The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Gastroesophageal reflux disease and patterns of reflux in patients with idiopathic pulmonary fibrosis using hypopharyngeal multichannel intraluminal impedance.

Idiopathic pulmonary fibrosis (IPF) is a diffuse fibrotic lung disease of unknown etiology. The association between IPF and gastroesophageal reflux disease (GERD) has been suggested. The objective of this study was to determine the prevalence of GERD and assess the proximity of reflux events in patients with histologically proven IPF using hypopharyngeal multichannel intraluminal impedance (HMII). This is a retrospective review of prospectively collected data from patients with histologically confirmed IPF (via lung biopsy) who underwent objective esophageal physiology testing including high-resolution manometry and HMII. Defective lower esophageal sphincter (LES) was defined as either LES pressure of <5.0 mmHg, total length of LES of <2.4 cm, or intra-abdominal length of LES of <0.9 cm. Abnormal esophageal motility was considered present when failed swallows ≥30% and/or mean wave amplitude <30 mmHg was present. HMII used a specialized impedance catheter to directly measure laryngopharyngeal reflux (LPR) and full column reflux (reflux 2 cm distal to the upper esophageal sphincter). Based on the previous study of healthy subjects, abnormal proximal exposure was considered present when LPR ≥1/day and/or full column reflux ≥5/day were present. From October 2009 to June 2011, 46 patients were identified as having pulmonary fibrosis and sufficient HMII data. Of 46, 10 patients were excluded because of concomitant connective tissue diseases, and 8 patients were excluded because they had undergone lung transplantation, which may impact the patterns of reflux. The remaining 28 patients with histologically confirmed IPF (male 16, female 12) were included in this study. Mean age and BMI were 60.4 years (range, 41-78) and 28.4 (range, 21.1-38.1), respectively. All patients except one were symptomatic; 23 (82%) patients had concomitant typical GERD symptoms such as heartburn, whereas 4 (14%) patients had isolated pulmonary symptoms such as cough. Esophageal mucosal injury such as esophagitis and Barrett's esophagus was found in 17 (71%) patients, whereas hiatal hernia was found in 19 (73%) patients. Abnormal proximal exposure, which occurred almost exclusively in the upright position, was present in 54% (15/28) of patients. There was no significant difference in clinical symptoms, objective findings of GERD, and pulmonary functions such as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) between patients with and without abnormal proximal exposure. Although the total number of reflux events was significantly higher in patients with abnormal proximal exposure, a large number of patients had a negative DeMeester score regardless of whether abnormal proximal exposure was present (patients with, 80%; those without, 85%). Patients with abnormal proximal exposure more likely had a defective LES compared with those without (93% vs. 75%). Fourteen patients (56%) had abnormal esophageal motility including aperistaltic esophagus (n = 9). This first study of HMII in patients with IPF demonstrated that GERD is highly prevalent (>70%), and abnormal proximal reflux events such as LPR and full column reflux are common despite a frequently negative DeMeester score. HMII may be beneficial in the work-up of GERD in patients with IPF.

Recombinant vascular endothelial growth factor165 gene therapy improves anastomotic healing in an animal model of ischemic esophagogastrostomy.

