Comparison of changes in lipid profile after bilio-intestinal bypass and gastric banding in patients...

© FD-Communications Inc. Obesity Surgery, 15, 2005 367

Obesity Surgery, 15, 367-377

Background: The presence of hypercholesterolemia iscurrently not considered a selection criteria for perform-ing gastric restrictive or diversionary bariatric surgery.

Methods: We prospectively investigated the effectsof the bilio-intestinal bypass (BI-bypass) with a widecholecysto-jejunal anastomosis and of adjustablegastric banding (AGB) on blood lipid concentrationsin obese patients. To clarify the mechanism of thehypocholesterolemic effect of the BI-bypass, dailyfecal sterol excretion was measured by gas-liquidchromatography (GLC).

Results: At 1 year after BI-bypass compared tobaseline, the hypercholesterolemic (n=18) and thenormocholesterolemic (n=19) patients significantlyreduced total (-38% and -27%, respectively), LDL(-47% and -24%, respectively) and HDL (-11% and-13%, respectively) cholesterol and total / HDL cho-lesterol ratio (-25% and -13%, respectively). At 1 yearafter AGB, the total / HDL cholesterol ratio was signif-icantly decreased (-11%) compared to baseline inhypercholesterolemic (n=12) but not in normocholes-terolemic (n=6) patients, while total and LDL choles-terol were not affected in both groups. At 3 years afterBI-bypass compared to baseline, the hypercholes-terolemic (n=9) and the normocholesterolemic (n=11)patients significantly reduced total (-43% and -28%,

respectively) and LDL (-53% and -29%, respectively)cholesterol and total / HDL cholesterol ratio (-38% and-21%, respectively). The BI-bypass induced a signifi-cant (P<0.005; n=7) 6-fold increase in mean fecal cho-lesterol output.

Conclusions: The BI-bypass but not the AGB leadsto a persistent and marked beneficial effect on bloodLDL cholesterol associated with an increased choles-terol fecal output. BI-bypass but not AGB is indicatedin morbidly obese patients with hypercholesterolemia.

Key words: Bilio-intestinal bypass, cholecysto-jejunal anas-tomosis, gastric banding, bariatric surgery, morbid obesity,cholesterol malabsorption, total and LDL cholesterol

Abbreviatons: BI-bypass, bilio-intestinal bypass, AGB,adjustable gastric banding, GLC, gas-liquid chromatogra-phy, FPLC, fast protein liquid chromatography

Introduction

Bariatric surgery is indicated in morbidly obese(BMI ≥40 kg/m2) and in severely obese (BMI 35-40kg/m2) patients with accompanying co-morbid con-ditions.1 The goal of bariatric surgery is not toreduce weight per se, but to treat also the co-mor-

Comparison of Changes in Lipid Profile afterBilio-intestinal Bypass and Gastric Banding inPatients with Morbid Obesity

Stefano Ginanni Corradini, MD, PhD1; Annarita Eramo, MD1; CarlaLubrano, MD2; Giovanni Spera, MD2; Alessandra Cornoldi, MD, PhD2;Antonio Grossi, MD1; Francesca Liguori, MD1; Maria Siciliano1; MassimoCodacci Pisanelli, MD3; Gerald Salen, MD4; Ashok Kumir Batta, PhD4;Adolfo Francesco Attili, MD1; Marco Badiali, MD5

1Dipartimento di Medicina Clinica Divisione di Gastroenterologia, 2Dipartimento diFisiopatologia Medica, 3IV Patologia Chirurgica, Dipartimento di Medicina Sperimentale ePatologia, 5Dipartimento Scienze Chirurgiche, Università “La Sapienza” Roma I e II Facoltà,Italy; 4Department of Medicine (Gastroenterology Division) University of Medicine and Dentistry-New Jersey Medical School, Newark, NJ, USA

Reprint requests to: Stefano Ginanni Corradini, MD, PhD, ViaAsmara 9-A, 00199 Rome, Italy. Fax 39-06-4453319;e-mail: [email protected]

bidities of obesity when present.1 The presence ofhypercholesterolemia has not been identified as aselection criteria for performing pure gastric restric-tive or malabsorptive surgery.1,2 Lowering LDL cho-lesterol, a primary contributor to the atheroscleroticprocess, is the main goal to prevent coronary heartdisease.3,4 Current U.S. lipid-lowering guidelinesindicate that optimal blood levels of LDL choles-terol are <100 mg/dl. However, there is accumulat-ing evidence that reduction to even lower LDL tar-get values in high-risk patients, including those withthe metabolic syndrome, may provide additionalbenefit in coronary heart disease prevention.3,4

Total and LDL cholesterol have been mostlyreported to be unchanged or only slightly reducedafter pure restrictive bariatric surgery.5-10 A reduc-tion of total and LDL serum cholesterol in the 10-13% range has been reported in two studies.11,12

