BACKGROUND Liver metastases are very common in pancreatic neuroendocrine tumors(pNETs).When surgical resection is possible,it is typically associated with survival benefits in patients with pNET and liver metastases.P...BACKGROUND Liver metastases are very common in pancreatic neuroendocrine tumors(pNETs).When surgical resection is possible,it is typically associated with survival benefits in patients with pNET and liver metastases.Patient-derived organoids are a powerful preclinical platform that show great potential for predicting treatment response,and they have been increasingly applied in precision medicine and cancer research.CASE SUMMARY A 51-year-old man was admitted to the hospital with the chief complaint of in-termittent dull pain in the upper abdomen for over 3 years.Computerized to-mography showed multiple space-occupying lesions in the liver and a neoplasm in the pancreatic body.Pathological results suggested a grade 3 pancreas-derived hepatic neuroendocrine tumor.In combination with relevant examinations,the patient was diagnosed with pNET with liver metastases(grade 3).Transarterial chemoembolization was initially performed with oxaliplatin and 5-fluorouracil,after which the chemotherapy regimen was switched to liposomal irinotecan and cisplatin for a subsequent perfusion,guided by organoid-based drug sensitivity testing.Following interventional treatment,the tumor had decreased in size.However,due to poor treatment compliance and the patient’s preference for sur-INTRODUCTION Pancreatic neuroendocrine tumors(pNETs)are a rare and heterogeneous group of neoplasms arising from pancreatic islet cells,with variations in histology,clinical characteristics,and prognosis[1].They may present as non-infiltrative,slow-growing tumors,locally invasive tumors,or even rapidly metastasizing tumors[2].Most metastases localize to the liver,and approximately 28%-77%of patients with pNETs will experience liver metastases in their lifetime[3].Patients with liver metastases may be subjected to local complications such as biliary obstruction,liver insufficiency,and carcinoid syndrome.Additionally,liver metastases are a major risk factor for the prognosis of patients with pNETs[4].When feasible,surgical resection is significantly associated with the best long-term survival outcomes[5].Therefore,for patients with pNET liver metastases,comprehensive assessment and multidisciplinary approaches are required to determine the feasibility of surgical resection and the optimal treatment to improve the prognosis.Over the past decade,the advent of in vitro three-dimensional technologies including organoids has revolutionized the development of human cancer models.Patient-derived organoids(PDOs),an in vitro three-dimensional microstructure,can faithfully recapitulate the intricate spatial architecture and cell heterogeneity of the tissue,and simulate the biological behaviors and functions of parental tumors while preserving biological,genetic and molecular features[6,7].As a po-werful preclinical platform,PDOs have been increasingly applied in precision medicine and cancer research.Importantly,there is a significant association between the use of PDO-based drug sensitivity testing and clinical responses to chemotherapy,radiotherapy and targeted therapy in multiple cancer types[8-10].Although gastroenteropancreatic neuroendocrine neoplasm organoids have been confirmed to retain the pathohistological and functional phenotypes of parental tumors[7],their roles in the prediction of clinical outcomes have not been presented.Here,we report a case of pNET with liver metastases who successfully received surgical resection after personalized treatment guided by PDO-based drug sensitivity testing,resulting in a favorable prognosis.展开更多
Retainer-based medicine is growing increasingly in the United States and in some jurisdictions constitutes at least 10%of medical care services.It is to be distinguished from primary care medicine in that it involves ...Retainer-based medicine is growing increasingly in the United States and in some jurisdictions constitutes at least 10%of medical care services.It is to be distinguished from primary care medicine in that it involves the regular payment of a retainer fee that allows the patient privileged and expedited access to providers and is associated with a decreased patient burden for the primary care providers who participate in such an arrangement.Purpose:To assess the current ethical issues associated with retainer-based care.A literature review over the 22-year interval since the concept was first identified assessing in particular the extent to which distributive ethics are impacted by retainer-based care.Estimates on the ultimate impact of the availability and distribution of primary care are also considered based on available demographic data.The impact of retainer-based care on distributive ethics are analyzed by relationship to utilitarianism,egalitarianism,libertarianism,and communitarianism.Retainer-based care while ubiquitous and in some fashion longstanding,is occurring increasing especially in the USA and annually its prevalence there is increasing to about 10%of all primary care.This has a major impact on the overall availability of access to primary care physicians.The ethical issues attendant with this do not affect autonomy or malfeasance so much as they do impact distributive ethics.The increases in retainer-based care in the US has spurred ethical studies.Retainer-based care does not affect libertarianism but has a profound impact on the other three aspects of distributive ethics:The exact demographic impact on primary care is difficult to estimate but If retainer-based medicine continues to grow in frequency,it will result in the continued shortage of care for communities with impaired access to primary care physicians,in particular those with indigent individuals.Additional ethical studies are needed to assess the impact of retainer-based medicine on society.展开更多
AIM:To investigate the predictors of proximal kidney tubular dysfunction(PKTD)induced by adefovir dipivoxil(ADV)treatment for chronic hepatitis B.METHODS:Seventy-nine patients(age at the evaluation of PKTD:56.9±1...AIM:To investigate the predictors of proximal kidney tubular dysfunction(PKTD)induced by adefovir dipivoxil(ADV)treatment for chronic hepatitis B.METHODS:Seventy-nine patients(age at the evaluation of PKTD:56.9±10.7 years)with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively recruited.PKTD was defined by the presence of at least two of the following five abnormalities:phosphate diabetes,nondiabetic glucosuria,metabolic acidosis,β2-microglobulinuria,or renal hypouricemia.The single-nucleotide polymorphisms(SNPs)in the SLC22A6 gene encoding human organic anion transporter 1(h OAT1)and ABCC2 encoding multidrug resistance protein 2(MRP2)were analyzed using the Taq Man Allelic Discrimination Demonstration Kit.RESULTS:Nine(30.0%)of the 30 ADV-treated patients were diagnosed with PKTD,while no patients without ADV developed PKTD(P<0.001).Three patients with ADV were diagnosed with symptomatic osteomalacia.Among the patients who took ADV,those with PKTD were of higher age at initiation,had significantly longer treatment duration,and had a significantly lower body mass index than those without PKTD.The incidence of PKTD dramatically increased after 96 mo from the start of ADV administration.In contrast,the SNPs were not correlated with PKTD.Logistic regression analysis extracted older age at initiation(OR=5.0,95%CI:1.1-23.4;P=0.040)and longer treatment duration(OR=3.2,95%CI:1.2-8.6;P=0.020)as significant factors associated with PKTD.CONCLUSION:Our results suggest that the tubular function of the kidney of older patients undergoing longterm ADV treatment should be carefully evaluated.展开更多
Objective:To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.Methods:A total of 60 newborn SD rats were equally randomized into normal saline(NS) group,LPS control group,bilirubin con...Objective:To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.Methods:A total of 60 newborn SD rats were equally randomized into normal saline(NS) group,LPS control group,bilirubin control group,low-dose group and high-dose group.After anesthesia,0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups;1 h later,the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups.After 5 or 24 hours of model establishment,spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method.After 24 hours of model establishment,scrum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry.Results:In contrast to low-dose bilirubin,high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS.After 5 hours of model establishment,compared with NS group.MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced(P<0.05).In high-dose group,inflammotory factors levels and CD8^+T cells percentage were all higher than LPS control and NS group(P<0.05),while CD4^+ T cells percentage was lower than NS group(P<0.05).Conclusions:High-concentration plasma bilirubin in coordination with LPS could inhibit NF- κB signal pathways activation and aggravate inflammatory reaction,thus caused immunosuppression with inflammation cascade,which resulted in the immune dysfunction.展开更多
