Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Evaluation of the Effect and Efficiency of Ear Tip Bloodletting Combined with Xianfang Huoming Yin in the Treatment of Early-Stage Wheals

Objective:To evaluate the effect and efficiency of ear tip bloodletting combined with Xianfang Huoming Yin(XFH)in the treatment of early-stage wheals.Methods:70 patients with early-stage wheals admitted from September 2020 to September 2022 were divided into two groups by randomized numerical table method,with 35 cases/group.Both groups received conventional treatment,the control group combined with XFH,and the observation group combined with ear tip bloodletting therapy and XFH.Conscious symptom scores,ocular indexes,therapeutic effects,and sleep quality between the two groups were compared.Results:After the treatment,the patients in the observation group had lower self-awareness symptom scores and sleep quality scores as compared to those in the control group;the diameter of the mass in the observation group was smaller than that of the control group after treatment;the average tear film rupture time and the time taken for the first non-contact tear film to rupture were longer in the observation group than those in the control group;the total effective rate of the treatment in the observation group was higher than that of the control group(P<0.05).Conclusion:Ear tip bloodletting combined with XFH was ideal for the treatment of early-stage wheals and has a high effective rate.

Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis

BACKGROUND Primary biliary cholangitis(PBC)is a chronic progressive autoimmune cholestatic disease.The main target organ of PBC is the liver,and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis.AIM To explore the clinical characteristics of early-stage PBC,identify PBC in the early clinical stage,and promptly treat and monitor PBC.METHODS The data of 82 patients with PBC confirmed by pathology at Tianjin Second People’s Hospital from January 2013 to November 2021 were collected,and the patients were divided into stage I,stage II,stage III,and stage IV according to the pathological stage.The general data,serum biochemistry,immunoglobulins,and autoimmune antibodies of patients in each stage were retrospectively analyzed.RESULTS In early-stage(stages I+II)PBC patients,50.0%of patients had normal alanine aminotransferase(ALT)levels,and 37.5%had normal aspartate aminotransferase(AST)levels.For the remaining patients,the ALT and AST levels were mildly elevated;all of these patients had levels of<3 times the upper limit of normal values.The AST levels were significantly different among the three groups(stages I+II vs stage III vs stage IV,P<0.05).In the early stage,29.2%of patients had normal alkaline phosphatase(ALP)levels.The remaining patients had different degrees of ALP elevation;6.3%had ALP levels>5 times the upper limit of normal value.Moreover,γ-glutamyl transferase(GGT)was more robustly elevated,as 29.2%of patients had GGT levels of>10 times the upper limit of normal value.The ALP values among the three groups were significantly different(P<0.05).In early stage,the jaundice index did not increase significantly,but it gradually increased with disease progression.However,the above indicators were significantly different(P<0.05)between the early-stage group and the stage IV group.With the progression of the disease,the levels of albumin and albumin/globulin ratio tended to decrease,and the difference among the three groups was statistically significant(P<0.05).In early-stage patients,IgM and IgG levels as well as cholesterol levels were mildly elevated,but there were no significant differences among the three groups.Triglyceride levels were normal in the early-stage group,and the differences among the three groups were statistically significant(P<0.05).The early detection rates of anti-mitochondria antibody(AMA)and AMA-M2 were 66.7%and 45.8%,respectively.The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC.When AMA and AMA-M2 were negative,in the early stage,the highest autoantibody was anti-nuclear antibody(ANA)(92.3%),and in all ANA patterns,the highest was ANA centromere(38.5%).CONCLUSION In early-stage PBC patients,ALT and AST levels are normal or mildly elevated,GGT and ALP levels are not elevated in parallel,GGT levels are more robustly elevated,and ALP levels are normal in some patients.When AMA and AMA-M2 are negative,ANA especially ANA centromere positivity suggests the possibility of early PBC.Therefore,in the clinic,significantly elevated GGT levels with or without normal ALP levels and with ANA(particularly ANA centromere)positivity(when AMA and AMA-M2 are negative)may indicate the possibility of early PBC.

