Incidental diagnosis of pancreatic neuroendocrine tumors (PanNETs) greatly increased in the last years. In particular, more frequent diagnosis of small PanNETs leads to many challenging clinical decisions. These tumors are mostly indolent, although a percentage (up to 39%) may reveal an aggressive behaviour despite the small size. Therefore, there is still no unanimity about the best management of tumor smaller than 2 cm. The risks of under/overtreatment should be carefully evaluated with the patient and balanced with the potential morbidities related to surgery. The importance of the Ki-67 index as a prognostic factor is still debated as well. Whenever technically feasible, parenchyma-sparing surgeries lead to the best chance of organ preservation. Lymphadenectomy seems to be another important prognostic issue and, according to recent findings, should be performed in noninsulinoma patients. In the case of enucleation of the lesion, a lymph nodal sampling should always be considered. The relatively recent introduction of minimally invasive techniques (robotic) is a valuable option to deal with these tumors. The current management of PanNETs is analysed throughout the many available published guidelines and evidences with the aim of helping clinicians in the difficult decision-making process.

Human body is colonized by a huge amount of microorganisms mostly located in the gastrointestinal tract. These dynamic communities, the environment and their metabolites constitute the microbiota. Growing data suggests a causal role of a dysbiotic microbiota in several pathologies, such as metabolic and neurological disorders, immunity dysregulations and cancer, especially the well-studied colorectal cancer development. However, many were preclinical studies and a complete knowledge of the pathogenetic mechanisms in humans is still absent. The gut microbiota can exert direct or indirect effects in different phases of colorectal cancer genesis. For example, Fusobacterium nucleatum promotes cancer through cellular proliferation and some strains of Escherichia coli and Bacteroides fragilis produce genotoxins. However, dysbiosis may also cause a proinflammatory state and the stimulation of a Th17 response with IL-17 and IL-22 secretion that have a pro-oncogenic activity, as demonstrated for Fusobacterium nucleatum. Microbiota has a crucial role in several stages of postoperative course; dysbiosis in fact seems related with surgical site infections and Enterococcus faecalis (and other collagenase-producers microbes) are suggested as a cause of anastomotic leak. Consequently, unbalanced presence of some species, together with altered immune response may also have a prognostic role. Microbiota has also a substantial role in effectiveness of chemotherapy, chemoresistance and in the related side effects. In other words, a complete knowledge of the fine pathological mechanisms of gut microbiota may provide a wide range of new diagnostic tools other than therapeutic targets in the light of tailored medicine.

Background Surgical treatment is the cornerstone in the management of colorectal cancer (CRC) liver metastases. The aim of this study is to identify clinicopathological factors affecting disease-free (DFS) and overall survival (OS) in patients undergoing potentially curative liver resection for CRC metastasis. Methods All consecutive patients undergoing liver resection for first recurrence of CRC from February 2006 to February 2018 were included. Prognostic impact of factors related to the patient, primary and metastatic tumors, was retrospectively tested through univariate and multivariate analyses. Results Seventy patients were included in the study. Median postoperative follow-up was 37 months (range 1–119). Median DFS and OS were 15.2 and 62.7 months, and 5-year DFS and OS rates were 16% and 53%. In univariate analysis, timing of metastasis presentation/treatment (combined colorectal and liver resection, “bowel first” approach or metachronous presentation) (p < 0.0001), ASA score (p = 0.003), chemotherapy after liver surgery (p = 0.028), T stage (p = 0.021), number of resected liver lesions (p < 0.0001), and liver margin status (p = 0.032) was significantly associated with DFS while peritoneal resection at colorectal surgery (p = 0.026), ASA score (p = 0.036), extension of liver resection (p = 0.024), chemotherapy after liver surgery (p = 0.047), and positive nodes (p = 0.018) with OS. In multivariate analysis, timing of metastasis presentation/treatment, ASA score, and chemotherapy (before and after liver surgery) resulted significantly associated with DFS and timing of metastasis presentation/treatment, positive nodes, peritoneal resection at colorectal surgery, and surgical approach (open or minimally invasive) of colorectal resection with OS. Conclusions Surgery may provide good DFS and OS rates for CRC liver metastasis. Patient selection for surgery and correct timing of intervention within a multidisciplinary approach may be improved by taking into account negative prognostic factors which stress the importance of systemic therapy.

BackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common liver primary tumour after hepatocellular carcinoma and represents 20% of all the cholangiocarcinomas. Its incidence is increasing and mortality rates are rising. Surgical resection is the only option to cure the disease, despite the high recurrence rates reported to be up to 80%. Intrahepatic recurrences may be still treated with curative intent in a small percentage of the patients. Unfortunately, due to lack of specific symptoms, most patients are diagnosed in a late stage of disease and often unsuitable for resection. Liver transplantation for ICC is still controversial. After the first published poor results, improving outcomes have been reported in highly selected cases, including locally advanced ICC treated with neoadjuvant chemotherapy, when successful in controlling tumour progression. Thus, liver transplantation should be considered a possible option within study protocols. When surgical management is not possible, palliative treatments include chemotherapy, radiotherapy and loco-regional treatments such as radiofrequency ablation, trans-arterial chemoembolization or radioembolization.ConclusionsThis update on the management of ICC focusses on surgical treatments. Known and potential prognostic factors are highlighted in order to assist in treatment selection.

BACKGROUND Hepatocellular carcinoma (HCC) is a common tumour often diagnosed with a multifocal presentation. Patients with multifocal HCC represent a heterogeneous group. Although Trans-Arterial ChemoEmbolization (TACE) is the most frequently employed treatment for these patients, previous data suggested that liver resection (LR) could be a safe and effective procedure. AIM To compare LR and TACE in patients with multifocal HCC in terms of procedure-related morbidity and oncologic outcomes. METHODS All patients with multifocal HCC who underwent LR or TACE as the first procedure between May 2011 and March 2021 were enrolled. The decision to perform surgery or TACE was made after a multidisciplinary team evaluation. Only patients in Child-Pugh class A or B7 and stage B (according to the Barcelona Clinic Liver Cancer staging system, without severe portal hypertension, vascular invasion, or extrahepatic spread) were included in the final analysis. Propensity score matching was used to adjust the baseline differences between patients undergoing LR and the TACE group [number and diameter of lesions, presence of cirrhosis, alpha-fetoprotein (AFP) levels, and Model for End-Stage Liver Disease score]. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). The outcomes of LR and TACE were compared using the log-rank test. RESULTS After matching, 30 patients were eligible for the final analysis, 15 in each group. Morbidity rates were 42.9% and 40% for LR and TACE, respectively ( P = 0.876). Median OS was not different in the LR and TACE groups (53 mo vs 18 mo, P = 0.312), while DFS was significantly longer with LR (19 mo vs 0 mo, P = 0.0001). Subgroup analysis showed that patients in the Italian Liver Cancer (ITA.LI.CA) B2 stage, with AFP levels lower than 400 ng/mL, less than 3 lesions, and lesions bigger than 41 mm, benefited more from LR in terms of DFS. Patients classified as ITA.LI.CA B3, with AFP levels higher than 400 ng/mL and with more than 3 lesions, appeared to receive more benefit from TACE in terms of OS. CONCLUSION In a small cohort of patients with multifocal HCC, LR confers longer DFS compared with TACE, with similar OS and post-procedural morbidity.