Partial Ileal Bypass Research Articles

Abstract 10882: Homozygous Familial Hypercholesterolemia: Luck Meets Opportunity Meets Knowledge

Introduction: Homozygous familial hypercholesterolemia (HoFH) is an inherited autosomal co-dominant disorder characterized by severely elevated circulating low-density lipoprotein (LDL). Monoclonal antibodies are now a treatment focus. Inhibition of proprotein convertase subtilisin kexin type 9 (PCSK9) increases the number of LDL receptors. Inhibition of angiopoietin-like 3 (ANGPTL3) inhibitor is associated with hypolipidemia and reduced risk of cardiovascular disease. We present the case of one of the oldest living patients with HoFH. Case Description: The patient is a 67-year-old black woman diagnosed with corneal arcus senilis and xanthomas at the age of 11, with total cholesterol (TC) levels >1000 mg/dL. At age 12, she underwent a partial ileal bypass (PIB) that lowered her TC by 39%. At age 32, she began statin therapy (Lovastatin, intensified to Atorvastatin at age 43). Despite concomitant dietary changes, her LDL levels remained elevated (>400 mg/dL). At age 34, multivessel coronary artery disease was detected and she initiated lipoprotein apheresis. Her LDL-C was reasonably well-controlled over the 20 years on LDL apheresis and high intensity statin therapy. Combined therapy with PCSK9 inhibitors (Evolocumab at age 61, replaced by Alirocumab at age 67) and ANGPTL3 inhibitor Evinacumab (age 67) lowered her LDL-C significantly. Genetic analysis confirmed two LDLR mutations: c.1846-1G>A and c.907C>T. Conclusion: Elevated cholesterol levels are linked to a higher risk of premature myocardial infarction and stroke. We report a case of HoFH with successful lowering of LDL levels on dual antibody and high intensity statin therapy along with PIB. Unlike PCSK9 inhibitors, ANGPTL3 inhibitors work independently of LDLRs by stimulating lipoprotein & endothelial lipase. This case offers insight into early surgical and combination drug therapy in HoFH and describes one of the longest living patients with HoFH illustrating treatment evolution.

Outcome After Partial Ileal Bypass for the Treatment of Ileocecal Intussusception in 6 Horses

Outcome After Partial Ileal Bypass for the Treatment of Ileocecal Intussusception in 6 Horses

Partial ileal bypass affords protection from onset of type 2 diabetes

BackgroundPartial ileal bypass (PIB) in the National Institutes of Health–sponsored Program on the Surgical Control of the Hyperlipidemias (POSCH) randomized controlled trial was found to reduce plasma cholesterol, in particular low density lipoprotein cholesterol, with concomitant retardation of atherosclerotic cardiovascular disease and increased life expectancy. Glucagon-like peptide-1, related to amelioration of type 2 diabetes, is increased over 5-fold after PIB. We hypothesized that PIB, in addition to its action on cholesterol metabolism, may also prevent type 2 diabetes. MethodsWe surveyed by telephone inquiry of former POSCH patients the 30+year posttrial incidence of type 2 diabetes or prediabetes, the presence of which was a trial exclusion criteria. We were able to contact 17.4% (n = 838) of the original POSCH population. ResultsOf 66 control responders, 17 contracted type 2 diabetes (25.8%); of 80 PIB responders, 8 contracted type 2 diabetes (10%). The difference between groups was significant (P = .015 by Fisher exact test) with an odds ratio of .320 for the PIB group and an over 2-fold (2.6) increase in the incidence of type 2 diabetes in the controls. Including borderline type 2 diabetes (prediabetic) patients, these values were 22 of 66 controls (33.3%) and 10 of 80 PIB patients (12.5%), with an odds ratio of .286 and a P<.004, and again an over 2-fold (2.7) increase in the incidence of type 2 diabetes in the control patients. ConclusionPIB appears to afford partial protection from the onset of type 2 diabetes for over 30 years.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) and the Lipid Regulatory Hypothesis

