Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Multicenter study of the clinicopathological features and recurrence risk prediction model of early-stage breast cancer with low-positive human epidermal growth factor receptor 2 expression in China (Chinese Society of Breast Surgery 021)

Background:Breast cancer with low-positive human epidermal growth factor receptor 2(HER2)expression has triggered further refinement of evaluation criteria for HER2 expression.We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors.Methods:Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association,from January 2015 to December 2016 were collected.The prognostic factors of these patients were analyzed.Results:Twenty-nine hospitals provided valid cases.From 2015 to 2016,a total of 25,096 cases of early-stage breast cancer were treated,7642(30.5%)of which had low-positive HER2 expression and were included in the study.After ineligible cases were excluded,6486 patients were included in the study.The median follow-up time was 57 months(4-76 months).The disease-free survival rate was 92.1%at 5 years,and the overall survival rate was 97.4%at 5 years.At the follow-up,506(7.8%)cases of metastasis and 167(2.6%)deaths were noted.Multivariate Cox regression analysis showed that tumor stage,lymphvascular invasion,and the Ki67 index were related to recurrence and metastasis(P<0.05).The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815(95%confidence interval:0.750-0.880).Conclusions:Early-stage breast cancer patients with low-positive HER2 expression account for 30.5%of all patients.Tumor stage,lymphvascular invasion,and the Ki67 index are factors affecting prognosis.The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years.Trial registration:ChiCTR.org.cn,ChiCTR2100046766.

A clinical analysis of risk factor with lymph node metastatic recurrence in patients with N0 esophageal cancer after Ivor-Lewis Esophagectomy

Objective To investigate the risk factors with lymph node metastatic recurrence in patients with N0 esophageal cancer after Ivor-Lewis Esophagectomy. Methods The subjects were 82 patients with pN0 esophagea cancer who underwent Ivor-Lewis esophagectomy from January 2001 to January 2005. By using RT-PCR,VEGF C mRNA was detected in tumor issues,and Mucin (MUC1) mRNA was detected in lymph nodes. The Kaplan-Meier method was used to calculate the survival

Postoperative Stimulated Thyroglobulin Level and Recurrence Risk Stratification in Differentiated Thyroid Cancer

Background： Postoperative preablative stimulated thyroglobulin （ps-Tg） has been evaluated in predicting prognosis and success of ablation regarding differentiated thyroid cancer （DTC）; however, its relationship with recurrence risk and radioiodine decision-making remains uncertain, especially in Chinese DTC patients. We aimed to evaluate the association between ps-Tg and recurrence risk stratification in DTC, to provide incremental values for ps-Tg in postoperative assessment and radioiodine management. Methods： Seven hundred and seven patients with DTC were included; low-risk （L; n = 90）, intermediate-risk （I; n = 283）, and high-risk （H; n = 334, 117 with distant metastasis [M 1 ]） patients were divided according to recurrence risk stratification. The M 1 group was further analyzed regarding evidence of metastasis. Cut-off values of ps-Tg were obtained using receiver operating characteristic analysis. Results： Patients with more advanced disease at initial risk stratification were more likely to have higher ps-Tg levels （I vs. L： P 〈 0.05; H vs. 1： P 〈 0.001; H vs. L： P 〈 0.001）. The corresponding cut-off value of ps-Tg for distinguishing sensitivity and specificity in each of the two groups was 2.95 ng/ml （1 vs. L： 61.5%, 63.3%）, 29.5 ng/ml （H vs, I： 41.9%, 92.6%）, 47.1 ng/ml （M1 vs. M0 in the H group： 79.5%, 88.9%） and 47.1 ng/ml （MI vs. M0 in all patients： 79.5%, 93.7%）. With the cut-offvalue at 47.1 ng/ml, ps-Tg was the only factor that could be used to identify distant metastases, and consequently if measured before radioiodine therapy would prevent 10.26% of patients with M1 from undertreatment, Conclusions： Ps-Tg, as an ongoing reassessment marker, favors differential recurrence risk grading and provides incremental values for radioiodine treatment decision-making.