Proper anastomotic healing is dependent upon many factors including adequate blood flow to healing tissue. The aim of this study was to investigate the impact of vascular endothelial growth factor (VEGF(165)) transfection on anastomotic healing in an ischemic gastrointestinal anastomosis model. Utilizing an established opossum model of esophagogastrectomy followed by esophageal-gastric anastomosis, the gastric fundus was transfected with recombinant human vascular endothelial growth factor via direct injection of a plasmid-based nonviral delivery system. Twenty-nine animals were divided into three groups: two concentrations of VEGF and a control group. Outcomes included VEGF mRNA transcript levels, neovascularization, tissue blood flow, and anastomotic bursting pressure. To determine whether local injection resulted in a systemic effect, distant tissues were evaluated for VEGF transcript levels. Successful gene transfection was demonstrated by quantitative polymerase chain reaction analysis of anastomotic tissue, with significantly higher VEGF mRNA expression in treated animals compared to controls. At the gastric side of the anastomosis, there was significantly increased neovascularization, blood flow, and bursting pressure in experimental animals compared to controls. There were no differences in outcome measures between low- and high-dose VEGF groups; however, the high-dose group demonstrated increased VEGF mRNA expression across the anastomosis. VEGF production was not increased at distant sites in treated animals. In this animal model, VEGF gene therapy increased VEGF transcription at a healing gastrointestinal anastomosis without systemic VEGF upregulation. This treatment led to improved healing and strength of the acutely ischemic anastomosis. These findings suggest that VEGF gene therapy has the potential to reduce anastomotic morbidity and improve surgical outcomes in a wide array of patients.

Trends in the management of esophageal carcinoma based on provider volume: treatment practices of 618 esophageal surgeons.

Controversy exists regarding optimal treatment practices for esophageal cancer. Esophagectomy has received focus as one of the index procedures for both hospital and surgical quality despite a relative paucity of controlled trials to define best practices. A survey was created to determine the degree of heterogeneity in the treatment of esophageal cancer among a diverse group of surgeons and to use high-volume (HV) (>/=15 cases/year) and low-volume (LV) (<15 cases/year) designations to discern specific differences in the management of esophageal cancer from the surgeon's perspective. Based on society rosters, surgeons (n = 4000) in the USA and 15 countries were contacted via mail and queried regarding their treatment practices for esophageal cancer using a 50-item survey instrument addressing demographics, utilization of neoadjuvant chemoradiotherapy, and choice of surgical approach for esophageal resection and palliation. There were 618 esophageal surgeons among respondents (n = 1447), of which 77 (12.5%) were considered HV. The majority of HV surgeons (87%) practiced in an academic setting and had cardiothoracic training, while most LV surgeons were general surgeons in private practice (52.3%). Both HV and LV surgeons favored the hand-sewn cervical anastomosis and the stomach conduit. Minimally invasive esophagectomy is performed more frequently by HV surgeons when compared with LV surgeons (P = 0.045). Most HV surgeons use neoadjuvant therapy for patients with nodal involvement, while LV surgeons are more likely to leave the decision to the oncologist. With a few notable exceptions, substantial heterogeneity exists among surgeons' management strategies for esophageal cancer, particularly when grouped and analyzed by case volume. These results highlight the need for controlled trials to determine best practices in the treatment of this complex patient population.

Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-gamma in inflammation in human adipose tissue.

BACKGROUND: Adipose tissue is a primary in vivo site of inflammation in obesity. Excess visceral adipose tissue (VAT), when compared to subcutaneous adipose tissue (SAT), imparts an increased risk of obesity-related comorbidities and mortality, and exhibits differences in inflammation. Defining depot-specific differences in inflammatory function may reveal underlying mechanisms of adipose-tissue-based inflammation. METHODS: Stromovascular cell fractions (SVFs) from VAT and SAT from obese humans undergoing bariatric surgery were studied in an in vitro culture system with transcriptional profiling, flow cytometric phenotyping, enzyme-linked immunosorbent assay and intracellular cytokine staining. RESULTS: Transcriptional profiling of SVF revealed differences in inflammatory transcript levels in VAT relative to SAT, including elevated interferon-gamma (IFN-gamma) transcript levels. VAT demonstrated a broad leukocytosis relative to SAT that included macrophages, T cells and natural killer (NK) cells. IFN-gamma induced a proinflammatory cytokine expression pattern in SVF and adipose tissue macrophages (ATM). NK cells, which constitutively expressed IFN-gamma, were present at higher frequency in VAT relative to SAT. Both T and NK cells from SVF expressed IFN-gamma on activation, which was associated with tumor necrosis factor-alpha expression in macrophages. CONCLUSION: These data suggest involvement of NK cells and IFN-gamma in regulating ATM phenotype and function in human obesity and a potential mechanism for the adverse physiologic effects of VAT.

