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IMPORTANCE: The 2022 Barcelona Clinic Liver Cancer algorithm currently discourages liver resection (LR) for patients with multinodular hepatocellular carcinoma (HCC) presenting with 2 or 3 nodules that are each 3 cm or smaller. OBJECTIVE: To compare the efficacy of liver resection (LR), percutaneous radiofrequency ablation (PRFA), and transarterial chemoembolization (TACE) in patients with multinodular HCC. DESIGN, SETTING, AND PARTICIPANTS: This cohort study is a retrospective analysis conducted using data from the HE.RC.O.LE.S register (n = 5331) for LR patients and the ITA.LI.CA database (n = 7056) for PRFA and TACE patients. A matching-adjusted indirect comparison (MAIC) method was applied to balance data and potential confounding factors between the 3 groups. Included were patients from multiple centers from 2008 to 2020; data were analyzed from January to December 2023. INTERVENTIONS: LR, PRFA, or TACE. MAIN OUTCOMES AND MEASURES: Survival rates at 1, 3, and 5 years were calculated. Cox MAIC-weighted multivariable analysis and competing risk analysis were used to assess outcomes. RESULTS: A total of 720 patients with early multinodular HCC were included, 543 males (75.4%), 177 females (24.6%), and 350 individuals older than 70 years (48.6%). There were 296 patients in the LR group, 240 who underwent PRFA, and 184 who underwent TACE. After MAIC, LR exhibited 1-, 3-, and 5-year survival rates of 89.11%, 70.98%, and 56.44%, respectively. PRFA showed rates of 94.01%, 65.20%, and 39.93%, while TACE displayed rates of 90.88%, 48.95%, and 29.24%. Multivariable Cox survival analysis in the weighted population showed a survival benefit over alternative treatments (PRFA vs LR: hazard ratio [HR], 1.41; 95% CI, 1.07-1.86; P = .01; TACE vs LR: HR, 1.86; 95% CI, 1.29-2.68; P = .001). Competing risk analysis confirmed a lower risk of cancer-related death in LR compared with PRFA and TACE. CONCLUSIONS AND RELEVANCE: For patients with early multinodular HCC who are ineligible for transplant, LR should be prioritized as the primary therapeutic option, followed by PRFA and TACE when LR is not feasible. These findings provide valuable insights for clinical decision-making in this patient population.

Few studies have assessed the clinical implications of the combination of different prognostic indicators for overall survival (OS) and disease-free survival (DFS) of resected hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic factors in HCC patients for OS and DFS outcomes and establish a nomogram-based prognostic model to predict the DFS of HCC. A multicenter, retrospective European study was conducted through the collection of data on 413 consecutive treated patients with a first diagnosis of HCC between January 2010 and December 2020. Univariate and multivariate Cox regression analyses were performed to identify all independent risk factors for OS and DFS outcomes. A nomogram prognostic staging model was subsequently established for DFS and its precision was verified internally by the concordance index (C-Index) and externally by calibration curves. For OS, multivariate Cox regression analysis indicated Child–Pugh B7 score (HR 4.29; 95% CI 1.74–10.55; p= 0.002) as an independent prognostic factor, along with Barcelona Clinic Liver Cancer (BCLC) stage ≥ B (HR 1.95; 95% CI 1.07–3.54; p= 0.029), microvascular invasion (MVI) (HR 2.54; 95% CI 1.38–4.67; p= 0.003), R1/R2 resection margin (HR 1.57; 95% CI 0.85–2.90; p= 0.015), and Clavien–Dindo Grade 3 or more (HR 2.73; 95% CI 1.44–5.18; p= 0.002). For DFS, multivariate Cox regression analysis indicated BCLC stage ≥ B (HR 2.15; 95% CI 1.34–3.44; p= 0.002) as an independent prognostic factor, along with multiple nodules (HR 2.04; 95% CI 1.25–3.32; p= 0.004), MVI (HR 1.81; 95% CI 1.19–2.75; p= 0.005), satellite nodules (HR 1.63; 95% CI 1.09–2.45; p= 0.018), and R1/R2 resection margin (HR 3.39; 95% CI 2.19–5.25; < 0.001). The C-Index of the nomogram, tailored based on the previous significant factors, showed good accuracy (0.70). Internal and external calibration curves for the probability of DFS rate showed optimal consistency and fit well between the nomogram-based prediction and actual observations. MVI and R1/R2 resection margins should be considered as significant OS and DFS predictors, while satellite nodules should be included as a significant DFS predictor. The nomogram-based prognostic model for DFS provides a more effective prognosis assessment for resected HCC patients, allowing for individualized treatment plans.

