A Whole-Food-Based Health Product (A-F Betafood®) Improves Gallbladder Function in Humans at Risk of Gallbladder Insufficiency: A Randomized, Placebo-Controlled Clinical Trial.

A-F Betafood® is a whole food-based health product. The product contains phytonutrients and bioactives with antioxidant properties that may support gallbladder and liver function. Herein, we investigated the efficacy of A-F Betafood® on gallbladder and liver function. In this randomized, placebo-controlled, parallel study fifty overweight but otherwise healthy adults received A-F Betafood® or placebo for 12 weeks. Gallbladder function as assessed by gallbladder volume, ejection fraction (GBEF), ejection rate, wall thickness and liver function determined via aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase, and high-sensitivity c-reactive protein analysis at baseline and week 12 were the primary outcomes. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, and oxidative stress markers including oxidized low-density lipoprotein, tumor necrosis factor-α, adiponectin and malonyldialdehyde (MDA) were assessed as secondary outcomes. A-F Betafood®-supplementation significantly reduced gallbladder wall thickness (p = 0.049) by 9% compared to placebo from baseline to week 12. The A-F Betafood® group alone had significant improvements in gallbladder volume (32%; p = 0.044) and GBEF (19%; p = 0.047) at week 12. There were no changes in liver function, oxidative stress markers or blood lipid concentrations, though MDA concentrations decreased in both groups. Our findings demonstrate A-F Betafood®-supplementation significantly improves measures of gallbladder function and support healthy gallbladder function in the individuals with gall bladder condition.

Systematic review of management of gallbladder disease in patients undergoing minimally invasive bariatric surgery.

The introduction and subsequent widespread adaptation of minimally invasive approaches for bariatric surgery have not only changed the outcomes of bariatric surgery but also called into question the management of co-morbid surgical conditions, in particular gallbladder disease. The American Society for Metabolic and Bariatric Surgery Foregut Committee performed a systematic review of the published literature from 1995-2018 on management of gallbladder disease in patients undergoing bariatric surgery. The papers reviewed generated the following results. (1) Routine prophylactic cholecystectomy at the time of bariatric surgery is not recommended. (2) In symptomatic patients who are undergoing bariatric surgery, concomitant cholecystectomy is acceptable and safe. (3) Ursodeoxycholic acid may be considered for gallstone formation prophylaxis during the period of rapid weight loss. (4) Routine preoperative screening and postoperative surveillance ultrasound is not recommended in asymptomatic patients. In the era of minimally invasive surgery, the management of gallbladder disease in patients undergoing bariatric surgery continues to evolve.

Vegetable protein intake is associated with lower gallbladder disease risk: Findings from the Women's Health Initiative prospective cohort.

OBJECTIVE: This study aimed to measure associations between gallbladder disease and protein intake patterns, separated by quantity and type (vegetable vs. animal), among postmenopausal women. METHODS: Analyses were based on 130,859 postmenopausal women enrolled from 1993 to 1998 at 40 U.S. clinical centers in the Women's Health Initiative clinical trials and observational study. Women were excluded if they reported a history of gallbladder disease prior to baseline. Cox proportional hazards regression models, adjusted for gallbladder disease risk factors, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between energy-adjusted protein intake and gallbladder disease. RESULTS: In this study sample, 8.1% of postmenopausal women self-reported incident gallbladder disease. In multivariate analysis, women in the highest quintile of energy-adjusted vegetable protein intake (>24.0g/d) had a lower risk of gallbladder disease (HR, 0.87; 95% CI, 0.81-0.93) as compared to women in the lowest quintile (<16.3g/d) (Ptrend<0.001). Total protein intake was modestly protective against gallbladder disease (Ptrend<0.021). Animal protein intake was not associated with gallbladder disease risk. The protective effect of vegetable protein held stable only for women without history of diabetes (HR, 0.86; 95% CI, 0.80-0.92) and without recent weight loss (HR, 0.88; 95% CI, 0.80-0.97). CONCLUSIONS: Vegetable protein intake is inversely associated with gallbladder disease risk in our sample of postmenopausal women. In addition to weight management, healthcare providers could emphasize vegetable protein as an additional dietary modality to promote lower risk for gallbladder disease.

Concomitant cholecystectomy should be routinely performed with laparoscopic Roux-en-Y gastric bypass.