However, most studies have shown a postoperativeincrease of HDL after restrictive surgery with con-sequent reduction of the total cholesterol to HDLcholesterol ratio.5,6,8-11

The jejunoileal (JI) bypass, an abandoned opera-tion because of its serious complications, is a puremalabsorptive operation associated with a stronghypocholesterolemic effect.13 The BI-bypass is aclinically safe purely malabsorptive operation inwhich the blind intestinal loop of the JI-bypass isanastomosed to the gallbladder, allowing a portionof the bile to transit into it.14-19 This cholecystojeju-nal anastomosis eliminates stasis in the bypassedbowel and reduces the amount of bile salts malab-sorbed with respect to the JI-bypass.15-17,19 A 25%decrease of serum cholesterol has been reported afterthe BI-bypass performed with a termino-terminalcholecystojejunal anastomosis to the fundus of thegallbladder.16

In the present study, we prospectively studied theeffects on blood lipid concentrations induced by theBI-bypass performed with a wide latero-lateralcholecystojejunal anastomosis to the body of thegallbladder and by the AGB in two comparablegroups of morbidly obese patients. In addition, weinvestigated whether the hypocholesterolemic effectof the BI-bypass is persistent and whether it is director mediated by weight loss.

Materials and Methods

The study protocol was in compliance with ourinstitute's ethical guidelines for human studies, andconsent was obtained from all patients.

Patients and Blood Lipid Studies

Two groups of morbidly obese patients wereprospectively followed up: a) 37 consecutive patients(BMI 48.0 ± 1.0 kg/m2, age 35.4 ± 1.2 years, serumcholesterol 194.3 ± 5.3 mg/dl, serum triglycerides140.2 ± 22.8; means ± SEM; Male/Female 17/20, 4diabetics, 18 hypercholesterolemic, 4 hypertriglyc-eridemic) submitted to the BI-bypass; b) 18 consec-utive patients (BMI 43.7 ± 1.4 kg/m2, age 42.3 ± 2.3years, serum cholesterol 218.7 ± 8.7 mg/dl, serumtriglycerides 158.0 ± 18.7; means ± SEM;Male/Female 6M/12F, 2 diabetics, 12 hypercholes-terolemics, 3 hypertriglyceridemics) submitted to theAGB. Serum lipid levels and BMI were measured atbaseline (within 2 months before the operation), and1, 6 and 12 months after the operation, and at 12-month intervals thereafter. Patients with total serumcholesterol concentration >200 mg/dl and/or LDLserum concentration >130 mg/dl were consideredhypercholesterolemic. No patient took hypolipi-demic drugs at any time before and during the study.

To investigate the time sequence of blood choles-terol changes immediately after the BI-bypass, inthe short-term study plasma lipid levels were com-pared immediately before and after surgery in 8patients (BMI 47.4 ± 2.3 kg/m2, plasma cholesterol163.7±14.8 mg/dl, plasma triglycerides 102.6±9.4;age 39.1±3.5 years; means± SEM; Male/Female4/4) who had an ideal postoperative period and wereable to ingest the standard diet beginning from the9th or 10th postoperative day. Blood samples wereobtained at 0800 hours in all occasions: a) after an84 hour standard diet (2334 Kcalories/day, 61% car-bohydrates, 17% fats, 22% proteins, cholesterol260 mg/day, plant sterols 53 mg/day) followed by a12-hour fasting period, both on the day of surgerybefore the operation was commenced, and on the9th or 10th postoperative day; b) after a 36-hourfasting period during which patients were allowedto drink only water and received saline (1000 ml),glucose 5% (1000 ml) and Ringers lactate (500 ml)

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Obesity Surgery, 15, 2005 369

solutions I.V., followed by a 12-hour fasting withoutI.V. infusion, both on the fourth preoperative and onthe second postoperative day; c) under free diet con-ditions, followed by 12-hour fasting, both on the 7thpreoperative and on the 30th postoperative day.

To verify that the plasma lipid changes whichimmediately followed the BI-bypass were specificfor this operation, a short-term plasma lipid studyunder the same standard diet and time schedule wasalso performed on 6 non-obese patients (BMI 25.1± 1.4 kg/m2, plasma cholesterol 155.3 ± 10.9 mg/dl,plasma triglycerides 105.4 ± 7.5; age 49.0 ± 6.1years; means ± SEM; Male/Female 5/1) submittedto major surgery not involving the upper gastroin-testinal tract, small bowel and biliary tract (2 subto-tal colectomies for cancer and 1 for villous ade-noma, 1 hysterectomy for uterine fibromatosis, 2nephrectomies for non-neoplastic disease). This wasconsidered as the control surgery group.

