A nomogram to predict early postoperative recurrence of hepatocellular carcinoma with portal vein tumour thrombus after R0 liver resection: A large-scale,multicenter study

BackgroundPortal vein tumour thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch or above of the main portal vein (MPV) could benefit from R0 liver resection (LR). A nomogram is needed to predict early postoperative recurrence (ER) in HCC patients with PVTT and to guide selection of these patients for adjuvant therapy to reduce postoperative recurrence risks.MethodsHCC patients with PVTT limited to a first-order branch or above of the MPV after R0 LR as an initial therapy were included. A nomogram using data from a retrospective training cohort was developed with the Cox regression model. The model was tested in a prospective internal validation cohort and three external validation cohorts.ResultsOf 979 patients, 657 developed postoperative ER (67.1%). ER occurred in 165 of 264 patients (62.5%) in the training cohort, 146 of 218 patients (70.0%) in the internal validation cohort, and 204 of 284 patients (71.8%), 77 of 113 patients (68.1%), and 65 of 100 patients (65%) in the three external validation cohorts, respectively. The nomogram included the following variables: hepatitis B surface antigen (HBsAg), PVTT, HBV DNA, satellite nodules, α-fetoprotein, and tumour diameter. The ROC were 0.836, 0.763, 0.802, 0.837, and 0.846 in predicting ER in the five respective cohorts.ConclusionA nomogram was developed and validated to predict postoperative ER in patients with HCC with PVTT after R0 LR. This nomogram could select appropriate patients with high ER risks for postoperative adjuvant therapy.     

Impact of ABO-incompatibility on hepatocellular carcinoma recurrence after living donor liver transplantation

BackgroundABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has been reported to have acceptable outcomes in the era of rituximab-based prophylaxis. However, the outcomes of ABO-I LDLT for hepatocellular carcinoma (HCC) remain to be elucidated. This study aimed to clarify the impact of ABO-Incompatibility on oncologic outcomes of LDLT for HCC.MethodsPatients with HCC who underwent ABO-I LDLT were randomly matched by 1:2 ratio to those who underwent ABO-compatible (ABO-C) LDLT according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan-Meier method and log-rank test.ResultsBetween January 2012 and December 2015, a total of 160 patients underwent LDLT for HCC confirmed by pathology analysis of liver explants. Thirty-nine consecutive patients underwent ABO-I LDLT for HCC, and 78 ABO-C LDLT patients were selected by propensity score matching, which made no significant difference between the two groups in baseline, perioperative, and tumor characteristics. The 1-, 3-, and 5-year recurrence-free survival rates in the ABO-I and ABO-C LDLT groups were 76.9%, 68.5%, 63.6% and 74.4%, 70.5%, 70.5%, respectively (p = 0.77). The site distribution of initial recurrence showed no significant difference between the two groups. The overall survival rates over the same period in the ABO-I and ABO-C LDLT groups were 82.1%, 73.5%, 73.5% and 92.2%, 80.3%, 80.3%, respectively (p = 0.34).ConclusionsABO-I LDLT, having no adverse impact on oncological outcomes, can be a feasible transplant option for HCC.     

Development and validation of a new clinical staging system to predict survival for esophageal squamous cell carcinoma patients: Application of the nomogram

IntroductionSurvival of patients with the same clinical stage varies widely and effective tools to evaluate the prognosis utilizing clinical staging information is lacking. This study aimed to develop a clinical nomogram for predicting survival of patients with Esophageal Squamous Cell Carcinoma (ESCC).Materials and methodsOn the basis of data extracted from the SEER database (training cohort, n = 3375), we identified and integrated significant prognostic factors for nomogram development and internal validation. The model was then subjected to external validation with a separate dataset obtained from Jinling Hospital of Nanjing Medical University (validation cohort, n = 1187). The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index), Akaike information criterion (AIC) and calibration curves. And risk group stratification was performed basing on the nomogram scores.ResultsOn multivariable analysis of the training cohort, seven independent prognostic factors were identified and included into the nomogram. Calibration curves presented good consistency between the nomogram prediction and actual observation for 1-, 3-, and 5-year OS. The AIC value of the nomogram was lower than that of the 8th edition American Joint Committee on Cancer TNM (AJCC) staging system, whereas the C-index of the nomogram was significantly higher than that of the AJCC staging system. The risk groups stratified by CART allowed significant distinction between survival curves within respective clinical TNM categories.ConclusionsThe risk stratification system presented better discriminative ability for survival prediction than current clinical staging system and might help clinicians in decision making.     

