Second Hepatectomy Improves Survival in Patients With Microvascular Invasive Hepatocellular Carcinoma Meeting the Milan Criteria

Microvascular invasion (MVI) is a strong risk factor for patients with hepatocellular carcinoma (HCC) meeting the Milan criteria and who have received curative hepatectomy. The relevance of a second hepatectomy in patients with MVI-positive recurrent HCC remains controversial.We had 329 cases of HCC hepatectomy meeting the Milan criteria and compared data on patient demographics, liver function, and tumor pathology between MVI-positive and MVI-negative group. We analyzed potential risk factors of overall survival (OS) and disease-free survival (DFS). Furthermore, newly developed pathological features following the second hepatectomy were also analyzed.The median OS and DFS were significantly superior in the MVI-negative group than in the MVI-positive group, 61 (10–81) versus 49 (11–82) months (P < 0.01) and 41 (7–75) versus 13 (3–69) months (P < 0.01), respectively. The presence of MVI and a total tumor diameter >3 cm were independent risk factors associated with both OS and DFS. Overall survival was significantly improved by a second hepatectomy in the MVI-positive group compared with the original MVI-positive group, 60 (26–82) versus 49 (11–82) months, respectively. This was now comparable to the MVI-negative group, 60 (26–82) versus 61 (10–81) months (P = 0.72). A second hepatectomy was consistently associated with better survival in the MVI-negative group as compared to the MVI-positive group.A second hepatectomy improves survival in patients with MVI HCC meeting the Milan criteria. The biology of MVI may change following a second hepatectomy. The absence of MVI is a good prognostic sign for patients undergoing second hepatectomy.     

Long-Term Survival in Patients With T2 Hepatocellular Carcinoma After Primary Curative Resection Can Be Further Stratified by Tumor Size

Insufficient data are available regarding the validation of long-term survival in patients with T2 (solitary tumor with microvascular invasion [MVI] or multiple tumors, none >5 cm) hepatocellular carcinoma (HCC) after primary hepatectomy. We aim to evaluate the survival and relevant risk factors for T2 HCC patients. Between 2001 and 2007, 312 T2 HCC patients who underwent primary hepatectomy were included. Survival was estimated using the Kaplan–Meier method and compared using Cox proportional hazard model with adjusted independent prognostic factors. The 1, 3, and 5-year overall survival rates of patients with MVI were 85.7%, 68.7%, and 64.8%, respectively; these were inferior to the rates in patients without MVI, which were 93.0%, 89.3%, and 73.7%, respectively (P = 0.037). Within the with-MVI group, the survival rate of patients with tumor sizes ≥5 cm was inferior to that of patients with tumors <5 cm (overall, P = 0.01; recurrence-free, P < 0.0001). For patients with the largest tumors in the <5-cm group, those without MVI tended to have a higher probability of recurrence for 2 years after resection (P = 0.088) but a similar overall survival rate relative to those with MVI (P = 0.31). The crude metastasis-free survival was higher in the without-MVI group than in the with-MVI group (P = 0.012). The T2 HCC category comprised heterogeneous patients with differences in survival rates. Extrahepatic recurrence occurred more frequently in patients with MVI than in those without MVI. These results provide evidence for an updated definition of T2 HCC.     

Hepatic Resection as a Safe and Effective Treatment for Hepatocellular Carcinoma Involving a Single Large Tumor,Multiple Tumors,or Macrovascular Invasion

