Search

Combined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Patients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching. During the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan–Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P =.0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P =.19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype. Despite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments. [ABSTRACT FROM AUTHOR]

Background: Surgical resection (SR) is a potentially curative treatment of hepatocellular carcinoma (HCC) hampered by high rates of recurrence. New drugs are tested in the adjuvant setting, but standardised risk stratification tools of HCC recurrence are lacking. Objectives: To develop and validate a simple scoring system to predict 2‐year recurrence after SR for HCC. Methods: 2359 treatment‐naïve patients who underwent SR for HCC in 17 centres in Europe and Asia between 2004 and 2017 were divided into a development (DS; n = 1558) and validation set (VS; n = 801) by random sampling of participating centres. The Early Recurrence Score (ERS) was generated using variables associated with 2‐year recurrence in the DS and validated in the VS. Results: Variables associated with 2‐year recurrence in the DS were (with associated points) alpha‐fetoprotein (<10 ng/mL:0; 10–100: 2; >100: 3), size of largest nodule (≥40 mm: 1), multifocality (yes: 2), satellite nodules (yes: 2), vascular invasion (yes: 1) and surgical margin (positive R1: 2). The sum of points provided a score ranging from 0 to 11, allowing stratification into four levels of 2‐year recurrence risk (Wolbers' C‐indices 66.8% DS and 68.4% VS), with excellent calibration according to risk categories. Wolber's and Harrell's C‐indices apparent values were systematically higher for ERS when compared to Early Recurrence After Surgery for Liver tumour post‐operative model to predict time to early recurrence or recurrence‐free survival. Conclusions: ERS is a user‐friendly staging system identifying four levels of early recurrence risk after SR and a robust tool to design personalised surveillance strategies and adjuvant therapy trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Intrahepatic cholangiocarcinoma is a disease with increasing incidence and poor prognosis. The clinicians have a limited capability to predict tumor behavior because the strongest predictors of survival are the pathology data that, unfortunately, can be determined only after surgery. Recently, radiomics, i.e., the mathematical analysis of imaging modalities, led to a major improvement in the non-invasive prediction of microscopic characteristics of several tumors. In this multicenter study, we collected a large number of patients affected by intrahepatic cholangiocarcinoma and we demonstrated that the radiomic data of the tumor and peritumoral tissue extracted from the computed tomography at diagnosis have a strong association with tumor grading and microscopic vascular invasion, which are two major biomarkers of tumor aggressiveness. The combination of radiomic and clinical data maximizes the accuracy of prediction. The integration of radiomics into clinical decision processes is probably one of the following steps toward a precision medicine approach in patients affected by intrahepatic cholangiocarcinoma. Standard imaging cannot assess the pathology details of intrahepatic cholangiocarcinoma (ICC). We investigated whether CT-based radiomics may improve the prediction of tumor characteristics. All consecutive patients undergoing liver resection for ICC (2009-2019) in six high-volume centers were evaluated for inclusion. On the preoperative CT, we segmented the ICC (Tumor-VOI, i.e., volume-of-interest) and a 5-mm parenchyma rim around the tumor (Margin-VOI). We considered two types of pathology data: tumor grading (G) and microvascular invasion (MVI). The predictive models were internally validated. Overall, 244 patients were analyzed: 82 (34%) had G3 tumors and 139 (57%) had MVI. For G3 prediction, the clinical model had an AUC = 0.69 and an Accuracy = 0.68 at internal cross-validation. The addition of radiomic features extracted from the portal phase of CT improved the model performance (Clinical data+Tumor-VOI: AUC = 0.73/Accuracy = 0.72; +Tumor-/Margin-VOI: AUC = 0.77/Accuracy = 0.77). Also for MVI prediction, the addition of portal phase radiomics improved the model performance (Clinical data: AUC = 0.75/Accuracy = 0.70; +Tumor-VOI: AUC = 0.82/Accuracy = 0.73; +Tumor-/Margin-VOI: AUC = 0.82/Accuracy = 0.75). The permutation tests confirmed that a combined clinical–radiomic model outperforms a purely clinical one (p < 0.05). The addition of the textural features extracted from the arterial phase had no impact. In conclusion, the radiomic features of the tumor and peritumoral tissue extracted from the portal phase of preoperative CT improve the prediction of ICC grading and MVI. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma is a rare disease with a poor prognosis. In patients where surgical resection is possible, outcome is influenced by perioperative morbidity and lymph node status. Laparoscopic liver resection is associated with improved clinical and oncological outcomes in primary and metastatic liver cancer compared with open liver resection, but evidence on intrahepatic cholangiocarcinoma is still insufficient. The primary aim of this study was to compare overall survival for a large series of patients treated for intrahepatic cholangiocarcinoma by open or laparoscopic approach. Secondary objectives were to compare disease-free survival, predictors of death, and recurrence. Patients treated with laparoscopic or open liver resection for intrahepatic cholangiocarcinoma from 2000 to 2018 from 3 large international databases were analyzed retrospectively. Each patient in the laparoscopic resection group (case) was matched with 1 open resection control (1:1 ratio), through a propensity score calculated on clinically relevant preoperative covariates. Overall and disease-free survival were compared between the matched groups. Predictors of mortality and recurrence were analyzed with Cox regression, and the Textbook Outcomes were described. During the study period, 855 patients met the inclusion criteria (open liver resection = 709, 82.9%; laparoscopic liver resection = 146, 17.1%). Two groups of 89 patients each were analyzed after propensity score matching, with no significant difference regarding pre- and postoperative variables. Overall survival at 1, 3, and 5 years was 92%, 75%, and 63% in the laparoscopic liver resection group versus 92%, 58%, and 49% in the open liver resection group (P =.0043). Adjusted Cox regression revealed severe postoperative complications (hazard ratio: 10.5, 95% confidence interval [1.01–109] P =.049) and steatosis (hazard ratio: 13.8, 95% confidence interval [1.23–154] P =.033) as predictors of death, and transfusion (hazard ratio: 19.2, 95% confidence interval [4.04–91.4] P <.001) and severe postoperative complications (hazard ratio: 4.07, 95% confidence interval [1.15–14.4] P =.030) as predictors of recurrence. The survival advantage of laparoscopic liver resection over open liver resection for intrahepatic cholangiocarcinoma is equivocal, given historical bias and missing data. [ABSTRACT FROM AUTHOR]

Background: Recent reports suggest that, following pancreatic resection, serum amylase elevation (SAE) may be a surrogate indicator of post‐operative acute pancreatitis (PAP) and predict post‐operative pancreatic fistula (POPF). However, POPF may not account for the majority of complications when pancreatoenteric continuity is restored by pancreatogastrostomy. We aimed to evaluate, among patients undergoing pancreatoduodenectomy with pancreatogastrostomy, the correlation between SAE, radiological changes consistent with PAP and types of post‐operative complications overall and specific for pancreatic surgery. Methods: Perioperative data from 102 patients who underwent pancreatoduodenectomy with pancreatogastrostomy at two Italian hospitals (January 2015–January 2017) were retrospectively analysed. SAE was defined as serum amylase more than three times the normal concentration at post‐operative day 1. Post‐operative abdominal computed tomography scan was routinely performed and retrospectively and blindly re‐assessed for findings consistent with PAP. Results: Among 102 study patients, overall and major complications and mortality occurred in 68% and 24% and 3% of cases, respectively. POPF and post‐pancreatectomy haemorrhage (PPH) occurred in 12% and 21%, respectively. In 75% of patients developing PPH, it occurred in the absence of POPF. SAE occurred in 36 patients who, compared to 66 non‐SAE patients, more frequently showed computed tomography scan findings consistent with pancreatic stump inflammation (P = 0.002), confirming association between SAE and PAP. SAE was independently associated with the occurrence of major complications, POPF and PPH (hazard ratio (HR) 3.27, P = 0.032; HR 3.94, P = 0.012; HR 12.26, P = 0.002). Conclusion: SAE can be considered a valid surrogate of PAP and is strongly associated with a higher rate of post‐operative major complications, both overall and specific for pancreatic resection. [ABSTRACT FROM AUTHOR]

