Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts.

BACKGROUND: Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, such as DNA methylation, in the offspring. Oocyte maturation and early embryo development coincide with methylation changes and both are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect establishment and maintenance of DNA methylation in oocytes and embryos, subsequently altering transcriptomic profiles and developmental competence of resultant blastocysts. RESULTS: Bovine oocytes and embryos were exposed to different NEFA concentrations in separate experiments. In the first experiment, oocytes were matured in vitro for 24 h in medium containing: 1) physiological ("BASAL") concentrations of oleic (OA), palmitic (PA) and stearic (SA) acid or 2) pathophysiological ("HIGH COMBI") concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. Developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray. DNA methylation data were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to BASAL-exposed counterparts (19.3% compared to 23.2% and 18.2% compared to 25.3%, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to adverse environments. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. CONCLUSIONS: Overall, high variation in methylation between blastocysts made it difficult to draw conclusions concerning methylation of individual genes, although a clear overview of affected pathways was obtained. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later life observed in offspring from mothers displaying lipolytic disorders.

Selenazolidine: a selenium containing proline surrogate in peptide science.

In the search for new peptide ligands containing selenium in their sequences, we investigated l-4-selenazolidine-carboxylic acid (selenazolidine, Sez) as a proline analog with the chalcogen atom in the γ-position of the ring. In contrast to proteinogenic selenocysteine (Sec) and selenomethionine (SeMet), the incorporation within a peptide sequence of such a non-natural amino acid has never been studied. There is thus a great interest in increasing the possibility of selenium insertion within peptides, especially for sequences that do not possess a sulfur containing amino acid (Cys or Met), by offering other selenated residues suitable for peptide synthesis protocols. Herein, we have evaluated selenazolidine in Boc/Bzl and Fmoc/tBu strategies through the synthesis of a model tripeptide, both in solution and on a solid support. Special attention was paid to the stability of the Sez residue in basic conditions. Thus, generic protocols have been optimized to synthesize Sez-containing peptides, through the use of an Fmoc-Xxx-Sez-OH dipeptide unit. As an example, a new analog of the vasopressin receptor-1A antagonist was prepared, in which Pro was replaced with Sez [3-(4-hydroxyphenyl)-propionyl-d-Tyr(Me)-Phe-Gln-Asn-Arg-Sez-Arg-NH2]. Both proline and such pseudo-proline containing peptides exhibited similar pharmacological properties and endopeptidase stabilities indicating that the presence of the selenium atom has minimal functional effects. Taking into account the straightforward handling of Sez as a dipeptide building block in a conventional Fmoc/tBu SPPS strategy, this result suggested a wide range of potential uses of the Sez amino acid in peptide chemistry, for instance as a viable proline surrogate as well as a selenium probe, complementary to Sec and SeMet, for NMR and mass spectrometry analytical purposes.

Mitochondrial DNA haplogroups and mutations in children with acquired central demyelination.

OBJECTIVE: We investigated mitochondrial DNA (mtDNA) variants in children with a first episode of acquired demyelinating syndromes (PD-ADS) of the CNS and their relationship to disease phenotype, including subsequent diagnosis of multiple sclerosis (MS). METHODS: This exploratory analysis included the initial 213 children with PD-ADS in the prospective Canadian Pediatric Demyelinating Study and 166 matched healthy sibling controls from the Canadian Autism Genome Project. A total of 31 single nucleotide polymorphisms (SNPs) were analyzed, including haplogroup-defining SNPs and mtDNA variants previously reported to be associated with MS. RESULTS: Primary Leber hereditary optic neuropathy (LHON) mutations and other known pathogenic mtDNA mutations were absent in both patients with pediatric acquired demyelinating syndromes and controls. The 13708A haplogroup J-associated variant, previously linked to adult MS, was more frequent among subjects with PD-ADS (13.0%) compared to controls (6.2%; odds ratio [OR] 2.27; 95% confidence interval [CI] 1.06 to 4.83) and haplogroup M was associated with an earlier age at onset of PD-ADS (-1.74 years; 95% CI -3.33 to -0.07). In contrast, the haplogroup cluster UKJT, as well as 3 other SNPs, were each associated with a lower risk of PD-ADS. A total of 33 subjects with PD-ADS were diagnosed with MS during a mean follow-up period of 3.11 ± 1.14 (SD) years. No single SNP was associated with the risk of subsequent diagnosis of MS. However, haplogroup H was associated with an increased risk of MS (OR 2.60; 95% CI 1.21 to 5.55). CONCLUSION: These data suggest an association between mtDNA variants and the risk of PD-ADS and of a subsequent MS diagnosis. Replication of these findings in an independent population of subjects with PD-ADS is required.