Psychiatric illness delays diagnosis of esophageal cancer.

Evidence suggests that patients with psychiatric illnesses may be more likely to experience a delay in diagnosis of coexisting cancer. The association between psychiatric illness and timely diagnosis and survival in patients with esophageal cancer has not been studied. The specific aim of this retrospective cohort study was to determine the impact of coexisting psychiatric illness on time to diagnosis, disease stage and survival in patients with esophageal cancer. All patients with a diagnosis of esophageal cancer between 1989 and 2003 at the Portland Veteran's Administration hospital were identified by ICD-9 code. One hundred and sixty patients were identified: 52 patients had one or more DSM-IV diagnoses, and 108 patients had no DSM-IV diagnosis. Electronic charts were reviewed beginning from the first recorded encounter for all patients and clinical and demographic data were collected. The association between psychiatric illness and time to diagnosis of esophageal cancer and survival was studied using Cox proportional hazard models. Groups were similar in age, ethnicity, body mass index, and history of tobacco and alcohol use. Psychiatric illness was associated with delayed diagnosis (median time from alarm symptoms to diagnosis 90 days vs. 35 days in patients with and without psychiatric illness, respectively, P < 0.001) and the presence of advanced disease at the time of diagnosis (37% vs. 18% of patients with and without psychiatric illness, respectively, P= 0.009). In multivariate analysis, psychiatric illness and depression were independent predictors for delayed diagnosis (hazard ratios 0.605 and 0.622, respectively, hazard ratio < 1 indicating longer time to diagnosis). Dementia was an independent risk factor for worse survival (hazard ratio 2.984). Finally, psychiatric illness was associated with a decreased likelihood of receiving surgical therapy. Psychiatric illness is a risk factor for delayed diagnosis, a diagnosis of advanced cancer, and a lower likelihood of receiving surgical therapy in patients with esophageal cancer. Dementia is associated with worse survival in these patients. These findings emphasize the importance of prompt evaluation of foregut symptoms in patients with psychiatric illness.

Endoscopic ultrasound for the evaluation of Nissen fundoplication integrity: a blinded comparison with conventional testing.

BACKGROUND: For patients whose symptoms develop after Nissen fundoplication, the precise mechanism of anatomic failure can be difficult to determine. The authors have previously reported the endosonographic hallmarks defining an intact Nissen fundoplication in swine and the known causes of failure. The current clinical trial tested the hypothesis that a defined set of endosonographic criteria can be applied to determine fundoplication integrity in humans. METHODS: The study enrolled seven symptomatic and nine asymptomatic subjects at a mean of 6 years (range, 1-30 years) after Nissen fundoplication. A validated gastroesophageal reflux disease (GERD)-specific questionnaire and medication history were completed. Before endoscopic ultrasound (EUS), all the patients underwent complete conventional testing (upper endoscopy, esophagram, manometry, 24-h pH). A diagnosis was rendered on the basis of combined test results. Then EUS was performed by an observer blinded to symptoms, medication use, and conventional testing diagnoses. Because EUS and esophagogastroduodenoscopy (EGD) are uniformly performed in combination, the EUS diagnosis was rendered on the basis of previously established criteria combined with the EGD interpretation. The diagnoses then were compared to examine the contribution of EUS in this setting. RESULTS: The technique and defined criteria were easily applied to all subjects. All symptomatic patients had heartburn and were taking proton pump inhibitors (PPI). No asymptomatic patients were taking PPI. All diagnoses established with combined conventional testing were detected on EUS with upper endoscopy. Additionally, EUS resolved the etiology of a low lower esophageal sphincter pressure in two symptomatic patients and detected the additional diagnoses of slippage in two subjects. Among asymptomatic subjects, EUS identified additional diagnoses in two subjects considered to be normal by conventional testing methods. CONCLUSION: According to the findings, EUS is a feasible method for evaluating post-Nissen fundoplication hiatal anatomic relationships. The combination of EUS and EGD allows the mechanism of failure to be detected in patients presenting with postoperative symptoms after Nissen fundoplication.

