Bugbee flexible electrocautery facilitates choledochoscopic biopsy,fulguration,and debulking of a high grade intraductal papillary neoplasm of the bile duct

To the Editor:Intraductal papillary neoplasm of the bile duct(IPNB)may occur in the setting of primary sclerosing cholangitis,choledochal cysts or hepatolithiasis[1].The entity may be a precursor of cancer or intrahepatic cholangiocarcinoma.Invasive carcinoma,tubular or mucinous adenocarcinoma is present in approximately 40%-80%of IPNBs[1–3].IPNB is frequently found in the resection margins of patients undergoing hepatectomy for cholangiocarcinoma[4].

Multiple therapeutic and preventive effects of 3,3'-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia

Cruciferous vegetables belong to the plant family that has flowers with four equal-sized petals in the pattern of a crucifer cross.These vegetables are an abundant source of dietary phytochemicals,including glucosinolates and their hydrolysis products such as indole-3-carbinol（I3C） and 3,3＇-diindolylmethane（DIM）.By 2013,the total number of natural glucosinolates that have been documented is estimated to be 132.Recently,cruciferous vegetable intake has garnered great interest for its multiple health benefits such as anticancer,antiviral infections,human sex hormone regulation,and its therapeutic and preventive effects on prostate cancer and high grade prostatic intraepithelial neoplasia（HGPIN）.DIM is a hydrolysis product of glucosinolates and has been used in various trials.This review is to provide an insight into the latest developments of DIM in treating or preventing both prostate cancer and HGPIN.

Temozolomide resistance in high grade gliomas

High grade gliomas are always the research focus in the field of neurosurgery due to their poor prognosis despite the current standard therapeutic regimen of surgical resection followed by radiation therapy and chemotherapy. Alkylating agent temozolomide has been established as the standard chemotherapy while its resistance inevitable during treatment. This phenomenon seriously influences the prognosis of patients suffering from high grade gliomas. This review aims to elucidate temozolomide chemoresistance mechanisms through three chapters including O^6-methylguanine-DNA methyltransferase(MGMT) methylation, mismatch repair mutation and epigenetic regulation consisting of p21, chromatin and histone, Y-box binding protein-1 and micro RNAs.

A New Sound Alloy for High Grade Wind Instruments

A new sound alloy, abbreviated to S, has been developed by the General Research Institutefor Non-ferrous Metals, Beijing. The alloy is very suitable for making trumpets, trombones, tenorhorns, saxaphones and other kinds of wind instruments. Beijing Wind Instrument Factory, which is the largest one in China, has used Salloy formanufacturing 5200 type trompets, the sound performance of which has been examined with fre-quency analysis and experimented by famous musical experts. The results show that the 5200 typetrumpets made of Salloy have excellent quality, accurate intonation and ease of response at

High Grade Muscle-Invasive Urinary Bladder Cancer in A 36 Year Old Male Patient:A Case Report&Review of Literature

We are reporting a case of urothelial bladder cancer in a 36 year old male patient with no history or exposure to any risk factors.The incidence of urothelial bladder cancer is very low in young individuals i.e.below 40 years of age with reported rate of incidence around 0.1-0.4%.Most of the times,these young individuals present with non-muscle invasive bladder cancer with low grade and low stage.As the age increases,the incidence of high grade bladder cancer increases along with it.The index case presented with high grade muscle invasive bladder cancer at the time of diagnosis without any known risk factors.The 5-year survival of urothelial bladder cancer is better in young patients(93.8%)as compared to older people(85.1%).Cigarette smoking is responsible for development of bladder cancer in majority of patients followed by exposure to occupational carcinogens.Role of genetic alterations in development of bladder cancer is still under research and process of urothelial bladder carcinogenesis is unanswered in young individuals.

360° fusion for realignment of high grade cervical kyphosis by one step surgery: Case report

Surgical treatment for cervical kyphotic deformity is still controversial. Circumferential approach has been well described in the literature but long terms outcomes are not well reported. Important to decide the correct treatment option is the preoperative radiological exams to value the type of deformity(flexible or fixed). We report the case of a 67-year-old woman affected by a severe cervical kyphotic deformity who underwent combined anterior/posterior surgical approach, getting a good reduction of the deformity and an optimal stability in a long term follow up.

