Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma

BACKGROUND Programmed death receptor-1(PD-1)inhibitors have been approved as secondline treatment regimen in hepatocellular carcinoma(HCC),but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy.AIM To estimate the clinical outcome of transarterial chemoembolization(TACE)and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC(uHCC).METHODS We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022.45 patients received the PD-1 inhibitors,lenvatinib,TACE(PD-1-Lenv-T)therapy,and 20 received the lenvatinib,TACE(Lenv-T)therapy.In terms of the dose of lenvatinib,8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg.Of the patients in the PD-1 inhibitor combination group,15 received Toripalimab,14 received Toripalimab,14 received Camrelizumab,4 received Pembrolizumab,9 received Sintilimab,and 2 received Nivolumab,1 with Tislelizumab.According to the investigators’assessment,TACE was performed every 4-6 wk when the patient had good hepatic function(Child-Pugh class A or B)until disease progression occurred.We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors(mRECIST criteria).We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events,v 5.0.The key adverse events(AEs)after the initiation of combination therapy were observed.RESULTS Patients with uHCC who received PD-1-Lenv-T therapy(n=45)had a clearly longer overall survival than those who underwent Lenv-T therapy(n=20,26.8 vs 14.0 mo;P=0.027).The median progression-free survival time between the two treatment regimens was also measured{11.7 mo[95%confidence interval(CI):7.7-15.7]in the PD-1-Lenv-T group vs 8.5 mo(95%CI:3.0-13.9)in the Lenv-T group(P=0.028)}.The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4%and 20%(P=0.059)according to the mRECIST criteria,meanwhile the disease control rates were 93.3%and 64.0%(P=0.003),respectively.The type and frequency of AEs showed little distinction between patients received the two treatment regimens.CONCLUSION Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.

Dispersal behaviors stimulated by habitat alterations in golden snub-nosed monkeys(Rhinopithecus roxellana)in the Qinling Mountains, China

DEAR EDITOR,Combining location data, species distribution modeling(Max Ent), and major conservation events, we analyzed historical distribution changes in golden snub-nosed monkeys(Rhinopithecus roxellana) in the Qinling Mountains of China.

Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients

AIM To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma(GBC).METHODS The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic(ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0.RESULTS ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival(OS)(HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735(for preoperative plasma fibrinogen only) and 0.729(for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199(P < 0.001), resection margin(P < 0.001) and TNM stage(P = 0.010) were independent prognostic factors for GBC.CONCLUSION The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.

Prognostic significance of the fibrinogen-to-albumin ratio in gallbladder cancer patients

AIM To investigate the prognostic role of fibrinogen-toalbumin ratio(FAR) on patients with gallbladder cancer(Gbc) in this study.METHODS One hundred and fifty-four Gbc patients were retro-spectively analyzed, who received potentially curative cholecystectomy in our institute from March 2005 to December 2017. Receiver operating characteristic curve(ROc curve) was used to determine the optimal cut-offs for these biomarkers. In addition, Kaplan-Meier survival analysis as well as multivariate analysis were applied for prognostic analyses.RESULTS ROc curve revealed that the optimal cut-off value for FAR was 0.08. FAR was significantly correlated with age(P = 0.045), jaundice(P < 0.001), differentiation(P = 0.002), resection margin status(P < 0.001), T stage(P < 0.001), TNM stage(P < 0.001), and c A199(P < 0.001) as well as albumin levels(P < 0.001). Multivariate analysis indicated that the resection margin status [hazard ratio(HR): 2.343, 95% confidence interval(c I): 1.532-3.581, P < 0.001], TNM stage(P = 0.035), albumin level(HR = 0.595, 95%c I: 0.385-0.921, P = 0.020) and FAR(HR: 2.813, 95%c I: 1.765-4.484, P < 0.001) were independent prognostic factors in Gbc patients.CONCLUSION An elevated preoperative FAR was significantly correlated with unfavorable overall survival in Gbc patients, while an elevated preoperative albumin level was a protective prognostic factor for patients with Gbc. The preoperative FAR could be used to predict the prognosis of Gbc patients, which was easily accessible, costeffective and noninvasive.

