Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy

BACKGROUND Current tumor regression grade(TRG)evaluations are based on various systems which brings confusion for oncologists and pathologists when interpreting results.The recent six-tier system(JGCA2017-TRG)recommended by the Japanese Gastric Cancer Association(JGCA)is worth investigating,as four-tier TRG systems are favored in various parts of the world.AIM To compare the predictive accuracies of five published TRG systems.METHODS Data were retrospectively collected from patients with locally advanced gastric cancer(LAGC)who underwent neoadjuvant chemotherapy followed by D2 Lymphadenectomy between January 2005 and January 2014 at our institution.Outcomes were overall survival(OS)and disease-free survival(DFS),which were evaluated separately using the following TRG systems:JGCA2017,JGCA,Becker,AJCC/CAP,and Mandard.RESULTS All five published TRG systems were independent predictors for OS and DFS.Concordance indices of the JGCA2017,JGCA,Becker,AJCC/CAP-TRG,and Mandard systems were 0.651/0.6480.652/0.649,0.693/0.695,0.688/0.685,and 0.674/0.675 for OS and DFS,respectively.The four-tier Becker system showed the highest c-index,which was significantly greater than that of the six-tier JGCA2017 and five-tier JGCA systems(P<0.05 in OS and DFS).When residual tumor percentages were reset as:“no residual tumor”,<10%,<100%,and“no response”,the rearranged cutoff values achieved a maximum c-index with 0.728 for OS and 0.737 for DFS,which was superior to the other five systems.CONCLUSION The newly introduced six-tier JGCA-TRG system cannot increase prognostic stratification.The four-tier Becker system is more suitable for LAGC patients.A population-based study is warranted to define the optimal criterion for TRG in LAGC patients.

Analysis of long-term outcomes and application of the tumor regression grading system in the therapeutic assessment of resectable limited-disease small cell lung cancer

Objective The present study attempted to evaluate the value of neoadjuvant chemotherapy in limiteddisease small cell lung cancer(LD-SCLC),and to identify the predictive value of the tumor regression grading(TRG) system in LD-SCLC treatment-response and prognosis.Methods The records of patients with LD-SCLC(p-Stage I–IIIa) who underwent definitive radical resection at Shaanxi Provincial People's Hospital between March 1,2000 and March 31,2014 were retrospectively analyzed.We compared the disease-free survival(DFS) and overall survival(OS) rates between Group A patients(patients who underwent surgery combined with pre-and post-operative chemotherapy) and Group B patients(patients who underwent surgery combined with adjuvant chemotherapy only) using the Kaplan-Meier method and the Mantel-Cox test.The specimens of patients who received neoadjuvant chemotherapy were reassessed according to the TRG system.Results The median DFS for 27 patients was 16.267 months and the median OS was 81.167 months(1-year OS,74.07%;3-year OS,22.22%;5-year OS,14.81%).Thirteen patients received neoadjuvant chemotherapy,and their specimens were reassessed by TRG(pathological complete remission,3/13,23.08%).Patients in group A had a longer OS than those in group B(mean,93.782 months versus 42.322 months,P = 0.025),although there was no significant difference in DFS between the two groups(median 20.100 months versus 14.667 months,P = 0.551).Statistical analysis revealed that TRG Grade(G) 0(mean,61.222 months) was associated with better OS than G1-2(mean,31.213 months)(P = 0.311).Conclusion Our study indicated that neoadjuvant chemotherapy combined with surgical resection may represent a feasible treatment method for patients with LD-SCLC.The TRG system may be a valuable prediction tool to assess neoadjuvant chemotherapeutic efficacy,especially in patients with G0 disease as determined by TRG;these patients may attain an improved survival benefit with neoadjuvant chemotherapy.

Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor:A case report

BACKGROUND Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms(MiNENs)are rare malignancies affecting the pancreas.The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components,each constituting 30%or more of the tumor volume.Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination.A well-differentiated neuroendocrine tumor(NET)component is rarely reported in MiNENs.CASE SUMMARY Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas.The two tumors show distinct histology and significant differentiation discrepancy(poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET),and also present as metastases in separate lymph nodes.Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma,but no genetic alterations in the NET,suggesting divergent origins for these two components.Although tumors like this meet the diagnostic criteria for MiNEN,clinicians often find the diagnosis and staging confusing and impractical for clinical management.CONCLUSION Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

Histo-and clinico-pathological analysis of a large series of triple-negative breast cancer in a single center in China:Evidences on necessity of histological subtyping and grading

Objective: To investigate histo-pathological distribution and clinico-pathological significance in a large Chinese triple-negative breast cancer(TNBC) patients serials based on the latest understanding of its clinico-pathological diversity, and to provide more information to clinicians to improve precision of individualized treatment of TNBC.Methods: A retrospective analysis was performed on patients with TNBC at Breast Disease Center, Peking University First Hospital between January 2010 and December 2019. Histo-and clinico-pathological characteristics were analyzed by Chi-square test and Student's t-test, and prognoses were calculated using KaplanMeier method and a Cox proportionate hazards model. Bonferroni correction was used to correct for multiple comparison.Results: Conventional type of TNBC(c TNBC) were identified in 73.7% of 582 TNBC, while special type of TNBC(s TNBC) were 26.3%, including 71 apocrine carcinoma, 20 medullary carcinoma, 31 metaplastic carcinoma, 18 invasive lobular carcinoma, 7 invasive micropapillary carcinoma, 5 adenoid cystic carcinoma and 1 acinic cell carcinoma. Compared to s TNBC, c TNBC was associated with high histologic grade(P<0.001) and lower androgen receptor(AR) expression(P<0.001). TNM stage of low-grade c TNBC was significantly lower than that of high-grade c TNBC(P=0.002). Although no significant difference, there was a trend that the rate of 5-year disease-free survival(DFS) and 5-year overall survival(OS) were longer in high-grade c TNBC than in high-grade s TNBC(P=0.091 and 0.518), and were longer in low-grade s TNBC than in high-grade s TNBC(P=0.051 and0.350). Metaplastic carcinomas showed larger tumor size(P=0.008) and higher proliferative Ki67 index(P=0.004)than c TNBCs.Conclusions: Results from our cohort imply that sub-categorization or subtyping and histological grading could be meaningful in pathological evaluation of TNBC, and need to be clarified in more large collections of TNBC.

Clinical characteristics and outcome of primary hepatic neuroendocrine tumors after comprehensive therapy

BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs),a group of neuroendocrine neoplasms,are extremely rare.There are only few case reports about PHNETs in the literature.The lack of large samples and multicenter research results in poor diagnostic and therapeutic approaches.AIM To discuss the clinical characteristics,diagnosis,and treatment of PHNETs and risk factors related to survival.METHODS We retrospectively analyzed the clinical data,imaging features,immunohistochemistry data,and treatment efficacy of 40 patients who were pathologically diagnosed with PHNETs and admitted to The First Affiliated Hospital of Zhengzhou University from January 1,2014 to November 15,2019.Finally,survival analysis was performed to identify the risk factors for survival.RESULTS The main symptoms and signs included intermittent abdominal pain(19 patients,47.5%)and bloating(8 patients,20.0%).The positive rates of tested tumor markers were recorded as follows:Carbohydrate antigen 19-9(CA19-9)(6 patients,15.0%),CA72-4(3 patients,7.5%),carcinoembryonic antigen(7 patients,17.5%),and alpha-fetoprotein(6 patients,15.0%).Immunohistochemical staining results showed positivity for Syn in 38(97.4%)of 39 patients,for chromogranin A in 17(65.4%)of 26 patients,for CD56 in 35(94.6%)of 37 patients,for AE1/AE3 in 28(87.5%)of 32 patients,and for Ki-67 in all 40(100.0%)patients.The overall survival rate was significantly related to the tumor grade,AE1/AE3,and Ki-67.tumor number,tumor size,metastasis,and treatment)and overall survival.CONCLUSION Higher grade,negative AE1/AE3,and higher Ki-67 are associated with a worse survival rate.Kinds of treatment and other parameters have no significant influence on overall survival.

