The pan - COVID - AGICT study. The impact of COVID-19 pandemic on surgically treated pancreatic cancer patients. A multicentric Italian study.

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic. METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020. RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001). CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.

Impact of neoadjuvant chemotherapy on short-term outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases: A propensity-score matched and coarsened exact matched study.

BACKGROUND: In the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood. METHODS: A multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed. RESULTS: 2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy. CONCLUSION: Neoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases.

[The telephone follow-up by a nurse case manager in major surgery. A prospective observational study]. / Il follow-up infermieristico telefonico nell'ambito del case management in chirurgia maggiore. Uno studio osservazionale prospettico.

. The telephone follow-up by a nurse case manager in major surgery. A prospective observational study. INTRODUCTION: One of the methods used in case management is a structured telephone follow-up, helpful in improving patient satisfaction, supporting autonomy, and addressing information needs post-discharge. OBJECTIVE: To describe the experience of nursing case management and post-hospital telephone follow-up in patients undergoing major abdominal surgery. METHOD: Single-centre prospective observational study. All consecutive patients undergoing major abdominal surgery from April 2021 to May 2022 were included. Symptoms and nursing care needs during the post-discharge period, along with case management interventions, were described. RESULTS: Of the 205 patients included in the study, 89.8% underwent elective surgery and 135 (65.9%) did not develop postoperative complications, with a median hospital stay of 8 days. 182 (88.8%) patients reported at least one postoperative symptom, with fatigue, altered bowel movements, pain, and lack of appetite being the most common. Interventions provided by the case manager decreased progressively over time, from 149 at the first telephone contact (72%) to 44 at the third (25%). A total of 22 patients (10.7%) were readmitted to the hospital, 12 of whom on the recommendation of the case manager. CONCLUSIONS: After discharge, patients experience numerous issues: although the symptoms encountered are common during the post-operative period, they often require support beyond the patient's capacity. The intervention of the case manager with information and support for self-management of symptoms enabled the early identification of risk situations.

Laparoscopic versus open parenchymal sparing liver resections for high tumour burden colorectal liver metastases: a propensity score matched analysis.

BACKGROUND: Laparoscopic liver resection (LLR) has proved effective in the treatment of oligometastatic disease (1 or 2 colorectal liver metastases CRLM) with similar long-term outcomes and improved short-term results compared to open liver resection (OLR). Feasibility of parenchymal sparing LLR for high tumour burden diseases is largely unknown. Aim of the study was to compare short and long-term results of LLR and OLR in patients with ≥ 3 CRLM. METHODS: Patients who underwent first LR of at least two different segments for ≥ 3 CRLM between 01/2012 and 12/2021 were analysed. Propensity score nearest-neighbour 1:1 matching was based on relevant prognostic factors. RESULTS: 277 out of 673 patients fulfilled inclusion criteria (47 LLR and 230 OLR). After match two balanced groups of 47 patients with a similar mean number of CRLM (5 in LLR vs 6.5 in OLR, p = 0.170) were analysed. The rate of major hepatectomy was similar between the two group (10.6% OLR vs. 12.8% LLR). Mortality (2.1% OLR vs 0 LLR) and overall morbidity rates (34% OLR vs 23.4% LLR) were comparable. Length of stay (LOS) was shorter in the LLR group (5 vs 9 days, p = 0.001). No differences were observed in median overall (41.1 months OLR vs median not reached LLR) and disease-free survival (18.3 OLR vs 27.9 months LLR). CONCLUSION: Laparoscopic approach should be considered in selected patients scheduled to parenchymal sparing LR for high tumour burden disease as associated to shorter LOS and similar postoperative and long-term outcomes compared to the open approach.

Colorectal metastases with intrabiliary growth: incidence, treatment, and outcomes.

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. From 01/2010 to 12/2020, 999 patients underwent hepatectomy for colorectal metastases. Clinicopathological variables were retrospectively analyzed from a prospective-collected database of patients with or without IG. A propensity score matched (PSM) analysis to compare OS and DFS was performed. 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 tumor 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 (1.4 mm) and no-IG (2 mm). Five-year 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. According to PSM, 145 patients with no-IG were compared to 29 of IG group. After PSM, OS and DFS did not show any statistically significant difference. IG has similar oncological outcomes of resected colorectal metastases without IG, although it affects surgical management.

