Giant cavernous hemangioma of the liver with satellite nodules:Aspects on tumour/tissue interface:A case report

BACKGROUND Giant hepatic cavernous hemangioma with multiple satellite nodules is a rare subtype of hepatic cavernous hemangioma,the most common vascular liver tumor.We report on a tumor with unusual histologic features:(1)Finger-like infiltration pattern;(2)lack of encapsulation;(3)blurred tumor/liver interface;and(4)massive satellitosis-referring to the article“Hepatic cavernous hemangioma:underrecognized associated histologic features”.CASE SUMMARY A 60-year-old man presented with increasing uncharacteristic abdominal discomfort and mildly elevated blood parameters of acute inflammation.Imaging revealed an unclear,giant liver tumor of the left liver lobe.A massive vascular tumor with extensive satellitosis broadly infiltrating the adjacent liver parenchyma was resected via hemihepatectomy of segmentsⅡ/Ⅲ.Histopathological diagnosis was giant hepatic cavernous hemangioma with multiple satellite nodules,featuring unusual characteristics hardly portrayed in the literature.Retrospectively,this particular morphology can explain the difficult pre-and perioperative diagnosis of a vascular liver tumor that is usually readily identifiable by modern imaging methods.CONCLUSION This case emphasizes the exact histological workup of tumor and tumor-induced parenchyma changes in radiologically unclassifiable liver tumors.

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases

AIM:To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD).METHODS:DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n=263) and AFLD (n=100) were analyzed by Real-time polymerase chain reaction using allele-specific probes.RESULTS:In the NAFLD and the AFLD collective,3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele,differing from only 1.5% cases in the healthy population.In NAFLD patients,a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease.However,we observed a significantly higher risk (odds ratio=2.50,CI:1.05-5.90,P=0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory alterations.The linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of NAFLD.CONCLUSION:In AFLD patients,the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis.

In vivo imaging of endogenous neural stem cells in the adult brain

The discovery of endogenous neural stem cells(e NSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those e NSCs can be mobilized in vivo, enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor e NSC activation in a longitudinal and intraindividual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor e NSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography(PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3'-deoxy-3'-[18F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of e NSCs, and will help to facilitate a translation into the clinical setting.

Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-Hodgkin's lymphoma infi ltration

To investigate the simultaneous occurrence of hepatocellular carcinoma and non-Hodgkin's lymphoma, we report the case of a 70 year old patient with a primary diagnosis of non-Hodgkin's lymphoma in 2002. In a routine follow up investigation of his chronic lymphocytic leukemia a newly detected mass in the Couinaud's segments 2 and 3 was found. No hepatitis C virus or hepatitis B virus infection or cirrhosis was evident. After laparoscopic segmentectomy the histological examination revealed a hepatocellular carcinoma. While the relation between liver parenchyma damages and hepatocellular carcinoma or non-Hodgkin's lymphoma is well known, only a few publications have focused on the coexistence of hepatocellular carcinoma and non-Hodgkin's lymphoma. With this case we demonstrate the coexistence of these diseases without having a pre- damaged liver parenchyma.

Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations:A case report and review of the literature

Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.

Cost-analysis of inpatient and outpatient parenteral antimicrobial therapy in orthopaedics: A systematic literature review

BACKGROUND Increasing numbers of total joint arthroplasties and consecutive revision surgery are associated with the risk of periprosthetic joint infections (PPJI). Treatment of PPJI is complex and associated with immense socio-economic burden. One treatment aspect is parenteral antiinfective therapy, which usually requires an inpatient setting [Inpatient parenteral antibiotic therapy (IPAT)]. An alternative is outpatient parenteral treatment [Outpatient parenteral antibiotic therapy (OPAT)]. To conduct a health economic cost-benefit analysis of OPAT, a detailed cost analysis of IPAT and OPAT is required. So far, there is a lack of knowledge on the health economic effects of IPAT and OPAT for PPJI. AIM To review an economic comparison of IPAT and OPAT. METHODS A systematic literature review was performed through Medline following the PRISMA guidelines. RESULTS Of 619 identified studies, 174 included information of interest and 21 studies were included for quantitative analysis of OPAT and IPAT costs. Except for one study, all showed relevant cost savings for OPAT compared to IPAT. Costs for IPAT were between 1.10 to 17.34 times higher than those for OPAT. CONCLUSION There are only few reports on OPAT for PPJI. Detailed analyses to support economic or clinical guidelines are therefore limited. There is good clinical evidence supporting economic benefits of OPAT, but more high quality studies are needed for PPJI.

