Nutritional and Metabolic Diseases

Symptoms and General Pathology

All Conditions

Obesity

Hernia

Obesity, Morbid

Overweight

Overnutrition

Nutrition Disorders

Body Weight

Santiago Horgan, MD

The Minimally Invasive Surgery Team (MIST) are establishing a separate research database to find out more about patient's undergoing minimally invasive surgery (laparoscopic , open and robot assisted) procedures at UCSD. The hope is that collection of this information will give physicians a better knowledge and understanding of the benefits of minimally invasive surgery and possibly assist physicians to better manage future patients.

Minimally invasive surgery has become the gold standard in surgical treatment for many indications, such as treatment of gallstones and acute appendicitis. For many other indications, the potential for minimally invasive approaches exist, but the data does not yet exist to establish it as the gold standard. In addition, there are certain patient factors such as age or weight that may influence the success of a minimally invasive procedure.

While there are numerous articles in the literature reporting outcomes for minimally invasive therapies, these series are often notable for small patient populations and varying definitions of treatment success from study to study. Due to the lack of uniformity in reporting patient outcomes, an opportunity exists to establish a standardized database of a large number of patients undergoing these procedures.

A standardized database will facilitate conducting prospective research of the risk factors and benefits of minimally invasive surgery. This analysis will not only enhance the care provided to these patients, it will reduce the use of ineffective therapy, thus promoting improved efficiency while increasing the quality of care provided within the UCSD system.

This is our initial application. Several other departments at UCSD have developed similar databases. There are numerous examples of prospective databases used for similar purposes in the literature. Smithers, et al, used a prospective database of 446 patients undergoing esophagectomy to compare open to laparoscopic outcomes. Nesset, et al, maintained a database of bariatric surgery patients for two decades and was able to draw conclusions from a data set of 1584 patients. Even at smaller numbers, a prospective database is useful. Andrew, et al, described the improvement in outcomes over the learning curve in the first 201 patients undergoing laparoscopic roux-en-Y gastric bypass using such a database. Though labor intensive, Clemmesen, et al, found maintaining a database allowed them to improve care for their patients.

Minimally Invasive Surgery (MIS) Database for the Purpose of Research

Minimally Invasive Surgery (MIS) Database Looking at Patterns of Care, Outcomes, and Prognostic Analysis for the Purpose of Research

Post-operative outcomes including:

30 day morbidity 30 day mortality 30 day readmission Surgical site infection Surgical site occurrences Surgical Reintervention Specific Surgical outcomes (staple line leak, etc)

University of California, San Diego

Professor of Surgery

All patients in the minimally invasive surgery database are patients who have undergone surgical intervention by the Minimally Invasive Surgery faculty. Patients can be further stratified based on the type of procedure that they received. Since this study is primarily creation of a comprehensive database, patient's are not intentionally placed in a certain study arm aside from their procedure type.

Surgical Intervention

Age, Categorical

Age, Continuous

Sex: Female, Male

Dr. Jonathan Li

30 day morbidity

30 day mortality

30 day readmission

surgical site infection

Post Operative Outcomes

Overall Study

Neoplasms

Digestive System Diseases

Rare Diseases

Syndrome

Carcinoma

Cholangiocarcinoma

Metabolic Syndrome

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Insulin Resistance

Hyperinsulinism

Metabolic Diseases

Glucose Metabolism Disorders

Bile Duct Cancer

Biliary Tract Cancer

Gastrointestinal Agents

All Drugs and Chemicals

Bile Acids and Salts

Patients with morbid obesity and vertical sleeve gastrectomy

Gabriel PERLEMUTER, MD, PhDi

Increasing rates of highly malignant hepatocellular carcinoma (HCC) and biliary tract cancers (GBTC) observed in Western populations may be related to obesogenic lifestyle factors and their metabolic consequences, such as metabolic syndrome (MetS), inflammation and altered production of bile acids (BA). Such lifestyle behaviours may induce changes in the gut microflora which in turn affect BA profiles, increasing their carcinogenicity. Some elevated BA may be oncogenic in exposed liver, bile ducts and gall bladder. Vertical sleeve gastrectomy may change bile acid composition.

