C634Y mutation in RET-induced multiple endocrine neoplasia type 2A:A case report

BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.

Detection of Endocrine Disruptors in Water around Landfills

[Objectives]This study was conducted to explore the occurrence levels of endocrine disruptors(EDCs)in rural areas around a county landfill in Tongren City.[Methods]The water around the landfill was sampled and analyzed.A solid-phase extraction and high performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS)method was established for the determination of 27 EDCs.After the HLB solid-phase extraction column was activated,a water sample,which was adjusted with phosphoric acid to a pH of 2(±0.5)and added with 500 mg of disodium EDTA,was loaded,and 5 ml of water and 20%methanol water was added for washing.Next,10 ml of elution solution was added for elution,and the collected eluate was evaporated under reduced pressure at 40℃to near dryness,and 1 ml of reconstitution solution was added to a constant volume.An ACQUITY UPLC BEH C18(100×2.1 mm,2.6μm)chromatographic column was adopted for LC separation by gradient elution with pure water solution-acetonitrile as the mobile phase.For MS detection,the MRM mode was adopted for collection,and the positive and negative ion modes were switched for simultaneous determination,and the internal standard method was used for quantification.[Results]The correlation coefficient R2 was greater than 0.99 in the linear range of each target substance.The limits of quantitation in the method were between 0.05 and 2.00 ng/L,and the recoveries ranged from 75.3%to 105.7%.[Conclusions]The method has high sensitivity,good accuracy and strong practical value.

Myo-inositol versus metformin effects on clinical features, endocrine and metabolic profiles in infertile women with polycystic ovary syndrome: A randomized controlled trial

Objective:To compare the effectiveness of inositol and metformin on the clinical characteristics,and endocrine and metabolic profiles of infertile polycystic ovarian syndrome(PCOS)women from Vietnam.Methods:From June 2018 to August 2022,a randomized trial was undertaken at the Hue Center for Endocrinology and Reproduction on infertile women aged 18 to 40 years with polycystic ovarian syndrome.The clinical,endocrine,and metabolic features of these individuals were assessed before and after 3 months of treatment with 2 g of inositol or 1700 mg of metformin per day.Natural pregnancy rates,adverse effects,and tolerance of inositol were recorded.Results:The study included 171 infertile PCOS women who were eligible to participate and took part in the baseline assessment,of whom 132 women participated in data analysis after 3 months.After metformin treatment,42.1%of women with oligomenorrhea experienced regular menstruation.Metformin significantly lowered body mass index(BMI),waist circumference and testosterone levels,but had no effect on other clinical characteristics,endocrine profiles,or metabolic profiles.29.2%Of women reported experiencing side effects.21%Of them attained pregnancy,which resulted in 17.1%of live births.In the inositol group,the rate of regular cycle increased by 18.2%and the total testosterone concentration significantly decreased.In overweight/obese women with PCOS,inositol significantly decreased weight,BMI,waist and hip circumferences(P<0.05).100%Of women tolerated inositol and continued treatment.18.9%Of them became pregnant,leading to 17%of live births.Conclusions:Metformin and inositol can improve weight and waist circumference in overweight/obese infertile women with PCOS.Metformin is associated with a higher rate of regular menstruation,whereas inositol is associated with a lower rate of adverse effects.The spontaneous conception,clinical pregnancy,and live birth rates between two groups are comparable.

Systematic review and meta-analysis of endometrial thickening during endocrine therapy combined with Chinese herbal medicine intervention after breast cancer surgery

