Ralph Peterli

Impaired mitochondrial function is important in obesity and the development of insulin resistance and diabetes. The aim of this study was to identify human adipocyte-derived mitochondrial proteins associated with obesity. Mitochondrial proteins from 20 abdominal omental adipose tissue biopsies (13 obese and 7 control subjects) were separated by anion-exchange chromatography coupled to SDS-PAGE. Protein contents were compared and identified by MALDI-TOF-TOF mass spectrometry. Proteins of interest were validated, verified and quantified using immuno dot blot assays in a total of 76 mitochondrial preparations from both obese and non-obese patients. Mass spectrometric comparison of 20 mitochondrial proteomes yielded 62 proteins that were differentially expressed in adipose tissue of obese subjects. The immunological quantification of 12 mitochondrial proteins from 76 omental adipose tissue biopsies revealed four proteins, citrate synthase, HADHA, LETM1 and mitofilin inversely being asso...

Mutations of the melanocortin-4 receptor (MC4R) gene are associated with up to 5.8% of monogenetic causes of obesity. Correlations between defects in MC4R and complications after laparoscopic adjustable gastric banding (LAGB) have recently been reported. The aim of this study was to investigate whether in our patient population band-associated complications can be correlated with MC4R defects, which in turn could be a contraindication for gastric banding. Of 370 morbidly obese patients operated between Dec 1996 and May 2004 with LAGB, 37 required re-operation, by re-banding or biliopancreatic diversion/duodenal switch for band-associated complications. Genomic DNA was extracted from leucocytes of these 37 patients using standard methods. The entire MC4R-gene was amplified by PCR and sequenced on an ABI Prism 3100 automated DNA sequencer. Any detected mutation or polymorphism was verified utilizing a high-fidelity proofreading polymerase. No mutation was seen in 35 patients (95%). The polymorphism Ile251Leu (A1144C) which was found in one patient is known not to be associated with obesity. A silent mutation Ile198Ile (C594T) was found in another patient. Based on published data, approximately 12 patients of the 37 would have been expected to carry one of the known obesity-associated MC4R mutations, but none of these was found. In our patient material, we could not confirm the observation previously published that MC4R defects are associated with a higher complication rate following LAGB. Thus, we do not recommend routine general screening for MC4R defects before LAGB.

Impairment of mitochondrial function plays an important role in obesity and the development of insulin resistance. The aim of this project was to investigate the mitochondrial DNA copy number in human omental adipose tissue with respect to obesity. The mitochondrial DNA (mtDNA) content per single adipocyte derived from abdominal omental adipose tissue was determined by quantitative RT-PCR in a group of 75 patients, consisting of obese and morbidly obese subjects, as well as non-obese controls. Additionally, basal metabolic rate and fat oxidation rate were recorded and expressed as total values or per kilogram fat mass. MtDNA content is associated with obesity. Higher body mass index (BMI) resulted in a significantly elevated mtDNA count (ratio = 1.56; p = 0.0331) comparing non-obese (BMI < 30) to obese volunteers (BMI >or= 30). The mtDNA count per cell was not correlated with age or gender. Diabetic patients showed a trend toward reduced mtDNA content. A seasonal change in mtDNA copy number could not be identified. In addition, a substudy investigating the basal metabolic rate and the fasting fat oxidation did not reveal any associations to the mtDNA count. The mtDNA content per cell of omental adipose tissue did not correlate with various clinical parameters but tended to be reduced in patients with diabetes, which may partly explain the impairment of mitochondrial function observed in insulin resistance. Furthermore, the mtDNA content was significantly increased in patients suffering from obesity (BMI above 30). This might reflect a compensatory response to the development of obesity, which is associated with impairment of mitochondrial function.