OBJECTIVE: To evaluate the reporting quality of randomized controlled trials(RCT) that compared Bo's abdominal acupuncture with conventional body acupuncture, and compare the efficacy and safetybetweenthembyperfor...OBJECTIVE: To evaluate the reporting quality of randomized controlled trials(RCT) that compared Bo's abdominal acupuncture with conventional body acupuncture, and compare the efficacy and safetybetweenthembyperforminga Meta-analysis.METHODS: All RCTs comparing Bo's abdominalacupuncture with conventional body acupuncture were included. English and Chinese databases were searched from their respective inceptions to March 2014. The reporting quality was assessed according to the "Consolidated Standards of Reporting Trials"(CONSORT) checklist for parallel RCTs and the revised "Standards for Reporting Interventions in Clinical Trials of Acupuncture"(STRICTA). A Meta-analysis was conducted to synthesize the effect sizes,and publication bias was evaluated by the Egger linear regression test using Stata.RESULTS: Ninety-seven studies were included, of which most lacked adequate reporting information, and 80.4% showed that the efficacy of abdominal acupuncture is superior to conventional body acupuncture, especially for the following diseases:lumbar disc herniation, cervical spondylosis, omarthritis and cervical vertigo, except simple obesity.Effect-sizes were controversial when evaluating different outcomes.CONCLUSION: The international standard CONSORT statement and STRICTA guidelines should be strictly applied when reporting acupuncture RCTs in the future. Abdominal acupuncture appears to be more effective compared with conventional body acupuncture for some diseases. However, further high quality blind RCTs using validated outcomeindexesandstandardreportingarewarranted.展开更多
AIM： To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate （YMDD） mutants （reverse transcription; rtM204I/V） and deterioration of liver function during long-term lamivudine...AIM： To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate （YMDD） mutants （reverse transcription; rtM204I/V） and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus （HBV） infection. METHODS： The data of 61 consecutive Japanese pa- tients with chronic hepatitis B who underwent continu- ous lamivudine treatment for more than 24 mo and had a virological response were analyzed. Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo （mean, 50.8 too; range, 24-90 too）.RESULTS： A mixed mutant-type （YMDD ＋ tyrosine-iso- leucine-asparatate-asparatate： YIDD or tyrosine-valineasparatate-asparatate： YVDD） or a mutant-type （YIDD or YVDD） were found in 57.4% of 61 patients at i year, 78.7% of 61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at 4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and 33.3% of 6 patients at 7 years. Of the 61 patients, 56 （92%） had mixed mutant- or a mutant-type. Only 5 （8%） had no mutants at each observation point. Vi- rological breakthrough was found in 26 （46.4%） of 56 patients with YMDD mutants, 20 of whom had a hepa- titis flare-up： the remaining 30 （53.6%） had neither a virological breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment. CONCLUSION： Our results suggest that it is possible to continue lamivudine treatment, even after the emergence of YMDD mutants, up to the time that the patients develop a hepatitis flare-up.展开更多
A 19-year-old female was diagnosed with ulcerative colitis when she presented with persistent melena, and has been treated with 5-aminosalicylic acid for 4 years, with additional azathioprine for 2 years at our hospit...A 19-year-old female was diagnosed with ulcerative colitis when she presented with persistent melena, and has been treated with 5-aminosalicylic acid for 4 years, with additional azathioprine for 2 years at our hospital. The patient experienced high-grade fevers, chills, and cough fve d prior to presenting to the outpatient unit. At frst, the patient was suspected to have developed neutropenic fever; however, she was diagnosed with Epstein-Barr virus-associated hemophagocytic syndr-ome （EB-VAHS） upon fulfilling the diagnostic criteria after bone marrow aspiration. When patients withinflammatory bowel disease treated with immunomo-dulators, such as thiopurine preparations, develop fever, EB-VAHS should be considered in the differential diagnosis.展开更多
AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.METHODS:The human genomic DNA of all pati...AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.METHODS:The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P=0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P=0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P=0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P=0.044). Multivariate analysis identified only the percentage of RBV dose as a predictor for Hb decline. Platelet decline was significantly higher in non-CC patients than CC patients at weeks 12, 24 and 48 (P=0.018, 0.009 and 0.026, respectively). CONCLUSION: Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment-induced anemia and the need for RBV dose reduction in Egyptian HCV patients.展开更多
AIM: To study the chemical constituents of stems of Gymnema sylvestre(Retz.) Schult. METHODS: Chromatographic techniques using silica gel, C18 reversed phase silica gel, and prep-HPLC were used. The structures were el...AIM: To study the chemical constituents of stems of Gymnema sylvestre(Retz.) Schult. METHODS: Chromatographic techniques using silica gel, C18 reversed phase silica gel, and prep-HPLC were used. The structures were elucidated on the basis of MS and spectroscopic analysis(1D and 2D NMR), as well as chemical methods. RESULTS: Seven compounds were isolated and their structures were elucidated as conduritol A(1), stigmasterol(2), lupeol(3), stigmasterol-3-O-β-D-glucoside(4), the sodium salt of 22α-hydroxy-longispinogenin-3-O-β-D-glucopyranosyl-(1→3)-β-D-glucurono-pyranosyl-28-O-α-L-rhamnopyranoside(5), oleanolic acid-3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside(6), and the sodium salt of 22α-hydroxy-longispinogenin 3-O-β-D-glucuronopyranosyl-28-O-α-L-rhamnopyranoside(7). The inhibition activities of compounds 1, 5-7 on non-enzymatic glycation of protein in vitro were evaluated. CONCLUSION: Compound 7 is a new triterpenoid saponin. It was shown that compounds 1, 5-7 have weak inhibition activities for non-enzymatic glycation of protein in vitro.展开更多
To evaluate the psychometric properties of a newly developed questionnaire,known as the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test(GERD-TEST),in patients with GERD.METHODSJapanese...To evaluate the psychometric properties of a newly developed questionnaire,known as the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test(GERD-TEST),in patients with GERD.METHODSJapanese patients with predominant GERD symptoms recruited according to the Montreal definition were treated for 4 wk using a standard dose of proton pump inhibitor(PPI).The GERD-TEST and the Medical Outcome Study Short Form-8 Health Survey(SF-8)were administered at baseline and after 4 wk of treatment.The GERD-TEST contains three domains:the severity of GERD and functional dyspepsia(FD)symptoms(5 items),the level of dissatisfaction with daily life(DS)(4 items),and the therapeutic efficacy as assessed by the patients and medication compliance(4 items).RESULTSA total of 290 patients were eligible at baseline;198 of these patients completed 4 wk of PPI therapy.The internal consistency reliability as evaluated using the Cronbach’sαvalues for the GERD,FD and DS subscales ranged from 0.75 to 0.82.The scores for the GERD,FD and DS items/subscales were significantly correlated with the physical and mental component summary scores of the SF-8.After 4 wk of PPI treatment,the scores for the GERD items/subscales were greatly reduced,ranging in value from 1.51 to 1.87 and with a large effect size(P<0.0001,Cohen’s d;1.29-1.63).Statistically significant differences in the changes in the scores for the GERD items/subscales were observed between treatment responders and non-responders(P<0.0001).CONCLUSIONThe GERD-TEST has a good reliability,a good convergent and concurrent validity,and is responsive to the effects of treatment.The GERD-TEST is a simple,easy to understand,and multifaceted PRO instrument applicable to both clinical trials and the primary care of GERD patients.展开更多
