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BACKGROUND: The use of a simultaneous resection (SIMR) in patients with synchronous colorectal liver metastases (sCRLM) has increased over the past decades. However, it remains unclear when a SIMR is beneficial and when it should be avoided. The aim of this retrospective cohort study was therefore to compare the outcomes of a SIMR for sCRLM in different settings, and to assess which factors are independently associated with unfavorable outcomes.METHODS: To perform this retrospective cohort study, patients with sCRLM undergoing SIMR (2004-2019) were extracted from an international multicenter database, and their outcomes were compared after stratification according to the type of liver and colorectal resection performed. Factors associated with unfavorable outcomes were identified through multivariable logistic regression.RESULTS: Overall, 766 patients were included, encompassing colorectal resections combined with a major liver resection (n=122), minor liver resection in the anterolateral (n=407), or posterosuperior segments ('Technically major', n=237). Minor and technically major resections, compared to major resections, were more often combined with a rectal resection (29.2 and 36.7 vs. 20.5%, respectively, both P=0.003) and performed fully laparoscopic (22.9 and 23.2 vs. 6.6%, respectively, both P = 0.003). Major and technically major resections, compared to minor resections, were more often associated with intraoperative transfusions (42.9 and 38.8 vs. 20%, respectively, both P = 0.003) and unfavorable incidents (9.6 and 9.8 vs. 3.3%, respectively, both P≤0.063). Major resections were associated, compared to minor and technically major resections, with a higher overall morbidity rate (64.8 vs. 50.4 and 49.4%, respectively, both P≤0.024) and a longer length of stay (12 vs. 10 days, both P≤0.042). American Society of Anesthesiologists grades ≥3 [adjusted odds ratio (aOR): 1.671, P=0.015] and undergoing a major liver resection (aOR: 1.788, P=0.047) were independently associated with an increased risk of severe morbidity, while undergoing a left-sided colectomy was associated with a decreased risk (aOR: 0.574, P=0.013).CONCLUSIONS: SIMR should primarily be reserved for sCRLM patients in whom a minor or technically major liver resection would suffice and those requiring a left-sided colectomy. These findings should be confirmed by randomized studies comparing SIMR with staged resections.

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Only a fraction of patients with metastatic colorectal cancer receive clinical benefit from therapy with anti-epidermal growth factor receptor (EGFR) antibodies, which calls for the identification of novel biomarkers for better personalized medicine. We produced large xenograft cohorts from 85 patient-derived, genetically characterized metastatic colorectal cancer samples (“xenopatients”) to discover novel determinants of therapeutic response and new oncoprotein targets. Serially passaged tumors retained the morphologic and genomic features of their original counterparts. A validation trial confirmed the robustness of this approach: xenopatients responded to the anti-EGFR antibody cetuximab with rates and extents analogous to those observed in the clinic and could be prospectively stratified as responders or nonresponders on the basis of several predictive biomarkers. Genotype–response correlations indicated HER2 amplification specifically in a subset of cetuximab-resistant, KRAS/NRAS/BRAF/PIK3CA wild-type cases. Importantly, HER2 amplification was also enriched in clinically nonresponsive KRAS wild-type patients. A proof-of-concept, multiarm study in HER2-amplified xenopatients revealed that the combined inhibition of HER2 and EGFR induced overt, long-lasting tumor regression. Our results suggest promising therapeutic opportunities in cetuximab-resistant patients with metastatic colorectal cancer, whose medical treatment in the chemorefractory setting remains an unmet clinical need.Significance: Direct transfer xenografts of tumor surgical specimens conserve the interindividual diversity and the genetic heterogeneity typical of the tumors of origin, combining the flexibility of preclinical analysis with the informative value of population-based studies. Our suite of patient-derived xenografts from metastatic colorectal carcinomas reliably mimicked disease response in humans, prospectively recapitulated biomarker-based case stratification, and identified HER2 as a predictor of resistance to anti-epidermal growth factor receptor antibodies and of response to combination therapies against HER2 and epidermal growth factor receptor in this tumor setting. Cancer Discovery; 1(6); 508–23. ©2011 AACR.Read the Commentary on this article by Ciardiello and Normanno, p. 472This article is highlighted in the In This Issue feature, p. 457