Transarterial chemoembolization versus best supportive care for patients with hepatocellular carcinoma with portal vein tumor thrombus：a multicenter study

BackgroundThis study aims to compare the efficacy and safety of treatment after transarterial chemoembolization(TACE) with best supportive care (BSC) in patients with hepatocellular carcinoma (HCC) with PVTT.MethodsThis retrospective study was conducted on 1,040 patients with HCC with PVTT who were treated either with TACE (n = 675) or BSC (n = 365). BSC did not include sorafenib. The two groups of patients were compared with or without propensity score matching. A subgroup analysis was subsequently performed by stratifying patients according to the stages of PVTT in the Cheng's PVTT classification.ResultsIn PVTTtypes I-III, TACE was associated with significantly better overall survival (OS) thanBSC (P < 0.05). Within each type of PVTT for patients who received TACE or BSC, OS was significantly worse in patients with type IVPVTT than in any of the other three types of PVTT (all P < 0.05). TACE was associated with better long-termOS than BSC after propensity score matching or on stratification by the PVTT types.ConclusionTACE was associated with better OS than BSC in HCC patients with PVTT types I-III but not type IV. Patients with type IV PVTT showed the worst prognosis, regardless of whether TACE or BSC was used.     

Long-term outcomes of deceased donor liver transplantation in hepatocellular carcinoma patients with portal vein tumor thrombus: A multicenter study

BackgroundThe incidence of portal vein tumor thrombus (PVTT) has been reported to be as high as approximately 10%–40% in patients with hepatocellular carcinoma (HCC). The long-term prognosis of deceased donor liver transplantation (DDLT) in HCC patients with PVTT remains unknown.MethodsData of 961 HCC patients who underwent DDLT between 2015 and 2018 in six centers were analyzed. Based on the Milan criteria (MC) and Cheng's classification of PVTT, the patients were divided into 4 groups: within MC, beyond MC without PVTT, type 1 PVTT, and type 2 PVTT groups.Results489 (50.9%) were within the MC, 296 (30.8%) beyond the MC but without PVTT, 83 (8.6%) type 1 PVTT, and 93 (9.7%) type 2 PVTT. Kaplan-Meier analysis showed that type 1 or 2 PVTT patients with alpha-fetoprotein (AFP) ≤ 100 ng/mL had overall survival (OS) similar to that of patients within the MC (P = 0.957), and superior OS (P = 0.003 and 0.009) and recurrence-free survival (RFS) (P = 0.038 and <0.001) than those of patients beyond the MC and PVTT patients with AFP > 100 ng/mL. Multivariable Cox-regression analysis identified type 1 and 2 PVTT to be independent risk factor for RFS [hazard ratio (HR) 1.523 95% confidence interval (CI) 1.162–1.997, P = 0.002], but not for OS (HR 1.283, 95%CI 0.922–1.786, P = 0.139).ConclusionHCC patients with type 1 or 2 PVTT may be acceptable candidates for DDLT. To achieve better outcomes, preoperative AFP levels should be seriously considered when selecting patients with PVTT for DDLT.     

Liver resection is justified for multinodular hepatocellular carcinoma in selected patients with cirrhosis: A multicenter analysis of 1,066 patients

