Martin I. Montenovo

Pepsin detection in patients with laryngopharyngeal reflux before and after fundoplication

BackgroundSome patients with gastroesophageal reflux disease (GERD) suffer from laryngopharyngeal reflux (LPR). There is no reliable diagnostic test for LPR as there is for GERD. We hypothesized that detection of pepsin (a molecule only made in the stomach) in laryngeal epithelium or sputum should provide evidence for reflux of gastric contents to the larynx, and be diagnostic of LPR. We tested this hypothesis in a prospective study in patients with LPR symptoms undergoing antireflux surgery (ARS).MethodsNine patients undergoing ARS for LPR symptoms were studied pre- and postoperatively using a clinical symptom questionnaire, laryngoscopy, 24-h pH monitoring, biopsy of posterior laryngeal mucosa, and sputum collection for pepsin Western blot assay.ResultsThe primary presenting LPR symptom was hoarseness in six, cough in two, and globus sensation in one patient. Pepsin was detected in the laryngeal mucosa in eight of nine patients preoperatively. There was correlation between biopsy and sputum (+/+ or −/−) in four of five patients, both analyzed preoperatively. Postoperatively, pH monitoring improved in all but one patient and normalized in five of eight patients. Eight of nine patients reported improvement in their primary LPR symptom (six good, two mild). Only one patient (who had negative preoperative pepsin) reported no response to treatment of the primary LPR symptom. Postoperatively, pepsin was detected in only one patient.ConclusionsPepsin is often found on laryngeal epithelial biopsy and in sputum of patients with pH-test-proven GERD and symptoms of LPR. ARS improves symptoms and clears pepsin from the upper airway. Detection of pepsin improves diagnostic accuracy in patients with LPR.

Outcomes of laparoscopic‐assisted transhiatal esophagectomy for adenocarcinoma of the esophagus and esophago‐gastric junction

Esophagectomy is associated with substantial morbidity and mortality, yet it is the only modality that offers the possibility of cure for esophageal and gastroesophageal junction (E-GEJ) adenocarcinoma. Several minimally invasive techniques have been developed to decrease the morbidity of the operation, but to date, the results have not led to its wide adoption in part due to their complexity. We developed a technique of laparoscopic-assisted transhiatal esophagectomy (LA-THE) with the idea of preserving some of the advantages of the minimally invasive approach while eliminating the degree of complexity and the time required to complete the operation solely using laparoscopy. The course of all patients who underwent LA-THE for E-GEJ adenocarcinoma at the University of Washington Medical Center was determined by analysis of all hospital records to determine perioperative variables, complications, and survival. Patients were also given a follow-up survey in order to assess long-term health-related quality of life (Gastrointestinal Quality of Life Index or GIQLI). Seventy-two patients underwent LA-THE between 1995 and 2007. Median age was 64 years (range, 42-83 years), and the median body mass index was 28 (range 17-35). Twenty-eight tumors (39%) were categorized as Siewert I, 41 (57%) as Siewert II, and 3 (4%) as Siewert III. Median operative time was 299min (range, 212-700min). All the resections were R-0. The median number of lymph nodes harvested was 11 (range, 2-32). Using the Dindo-Clavien classification of surgical complication, we had a total of 48 postoperative complications in 37 patients: 26 (53%) grade I, 20 (41%) grade II, 1 (2%) grade IIIb, 1 (2%) grade IVb, and 1 (2%) grade V complications. Median length of hospital stay was 9 days (range, 7-58 days). One patient (1.4%) died within 30 days. Overall, 3- and 5-year survival (calculated Kaplan-Meier) was 68% and 63%, respectively. Forty-nine patients (90% of those still alive) answered the GIQLI survey. Median follow-up was 26 months (range, 6-144 months). The mean GIQLI score was 108 (range, 74-138) from a maximum possible value of 144. Our study shows that LA-THE is feasible, safe, and effective in the treatment of adenocarcinoma of the esophagus and GEJ and should probably be considered an alternative to open esophagectomy and other minimally invasive techniques in the treatment of this disease.

Donor hepatitis C sero-status does not impact survival in liver transplantation.