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Purpose: intrabiliary growth (IG) is an unusual modality for colorectal metastases to spread. Relatively little is known about this condition because large series are lacking. The aim of the study was to compare the surgical and oncological outcomes of patients with or without IG. Methods: From 01/2010 to 12/2020, 999 patients underwent hepatectomy for colorectal metastases. Clinicopathological variables were retrospectively analysed from a prospective-collected database of patients with or without IG. Results: At first hepatectomy, 29 patients (2.9%) had IG: 7 isolated IG and 22 mixed-type (mass-forming lesion with IG). 4 patients presented IG at repeat hepatectomy for recurrence, of whom 3 had no biliary invasion at initial surgery. IG resulted to be more common in older patients (median age 70 in IG vs 60 years of no-IG, p=0.004). Mean time from colorectal tumour was longer in IG (20.4 months) than no-IG (12.9 months), p=0.038. Major hepatectomies (55.2% IG vs 29.7% no-IG, p=0.003) and anatomic resections (89.7% vs 58.2%, p=0.001) were more frequently required to treat IG. In 5 (17%) of IG a resection of main bile duct was performed. Overall postoperative mortality and complications were similar in the two groups, while bile leak was 17.2% IG vs 5.6% no-IG (p=0.024). Median margin width was comparable in IG (1.4mm) and no-IG (2mm). Five years-Overall Survival(IG 45.9% vs no-IG 44.5%) and Disease-Free Survival (IG 35.9% vs no-IG 36.6%) were similar in the two groups. Conclusion: IG has similar oncological outcomes of resected colorectal metastases without IG, although it affects surgical management.

The difficulty of laparoscopic right liver resections (LRLR) is mainly associated with their poor accessibility. Anthropometric data rather than BMI was reported to predict transection time and blood loss. Aim of the study was to evaluate the correlation between anthropometric data and preparatory manoeuvres difficulties during LRLR.All patients who underwent LRLR requiring full right liver mobilization from November 2019 to March 2021 were prospectively included in the study. Data on surgeons' difficulty perceptions on liver mobilization (LM), isolation of right hepatic vein (RHVI), liver manageability and visibility were rated with a 5-point scale. Data on cranio-caudal liver diameters (CCliv), CHALLENGE Index (CCliv/latero-lateral abdomen diameter), times needed to LM and RHVI were collected.Sixty-five patients (29 wedge and 36 anatomical resections) with a median BMI of 25.5 were analysed. One patient required open conversion due to oncological reason. No correlations between BMI and CCliv or CHALLENGE Index were found. Larger CCliv diameter correlated with longer time for both RHVI (r = 0.589, p = 0.002) and LM (r = 0.222, p = 0.049). Higher CHALLENGE index correlated with longer time for RHVI (r = 0.589, p = 0.002). The CHALLENGE index showed a linear correlation with difficulty to the isolation of RHV (r = 0.327, p = 0.045), whilst the liver manipulation difficulty increased with latero-lateral liver diameter (r = 0.244, p = 0.033). BMI had no correlation with the duration of preparatory maneuvers neither with surgeons' difficulties.Anthropometric data can help to anticipate the difficulty of preparatory maneuvers during laparoscopic right liver resections.

Background: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. Aims: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. Materials and methods: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. Results: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) (https://childb.shinyapps.io/NomogramMajorMorbidity90days/). Conclusions: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Purpose The effect size between total pancreatectomy (TP) over pancreatico-duodenectomy (PD) remains not well established due to the lack of high-level evidences. Aim of the study was to evaluate the average treatment effect on the patients treated (ATT) with PD in the case they received TP. Methods A reweighting scheme was applied to 202 TPs patients to equal 415 PDs (2016–2020), providing what would have happened to PD patients if they received TP. Superiority, non-inferiority and equivalence of PD and TP were assessed for outcomes’ risk ratios (RR). Results Balancing was perfect providing a robust estimation of ATT. If PDs were treated with TP they would more frequently experienced difficult glycemic control (RR: 1.44; 95%C.I.:1.21–1.73; p = 0.001) and received red blood cell (RBC) transfusion (RR: 1.23; 95%C.I.:1.04–1.46; p = 0.017). Conversely, TP would have reduced delayed gastric emptying (DGE; RR: 0.68; 95%C.I.:0.42–0.88; p = 0.008) as the likely avoidance of post-operative pancreatic fistula. Major morbidity and failure-to-rescue were within equivalence margins. In subgroups, TP would have not worsened glycemic control in patients already diabetics, transfusions would have not increased in patients with worse general conditions, and TP would have not reduced DGE in older, diabetics and female patients, more susceptible to gastric motility disorders. Post-operative stay and 30-day readmission were within equivalence margins. Conclusion If PD is feasible, the adoption of TP would be potentially more harmful than beneficial except in some clinical circumstances, supporting this choice in these cases. Both procedures finally provided similar major morbidity, failure-to-rescue, mortality, in-hospital stay and readmission rate.

