Maria Laura Cossu

Biliopancreatic diversion preserving the stomach and pylorus in the treatment of hypercholesterolemia and diabetes type II: Results in the first 10 cases

Background: Besides weight loss Scopinaros operation produces correction of hypercholesterolemia and noninsulin dependent diabetes mellitus in all patients who suffer from these conditions. These results encouraged us to perform biliopancreatic diversion (BPD) without gastric resection, thus preserving the functions of the stomach and pylorus in moderately overweight patients with hypercholesterolemia associated with diabetes type II and hypertriglyceridemia. Methods: Between March 1996 and July 1997 we performed BPD without gastric resection on 10 moderately overweight patients [mean body mass index (BMI) = 33.2 kg/m2]. All patients had suffered from hypercholesterolemia and hypertriglyceridemia for more than 5 years. Ten patients suffered from diabetes type II; four of them had had insulin treatment or oral anti-diabetic agents; the other patients all had hyperglycaemia in the fasted state and diabetes confirmed by preoperative oral glucose tolerance test (OGTT). Five patients suffered from hypertension. Results: In all patients, cholesterol and triglyceride levels returned to normal within the first postoperative month. Glycemia also stabilized at normal values in nine patients within the early weeks after surgery. One patient who took 70 U of insulin reduced his daily intake to 35 U 2 months postoperatively. In all patients blood pressure returned to normal. Weight loss was predictably slight (10-15 kg). Conclusions: Our experience with the procedure found that this new method seems to be as effective in controlling lipidic metabolism and diabetes II as the original version of BPD. As expected, weight loss is only moderate, so that the modified BPD is not suitable for very obese patients.

Reversal of antidepressant-induced dopaminergic behavioural supersensitivity after long-term chronic imipramine withdrawal.

Chronic antidepressant treatments enhance dopaminergic neurotransmission in the mesolimbic dopamine system. We suggested that this potentiation might underlie both the antidepressant therapeutic effect and the antidepressant-induced switch from depression to mania, which in turn, might be involved in the development of rapid cycling in bipolar patients. In this study, we investigated the changes occurring in the sensitivity of the mesolimbic dopamine system up to 40 days after antidepressant withdrawal. Male Sprague-Dawley rats were treated for 3 weeks with imipramine (20 mg/kg) and tested for motor activity 24 h, 12, 33 and 40 days after treatment withdrawal. Ambulatory activity and rearing counts were recorded after challenge with the dopamine D2-like receptor agonist quinpirole (0.15 mg/kg). Imipramine increased the motor response to quinpirole, 24 h after treatment discontinuation. No relevant differences between the groups were found after 12 and 33 days. After 40 days, a decreased level of rearing was observed in the group treated with imipramine. These results show a reversal of the imipramine-induced dopaminergic supersensitivity after 40 days of chronic imipramine withdrawal and suggest that the mood-switches observed in bipolar patients following antidepressant treatment and subsequent withdrawal, i.e. mania followed by rebound depression, might depend upon parallel changes in the mesolimbic dopamine system sensitivity.

Biliopancreatic Diversion for Treatment of Morbid Obesity: Experience in 50 Cases

Background: Biliopancreatic diversion (BPD) by Scopinaros method is an operation advocated by some surgeons as an effective treatment for morbid obesity. Methods: Between February 1995 and April 1997 we performed BPD by Scopinaros method on 50 patients with morbid obesity (23 males), average age 41.4 years (range 20-63 years), average body weight 135.08 kg (range 89-256 kg), mean body mass index (BMI) 50.65 kg/m2 (range 37.01-81.56 kg/m2). Results: In all cases a gradual decrease in weight was obtained [mean BMI at 1 month: 44.8 kg/m2, at 6 months (31 patients): 35.09 kg/m2, at 1 year (23 patients): 31.36 kg/m2, at 18 months (14 patients): 29.89 kg/m2 and at 2 years (5 patients): 29.27 kg/m2]. At the same time a significant improvement in the pathological conditions associated with morbid obesity was observed. The patients were able to suspend oral antihypertensive and antidiabetic therapy as these parameters spontaneously returned to normal values by the sixth postoperative month; all cases showed a marked reduction in hypercholesterolemia and hypertriglyceridemia. Postoperative complications were: one death (2%) on the third day due to heart failure; two late intestinal occlusions (4%); one acute dilatation of the stomach (2%); one peritonitis caused by early dehiscence of the anastomosis (2%); five anastomotic ulcers (10%); two cases of protein malnutrition (4%). Conclusions: BPD by Scopinaros method is a bariatric procedure which is technically complex. However is it safe and reproducible and it induces a substantial weight loss.

