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Background: Treatment of hepatocellular carcinoma (HCC) is predicated on early diagnosis such that 'curative therapies' can be successfully applied. The term 'curative' is, however, poorly quantitated. We aimed to complement our previous work by developing a statistical model to predict cure after ablation and to use this analysis to compare the true curative potential of the various 'curative' therapies. Methods: We accessed data from 1571 HCC patients treated in 5 centres receiving radiofrequency (RFA) or microwave (MWA) ablation and used flexible parametric modelling to determine the curative fraction. The results of this analysis were then combined with our previous estimations to provide a simple calculator applicable to all patients undergoing potentially curative therapies. Results: The cure fraction was 18.3% rising to about 40% in patients with good liver function and very small tumours. Conclusion: Cure for HCC treated with ablation occurs in the order of 20% to 30%, similar to that achievable by resection but much inferior to transplantation where the analogous figure is >70%. We provide a 'calculator' that permits clinicians to estimate the chance of cure for any individual patient, based on readily available clinical features. [ABSTRACT FROM AUTHOR]

Background: This cross-sectional survey aimed to determine whether fluorescence cholangiography using indocyanine green (ICG-FC) can improve the detection of the cystic duct and the main bile duct during laparoscopic cholecystectomy (LC). Methods: The survey was distributed to 214 surgeons (residents/faculties) in 2021. The confidence in the identification of the cystic duct and of the main bile duct was elicited on a 10-point Likert scale before/after the use of ICG-FC. This was repeated for three LCs ranging from a procedure deemed easy to a LC for acute cholecystitis. Results: There were 149 responses. ICG-FC increased the responders' confidence in identifying the cystic duct, raising the median value from 6 (IQR, 5–8) with white light up to 9 (IQR, 9–10) with ICG-FC (paired p < 0.001). This increase was even more evident when identifying the main bile duct, where the median confidence value increased from 5 (IQR, 4–7) with white light to 9 (IQR, 8–10) with the use of ICG-FC (p < 0.001). ICG-FC significantly increased the detection of residents of the main bile duct in case of intermediate difficulty LCs and in LCs for acute cholecystitis. Conclusions: The results support that the use of near-infrared imaging can ameliorate detection of biliary structures, especially of the main bile duct and this was particularly true for young surgeons and in more complex situations. [ABSTRACT FROM AUTHOR]

Background: Although gallstone disease increases with aging, elderly patients are less likely to undergo cholecystectomy. This is because age itself is a negative predictor after cholecystectomy. The ACS-NSQIP risk calculator can therefore help surgeons decide whether to operate or not. However, little is known about the accuracy of this model outside the ACS National Surgical Quality Improvement Program. The aim of the present study is to evaluate the ability of the ACS-NSQIP model to predict the clinical outcomes of patients aged 80 years or older undergoing elective or emergency cholecystectomy. Study design: The study focused on 263 patients over 80 years of age operated on between 2010 and 2019: 174 were treated as emergencies because of acute cholecystitis (66.2%). Outcomes evaluated are those predicted by the ACS-NSQIP calculator within 30 days of surgery. The ACS-NSQIP model was tested for both discrimination and calibration. Differences among observed and expected outcomes were evaluated. Results: When considering all patients, the discrimination of mortality was very high, as it was that of severe complications. Considering only the elective cholecystectomies, the discrimination capacity of ACS-NSQIP risk calculator has consistently worsened in each outcome while it remains high considering the emergency cholecystectomies. In the evaluation of the emergency cholecystectomy, the model showed a very high discriminatory ability and, more importantly, it showed an excellent calibration. Comparisons between main outcomes showed small or even negligible differences between observed and expected values. Conclusion: The results of the present study suggest that clinical decisions on cholecystectomy in a patient aged 80 years or older should be assisted through the ACS-NSQIP model. [ABSTRACT FROM AUTHOR]

This study investigated how material deprivation in Italy influences the stage of hepatocellular carcinoma (HCC) at diagnosis and the chance of cure. 4114 patients from the Italian Liver Cancer database consecutively diagnosed with HCC between January 2008 and December 2018 were analysed about severe material deprivation (SMD) rate tertiles of the region of birth and region of managing hospitals, according to the European Statistics on Income and Living Conditions. The main outcomes were HCC diagnosis modalities (during or outside surveillance), treatment adoption and overall survival. In more deprived regions, HCC was more frequently diagnosed during surveillance, while the incidental diagnosis was prevalent in the least deprived. Tumour characteristics did not differ among regions. The proportion of patients undergoing potentially curative treatments progressively decreased as the SMD worsened. Consequently, overall survival was better in less deprived regions. Patients who moved from most deprived to less deprived regions increased their probability of receiving potentially curative treatments by 1.11 times (95% CI 1.03 to 1.19), decreasing their mortality likelihood (hazard ratio 0.78 95% CI 0.67 to 0.90). Socioeconomic status measured through SMD does not seem to influence HCC features at diagnosis but brings a negative effect on the chance of receiving potentially curative treatments. Patient mobility from the most deprived to the less deprived regions increased the access to curative therapies, with the ultimate result of improving survival. • A Multicentre Italian study on the impact of material deprivation on hepatocellular carcinoma (HCC) outcome. • Patients were stratified according to the material deprivation rate of Italian regions. • HCC survival was better in less deprived Italian regions. • Migration from most to less deprived regions improved HCC survival. • Effect of deprivation was mainly because of different access to HCC curative treatments. [ABSTRACT FROM AUTHOR]

Background and aims: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. Methods: We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008‐2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter‐relationship determining overall survival. Results: MaVI prevalence was 11.1%, and median survival of these patients was 6.0 months (95% CI, 5.1‐7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4 months in those with PS > 1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1 months in patients with PS 0‐1, no ascites and Vp1‐Vp2 MaVI (treated with surgery in 19.1% of cases). Conclusions: MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions. [ABSTRACT FROM AUTHOR]

