Francesco Papadia

A 15-year evaluation of biliopancreatic diversion according to the Bariatric Analysis Reporting Outcome System (BAROS).

Background: Biliopancreatic diversion (BPD) is the most effective bariatric procedure in terms of weight loss. However, analysis of the quality of life (QoL) has never been reported. The BAROS, giving a score to each operated patient on weight loss, improvement in medical conditions, QoL, complications and reoperations, has proven to be a standard reference for evaluating bariatric surgery outcomes. Methods: In order to apply the BAROS to BPD, we sent a questionnaire to 1,800 BPD patients who had been operated between 1984 and 1998.The responserate was 51.2%. Out of 1,709 questionnaires which actually reached their destination, we had 858 fully compiled returned. There were 615 women. 596 patients had had an ad hoc stomach (AHS) BPD, and 262 had had an ad hoc stomach ad hoc alimentarylimb (AHS-AHAL) BPD. Results: According to the scoring key, 3.5% were classified as a failure, 11% were fair results, 22.8% good, 39.5% very good , and 23.2% excellent results. Considering AHS BPD and AHS-AHAL BPD separately,while the mean excess weight percent loss was 70.5±23 and 64.7±17 respectively, the failure rate was 6% in the first group and 2% in the AHAL group, while 11% and 6% of cases respectively were fair results, 24% and 20% good, 36% and 47% very good, 23% and 25% excellent results. Conclusion: The BAROS evaluation of BPD highlights the importance of its flexibility: the new policy of adapting the procedure to individual characteristics caused a drop in the failure rate and an increase in good, very good and excellent results.

Energy and Nitrogen Absorption after Biliopancreatic Diversion

Background: The strict long-term weight maintenance in good nutritional conditions observed after biliopancreatic diversion (BPD) needs to be explained. Materials and Methods: 15 operated subjects were maintained at an isoenergetic and isonitrogenic diet as similar as possible to their usual diet. Apparent absorption (AA) of energy, fat, nitrogen and calcium was calculated subtracting the fecal content, measured directly, from the oral intake, derived from tables.The alimentary protein absorption was directly determined by I125 albumin oral administration. Results: Mean AA for energy and fat was 57% and 32%, respectively; AAs were unrelated as absolute value and negatively associated as percent of the intake with the energy and fat intake. I125 intestinal absorption was 73%, while nitrogen percent AA was 57%, indicating higher than normal loss of endogenous nitrogen. Calcium AA was 551 mEq/day, 26% of the intake. A positive correlation between nitrogen and calcium AA as absolute values and alimentary intake was observed, while there was no correlation when AA were considered as per cent of the intake. Conclusions: For energy and fat, an increase in intake corresponds to an increase in percent malabsorption, so that the absolute amount absorbed tends to remain constant, accounting for the excellent weight maintenance observed following BPD. This was confirmed by a long-term hypernutrition study after BPD. On the contrary, for nitrogen and calcium, the percent absorption tends to remain constant when intake varies, so that an increase in alimentary intake results in an increased absolute amount absorbed.

Liver damage in severely obese patients: a clinical-biochemical-morphologic study on 1,000 liver biopsies.

Background: Preoperative clinical and biochemical data and intraoperative liver biopsy of 1,000 obese patients submitted to biliopancreatic diversion (BPD) were analyzed, and correlations investigated. Methods: Of 2,645 patients submitted to BPD between May 1976 and November 2002, the last 1,000 consecutive obese patients with no history of alcohol consumption or infectious hepatitis were selected. Clinical data included: age, body weight, BMI, waist-to-hip ratio (W/H), arterial blood pressure, serum glucose, triglycerides, cholesterol, albumin/γ-globulin ratio, total, conjugated and unconjugated bilirubin, γ-GT, alkaline phosphatase, AST, ALT, and prothrombin time. The degree of steatosis, inflammation and fibrosis on intraoperative wedge liver biopsy was determined and scored. Liver steatosis >70% and presence of bridging fibrosis were analyzed separately. Results: Mean BMI was 48 kg/m2. 263 patients had steatosis of >70%, and 79 had bridging fibrosis. Regression analysis showed an association between steatosis and AST, ALT, AST/ALT ratio, body weight, W/H, serum glucose, serum tryglicerides, BMI, γ-GT, age, and unconjugated bilirubin. Inflammation was significantly greater in older patients. Patients with bridging fibrosis had significantly higher values of serum glucose, AST, γ-GT, serum cholesterol and were significantly older. Bridging fibrosis was associated with diabetes, W/H >1, hypertension, albumin/γ-globulin ratio <1. Conclusion: Severe steatosis and bridging fibrosis seem to be associated with the metabolic syndrome. No reliable biochemical data could identify patients with severe chronic liver damage with sufficient sensitivity to avoid liver biopsy for diagnosis and staging of the disease.