B2 adrenergic receptors and morphological changes of the enteric nervous system in colorectal adenocarcinoma

To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer.METHODSIn this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2A receptors as well as the morphological changes of the enteric nervous system (ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni’s post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson’s correlation coefficient.RESULTSB2A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis (P < 0.05), while there were no statistically significant associations with gender, CRC location and gross appearance (P > 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2A area showed an inverse correlation with the Auerbach plexus areas [r(14) = -0.531, P < 0.05], while for G2 tumors, epithelial B2A areas showed an indirect variation with both the Auerbach plexus areas [r(14) = -0.453, P < 0.05] and the Meissner areas [r(14) = -0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) = -0.587, P < 0.05] and Meissner [r(14) = -0.934, P < 0.05] plexuses.CONCLUSIONB2A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer may lead to targeted molecular therapies.

Clinical and pathological characteristics and prognosis of 132 cases of rectal neuroendocrine tumors

BACKGROUND Neuroendocrine tumors(NETs)frequently occur in the gastrointestinal tract,lung,and pancreas,and the rectum and appendix are the sites with the highest incidence.Epidemiology statistics show that an estimated 8000 people every year in the United States are diagnosed with NETs occurring in the gastrointestinal tract,including the stomach,intestine,appendix,colon,and rectum.The pathological changes and clinical symptoms of NETs are not specific,and therefore they are frequently misdiagnosed.AIM To investigate the clinical symptoms,pathological characteristics,treatment,and prognosis of rectal neuroendocrine tumors(RNETs)by analyzing the clinical and pathological data of 132 RNET cases at our hospital.METHODS All RNETs were graded according to Ki-67 positivity and mitotic events.The tumors were staged as clinical stages I,II,III,and IV according to infiltrative depth and tumor size.COX proportional hazard model was used to assess the main risk factors for survival.RESULTS These 132 RNETs included 83 cases of G1,21 cases of G2,and 28 cases of G3(neuroendocrine carcinoma)disease.Immunohistochemical staining showed that 89.4%of RNETs were positive for synaptophysin and 39.4%positive for chromogranin A.There were 19,85,23,and 5 cases of clinical stages I,II,III,and IV,respectively.The median patient age was 52.96 years.The diameter of tumor,depth of invasion,and pathological grade were the main reference factors for the treatment of RNETs.The survival rates at 6,12,36,and 60 mo after operation were 98.5%,94.6%,90.2%,and 85.6%,respectively.Gender,tumor size,tumor grade,lymph node or distant organ metastasis,and radical resection were the main factors associated with prognosis of RNETs.Multivariate analysis showed that tumor size and grade were independent prognostic factors.CONCLUSION The clinical symptoms of RNETs are not specific,and they are easy to misdiagnose.Surgery is the main treatment method.The grade and stage of RNETs are the main indices to evaluate prognosis.

Correlation between radiologic features on contrastenhanced CT and pathological tumor grades in pancreatic neuroendocrine neoplasms

Contrast-enhanced computed tomography(CT)contributes to the increasing detection of pancreatic neuroendocrine neoplasms(PNENs).Nevertheless,its value for differentiating pathological tumor grades is not well recognized.In this report,we have conducted a retrospective study on the relationship between the 2017 World Health Organization(WHO)classification and CT imaging features in 94 patients.Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2,including tumor size,shape,margin,heterogeneity,intratumoral blood vessels,vascular invasion,enhancement pattern in both contrast phases,enhancement degree in both phases,tumor-to-pancreas contrast ratio in both phases,common bile duct dilatation,lymph node metastases,and liver metastases.Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve(AUC)of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis.The portal enhancement ratio(PER)was shown the highest AUC of 0.855 in terms of quantitative features.Our data suggest that the traditional contrastenhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.