This systematic review examined whether the available evidence justifies using hepatic resection (HR) during later stages of hepatocellular carcinoma (HCC), which contravenes treatment guidelines but is current practice at many medical centers.Official guidelines and retrospective studies recommend different roles for HR for patients with large/multinodular HCC or with HCC involving macrovascular invasion (MVI).Several databases were systematically searched for studies examining the safety and efficacy of HR for treating HCC involving a single large tumor (>5 cm) or multiple tumors, or for treating HCC involving MVI.We identified 50 studies involving 14 808 patients that investigated the use of HR to treat large/multinodular HCC, and 24 studies with 4389 patients that investigated HR to treat HCC with MVI. Median in-hospital mortality for patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non-Asian studies (7.3%, P < 0.001). Median overall survival (OS) was significantly higher for all Asian patients with large/multinodular HCC than for all non-Asian patients at both 1 year (81% vs 65%, P < 0.001) and 5 years (42% vs 32%, P < 0.001). Similar results were obtained for median disease-free survival at 1 year (61% vs 50%, P < 0.001) and 5 years (26% vs 24%, P < 0.001). However, median OS was similar for Asian and non-Asian patients with HCC involving MVI at 1 year (50% vs 52%, P = 0.45) and 5 years (18% vs 14%, P = 0.94). There was an upward trend in 5-year OS in patients with either type of HCC.HR is reasonably safe and effective at treating large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for HR in official treatment guidelines.     

Thymosin alpha-1 therapy improves postoperative survival after curative resection for solitary hepatitis B virus-related hepatocellular carcinoma: A propensity score matching analysis

Thymosin alpha-1 (Tα1) is an immunomodulatory and antiviral agent with potential effects on chronic hepatitis B and liver cancer. Its impact on solitary hepatocellular carcinoma (HCC) remains controversial, so we aimed to investigate the efficacy of Tα1 in solitary HBV-related HCC patients after curative resection.Between May 2010 and April 2016, 468 patients with solitary HBV-related HCC after curative resection were analyzed. Propensity score matching (PSM) was used to minimize confounding variables. Risk factors were identified by the Cox proportional hazards model. Recurrence-free survival (RFS) rates, overall survival (OS) rates, immunological, and virologic response were compared.The median follow up was 60.0 months. Immunological response improved in the Tα1 group compared with the control group (P < .001) but the virologic response was similar between 2 groups after 24 months. Patients with Tα1 therapy had better RFS and OS before (P = .018 and P < .001) and after (P = .006 and P < .001) propensity matching. Multivariate analysis revealed that Tα1 therapy was an independent prognostic factor for both OS (P < .001, HR = 0.308, 95% CI: 0.175–0.541) and RFS (P < .001, HR = 0.381, 95% CI: 0.229–0.633).Tα1 as an adjuvant therapy improves the prognosis of solitary HBV-related HCC patients after curative liver resection.     

Tumor PHD2 Expression Is Correlated With Clinical Features and Prognosis of Patients With HCC Receiving Liver Resection

The role of prolyl hydroxylase domain protein 2 (PHD2) in carcinogenesis has been studied in a variety of cancer types. However, the association between PHD2 and human hepatocellular carcinoma (HCC) has not been documented.A total of 220 patients with primary HCC who underwent a curative liver resection were enrolled in this study. The tumor samples were obtained during the surgical procedure from each patient for PHD2 immunohistological staining. All the patients were followed up and the disease-free survival (DFS) and overall survival (OS) were evaluated.We found that that high PHD2 expression was significantly associated with higher stage (stages III + IV) (odds ratio [OR] = 5.576, P < 0.001), larger tumor size (>5 cm) (OR = 6.176, P < 0.001), poorer tumor differentiation (OR = 1.424, P = 0.003), and higher serum alpha fetoprotein (AFP) level (OR = 6.861, P < 0.001). Compared to those with high PHD2 expressions, patients with low PHD2 expression had significantly longer DFS and OS periods (both P < 0.001). Cox regression analyses revealed that higher levels of PHD2, tumor size, tumor stage, as well as serum AFP level were predictors for a worse prognosis in patients with HCC.PHD2 expression in the tumors is associated with the clinical features and prognosis of patients with HCC; it may be used as a histological marker for HCC.     