Barrett's esophagus with high grade dysplasia is associated with non-esophageal cancer

AIM To study factors associated with esophageal and nonesophageal cancer morbidity among Barrett's esophagus(BE) patients. METHODS A cohort study within a single tertiary center included 386 consecutive patients with biopsy proven BE, who were recruited between 2004-2014. Endoscopic and histologic data were prospectively recorded. Cancer morbidity was obtained from the national cancer registry. Main outcomes were BE related(defined as esophagus and cardia) and non-BE related cancers(all other cancers). Cancer incidence and all-causemortality were compared between patients with highgrade dysplasia(HGD) and with low-grade or no dysplasia(non-HGD) using Kaplan-Meier curves and cox regression models.RESULTS Of the 386 patients, 12 had HGD, 7 had a BE related cancer. There were 75(19.4%) patients with 86 cases of lifetime cancers, 76 of these cases were non-BE cancers. Seven(1.8%) and 18(4.7%) patients had BE and non-BE incident cancers, respectively. Twelve(3.1%) patients had HGD as worst histologic result. Two(16.7%) and 16(4.4%) incident non-BE cancers occurred in the HGD and non-HGD group, respectively. Ten-year any cancer and non-BE cancer free survival was 63% and 82% in the HGD group compared to 93% and 95% at the non-HGD group, respectively. Log-rank test for patients with more than one endoscopy, assuring longer follow up, showed a significant difference(P < 0.001 and P = 0.017 respectively). All-cause mortality was not significantly associated with BE HGD.CONCLUSION Patients with BE and HGD, may have a higher risk for all-cause cancer morbidity. The implications on cancer prevention recommendations should be further studied.

Synthesis of high grade octahedron diamond through epitaxial growth

The work was based on the relationship between the crystal structure and parameters of diamonds in the synthetic process, in which Ni Mn C powder catalyst was used. At first, the diamond crystals nucleated in a cubic octahedron morphology through controlling such synthetic parameters as temperature and pressure in a parameter region where cubic octahedron ctystals can be obtained. Then the diamond nuclei grew epitaxially into crystals with a perfect octahedron morphology through increasing the synthesis temperature and decreasing the synthesis pressure in a parameter region where octahedron crystals can be obtained.

Primary Endometrial High Grade Neuroendocrine Carcinoma: A Case Report with Cytological, Histopathological and Immunohistochemical Features

An 84-year-old woman suffered from post-menopausal genital bleeding for 3 months. Based on the endometrial cytological findings (suggestive of high grade neuroendocrine carcinoma) showing that there were rosette-like and cord-like structures consisting of small rounded tumor cells with oval nuclei and scanty cytoplasm, radical hysterectomy was performed. Histopathological and immunohistochemical examinations on the operated specimens revealed primary high grade neuroendocrine carcinoma of the endometrium. Despite the extensive treatment against the malignancy, the patient died due to widespread metastases after 5 months after the surgery and autopsied.

Phase change,micro-structure and reaction mechanism during high temperature roasting of high grade rare earth concentrate

The deposit of Bayan Obo in Inner Mongolia is the world’s largest rare earth element(abbreviated as REE)resource.The exploration of the theory of mineral formation of Bayan Obo is an important foundation for mineralogical research,and is the scientific basis for mining,industrial beneficiation,smelting and extraction,and processing and utilization.With the rapid development of science and technology,the demand for the utilization of rare earth elements is increasing,and the separation process between rare earth elements needs to be developed.The purpose of this paper is to provide high temperature experimental information for the formation and application of rare earth minerals.To this end,the mineral evolution of high-grade rare earth concentrates with increasing temperature and the migration of rare earths at different stages and their reaction mechanisms were studied.According to thermogravimetric analysis and differential scanning calorimetry(TG-DSC),calcination was carried out at different temperature ranges,and the calcined products were characterized by X-ray diffraction(XRD),Fourier transform infrared spectroscopy(FT-IR),scanning electron micro scope and energy dispers ive spectrometer(SEM-EDS)and other analytical techniques.The re sults are shown in this process,the ra re earth phase is first converted into rare earth oxide and rare earth oxyfluoride.As the temperature increases,Ca5(PO4)3 F and a large number of self-shaped spherical Ca-RE-OF and Ca-RE-PO4 particles are formed,and the separation of La and Ce elements is discovered.Acco rding to the phase diagram analysis,the production of Ca5(PO4)3 F is due to the reaction of monazite and fluorite,and the phases CeF2 and Ce F3 are formed during the reaction.When it reaches 1500℃,barium ferrite is produced and a new substance containing Ba2+is formed.