Investigation of the factors influencing surgical treatment of duodenal gastrointestinal stromal tumors

BACKGROUND Duodenal gastrointestinal stromal tumor(DGIST)is a rare tumor with a specific anatomic site and biological characteristics.As the incidence of lymph node metastasis is very low,the main treatment method is surgery.Two main surgical techniques(local resection and Whipple)are performed in patients with DGISTs.The critical question is which surgical technique to choose.AIM To identify factors influencing the choice of surgery for DGISTs.METHODS The clinicopathological data of patients with DGISTs who underwent surgery between January 1999 and January 2021 were analyzed.We used the Student’s ttest or Mann-Whitney U-test and theχ2 test or Fisher’s exact test to determine the differences between the two groups of patients.Furthermore,we used logistic analysis to identify the relevant factors and independent factors related to the type of surgery.The Kaplan-Meier method was used to analyze the patient’s survival information and Cox regression analysis was performed to determine prognostic risk factors.RESULTS Overall,86 patients were analyzed,including 43 men(50%)and 43 women(50%).We divided the patients into two groups based on surgical technique(local resection or Whipple surgery).There were no differences in the age,mitotic figures,and complications between the two groups;however,the tumor size,tumor location,risk grade,postoperative hospital stay,and abdominal drainage time were significantly different.Based on univariate logistic analysis,the Whipple procedure was chosen if the tumor size was≥5.0 cm,the tumor was located in the descending part of the duodenum,or the risk grade was medium or high.In our research,the five-year overall survival rate of patients was more than 90%.We also describe two DGIST patients with liver metastases at first diagnosis and analyzed their management in order to provide advice on complicated cases.CONCLUSION The Whipple procedure was performed if the primary tumor was in the descending part of the duodenum,tumor size was≥5.0 cm,or the tumor risk grade was medium or high.

RELATION BETWEEN MORPHOMETRIC GRADES OF BLADDER TUMOR AND PROGNOSIS

The relation between morphometric grades (M grading) of 84 cases of bladder tumor and prognoses was evaluated. The results shown that the higher the M grading, the lower the survival rate and the higher the recurrence rate. As the M grade increases, the tumor has partial of total absence of ABO(H) antigens of tumor cell surface and could be accompanied with muscular invasion. When recurring, the tumor has a poor prognosis if M grading increases from lower to higher grades. The morphometric grading system is able to make a quantitative pathologic diagnosis and can predict the biological behavior of bladder tumors.

Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC.METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020.Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to NAC.RESULTS In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 years.According to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was 0.806.The calibration curve revealed that the predicted value exhibited good agreement with the actual value.Decision curve analysis showed that the nomogram had a good value in clinical application.CONCLUSION A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers

BACKGROUND Gastric cancer(GC)is the fifth most common and the fourth most lethal malignant tumour in the world.Most patients are already in the advanced stage when they are diagnosed,which also leads to poor overall survival.The effect of posto-perative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence.AIM To investigate the safety and efficacy of a programmed cell death 1(PD-1)inhibitor combined with oxaliplatin and S-1(SOX)in the treatment of Borrmann large type III and IV GCs.METHODS A retrospective analysis(IRB-2022-371)was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy(NAT)from January 2020 to December 2021.According to the different neoadjuvant treatment regimens,the patients were divided into the SOX group(61 patients)and the PD-1+SOX(P-SOX)group(28 patients).RESULTS The pathological response(tumor regression grade 0/1)in the P-SOX group was significantly higher than that in the SOX group(42.86%vs 18.03%,P=0.013).The incidence of ypN0 in the P-SOX group was higher than that in the SOX group(39.29%vs 19.67%,P=0.05).The use of PD-1 inhibitors was an independent factor affecting tumor regression grade.Meanwhile,the use of PD-1 did not increase postoperative complications or the adverse effects of NAT.CONCLUSION A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

Phosphatidylinositol 3-kinase CB association with preoperative radiotherapy response in rectal adenocarcinoma

AIM: To examine the correlation of phosphatidylinositol 3-kinase (PIK3) CB expression with preoperative radiotherapy response in patients with stage II/III rectal adenocarcinoma.