Objectives: Results after trans-arterial radioembolisation (TARE) for intrahepatic cholangiocarcinoma (iCC) depend on the architecture of the tumour. This latter can be quantified through computed tomography (CT) texture analysis. The aims of the present study were to analyse relationships between CT textural features prior to TARE and objective response (OR), progression-free survival (PFS), and overall survival (OS).Methods: Texture analysis was retrospectively applied to 55 pre-TARE CT scans of iCCs, focusing attention on the histogram-based features and the grey-level co-occurrence matrix (GLCM). Texture features were harmonised using the ComBat procedure. Objective response was assessed using the Response Evaluation Criteria In Solid Tumours 1.1. The least absolute shrinkage and selection operator (LASSO) method was applied to select the most useful textural features related to OR.Results: Of the 55 patients, 53 had post-TARE imaging available, showing OR in 56.6% of cases. Texture analysis showed that iCCs showing OR after TARE had a higher uptake of iodine contrast in the arterial phase (higher mean histogram values, p < 0.001) and more homogeneous distribution (lower kurtosis, p = 0.043; GLCM contrast, p = 0.004; GLCM dissimilarity, p = 0.005, and higher GLCM homogeneity, p = 0.005; and GLCM correlation p = 0.030) at the pre-TARE CT scan. A favourable radiomic signature was calculated and observed in 15 of the 55 patients. The median PFS of these 15 patients was 12.1 months and that of the remaining 40 patients was 5.1 months (p = 0.008).Conclusions: Texture analysis of pre-TARE CT scans can quantify vascularisation and homogeneity of iCC architecture, providing clinical information useful in identifying ideal TARE candidates.Key Points: • Hypervascular tumours with a more homogeneous uptake of iodine contrast in the arterial phase were those most likely to be effectively treated by TARE. • The arterial phase was observed to be the best acquisition phase for providing information regarding the "sensitivity" of the tumour to TARE. • Patients with favourable radiomic signature showed a median progression-free survival of 12.1 months versus 5.1 months of patients with an unfavourable signature (p = 0.008). [ABSTRACT FROM AUTHOR]

In the context of liver transplantation (LT) for hepatocellular carcinoma (HCC), prediction models are used to ensure that the risk of post-LT recurrence is acceptably low. However, the weighting that 'response to neoadjuvant therapies' should have in such models remains unclear. Herein, we aimed to incorporate radiological response into the Metroticket 2.0 model for post-LT prediction of "HCC-related death", to improve its clinical utility. Data from 859 transplanted patients (2000-2015) who received neoadjuvant therapies were included. The last radiological assessment before LT was reviewed according to the modified RECIST criteria. Competing-risk analysis was applied. The added value of including radiological response into the Metroticket 2.0 was explored through category-based net reclassification improvement (NRI) analysis. At last radiological assessment prior to LT, complete response (CR) was diagnosed in 41.3%, partial response/stable disease (PR/SD) in 24.9% and progressive disease (PD) in 33.8% of patients. The 5-year rates of "HCC-related death" were 3.1%, 9.6% and 13.4% in those with CR, PR/SD, or PD, respectively (p <0.001). Log 10 AFP (p <0.001) and the sum of number and diameter of the tumour/s (p <0.05) were determinants of "HCC-related death" for PR/SD and PD patients. To maintain the post-LT 5-year incidence of "HCC-related death" <30%, the Metroticket 2.0 criteria were restricted in some cases of PR/SD and in all cases with PD, correctly reclassifying 9.4% of patients with "HCC-related death", at the expense of 3.5% of patients who did not have the event. The overall/net NRI was 5.8. Incorporating the modified RECIST criteria into the Metroticket 2.0 framework can improve its predictive ability. The additional information provided can be used to better judge the suitability of candidates for LT following neoadjuvant therapies. In the context of liver transplantation for patients with hepatocellular carcinoma, prediction models are used to ensure that the risk of recurrence after transplantation is acceptably low. The Metroticket 2.0 model has been proposed as an accurate predictor of "tumour-related death" after liver transplantation. In the present study, we show that its accuracy can be improved by incorporating information relating to the radiological responses of patients to neoadjuvant therapies. • Combining morphology and biology represents the most useful approach to select candidates for LT in the context of HCC. • To maintain post-LT 5-year incidence of "HCC-related death" <30%, Metroticket 2.0 criteria had to be restricted in some cases. • Adding mRECIST criteria to Metroticket 2.0 led to correct reclassification of 9.4% of patients with "HCC-related death". • This additional information can be used to better judge the suitability of candidates for LT following neoadjuvant therapies. [ABSTRACT FROM AUTHOR]

The popular sense of the word "cure" implies that a patient treated for a specific disease will return to have the same life expectancy as if he/she had never had the disease. In analytic terms, it translates into the concept of statistical cure which occurs when a group of patients returns to having similar mortality to a reference population. The aim of this study was to assess the probability of being cured from hepatocellular carcinoma (HCC) by hepatic resection. Data from 2,523 patients undergoing resection for HCC were used to fit statistical cure models, to compare disease-free survival (DFS) after surgery to the survival expected for patients with chronic hepatitis and/or cirrhosis and the general population, matched by sex, age, race/ethnicity and year of diagnosis. The probability of resection enabling patients with HCC to achieve the same life expectancy as those with chronic hepatitis and/or cirrhosis was 26.3%. The conditional probability of achieving this result was time-dependent, requiring about 8.9 years to be accomplished with 95% certainty. Considering the general population as a reference, the cure fraction decreased to 17.1%. Uncured patients had a median DFS of 1.5 years. In multivariable analysis, patient's age and the risk of early HCC recurrence (within 2 years) were independent determinants of the chance of cure (p <0.001). The chances of being cured ranged between 36.0% for individuals at low risk of early recurrence to approximately 3.6% for those at high risk. Estimates of the chance of being cured of HCC by resection showed that cure is achievable, and its likelihood increases with the passing of recurrence-free time. The data presented herein can be used to inform decision making and to provide patients with accurate information. Data from 2,523 patients who underwent resection for hepatocellular carcinoma were used to estimate the probability that resection would enable treated patients to achieve the same life expectancy as patients with chronic hepatitis and/or cirrhosis, and the general population. Herein, the cure model suggests that in patients with hepatocellular carcinoma, resection can enable patients to achieve the same life expectancy as those with chronic liver disease in 26.3% of cases and as the general population in 17.1% of cases. • DFS in resected patients with HCC was compared to DFS in those with chronic liver disease w/o HCC, and the general population. • Resected patients with HCC could achieve the same life expectancy as those with chronic liver disease in 26.3% of cases. • Resection enables patients with HCC to achieve the same life expectancy as the general population in 17.1% of cases. • Patients resected in more recent years had higher cure probabilities, probably due to effective antiviral therapies. [ABSTRACT FROM AUTHOR]

Background: An aging population combined with an increased colorectal cancer (CRC) incidence in the older population will increase its prevalence in the elderly, questioning how many years of life are lost (YLLs) in these patients. Patients and methods: Data from 32,568 Dutch CRC patients ≥ 80 years were used to estimate the number of YLLs after diagnosis, using a reference age-, sex- and year-of-onset-matched cohort derived from national life tables. YLLs were additionally adjusted by comorbidities. Number needed to treat (NNT) was used as measure of surgical effect size. Results: Surgery was applied in 74.9% of patients leading to 1.3 YLLs, being superior in 86.1% of cases with respect to alternative therapies (YLLs 4.8 years) and resulting in a number of two patients needed to operate to achieve one positive outcome. YLLs and NNTs depended on CRC stage, patient' age and comorbidities. For Stage I–II patients in the best clinical conditions (80–85 years without comorbidities), YLLs increased up to 4.1 years after surgery and up to 8.8 years without surgery (NNT 3). For Stage III patients, the NNT of surgery varied between 2 when they were in the best clinical conditions and 4 when they were older with high comorbidities. In Stage IV patients, the NNT ranged between 6 and 31. Conclusions: YLLs represents a novel approach to evaluate CRC prognosis. Stage I–III surgical patients can have a life expectancy similar to that of general population, being the NNT of surgery reasonably small compared with alternatives. Personalized comorbidity data are needed to confirm present findings. [ABSTRACT FROM AUTHOR]