The aim of this study was to assess the use of mechanical bowel preparation (MBP) and antimicrobial prophylaxis in elective colorectal surgery in Switzerland. Ninety-eight heads of surgical departments in Switzerland and 42 visceral surgeons in private practice were asked to answer an 18-item questionnaire in October 2008 about arguments in favor of or against MBP. The participants also indicated whether they use MBP and antimicrobial prophylaxis in colorectal surgery, and if so, what agents were used. Of the participants, 117/140 (83%) responded. Additional data were collected pertaining to the respondents' experience and work situation. MBP was used significantly more often for rectal surgery than for left colonic resections (83% vs. 53%; p < 0.001) and more often for left than for right colonic resections (53% vs. 43%; p = 0.001), regardless of the open or laparoscopic approach. Younger surgeons and surgeons with a higher case load in colorectal surgery used MBP significantly less frequently in open right colonic resections. For MBP, cathartics were used in 90% of patients, and enemas were used in 10% of patients. Of the respondents, 37% considered MBP to be useful, even very useful. Based on the literature, because of introduction of fast-track protocols or for considerations of patient comfort, 86% of the respondents had changed the bowel preparation regime during the last 10 years in terms of a reduction of the quantity of cathartics or restricted the indications for MBP. Antimicrobial prophylaxis was used by 100% of the respondents, 88% used a single prophylactic dose only, while 70% administered the antibiotics 30-59 min before the incision. Most of the surgeons used second-generation cephalosporins in combination with metronidazole, and 24% changed the antibiotic agent or reduced the duration of administration of antibiotics during the last 10 years. MBP is often used in open and laparoscopic rectal surgery, but not in right colonic resections. Scientific evidence regarding MBP has yielded a rethinking about rigorous bowel preparation regimes. As of now, surgeons in Switzerland are not yet unanimously ready to abandon MBP in elective colorectal surgery. In Switzerland, surgeons are influenced by the benefit of antimicrobial prophylaxis in colorectal surgery.

To evaluate the outcome of antireflux surgery, we assessed disease-specific symptoms and quality of life of all patients treated by laparoscopic fundoplication at our center between 1992 and 2002. Preoperative symptoms and details of surgery were evaluated for 186 laparoscopic fundoplications. Disease-specific symptoms and quality of life were assessed using a questionnaire. Of 186 patients, 143 returned the questionnaire. The most common preoperative symptoms under medical antireflux therapy were regurgitation (54%) and heartburn (30%). Indications for surgery were refractory symptoms (88%) and the patient denying long-term medication (42%). The surgical approaches were Nissen fundoplication (98%) or Toupet fundoplication (2%, for heavy esophageal motility disorder). The conversion rate was 10%. There were no deaths, and 6 patients (3%) had to be reoperated. The questionnaire revealed that in 82% of the patients who responded, the preoperative reflux symptoms were gone, and 94% were satisfied with the result and would undergo surgery again. The average gastrointestinal quality of life index was 115 points (healthy volunteers in the literature, 120.8 points). Laparoscopic fundoplication is a safe antireflux therapy resulting in high levels of patient satisfaction and near-normal quality of life in the long term.

Two techniques for treatment of Zenker's diverticulum, endoscopic stapler-assisted esophagodiverticulostomy and open cricopharyngeal myotomy by transcervical approach, were compared with regard to patient satisfaction and quality of life. Between January 1994 and December 2004 a total of 47 patients with Zenker's diverticulum underwent surgery in our department. Besides the usual retrospective evaluation of details of surgery, all patients were sent a questionnaire on their actual complaints and quality of life according to the Gastrointestinal Quality of Life Index (GIQLI). Twenty patients had the endoscopic procedure (Group A), and 27 the open procedure (Group B). The preoperative symptoms were dysphagia in 96%, regurgitation of undigested food in 60%, cough in 19%, and pneumonia caused by recurrent aspiration in 9%. The length of surgery was on average 32 min (range 5-70 min) in Group A and 106 min (range 45-165 min) in Group B, and the length of hospital stay was 5.5 days (range 1-10 days) and 12.3 days (range 7-25 days), respectively. The results of the questionnaire showed that the preoperative symptoms had disappeared in up to 83%, and 91% in Group A and 100% in Group B would be willing to undergo surgery again. The mean GIQLI was 123 points in Group A and 118 points in Group B (healthy volunteers in the literature, 125 points). Both techniques showed good results in a long-term follow-up with regard to relief of symptoms and patient satisfaction. Both groups had an excellent Gastrointestinal Quality of Life Index, comparable to that of a healthy standard population.

