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.

A strength model for cement-stabilized mud subjected to various curing temperatures and its early-stage quality control

The influence of curing temperature on the strength development of cement-stabilized mud has been well documented in terms of strength-increase rate and ultimate strength.However,the strength development model is not mature for the extremely early stages.In addition,there is a lack of studies on quality control methods based on early-stage strength development.This paper presents a strength model for cement-stabilized mud to address these gaps,considering various curing temperatures and early-stage behaviors.In this study,a series of laboratory experiments was conducted on two types of muds treated with Portland blast furnace cement and ordinary Portland cement under four different temperatures.The results indicate that elevated temperatures expedite strength development and lead to higher long-term strength.The proposed model,which combines a three-step conversion process and a hyperbolic model at the reference temperature,enables accurate estimate of the strength development for cement-treated mud with any proportions cured under various temperatures.With this model,a practical early quality control method is introduced for applying cement-stabilized mud in field projects.The back-analysis parameters obtained from a 36-h investigation at temperature of 60C demonstrated a sufficient accuracy in predicting strength levels in practical applications.

Early gastric composite tumor comprising signet-ring cell carcinoma and mucosa-associated lymphoid tissue lymphoma:A case report

BACKGROUND Composite tumors are neoplasms comprising two distinct,yet intermingling,cell populations.This paper reports a rare phenomenon where early gastric signet-ring cell carcinoma(SRCC)and gastric mucosa-associated lymphoid tissue(MALT)lymphoma coexist within the same lesion.CASE SUMMARY A 40-year-old woman presented to the West China Hospital for examination,which revealed a whitish,shallow,and uneven mucosal lesion in the stomach.The lesion was diagnosed as a poorly differentiated adenocarcinoma,including SRCC with atypical lymphoid hyperplasia associated with Helicobacter pylori infection,based on histopathological examination of the biopsy specimen.The lesion was excised using segmental gastrectomy.However,histological exami-nation of the surgical specimen confirmed that it was a poorly differentiated gastric adenocarcinoma with features of SRCC and MALT lymphoma.These two entities were stage I and coexisted in the same lesion.CONCLUSION It is uncommon for gastric SRCC and MALT lymphoma to coexist without distinct borders.Surgical resection is effective for these lesions.

Radical cholecystectomy without liver resection for peritoneal side early incidental gallbladder cancer

Gallbladder cancer(GBC)is a rare disease with a poor prognosis.Simple cholecystectomy may be an adequate treatment only for very early disease(Tis,T1a),whereas reoperation is recommended for more advanced disease(T1b and T2).Radical cholecystectomy should have two fundamental objectives:To radically resect the liver parenchyma and to achieve adequate clearance of the lymph nodes.However,recent studies have shown that compared with lymph node dissection alone,liver resection does not improve survival outcomes.The oncological roles of lymphadenectomy and liver resection is distinct.Therefore,for patients with incidental GBC without liver invasion,hepatic resection is not always mandatory.

Autophagy-dependent ferroptosis may play a critical role in early stages of diabetic retinopathy

Diabetic retinopathy(DR),as one of the most common and significant microvascular complications of diabetes mellitus(DM),continues to elude effective targeted treatment for vision loss despite ongoing enrichment of the understanding of its pathogenic mechanisms from perspectives such as inflammation and oxidative stress.Recent studies have indicated that characteristic neuroglial degeneration induced by DM occurs before the onset of apparent microvascular lesions.In order to comprehensively grasp the early-stage pathological changes of DR,the retinal neurovascular unit(NVU)will become a crucial focal point for future research into the occurrence and progression of DR.Based on existing evidence,ferroptosis,a form of cell death regulated by processes like ferritinophagy and chaperone-mediated autophagy,mediates apoptosis in retinal NVU components,including pericytes and ganglion cells.Autophagy-dependent ferroptosis-related factors,including BECN1 and FABP4,may serve as both biomarkers for DR occurrence and development and potentially crucial targets for future effective DR treatments.The aforementioned findings present novel perspectives for comprehending the mechanisms underlying the early-stage pathological alterations in DR and open up innovative avenues for investigating supplementary therapeutic strategies.

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.

Study on Growth and Development of Early Postembryonic Stage of Onychostoma sima

[Objective] The paper was to study the growth and development of Onychostoma sima in postembryonic development stage. [Method] The oosperm was obtained by artificial spawning and artificial insemination method, and hatched under laboratory condition. The indexes such as body weight, body length, length in front of anus and body height were measured to establish larvae growth model. [Result] When the water temperature was （20±1.5） ℃, the body length and body weight of newly hatched larvae were （10.28±0.05） mm and （7.79±0.08） mg, respectively. O. sima larvae begin to feed on the 4 th day after hatching, the initial feeding rate was 48%, the highest feeding rate was 100% on the 6 th d. The-point-of-no-return （PNR） was 13.5 d. In addition, it was also observed that the appearance time of PNR point of O. sima larvae was close to death time of completely starved group, being only 2 d, indicating that once O. sima larvae reached the PNR point, they would face death threats within short time. Therefore, various growth conditions for O. sima larvae should be satisfied to ensure full development of all organs, thereby reducing death and growth stagnation caused by adverse environment in early postembryonic stage. [Conclusion] The study provided theoretical basis for solving the problems in artificial breeding.