Systematic patients' hand disinfection: impact on meticillin-resistant Staphylococcus aureus infection rates in a community hospital.

The role of patients and their relatives as unidentified transient meticillin-resistant Staphylococcus aureus (MRSA) carriers and sources of dissemination in healthcare institutions has not been systematically addressed. Patients' and their relatives' hands may represent a substantial and 'unaccounted for' mode of transmission. This study aimed to verify this hypothesis in our 250-bed community hospital. The trial consisted of a systematic waterless washing and gel rinse disinfection of all patients' and visiting relatives' hands for a period of one year, along with retrospective comparison of the nosocomial infection rates. Under the supervision of infection control personnel, a team of four full-time and four part-time attendants was trained to meet all patients and visiting relatives and encourage them to clean their hands with an alcohol gel rinse twice a day on every weekday. Rates of MRSA infections per thousand admissions, cost-benefit analysis and staff hand hygiene compliance were audited throughout. From the comparative year, the rate of MRSA nosocomial infections per thousand admissions decreased by 51%. Assuming that the incidence of MRSA was maintained from comparative to study year, the intervention may have prevented 51 cases of MRSA infection and resulted in substantial savings. While focusing extensively on staff behaviour to prevent MRSA transmission, we may have overlooked hand hygiene practices by patients and their relatives as a potential mode of transmission. Systematic hand hygiene of patients and relatives appears to be an inexpensive and highly effective preventive measure against MRSA nosocomial transmission.

Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis.

Anti-myelin basic protein (MBP) antibodies in pediatric-onset MS and controls were characterized. Serum samples were obtained from 94 children with MS and 106 controls. Paired CSF and serum were obtained from 25 children with MS at time of their initial episode of acute demyelinating syndrome (ADS). Complementary assays were applied across samples to evaluate the presence, and the physical binding properties, of anti-MBP antibodies. While the prevalence and titers of serum anti-MBP antibodies against both immature and mature forms of MBP were similar in children with MS and in controls, binding characteristics and formal Surface Plasmon Resonance (SPR) studies indicated surprisingly high binding affinities of all pediatric anti-MBP antibodies. Serum levels of anti-MBP antibodies correlated significantly with their CSF levels, and their presence in children with MS was associated with significantly increased risk of an acute disseminated encephalomyelitis-like initial clinical presentation. While antibodies to both immature and mature forms of MBP can be present as part of the normal pediatric humoral repertoire, these anti-myelin antibodies are of surprisingly high affinity, can access the CNS during inflammation, and have the capacity to modulate disease expression. Our findings identify an immune mechanism that could contribute to the observed heterogeneity in spectrum of clinical presentations in early-onset MS.

A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis.

OBJECTIVE: Low vitamin D status has been associated with multiple sclerosis (MS) prevalence and risk, but the therapeutic potential of vitamin D in established MS has not been explored. Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical, immunologic, and clinical outcomes in patients with MS prospectively. METHODS: An open-label randomized prospective controlled 52-week trial matched patients with MS for demographic and disease characteristics, with randomization to treatment or control groups. Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [25(OH)D] rapidly and assess tolerability, followed by 10,000 IU/day (12 weeks), and further downtitrated to 0 IU/day. Calcium (1,200 mg/day) was given throughout the trial. Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups. Secondary endpoints included 25(OH)D and other biochemical measures, immunologic biomarkers, relapse events, and Expanded Disability Status Scale (EDSS) score. RESULTS: Forty-nine patients (25 treatment, 24 control) were enrolled [mean age 40.5 years, EDSS 1.34, and 25(OH)D 78 nmol/L]. All calcium-related measures within and between groups were normal. Despite a mean peak 25(OH)D of 413 nmol/L, no significant adverse events occurred. Although there may have been confounding variables in clinical outcomes, treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls. CONCLUSIONS: High-dose vitamin D (approximately 10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects. CLASSIFICATION OF EVIDENCE: This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation. The trial, however, lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures (relapses and Expanded Disability Status Scale scores), providing only Class level IV evidence for these outcomes.