Combined Biliary and Duodenal Stenting for Palliation of Pancreatic Cancer

The aim of this case report was to evaluate the usefulness of combined biliary and duodenal stenting in the palliation of pancreatic cancer. We report a series of 4 consecutive patients (2 men and 2 women, mean age 58.5 years, range 38–77 years) who underwent combined biliary and duodenal stenting in our department between March 2000 and April 2001. All patients had cancer of the head of the pancreas causing stricture of the common bile duct and second portion of the duodenum. Biliary and duodenal stents were successfully positioned, with relief of symptoms in all cases. No early complications were observed, except for a transient increase in serum lipase and amylase in one case. Mean follow‐up was 7.5 months (range 5–14 months). One patient presenting recurrence of vomiting after 4 months because of tumour overgrowth at the distal edge of the prosthesis was successfully treated by insertion of a partially overlapping second coaxial stent. Combined biliary and duodenal stenting for the palliation of pancreatic cancer was performed safely and successfully. Stents allowed effective re‐canalization of the biliary tract and duodenum, relieving both jaundice and vomiting. This procedure should be considered as an alternative to palliative surgery, especially in critically ill patients.

Nephrotic syndrome and angiotropic lymphoma report of a case.

A case of angiotropic lymphoma involving renal glomeruli and interstitial vessels associated with nephrotic syndrome and with minor lesions in the glomerular basal membrane is reported. A 56-year-old woman had fever, weakness and clinical findings of a nephrotic syndrome with normal renal function. Renal biopsy revealed that the glomeruli were infiltrated by neoplastic lymphoid cells positive for CD20 and CD45; the glomerular basement membranes showed a pattern of minimal change disease. This case and our review of the literature suggest that the rare association of intravascular lymphoma and glomerular disease is more than coincidental.

Dopamine D1 receptor agonists induce penile erections in rats

The dopamine receptor agonist apomorphine has been recently introduced in the treatment of erectile dysfunction. While it is well established that dopamine D2-like receptors play a crucial role in this effect, conflicting result are reported in the literature as for the role of dopamine D1-like receptors. The aim of this study was to determine the effect of systemic administration of dopamine D1-like receptor agonists on penile erection in rats. Male Wistar rats were treated with three different, and not structurally related, dopamine D1-like receptor agonists: the partial agonists SKF38393 ((+) 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) and CY 208-243 ((-)-4,6,6a,7,8,12b-exahydro-7-methylindole [4,3-ab]fenantridine), and the full agonist A 77636 ((-)-(1R,3S)-3-Adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyran hydrochloride). All three compounds dose-dependently increased the number of penile erections, with the full agonist A77636 showing a more pronounced effect with respect to the other two. Moreover, the dopamine D1-like receptor antagonist SCH 23390 ((R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) dose-dependently antagonised A77636 effect. These results show that systemic administration of dopamine D1-like receptor agonists induce penile erection in rats. This observation suggests that dopamine D1-like receptor agonists might be considered as a possible alternative to apomorphine in the treatment of erectile dysfunction, thus avoiding the typical side effects related to the stimulation of dopamine D2-like receptors such as nausea.

Evaluation of serum leptin levels and thyroid function in morbidly obese patients treated with bariatric surgery

Biliopancreatic diversion (BPD), a gastrectomy with a long ROUX en Y reconstruction, reduces intestinal absorption by delaying the mixing of food and biliopancreatic juices, and induces persistent weight loss in obese patients unresponsive to medical treatments. The levels of leptin (a plasma protein synthesised in human adipose tissue) are increased in obese subjects and significantly decrease after a major weight loss. A possible role of thyroid hormones in regulating adipose tissue metabolism in humans has been proposed, but it is not universally accepted and the relationship between thyroid function and leptin levels has not yet been clearly defined. We studied serum leptin, TSH, fT4 and fT3 levels in 38 obese patients (26 women and 12 men), before and 12 months after BPD. There was a significant post-surgical decrease in BMI and circulating leptin levels in all of the treated subjects, but thyroid function did not seem to be affected (TSH and fT4 levels were unchanged). However, fT3 levels significantly decreased after surgery. Our data suggest that BPD-induced malabsorption has no direct effect on thyroid function, but possibly reduces the peripheral conversion of thyroxine to T3. Further studies seem to be necessary to clarify the clinical relevance of these observations.

