Endoscopic Ultrasound Quality Metrics in Clinical Practice.

Recent advances in endoscopic ultrasound (EUS), particularly EUS-guided tissue acquisition, may have affected EUS procedural performance as measured by current American Society for Gastrointestinal Endoscopy (ASGE)/American College of Gastroenterology (ACG) quality indicators. Our study aims to assess how these quality metrics are met in clinical practice. We retrospectively analyzed 732 EUS procedures; data collected were procedural indications, technical aspects and outcomes, completeness of documentation, and malignancy staging. EUS was performed in 660 patients for a variety of indications. All ASGE/ACG EUS procedural quality metrics were met or exceeded. Intervention was successful in 97.7% (715/732) of cases, with complication rate of 0.4% (3/732). EUS outcomes changed clinical management in 58.7% of all cases and in 91.2% of malignancy work-up cases; in 26.0% of suspected choledocholithiasis cases, endoscopic retrograde cholangiopancreatography (ERCP) was avoided after EUS. Locoregional EUS staging was accurate in 61/65 (93.8%) cases of non-metastatic disease and in 15/22 (68.2%) cases of metastatic disease. Pancreatic mass malignancy detection rate with EUS-guided fine needle aspiration (FNA) or fine needle biopsy (FNB) was 75.8%, with a sensitivity of 96.2%; a significant increase in detection rate from 46.2% (6/13) to 95.0% (19/20) (p = 0.0026) was observed with a transition to the predominant use of FNB for tissue acquisition. All ASGE/ACG EUS quality metrics were met or exceeded for EUS procedures performed for a wide variety of indications in a diverse patient population. EUS was instrumental in changing clinical management, with a low complication rate. The malignancy detection rate in pancreatic masses significantly increased with FNB use.

Work-related exposure to organic solvents and the risk for multiple sclerosis-a systematic review.

PURPOSE: Multiple sclerosis (MS) is a chronic progressive neurological disorder. Several environmental factors have been discussed as possible causing agents, e.g. organic solvents, whose impact on the disease is analysed in this review. METHODS: Systematic search strategies were used to identify high-quality studies of workers exposed to organic solvents, published up to September 30, 2019, in databases, such as PubMed, Cochrane library and Scopus. The exposure was in most studies obtained by questionnaires, supplemented with telephone interviews. The diagnosis MS was mainly detemined following a thorough neurological examination. Finally, fourteen case-control studies and two cohort studies met the inclusion criteria and were included in the meta-analysis. Random effects models were used to pool the results of the studies. RESULTS: The odds ratios from the 14 case-control studies included in the meta-analysis ranged from 0.12-4.0. Five case-control studies and one cohort study showed a significant association between the development of multiple sclerosis and exposure to organic solvents. The results from the other nine case-control studies and from one of the two cohort studies did not reach statistical significance. The pooled data from the 14 case-control studies gave an OR of 1.44 (95% CI 1.03-1.99), which shows a moderately increased risk of developing MS after exposure to organic solvents. CONCLUSIONS: The final interpretation of the result is that organic solvents may be slightly associated with an increased risk to develop MS. In addition, other factors, e.g. genetic markers and smoking, may contribute to the development of the disease.

Efficacy and patient satisfaction of single-session transoral incisionless fundoplication and laparoscopic hernia repair.