Intraductal papillary neoplasm of the bile duct

Intraductal papillary neoplasm of the bile duct(IPNB)is a variant of bile duct carcinoma that is characterized by intraductal growth and better outcomes compared with common cholangiocarcinoma.IPNBs are mainly found in patients from Far Eastern areas,where hepatolithiasis and clonorchiasis are endemic.According to the immunohistochemical profiles of the mucin core proteins,IPNBs are classified into four types:pancreaticobiliary,intestinal,gastric,and oncocytic.Approximately 40%-80%of IPNBs contain a component of invasive carcinoma or tubular or mucinous adenocarcinoma,suggesting that IPNB is a disease with high potential for malignancy.It is difficult to make an accurate preoperative diagnosis because of IPNB’s low incidence and the lack of specificity in its clinical manifestation.The most common abnormal preoperative imaging findings of IPNB are intraductal masses and the involvement of bile duct dilation.Simultaneous proximal and distal bile duct dilation can be detected in some cases,which has diagnostic significance.Cholangiography and cholangioscopy are needed to confirm the pathology and demonstrate the extent of the lesions.However,pathologic diagnosis by biopsy cannot reflect the actual stage in many cases because different foci may be of different stages and because mixed pathologic findings may exist in the same lesion.Surgical resection is the major treatment.Systematic cholangioscopy with staged biopsies and frozen sections is recommended during resection to ensure that no minor tumors are left and that curative resection is achieved.Staging,histologic subtype,curative resection and lymph node metastasis are factors affecting long-term survival.

Nomogram to predict overall survival after gallbladder cancer resection in China

AIM To integrate clinically significant variables related to prognosis after curative resection for gallbladder carcinoma(GBC) into a predictive nomogram.METHODS One hundred and forty-two GBC patients who underwent curative intent surgical resection at Peking Union Medical College Hospital(PUMCH) were included. This retrospective case study was conducted at PUMCH of the Chinese Academy of Medical Sciences and Peking Union Medical College(CAMS & PUMC) in China from January 1, 2003 to January 1, 2018. The continuous variable carbohydrate antigen 19-9(CA19-9) was converted into a categorical variable(cCA19-9) based on the normal reference range. Stages 0 to IIIA were merged into one category, while the remaining stages were grouped into another category. Pathological grade X(GX) was treated as a missing value. A multivariate Cox proportional hazards model was used to select variables to construct a nomogram. Discrimination and calibration of the nomogram were performed via the concordance index(C-index) and calibration plots. The performance of the nomogram was estimated using the calibration curve. Receiver operating characteristic(ROC) curve analysis and decision curve analysis(DCA) were performed to evaluate the predictive accuracy and net benefit of the nomogram, respectively.RESULTS Of these 142 GBC patients, 55(38.7%) were male, and the median and mean age were 64 and 63.9 years, respectively. Forty-eight(33.8%) patients in this cohort were censored in the survival analysis. The median survival time was 20 months. A series of methods, including the likelihood ratio test and Akaike information criterion(AIC) as well as stepwise, forward, and backward analyses, were used to select the model, and all yielded identical results. Jaundice [hazard ratio(HR) = 2.9; 95% confidence interval(CI): 1.60-5.27], cCA19-9(HR = 3.2; 95%CI: 1.91-5.39), stage(HR = 1.89; 95%CI: 1.16-3.09), and resection(R)(HR = 2.82; 95%CI: 1.54-5.16) were selected as significant predictors and combined into a survival time predictive nomogram(C-index = 0.803; 95%CI: 0.766-0.839). High prediction accuracy(adjusted C-index = 0.797) was further verified via bootstrap validation. The calibration plot demonstrated good performance of the nomogram. ROC curve analysis revealed a high sensitivity and specificity. A high net benefit was proven by DCA.CONCLUSION A nomogram has been constructed to predict the overall survival of GBC patients who underwent radical surgery from a clinical database of GBC at PUMCH.

Research progress and prospects of markers for liver cancer stem cells

Liver cancer is a common malignancy and surgery is the main treatment strategy. However, the prognosis is still poor because of high frequencies of postoperative recurrence and metastasis. In recent years, cancer stem cell(CSC) theory has evolved with the concept of stem cells, and has been applied to oncological research. According to cancer stem cell theory, liver cancer can be radically cured only by eradication of liver cancer stem cells(LCSCs). This notion has lead to the isolation and identification of LCSCs, which has become a highly researched area. Analysis of LCSC markers is considered to be the primary method for identification of LCSCs. Here, we provide an overview of the current research progress and prospects of surface markers for LCSCs.