Tumors involving the hepatic veins at the hepatocaval confluence often require major or extended hepatectomies. Color Doppler intraoperative ultrasonography (CD-IOUS) evaluation of liver hemodynamics to assess congestion in the veno-occlusive parenchyma provides real-time information helpful in parenchyma-sparing surgery (PSS). This study evaluated the feasibility of CD-IOUS in patients undergoing laparoscopic liver resections for such tumors and its capacity to allow PSS.Consecutive patients undergoing laparoscopic liver resection for tumors at the hepatocaval confluence requiring resection of at least one hepatic vein between January 2010 and August 2020 were included. Patients were divided in 3 groups: (A) patients not assessed with CD-IOUS because it would not change the scheduled operation; patients assessed with CD-IOUS and treated with (B) PSS and (C) no-PSS. Portal blood flow in the veno-occlusive parenchyma was assessed using CD-IOUS at baseline and after clamping the concerned hepatic vein.The study included 43 out of 47 patients with tumors at the hepatocaval confluence. There were 19 patients in group A. Among patients assessed with CD-IOUS, the resection of 26 hepatic veins was planned: 25 were resected, and 1 was spared. Group B included 22 patients treated with PSS, whereas group C included 2 patients with resection of all veno-occlusive parenchyma. No postoperative mortality or major morbidity was observed. The median length of hospital stay was 5 days.Selected patients with tumors involving the hepatocaval confluence can be safely approached using laparoscopy. CD-IOUS evaluation of the veno-occlusive area can increase the success rate of PSS.

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.

The high technical difficulty of using a laparoscopic approach to reach the posterosuperior liver segments is mainly associated with their poor accessibility. This study was performed to analyze correlations between anthropometric data and intraoperative outcomes.All patients who underwent segmentectomy or wedge laparoscopic liver resection (LLR) of segments seven and/or eight from June 2012 to November 2019 were retrospectively analyzed. The exclusion criteria were intrahepatic cholangiocarcinoma, associated resection, multiple concomitant LLR, redo resection, and lack of preoperative imaging. Anthropometric data were correlated with intraoperative outcomes.Forty-one patients (wedge resection, n = 32; segmentectomy, n = 9) were analyzed. A strong correlation was found between the craniocaudal liver diameter (CCliv) and liver volume (r = 0.655, p 0.001). The anteroposterior liver diameter was moderately correlated with both the laterolateral abdominal diameter (LLabd) (r = 0.372, p = 0.008) and anteroposterior abdominal diameter (r = 0.371, p = 0.008). The body mass index (BMI) was not correlated with liver diameters. Women had a longer CCliv (p = 0.002) and shorter LLabd (p 0.001) than men. The liver and abdominal measurements were combined to reduce this sex-related disparity. The CCliv/LLabd ratio (CHALLENGE index) was significantly correlated with the time of transection (r = 0.382, p = 0.037) and blood loss (r = 0.352, p = 0.029). The association between the CHALLENGE index and intraoperative blood loss was even stronger when considering only anatomical resection (r = 0.577, p = 0.048). A CHALLENGE index of 0.4 (area under the curve, 0.757; p = 0.046) indicated a higher bleeding risk. The BMI predicted no intraoperative outcomes.Anthropometric data rather than the BMI can help anticipate the difficulty of LLR of segments seven and eight.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers.METHOD: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed.RESULTS: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival.CONCLUSION: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.

Laparoscopic segment 7 segmentectomy and segment 6–7 bisegmentectomy are challenging resections because of the posterior position and the lack of landmarks. The anatomy of the right posterior Glissonean pedicle and the caudal view of laparoscopy make such resections suitable for the Glissonean pedicle-first approach. The study population included all consecutive patients treated with laparoscopic liver resection from August 2019 to February 2020. The approach is based on the ultrasonographic identification of the right posterior or segmental pedicle from the dorsal side of the liver after complete mobilization. The pedicle of interest is isolated through mini-hepatotomy and clamped. The segment anatomy is defined by ischemia. The transection starts from the ventral side, close to the right hepatic vein that is exposed and followed craniocaudally. Ten patients underwent anatomical laparoscopic resection of right posterolateral segments. There were 7 colorectal liver metastases, 2 hepatocellular carcinoma, and 1 biliary cysto-adenoma. Five patients underwent Sg7 resection, one patient underwent a Sg7 subsegmentectomy, and 4 underwent Sg6-7 bisegmentectomy. The Glissonean pedicle-first approach was feasible in eight patients. The craniocaudal approach to the RHV was feasible in six patients, not indicated in three cases and was abandoned in one patient for technical difficulty. There was no operative morbidity or mortality. Median post-operative hospital stay was 5 days. The Glissonean pedicle-first approach is safe and effective for laparoscopic anatomic resections of the right posterior sector. The craniocaudal approach to right hepatic vein from the ventral side is a convenient procedure to follow the segmental anatomy deep in the parenchyma.