The association between critical life events, sociodemographic data and physical activity in the development of myocardial infarction in smokers and ex-smokers

Background: Psychosocial factors attract interest in investigating the occurrence of cardiovascular disease. Design This study aimed to examine the impact of critical life events on the development of myocardial infarction in smokers and ex-smokers. We hypothesized that critical life events increase the risk of the disease. Methods: Data were taken from the Cologne Smoking Study (CoSmoS), a retrospective multicentre case-control study that examines which psychosocial factors may lead to a higher risk for smokers and ex-smokers of suffering from a myocardial infarction. Our sample consisted of n = 278 myocardial infarction participants and control participants. Both groups had a history of smoking. Logistic regression was used in the analysis. Results: The study results of the smoking and ex-smoking participants showed that sociodemographic data like gender and age have an effect on the development of myocardial infarction. Physical activity seems to offer protection aganist myocardial infarction. Final, the unexpected result that the experience of at least one critical life event seems to have a positive effect on health and so lowers the risk of myocardial infarction. Conclusions: Socio-demographic data and physical activity have an effect on the development of myocardial infarction. Participants with experience of critical life events appear to be strengthened after the events and possess adequate resources to protect their health.

The Treatment of Peripheral Vestibular Dysfunction Using Caloric Vestibular Stimulation in Patients with Cerebral Hypertensive Crisis

Background: To verify the efficacy of caloric vestibular stimulation in patients with peripheral vestibular dysfunction after cerebral hypertensive crisis. Methods: Enrolled in the study were 60 patients with peripheral vestibular dysfunction caused by a cerebral hypertensive crisis, docu-mented by vestibulometry. Thirty patients underwent standard treatment plus caloric vestibular stimulation, and 30 control group patients received standard treatment alone. Results: After the two-week treatment course, the sensation of vertigo was observed in 40.0% ± 8.9% of treatment group patients compared with 80.0% ± 7.3% of control group patients (t = 3.46;p < 0.001). Spontaneous vestibular somatic reactions were found in 46.7% ± 9.1% of the study treatment group in contrast to 86.7% ± 6.2% of the control group (t = 3.63;p < 0.001). Spontaneous nystagmus was seen in 40.0% ± 8.9% of treatment group patients compared with 93.3% ± 4.6% of control subjects (t = 5.31;p < 0.001). Spontaneous vestibular vegetative reactions were observed in 33.3% ± 8.6% of patients receiving study treatment in contrast to 93.3% ± 4.6% of control group patients (t = 6.16;p < 0.001). Also, 53.3% ± 9.1% of study treatment group patients showed asymmetry of labyrinths compared with 86.7% ± 6.2% of patients from the control group (t = 3.03;p < 0.001). Conclusion: Caloric vestibular stimulation was shown to be an effective treatment for peripheral vestibular dysfunction in patients with cerebral hypertensive crisis. During the 14-day treatment of cerebral hypertensive crisis, complete labyrinthine function recovery occurred in 46.7% of treatment group patients who underwent caloric vestibular stimulation as opposed to 13.3% of control group patients who received standard treatment alone.