This is because, outside well-defined protocols, patients can repeat TACE, can attempt radioembolization, can be resected or transplanted.13 That is, an uncritical use of TTP/PFS may introduce a bias in the medical decision-making, as tumour progression usually triggers treatment interruption. Trans-arterial chemoembolization (TACE) is the most common treatment adopted for patients with hepatocellular carcinoma (HCC) 1,2. Subsequently, authors reconstructed published survival curves after TACE,7 and pooled them using a random effect model.8 Because of the lack of some TTP or PFS data, these latter were pooled to TTP when necessary (producing a TTP/PFS). Using HRs, the R SP 2 sp consistently ameliorated being 0.65, meaning that the HR of TTP/PFS between TACE vs controls can be an adequate proxy of the final HR that will be observed for the OS. [Extracted from the article]

Hepatocellular carcinoma (HCC) as an indication to liver transplant (LT) started as palliative treatment, then moved to potentially curative anti-cancer therapy and more recently entered the era of competition with non-cancer indications, consequent to the need of the society to target equal distribution of the limited resource of donated organs among different indications. Nowadays HCC is a leading indication to LT, currently representing up to 50% of the indications in most transplant Centers. The risk of post-transplant death and the causes of mortality significantly vary along the post-transplant follow-up. Overall, the main causes of death after LT are multiple organ failure and cerebrovascular, cardiovascular, pulmonary, and renal complications. However, after the first post-LT year, mortality for technical complications, infections and general complications significantly decrease, while recurrence of primary liver diseases (particularly malignancies) increase, turning to be the main causes of death. In studies with time-to-event or survival outcomes, a competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. In the setting of LT for HCC, when the primary outcome of interest is death due to HCC recurrence, death due to causes different from this serves as a competing event because subjects who die from such different causes are no longer at risk of death due to HCC recurrence. The introduction of HCC-specific survival as a primary endpoint in studies assessing the outcomes of LT for HCC allows the identification of independent oncologic determinants of post-LT survival and their relative weight on patients' prognosis. In this view, a continuous model based on level of AFP, tumor size and tumor number that allows to determine the risk of death from HCC-related factors after liver transplantation ( www.hcc-olt-metroticket.org/ ) has been recently developed. Since the endpoint of HCC-specific survival is not influenced by the changes observed in short-term post-LT survival (thanks to advances in the clinical management) nor in long-term post-LT survival (thanks to the introduction of effective treatments achieving control of hepatitis B and C viruses), a model predicting HCC-specific survival will be an helpful prognostic tool in the context of the changing scenarios of LT for HCC. [ABSTRACT FROM AUTHOR]

Background & Aims Selective internal radiation therapy ( SIRT) is emerging as a potential therapy for unresectable intra-hepatic cholangiocarcinoma ( iCCA) able to prolong life-expectancy. Aim of this study was to collect available literature meta-analyse data and results and investigate sources of heterogeneity through a meta-regression approach before suggesting SIRT as a valuable option. Methods A systematic review of studies published until 1 September 2016 in PubMed and Scopus databases was performed. Patient survival was the primary outcome measure. Meta-analysis was performed using a random-effects model. Meta-regression was applied to investigate relationships existing between clinical and tumour features and the primary outcome. Results Nine observational studies were included in the analysis involving 224 patients. The 1-, 2- and 3-year pooled survival estimates were 55.7%, 33.1% and 20.2%. Clinical and tumour characteristics showed medium-to-considerable heterogeneity ( I2>50%). Meta-regression analysis showed that determinants of best survivals were the presence of mass-forming iCCA type (median survival=19.9 months vs 8.1 months for the infiltrative type; P=.002) that also accounted for most of the heterogeneity between included studies (residual I2=0); SIRT as first-line therapy (median survival=24 months vs 11.5 months for non-naïve patients; P=.048) and the adoption of concomitant chemotherapy (median survival 19.5 months vs 5.5 months in patients not receiving chemotherapy; P=.042). Conclusions There is considerable heterogeneity between studies highlighting that indications for SIRT are extremely varied. To ameliorate SIRT results naïve patients with mass-forming iCCA should be selected as the best candidates with the possibility of adding concomitant standard chemotherapy. [ABSTRACT FROM AUTHOR]

Background: In treating pancreatic ductal adenocarcinoma (PDAC), age does not represent a contraindication to surgery, even if aging is known to increase postoperative mortality and morbidity. Furthermore, long-term outcome remains poor and there is much debate on whether to operate or not in elderly patients. The aim of this study was to provide a general framework to evaluate the health gain obtainable from surgery for PDAC in relationship with age and tumor stage. Methods: A Monte Carlo simulation model was built taking into consideration pertinent literature from population-based studies regarding surgical and non-surgical outcomes for stages I-II PDAC. The health gain obtainable from surgery, in comparison to the choice of not resecting patients, was measured through number needed-to-treat (NNT) calculation. Results: Considering the typical stage I-II PDAC characteristics, the model showed that the mean lifespan after surgery was 28.1 ± 3.9 months and 9.3 ± 1.5 months after non-surgical therapies. The NNT with surgery in order to prevent one death at 5 years was 6 (95% CI 4-10), indicating an overall high gain obtainable from surgery. Sensitivity analyses on patient age and tumor stage suggested that starting from 76 years onward, the NNT progressively increases, resulting in a low cure rate of surgery in the elderly and becoming potentially harmful for patients aged above 80 years. These figures were more pronounced for tumor stages IIA and IIB. Conclusions: The present general framework suggests that the lifespan benefit obtainable from pancreatectomy in elderly patients is uncertain especially with the advancing of the tumor stage. [ABSTRACT FROM AUTHOR]

Aim Length time bias is a selection bias which can lead to an overestimation of survival of screening-detected cases caused by the relative excess of slower-growing tumors detected with respect to symptomatic cases. This leads to the incorrect perception that screening improves outcomes when it only selects tumors with a favorable biology. Data regarding this bias in surveillance for hepatocellular carcinoma (HCC) have never been provided. Methods A semi-Markov model was developed to investigate this issue. An exponential tumor growth was applied. During its growth, tumor diagnosis 'at surveillance appointments' was made when tumor attained a size equal to or above the size of tumors diagnosed in surveilled patients obtained from pertinent published reports, or 'in-between appointments' (due to the development of symptoms) if tumor size attained the size of symptomatic diagnosis, derived from published reports; otherwise the tumor continued to grow until the time horizon had been reached. Tumor doubling time (DT) values were recorded according to the method of diagnosis. Results In a theoretical cohort of 1000 patients submitted to semiannual surveillance, 72.5% will be diagnosed at a surveillance appointment and 18% because of symptom development, although under surveillance. Patients diagnosed with HCC at a surveillance appointment had a median tumor DT of 100 days (interquartile range, 68-143 days), whereas those diagnosed because of symptoms had a median DT of 42 days (interquartile range, 29-58 days) although under surveillance. Conclusion The surveillance propensity to detect slower-growth tumors is relevant, and practical suggestions to minimize this bias in longitudinal studies are provided. [ABSTRACT FROM AUTHOR]

