A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Cost utility analysis of HIV pre exposure prophylaxis among men who have sex with men in Israel.

BACKGROUND: Between 2011 and 2015, Men who have sex with men (MSM) accounted for nearly half of new HIV cases among men in Israel. This study carries out a cost-utility analysis of PrEP (HIV Pre Exposure Prophylaxis), an antiretroviral medication that can protect against the acquisition of HIV infection, whose incidence rate in Israel is around 1.74 per 1000 MSM. METHOD: Epidemiological, demographic, health service utilisation and economic data were integrated into a spread-sheet model in order to calculate the cost per averted disability-adjusted life year (DALY) of the intervention from a societal perspective, in mid-2018 US$ using a 3% discount rate. Cost utility analyses were performed for both types of PrEP delivery (continuous regimen and on-demand), together with sensitivity analyses on numbers of condom users who take up PrEP (baseline 25%) and subsequently abandon condom use (baseline 75%), PrEP efficacy (baseline 86%), PrEP prices and monitoring costs. RESULTS: Around 21.3% of MSM are high risk (as defined by having unprotected anal intercourse). Offering PrEP to this group would have a ten year net cost of around 1563 million USD, preventing 493 persons from becoming HIV-positive, averting around 1616 DALYs at a cost per averted DALY of around 967,744 USD. This will render the intervention to be not cost-effective. PrEP drug prices would have to fall dramatically (by 90.7%) for the intervention to become cost-effective (i.e. having a cost per averted DALY less than thrice GNP per capita) in Israel. PrEP remains not cost-effective (at 475,673 USD per averted DALY) even if intervention costs were reduced by using an "on demand" instead of a daily schedule. Even if there were no changes in condom use, the resultant 411,694 USD cost-utility ratio is still not cost-effective. CONCLUSIONS: Despite PrEPs high effectiveness against HIV, PrEP was found not to be cost-effective in the Israeli context because of a combination of relatively low HIV incidence, high PrEP costs, with a likelyhood that some low-risk MSM (ie: who use condoms) may well begin taking PrEP and as a consequence many of these will abandon condom use. Therefore, ways of minimizing these last two phenomena need to be found.

Comparison of carcinogenic potency across life stages: implications for the assessment of transplacental cancer risk.

Cancer development from in utero exposure has been documented for a variety of agents with the most commonly studied compounds exhibiting mutagenic and genotoxic carcinogen properties. Age-dependent adjustment factors (ADAFs) are applied by the US Environmental Protection Agency to many such carcinogens when assessing cancer risk from early postnatal (PN) exposures; however, this approach has not been widely considered for transplacental (TP) exposure. To explore this question and further evaluate prenatal susceptibility a database of early life animal studies developed by California Office of Environmental Health Hazard Assessment (OEHHA) enhanced with additional literature searching was evaluated. Nine genotoxic carcinogens and one mixture (cigarette smoke) have data available via TP only, PN only and adult-only protocols. Potency comparisons across these lifestages displayed similarly greater potency in male liver and brain compared to adult-only exposure. Both TP and PN exposures were not markedly different than adult-only for other targets such as female liver and blood-borne tumors. Similarity in TP and PN targets and potency for carcinogen action suggests that a 10-fold ADAF may be applied for TP exposure as is currently applied to PN exposure. A similar conclusion was reached by OEHHA. The implications of this heightened TP vulnerability are greatest for less-than-lifetime exposure and this approach might be used to assess the level of cancer risk from exposures during pregnancy. A case example employing a mutagenic flame retardant was used to exemplify application of a TP ADAF for evaluating risks during pregnancy.

Adherence to the 2011 American Gastroenterological Association medical position statement for the diagnosis and management of Barrett's esophagus.