Translocation and Distribution of Carbon-Nitrogen in Relation to Rice Yield and Grain Quality as Affected by High Temperature at Early Panicle Initiation Stage

Due to climate change, extreme heat stress events have become more frequent, adversely affecting rice yield and grain quality. The accumulation and translocation of dry matter and nitrogen substances are essential for rice yield and grain quality. To assess the impact of high temperature stress(HTS) at the early panicle initiation(EPI) stage on the accumulation, transportation, and distribution of dry matter and nitrogen substances in various organs of rice, as well as the resulting effects on rice yield and grain quality, pot experiments were conducted using an indica rice cultivar Yangdao 6(YD6) and a japonica rice cultivar Jinxiangyu 1(JXY1) under both normal temperature(32 ℃/26 ℃) and high temperature(38 ℃/29 ℃) conditions. The results indicated that exposure to HTS at the EPI stage significantly decreased rice yield by reducing spikelet number per panicle, grain-filling rate, and grain weight. However, it improved the nutritional quality of rice grains by increasing protein and amylose contents. The reduction in nitrogen and dry matter accumulation accounted for the changes in spikelet number per panicle, grain-filling rate, and grain size. Under HTS, the decrease in nitrogen accumulation accompanied by the reduction in dry matter may be due to the down-regulation of leaf net photosynthesis and senescence, as evidenced by the decrease in nitrogen content. Furthermore, the decrease in sink size limited the translocation of dry matter and nitrogen substances to grains, which was closely related to the reduction in grain weight and the deterioration of grain quality. These findings significantly contribute to our understanding of the mechanisms of HTS on grain yield and quality formation from the perspective of dry matter and nitrogen accumulation and translocation. Further efforts are needed to improve the adaptability of rice varieties to climate change in the near future.

Medication Rules of Traditional Chinese Medicine for Treating Threatened Abortion in the Early Stage of Pregnancy with Subchorionic Haematoma Based on Data Mining

Objective:Using data mining technology to explore the rules of traditional Chinese medicine(TCM)in the treatment of threatened abortion in the early stage of pregnancy with sub-chorionic haematoma(SCH).Methods:Literature of TCM in the treatment of threatened abortion in the early stage of pregnancy with SCH were retrieved from CNKI,VIP,WANFANG and Pubmed,EMBASE.The literature information database was established to be used for descriptive analysis,association rule analysis and cluster analysis of relevant data.Results:A total of 100 literatures were included,involving 114 Chinese herbs.The efficacy of Chinese herbs were mainly tonic drugs,hemostatic drugs,heat-clearing drugs,dissolving blood stasis and hemostatic drugs.The medicinal properties were mostly mild and warm,and the taste of the drug was mainly sweet,bitter and pungent.The liver meridian,spleen meridian and kidney meridian were frequently used.The commonly used drug pair combination was"Xu duan(Radix dipsaci,续断)-Tusizi(Semen Cuscutae,菟丝子)",and the core combination was"Tusizi-Xu duan-Ejiao(Donkeyhide gelatin,阿胶)-Baizhu(Atractylodes macrocephala,白术)-Dangshen(Codonopsis pilosula,党参)".Commonly used drugs for removing blood stasis and hemostasis were with Sanqi(Panax notoginseng,三七),Puhuang(cattail pollen,蒲黄),and Qiancao(Radix Rubiae,茜草).Conclusion:Data mining traditional Chinese medicine for the treatment of threatened abortion in the early stage of pregnancy with SCH clinically commonly used drug efficacy,taste,meridian,commonly used drug pairs,core combination and commonly used blood stasis hemostatic drugs,has important reference significance for the treatment of threatened abortion in the early stage of pregnancy combined with SCH.