Combined hepatocellular cholangiocarcinoma: Controversies to be addressed

Combined hepatocellular cholangiocarcinoma(CHC) accounts for 0.4%-14.2% of primary liver cancer cases and possesses pathological features of both hepatocellular carcinoma and cholangiocarcinoma. Since this disease was first described and classified in 1949, the classification of CHC has continuously evolved. The latest definition and classification of CHC by the World Health Organization is based on the speculation that CHC arises from hepatic progenitor cells. However, there is no evidence demonstrating the common origin of different components of CHC. Furthermore, the definition of CHC subtypes is still ambiguous and the identification of CHC subtype when a single tumor contains many components has remained unresolved. In addition, there is no summary on the newly recognized histopathology features or the contribution of CHC components to prognosis and outcome of this disease. Here we provide a review of the current literature to address these questions.

Prognostic impact of the red cell distribution width in esophageal cancer patients: A systematic review and meta-analysis

AIM To clarify the previous discrepant conclusions, we performed a meta-analysis to evaluate the prognostic value of red cell distribution width(RDW) in esophageal cancer(EC). METHODS We searched the PubM ed, EMBASE, Web of Science and Cochrane Library databases to identify clinical studies, followed by using STATA version 12.0 for statistical analysis. Studies that met the following criteria were considered eligible:(1) Studies including EC patients who underwent radical esophagectomy;(2) studies including patients with localized disease without distant metastasis;(3) studies including patients without preoperative neoadjuvant therapy;(4) studies including patients without previous antiinflammatory therapies and with available preoperative laboratory outcomes;(5) studies reporting association between the preoperative RDW and overall survival(OS)/disease-free survival(DFS)/cancer-specific survival(CSS); and(6) studies published in English.RESULTS A total of six articles, published between 2015 and 2017, fulfilled the selection criteria in the end. Statistical analysis showed that RDW was not associated with the prognosis of EC patients, irrespective of OS/CSS [hazard ratio(HR) = 1.27, 95% confidence interval(CI): 0.97-1.57, P = 0.000] or DFS(HR = 1.42, 95%CI: 0.96-1.88, P = 0.000). Subgroup analysis indicated that elevated RDW was significantly associated with worse OS/CSS of EC patients when RDW > 13%(HR = 1.45, 95%CI: 1.13-1.76, P = 0.000), when the patient number ≤ 400(HR = 1.45, 95%CI: 1.13-1.76, P = 0.000) and when the study type was retrospective(HR = 1.42, 95%CI : 1.16-1.69, P = 0.000).CONCLUSION Contrary to our general understanding, this meta-analysis revealed that RDW cannot serve as an indicator of poor prognosis in patients with EC. However, it may still be a useful predictor of unfavorable prognosis using an appropriate cut-off value.

Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma

The low resection and high recurrence rates in hepatocellular carcinoma(HCC)are the major challenges to improving prognosis.Neoadjuvant and conversion therapies are underlying strategies to overcome these challenges.To date,no guideline or consensus has been published on the neoadjuvant and conversion therapies in HCC.Recent studies showed that neoadjuvant therapy for resectable HCC and conversion therapy for unresectable HCC are safe,feasible,and effective.Neoadjuvant and conversion therapies have the following advantages in treating HCC:R0 resection with sufficient volume of future liver remnant,relatively simple operation,and wide applicability.Therefore,it was necessary to conduct a widely accepted consensus among the experts in China who have extensive expertise and experience in treating HCC using neoadjuvant and conversion therapies,which is important to standardize the application of neoadjuvant and conversion therapies for the management of HCC.The strategies of neoadjuvant therapy include the selection of the eligible patients,therapy regimen,cycles,effect evaluations,and multidisciplinary treatment.The management of patients with insufficient volume of future liver remnant and patients who cannot achieve R0 resection is the key to the strategies of conversion therapy.Here,we present the resultant evidence-and experience-based consensus to guide the application of neoadjuvant and conversion therapies in clinical practice.