Shorter recurrence-free survival time, higher risk of multiple recurrences： a retrospective study of non-muscle invasive bladder cancer after transurethral resection

Background Multiple recurrences are common in non-muscle invasive bladder cancer, but the-risk of multiple recurrences has not been fully described. Identifying patients at high risk of multiple recurrences will help to select an optimal therapeutic strategy and to improve prognosis. This study was conducted to identify the risk factors for multiple recurrences of non-muscle invasive bladder cancer. Methods We reviewed the clinical data of all patients with non-muscle invasive bladder cancer in our hospital between January 2003 and February 2010. Patients with at least one recurrence were included. Multivariate analysis was performed for theorized risk factors （age, gender, tumor stage, grade, size, location, number of lesions, adjuvant intra-vesical chemotherapy after transurethral resection, and recurrence-free survival after each resection） to clarify risk factors for multiple recurrences of non-muscle invasive bladder cancer. Results Of the 278 patients with non-muscle invasive bladder cancer, 84 were with at least one recurrence and a total of 222 recurrences among them were followed up for 6-70 months （mean, 36.1 months）. Recurrence-free survival after initial resection predicted the overall frequency of bladder cancer recurrence （risk ratio （RR） = 37.83, 95% confidence interval （C/）=3.45-396.13, P=0.001） and second recurrence （RR=6.15, 95% C/=1.28-29.57, P=0.023）. Similarly, recurrence-free survival after a second resection was the only significant risk factor for third recurrence （RR=31.08, 95% C1=2.53-381.47, P=0.007）. Moreover, recurrence-free survival after initial resection was the only significant factor to predict later progression to muscle invasive bladder cancer （RR=8.62, 95% C1=1.47-58.34, P=0.001）. Conclusions Recurrence-free survival after resection is an independent predictor of multiple recurrences of non-muscle invasive bladder cancer. The shorter the period between resection and recurrence is, the higher the risk of multiple recurrences.

Inflammatory myofibroblastic tumor of the central nervous system:A case report

BACKGROUND An inflammatory myofibroblastic tumor(IMT)occurring in the central nervous system is very rare,and thus its pathogenesis is unknown.This case report and literature review aimed to explore the pathogenesis,clinical features,imaging findings,pathological characteristics,immunohistochemical characteristics,diagnoses,treatments,and risks of postoperative recurrence of IMT in the central nervous system.CASE SUMMARY A 67-year-old woman was admitted to the hospital with an exophthalmic protrusion and double vision in the left eye that had persisted for 3 mo.Magnetic resonance imaging(MRI)showed a 2.4 cm×1.3 cm heterogeneous large mass in the bottom of the left anterior cranial fossa,which was closely related to the dura mater.Before surgery,we suspected the mass to be meningioma.The entire mass was successfully removed under neuronavigation and electrophysiological monitoring,and postoperative pathology indicated an IMT with extensive infiltration of chronic inflammatory cells and scattered multinucleated giant cells.Head MRI at the 3-mo follow-up showed that the tumor at the bottom of left anterior cranial fossa had been completely resected without recurrence.CONCLUSION From the histological,immunohistochemical,and genetic analyses,the present case suggests that the pathogenesis of IMT-CNS is related to autoimmunity.

Comprehensive characterization of the genetic landscape of familial Hirschsprung's disease

Background Hirschsprung's disease(HSCR)is one of the most common congenital digestive tract malformations and can cause stubborn constipation or gastrointestinal obstruction after birth,causing great physical and mental pain to patients and their families.Studies have shown that more than 20 genes are involved in HSCR,and most cases of HSCR are sporadic.However,the overall rate of familial recurrence in 4331 cases of HSCR is about 7.6%.Furthermore,familial HSCR patients show incomplete dominance.We still do not know the penetrance and genetic characteristics of these known risk genes due to the rarity of HSCR families.Methods To find published references,we used the title/abstract terms"Hirschsprung"and"familial"in the PubMed data-base and the MeSH terms"Hirschsprung"and"familial"in Web of Science.Finally,we summarized 129 HSCR families over the last 40 years.Results The male-to-female ratio and the percentage of short segment-HSCR in familial HSCR are much lower than in sporadic HSCR.The primary gene factors in the syndromic families are ret proto-oncogene(RET)and endothelin B receptor gene(EDNRB).Most families show incomplete dominance and are relevant to RET,and the RET mutation has 56%pen-etrance in familial HSCR.When one of the parents is a RET mutation carrier in an HSCR family,the offspring's recurrence risk is 28%,and the incidence of the offspring does not depend on whether the parent suffers from HSCR.Conclusion Our findings will help HSCR patients obtain better genetic counseling,calculate the risk of recurrence,and provide new insights for future pedigree studies.