Provision of Fertility Preservation for Young Women with Early-Stage Breast Cancer

Breast cancer is the most common cancer in women worldwide, constituting 25% of all cancer diagnoses. Even though it is only affecting 4% - 6% of women under the age of 40, it remains the most common malignancy among younger patients. Advancement in the treatment and earlier detection gives excellent 5 years of survival. However, the standard treatment that comprises surgical-chemo radiation therapy or hormonal treatment often results in an increased incidence of treatment-induced infertility. Therefore, adding fertility preservation to primary cancer treatment may offer the best opportunity for future fertility. However, despite advancements in Assisted Reproductive Technology (ART), the uptake of fertility services in this group remains low. In this review, we highlighted the effect of all breast cancer treatments on women’s fertility, the effectiveness and safety of ART in breast cancer patients as well as the safety of pregnancy in breast cancer survivors. Our aim is to improve awareness of fertility preservation for breast cancer to ensure all women diagnosed with breast cancer have multidisciplinary approaches with early referral to fertility specialists to discuss regarding potential risks and benefits of fertility preservation to improve the uptake of fertility preservation among this group of patients.

Early Building Design:Informed decision-making by exploring multidimensional design space using sensitivity analysis

This paper describes a novel approach to explore a multidimensional design space and guide multi-actor decision making in the design of sustainable buildings.The aim is to provide proactive and holistic guidance of the design team.We propose to perform exhaustive Monte Carlo simulations in an iterative design approach that consists of tw o steps:1) preparation by the modeler,and 2) a multi-collaborator meeting.In the preparation phase,the simulation modeler performs Morris sensitivity analysis to fixate insignificant model inputs and to identify non-linearity and interaction effects.Next,a representation of the global design space is obtained from thousands of simulations using low-discrepancysequences(LPτ) for sampling.From these simulations,the modeler constructs fast metamodels and performs quantitative sensitivity analysis.During the meeting,the design team explores the global design space by filtering the thousands of simulations.Variable filter criteria are easily applied using an interactive parallel coordinate plot w hich provide immediate feedback on requirements and design choices.Sensitivity measures and metamodels show the combined effects of changing a single input and how to remedy unw anted output changes.The proposed methodology has been developed and tested through real building cases using a normative model to assess energy demand,thermal comfort,and daylight.

Portosplenomesenteric vein thrombosis in patients with early-stage severe acute pancreatitis

AIM To investigate the incidence and risk factors of portosplenomesenteric vein thrombosis(PSMVT) in the early stage of severe acute pancreatitis(SAP).METHODS Patients with SAP in a tertiary care setting from January 2014 to December 2016 were retrospectively reviewed. All contrast-enhanced computed tomography(CT) studies were reassessed and reviewed. Clinical outcome measures were compared between SAP patients with and without PSMVT in the early stage of the disease. Univariate and multivariate logistic regression analyses were sequentially performed to assess potential risk factors for the development of PSMVT in SAP patients. A receiver operating characteristic(ROC) curve was generated for the qualifying independent risk factors.RESULTS Twenty-five of the one hundred and forty(17.86%) SAP patients developed PSMVT 6.19 ± 2.43 d after acute pancreatitis(AP) onset. PSMVT was confirmed by contrast-enhanced CT. Multivariate stepwise logistic regression analyses showed that Balthazar's CT severity index(CTSI) scores [odds ratio(OR): 2.742; 95% confidence interval(CI): 1.664-4.519; P = 0.000], hypoalbuminemia(serum albumin level < 25 g/L)(OR: 32.573; 95%CI: 2.711-391.353; P = 0.006) and gastrointestinal wall thickening(OR: 4.367, 95%CI: 1.218-15.658; P = 0.024) were independent risk factors for PSMVT developed in patients with SAP. The area under the ROC curve for Balthazar's CTSI scores was 0.777(P = 0.000), the sensitivity was 52%, and the specificity was 93% at a cut-off value of 5.5.CONCLUSION High Balthazar's CTSI scores, hypoalbuminemia and gastrointestinal wall thickening are independent risk factors for PSMVT developed in the early stage of SAP.