Absence of association between pretransplant serum soluble programmed death protein-1 level and prognosis following living donor liver transplantation in patients with hepatocellular carcinoma

Programmed death protein 1 (PD-1) pathway is one of the most critical mechanisms in tumor biology of hepatocellular carcinoma (HCC). The study aimed to assess the prognostic influence of pretransplant serum soluble PD-1 (sPD-1) in patients undergoing liver transplantation for treatment of HCC.Data from 229 patients with HCC who underwent living donor liver transplantation between January 2010 and December 2015 were retrospectively evaluated. Stored serum samples were used to measure sPD-1 concentrations.Overall survival (OS) and disease-free survival (DFS) rates were 94.3% and 74.5% at 1 year; 78.2% and 59.2% at 3 years; and 75.4% and 55.5% at 5 years, respectively. Prognostic analysis using pretransplant serum sPD-1 with a cut-off of 93.6 μg/mL (median value of the study cohort) did not have significant prognostic influence on OS (P = .69) and DFS (P = .26). Prognostic analysis using sPD-1 with a cut-off of 300 μg/mL showed similar OS (P = .46) and marginally lower DFS (P = .070). Combination of Milan criteria and sPD-1 with a cutoff of 300 μg/mL showed similar outcomes of OS and DFS in patients within and beyond Milan criteria. Multivariate analysis revealed that only Milan criteria was an independent prognostic for OS and DFS, but pretransplant sPD1 with a cut-off of 300 μg/mL did not become a prognostic factor.The results of this study demonstrate that pretransplant serum sPD-1 did not show significant influences on post-transplant outcomes in patients with HCC. Further large-scale, multicenter studies are necessary to clarify the role of serum sPD-1 in liver transplantation recipients.     

Serosal Invasion Strongly Associated With Recurrence After Curative Hepatic Resection of Hepatocellular Carcinoma: A Retrospective Study of 214 Consecutive Cases

The purpose of this study was to clarify the individual prognostic factors after curative and primary resection of hepatocellular carcinoma (HCC).Reliable prognostic factors and tumor staging for HCC have been required to predict an appropriate prognosis. However, in HCC, no staging system has received universal acceptance, and several tumor factors seem to relate to HCC prognosis, but they are not definitive. At present, few studies have mentioned the importance of serosal invasion as a prognostic factor.A retrospective search of our database identified 214 consecutive patients who underwent primary and curative hepatectomy for HCC at our department between January 1998 and December 2011. Risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed with Cox proportional hazard model, Kaplan-Meier method, and log-rank tests.Multivariate analyses showed that serosal invasion (hazard ratio [HR], 2.75; P = 0.0005) and vascular invasion (HR, 1.71; P = 0.0331) were independently correlated with RFS. Serosal invasion was significantly correlated with HCC recurrence (P = 0.0230). The Kaplan–Meier method and log-rank tests revealed that the patients with serosal invasion showed significantly worse prognosis both in RFS (P < 0.0001) and OS (P = 0.0016).Serosal invasion should be regarded as a strong independent predictor for recurrence in curatively resected HCC cases.     

Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer: A Randomized,Controlled Study

Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients.Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS).The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P < 0.05). The DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC.Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts.     

Microvascular invasion may be the determining factor in selecting TACE as the initial treatment in patients with hepatocellular carcinoma

The aim of this study was to investigate factors affecting tumor necrosis with transcatheter arterial chemoembolization (TACE). Factors associated with early hepatocellular carcinoma recurrence after curative hepatectomy were also evaluated.Data of 51 patients who underwent surgery after a single session of TACE at a single university hospital were retrospectively analyzed. Factors that might affect tumor necrosis were determined by evaluating the TACE approach and by analyzing computed tomography and TACE findings, pathologic reports, and laboratory findings.In univariate analysis, microvascular invasion (MVI), radiological capsule appearance on the computed tomography, chronic hepatitis B, diabetes mellitus and serum albumin, MVI were significantly associated with tumor necrosis by TACE (P < .02). In multivariate analysis, MVI was the only statistically significant factor in TACE-induced tumor necrosis (P = .001). In univariate and multivariate analysis, MVI was the strongest factor for recurrence-free survival rate within 2 years (P = .008, P = .002).MVI could be a crucial factor in determining TACE as an initial treatment for hepatocellular carcinoma. MVI is also a strong indicator of recurrence within 2 years after curative hepatic resection.     