Objective:To systematically evaluate the endometrial thickening and Chinese herbal medicine intervention effects during endocrine therapy following breast cancer surgery.Methods:Computerized searches were performed on CNKI,CBM,Wanfang,VIP,Pub Med,Embase,and Cochrane to gather randomized controlled trials(RCTs)of endometrial thickening combined with Chinese herbal medicine intervention during endocrine therapy after breast cancer surgery.The meta analysis is done using Rev Man 5.4,and the retrieval range is from the database's creation to January 2023.Results:There were 710 patients enrolled in a total of 12 RCTs.The results of Meta-analysis were as follows:combined with Chinese herbal medicine treatment for 3 months of endometrial thickness(MD=-1.12,95%CI[-1.47,0.77],P<0.00001);6 months endometrial thickness(MD=-1.90,95%CI[-2.38,-1.42],P<0.00001);endometrial thickness at 12 months(MD=-2.24,95%CI[-2.96,-1.52],P<0.00001);modified Kupperman score(MD=-10.45,95%CI[-19.10,-1.80],P=0.02);TCM syndrome score(SMD=-1.53,95%CI[-1.84,-1.22],P<0.00001);KPS score(MD=3.75,95%CI[2.81,4.68],P<0.00001);there was no significant difference in CA153,CEA,FSH and E2 between the two groups.Conclusion:After breast cancer surgery,endocrine therapy combined with Chinese herbal medicine can significantly lessen endometrial thickening and enhance patient quality of life.

Endocrine-Disrupting Chemicals: Possible Genesis of Ovarian Tumors

Background: Prolonged exposure to environmental toxicants like endocrine-disrupting chemicals has been linked to several ovarian pathologies. Exposure to endocrine-disrupting chemicals may start at any time of life from the fetal stage to adulthood resulting in various health complications The purpose of our study is to compare the concentration levels and association of benzopyrene, bisphenol A and genistein in patients with ovarian tumors and normal control group. We also sort to evaluate the predictive performance of benzopyrene, bisphenol A and genistein in patients with ovarian tumors. Methods: A case-control study was conducted for randomly selected participants involving 30 patients and 30 controls. 30 patients with radiologically diagnosed and histopathological confirmed ovarian tumors were included in the study between January 2022 and December 2022. Urine samples from each group were analyzed using liquid chromatography-mass spectrometry. Descriptive analysis for normally distributed continuous variables was done accordingly. Concentration levels of endocrine-disrupting chemicals were assessed using the Mann-Whitney test. The association of endocrine-disrupting chemicals with pathological ovarian tumors was analyzed using binary logistic regression. Evaluation of the diagnostic performance of endocrine-disrupting chemicals was analyzed using the ROC curve. Results: Overall, patients were significantly (P = 0.000) older than the healthy controls. Mean years (SD) were 36.7 (7.90) and 28.8 years (4.89) for patients and normal women respectively. Endometriomas had the highest incidence of 50%. The level of benzopyrene and bisphenol A in patients was significantly higher than those in the control group, while the level of genistein was significantly higher in normal controls. Benzopyrene and bisphenol A were significantly associated with ovarian cysts, and the incidence of pathological ovarian cysts was positively correlated to these EDCs, with OR value 64.79 (P = 0.005) for benzopyrene and 9.609 (P = 0.001) for bisphenol A. Genistein was significantly negatively correlated with the incidence of pathological ovarian tumors, with OR value of 0.153 (P = 0.007). Diagnostic performance on the AUC for benzopyrene, bisphenol A and genistein&l.

关于Endocrine Disruptors的译名

当今环境科学的发展十分迅速 ,新的名词术语大量涌现 ,但由于对这些名词翻译和使用上的不统一 ,给广大的科技工作者和关心环境问题的普通百姓造成了工作中或认识上的麻烦和混乱。例如 ,“一类来源于环境中的、能干扰生物体内分泌功能的物质” ,就有“环境内分泌干扰物”、“内分泌干扰物”、“内分泌紊乱剂”、“环境激素”、“环境荷尔蒙”等多种中文名称 ,其英文名称也有“endocrinedisruptors”、“environ mentalendocrinedisruptors”、“endocrinedisruptingchemicals”、“environmentalhormones”等多种表述 ,并且对这类物质的定义 ,在国际上还没有达到完全一致 ,亟待统一和规范。为了尽快统一和规范环境科学的名词术语 ,我们邀请有关专家在本刊对一些新近出现的影响较大、分歧较多的环境科学名词术语进行研究和讨论 ,以期为将来名词的最终审定奠定基础。我们欢迎广大读者来稿发表意见 ,以使审定的名词更科学、更准确、更有利于普及利用。

Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer

The estrogen receptor(ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, posttranslational modification of ER, deregulation of ER coactivators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin(m TOR), Mitogen activated kinase(MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modificationincluding dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific micro RNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations that may be exploited as potential therapeutic targets and biomarkers of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the m TOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in Pub Med, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at Clinical Trials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer. We summarize clinical trials utilizing novel strategies to overcome therapeutic resistance, highlighting the need to better identify the appropriate patients whose diseases are most likely to benefit from these specific strategies.