BACKGROUND Liver disease caused by hepatitis C virus (HCV) is the main indication for liver transplantation (LT) among adults in the US. Recurrent HCV impairs patient and graft survival after LT. The high prevalence of HCV along with scarce organs has lead to increased utilization of HCV+ organs. We estimated the impact of HCV+ donors on patient and graft survival. MATERIAL AND METHODS We conducted a cohort study of LT recipients age 18 years or older from February 2002 through December 2012 utilizing UNOS data. We evaluated differences in patient characteristics between HCV+ and HCV- recipients. We also compared patient and graft survival between these groups and among HCV+ recipients who received HCV+ versus HCV- donor organs using the Kaplan-Meier estimator and multivariate stratified Cox regression models. RESULTS We identified 59,899 LT recipients. Among those, 1,695 (2.8%) were HCV+ who received HCV+ grafts. HCV+ recipients of HCV- grafts were more likely to be female, hospitalized, in the ICU, on a ventilator, had higher MELD scores, and higher bilirubin. Patient and graft survival at 1, 5, and 10 years in HCV+ recipients was inferior to HCV- recipients, but HCV+ recipients who received HCV+ versus HCV- grafts were equivalent. Multivariate regression revealed multiple variables associated with worse outcomes. CONCLUSIONS The use of HCV+ grafts in HCV+ recipients is not associated with worse outcomes. With the increase in HCV+ patients awaiting an organ, more consideration should be given to HCV+ donors.

Laparoscopic splenopexy for wandering spleen: case report and review of the literature.

Wandering spleen is a rare condition in which the spleen lacks retroperitoneal fixation, thus its vascular pedicle can twist resulting in ischemia. Although splenectomy has traditionally been used for this condition, splenopexy is increasingly used in the pediatric population to anchor the spleen and preserve splenic function. We report an unusual case of wandering spleen in an adult with chronic torsion managed with laparoscopic splenopexy, suggesting splenic preservation is possible in adults with this presentation as well.

A broad assessment of clinical outcomes after laparoscopic antireflux surgery

Objectives: There is considerable discussion regarding “success” rates for laparoscopic antireflux surgery (LARS). We hypothesized that, in part, this was a reflection of the outcome variables used. We, therefore, defined 8 specific variables (within 3 categories) and assessed outcomes for each in a large cohort of patients. Methods: Four hundred patients (208 women; median age 52 years old) who underwent LARS at the University of Washington from 1993 to 2008 were given a comprehensive questionnaire to assess various aspects of their outcomes from LARS. In addition, we analyzed all functional studies and all endoscopies performed in these patients in our institution, whether the patients had symptoms or not, and compared the findings to all available preoperative values. Results: The median follow-up was 92 (6–175) months. Symptoms Effect on presenting symptoms: Heartburn (N = 376) improved in 326 (87%), regurgitation (N = 365) improved in 331 (91%), and chest pain (N = 265) improved in 207 (78%) patients, measured by patients perception. Durability: The percentage of patients with successful control of gastroesophageal reflux disease (GERD) symptoms: 88% at 1 year, 83% at 2 years, 77% at 5 years, and 74% after 10 years. Development of new symptoms (side-effects): The following side-effects developed (ie, were new) or worsened (ie, were present before surgery): dysphagia in 72 (18%), bloating in 96 (24%), and diarrhea in 61 (15%) patients. The severities (0–10 scale) of these symptoms were: dysphagia 5.1 ± 2.6, bloating 6.5 ± 2.2, diarrhea 6.5 ± 2.9. Patient perception of overall success: Currently, 279 (70%) patients rate their operation as a complete success, 86 (22%) as partially successful, and 35 (8%) as unsuccessful. Those with partial or no success cited recurrent reflux (n = 70), a side-effect (n = 37), or both (n = 14) as the reason. Effects on esophageal function and mucosal integrity Esophageal acid exposure: The average preoperative DeMeester (DM) score was 56.8 ± 48.1 (n = 320), which decreased to 16.0 ± 31 in patients who underwent postoperative testing between 1 month and 1 year (n = 149). Among 129 patients who had both preoperative and postoperative values available, 92 (71%) had normalization of a previous abnormal DM score whereas 114 (88%) had at least some improvement. Mucosal integrity: Progression of Barretts esophagus: Of the 58 patients with Barretts esophagus before LARS, 2 developed high-grade dysplasia/cancer (or 1 per 258 patient years). Of 342 patients in our study without Barretts esophagus before LARS, 9 developed Barretts esophagus at a rate of 1 per 275 patient years (0.36% per year). Need for additional Therapy Medication use: 236 (59%) patients remain completely off medications for GERD, 164 (41%) are using antireflux medications. Of these, 73 (45%) patients are taking less medication than before LARS. The most common reasons for continuing GERD medication after LARS were heartburn (n = 100) 60%, regurgitation (n = 13) 8%, and Barretts esophagus (n = 13) 8%. Reoperations: Fifteen (3.7%) patients required reoperations, 9 for recurrent reflux and 6 for side-effects. Conclusions: The success or failure of LARS cannot be defined in a single domain. A comprehensive analysis of outcomes requires categorization that includes symptom response, side-effects, patients perception and objective measurement of acid exposure, mucosal integrity, and the need for additional medical or surgical treatment. Only then can patients and physicians better understand the role of LARS and make informed decisions.

