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Simple Summary: Uveal melanoma often metastasizes to the liver. Immune checkpoint inhibitors showed low efficacy in this disease. Liver directed therapies are widely employed despite limited results. The addition of hepatic radiotherapy to anti-PD-1 could enhance the efficacy of immune checkpoint inhibitor alone. In this study, efficacy and safety of radiotherapy on liver metastases combined with pembrolizumab have been retrospectively analyzed in previously untreated metastatic patients. This combination allowed encouraging results without increasing toxicity of anti-PD-1. Therefore, hepatic radiotherapy and anti-PD-1 can be considered a valid choice for untreated HLA A 02:01 negative patients as well as for second line systemic therapy after tebentafusp. Prospective trials should be conducted to confirm these observations. Uveal melanoma is the most common ocular tumor with frequent metastatic spread to the liver. Immune checkpoint inhibitors have demonstrated poor results in this disease. The addition of hepatic radiotherapy to anti-PD-1 could enhance the sensitivity to immunotherapy. In this study, patients treated with pembrolizumab and who have undergone hepatic radiotherapy have been retrospectively evaluated. Twenty-two patients have been considered. Six patients (27.3%) achieved a partial response and 3 (13.6%) a stable disease. Disease control rate was 40.9%. Thirteen patients (59.1%) had progression as best response. The median PFS was 4.8 months and 6 months PFS rate 45.4%. The median OS was 21.2 months, while 1 year OS rate was 72.7%. Longer survival was observed in patients who achieved a partial response on irradiated metastases (HR 0.23, 95% CI 0.06–0.83) or progressed after 6 months (HR 0.12—95% CI 0.03–0.44). No radiotherapy-related or grade 3–4 adverse events were reported. This study demonstrates that the addition of hepatic radiotherapy to anti-PD-1 treatment can be a valid option for the treatment of metastatic uveal melanoma, particularly for HLA A 02:01 negative patients. Prospective studies should be conducted to confirm these data. [ABSTRACT FROM AUTHOR]

Despite the increasing trend in liver resections for non-colorectal non-neuroendocrine liver metastases (NCNNLM), the role of surgery for these liver malignancies is still debated. Registries are an essential, reliable tool for assessing epidemiology, diagnosis, and therapeutic approach in a single hub, especially when data are dispersive and inconclusive, as in our case. The dissemination of this preliminary survey would allow us to understand if the creation of an International Registry is a viable option, while still offering a snapshot on this issue, investigating clinical practices worldwide. The steering committee designed an online questionnaire with Google Forms, which consisted of 37 questions, and was open from October 5th, 2022, to November 30th, 2022. It was disseminated using social media and mailing lists of the Italian Society of Endoscopic Surgery and New Technologies (SICE), the Association of Italian Surgeons in Europe (ACIE), and the Spanish Chapter of the American College of Surgeons (ACS). Overall, 141 surgeons (approximately 18% of the total invitations sent) from 27 countries on four continents participated in the survey. Most respondents worked in general surgery units (62%), performing less than 50 liver resections/year (57%). A multidisciplinary discussion was currently performed to validate surgical indications for NCNNLM in 96% of respondents. The most commonly adopted selection criteria were liver resectability, RECIST criteria, and absence of extrahepatic disease. Primary tumors were generally of gastrointestinal (42%), breast (31%), and pancreaticobiliary origin (13%). The most common interventions were parenchymal-sparing resections (51% of respondents) of metachronous metastases with an open approach. Major post-operative complications (Clavien-Dindo > 2) occurred in up to 20% of the procedures, according to 44% of respondents. A subset analysis of data from high-volume centers (> 100 cases/year) showed lower post-operative complications and better survival. The present survey shows that NCNNLM patients are frequently treated by surgeons in low-volume hospitals for liver surgery. Selection criteria are usually based on common sense. Liver resections are performed mainly with an open approach, possibly carrying a high burden of major post-operative complications. International guidelines and a specific consensus on this field are desirable, as well as strategies for collaboration between high-volume and low-volume centers. The present study can guide the elaboration of a multi-institutional document on the optimal pathway in the management of patients with NCNNLM., (© 2023. Italian Society of Surgery (SIC).)