Robotic versus Laparoscopic Liver Resection in Various Settings: An International Multicenter Propensity Score Matched Study of 10.075 Patients.

OBJECTIVE: The aim of this study was to compare the perioperative outcomes of robotic liver surgery (RLS) and laparoscopic liver surgery (LLS) in various settings. SUMMARY BACKGROUND DATA: Clear advantages of RLS over LLS have rarely been demonstrated, and the associated costs of robotic surgery are generally higher than those of laparoscopic surgery. Therefore, the exact role of the robotic approach in minimally invasive liver surgery remains to be defined. METHODS: In this international retrospective cohort study, the outcomes of patients who underwent RLS and LLS for all indications between 2009 and 2021 in 34 hepatobiliary referral centers were compared. Subgroup analyses were performed to compare both approaches across several types of procedures: minor resections in the anterolateral (2, 3, 4b, 5, and 6) or posterosuperior segments (1, 4a, 7, 8), and major resections (≥3 contiguous segments). Propensity score matching (PSM) was used to mitigate the influence of selection bias. The primary outcome was textbook outcome in liver surgery (TOLS), previously defined as the absence of intraoperative incidents ≥grade 2, postoperative bile leak ≥grade B, severe morbidity, readmission, and 90-day or in-hospital mortality with the presence of an R0 resection margin in case of malignancy. The absence of a prolonged length of stay was added to define TOLS+. RESULTS: Among the 10.075 included patients, 1.507 underwent RLS and 8.568 LLS. After PSM, both groups constituted 1.505 patients. RLS was associated with higher rates of TOLS (78.3% vs. 71.8%, P<0.001) and TOLS+ (55% vs. 50.4%, P=0.026), less Pringle usage (39.1% vs. 47.1%, P<0.001), blood loss (100 vs. 200 milliliters, P<0.001), transfusions (4.9% vs. 7.9%, P=0.003), conversions (2.7% vs 8.8%, P<0.001), overall morbidity (19.3% vs. 25.7%, P<0.001) and R0 resection margins (89.8% vs. 86%, P=0.015), but longer operative times (190 vs. 210 min, P=0.015). In the subgroups, RLS tended to have higher TOLS rates, compared to LLS, for minor resections in the posterosuperior segments (n=431 per group, 75.9% vs. 71.2%, P=0.184) and major resections (n=321 per group, 72.9% vs. 67.5%, P=0.086), although these differences did not reach statistical significance. CONCLUSIONS: While both producing excellent outcomes, RLS might facilitate slightly higher TOLS rates than LLS.

HistoEM: A Pathologist-Guided and Explainable Workflow Using Histogram Embedding for Gland Classification.

Pathologists have, over several decades, developed criteria for diagnosing and grading prostate cancer. However, this knowledge has not, so far, been included in the design of convolutional neural networks (CNN) for prostate cancer detection and grading. Further, it is not known whether the features learned by machine-learning algorithms coincide with diagnostic features used by pathologists. We propose a framework that enforces algorithms to learn the cellular and subcellular differences between benign and cancerous prostate glands in digital slides from hematoxylin and eosin-stained tissue sections. After accurate gland segmentation and exclusion of the stroma, the central component of the pipeline, named HistoEM, utilizes a histogram embedding of features from the latent space of the CNN encoder. Each gland is represented by 128 feature-wise histograms that provide the input into a second network for benign vs cancer classification of the whole gland. Cancer glands are further processed by a U-Net structured network to separate low-grade from high-grade cancer. Our model demonstrates similar performance compared with other state-of-the-art prostate cancer grading models with gland-level resolution. To understand the features learned by HistoEM, we first rank features based on the distance between benign and cancer histograms and visualize the tissue origins of the 2 most important features. A heatmap of pixel activation by each feature is generated using Grad-CAM and overlaid on nuclear segmentation outlines. We conclude that HistoEM, similar to pathologists, uses nuclear features for the detection of prostate cancer. Altogether, this novel approach can be broadly deployed to visualize computer-learned features in histopathology images.

Laparoscopic Liver Tunnel for Tumors at the Hepatocaval Confluence.