Effect of cerium addition on microstructure and mechanical properties of as-cast high grade knives steel

The carbides and mechanical properties of as-cast high grade knives steel with and without cerium(Ce)addition were studied.The as-cast microstructure of the steel,the size of carbide precipitation,carbide morphology,and mechanical properties were systematically studied through optical microscopy,scanning electron microscopy,and X-ray diffraction.Besides,through the Equilib module of the FactSage thermodynamics software,the changes in the precipitation type of the inclusions with Ce during the solidification of the steel were calculated.The results indicate that the rare earth Ce is added into the steel to refine the as-cast microstructure of the steel.The types of inclusions in the steel are changed by the addition of Ce.The precipitated carbide morphology changes from a complex rod shape to a relatively single lamellar shape.The rare earth inclusions formed in steel by a moderate addition of Ce can be severed as the core of heterogeneous nucleation of carbides,which reduce the size of carbide precipitation,promote the uniform distribution of carbide in the as-cast steel,and improve the mechanical properties of the as-cast high grade knives steel.

Effect of Finish Rolling Temperature on Microstructure and Mechanical Properties of High Grade Pipeline Steel

The correlation among finish rolling temperature (FRT),microstructure and mechanical property of the high grade pipeline steel was investigated in this study.The microstructure of the steels with different finish rolling temperatures was observed with scanning electronic microscope (SEM) and transmission electronic microscope (TEM).The martensite/austenite (M/A) islands distribution was fixed by colour metallography,and the mechanical properties of the steels were tested with quasi-static tensile testing machine.The result shows that the fraction of M/A island increased with the finish rolling temperature decreasing,and when the finish rolling temperature is 800℃,the mechanical properties are the best.

Safety and efficacy of Endovascular Management of high-grade blunt renal injury

Objectives:To provide data on the safety and efficacy of renal arterial embolization(RAE)in patients with highgrade blunt renal injury.Materials and methods:Fifteen patients with high-grade blunt renal injury(AAST grades IV-V)admitted to our hospital from July 2014 to December 2019 were retrospectively reviewed in this study.Their clinical success rate and complications were investigated accordingly.Results:Fifteen patients with high-grade blunt renal injury,13 men and 2 women with an average age of 41.6 years,including 11 hemodynamically unstable patients and 4 stable patients,were treated with RAE.Among these patients,73.3%(11 of 15)had grade IV,and 26.7%(4 of 15)had grade V injuries,while 53.3%(8 of 15)patients had concomitant injuries.One patient received main RAE and 14 patients received selective RAE.The clinical success rate after the first embolization was 93.3%(14 of 15).RAE was repeated and was successfully performed in one patient with sustained hematuria.No significant difference in creatinine levels was found before and after embolization.During the follow-up period of 2–82 months,two patients required tube drainage due to urine leaks,one patient developed renal failure requiring renal replacement therapy,and one patient developed secondary hypertension.Conclusions:RAE can provide a high success rate of hemostasis for both hemodynamically stable and unstable patients with high-grade blunt renal injury,and only minor complications are observed with this procedure.

Neuro-oncogenesis and the adult human sub-ventricular zone in high grade glioma

The last fifteen years have seen the application of the cancer stem cell hypothesis to tumors of the central nervous system,in particular to high grade glioma(HGG),the most aggressive and common brain cancer in adults.Seminal studies have shown that cancer stem cells(alternatively named tumor-initiating cells)are capable of self-renew and multipotency,similar to their normal counterpart.More importantly they give rise to tumors that closely mimic the phenotype and genotype of human HGG.The identification of neurogenic niches in adult rodent and human brain has further reinforced the hypothesis that HGG might derive from the malignant transformation occurring in these areas,especially in the sub-ventricular zone(SVZ),the largest and most well characterised stem cell niche.Following from evidence of animal model studies supporting this hypothesis,recently we investigated the role of the SVZ in neuro-oncogenesis using tissue material derived from HGG patients.We also described response to conventional chemo-therapies of cancer stem cells isolated from the SVZ and the tumor mass(T)of the same patients and reconstructed tumor evolution.In this review,such findings will be discussed in the context of the current literature on the biology of the SVZ in the normal and disease brain.