The Bilio-intestinal Bypass and GastricBanding Operations

All operations were performed between 1998 and2001 at the Hospital of the University “LaSapienza”of Rome. Obese patients free of primitiveendocrine diseases, major psychiatric diseases andpreviuos severe medical conditions apart from obe-sity were selected for surgical treatment of obesity.For the BI-bypass, patients were selected who eitherhad an eating disorder (binge eating, grazing, nighteating, emotional eating) and/or did not want tochange their dietary habits.19 AGB was performed inpatients without eating disorders who agreed tochange their dietary habits. The BI-bypass surgicalprocedure with a cholecystojejunal anastomosis(Figure 1) was as previously described but withminor changes.14-17 The jejunum was transected 30cm distal to the ligament of Treitz and anastomosedto the terminal ileum with a latero-lateral anastomo-sis 12-20 cm proximal to the ileocecal valve using aGIA-60 stapler (Autosuture Multifire, Norwalk, CT,USA). The blind loop was laterally anastomosed tothe body of the gallbladder using the longest GIAstapler possible (Ethicon Endo-Surgery Inc,Cincinnati, OH, USA), to obtain a long anastomosisto facilitate bile transit and avoid its closure.Particular care was taken to avoid bile removal fromthe gallbladder during the operation.

The AGB operation was as previously describedto obtain a 15-20 ml gastric pouch.20 All patients inthe AGB group were operated using the peri-gastrictechnique with the 9.75-cm Lap-Band® system(Inamed Health, Santa Barbara, CA). Amongpatients submitted to AGB, 10 were operated with alaparotomic and 8 with a laparoscopic approach.

Lipid Analysis

Serum total and HDL cholesterol and triglyceride con-centrations were measured on fresh serum by the auto-mated enzymatic method (Dimension Dade BehringAnalyzer and reagent cartridges from Dade BehringS.p.A., Milan, Italy). All samples were assayed induplicate with intrassay and interassay mean coeffi-cients of variation of 2% and 4%, respectively.

In the short-term plasma lipid study, total choles-terol and triglycerides were measured on freshplasma by enzymatic kits (Bayer S.p.A DivisioneDiagnostici, Milan, Italy). All samples were assayedin duplicate with intrassay and interassay mean

Hypocholesterolemic Effect of Bilio-intestinal Bypass

Figure 1. Schematic diagram of BI-bypass with cholecys-tojejunal anastomosis. Proximal jejunum is transected 30-35 cm from the ligament of Treitz and anastomosed to ter-minal ileum with a latero-lateral anastomosis 12-20 cmfrom ileocaecal valve. The blind loop is laterally anasto-mosed to the body of the gallbladder to obtain a 6-7.5 cmlong anastomosis. CJA: cholecysto-jejunal anastomosis;JIA: jejuno-ileal anastomosis. A major fraction of bile isshunted through the CJA away from the duodenum andproximal jejunum (depicted in grey).

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coefficients of variation of 4% and 7%, respectively.To standardize for the different degree of hydration,in the short-term plasma lipid studies, total lipidplasma levels were compared before and after sur-gery under each nutritional condition, by multiply-ing each postoperative measured concentration forthe ratio between the preoperative and the respectivepostoperative hematocrit value.21 In the short-termstudy, lipoproteins were measured in fresh plasmaby Fast Protein Liquid Chromatography (FPLC)using a Superose 6 column (Pharmacia, Uppsala,Sweden) as previously described.22 Recoveries fromthe FPLC column were 92.7 ± 2.2% and 92.7 ±3.9% for cholesterol and triglycerides, respectively(means±SEM).

Fecal Sterol Measurement

Seven patients operated by BI-bypass, after 48 hoursof standard diet (see the Methods section for dietcomposition), collected their 24-hour stool on the 2ndpreoperative day and on the 9th or 10th postoperativeday. Patients who did not completely assume thestandard diet were excluded. Stools were weighed,homogenized and frozen at -80˚C in aliquots andfreeze-dried. Fecal bile acids and neutral sterols werequantified by GLC, as previously described.23

Statistical Analysis

Data were expressed as mean ± SEM. The mean val-ues of blood lipid concentrations before and aftersurgery were compared by the Student’s t-test forpaired data. The mean percent changes of totaltriglycerides, total cholesterol and BMI after the BI-bypass and the AGB were compared, at the sametime-point, by Student’s t-test for unpaired data.Significance was set at 0.05.

Results

Comparison of Effect on BMI and Blood LipidLevels of BI-bypass with a CholecystojejunalAnastomosis and the AGB

As shown in Figure 2, panel A, 1 month after sur-gery, the BMI percent reduction did not differ afterthe two operations, while at 6 and 12 months the BI-

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Figure 2. Percent sequential reductions (means±SEM) ofBMI (Panel A), serum triglycerides (Panel B), and totalserum cholesterol (Panel C) after the BI-bypass (circles;n=37) and the AGB (squares; n=18), compared to therespective preoperative values.*P<0.01, **P<0.001, ***P<0.00001 BI-bypass vs AGB atthe same time-point (unpaired Student's two-tailed t-test).