BACKGROUND AND AIMS: Transoral incisionless fundoplication (TIF) is an effective endoscopic treatment for refractory GERD with small or absent hiatal hernia (< 2 cm in length and width). The single-session laparoscopic hernia repair followed by transoral incisionless fundoplication (HH + TIF) aims to repair mechanical defects in the lower esophageal sphincter that leads to GERD in patients with hiatal hernias ≥ 2 cm. The procedure effectively treats GERD without causing added post-surgical dysphagia and gas bloating commonly associated with partial laparoscopic fundoplication. We aimed to assess patient satisfaction, symptom resolution, safety, and proton pump inhibitor use following the HH + TIF procedure. METHODS: Thirty-three patients underwent single-session laparoscopic hernia repair with intraoperative TIF using the EsophyX Z device (EndoGastric Solutions, Inc.) between June 2015 and June 2018. The presence of GERD and normal esophageal motility were confirmed with pH testing and manometry prior to the procedure. Data were collected on pre- and post-procedure symptoms, patient satisfaction, PPI use, and complications. Median post-procedure follow-up with symptom surveys was 9 months (11-29 months). RESULTS: Patients reported significant decreases in common GERD symptoms including heartburn, regurgitation, cough, and hoarse voice. Eighty-one percent (27/33) of patients were off daily PPIs. Ninety-four percent (31/33) of patients reported 75% or greater satisfaction with the procedure and outcomes. One patient had a superficial mucosal laceration after the procedure, likely due to vomiting, which was treated conservatively. CONCLUSIONS: The majority of patients reported 75% or greater satisfaction with the procedure and had an improvement in GERD symptoms as well as decreased PPI use. There were no serious adverse events.

Improved diagnostic yield of endoscopic ultrasound-fine needle biopsy with histology specimen processing.

BACKGROUND: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) has emerged as a safe, efficacious alternative to fine needle aspiration (FNA) for tissue acquisition. EUS-FNB is reported to have higher diagnostic yield while preserving specimen tissue architecture. However, data on the optimal method of EUS-FNB specimen processing is limited. AIM: To evaluate EUS-FNB with specimen processing as histology vs EUS-FNA cytology with regards to diagnostic yield and specimen adequacy. METHODS: All EUS-FNA and EUS-FNB performed at our institution from July 1, 2016, to January 31, 2018, were retrospectively analyzed. We collected data on demographics, EUS findings, pathology, clinical outcomes, and procedural complications in two periods, July 2016 through March 2017, and April 2017 through January 2018, with predominant use of FNB in the second data collection time period. FNA specimens were processed as cytology with cell block technique and reviewed by a cytopathologist; FNB specimens were fixed in formalin, processed for histopathologic analysis and immunohistochemical staining, and reviewed by an anatomic pathologist. Final diagnosis was based on surgical pathology when available, repeat biopsy or imaging, and length of clinical follow up. RESULTS: One hundred six EUS-FNA and EUS-FNB procedures were performed. FNA alone was performed in 17 patients; in 56 patients, FNB alone was done; and in 33 patients, both FNA and FNB were performed. For all indications, diagnostic yield was 47.1% (8/17) in FNA alone cases, 85.7% (48/56) in FNB alone cases, and 84.8% (28/33) in cases where both FNA and FNB were performed (P = 0.0039). Specimens were adequate for pathologic evaluation in 52.9% (9/17) of FNA alone cases, in 89.3% (50/56) of FNB alone cases, and 84.8% (28/33) in cases where FNA with FNB were performed (P = 0.0049). Tissue could not be aspirated for cytology in 10.0% (5/50) of cases where FNA was done, while in 3.4% (3/89) of FNB cases, tissue could not be obtained for histology. In patients who underwent FNA with FNB, there was a statistically significant difference in both specimen adequacy (P = 0.0455) and diagnostic yield (P = 0.0455) between the FNA and FNB specimens (processed correspondingly as cytology or histology). CONCLUSION: EUS-FNB has a higher diagnostic yield and specimen adequacy than EUS-FNA. In our experience, specimen processing as histology may have contributed to the overall increased diagnostic yield of EUS-FNB.

Evaluating the risk of adverse events with interventional endoscopic retrograde cholangiopancreatography and endoscopic ultrasound procedures in cirrhotic patients.