Serum leptin levels, hepatic leptin receptor transcription, and clinical predictors of non-alcoholic steatohepatitis in obese bariatric surgery patients.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a major cause of liver disease in morbidly obese patients. Clinical predictors of NASH remain elusive, as do molecular mechanisms of pathogenesis. METHODS: A series of 35 morbidly obese patients undergoing bariatric surgery had a liver biopsy performed for standard histologic analysis. In addition, RNA was obtained from liver tissue and analyzed for leptin receptor gene expression. Regression analysis was used to correlate clinical variables, including serum leptin levels and hepatic leptin receptor gene expression, with the presence of histologically confirmed NASH. RESULTS: Of the 35 subjects enrolled, 29% had steatosis only, 60% had NASH, and 11% had normal liver histology. Among the clinical variables studied, only diabetes mellitus was an independent predictor of NASH. There was a trend toward lower levels of mRNA encoding the long form of the leptin receptor in hepatic tissue from patients with NASH compared to those with steatosis only. CONCLUSIONS: Diabetes mellitus is associated with an increased risk of NASH in obese patients. Downregulation of hepatic leptin receptor may play a role in the pathogenesis of NASH.

A research agenda for gastrointestinal and endoscopic surgery.

BACKGROUND: Development of a research agenda may help to inform researchers and research-granting agencies about the key research gaps in an area of research and clinical care. The authors sought to develop a list of research questions for which further research was likely to have a major impact on clinical care in the area of gastrointestinal and endoscopic surgery. METHODS: A formal group process was used to conduct an iterative, anonymous Web-based survey of an expert panel including the general membership of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES). In round 1, research questions were solicited, which were categorized, collapsed, and rewritten in a common format. In round 2, the expert panel rated all the questions using a priority scale ranging from 1 (lowest) to 5 (highest). In round 3, the panel re-rated the 40 questions with the highest mean priority score in round 2. RESULTS: A total of 241 respondents to round 1 submitted 382 questions, which were reduced by a review panel to 106 unique questions encompassing 33 topics in gastrointestinal and endoscopic surgery. In the two successive rounds, respectively, 397 and 385 respondents ranked the questions by priority, then re-ranked the 40 questions with the highest mean priority score. High-priority questions related to antireflux surgery, the oncologic and immune effects of minimally invasive surgery, and morbid obesity. The question with the highest mean priority ranking was: "What is the best treatment (antireflux surgery, endoluminal therapy, or medication) for GERD?" The second highest-ranked question was: "Does minimally invasive surgery improve oncologic outcomes as compared with open surgery?" Other questions covered a broad range of research areas including clinical research, basic science research, education and evaluation, outcomes measurement, and health technology assessment. CONCLUSIONS: An iterative, anonymous group survey process was used to develop a research agenda for gastrointestinal and endoscopic surgery consisting of the 40 most important research questions in the field. This research agenda can be used by researchers and research-granting agencies to focus research activity in the areas most likely to have an impact on clinical care, and to appraise the relevance of scientific contributions.

Postoperative function following laparoscopic collis gastroplasty for shortened esophagus.