BackgroundThe role of liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) remains unclear, especially among patients with severe underlying liver disease. We sought to evaluate surgical outcomes among patients with cirrhosis and multinodular HCC undergoing liver resection.MethodsUsing a multicenter database, outcomes among cirrhotic patients who underwent curative-intent resection of HCC were examined stratified according to the presence or absence of multinodular disease. Perioperative mortality and morbidity, as well as overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups.ResultsAmong 1066 cirrhotic patients, 906 (85.0%) had single- or double-nodular HCC (the non-multinodular group), while 160 (15.0%) had multinodular HCC (the multinodular group). There were no differences in postoperative 30-day mortality and morbidity among non-multinodular versus multinodular patients (1.8% vs. 1.9%, P = 0.923, and 36.0% vs. 39.4%, P = 0.411, respectively). In contrast, 5-year OS and RFS of multinodular patients were worse compared with non-multinodular patients (34.6% vs. 58.2%, and 24.7% vs. 44.5%, both P < 0.001). On multivariable analyses, tumor numbers ≥5, total tumor diameter ≥8 cm and microvascular invasion were independent risk factors for decreased OS and RFS after resection of multinodular HCC in cirrhotic patients.ConclusionsLiver resection can be safely performed for multinodular HCC in the setting of cirrhosis with an overall 5-year survival of 34.6%. Tumor number ≥5, total tumor diameter ≥8 cm and microvascular invasion were independently associated with decreased OS and RFS after resection in cirrhotic patients with multinodular HCC.     

The cost-effectiveness of TheraSphere in patients with hepatocellular carcinoma who are eligible for transarterial embolization

IntroductionThe aim of the study is to estimate the cost-effectiveness of TheraSphere against other embolic treatments in a population with early to intermediate stage hepatocellular carcinoma (HCC) who are unresectable at presentation and are eligible for transarterial embolization (TAE), conventional transarterial chemoembolization (cTACE) or drug-eluting bead TACE (DEB-TACE).Materials and methodsA Markov model was constructed using a UK National Health Service (NHS) perspective, a 20-year time horizon, and four-week cycles. The eight health states included ‘watch and wait’, ‘transplantation’ (pre-, post and post (No HCC)), ‘resection’, ‘no HCC other’, ‘pharmacological management’ and ‘death’. Clinical data were sourced from literature and expert opinion. Resource use and costs were reflective of the NHS, and benefits were quantified using Quality-Adjusted Life Years (QALYs), with utility weights sourced from literature.Comparators were TAE, cTACE and DEB-TACE. The primary output was the Incremental Cost-Effectiveness Ratio (ICER) expressed as cost per QALY gained. An ICER of under £20,000/QALY gained for an intervention is cost-effective and represents efficient use of healthcare resources. Extensive deterministic and probabilistic sensitivity analyses were undertaken.ResultsTheraSphere patients were predicted to gain 0.7 additional QALYs compared to all other treatments. The base case ICERs for TheraSphere were £17,300, £17,279 and £23,020 per QALY gained compared to TAE, cTACE and DEB-TACE, respectively. In the TheraSphere cohort, 87% more patients were predicted to achieve downstaging compared to all other treatment options.ConclusionsThis study indicates that treatment with TheraSphere is a potentially cost-effective option for patients with early to intermediate stage HCC.     

Association of primary tumor location with long-term oncological prognosis following hepatectomy for hepatocellular carcinoma:A multicenter propensity score matching analysis

PurposeThere is a striking laterality in the site of hepatocellular carcinoma (HCC), with a strong predominance for the right side; however, the impact of primary tumor location on long-term prognosis after hepatectomy of HCC remains unclear. This study aimed to investigate the effect of primary tumor location on long-term oncological prognosis after hepatectomy for HCC.Patients and methodsData of consecutive patients undergoing curative hepatectomy for HCC between 2008 and 2017 were analyzed. Overall survival (OS) and recurrence-free survival (RFS) of left-sided HCC (LS group) and right-sided HCC (RS group) were compared by using propensity score matching (PSM) analysis. COX regression analysis was performed to assess the adjusted effect of tumor location on long-term oncological prognosis.ResultsOf the 2799 included patients, 707 (25.3%) and 2092 (74.7%) were in the LS and RS groups, respectively. Using PSM analysis, 650 matched pairs of patients were created. In the PSM cohort, median OS (66.0 vs. 72.0 months, P = 0.001) and RFS (28.0 vs. 51.0 months, P < 0.001) were worse among patients in the LS group compared to individuals in the RS group. After further adjustment for other confounders using multivariable COX regression analyses, HCC located on the left side remained independently associated with worse OS and RFS.ConclusionTumors located on the left side are associated with poorer OS and RFS after hepatectomy for HCC. Careful surgical options selection and frequent follow-up to improve long-term survival may be justified for HCC patients with left-sided primary tumors.     