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bypass induced a significantly greater BMI percentreduction than the AGB. At 12 months after theoperation, BMI reduction was 34.5 ± 0.8 vs 48.0±1.0 kg/m2 (12 months vs baseline, respectively) inthe BI-bypass group and 35.3 ± 1.5 vs 43.7 ± 1.4kg/m2 (12 months vs baseline, respectively) in theAGB group. As shown in Figure 2, panel B, 1 monthafter the operation, AGB induced a significantlygreater percent reduction of serum triglycerides thanBI-bypass. At 6 and 12 months after the operations,both operations induced similar triglyceride percentreductions. In fact, at 12 months after the operation,triglyceride concentration was 87.5 ± 9.5 vs 140.2 ±22.8 mg/dl (12 months vs baseline, respectively) inthe BI-bypass group and 101.6 ± 12.4 vs 158.0 ±18.7 mg/dl (12 months vs baseline, respectively) inthe AGB group.

As shown in Figure 2, panel C, at each time-pointthe BI-bypass induced a significantly greater per-cent reduction of serum total cholesterol than theAGB. Already 1 month after the BI-bypass totalserum cholesterol was decreased by 33% comparedto baseline (128.4 ± 3.9 vs 194.3 ± 5.3 mg/dl, 1month vs baseline, respectively) and LDL choles-terol was decreased by 36% compared to baseline(74.0 ± 3.7 vs 120.5 ± 5.4 mg/dl, 1 month vs base-line, respectively). The reduction of serum total cho-lesterol concentration compared to baseline, wasconstant at 6 months and 1 year after the BI-bypass,while total cholesterol was not affected by the AGBat that time (Figure 2, panel C). At 1 year after theBI-bypass, LDL cholesterol was significantlydecreased (P<0.0001) by 35% compared to baseline(74.8 ± 2.8 vs 120.5 ± 5.4 mg/dl, 1 year vs baseline,respectively), while LDL cholesterol was notaffected by AGB (136.8 ± 6.4 vs 134.5 ± 5.9 mg/dl,1 year vs baseline, respectively). One year after theBI-bypass serum HDL cholesterol concentrationwas significantly reduced (P<0.001) by 12% com-pared to baseline (37.8 ± 1.0 vs 44.8 ± 1.9 mg/dl, 1year vs baseline, respectively), while AGB inducedan increase in HDL cholesterol, although the differ-ence did not reach statistical significance (60.3 ± 3.0vs 52.2 ± 4.7 mg/dl, 1 year vs baseline, respec-tively). At 1 year after the BI-bypass, the total cho-lesterol to HDL cholesterol ratio was significantlyreduced (P<0.0001) by 19% (3.48 ± 0.14 vs 4.50 ±0.19, 1 year vs baseline, respectively). One yearafter the AGB the total cholesterol to HDL choles-

terol ratio was significantly reduced (P<0.05) by14% (3.69 ± 0.18 vs 4.46 ± 0.23, 1 year vs baseline,respectively).

When patients were divided according to the pre-operative presence or absence of hypercholes-terolemia, all the hypercholesterolemic patients nor-malized their serum cholesterol already 1 monthafter the BI-bypass, but none of the patients in theAGB group achieved the normalization at any time-point. The total and LDL serum cholesterol percentreductions induced by the BI-bypass at 1 year afteroperation compared to baseline were significantlyhigher in patients with hypercholesterolemia than inthose normocholesterolemic (Table 1).

There was no mortality after both operations. Post-surgery clinical adverse events after the BI-bypasswere as follows: rectal abscesses, anus inflammationor hemorrhoids were common but disappeared within3 months after surgery when bowel movements werereduced; seromas (8.1%), all resolved within 30 daysafter surgery; abdominal hernias (13.5%); gallblad-der-jejunum anastomotic fistulas (5.4%), closedwithin few days. An event of acute renal failureimmediately after surgery (2.7%) resolved with phar-macological therapy; hypoglycemic crisis (5.4%)resolved with correct nutritional intervention. Allpatients experienced a mild transient (3-6 months)serum aminotransferase increase. Mineral and vita-min supplements were taken by all patients duringthe first 2 postoperative years, and no alterations ofthese nutrients were observed.

Long-term Follow-up after BI-bypass withCholecystojejunal Anastomosis

A total of 20 patients in the BI-bypass group hadreached the 3-year follow-up at the time of study com-pletion (Table 2). BMI reduction occurred rapidlyafter the operation and reached a plateau 2 years afterthe operation. At 3 years after BI-bypass, the BMIreduction was 30.7±0.8 vs 46.2±1.6 kg/m2 (3 years vsbaseline, respectively) corresponding to a percentBMI reduction of 33.3±2.3%. Serum triglyceridereduction was slow. At 3 years after the operation,serum triglyceride concentration was significantlyreduced (P<0.05) compared to baseline (68.6±5.4 vs155.7±41.0 mg/dl, respectively) corresponding to apercent triglyceride reduction of 37.6±6.3%.