Background: The main aim of this prospective study was to evaluate the efficacy of drug-eluting beads with irinotecan (DEBIRI) for liver metastases from colorectal cancer. Secondary aims were to evaluate survival and toxicity. Methods: Twenty-five patients with metastases in, 50% of the liver and without extrahepatic involvement were enrolled. Treatment response assessment was performed by multidetector contrast enhancement computed tomography (MDCT) with evaluation of the enhancement pattern of the target lesion and tumor response rates according to modified Response Evaluation Criteria in Solid Tumors (mRECIST, Version 1.1). All adverse events were recorded by the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events, Version 3.0. Associations of tumor response and variables were calculated using the chi-squared test. Overall survival (OS) was calculated using the Kaplan-Meier method. Comparisons were made using the log-rank test. Results: According to mRECIST, complete response (CR) was observed in 21.8% of patients, partial response (PR) in 13%, stable disease (SD) in 52.2% and progressive disease (PD) in 13% of patients. Response rate (RR = CR + PR) was 34.8%. No associations between treatment response and variables such as Dukes' classification, grading and Kras status were found (P.0.05). The median OS was 37 months (95% CI: 13.881 to 60.119). Cox regression model showed that neither site, Dukes' classification, grading, Kras status nor number of chemotherapy treatments pre-DEBIRI influenced the OS. The log-rank test showed no statistically significant difference in OS among patients who underwent 1, 2 or 3 DEBIRI treatments (χ²=2.831, P=0.09). In our study, the main toxicities included postembolization syndrome (PES), hypertransaminasemia and fever. Conclusion: The favorable tumor response and the favorable toxicity profile make DEBIRI treatment a potential third-line therapy. Although further larger studies are needed to confirm these data, we can state that DEBIRI is an attractive emerging treatment in these patients. [ABSTRACT FROM AUTHOR]

The MicroWave Ablation (MWA) is a mini-invasive technique, based on dielectric heating, used to treat small hepatic tumors or liver metastases in the adult population. The heat-energy is delivered to the target area, causing tumor necrosis, usually under ultrasound or computed tomography guidance. This procedure can be performed as pure percutaneous or with laparoscopic assistance. A laparoscopic US-guided microwave ablation of the pancreatoblastoma hepatic metastasis was performed in an 11-year old girl. A standard three-port laparoscopic technique was used: the camera port at the umbilicus, and two working port at the upper right quadrant. After adhesiolysis, the intra-operative liver ultrasonography confirmed the pre-operative morphological imaging study and the nodules ablation was performed by using microwaves (MWA), emitted by AMICA probe (Apparatus for MICrowave Ablation; HS Hospital Service, Aprilia, LT, Italy), set at 40 W. Laparoscopic MWA is a tissue-sparing technique to treat in a mini-invasive fashion unresectable liver tumors or metastases. This technique has been extensively described in adult population, and rarely in children. These preliminary and satisfactory results make MWA promising when treating pediatric patients with malignant primary or secondary liver tumors. Further studies may provide data on its long-term efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: Stage IV rectal cancer occurs in 25% of patients and locoregional control of primary tumor is usually poorly considered, since priority is the treatment of metastatic disease., Aims: This study evaluates impact of neoadjuvant chemoradiation followed by surgery (nCHRTS) vs. upfront surgery on locoregional control and overall survival in stage IV rectal cancer., Methods: All patients diagnosed with stage IV rectal carcinoma between 2009 and 2019, undergone elective surgery at the National Cancer Institute of Milan (Italy), were included. Propensity score-based matching was performed between the two study groups. Loco-regional recurrence-free survival (LRRFS) and overall survival (OS) were analysed using Kaplan-Meyer method., Results: A total of 139 patients were analyzed. After propensity score matching, 88 patients were included in the final analysis. The 3-yr LRRFS rates were 80.3% for nCHRTS vs. 90.4% for upfront surgery patients (p = 0.35). The 3-yr OS rates were respectively 81.8% vs. 58% (p = 0.36). KRAS mutation (HR 2.506, p = 0.038) and extra-liver metastases (HR 4.308, p = 0.003) were both predictive of worse OS in univariate analysis., Conclusion: The present study failed to demonstrate a significant impact of nCHRTS on LRRFS or OS in stage IV rectal cancer., Competing Interests: Conflict of interest None declared., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Imaging is an essential tool in the management of patients with Colorectal cancer (CRC) by helping evaluate number and sites of metastases, determine resectability, assess response to treatment, detect drug toxicities and recurrences. Although multidetector computed tomography (MDCT) is the first tool used for staging and patient's surveillance, magnetic resonance imaging (MRI) is the most reliable imaging modality that allows to assess liver metastases. Our purpose is to compare the diagnostic performance of gadoxetic acid-(Gd-EOB) enhanced liver MRI and contrast-enhanced MDCT in the detection of liver metastasis from colorectal cancer (mCRC)., Methods: One hundred and twenty-eight patients with pathologically proven mCRC (512 liver metastases) underwent Gd-EOB MRI and MDCT imaging. An additional 46 patients without mCRC were included as control subjects. Three radiologists independently graded the presence of liver nodules on a five-point confidence scale. Sensitivity and specificity for the detection of metastases were calculated. Weighted к values were used to evaluate inter-reader agreement of the confidence scale regarding the presence of the lesion., Results: MRI detected 489 liver metastases and MDCT 384. In terms of per-lesion sensitivity in the detection of liver metastasis, all three readers had higher diagnostic sensitivity with Gd-EOB MRI than with MDCT (95.5% vs. 72% reader 1; 90% vs. 72% reader 2; 96% vs. 75% reader 3). Each reader showed a statistical significant difference (p < <.001 at Chi square test). MR imaging showed a higher performance than MDCT in per-patient detection sensitivity (100% vs. 74.2% [p < <.001] reader 1, 98% vs. 73% [p < <.001] reader 2, and 100% vs. 78% [p < <.001] reader 3). In the control group, MRI and MDCT showed similar per-patient specificity (100% vs. 98% [p = 0.31] reader 1, 100% vs. 100% [p = 0.92] reader 2, and 100% vs. 96% [p = 0.047] reader 3). Inter-reader agreement of lesion detection between the three radiologists was moderate to excellent (k range, 0.56-0.86) for Gd-EOB MRI and substantial to excellent for MDCT (k range, 0.75-0.8)., Conclusion: Gadoxetic acid-enhanced MRI performs significantly better in the detection of mCRC, than MDCT, particularly in patients treated with chemotherapy, in subcapsular lesions, and in peribiliary metastases.