BACKGROUND: Collis gastroplasty is indicated when tension-free fundoplication is not possible. Few studies have described the physiological results of this procedure, and no studies have evaluated outcomes of the endoscopic approach. OBJECTIVE: To assess the long-term outcomes of patients treated with laparoscopic Collis gastroplasty and fundoplication. DESIGN: Case series. SETTING: Tertiary care teaching hospital and esophageal physiology laboratory. PATIENTS: Fifteen consecutive patients with refractory esophageal shortening diagnosed at operation. Complicated gastroesophageal reflux disease or type III paraesophageal hernia (or both) was preoperatively diagnosed with esophagogastroduodenoscopy, 24-hour pH monitoring, esophageal motility, and barium esophagram. Fourteen (93%) of the 15 patients were available for long-term objective follow-up. INTERVENTIONS: Laparoscopic Collis gastroplasty with fundoplication and esophageal physiological testing. OUTCOME MEASURES: Preoperative and postoperative symptoms, operative times, and complications were prospectively recorded on standardized data forms. Late follow-up at 14 months included manometry, 24-hour pH monitoring, and esophagogastroduodenoscopy with endoscopic Congo red testing and biopsy. RESULTS: Presenting symptoms included heartburn (13 patients [87%]), dysphagia (11 patients [73%]), regurgitation (7 patients [47%]), and chest pain (7 patients). An endoscopic Collis gastroplasty was performed, followed by fundoplication (12 Nissen and 3 Toupet). There were no conversions to celiotomy and no deaths. Long-term follow-up occurred at 14 months. Esophagogastroduodenoscopy revealed that all wraps were intact with no mediastinal herniations. Manometry demonstrated an intact distal high-pressure zone with a 93% increase in resting pressure over the preoperative values. Two (14%) of these patients reported heartburn, and 7 (50%) patients had abnormal results on postoperative 24-hour pH studies (mean DeMeester score, 100). Biopsy of the neoesophagus revealed gastric oxyntic mucosa in all patients. Endoscopic Congo red testing showed acid secretion in only those patients with abnormal DeMeester scores. Of these 7 patients, 5 (36%) had persistent esophagitis and 6 (43%) had manometric evidence of distal esophageal body aperistalsis that was not present preoperatively. CONCLUSIONS: Collis gastroplasty allows a tension-free fundoplication to be performed to correct a shortened esophagus. It results in an effective antireflux mechanism but can be complicated by the presence of acid-secreting gastric mucosa proximal to the intact fundoplication and a loss of distal esophageal motility. These patients require close objective follow-up and maintenance acid-suppression therapy.

Laparoscopic Toupet fundoplication is an inadequate procedure for patients with severe reflux disease.

Recently we have shown that laparoscopic Toupet fundoplication is associated with a high degree of late failure when employed as a primary treatment for gastroesophageal reflux disease (GERD). This study defines preoperative risk factors that predispose patients to failure. Data from 48 patients with objective follow-up performed as part of a prospective long-term outcomes project (24-hour pH monitoring, manometry, and esophagogastroduodenoscopy [EGD] at 6 months, 3 years, and 6 years) was analyzed. Preoperative studies of patients with documented postoperative failure (n = 22), defined as an abnormal 24-hour pH study (DeMeester score >14.9), were compared to preoperative studies of patients with normal 24-hour pH studies (n = 26). Outcomes were assessed at a mean of 22 months (range 18 to 37 months) postoperatively. Of the 22 patients in the failure group, 16 (77%) were symptomatic and the majority (64%) had resumed proton pump inhibitor therapy. Preoperative indices of severe reflux were significantly more prevalent in the failure group including a very low or absent lower esophageal sphincter (LES) pressure on manometry, biopsy-proved Barrett's metaplasia, presence of a stricture, grade III or greater esophagitis, and a DeMeester score greater than 50 with ambulatory 24-hour pH testing. Comparison of pre- and postoperative manometric analysis of the LES revealed adequate augmentation of the LES in both groups and there were no wrap disruptions documented by postoperative EGD or manometry, indicating that reflux was most likely occurring through an intact wrap in the failure group. Esophageal dysmotility was present before surgery in four of the nonrefluxing patients and in three of the failures. Intact wraps were noted to have herniated in eight patients, all of whom had postoperative reflux. Laparoscopic Toupet fundoplication is associated with a high rate of failure both clinically and by objective testing. Surgery is more likely to fail in patients with severe GERD than in patients with uncomplicated or mild disease. A preoperative DeMeester score greater than 50 was 86% sensitive for predicting failure in our patient population. Laparoscopic Toupet fundoplication should not be used as a standard antireflux procedure particularly in patients with severe or complicated reflux disease.