INTRODUCTION: As the popularity of a laparoscopic Roux-en-Y Gastric Bypass (RYGB) surpassed that of an open approach, practice of concomitant cholecystectomy declined. Low rates of gallbladder disease following RYGB and high complication rates of concomitant cholecystectomy have been published, but these population-based studies have lacked long-term outcomes and survival data. STUDY DESIGN: The California Office of Statewide Health Planning and Development longitudinal database was queried for patients who underwent RYGB with or without cholecystectomy between 1995 and 2009. Additionally, patients who underwent cholecystectomy after RYGB were compared to all cholecystectomy patients. Primary outcome was survival; secondary long-term outcomes included cholangitis, common duct stones, dumping syndrome, metabolic derangements, ventral hernia, any hernia, marginal ulcers, and reoperation. Cox proportional hazard analysis was performed to determine adjusted survival and outcomes. RESULTS: Of 134,584 RYGB patients, 21,022 underwent concomitant cholecystectomy. Concomitant cholecystectomy improved both survival (HR[95 % CI] 0.51[.48-.54]) and long-term outcomes (HR 0.84[.77-.91]). Incidence of gallbladder disease following RYGB was 6.8 and 15.2 % at 1 and 5 years. In subsequent analysis of 829,333 cholecystectomy patients, 7,099 underwent prior RYGB with higher risk of conversion to open (HR 1.58[1.41-1.78]), post-operative complication (HR 1.47[1.36-1.6]) and death (HR 1.32[1.17-1.5]). CONCLUSIONS: Concomitant cholecystectomy is safe for RYGB patients. Given high rates of gallbladder disease and increased risk when cholecystectomy is performed following RYGB, cholecystectomy should be considered at the time of RYGB.

Effect of preserving the hepatic vagal nerve during laparoscopic Nissen fundoplication on postoperative biliary functions.

BACKGROUND: Cutting the hepatic branch of the anterior vagus nerve (HB-AVn) technically facilitates the laparoscopic Nissen fundoplication. The aim of this study was to investigate the effects of preserving or sacrificing this branch on postoperative gallbladder functions. METHODS: The patients (n = 40) were prospectively randomized into two groups. The HB-AVn was preserved during the dissection of the lesser omentum in the first group. The nerve was cut in the second group. Postoperative fasting gallbladder volumes were calculated by ultrasonography. Postoperative gallbladder ejection fraction (GEF) and gallbladder emptying time (GET) were determined by calculating intestinal transit time scintigraphically. RESULTS: Fasting gallbladder volumes and GEF values were not different between the groups. On the other hand, in patients with HB-AVn preserved, GET measurements were found to be significantly shorter than those with HB-AVn sacrificed. CONCLUSIONS: Sacrificing the hepatic branch causes prolongation in the GET. This change in the motor functions of the gallbladder does not cause any symptomatic effect during the early postoperative period. However, the delay in the GET may increase the risk of gallbladder stone formation in the long term.

Menopausal hormone therapy for the primary prevention of chronic conditions. U.S. Preventive Services Task Force recommendation statement.

Since the early 20th century, scientists have been tantalized with the hypothesis that premenopausal health benefits in women can be preserved in postmenopausal women with the supplementation of exogenous hormone replacement therapy (HRT) of estrogen (alone/with progesterone). This hypothesis was shattered when the results of 2 large randomized controlled trials (RCTs), the Heart Estrogen/Progesterone Replacement Study (HERS) and Women's Health Initiative (WHI), reported an increased risk of adverse clinical outcomes including coronary heart disease, thromboembolic events, stroke, dementia, urinary incontinence, gallbladder disease, and breast cancer. However, since the WHI was published, firestorms of critique, controversy, and multiple subgroup analyses have populated the medical literature, predominantly focused around the analysis of the age of women at entry into the trials (hypothesized as an effect modifier) and suggesting lower-dose preparations including using bioidentical hormones. Recently, the U.S. Preventive Services Task Force (USPSTF) along with other professional groups have issued recommendations against the use of HRT to prevent chronic conditions. In this review, we review the most recent evidence, including the long-term follow-up data from RCTs along a multitude of health outcomes.

Menopausal hormone therapy for the primary prevention of chronic conditions: U.S. Preventive Services Task Force recommendation statement.

DESCRIPTION: Update of the 2005 U.S. Preventive Services Task Force (USPSTF) recommendation statement on hormone therapy for the prevention of chronic conditions in postmenopausal women. METHODS: The USPSTF commissioned a review of the literature to update evidence about the benefits and harms of using menopausal hormone therapy to prevent chronic conditions, as well as whether the benefits and harms of hormone therapy differ by population subgroups defined by age; the presence of comorbid medical conditions; and the type, dose, and method of hormonal delivery. POPULATION: This recommendation applies to postmenopausal women who are considering hormone therapy for the primary prevention of chronic medical conditions. It does not apply to women who are considering hormone therapy for the management of menopausal symptoms, such as hot flashes or vaginal dryness. It also does not apply to women younger than 50 years who have had surgical menopause. RECOMMENDATION: The USPSTF recommends against the use of combined estrogen and progestin for the prevention of chronic conditions in postmenopausal women. (Grade D recommendation).The USPSTF recommends against the use of estrogen for the prevention of chronic conditions in postmenopausal women who have had a hysterectomy. (Grade D recommendation).

Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U.S. Preventive Services Task Force recommendations.

BACKGROUND: Menopausal hormone therapy to prevent chronic conditions is currently not recommended because of its adverse effects. PURPOSE: To update evidence about the effectiveness of hormone therapy in reducing risk for chronic conditions and adverse effects, and to examine whether outcomes vary among women in different subgroups. DATA SOURCES: MEDLINE (January 2002 to November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the 3rd quarter of 2011), Scopus, and reference lists. STUDY SELECTION: Randomized, placebo-controlled trials of menopausal hormone therapy published in English since 2002 that assessed primary prevention of chronic conditions. DATA EXTRACTION: Investigators extracted data on participants, study design, analysis, follow-up, and results; 2 investigators independently rated study quality by using established criteria. DATA SYNTHESIS: 9 fair-quality trials met the inclusion criteria. The Women's Health Initiative reported most of the results, had 11 years of follow-up, and had data most applicable to postmenopausal women in the United States. It showed that estrogen plus progestin therapy reduced fractures (46 fewer per 10 000 woman-years) and increased invasive breast cancer (8 more per 10 000 woman-years), stroke (9 more per 10 000 woman-years), deep venous thrombosis (12 more per 10 000 woman-years), pulmonary embolism (9 more per 10 000 woman-years), lung cancer death (5 more per 10 000 woman-years), gallbladder disease (20 more per 10 000 woman-years), dementia (22 more per 10 000 woman-years), and urinary incontinence (872 more per 10 000 woman-years). Estrogen-only therapy reduced fractures (56 fewer per 10 000 woman-years), invasive breast cancer (8 fewer per 10 000 woman-years), and death (2 fewer per 10 000 woman-years) and increased stroke (11 more per 10 000 woman-years), deep venous thrombosis (7 more per 10 000 woman-years), gallbladder disease (33 more per 10 000 woman-years), and urinary incontinence (1271 more per 10 000 woman-years). Outcomes did not consistently differ by age or comorbid conditions. LIMITATION: Limitations of the trials included low adherence, high attrition, inadequate power to detect risks for some outcomes, and evaluation of few regimens. CONCLUSION: Estrogen plus progestin and estrogen alone decreased risk for fractures but increased risk for stroke, thromboembolic events, gallbladder disease, and urinary incontinence. Estrogen plus progestin increased risk for breast cancer and probable dementia, whereas estrogen alone decreased risk for breast cancer. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

The treatment of climacteric symptoms.

BACKGROUND: Peri- and postmenopausal women commonly suffer from climacteric symptoms. In this article, we provide information to help physicians recognize climacteric symptoms and treat them appropriately. METHODS: The information presented here is based on a selective search of the literature for pertinent articles that appeared from 2008 to early 2011, including the German S3 guideline on hormone therapy (HT) during and after menopause, which was published in 2009. RESULTS: Perimenopausal women often suffer from climacteric symptoms. Typically, women undergoing menopause complain of heat waves and vaginal dryness. According to randomized controlled trials as well as national and international guidelines, HT is the most effective treatment for vasomotor symptoms and also improves vulvovaginal atrophy; for the latter indication, HT is preferably administered locally. Vaginal estrogen therapy lowers the frequency of recurrent urinary tract infections. However, HT is associated with an increased risk for a number of diseases, including stroke, thromboembolic events, gall-bladder diseases, and breast cancer. Alternative treatments for climacteric symptoms have little or no efficacy. CONCLUSION: HT should only be used to treat climacteric symptoms after extensive patient education about its benefits and risks. Participatory decision-making is desirable. The generalized use of HT by all women with climacteric symptoms cannot be recommended.

[Obesity and gallbladder diseases].

Obesity is an important health problem in the world and related to many critical diseases, such as diabetes, cardiovascular disease, and metabolic syndrome. Obesity leads to fat infiltration of multiple organs and infiltrated adipose tissue produces many cytokines resulting in the dysfunction of organs such as the gallbladder. In the biliary diseases, obesity and overweight have been known as a major risk factor for gallstones. According to current studies, obesity, insulin resistance, hyperinsulinemia, and metabolic syndrome are related to various gallbladder diseases including gallbladder stones, cholecystitis, gallbladder polyps, and gallbladder cancers. We reviewed further literature on the obesity and gallbladder diseases, in aspects of epidemiology, mechanism, pathology and prevention.