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.

Early gastric cancer frequently has high expression of KKLC-1, a cancer-testis antigen

AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.

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.

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Circulating MicroRNA Deregulation in Early Lung Carcinogenesis

Objective To study the alteration of circulating microRNAs in 4-（methylnitrosamino）-l-（3-pyridyl） -l-butanone （NNK）-induced early stage lung carcinogenesis. Methods A lung cancer model of male F344 rats was induced with systemic NNK and levels of 8 lung cancer-associated miRNAs in whole blood and serum of rats were measured by quantitative RT-PCR of each at weeks 2, 5, 20, and 20 following NNK treatment. Results No lung cancer was detected in control group and NNK treatment group at week 20 following NNK treatment. The levels of some circulating miRNAs were significantly higher in NNK treatment group than in control group. The miR-210 was down-regulated and the miR-206 was up-regulated in NNK treatment group. The expression level of circulating miRNAs changed from week 1 to week 20 following NNK treatment. Conclusion The expression level of circulating miRNAs is related to NNK-induced early stage lung carcinogenesis in rats and can therefore serve as its potential indicator.

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.

Early Growth and Development of Boer Goats from Embryo Transplant

[ Objective] To study the growth-development of Boer goats from embryo transplant. [ Method] With Boer goats from embryo transplant as the tested animals and natural breeding Boer goats born in the same period as CK, the weight of Boer goats at birth and at the age of 1,3 and 6 months as well as the body size at the age of 3 and 6 months were investigated in this study, while their health conditions were also observed and recorded. [ Result] Under the normal feeding conditions, Boer goats from embryo transplant developed well at early stage, and their meat-using body type were also obvious. The average birth weight of bucks was （4.25±0.95） kg, and that of does was （3.74±0.10） kg. The average weight of bucks at the age of 6 months was （31.90 ±0.74） kg and that of was （25.90 ±0.67） kg. The daily gains of bucks and ewes from birth to 6 months of age were 153.64 and 123.11 g respectively, while their body length, body height and chest circumference increased obviously, and there was no significant difference in body weight or body size between them and natural breeding goats. [ Condusioa] The study lays a foundation for further studies on the breedinq and utilization of Boer noats from embryo transplant at early staae.

Characterization of Early Fatigue Microstructure in AISI 321 Steel Using Eddy Current Non-destructive Methodology

Accumulative damage during early stage of fatigue in AISI 321 steel was investigated by eddy current test, atomic force microscopy, X-ray diffraction and transmission electron microscopy. Surface slip, dislocation, and strain-induced martensite were determined as the main damage types. Moreover, damage during the fatigue was found to be increased with the increasing fatigue cycles and load amplitude. The contribution of strain-induced martensite to the total eddy current amplitude （V） was enhanced with the increase in its volume fraction. Finally, a linear relationship between V I~, and the height of surface slip was established.

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.

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.

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.

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.

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.

Preoperative [18]fluorodeoxyglucose-positron emission tomography/computed tomography in early stage breast cancer: Rates of distant metastases

AIM To investigate rates of distant metastases(DM) detected with [18]fluorodeoxyglucose-positron emissiontomography/computed tomography(^(18)FDG-PET/CT) in early stage invasive breast cancer.METHODS We searched the English language literature databases of PubM ed, EMBASE, ISI Web of Knowledge, Web of Science and Google Scholar, for publications on DM detected in patients who had ^(18)FDG-PET/CT scans as part of the staging for early stages of breast cancer(stage Ⅰ?and Ⅱ), prior to or immediately following surgery. Reports published between 2011 and 2017 were considered. The systematic review was conducted according to the PRISMA guidelines.RESULTS Among the 18 total studies included in the analysis, the risk of DM ranged from 0% to 8.3% and 0% to 12.9% for stage Ⅰ?and Ⅱ invasive breast cancer, respectively. Among the patients with clinical stage Ⅱ, the rate of occult metastases diagnosed by ^(18)FDG-PET/CT was 7.2%(range, 0%-19.6%) for stage ⅡA and 15.8%(range, 0%-40.8%) for stage ⅡB. In young patients(< 40-yearold), ^(18)FDG-PET/CT demonstrated a higher prevalence of DM at the time of diagnosis for those with aggressive histology(i.e., triple-negative receptors and poorly differentiated grade).CONCLUSION Young patients with poorly differentiated tumors and stage ⅡB triple-negative breast cancer may benefit from ^(18)FDG-PET/CT at initial staging to detect occult DM prior to surgery.