Gastrojejunal strictures following laparoscopic Roux-en-Y gastric bypass for morbid obesity.

BACKGROUND: Gastrojejunal strictures following laparoscopic Roux-en-Y gastric bypass (LRYGBP) present with dysphagia, nausea, and vomiting. Diagnosis is made by endoscopy and/or radiographic studies. Therapeutic options include endoscopic dilation and surgical revision. METHODS: Of 369 LRYGBP performed, 19 patients developed anastomotic stricture (5.1%). One additional patient was referred from another facility. Pneumatic balloons were used for initial dilation in all patients. Savary-Gilliard bougies were used for some of the subsequent dilations. RESULTS: Flexible endoscopy was diagnostic in all 20 patients allowing dilation in 18 (90%). Two patients did not undergo endoscopic dilation because of anastomotic obstruction and ulcer. The median time to stricture development was 32 days (range: 17-85). Most patients (78%) required more than two dilations. The complication rate was 1.6% (one case of microperforation). At a mean follow-up of 21 months, all patients were symptom-free. CONCLUSIONS: Gastrojejunostomy stricture following LRYGBP is associated with substantial morbidity and patient dissatisfaction. Based on our experience, we propose a clinical grading system and present our strategy for managing gastrojejunal strictures.

Microsphere intestinal blood flow analysis during pneumoperitoneum using carbon dioxide and helium.

BACKGROUND: Pneumoperitoneum has been associated with a decreased flow in the superior mesenteric artery and portal venous system. Intestinal blood flow was studied during a 2-h pneumoperitoneum with carbon dioxide (CO2) or helium in a porcine model using colored microspheres. METHODS: For this study, 12 pigs were divided into two groups (6 CO2 and 6 helium). Different colored microspheres were injected directly into the left ventricle before, 40, 80, and 120 min after insufflation with either gas at a pressure of 15 mmHg. Microsphere concentration was measured in the mucosa and muscularis/serosa layers of the jejunum, cecum, and sigmoid colon to calculate blood flow. RESULTS: Intestinal perfusion initially increases with insufflation and returns to near baseline levels during pneumoperitoneum of 2 h. The effect of helium on tissue perfusion is similar to that of carbon dioxide. CONCLUSIONS: Intestinal perfusion does not change significantly during prolonged pneumoperitoneum at a pressure of 15 mmHg with CO2 or helium.

Laparoscopic repair of large paraesophageal hernia is associated with a low incidence of recurrence and reoperation.

BACKGROUND: Laparoscopic repair of paraesophageal hernia (LRPEH) is a feasible and effective technique. There have been some recent concerns regarding possible high recurrence rates following laparoscopic repair. METHODS: We reviewed our experience with LRPEH from 5/1996 to 8/2002. Large paraesophageal hernia (PEH) was defined by the presence of more than one-third of the stomach in the thoracic cavity. Principles of repair included reduction of the hernia, excision of the sac, approximation of the crura, and fundoplication. Pre- and postoperative symptoms were evaluated utilizing visual analogue scores (VAS) on a scale ranging from 0 to 10. Patients were followed with VAS and barium esophagram studies. Statistical analysis was performed using two-tailed Student's t-test. RESULTS: A total of 166 patients with a mean age of 68 years underwent LRPEH. PEH were type II ( n = 43), type III ( n = 104), and type IV ( n = 19). Mean operative time was 160 min. Fundoplications were Nissen (127), Toupet (23), Dor (1), and Nissen-Collis (1). Fourteen patients underwent a gastropexy. One patient required early reoperation to repair an esophageal leak. Mean hospital stay was 3.9 days. At 24 months postoperatively there was statistically significant improvement in the mean symptom scores: heartburn from 6.8 to 0.5, regurgitation from 5.9 to 0.3, dysphagia from 4.0 to 0.5, chest pain from 3.7 to 0.3. Radiographic surveillance was obtained in 120 patients (72%) at a mean of 15 months postoperatively. Six patients (5%) had radiographic evidence of a recurrent paraesophageal hernia (two required surgery), 24 patients (20%) had a sliding hernia (two required surgery), and four patients (3.3%) had wrap failure (all four required surgery). Reoperation was required in 10 patients (6%); two for symptomatic recurrent PEH (1.2%), four for recurrent reflux symptoms (2.4%), and four for dysphagia (2.4%). Patients with abnormal postoperative barium esophagram studies who did not require reoperation have remained asymptomatic at a mean follow up of 14 months. CONCLUSION: LPEHR is a safe and effective treatment for PEH. Postoperative radiographic abnormalities, such as a small sliding hernia, are often seen. The clinical importance of these findings is questionable, since only a small percentage of patients require reoperation. True PEH recurrences are uncommon and frequently asymptomatic.