BACKGROUND: Tumors at the hepatocaval confluence can be treated with parenchyma-sparing surgery, also with minimally invasive approach.1,2 The "Liver Tunnel" was described for tumors involving the paracaval portion of Sg1 in contact or infiltrating the middle hepatic vein (MHV).3 A "Liver Tunnel" with laparoscopic approach is proposed. METHODS: A 48-year-old woman was referred for three synchronous colorectal liver metastases in the paracaval portion of Sg1 in contact with the inferior vena cava and the MHV, in Sg8 ventral and in Sg6, after an urgent left laparoscopic hemicolectomy for an obstructing carcinoma. A laparoscopic Sg1 resection extended to Sg8 ventral were planned after neoadjuvant chemotherapy. Estimated future liver remnant (FLR) was 75% (840 ml) of healthy liver (Fig. 1). In case of right hepatectomy extended to Sg1, estimated FLR was 25% (280 ml) of healthy liver. Fig. 1 3D reconstruction and intraoperative images of Liver Tunnel (A) and Sg6 resection (B). Total liver volume: 1110 ml. Total resected liver volume 270 ml: Liver Tunnel 93 ml; Sg6 177 ml. Liver volumes were measured with HA3D™ technology with Medics3D software (Medics3D, Turin, Italy) RESULTS: Pneumoperitoneum is established, and four operative ports are placed. Sg1 is approached from the left, dividing the Glissonean pedicles and short hepatic veins. MHV is approached cranio-caudally from the dorsal side. The resection continues on the ventral side, according to our "Ultrasound Liver Map technique" with a cranio-caudal approach to the MHV.4 Sg8 ventral pedicles are divided and the resection completed with aid of indocyanine green negative staining. A Sg6 resection is then performed. Operative time was 480 min. Blood loss was 100 ml. The postoperative course was uneventful, and the patient was discharged on fourth postoperative day. The two parenchyma-sparing resections saved an estimated volume of 75% (840 ml) of healthy liver (Fig. 1). The estimated remnant liver volume after a right hepatectomy extended to Sg1 would have been only 25%. CONCLUSIONS: Tumors at the hepatocaval confluence involving Sg1 can be removed with the "Liver Tunnel," which can be performed with minimally invasive approach. The "Laparoscopic Liver Tunnel" pushes further the limit of minimally invasive parenchyma-sparing surgery for ill-located tumors with complex vascular relationship.

Combined hepatocellular-cholangiocarcinoma compared to hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Different survival, similar recurrence: Report of a large study on repurposed databases with propensity score matching.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Trends in the characteristics and perioperative outcomes of patients undergoing laparoscopic and open resections for benign liver lesions: An international multicenter retrospective cohort study of 845 patients.

BACKGROUND: Solid benign liver lesions (BLL) are increasingly discovered, but clear indications for surgical treatment are often lacking. Concomitantly, laparoscopic liver surgery is increasingly performed. The aim of this study was to assess if the availability of laparoscopic surgery has had an impact on the characteristics and perioperative outcomes of patients with BLL. METHODS: This is a retrospective international multicenter cohort study, including patients undergoing a laparoscopic or open liver resection for BLL from 19 centers in eight countries. Patients were divided according to the time period in which they underwent surgery (2008-2013, 2014-2016, and 2017-2019). Unadjusted and risk-adjusted (using logistic regression) time-trend analyses were performed. The primary outcome was textbook outcome (TOLS), defined as the absence of intraoperative incidents ≥ grade 2, bile leak ≥ grade B, severe complications, readmission and 90-day or in-hospital mortality, with the absence of a prolonged length of stay added to define TOLS+. RESULTS: In the complete dataset comprised of patients that underwent liver surgery for all indications, the proportion of patients undergoing liver surgery for benign disease remained stable (12.6% in the first time period, 11.9% in the second time period and 12.1% in the last time period, p = 0.454). Overall, 845 patients undergoing a liver resection for BLL in the first (n = 374), second (n = 258) or third time period (n = 213) were included. The rates of ASA-scores≥3 (9.9%-16%,p < 0.001), laparoscopic surgery (57.8%-77%,p < 0.001), and Pringle maneuver use (33.2%-47.2%,p = 0.001) increased, whereas the length of stay decreased (5 to 4 days,p < 0.001). There were no significant changes in the TOLS rate (86.6%-81.3%,p = 0.151), while the TOLS + rate increased from 41.7% to 58.7% (p < 0.001). The latter result was confirmed in the risk-adjusted analyses (aOR 1.849,p = 0.004). CONCLUSION: The surgical treatment of BLL has evolved with an increased implementation of the laparoscopic approach and a decreased length of stay. This evolution was paralleled by stable TOLS rates above 80% and an increase in the TOLS + rate.