肝细胞在HBx刺激和低氧压力时表达IL-2（英文）

肝细胞肝癌有极端坏的预后,主要归因于它的高转移性复发.我们曾经报道过对于乙型肝炎相关性肝癌患者,癌周组织的白介素2(IL-2)水平越高就倾向于有更低的肝内转移复发率,而且IL-2的免疫组化显示主要着色于癌周的肝细胞.然而,是否肝细胞能在体外表达IL-2以及其内在机制仍未被揭示.本研究里,比较了有和没有肝炎病史的肝癌患者的癌周组织IL-2表达水平,然后在永生化的成人肝细胞THLE-2里过表达了乙型肝炎病毒x蛋白(HBx),并用过氧化氢处理模拟氧压力微环境.实验证实肝细胞在HBx刺激和低氧压力同时存在下能通过MAP3K7/NF-κB通路表达IL-2.研究结果提示靶向调节微环境氧化压力为预防和治疗乙肝相关性肝癌的转移复发提供了新的方向.

Regional lymphadenectomy strongly recommended in T1b gallbladder cancer

This article discusses the adequate treatment of early gallbladder cancer （Tla, Tlb） and is based on published studies extending over nearly 3 decades. Ran- domized studies and meta analyses comparing different surgical treatments do not exist. The literature shows that in up to 20% of patients lymph node metastasis are found in Tlb gallbladder cancer. Due to high malignancy with early angiolymphatic spread and resistance to chemotherapy and radiation on the one hand, and the relative low operative risk of extended cholecystectomy （cholecystectomy and regional lymphadenectomy） on the other hand, we believe that this procedure is mandatory in early gallbladder cancer.

Central corneal epithelium self-healing after ring-shaped glycerin-cryopreserved lamellar keratoplasty in Terrien marginal degeneration

Dear Sir, I am Dr Yan-Long Bi, from the Department of Ophthalmology, Tongji University Affiliated to Tongji University School of Medicine, Shanghai, China. I write to present a case report of total limbal stem cells deficiency after treatment with ring-shaped lamellar keratoplasty secondary to Terrien marginal degeneration. During 3 years

Neoadjuvant chemoradiotherapy for esophageal cancer:Impact on extracapsular lymph node involvement

AIM:To assess the effects of neoadjuvant chemoradiotherapy(CRT) on the presence of extracapsular lymph node involvement(LNI) and its prognostic value in patients with resected esophageal cancer.METHODS:Two hundred and ninety-eight patients with advanced esophageal cancer underwent esophagectomy between 1997 and 2006.One hundred and ninety patients(63.8%) were treated with neoadjuvant CRT prior to resection.A total of 986 metastatic LNs were examined.Survival of the patients was analyzed according to intra-and extra-capsular LNI.RESULTS:Five-year survival rate was 22.5% for the entire patient population.Patients with extracapsular LNI had a 5-year survival rate of 16.7%,which was comparable to the 15.8% in patients with infiltrated nodes of the celiac trunk(pM1lymph).In contrast to patients treated with surgery alone,neoadjuvant therapy resulted in signif icantly(P = 0.001) more patients with pN0/M0(51.6% vs 25.0%).In 17.6% of the patients with surgery alone vs 16.8% with neoadjuvant CRT,extracapsular LNI was detected.Neoadjuvant therapy does not reduce the occurrence of extracapsular LNI.CONCLUSION:Extracapsular LNI is an independent negative prognostic factor not influenced by neoadjuvant CRT.In a revised staging system for esophageal cancer,extracapsular LNI should be considered.

Mixed hepatocellular-cholangiocarcinoma may derive from "hepatogones"

The Editor welcomes submissions for possible publication in the Letters to the Editor section that consist of commentary on an article published in the Journal or other relevant issues. Letters commenting on an article published in the Journal will be considered if they are received within 6 weeks of the time the article was published. Authors of the article being commented on will be given an

Neoadjuvant chemoradiation changes podoplanin expression in esophageal cancer patients