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective:The accurate prediction of tumor response to neoadjuvant chemoradiotherapy(nCRT)remains challenging.Few studies have investigated pathologic complete response(ypCR)prediction in patients with residual flat mucosal lesions after treatment.This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer(LARC).Methods:Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital.Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed,and a nomogram was constructed by incorporating the significant predictors.Results:Of the 246 patients with residual flat mucosal lesions included in the final analysis,56(22.8%)had ypCR.Univariate and multivariate analyses showed that pretreatment cT stage(pre-cT)≤T2(P=0.016),magnetic resonance tumor regression grade(MR-TRG)1-3(P=0.001)and residual mucosal lesion depth=0 mm(P<0.001)were associated with a higher rate of ypCR.A nomogram was developed with a concordance index(C-index)of0.759 and the calibration curve showed that the nomogram model had good predictive consistency.The follow-up time ranged from 3.0 to 113.3 months,with a median follow-up time of 63.77 months.The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival(DFS)or overall survival(OS).Conclusions:Completely flat mucosa,early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT.Endoscopic mucosal re-evaluation before surgery is important,as it may contribute to decision-making and facilitate nonoperative management or organ preservation.

Neutrophile-to-lymphocyte,lymphocyte-to-monocyte,and platelet-tolymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer

BACKGROUND Perioperative fluorouracil plus leucovorin,oxaliplatin,and docetaxel(FLOT)improves prognosis in locally advanced gastric cancer(LAGC).Neutrophil-to-lymphocyte(NLR),lymphocyte-tomonocyte(LMR),and platelet-to-lymphocyte(PLR)ratios are prognostic biomarkers but not predictive factors.AIM To assess blood ratios’(NLR,LMR and PLR)potential predictive response to FLOT and survival outcomes in resectable LAGC patients.METHODS This was a multicentric retrospective study investigating the clinical potential of NLR,LMR,and PLR in resectable LAGC patients,treated with at least one preoperative FLOT cycle,from 12 Portuguese hospitals.Means were compared through non-parametric Mann-Whitney tests.Receiver operating characteristic curve analysis defined the cut-off values as:High PLR>141 for progression and>144 for mortality;high LMR>3.56 for T stage regression(TSR).Poisson and Cox regression models the calculated relative risks/hazard ratios,using NLR,pathologic complete response,TSR,and tumor regression grade(TRG)as independent variables,and overall survival(OS)as the dependent variable.RESULTS This study included 295 patients(mean age,63.7 years;59.7% males).NLR was correlated with survival time(r=0.143,P=0.014).PLR was associated with systemic progression during FLOT(P=0.022)and mortality(P=0.013),with high PLR patients having a 2.2-times higher risk of progression[95% confidence interval(CI):0.89-5.26]and 1.5-times higher risk of mortality(95%CI:0.92-2.55).LMR was associated with TSR,and high LMR patients had a 1.4-times higher risk of achieving TSR(95%CI:1.01-1.99).OS benefit was found with TSR(P=0.015)and partial/complete TRG(P<0.001).Patients without TSR and with no evidence of pathological response had 2.1-times(95%CI:1.14-3.96)and 2.8-times(95%CI:1.6-5)higher risk of death.CONCLUSION Higher NLR is correlated with longer survival time.High LMR patients have a higher risk of decreasing T stage,whereas high PLR patients have higher odds of progressing under FLOT and dying.Patients with TSR and a pathological response have better OS and lower risk of dying.

Simple cholecystectomy is an adequate treatment for grade I T1bN0M0 gallbladder carcinoma:Evidence from 528 patients