Early stage colon cancer

Evidence has now accumulated that colonoscopy and removal of polyps,especially during screening and surveillance programs,is effective in overall risk reduction for colon cancer.After resection of malignant pedunculated colon polyps or early stage colon cancers,long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers.Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs,lymph nodes or distant sites.This differs from the clinical setting of an apparent"curative"resection later pathologically upstaged following detection of malignant cells extending into adjacent organs,peritoneum,lymph nodes or other distant sites,including liver.This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer.Precise staging is important,not only for assessing the need for adjuvant chemotherapy,but also for patient selection for continued surveillance.With advanced stages of colon cancer and a more guarded outlook,repeated surveillance should be limited.In future,novel imaging technologies(e.g.,confocal endomicroscopy),coupled with increased pathological recognition of high risk markers for lymph node involvement(e.g.,"tumor budding")should lead to improved staging and clinical care.

Pathological changes in the cellular structures of retina and choroidea in the early stages of alloxan-induced diabetes

AIM To investigate the temporal sequence of pathological changes in the cellular structures of retina and choroidea in the early stages of diabetes in laboratory animals.METHODS Experimental type 1 diabetes was modeled by three intraperitoneal injections of an alloxan solution into 30 male nonlinear rats at 16 wk of age. The 30 th and 60 th days from the final alloxan injection were chosen as the endpoints. Light and electron microscopy and morphometric and immunohistochemical studies were performed on histological slices of eyeballs from experimental animals.RESULTS Diabetic disturbances progressed to 60 d of the experiment. Thus, in the retina, a partial destruction of photoreceptors accompanied by interstitial edema was observed. The morphometric analysis revealed a reduction in the thickness of the retina. A reduction in the number of blood vessels of the choroid with disturbances of the endothelial cells and the vascular walls and a persistent reduction in the number of melanocytes were observed. The number of proliferating Ki-67 positive cells decreased, and the number of macrophages increased with diabetes development.CONCLUSION The starting point in the development of destructive changes involves early reduction in the number of melanocytes of the choroidea and alterations in the retinal pigment epithelium.

Partial improvement in performance of patients with severe Alzheimer's disease at an early stage of fornix deep brain stimulation

Deep brain stimulation is a therapy for Alzheimer＇s disease（AD） that has previously been used for mainly mild to moderate cases. This study provides the first evidence of early alterations in performance induced by stimulation targeted at the fornix in severe AD patients. The performance of the five cases enrolled in this study was scored with specialized assessments including the Mini-Mental State Examination and Clinical Dementia Rating, both before and at an early stage after deep brain stimulation. The burden of caregivers was also evaluated using the Zarit Caregiver Burden Interview. As a whole, the cognitive performance of patients remained stable or improved to varying degrees, and caregiver burden was decreased. Individually, an improved mental state or social performance was observed in three patients, and one of these three patients showed remarkable improvement in long-term memory. The conditions of another patient deteriorated because of inappropriate antipsychotic medications that were administered by his caregivers. Taken together, deep brain stimulation was capable of improving some cognitive aspects in patients with severe AD, and of ameliorating their emotional and social performance, at least at an early stage. However, long-term effects induced by deep brain stimulation in patients with severe AD need to be further validated. More research should focus on clarifying the mechanism of deep brain stimulation. This study was registered with ClinicalTrials.gov（NCT03115814） on April 14, 2017.