Albumin-to-alkaline phosphatase ratio: A novel prognostic index of overall survival in cholangiocarcinoma patients after surgery

AIM To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio(AAPR) in cholangiocarcinoma(CCA) subjects receiving surgery.METHODS In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics(including AAPR) were analyzed to determine predictors of postoperative overall survival and recurrence-free survival(RFS). In addition,univariate and multivariate Cox proportional hazards models were conducted,followed by application of time-dependent receiver operating curves to identify the optimal cut-off.RESULTS Univariate and multivariate analyses revealed both decreased overall survival[hazard ratio(HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival(HR: 2.31,95%CI: 1.40–3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253(83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low(< 0.41) AAPR group, which were significantly lower than those in the high(≥ 0.41) AAPR group(81.7%, 53.9%, and 33.4%,respectively)(P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis.CONCLUSION Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.

Response of BRCA1-mutated gallbladder cancer to olaparib: A case report

gallbladder cancer(gbc), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. the late diagnosis and abysmal prognosis present challenges to treatment. the overall 5-year survival rate for metastatic gbc patients is extremely low. BRC A1 and BRCA2 are the breast cancer susceptibility genes and their mutation carriers are at a high risk for cancer development, both in men and women. Olaparib, an oral poly ADP-ribose polymerase inhibitor, has been approved by the Food and Drug Administration and the European commission for the treatment of ovarian cancer with any BRCA1/2 mutations. the first case of BRCA1-mutated gbc patient who responded to olaparib treatment is reported here.

Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China

BACKGROUND Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma(aHCC).Several recent real-world studies appear to have confirmed this;however,there are etiological differences.This necessitates further real-world studies of lenvatinib across diverse populations,such as in China.AIM To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions.METHODS This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy.Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.Baseline characteristics and adverse events(AEs)were recorded throughout the entire study.RESULTS In total,54 HCC patients treated with lenvatinib monotherapy were included for final analysis.The objective response rate was 22%(n=12)with a progressionfree survival(PFS)of 168 d;however,AEs occurred in 92.8%of patients.Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage[hazard ratio(HR)0.465;95%CI:0.23-0.93;P=0.031],portal vein tumor thrombus(HR 0.38;95%CI:0.15-0.94;P=0.037)and Child-Pugh classifications(HR 0.468;95%CI:and specificity(83.3%)of decreasing serum biomarkers including alphafetoprotein were calculated in order to predict tumor size reduction.Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib.CONCLUSION Our findings confirm previous evidence from the phase III REFLECT study.The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC.However,further analysis suggested that baseline characteristics,changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses.Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.

Complete or partial split in associating liver partition and portal vein ligation for staged hepatectomy: A systematic review and meta-analysis

BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has been adopted by liver surgeons in recent years.However,high morbidity and mortality rates have limited the promotion of this technique.Some recent studies have suggested that ALPPS with a partial split can effectively induce the growth of future liver remnant(FLR)similar to a complete split with better postoperative safety profiles.However,some others have suggested that ALPPS can induce more rapid and adequate FLR growth,but with the same postoperative morbidity and mortality rates as in partial split of the liver parenchyma in ALPPS(p-ALPPS).AIM To perform a systematic review and meta-analysis on ALPPS and p-ALPPS.METHODS A systematic literature search of PubMed,Embase,the Cochrane Library,and ClinicalTrials.gov was performed for articles published until June 2019.Studies comparing the outcomes of p-ALPPS and ALPPS for a small FLR in consecutive patients were included.Our main endpoints were the morbidity,mortality,and FLR hypertrophy rates.We performed a subgroup analysis to evaluate patients with and without liver cirrhosis.We assessed pooled data using a random-effects model.RESULTS Four studies met the inclusion criteria.Four studies reported data on morbidity and mortality,and two studies reported the FLR hypertrophy rate and one study involved patients with cirrhosis.In the non-cirrhotic group,p-ALPPS-treated patients had significantly lower morbidity and mortality rates than ALPPStreated patients[odds ratio(OR)=0.2;95%confidence interval(CI):0.07–0.57;P=0.003 and OR=0.16;95%CI:0.03-0.9;P=0.04].No significant difference in the FLR hypertrophy rate was observed between the two groups(P>0.05).The total effects indicated no difference in the FLR hypertrophy rate or perioperative morbidity and mortality rates between the ALPPS and p-ALPPS groups.In contrast,ALPPS seemed to have a better outcome in the cirrhotic group.CONCLUSION The findings of our study suggest that p-ALPPS is safer than ALPPS in patients without cirrhosis and exhibits the same rate of FLR hypertrophy.