BACKGROUND Locally advanced adenocarcinoma of the esophagus(EAC) and squamous cell carcinoma(ESCC) result in a worse prognosis. Neoadjuvant treatment improves survival, however, only for responders. The transmembrane glycoprotein podoplanin is overexpressed in squamous cell carcinomas, mi RNA-363 is associated to its regulation in head and neck cancer.AIM To predict therapy response and prognosis markers, and targets for novel therapies would individualize treatments leading to more favourable outcomes.METHODS Expression of podoplanin protein has been visualized by immunohistochemistry in surgical specimens of 195 esophageal cancer patients who underwent transthoracic esophagectomy: 90 ESCC and 105 EAC with clinical T2-3, Nx, M0.One hundred and six patients received neoadjuvant chemoradiation. RNA was extracted from paraffin-embedded tissue, and mi RNA-363 quantified by realtime Taq Man-real-time-PCR. D2-40 mab staining of > 5% was scored as high podoplanin expression(HPE). We related podoplanin and mi RNA-363 expression to histopathologic response after neoadjuvant treatment and clinicopathological characteristics, such as histological tumor type, survival rate or clinical tumor category.RESULTSWe confirmed expression of membrane-bound podoplanin in 90 ESCC patients.26% showed HPE of > 5%. In addition, absence in EAC patients(only 2% with HPE) was shown. Lower podoplanin expression has been detected in resectionspecimen of 58 ESCC patients after neoadjuvant(RTx/CTx) treatment, only 11% with HPE, compared to 50% HPE of 32 non-pretreated primary surgery patients,P = 0.0001. This difference of podoplanin expression was confirmed comparing pre-treatment biopsies with matching post-treatment surgical specimens, P <0.001. Podoplanin has been identified as a prognostic marker in 32 patients that underwent primary surgery without neoadjuvant treatment. Low(0-5%)podoplanin expression was associated with better prognosis compared to patients with HPE, P = 0.013. Podoplanin expression has been associated with post-transcriptional regulation by mi RNA-363. At a cut-off value of miR-363 < 7,lower mi R-363 expression correlated with HPE in surgical tissue specimens of primary surgery patients, P = 0.013. Therefore, ESCC patients with mi RNA-363 expression < 7 had a worse prognosis than patients expressing mi RNA-363 ≥ 7, P= 0.049.CONCLUSION Analysis of the molecular process that leads to decrease in podoplanin expression during neoadjuvant treatment and its regulation may provide novel markers and targets to improve targeted therapy of ESCC.

Recurrent interface abscess secondary to Acanthamoeba keratitis treated by deep anterior lamellar keratoplasty

Dear Sir,I am Dr. Yan-Long Bi, from the Department of Ophthalmology of the Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China. I write to present a case report of recurrent amoebic corneal abscess

Coronary surgery following prior pneumonectomy —A challenging clinical scenario with excellent results

Coronary artery bypass grafting (CABG) in patients with prior pneumonectomy is challenging because of the decreased pulmonary function and the anatomical alterations of the thoracic cavity. Due to extended morbidity and mortality in this special patient cohort, only very few reports in the world literature focus on this topic. Overall, no general recommendations exist with regard to the optimal management of this continuously growing patient cohort. We present our experience with another successful case.

Pterygium:new insights into risk factors?

Introduction The word pterygium comes from two Greek words:(pteryx)meaning wing and(pterygion)fin(1-3).Pterygium,one of the most common benign tumors of the ocular surface,is a focal fibrovascular proliferation of conjunctival tissue onto the cornea(1-6).The pterygium is usually triangular in shape and localized in the nasal palpebral fissure(1-6).Histopathologically,there is usually a nonkeratinizing epithelium and loss of goblet cells(4).Some cases show also the development of a multilayered keratinizing squamous epithelium.Subepithelial features include thickened collagen fibers,numerous vascular incisions,and pathognomonic elastoid degeneration.Sometimes,chronic inflammation,such as lymphocytic infiltration,can also be seen(2-6).Furthermore,the head of the pterygium,which is firmly fused to the cornea,can also grow into the upper corneal layers and fragment Bowman’s lamella(1-4).