BACKGROUND T1b gallbladder carcinoma(GBC)is defined as a tumor that invades the perimuscular connective tissue without extension beyond the serosa or into the liver.However,controversy still exists over whether patients with T1b GBC should undergo cholecystectomy alone or radical GBC resection.AIM To explore the optimal surgical approach in patients with T1b gallbladder cancer of different pathological grades.METHODS Patients with T1bN0M0 GBC who underwent surgical treatment between 2000 and 2017 were included in the Surveillance,Epidemiology,and End Results database.The Kaplan-Meier method and log-rank test were used to analyze the overall survival(OS)and disease-specific survival(DSS)of patients with T1b GBC of different pathological grades.Cox regression analysis was used to identify independent predictors of mortality and explore the selection of surgical methods in patients with T1b GBC of different pathological grades and their relationship with prognosis.RESULTS Of the 528 patients diagnosed with T1bN0M0 GBC,346 underwent simple cholecystectomy(SC)(65.5%),131 underwent SC with lymph node resection(SC+LN)(24.8%),and 51 underwent radical cholecystectomy(RC)(9.7%).Without considering the pathological grade,both the OS(P<0.001)and DSS(P=0.003)of T1b GBC patients who underwent SC(10-year OS:27.8%,10-year DSS:55.1%)alone were significantly lower than those of patients who underwent SC+LN(10-year OS:35.5%,10-year DSS:66.3%)or RC(10-year OS:50.3%,10-year DSS:75.9%).Analysis of T1b GBC according to pathological classification revealed no significant difference in OS and DSS between different types of procedures in patients with grade Ⅰ T1b GBC.In patients with grade Ⅱ T1b GBC,obvious survival improvement was observed in the OS(P=0.002)and DSS(P=0.039)of those who underwent SC+LN(10-year OS:34.6%,10-year DSS:61.3%)or RC(10-year OS:50.5%,10-year DSS:78.8%)compared with those who received SC(10-year OS:28.1%,10-year DSS:58.3%).Among patients with grade Ⅲ or Ⅳ T1b GBC,SC+LN(10-year OS:48.5%,10-year DSS:72.2%),and RC(10-year OS:80%,10-year DSS:80%)benefited OS(P=0.005)and DSS(P=0.009)far more than SC(10-year OS:20.1%,10-year DSS:38.1%)alone.CONCLUSION Simple cholecystectomy may be an adequate treatment for grade Ⅰ T1b GBC,whereas more extensive surgery is optimal for grades Ⅱ-Ⅳ T1b GBC.

Assessment of XAF1 as A Biomarker to Differentiate Hepatocellular Carcinoma from Nonneoplastic Liver Tissues

Objective： XIAP-associated factor 1 （XAF1） expression has been shown to be related with apoptosis in hepatocellular carcinoma （HCC）. However, the correlation of XAF1 expression with HCC tumor grade has not been intensively assessed. XIAP-associated factor-1 （XAF1） is an important apoptosis inducer in human HCC. The aim of this study is to determine the correlation between XAF1 expression and HCC histopathological grades. Methods： The mRNA levels of XAF1 in 24 paired HCC-nonneoplastic specimens were quantified by real-time reverse transcription PCR （RT-PCR）. Protein levels of XAF1 in 110 paired HCC-noncancer tissues were investigated by immunostaining specimens on a tissue microarray （TMA）. Correlations between XAF1 mRNA levels or protein expression and clinicopathological features were assessed by statistical analysis. Results： Both XAF1 mRNA and protein were significantly under-expressed in HCC tissues compared to their non-neoplastic counterparts. No significant relationship was found between XAF1 mRNA or protein expression and histological tumor grade. Conclusion： All these data suggest that XAF1 is a potential biomarker for differentiating HCC with noncancerous tissues.

Value of Pretreatment Inflammation-nutrition Score to Predict Non-response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Objective To investigate the value of pretreatment inflammatory-nutritional biomarkers in predicting the pathological response of locally advanced rectal cancer(LARC)after neoadjuvant chemotherapy(nCT).Methods This retrospective study included eligible participants who underwent nCT followed by radical surgery.Pretreatment inflammatory nutritional biomarkers were calculated within one week prior to nCT.Correlations between biomarkers and pathological responses were analyzed.The cut-off values of the pretreatment biomarkers for predicting non-response were determined using receiver operating characteristic(ROC)curve analysis.The inflammation-nutrition score was calculated using the lymphocyte level,neutrophil-to-lymphocyte ratio(NLR),and prognostic nutritional index(PNI).Results A total of 235 patients were retrospectively recruited between January 2017 and September 2022.Lower lymphocyte levels,lymphocyte monocyte ratio(LMR),and PNI,and higher NLR and platelet-to-lymphocyte ratio(PLR)were observed in patients without response.Multivariate logistic regression analysis revealed that NLR could independently predict non-response to nCT in patients with LARC.The sensitivity and specificity of the inflammation-nutrition score for predicting nonresponse were 71.2%and 61.7%,respectively.Conclusion The pretreatment inflammation-nutrition score is a practical parameter for predicting nonresponse to nCT in patients with LARC.Patients with high scores were more likely to respond poorly to nCT.