Liver surgery is the first line treatment for hepatocarcinoma. Hepatocarcinoma Recurrence on the Liver Study (HERCOLES) Group was established in 2018 with the goal to create a network of Italian centres sharing data and promoting scientific research on hepatocellular carcinoma (HCC) in the surgical field. This is the first national report that analyses the trends in surgical and oncological outcomes. Register data were collected by 22 Italian centres between 2008 and 2018. One hundred sixty-four variables were collected, regarding liver functional status, tumour burden, radiological, intraoperative and perioperative data, histological features and oncological follow-up. 2381 Patients were enrolled. Median age was 70 (IQR 63–75) years old. Cirrhosis was present in 1491 patients (62.6%), and Child-A were 89.9% of cases. HCC was staged as BCLC0-A in almost 50% of cases, while BCLC B and C were 20.7% and 17.9% respectively. Major liver resections were 481 (20.2%), and laparoscopy was employed in 753 (31.6%) cases. Severe complications occurred only in 5%. Postoperative ascites was recorded in 10.5% of patients, while posthepatectomy liver failure was observed in 4.9%. Ninety-day mortality was 2.5%. At 5 years, overall survival was 66.1% and disease-free survival was 40.9%. Recurrence was intrahepatic in 74.6% of cases. Redo-surgery and thermoablation for recurrence were performed up to 32% of cases. This is the most updated Italian report of the national experience in surgical treatment for HCC. This dataset is consistently allowing the participating centres in creating multicentric analysis which are already running with a very large sample size and strong power.

IMPORTANCE: Clear indications on how to select retreatments for recurrent hepatocellular carcinoma (HCC) are still lacking. OBJECTIVE: To create a machine learning predictive model of survival after HCC recurrence to allocate patients to their best potential treatment. DESIGN, SETTING, AND PARTICIPANTS: Real-life data were obtained from an Italian registry of hepatocellular carcinoma between January 2008 and December 2019 after a median (IQR) follow-up of 27 (12-51) months. External validation was made on data derived by another Italian cohort and a Japanese cohort. Patients who experienced a recurrent HCC after a first surgical approach were included. Patients were profiled, and factors predicting survival after recurrence under different treatments that acted also as treatment effect modifiers were assessed. The model was then fitted individually to identify the best potential treatment. Analysis took place between January and April 2021. EXPOSURES: Patients were enrolled if treated by reoperative hepatectomy or thermoablation, chemoembolization, or sorafenib. MAIN OUTCOMES AND MEASURES: Survival after recurrence was the end point. RESULTS: A total of 701 patients with recurrent HCC were enrolled (mean [SD] age, 71 [9] years; 151 [21.5%] female). Of those, 293 patients (41.8%) received reoperative hepatectomy or thermoablation, 188 (26.8%) received sorafenib, and 220 (31.4%) received chemoembolization. Treatment, age, cirrhosis, number, size, and lobar localization of the recurrent nodules, extrahepatic spread, and time to recurrence were all treatment effect modifiers and survival after recurrence predictors. The area under the receiver operating characteristic curve of the predictive model was 78.5% (95% CI, 71.7%-85.3%) at 5 years after recurrence. According to the model, 611 patients (87.2%) would have benefited from reoperative hepatectomy or thermoablation, 37 (5.2%) from sorafenib, and 53 (7.6%) from chemoembolization in terms of potential survival after recurrence. Compared with patients for which the best potential treatment was reoperative hepatectomy or thermoablation, sorafenib and chemoembolization would be the best potential treatment for older patients (median [IQR] age, 78.5 [75.2-83.4] years, 77.02 [73.89-80.46] years, and 71.59 [64.76-76.06] years for sorafenib, chemoembolization, and reoperative hepatectomy or thermoablation, respectively), with a lower median (IQR) number of multiple recurrent nodules (1.00 [1.00-2.00] for sorafenib, 1.00 [1.00-2.00] for chemoembolization, and 2.00 [1.00-3.00] for reoperative hepatectomy or thermoablation). Extrahepatic recurrence was observed in 43.2% (n = 16) for sorafenib as the best potential treatment vs 14.6% (n = 89) for reoperative hepatectomy or thermoablation as the best potential treatment and 0% for chemoembolization as the best potential treatment. Those profiles were used to constitute a patient-tailored algorithm for the best potential treatment allocation. CONCLUSIONS AND RELEVANCE: The herein presented algorithm should help in allocating patients with recurrent HCC to the best potential treatment according to their specific characteristics in a treatment hierarchy fashion.