Clostridium difficile colitis: an increasing hospital-acquired illness.

BACKGROUND: Colitis caused by Clostridium difficile is receiving increased attention as a nosocomial hospital-acquired infection. METHODS: To determine the incidence of C difficile colitis in our facility and the relative proportion of patients dying from the colitis or requiring colectomy for it, we retrospectively reviewed 201 cases of colitis caused by C difficile from 1984 to 1994. RESULTS: The incidence of C difficile colitis appears to be sharply increasing and is associated with the use of cephalosporins. Among patients who subsequently developed C difficile colitis, the most frequent indication for antibiotic use was perioperative prophylaxis; surgical patients comprised 55% of the total cases. Surgical intervention was required for 5% of patients with C difficile colitis, with an operative mortality of 30%. The overall mortality was 3.5% and was associated with a delay in diagnosis. The only discriminative factor between patients who died and those who survived was length of time from symptoms to treatment--5.43 days for survivors versus 10.7 days for those who died (P < 0.05). CONCLUSIONS: Most cases of C difficile colitis seen by surgeons have followed the use of perioperative prophylactic antibiotics. Strict guidelines for using perioperative antibiotics should be observed. Prompt recognition of C difficile colitis and aggressive therapy for it are essential for a favorable outcome.

Esophageal motility and outcomes following laparoscopic paraesophageal hernia repair and fundoplication.

BACKGROUND: The addition of an antireflux procedure to all giant paraesophageal hernia (PEH) repairs remains controversial. In addition there are no series evaluating the impact of hernia repair and fundoplication on esophageal physiology. This study examines the outcomes of PEH repair with fundoplication and examines the results of preoperative and postoperative motility and pH testing. METHODS: An analysis of a data base containing all patients undergoing PEH repair between September 1994 and December 1997. Patients underwent laparoscopic sac reduction, hernia repair, and fundoplication. Follow-up was performed under protocol and consisted of a symptoms assessment form, 24 hour pH, and manometry. RESULTS: Fifty-two patients (mean age 63) were treated: 59% complained of heartburn, 50% dysphagia, and 27% chest pain; 26% had a body motility disorder. Complete manometry was not possible in 41%. Mean operative time was 4 hours. There were 48 Nissen, 4 Toupet, and 7 Collis-Nissen procedures. There were 3 (6%) intraoperative and 3 (6%) postoperative complications. There were no operative mortalities. Hospital stay was 3 days (1 to 29). Late follow-up (18 months) was available for 96% of patients and showed dysphagia in 6%, heartburn in 10%, and recurrent herniation in 8%. Objective postoperative testing was available in 61 % of the patients at a mean of 8 months. Twenty-four hour pH tests were abnormal in 4 patients (2 asymptomatic and 2 with a Collis). Lower esophageal sphincter pressures increased 63% and functioned well in 71% of patients; 50% of preoperative motility disorders improved following repair. CONCLUSIONS: Laparoscopic repair of giant PEH is technically difficult but feasible. Routine addition of a fundoplication is advised, as preoperative testing is unreliable for a selective approach and fundoplications are well tolerated in this group of patients.

Esophageal motility disorders after gastric banding.

The long-term effects of gastric banding on esophageal function are not well described. This report describes a 28-year-old woman who developed signs and symptoms of abnormal esophageal motility and lower esophageal sphincter hypotension after gastric banding for morbid obesity. The current literature addressing the effects of gastric banding on esophageal function in light of this case report is discussed.

Alterations in peripheral blood lymphocyte cytokine expression in obesity.