A preoperative risk score (PRS) to predict outcome of patients with intrahepatic cholangiocarcinoma treated by liver surgery could be clinically relevant.To assess accuracy for broadly adoption, external validation of predictive models on independent datasets is crucial. The objective of this study was to externally validate the score for prediction of long-term outcomes after liver surgery for intrahepatic cholangiocarcinoma proposed by Sasaki et al. and based on preoperative albumin, neutrophil-to-lymphocytes-ratio, CA19-9 and tumor size. Patients treated by liver surgery for intrahepatic cholangiocarcinoma at 11 international HPB centers from 2001 to 2018 were included in the external validation cohort. Harrell's c-index and Hosmer-Lemeshow analyses were used to test PRS discrimination and calibration. Kaplan–Meier curve for risk groups as described in the original study were displayed. A total of 355 patients with 174 deaths during the follow-up period (median = 41.7 months, IQR 32.8–50.6) were included. The median PRS value was 14.7 (IQR 10.7–20.6), with normal distribution across the cohort. A Cox regression on PRS covariates found coefficients similar to those of the derivation cohort, except for tumor size. Measures of discrimination estimated by Harrell's c-index was 0.61(95%CI:0.56–0.67) and Hosmer-Lemeshow p = 0.175. The Kaplan-Meyer estimation showed reasonable discrimination across risk groups, with 5years survival rate ranging from 20.1% to 0%. In this external validation cohort, the PRS had mild discrimination and poor calibration performance, similarly to the original publication. Nevertheless, its ability to identify different classes of risk is clinically useful, for a better tailoring of a therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background. To assess the efficacy of intraoperative ultrasound (IOUS) compared with liver-specific magnetic resonance imaging (MRI) in patients with colorectal liver metastases (CRLMs). Methods. From January 2010 to December 2017, 721 patients underwent MRI as a part of preoperative workup within 1 month before hepatectomy and were considered for the study. Early intrahepatic recurrence (relapse at cut surface excluded) was assessed 6 months after the resection and was considered as residual disease undetected by IOUS and/or MRI. IOUS and MRI performance was compared on a patient-by-patient basis. Long-term results were also studied. Results. A total of 2845 CRLMs were detected by MRI, and the median number of CRLMs per patient was 2 (1–31). Preoperative chemotherapy was administered in 489 patients (67.8%). In 177 patients, 379 new nodules were intraoperatively found and resected. Among 379 newly identified nodules, 317 were histologically proven CRLMs (11.1% of entire series). The median size of new CRLMs was 6 ± 2.5 mm. Relationships between intrahepatic vessels and tumors differed between IOUS and MRI in 128 patients (17.7%). The preoperative surgical plan was intraoperatively changed for 171 patients (23.7%). Overall, early intrahepatic recurrence occurred in 8.7% of cases. To assess the diagnostic performance, 24 (3.3%) recurrences at the cut surface were excluded; thus, 5.4% of early relapses were considered for analysis. The sensitivity of IOUS was superior to MRI (94.5% vs 75.1%), while the specificity was similar (95.7% vs 95.9%). Multivariate analysis at the hepatic dome or subglissonian and mucinous histology revealed predictive factors of metastases missing at MRI. The 5-year OS (52.1% vs 37.8%, p=0.006) and DF survival (45.1% vs 33%, p=0.002) were significantly worse among patients with new CRLMs than without. Conclusions. IOUS improves staging in patients undergoing resection for CRLMs even in the era of liver-specific MRI. Intraoperative detection of new CRLMs negatively affects oncologic outcomes. [ABSTRACT FROM AUTHOR]

Background: The albumin–indocyanine green evaluation (ALICE) model based on serum albumin and indocyanine retention rate has been shown to be an effective method for predicting postoperative outcomes in hepatocellular carcinoma patients. Aim of the study was to validate the ALICE model in a large Western cohort of patients by comparing the albumin–bilirubin (ALBI) score and Child–Turcotte–Pugh (CTP) score. Methods: A total of 400 patients who underwent hepatic resection from January 2005 to June 2016 at three centers were enrolled. The ALICE, ALBI, and CTP scores were computed for all patients. Results: The ALICE score correlated better with ALBI (r = 0.428) than with CTP score (r = 0.302). Both the ALICE (grade 1: 49%; grade 2: 51%) and the ALBI (grade 1: 52.5%; grade 2: 47.5%) scores stratified the CTP class A patients into two distinct classes. The incidence of ascites (grades 1–3: ALICE 11%, 20%, 58%; ALBI 11%, 23%, 50%) and severe liver failure (ALICE 8.7%, 10.5%, 41.7%; ALBI 8.6%, 12%, 50%) increased with increasing ALBI and ALICE grade and were similar for the same grade. Conclusions: The ALICE model can assess hepatic functional reserve and predict postoperative outcomes with efficacy comparable with the ALBI grade and better than the CTP score. Highlight Russolillo and colleagues validated the usefulness of the ALICE model, based on the serum albumin and indocyanine green retention rate, in predicting postoperative outcomes after resection for HCC. The efficacy of the ALICE model was comparable with that of the albumin‐bilirubin grade and better than that of the Child‐Turcotte‐Pugh score. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to assess the capacity of indocyanine green retention test at 15 min (ICGR15) to predict chemotherapeutic-associated liver injuries (CALI).Methods: Patients undergoing liver resection for CLM that received preoperative oxaliplatin and/or irintecan-based chemotherapy within 3 months before surgery and scheduled first hepatectomy were considered.Results: 166 out of 983 patients treated between 01/2001 and 04/2014 fulfilled the inclusion criteria. The median number of cycles of preoperative chemotherapy was 6.0 ± 4.87. Chemotherapy was mainly based on oxaliplatin in 123 (74.1%). Bevacizumab was associated in 51(31%) patients. A total of 102 (61.4%) patients had at least 1 CALI. Grade 2-3 steatosis occurred in 56 (33.7%) patients and steatohepatitis in19(11.5%). Sinusoidal obstructive syndrome (SOS) was presented in 93 (56%) patients. 23(13.8%) patients had nodular regeneration hyperplasia. At multivariate analysis the only predictive factor of ICGR≥10% was age≥65 years (p = 0.001). A median split (ICGR15 = 8%) was used to categorized ICGR15 value. Multivariate analysis showed that age≥ 65 [OR 2.530 (CI95% 1.28-4.97) p < 0.001], male sex [OR 2.614 (CI95% 1.31-5.20) p < 0.001], SOS [OR 1.954 (CI95% 1.00-3.81) p = 0.050] and administration of Bevacizumab [OR 2.201 (CI95% 1.07-4.50) p = 0.031] were predictive factors for ICGR≥8%.Conclusions: ICGR15 test can predict the diagnosis of SOS. High ICGR15 value is more common in elderly male patients and after bevacizumab administration. [ABSTRACT FROM AUTHOR]

Background: Intratumoral bleeding and/or intraperitoneal rupture occurs in up to 20% of patients with hepatocellular adenoma (HCA). Hepatectomy in the presence of haemorrhagic HCA has been associated with increased morbidity and mortality rates. This study evaluates the outcomes of hepatectomy for haemorrhagic HCA at a single institution.Methods: Between January 1997 and December 2012, 52 consecutive patients underwent liver resection for HCA. Among them, 14 patients were resected for haemorrhagic (H)-HCAs (including 9 cases of intratumoural bleeding and 5 cases of intraperitoneal bleeding) and 38 for non-haemorrhagic (NH)-HCAs.Results: The preoperative characteristics were similar between the two groups except for younger age (p = .001) and shorter duration of hormonal use (p = .001) in (H)-HCAs. There were no mortalities. Intraoperative blood loss, transfusion rate, and postoperative morbidity were comparable between the two groups of patients (p = ns). The length of hospital stay was significantly longer in (H)-HCAs (p = .03). In all the resected H-HCAs, pathology showed central haemorrhagic changes with tumoral cells at the periphery of the lesions.Conclusions: Liver resection for H- and NH-HCAs can be achieved with no mortality and comparable short-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Nodular regenerative hyperplasia (NRH) is a severe form of chemotherapy-related liver injury (CALI) that may worsen the short-term outcome of liver resection (LR) for colorectal metastases (CRLM). The present study aimed to clarify the incidence, risk factors, preoperative assessment, and clinical impact of NRH. Methods: Overall, 406 patients undergoing 478 LRs for CRLM after chemotherapy between 2000 and 2012 were studied. All resection specimens were reviewed. After Gomori staining, NRH was graded according to the Wanless score. Results: NRH was diagnosed in 87 (18.2 %) patients, grades 2-3 in 14 (2.9 %) patients. At multivariate analysis, the prevalence of NRH was increased after oxaliplatin administration (21.4 vs. 8.4 %; p = 0.003), and reduced by the addition of bevacizumab (11.7 vs. 19.8 %; p = 0.020). Two parameters predicted the presence of NRH: the APRI score (AST to platelet ratio index: 25.5 % if >0.36 vs. 9.8 % if ≤0.36; p = 0.004), and the platelet count (63.6 % if <100 × 10/mm vs. 25.3 % if 100-200 × 10/mm vs. 11.9 % if >200 × 10/mm; p = 0.032). Ninety-day mortality and liver failure rates were 0.6 and 3.6 %. NRH was an independent predictor of postoperative liver failure (9.2 % if present vs. 2.3 % if not present; p = 0.021). In patients with grades 2-3 NRH, the rate of liver failure was 14.3 %, 25.0 % after major hepatectomy. No other forms of CALI impacted short-term outcomes. Conclusions: NRH was the most relevant form of CALI, increasing the risk of postoperative liver failure. Oxaliplatin increased the incidence of NRH, while bevacizumab decreased it. The APRI score and platelet count were useful tools for predicting NRH. [ABSTRACT FROM AUTHOR]