Retrospective Comparison of Fludarabine in Combination With Intermediate-Dose Cytarabine Versus High-Dose Cytarabine As Consolidation Therapies for Acute Myeloid Leukemia

This retrospective study compared efficacy and safety of fludarabine combined with intermediate-dose cytarabine (FA regimen) versus high-dose cytarabine (HiDAC regimen) as consolidation therapy in acute myeloid leukemia (AML) patients who achieved complete remission.Disease-free survival (DFS) and overall survival (OS) based on age (≥60, <60 years) and cytogenetics were evaluated from data between January 2005 and March 2013.Total 82 patients (FA, n = 45; HiDAC, n = 37; 14–65 years) were evaluated. Five-year DFS was 32.0% and 36.2% for FA and HiDAC groups, respectively (P = 0.729), and 5-year OS was 39.5% and 47.8% (P = 0.568), respectively. Among older patients (≥60 years), 3-year DFS was 26.0% for FA group and 12.5% for HiDAC group (P = 0.032), and 3-year OS was 34.6% and 12.5%, respectively (P = 0.026). In FA group, hematological toxicities were significantly lower. FA regimen was as effective as HiDAC regimen in patients with good/intermediate cytogenetics and significantly improved DFS and OS in older patients.     

Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma

This study aims to clarify the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) for patients with hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR). The prognostic value of the NLR for HCC patients has not been definitely reviewed by large studies, especially for those with different Barcelona Clinic Liver Cancer (BCLC) stages.A consecutive sample of 963 HCC patients who underwent potentially curative HR was classified as having low or high NLR using a cut-off value of 2.81. Overall survival (OS) and tumor recurrence were compared for patients with low or high NLR across the total population, as well as in subgroups of patients in BCLC stages 0/A, B, or C. Clinicopathological parameters, including NLR, were evaluated to identify risk factors of OS and tumor recurrence after potentially curative hepatic resection. Multivariate analyses were performed using the Cox proportional hazards model or subdistribution hazard regression model.Multivariate analyses showed that NLR (>2.81), tumor number (>3), incomplete capsule, serum albumin (≤35 g/L), alanine transaminase activity (>40 U/L), and macrovascular invasion were risk factors for low OS, whereas NLR (>2.81), tumor size (>5 cm), alpha fetal protein concentration (>400 ng/L), and macrovascular invasion were risk factors for low tumor recurrence. NLR > 2.81 was significantly associated with poor OS and tumor recurrence in the total patient population (both P < 0.001), as well as in the subgroups of patients in BCLC stages 0/A or B (all P < 0.05). Moreover, those with high NLR were associated with low OS (P = 0.027), and also with slightly higher tumor recurrence than those with low NLR for the subgroups in BCLC stage B (P = 0.058). Neither association, however, was observed among patients with BCLC stage C disease.NLR may be an independent predictor of low OS and tumor recurrence after potentially curative HR in HCC patients in BCLC stages 0/A or B.     

The impact of resection margin and microvascular invasion on long-term prognosis after curative resection of hepatocellular carcinoma: a multi-institutional study

BackgroundThe resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for hepatocellular carcinoma (HCC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes.MethodsUsing multi-institutional data, the different impact of the RM status (narrow, <1 cm, or wide, ≥1 cm) and MVI (positive or negative) on overall survival (OS) and recurrence-free survival (RFS) after curative liver resection of solitary HCC without macrovascular invasion was analyzed.ResultsIn 801 patients, 306 (38%) had a narrow RM and 352 (44%) had positive MVI. The median OS and RFS were 109.8 and 74.8 months in patients with wide RM & negative MVI, 93.5 and 53.1 months with wide RM & positive MVI, 79.2 and 41.6 months with narrow RM & negative MVI, and 69.2 and 37.5 months with narrow RM & positive MVI (both P < 0.01). On multivariable analyses, narrow RM & positive MVI had the highest hazard ratio with reduced OS and RFS (HR 2.96, 95% CI 2.11–4.17, and HR 3.15, 95% CI, 2.09–4.67, respectively).ConclusionsConcomitant having narrow RM and positive MVI increases the risks of postoperative death and recurrence by about 2-fold in patients with solitary HCC.     