The management of jaundice and cholangitis is important for improving the prognosis and quality of life of patients with unresectable malignant hilar biliary strictures(UMHBS). In addition, effective chemotherapy, suc...The management of jaundice and cholangitis is important for improving the prognosis and quality of life of patients with unresectable malignant hilar biliary strictures(UMHBS). In addition, effective chemotherapy, such as a combination of gemcitabine and cisplatin, requires the successful control of jaundice and cholangitis. However, endoscopic drainage for UMHBS is technical demanding, and continuing controversies exist in the selection of the most appropriate devices and techniques for stent deployment. Although metallic stents(MS) are superior to the usual plastic stents in terms of patency, an extensive comparison between MS and "inside stents", which are deployed above the sphincter of Oddi, is necessary. Which techniques are preferred remains as yet unresolved: for instance, whether to use a unilateral or bilateral drainage, or a stent-in-stent or side-by-side method for the deployment of bilateral MS, although a new cell design and thin delivery system for MS allowed us to accomplish successful deployments of bilateral MS. The development of techniques and devices for re-intervention after stent occlusion is also imperative. Further critical investigations of more effective devices and techniques, and increased randomized controlled trials are warranted to resolve these important issues.展开更多
BACKGROUND Contrast enhanced harmonic endoscopic ultrasound(CEH-EUS) is a spreading technique; some studies have shown its value in the diagnosis of pancreatic adenocarcinoma using quantitative analysis.AIM To examine...BACKGROUND Contrast enhanced harmonic endoscopic ultrasound(CEH-EUS) is a spreading technique; some studies have shown its value in the diagnosis of pancreatic adenocarcinoma using quantitative analysis.AIM To examine the value of CEH-EUS for differentiating various pancreatic lesions in everyday routine with qualitative and quantitative analysis.METHODS Data of 55 patients with pancreatic lesions who underwent CEH-EUS were analysed retrospectively. Perfusion characteristics were classified by the investigator qualitatively immediately upon investigation, quantitative analysis was performed later on. Samples from fine needle aspiration(EUS-FNA) or surgical specimen served as gold standard.RESULTS CEH-EUS showed 39 hypoenhanced lesions, 3 non-enhanced and 13 hyperenhanced lesions. Concordance of the investigators qualitative classification of peak contrast enhancement with quantitative analysis later on was 100%, while other parameters such as arrival time, time to peak or area under the curve did not show additional value. 34 of 39 hypoenhanced lesions were pancreatic adenocarcinoma; of the hyperenhanced lesions 4 were inflammatory, 3 neuroendocrine carcinomas, 1 lymphoma, 1 insulinoma and 4 metastases(2 of renal cell carcinoma, 2 of lung cancer). Non-enhanced lesions showed up as necroses. Sensitivity for the detection of pancreatic adenocarcinoma was 100%,specificity 87.2% for hypoenhancement alone; in otherwise healthy pancreatic tissue all hypoenhanced lesions were pancreatic adenocarcinoma(sensitivity and specificity 100%, PPV and NPV for adenocarcinoma 100%).CONCLUSION This study again shows the excellent value of CEH-EUS in everyday routine for diagnostics of various focal pancreatic lesions suggesting that qualitatively assessed hypoenhancement is highly predictive for adenocarcinoma. Additional quantitative analysis of perfusion parameters does not add diagnostic yield. In case of the various hyperenhanced pancreatic lesions in our data set, histologic sampling is essential for further treatment.展开更多
AIM:To evaluate the prognostic value of electrophysiological stimulation(EPS) in the risk stratification for tachyarrhythmic events and sudden cardiac death(SCD).METHODS:We conducted a prospective cohort study and ana...AIM:To evaluate the prognostic value of electrophysiological stimulation(EPS) in the risk stratification for tachyarrhythmic events and sudden cardiac death(SCD).METHODS:We conducted a prospective cohort study and analyzed the long-term follow-up of 265 consecutive patients who underwent programmed ventricular stimulation at the Luzerner Kantonsspital(Lucerne,Switzerland) between October 2003 and April 2012. Patients underwent EPS for SCD risk evaluation because of structural or functional heart disease and/or electrical conduction abnormality and/or after syncope/cardiac arrest. EPS was considered abnormal,if a sustained ventricular tachycardia(VT) was inducible. The primary endpoint of the study was SCD or,in implanted patients,adequate ICD-activation.RESULTS:During EPS,sustained VT was induced in 125 patients(47.2%) and non-sustained VT in 60 patients(22.6%); in 80 patients(30.2%) no arrhythmia could be induced. In our cohort,153 patients(57.7%) underwent ICD implantation after the EPS. During follow-up(mean duration 4.8 ± 2.3 years),a primary endpoint event occurred in 49 patients(18.5%). The area under the receiver operating characteristic curve(AUROC) was 0.593(95%CI:0.515-0.670) for a left ventricular ejection fraction(LVEF) < 35% and 0.636(95%CI:0.563-0.709) for inducible sustained VT during EPS. The AUROC of EPS was higher in the subgroup of patients with LVEF ≥ 35%(0.681,95%CI:0.578-0.785). Cox regression analysis showed that both,sustained VT during EPS(HR:2.26,95%CI:1.22-4.19,P = 0.009) and LVEF < 35%(HR:2.00,95%CI:1.13-3.54,P = 0.018) were independent predictors of primary endpoint events.CONCLUSION:EPS provides a benefit in risk stratificationfor future tachyarrhythmic events and SCD and should especially be considered in patients with LVEF ≥ 35%.展开更多
BACKGROUND Adjuvant chemotherapy using intraperitoneal(IP)treatment has demonstrated survival benefit over intravenous(IV)therapy alone in patients treated with upfront debulking surgery for advanced stage ovarian can...BACKGROUND Adjuvant chemotherapy using intraperitoneal(IP)treatment has demonstrated survival benefit over intravenous(IV)therapy alone in patients treated with upfront debulking surgery for advanced stage ovarian cancer.Neoadjuvant chemotherapy followed by interim surgery and adjuvant chemotherapy has similar outcome in survival as compared to upfront surgery followed by adjuvant IV chemotherapy.IP chemotherapy has not been widely adopted in clinical practice for a number of reasons.Whether IP chemotherapy delivered in the patients who received neoadjuvant chemotherapy can be well tolerated or confers any clinical benefit has not been well studied.AIM To evaluate the experience of adjuvant IP chemotherapy in the community cancer clinic setting,and the clinical benefit and tolerability of incorporating IP chemotherapy in patients who received neoadjuvant treatment.METHODS We retrospectively evaluated toxicities and outcomes of patients with stage III and IV ovarian cancer diagnosed at our institution between 07/2007 and 07/2015 who received intraperitoneal chemotherapy after cytoreductive surgery(group 1)or after neoadjuvant chemotherapy followed by interim surgery(group 2).RESULTS Thirty eight patients were treated with IP chemotherapy,median age was 54 years old(range 38.6 to 71 years).In group 1(n=25),12(48%)of the patients completed 4 or more cycle of IP treatment after upfront debulking surgery;while in group 2(n=13),8(61.5%)of the patients completed all 3 cycles of the assigned IP chemotherapy after receiving neoadjuvant IV chemotherapy followed by surgery,and 2(15.4%)more patients tolerated more than 3 cycles.In those patients who did not get planned IP chemotherapy,most of them were treated with substitutional IV chemotherapy,and the completion rate for 6 cycles of IV+IP was 92%.Abdominal pain,(64%in group 1 and 38%in group 2),vomiting,(36%in group 1 and 30.8%in group 2),dehydration(16%in group 1 and 15.4%in group 2),and hypomagnesemia(12%in group 1 and 15.4%in group 2)were the most common adverse effects in all patients,while patients who have received neoadjuvant chemotherapy were more likely to get hypokalemia,fatigue and renal insufficiency.Progression free survival(PFS)was 26.5 mo(95%CI 14.9,38.0)in group 1 and 27.6 mo(95%CI 13.1,42.1)in group 2.The overall survival was 100.2 mo(95%CI 67.9,132.5)for group 1 and 68.2 mo(95%CI 32.2,104.0)for group 2.For the entire cohort,PFS was 26.5 mo(95%CI 15.9,37.0)and OS was 78.8 mo(95%CI 52.3,105.4).CONCLUSION The use of IP/IV chemotherapy can be safely administrated in the community cancer clinic setting.The use of IP/IV chemotherapy in patients who have received neoadjuvant chemotherapy followed by surgery is feasible and tolerable.Despite various modification of the IP regimen,incorporation of IP chemotherapy in the adjuvant setting appears to be associated with improved PFS and overall survival.展开更多