Background & Aims To develop an individual prognostic calculator for patients with unresectable hepatocellular carcinoma ( HCC) undergoing trans-arterial chemo-embolization ( TACE). Methods Data from two prospective databases, regarding 361 patients who received TACE as first-line therapy (2000-2012), were reviewed in order to refine available prognostic tools and to develop a continuous individual web-based prognostic calculator. Patients with neoplastic portal vein invasion were excluded from the analysis. The model was built following a bootstrap resampling procedure aimed at identifying prognostic predictors and by carrying out a 10-fold cross-validation for accuracy assessment by means of Harrell's c-statistic. Results Number of tumours, serum albumin, serum total bilirubin, alpha-foetoprotein and maximum tumour size were selected as predictors of mortality following TACE with the bootstrap resampling technique. In the 10-fold cross-validation cohort, the model showed a Harrell's c-statistic of 0.649 (95% CI: 0.610-0.688), significantly higher than that of the Hepatoma Arterial-embolization Prognostic ( HAP) score (0.589; 95% CI: 0.552-0.626; P = 0.001) and of the modified HAP- II score (0.611; 95% CI: 0.572-0.650; P = 0.005). Akaike's information criterion for the model was 2520; for the mHAP- II it was 2544 and for the HAP score it was 2554. A web-based calculator was developed for quick consultation at . Conclusions The proposed individual prognostic model can provide an accurate prognostic prediction for each patient with unresectable HCC following treatment with TACE without class stratification. The availability of an online calculator can help physicians in daily clinical practice. [ABSTRACT FROM AUTHOR]

Backgrounds & Aims To assess the relationship existing between hepatic venous pressure gradient (HVPG) and the occurrence of post-hepatectomy liver failure (PHLF) grade B/C after resection of hepatocellular carcinoma (HCC) and persistent worsening of liver function. Methods Data from 70 consecutive prospectively enrolled HCC patients undergoing resection were collected and analysed. PHLF grade B/C was defined by the International Study Group of Liver Surgery recommendations. The appearance of unresolved decompensation was also analysed. Results Postoperative and 90-day mortality were null. The median HVPG value was 9 mmHg (range: 4–18) and the median Model for End-stage Liver Disease (MELD) score was 8 (range: 6–14); 34 patients had an HVPG ⩾10 mmHg (48.6%). Forty-nine patients had an uneventful (Grade A) postoperative course, including 17 with an HVPG ⩾10 mmHg (24.2% of 70 patients). Grade B complications occurred in 20 patients (3 with an HVPG <10 mmHg and 17 with an HVPG ⩾10 mmHg; p <0.001); only one grade C complication occurred in a patient with an HVPG <10 mmHg, subsequently successfully undergoing liver transplantation. Median MELD score returned to preoperative values after a transient postoperative increase, regardless of the HVPG values; after three months, it returned to the preoperative of 8 in patients with an HVPG <10 mmHg and of 9 in patients with an HVPG ⩾10 mmHg ( p = 0.077 and 0.076 at paired test, respectively). Conclusions The hepatic venous pressure gradient can be used before surgery to stratify the risk of PHLF but the proposed cut-off of 10 mmHg excludes approximately one-quarter of the patients who would benefit from surgery without short to mid-term postoperative sequelae. [ABSTRACT FROM AUTHOR]

Background: Whether patients with small (<2 cm), sporadic nonfunctioning pancreatic endocrine tumors (NF-PETs) should directly undergo pancreatic surgery or should be followed longitudinally to detect growth and malignancy still has to be defined. Study Design: Based on the pertinent literature of the past decade, a Markov model was developed to investigate this issue. In the wait-and-see strategy arm, surgery was performed if the tumor attained a size ≥2 cm or surpassed 20% of the initial size. In a Monte Carlo probabilistic analysis, 100 hypothetical patients undergoing a wait-and-see strategy were compared to 100 patients directly undergoing surgery, with the aim of investigating the efficacy and cost-effectiveness of the two strategies. Results: During the postdiagnostic lifetime, 63 NF-PETs in the wait-and-see group showed significant growth and underwent surgery: 38 were stage I, 10 were stage II, 15 were stage III and none were stage IV. In the base-case scenario, the mean life expectancy and quality-adjusted life expectancy were found to be superior after immediate surgery [26.1 years and 11.8 quality-adjusted life years (QALYs)] than with the wait-and-see strategy (22.1 years and 8.3 QALYs) as the consequence of ageing during the wait-and-see follow-up which increased mortality due to surgery, when surgery was needed. The model was sensitive to starting age and length of follow-up; in particular, for patients >65 years of age, the two strategies provided similar results but the wait-and-see strategy was more cost-effective. Conclusions: The wait-and-see strategy for NF-PETs <2 cm represents a reasonable approach in patients over 65 years of age; otherwise, immediate surgery is preferable. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background & Aims Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Methods One-thousand three-hundred and eighty Child-Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n=850), annual surveillance (n=234) or when patients came when symptomatic (n=296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. Results The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p<0.001). In a 10-year follow-up perspective, the median lead-time calculated for all surveilled patients was 6.5months (7.2 for semiannual and 4.1 for annual surveillance). Lead-time bias accounted for most of the surveillance benefit until the third year of follow-up after HCC diagnosis. However, even after lead-time adjustment, semiannual surveillance maintained a survival benefit over symptomatic diagnosis (number of patients needed to screen=13), as did annual surveillance (18 patients). Conclusions Lead-time bias is the main determinant of the short-term benefit provided by surveillance for HCC, but this benefit becomes factual in a long-term perspective, confirming the clinical utility of an anticipated diagnosis of HCC. [ABSTRACT FROM AUTHOR]