Paracrine and endocrine actions of bone——the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts

The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes,and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin（SOST） that inhibits osteoblast differentiation and promotes osteoclast differentiation. Osteoclasts secrete factors including BMP6, CTHRC1, EFNB2, S1P, WNT10B, SEMA4D, and CT-1 that act on osteoblasts and osteocytes, and thereby influencea A osteogenesis. Osteoclast precursors produce the angiogenic factor PDGF-BB to promote the formation of Type H vessels, which then stimulate osteoblastogenesis. Besides, the evidences over the past decades show that at least three hormones or ＂osteokines＂from bone cells have endocrine functions. FGF23 is produced by osteoblasts and osteocytes and can regulate phosphate metabolism. Osteocalcin（OCN） secreted by osteoblasts regulates systemic glucose and energy metabolism, reproduction, and cognition. Lipocalin-2（LCN2） is secreted by osteoblasts and can influence energy metabolism by suppressing appetite in the brain.We review the recent progresses in the paracrine and endocrine functions of the secretory proteins of osteoblasts, osteocytes, and osteoclasts, revealing connections of the skeleton with other tissues and providing added insights into the pathogenesis of degenerative diseases affecting multiple organs and the drug discovery process.

Endocrine disruptors and estrogenic effects on male reproductive axis

Endocrine disruptors （e.g., polychlorinated biphenyls [PCBs], dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides） are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions. The development of intra-cytoplasmic sperm injection （ICSI） is beyond doubt the most important recent breakthrough in the treatment of male infertility, but it does not necessarily treat the cause and may inadvertently pass on adverse genetic consequences. Many well-controlled clinical studies and basic scientific discoveries in the physiology, biochemistry, and molecular and cellular biology of the male reproductive system have helped in the identification of greater numbers of men with male factor problems. Newer tools for the detection of Y-chromosome deletions have further strengthened the hypothesis that the decline in male reproductive health and fertility may be related to the presence of certain toxic chemicals in the environment. Thus the etiology, diagnosis, and treatment of male factor infertility remain a real challenge. Clinicians should always attempt to identify the etiology of a possible testicular toxicity, assess the degree of risk to the patient being evaluated for infertility, and initiate a plan to control and prevent exposure to others once an association between occupation/toxicant and infertility has been established.

Overcoming endocrine resistance in metastatic breast cancer: Current evidence and future directions

About 75% of all breast cancers are estrogen receptor(ER)-positive. They generally have a more favorable clinical behavior, prognosis, and pattern of recurrence, and endocrine therapy forms the backbone of treatment. Anti-estrogens(such as tamoxifen and fulvestrant) and aromatase inhibitors(such as anastrozole, letrozole, and exemestane) can effectively control the disease and induce tumor responses in a large proportion of patients. However, the majority of patients progress during endocrine therapy(acquired resistance) and a proportion of patients may fail to respond to initial therapy(de novo resistance). Endocrine resistance is therefore of clinical concern and there is great interest in strategies that delay or circumvent it. A deeper knowledge of the molecular mechanisms that drive endocrine resistance has recently led to development of new strategies that have the promise to effectivelyovercome it. Many resistance mechanisms have been described, and the crosstalk between ER and growth factor receptor signaling pathways seems to represent one of the most relevant. Compounds that are able to inhibit key elements of these pathways and restore endocrine sensitivity have been studied and more are currently under development. The aim of this review is to summarize the molecular pathophysiology of endocrine resistance in breast cancer and its impact on current clinical management.

Primary large cell neuroendocrine carcinoma in the common bile duct:First Asian case report

Large cell neuroendocrine carcinoma(LCNEC)in the biliary system is a poorly differentiated,high-grade neuroendocrine tumor.These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases.Herein,we report an unusual case of a pure primary LCNEC of the common bile duct(CBD).A 75-year-old female presented with nausea and jaundice.The patient underwent a CBD excision with lymph node dissection.Upon histological and immunohistochemical examination,the tumor exhibited pure large cell-type neuroendocrine features.Metastases were noted in two of the eight lymph nodes.The patient was administered adjuvant chemotherapy.The patient’s cancer recurred 7 mo after surgery,and the patient died from liver failure 5 mo after recurrence.The prognosis of LCNEC of CBD remains poor despitecurative resection and adjuvant chemotherapy.The role of additional therapies,such as multimodal treatment including radiation therapy,must be further studied to improve the prognoses of patients.