Effects of acupuncture therapy on plasma neuropeptide Y levels and resuscitation in patients with very early stage acute cerebral infarction A randomized controlled study

BACKGROUND： It is known that acupuncture therapy can decrease plasma neuropeptide Y （NPY） levels in patients with cerebral infarction, but different types of acupuncture therapy used in various stages of cerebral infarction have not been evaluated. OBJECTIVE： To explore the effect of acupuncture therapy on resuscitation （Xingnao Kaiqiao） and plasma NPY levels in patients with very early stage acute cerebral infarction. DESIGN, TIME AND SETTING： This case-controlled study was performed at the Affiliated Hospital of the Medical College of the Chinese People＇s Armed Police Force between September 2004 and October 2005. PARTICIPANTS： Sixty patients with acute cerebral infarction of ≤ 6 hours were used in this study. Patients were randomly divided into an acupuncture therapy group （n = 30） and a routine treatment group （n = 30）. Another 30 healthy subjects were used as the control group. METHODS： The acupuncture therapy of Xingnao Kaiqiao used in the acupuncture therapy group was based on routine western medical treatment and was performed at bilateral Neiguan （PCG） using the twirling, reinforcing-reducing method, Renzhong （DU26） using heavy bird-pecking needling, Sanyinjiao （SPG） using reinforcing and reducing by lifting and thrusting the needle, Jiquan （HT1）, Weizhong （BL40） and Chize （LU5） using reinforcing and reducing by lifting and thrusting the needle. The acupuncture lasted for 14 days. Patients in the routine treatment group underwent routine medical treatment and no intervention was given to subjects in the control group. MAIN OUTCOME MEASURES： A 4 mL venous blood sample was obtained at different time points, i.e., immediately after hospitalization, the next morning, 7 and 14 days after treatment, to measure plasma NPY levels pre- and post-treatment using the radio-immunity method. RESULTS： The plasma NPY levels were significantly higher in both the routine treatment group and the acupuncture therapy group than in the control group pre- and post-treatment （P 〈 0.01）. In particular, the plasma NPY levels in both the acupuncture therapy group and the routine treatment group were increased 7 days post-treatment but decreased from 7-14 days post-treatment. In addition, the plasma NPY levels were significantly lower in the acupuncture therapy group than in the routine treatment group on day 7 and 14 post-treatment （P 〈 0.01）. CONCLUSION： Acupuncture therapy of Xingnao Kaiqiao can decrease plasma NPY levels in patients with very early stage acute cerebral infarction. In addition, the therapeutic effect of acupuncture with a prolonged therapy time is superior to routine treatment.

Pancreas-sparing duodenectomy with regional lymph node dissection for early-stage ampullary carcinoma: A case control study using propensity scoring methods

AIM:To investigate the outcomes of pancreas-sparing duodenectomy(PSD)with regional lymph node dissection vs pancreaticoduodenectomy(PD).METHODS:Between August 2001 and June 2014,228 patients with early-stage ampullary carcinoma(Amp Ca)underwent surgical treatment(PD,n=159;PSD with regional lymph node dissection,n=69).The patients were divided into two groups:the PD group and the PSD group.Propensity scoring methods were used to select patients with similar disease statuses.A total of 138 matched cases,with 69 patients in each group,were included in the final analysis.RESULTS:The median operative time was shorter among the patients in the PSD group(435 min)compared with those in the PD group(481 min,P=0.048).The median blood loss in the PSD group was significantly less than that in the PD group.The median length of hospital stay was shorter for patients in the PSD group vs the PD group.The incidence of pancreatic fistula was higher among patients in the PD group vs the PSD group.The 1-,3-,and 5-year overall survival and disease-free survival rates for patients in the PSD group were 83%,70%,44%and 73%,61%,39%,respectively,and these values were not different than compared with those in the PD group(P=0.625).CONCLUSION:PSD with regional lymph node dissection presents an acceptable morbidity in addition to its advantages over PD.PSD may be a safe and feasible alternative to PD in the treatment of earlystage Amp Ca.

Early-stage primary signet ring cell carcinoma of the colon

Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its progno-sis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the co-lon. Colonoscopic examination revealed a Ⅱa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen re-vealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant me-tastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node me-tastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.