Background: The Lipid Regulatory Hypothesis (LRH) states that the best way to regress atherosclerotic plaque is to simultaneously decrease the cholesterol being transported into the arterial wall by low-density lipoprotein (LDL) and increase the cholesterol being removed from the arterial wall, via reverse cholesterol transport, by high-density lipoprotein (HDL). The cholesterol retention fraction (CRF) is defined as (LDL cholesterol minus HDL cholesterol) divided by LDL cholesterol. The Program on the Surgical Control of the Hyperlipidemias (POSCH), which employed partial ileal bypass as the intervention modality, was selected for verification of the LRH and the validity of the CRF. Methods: POSCH coronary arteriographic plaque progression or non-progression (stabilisation/regression) from baseline to 3 years was stratified on a five-by-five factorial grid with 25 cohort cells combining LDL cholesterol and HDL cholesterol changes from baseline to 1 year following intervention. Predictive capacity for arteriography changes of LDL cholesterol and CRF were compared. Statistics used were logistic regressions. Results: There were 731 paired arteriographic assessments of individual POSCH patients: 163 progression (22%) and 568 non-progression (stabilisation/regression) (78%). A reciprocal LDL cholesterol and HDL cholesterol relationship represented as a five-by-five factorial showed non-progression above and progression below the dividing diagonal. 100% (163/163) of patients with plaque progression had a rise in their CRF; and 100% (568/568) of patients with plaque non-progression had a fall in their CRF. LDL cholesterol, HDL cholesterol, and CRF were all highly significant predictors of plaque progression and non-progression (p&lt;0.0001). Conclusion: In POSCH, the partial ileal bypass-induced changes in the LDL cholesterol, HDL cholesterol, and the CRF are highly correlated with the sequential coronary arteriography changes of plaque progression and non-progression. This study affirms that individual patient prognosis can be predicted by the magnitude of response to lipid intervention.

Interview: Metabolic/bariatric surgery

Attended Columbia College (Valedictorian, 1954) and the College of Physicians and Surgeons of Columbia University. He studied under Drs Wangensteen and Varco at the University of Minnesota (USA). He is Professor of Surgery and Biomedical Engineering at the University of Minnesota, and was the first Owen H and Sarah Davidson Wangensteen Chair in Experimental Surgery at the University of Minnesota. Dr Buchwald served as President of the International Federation for the Surgery of Obesity (IFSO), American Society for Metabolic/Bariatric Surgery (ASMBS), Central Surgical Association, International Study Group for Implantable Insulin Delivery Devices and the Owen H Wangensteen Society. He was principal investigator of the Program on the Surgical Control of the Hyperlipidemias (POSCH), the first randomized clinical trial to demonstrate, in 1990, that cholesterol lowering via the partial ileal bypass resulted in reductions in myocardial infarctions, angina pectoris and peripheral vascular disease; arteriographic...

Metabolic surgery: an evolution through bariatric animal models

Metabolic surgery was developed through the application and experience gained from bariatric or weight loss procedures. Much of our knowledge from the procedures comes from the study of animal models, where they have revealed anatomic feasibility, systemic physiological elements and cellular metabolic effects. The first generation of operation included the jejunoileal bypass and partial ileal bypass that led to the development of the current procedures including Roux-en-Y gastric bypass, biliopancreatic diversion, adjustable gastric banding and sleeve gastrectomy. These operations carry significant metabolic benefits and can reduce the risk of diabetes, heart disease and cancer. Further insights from these animal models can reveal genetic, molecular and systemic effects that can enhance and develop the next generation of metabolic operations.

Metabolic Surgery. A New Surgical Discipline

Metabolic surgery can be considered as part of functional surgery, where the function to be corrected is a metabolic one. The first known example of metabolic surgery is probably the partial ileal bypass for the treatment of hypercholesterolemia. Modern metabolic surgery was preceded and inspired by bariatric surgery, basing on the strong metabolic effect of some obesity surgery operations, especially gastric bypass and biliopancreatic diversion (BPD), mainly active on type 2 diabetes mellitus. A true metabolic operation, primarily aimed at obtaining a favourable metabolic change, should on one side not provoke undue weight loss, on the other side act through specific mechanisms independent of weight changes. BPD, in clinical use since the late 70s, has proven to meet these requirements and is successfully used today in clinical trials for the treatment of the metabolic syndrome. New developed metabolic operations are represented by duodenal-jejunal bypass, endointestinal sleeve, and ileal interposition. All the efforts should be aimed at conceiving an operation equally effective as BPD, yet less invasive.