The aims of this study are:

1. whether specific presurgical bila acid profiles are predictive of efficacy of vertical sleeve gastrectomy, reflective of liver function and metabolic dysfunction;
2. whether specific presurgical bile acid profiles are predictive of the efficacy of sleeve gastrectomy

"Increasing rates of highly malignant hepatocellular carcinoma (HCC) and biliary tract cancers (GBTC) observed in Western populations may be related to obesogenic lifestyle factors and their metabolic consequences, such as metabolic syndrome (MetS), inflammation and altered production of bile acids (BA). Such lifestyle behaviours may induce changes in the gut microflora which in turn affect BA profiles, increasing their carcinogenicity. Some elevated BA may be oncogenic in exposed liver, bile ducts and gall bladder. Data from case-control studies show higher blood BA in patients with various liver diseases, but from these designs it is unclear if the differences in BA levels are etiologic or consequential. To date no prospective studies have investigated the role of circulating BA levels in the development of HCC/GBTC, nor any potential interactions with diet, obesity and MetS. Interestingly, Vertical Sleeve Gastrectomy (VSG), an anti-obesity intervention, may alter BA profiles in some patients towards a potentially detrimental composition, but this is largely unexplored.

Project description: This project is composed of two complementary studies designed to explore the role of BA in obesity, liver function and tumourigenesis. The 1st study is a case-control study of hepatobiliary cancers (191 HCC; 266 GBTC; 457 matched controls) nested within a large prospective cohort of Franco-European populations (EPIC, \>520,000 subjects) with extensive and detailed dietary/lifestyle data, body size measures and biological samples taken at baseline prior to disease development. The aim of this study is to explore associations between pre-diagnostic MetS markers and BA levels and the risk of HCC and GBTC, and to establish whether the observed associations are modulated, in part, by dietary/lifestyle factors or metabolic dysfunction.

The 2nd study is based on a clinical setting and aims to recruit 100 morbidly obese subjects undergoing VSG to compare their BA and metabolic profiles pre- to 1 year post-surgery. This study is based on observations that post-VSG BA synthesis is increased, but changes in BA composition towards possibly harmful profiles have not previously been studied. It is also hypothesized that the degree of weight loss and metabolic improvement in VSG patients may be related to pre-surgical BA profiles.

In both studies, comprehensive panel of 17 serum BA (primary, secondary, (un)-conjugated, sulphated) and metabolic biomarkers (inflammation, liver function, dyslipidemia, HbA1c, MetS indicators, hepatitis status) will be assessed using validated methods. Study 2 will also assess expression of liver FXR, a BA receptor gene. Statistical Methods: Study 1 will calculate odds ratios and 95% confidence intervals for circulating BA levels/MetS markers in relation to HCC and GBTC risk by multivariable conditional logistic regression, controlling for potential confounding variables and effect modifiers. Receiver operating characteristics (ROC) analyses will be performed to assess a combination of BA and metabolic markers with best performance to prospectively distinguish between cancer cases and controls. In study 2, GLM (repeated measures) ANOVA will be used to compare pre-/post-surgery changes in biomarkers. BA profiles from both studies, will be compared and correlations between BA and other biomarkers, lifestyle and body size measures will be assessed.

Expected results: This project is based on two related concepts. First, that lifestyle behaviours and obesity may alter gut microflora leading to changes in BA metabolism, enhancing production of specific BA known to be cancer promoting. Second, observations of increased BA levels post-VSG surgery, which may improve metabolic function, but some BA may be pro-carcinogenic over the longer term. The project will provide improved understanding of the inter-relations between BA, lifestyle behaviours and metabolic factors and the development of hepatobiliary cancers. It will also identify specific BA most strongly associated with these highly malignant cancers. The findings will contribute to the evidence base for advice on lifestyle and metabolic modifications for cancer prevention. The clinical implications are two-fold. First, the findings will provide insight as to whether BA profiles are predictive of the efficacy of VSG with potential implications in personalized medicine, and second, identified biomarker profiles may be used for more refined risk stratification for development of these cancers and subsequent closer patients' surveillance for early detection "

Metabolic Syndrome, Bile Acids, Hepatocellular Carcinoma and Cholangiocarcinoma

The Influence of Metabolic Syndrome and Circulating Bile Acid Levels on the Development of Hepatocellular Carcinoma and Biliary Tract Cancers