Autonomic and endocrine control of cardiovascular function

The function of the heart is to contract and pump oxygenated blood to the body and deoxygenated blood to the lungs.To achieve this goal,a normal human heart must beat regularly and continuously for one's entire life.Heartbeats originate from the rhythmic pacing discharge from the sinoatrial(SA) node within the heart itself.In the absence of extrinsic neural or hormonal influences,the SA node pacing rate would be about 100 beats per minute.Heart rate and cardiac output,however,must vary in response to the needs of the body's cells for oxygen and nutrients under varying conditions.In order to respond rapidly to the changing requirements of the body's tissues,the heart rate and contractility are regulated by the nervous system,hormones,and other factors.Here we review how the cardiovascular system is controlled and influenced by not only a unique intrinsic system,but is also heavily influenced by the autonomic nervous system as well as the endocrine system.

Neuroendocrine tumors of the small bowels are on the rise:Early aspects and management

Neuroendocrine tumors of the small bowel are on the rise. In the US they have increased by 300%-500% in the last 35 years. At the same time their prognosis is much improved. Today,most neuroendocrine tumors (NETs) of the duodenum are detected "incidentally" and therefore recognized at an early stage. Duodenal NETs which are well differentiated,not larger than 10 mm and limited to the mucosa/submucosa can be endoscopically resected. The management of duodenal NETs ranging between 10 and 20 mm needs an interdisciplinary discussion. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is recommended for well-differentiated duodenal NET tumors greater than 20 mm,for localized sporadic gastrinomas (of any size) and for localized poorly differentiated NE cancers. Surgery is recommended for any ileal NET. Advanced ileal NETs with a carcinoid syndrome are treated with longacting somatostatin analogs. This treatment significantly improves (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management,tumor biology,type,localization and stage of the neoplasm,as well as the patient's individual circumstances have to be taken into account.

Pathological differential diagnosis of solid-pseudopapillary neoplasm and endocrine tumors of the pancreas

AIM:To investigate differential points of solid-pseudo-papillary neoplasm (SPN) of the pancreas and pancre-atic endocrine tumor (PET).METHODS:Ten cases of SPN and fourteen cases of PET were studied in this retrospective study. Clinical and pathologic features,immunostaining reactions and β-catenin gene mutations were analyzed.RESULTS:The mean age of SPN patients was 25.6 years and these patients had no specific symptoms. The mean diameter of the tumors was 11.0 cm,9/10 cases were cystic or a mixture of solid and cystic structures,and there was hemorrhage and necrosis on the cut surface in 8/10 (80%) cases. Characteristic pseudo-papillary structure and discohesive appearance of the neoplastic cells were observed in all 10 (100%) cases. The results of immunostaining showed that nuclear expression of β-catenin and loss of E-cadherin in all the cases,was only seen in SPN. Molecular studies discov-ered that 9/10 (90%) cases harbored a point mutation of exon 3 in β-catenin gene. On the other hand,the mean age of PET patients was 43.1 years. Eight of 14 cases presented with symptoms caused by hypoglyce-mia,and the other 6 cases presented with symptoms similar to those of SPN. The mean size of the tumors was 2.9 cm,most of the tumors were solid,only 3/14 (21%) were a mixture of solid and cystic structures,and macroscopic hemorrhage and necrosis were much less common (3/14,21%). Histologically,tumor cells were arranged in trabecular,acinar or solid patterns and demonstrated no pseudopapillary structure and discohesive appearance in all 14 (100%) cases. The results of immunostaining and mutation detection were completely different with SPN that membrane and cytoplastic expression of β-catenin without loss of E-cadherin,as well as no mutation in β-catenin gene in all the cases. CONCLUSION:Both macroscopic and microscopic features of SPN are quite characteristic. It is not difficult to distinguish it from PET. If necessary,immunos-taining of β-catenin and E-cadherin is quite helpful to make the differential diagnosis.