每天少量摄入可可对血压和生物活性NO的作用:一项随机对照试验

背景:观察性研究显示规律性摄入含有可可的食物与心血管性死亡率的降低相关。至多2周的短期干预显示,由于可可多酚的作用,大剂量的可可能够改善内皮功能并且降低血压,但是每天少量摄入可可对血压的临床作用以及潜在降压机制尚不清楚。目的:确定少量摄入富含多酚的黑巧克力对血压的影响。

The Endocannabinoid,Anandamide,Induces Cannabinoid Receptor-Independent Cell Death in Renal Proximal Tubule Cells

Background: The endocannabinoid (EC) system is well characterized in the central nervous system but scarcely studied in peripheral organs. In this paper, we newly identify the effect of the EC anandamide (AEA) upon renal proximal tubule cells. Methods: Measurement of lactate dehydrogenase (LDH) release after treatment of primary renal proximal tubule cells (RPTEC) and renal carcinoma cell line (Caki-1) with AEA, arachidonic acid (AA), ethanolamide (EtAm), EC receptor CB1 antagonist (AM251), CB2 receptor antagonist (SR144528), TRPV1 receptor antagonist (capsazepine), degradation enzyme fatty acid amide hydrolase (FAAH) antagonist (URB597), antioxidants GSH-EE;Trolox, GSH depletor BSO, membrane cholesterol depletor (MCD), apoptosis inhibitor zVAD, necroptosis inhibitor Nec-1 or ferroptosis inhibitor Fer-1. Western blot and qRT-PCR analysis plus determination of reactive oxygen species (ROS) via H2-DCFDA were performed. Histology for EC enzymes, N-acetylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) and FAAH, as well as the determination of physiological levels of ECs in human and rat renal tissue via liquid chromatography were conducted. Results: AEA both dose- and time-dependently induces cell death in RPTEC and Caki-1 within hours, characterized by cell blebbing, not influenced by blocking the described EC receptors by AM251, SR144528, capsazepine or FAAH by URB597 or MCD. Cell death is mediated via ROS. There is no difference found in the histology of the enzymes FAAH and NAPE-PLD in human renal tissue with interstitial nephritis. Blocking of apoptotic, necroptotic or ferroptotic cell death does not lead to a reduction in LDH release in vitro. Conclusion: The endocannabinoid anandamide induces cell death in renal proximal tubule cell in a time- and dose-dependent manner. This pathway is mediated via ROS and is independent of cannabinoid receptors, membrane cholesterol or FAAH activity.

Insulin-like growth factor 1-induced enolase 2 deacetylation by HDAC3 promotes metastasis of pancreatic cancer

Enolase 2(ENO2)is a key glycolytic enzyme in the metabolic process of glycolysis,but its potential function in pancreatic ductal adenocarcinoma(PDAC)is unclear.In this study,we observed a significant overexpression of ENO2 in PDAC tissues,and its expression was correlated with metastasis and poor prognosis in PDAC patients.K394 was identified as a major acetylation site in ENO2 that regulates its enzymatic activity,cell metabolism and PDAC progression.Knockdown of ENO2 suppressed tumor growth and liver metastasis in PDAC.Re-expression of wild-type(WT)ENO2,but not the K394 acetylation mimetic mutant,could reverse the decreased tumor malignancy.We further characterized histone deacetylase 3(HDAC3)and P300/CBP-associated factor(PCAF)as the potential deacetylase and acetyltransferase for ENO2,respectively.HDAC3-mediated deacetylation was shown to lead to ENO2 activation and enhancement of glycolysis.Importantly,insulin-like growth factor-1(IGF-1)was found to decrease K394 acetylation and stimulate ENO2 activity in a dose-and time-dependent manner.The PI3K/AKT/mTOR pathway facilitated the phosphorylation of HDAC3 on S424,which promoted K394 deacetylation and activation of ENO2.Linsitinib,an oral small-molecule inhibitor of IGF-1R,could inhibit IGF-1-induced ENO2 deacetylation by HDAC3 and the PI3K/AKT/mTOR pathway.Furthermore,linsitinib showed a different effect on the growth and metastasis of PDAC depending on the overexpression of WT versus K394-mutant ENO2.Our results reveal a novel mechanism by which acetylation negatively regulates ENO2 activity in the metastasis of PDAC by modulating glycolysis.Blockade of IGF-1-induced ENO2 deacetylation represents a promising strategy to prevent the development of PDAC.