Obesity is characterized by alterations in immune and inflammatory function. In order to evaluate the potential role of cytokine expression by peripheral blood mononuclear cells (PBMC) in obesity-associated inflammation, we studied serum protein levels and mRNA levels in PBMC of interleukin (IL)-6, IL-1beta, tumour necrosis factor (TNF)-alpha and IL-1Ra in nine lean and 10 obese subjects. Serum IL-1beta was undetectable, IL-1Ra serum levels were elevated, serum levels of TNF-alpha were decreased and serum levels of IL-6 were similar in obese subjects compared to lean subjects, while transcript levels of IL-6, IL-1beta and TNF-alpha, but not IL-1Ra, were decreased in PBMC from obese subjects. PBMC from obese subjects did, however, up-regulate cytokine expression in response to leptin. Thus, obesity-associated changes in IL-1Ra serum levels and IL-6 mRNA levels were not correlated with changes in cognate mRNA and serum levels, respectively, while TNF-alpha serum levels and PBMC mRNA levels were both decreased in obese patients. While immune alterations in obesity are manifest in peripheral blood lymphocytes, the general lack of correlation between altered serum levels and altered PBMC gene expression suggests that PBMC may not be the source of aberrant serum cytokine levels in obesity.

The short esophagus: pathophysiology, incidence, presentation, and treatment in the era of laparoscopic antireflux surgery.

OBJECTIVE: To discuss the pathophysiology and incidence of the short esophagus, to review the history of treatment, and to describe diagnosis and possible treatments in the era of laparoscopic surgery. SUMMARY BACKGROUND DATA: The entity of the short esophagus in antireflux surgery is seldom discussed in the laparoscopic literature, despite its emphasis in the open literature for more than 40 years. This may imply that many laparoscopic patients with short esophagi are unrecognized and perhaps treated inappropriately. Intrinsic shortening of the esophagus most commonly occurs in patients with chronic gastroesophageal reflux disease that involves recurring cycles of inflammation and healing, with subsequent fibrosis. The actual incidence of the short esophagus is estimated to be approximately 10% of patients undergoing antireflux surgery. Of this group, 7% can be appropriately managed with extensive mediastinal mobilization of the esophagus to achieve the required esophageal length. The remaining 3% require an aggressive surgical approach, including the use of gastroplasty procedures, to create an adequate length of intraabdominal esophagus to perform a wrap. Several effective minimally invasive techniques have been developed to deal with the short esophagus. CONCLUSIONS: Because a short esophagus is uncommon, there is a natural concern that many surgeons will not perform enough antireflux procedures to become familiar with its diagnosis and management. A complete understanding of the short esophagus and methods for surgical correction are critical to avoid "slipped" wraps and mediastinal herniation and to achieve the best patient outcome.

Hyperglycemia as a paraneoplastic endocrinopathy in renal cell carcinoma: a case report and review of the literature.

A case of renal cell carcinoma presenting with severe hyperglycemia, ketoacidosis, and hyperosmolar coma is described. Hyperglycemia was difficult to control but improved dramatically after nephrectomy and required no further insulin therapy. Hyperglycemia as a paraneoplastic endocrinopathy in renal cell carcinoma is suggested.

Totally laparoscopic abdominal aortic aneurysm repair.

On the basis of our previous animal and clinical experience with laparoscopic intra-abdominal vascular reconstructions, and due to the prevalence of abdominal aortic aneurysms (AAA), we have recently broadened our scope to tackle more difficult aortic surgery laparoscopically. We present a case report of our first clinical experience with laparoscopic AAA repair using specialized laparoscopic vascular instrumentation. The patient was an 84-year-old hypertensive male with a 7-cm asymptomatic infrarenal abdominal aortic aneurysm that was discovered incidentally. He presented with postcoronary artery bypass grafting and had moderate chronic obstructive pulmonary disease (COPD). A spiral computed tomograph (CT) angiogram revealed an adequate infrarenal neck and aneurysmal involvement of the proximal iliac arteries. An eight-port transabdominal technique was used with the patient in the supine position. Proximal and distal control was achieved without difficulty. The aneurysm was excluded using endoscopic stapling devices, and an aortobiiliac reconstruction was performed with a 16 x 9-mm bifurcated dacron graft. Estimated blood loss was 1000 ml, and the operative time was approximately 7 hours. The patient was ambulating without assistance on postoperative day 3. Total hospitalization was 7 days (delayed secondarily to postoperative ileus). Minimal quantities of narcotics were required for analgesia. At 6-months follow-up, the patient has palpable peripheral pulses and no complications related to surgery. This case report shows that a completely laparoscopic approach to the abdominal aortic aneurysm is possible using instrumentation specifically designed for laparoscopic vascular surgery. The exact role that laparoscopic techniques will hold in vascular surgery remains to be determined because these procedures are time consuming and technically difficult.