Isolated Limb Perfusion With the Tumor-Targeting Human Monoclonal Antibody-Cytokine Fusion Protein L19-TNF Plus Melphalan and Mild Hyperthermia in Patients with Locally Advanced Extremity Melanoma

L19‐TNF is a tumor‐targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED‐B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19‐TNF plus melphalan‐containing isolated limb perfusion (ILP) in extremity melanoma patients.

Biliopancreatic Diversion in Nonobese Patients With Type 2 Diabetes: Impact and Mechanisms

CONTEXT Diabetes remission is frequent after biliopancreatic diversion (BPD) in morbidly obese patients with type 2 diabetes (T2D). Data, mechanisms, and clinical indications in nonobese T2D patients are scanty. OBJECTIVE The objective of the study was to assess remission and investigate insulin sensitivity and β-cell function after BPD in nonobese patients with long-standing T2D. DESIGN, SETTING, AND PATIENTS This was a clinical research study comparing 15 T2D patients (aged 55 ± 1 years, duration of 16 ± 2 years, body mass index of 28.3 ± 0.6 kg/m², glycosylated hemoglobin 8.6% ± 1.3%) with 15 gender-, age-, and body mass index-matched nondiabetic controls. Before surgery and 2 months and 1 year later, a 3-hour oral glucose tolerance test, a 5-hour mixed-meal test, and a 3-hour euglycemic clamp were performed. INTERVENTION The intervention included a BPD (distal gastrectomy, proximal ileum anastomosed to remaining stomach, biliopancreatic limb anastomosed to ileum 50 cm from the ileocecal valve). RESULTS Glycemia improved in all patients, but remission (glycosylated hemoglobin < 6.5% and normal oral glucose tolerance test) occurred in 6 of 15 patients. Insulin resistance (19.8 ± 0.8 μmol · min⁻¹ · kg(ffm)⁻¹, P < .001 vs 40.9 ± 5.3 of controls) resolved already at 2 months (34.2 ± 2.8) and was sustained at 1 year (34.7 ± 1.6), although insulin-mediated suppression of endogenous glucose production remained impaired. In contrast, β-cell glucose sensitivity (19 [12] pmol · min⁻¹ · m⁻² · mM⁻¹ vs 96 [73] of controls, P < .0001) rose (P = .02) only to 31 [26] at 1 year and was lower in nonremitters (16 [18]) than remitters (46 [33]). CONCLUSIONS In nonobese patients with long-standing T2D, BPD improves metabolic control but induces remission in only approximately 40% of patients. Peripheral insulin sensitivity is restored early after surgery and similarly in remitters and nonremitters, indicating a weight-independent effect of the operation. The initial extent of β-cell incompetence is the main predictor of the metabolic outcome.

Outcome of Biliopancreatic Diversion in Subjects with Prader-Willi Syndrome

Background: In Prader-Willi Syndrome (PWS), mental retardation and compulsive hyperphagia cause early obesity, the co-morbidities of which lead to short life-expectancy, with death usually occurring in their 20s. Long-term weight loss is mandatory to lengthen the survival; therefore, the lack of compliance in voluntary food restriction requires a surgical malabsorptive approach. Methods: 15 PWS subjects were submitted to biliopancreatic diversion (BPD) and followed (100%) for a mean period of 8.5 (4-13) years. BPD consists of a distal gastrectomy with a long Roux-en-Y reconstruction which, by delaying the meeting between food and biliopancreatic juices, causes an intestinal malabsorption. Indication for BPD was BMI >40 or >35 with metabolic complications. Preoperative mean age was 21±5 years, mean weight 127±26 kg, and mean Body Mass Index (BMI, kg/m2) 53±10. According to Holms criteria, all of the subjects had a total score ≥8. IQ assessment was performed in each subject, with a mean score of 72±10. An arbitrary lifestyle score was given to each subject. Results: No perioperative complications were observed. Percent excess weight loss (%EWL) was 59±15 at 2 years and 56±16 at 3 years, and then progressive regain occurred; at 5 years %EWL was 46±22 and at 10 years 40±27. Spearman rank test failed to demonstrate any correlation between weight loss at 5 years and patient data, except with lifestyle score (Spearman r=0.8548, p<.0001). Current mean age is 31±7 years. Conclusion: BPD has to be considered for its value in prolonging and qualitatively improving the PWS patients life.