Intraoperative liver ultrasound appears superior to liver-specific contrast-enhanced magnetic resonance imaging (MRI) to stage colorectal liver metastases (CRLMs). Most of the data come from studies on open surgery. Laparoscopic ultrasound (LUS) is technically demanding and its reliability is poor investigated. Aim of the study was to assess the accuracy of LUS staging for CRLMs compared to MRI. All patients with CRLMs scheduled for laparoscopic liver resection (LLR) between 01/2010 and 06/2019 who underwent preoperative MRI were considered for the study. LUS and MRI performance was compared on a patient by patient basis. Reference standards were final pathology and 6 months follow-up results. Amongst 189 LLR for CRLMs, 146 met inclusion criteria. Overall, 391 CRLMs were preoperatively detected by MRI. 24 new nodules in 16 (10.9%) patients were found by LUS and resected. Median diameter of new nodules was 5.5 mm (2–10 mm) and 10 (41.6%) were located in the hepatic dome. Pathology confirmed 17 newly detected malignant nodules (median size 4 mm) in 11 (7.5%) patients. Relationships between intrahepatic vessels and tumours differed between LUS and MRI in 9 patients (6.1%). Intraoperative surgical strategy changed according LUS findings in 19 (13%) patients, requiring conversion to open approach in 3 (15.8%) of them. The sensitivity of LUS was superior to MRI (93.1% vs 85.6% whilst specificity was similar (98.6% MRI vs 96.5% LUS). Laparoscopic liver ultrasound improves liver staging for CRLMs compared to liver-specific MRI.

Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined.Patients were identified from the Italian national registry HE.RC.O.LE.S. The Achievable Benchmark of Care (ABC) method was employed to identify the benchmarks. The outcomes assessed were the rate of complications, major comorbidities, post-operative ascites (POA), post-hepatectomy liver failure (PHLF), 90-day mortality. Benchmarking was stratified for surgical complexity (CP1, CP2 and CP3).A total of 978 of 2698 patients fulfilled the inclusion criteria. 431 (44.1%) patients were treated with CP1 procedures, 239 (24.4%) with CP2 and 308 (31.5%) with CP3 procedures. Patients submitted to CP1 had a worse underlying liver function, while the tumor burden was more severe in CP3 cases. The ABC for complications (13.1%, 19.2% and 28.1% for CP1, CP2 and CP3 respectively), major complications (7.6%, 11.1%, 12.5%) and 90-day mortality (0%, 3.3%, 3.6%) increased with the surgical difficulty, but not POA (4.4%, 3.3% and 2.6% respectively) and PHLF (0% for all groups).We propose benchmarks for open liver resections in HCC cirrhotic patients, stratified for surgical complexity. The difference between the benchmark values and the results obtained during everyday practice reflects the room for potential growth, with the aim to encourage constant improvement among liver surgeons.

Background: Despite the worldwide increase of both obesity and the use of minimally invasive liver surgery (MILS), evidence regarding the safety and eventual benefits of MILS in obese patients is scarce. The aim of this study was therefore to compare the outcomes of non-obese and obese patients (BMI 18.5-29.9 and BMI≥30, respectively) undergoing MILS and OLS, and to assess trends in MILS use among obese patients.Methods: In this retrospective cohort study, patients operated at 20 hospitals in eight countries (2009-2019) were included and the characteristics and outcomes of non-obese and obese patients were compared. Thereafter, the outcomes of MILS and OLS were compared in both groups after propensity-score matching (PSM). Changes in the adoption of MILS during the study period were investigated.Resuls: Overall, 9963 patients were included (MILS: n = 4687; OLS: n = 5276). Compared to non-obese patients (n = 7986), obese patients(n = 1977) were more often comorbid, less often received preoperative chemotherapy or had a history of previous hepatectomy, had longer operation durations and more intraoperative blood loss (IOBL), paralleling significantly higher rates of wound- and respiratory-related complications. After PSM, MILS, compared to OLS, was associated, among both non-obese and obese patients, with less IOBL (200 ml vs 320 ml, 200 ml vs 400 ml, respectively), lower rates of transfusions (6.6% vs 12.8%, 4.7% vs 14.7%), complications (26.1% vs 35%, 24.9% vs 34%), bile leaks(4% vs 7%, 1.8% vs 4.9%), liver failure (0.7% vs 2.3%, 0.2% vs 2.1%), and a shorter length of stay(5 vs 7 and 4 vs 7 days). A cautious implementation of MILS over time in obese patients (42.1%-53%, p < .001) was paralleled by stable severe morbidity (p = .433) and mortality (p = .423) rates, despite an accompanying gradual increase in surgical complexity.Conclusions: MILS is increasingly adopted and associated with perioperative benefits in both non-obese and obese patients.

Laparoscopic liver resection (LLR) is safer and more advantageous than open surgery regarding morbidity, blood loss, and length of hospital stay. Several radiological studies and liver surgical strategies confirmed that the anatomy of the liver is more complex than what Couinad described. Intraoperative ultrasound (IOUS) has become an indispensable tool to identify the “real anatomy” and to plan a tailored LLR because of wide sub-segmentary variability and lack of external indicators for small functional liver cores. We schematized our standard ultrasound guidance technique during anatomical and non-anatomical LLR as a four-step method called the Ultrasound Liver Map Technique: (1) Compose the three-dimensional mind map to study the relationships between lesions and surrounding vascular elements; (2) create a sketch on the Glissonian using cautery to help the surgeon recall the mind liver anatomy map; (3) check the section plane while proceeding with the transection; and (4) correct the direction of resection plan to ensure a healthy margin concerning the lesion and to point out the pedicle section correctly and not affected structures. Finally, IOUS-Doppler can be used to study the segmental portal flow to assess venous drainage of the remnant parenchyma, avoiding ischemia and increasing the possibility of performing parenchyma-sparing surgery.