We describe a young female patient suffering from a PEComa (perivascular epithelioid cell tumor) of the cecum, incidentally found at an examination made by her family physician. The perivascular epithelioid cell tumor is a very rare tumor, until today reported in a few cases in falciform ligament, uterus, jejunum, terminal ileum, rectum, liver, kidney, lung, pancreas, prostate, and soft tissue of the thigh. This tumor is part of a new group of tumors, comprised of angiomyolipoma, lymphangiomyolipoma, and clear-cell myomelanocytic "sugar" tumor. Defined by coexpression of melanocytic (HMB-45) and muscle markers (smooth muscle actin and desmin) the perivascular epithelioid cell tumor does not have predictable histopathologic behavior. Some cases of metastasis are described, comorbidities such as tuberous sclerosis of the brain "Bourneville" and lymphangioleiomyomatosis have to be excluded. The therapy consists of the radical resection. An adjuvant therapy is not known. Recommended is a close and long-term follow-up clinically and by CT scan.

Perioperative morbidity and long-term results after hemorrhoidectomy (Ferguson's technique) were evaluated as a basis for comparison with new methods such as stapled hemorrhoidectomy. All records of patients who underwent conventional hemorrhoidectomy between January 1, 1993 and December 31, 1997 (five years) were retrospectively analyzed. The surgical technique was Ferguson closed hemorrhoidectomy. Long-term results were evaluated with a standardized questionnaire that was sent to all patients. Five-hundred-fourteen patients (195 female, 319 male) with a mean age of 52 (range, 22-96) years were evaluated. Postoperatively, seven patients had a relevant hemorrhage, and two had to undergo reoperation (reoperation rate within 30 days, 0.4 percent). In 15 cases (3 percent) patients received urinary catheters for postoperative urinary retention. Mortality was 0 percent. The questionnaire was returned by 403 patients (78.4 percent). The mean follow-up was 4.7 (range, 2.1-7.8) years. The leading symptom was relieved in 275 patients (67.4 percent), ameliorated in 111 (27.2 percent), and unchanged or worse in 22 (5.4 percent). Incontinence (soiling) was not present in 291 (71.7 percent) patients, light in 86 (21.2 percent), moderate in 25 (6.1 percent), and severe in 4 (0.98 percent). Reoperation rate for recurrent hemorrhoids was 0.8 percent. Patients evaluated the surgical result as excellent in 286 (70.5 percent) cases, good in 87 (21.4 percent), moderate in 25 (6.2 percent), and bad in 8 (1.9 percent) cases. Ferguson closed hemorrhoidectomy results in very low rates of perioperative morbidity. Long-term results demonstrate high patient satisfaction and low incontinence and reoperation rates. It could be the gold standard to which other techniques are compared.

The melanocortin (MC) receptor type-1 (MC1-R) is the only one of the five MC receptor subtypes expressed in human adipose tissue explants, human mesenchymal stem cells (MSCs), and MSC-derived adipocytes. Following our recent expression studies (Obesity 2007, 15, 40-49), we now investigated the functional role of MC1-R in these tissues and cells to deduce the coupling state of MC1-R to intracellular output signals in human fat cells and tissue. Expression of MC1-R by undifferentiated and differentiated MSCs was quantified by real-time TaqMan PCR. Intracellular output signals (cAMP, lipolysis, secretion of IL-6, IL-10, and TNF-alpha), as well as effects on the metabolic rate and proliferation of human MSCs were analyzed by standard assays, exposing undifferentiated and differentiated MSCs and, in part, human adipose tissue explants to the potent MC1-R agonist, [Nle(4), D-Phe(7)]-alpha-MSH (NDP-MSH). This agonist induced a weak cAMP signal in MSC-derived adipocytes. However, it did not affect lipolysis in these cells or in adipose tissue explants, nor did it modulate cytokine release and mRNA expression of IL-6, IL-8, and TNF-alpha upon LPS stimulation. In undifferentiated MSCs, NDP-MSH did not alter the metabolic rate, but it showed a significant antiproliferative effect. Therefore, it appears that MC1-R-effector coupling in (differentiated) human adipocytes is too weak to induce a regulatory effect on lipolysis or inflammation; by contrast, MC1-R stimulation in undifferentiated MSCs induces an inhibitory signal on cell proliferation.