Clinical Significance of Preoperative Serum High Density Lipoprotein Cholesterol Levels in Soft Tissue Sarcoma

The prognostic value of lipid profile remains unclear in soft tissue sarcoma. The aim of the present study was to validate the prognostic value of preoperative plasma lipid profile (high density lipoprotein-cholesterol [HDL-C], low density lipoprotein-cholesterol [LDL-C], cholesterol, and triglycerides) levels on disease-free survival (DFS) and overall survival (OS) in soft tissue sarcoma (STS) patients undergoing extensive and radical surgical resection.The preoperative plasma lipid profile levels of 234 STS patients, who were operated on between 2000 with 2010, were retrospectively evaluated. Kaplan-Meier curves and multivariate Cox proportional models were calculated for DFS and OS.In univariate analysis, a decreased HDL-C level was significantly associated with decreased OS (hazard ratio [HR], 3.405; 95% confidence interval (CI), 1.445–8.021, P = 0.005) and remained significant in the multivariate analysis (HR, 5.615; 95% CI, 1.243–25.378, P = 0.025). Patients with HDL-C < 1.475 mmol/L showed a median OS of 71 months. In contrast, patients with HDL-C ≥1.475 mmol/L had a median OS of 101 months. In univariate analysis, a decreased HDL-C level was significantly associated with decreased DFS (HR, 2.085; 95% CI, 1.271–3.422, P = 0.004) and remained significant in the multivariate analysis (HR, 1.808; 95% CI, 1.118–2.924, P = 0.016). Patients with HDL-C <1.475 mmol/L presented with a median DFS of 47 months, whereas patients with HDL-C ≥1.475 mmol/L had a median DFS of 78 months. In univariate analysis and multivariate analyses regarding OS and DFS, there was no significant association between the groups in terms of LDL-C, CHO and TG.Our study investigated the potential prognostic utility of preoperative plasma HDL-C levels as an independent factor in STS patients who had undergone radical surgical resection.     

The Association Between Body Mass Index and the Prognosis and Postoperative Complications of Hepatocellular Carcinoma: A Meta-Analysis

Previous studies have reported the association between excess body mass index (BMI) and increased risk of hepatocellular carcinoma (HCC). However, whether BMI is associated with the prognosis and postoperative complications of HCC is still not clear.We searched PubMed and Embase for relevant studies published until the date of August 30, 2014. Additional studies were manually identified by searching reference lists of retrieved articles. Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) for overall survival (OS), disease-free survival (DFS), and risk ratios (RRs) with 95% CIs for postoperative complications were calculated using random effects or fixed effects models according to heterogeneities between studies.A total of 14 studies were included in the present meta-analysis. The pooled results showed that excess BMI was not significantly associated with improved OS (HR = 0.94; 95% CI: 0.74–1.19, P = 0.588) or DFS (HR = 0.93; 95% CI: 0.79–1.10, P = 0.382). In addition, higher BMI was not associated with increased rate of a number of complications including ascites (RR = 1.25, 95% CI: 0.94–1.65, P = 0.119), bile leaks (RR = 1.22, 95% CI: 0.81–1.83, P = 0.345), and 30-day mortality (RR = 1.05, 95% CI: 0.57–1.96, P = 0.871). However, HCC patients with higher BMI had increased incidence of wound infections (RR = 2.17, 95% CI: 1.28–3.68, P = 0.004).BMI was not an independent prognostic factor for the evaluation of the prognosis in HCC patients, and it was not associated with postoperative complications except for wound infections that as significantly associated with higher BMI scores.     

Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After Laparoscopic Total Mesorectal Excision: The Korean Laparoscopic Colorectal Surgery Study Group

This study aims to validate the oncologic outcomes of anastomotic leakage (AL) after laparoscopic total mesorectal excision (TME) in a large multicenter cohort.The impact of AL after laparoscopic TME for rectal cancer surgery has not yet been clearly described.This was a multicenter retrospective study of 1083 patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0–III). AL was defined as an anastomotic complication within 30 days of surgery irrespective of requiring a reoperation or interventional radiology. Estimated local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were compared between the leakage group and the no leakage group using the log-rank method. Multivariate Cox-regression analysis was used to adjust confounding for survival.The incidence of AL was 6.4%. Mortality within 30 days of surgery occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P = 0.011). Five-year DFS and OS were significantly lower in the leakage group than the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P = 0.007). Multivariate analysis showed that AL was an independent poor prognostic factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.0–2.6; P = 0.042, HR = 2.1; 95% CI: 1.0–4.2; P = 0.028, respectively).AL after laparoscopic TME was significantly associated with an increased rate of LR, systemic recurrence and poor OS.     

Postoperative adjuvant sorafenib improves survival outcomes in hepatocellular carcinoma patients with microvascular invasion after R0 liver resection: a propensity score matching analysis

BackgroundMicrovascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR).MethodsThe data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed.Results728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease.ConclusionsPA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.     

Elevated CA19-9 as the Most Significant Prognostic Factor in Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy

It remains controversial regarding the prognostic significance of carbohydrate antigen 19-9 (CA19-9) for locally advanced rectal cancer (LARC) (T3–4/N+) patients with neoadjuvant chemoradiotherapy (neo-CRT). And it is unknown whether CA19-9 can identify patients who may benefit from adjuvant chemotherapy.Overall, 303 LARC patients with neo-CRT between 2004 and 2010 were recruited. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival across pretreatment CA19-9 were estimated by Kaplan–Meier method and Cox regression model.In univariate analysis, elevated CA19-9 (>35 U/mL) was significantly correlated with poor OS (P = 0.003), DFS (P = 0.001), and DMFS (P = 0.039). Adjusting for the known covariates, CA19-9 was significantly associated with OS (HR = 1.86, 95% CI 1.03–3.34, P = 0.039) and DFS (HR = 1.74, 95% CI 1.08–2.80, P = 0.024). In the elevated CA19-9 subgroup, patients with adjuvant chemotherapy got much better OS (P < 0.001) and DFS (P = 0.016) than those without. In consideration of both CA19-9 and carcinoembryonic antigen (CEA), we found that patients with both elevated CA19-9 and CEA (>5 ng/mL) got the worst OS (P = 0.021) and DFS (P = 0.006), and significantly benefited from adjuvant chemotherapy in OS (P < 0.001) and DFS (P = 0.026).Pretreatment CA19-9 level is a significant prognostic indicator in patients with LARC following neo-CRT. The addition of CA19-9 to CEA is valuable to discriminate the appropriate patients for adjuvant chemotherapy.     

A systematic review and meta-analysis of adjuvant transarterial chemoembolization after curative resection for patients with hepatocellular carcinoma

BackgroundThe aim of this study was to systematically evaluate and determine those patients with hepatocellular carcinoma (HCC) that would benefit from the administration of postoperative adjuvant transarterial chemoembolization (PA-TACE).MethodsPubMed, Embase and Cochrane Library were searched for randomized controlled trials (RCTs) and observational studies up to July 30, 2019. The outcome of Overall survival (OS) and disease-free survival (DFS) were extracted and converted to hazard ratios (HRs) with 95% confidence intervals (95%CIs).ResultsA total of 40 studies (10 RCTs and 30 non-RCTs) involving 11,165 patients were included. Overall, PA-TACE was associated with an increased OS [HR, 0.71 (95% CI, 0.65–0.77); P < 0.001] and DFS [HR, 0.73 (95% CI, 0.66–0.80); P < 0.001]. Subgroup analysis in patients with microvascular invasion (MVI), tumor diameter >5 cm or multinodular tumors demonstrated that PA-TACE improved OS and DFS. In patients without MVI, PA-TACE showed no improvement in OS [HR, 1.14 (95% CI, 0.85–1.53); P = 0.370], and resulted in worse DFS than curative resection alone [HR, 1.20 (95% CI, 1.03–1.39); P = 0.002].ConclusionThis meta-analysis indicated that PA-TACE was beneficial in patients with HCC who were at high risk of postoperative recurrence including tumor diameter >5 cm, multinodular tumors and MVI-positive. In patients with tumor diameter ≤5 cm, single tumor or MVI-negative. PA-TACE does not appear to improve outcomes and may potentially promote postoperative recurrence in certain patients.     