Fallo hepático neonatal como forma de presentación de colestasis intrahepática familiar progresiva

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomic-recessive inherited cholestatic disorders that begin in the neonatal period or in the first years of life. There are three types of PFIC defined by different mutations located in the gene responsible for the bile flow through the intrahepatic canalicular transporter system. These disorders usually present in children or young adults and the main clinical manifestations are cholestasis, jaundice and pruritus, and they progress slowly towards liver fibrosis in adult life. PFIC diagnosis is based on clinical suspicion, biochemical findings (that include normal gamma-glutamyl transpeptidase in type 1 and 2, but increased levels in type 3), image techniques that rule-out other disorders, and histological confirmation. Initial treatment consists of symptomatic relief of cholestatic symptoms with choleretic agents (urso-deoxycholic acid). Partial biliary derivation and ileal bypass are intermediate therapeutic options. In case of no response to these treatments, liver transplantation is indicated. We report the case of a neonate with PFIC type 2 presenting as a liver failure.

Abstract: 98 METABOLIC SURGERY FOR THE METABOLIC SYNDROME

The purpose of this study was to examine the effects of aspirin use on mortality and morbidity rates in a subset of the control group of the Program on the Surgical Control of the Hyperlipidemias (POSCH) that was stratified by cigarette smoking status at the time of randomization. The clinical impact of aspirin intake in cigarette smokers and former cigarette smokers has not been well studied. POSCH was a randomized, controlled, clinical trial designed to ascertain the effects of lipid modification by the partial ileal bypass operation on clinical end-points and arteriographic changes in postmyocardial infarction subjects with hypercholesterolemia. Cohorts of cigarette smokers in the diet-control group were evaluated for overall and atherosclerotic coronary heart disease (ACHD) mortality rates and recurrent confirmed nofatal myocardial infarction rates. In current cigarette smokers at baseline (n = 90) with a mean follow-up of 8.3 years, the overall mortality rate was 45.2% in patients with no aspirin use and 10.4% in patients who reported even infrequent aspirin use (relative risk = 4.3, 95% confidence interval (CI) = 2.4 to 10.6, p < 0.001). For ACHD mortality in this cohort, the relative risk was 17.1 (35.7% vs 2.1%, 95% CI = 1.4 to 125.0, p < 0.001); for the combined end-point of ACHD mortality and nonfatal myocardial infarction, the relative risk was 2.4 (40.5% vs 16.7%, 95% CI = 1.25 to 5.1, p = 0.018). In former cigarette smokers with no aspirin use at baseline (n = 92) with a mean follow-up of 8.8 years, the relative risk of overall mortality was 3.1 (20.0% vs 6.5%, 95% CI = 1.0 to 10.2, p = 0.07), ACHD mortality, 3.4 (167.% vs 4.8%, 95% CI = 0.9 to 13.5, p = 0.11); and combined ACHD mortality and confirmed nonfatal myocardial infarction, 1.1 (23.3% vs 21.0%, 95% CI = 0.5 to 2.5, p = 0.79). After adjustment for age, gender, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, Quetelet index, ejection fraction, extent of coronary disease at baseline, and length of follow-up, none of these relative risks changed appreciably. The risk of overall mortality, aCHD mortality, and combined ACHD mortality and recurrent confirmed nonfatal myocardial infarction may be significantly reduced by aspirin use in post-myocardial infarction cigarette smokers. However, the subjects included in this analysis were highly selected and may not be totally representative of postmyocardial infarction patients. Nonetheless, when extensive counseling regarding the negative consequences of continued cigarette smoking fails to cause smoking cessation in postmyocardial infarction patients, it may be exceedingly prudent to recommended aspirin usage.