Lymph-nodal status is an important predictor of survival in intrahepatic cholangiocarcinoma (iCCA), but the need to perform lymphadenectomy in patients with clinically node-negative (cN0) iCCA is still under debate. The aim of this study was to determine whether adequate lymphadenectomy improves long-term outcomes in patients undergoing liver resection for cN0 iCCA. We performed a retrospective cohort study on consecutive patients who underwent radical liver resection for cN0 iCCA at five tertiary referral centers. A propensity score based on preoperative data was calculated and used to generate stabilized inverse probability of treatment weight (IPTW). Overall and recurrence-free survival of patients undergoing adequate (≥6 retrieved lymph nodes) vs. inadequate lymphadenectomy were compared. Interactions between adequacy of lymphadenectomy and clinical variables of interest were explored through Cox IPTW regression. The study includes 706 patients who underwent curative surgery for cN0 iCCA. Four-hundred and seventeen (59.1%) received adequate lymphadenectomy. After a median follow-up of 33 months (IQR 18-77), median overall survival was 39 months (IQR 23-109) and median recurrence-free survival was 23 months (IQR 8-74). After stratification according to nodal status at final pathology, node-positive patients had longer overall survival (28 vs. 23 months; hazard ratio 1.82; 95% CI 1.14-2.90; p = 0.023) and disease-free survival (13 vs. 9 months; hazard ratio 1.35; 95% CI 1.14-1.59; p = 0.008) after adequate lymphadenectomy. Adequate lymphadenectomy significantly improved survival outcomes in patients without chronic liver disease, and in patients with less-advanced tumors (solitary tumors, tumor size <5 cm, carbohydrate antigen 19-9 <200 U/ml). Adequate lymphadenectomy provided better survival outcomes for patients with cN0 iCCA who were found to be node-positive at pathology, supporting the routine use of adequate lymphadenectomy for cN0 iCCA. Lymphadenectomy is essential for the surgical staging of intrahepatic cholangiocarcinoma (iCCA). While its role in patients with preoperative suspicion of nodal metastases is implicit, the impact of lymphadenectomy on survival of patients with clinically node-negative (cN0) disease is still under debate. In this large retrospective study on patients who underwent surgical resection for cN0 iCCA, we show that adequate lymphadenectomy (i.e. retrieving ≥6 lymph nodes) significantly improves survival and lowers the risk of tumor recurrence. Lymphadenectomy during surgical resection of iCCA is actually underperformed by the surgical community, resulting in inadequate staging and possibly worse long-term outcomes. The results of this study should empower surgeons and clinicians to push for adequate lymphadenectomy even for cN0 iCCA. Since patients with no chronic liver disease and with less-advanced tumors receive a significant benefit from lymphadenectomy, our results might guide decision making in patients at high-risk of postoperative complications. [Display omitted] • Nodal metastases drive the prognosis of intrahepatic cholangiocarcinoma. • Lymphadenectomy is essential for surgical staging of intrahepatic cholangiocarcinoma. • In clinically node-negative patients, lymphadenectomy provides a survival benefit. • The benefit of lymphadenectomy is significant in early tumors and healthy livers. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Hirsch index (h-index) is recognized as an effective way to summarize an individual's scientific research output. However, a benchmark for evaluating surgeon scientists in the field of hepatic surgery is still not available. METHODS: A total of 3,251 authors who published between 1949 and 2011 were identified using the Scopus identification number. The h-index, the total number of cited document, the total number of citations, and the scientific age were calculated for each author using both Scopus and Google Scholar. RESULTS: The median h-index was 6 and the median scientific age, assessed with Google Scholar, was 19 years. The numbers of cited documents, numbers of citations, and h-indexes obtained from Scopus and Google Scholar showed good correlation with one another; however, the results from the 2 databases were modified in different ways by scientific age. By plotting scientific age against h-index percentiles an h-index growth chart for both Scopus database and Google Scholar was provided. CONCLUSIONS: This analysis provides a first benchmark to assess surgeon scientists' productivity in the field of liver surgery. [ABSTRACT FROM AUTHOR]

Background & Aims: Both hepatic resection and radiofrequency ablation (RFA) are considered curative treatments for hepatocellular carcinoma (HCC), but their economic impact still remains not determined. Aim of the present study was to analyze the cost-effectiveness (CE) of these two strategies in early stage HCC (Milan criteria). Methods: As first step, a meta-analysis of the pertinent literature of the last decade was performed. Seventeen studies fulfilled the inclusion criteria: 3996 patients underwent resection and 4424 underwent RFA for early HCC. Data obtained from the meta-analysis were used to construct a Markov model. Costs were assessed from the health care provider perspective. A Monte Carlo probabilistic sensitivity analysis was used to estimate outcomes with distribution samples of 1000 patients for each treatment arm. Results: In a 10-year perspective, for very early HCC (single nodule <2cm) in Child–Pugh class A patients, RFA provided similar life-expectancy and quality-adjusted life-expectancy at a lower cost than resection and was the most cost-effective therapeutic strategy. For single HCCs of 3–5cm, resection provided better life-expectancy and was more cost-effective than RFA, at a willingness-to-pay above €4200 per quality-adjusted life-year. In the presence of two or three nodules ⩽3cm, life-expectancy and quality-adjusted life-expectancy were very similar between the two treatments, but cost-effectiveness was again in favour of RFA. Conclusions: For very early HCC and in the presence of two or three nodules ⩽3cm, RFA is more cost-effective than resection; for single larger early stage HCCs, surgical resection remains the best strategy to adopt as a result of better survival rates at an acceptable increase in cost. [Copyright &y& Elsevier]

Objective: The aim of this study was to determine the prognostic significance of the preoperatively assessed tumor doubling time (DT) in patients undergoing liver resection for mass-forming intrahepatic cholangiocarcinoma (IHC). Methods: We evaluated 79 patients who underwent curative resection for IHC, and in whom the same imaging technique was preoperatively available in two consecutive occasions, to allow the calculation of the DT. The influence of DT and other clinical and pathological variables on tumor recurrence and patient survival was determined by the Kaplan-Meier method and uni- and multivariate analysis. Results: Median overall survival was 40 months; 1-, 3-, and 5-year survival rates were 86.1, 55.1, and 35.1 %, respectively. Median disease-free survival was 17 months; 1-, 3-, and 5-year disease-free survival rates were 62.0, 29.1, and 23.3 %, respectively. At univariate analysis, DT <70 days ( p < 0.001) and advanced tumor stage ( p = 0.024) were associated with worse overall survival and maintained significance at multivariate analysis. Conclusions: DT is a clinically useful parameter to estimate the prognosis of 'mass-forming' IHC in patients undergoing liver resection. [ABSTRACT FROM AUTHOR]

Summary: The practice of treating candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC), with locoregional therapies, is common in most transplant centers. However, for T1 tumors and expected waiting times to LT <6months, there is no evidence that these treatments are beneficial. For T2 tumors and for longer waiting times, neo-adjuvant treatments are usually performed with transarterial chemoembolization (TACE), ablation techniques and liver resection in selected cases. The treatment choice should be based on the BCLC staging system. At present, there is no evidence of the superiority of ablation/resection vs. TACE, but some studies showed better results of the former in achieving a complete response. The response to neo-adjuvant treatments should be evaluated through mRECIST criteria, but few studies adopted these criteria and properly analyzed factors affecting response. The simultaneous evaluation of the impact of neo-adjuvant therapies on dropout rate, post-LT HCC recurrence and patient survival is rarely reported. Tumor stage and volume, alpha-fetoprotein levels, response to treatments and liver function affect pre-LT outcomes. These same factors, together with vascular invasion and poor tumor differentiation, are major determinants of poor post-LT outcomes. Due to the low number of prospective studies with well-defined entry criteria and the variability of results, the role of downstaging is still to be defined. Novel molecular markers seem promising for the estimation of prognosis and/or response to treatments. With a persistent scarcity of organ donors, neo-adjuvant treatments can help identify patients with different probabilities of cancer progression, and consequently balance the priority of HCC and non-HCC-candidates through revised additional scores for HCC. [ABSTRACT FROM AUTHOR]