Missed diagnosis of early gastric cancer or high-grade intraepithelial neoplasia

AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.

Radiotherapy of high-grade gliomas: current standards and new concepts, innovations in imaging and radiotherapy, and new therapeutic approaches

The current standards in radiotherapy of high-grade gliomas(HGG) are based on anatomic imaging techniques, usually computed tomography(CT) scanning and magnetic resonance imaging(MRI). The guidelines vary depending on whether the HGG is a histological grade 3 anaplastic glioma(AG) or a grade 4 glioblastoma multiforme(GBM). For AG, T2-weighted MRI sequences plus the region of contrast enhancement in T1 are considered for the delineation of the gross tumor volume(GTV), and an isotropic expansion of 15 to 20 mm is recommended for the clinical target volume(CTV). For GBM, the Radiation Therapy Oncology Group favors a two-step technique, with an initial phase(CTV1) including any T2 hyperintensity area(edema) plus a 20 mm margin treated with up to 46 Gy in 23 fractions, followed by a reduction in CTV2 to the contrast enhancement region in T1 with an additional 25 mm margin. The European Organisation of Research and Treatment of Cancer recommends a single-phase technique with a unique GTV, which comprises the T1 contrast enhancement region plus a margin of 20 to 30 mm. A total dose of 60 Gy in 30 fractions is usually delivered for GBM, and a dose of 59.4 Gy in 33 fractions is typically given for AG. As more than 85% of HGGs recur in field, dose-escalation studies have shown that 70 to 75 Gy can be delivered in 6 weeks with relevant toxicities developing in < 10% of the patients. However, the only randomized dose-escalation trial, in which the boost dose was guided by conventional MRI, did not show any survival advantage of this treatment over the reference arm. HGGs are amongst the most infiltrative and heterogeneous tumors, and it was hypothesized that the most highly aggressive areas were missed; thus, better visualization of these high-risk regions for radiation boost could decrease the recurrence rate. Innovations in imaging and linear accelerators(LINAC) could help deliver the right doses of radiation to the right subvolumes according to the dose-painting concept. Advanced imaging techniques provide functional information on cellular density(diffusion MRI), angiogenesis(perfusion MRI), metabolic activity and cellular proliferation [positron emission tomography(PET) and magnetic resonance spectroscopy(MRS)]. All of these non-invasive techniques demonstrated good association between the images and histology, with up to 40% of HGGs functionally presenting a high activity within the non- contrast-enhanced areas in T1. New LINAC technologies, such as intensity-modulated and stereotactic radiotherapy, help to deliver a simultaneous integrated boost(SIB) > 60 Gy. Trials delivering a SIB into a biological GTV showed the feasibility of this treatment, but the final results, in terms of clinical benefits for HGG patients, are still pending. Many issues have been identified: the variety of MRI and PET machines(and amino-acid tracers), the heterogeneity of the protocols used for image acquisition and post-treatment, the geometric distortion and the unreliable algorithms for co-registration of brain anatomy with functional maps, and the semi-quiescent but highly invasive HGG cells. These issues could be solved by the homogenization of the protocols and software applications, the simultaneous acquisition of anatomic and functional images(PET-MRI machines), the combination of complementary imaging tools(perfusion and diffusion MRI), and the concomitant addition of some ad hoc targeted drugs against angiogenesis and invasiveness to chemoradiotherapy. The integration of these hybrid data will construct new synthetic metrics for fully individualized treatments.