Objective: Major hepatectomy in cirrhotic patients still represents a great challenge for liver surgeons. Hence, the aim in the present study is to investigate the clinical impact of major hepatectomy and to assess whether the surgical approach influences the outcome of cirrhotic patients. Methods: Multicenter retrospective study including cirrhotic patients undergoing major laparoscopic (mjLLR) and open liver resection (mjOLR) in 14 Western liver centers was performed (2009–2020). Clinical, demographic, and perioperative data were compared using propensity score matching (PSM). Long-term outcome after resection for hepatocellular carcinoma was analyzed. Results: Overall, 352 patients were included; 108 after mjLLR and 244 after mjOLR. After PSM, 88 patients were matched in each group. In the mjLLR group, compared to mjOLR, less blood loss (P=.042), lower overall and severe complication (P&nbsp

We aimed to evaluate, in a large Western cohort, perioperative and long-term oncological outcomes of salvage hepatectomy (SH) for recurrent hepatocellular carcinoma (rHCC) after primary hepatectomy (PH) or locoregional treatments.Data were collected from the Hepatocarcinoma Recurrence on the Liver Study Group (He.RC.O.Le.S.) Italian Registry. After 1:1 propensity score-matched analysis (PSM), two groups were compared: the PH group (patients submitted to resection for a first HCC) and the SH group (patients resected for intrahepatic rHCC after previous HCC-related treatments).2689 patients were enrolled. PH included 2339 patients, SH 350. After PSM, 263 patients were selected in each group with major resected nodule median size, intraoperative blood loss and minimally invasive approach significantly lower in the SH group. Long-term outcomes were compared, with no difference in OS and DFS. Univariate and multivariate analyses revealed only microvascular invasion as an independent prognostic factor for OS.SH proved to be equivalent to PH in terms of safety, feasibility and long-term outcomes, consistent with data gathered from East Asia. In the awaiting of reliable treatment-allocating algorithms for rHCC, SH appears to be a suitable alternative in patients fit for surgery, regardless of the previous therapeutic modality implemented.

(1) Background: Tumor recurrence after liver resection (LR) for intrahepatic cholangiocarcinoma (ICC) is common. Repeat liver resection (RLR) for recurrent ICC results in good survival outcomes in selected patients. The aim of this study was to investigate factors affecting the chance of resectability of recurrent ICC. (2) Methods: LR for ICC performed between January 2001 and December 2020 were retrospectively reviewed. Patients who had undergone first LR were considered for the study. Data on recurrences were analyzed. A logistic regression model was used for multivariable analysis of factors related to RLR rate. (3) Results: In total, 140 patients underwent LR for ICC. Major/extended hepatectomies were required in 105 (75%) cases. The 90-day mortality was 5.7%, Clavien–Dindo grade 3, 4 complications were 9.3%, N+ disease was observed in 32.5%, and the median OS was 38.3 months. Recurrence occurred in 91 patients (65%). The site of relapse was the liver in 53 patients (58.2%). RLR was performed in 21 (39.6%) patients. Factors that negatively affected RLR were time to recurrence ≤12 months (OR 7.4, 95% CI 1.68–33.16, p = 0.008) and major hepatectomy (OR 16.7, 95% CI 3.8–73.78, p &lt, 0.001) at first treatment. Survival after recurrence was better in patients who underwent RLR as compared with not resected patients (31 vs. 13.2 months, p = 0.02). (4) Conclusions: Patients with ICC treated at first resection with major hepatectomy and those who recurred in ≤12 months had significantly lower probability to receive a second resection for recurrence.

Despite many developments, postoperative bile leakage (POBL) remains a relatively common postoperative complication after laparoscopic liver resection (LLR) and open liver resection (OLR). Previous studies regarding the incidence and clinical impact of POBL have mainly focused on patients undergoing OLR. The aim of this study is to compare the incidence and clinical impact of POBL between patients undergoing LLR and OLR in a large international multicenter cohort using a propensity score matched analysis.

Early hospital readmission for dehydration represents a relevant problem among patients with diverting or terminal ileostomy. The aim of the study was to evaluate the efficacy of a new multidisciplinary individualized multistep protocol in terms of reduction of hospital readmission for dehydration. Since January 2016, our institution adopted a new protocol for patients with ileostomy. Protocol key points were: preoperative personalized education in stoma management; early recognition of dehydration symptoms; multidisciplinary counseling; patient autonomy in stoma management through post-operative recall schedule. The study compared a series of consecutive patients treated before (2014-2015) and after (2016-2017) the protocol application. The primary endpoint was hospital readmission rate after protocol use. The secondary endpoint was the identification of possible risk factors for readmission. The entire cohort was composed of 296 patients, 129 in the protocol group and 167 in the control one. The two groups were homogeneous for baseline characteristics. Hospital readmission rate within 30 days post-discharge for dehydration dropped from 9 to 3.9% after protocol application. Specifically, the number of avoided potential readmissions was 29/129 (22.4%). The number needed to treat (NNT) was 20. Univariate analysis identified three relevant variables: patient comorbidities, diuretics use as risk factors and protocol application as the protective one. The multivariate analysis confirmed patient comorbidity as the risk factor. Dehydration related to ileostomy is a potentially avoidable problem, by employing preventive strategies, especially in high-risk patients. Our new protocol could be a simple and cost-saving method, effective in preventing hospital readmissions.