Five-Year Follow-up after Laparoscopic Roux-en-Y Gastric and Partial Ileal Bypass for Treatment of Morbid Obesity and Uncontrolled Hyperlipidemia

Morbid obesity is associated with significant co-morbid illnesses and mortality. Hyperlipidemia is strongly associated with atherosclerosis and cardiovascular disease. Laparoscopic Roux-en-Y gastric bypass (LRYGB) is a proven and effective procedure for the treatment of morbid obesity and its related co-morbid illnesses. In a randomized prospective clinical trial, partial ileal bypass showed sustained control of hyperlipidemia and reduced comorbidities. Given risks of surgery, pharmacologic agents are the current primary therapy for hyperlipidemia. However, a morbidly obese patient with medically refractory hyperlipidemia may benefit from a combined laparoscopic Roux-en-Y gastric bypass and partial ileal bypass. We are describing the first case of a totally laparoscopic approach. A 56-year-old female patient with morbid obesity (BMI 45.2 kg/m(2)) and medically refractive hyperlipidemia underwent a combined LRYGB and partial ileal bypass in 2002. She was continuously followed for 5 years for weight profile, hyperlipidemia, post-operative complications, and morbidity. Five-year follow-up of the patient showed sustained excess body weight loss. Her lipid profile has approached normal ranges with less medication. She experienced no comorbidities related to surgery or hyperlipidemia. Laparoscopic Roux-en-Y gastric bypass and partial ileal bypass may be the best option for the patient who has morbid obesity and medically refractory hyperlipidemia and should be considered for select patients.

Surgical Intervention For The Treatment Of Morbid Obesity And The Dyslipidemias

To meet the expanding epidemic of worldwide morbid obesity, giving rise to significant dyslipidemia, knowledge of the surgical history of the development of the partial ileal bypass operation, the contribution of the Program on the Surgical Control of the Hyperlipidemias (POSCH), and the efficacious outcomes of bariatric surgery procedures is essential to the armamentarium of the researcher and the practitioner. This review provides a brief summary of metabolic surgery as applied to the normalization of circulating lipid concentrations, the impact of this modification on body lipid mechanisms and the practical use of bariatric surgery procedures today.

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part IV: The 1984 Coronary Primary Prevention Trial ends it—almost

As of the early 1980s, despite the wealth of evidence from experimental animal models, the extensive epidemiologic evidence, the powerful genetic evidence, and the strongly suggestive clinical intervention trial results, most clinicians still remained unpersuaded regarding the relevance of the lipid hypothesis. What was needed was a well-designed, large-scale, long-term, double-blind study demonstrating a statistically significant impact of treatment on coronary heart disease events. The National Institutes of Health (NIH) had laid the groundwork for such a study as early as 1970, but the study was not completed and the results published until 1984. This study, the Coronary Primary Prevention Trial, showed that treatment with a bile acid binding resin reduced major coronary events in hypercholesterolemic men by 19%, with a P value of 0.05. The NIH followed this up with a national Consensus Development Conference on Lowering Blood Cholesterol to Prevent Heart Disease. For the first time, the NIH now went on record advocating screening for hypercholesterolemia and urging aggressive treatment for those at high risk. The Institute initiated a national cooperative program to that end, the National Cholesterol Education Program. For the first time, preventing coronary heart disease became a national public health goal.

Heparin-mediated extracorporeal low-density lipoprotein precipitation: rationale for a specific adjuvant therapy in cardiovascular disease

Various radical measures for the treatment of severe hypercholesterolemia such as partial ileal bypass, portocaval shunt, liver transplantation and plasma exchange have been tested in patients in whom drug and diet failed or were insufficient. Although effective, most of these treatments have severe side effects and are not routinely used. For hypercholesterolemic patients LDL-apheresis has proved to be the most promising and safe way as an adjuvant therapy. Several LDL-apheresis procedures with a varying degree of selectivity and efficiency have subsequently been developed. One of them is the H.E.L.P. system which was introduced in 1984 and has now been widely used. Besides the marked reduction of LDL particles by all techniques it has become apparent that only the H.E.L.P. system results in an equally significant change in hemostaseology, hemorheology and vasomotion because of its simultaneously removal of LDL, Lp(a), fibrinogen and CRP. This contribution reviews the application of the H.E.L.P. system as a valuable therapeutic tool for the treatment of various atherothrombotic and microcirculatory disorders such as prevention of early graft occlusion after coronary artery bypass grafting, treatment of peripheral vascular disease, stroke and preeclampsia.