Eocene high grade metamorphism and crustal anatexis in the North Himalaya Gneiss Domes,Southern Tibet

Determination of the timing and geochemical nature of early metamorphic and anatectic events in the Himalayan orogen may provide key insights into the physical and chemical behavior of lower crustal materials during the early stage of tectonic evolution in large-scale collisional belts.The Yardoi gneiss dome is the easternmost dome of the North Himalayan Gneiss Domes(NHGD),and contains three types of amphibolites with distinct mineral assemblage,elemental and radiogenic isotope geochemistry,as well as various types of gneisses.SHRIMP zircon U/Pb analyses on the garnet amphibolite and garnet-bearing biotite granitic gneiss yield ages of nearly peak metamorphism at 45.0±1.0 Ma and 47.6±1.8 Ma,respectively,which are 2 to 4 Ma older than the age for partial melting in migmatitic garnet amphibolite(43.5±1.3 Ma).Available data have demonstrated that ultra-high pressure metamorphism in the Tethyan Himalaya occurred at ～55 Ma,and high amphibolite facies to granulite facies metamorphism at 45 to 47 Ma.In addition,partial melting at thickened crustal conditions occurred at 43.5±1.3 Ma,which led to the formation of high Sr/Y ratios two-mica granites.The high-grade metamorphic rocks in the NHGD may represent the subducted front of the Indian continental lithosphere.In large collisional belts,fertile components in crustal materials could melt and form granitic melts with relatively high Na/K and Sr/Y ratios under thickened crustal conditions,significantly different from those formed by decompressional melting during rapid exhumation.

Photodynamic therapy for high-grade dysplasia of bile duct via a choledochoscope

When a distal common bile duct neoplasm is at the stage of carcinoma in situ or high-grade dysplasia,it is difficult for the surgeon to decide whether to perform pancreaticoduodenectomy.Here we describe a patient with a progressive dysplastic lesion in the common bile duct,which developed from moderate-high to highgrade dysplasia in approximately 2 mo.The patient refused major surgery.Therefore,endoscopic-assisted photodynamic therapy was performed.The result at follow-up using a trans-T-tube choledochoscope showed that the lesion was completely necrotic.This report is the first to describe the successful treatment of highgrade dysplasia of the distal bile duct using photodynamic therapy via a choledochoscope.

Endoscopic mucosal resection for high-grade dysplasia and intramucosal carcinoma in Barrett's esophagus: An Italian experience

AIM: To evaluate endoscopic mucosal resection (EMR)in patients with high-grade dysplasia (HGD) and/or intramucosal cancer (IMC) in Barrett's esophagus (BE).METHODS: Between June 2000 and December 2003,39 consecutive patients with HGD (35) and/or IMC (4)underwent EMR. BE ＞30 mm was present in 27 patients.In three patients with short segment BE (25.0%), HGDwas detected in a normal appearing BE. Lesions had a mean diameter of 14.8±10.3 mm. Mucosal resection was carried out using the cap method.RESULTS: The average size of resections was 19.7±9.4×14.6±8.2 mm. Histopathologic assessment postresection revealed 5 low-grade dysplasia (LGD) (12.8%),27 HGD (69.2%), 2 IMC (5.1%), and 5 SMC (-12.8%).EMR changed the pre-treatment diagnosis in 10 patients (25.6%). Three patients with SMC underwehtsurgery.Histology of the surgical specimen revealed 1 T0N0 and 2 T1N0 lesions. The remaining two patients were cancer free at 32.5 and 45.6 mo, respectively. A metachronous lesion was detected after 25 mo in one patient with HGD. Intra-procedural bleeding, controlled at endoscopy,occurred in four patients (10.3%). After a median followup of 34.9 mo, all patients remained in remission.CONCLUSION: In the medium term, EMR is effective and safe to treat HGD and/or IMC within BE and is a valuable staging method. It could become an alternative to surgery.

High-grade gliomas: reality and hopes

In this issue of the Chinese Journal of Cancer, European experts review current standards, trends, and future prospects in the difficult domain of high-grade glioma. In all fields covered by the different authors, the progress has been impressive. For example, discoveries at the molecular level have already impacted imaging, surgery, radiotherapy, and systemic therapies, and they are expected to play an increasing role in the management of these cancers. The European Organization for Research and Treatment of Cancer(EORTC) has pioneered new treatment strategies and contributed to new standards. The articles in this issue will cover basic molecular biological principles applicable today, novel surgical approaches, innovations in radiotherapy planning and delivery, evidence-based standards for radiotherapy alone or combined with chemotherapy, current standards and novel approaches for systemic treatments, and the important but often neglected field of health-related quality of life. Despite the advances described in these articles, the overall prognosis of high-grade glioma, especially glioblastoma, remains poor, and more research is needed to address this problem.