Complications of endoscopic ultrasonography.

Since its development in the 1980s, endoscopic ultrasonography (EUS) has undergone a great deal of technological modifications. EUS has become an important tool in the evaluation of patients with various clinical disorders and is increasingly being utilized in many centers. EUS has been evolving over the years; EUS-guided fine needle aspiration (FNA) for cytological and/or histological diagnosis has become standard practice and a wide array of interventional and therapeutic procedures are performed under EUS guidance for diseases which otherwise would have needed surgery, with its associated morbidities. EUS shares the risks and complications of other endoscopic procedures. This article addresses the specific adverse effects and risks associated with EUS, EUS-FNA and interventional EUS, namely perforation, bleeding, pancreatitis and infection. Measures to help minimizing these risks will also be discussed.

Statin administration and risk of cholecystectomy: a population-based case-control study.

BACKGROUND: Gallstone disease is common in Western countries. Statins reduce biliary cholesterol secretion and have anti-inflammatory effects, suggesting that they may play a role in reducing the incidence of surgically treated gallstone disease. AIM: To examine a potential association between statin administration and risk of cholecystectomy. METHODS: We conducted a population-based case-control study of surgically treated gallstone disease using the database of Clalit Health Services (CHS). The study population consisted of all individuals age 40 - 85 enrolled with the central region of CHS during the period 1 January 2000 to 31 December 2006. We identified patients who underwent cholecystectomy between 1 January 2003 and 31 December 2006 (n = 1465). Controls (n = 5860) were individually matched on year of birth and sex in a 4:1 ratio. Multivariable conditional logistic regression models to compute the odds ratio of cholecystectomy associated with statin therapy were constructed to control for patients' clinical and socio-demographic characteristics. RESULTS: Statin use with at least 80% adherence to treatment was associated with about 30% reduction in the risk of cholecystectomy (adjusted odds ratio 0.69; 95% CI 0.57 - 0.84). CONCLUSION: The results of our large population-based study suggest that the use of statins reduces the risk of surgery for gallstone disease.

Management of gallstones and gallbladder disease in patients undergoing gastric bypass.

The appropriate management of gallstones and gallbladder disease in patients undergoing gastric bypass remains unknown. Several therapeutic modalities are used and include performing cholecystectomy on all patients at the time of gastric bypass, performing concomitant cholecystectomy only when patients have gallstones and performing cholecystectomy only in the presence of both symptoms and gallstones. Some groups administer ursodeoxycholic acid for gallstone prevention in the postoperative period. All treatment modalities are analyzed and their results and rationality are discussed.

Reduction of biliary complication rate using continuous suture and no biliary drainage for duct-to-duct anastomosis in whole-organ liver transplantation.

Biliary complications (BC) following orthotopic liver transplantation (OLT) are related to various factors including surgical technique and use of biliary drains for a duct-to-duct (DD) anastomosis. Herein we have reported the influence of changes in surgical technique on BC following OLT in our center. From February 2002 to February 2007, we performed 101 whole-organ OLT with a DD anastomosis in 99 adults, of whom we analyzed 84 subjects. We excluded recipients who died within 30 days of OLT without any evidence of BC and 1 patient with a biliary stricture secondary to a hepatic artery thrombosis. Until late 2004, a DD anastomosis with interrupted sutures over an external biliary drain (DD/BD) was performed in 35 patients (Group I). Subsequently, no biliary drain was used for the DD anastomosis (DD/non-BD), using a continuous suture in 49 patients (Group II). The DD anastomosis with interrupted sutures over a biliary drain was associated with a higher incidence of both total (31% vs 8%; P = .008) and late BC (>30 days; 20% vs 2%; P = .008) with a trend toward more leaks (17% vs 4%; P = .06). All biliary leaks in patients with DD/BD reconstruction occurred at the exit site of the biliary drain following its removal. No significant differences were observed when we compared the incidence of biliary strictures and the necessity for surgical intervention. One patient died due to a BC. Our results indicated that a DD anastomosis performed with a continuous suture technique and no external biliary drainage reduced the incidence of BC after whole-organ OLT.

Separate and joint effects of alcohol and smoking on the risks of cirrhosis and gallbladder disease in middle-aged women.

