The LIver SEntinel LYmph-node (LISELY) study: A prospective intraoperative real time evaluation of liver lymphatic drainage and sentinel lymph-node using near-infrared (NIR) imaging with Indocyanine Green (ICG).

Near-infrared (NIR) imaging with Indocyanine green (ICG) has been recently proposed for the sentinel lymph node (SLN) and lymphatic out-flow detection in several tumors. Nowadays its application in primary and secondary liver (LCs) and biliary cancers (BTCs) remains uninvestigated. A proof-of-concept prospective observational study including 18 patients underwent surgery for LCs and BTCs from September 2021 to November 2021 was carried out. The intraoperative NIR imaging with ICG was detected at predefined temporary intervals in order to identify the main lymphatic out-flow and the SLN. In 14 patients (77.8%) the lymphatic outflow pathway was visualized with a median time of 3 min after ICG injection (IQR 3-10). The SLN was detected and confirmed at the histological examination in 12 patients (66.7%). Intraoperative NIR imaging with ICG is a safe and feasible method to identify the lymphatic out-flow and SLN in LCs and BTCs.

Role of Inflammatory and Immune-Nutritional Prognostic Markers in Patients Undergoing Surgical Resection for Biliary Tract Cancers.

The relationship between immune-nutritional status and tumor growth; biological aggressiveness and survival, is still debated. Therefore, this study aimed to evaluate the prognostic performance of different inflammatory and immune-nutritional markers in patients who underwent surgery for biliary tract cancer (BTC). The prognostic role of the following inflammatory and immune-nutritional markers were investigated: Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Neutrophil to Lymphocyte ratio (NLR), Platelet to Lymphocyte ratio (PLR), Lymphocyte to Monocyte ratio (LMR), Prognostic Nutritional Index (PNI). A total of 282 patients undergoing surgery for BTC were included. According to Cox regression and ROC curves analysis for survival, LMR had the best prognostic performances, with hazard ratio (HR) of 1.656 (p = 0.005) and AUC of 0.652. Multivariable survival analysis identified the following independent prognostic factors: type of BTC (p = 0.002), T stage (p = 0.014), N stage (p < 0.001), histological grading (p = 0.045), and LMR (p = 0.025). Conversely, PNI was related to higher risk of severe morbidity (p < 0.001) and postoperative mortality (p = 0.005). In conclusion, LMR appears an independent prognostic factor of long-term survival, whilst PNI seems associated with worse short-term outcomes.

Simultaneous approach for patients with synchronous colon and rectal liver metastases: Impact of site of primary on postoperative and oncological outcomes.

BACKGROUND AND AIMS: We aimed to investigate the impact of the site of the primary on postoperative and oncological outcomes in patients undergone simultaneous approach for colon (CC) and rectal cancer (RC) with synchronous liver metastases (SCRLM). PATIENTS AND METHODS: Of the 220 patients with SCRLM operated on between Mar 2006 and Dec 2017, 169 patients (76.8%) were treated by a simultaneous approach and were included in the study. Two groups were considered according to the location of primary tumor RC-Group (n = 47) and CC-group (n = 122). RESULTS: Multiple liver metastases were observed in 70.2% in RC-Group and 77.0% in CC-Group (p = 0.233), whilst median Tumor Burden Score (TBS) was 4.7 in RC-Group and 5.4 CC-Group (p = 0.276). Severe morbidity (p = 0.315) and mortality at 90 days (p = 0.520) were comparable between RC-Group and CC-Group. The 5-year overall survival (OS) rate was similar comparing RC-Group and CC-Group (48.2% vs. 45.3%; p = 0.709), but it was significantly different when considering left-CC, right-CC and RC separately (54.5% vs. 35.2% vs. 48.2%; p = 0.041). Primary tumor location (right-CC, p = 0.001; RC, p = 0.002), microscopic residual (R1) disease at the primary (p < 0.001), TBS ≥6 (p = 0.012), bilobar metastases (p = 0.004), and chemotherapy strategy (preoperative ChT, p = 0.253; postoperative ChT, p = 0.012; and perioperative ChT, p < 0.001) resulted to be independent prognostic factors at multivariable analysis. CONCLUSION: In patients with SCRLM, simultaneous resection of the primary tumor and liver metastases seems feasible and safe and allows satisfactory oncological outcomes both in CC and RC. Right-CC shows a worse prognosis when compared to left-CC and RC.