Total serum cholesterol was already markedly




reduced by 32% at 1 month after the BI-bypasscompared to baseline and remained stable up to 3years after the operation. Total and LDL serum cho-lesterol were significantly reduced at 3 years afterBI-bypass compared to baseline, while HDL cho-lesterol did not change (Table 2). At 3 years after theoperation, the total cholesterol to HDL cholesterolratio was significantly reduced by the BI-bypass.

When patients were divided in two groups accord-ing to the preoperative presence or absence ofhypercholesterolemia, all the hypercholesterolemicpatients normalized their serum cholesterol. Thetotal, LDL cholesterol and total cholesterol to HDLcholesterol ratio percent reductions induced by theBI-bypass at 3 years after the operation compared tobaseline were significantly higher in patients whohad had hypercholesterolemia than in those who hadbeen normocholesterolemic (Table 2).

Twenty percent of patients had abdominal bloat-ing/distention, arthralgia and/or dermatitis, likelydue to anaerobic bacterial overgrowth from somereflux at the jejunoileal anastomosis. These compli-cations resolved upon intestinal antibiotic treatmentwith metronidazole, which was highly effective. At

3 years after BI-bypass, serum transaminases didnot differ from baseline values (ALT: 43.2±7.1 vs45.2±7.3 U/L, respectively) and (AST: 23.4±3.6 vs23.1±2.3 U/L, respectively). Also serum proteinconcentration did not differ from baseline values(7.03±0.11 vs 7.30±0.13 g/dl, respectively). Duringthe long-term follow-up, prolonged prothrombintime occurred in 20% of patients and normalizedafter vitamin K supplementation. Small asympto-matic kidney stones occurred in 10% (two patients)who did not take calcium supplement for >6 months.

Immediate Postoperative Effect of BI-bypass with Cholecystojejunal Anastomosison Blood Lipid Concentrations and FecalSterol Excretion

To investigate whether the reduction of blood cho-lesterol was a direct effect of the BI-bypass, plasmalipid concentrations and fecal sterol excretion weremeasured preoperatively and in the immediate post-operative period under controlled nutritional condi-tions in 8 patients. The mean plasma total choles-terol concentration was significantly lower at day 2

Table 1. Effect of the BI-bypass and AGB on serum cholesterol levels 1 year after operation in obese patients whowere hypercholesterolemic and normocholesterolemic at baseline

Hyper-C BI-bypass Normo-C BI-bypass Hyper-C AGB Normo-C AGB(n=18) (n=19) (n=12) (n=6)

Pre-op TC (mg/dl) 220.5±5.2e 169.4±34.0 239.3±7.4e 177.5±4.6Post-op TC (mg/dl) 137.4±6.6c 123.4±4.1c 234.5±6.6e 178.1±7.2Post-op TC change (%) -37.6±2.7d -26.9±2.3 -1.7±2.2 +0.6±4.3

Pre-op LDL-C (mg/dl) 150.2 ±4.7e 95.7±3.7 147.0±6.1e 109.5±1.6Post-op LDL-C (mg/dl) 78.5±4.6c 71.7±3.4c 152.0±4.0d 106.4±8.3Post-op LDL-C change (%) -47.4±3.1e -24.2±3.4 +5.0±4.3 -2.4±8.4

Pre-op HDL-C (mg/dl) 44.9±2.9 43.2±3.4 57.2±6.6 42.2±1.8Post-op HDL-C (mg/dl) 37.7±1.6 37.8±1.5a 61.9±3.4 57.1±6.0Post-op HDL-C change (%) -11.3±5.4 -13.2±3.4 +16.6±9.6 +43.6±14.5

Pre-op TC/HDL (ratio) 5.13±0.24d 3.97±0.23 4.56±0.33 4.26±0.27Post-op TC/HDL (ratio) 3.62±0.19b 3.35±0.20b 3.89±0.20a 3.30±0.37Post-o TC/HDL change (%) -25.3±7.0 -13.3±4.4 -10.7±6.3 -20.6±10.5

Values are mean±SEM. Hyper-C= hypercholesterolemic patients at baseline; Normo-C= normocholesterolemicpatients at baseline; TC= serum total cholesterol; LDL-C= serum LDL cholesterol; HDL-C= serum HDL cholesterol.aP<0.05, bP<0.005, cP<0.0001 postoperative vs respective preoperative value (paired Student’s two-tailed t-test).dP<0.005, eP<0.0001 hypercholesterolemic vs normocholesterolemic patients submitted to the same operation(unpaired Student’s two-tailed t test).


under fasting conditions (115.8±11.4 vs 156.1±15.9mg/dl), at day 9 under standard diet (120.4±11.5 vs170.1±13.2 mg/dl), and at day 30 after the operationunder free diet (117.4±8.3 vs 163.8±14.8 mg/dl),compared to the respective preoperative value(Figure 3, Panel A). The mean plasma triglycerideconcentrations did not differ before and after theoperation (Figure 3, Panel B).