Siniscalchi A, Cucchetti A, Miklosova Z, Lauro A, Zanoni A, Spedicato S, Bernardi E, Aurini L, Pinna AD, Faenza S. Post-reperfusion syndrome during isolated intestinal transplantation: outcome and predictors. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01530.x © 2011 John Wiley & Sons A/S. Abstract: Background: Post-reperfusion syndrome (PRS) during isolated intestinal transplantation (ITx) is characterized by decreased systemic blood pressure, systemic vascular resistance, and cardiac output and by a moderate increased pulmonary arterial pressure. We hypothesize that the more severe PRS causes a poorer long-term outcome. The primary aim of this study was to determine the independent clinical predictors of intra-operative PRS, as well as to investigate the link between the severity of PRS and the intra-operative profiles and to examine the post-operative complications and their relationship with transplant outcome. Methods: This observational study was conducted on 27 patients undergoing isolated ITx in a single adult liver and multivisceral transplantation center. PRS was considered when the mean arterial blood pressure was 30% lower than the pre-unclamping value and lasted for at least one min within 10 min after unclamping. Results and conclusions: The main results of this study can be summarized in two findings: in patients undergoing ITx, the duration of cold ischemia and the pre-operative glomerular filtration rate were independent predictors of PRS and the occurrence of intra-operative PRS was associated with significantly more frequent post-operative renal failure and early post-operative death. [ABSTRACT FROM AUTHOR]

Background & Aims: It was recently shown that semi-annual surveillance for hepatocellular carcinoma (HCC) in cirrhotic patients provides a prognostic advantage over the annual program; however, its cost-effectiveness (CE) in the general cirrhotic population still needs to be defined. Methods: A Markov model was built to compare CE of these two strategies, considering literature results and treatment modalities of 918 cirrhotic patients from the Italian Liver Cancer (ITA.LI.CA) database. Results: Results from the Markov model suggest that, compared to annual surveillance, semi-annual surveillance leads to a gain in quality-adjusted life expectancy, in an unselected cirrhotic population, of 1.35 quality-adjusted life-months (QALMs) over 10years since surveillance start in compensated patients, and of 0.73 QALMs in decompensated patients. Semi-annual surveillance was more cost-effective in compensated than in decompensated cirrhosis, with an incremental CE ratio (ICER) of 1997 and 3814€/QALM, respectively. In compensated cirrhosis, semi-annual surveillance was more cost-effective than the annual program when the annual HCC incidence was ⩾3.2% and the relative survival gain after cancer diagnosis was ⩾20% with respect to the annual program. In decompensated cirrhosis, semi-annual surveillance was cost-effective in patients amenable to liver transplantation. In both groups, CE of semi-annual surveillance improved with the increase of annual incidence and the survival benefit obtainable with HCC treatment. Conclusions: Both surveillance strategies for HCC in cirrhotic patients can be recommended, according to the individual risk profile for HCC occurrence and the expected survival gain obtainable after tumor diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between neo-adjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases and post-operative morbidity still has to be clarified. Methods: Data from 242 patients undergoing hepatectomy for colorectal liver metastases, judged resectable at first observation, were reviewed and their clinical outcome was related to neo-adjuvant chemotherapy (125 patients). Selection biases were outlined and properly handled by means of propensity score analysis. Results: Post-operative death was 1.2% and morbidity 40.9%. Pre-operative chemotherapy was only apparently related to higher morbidity ( P = 0.021): multivariate analysis identified extension of hepatectomy and intra-operative blood loss as independent prognostic variables ( P < 0.05). Patients receiving and not receiving neo-adjuvant chemotherapy were significantly different for several covariates, including extension of hepatectomy ( P = 0.049). After propensity score adjustment, 94 patients were identified as having similar covariate distribution (standardized differences <|0.1|) except for neo-adjuvant treatment (47 patients for each group). In this matched sample, mortality was similar and post-operative complications were only slightly higher (hazard ratio = 1.38) in treated patients. A significantly higher need for fluid replacement was only observed in patients receiving neo-adjuvant chemotherapy ( P = 0.038). Conclusions: Neo-adjuvant chemotherapy showed a limited role in determining post-operative morbidity after hepatic resection and did not modify mortality. [ABSTRACT FROM AUTHOR]

Abstract: Background: The role of neo-adjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases is currently a matter of debate. The aim of the present study was to analyse life-expectancy, quality adjusted life-expectancy and cost-effectiveness of the two chemotherapeutic strategies. Methods: A Markov decision model was developed, on the basis of parameters derived from an extensive literature search of the last ten years, to compare outcomes of peri-operative versus post-operative chemotherapy. Results: Life-expectancy observed for peri-operative chemotherapy was 54.56months and 52.62months with post-operative chemotherapy only; the quality-adjusted life-expectancy with peri-operative chemotherapy was 39.33 quality-adjusted life-months (QALMs) and 37.84 QALMs with post-operative chemotherapy. Peri-operative chemotherapy results in an increase in total costs of 1180€ over ten years and in an incremental cost-effectiveness ratio (ICER) of 791.9€/QALM. The model was more sensitive to the expected 3-year recurrence-free survival (RFS) and cost of hepatic resection: with respect to an expected 3-year RFS⩽25% the peri-operative approach was more cost-effective than post-operative strategy but differences in average cost-effectiveness were small. The relationship between ICER and cost of hepatic resection was inverse because the higher the cost of hepatic resection, the higher the cost saving due to patients becoming unresectable during neo-adjuvant therapy. Conclusions: In the treatment of resectable colorectal liver metastases, the addition of neo-adjuvant chemotherapy could be cost-effective because it makes it possible to avoid hepatic resection in patients who do not respond to the neo-adjuvant approach; however, the life-expectancy of the two strategies is very similar. [Copyright &y& Elsevier]

Summary [ABSTRACT FROM AUTHOR]