Outcomes of vascular resection associated with curative intent hepatectomy for intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: We aimed to investigate the impact of vascular resection (VR) on postoperative outcomes and survival of patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). METHODS: A retrospective analysis of a multi-institutional series of 270 patients with resected ICC was carried out. Patients were divided into three groups: portal vein VR (PVR), inferior vena cava VR (CVR) and no VR (NVR). Univariate and multivariate analysis were applied to define the impact of VR on postoperative outcomes and survival. RESULTS: Thirty-one patients (11.5%) underwent VR: 15 (5.6%) to PVR and 16 (5.9%) to CVR. R0 resection rates were 73.6% in NVR, 73.3% of PVR and 68.8% in CVR. The postoperative mortality rate was increased in VR groups: 2.5% in NVR, 6.7% in PVR and 12.5% in CVR. The 5-years overall survival (OS) rates progressively decreased from 38.4% in NVR, to 30.1% in CVR and to 22.2% in PVR, p = 0.030. However, multivariable analysis did not confirm an association between VR and prognosis. The following prognostic factors were identified: size ≥50 mm, patterns of distribution of hepatic nodules (single, satellites or multifocal), lymph-node metastases (N1) and R1 resections. In the VR group the 5-years OS rate in patients without lymph-node metastases undergoing R0 resection (VRR0N0) was 44.4%, while in N1 patients undergoing R1 resection was 20% (p < 0.001). CONCLUSION: Vascular resection (PVR and CVR) is associated with higher operative risk, but seems to be justified by the good survival results, especially in patients without other negative prognostic factors (R0N0 resections).

Multigene mutational profiling of biliary tract cancer is related to the pattern of recurrence in surgically resected patients.

The aim of the present study was to investigate the relationship between the mutational gene profile and recurrence in biliary tract cancers (BTC). A total of 103 specimens of patients with BTC, who underwent curative surgery in a single tertiary HPB surgery referral center from 1990 to 2012, were assessed for mutational status in 52 cancer-related genes. Considering the different types of BTC, the 5-year recurrence-free survival (RFS) rate was 16.7% (median RFS 7 months) in gallbladder cancer, 42.9% (median RFS 26.4 months) in intrahepatic cholangiocarcinoma, and 19.7% (median RFS 16.5 months) in perihilar cholangiocarcinoma, p = 0.166. At the multivariate analysis including clinical, pathological, and molecular features, the factors independently related to RFS were radicality of surgery (OR 2.050, CI 1.104-3.807, p = 0.023), LN status (OR 1.835, CI 1.006-3.348, p = 0.048), mutational status of ARID1A (OR 2.566, CI 1.174-5.608, p = 0.018), and TP53 (OR 2.805, CI 4.432-5.496, p = 0.003). ARID1A mutation was associated with a local and systemic recurrence in the 43% and 29% of cases, respectively; and TP53 mutation was associated with a local and systemic recurrence in the 29% and 41% of cases. Moreover, TP53 was most commonly mutated in tumor of patients with early recurrence, p = 0.044. ARID1A and TP53 mutations seem to be related to poor outcome after surgery and may be considered molecular predictors of the biological aggressiveness in BTC.

The albumin-bilirubin score stratifies the outcomes of Child-Pugh class A patients after resection of hepatocellular carcinoma.

BACKGROUND: The albumin-bilirubin (ALBI) score is a mathematical model including serum albumin and bilirubin, recently proposed as an alternative prognostic tool in patients with hepatocellular carcinoma (HCC). The aims of this study were to provide evidence that the ALBI score can identify different prognostic groups in Child-Pugh (CP) class A patients undergoing liver resection with curative intent and to verify the ability of the ALBI score to predict short-term and long-term outcomes. METHODS: We performed a retrospective analysis on patients classified as class A according to the CP score who underwent liver resection with curative intent for HCC between 2006 and 2016 in the Division of Hepatobiliary Surgery at the University of Verona. Patients were divided according to the ALBI score and the presence or absence of preoperative clinically significant portal hypertension (CSPH). RESULTS: Among the 187 CP class A patients, 125 patients (66.8%) were ALBI 1 and 62 patients (33.2%) were ALBI 2. The 5-year overall survival (OS) was 49.2% in the entire cohort and was 57.1% and 33.5% for ALBI 1 and ALBI 2, respectively (P=0.0014). ALBI 2 patients showed a higher rate of post-hepatectomy liver failure (PHLF), 9.7% vs. 2.4% for ALBI 1 (P=0.027). In the multivariate analysis, the ALBI score [hazard ratio (HR) 1.9, P=0.026], stage of fibrosis (HR 2.0, P=0.02) and vascular invasion (HR 3.1, P<0.001) were the independent factors associated with OS. CSPH was identified in 60 (32.1%) patients. Of the patients with CSPH, the 5-year OS was 44.6% and 25.2% for ALBI 1 and ALBI 2, respectively (P=0.031). Of the patients without CSPH, the 5-year OS was 62.5% and 37.6% for ALBI 1 and ALBI 2, respectively (P=0.021). CONCLUSIONS: The ALBI score represents a simple tool to stratify the risk of PHLF and OS in CP class A HCC patients undergoing surgery and to evaluate the prognosis in patients with CSPH. This study justifies the use of the ALBI score in clinical practice to better select patients before surgery.