Background and Aims Endoscopic submucosal dissection (ESD) is an endoscopic resection technique for lesions suspicious of superficial malignancy. It is performed using an ESD knife on its own ...(standard technique) or by the sequential use of a knife and a snare (hybrid technique). The experience with these techniques is different in Asian and non-Asian countries. We performed a systematic review and meta-analysis of available evidence on colorectal ESD. Methods Electronic databases were searched up to August 2016 for studies evaluating R0, en bloc resection, and adverse event rates of both techniques for the treatment of colorectal lesions. Proportions were pooled by a random effects model. Results Ninety-seven studies (71 performed in Asia) evaluated the standard technique and 12 studies (7 in Asia) the hybrid technique. The R0 resection rate of the standard technique was 82.9%, and it was significantly lower in non-Asian versus Asian countries: 71.3% versus 85.6%. The en bloc resection rate was 91% and was significantly lower in non-Asian versus Asian countries (81.2% vs 93%, respectively). Surgery was needed in 1.1% of the ESD-related adverse events, with a significant difference between non-Asian and Asian countries (3.1% vs 0.8%). The R0 and en bloc resection rates with the hybrid technique were significantly lower than those achieved with the standard technique: 60.6% and 68.4%, respectively, with similar adverse event rates. Conclusions In non-Asian countries the standard ESD technique is still failing to achieve acceptable levels of performance. The hybrid technique showed low R0 resection rates and should not be considered as an adequate alternative to the standard technique.
Outcomes of liver transplantation for hepatocellular carcinoma (HCC) are determined by cancer-related and non-related events. Treatments for hepatitis C virus infection have reduced non-cancer events ...among patients receiving liver transplants, so reducing HCC-related death might be an actionable end point. We performed a competing-risk analysis to evaluate factors associated with survival of patients with HCC and developed a prognostic model based on features of HCC patients before liver transplantation.
We performed multivariable competing-risk regression analysis to identify factors associated with HCC-specific death of patients who underwent liver transplantation. The training set comprised 1018 patients who underwent liver transplantation for HCC from January 2000 through December 2013 at 3 tertiary centers in Italy. The validation set comprised 341 consecutive patients who underwent liver transplantation for HCC during the same period at the Liver Cancer Institute in Shanghai, China. We collected pretransplantation data on etiology of liver disease, number and size of tumors, patient level of α-fetoprotein (AFP), model for end-stage liver disease score, tumor stage, numbers and types of treatment, response to treatments, tumor grade, microvascular invasion, dates, and causes of death. Death was defined as HCC-specific when related to HCC recurrence after transplantation, disseminated extra- and/or intrahepatic tumor relapse and worsened liver function in presence of tumor spread. The cumulative incidence of death was segregated for hepatitis C virus status.
In the competing-risk regression, the sum of tumor number and size and of log10 level of AFP were significantly associated with HCC-specific death (P < .001), returning an average c-statistic of 0.780 (95% confidence interval, 0.763−0.798). Five-year cumulative incidence of non−HCC-related death was 8.6% in HCV-negative patients and 18.1% in HCV-positive patients. For patients with HCC to have a 70% chance of HCC-specific survival 5 years after transplantation, their level of AFP should be <200 ng/mL and the sum of number and size of tumors (in centimeters) should not exceed 7; if the level of AFP was 200−400 ng/mL, the sum of the number and size of tumors should be ≤5; if their level of AFP was 400−1000 ng/mL, the sum of the number and size of tumors should be ≤4. In the validation set, the model identified patients who survived 5 years after liver transplantation with 0.721 accuracy (95% confidence interval, 0.648%−0.793%). Our model, based on patients’ level of AFP and HCC number and size, outperformed the Milan; University of California, San Francisco; Shanghai-Fudan; Up-to-7 criteria (P < .001); and AFP French model (P = .044) to predict which patients will survive for 5 years after liver transplantation.
We developed a model based on level of AFP, tumor size, and tumor number, to determine risk of death from HCC-related factors after liver transplantation. This model might be used to select end points and refine selection criteria for liver transplantation for patients with HCC. To predict 5-year survival and risk of HCC-related death using an online calculator, please see www.hcc-olt-metroticket.org/. ClinicalTrials.gov ID NCT02898415.
Sorafenib is the current standard of care for patients with advanced hepatocellular carcinoma (aHCC) and has been shown to improve survival by about 3 months compared to placebo. However, survival ...varies widely from under three months to over two years. The aim of this study was to build a statistical model that allows personalised survival prediction following sorafenib treatment.