Concentration of soluble intercellular adhesion molecule-1 in serum samples from patients with endometriosis collected during the luteal phase of the menstrual cycle.

BACKGROUND: Soluble intercellular adhesion molecule-1 (sICAM-1), released by endometriotic lesions, is involved in the regulation of cytotoxic processes. Altered levels of sICAM-1 in the circulation could parallel its deregulation in the peritoneal cavity. We therefore investigated whether sICAM-1 could represent a serum marker for endometriosis. METHODS: sICAM-1 levels were measured by enzyme-linked immunosorbent assay in serum samples from 176 subjects with surgically confirmed endometriosis (134 patients with stage I-II and 42 patients with stage III-IV) and 198 controls with no surgical evidence of the disease. All serum samples were collected during the luteal phase of the menstrual cycle. Detailed information about demographics, symptoms and clinical profile were collected. RESULTS: Mean levels of sICAM-1 appeared significantly reduced in patients with stage III-IV endometriosis in a crude comparison of means. However, when means were adjusted for potential confounders such as the pre-operative indication or fertility status, no significant difference between cases with stage III-IV disease and controls was observed. CONCLUSIONS: Serum levels of sICAM-1 during the luteal phase of the cycle are not able to discriminate women suffering from endometriosis from controls when confounders are taken into account. These results underline the importance of careful identification of confounders, based on patients' demographic and clinical data in studies aiming at discovering diagnostic markers for endometriosis.

Modified extraperitoneal endoscopic separation of parts for abdominal compartment syndrome.

BACKGROUND: Standard therapy for abdominal compartment syndrome (ACS) is laparotomy and temporary abdominal wall closure with significant morbidity. The component separation technique allows for difficult abdominal closure. We studied a modified extraperitoneal endoscopic separation of parts technique on an animal model of ACS. METHODS: Twelve anesthetized pigs were instrumented for measurement of central venous pressure, arterial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, and intraabdominal pressure (IAP). ACS to 25 mmHg was created by infusing saline into an intraabdominally placed bag. Animals were divided in two equal groups. Pigs in group A underwent minimally invasive resection of the nerves supplying the rectus muscles bilaterally. Pigs in group B underwent minimally invasive modified component separation technique bilaterally. Change in IAP and other physiological parameters were recorded. RESULTS: (Group A) IAP increased significantly from 7.3 mmHg +/- 3.8 to 25.2 mmHg +/- 1.5 with infusion of saline. Following nerve transection on the right side there was a nonsignificant decrease in IAP from 25.2 mmHg +/- 1.5 to 22.3 mmHg +/- 1.4 and following nerve transection on the left side there was a further decrease in IAP to 20.3 mmHg +/- 1.9. (Group B) IAP increased significantly from 3.8 mmHg +/- 0.4 to 24.7 mmHg +/- 0.5 with infusion of saline. Following separation of parts on the right side there was a significant decrease in IAP from 24.7 mmHg +/- 0.5 to 15.0 mmHg +/- 1.7 and there was a further decrease in IAP to 11.3 mmHg +/- 1.4 following separation of parts on the left side. The only significant change in the physiological parameters measured was observed in CVP in both groups. CONCLUSION: We present a porcine model of extraperitoneal endoscopic release of abdominal wall components as a treatment option for ACS.

Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis.

BACKGROUND: Elevated concentrations of vascular endothelial growth factor (VEGF) have been detected in the peritoneal fluid of patients with endometriosis. Furthermore, it was postulated that VEGF is involved in the development of endometriotic lesions. The present study is aimed at determining whether high levels of VEGF could also be found in the serum of patients with endometriosis. METHODS: VEGF levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum from 131 subjects with surgically confirmed endometriosis and 146 controls with no clinical evidence of the disease or detectable endometriotic lesions at the time of surgical examination. Parameters such as demographics, personal habits, menstrual characteristics and clinical profile were collected from each subject included in this study. RESULTS: The mean VEGF levels were not significantly modulated in serum samples of cases compared with controls in a crude general linear model and in a model adjusted for possible confounders. VEGF serum levels did not correlate with the score, stage of endometriosis or the presence of benign gynaecological disorders. However, a correlation was found between circulating concentrations of VEGF and body mass index. CONCLUSION: Although VEGF seems to play a pivotal role locally in the implantation and development of endometriotic lesions, the disease is not associated with a significant modulation in the levels of circulating VEGF.

Effectiveness of laparoscopic fundoplication in relieving the symptoms of gastroesophageal reflux disease (GERD) and eliminating antireflux medical therapy.

BACKGROUND: Recent reports have suggested that antireflux surgery should not be advised with the expectation of elimination of medical treatment. We reviewed our results with laparoscopic fundoplication as a means of eliminating the symptoms of gastroesophageal reflux disease (GERD), improving quality of life, and freeing patients from chronic medical treatment for GERD. METHODS: A total of 297 patients who underwent laparoscopic fundoplication (Nissen, n = 252; Toupet, n = 45) were followed for an average of 31.4 months. Preoperative evaluation included endoscopy, barium esophagram, esophageal manometry, and 24-h pH analysis. A preoperative and postoperative visual analogue scoring scale (0-10 severity) was used to evaluate symptoms of heartburn, regurgitation, and dysphagia. A GERD score (2-32) as described by Jamieson was also utilized. The need for GERD medications before and after surgery was assessed. RESULTS: At 2-year follow-up, the average symptom scores decreased significantly in comparison to the preoperative values: heartburn from 8.4 to 1.7, regurgitation from 7.2 to 0.7, and dysphagia from 3.7 to 1.0. The Jamieson GERD score also decreased from 25.7 preoperatively to 4.1 postoperatively. Only 10% of patients were on proton pump inhibitors (PPI) at 2 years after surgery for typical GERD symptoms. A similar percentage of patients (8.7%) were on PPI treatment for questionable reasons, such as Barrett's esophagus, "sensitive" stomach, and irritable bowel syndrome. Seventeen patients (5.7%) required repeat fundoplication for heartburn ( n = 9), dysphagia ( n = 5), and gas/bloating ( n = 3). CONCLUSIONS: Laparoscopic fundoplication can successfully eliminate GERD symptoms and improve quality of life. Significant reduction in the need for chronic GERD medical treatment 2 years after antireflux surgery can be anticipated.

Presence of LH receptor mRNA in granulosa cells as a potential marker of oocyte developmental competence and characterization of the bovine splicing isoforms.

As the expression of the LH receptor (LH-R) in granulosa cells is thought to be associated with later stages of folliculogenesis, this study was undertaken to evaluate the presence of LH-R mRNA as a suitable marker for developmental competence of oocytes. Granulosa cells and cumulus-oocyte complexes (COCs) were recovered from cows that had received ovarian stimulation. The COCs were subjected to embryo production procedures in vitro to assess the embryonic potential of the oocyte, and the corresponding granulosa cells were used to evaluate the presence of LH-R mRNA by RT-PCR. The presence of LH-R transcripts in granulosa cells is not a key characteristic of a follicle bearing a competent oocyte, although a higher proportion of oocytes reach the blastocyst stage when LH-R mRNA is detected in the granulosa cells. Different LH-R isoforms were cloned and sequence discrepancies among six of the isoforms enabled the design of specific oligonucleotides to study the presence of the isoforms in different follicular cells. All LH-R transcripts studied and the 80 kDa protein product corresponding to the full length receptor were found in granulosa cells of small (< 4 mm) and large (> 5 mm) follicles. When the granulosa cells were cultured, the transcripts were downregulated by the culture conditions; downregulation was more acute in granulosa cells from small follicles. The addition of LH to the culture media enhanced LH-R mRNA downregulation. The presence of several LH-R transcript isoforms was tissue specific and in the theca cells LH-R mRNA was restricted mainly to cells from larger follicles. This finding indicates that the expression and the splicing of LH-R mRNA are regulated in a cell-specific and follicular size-specific manner.