Evaluation of laparoscopic Toupet fundoplication as a primary repair for all patients with medically resistant gastroesophageal reflux.

BACKGROUND: This prospective study assesses the outcome results in 100 consecutive patients with gastroesophageal reflux disease (GERD) treated with a laparoscopic Toupet fundoplication. METHODS: GERD was confirmed by 24-h pH study and/or esophagogastroduodenoscopy (EGD). Pre- and postoperative symptoms, operative times, and perioperative complications were recorded on standardized data forms. Early follow-up was at 3 months and late follow-up, including 24-h pH, manometry, and EGD was at 22 months. RESULTS: Preoperative symptoms included heartburn (92%), regurgitation (58%), water brash (39%), and dysphagia (39%). Mean operative time was 3.2 hours. There were no conversions to celiotomy and there were no mortalities. The perioperative complication rate was 14%; 6% (5/83) of patients reported heartburn at 3 months and 20% (15/74) at 22 months. Early and late dysphagia was 20% (17/83) and 9% (7/74), respectively; 24-h pH testing was abnormal in 90% of symptomatic patients (9/10), 39% of asymptomatic patients (12/31), and 51% overall. CONCLUSIONS: Despite early improvement in reflux symptoms following laparoscopic Toupet fundoplications, there is a high incidence of recurrent GERD. Symptomatic follow-up underestimates the true incidence of 24-h pH-documented reflux. Based on these results we cannot recommend the laparoscopic Toupet repair for GERD patients with normal esophageal motility.

Laparoscopic management of accessory spleens in immune thrombocytopenic purpura.

BACKGROUND: A disparity exists between the incidence of accessory spleens reported in the open (15-30%) versus the laparoscopic (0-12%) literature. This disparity implies that a percentage of laparoscopic patients will require a reoperation for accessory splenectomy. We present our experience with the laparoscopic management of accessory spleens discovered after primary splenectomy for idiopathic thrombocytopenic purpura (ITP). METHODS: Seventeen patients who underwent primary splenectomy for ITP were reviewed (1 open, 16 laparoscopic). In the laparoscopic group, the incidence of accessory spleens was 3 in 16 (19%). In 1 of these 3 patients, the accessory spleen was found and removed at the initial operation, whereas in 2 of the 16 patients (13%), the accessory spleens were missed. A third patient, whose initial operation was open, presented with recurrent thrombocytopenia after primary splenectomy. After recurrent thrombocytopenia developed, radio nuclide spleen scans were performed showing accessory spleens in all three patients. These three patients underwent accessory splenectomy using a four-port laparoscopic approach. RESULTS: Laparoscopic accessory splenectomy was successfully performed in all three patients. Location of accessory spleens correlated with the spleen scan in each case. Mean operation time was 180 min. There were no conversions to open surgery and no complications. All patients were discharged from the hospital on postoperation day 1. The three patients had a good clinical response and were weaned effectively from their steroid medications. CONCLUSIONS: Patients undergoing a laparoscopic splenectomy for chronic ITP have a higher probability of requiring a reoperation for a missed accessory spleen. To minimize missing an accessory spleen, a systematic search should be made at the beginning of the laparoscopic operation. We have found that preoperation imaging with heat-treated erythrocyte scans is valuable for locating accessory spleens before reoperation. When reoperation for accessory splenectomy is necessary, a laparoscopic approach is safe and effective.