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.     

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.     

Spontaneous rupture of hepatocellular carcinoma: Optimal timing of partial hepatectomy

BackgroundPartial hepatectomy has been used to treat patients with resectable hepatocellular carcinoma (HCC) which spontaneously ruptured. It is still controversial as to whether emergency partial hepatectomy (EmPH) should be carried out at the time of rupture, or the patients should initially be managed by operative or non-operative treatment to stop the bleeding, followed by staged early or delayed partial hepatectomy when the patient's condition becomes stable.MethodsConsecutive 10-year patients with ruptured HCC managed at our center were included in this study. Patients who underwent partial hepatectomy were further subdivided into the EmPH group, the staged early partial hepatectomy (SEPH) group, and the staged delayed partial hepatectomy (SDPH) group. Univariate and multivariate analyses of factors affecting overall survival(OS) were conducted before and after propensity score matching analyses amongst the included patients. OS, postoperative mortality, recurrence free survival (RFS), and peritoneal metastatic rates were compared. The risk factors of peritoneal metastases were determined using the COX regression analysis.ResultsThe 130 patients who underwent partial hepatectomy were subdivided into the EmPH group (surgery at the time of rupture, n = 30), the SEPH group (surgery ≤ 8 days of rupture, n = 67), and the SDPH group (surgery > 8 days of rupture, n = 33). The remaining 86 patients underwent non-surgical treatment. Partial hepatectomy was an independent predictor of better OS (HR 2.792, P < 0.001). For resectable HCC, the 30-day mortality, OS, and RFS were similar between the EmPH group, and the staged partial hepatectomy (SPH) group which included the patients who underwent SEPH and SDPH. The SEPH group had significantly better OS and RFS. Multivariate COX regression analysis demonstrated that SDPH was strongly associated with postoperative peritoneal dissemination (OR 28.775, P = 0.003).ConclusionPartial hepatectomy provided significantly better survival than non-surgical treatment for patients who presented with ruptured HCC. Early partial hepatectomy within 8 days of rupture which included EmPH (carefully selected) and SEPH, resulted in significantly less patients with peritoneal dissemination and better long-term survival outcomes (especially RFS) than SDPH.     

Systemic Chemotherapy With or Without Hepatic Arterial Infusion Chemotherapy for Liver Metastases From Pancreatic Cancer: A Propensity Score Matching Analysis

BackgroundThe significance of systemic chemotherapy (SCT) combined with hepatic arterial infusion (HAI) chemotherapy in the treatment of pancreatic ductal adenocarcinoma with liver metastases (PACLM) remains unclear. Based on previous studies, this single-center propensity score matching (PSM) study aimed to explore the efficacy of SCT with or without HAI for PACLM.Patient and MethodsThe PSM method was used to screen 661 cases of PACLM who received SCT at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2020. According to the 1:6 ratio with PSM, 385 patients were divided into the SCT+HAI group (n = 55) and the SCT group (n = 330). After a median follow-up of 49 (range 7-153) months, overall survival (OS) and survival-related prognostic factors were analyzed.ResultsThe main baseline characteristics of the SCT+HAI group and the SCT alone group were matched appropriately (P > .05). After PSM, the median OS for patients in the 2 groups was 10.6 and 7.6 months, respectively (P = .02). Multivariate analysis revealed that peritoneal metastases (P = .03), CA199 ≥ 500U/mL (P = .03), and lactate dehydrogenase (LDH) ≥ 250U/L (P = .03) were prognostic factors of poor survival, modern SCT plus HAI (P = .04) was a protective factor.ConclusionOur findings indicated that adequate cycles of SCT+HAI result in better survival than SCT alone in patients with PACLM. Patients with peritoneal metastases, markedly elevated CA19-9 and LDH have a poorer prognosis. The conclusion has yet to be validated in randomized controlled clinical trials.     

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.     

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.     

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.     

Comparison of anatomic and non-anatomic resections for very early-stage hepatocellular carcinoma: The importance of surgical resection margin width in non-anatomic resection

BackgroundThe superiority of anatomic resection (AR) over non-anatomic resection (NAR) for very early-stage hepatocellular carcinoma (HCC) has remained a topic of debate. Thus, this study aimed to compare the prognosis after AR and NAR for single HCC less than 2 cm in diameter.MethodsConsecutive patients with single HCC of diameter less than 2 cm who underwent curative hepatectomy between 1997 and 2017 were included in this retrospective study.ResultsIn total, 159 patients were included in this study. Of these, 52 patients underwent AR (AR group) and 107 patients underwent NAR (NAR group). No significant differences were noted in recurrence-free survival (RFS) and overall survival (OS) between the AR and NAR groups (P = 0.236 and P = 0.363, respectively). Multivariate analysis revealed that low preoperative platelet count and presence of satellite nodules were independent prognostic factors of RFS and OS. Wide surgical resection margin did not affect RFS (P = 0.692) in the AR group; however, in the NAR group, RFS was found to be higher with surgical resection margin widths ≥1 cm than with surgical resection margin widths <1 cm (P = 0.038).ConclusionsPrognosis was comparable between the NAR and AR groups for very early-stage HCC with well-preserved liver function. For better oncologic outcomes, surgeons should endeavor in keeping the surgical resection margin widths during NAR ≥1 cm.     