LDL cholesterol was significantly lower immedi-

ately after BI-bypass, under all the nutritional con-ditions tested (Table 3). VLDL cholesterol andtriglycerides were also significantly reduced imme-diately after the BI-bypass, under fasting and freediet (Table 3).

As an indirect proof that the plasma lipid changesimmediately following the BI-bypass were specificfor this operation, no statistical difference wasfound between the preoperative and 9-day postoper-


Table 2. Long term effect of BI-bypass on serum cholesterol levels in 20 obese patients followed for 3 years, accord-ing to the presence or absence of preoperative hypercholesterolemia

All Patients Hypercholesterolemic patients Normocholesterolemic patients(n=20) (n=9) (n=11)

Pre-op TC (mg/dl) 191.2±7.9 221.9±9.0e 166.1±4.8Post-op TC (mg/dl) 122.0±5.0c 125.1±8.0c 119.4±6.6b

Post-op TC change (%) -34.6±3.2 -43.1±3.7d -27.7±4.0

Pre-op LDL-C (mg/dl) 122.1±7.0 150.3 ±7.2e 99.0±3.9Post-op LDL-C (mg/dl) 69.9±3.2c 70.3±5.5c 69.5±3.9b

Post-op LDL-C change (%) -39.6±4.0 -52.5±4.0e -29.0±4.3

Pre-op HDL-C (mg/dl) 43.0±2.2 44.8±3.9 41.6±2.6Post-op HDL-C (mg/dl) 39.3±1.6 40.6±2.3 38.2±2.2Post-op HDL-C change (%) -5.2±5.3 -6.4±5.5 -4.2±8.7

Pre-op TC/HDL (ratio) 4.58±0.22 5.12±0.28d 4.13±0.26Post-op TC/HDL (ratio) 3.13±0.09c 3.09±0.09c 3.16±0.15a

Post-op TC/HDL change (%) -28.7±3.9 -38.4±3.6d -20.8±5.5

Values are mean±SEM. TC= serum total cholesterol; LDL-C= serum LDL cholesterol; HDL-C= serum HDL cholesterol.aP<0.05, bP<0.005, cP<0.0001 postoperative vs preoperative value (paired Student's two-tailed t-test).dP<0.05, eP<0.001 hypercholesterolemic vs the normocholesterolemic patients (unpaired Student's two-tailed t-test).

Figure 3. Total serum cholesterol (Panel A) and triglyceride (Panel B) concentrations (means±SEM) before (white bars)and after (black bars) BI-bypass, under free diet (7th preoperative and 30th postoperative day), under fasting (4th pre-operative and 2nd postoperative day), and under standard diet (day of surgery before operation and 10th postoperativeday).*P<0.05, **P<0.005 postoperative vs the respective preoperative value (paired Student's two-tailed t-test).

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ative plasma cholesterol in 6 non-obese patientssubmitted to control surgery examined under stan-dard diet (155.3±10.9 vs 144.0±15.2 mg/dl, respec-tively; means±SEM).

Table 4 shows the neutral sterol and bile acid 24-hour fecal excretion in a subgroup of patients understandard diet conditions before and after the BI-bypass. Fecal cholesterol was significantlyincreased after BI-bypass, while total plant steroland total bile acid excretion did not differ before andafter the operation.

Discussion

The main finding of this study was that BI-bypasswith a latero-lateral cholecystojejunal anastomosisto the body of the gallbladder, performed to treat

morbid obesity, caused a marked and rapid reductionof total and LDL cholesterol concentrations. In fact,total and LDL cholesterol were decreased by 33%and 36% at 1 month and by 32% and 35% at 1 yearafter BI-bypass compared to baseline, respectively.At 1 year after the operation, although HDL choles-terol concentration was decreased by 12% comparedto baseline, the total cholesterol to HDL cholesterolratio was significantly reduced by 19%. In addition,the beneficial effects of BI-bypass on serum choles-terol were persistent. In fact, total and LDL bloodcholesterol concentrations and the total cholesterolto HDL cholesterol ratio were significantlydecreased by 35%, 40% and 29% at 3 years after theoperation compared to baseline, respectively.Interestingly, all the hypercholesterolemic patientsnormalized their serum cholesterol already 1 monthafter BI-bypass and maintained normal levels for theentire follow-up. In addition, all the beneficial

Table 3. Plasma lipoprotein cholesterol and triglyceride concentrations of 8 patients before and after the BI-bypassunder the different nutritional conditions in the short-term plasma lipid study.