BACKGROUND: Hepatic cirrhosis is associated with greater adverse event rates following surgical procedures and is thought to have a higher risk of complications with interventional procedures in general. However, these same patients often require interventional gastrointestinal procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). While studies examining this scenario exist, the overall body of evidence for adverse event rates associated with ERCP/EUS procedures is more limited. We sought add to the literature by examining the incidence of adverse events after ERCP/EUS procedures in our safety-net hospital population with the hypothesis that severity of cirrhosis correlates with higher adverse event rates. AIM: To examine whether increasing severity of cirrhosis is associated with greater incidence of adverse events after interventional ERCP/EUS procedures. METHODS: We performed a retrospective study of patients diagnosed with hepatic cirrhosis who underwent ERCP and/or EUS-guided fine needle aspirations/fine needle biopsies from January 1, 2016 to March 14, 2019 at our safety net hospital. We recorded Child-Pugh and Model for End-stage Liver Disease (MELD-Na) scores at time of procedure, interventions completed, and 30-day post-procedural adverse events. Statistical analyses were done to assess whether Child-Pugh class and MELD-Na score were associated with greater adverse event rates and whether advanced techniques (single-operator cholangioscopy, electrohydraulic lithotripsy/laser lithotripsy, or needle-knife techniques) were associated with higher complication rates. RESULTS: 77 procedures performed on 36 patients were included. The study population consisted primarily of middle-aged Hispanic males. 30-d procedure-related adverse events included gastrointestinal bleeding (7.8%), infection (6.5%), and bile leak (2%). The effect of Child-Pugh class C vs class A and B significantly predicted adverse events (ß = 0.55, P < 0.01). MELD-Na scores also significantly predicted adverse events (ß = 0.037, P < 0.01). Presence of advanced techniques was not associated with higher adverse events (P > 0.05). When MELD-Na scores were added as predictors with the effect of Child-Pugh class C, logistic regression showed MELD-Na scores were a significant predictor of adverse events (P < 0.01). The findings held after controlling for age, gender, ethnicity and repeat cases. CONCLUSION: Increasing cirrhosis severity predicted adverse events while the presence of advanced techniques did not. MELD-Na score may be more useful in predicting adverse events than Child-Pugh class.

Traumatic bile duct neuroma presenting with acute cholangitis: A case report and review of literature.

Traumatic neuroma of the biliary tree has been previously reported as isolated case reports. In literature, these typically present following prior liver transplant or cholecystectomy, wherein the bile ducts have been disrupted in some form. Here we report the case of a 41-year old male who initially presented with acute cholangitis ten years after an open cholecystectomy complicated by a bile leak. Endoscopic retrograde cholangiography revealed a stricture within the mid distal common hepatic duct. The patient temporarily resolved his initial episode with stent placement, and he was eventually taken to the operating room for bile duct resection and hepaticojejunostomy given a persistent stricture and concern for underlying malignancy. Final pathology demonstrated a traumatic bile duct neuroma. This unusual entity should be considered in patients with benign appearing strictures presenting years after surgery, and awareness may aid in preoperative counseling as well.

Randomized trial of 1-week versus 2-week intervals for endoscopic ligation in the treatment of patients with esophageal variceal bleeding.

UNLABELLED: The appropriate interval between ligation sessions for treatment of esophageal variceal bleeding is uncertain. The optimal interval would provide variceal eradication as rapidly as possible to lessen early rebleeding while minimizing ligation-induced adverse events. We randomly assigned patients hospitalized with acute esophageal variceal bleeding who had successful ligation at presentation to repeat ligation at 1-week or 2-week intervals. Beta-blocker therapy was also prescribed. Ligation was performed at the assigned interval until varices were eradicated and then at 3 and 9 months after eradication. The primary endpoint was the proportion of patients with variceal eradication at 4 weeks. Four-week variceal eradication occurred more often in the 1-week than in the 2-week group: 37/45 (82%) versus 23/45 (51%); difference = 31%, 95% confidence interval 12%-48%. Eradication occurred more rapidly in the 1-week group (18.1 versus 30.8 days, difference = -12.7 days, 95% confidence interval -20.0 to -5.4 days). The mean number of endoscopies to achieve eradication or to the last endoscopy in those not achieving eradication was comparable in the 1-week and 2-week groups (2.3 versus 2.1), with the mean number of postponed ligation sessions 0.3 versus 0.1 (difference = 0.2, 95% confidence interval -0.02 to 0.4). Rebleeding at 4 weeks (4% versus 4%) and 8 weeks (11% versus 9%), dysphagia/odynophagia/chest pain (9% versus 2%), strictures (0% versus 0%), and mortality (7% versus 7%) were similar with 1-week and 2-week intervals. CONCLUSION: One-week ligation intervals led to more rapid eradication than 2-week intervals without an increase in complications or number of endoscopies and without a reduction in rebleeding or other clinical outcomes; the decision regarding ligation intervals may be individualized based on patient and physician preferences and local logistics and resources. (Hepatology 2016;64:549-555).