Transarterial chemoembolization plus immune checkpoint inhibitor as postoperative adjuvant therapy for hepatocellular carcinoma with portal vein tumor thrombus: A multicenter cohort study

PurposeThis study aimed to assess the efficacy and safety of postoperative adjuvant transarterial chemoembolization (PA-TACE) plus immune checkpoint inhibitor (ICI) for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Patients and methodsThis study was conducted on three centers from June 2018 to December 2020. Patients were divided into the PA-TACE (n = 48) and PA-TACE plus ICI groups (n = 42). The recurrence-free survival (RFS) and overall survival (OS) curves were depicted by Kaplan-Meier method, and the differences between the two groups were compared using log-rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for RFS and OS. Adverse events (AEs) were assessed according to the Common Terminology Criteria for AEs (CTCAE) version 5.0.ResultsThe median RFS of the PA-TACE plus ICI group was significantly longer than the PA-TACE group (12.76 months vs. 8.11 months; P = 0.038). The median OS of the PA-TACE plus ICI group was also significanfly better than the PA-TACE group (24.5 months vs. 19.1 months; P = 0.032). PA-TACE plus ICI treatment was an independent prognostic factor for RFS (HR: 0.54, 95% CI: 0.32–0.9, P = 0.019) and OS (HR: 0.47, 95% CI: 0.26–0.86, P = 0.014). Only one patient experienced grade ≥3 immune-related AEs in the PA-TACE plus ICI group.ConclusionsPA-TACE plus ICI treatment had better efficacy in preventing recurrence and prolonging survival than PA-TACE alone for HCC patients with PVTT after R0 resection. This novel treatment modality may be an appropriate option for HCC with PVTT.     

Partial hepatectomy vs. transcatheter arterial chemoembolization for multiple hepatocellular carcinomas of BCLC-B stage: A meta-analysis of high-quality studies

Background/aimThe Barcelona Clinic Liver Cancer (BCLC) recommends that transcatheter arterial chemoembolization (TACE) are indicated in patients with multiple hepatocellular carcinomas (HCCs) of BCLC-B stage. However, partial hepatectomy (PH) has increasely performed in these patients. The purpose of this meta-analyses is to illustrate the comparative survival benefits of PH and TACE for patients with multiple HCCs of BCLC-B stage.MethodElectronic databases were systematically searched for eligible studies that compared PH and TACE performed in patients with multiple HCCs of BCLC-B stage. Studies that met the inclusion criteria were reviewed systematically. The reported data were aggregated statistically using the RevMan5.3 software. Primary endpoint was overall survival (OS), and secondary endpoint were the 1-, 3-, and 5-year survival rates, postoperative 30-day mortality and postoperative complications.ResultsA total of seven high-quality studies (one randomized controlled trial [RCT], six propensity-score matching (PSM) nonrandomized comparative trials [non-RCTs] that met the inclusion criteria, which comprised of 2487 patients (1245 PH and 1242 TACE) in the meta-analysis. When compared with the TACE group, the PH group had a significantly higher OS (HR, 1.65; 95% CI, 1.48–1.84; P = 0.26; I² = 22%) and 1-, 3-, 5-year survival rates (OR, 1.96; 95% CI, 1.59–2.41; P = 0.0005; I² = 75%; P < 0.00001; OR, 2.92; 95% CI, 1.94–4.42; P = 0.0001; I² = 78%; P < 0.00001; OR, 2.60; 95% CI, 2.17–3.11; P = 0.13; I² = 44%; P < 0.00001; respectively). Survival benefits persisted across sensitivity and subgroup analyses; High heterogeneity remained after sensitivity and subgroup analyses for 3-year survival rates.ConclusionPH can provide more survival benefit for patients with multiple HCCs of BCLC-B stage compared with TACE.     