Thermodynamic modeling and elemental migration for the early stage of rodingitization:An example from the Xialu massif of the Xigaze ophiolite,southern Tibet

The analysis of early stage rodingite from the ultramafic rocks of the Xialu Massif in the Xigaze Ophiolite,Tibet,in China shows that the rodingitization involved continuous changes in fluid composition during different stages of subduction.The early stage prehnite-bearing rodingite was produced at low pressures and temperatures along extensional fractures.Samples of rodingite were collected along a profile from the center to the margin of a rodingitized intrusive igneous rock(^10 m×30 m),and they record wide variations in bulk composition,mineralogy,and texture.The mineral assemblages,from center to margin,vary from(1)relics of primary clinopyroxene(Cpx_(r))and primary amphibole(Amp_(r))+newly formed late amphibole(Act)+primary plagioclase(Pl_(r))+clinozoisite+prehnite+albite+chlorite+titanite+ilmenite(R1 rodingite),through(2)relics of primary clinopyroxene(Cpx_(r))+newly formed late clinopyroxene(Cpx_(n))+primary and late amphiboles(Amp_(r)+Act)+clinozoisite+prehnite+albite+chlorite+titanite(R2 rodingite),to(3)newly formed late clinopyroxene(Cpx_(n))and amphibole(Act)+clinozoisite+prehnite+albite+chlorite+titanite(R3 rodingite).As a result of the metasomatic process of rodingitization,the content of CaO in the whole rock chemical composition from R1 to R3 increases,SiO_(2) decreases,and Na_(2)O+K_(2)O is almost completely removed.Massbalance diagrams show enrichments in large ion lithophile elements such as Rb,Cs,Ba,and Pb as well as Ni during rodingitization.The central part of the rodingitized intrusion(R1 rodingite)was only slightly affected by metasomatism.On the other hand,the contents of the rare earth elements(REEs),high field strength elements(HFSEs;e.g.Zr,Nb,Ta,Hf,and Y),and some highly compatible elements such as Cr and Sc decreased slightly during rodingitization.Thermodynamic modeling based on equilibrium mineral assemblages indicates that the rodingite of the Xialu Massif formed in an H_(2)O-saturated,CO_(2)-rich environment.The estimated conditions of metamorphism were-281-323℃and 0.4-3.9 kbar,representing the subgreenschist facies.In this environment,REEs and HFSEs were soluble in the fluids and partly removed.Moreover,these prehnite rodingites formed in a progressively reducing and less alkaline environment,as indicated by decreases in f(O_(2))and bulk-rock Fe^(3+)/Fe^(2+) ratios,and the records of fluidΔpH from the center to the margin of the studied rodingitized intrusion.

Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

Accurate prediction of lymph node(LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer(EGC). However,consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search,we identified several independent variables associated with LN metastasis in EGC,which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand,even if we use these promising parameters,we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN(SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review,we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition,we evaluated the history of sentinel node navigation surgery and the usefulness for EGC.

Advances and controversies in the management of early stage nonsmall cell lung cancer

Complete resection continues to be the gold standard for the treatment of earlystage lung cancer.The landmark Lung Cancer Study Group trial in 1995 established lobectomy as the minimum intervention necessary for the management of early-stage non-small cell lung cancer,as it was associated with lower recurrence and metastasis rates than sublobar resection and lower postoperative morbidity and mortality than pneumonectomy.There is a growing tendency to perform sublobar resection in selected cases,as,depending on factors such as tumor size,histologic subtype,lymph node involvement,and resection margins,it can produce similar oncological results to lobectomy.Alternative treatments such as stereotactic body radiotherapy and radiofrequency ablation can also produce good outcomes in inoperable patients or patients who refuse surgery.