Endoscopic treatment options for cholangiocarcinoma.

Cholangiocarcinomas are often locally advanced or have metastasized, and at the time of diagnosis individuals often have a poor prognosis. Endoscopic treatment options traditionally include biliary decompression via stenting to allow for systemic chemotherapy and radiotherapy, with self-expanding metal biliary stents being preferred. Recent developments in locoregional therapy delivered endoscopically, such as photodynamic therapy and radiofrequency abalation, have shown promising results in improving patient survival.

Pre-ERCP imaging of the bile duct and gallbladder.

Advances in biliary imaging have improved making accurate diagnoses of the presence and causes of biliary obstruction. Abdominal ultrasound is a useful screening tool because it is highly specific for choledocholithiasis. New developments in CT and MRI have also been useful in the diagnosis of biliary disease. Although diagnosis of biliary disease can be achieved in a noninvasive manner, there are limitations to modern MRI and CT cholangiographic techniques; their use may not be necessary or cost effective. MRI and CT imaging of the biliary tract provides opportunities for less-invasive diagnostic techniques but should be used judiciously before interventional endoscopy.

Side effects after docetaxel treatment in Taiwanese breast cancer patients with CYP3A4, CYP3A5, and ABCB1 gene polymorphisms.

BACKGROUND: Breast cancer patients initiating TEC (including docetaxel, epirubicin, and cyclophosphamide) treatment were genotyped for CYP3A4, CYP3A5, and ABCB1 to identify variability factors of side effects for docetaxel. METHODS: The planned dose of docetaxel per course was formulated according to each patient's height and weight. Each participant had received TEC treatment for 6 consecutive cycles. The single nucleotide polymorphisms (SNPs) of CYP3A4*4 (352A > G), CYP3A4*5 (653C > G), and CYP3A4*18A (20070T > C) for the CYP3A4 gene, CYP3A5*3A (6986A > G) for the CYP3A5 gene, and -41A > G, -145C > G, 1236C > T, 2677G > T(A), and 3435C > T SNPs for the ABCB1 gene were determined by using the restriction fragment length polymorphism of polymerase chain reaction products and the restriction enzymes. RESULTS: Fifty-nine Taiwanese women (mean age, 46 y; range, 30-64 y) treated for breast cancer with TEC were recruited. We found that patients carrying the CYP3A5*1/*3 genotype demonstrated more side effects of fever, pleural effusion, and febrile neutropenia than those with the CYP3A5*3/*3 genotype (p = 0.075, 0.077, and 0.030, respectively); moreover, patients with the ABCB1 2677G/G genotype also showed more side effects of fever and febrile neutropenia than those with other genotypes (p = 0.024 and 0.027), In regard to ABCB1 3435C>T, patients with ABCB1 3435C/C tended to suffer leucopenia (p = 0.057). CONCLUSIONS: There could be correlations between certain side effects of docetaxel treatment and polymorphisms of these metabolic enzymes. Unfortunately, there is not so much evidence due to the small sample size of this study which restricts the statistical power.

A case-control study of the HER2 Ile655Val polymorphism and risk of breast cancer in Taiwan.