Cure Probabilities After Resection Of Pancreatic Ductal Adenocarcinoma: A Multi-Institutional Analysis Of 2554 Patients.

OBJECTIVE: To assess the probability of being cured from pancreatic ductal adenocarcinoma (PDAC) by pancreatic surgery. SUMMARY BACKGROUND DATA: Statistical cure implies that a patient treated for a specific disease will have the same life expectancy as if he/she never had that disease. METHODS: Patients who underwent pancreatic resection for PDAC between 2010 and 2021 were retrospectively identified using a multi-institutional database. A non-mixture statistical cure model was applied to compare disease-free survival to the survival expected for matched general population. RESULTS: Among 2554 patients, either in the setting of upfront (n=1691) or neoadjuvant strategy (n=863), the cure model showed that the probability that surgery would offer the same life-expectancy (and tumor-free) as the matched general population was 20.4% (95%CI: 18.3, 22.5). Cure likelihood reached the 95% of certainty (time-to-cure) after 5.3 years (95%CI: 4.7, 6.0). A preoperative model was developed based on tumor stage at diagnosis (P=0.001), radiological size (P=0.001), response to chemotherapy (P=0.007), American Society of Anesthesiology class (P=0.001) and pre-operative Ca19-9 (P=0.001). A post-operative model with the addition of surgery type (P=0.015), pathological size (P=0.001), tumour grading (P=0.001), resection margin (P=0.001), positive lymphnode ratio (P=0.001) and the receipt of adjuvant therapy (P=0.001) was also developed. CONCLUSIONS: Patients operated for PDAC can achieve a life-expectancy similar to that of general population and the likelihood of cure increases with the passage of recurrence-free time. An online calculator was developed and available at https://aicep.website/?cff-form=15.

Circulating autoantibodies to alpha-enolase (ENO1) and far upstream element-binding protein 1 (FUBP1) are negative prognostic factors for pancreatic cancer patient survival.

Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis due to a lack of early diagnostic markers and effective therapy. In PDA patients, the glycolytic enzyme and plasminogen receptor alpha-enolase (ENO1) and the transcription factor far upstream element-binding protein 1 (FUBP1) are upregulated and elicit the production of autoantibodies (aAb) that discriminate healthy subjects from PDA patients, with the latter mostly directed to post-translational phosphorylated isoforms. Here, the correlation of prognosis with circulating ENO1 and FUBP1aAb, and their protein tissue expression was analyzed in PDA patients. Circulating ENO1 and FUBP1 aAb was analyzed in two cohorts of PDA patients by ELISA (n = 470), while tissues expression was observed by immunohistochemistry (n = 45). Overall survival (OS) was estimated using the Kaplan-Meier method, while the Cox model was used to estimate the hazard ratios (HR) adjusted for the main prognostic factors. Logistic models were applied to assess associations between death and its risk indicators. All statistical analyses were performed with Stata version 15. Unlike ENO1 aAb, there was a significant correlation between FUBP1 aAb and FUBP1 expression in tumors (p = 0.0268). In addition, we found that high ENO1 (p = 0.016) and intermediate FUBP1 aAb levels (p = 0.013) were unfavorable prognostic factors. Notably, it was found that high anti-FUBP1 aAb level is a good prognostic marker for tail-body PDA (p = 0.016). Our results suggest that different levels of circulating aAb to ENO1 and FUBP1 predict a poor outcome in PDA patients and can be used to improve therapeutic strategies.

Radiomic Analysis of Intrahepatic Cholangiocarcinoma: Non-Invasive Prediction of Pathology Data: A Multicenter Study to Develop a Clinical-Radiomic Model.

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.

ERS: A simple scoring system to predict early recurrence after surgical resection for hepatocellular carcinoma.

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.

Results from the european survey on preoperative management and optimization protocols for PeriHilar cholangiocarcinoma.