High incidence combination of multiple primary malignant tumors of the digestive system

BACKGROUND Clinical reports of multiple primary malignant tumors(MPMTs)in the digestive system are increasing.In China,although the survival rate of patients with MPMTs is increasing,the quality of life is very low.Many patients have reached the advanced stage when the second primary tumor is found,resulting in no early intervention and treatment.This is due to the misunderstanding of MPMTs by clinicians,who treat such tumors as metastases.Therefore,before a patient has a second primary tumor,doctors should understand some common combinations of digestive system MPMTs to provide clinical guidance to the patient.AIM To explore the high incidence combination of digestive system MPMTs under heterochronism and synchronization.METHODS A total of 1902 patients with MPMTs at Peking Union Medical College Hospital were analyzed retrospectively.They were divided into metachronous MPMT and synchronous MPMT groups,and then the high incidence combinations of the first primary cancer and the second primary cancer in metachronous cancer and synchronous cancer were sorted.Sex and age differences between metachronous and synchronous tumors were tested by the chi square test and t test,respectively.A P value<0.05 was considered as statistically significant,and SPSS version 26.0(SPSS Inc.,Chicago,Illinois,United States)was used for statistical analysis.RESULTS Among the 1902 patients with MPMTs confirmed by pathology,1811(95.2%)cases were secondary primary cancers,89(4.7%)cases were tertiary primary cancers,and 2(0.1%)cases were quaternary primary cancers.Most(88.2%)of the secondary primary cancers were identified as metachronous multiple primary cancers six months after diagnosis of the first primary cancer.The top ten most common MPMTs in the first primary cancer group ranged from high to low as follows:Breast cancer,thyroid cancer,nonuterine cancer,lung cancer,colon cancer,kidney cancer,uterine cancer,bladder cancer,rectal cancer,and gastric cancer.The highest incidence rate of the first primary cancer in male metachronous cancer was lung cancer(11.6%),the highest incidence rate of the second primary cancer was still lung cancer(24.9%),the highest incidence rate of the first primary cancer in female metachronous cancer was breast cancer(32.7%),and the highest incidence rate of the second primary cancer was lung cancer(20.8%).Among them,breast cancer,nonuterine cancer and uterine cancer were female-specific malignant tumor types,and thyroid cancer also accounted for 79.6%of female patients.The top five metachronous cancer combinations,independent of female-specific malignant tumor types and thyroid cancer,were colon cancer and lung cancer(26 cases),kidney cancer and lung cancer(25 cases),rectal cancer and lung cancer(20 cases),gastric cancer and lung cancer(17 cases),and bladder cancer and lung cancer(17 cases).The most common synchronous cancer combination was colon cancer and rectal cancer(15 cases).CONCLUSION Screening for lung cancer should be performed six months after the detection of colon cancer while rectal cancer screening should be performed within six months.

Prognostic analysis of patients with combined hepatocellularcholangiocarcinoma after radical resection:A retrospective multicenter cohort study

BACKGROUND Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a form of rare primary liver cancer that combines intrahepatic cholangiocarcinoma(ICC)and hepatocellular carcinoma.AIM To investigate overall survival(OS)and recurrence-free survival(RFS)after radical resection in patients with cHCC-CCA,and the clinicopathological factors affecting prognosis in two center hospitals of China.METHODS We reviewed consecutive patients with cHCC-CCA who received radical resection between January 2005 and September 2021 at Peking Union Medical College and the 5th Medical Center of the PLA General Hospital retrospectively.Regular follow-up and clinicopathological characteristics were systematic collected for baseline and prognostic analysis.RESULTS Our study included 95 patients who received radical resection.The majority of these patients were male and 82.7%of these patients were infected with HBV.The mean tumor size was 4.5 cm,and approximately 40%of patients had more than one lesion.The median OS was 26.8(95%CI:18.5-43.0)mo,and the median RFS was 7.27(95%CI:5.83-10.3)mo.Independent predictors of OS were CA19-9≥37 U/mL(HR=8.68,P=0.002),Child-Pugh score>5(HR=5.52,P=0.027),tumor number>1(HR=30.85,P=0.002),tumor size and transarterial chemoembolization(TACE)after surgery(HR=0.2,P=0.005).CONCLUSION The overall postoperative survival of cHCC-CCA patients is poor,and most patients experience relapse within a short period of time after surgery.Preoperative tumor biomarker(CA19-9,alphafetoprotein)levels,tumor size,and Child-Pugh score can significantly affect OS.Adjuvant TACE after surgery prolongs RFS,suggesting that TACE is a possible option for postoperative adjuvant therapy in patients with cHCC-CCA.