BACKGROUND Ischemic gastritis is a clinically rare and highly fatal disease that occurs when the hemodynamics of a patient with vascular risk is disrupted.Early diagnosis and treatment are possible only with upper end...BACKGROUND Ischemic gastritis is a clinically rare and highly fatal disease that occurs when the hemodynamics of a patient with vascular risk is disrupted.Early diagnosis and treatment are possible only with upper endoscopy after symptom appearance.We report seven cases of ischemic gastritis and its clinical features,prognosis,and indicators that may help in early detection.CASE SUMMARY Of the seven patients,six had vascular risk and five died within 2 wk of diagnosis.Their symptoms included hematemesis and hypotension.Although surgery is a choice for radical treatment,not all patients were tolerant.For such patients,conservative treatment was selected,but all of them died.In contrast,patients who underwent repeat endoscopy showed improved mucosal findings,suggesting that this improvement may not affect prognosis.Some ischemic changes such as wall thickening,mural emphysema,and fluid retention in the stomach were observed before diagnosis through endoscopy and computed tomography(CT).The CT scan can be effective for early detection,and improvement in circulatory failure and aggressive treatment may save the lives of patients with this disease.CONCLUSION The characteristic CT findings enable early detection of ischemic gastritis.Early diagnosis increases the chance of survival if early therapeutic intervention and improvement of circulatory dynamics can be achieved in this highly fatal disease.展开更多
AIM: To compare the clinical efficacy of the secondgeneration H2 RA lafutidine with that of lansoprazole in Japanese patients with mild gastroesophageal reflux disease(GERD). METHODS: Patients with symptoms of GERD an...AIM: To compare the clinical efficacy of the secondgeneration H2 RA lafutidine with that of lansoprazole in Japanese patients with mild gastroesophageal reflux disease(GERD). METHODS: Patients with symptoms of GERD and a diagnosis of grade A reflux esophagitis(according to the Los Angeles classification) were randomized to receive lafutidine(10 mg, twice daily) or lansoprazole(30 mg, once daily) for an initial 8 wk, followed by maintenance treatment comprising half-doses of the assigned drug for 24 wk. The primary endpoint was the frequency and severity of heartburn during initial and maintenance treatment. The secondary endpoints were the sum score of questions 2 and 3 in the Gastrointestinal Symptom Rating Scale(GSRS), and the satisfaction score.RESULTS: Between April 2012 and March 2013, a total of 53 patients were enrolled, of whom 24 and 29 received lafutidine and lansoprazole, respectively. After 8 wk, the frequency and severity of heartburn was significantly reduced in both groups. However, lafutidine was significantly inferior to lansoprazole with regard to the severity of heartburn during initial and maintenance treatment(P = 0.016). The sum score of questions 2 and 3 in the GSRS, and satisfaction scores were also significantly worse in the lafutidine group than the lansoprazole group(P = 0.0068 and P = 0.0048, respectively).CONCLUSION: The clinical efficacy of lafutidine was inferior to that of lansoprazole, even in Japanese patients with mild GERD.展开更多
Varicella (chickenpox) is a generalized, self-limiting viral infection that is caused by varicella zoster virus (VZV). Chickenpox commonly infects children from 2 - 8 years without severe outcomes, but is particularly...Varicella (chickenpox) is a generalized, self-limiting viral infection that is caused by varicella zoster virus (VZV). Chickenpox commonly infects children from 2 - 8 years without severe outcomes, but is particularly severe when affecting adults.展开更多
Type 2 diabetes is in epidemic proportion in Papua New Guinea. Although many people are at high-risk of developing diabetes, there is no diabetes prevention policy and services in Papua New Guinea to address this prob...Type 2 diabetes is in epidemic proportion in Papua New Guinea. Although many people are at high-risk of developing diabetes, there is no diabetes prevention policy and services in Papua New Guinea to address this problem. A literature search was carried out to assess the available evidence in the primary prevention of type 2 diabetes mellitus among the population with pre-diabetes. The result shows that the primary preventative studies conducted on lifestyle modification and the use of metformin in prediabetes patients reduced overt type 2 diabetes mellitus. The application of the evidence in the prevention of the type 2 diabetes epidemic in Papua New Guinea, driven by a policy is feasible to address the diabetes epidemic.展开更多
A 48-year-old woman presented with bilateral enlarged ovaries, ascites, bilateral pleural effusion, and advanced gastric cancer. Pleural fluid cytology did not reveal malignant cells. Oophorectomy, performed as a pall...A 48-year-old woman presented with bilateral enlarged ovaries, ascites, bilateral pleural effusion, and advanced gastric cancer. Pleural fluid cytology did not reveal malignant cells. Oophorectomy, performed as a palliative procedure, was followed by rapid resolution of the pleural effusion and ascites. The patient was diagnosed with pseudo-Meigs’ syndrome, and underwent chemotherapy followed by partial gastrectomy. At the last follow-up, 84 mo following oophorectomy, she was alive, and free of disease recurrence, despite not receiving any further treatment. Pseudo-Meigs’ syndrome should be considered in patients with bilateral ovarian tumors, ascites and pleural effusion, and treatment such as oophorectomy may result in symptomatic improvement and better prognosis in similar patients.展开更多
To study Barrett’s esophagus (BE) in cirrhosis and assess progression to esophageal adenocarcinoma (EAC) compared to non-cirrhotic BE controls.METHODSCirrhotic patients who were found to have endoscopic evidence of B...To study Barrett’s esophagus (BE) in cirrhosis and assess progression to esophageal adenocarcinoma (EAC) compared to non-cirrhotic BE controls.METHODSCirrhotic patients who were found to have endoscopic evidence of BE confirmed by the presence of intestinal metaplasia on histology from 1/1/2000 to 12/1/2015 at Cleveland Clinic were included. Cirrhotic patients were matched 1:4 to BE controls without cirrhosis. Age, gender, race, BE length, hiatal hernia size, Child-Pugh (CP) class and histological findings were recorded. Cases and controls without high-grade dysplasia (HGD)/EAC and who had follow-up endoscopies were studied for incidence of dysplasia/EAC and to assess progression rates. Univariable conditional logistic regression was done to assess differences in baseline characteristics between the two groups.RESULTSA total of 57 patients with cirrhosis and BE were matched with 228 controls (BE without cirrhosis). The prevalence of dysplasia in cirrhosis and controls were similar with 8.8% vs 12% with low grade dysplasia (LGD) and 12.3 % vs 19.7% with HGD or EAC (P = 0.1). In the incidence cohort of 44 patients with median follow-up time of 2.7 years [interquartile range 1.0, 4.8], there were 7 cases of LGD, 2 cases of HGD, and 2 cases of EAC. There were no differences in incidence rates of HGD/EAC in nondysplastic BE between cirrhotic cases and noncirrhotic controls (1.4 vs 1.1 per 100 person- years, P = 0.8). In LGD, cirrhotic patients were found to have higher rates of progression to HGD/EAC compared to control group though this did not reach statistical significance (13.7 vs 8.1 per 100 person- years, P = 0.51). A significant association was found between a higher CP class and neoplastic progression of BE in cirrhotic patients (HR =7.9, 95%CI: 2.0-30.9, P = 0.003).CONCLUSIONCirrhotics with worsening liver function are at increased risk of progression of BE. More frequent endoscopic surveillance might be warranted in such patients.展开更多
基金Supported by Chongqing Natural Science Foundation General Project,No.CSTB2023NSCQ-MSX0182 and No.CSTB2023NSCQMSX0252Clinical Research Special Project of The Second Affiliated Hospital of Army Medical University,No.2024 F022.