Introduction: Adenoid cystic carcinomas (ACCs) account for 10% of all malignant salivary tumours. They are slow-growing but locally aggressive. Reports of liver and renal metastases are rare.Case description: A 58-year-old woman who had undergone resection of a left submandibular ACC in 1995 was referred to our centre for follow-up in 2018. A computed tomography scan revealed two lesions: one on segment six of the liver and the other on a kidney. A hepatic wedge resection and right nephrectomy were performed. The postoperative course was uneventful. At 2-year follow-up, the patient was alive and well with no evidence of disease.Conclusion: Management of ACC is a therapeutic challenge because of its tendency for distant metastases. The literature recommends regular follow-up imaging and radical surgical treatment but specific guidelines for the approach to recurrence are lacking.

Introduction Surgical resection offers the best chance of cure for patients with colorectal liver metastases (CRLMs). Two-stage hepatectomy (TSH) has been demonstrated to be safe and effective to obtain curative resection in patients with multiple, bilobar CRLMs that are unresectable in a single procedure. Up to now TSH has been the prerogative of dedicated liver surgery centers. The aim of this study was to assess the safety and effectiveness of TSH also in community hospitals.Methods Of 294 patients operated on for CRLMs between September 1997 and June 2012 in 2 district community hospitals (belonging to the same regional healthcare district), 43 (14.6%) were scheduled for TSH. Thirty-eight/43 received neoadjuvant and/or bridge chemotherapy (2 neoadjuvant only, 4 neoadjuvant and bridge, 32 bridge only).Results The mean follow-up was 35.74 ± 29.53 months. Five-year overall survival (OS) was 31.4%, with a median survival time of 31 months. Twenty-nine patients completed the planned procedure (OS: 42.9%; median 47 months), while 14 did not because of disease progression (OS: 0%; median 13 months). No operative mortality occurred within the first 90 days either after the first or second stage.Conclusions Our results suggest good efficacy and safety of TSH even when performed in a community hospital setting. Shifting patient selection from neoadjuvant to bridge chemotherapy had no impact on outcome once the clearing of the liver had been achieved. In patients presenting with synchronous CRLMs, simultaneous colorectal resection and clearing of the less involved hemiliver as the first surgical step is feasible without any negative impact on outcome.

Gastrointestinal stromal tumors are malignancies originating from stromal/mesenchymal tissues, most commonly in the stomach and small intestine, although they can be located everywhere in the gastrointestinal tract. Diagnosis is based on histological and immunohistochemical examination, and these rare tumors are characterized by c-kit (CD117) staining. Complete removal of the tumor is often curative in localized gastrointestinal stromal tumors and is always recommended. Clinically, their behavior is difficult to predict, and mitotic count and tumor size seem to be the most effective prognostic factors. We performed a retrospective analysis of clinical presentation and course, surgical management and pathological features of patients with gastrointestinal stromal tumors treated in our institution from 1995 to 2003. Twenty-two patients were enrolled in the study, and all of them underwent surgery. There were two perioperative deaths, and global morbidity was about 13%. Nineteen patients were followed (mean, 31 months): 4 patients had disease progression/recurrence and died, and one patient experienced a local recurrence and was reoperated with a curative intent; 14 patients were disease free. Our experience shows that histological and immunohistochemical examinations are fundamental for a definitive diagnosis and to assess the risk of aggressive behavior. Moreover, our results confirm that in stromal tumors complete surgical resection remains the mainstay of treatment in localized gastrointestinal stromal tumors, although the recurrence rate is relatively high. It is conceivable that treatment and prognosis of metastatic and non-resectable gastrointestinal stromal tumors, as well as the adjuvant treatment of high-risk, radically excised gastrointestinal stromal tumors will be strongly impacted by the c-kit target therapy.