Accuracy of tumor grade by preoperative curettage and associated clinicopathologic factors in clinical stage Ⅰ endometriod adenocarcinoma

Background Preoperative tumor grading becomes one of the most important predictors for lymphadenectomy at primary surgery for clinical stage Ⅰ endometriod adenocarcinoma. However, there is an inconsistency of tumor grade between preoperative curettage and final hysterectomy specimens, and its associated factors are poorly understood. This study aimed to evaluate the accuracy of tumor grade by preoperative curettage so as to achieve a better stratified management for clinical stage Ⅰ endometriod adenocarcinoma. Methods Clinical data of totally 687 patients with clinical stage Ⅰ endometriod adenocarcinoma who underwent preoperative curettage and primary surgery were retrospectively collected. Compared with final hysterectomy specimens, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of tumor grade by preoperative curettage were calculated and their associations with clinicopathologic parameters, including age, status of menopause, position of uterus, location and size of lesion, histological grade, depth of myometrial invasion, cervical invasion, extrauterine spread, peritoneal cytology, metastasis to retroperitoneal lymph node, serum CA125 level, and hormone receptor status, were analyzed. Results In final hysterectomy specimens, 139 of 259 grade 1 patients by curettage were upgraded to grade 1 or 2; 31 of 296 grade 2 were upgraded to grade 3, with a significantly discrepant rate of 40.9% （281/687） and an upgraded rate of 24.7% （170/687）. The specificity and negative predictive value for grade 3 were 90.7% and 89.9%, while the sensitivity and positive predictive value for grade 1 were 67.1% and 40.9%, respectively. Conclusions Preoperative tumor grade by curettage does not accurately predict final histological results, especially in those classified as grade 1. Complete surgical staging seems to be necessary for clinical stage Ⅰ endometriod adenocarcinoma.

A meta-analysis of randomized trials of maintenance bacillus Calmette-Guerin instillation efficacy against recurrence of T1G3 bladder tumor

Meta-analysis was used to determine whether maintenance intravesical bacillus Calmette-Guerin(BCG)could reduce recurrence after transurethral resection of tumor 1 grade 3(T1G3)superficial bladder cancer.All available published data of randomized clinical trials comparing transurethral resection plus intravesical BCG to either resection alone or resection plus another treat-ment on the treatment results in patients with superficial bladder cancer of T1G3 were selected for analysis.Both the fixed effects model and random effects model were applied,and the odds ratio(OR)with its 95%confidence interval(CI)was used as the effect size estimate.Sensitivity analysis and publication bias determination were performed by funnel plots and comparing ORs of different models.Within the follow-up period,375 of 915(41.0%)BCG-treated patients and 332 of 733(45.3%)non-BCG-treated patients developed tumor recurrence.In the combined results,a statistically signifi-cant difference in the ORs for tumor recurrence between the two treatment groups was found(randomized model combined effect OR 0.58,95%CI 0.41 to 0.83,P 50.003).The stratified meta-analysis did not show any statistically significant confounding effects on the results when strati-fied by BCG strains.The randomized model combined effect OR of Pasteur F and other strains were 0.50(95%CI 0.26 to 0.95,P 50.04)and 0.63(95%CI 0.40 to 0.99,P 50.04),respectively.Therefore,we came to the conclu-sion that adjuvant maintenance instillation BCG com-bined with transurethral resection of bladder tumor(TURBT)is an effective conservative treatment for pre-venting recurrence of T1G3 bladder cancer.