Background: Accurate knowledge of biliary anatomy and its variants is essential to ensure successful hepatic surgery; however, data from European countries are lacking.Methods: Two hundred cholangiograms obtained from patients submitted to whole liver transplantation were reviewed; donors' characteristics were related to the prevalence of typical biliary anatomy and its variants. A comprehensive literature search was performed with MEDLINE and EMBASE from 1980 to 2010 to investigate whether geographical origin could be related to biliary abnormalities.Results: Typical biliary anatomy was observed in 64.5% of cases, but female donors more frequently presented an anatomic variation; typical anatomy was present in 55.0% of females and in 74.0% of males (P = 0.005). Twenty-two reports were identified by the literature search with a total of 7,559 cases, including the present series; heterogeneity was low (Q = 14.60; I2 < 5.0%) after exclusion of three outlier reports. Prevalence of typical biliary anatomy was similar in Europeans and Americans (∼60%); a slightly higher prevalence was observed in Asiatics (∼65%).Conclusions: Anatomic variants seem to be more frequent in females, probably as a consequence of different embryologic development. Available data suggest that typical biliary anatomy can be more frequent in Asiatics, but an accurate means of classification is essential to making comparison realistic. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) prognosis strongly depends upon nuclear grade and the presence of microscopic vascular invasion (MVI). The aim of this study was to develop an artificial neural network (ANN) that is able to predict tumour grade and MVI on the basis of non-invasive variables. Methods: Clinical, radiological, and histological data from 250 cirrhotic patients resected (n =200) or transplanted (n =50) for HCC were analyzed. ANN and logistic regression models were built on a training group of 175 randomly chosen patients and tested on the remaining testing group of 75. Receiver operating characteristics curve (ROC) and k-statistics were used to analyze model accuracy in the prediction of the final histological assessment of tumour grade (G1–G2 vs. G3–G4) and MVI (absent vs. present). Results: Pathologic examination showed G3–G4 in 69.6% of cases and MVI in 74.4%. Preoperative serum alpha-fetoprotein (AFP), tumour number, size, and volume were related to tumour grade and MVI (p <0.05) and were used for ANN building, whereas, tumour number did not enter into the logistic models. In the training group, ANN area under ROC curves (AUC) for tumour grade and MVI prediction were 0.94 and 0.92, both higher (p<0.001) than those of logistic models (0.85 for both). In the testing group, ANN correctly identified 93.3% of tumour grades (k =0.81) and 91% of MVI (k =0.73). Logistic models correctly identified 81% of tumour grades (k =0.55) and 85% of MVI (k =0.57). Conclusion: ANN identifies HCC tumour grades and MVI on the basis of preoperative variables more accurately than the conventional linear model and should be used for tailoring clinical management. [Copyright &y& Elsevier]

Background: Macrovesicular steatosis of the liver is associated with early dysfunction or poor function of the graft after transplantation; however, it can be quantified accurately only through a liver biopsy that sometimes may not be available and whose result is anyway known when the recipient has already been selected. It would, therefore, be helpful to be able to predict the degree of steatosis, on the basis of non-invasive readily available variables. Methods: Data from 374 deceased liver donors from whom a liver biopsy had been taken were analyzed with the receiver operating characteristic area [area under the curve (AUC)] to identify variables that could predict the degree of macrovesicular steatosis classified as: absent to mild (0–30%) and moderate to severe (>30%). Results: Steatosis was associated significantly with donor age, increased body mass index (BMI), presence of type II diabetes, ultrasonographic features, heavy alcohol consumption, transaminases [aspartate-aminotransferase and alanine-aminotransferase (ALT)], gamma-glutamyl-transpeptidase, and glucose blood levels. The combination of BMI, elevation of ALT, presence of type II diabetes, history of heavy alcohol consumption, and ultrasonography signs of steatosis could identify steatosis >30% accurately with an AUC of 0.86 (95% CI = 0.81–0.91). Conclusion: Fatty infiltration in liver donors can be estimated based on clinical and biochemical parameters. [ABSTRACT FROM AUTHOR]

Background: Hepatectomy for hepatocellular carcinoma in cirrhosis is followed by an impairment of liver function that can lead to patient death. The model for end-stage liver disease (MELD) is considered an index of hepatic functional reserve, and its assessment on postoperative course may properly identify individuals at risk of liver failure. Study design: Two hundred hepatectomies for hepatocellular carcinoma in cirrhosis were reviewed. Irreversible postoperative liver failure was defined as an impairment of liver function after hepatectomy that led to patient death or required transplantation. The MELD scores at postoperative days (POD) 1, 3, 5, and 7 were calculated and kinetics of changes investigated with t-test; logistic regression was applied to identify predictive variables of postoperative liver failure. Results: Kinetics of postoperative MELD score showed an impairment of liver function between PODs 1 and 3; 185 patients in whom postoperative liver failure did not develop showed a considerable decrease in MELD score between PODs 3 and 5 (11.9±2.8 and 10.6±2.4, respectively, p < 0.001). On the contrary, 15 patients, who experienced the event, showed an increase in MELD score between PODs 3 and 5 (18.2±3.9 and 18.3±3.6, respectively; p=0.845). Multivariate analysis showed preoperative MELD score (p < 0.001), major hepatectomy (p=0.028), and MELD score increase between PODs 3 and 5 (p=0.011) as independent predictors of irreversible postoperative liver failure. Scores are reported as mean ± SD. Conclusions: Recovery from liver impairment after hepatectomy for hepatocellular carcinoma in cirrhosis starts from POD 3; MELD scores increasing between PODs 3 and 5 may identify patients at risk of liver failure and represents the trigger for beginning intensive treatment or evaluating salvage transplantation. [Copyright &y& Elsevier]

Background/Aims: Recurrence of hepatocellular carcinoma (HCC) following surgical resection is influenced by parameters detectable on the resection specimen or through a biopsy. The prognostic significance of HCC doubling time (DT) after surgery has never been investigated. Methods: We evaluated 62 patients who underwent curative resection of a single HCC on cirrhosis; tumors were assessed before surgery on two subsequent occasions with the same imaging technique allowing the calculation of DT. The influence of tumor DT, clinical and pathological parameters on recurrence-rate and patients survival was assessed with uni- and multivariate analysis. Relationship between DT and pathological features was also analyzed. Results: Three-year recurrence rate was 32.3% (20 patients): this was significantly higher in the presence of DT shorter than 100 days (58 versus 18% when equal to or longer; P=0.008), microvascular invasion (59 versus 17% when absent; P=0.008) or tumor undifferentiation (54 versus 25% when well/moderately differentiated; P=0.015). DT was the only independent predictor of recurrence (P=0.005). Patients survival was affected by Child-Pugh class only. DT was significantly shorter in tumors with microvascular invasion (P=0.007), undifferentiation (P=0.003) and high alpha-fetoprotein levels (P=0.011). Conclusions: DT is easy to estimate and indicates the prognosis of single HCCs prior to liver resection. [Copyright &y& Elsevier]

De Ruvo N, Cucchetti A, Lauro A, Masetti M, Di Benedetto F, Cautero N, La Barba G, Dazzi A, Di Francesco F, Molteni G, Romano A, Ramacciato G, Risaliti A, Pinna AD. Minimization of immunosuppression with thymoglobuline pre-treatment and HCV recurrence in liver transplantation.Clin Transplant 2005 DOI: 10.1111/j.1399-0012.2005.00333.x© Blackwell Munksgaard, 2005Induction with thymoglobuline, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LTx) has never been investigated. We report here on the outcome in 22 HCV+ patients receiving thymoglobuline pre-treatment and minimal immunosuppression after LTx. Patient survival and acute rejection rates were good, and remarkably low dosages and levels of immunosuppression were achieved with thymoglobuline, without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressor was also possible in the majority of patients without complications. The HCV recurrence rate was similar to what is reported in the literature, although lower HCV-RNA viral loads were obtained with thymoglobuline, with a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobuline is effective in protecting against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses the theme of the issue on patients with hypovascular hepatocellular carcinoma and its treatment using surgical resection (SR), percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA).