Dermoscopic Features of Basal Cell Carcinoma and Their Association with Histological Types in A Chinese Population:A Perspective Study

Objective:The treatments and prognoses of high-risk and low-risk basal cell carcinomas are quite different.This study aimed to examine the dermoscopic features of basal cell carcinomas and assess the association between the features and basal cell carcinomas recurrence risks in a Chinese population.Methods:Patients with histopathologically confirmed basal cell carcinomas examined from March 2016 to April 2020 were enrolled.The dermoscopic features were evaluated,and the correlations between these features and the histological types and recurrence risks were assessed.Results:The study cohort comprised 119 Chinese patients with a total of 119 skin lesions.The most common dermoscopic feature of basal cell carcinomas was the absence of a pigment network(119/119,100%),followed by shiny white streaks(105/119,88.24%),blue-gray ovoid nests(99/119,83.19%),multiple blue globules(78/119,65.55%),and arborizing vessels(78/119,65.55%);yellow-white structures were present in 29/119 lesions(24.37%).Leaf-like and spoke-wheel areas were significantly associated with superficial basal cell carcinomas(P<0.001),while arborizing vessels(P<0.001),blue-gray ovoid nests(P<0.001),and ulceration(P<0.05)were significantly associated with nonsuperficial basal cell carcinomas subtypes.The dermoscopic features of the high-risk and low-risk groups exhibited considerable overlap;however,the respective independent predictive factors for a high and low risk of basal cell carcinomas recurrence were short fine telangiectases(P<0.05)and blue-gray ovoid nests(P<0.05).Conclusion:Dermoscopy provides important information about basal cell carcinomas and is helpful in differentiating superficial basal cell carcinomas from other subtypes.The dermoscopic vascular structures and bluegray ovoid nests play a crucial role in evaluating the basal cell carcinomas risks preoperatively.

Coexistence of High Fibrinogen and Low High-density Lipoprotein Cholesterol Levels Predicts Recurrent Cerebral Venous Thrombosis

Background： Cerebral venous thrombosis （CVT） may lead to serious neurological disorders; however, little is known about the risk factors for recurrent CVT. Our aim was to determine the association between elevated fibrinogen and decreased high-density lipoprotein cholesterol （HDL-C） levels with recurrent CVT. Methods： This retrospective cohort study included participants if they had a first episode of objectively defined CVT and were admitted to Xuan Wu Hospital, Capital Medical University from August 2005 to September 2009. Demographic and clinical variables were collected, as well as laboratory parameters, inchiding plasma fibrinogen and HDL-C. Patients with CVT were tbllowed for recurrent symptomatic CVT. Follow-up was through the end of September 2010. Potential predictors of recurrence were analyzed using Cox survival analysis. Results： At tile end of the lbllow-up, 95 patients were eligible lbr the study. Twelve of 95 patients （12.6%） had recurred CVT. Tile median time of recurrence was 7 months （range： 1-39 months）. Eight of these 12 （66.7%） experienced rectirrence within the first 12 months alter their initial CVT. The recurrence rate of CVT was 2.76 per 100 patient-years. Multivariate Cox regression analysis demonstrated that the coexistence of high fibrinogen （〉4.00 g/L） and low HDL-C （〈1.08 mmol/L） levels at baseline was the only independent predictor for recurrent CVT （hazard ratio： 4.69; 95% confidence interval： 1.10-20,11; P 〈 0.05）. Of tile twelve patients with recurrent CVT in our study, 7 （58.3%） had high fibrinogen plus low HDL-C levels. All 7 of these patients took warfarin for 3-12 months, and 6 of 7 had rectirrent CVT after the discontinuation of anticoagulant treatment. Conclusions： Concomitant high fibrinogen and low HDL-C levels may be associated with recurrence of CVT. The ett＇ect of potential risk lhctors related to atherothrombosis on rectinent CVT should be closely monitored.