No touch isolation technique for the prevention of postoperative recurrence of hepatocellular carcinoma after liver transplantation-combined with trans-arterial radioembolization

IntroductionTransarterial radioembolization (TARE) is recently emerging treatment modality using radiation from Yttrium-90 through the transarterial approach. It usually is used in the intermediate stage and unresectable hepatocellular carcinoma (HCC).No touch isolation technique is a way to prevent the spread of tumors by pre-ligating the vessels around the tumor with minimal touch during surgery. We hoped that if we were to use these techniques, we would be able to control all viable tumors before liver transplantation. Then we could get better outcomes even in the advanced hepatocellular carcinoma patients.MethodsWe performed living donor liver transplantation using no touch isolation technique in the patients who had multinodular hepatocellular carcinoma and extremely high AFP, PIVKA-II level after TARE and conventional TACE.Results36 years old female patient had liver cirrhosis with hepatitis B virus infection and multiple hepatocellular carcinoma in both lobes. Hepatologist decided to do TARE and additional conventional TACE for viable tumors. After that treatment, AFP and PIVKA-II level were dramatically decreased, we decided to proceed of living donor liver transplantation because the patient's treatment response was extremely good.ConclusionsNo touch isolation technique combined with TARE for recipient hepatectomy might be helpful in advanced stage hepatocellular carcinoma patients.     

Chronic lymphocytic thyroiditis protects against recurrence in patients with cN0 papillary thyroid cancer

BackgroundChronic lymphocytic thyroiditis (CLT) frequently coexists with papillary thyroid carcinoma (PTC) that exhibits normal thyroid function. However, few studies have investigated the relationship between CLT and clinically lymph node (LN)-negative PTC. The aim of this study was to evaluate the relationship between subclinical central LN metastasis and CLT, and to assess the impact of CLT on the recurrence of clinically LN-negative PTC.MethodsWe investigated the medical records of 850 patients with PTC who underwent prophylactic bilateral central neck dissection as well as total thyroidectomy between 2004 and 2010; the median follow-up time was 95.5 months (range, 12–158 months).ResultsCLT was observed in 480 patients (56.5%). Female sex, a preoperative thyroid-stimulating hormone level >2.5 mU/L, a primary tumor ≤1 cm, no gross extrathyroidal extension, high number of harvested LNs, low number of metastatic LNs, and positive anti-thyroglobulin (Tg) antibody at 1 year post-initial treatment were significantly associated with the presence of CLT. Multivariate analysis revealed that patients with N1a stage (vs. N0 stage; hazard ratio [HR], 3.255; 95% confidence interval [CI], 1.290–8.213; p = 0.012) and positive anti-Tg antibody at 1 year post-initial treatment (vs. negative anti-Tg antibody; HR, 5.118; 95% CI, 2.130–12.296; p < 0.001) had poorer recurrence-free survival (RFS), while those with CLT (vs. no CLT; HR, 0.357; 95% CI, 0.157–0.812; p = 0.014) had favorable RFS outcomes.ConclusionsCLT is associated with less aggressive tumor characteristics and LN metastasis. Clinically LN-negative PTC patients with CLT experience longer RFS intervals than those without CLT.     

Clinical significance of cachexia index in patients with hepatocellular carcinoma after hepatic resection

BackgroundCancer cachexia has been associated with unfavorable outcomes in several malignancies. The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been proposed as a novel biomarker of cachexia. Therefore, we here investigated prognostic value of the CXI in patients with hepatocellular carcinoma (HCC) after hepatic resection.MethodsThe study comprised 213 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. First, the skeletal muscle index (SMI) was calculated as the area of the psoas muscle at the third lumbar vertebra/(the height)². The CXI was then calculated by the following formula: SMI x serum albumin level/neutrophil-to-lymphocyte ratio (NLR). We retrospectively investigated the relationship between the CXI and disease-free survival as well as overall survival.ResultsIn multivariate analyses, female (p < 0.01), hepatitis B surface antigen-positivity (p < 0.01), preoperative serum alpha-fetoprotein level ≥20 ng/mL (p = 0.01), preoperative serum protein induced by vitamin K absence or antagonist-II level ≥200 mAU/mL (p = 0.02), multiple tumors (p < 0.01), macrovascular invasion (p = 0.04), type of resection (p < 0.01), and low CXI (p = 0.03) were significant predictors of disease-free survival, while Child-Pugh grade B (p < 0.01), poor tumor differentiation (p = 0.05), multiple tumors (p = 0.01), macrovascular invasion (p = 0.04), NLR (p = 0.04), and low CXI (p < 0.01) were significant predictors of overall survival. In the subgroup analysis of advanced T stage, the CXI was associated with both disease-free (p < 0.01) and overall survival (p = 0.06).ConclusionsThe CXI can be a prognostic indicator in patients with HCC after hepatic resection, suggesting the importance of comprehensive biomarker which includes skeletal muscle, inflammation, and nutritional status.     

Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer

IntroductionPatients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices.Materials and methodsPatients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured.ResultsBefore treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression).ConclusionThese data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery.     

Real-world role of performance status in surgical resection for hepatocellular carcinoma: A multicenter study

BackgroundThe Barcelona Clinic Liver Cancer (BCLC) categorizes a patient with performance status (PS)-1 as advanced stage of hepatocellular carcinoma (HCC) and surgical resection is not recommended. In real-world clinical practice, PS-1 is often not a contraindication to surgery for HCC. The aim of current study was to define the impact of PS on the surgical outcomes of patients undergoing liver resection for HCC.Methods1,531 consecutive patients who underwent a curative-intent resection of HCC between 2005 and 2015 were identified using a multi-institutional database. After categorizing patients into PS-0 (n = 836) versus PS-1 (n = 695), perioperative mortality and morbidity, overall survival (OS) and recurrence-free survival (RFS) were compared.ResultsOverall perioperative mortality and major morbidity among patients with PS-0 (n = 836) and PS-1 (n = 695) were similar (1.4% vs. 1.6%, P = 0.525 and 9.7% vs. 10.2%, P = 0.732, respectively). In contrast, median OS and RFS was worse among patients who had PS-1 versus PS-0 (34.0 vs. 107.6 months, and 20.5 vs. 60.6 months, both P < 0.001, respectively). On multivariable Cox-regression analyses, PS-1 was independently associated with worse OS (HR: 1.301, 95% CI: 1.111–1.523, P < 0.001) and RFS (HR: 1.184, 95% CI: 1.034–1.358, P = 0.007).ConclusionsPatients with PS-1 versus PS-0 had comparable perioperative outcomes. However, patients with PS-1 had worse long-term outcomes as PS-1 was independently associated with worse OS and RFS. Routine exclusion of HCC patients with PS-1 from surgical resection as recommended by the BCLC guidelines is not warranted.     

The different survival impacts of body mass index in elderly and non-elderly patients with gastric carcinoma

BackgroundThe age-dependent survival impact of body mass index (BMI) remains to be fully addressed in patients with gastric carcinoma (GC). We investigated the prognostic impacts of BMI in elderly (≥70 years) and non-elderly patients undergoing surgery for GC.MethodsIn total, 1168 GC patients were retrospectively reviewed. Patients were stratified into 3 groups according to BMI; low (<20), medium (20–25) and high (>25). The effects of BMI on overall survival (OS) and cancer-specific survival (CSS) were assessed using univariate and multivariate Cox hazards models.ResultsThere were 242 (20.7%), 685 (58.7%) and 241 (20.6%) patients in the low-, medium- and high-BMI groups, respectively. The number of patients with high BMI but decreased muscle mass was extremely small (n = 13, 1.1%). Patients in the low-BMI group exhibited significantly poorer OS than those in the high- and medium-BMI group (P < 0.001). Notably, BMI classification significantly demarcated OS and CSS curves (both P < 0.001) in non-elderly patients, while did not in elderly patients (OS; P = 0.07, CSS; P = 0.54). Furthermore, the survival discriminability by BMI was greater in pStage II/III disease (P = 0.006) than in pStage I disease (P = 0.047). Multivariable analysis focusing on patients with pStage II/III disease showed low BMI to be independently associated with poor OS and CSS only in the non-elderly population.ConclusionsBMI-based evaluation was useful for predicting survival and oncological outcomes in non-elderly but not in elderly GC patients, especially in those with advanced GC.     