We had access to 1130 patients undergoing sorafenib treatment for aHCC as part of the control arm for two phase III randomised clinical trials (RCTs). A multivariable model was built that predicts survival based on baseline clinical features. The statistical approach permits both group-level risk stratification and individual-level survival prediction at any given time point. The model was calibrated, and its discrimination assessed through Harrell's c-index and Royston-Sauerbrei's R
.
The variables influencing overall survival were vascular invasion, age, ECOG score, AFP, albumin, creatinine, AST, extra-hepatic spread and aetiology. The model-predicted survival very similar to that observed. The Harrell's c-indices for training and validation sets were 0.72 and 0.70, respectively indicating good prediction.
Our model ('PROSASH') predicts patient survival using baseline clinical features. However, it will require further validation in a routine clinical practice setting.
Background
In the right colon surgery, there is a growing literature comparing the safety of robotic right colectomy (RRC) to that of laparoscopic right colectomy (LRC). With this paper we aim to ...systematically revise and meta-analyze the latest comparative studies on these two minimally invasive procedures.
Methods
A systematic review of studies published from 2000 to 2017 in the PubMed, Scopus, and Embase databases was performed. Primary endpoints were postoperative morbidity and mortality. Secondary endpoints were blood loss, conversion to open surgery, harvested lymph node anastomotic leak, postoperative hemorrhage, abdominal abscess, postoperative ileus, time to first flatus, non-surgical complications, wound infections, hospital stay, and incisional hernia and costs. A subgroup analysis was performed on those series presenting only extracorporeal anastomosis in both arms.
Results
After screening 355 articles, 11 articles with a total of 8257 patients were eligible for inclusion. Operative time was found to be significantly shorter for the laparoscopic procedures in the pooled analysis (SMD − 0.99 95% CI − 1.4 to − 0.6,
p
< 0.001). Conversion to open surgery was more common during laparoscopic procedures than during the robotic ones (RR 1.7; 95% CI 1.1–2.6,
p
= 0.02). No significant differences in mortality (RR 0.47; 95% CI 0.18–1.23,
p
= 0.124) and postoperative complications (RR 1.05; 95% CI 0.9–1.2,
p
= 0.5) were found between LRC versus RRC. The pooled mean time to first flatus was higher in the laparoscopic group (SMD 0.85 days; 95% CI 0.16–1.54,
p
= 0.016). Hospital costs were significantly higher in RRCs (SMD − 0.52; 95% CI − 0.52 to − 0.04,
p
= 0.035).
Conclusions
RRC can be regarded as a feasible and safe technique. Its superiority in terms of postoperative recovery must be confirmed by further large prospective series comparing RRC and LRC performed with the same anastomotic technique. RRC seemed to be associated with higher costs than LRC.
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 <2 cm) 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 3–5 cm, 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 ⩽3 cm, 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 ⩽3 cm, 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.
The aim of this study was to estimate probabilities of achieving the statistical cure from hepatocellular carcinoma (HCC) with hepatic resection (HR) and liver transplantation (LT).
Statistical cure ...occurs when the mortality of a specific population returns to values of that of general population. Resection and transplantation are considered potentially curative therapies for HCC, but their effect on the residual entire life-expectancy has never been investigated.
Data from 3286 HCC patients treated with LT (n = 1218) or HR (n = 2068) were used to estimate statistical cure. Disease-free survival (DFS) was the primary survival measure to estimate cure fractions through a nonmixture model. Overall survival (OS) was a secondary measure. In both, patients were matched with general population by age, sex, year, and race/ethnicity. Cure variations after LT were also adjusted for different waiting-list drop-outs.
Considering DFS, the cure fraction after LT was 74.1% and after HR was 24.1% (effect size >0.8). LT outperformed HR within all transplant criteria considered (effect size >0.8), especially for multiple tumors (>0.9) and even in presence of a drop-out up to 20% (>0.5). Considering OS, the cure fraction after LT marginally increased to 75.8%, and after that HR increased to 40.5%. The effect size of LT over HR in terms of cure decreased for oligonodular tumors (<0.5), became small for drop-out up to ∼20% (<0.2), and negligible for single tumors <5 cm (∼0.1).
As other malignancies, statistical cure can occur for HCC, primarily with LT and secondarily with HR, depending on waiting-list capabilities and efficacy of tumor recurrence therapies after resection.