文摘BACKGROUND Liver metastases are very common in pancreatic neuroendocrine tumors(pNETs).When surgical resection is possible,it is typically associated with survival benefits in patients with pNET and liver metastases.Patient-derived organoids are a powerful preclinical platform that show great potential for predicting treatment response,and they have been increasingly applied in precision medicine and cancer research.CASE SUMMARY A 51-year-old man was admitted to the hospital with the chief complaint of in-termittent dull pain in the upper abdomen for over 3 years.Computerized to-mography showed multiple space-occupying lesions in the liver and a neoplasm in the pancreatic body.Pathological results suggested a grade 3 pancreas-derived hepatic neuroendocrine tumor.In combination with relevant examinations,the patient was diagnosed with pNET with liver metastases(grade 3).Transarterial chemoembolization was initially performed with oxaliplatin and 5-fluorouracil,after which the chemotherapy regimen was switched to liposomal irinotecan and cisplatin for a subsequent perfusion,guided by organoid-based drug sensitivity testing.Following interventional treatment,the tumor had decreased in size.However,due to poor treatment compliance and the patient’s preference for sur-INTRODUCTION Pancreatic neuroendocrine tumors(pNETs)are a rare and heterogeneous group of neoplasms arising from pancreatic islet cells,with variations in histology,clinical characteristics,and prognosis[1].They may present as non-infiltrative,slow-growing tumors,locally invasive tumors,or even rapidly metastasizing tumors[2].Most metastases localize to the liver,and approximately 28%-77%of patients with pNETs will experience liver metastases in their lifetime[3].Patients with liver metastases may be subjected to local complications such as biliary obstruction,liver insufficiency,and carcinoid syndrome.Additionally,liver metastases are a major risk factor for the prognosis of patients with pNETs[4].When feasible,surgical resection is significantly associated with the best long-term survival outcomes[5].Therefore,for patients with pNET liver metastases,comprehensive assessment and multidisciplinary approaches are required to determine the feasibility of surgical resection and the optimal treatment to improve the prognosis.Over the past decade,the advent of in vitro three-dimensional technologies including organoids has revolutionized the development of human cancer models.Patient-derived organoids(PDOs),an in vitro three-dimensional microstructure,can faithfully recapitulate the intricate spatial architecture and cell heterogeneity of the tissue,and simulate the biological behaviors and functions of parental tumors while preserving biological,genetic and molecular features[6,7].As a po-werful preclinical platform,PDOs have been increasingly applied in precision medicine and cancer research.Importantly,there is a significant association between the use of PDO-based drug sensitivity testing and clinical responses to chemotherapy,radiotherapy and targeted therapy in multiple cancer types[8-10].Although gastroenteropancreatic neuroendocrine neoplasm organoids have been confirmed to retain the pathohistological and functional phenotypes of parental tumors[7],their roles in the prediction of clinical outcomes have not been presented.Here,we report a case of pNET with liver metastases who successfully received surgical resection after personalized treatment guided by PDO-based drug sensitivity testing,resulting in a favorable prognosis.
文摘Retainer-based medicine is growing increasingly in the United States and in some jurisdictions constitutes at least 10%of medical care services.It is to be distinguished from primary care medicine in that it involves the regular payment of a retainer fee that allows the patient privileged and expedited access to providers and is associated with a decreased patient burden for the primary care providers who participate in such an arrangement.Purpose:To assess the current ethical issues associated with retainer-based care.A literature review over the 22-year interval since the concept was first identified assessing in particular the extent to which distributive ethics are impacted by retainer-based care.Estimates on the ultimate impact of the availability and distribution of primary care are also considered based on available demographic data.The impact of retainer-based care on distributive ethics are analyzed by relationship to utilitarianism,egalitarianism,libertarianism,and communitarianism.Retainer-based care while ubiquitous and in some fashion longstanding,is occurring increasing especially in the USA and annually its prevalence there is increasing to about 10%of all primary care.This has a major impact on the overall availability of access to primary care physicians.The ethical issues attendant with this do not affect autonomy or malfeasance so much as they do impact distributive ethics.The increases in retainer-based care in the US has spurred ethical studies.Retainer-based care does not affect libertarianism but has a profound impact on the other three aspects of distributive ethics:The exact demographic impact on primary care is difficult to estimate but If retainer-based medicine continues to grow in frequency,it will result in the continued shortage of care for communities with impaired access to primary care physicians,in particular those with indigent individuals.Additional ethical studies are needed to assess the impact of retainer-based medicine on society.
基金Supported by(In part)Grant-in-Aid for Comprehensive Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan
文摘AIM:To investigate the predictors of proximal kidney tubular dysfunction(PKTD)induced by adefovir dipivoxil(ADV)treatment for chronic hepatitis B.METHODS:Seventy-nine patients(age at the evaluation of PKTD:56.9±10.7 years)with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively recruited.PKTD was defined by the presence of at least two of the following five abnormalities:phosphate diabetes,nondiabetic glucosuria,metabolic acidosis,β2-microglobulinuria,or renal hypouricemia.The single-nucleotide polymorphisms(SNPs)in the SLC22A6 gene encoding human organic anion transporter 1(h OAT1)and ABCC2 encoding multidrug resistance protein 2(MRP2)were analyzed using the Taq Man Allelic Discrimination Demonstration Kit.RESULTS:Nine(30.0%)of the 30 ADV-treated patients were diagnosed with PKTD,while no patients without ADV developed PKTD(P<0.001).Three patients with ADV were diagnosed with symptomatic osteomalacia.Among the patients who took ADV,those with PKTD were of higher age at initiation,had significantly longer treatment duration,and had a significantly lower body mass index than those without PKTD.The incidence of PKTD dramatically increased after 96 mo from the start of ADV administration.In contrast,the SNPs were not correlated with PKTD.Logistic regression analysis extracted older age at initiation(OR=5.0,95%CI:1.1-23.4;P=0.040)and longer treatment duration(OR=3.2,95%CI:1.2-8.6;P=0.020)as significant factors associated with PKTD.CONCLUSION:Our results suggest that the tubular function of the kidney of older patients undergoing longterm ADV treatment should be carefully evaluated.