Exploiting the Vascular Protective Effects of High-Density Lipoprotein and Its Apolipoproteins

“ An invasion of armies can be resisted but not an idea whose time has come.” —Victor Hugo. Vaso-occlusive disease resulting from atherosclerosis and thrombosis is the leading cause of death and morbidity in the United States and other industrialized nations. Although the precise cause of atherosclerosis is unclear, an emerging paradigm suggests that atherosclerosis involves multiple pathways in which lipoprotein entry and retention, injury to the vessel wall from diverse stimuli, and an associated long-term inflammatory and immune response seem to play a key role.1–4 Dyslipidemia characterized predominantly by elevated levels of one or more circulating non-HDL cholesterol lipoproteins [LDL, VLDL, lipoprotein(a), triglycerides] and/or reduced HDL cholesterol is one of the key risk factors for atherosclerosis and cardiovascular disease.5–16 Over the past several years, a number of large, prospective, randomized, controlled clinical trials have demonstrated both angiographic and clinical benefits of lipid-lowering therapy, with a significant reduction in fatal and nonfatal cardiovascular events.17–23 These studies have primarily targeted LDL cholesterol through pharmacotherapy (mostly statins), with or without dietary counseling, lifestyle modification, or surgery (intestinal bypass in Program on the Surgical Control of the Hyperlipidemias [POSCH] trial). Overall, a significant and clinically worthwhile relative risk reduction ranging from 20% to 40% in major cardiovascular events has been achieved with these strategies, without significant adverse effects or increased noncardiovascular mortality. These remarkable results prompted Brown and Goldstein24 to predict that heart attacks will be gone with the century. This clearly reflects an overoptimistic point of view, because 60% to 70% of adverse cardiovascular events continue to occur despite LDL-lowering therapy. Potential reasons why cardiovascular events may continue to occur despite low LDL levels or despite LDL-lowering therapy include the following: (1) we may not be lowering LDL cholesterol to optimal levels, because optimal levels are not clearly …

Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials

Objective: To investigate the association between cholesterol lowering interventions and risk of death from suicide, accident, or trauma (non-illness mortality).Design: Meta-analysis of the non-illness mortality outcomes of large, randomised clinical...

Surgical Management of Dyslipidemia: Clinical and Experimental Evidence

Coronary artery disease (CAD) is still a major cause of mortality in developed countries, and dyslipidemia is one of its major causes. In an attempt to reduce both mortality and morbidity from CAD, several dietary, pharmacological, and surgical approaches have been used to reduce plasma cholesterol levels. In this brief review, we summarize the evidence for cholesterol-lowering effects and safety of partial ileal bypass (PIB) procedure in both human and animal studies. The results of the Program on the Surgical Control of the Hyperlipidemias (POSCH), which involved a total of 838 subjects with myocardial infarction, are promising. A 5-year follow-up of this study revealed significant reductions of up to 27% in total cholesterol (TC) and up to 42% in low-density lipoprotein (LDL) cholesterol levels along with an increase of up to 8% in high-density lipoprotein (HDL) cholesterol levels as compared to controls. These changes were associated with other benefits such as increased HDL/TC and HDL/LDL ratios, and a significant decrease in apolipoprotein (apo) B100 and increase in apo AI levels. Similar results were also demonstrated by other studies. PIB surgery is one of the most effective methods for reduction of plasma cholesterol levels, particularly in patients with heterozygous familial hypercholesterolemia. This procedure is also applicable to treatment of sitosterolemia, a rare genetic disorder in which the absorption of plant sterols is abnormally high. Although no major complications of this method have been reported, more extensive studies are required to evaluate its long-term effects on renal and hepatic function. Similarly, long-term impact of this procedure on progression/regression of atherosclerotic lesions must be documented. Finally, indications for this procedure should be carefully considered, particularly in view of availability of other treatments of dyslipidemia.