Background Preoperative biliary drainage may be essential to reduce the risk of postoperative liver failure after hepatectomy for perihilar cholangiocarcinoma. However, infectious complications related to preoperative biliary drainage may increase the risk of postoperative mortality. The strategy and optimal drainage method continues to be controversial. Methods This is a retrospective multicenter study including patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2016 at 14 Italian referral hepatobiliary centers. The primary end point was to evaluate independent predictors for postoperative outcome in patients undergoing liver resection for perihilar cholangiocarcinoma after preoperative biliary drainage. Results Of the 639 enrolled patients, 441 (69.0%) underwent preoperative biliary drainage. Postoperative mortality was 8.9% (12.5% after right-side hepatectomy versus 5.7% after left-side hepatectomy; P = .003). Of the patients, 40.5% underwent preoperative biliary drainage at the first admitting hospital, before evaluation at referral centers. Use of percutaneous preoperative biliary drainage was significantly more frequent at referral centers than at community hospitals where endoscopic preoperative biliary drainage was the most frequent type. The overall failure rate after preoperative biliary drainage was 43.3%, significantly higher at community hospitals than that at referral centers (52.7% v 36.9%; P = .002). Failure of the first preoperative biliary drainage was one of the strongest predictors for postoperative complications after right-side and left-side hepatectomies and for mortality after right-side hepatectomy. Type of preoperative biliary drainage (percutaneous versus endoscopic) was not associated with significantly different risk of mortality. Conclusion Failure of preoperative biliary drainage was significantly more frequent at community hospitals and it was an independent predictor for postoperative outcome. Centers’ experience in preoperative biliary drainage management is crucial to reduce the risk of failure that is closely associated with postoperative morbidity and mortality.

At the time of diagnosis synchronous colorectal cancer, liver metastases (SCRLM) account for 15–25% of patients. If primary tumour and synchronous liver metastases are resectable, good results may be achieved performing surgical treatment incorporated into the chemotherapy regimen. So far, the possibility of simultaneous minimally invasive (MI) surgery for SCRLM has not been extensively investigated. The Italian surgical community has captured the need and undertaken the effort to establish a National Consensus on this topic. Four main areas of interest have been analysed: patients’ selection, procedures, techniques, and implementations. To establish consensus, an adapted Delphi method was used through as many reiterative rounds were needed. Systematic literature reviews were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses instructions. The Consensus took place between February 2019 and July 2020. Twenty-six Italian centres participated. Eighteen clinically relevant items were identified. After a total of three Delphi rounds, 30-tree recommendations reached expert consensus establishing the herein presented guidelines. The Italian Consensus on MI surgery for SCRLM indicates possible pathways to optimise the treatment for these patients as consensus papers express a trend that is likely to become shortly a standard procedure for clinical pictures still on debate. As matter of fact, no RCT or relevant case series on simultaneous treatment of SCRLM are available in the literature to suggest guidelines. It remains to be investigated whether the MI technique for the simultaneous treatment of SCRLM maintain the already documented benefit of the two separate surgeries.

Aim: Textbook outcome (TO) is a new surgical quality measure that combines structure, process and surgical outcomes into a single element. Our study aimed to determine the incidence of TO after simultaneous rectal and liver surgery and to use the achievement of TO as a tool to identify the best candidates for these complex procedures. Methods: In total, 256 patients who underwent simultaneous liver and rectal surgery for Stage IV rectal cancer between January 2004 and August 2019 at five tertiary centres were enrolled. TO was defined as a lack of complication, prolonged length of stay, readmission and death. Results: Mortality rate at 90days and major morbidity rate were 2.3% and 15.6%, respectively. An overall TO was achieved in 59% of the patients, which is associated with significantly improved overall (median TO 86.3months vs. no TO 37.4months) and disease-free (median TO 70.6months vs. no TO 24.9months) survival. On multivariate analysis the presence of multi-comorbidities (OR 3.073) was associated with a reduced likelihood of achieving TO. Left lateral sectionectomy/limited resection was a protective factor (OR 0.416). Conclusion: TO was achieved in six of 10 patients undergoing simultaneous resections for rectal cancer and liver metastases. Achieving a TO is strongly associated with improved long-term survival. The best candidates for these procedures were patients without multiple comorbidities and those treated with left lateral sectionectomy/limited resection.