Laparoscopic management of complications following laparoscopic Roux-en-Y gastric bypass for morbid obesity.

BACKGROUND: We reviewed our experience with complications following laparoscopic Roux-en-Y gastric bypass (LRYGB) that were managed laparoscopically. METHODS: A total of 246 consecutive morbidly obese patients (mean body mass index, 50.9 kg/m2) underwent LRYGB by three surgeons at two institutions. All patients met National Institutes of Health criteria for surgical treatment of morbid obesity. Patients were followed prospectively. RESULTS: A total of 62 patients (25.2%) developed 64 complications, 34 of which (13.8%) required a surgical intervention. Twenty-seven of the 34 procedures were performed laparoscopically. Gastrojejunostomy stricture was the most common complication (8.9%), followed by intestinal obstruction (7.3%) and gastrointestinal bleeding (4%). The intestinal obstruction was secondary to adhesions (n = 6), internal hernia at the level of the transverse mesocolon (n = 3), jejunojejunostomy stricture (n = 3), and cicatrix around the Roux limb at the level of the transverse mesocolon (n = 3). Other complications included gastrojejunostomy leak (1.6%), symptomatic gallstone disease (2.8%), and gastric remnant perforation (0.8%). One patient underwent a negative laparoscopy to rule out anastomotic leak. There were 3 deaths in this series of patients, 2 attributable to anastomotic leak. CONCLUSIONS: A variety of complications can present after LRYGB. Laparoscopy is an excellent technique to treat these complications.

Laparoscopic revision of failed open bariatric procedures.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is considered the surgical procedure of choice for morbid obesity. Patients who fail to meet weight loss goals after restrictive or malabsorptive surgery can be offered revision. We present five cases in which prior open bariatric procedures were revised laparoscopically. PATIENTS: Five patients presented for laparoscopic revision having regained weight after initial success with prior bariatric surgery. RESULTS: Preoperative body mass index averaged 46 kg/m2. Average operative time was significantly longer (344 min) than we had experienced with 56 primary RYGB during the same 4-month period (206 min). In one patient, a stricture had developed at the gastrojejunostomy requiring endoscopic dilation. There were no other complications and no deaths. All the patients had lost weight at the 6-month follow-up assessment. CONCLUSIONS: Laparoscopic revision of failed open bariatric procedures, although requiring longer operative times than primary RYGB, can be performed safely in the hands of an experienced minimally invasive surgeon.

Prediction of postoperative gas bloating after laparoscopic antireflux procedures based on 24-h pH acid reflux pattern.

BACKGROUND: Postoperative gas/bloating (G/B) is a common sequelae after laparoscopic fundoplication. Patients with "upright" reflux are thought to have more aerophagic tendencies contributing to their GERD symptoms than patients with significant "supine" patterns of reflux. The risk of postoperative G/B developing was analyzed in relation to patient preoperative patterns of upright, mixed, or supine 24-h pH scores. METHODS: In this study, 339 patients undergoing fundoplication (278 Nissen and 61 Toupet) were evaluated for preoperative G/B symptoms using a 0 to 10 severity visual analogue scale. Reflux patterns were classified as upright, supine, or mixed according to 24-h pH studies. RESULTS: As compared with preoperative values, 46% of the patients with a preoperative G/B score less than 3 and an upright or mixed reflux pattern had a significant increase in their average G/B score at 2 years (upright, from 0.9 to 4.2; mixed, from 1.1 to 4.1). However, the patients with a supine reflux pattern did not have a statistically significant change (from 2.0 to 2.2; p > 0.05). The patients with established aerophagic tendencies preoperatively (G/B score > 3) showed significant improvement in these symptoms at 2 years across all three reflux patterns (average G/B score, from 7.7 preoperatively to 4.8 at 2 years). There was no gender predisposition, nor was there any difference in the incidence of G/B between complete and partial fundoplication. CONCLUSIONS: The pattern of 24-h acid reflux can be predictive of G/B after antireflux surgery. Patients with mild preoperative G/B symptoms (score <3) and upright or mixed patterns of 24-h acid reflux appear to have an increased postoperative risk for chronic G/B as compared with patients who have supine reflux and mild preoperative G/B. Patients with moderate to severe preoperative G/B symptoms (score, 3-10) appear to have a general improvement in G/B symptoms at 2 years after fundoplication.