Endocrine Disruption Activity of 30-day Dietary Exposure to Decabromodiphenyl Ethane in Balb/C Mouse

Objective This study aimed to evaluate the hepatotoxicity, metabolic disturbance activity and endocrine disrupting activity of mice treated by Decabromodiphenyl ethane （DBDPE）. Methods In this study, Balb/C mice were treated orally by gavage with various doses of DBDPE. After 30 days of treatment, mice were sacrificed; blood, livers and thyroid glands were obtained, and hepatic microsomes were isolated. Biochemical parameters including 8 clinical chemistry parameters, blood glucose and hormone levels including insulin and thyroid hormone were assayed. The effects of DBDPE on hepatic cytochrome P450 （CYP） levels and activities and uridinediphosphate-glucuronosyltransferase （UDPGT） activities were investigated. Liver and thyroid glands were observed. Results There were no obvious signs of toxicity and no significant treatment effect on body weight, or liver-to-body weight ratios between treatment groups. The levels of ALT and AST of higher dose treatment groups were markedly increased. Blood glucose levels of treatment groups were higher than those of control group. There was also an induction in TSH, T3, and f T3. UDPGT, PROD, and EROD activities were found to have been increased significantly in the high dose group. Histopathologic liver changes were characterized by hepatocyte hypertrophy and cytoplasmic vacuolization. Our findings suggest that DBDPE can cause a certain degree of mouse liver damage and insufficiency. Conclusion DBDPE has the activity of endocrine disruptors in Bal/C mice, which may induce drug-metabolizing enzymes including CYPs and UDPGT, and interfere with thyroid hormone levels mediated by Ah R and CAR signaling pathways. Endocrine disrupting activity of DBDPE could also affect the glucose metabolism homeostasis.

Recent standardization of treatment strategy for pancreatic neuroendocrine tumors

Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors(PNET).For patients with sporadic functioning PNET,curative resection surgery has been established by localization with the SASI test using secretin or calcium.For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1(MEN 1) which are usually multiple and sometimes numerous,resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test.As resection surgery of PNET has increased,several important pathological features of PNET have been revealed.For example,in patients with Zollinger-Ellison syndrome(ZES),duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma,and in patients with MEN 1 and ZES,gastrinomas have been located mostly in the duodenum,and pancreatic gastrinoma has been found to co-exist in 13% of patients.Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation.The most important prognos-tic factor in patients with PNET is the development of hepatic metastases.The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit.The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.

Current surgical management of pancreatic endocrine tumor liver metastases

BACKGROUND: The management of metastatic disease in pancreatic endocrine tumors (PETs) demands a multidisciplinary approach and the cooperation of several medical specialties. The role of surgery is critical, even when a radical excision cannot always be achieved. DATA SOURCES: A PubMed search of relevant articles published up to February 2011 was performed to identify current information about PET liver metastases regarding diagnosis and management, with an emphasis on surgery. RESULTS: The early diagnosis of metastases and their accurate localization, most commonly in the liver, is very important. Surgical options include radical excision, and palliative excision to relieve symptoms in case of failure of medical treatment. The goal of the radical excision is to remove the primary tumor bulk and all liver metastases at the same time, but unfortunately it is not feasible in most cases. Palliative excisions include aggressive tumor debulking surgeries in well-differentiated carcinomas, trying to remove at least 90% of the tumor mass, combined with other additional destructive techniques such as hepatic artery embolization or chemoembolization to treat metastases or chemoembolization to relieve symptoms in cases of rapidly growing tumors. The combination of chemoembolization and systemic chemotherapy results in better response and survival rates. Other local destructive techniques include ethanol injection, cryotherapy and radiofrequency ablation. CONCLUSION: It seems that the current management of PETs can achieve important improvements, even in advanced cases.