文摘Objective:To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.Methods:A total of 60 newborn SD rats were equally randomized into normal saline(NS) group,LPS control group,bilirubin control group,low-dose group and high-dose group.After anesthesia,0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups;1 h later,the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups.After 5 or 24 hours of model establishment,spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method.After 24 hours of model establishment,scrum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry.Results:In contrast to low-dose bilirubin,high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS.After 5 hours of model establishment,compared with NS group.MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced(P<0.05).In high-dose group,inflammotory factors levels and CD8^+T cells percentage were all higher than LPS control and NS group(P<0.05),while CD4^+ T cells percentage was lower than NS group(P<0.05).Conclusions:High-concentration plasma bilirubin in coordination with LPS could inhibit NF- κB signal pathways activation and aggravate inflammatory reaction,thus caused immunosuppression with inflammation cascade,which resulted in the immune dysfunction.
基金Guangdong Provincial Science&Technology Department and the Guangdong Provincial Academy of Chinese Medical Sciences(Development of Evidence-based Knowledge Management System for Traditional Chinese Medicine,No.2012A032500009)
文摘OBJECTIVE: To evaluate the reporting quality of randomized controlled trials(RCT) that compared Bo's abdominal acupuncture with conventional body acupuncture, and compare the efficacy and safetybetweenthembyperforminga Meta-analysis.METHODS: All RCTs comparing Bo's abdominalacupuncture with conventional body acupuncture were included. English and Chinese databases were searched from their respective inceptions to March 2014. The reporting quality was assessed according to the "Consolidated Standards of Reporting Trials"(CONSORT) checklist for parallel RCTs and the revised "Standards for Reporting Interventions in Clinical Trials of Acupuncture"(STRICTA). A Meta-analysis was conducted to synthesize the effect sizes,and publication bias was evaluated by the Egger linear regression test using Stata.RESULTS: Ninety-seven studies were included, of which most lacked adequate reporting information, and 80.4% showed that the efficacy of abdominal acupuncture is superior to conventional body acupuncture, especially for the following diseases:lumbar disc herniation, cervical spondylosis, omarthritis and cervical vertigo, except simple obesity.Effect-sizes were controversial when evaluating different outcomes.CONCLUSION: The international standard CONSORT statement and STRICTA guidelines should be strictly applied when reporting acupuncture RCTs in the future. Abdominal acupuncture appears to be more effective compared with conventional body acupuncture for some diseases. However, further high quality blind RCTs using validated outcomeindexesandstandardreportingarewarranted.
文摘AIM： To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate （YMDD） mutants （reverse transcription; rtM204I/V） and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus （HBV） infection. METHODS： The data of 61 consecutive Japanese pa- tients with chronic hepatitis B who underwent continu- ous lamivudine treatment for more than 24 mo and had a virological response were analyzed. Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo （mean, 50.8 too; range, 24-90 too）.RESULTS： A mixed mutant-type （YMDD ＋ tyrosine-iso- leucine-asparatate-asparatate： YIDD or tyrosine-valineasparatate-asparatate： YVDD） or a mutant-type （YIDD or YVDD） were found in 57.4% of 61 patients at i year, 78.7% of 61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at 4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and 33.3% of 6 patients at 7 years. Of the 61 patients, 56 （92%） had mixed mutant- or a mutant-type. Only 5 （8%） had no mutants at each observation point. Vi- rological breakthrough was found in 26 （46.4%） of 56 patients with YMDD mutants, 20 of whom had a hepa- titis flare-up： the remaining 30 （53.6%） had neither a virological breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment. CONCLUSION： Our results suggest that it is possible to continue lamivudine treatment, even after the emergence of YMDD mutants, up to the time that the patients develop a hepatitis flare-up.
文摘A 19-year-old female was diagnosed with ulcerative colitis when she presented with persistent melena, and has been treated with 5-aminosalicylic acid for 4 years, with additional azathioprine for 2 years at our hospital. The patient experienced high-grade fevers, chills, and cough fve d prior to presenting to the outpatient unit. At frst, the patient was suspected to have developed neutropenic fever; however, she was diagnosed with Epstein-Barr virus-associated hemophagocytic syndr-ome （EB-VAHS） upon fulfilling the diagnostic criteria after bone marrow aspiration. When patients withinflammatory bowel disease treated with immunomo-dulators, such as thiopurine preparations, develop fever, EB-VAHS should be considered in the differential diagnosis.
基金Supported by A Grant–in-Aid for Comprehensive Research from the Ministry of Education, Culture, Sports Science and Technology of Japan
文摘AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) patients.METHODS:The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P=0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P=0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P=0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P=0.044). Multivariate analysis identified only the percentage of RBV dose as a predictor for Hb decline. Platelet decline was significantly higher in non-CC patients than CC patients at weeks 12, 24 and 48 (P=0.018, 0.009 and 0.026, respectively). CONCLUSION: Rs1127354 ITPA polymorphism plays a decisive role in protecting against treatment-induced anemia and the need for RBV dose reduction in Egyptian HCV patients.
基金supported by Program for the Development of Scientific and Technological Plan of Jilin Province(No.20100122)
文摘AIM: To study the chemical constituents of stems of Gymnema sylvestre(Retz.) Schult. METHODS: Chromatographic techniques using silica gel, C18 reversed phase silica gel, and prep-HPLC were used. The structures were elucidated on the basis of MS and spectroscopic analysis(1D and 2D NMR), as well as chemical methods. RESULTS: Seven compounds were isolated and their structures were elucidated as conduritol A(1), stigmasterol(2), lupeol(3), stigmasterol-3-O-β-D-glucoside(4), the sodium salt of 22α-hydroxy-longispinogenin-3-O-β-D-glucopyranosyl-(1→3)-β-D-glucurono-pyranosyl-28-O-α-L-rhamnopyranoside(5), oleanolic acid-3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside(6), and the sodium salt of 22α-hydroxy-longispinogenin 3-O-β-D-glucuronopyranosyl-28-O-α-L-rhamnopyranoside(7). The inhibition activities of compounds 1, 5-7 on non-enzymatic glycation of protein in vitro were evaluated. CONCLUSION: Compound 7 is a new triterpenoid saponin. It was shown that compounds 1, 5-7 have weak inhibition activities for non-enzymatic glycation of protein in vitro.