Fasting Fasting Standard Diet Standard Diet Free Diet Free DietPre-op Post-op Pre-op Post-op Pre-op Post-op

Day of sampling - 4 + 2 0 + 9 - 7 + 30VLDL Cholesterol 10.1 ± 2.2 2.5 ± 1.5 * 6.2 ± 1.0 5.0 ± 2.1 7.6 ± 0.8 2.6 ± 1.0 **LDL Cholesterol 121.4 ± 17.3 84.0 ± 14.0 * 127.2 ± 13.6 80.1 ± 12.5 * 117.8 ± 1 3.2 77.4 ± 7.0 *HDL Cholesterol 32.3 ± 3.5 35.4 ± 3.0 33.0 ± 3.5 31.0 ± 9.0 32.8 ± 2.3 27.4 ± 2.4VLDL Triglycerides 38.4 ± 5.2 18.6 ± 3.3 * 44.4 ± 15.3 35.5 ± 10.9 50.5 ± 11.2 22.3 ± 4.7 *LDL Triglycerides 39.4 ± 2.9 42.3 ± 2.3 49.1 ± 7.2 67.8 ± 2.2 39.0 ± 5.2 52.8 ± 3.8HDL Triglycerides 17.5 ± 3.4 23.1 ± 4.5 19.2 ± 3.9 22.0 ± 2.8 11.0 ± 2.0 22.6 ± 1.4

Values are expressed as mg/dl (means±SEM). Day of sampling 0 was the day of surgery before the operation wascommenced.*P<0.05, **P<0.005 preoperative vs the respective postoperative value (paired Student's two-tailed t-test).

Table 4. Fecal neutral sterol and bile acid excretions before and after the BI-bypass

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Mean±SEM

Coprostanol Pre-op 20.2 395.5 27.4 275.8 422.7 310.6 372.9 260.7 ± 64.0Coprostanol Post-op 43.2 52.0 723.5 86.9 115.1 183.9 241.1 206.5 ± 90.3

Cholesterol Pre-op 610.4 39.0 8.4 27.6 135.2 110.3 63.6 142.1 ± 79.9*Cholesterol Post-op 829.1 1102.3 625.1 254.5 1256.1 1341.1 857.9 895.2 ± 143.2

Plant sterols Pre-op 84.3 92.1 8.6 55.3 144.1 66.9 97.7 78.4 ± 15.8Plant sterols Post-op 86.4 74.5 65.6 54.8 54.3 65.5 70.9 67.4 ± 4.3

Bile acids Pre-op 505.1 214.5 19.0 174.6 424.5 301.9 243.7 269.1 ± 61.0Bile acids Post-op 993.2 1316.5 642.6 465.6 424.3 315.7 247.8 629.4 ± 147.9

Fecal sterol outputs are expressed as mg/day.*P< 0.005 vs the respective preoperative value by paired Student’s two-tailed t-test.


effects of the BI-bypass on serum cholesterol levelswere significantly higher in the obese patients whohad been hypercholesterolemic before surgery thanin those who had been normocholesterolemic. At 3years after BI-bypass, mean total and LDL serumcholesterol concentrations were similar in patientswho had been hypercholesterolemic and in thosewho had been normocholesterolemic before surgery.Total cholesterol was reduced by 43% and 28% andLDL by 52% and 29% in the hypercholesterolemicand in the normocholesterolemic patients, respec-tively. These findings have two clinical implications.First, the BI-bypass is indicated in hypercholes-terolemic obese patients and, second, it does not leadto potentially harmful very low blood cholesterollevels in normocholesterolemic obese subjects.

A second important finding of this study was that,at 1 year after operation, the AGB did not have anybeneficial effect on total and LDL cholesterol levels,which are considered the primary target of optimalcardiovascular disease prevention.3,4 This occurredeven if this operation induced a reduction of serumtriglyceride concentration of the same degree as thatinduced by the BI-bypass at 1 year after surgery. Inagreement with our results, total and LDL choles-terol have been mostly reported to be unchanged oronly slightly reduced after purely restrictivebariatric surgery.5-10 A reduction of total and LDLserum cholesterol in the 10-13% range have beenreported in two studies only.11,12 Most studies haveshown a postoperative increase of HDL after restric-tive surgery, with consequent reduction of the totalcholesterol to HDL cholesterol ratio ranging from9% to 21% compared to the preoperative value.5,6,8-

11 In the present study, we confirmed that the AGBreduced the total cholesterol to HDL cholesterolratio, but less efficiently than the BI-bypass in thehypercholesterolemic patients. Even if we did notrandomize our patients to the BI-bypass or to theAGB, because we consider the preoperative psychi-atric evaluation as an unavoidable step for thechoice of the type of bariatric surgery, our presentdata lead to the conclusion that the presence ofhypercholesterolemia in morbidly obese patientsprompts the indication for malabsorptive and notpurely restrictive surgery.