Considerable variability exists in adherence to practice guidelines for Barrett's esophagus (BE). Rapid advances in management approaches to BE led to a new American Gastroenterological Association (AGA) medical position statement in 2011. Our aim was to assess how well members of the AGA Clinical Practice section adhered to these guidelines. A self-administered survey incorporating questions on diagnostic criteria, cancer risk estimates, screening, surveillance, and therapeutics for BE was distributed electronically to 5850 North American members of the AGA Clinical Practice section. The response rate was 470 of 2040 opened e-mails (23%). Intestinal metaplasia was required for diagnosis of BE by 90%, but the Prague classification was used by only 53% of those aware of it. The annual risk of progression to esophageal adenocarcinoma was reported as 0.1-0.5% by 76%. Screening practices were variable, with 35% screening all patients with chronic gastroesophageal reflux disease and 15% repeating endoscopy in patients with gastroesophageal reflux disease following a negative screening. Surveillance guidelines were followed by 79% for nondysplastic BE and 86% for low-grade dysplasia, with expert pathology confirmation of dysplasia reported by 86%. Proton pump inhibitor dosing was variable, with 18% administering twice-daily doses and 30% titrating dose to symptoms. Ablation therapy was recommended by 6% for nondysplastic BE, 38% for low-grade dysplasia, and 52% for high-grade dysplasia. There is satisfactory adherence to the new AGA guidelines with respect to diagnosis, cancer risk estimates, and surveillance intervals in a select group of respondents. However, adherence continues to be variable in the use of the Prague classification, screening, and dosing of antisecretory therapy. Use of ablation therapy increases with grade of dysplasia. The reason for continued variability in adherence to BE practice guidelines remains unclear, and more evidence-based guidance is required to enhance clinical practice.

Methylmercury-induced inhibition of paraoxonase-1 (PON1)-implications for cardiovascular risk.

Methylmercury (MeHg) has been associated with increased risk for cardiovascular disease in some but not all epidemiology studies. These inconsistent results may stem from the fact that exposure typically occurs in the context of fish consumption, which is also associated with cardioprotective factors such as omega-3 fatty acids. Mechanistic information may help to understand whether MeHg represents a risk to cardiovascular health. MeHg is a pro-oxidant that inactivates protein sulfhydryls. These biochemical effects may diminish critical antioxidant defense mechanism(s) involved in protecting against atherosclerosis. One such defense mechanism is paraoxonase-1 (PON1), an enzyme present on high-density lipoproteins and that prevents the oxidation of blood lipids and their deposition in vascular endothelium. PON1 is potentially useful as a clinical biomarker of cardiovascular risk, as well as a critical enzyme in the detoxification of certain organophosphate oxons. MeHg and other metals are known to inhibit PON1 activity in vitro. MeHg is associated with lowered serum PON1 activity in a fish-eating population. The implications of lowering PON1 are evaluated by predicting the shift in PON1 population distribution induced by various doses of MeHg. An MeHg dose of 0.3 µg/kg/d is estimated to decrease the population average PON1 level by 6.1% and to increase population risk of acute cardiovascular events by 9.7%. This evaluation provides a plausible mechanism for MeHg-induced cardiovascular risk and suggests means to quantify the risk. This case study exemplifies the use of upstream disease biomarkers to evaluate the additive effect of chemical toxicity with background disease processes in assessing human risk.

Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report.

Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate.

Relationship between intragastric acid control and healing status in the treatment of moderate to severe erosive oesophagitis.

AIM: To assess the relationship between the percentage of time intragastric pH >4.0 and healing of erosive oesophagitis. METHODS: In this proof-of-concept study, adults with endoscopically verified Los Angeles grade C or grade D erosive oesophagitis were randomly assigned to oral esomeprazole 10 or 40 mg once daily for 4 weeks. On day 5, patients underwent 24-h pH monitoring. At 4 weeks, erosive oesophagitis healing status was endoscopically assessed. Investigators scored gastro-oesophageal reflux disease symptoms on a 4-point scale [none to severe (0-3)] before and 4 weeks after treatment. The percentage of time intragastric pH was >4.0 and healing status were correlated and tested for significance using a Spearman rank correlation (r). RESULTS: 103 patients had evaluable data (mean age, 48.7 years; 65% men). Mean percentages of time with intragastric pH >4.0 on day 5 in patients with healed and unhealed erosive oesophagitis were 61% and 42%, respectively (P = 0.0002), indicating that erosive oesophagitis healing rates were positively related to the percentage of time intragastric pH was >4.0. Greater intragastric acid control correlated with lower final daytime and night-time heartburn and acid regurgitation symptom scores (r = -0.029, -0.029 and -0.021; P = 0.003, 0.003 and 0.032, respectively). CONCLUSION: A positive relationship between intragastric acid control and erosive oesophagitis healing was demonstrated.