Background/aims: Pancreatic neuroendocrine tumors (pan-NENs) represent an increasingly common indication for pancreatic resection, but there are few data regarding possible recurrence after surgery. The aim of the study was to describe the frequency, timing, and patterns of recurrence after resection for pan-NENs with consequent implications for postoperative follow-up., Methods: We performed a retrospective analysis of pan-NENs resected between 1990 and 2015 at The Pancreas Institute, University of Verona Hospital Trust. Predictors of recurrence were assessed. Survival analysis was conducted using the Kaplan-Meier and conditional survival (CS) methods., Results: The cohort consisted of 487 patients with a median follow-up of 71 months. Recurrence developed in 12.3%: 54 (11.1%) liver metastases, 11 (2.3%) local recurrence, 10 (2.1%) nodal recurrence, and 8 (1.6%) metastases in other organs. Thirty-one (6.4%) died due to disease recurrence. Size > 21 mm, G3 grade, nodal metastasis, and vascular infiltration were independent predictors of overall recurrence. Recurrence occurred either during the first year of follow-up (n = 9), or after 10 years (n = 4). CS analysis revealed that nonfunctioning G1 pan-NEN ≤20 mm without nodal metastasis or vascular invasion had a negligible risk of developing recurrence. In the present series, after 5 years of follow-up without developing recurrence, tumor recurrence occurred only in the form of liver metastases., Conclusions: Recurrence of pan-NENs is rare and is predicted by tumor size, nodal metastasis, grading, and vascular invasion. Patients with G1 pan-NEN without nodal metastasis and vascular invasion may be considered cured by surgery. After 5 years without recurrence, follow-up should focus on excluding the development of liver metastases., (© 2018 S. Karger AG, Basel.)

Abstract: Single liver metastases of colorectal cancer can be cured by surgery; disseminated liver metastases are incurable. A research group in Pavia, Italy, used BNCT as an experimental method to irradiate in curative intention the explanted liver of patients suffering from disseminated hepatic metastases. The situation in Pavia, where a reactor with a specially adapted thermal column and the hospital are close by, is unique. For the purpose of the present study, it was necessary to investigate how the Pavia experience can be repeated with transplantation centers located at distance from a reactor. Some basic investigations of the logistics of such a procedure are reported. [Copyright &y& Elsevier]