Type 2 Diabetes and Weight Loss following Biliopancreatic Diversion for Obesity

Background: The authors investigated the weight loss and maintenance in type 2 diabetic obese patients undergoing biliopancreatic diversion (BPD). Methods: Two series of diabetic and non-diabetic obese patients matched for gender, age and baseline body mass index (BMI) were evaluated prior to BPD, on the occasion of the regular follow-up visit at 1, 2 and 3 years following the operation, and at the fifth postoperative year. At each follow-up point, body weight (BW), BMI, and serum glucose concentration were measured. Results: In all type 2 diabetic patients, the serum glucose level fell to within the normal range at the first postoperative year and remained within normal limits without any medication throughout all the follow-up period. In preoperatively diabetic subjects, mean values of BW and BMI were closely similar to those of non-diabetic subjects at all follow-up points, and the stabilization weight was independently related to age and to initial BW values. Conclusions: In obese patients with type 2 diabetes, the glucose level steadily normalized in every case following BPD, and values remained unchanged throughout the follow-up period. After the operation, the type 2 diabetic obese patients experienced the same stable weight reduction as their non-diabetic counterparts.

Biliopancreatic Diversion Reduces QT Interval and Dispersion in Severely Obese Patients

Objectives: The objectives were to evaluate QT interval (QTc) and QT‐interval dispersion (QTd) in severely obese individuals and to determine the effects of biliopancreatic diversion (BPD) and weight loss after BPD on ventricular repolarization parameters.

Short-Term Liver Function after Biliopancreatic Diversion

Background: Liver failure after biliopancreatic diversion (BPD) has been reported. Although in our series of 2,515 BPD with a minimum follow-up of 12 months we have never observed this complication, a transitory and significant rise in serum AST and ALT has been detected in some cases, suggesting the occurrence of transient liver damage. To assess if risk factors for acute liver damage after BPD could be identified, we studied the evolution of hepatic biochemistry in a sample of our operated subjects. Methods: We studied 99 consecutive patients submitted to the same type of BPD (ad hoc stomach, ad hoc alimentary limb). Patients with a history of alcohol consumption or positive hepatic serology were excluded. Preoperative body weight (BW), body mass index (BMI), excess weight (EW), % excess weight (%EW), fasting serum glucose level (SG), hepatic histology (HI), weight loss (WL) at 2, 4 and 12 months, and excess weight % loss (IEW%L) at the same time were correlated with preoperative and 2, 4 and 12 months hepatic biochemistry. Results: Compared with preoperative values, AST levels at 2 months significantly increased (Students t-test, P=0.0003) and significantly decreased at 12 months (P=0.0001). Spearmans Rank test showed significant correlations between 2 months AST levels and WL at 2 months (P =0.005), preoperative BW (P <0.0001), SG (P =0.01), and HI (inflammation P<0.0001, fibrosis P=0.001). Conclusion: Hepatocellular necrosis in our series peaks at 2 months, and decreases afterwards.WL at 2 months, preoperative BW, SG and HI seem to be of help in identifying patients at increased risk for acute liver damage, prompting the need for an enhanced surveillance.

Effect of biliopancreatic diversion on hypertension in severely obese patients

Hypertension is a medical disorder frequently associated with severe obesity, and the effect of weight loss on the reduction of blood pressure has been well established. In this study, the relationships between the weight loss surgically obtained by biliopancreatic diversion and blood pressure were investigated in a population of severely obese patients with preoperative hypertension. At 1 year following the operation, blood pressure was normalized in more than half of patients; in a further 10% of cases the hypertensive status resolved within the 3-year follow-up period. The resolution of hypertension was independently associated with age and body weight and was unrelated to sex, the amount of weight loss, or body fat distribution. In severely obese patients with hypertension undergoing bariatric surgery, biliopancreatic diversion is advisable since it achieves and supports the maintenance of body weight close to the ideal value.