Clinical outcome of patients with familial hypercholesterolemia and coronary artery disease undergoing partial ileal bypass surgery.

Familial hypercholesterolemia is characterized by high serum levels of total cholesterol and LDL-cholesterol. It may be homozygous or heterozygous. In homozygous patients, LDL-cholesterol levels range from 500 to 1000 mg/dL and coronary artery disease is precocious, usually manifesting itself between the 2nd and 3rd decades of life. The diagnosis is often made by the presence of xanthoma tuberosum and tendinous xanthomas that appear between the 1st and 2nd decades of life. The use of high doses of statins or even unusual procedures (apheresis, partial ileal bypass surgery, liver transplantation, gene therapy), or both, is necessary for increasing survival and improving quality of life, because a reduction in cholesterol levels is essential for stabilizing the coronary artery disease and reducing xanthomas. We report our experience with 3 patients with xanthomatous familial hypercholesterolemia and coronary artery disease, who underwent partial ileal bypass surgery. Their follow-up over the years (approximately 8 years) showed a mean 30% reduction in total cholesterol, with a significant reduction in the xanthomas and stabilization of the coronary artery disease.

Lipid distress-syndrome in surgery

The paper reviews the results of treatment of lipid distress-syndrome manifested in obliterating atherosclerosis, gallbladder cholesterosis, chronic abdominal ischemia, lipid pancreatitis, and lipid hepatosis. New diagnostic methods for these diseases are described. The efficiency of partial ileal bypass and conservative treatment with mineral oil-pectin emulsion Fishant in correcting dyslipoproteinemia is demonstrated. The therapeutic results are confirmed by radioisotopic and ultrasonic studies.

Role of the surgeon in managing hypercholesterolemia

In 1962 the partial ileal bypass (PIB) was introduced as the first operation specifically designed to treat hypercholesterolemia.1 Ten years later the Program on the Surgical Control of the Hyperlipidemias (POSCH) was launched, with PIB used as the intervention modality. POSCH (1972 to 1997) has been the only surgical randomized clinical trial to test the efficacy of cholesterol lowering in the management of atherosclerosis and its clinical manifestations.2-4 PIB and POSCH are the subjects of this short review of the role of the surgeon in managing hypercholesterolemia.

Role of the surgeon in managing hypercholesterolemia

In 1962 the partial ileal bypass (PIB) was introduced as the first operation specifically designed to treat hypercholesterolemia. 1 Buchwald H. Surgical operation to lower circulating cholesterol. Circulation. 1963; 28: II649 Google Scholar Ten years later the Program on the Surgical Control of the Hyperlipidemias (POSCH) was launched, with PIB used as the intervention modality. POSCH (1972 to 1997) has been the only surgical randomized clinical trial to test the efficacy of cholesterol lowering in the management of atherosclerosis and its clinical manifestations. 2 Buchwald H Varco RL Matts JP Long JM Fitch LL Campbell GS et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. N Engl J Med. 1990; 323: 946-955 Crossref PubMed Scopus (853) Google Scholar , 3 Buchwald H Matts JP Fitch LL Campos CT Sanmarco ME Amplatz K et al. Changes in sequential coronary arteriograms and subsequent coronary events. JAMA. 1992; 268: 1429-1433 Crossref PubMed Scopus (163) Google Scholar , 4 Buchwald H Campos CT Varco RL Boen JR Williams SE Hansen BJ et al. Effective lipid modification by partial ileal bypass reduced long-term coronary heart disease mortality and morbidity: five-year posttrial follow-up report from the POSCH. Arch Intern Med. 1998; 158: 1253-1261 Crossref PubMed Scopus (115) Google Scholar PIB and POSCH are the subjects of this short review of the role of the surgeon in managing hypercholesterolemia.