Among the other malabsorptive operations used totreat obesity, the JI-bypass and the biliopancreaticdiversion (BPD) have been shown to induce a

marked decrease in total and LDL cholesterol lev-els.24-26 The gastric bypass (GBP) has been reportedto have a weak effect on total and LDL blood cho-lesterol, while HDL showed substantial increase.27-34

A strong reduction of total serum cholesterol 3 to 9moths after GBP has been reported in one study inwhich HDL cholesterol was not reported.35 A poten-tial advantage of the BI-bypass with respect to theother currently performed malabsorptive operationsis that the patient’s anatomy can be reversed to nor-mal with the only exception of a cholecystectomy.The JI-bypass is no longer performed because it wasoccasionally followed by serious complications,including hepatic failure, cirrhosis, multiple meta-bolic deficiences and severe diarrhea caused by bilesalt malabsorption.13 A strong bile salt malabsorp-tion is also the main reason for the hypocholes-terolemic effect of the JI-bypass, because the high-est bile acid absorption efficiency is in the distalileum.36,37 In the BI-bypass, the blind intestinal loopof the JI-bypass is anastomosed to the gallbladder,allowing a portion of the bile to transit into it withconsequent reduction of bile acid malabsorp-tion.14,15 In accordance, in the present study wefound that bile acid fecal excretion only slightlyincreased 9 days after the operation compared to thepreoperative value. Our finding of a six-foldincrease in fecal cholesterol daily excretion after theBI-bypass compared to the preoperative value,strongly suggests that cholesterol malabsorption isthe main mechanism by which the BI-bypassreduces serum cholesterol levels. From our presentdata, we cannot exclude that an increased liver cho-lesterol secretion could partially contribute to theincreased postoperative fecal cholesterol output.However, no increase of biliary cholesterol secre-tion has been reported in pigs subjected to 75%resection of the proximal small intestine, a surgicalmodel to reduce cholesterol intestinal absorp-tion.38,39 Biliary cholesterol malabsorption in theintestine after the BI-bypass can be explained, inaddition to the shunt of food away from the distaljejunum, by the postoperative shunt through thecholecysto-jejunal anastomosis of a fraction of bilethat does not enter into contact with the mucosa ofthe duodenum and proximal jejunum which are themain sites of cholesterol absorption in the gut.40-43

In agreement with the hypothesis that the BI-bypassinduces cholesterol malabsorption, we found that




the hypocholesterolemic effect was obtainedalready 2 days after surgery and it was not unspecif-ically caused by the surgical stress because controlsurgery did not influence plasma cholesterol levels.

In a previous report, Boman et al16 followed alarge group of patients submitted to the BI-bypassfor >10 years without reporting any serious hepaticcomplication and with very few metabolic disor-ders. Although the follow-up was only 3 years, weconfirmed in our patients the safety of the BI-bypass.19 In particular, our patients experiencedonly a mild transient serum aminotransferaseincrease and a small percentage of them had slightlyprolonged prothrombin time and renal lithiasis asso-ciated with prolonged lack of calcium supplementa-tion. In addition, symptoms related to bacterialgrowth occurred in 20% of cases which resolvedupon intestinal antibiotic treatment.

The higher mean percent reduction of serum cho-lesterol in our present prospective study, as com-pared to the Swedish patients, could be explained bytwo reasons. First, we have shown that the percentreduction of serum cholesterol in our hypercholes-terolemic patients was much greater than that in ournormocholesterolemic subjects and the number ofpatients with hypercholesterolemia was not reportedin the Swedish study.16 Second, a greater hypocho-lesterolemic effect in our patients could beexplained by a higher cholesterol malabsorption if alarger fraction of bile flow was shunted through thelatero-lateral cholecystojejunal anastomosis to thebody of the gallbladder performed in our patients,compared to the Swedish patients in which the anas-tomosis was termino-terminal to the fundus of thegallbladder. In this respect, we have shown by99mTcDyethyl-HIDA biliary scintigraphy that, withour large latero-lateral cholecystojejunal anastomo-sis, a mean 71% of bile secreted by the liver tran-sits through the cholecystojejunal anastomosisrather than into the choledochus.18

In conclusion, in hypercholesterolemic obesepatients the BI-bypass with a wide latero-lateralcholecystojejunal anastomosis causes a strong andpersistent reduction of total and LDL serum choles-terol and the total cholesterol to HDL ratio. At vari-ance, the AGB does not affect total and LDL cho-lesterol levels and reduces the total cholesterol toHDL ratio less efficiently than the BI-bypass inhypercholesterolemic patients. Hypercholesterol-

emia should be considered as a criteria to selectpatients for malabsorptive rather than pure restric-tive obesity surgery.

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(Received October 25, 2004; accepted December 12, 2004)


Comparison of changes in lipid profile after bilio-intestinal bypass and gastric banding in patients...

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