OBJECTIVES: To investigate the HER2 Ile655Val polymorphism in relation to risk of breast cancer in a case-control study in Taiwan. DESIGN AND METHODS: The HER2 polymorphism at codon 655 was analyzed in 424 patients with breast cancer and 318 controls by using the polymerase chain reaction methodology, followed by the restriction fragment-length polymorphism (PCR-RFLP) analysis. RESULTS: There was a 1.48-fold (95% CI=1.00-2.24) increase in the risk of patients with breast cancer who are Val carrier (Ile/Val and Val/Val genotypes). Furthermore, for the early onset (less than 45 years old) breast cancers with Val carrier, there was a 2.24-fold (95% CI=1.17-4.34) increase in the risk of breast cancer. CONCLUSIONS: Our results indicate that the Val carrier was associated with increased risks in patients with breast cancer in Taiwan. The association was more apparent in patients who were younger than or equal to 45 years of age.

The association between lipid profiles and breast cancer among Taiwanese women.

BACKGROUND: Breast cancer incidence increased seven-fold from 1979 to 2002, and it has become the second most common cancer in Taiwanese women. Although the relationship between high-density lipoprotein cholesterol (HDL-C) and breast cancer has been studied, no consistent association has been explicitly confirmed. The aim of this study was to demonstrate the relationship between breast cancer and lipid profiles in Taiwanese women. METHODS: A total of 150 breast cancer patients before treatment and 71 healthy controls were enrolled. Lipid profiles in fasting serum were measured after participants gave their consent. RESULTS: The breast cancer patients had significantly lower values for HDL-C and apolipoprotein A-I (apoA-I), lower apoA-I/apoB ratios and higher values for very-low-density lipoprotein cholesterol (VLDL-C) than controls. After logistic regression analysis, the breast cancer patients had significantly higher values for VLDL-C and lower values for apoA-I after controlling for HDL-C and the apoA-I/apoB ratio. CONCLUSIONS: Our findings demonstrate that higher VLDL-C and lower apoA-I values were significantly associated with breast cancer, with a greater association between apoA-I values and the development of breast cancer than for HDL-C values.

Studies of the central nervous system-derived CAD cell line, a suitable model for intraneuronal transport studies?

The CAD cell line is a variant of a CNS-derived Cath.a cell line established by targeted oncogenesis in transgenic mice. Cell differentiation of the cell line can be induced by "starvation," i.e., removal of serum from the culture medium (protein-free medium). The differentiated CAD cells extend long processes, which ultrastructurally contain abundant microtubules, intermediate filaments, and various synaptic vesicles/organelles in the varicose enlargements, thus resembling neurites. Histochemical studies demonstrated that the differentiated cells express a number of synaptic vesicle proteins, cytoskeletons, different neurotransmitter enzymes, neuropeptides, and glia proteins. The data suggest that the differentiated CAD cells may be a suitable model for studies of intraneuronal transport, recycling of receptors, and pharmacological investigations.

Interaction of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferase M1 to breast cancer in Taiwanese woman without smoking and drinking habits.

P450 (CYP) and glutathione S-transferase (GST) are involved in the activation and detoxification of many potential carcinogens. Although, the interaction between environmental exposure and genetic polymorphisms of cytochrome P450 2E1 (CYP2E1) and glutathione S-transferase M1 (GSTM1) in breast cancer has been assessed, the gene-gene interactions between CYP2E1 and GSTM1 related to breast cancer have not been focused on and reported. We conducted a hospital-based case-control study to investigate whether the genetic interaction effects of CYP2E1 and GSTM1 modify the risk of developing breast cancer independent of the effect of cigarette smoking and alcohol consumption. Individuals with the C2/C2 genotype of CYP2E1 had a lower risk (OR = 0.24, 95% CI = 0.08-0.74) when compared with those with the C1/C1 genotype. However, there was no significant difference (OR = 1.05, 95% CI = 0.73-1.50) in the GSTM1 genotype frequency between the cases with breast cancer and that of the controls. When individuals with the genotype of C1/C1 or C1/C2 of CYP2E1 and the wild-type of GSTM1 were compared with those of C2/C2 of CYP2E1 and the null-type of GSTM1 however, we found a significantly increased risk (OR = 3.50, 95% CI = 1.01-16.55) in the breast cancer patients. Our findings indicated a gene-gene interaction between CYP2E1 and GSTM1 was accessible to developing breast cancer in Taiwanese women without the habits of cigarette smoking and alcohol consumption even though independent effects of CYP2E1 and GSTM1 were weak or non-significant and suggest that environmental carcinogen besides cigarette and alcohol consumption could induce breast cancer.