Neoadjuvant endocrine therapy: A potential strategy for ER-positive breast cancer

A potential strategy for patients with estrogen receptor(ER)-positive breast cancer is necessary to replace neoadjuvant chemotherapy which has limited benefit.Neoadjuvant endocrine therapy(NAE)has been indicated to be a favorable alternate approach to downstage large or locally advanced breast cancer in ER-positive,human epidermal growth factor receptor 2(HER2)-negative(ER+/HER2-)patients,especially postmenopausal women.Previous studies have demonstrated the efficacy of various endocrine agents in NAE.Aromatase inhibitors(AIs)have proven superiority over tamoxifen as a suitable choice to optimize treatment efficacy.Fulvestrant was recently reported as an effective agent,similar to AIs.Furthermore,the addition of targeted agents exerts synergistic antiproliferative effects with endocrine agents and rapidly improves response rates in both endocrine sensitive and resistant tumors.The neoadjuvant platform provides a unique opportunity to define the appropriate strategy and address the mechanisms of endocrine resistance.In addition,the predictive value of biomarkers and genomic assays in NAE is under investigation to evaluate individual effects and validate biomarker-based strategies.In this review,we discuss the most relevant evidence on the potential of NAE for ER+breast cancer.The current understanding also offers new insights into the identification of the optimal settings and valuable predictive tools of NAE to guide clinical treatment decisions and achieve beneficial therapeutic effects.

Biliary tree gastrinomas in multiple endocrine neoplasia type 1 syndrome

AIM:To describe our patients affected with ectopic biliary tree gastrinoma and review the literature on this topic.METHODS:Between January 1992 and June 2012,28 patients affected by duodenopancreatic endocrine tumors in multiple endocrine neoplasia type 1(MEN1)syndrome underwent surgery at our institution.This retrospective review article analyzes our experience regarding seventeen of these patients subjected to duodenopancreatic surgery for Zollinger-Ellison syndrome(ZES).Surgical treatment consisted of duodenopancreatectomy(DP)or total pancreatectomy(TP).Regional lymphadenectomy was always performed.Any hepatic tumoral lesions found were removed during surgery.In MEN1 patients,removal of duodenal lesions can sometimes lead to persistence or recurrence of hypergastrinemia.One possible explanation for this unfavorable outcome could be unrecognized ectopic localization of gastrin-secreting tumors.This study described three cases among the seventeen patients who were found to have an ectopic gastrinoma located in the biliary tree.RESULTS:Seventeen MEN1 patients affected with ZES were analyzed.The mean age was 40 years.Fifteen patients underwent DP and two TP.On histopathological examination,duodeno pancreatic endocrine tumors were found in all 17 patients.Eighty-one gastrinomas were detected in the first three portions of the duodenum.Only one gastrinoma was found in the pancreas.The mean number of gastrinomas per patient was 5(range 1-16).Malignancy was established in 12 patients(70.5%)after lymph node,liver and omental metastases were found.Three patients exhibited biliary tree gastrinomas as well as duodenal gastrinoma(s).In two cases,the ectopic gastrinoma was removed at the same time as pancreatic surgery,while in the third case,the biliary tree gastrinoma was resected one year after DP because of recurrence of ZES.CONCLUSION:These findings suggest the importance of checking for the presence of ectopic gastrinomas in the biliary tree in MEN1 patients undergoing ZES surgery.

The acute lethality and endocrine effect of 1,2,3,7,8-PeCDD in juvenile goldfish (Carassius auratus) in vivo

1,2,3,7,8-PeCDD was administrated to juvenile goldfish （Carassius auratus） by peritoneal injections to explore the acute lethality and endocrine effects of 1,2,3,7,8-PeCDD in vivo. The value of acute median lethal dosage （LD50） of 1,2,3,7,8-PeCDD was determined in acute lethality tests. The endocrine effect of 1,2,3,7,8-PeCDD, whose exposed concentrations were determined based on the LD50 （1.84 mg/kg）, was studied by measuring the plasma vitellogenin （Vtg） content in juvenile male goldfish with enzyme-linked immunosorbent assays （ELISA）. Due to its significant induction of the plasma Vtg after one week＇s exposure in vivo in the 1/2 LD50 and LD30 groups, 1,2,3,7,8-PeCDD might be one of the important contributors to the estrogenic effect of PCDDs in the environment. The values of 1/2 LD50 and LD30 were within the range of the effective dosages of 1,2,3,7,8-PeCDD, indicating that there was a certain relationship between the estrogenic effective dosages and the LD50.