基金Supported by Financial support for this clinical study was provided by GERD Society(Osaka,Japan)
文摘To evaluate the psychometric properties of a newly developed questionnaire,known as the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test(GERD-TEST),in patients with GERD.METHODSJapanese patients with predominant GERD symptoms recruited according to the Montreal definition were treated for 4 wk using a standard dose of proton pump inhibitor(PPI).The GERD-TEST and the Medical Outcome Study Short Form-8 Health Survey(SF-8)were administered at baseline and after 4 wk of treatment.The GERD-TEST contains three domains:the severity of GERD and functional dyspepsia(FD)symptoms(5 items),the level of dissatisfaction with daily life(DS)(4 items),and the therapeutic efficacy as assessed by the patients and medication compliance(4 items).RESULTSA total of 290 patients were eligible at baseline;198 of these patients completed 4 wk of PPI therapy.The internal consistency reliability as evaluated using the Cronbach’sαvalues for the GERD,FD and DS subscales ranged from 0.75 to 0.82.The scores for the GERD,FD and DS items/subscales were significantly correlated with the physical and mental component summary scores of the SF-8.After 4 wk of PPI treatment,the scores for the GERD items/subscales were greatly reduced,ranging in value from 1.51 to 1.87 and with a large effect size(P<0.0001,Cohen’s d;1.29-1.63).Statistically significant differences in the changes in the scores for the GERD items/subscales were observed between treatment responders and non-responders(P<0.0001).CONCLUSIONThe GERD-TEST has a good reliability,a good convergent and concurrent validity,and is responsive to the effects of treatment.The GERD-TEST is a simple,easy to understand,and multifaceted PRO instrument applicable to both clinical trials and the primary care of GERD patients.
文摘The management of jaundice and cholangitis is important for improving the prognosis and quality of life of patients with unresectable malignant hilar biliary strictures(UMHBS). In addition, effective chemotherapy, such as a combination of gemcitabine and cisplatin, requires the successful control of jaundice and cholangitis. However, endoscopic drainage for UMHBS is technical demanding, and continuing controversies exist in the selection of the most appropriate devices and techniques for stent deployment. Although metallic stents(MS) are superior to the usual plastic stents in terms of patency, an extensive comparison between MS and "inside stents", which are deployed above the sphincter of Oddi, is necessary. Which techniques are preferred remains as yet unresolved: for instance, whether to use a unilateral or bilateral drainage, or a stent-in-stent or side-by-side method for the deployment of bilateral MS, although a new cell design and thin delivery system for MS allowed us to accomplish successful deployments of bilateral MS. The development of techniques and devices for re-intervention after stent occlusion is also imperative. Further critical investigations of more effective devices and techniques, and increased randomized controlled trials are warranted to resolve these important issues.
文摘BACKGROUND Contrast enhanced harmonic endoscopic ultrasound(CEH-EUS) is a spreading technique; some studies have shown its value in the diagnosis of pancreatic adenocarcinoma using quantitative analysis.AIM To examine the value of CEH-EUS for differentiating various pancreatic lesions in everyday routine with qualitative and quantitative analysis.METHODS Data of 55 patients with pancreatic lesions who underwent CEH-EUS were analysed retrospectively. Perfusion characteristics were classified by the investigator qualitatively immediately upon investigation, quantitative analysis was performed later on. Samples from fine needle aspiration(EUS-FNA) or surgical specimen served as gold standard.RESULTS CEH-EUS showed 39 hypoenhanced lesions, 3 non-enhanced and 13 hyperenhanced lesions. Concordance of the investigators qualitative classification of peak contrast enhancement with quantitative analysis later on was 100%, while other parameters such as arrival time, time to peak or area under the curve did not show additional value. 34 of 39 hypoenhanced lesions were pancreatic adenocarcinoma; of the hyperenhanced lesions 4 were inflammatory, 3 neuroendocrine carcinomas, 1 lymphoma, 1 insulinoma and 4 metastases(2 of renal cell carcinoma, 2 of lung cancer). Non-enhanced lesions showed up as necroses. Sensitivity for the detection of pancreatic adenocarcinoma was 100%,specificity 87.2% for hypoenhancement alone; in otherwise healthy pancreatic tissue all hypoenhanced lesions were pancreatic adenocarcinoma(sensitivity and specificity 100%, PPV and NPV for adenocarcinoma 100%).CONCLUSION This study again shows the excellent value of CEH-EUS in everyday routine for diagnostics of various focal pancreatic lesions suggesting that qualitatively assessed hypoenhancement is highly predictive for adenocarcinoma. Additional quantitative analysis of perfusion parameters does not add diagnostic yield. In case of the various hyperenhanced pancreatic lesions in our data set, histologic sampling is essential for further treatment.
文摘AIM:To evaluate the prognostic value of electrophysiological stimulation(EPS) in the risk stratification for tachyarrhythmic events and sudden cardiac death(SCD).METHODS:We conducted a prospective cohort study and analyzed the long-term follow-up of 265 consecutive patients who underwent programmed ventricular stimulation at the Luzerner Kantonsspital(Lucerne,Switzerland) between October 2003 and April 2012. Patients underwent EPS for SCD risk evaluation because of structural or functional heart disease and/or electrical conduction abnormality and/or after syncope/cardiac arrest. EPS was considered abnormal,if a sustained ventricular tachycardia(VT) was inducible. The primary endpoint of the study was SCD or,in implanted patients,adequate ICD-activation.RESULTS:During EPS,sustained VT was induced in 125 patients(47.2%) and non-sustained VT in 60 patients(22.6%); in 80 patients(30.2%) no arrhythmia could be induced. In our cohort,153 patients(57.7%) underwent ICD implantation after the EPS. During follow-up(mean duration 4.8 ± 2.3 years),a primary endpoint event occurred in 49 patients(18.5%). The area under the receiver operating characteristic curve(AUROC) was 0.593(95%CI:0.515-0.670) for a left ventricular ejection fraction(LVEF) < 35% and 0.636(95%CI:0.563-0.709) for inducible sustained VT during EPS. The AUROC of EPS was higher in the subgroup of patients with LVEF ≥ 35%(0.681,95%CI:0.578-0.785). Cox regression analysis showed that both,sustained VT during EPS(HR:2.26,95%CI:1.22-4.19,P = 0.009) and LVEF < 35%(HR:2.00,95%CI:1.13-3.54,P = 0.018) were independent predictors of primary endpoint events.CONCLUSION:EPS provides a benefit in risk stratificationfor future tachyarrhythmic events and SCD and should especially be considered in patients with LVEF ≥ 35%.
文摘BACKGROUND Adjuvant chemotherapy using intraperitoneal(IP)treatment has demonstrated survival benefit over intravenous(IV)therapy alone in patients treated with upfront debulking surgery for advanced stage ovarian cancer.Neoadjuvant chemotherapy followed by interim surgery and adjuvant chemotherapy has similar outcome in survival as compared to upfront surgery followed by adjuvant IV chemotherapy.IP chemotherapy has not been widely adopted in clinical practice for a number of reasons.Whether IP chemotherapy delivered in the patients who received neoadjuvant chemotherapy can be well tolerated or confers any clinical benefit has not been well studied.AIM To evaluate the experience of adjuvant IP chemotherapy in the community cancer clinic setting,and the clinical benefit and tolerability of incorporating IP chemotherapy in patients who received neoadjuvant treatment.METHODS We retrospectively evaluated toxicities and outcomes of patients with stage III and IV ovarian cancer diagnosed at our institution between 07/2007 and 07/2015 who received intraperitoneal chemotherapy after cytoreductive surgery(group 1)or after neoadjuvant chemotherapy followed by interim surgery(group 2).RESULTS Thirty eight patients were treated with IP chemotherapy,median age was 54 years old(range 38.6 to 71 years).In group 1(n=25),12(48%)of the patients completed 4 or more cycle of IP treatment after upfront debulking surgery;while in group 2(n=13),8(61.5%)of the patients completed all 3 cycles of the assigned IP chemotherapy after receiving neoadjuvant IV chemotherapy followed by surgery,and 2(15.4%)more patients tolerated more than 3 cycles.In those patients who did not get planned IP chemotherapy,most of them were treated with substitutional IV chemotherapy,and the completion rate for 6 cycles of IV+IP was 92%.Abdominal pain,(64%in group 1 and 38%in group 2),vomiting,(36%in group 1 and 30.8%in group 2),dehydration(16%in group 1 and 15.4%in group 2),and hypomagnesemia(12%in group 1 and 15.4%in group 2)were the most common adverse effects in all patients,while patients who have received neoadjuvant chemotherapy were more likely to get hypokalemia,fatigue and renal insufficiency.Progression free survival(PFS)was 26.5 mo(95%CI 14.9,38.0)in group 1 and 27.6 mo(95%CI 13.1,42.1)in group 2.The overall survival was 100.2 mo(95%CI 67.9,132.5)for group 1 and 68.2 mo(95%CI 32.2,104.0)for group 2.For the entire cohort,PFS was 26.5 mo(95%CI 15.9,37.0)and OS was 78.8 mo(95%CI 52.3,105.4).CONCLUSION The use of IP/IV chemotherapy can be safely administrated in the community cancer clinic setting.The use of IP/IV chemotherapy in patients who have received neoadjuvant chemotherapy followed by surgery is feasible and tolerable.Despite various modification of the IP regimen,incorporation of IP chemotherapy in the adjuvant setting appears to be associated with improved PFS and overall survival.