Association between the apolipoprotein E genotypes and breast cancer patients in Taiwanese.

To display the association between the apolipoprotein E (APOE) genotypes and breast cancer patients, a cross sectional study including 291 patients and 148 controls was performed. The APOE genotypes were measured in all participants, and the pathological diagnosis, estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER-2) among breast cancer patients were collected. The results showed the APOE allele frequency in breast cancer patients was 11.7% epsilon2 carriers, 74.6% epsilon3 carriers and 13.7% epsilon4 carriers, and there was no significant difference when they were compared with those of the control group (15.5% epsilon2 carriers, 74.3% epsilon3 carriers and 10.1% epsilon4 carriers; p=0.342). Among the patients in pre-menopause, showed a higher frequency of epsilon2 carriers had the cancer site on the left than that of the epsilon3 carriers (78.6% versus 40.3%; p=0.019). Among breast cancer patients, there was no significant association between the APOE genotypes and menopausal status, pathological diagnosis, estrogen receptor, progesterone receptor, and HER-2. Our findings demonstrated that the APOE genotypes were not associated with breast cancer patients, and epsilon2 allele tended to induce breast cancer on the left site among those patients in pre-menopause.

A study of glutathione status in the blood and tissues of patients with breast cancer.

Glutathione plays an important role in the antioxidant system that is required for the maintenance of the redox status of the cell, defence against free radicals and detoxification of toxic compounds. Reduced glutathione (redGSH) can be converted to oxidized glutathione (GSSG) during oxidative stress. The ratio of redGSH/total glutathione can be regarded as an index of the redox status and a useful indicator of disease risks. We conducted experiments by the capillary zone electrophoresis method to investigate the alterations of the glutathione status in the blood and tissue samples from patients with breast cancer. The results showed that the levels of redGSH, GSSG, total glutathione and the ratio of redGSH/total glutathione were significantly decreased in the blood of the patients with breast cancer compared to those of the control subjects. The levels of various forms of glutathione were lower and more pronounced in stage III. In contrast, the levels of redGSH, GSSG, total glutathione and the redGSH/total glutathione ratio in breast cancer tissues were significantly increased relative to those of the adjacent cancer-free tissues, especially in stage II. We suggest that the high redGSH levels are associated with the enhancement of cell proliferation and resistance to apoptosis in the cancer cells, and the loss of the large amount of erythrocyte redGSH may be due to increased detoxification capacities and defence against oxidative stress. We propose that redGSH should be regarded as an important biochemical parameter for detecting breast malignancy.

Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer.

BACKGROUND: Reactive oxygen species (ROS), including superoxide anion radical (O2(-)), plays an important role in carcinogenesis. The human body has developed different antioxidant systems to defend against free radical attacks. We investigated the changes of the antioxidant status in the blood of patients with breast cancer. METHODS: The O2(-) generation and the levels of malondialdehyde (MDA) were measured as an index of lipid peroxidation along with the examination of the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), the levels of reduced glutathione (GSH), oxidized glutathione (GSSG), and vitamins A, C, and E. RESULTS: The results showed that the levels of O2(-) and MDA, and the activities of antioxidant enzymes in the blood of the patients with breast cancer were significantly higher than the controls. However, the levels of vitamin C, GSH, GSSG and ratio of GSH/GSSG in the blood of the patients with breast cancer were significantly decreased compared to control subjects. CONCLUSIONS: Oxidative stress may be involved in breast cancer. The increased activities of erythrocyte antioxidant enzymes may be a compensatory upregulation in response to the increased oxidative stress.