Sirolimus-based immunosuppression improves the prognosis of liver Transplantation Recipients with low TSC1/2 expression in hepatocellular carcinoma beyond the Milan Criteria

BackgroundThe use of the immunosuppressive agent sirolimus (SRL) following liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) is controversial. Sirolimus is a typical mammalian target of rapamycin (mTOR) inhibitor, and tuberous sclerosis 1-tuberous sclerosis 2 complex (TSC1/TSC2) is an important negative effector in the mTOR pathway. In this study, we investigated the effect of SRL-based immunosuppression on the prognosis of LT recipients with HCC beyond the Milan criteria based on TSC1/2 expression and explored the effect of TSC1 on HCC in vitro and in vivo.MethodsWe retrospectively analyzed 120 HCC patients who underwent LT in our hospital between January 1, 2015 and December 30, 2018. All patients had HCC beyond the Milan criteria and were divided into the SRL group (n = 50) and non-SRL group (n = 70). TSC1/2 expression levels in paraffin-embedded tissues were determined by immunohistochemistry (IHC) and then analyzed as subgroups. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. TSC1 expression was silenced in Huh-7 and Bel-7402 cell lines for further cell function experiments.Results88.3% of patients were HBV LT recipients. The SRL group exhibited better DFS and OS compared to the non-SRL group (P = 0.02, P = 0.003). Subgroup (TSC1-based or TSC2-based) analyses revealed that patients with low TSC1 or TSC2 expression benefited from sirolimus (DFS: P = 0.046, OS: P = 0.006 for TSC1; DFS: P = 0.05, OS: P = 0.003 for TSC2) compared with patients with high expression. TSC1 knockdown in Huh-7 and Bel-7402 HCC cell lines activated the mTORC1 pathway and enhanced cell proliferation, migration and sensitivity to SRL in vitro and in vivo.ConclusionTSC1/2 expression could be used to predict the prognosis of patients with HCC beyond the Milan criteria who underwent SRL-based immunosuppression following LT. TSC1 knockdown promoted HCC malignancy and enhanced sensitivity to SRL.     

Long-term surgical outcomes of Non alcoholic fatty liver disease associated hepatocellular carcinoma

BackgroundThe global burden of non-alcoholic fatty liver disease (NAFLD) and NAFLD-associated hepatocellular carcinoma (HCC) is steadily rising. We pursued to investigate the results after liver resection for NAFLD-HCC versus hepatitis B virus (HBV)-HCC exploiting Kaplan Meier method, log-rank test and uni/multivariate analysis with the logistic regression models”.MethodsPatients who underwent liver resection for HCC between January 2004 and December 2018 were included. The outcomes of NAFLD-associated HCC were analyzed.ResultsThe prevalence of NAFLD-associated HCC was 8.4%. A significant number of NAFLD patients had no cirrhosis (21 patients; 38.8%). Although NAFLD patients had a significantly better 5-year survival (P = 0.033), NAFLD was not significantly associated with overall survival in multivariate analysis (P = 0.287). However, survival after 5 years declined in NAFLD patients and was similar to HBV. NAFLD was protective against systemic recurrence compared with HBV (P = 0.018), and this was confirmed in multivariate analysis (P = 0.044). Five-year systemic recurrence (P = 0.044) was significantly lower in NAFLD patients and decreased with time from surgery. Multivariate analysis revealed that anatomical liver resection was independently associated with decreased recurrence in NAFLD patients (HR = 0.337; P = 0.033).ConclusionOverall survival is similar between NAFLD-associated HCC and HBV-associated HCC. Despite there being no significant difference between liver function tests, type of surgery performed, liver cirrhosis, size of tumor, number of tumors, pathological factors like satellite nodules and Edmonson Steiner staging, NAFLD-associated HCC shows lower systemic recurrence compared to HBV-associated HCC.     

Comparing surgical and oncologic outcomes between laparoscopic gastrectomy and open gastrectomy in advanced gastric cancer with serosal invasion: A retrospective study with propensity score matching

PurposeLaparoscopic gastrectomy (LG) has gradually increased for treating advanced gastric cancer (AGC). However, there is a lack of evidence on oncologic safety for AGC, especially with serosal invasion. This study evaluates the surgical and oncologic outcomes between laparoscopic and open gastrectomy (OG) for gastric cancer with serosal invasion.MethodsWe retrospectively reviewed 256 patients who underwent OG and 147 patients who underwent LG for gastric cancer with serosal invasion between August 2005 and December 2017. Finally, 124 patients in the LG group and 124 in the OG group were enrolled according to one-to-one propensity score matching (PSM) analysis. We evaluated surgical and oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS).ResultsThere were no statistical differences in hospital stay and major complications between the two groups. The retrieved lymph nodes of the LG group were similar to those of OG (40 ± 16.23 vs. 38 ± 14.42, p = 0.306), and it showed a similar operation time compared with the other (164 ± 43.86 vs. 156 ± 37.66, p = 0.063). There was no statistical difference in OS (p = 0.761) and RFS (p = 0.121) for survival analysis between the two groups.ConclusionLG for gastric cancer with serosal invasion is feasible and could be considered as a standard treatment.     