A letter to the editor is presented in response to the article "Should hepatic resection be recommended to patients with hepatocellular carcinoma and portal vein invasion?," by Hui-Lin Wang and colleagues in the 2016 issue.

A response is presented by Alessandro Cucchetti to a letter to the editor on his article "Hepatic venous pressure gradient in the preoperative assessment of patients with resectable hepatocellular carcinoma."

A letter to the editor is presented in response to the article "Liver Resection for Advanced Intrahepatic Cholangiocarcinoma: A Cost-Utility Analysis" by U. Cillo et al. published in a previous issue of the journal.

Aim: To assess the impact of the laparoscopic anatomic resections (LARs) on hepatocellular carcinoma (HCC) patients, analyzing the pooled short- and long-term outcomes of this technique and comparing it with the standard open approach [open anatomic resections (OAR)]. Material and Methods: A systematic literature search was performed in PubMed, Embase, and Scopus for studies published between 2010 and 2020 concerning LAR for HCC. Results: After screening 311 articles, 10 studies with a total of 398 patients who underwent LAR for HCC were included. The pooled cohort included mostly male (76.6%), Child A (98.2%), with hepatitis B virus (HBV)-related disease (60.5%). The pooled conversion rate was 7.3%. The pooled overall complication rate was 10.2 with a mortality rate of 1.0%. In the pooled analyses of only comparative studies, LAR group included 378 versus 455 in OAR. Operative time was longer in the LAR group (329 minutes versus 248; P = .001). Blood loss (179 versus 331 mL; P = .018) was lower in the LAR group. The pooled mean length of hospital stay was 8.4 days in LARs and 11.3 in OARs (P = .002). The pooled rate of postoperative complications was higher in the OAR group (25.3 versus 13.8; P = .009), while mortality rates were similar. The LAR group had a pooled 3- and 5-year overall survival of 90.1 and 81.9 versus 83.5 and 80.7 of the OARs (P > .05), respectively. Conclusions: In conclusion, the LAR for HCC is safe and associated with decreased blood loss and length of hospital stay. Survival rates are comparable with those of the conventional open approach. [ABSTRACT FROM AUTHOR]

The percutaneous approach (PA) for management of biliary stones (BS) with or without an underlying biliary stenosis is an option for patients in whom an endoscopic approach (EA) is not possible. The aim of this study was to evaluate the efficacy of a PA in patients with BS unsuitable for an EA. A retrospective review of a database was performed. Inclusion criteria included patients with benign disease, BS who had undergone a PA. The outcomes were technical success rate, short (≤90 days) and long-term (>90 days) efficacy and safety. A total of 91 patients enrolled were divided into those with (n = 38) or without (n = 53) a biliary stenosis. A median of 5 (IQR:3–7) treatments/patient were performed. During a median follow-up of 23 months (IQR:3–52), the median time free from recurrence was 21 months (CI:14–29). In the long term, the PA was most efficacious in those patients without a biliary stenosis with long term success in 68% of patients as compared to 36% of patients with a biliary stenosis (p = 0.003). A PA is an effective procedure with high initial success rate, however the coexistence of stenosis affects long-term efficacy, especially in patients with chronic biliary disease. [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]

A letter to the editor is presented in response to an article related to hepatocellular carcinoma (HCC) patients with high serum alpha-foetoprotein (AFP).

A response from the authors of the article about hepatocellular carcinoma which appeared in a 2016 issue of the periodical is presented.

A letter to the editor on hepatocellular carcinoma is presented.

Direct endoscopic necrosectomy (DEN) is a challenging procedure for the debridement of walled-off pancreatic necrosis (WOPN), which may be complicated by several adverse events, primarily bleeding which may require radiological embolization or even surgery. The lack of dedicated devices for this purpose largely affects the possibility of safely performing DEN which increases the risk of complications. We present the case of a 63 years-old man who underwent an endoscopic ultrasound (EUS)-guided drainage of a WOPN, and who was readmitted one month after stent removal with clinical, endoscopic, and radiological signs of infected necrosis involving the splenic artery. A second EUS-guided drainage was performed, with clear visualization of the arterial vessel in the midst of a large amount of solid necrosis. Due to the high risk of major bleeding during DEN, a hybrid procedure in the angiographic room was performed, in order to identify and avoid, under fluoroscopic control, the splenic artery during the entire procedure guide, which was successfully performed using the EndoRotor system. We hereby review the current literature regarding DEN using the EndoRotor system. The case reported, with a literature overview, may help the management of these patients affected by benign but life-threatening conditions which involve a multidisciplinary setting. [ABSTRACT FROM AUTHOR]

Background: The performance of parenchymal-sparing hepatectomy (PSH) versus major hepatectomy (MH) in patients with multiple colorectal liver metastases (CLM) is a matter that is yet debated. We investigated the outcome of patients with multiple CLM undergoing PSH instead of MH. Methods: Databases at 2 institutions were reviewed. A propensity score-matched analysis was applied. Among 554 patients, 110 undergoing PSH and 110 undergoing MH were matched. They were similar in baseline characteristics, comorbidity, and tumor features. Primary outcomes were short- and long-term outcomes. Results: Morbidity was significantly higher in the MH group, while mortality was not significantly different. There were no differences in free-margins width, but a trend of increased survival was seen in the PSH group with a median advantage of 6 months over the MH group. Among the prognostic factors, the T status (hazard ratio [HR] 2.6; p = 0.001), the N status (HR 2.9; p = 0.001), the timing of CLM diagnosis (HR 2.1; p = 0.002), the tumor number (HR 2.0; p = 0.001), the tumor size (HR 2.2; p = 0.015), and the neo-adjuvant chemotherapy (HR 1.7; p = 0.023) were found to be statistically and independently significant for survival. Conclusions: PSH conveys advantage over MH in terms of decreased postoperative morbidity, and a trend of survival benefit. PSH should be considered a suitable alternative to MH whenever it is technically feasible. [ABSTRACT FROM AUTHOR]