BACKGROUND: Major surgery, along with preoperative cholestasis-related complications, are responsible for the increased risk of morbidity and mortality in perihilar cholangiocarcinoma (pCCA). The aim of the present survey is to provide a snapshot of current preoperative management and optimization strategies in Europe. METHODS: 61 European centers, experienced in hepato-biliary surgery completed a 59-questions survey regarding pCCA preoperative management. Centers were stratified according to surgical caseload (<5 and ≥ 5 cases/year) and preoperative management protocols' application. RESULTS: The overall case volume consisted of 6333 patients. Multidisciplinary discussion was routinely performed in 91.8% of centers. Most respondents (96.7%) recognized the importance of a well-structured preoperative protocol. The preferred method for biliary drainage was percutaneous transhepatic biliary drainage (60.7%) while portal vein embolization was the preferred technique for liver hypertrophy (90.2%). Differences in preoperative pathologic confirmation of malignancy (35.8% vs 28.7%; p < 0.001), number of mismanaged referred patients (88.2% vs 50.8%; p < 0.001), biliary drainage (65.1% vs 55.6%; p = 0.015) and liver function evaluation (37.2% vs 5.6%; p = 0.001) were found between centers according to groups' stratification. CONCLUSION: The importance of a correct preoperative management is recognized. Nevertheless, the current lack of guidelines leads to wide heterogeneity of behaviors among centers. This survey can provide recommendations to improve pCCA perioperative outcomes.

Impact of liver cirrhosis and portal hypertension on minimally invasive limited liver resection for primary liver malignancies in the posterosuperior segments: An international multicenter study.

INTRODUCTION: To assess the impact of cirrhosis and portal hypertension (PHT) on technical difficulty and outcomes of minimally invasive liver resection (MILR) in the posterosuperior segments. METHODS: This is a post-hoc analysis of patients with primary malignancy who underwent laparoscopic and robotic wedge resection and segmentectomy in the posterosuperior segments between 2004 and 2019 in 60 centers. Surrogates of difficulty (i.e, open conversion rate, operation time, blood loss, blood transfusion, and use of the Pringle maneuver) and outcomes were compared before and after propensity-score matching (PSM) and coarsened exact matching (CEM). RESULTS: Of the 1954 patients studied, 1290 (66%) had cirrhosis. Among the cirrhotic patients, 310 (24%) had PHT. After PSM, patients with cirrhosis had higher intraoperative blood transfusion (14% vs. 9.3%; p = 0.027) and overall morbidity rates (20% vs. 14.5%; p = 0.023) than those without cirrhosis. After coarsened exact matching (CEM), patients with cirrhosis tended to have higher intraoperative blood transfusion rate (12.1% vs. 6.7%; p = 0.059) and have higher overall morbidity rate (22.8% vs. 12.5%; p = 0.007) than those without cirrhosis. After PSM, Pringle maneuver was more frequently applied in cirrhotic patients with PHT (62.2% vs. 52.4%; p = 0.045) than those without PHT. CONCLUSION: MILR in the posterosuperior segments in cirrhotic patients is associated with higher intraoperative blood transfusion and postoperative morbidity. This parameter should be utilized in the difficulty assessment of MILR.

Impact of Tumor Size on the Difficulty of Laparoscopic Major Hepatectomies: An International Multicenter Study.

INTRODUCTION: Although tumor size (TS) is known to affect surgical outcomes in laparoscopic liver resection (LLR), its impact on laparoscopic major hepatectomy (L-MH) is not well studied. The objectives of this study were to investigate the impact of TS on the perioperative outcomes of L-MH and to elucidate the optimal TS cutoff for stratifying the difficulty of L-MH. METHODS: This was a post-hoc analysis of 3008 patients who underwent L-MH at 48 international centers. A total 1396 patients met study criteria and were included. The impact of TS cutoffs was investigated by stratifying TS at each 10-mm interval. The optimal cutoffs were determined taking into consideration the number of endpoints which showed a statistically significant split around the cut-points of interest and the magnitude of relative risk after correction for multiple risk factors. RESULTS: We identified 2 optimal TS cutoffs, 50 mm and 100 mm, which segregated L-MH into 3 groups. An increasing TS across these 3 groups (≤ 50 mm, 51-100 mm, > 100 mm), was significantly associated with a higher open conversion rate (11.2%, 14.7%, 23.0%, P < 0.001), longer operating time (median, 340 min, 346 min, 365 min, P = 0.025), increased blood loss (median, 300 ml,  ml, 400 ml, P = 0.002) and higher rate of intraoperative blood transfusion (13.1%, 15.9%, 27.6%, P < 0.001). Postoperative outcomes such as overall morbidity, major morbidity, and length of stay were comparable across the three groups. CONCLUSION: Increasing TS was associated with poorer intraoperative but not postoperative outcomes after L-MH. We determined 2 TS cutoffs (50 mm and 10 mm) which could optimally stratify the surgical difficulty of L-MH.