文摘BACKGROUND Ischemic gastritis is a clinically rare and highly fatal disease that occurs when the hemodynamics of a patient with vascular risk is disrupted.Early diagnosis and treatment are possible only with upper endoscopy after symptom appearance.We report seven cases of ischemic gastritis and its clinical features,prognosis,and indicators that may help in early detection.CASE SUMMARY Of the seven patients,six had vascular risk and five died within 2 wk of diagnosis.Their symptoms included hematemesis and hypotension.Although surgery is a choice for radical treatment,not all patients were tolerant.For such patients,conservative treatment was selected,but all of them died.In contrast,patients who underwent repeat endoscopy showed improved mucosal findings,suggesting that this improvement may not affect prognosis.Some ischemic changes such as wall thickening,mural emphysema,and fluid retention in the stomach were observed before diagnosis through endoscopy and computed tomography(CT).The CT scan can be effective for early detection,and improvement in circulatory failure and aggressive treatment may save the lives of patients with this disease.CONCLUSION The characteristic CT findings enable early detection of ischemic gastritis.Early diagnosis increases the chance of survival if early therapeutic intervention and improvement of circulatory dynamics can be achieved in this highly fatal disease.
文摘AIM: To compare the clinical efficacy of the secondgeneration H2 RA lafutidine with that of lansoprazole in Japanese patients with mild gastroesophageal reflux disease(GERD). METHODS: Patients with symptoms of GERD and a diagnosis of grade A reflux esophagitis(according to the Los Angeles classification) were randomized to receive lafutidine(10 mg, twice daily) or lansoprazole(30 mg, once daily) for an initial 8 wk, followed by maintenance treatment comprising half-doses of the assigned drug for 24 wk. The primary endpoint was the frequency and severity of heartburn during initial and maintenance treatment. The secondary endpoints were the sum score of questions 2 and 3 in the Gastrointestinal Symptom Rating Scale(GSRS), and the satisfaction score.RESULTS: Between April 2012 and March 2013, a total of 53 patients were enrolled, of whom 24 and 29 received lafutidine and lansoprazole, respectively. After 8 wk, the frequency and severity of heartburn was significantly reduced in both groups. However, lafutidine was significantly inferior to lansoprazole with regard to the severity of heartburn during initial and maintenance treatment(P = 0.016). The sum score of questions 2 and 3 in the GSRS, and satisfaction scores were also significantly worse in the lafutidine group than the lansoprazole group(P = 0.0068 and P = 0.0048, respectively).CONCLUSION: The clinical efficacy of lafutidine was inferior to that of lansoprazole, even in Japanese patients with mild GERD.
文摘Varicella (chickenpox) is a generalized, self-limiting viral infection that is caused by varicella zoster virus (VZV). Chickenpox commonly infects children from 2 - 8 years without severe outcomes, but is particularly severe when affecting adults.
文摘Type 2 diabetes is in epidemic proportion in Papua New Guinea. Although many people are at high-risk of developing diabetes, there is no diabetes prevention policy and services in Papua New Guinea to address this problem. A literature search was carried out to assess the available evidence in the primary prevention of type 2 diabetes mellitus among the population with pre-diabetes. The result shows that the primary preventative studies conducted on lifestyle modification and the use of metformin in prediabetes patients reduced overt type 2 diabetes mellitus. The application of the evidence in the prevention of the type 2 diabetes epidemic in Papua New Guinea, driven by a policy is feasible to address the diabetes epidemic.
文摘A 48-year-old woman presented with bilateral enlarged ovaries, ascites, bilateral pleural effusion, and advanced gastric cancer. Pleural fluid cytology did not reveal malignant cells. Oophorectomy, performed as a palliative procedure, was followed by rapid resolution of the pleural effusion and ascites. The patient was diagnosed with pseudo-Meigs’ syndrome, and underwent chemotherapy followed by partial gastrectomy. At the last follow-up, 84 mo following oophorectomy, she was alive, and free of disease recurrence, despite not receiving any further treatment. Pseudo-Meigs’ syndrome should be considered in patients with bilateral ovarian tumors, ascites and pleural effusion, and treatment such as oophorectomy may result in symptomatic improvement and better prognosis in similar patients.
文摘To study Barrett’s esophagus (BE) in cirrhosis and assess progression to esophageal adenocarcinoma (EAC) compared to non-cirrhotic BE controls.METHODSCirrhotic patients who were found to have endoscopic evidence of BE confirmed by the presence of intestinal metaplasia on histology from 1/1/2000 to 12/1/2015 at Cleveland Clinic were included. Cirrhotic patients were matched 1:4 to BE controls without cirrhosis. Age, gender, race, BE length, hiatal hernia size, Child-Pugh (CP) class and histological findings were recorded. Cases and controls without high-grade dysplasia (HGD)/EAC and who had follow-up endoscopies were studied for incidence of dysplasia/EAC and to assess progression rates. Univariable conditional logistic regression was done to assess differences in baseline characteristics between the two groups.RESULTSA total of 57 patients with cirrhosis and BE were matched with 228 controls (BE without cirrhosis). The prevalence of dysplasia in cirrhosis and controls were similar with 8.8% vs 12% with low grade dysplasia (LGD) and 12.3 % vs 19.7% with HGD or EAC (P = 0.1). In the incidence cohort of 44 patients with median follow-up time of 2.7 years [interquartile range 1.0, 4.8], there were 7 cases of LGD, 2 cases of HGD, and 2 cases of EAC. There were no differences in incidence rates of HGD/EAC in nondysplastic BE between cirrhotic cases and noncirrhotic controls (1.4 vs 1.1 per 100 person- years, P = 0.8). In LGD, cirrhotic patients were found to have higher rates of progression to HGD/EAC compared to control group though this did not reach statistical significance (13.7 vs 8.1 per 100 person- years, P = 0.51). A significant association was found between a higher CP class and neoplastic progression of BE in cirrhotic patients (HR =7.9, 95%CI: 2.0-30.9, P = 0.003).CONCLUSIONCirrhotics with worsening liver function are at increased risk of progression of BE. More frequent endoscopic surveillance might be warranted in such patients.
