nodes or positive surgical margins. However, at multivariable analysis adjusted for all confounders, presence of BHV at TURBT was an independent predictor for recurrence after RC, but not for survival. Conversely, the presence of BHV at RC was an independent predictor for both recurrence and survival. Conclusion: There was a moderate agreement between TURBT and RC histopathological findings. TURBT, alone, could not provide an accurate and definitive histological diagnosis. Detection of BHV in TURBT specimens is not an independent predictor of oncological outcomes; indeed, only pathological features at RC are associated with worse survival. However, BHV presence in cystectomy specimens resulted as an independent predictor of both cancer-specific and overall mortality.

Background and Aim: Hepatocellular carcinoma (HCC) recurrence rates after liver transplantation (LT) range between 8 and 20%. Alpha-fetoprotein (AFP) levels at transplant can predict HCC recurrence, however a defined cut-off value is needed to better stratify patients. The aim of this study was to evaluate the rate of HCC recurrence at our centre and to identify predictors, focusing on AFP. Methods: We retrospectively analysed 236 consecutive patients that were waitlisted for HCC who all met the Milan criteria from January 2001 to December 2017 at our liver transplant centre. A total of twenty-nine patients dropped out while they were waitlisted, and 207 patients were included in the final analysis. All survival analyses included the competing-risk model. Results: The mean age was 56.8 ± 6.8 years. A total of 14% were female (n = 29/207). The median MELD (model for end-stage liver disease) at LT was 12 (9–16). The median time on the waitlist was 92 (41–170) days. The HCC recurrence rate was 16.4% (n = 34/208). The mean time to recurrence was 3.3 ± 2.8 years. The median AFP levels at transplant were higher in patients with HCC recurrence (p < 0.001). At multivariate analysis, the AFP value at transplant that was greater than 25.5 ng/mL (AUC 0.69) was a strong predictor of HCC recurrence after LT [sHR 3.3 (1.6–6.81); p = 0.001]. The HCC cumulative incidence function (CIF) of recurrence at 10 years from LT was significantly higher in patients with AFP > 25.5 ng/mL [34.3% vs. 11.5% (p = 0.001)]. Moreover, an increase in AFP > 20.8%, was significantly associated with HCC recurrence (p = 0.034). Conclusions: In conclusion, in our retrospective study, the AFP level at transplant > 25.5 ng/mL and its increase greater than 20.8% on the waitlist were strong predictors of HCC recurrence after LT in a cohort of patients that were waitlisted within the Milan criteria. However further studies are needed to validate these data.