The separate and joint effects of alcohol and smoking on incidences of liver cirrhosis and gallbladder disease were examined in a prospective study of 1,290,413 United Kingdom women (mean age, 56 years) recruited during 1996-2001. After a mean follow-up of 6.1 years (1996-2005), incidence rates of cirrhosis and gallbladder disease were 1.3 per 1,000 persons (n = 2,105) and 15 per 1,000 persons (n = 23,989), respectively, over 5 years. Cirrhosis risk increased with increasing alcohol consumption, while the risk of gallbladder disease decreased (P(trend) < 0.0001 for each). Comparing women who drank > or =15 units/week with those who drank 1-2 units/week, the relative risk was 4.32 (95% confidence interval (CI): 3.71, 5.03)) for cirrhosis and 0.59 (95% CI: 0.55, 0.64) for gallbladder disease. Increasing numbers of cigarettes smoked daily increased the risk of both conditions (P(trend) < 0.0001 for each). Comparing current smokers of > or =20 cigarettes/day with never smokers, the relative risk was 3.76 (95% CI: 3.25, 4.34) for cirrhosis and 1.29 (95% CI: 1.22, 1.37) for gallbladder disease. Effects of alcohol and smoking were more than multiplicative for cirrhosis (P(interaction) = 0.02) but not for gallbladder disease (P(interaction) = 0.4). Findings indicate that alcohol and smoking affect the risks of the 2 conditions in different ways. For cirrhosis, alcohol and smoking separately increase risk, and their joint effects are particularly hazardous. For gallbladder disease, alcohol reduces risk and smoking results in a small risk increase.

Childbearing, breastfeeding, other reproductive factors and the subsequent risk of hospitalization for gallbladder disease.

BACKGROUND: While parous women are known to be at an increased risk of gallbladder disease, little is known about the effects of other reproductive factors such as breastfeeding, age at menarche and age at menopause. METHODS: The Million Women Study is a prospective cohort study of 1.3 million middle-aged women in England and Scotland recruited from 1996 to 2001. Participants were followed-up by record-linkage for a mean of 6.1 years for admissions to hospital. The adjusted relative risk of hospital admission for cholelithiasis, cholecystitis or cholecystectomy according to parity, breastfeeding, age at menarche and age at menopause was examined. RESULTS: During follow-up of 1 289 029 eligible women, 25 111 were admitted to hospital for gallbladder disease, of whom 21 735 (87%) had a cholecystectomy. The hospital admission rate over 5 years for gallbladder disease was 1.6/100 women and for cholecystectomy was 1.4/100 women. The adjusted relative risk of gallbladder disease increased with increasing parity by 8% (95% CI 7-9%, P < 0.0001) for each birth. Among women of a given parity, breastfeeding reduced the risk of gallbladder disease, the relative risk decreasing by 7% (95% CI 5-10%, P < 0.0001) per year of breastfeeding. Women's age of menarche and age at menopause did not alter the risk of gallbladder disease (P = 0.4 and P = 0.3, respectively for linear trend). CONCLUSION: Hospitalization for gallbladder disease is common in middle-aged women. The risk increases the more children a woman has had, but decreases the longer she breastfeeds. The increased risk of gallbladder disease associated with having children can be offset by breastfeeding.

Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study.

OBJECTIVE: To determine whether transdermal compared with oral use of hormone replacement therapy reduces the risk of gallbladder disease in postmenopausal women. DESIGN: Prospective cohort study (Million Women Study). SETTING: Women registered with the National Health Service (NHS) in England and Scotland. PARTICIPANTS: 1,001,391 postmenopausal women (mean age 56) recruited between 1996 and 2001 from NHS breast screening centres and followed by record linkage to routinely collected NHS hospital admission data for gallbladder disease. MAIN OUTCOME MEASURES: Adjusted relative risk and standardised incidence rates of hospital admission for gallbladder disease or cholecystectomy according to use of hormone replacement therapy. RESULTS: During follow-up 19 889 women were admitted for gallbladder disease; 17 190 (86%) had a cholecystectomy. Compared with never users of hormone replacement therapy, current users were more likely to be admitted for gallbladder disease (relative risk 1.64, 95% confidence interval 1.58 to 1.69) but risks were substantially lower with transdermal therapy than with oral therapy (relative risk 1.17, 1.10 to 1.24 v 1.74, 1.68 to 1.80; heterogeneity P<0.001). Among women using oral therapy, equine oestrogens were associated with a slightly greater risk of gallbladder disease than estradiol (relative risk 1.79, 1.72 to 1.87 v 1.62, 1.54 to 1.70; heterogeneity P<0.001) and higher doses of oestrogen increased the risk more than lower doses: for equine oestrogens >0.625 mg, 1.91 (1.78 to 2.04) v 1 mg, 1.68 (1.59 to 1.77) v