Background: Hepatocellular carcinoma (HCC) is frequently diagnosed as multinodular. This study aims to assess prognostic factors for survival and identify patients with multiple HCC who may benefit from surgery beyond the Barcelona Clinic Liver Cancer classification indications. Methods: This retrospective study included all the consecutive patients from 4 Italian tertiary centers receiving liver resection for naive multiple HCC between 1990 and 2012 to have a potential follow-up of 5 years. Results: Included patients were 144. Ninety-day morbidity and mortality rates were 38.3% and 8.3%, respectively. The 5-year overall and disease-free survival rates were 33.3% and 19.1%, respectively. Tumor size

and purpose: FDG-PET/CT has gained acceptance for tumours staging. Few and conflicting data exist on the sensitivity of FDG-PET/CT in identifying colorectal mucinous liver metastases (mucCRLM). The aim of this study was to evaluate the diagnostic performance of the FDG-PET/CT in patients with mucCRLM who underwent liver surgery.All patients affected by mucCRLM scheduled for liver resection who had undergone preoperative FDG-PET/CT between 2005 and 2018 were analyzed. Diagnostic performance of FDG-PET/CT was assessed in organ and lesion-based analysis.58 patients out of 131 (44.2%) affected by mucCRLM fulfilled the inclusion criteria. 118 mucCRLM were detected. FDG-PET/CT confirmed 71 (60.2%) CRLM in 51 patients. The sensitivity and specificity of FDG-PET/CT were 89.4% and 100% in the organ-based analysis and 60.7% and 100% in lesion-based analysis. Absence of micro-vascular invasion (100% vs. 23%, p 0.001) and median percentage of viable tumour cells were associated with FDG-PET/CT false negative (15% vs. 60%, p = 0.007). At ROC analysis viable tumour cells percentage25% was associated with low risk of false negative (AUC 0.848; p = 0.006).FDG-PET/CT had a significant rate of false negative results in patients with mucinous colorectal liver metastases. Negative FDG-PET/CT in patients with low percentage of viable tumour cells after chemotherapy should be considered with caution.

Background Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child–Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child–Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child–Pugh B cirrhosis. Methods Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. Results Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child–Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P Conclusion Patients without preoperative portal hypertension and Child–Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

Background: Only one third of patients with hepatocellular carcinoma can benefit from curative treatments at the time of first diagnosis. Tumor downstaging by radioembolization may enable initially unresectable hepatocellular carcinoma (HCC) to be treated with surgery lenghtening survival. Methods: From June 2011 through June 2014, all patients with a first diagnosis of unresectable HCC with intrahepatic portal vein thrombosis were treated in our center with radioembolization using 90-yttrium resin microspheres. A 3-year enrollment period and a 5-year follow-up were planned to adequately investigate survivals. Results: Twenty-four patients were enrolled, five were downstaged to surgery, eight did not reach downstaging but achieved partial response or stable disease, and eleven showed HCC progression despite radioembolization. High tumor absorbed radiation doses (454 vs . 248 and 138 Gy, P=0.005) and low serum AFP levels (53 vs . 1,447 and 4,603 ng/mL, P=0.05) were the variables significantly associated with successful downstaging. Mean and median survivals were 54, 30 and 11 months and 70, 24 and 11 months in the three groups respectively. No severe side effects were registered. Conclusions: In our center, about 20% of patients with locally advanced unresectable hepatocellular carcinoma were successfully downstaged to surgery after radioembolization. This strategy increases survival and is associated with an excellent safety profile.

Background: We aimed to assess the ability of comprehensive complication index (CCI) and Clavien-Dindo complication (CDC) scale to predict excessive length of hospital stay (e-LOS) in patients undergoing liver resection for hepatocellular carcinoma. Methods: Patients were identified from an Italian multi-institutional database and randomly selected to be included in either a derivation or validation set. Multivariate logistic regression models and ROC curve analysis including either CCI or CDC as predictors of e-LOS were fitted to compare predictive performance. E-LOS was defined as a LOS longer than the 75th percentile among patients with at least one complication. Results: A total of 2669 patients were analyzed (1345 for derivation and 1324 for validation). The odds ratio (OR) was 5.590 (95%CI 4.201, 7.438) for CCI and 5.507 (4.152, 7.304) for CDC. The AUC was 0.964 for CCI and 0.893 for CDC in the derivation set and 0.962 vs. 0.890 in the validation set, respectively. In patients with at least two complications, the OR was 2.793 (1.896, 4.115) for CCI and 2.439 (1.666, 3.570) for CDC with an AUC of 0.850 and 0.673, respectively in the derivation cohort. The AUC was 0.806 for CCI and 0.658 for CDC in the validation set. Conclusions: When reporting postoperative morbidity in liver surgery, CCI is a preferable scale.