Differential Rates of Ischemic Cholangiopathy and Graft Survival Associated With Induction Therapy in DCD Liver Transplantation

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan–Meier estimated 5‐year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first‐year posttransplant from IC. Our program has almost exclusively utilized either anti‐thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era.

Impact of Cold Ischemia Time on Outcomes of Liver Transplantation: A Single Center Experience

BACKGROUND Significant geographic disparities exist in access to liver transplantation and consequently the current liver allocation system is being challenged. We sought to describe our unique experience with using organs with long cold ischemia times from the largest donation service area. MATERIAL AND METHODS From 2009-2014 we performed 350 liver transplants. 167 (48%) had a cold ischemia time <8 hours, 134 (38%) between 8 and 12 hours, and 49 (14%) greater than 12 hours. RESULTS Early allograft dysfunction was observed more commonly with increasing cold ischemia times. 53% of the recipients in the >12 h group had early allograft dysfunction compared to 28% in the 8-12 h group, and 18% in the <8 h group (P<0.001). We found no correlation between early allograft dysfunction and allograft or patient survival. One-year liver allograft survival was 92%, 94%, 87%, three-year graft survival was 82%, 89%, and 87%, and five-year graft survival was 82%, 89%, and 79% in the <8 h, 8-12 h, and >12 h cold ischemia time groups, respectively. One-year patient survival was 95%, 94%, and 92% and five-year patient survival was 90%, 89%, and 83% in the <8 h, 8-12 h, and >12 h cold ischemia time groups, respectively. Both unadjusted and multivariate Cox regression analyses indicated no statistically significant associations between cold ischemia time and graft or patient survival. CONCLUSIONS In conclusion, the prolonged cold ischemia time led to early allograft dysfunction but did not have a deleterious association with graft or patient survival.

Cost-effectiveness of liver transplantation in methylmalonic and propionic acidemias

Propionic acidemia (PA) and classical methylmalonic acidemia (MMA) are rare inborn errors of metabolism that can cause early mortality and significant morbidity. The mainstay of disease management is lifelong protein restriction. As an alternative, liver transplantation (LT) may improve survival, quality of life, and prevent further neurological deterioration. The aim of our study was to estimate the incremental costs and outcomes of LT versus nutritional support in patients with early‐onset MMA or PA. We constructed a Markov model to simulate and compare life expectancies, quality‐adjusted life years (QALYs), and lifetime direct and indirect costs for a cohort of newborns with MMA or PA who could either receive LT or be maintained on conventional nutritional support. We conducted a series of 1‐way and probabilistic sensitivity analyses. In the base case, LT on average resulted in 1.5 more life years lived, 7.9 more QALYs, and a savings of

Interventional and Surgical Techniques in Solid Organ Transplantation.

582,369 for lifetime societal cost per individual compared to nutritional support. LT remained more effective and less costly in all 1‐way sensitivity analyses. In the probabilistic sensitivity analysis, LT was cost‐effective at the

Outcomes of adult liver re‐transplant patients in the model for end‐stage liver disease era: is it time to reconsider its indications?

100,000/QALY threshold in more than 90% of the simulations and cost‐saving in over half of the simulations. LT is likely a dominant treatment strategy compared to nutritional support in newborns with classical MMA or PA. Liver Transpl 21:1208‐1218, 2015.