Multicenter comparative trial of the V-scope system for therapeutic ERCP.

BACKGROUND AND STUDY AIMS: A new duodenoscope (the V-scope), with a modified elevator used in combination with a dedicated short guide wire, constitutes the V-system. This system is intended to allow fixation of the guide wire at the elevator lever, thereby enhancing the speed and reliability of accessory exchange over a guide wire during ERCP. The aim of this study was to evaluate the extent to which the V-system provides improved efficiency in comparison with conventional duodenoscope and guide wire combinations. PATIENTS AND METHODS: This was an industry-sponsored multicenter randomized trial. Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) procedures in which treatment was anticipated were randomly assigned to the V-system or to a conventional duodenoscope and accessories used routinely in each center. The parameters recorded included the total case time, fluoroscopy time, catheter/guide wire exchange time, guide wire repositioning, loss of guide wire access, and success or failure of guide wire fixation when using the V-system. RESULTS: Fifty patients were included, 22 in the conventional group and 28 in the V-system group. A total of 135 exchanges were carried out. The patients had up to six exchanges. The median exchange time was 19.4 s with the V-system and 31.7 s with the conventional systems ( P < 0.001). Guide wire repositioning was required less often in the V-system group ( P = 0.0005). The V-system effectively locked the guide wire in 63 of 71 exchanges (89 %). Loss of guide wire access occurred in two patients in the conventional group and four in the V-system group, attributable to failure to lock the guide wire early during the experience (no significant differences). CONCLUSIONS: The V-system can effectively secure the guide wire during accessory exchange in ERCP and reduces the time required to exchange accessories. This may enhance overall efficiency during ERCP.

Biliary complications after liver transplantation: the role of endoscopy.

Biliary complications are important causes of early and late postoperative morbidity and mortality after liver transplantation and are seen in 10-20 % of the patients. The common biliary complications include bile leaks, stones or debris, and anastomotic strictures. Less common complications are hilar strictures, intrahepatic strictures, and papillary stenosis/dysfunction. The complications are similar in living-donor and cadaveric liver transplantations, except for a higher incidence of bile leaks among living-donor transplant recipients. The clinical presentation of post-liver transplant bile duct complications is often subtle, and noninvasive imaging studies may sometimes fail to detect mild but clinically significant stenoses or small leaks. Early recognition and prompt treatment of biliary complications following liver transplantation reduces the morbidity and improves long-term graft and patient survival. In this report, we discuss the role of endoscopy in the diagnosis, treatment options, and the outcome for patients with biliary complications following liver transplantation.

Cost containment analysis of childhood vaccination against varicella in Israel.

OBJECTIVES: The low cost of safe and effective vaccines prompted a cost-containment evaluation of a nationwide vaccination campaign against varicella. METHODS: A model incorporating demographic, epidemiologic and economic data from Israeli sources (supplemented by data from International literature) was constructed to estimate the decrease in morbidity and the consequent reductions in treatment costs and time-off work of a nationwide programme vaccinating children at 12 months. RESULTS: A policy of aiming to immunize a cohort of all 1-year-olds in Israel in the year 2002, for an annual cost of $1.10 million to the health services and $1.27 million to society (including lost work and transport costs), would reduce the number of cases of varicella during the lifetime of a cohort from 123,984 to 10,170 cases. This morbidity reduction would reduce national expenditures by $1.80 million in health service resources alone and by $24.5 million to society, mainly due to inaverted work absences. In addition an estimated 0.93 lives, representing 38.6 life years will be saved in the cohort. CONCLUSIONS: Under an assumption of neutrality relating to the potential effects of vaccination on herpes zoster virus, our model based calculations show that a national varicella vaccination programme is likely to be cost saving, not only from a societal perspective but also from the narrower health service perspective.