Background Several studies have described a worse prognosis for right-sided colon cancer compared to left-sided. The aim of this study was to compare patterns of recurrence and survival following resection of liver metastases (LM) from right-sided (RS) versus left-sided (LS) colon cancer. Methods Patients undergoing resection for colon cancer LM between 2000 and 2017 were analyzed. Rectal cancer, multiple primaries and unknown location were excluded. Results Out of 995 patients, 686 fulfilled inclusion criteria (RS-LM = 322, LS-LM = 364). RS colon cancer had higher prevalence of metastatic lymph nodes (67.4% vs. 57.1%, P = 0.008). RS-LM were more often mucinous (16.8% vs. 8.5%, P = 0.001) and G3 (58.3% vs. 48.9%, P = 0.014). 451 (65.7%) patients experienced recurrence (RS-LM 68.9% vs. LS-LM 62.9%). In RS-LM group, recurrence was more often encephalic (2.3% vs. 0%, P = 0.029) and at multiple sites (34.2% vs. 23.5%, P = 0.012). The rate of re-resection was lower in RS-LM patients (27.9% vs. 37.5%, P = 0.024). Multivariate analysis showed RS-LM to have worse 5-year overall (35.8% vs. 51.2%, P = 0.002) and disease-free survival (26% vs. 43.6%, P = 0.002). Conclusions RS-LM is associated with worse survival and aggressive recurrences, with lower chance of re-resection.

This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry.LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment.A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis.Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.Este estudio tuvo como objetivo evaluar los mejores resultados que se pueden conseguir en la resección hepática laparoscópica (laparoscopic liver resection, LLR) después del ajuste por riesgos basado en la dificultad de la técnica quirúrgica utilizando un registro nacional. MÉTODOS: Se consideraron las LLRs incluidas en el Registro del Grupo Italiano de Cirugía Hepática Mínimamente Invasiva desde 11/2014 a 03/2018. Los resultados de referencia (benchmarks) se calcularon de acuerdo con el Achievable Benchmark of Care (ABC™). Las LLRs de cada uno de los centros se dividieron en 3 grupos (Grupo I, II y III) en base a la clasificación de Kawaguchi. Se calculó el ABC de la morbilidad global y de la morbilidad mayor para cada grupo. Se realizó un análisis multivariable para identificar los factores independientes de riesgos para la morbilidad global y morbilidad mayor. Se utilizaron variables significativas para realizar ajustes de riesgo adicionales.Un total de 1.752 pacientes de los 2.263 cumplían los criterios de inclusión, de los cuales 1.096 (62,6%) se incluyeron en el Grupo I, 435 (24,8%) en el Grupo II y 221 (12,6%) en el Grupo III. El ABC de la morbilidad global (7,8%, 14,2%, 26,4%) y de la morbilidad mayor (1,4%, 2,2%, 5,7%) aumentó del Grupo I al Grupo III. El análisis multivariable mostró un incremento del riesgo para la morbilidad global asociada con múltiples LLRs (razón de oportunidades, odds ratio, OR 1,349), resección intestinal simultánea (OR 3,760) y cirrosis (OR 1,825), y para la morbilidad mayor con la resección intestinal (OR 4,606). Los ABC de la morbilidad global y morbilidad mayor fueron 14,4% y 3,2% para las LLR múltiples, 30% y 11% para la resección intestinal, y 14,9% y 4,8% para la cirrosis, respectivamente. CONCLUSIÓN: Los resultados de referencia (benchmark) para la morbilidad global y morbilidad mayor en la LLR variaron entre un 8% y un 26% y entre un 1,4% y un 5,7%, dependiendo de la complejidad. Los valores de referencia deberían ajustarse de acuerdo con la práctica de LLRs múltiples o resección intestinal simultánea y cirrosis.

Failure of portal vein ligation (PVL) to induce hypertrophy is not uncommon. The aim of the study was to evaluate the impact of intraportal alcohol injection prior to ligation on liver regeneration.Forty-two patients with colorectal liver metastases who underwent PVL between 01/2004 and 06/2014 were analyzed. Beginning in 09/2011, alcohol was injected prior to PVL. Patients treated with PVL alone (Alc- group) were compared with those treated with alcohol injection plus PVL (Alc+ group). Liver regeneration was assessed by volumetric increase (VI).Alc+ (23 patients) and Alc- (19 patients) groups were similar in terms of age, sex and pre-PVL FLRV. Alc- group had a higher risk of recanalization (12 vs. 1, p 0.001) and cavernous transformation (7 vs. 2, p = 0.055) of the occluded portal vein. Post-PVL FLRV (43.3 ± 14.3% vs. 34.6 ± 6.4%, p = 0.013) and VI (0.44 ± 0.24 vs. 0.28 ± 0.20, p = 0.029) were higher in Alc+ group. On multivariate analysis male sex (B = -0.149) and alcohol injection (B = 0.143) significantly predicted VI.Alcohol injection prior to PVL may increase the regeneration of the FLRV by reducing the recanalization of the occluded portal vein.