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.     

Increased expression of thyroid hormone receptor alpha and estrogen receptor alpha in breast cancer associated with thyroid cancer

IntroductionBreast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings.Material and methodsTissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERβ, TRα, and TRβ expression levels were analyzed by immunohistochemistry.ResultsTRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p < 0.001).ConclusionEnhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer.     

HER2 as a potential biomarker guiding adjuvant chemotherapy in stage II colorectal cancer

BackgroundHER2 is a well-established therapeutic target in breast and gastric cancers, while the role of HER2 in colorectal cancer is unclear, and no studies have explored the impact of HER2 on the outcome of stage II colorectal cancer patients treated with 5-fluorouracial based adjuvant chemotherapy.MethodsWe analyzed HER2 mRNA expression of 206 patients in GSE39582 dataset and explored the impact of HER2 expression on benefit from adjuvant chemotherapy for stage II colon cancer patients. We further validated the finding by retrospectively analyzing HER2 detection of immunohistochemistry in a cohort of 282 patients in Fudan University Shanghai Cancer Center (FUSCC).ResultsIn GSE39582 dataset, chemo-treated HER2-high patients had a better overall survival (OS) and relapse-free survival (RFS) versus chemo-naïve HER2-high patients (5-year OS: 100% vs 69.5%, 5-year RFS: 100% and vs 64%, P = 0.027 and 0.025, respectively). On the contrary, chemo-treated HER2-low patients had a worse RFS compared with chemo-naïve HER2-low patients (5-year RFS: 65.6% vs 82.1%, P = 0.022). In FUSCC cohort, chemo-treated HER2-positive patients exhibited better OS vs chemo-naïve HER2-positive patients (5-year OS: 100% vs 73.8%, P < 0.001), and showed marginal evidence of a lower probability of recurrence (5-year RFS: 74.4% vs 58.7%, P = 0.072). After stratifying by mismatch repair (MMR) status, the results only kept consistency in patients with pMMR status.ConclusionsHER2-positve patients with stage II colorectal cancer can benefit from 5-fluorouracial based adjuvant chemotherapy, especially for patients with pMMR status.     

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.     

Effectiveness of neoadjuvant chemotherapy on the survival outcomes of patients with resectable non-small-cell lung cancer: A meta-analysis of randomized controlled trials

PurposeTo determine the effectiveness of neoadjuvant chemotherapy (NACT) versus primary surgery on survival outcomes for resectable non-small-cell lung cancer (NSCLC) using an approach based on a meta-analysis.MethodsThe PubMed, EmBase, Cochrane library, and CNKI databases were systematically browsed to identify randomized controlled trials (RCTs) which met a set of predetermined inclusion criteria throughout January 2020. Hazard ratios (HRs) were applied for the pooled overall survival (OS) and progression-free survival (PFS) values, and the pooled survival rates at 1-year and 3-year were used as the relative risk (RR). All the pooled effect estimates with 95% confidence intervals (CIs) were calculated using the random-effects model.ResultsNineteen RCTs contained a total of 4372 NSCLC at I-III stages was selected for final meta-analysis. We noted NACT was significantly associated with an improvement in OS (HR: 0.87; 95%CI: 0.81–0.94; P < 0.001) and PFS (HR: 0.86; 95%CI: 0.78–0.96; P = 0.005). Moreover, the survival rate at 1-year (RR: 1.07; 95%CI: 1.02–1.12; P = 0.007) and 3-year (RR: 1.16; 95%CI: 1.06–1.27; P = 0.001) in the NACT group was significantly higher than the survival rate for the primary surgery group. Finally, the treatment effects of NACT versus primary surgery on survival outcomes might be different when stratified by the mean age of patients and the tumor stages.ConclusionsNACT could improve survival outcomes for patients with resectable NSCLC, suggesting its suitable future applicability for clinical practice. However, large-scale RCT should be conducted to assess the chemotherapy regimen on the prognosis of resectable NSCLC.     

Borderline or locally advanced pancreatic adenocarcinoma: A single center experience on the FOLFIRINOX induction regimen

IntroductionThis study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice.Material and methodsFrom 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment.ResultsThe 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3–16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P < 0.001). In resected patients, the ASA 3 score (P < 0.01), venous resection (P < 0.01), hemorrhage (P < 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P < 0.001).ConclusionsNeoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.