The Ashkelon Hypertension Detection and Control Program (AHDC Program): a community approach to reducing cardiovascular mortality.

BACKGROUND: Blood pressure (BP) reduction is crucial in reducing cardiovascular (CV) morbidity and mortality in the community. Subjects aged 20-65 seldom visit the primary care clinics, so they are unlikely to be detected without an active outreach screening program. The aim of the project was to prepare a professional doctor-nurse screening team, who will instruct those found to be at high risk in control of their risk factors, in order to reduce CV morbidity and mortality. METHODS: During a 10-year period (1980-1990), teams examined 12,202 subjects, (mean age 51 +/- 7 years, range 20-65 years) accounting for 23.4% of the total regional population. High risk subjects underwent an intensive CV risk factor control program. RESULTS: Subjects (3,506 or 28.6%) were found to have one or more CV risk factors (hypertension, obesity, smoking, hypercholesterolemia). During an average of 2 years, follow-up BP, weight reduction, and smoking cessation remained statistically significant. Total cholesterol was unchanged. Over this period, the standardized mortality ratio (SMR) in the area for acute MI fell from 100 to 76 (P < 0.01), for CV disease from 129 to 107 (P < 0.0001), and for hypertension from 121 to 87 (P < 0.1 NS). The project saved many life-years at no additional net cost to society, and cost effectiveness analysis showed positive results. CONCLUSIONS: A community approach with mainly nonpharmacological treatment is feasible and cost effective in reducing CV morbidity and mortality.

Risk factor profile and achievement of treatment goals among hypertensive patients from the Israeli Blood Pressure Control (IBPC) program--initial cost utility analysis.

AIMS: Blood pressure (BP) reduction is crucial in reducing cardiovascular morbidity and mortality. The IBPC (Israeli Blood Pressure Control) program was initiated in order to enhance the control of modifiable risk factors among high-risk hypertensive patients under follow-up by general practitioners in Israel. The cost effectiveness of an intervention program is an important factor in the decision-making process of its implementation and therefore was evaluated here. The objective of this evaluation is to estimate the costs, monetary savings and benefits in terms of QALYs (quality-adjusted life years) that would be expected if the program were to be expanded to 100 clinics nationwide, enabling around 14800 persons to be treated. METHODS: Hypertensive patients were screened in 30 general practice clinics, supervised by specialists in family medicine, each seeing 1000-5000 patients; 50-250 hypertensive patients were diagnosed at each participating clinic. BP levels, body mass index (BMI), lipid and glucose levels, as well as target organ damage and medications were recorded for all patients. RESULTS: A total of 4948 (2079, 42% males) were registered. Mean age was 64.8 +/- 12 years. After 1 year of follow-up versus baseline, the various parameters were as follows: BP control was achieved in 46.4% vs 29% of all hypertensive patients. LDL control (JNC VI criteria) was achieved in 41.7% vs 31.2% of all patients. Fasting plasma glucose control (glucose < 126 mg/dl) was achieved in 22% vs 19% of diabetic patients and 5.2% vs 3.1% of the diabetics had fasting plasma glucose levels > 200 mg/dl. Obesity (BMI > 30 kg/m2) was noted in 36.7% vs 43.8% at baseline. The cost utility analysis of the reduction in risk factors was calculated based on the international dicta applied to the reduction in risk factors as a result of treatment. For 100 clinics nationwide and 14800 persons to be treated the net saving to health services would be $977993 and the increase in QALYs would be 602 years. CONCLUSIONS: Better risk factor control in hypertensive patients by general practitioners could reduce morbidity and mortality as well as be cost effective.