Precision medicine: In need of guidance and surveillance

Precision medicine,currently a hotspot in mainstream medicine,has been strongly promoted in recent years. With rapid technological development,such as next-generation sequencing,and fierce competition in molecular targeted drug exploitation,precision medicine represents an advance in science and technology; it also fulfills needs in public health care. The clinical translation and application of precision medicine-especially in the prevention and treatment of tumors-is far from satisfactory; however,the aims of precision medicine deserve approval. Thus,this medical approach is currently in its infancy; it has promising prospects,but it needs to overcome numbers of problems and deficiencies. It is expected that in addition to conventional symptoms and signs,precision medicine will define disease in terms of the underlying molecular characteristics and other environmental susceptibility factors. Those expectations should be realized by constructing a novel data network,integrating clinical data from individual patients and personal genomic background with existing research on the molecular makeup of diseases. In addition,multi-omics analysis and multi-discipline collaboration will become crucial elements in precision medicine. Precision medicine deserves strong support,and its development demands directed momentum. We propose three kinds of impetus(research,application and collaboration impetus) for such directed momentum toward promoting precision medicine and accelerating its clinical translation and application.

Association of metabolic syndromes and risk factors with ampullary tumors development: A case-control study in China

AIM: To evaluate the risk factors for ampullary adenoma and ampullary cancer.

γ-glutamyl transferase-to-platelet ratio based nomogram predicting overall survival of gallbladder carcinoma

BACKGROUND Gallbladder carcinoma(GBC)carries a poor prognosis and requires a prediction method.Gamma-glutamyl transferase–to–platelet ratio(GPR)is a recently reported cancer prognostic factor.Although the mechanism for the relationship between GPR and poor cancer prognosis remains unclear,studies have demonstrated the clinical effect of both gamma-glutamyl transferase and platelet count on GBC and related gallbladder diseases.AIM To assess the prognostic value of GPR and to design a prognostic nomogram for GBC.METHODS The analysis involved 130 GBC patients who underwent surgery at Peking Union Medical College Hospital from December 2003 to April 2017.The patients were stratified into a high-or low-GPR group.The predictive ability of GPR was evaluated by Kaplan–Meier analysis and a Cox regression model.We developed a nomogram based on GPR,which we verified using calibration curves.The nomogram and other prognosis prediction models were compared using timedependent receiver operating characteristic curves and the concordance index.RESULTS Patients in the high-GPR group had a higher risk of jaundice,were older,and had higher carbohydrate antigen 19-9 levels and worse postoperative outcomes.Univariate analysis revealed that GPR,age,body mass index,tumor–node–metastasis(TNM)stage,jaundice,cancer cell differentiation degree,and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were related to overall survival(OS).Multivariate analysis confirmed that GPR,body mass index,age,and TNM stage were independent predictors of poor OS.Calibration curves were highly consistent with actual observations.Comparisons of timedependent receiver operating characteristic curves and the concordance index showed advantages for the nomogram over TNM staging.CONCLUSION GPR is an independent predictor of GBC prognosis,and nomogram-integrated GPR is a promising predictive model for OS in GBC.

Effects of age, sex and manual task on hand preference in wild Rhinopithecus roxellana

Golden snub-nosed monkeys(Rhinopithecus roxellana),as typical arboreal group-living Old World monkeys,provide an appropriate animal model to research manual laterality and explore the factors affecting hand preference in non-human primates(NHP).This study investigated hand preference based on63 subjects and four spontaneous manual tasks(including unimanual and bimanual feeding and grooming), and assessed the effects of age, gender and type of task on handedness in R. roxellana.A population-level left-handedness was found not only in the bimanual coordinated tasks(bimanual feeding and grooming), but also in one unimanual reaching task(unimanual feeding). There were no significant differences between the sexes in either direction or strength of hand preference among any task. However, a significant difference between adults and juveniles was found in the unimanual feeding task. This is the first report on handedness in unimanual and bimanual feeding tasks that require bipedal posture in wild R. roxellana. Furthermore,this study demonstrated spontaneous feeding tasks reported previously only in the quadrupedal posture in this species, supporting the importance of factors such as posture and task complexity in the evolution of primate manual lateralization.