National Cancer Institute, France

Centre International de la Recherche sur le Cancer

Institut National de la Santé Et de la Recherche Médicale, France

Assistance Publique - Hôpitaux de Paris

Hematinics

Liver Extracts

Patients aged 18 years old and older, affected by HCC with MS (metabolic syndrome) as unique risk factor who comply with the criteria for bariatric surgery, will undergo liver resection and sleeve gastrectomy with minimally-invasive technique in the same surgical procedure

Patients aged 18 years old and older, affected by HCC (hepatocellular carcinoma) with MS (metabolic syndrome) as unique risk factor who will undergo liver resection only

Patients in the experimental arm will undergo liver resection for HCC and sleeve gastrectomy for MS during the same surgical procedure.

Liver resection and simultaneous sleeve gastrectomy for HCC induced by metabolic syndrome

Patients in the active comparator arm will undergo liver resection for HCC

Liver resection for HCC induced by metabolic syndrome

Annarita Libia

Hepatocellular carcinoma (HCC) related to metabolic syndrome (MS) as unique risk factor is gradually overpassing the more common viral and alcohol etiology, becoming a global health issue. Liver surgery for metabolic syndrome-related HCC in this frail subset of patients constitute a challenge, due to high morbidity and mortality rate reported in literature, and contrasting results in term of oncologic outcome. The present multicentric prospective study aims to ascertain if the combination of sleeve gastrectomy and liver surgery in the same surgical procedure may have benefit in terms of reduced perioperative morbidity and prolonged Overall Survival and Recurrence Free Survival. Secondary outcome will be the evaluation of the consequences induced by sleeve gastrectomy on liver disease, in particular liver fibrosis evaluated in term of NFS score (Non-Alcoholic Fatty Liver Disease Fibrosis score), FIB-4 (Fibrosis-4 Index for Liver Fibrosis) score and Fibroscan transient elastography.

Obesity is a worldwide epidemic, with more than 2 billion people currently overweight and an additional 1.12 billion projected to be overweight by 2030. HCC (hepatocellular carcinoma) associated to obesity and its comorbidity is overcoming Hepatitis C Virus (HCV) related cancer and is already the leading cause of liver transplant in USA. HCC remains the sixth most common cancer in the world and the third cause of cancer-related death. Considering these epidemiological evidence, the incidence of MS-HCC (metabolic syndrome-related hepatocellular carcinoma) is expected to increase with huge cost efforts for the global healthcare system. The impaired performance status of patients with HCC and metabolic syndrome seems to explain high perioperative morbidity rate reported in literature. Literature reports several experiences of bariatric surgery combined to liver transplant for chronic liver disease related induced by non alcoholic steatohepatitis (NASH), performed before or after liver surgery, or even at the same time. Even if evidences are weak, outcomes reported seem to be promising. Since sleeve gastrectomy is not only a mere restrictive bariatric procedure, but it produces hormonal and metabolic changes, with the present study the investigators want to ascertain if sleeve gastrectomy at time of liver resection for MS-HCC (metabolic syndrome-related hepatocellular carcinoma) can modify short perioperative outcomes and long-term oncologic results.

Patients 18 years old and older, affected by hepatocellular carcinoma (HCC) with metabolic syndrome (MS) as unique risk factor, with compensated liver function (Child A) who are deemed suitable for liver resection and comply with the criteria for bariatric surgery, will undergo liver resection of HCC and simultaneous sleeve gastrectomy for morbid obesity during the same surgical procedure.

Patients affected by HCC related to metabolic syndrome who fall within exclusion criteria, will undergo liver resection for HCC without sleeve gastrectomy.