The burden of uncomplicated cases of chickenpox in Israel.

OBJECTIVE: The aim of this study was to assess the direct medical burden and work loss associated with uncomplicated chickenpox in Israel. METHODS: A total of 155 otherwise healthy children and adolescents with chickenpox were recruited from 10 physician offices in central Israel. Direct and indirect medical burdens were determined by caregiver interview. RESULTS: Mean age was 3.3 +/- 2.3 years. 51% of the patients were under three years of age. Each patient made on average 1.15 visits to a general practitioner. Most patients were taken to the Doctor's office only once during the illness while 23 patients (15%) were seen twice. Three patients were referred to the emergency room. Antihistamines (39%) and Calamine lotion (28%) were the most frequently prescribed medications, followed by acyclovir (17%) and antibiotics (6%). Following the patient's illness there were 72 cases of secondary spread of varicella to household members. The individuals who cared for the child missed a combined total of 2.5 days from work (on average per varicella episode). CONCLUSIONS: Israeli children acquire chickenpox at a younger age than children in North America and England and consume more prescribed medications. While the work loss in the present study was comparable to previous reports, the direct medical costs inflicted by this infection in Israel are not negligible even for uncomplicated cases.

A novel treatment for constipation-predominant irritable bowel syndrome using Padma Lax, a Tibetan herbal formula.

BACKGROUND AND AIMS: Padma Lax, a complex Tibetan herbal formula for constipation was evaluated for safety and effectiveness in treating constipation-predominant irritable bowel syndrome in a 3-month double-blind randomised pilot study. METHODS: Patients were recruited from Hadassah Hospital's Gastroenterology clinic, using the Rome I Criteria for irritable bowel syndrome, and the international consensus criteria for constipation. Symptom severity was evaluated monthly by patients and gastroenterologist, using categorical and numerical rating scales. A patient diary recorded daily stool habit and trial medication. RESULTS: In 61 patients, (34 Padma Lax, 27 placebo), significant improvement was demonstrated after 3 months in the Padma Lax group compared to placebo in constipation, severity of abdominal pain, and its effect on daily activities, incomplete evacuation, abdominal distension and flatus/flatulence. A global assessment indicated that significantly more Padma Lax patients, compared to placebo, rated the current treatment superior to previous therapies tried for irritable bowel. Laboratory parameters displayed no clinically significant changes. Side effects, primarily loose stools in 7 Padma Lax patients responded well to lowering treatment dosage from 2 to 1 capsule/day. CONCLUSIONS: Padma Lax is a safe and effective treatment for constipation-predominant irritable bowel syndrome and may offer an alternative to the current multi drug approach.

Accuracy of EUS in the evaluation of Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma.

BACKGROUND: Nonoperative therapy with intent to cure may be considered for patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma. However, a more advanced stage of disease must be precluded before such treatment. The potential of EUS for this purpose was evaluated. METHODS: EUS was performed in patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma based on endoscopy, endoscopic biopsies, and CT before esophagectomy. EUS findings were compared with surgical/pathologic evaluation. RESULTS: EUS suggested submucosal invasion in 6 patients and lymph node involvement in 5 patients. By surgical/pathologic evaluation, 5 of 22 patients (23%) had unsuspected submucosal invasion and 1 had lymph node involvement. EUS detected all 5 instances of submucosal invasion and the single instance of lymph node involvement. EUS was falsely positive for submucosal invasion in 1 patient and for lymph node involvement in 4 patients. Sensitivity, specificity, and negative predictive values of preoperative EUS for submucosal invasion were 100%, 94%, and 100%, and for lymph node involvement were 100%, 81%, and 100%, respectively. A nodule or stricture noted by endoscopy was associated with an increased likelihood of submucosal invasion. CONCLUSIONS: In patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma, EUS detected otherwise unsuspected submucosal invasion and lymph node involvement. Patients should be evaluated with EUS when nonoperative therapy is contemplated.