Outcome analysis of laparoscopic Roux-en-Y gastric bypass for morbid obesity. The first 116 cases.

BACKGROUND: Morbid obesity has been described as a continuing epidemic affecting a growing portion of our population. We report an outcome analysis of our early experience with laparoscopic Roux-en-Y gastric bypass (LRYGB) in the treatment of morbid obesity. METHODS: Two surgeons performed 116 consecutive LRYGBs at a single institution, creating a 25-ml pouch and a 90- to 150-cm Roux limb. The prospectively collected data included patient demographics, comorbidities, postoperative weight loss, and complications. RESULTS: All eight conversions to an open procedure occurred early during the experience of the surgeons. The mean operating room time for the first 50 cases was 272 min, which decreased to 198 min with experience. The mean length of hospital stay was 3 days. There were 34 complications in 27 patients (23.3%), 14 of which (12%) required reoperation. At 18 months postoperatively, the patients had lost 77% of their excess weight, and their body mass index had decreased from a mean of 49.3 to 32.6 kg/m2. As a result of LRYGB, 25% of the patients were rendered completely free of any pharmacologic treatment for their preexisting comorbidities. CONCLUSIONS: Although technically challenging, LRYGB can be performed safely with excellent long-term results. The mean operating room time and conversion rate improved with experience. As this study showed, LRYGB achieves an excellent rate of weight loss and improvement in preoperative comorbidities with a minimal length of hospital stay and an acceptable complication rate.

Laparoscopic transgastric endoscopic retrograde cholangiopancreatography for benign common bile duct stricture after Roux-en-Y gastric bypass.

Access to the gastric remnant and duodenum is lost after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Traditionally, a percutaneous transhepatic access to the common bile duct has been used to manage choledocholithiasis and duct strictures. We present a novel method of laparoscopic transgastric endoscopic retrograde cholangiopancreatography for managing a benign biliary stricture after a Roux-en-Y gastric bypass.

Immediate radiographic assessment following laparoscopic antireflux operations is unnecessary.

BACKGROUND: Laparoscopic antireflux operations (LAP) have become increasingly common for the treatment of gastroesophageal reflux disease (GERD). We sought to determine if routine postoperative barium contrast studies following LAP were clinically efficacious in identifying technical problems and life-threatening complications related to the surgical intervention. METHODS: From January 1996 to December 1997, 112 barium studies were performed following 112 LAP procedures (47 male/65 female patients; mean age, 51 years) (group I). This group was compared to a subsequent cohort of 67 patients who underwent LAP between January 1998 and July 1998 without routine early postoperative barium contrast study (group II). RESULTS: In 111/112 of the barium studies of group I, no radiographic abnormality was identified. The average length of stay (LOS) for these patients was 2.6 days. Routine barium studies were not utilized in group II. The average length of stay for patients in group II was 1.4 days. Twelve group II patients underwent early postoperative barium studies to evaluate suspicious clinical symptoms. None of these 12 postoperative studies identified important problems, nor did they alter the patients' clinical management. However, because of the barium study, their LOS was equivalent to those patients who had undergone routine barium study (2.4 days). There was an increase of $1451.80 in hospital charges in the group of patients who had a barium study, largely as a result of the increased LOS. CONCLUSION: The routine use of these studies results in increased patient charges and a prolongation in the length of hospital stay. Immediate postoperative barium studies following laparoscopic antireflux operations are of little value in determining important postoperative problems among patients undergoing LAO.