Liver Resection and Simultaneous Sleeve Gastrectomy for MS-HCC (LIRESS)

Liver Resection and Simultaneous Sleeve Gastrectomy for HCC Related to Metabolic Syndrome (LIRESS)

Calculated from the date of diagnosis to the date of death from any cause

Calculated from the date of surgery to the date of recurrence

Any deviation from the normal postoperative course measured on a scale from 0 (no complication) to 100 (death)

Fibrosis-4 Index for Liver Fibrosis score (FIB-4 score) will be calculated using the following formula:

FIB-4 score= Age (years)× aspartate aminotransferase (AST) (U/L)/\[platelet count (109/L)×√alanine aminotransferase (ALT) (U/L)\]

Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS score) will be calculated using the following formula:

NFS = -1.675 + 0.037 - age (years) + 0.094 - BMI (kg/m2) + 1.13 × impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 × aspartate aminotransferase/ alanine aminotransferase (AST/ALT) ratio - 0.013 × platelet count (×109/l) - 0.66 × albumin (g/dl).

The Fibroscan stiffness measurement relies on the propagation of elastic waves to assess the stiffness of the liver: the faster elastic waves propagates within the liver, the stiffer the organ is. The final liver stiffness value is the median of individual liver stiffness values using the valid measurements and is expressed in kilo Pascal (kPa).

Body Mass Index (BMI) is combination of bodyweight and body height and presented as kg/m\^2

Percent excess weight loss (%EWL) is calculated as follows: \[(initial weight - current weight) / (initial weight - ideal weight)\] × 100

Change of antihypertensive therapy assessed by medical history questionnaire

change of insulin therapy or oral hypoglycemics assessed by medical history questionnaire

Ospedale V. Fazzi

Doctor

Heart and Blood Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Coronary Artery Disease

Myocardial Ischemia

Coronary Disease

Heart Diseases

Polycystic Ovary Syndrome

Cysts

Ovarian Cysts

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Crispbread

Jøran Hjelmesæth, MD, PhD

Tom Tanbo, MD, PhD

Kirsten B Holven, PhD

Line Kristin Johnson, MSc

This study has two phases:

1. In phase 1 of the study (8 weeks),the effect of two different low calorie diets on manifestations of PCOS, including risk factors for the metabolic syndrome and cardiovascular risk profile will be compared.
2. In phase 2 the long term effect (next 44 weeks) on sustained weight-loss and the above mentioned parameters will be compared and evaluated.

Weight loss is an important and effective treatment of morbidly obese women with PCOS. Effective weight reduction will improve manifestations of PCOS and risk factors for developing type 2 diabetes and coronary heart diseases. We compare the effect of two isocaloric low calorie diets (LCD), - one powder-based shake-diet and a fiber rich diet on the above mentioned parameters. In addition we want to compare the weight-maintenance effect the next 44 weeks of two different follow-up programs: A usual care- and a lifestyle-program.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Minimally Invasive Surgery (MIS) Database for the Purpose of Research	NCT00535990	Morbid Obesity Hernia Colorectal Canc... Laparoscopy		18 Years -	University of California, San Diego
Metabolic Syndrome, Bile Acids, Hepatocellular Carcinoma and Cholangiocarcinoma	NCT02730611	Morbid Obesity Vertical Sleeve... Metabolic Syndr... Hepatocellular ... Cholangiocarcin... Disorder of Bil...		18 Years -	Assistance Publique - Hôpitaux de Paris
Metabolic Syndrome, Bile Acids, Hepatocellular Carcinoma and Cholangiocarcinoma	NCT02730611	Morbid Obesity Vertical Sleeve... Metabolic Syndr... Hepatocellular ... Cholangiocarcin... Disorder of Bil...		18 Years -	Assistance Publique - Hôpitaux de Paris
Minimally Invasive Surgery (MIS) Database for the Purpose of Research	NCT00535990	Morbid Obesity Hernia Colorectal Canc... Laparoscopy		18 Years -	University of California, San Diego
Liver Resection and Simultaneous Sleeve Gastrectomy for MS-HCC (LIRESS)	NCT06060847	Carcinoma, Hepa... Metabolic Syndr...	Liver resection... Liver resection...	18 Years -	Ospedale V. Fazzi
Liver Resection and Simultaneous Sleeve Gastrectomy for MS-HCC (LIRESS)	NCT06060847	Carcinoma, Hepa... Metabolic Syndr...	Liver resection... Liver resection...	18 Years -	Ospedale V. Fazzi
The Female Health Dietary Intervention Study	NCT00779571	Polycystic Ovar... Morbid Obesity	Crispbread	19 Years - 38 Years	The Hospital of Vestfold

Spots Global Cancer Trial Database for morbid obesity