Impact of concurrent splenectomy and esophagogastric devascularization on surgical outcomes of partial hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: A multicenter propensity score matching analysis

PurposePortal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED).Patients and methodsFrom a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM).ResultsOf the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P = 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P = 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001).ConclusionHepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.     

Stromal characteristics are adequate prognosticators for recurrence risk in ductal carcinoma in situ of the breast

BackgroundDuctal carcinoma in situ (DCIS) of the breast constitutes a heterogeneous group of non-obligate precursors for invasive breast cancer. To date, adequate risk stratification is lacking, which is presumed to result in overtreatment. We previously identified myxoid stromal architecture as a potential prognosticator for loco-regional recurrence. In the present study, we investigated the prognostic potential of stromal characteristics.MethodsHematoxylin and eosin stained slides from 211 DCIS patients were reviewed. The following histological features were dichotomously assessed: nuclear grade, DCIS architecture, presence of necrosis, intraductal calcifications, stromal inflammation and myxoid stromal architecture. Loco-regional recurrences constituted the primary endpoint. Results: Cox regression analysis showed that high nuclear grade, myxoid stromal architecture and moderate to extensive stromal inflammation were significantly associated with decreased recurrence-free survival, independent of radiotherapy. Based on these features, a combined risk score (CRS) was calculated, ranging from zero to three. A high CRS of three was associated with significantly shorter recurrence-free survival. Nineteen patients had a CRS of three, of which three relapsed (15.7%), whereas only one out of 113 patients with a CRS of zero relapsed (0.9%).ConclusionsWe were able to validate our previously reported findings regarding the prognostic potential of myxoid periductal stroma in an independent DCIS patient cohort. A CRS based on nuclear grade, myxoid stromal architecture and stromal inflammation might facilitate discrimination of low risk from high risk patients. Consequently, the CRS may tailor adjuvant therapy. Future research should investigate whether radiotherapy can be safely omitted in patients with a low CRS.     

Trans-arterial chemoembolization + radiofrequency ablation versus surgical resection in hepatocellular carcinoma – A meta-analysis

BackgroundHepatocellular Carcinoma (HCC) remains the third most common cause of cancer death worldwide, with countries in Asia being affected the most. The mainstay of curative therapy for early HCC is radiofrequency ablation (RFA) or surgery; either surgical resection (SR) or liver transplantation. Latest evidence however suggests that combination of TACE+ RFA may provide outcomes comparable to SR.AimTo compare oncologic outcomes and safety profile of TACE + RFA to SR alone in HCC.Materials and methodsA systematic review was conducted through Pubmed, EMBASE and Cochrane Library for literature published before April 2019. Outcomes measured were disease-free survival(DFS), overall survival(OS) and major complications. DFS was further divided into local tumour progression(LTP), intrahepatic distant recurrence(IDR) and distant metastasis(DM).ResultsEight retrospective studies and one randomized controlled trial, involving 1892 patients met eligibility criteria and were included. Unadjusted pooled analysis demonstrated no significant difference in 1-year, 3-year and 5-year OS and 1-year DFS between TACE+RFA and SR. SR had superior 3-year DFS (OR 0.78, 95% CI 0.62–0.98, p = 0.03) and 5-year DFS (OR 0.74, 95% CI 0.58–0.95, p = 0.02) compared to TACE+RFA. When analysing only the propensity matched data, the difference in 3-year DFS and 5-year DFS was not significant. TACE+RFA had a higher LTP rate (OR 2.48, 95% CI 1.05–5.86, p = 0.04) compared to SR but IDR and DM rates were not significant.Discussion and conclusionTACE+RFA offer comparable oncologic outcomes in patients with HCC as compared with SR and with added benefit of lower morbidity.     

Postoperative morbidity adversely impacts long-term oncologic prognosis following hepatectomy for hepatocellular carcinoma: A multicenter observational study

Background & aimsPostoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC.MethodsThe data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (>2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity.ResultsAmong 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P < 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P < 0.001) and TTR (median: 19.8 vs. 46.1 months; P < 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126–1.451; P < 0.001) and recurrence (1.187; 1.058–1.331; P = 0.004).ConclusionThis large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important.