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•Recurrence is frequent within 2 years of surgical resection of hepatocellular carcinoma.•In this large collaboration, we identify readily available, clinical parameters which ...influence early recurrence.•A simple and extensively validated statistical model for estimating early recurrence risk using an online calculator.•This facility will enhance patient counselling and will help in design of adjuvant clinical trials.
Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30–50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection.
A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application.
Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort – low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included ‘microvascular invasion’.
Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials.
The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence.
The recurrence of hepatocellular carcinoma,the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide,represents an important clinical problem,since it may occur ...after both surgical and medical treatment.The recurrence rate involves 2 phases:an early phase and a late phase.The early phase usually occurs within 2 years after resection;it is mainly related to local invasion and intrahepatic metastases and,therefore,to the intrinsic biology of the tumor.On the other hand,the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment.Since recent studies have reported that early and late recurrences may have different risk factors,it is clinically important to recognize these factors in the individual patient as soon as possible.The aim of this review was,therefore,to identify predicting factors for the recurrence of hepatocellularcarcinoma,by means of invasive and non-invasive methods,according to the different therapeutic strategies available.In particular the role of emerging techniques(e.g.,transient elastography)and biological features of hepatocellular carcinoma in predicting recurrence have been discussed.In particular,invasive methods were differentiated from non-invasive ones for research purposes,taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.
Purpose
Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, when unresectable; therefore, intra-arterial therapies (IAT) such as trans-arterial chemoembolization (TACE) and trans-arterial ...radioembolization (TARE) have been employed. With the present systematic review and meta-analysis, we aimed to analyse published studies to understand if one IAT can be superior to the alternative.
Materials and methods
A systematic search of PubMed and Web of Science databases was performed for articles published until 1 March 2020 relevant to IAT for ICC. Overall survival was the primary end point. Occurrence of clinical adverse events and tumour overall response were secondary outcome measures.
Results
A total of 31 articles (of 793, n.1695 patients) were selected for data extraction, 13 were on TACE (906 patients) and 18 were on TARE (789 patients). Clinical and tumour characteristics showed moderate heterogeneity between the two groups. The median survival after TACE was 14.2 months while after TARE was 13.5 months (95%C.I.: 11.4–16.1). The survival difference was small (
d
= 0.112) at 1 year and negligible at 2 years (
d
= 0.028) and at 3 years (
d
= 0.049). The radiological objective response after TACE was 20.6% and after TARE was 19.3% (
d
= 0.032). Clinical adverse events occurred in 58.5% after TACE, more frequently than after TARE (43.0%,
d
= 0.314).
Conclusion
In conclusion, IATs are promising treatments for improving outcomes for patients with unresectable ICC. To date, TACE and TARE provide similar good outcomes, except for adverse events. Therefore, the decision about techniques is determined by ability to utilize these resources and patient specific factors (liver function or lesion dimension).
Hepatocellular carcinoma （HCC） is one of the most frequent neoplasms worldwide and in most cases it is associated with liver cirrhosis. Liver resection is con- sidered the most potentially curative ...therapy for HCC patients when liver transplantation is not an option or is not immediately accessible. This review is aimed at investigating the current concepts that drive the surgi- cal choice in the treatment of HCC in cirrhotic patients; Eastern and Western perspectives are highlighted. An extensive literature review of the last two decades was performed, on topics covering various aspects of hepatic resection. Early post-operative and long-term outcome measures adopted were firstly analyzed in an attempt to define an optimal standardization useful for research comparison. The need to avoid the develop- ment of post-hepatectomy liver failure represents the ＂conditio sine qua non＂ of surgical choice and the role of the current tools available for the assessment of liver function reserve were investigated. Results of he-patic resection in relationship with tumor burden were compared with those of available competing strategies, namely, radiofrequency ablation for early stages, and trans-arterial chemoembolization for intermediate and advanced stages. Finally, the choice for anatomical versus non-anatomical, as well as the role of laparo- scopic approach, was overviewed. The literature re- view suggests that partial hepatectomy for HCC should be considered in the context of multi-disciplinary evaluation of cirrhotic patients. Scientific research on HCC has moved, in recent years, from surgical therapy toward non-surgical approaches and most of the lit- erature regarding topics debated in the present review is represented by observational studies, whereas very few well-designed randomized controlled trials are cur- rently available; thus, no robust recommendations can be derived.
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