Impact of Age on Long-Term Complications after Biliopancreatic Diversion

Background: The aim of the study is to evaluate the importance of age on the mid- and long-term results and complications after biliopancreatic diversion (BPD). Methods: Our study comprises 132 morbidly obese patients who underwent Scopinaro BPD from February 1995 to April 2001, with follow-up from 24 to 96 months. The patients, 53 males (40%) and 79 females (60%), with mean preoperative BMI 50.2 (35.4-81.5), and mean age 42 (20-65), were divided in 4 groups. Group A age 20-35, 43 patients; Group B age 36-45, 33 patients; Group C age 46-55, 31 patients and Group D age >55, 25 patients. Incidence of long-term specific complications after BPD were analyzed, including protein malnutrition, reversals, anastomotic ulcer, and incisional hernia. Results: Mean postoperative BMI was similar in all Groups. After 60 months the following BMI values were observed. Group A 30.8, Group B 34.9, Group C 35.9, Group D 32. Incidence of long-term complications were not significantly different (χ2) in the 4 Groups, and were respectively: protein malnutrition 6.9%, 12.1%, 6.4%, 16.0%; anastomotic ulcer 11.6%, 9%, 6.4%, 16.0%; reversal 2.3%, 9.0%, 1.32%, 8.0%; ventral hernia 34.8%, 45.4%, 54.8%, 32.0%. Conclusions: From the preliminary results, it appeared that the incidence of the complications was higher in group D (>55 years old), whereas group C (46-55 years old) showed a lower complication rate. However, the prevalence of complications in all groups was not statistically different on χ2 analysis. No age limit for bariatric surgery could be determined from the age ranges studied.

Melatonin and Vitamin D Interfere with the Adipogenic Fate of Adipose-Derived Stem Cells

Adipose-derived stem cells (ADSCs) represent one of the cellular populations resident in adipose tissue. They can be recruited under certain stimuli and committed to become preadipocytes, and then mature adipocytes. Controlling stem cell differentiation towards the adipogenic phenotype could have a great impact on future drug development aimed at counteracting fat depots. Stem cell commitment can be influenced by different molecules, such as melatonin, which we have previously shown to be an osteogenic inducer. Here, we aimed at evaluating the effects elicited by melatonin, even in the presence of vitamin D, on ADSC adipogenesis assessed in a specific medium. The transcription of specific adipogenesis orchestrating genes, such as aP2, peroxisome proliferator-activated receptor γ (PPAR-γ), and that of adipocyte-specific genes, including lipoprotein lipase (LPL) and acyl-CoA thioesterase 2 (ACOT2), was significantly inhibited in cells that had been treated in the presence of melatonin and vitamin D, alone or in combination. Protein content and lipid accumulation confirmed a reduction in adipogenesis in ADSCs that had been grown in adipogenic conditions, but in the presence of melatonin and/or vitamin D. Our findings indicate the role of melatonin and vitamin D in deciding stem cell fate, and disclose novel therapeutic approaches against fat depots.

Bowel obstruction after biliopancreatic diversion: a deceptive complication.

Background: Although obesity surgery is now practiced in most of the world, many general surgeons, faced with an emergency, are not experienced in the diagnostic problems associated with these techniques, or about the most suitable treatment to resolve the acute pathology while preserving the weight loss. The biliopancreatic diversion (BPD), because of its complexity, could cause a delay in the diagnosis and therapy, with possible catastrophic consequences for the patient. Methods: We report 3 patients with bowel obstruction after BPD. In the first patient intestinal occlusion was due to an adhesion obstructing the alimentary tract; in the other two patients the occlusion was localized to the biliopancreatic tract, due to a serrate stenosis of the entero-entero anastomosis in one patient and due to volvulus of the biliopancreatic loop in the other patient. Results: Signs and symptoms were different according to whether the obstruction was in the alimentary tract or the biliopancreatic tract. In all cases a prompt gastrointestinal x-ray with barium and ultrasound scan and/or CT scan induced us to a mandatory laparotomy with resolution of the obstruction. Conclusions: After BPD, diagnosis of an intestinal obstruction must be made promptly. Even colleagues who express doubts must be persuaded to perform immediately an upper gastrointestinal tract x-ray and an U/S or CT scan. In this way, it may be possible to avoid intestinal resection and catastrophic complications.