The Efficacy of Taxanes- and Oxaliplatin-Based Chemotherapy in the Treatment of Gastric Cancer After D2 Gastrectomy for Different Lauren Types

To investigate the efficacy of Taxanes- and Oxaliplatin-based chemotherapies (TC and OC) in the treatment of gastric cancer patients after D2 gastrectomy with different Lauren types. In this study, 299 patients of gastric adenocarcinoma with D2 lymph node dissection were reviewed between 2007 and 2014. Chemotherapies were classified as Oxaliplatin-based and Taxanes-based regimen. Treatment outcomes were analyzed according to different Lauren types, such as the intestinal type, diffuse type, and mixed type groups, respectively. The disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The log-rank test was used for univariate analysis, and Cox regression was used for multivariate analysis. In diffuse type gastric cancer, the Oxaliplatin-based arm had a longer median DFS and OS compared with Taxanes-based arm (DFS: 47.0 vs 28.6 months, P = 0.04; OS: 51.9 vs 34.5 months, P = 0.048). The chemotherapy regimen was an independent prognostic factor for DFS and OS of diffuse type gastric cancer patients by multivariate analysis (P = 0.01). In the intestinal type, although the DFS and OS of intestinal type patients in TC group were higher than those in OC group (DFS: 53.4 vs 42.4 months; OS: 69.7 vs 57.8 months), there was no statistical significance observed (both P > 0.05). For the mixed type, the 2 different chemotherapy regimens achieved similar median DFS and OS. In a conclusion, the patients of diffuse type were more sensitive to OC, and the intestinal type patients may be benefit from TC. Therefore, it will be of benefit for gastric patients by introducing Lauren classification clinically and to help the choice of chemotherapy regimen for gastric patients after D2 gastrectomy.     

Effect of mu Agonists on Long-Term Survival and Recurrence in Nonsmall Cell Lung Cancer Patients

Opioids are widely used for postoperative analgesia. Morphine may have an effect on cell replication, migration, and cancer recurrence. However, the association of postoperative mu agonists with outcome of nonsmall cell lung cancer (NSCLC) patients has not been fully investigated.We retrospectively evaluated the impact of postoperative mu agonists on overall survival (OS) and disease-free survival (DFS) in early stage NSCLC patients. Patients and relevant medical information were selected from the Bio-Bank of Shandong Provincial Hospital. Difference of clinicopathologic information in postoperative mu agonists group and no mu agonists group was analyzed by χ² test. Univariate and multivariate Cox regression analysis were conducted and represented as hazards ratio and 95% confidence interval form. The primary endpoint was OS and secondary endpoint was DFS.This retrospective study included 984 consecutive NSCLC patients who underwent surgery between January 2006 and December 2011. No significant difference existed between postoperative mu agonists usage group and no mu agonists usage group in clinicopathologic information except operation type (P = 0.041). Postoperative mu agonists usage was related to shorter OS (HR 1.514, 95% CI 1.197–1.916, P = 0.001) and shorter DFS (HR 1.415, 95% CI 1.123–1.781, P = 0.003) in the multivariate Cox regression model. For the patients who received postoperative chemotherapy or radiotherapy postoperative mu agonists also predict shorter survival (HR 1.437, 95% CI 1.041–1.982, P = 0.027). Subgroup analysis showed that administration of postoperative mu agonists was related to shorter OS, especially in males, more smoking, poor differential degree, bilobectomy or pneumonectomy, and stage III subgroup, respectively.Administration of postoperative mu agonists was related to shorter OS and DFS for the NSCLC patients who underwent surgery.