Endoscopic diagnosis of early-stage primary esophageal small cell carcinoma: Report of two cases

BACKGROUND Primary esophageal small cell carcinoma(PESCC)is a highly aggressive malignancy,and its detailed clinical behaviors have remained virtually unknown.Because of the rapid tumor progression,the diagnosis of esophageal small cell carcinoma at early stage is extremely difficult in clinical practice.Currently,only a handful of PESCC cases have been reported.CASE SUMMARY Case 1:A 62-year-old man was diagnosed with an esophageal submucosal tumor by endoscopy.Endoscopic ultrasonography showed a 0.8 cm low echo nodule in the muscularis mucosa.As the patient refused to undergo endoscopic resection,neoplasia was detected by endoscopy 1 year later.Case 2:A 68-year-old woman was diagnosed as having an esophageal submucosal tumor by endoscopy at a local hospital.About 2 wk later,we performed endoscopic ultrasonography and found a 1 cm low echo nodule in the muscularis mucosa;the submucosal was thinner than normal but still continuous;mucosal hyperemia and erosion were found on the surface of the tumor.Endoscopic submucosal dissection(ESD)was performed and the histopathological finding showed a small cell carcinoma invading the submucosal layer.CONCLUSION Early esophageal small cell carcinoma shows submucosal infiltrating growth with a hypoechoic mass in the muscularis mucosa as diagnosed by endoscopic ultrasonography.It is easily misdiagnosed as submucosal masses.Endoscopic manifestations should be identified and pathological biopsies should beemployed. ESD may be performed to provide an opportunity for early treatmentof PESCC.

Treatment patterns for adjuvant docetaxel-based chemotherapy in early-stage breast cancer in China：A pooled retrospective analysis of four observational studies

Objective：Adjuvant docetaxel-based chemotherapy is frequently used for operable early breast cancer（EBC）.This study investigated patterns of use of docetaxel（T）in real-life clinical practice in China.Methods：This was a retrospective pooled analysis of the Asia-Pacific Breast Initiatives（APBI）Ⅰ（2006–2008）and Ⅱ（2009–2011）registries,and two Chinese observational studies;BC STATE（2011–2014）and BC Local Registry（2007–2010）.Female Chinese adults（≥18 years）with operable breast cancer treated with docetaxel-based adjuvant chemotherapy were included in the analysis.Patients with metastatic disease were excluded.The primary endpoint was assessment of treatment patterns and patient profiles.A logistic regression analysis was conducted to identify factors associated with choice of adjuvant chemotherapy regimen.Results：Data from 3,020 patients were included.The most frequently used adjuvant regimen was docetaxel/anthracycline combination[n=1,421（47.1%）;of whom 52.0%received T/epirubicin（E）/cyclophosphamide（C）],followed by docetaxel/other[n=705（23.3%）;of whom 72.8%received TC],docetaxel/anthracycline sequential[n=447（14.8%）;of whom 40.9%and 39.6%received 5-Fu/EC-T and EC-T,respectively],and＂other＂[n=447（14.8%）;of whom 91.5%received T].A significant association was found between adjuvant therapy with docetaxel/anthracycline combination and patient weight,menopausal status and estrogen receptor status.Conclusions：Real-world data revealed that docetaxel/anthracycline combination is the most commonly used category of docetaxel-based adjuvant therapy for patients with operable breast cancer in China;of which TEC is the most frequently used regimen.

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

Patients with early-stage non-small-cell lung cancer(NSCLC)are candidates for curative surgery;however,despite multiple advances in lung cancer management,recurrence rates remain high.Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival(OS),but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients.The high efficacy of tyrosine kinase inhibitors(TKIs)against epidermal growth factor receptor-mutated(EGFR)in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease.Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment,in patients with resected EGFR-mutated NSCLC,and shown that they significantly prolong disease-free survival(DFS),but this benefit does not translate to OS.Recently,an interim analysis of the ADAURA trial demonstrated that,surprisingly,osimertinib improved DFS.This led to the study being stopped early,leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup.These targeted agents are also being evaluated in locally-advanced disease,with promising results,although prospective studies with larger sample sizes are needed to confirm these results.In this article,we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.