Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn.

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

Laparoscopic distal pancreatectomy for retrieval of a proximally migrated pancreatic stent.

BACKGROUND AND OBJECTIVES: Pancreatic stents placed by ERCP are common in the treatment of benign and malignant pancreatic and biliary disease. Proximal migration of the stent into the duct occurs in 2% to 5% of cases, often resulting in pancreatitis. Although technically challenging, proximally migrated pancreatic stents can usually be removed endoscopically. Little has been written about surgical management of irretrievable stents, and no reports of laparoscopic approaches were found. METHODS: We report on a case of unsuccessful ERCP retrieval of a proximally migrated pancreatic stent. RESULTS: Using laparoscopy, we exposed the pancreas and used ultrasound to locate the distal end of the stent. We incised the pancreas at that point, removed the stent, and completed the distal pancreatectomy with splenectomy. DISCUSSION: Several case series on retrieval of migrated pancreatic stents are reviewed. CONCLUSION: Although ERCP is often successful and sometimes requires several attempts, we recommend surgical consultation after the first or second failed ERCP.

Transgastric natural-orifice transluminal endoscopic surgery peritoneoscopy in humans: a pilot study in efficacy and gastrotomy site selection by using a hybrid technique.

BACKGROUND: Diagnostic natural-orifice transluminal endoscopic surgery (NOTES) peritoneoscopy can easily be performed with standard endoscopic equipment in animal studies. The efficacy and optimal transgastric site for NOTES access in humans, however, has not been determined. OBJECTIVE: To characterize the efficacy of various anterior gastric access locations for diagnostic transgastric NOTES peritoneoscopy in humans. DESIGN: Prospective clinical study. SETTING: Tertiary-care center with experience in NOTES peritoneoscopy. PATIENTS: Patients undergoing planned laparoscopic gastrectomy or gastrotomy involving the anterior aspect of the stomach were eligible. INTERVENTIONS: An anterior gastric site for NOTES gastrotomy was chosen and transgastric NOTES access was independently established after laparoscopic abdominal exploration. Peritoneoscopy was then performed. The site of gastrotomy was closed as part of the intended laparoscopic procedure. MAIN OUTCOME MEASURES: The ability to visualize the abdominal and pelvic organs in all four quadrants was determined. Patients were evaluated postoperatively for complications. RESULTS: Eight patients requiring 9 procedures were studied. Gastrotomy sites were classified as body (n = 3), lesser curvature (n = 3), greater curvature (n = 1), fundus (n = 1), and antrum (n = 1). Satisfactory navigation could only be performed to the right upper and both lower quadrants. The left upper quadrant, specifically the spleen, was adequately visualized in only 1 case (11%), where the gastrotomy site was at the greater curvature. One patient developed a surgical site infection requiring oral antibiotic therapy. The median postoperative stay was 2 days (range, 0-3 days). LIMITATIONS: Small number of patients. CONCLUSION: NOTES peritoneoscopy with a gastrotomy on the anterior stomach permits adequate visualization of organs in the right upper and both lower quadrants. Visualization of the left upper quadrant and spleen is, however, limited unless access is gained on the greater curvature of the stomach. The accuracy of NOTES in identifying intra-abdominal pathology compared with laparoscopy remains to be determined.

Use of abdominal wall allotransplantation as an alternative for the management of end stage abdominal wall failure in a porcine model.

BACKGROUND: We describe a novel approach for treating end stage abdominal wall failure using isolated abdominal wall allotransplantation in a porcine model. METHODS: Full thickness abdominal wall transplants were performed in 13 pairs of genetically mismatched pigs. All recipients received daily immunosuppresion after transplantation. Rejection was assessed by visual inspection and skin biopsies. At the end of the 28 d study period, thickness, stiffness, and tensile strength of the transplanted rectus muscle was measured and compared with native rectus muscle. RESULTS: Eight grafts were viable and showed no signs of herniation. Four grafts failed within the first week secondary to vascular thrombosis. One animal had viable graft but was euthanized due to an incarcerated inguinal hernia. Rejection was minimal in six of the eight recipients. At necropsy, the gross thickness of the transplanted muscle flap was reduced compared with the native muscle (4.3 mm versus 7.7 mm, P < 0.001). Histologically, the diameter of the muscle fiber decreased from 0.15 mm to 0.09 mm (P < 0.0001). While the stiffness measurements between the transplanted and native muscles were comparable, the transplanted muscles had significantly lower tensile strength than the native muscles. CONCLUSION: This study demonstrates the feasibility of isolated abdominal wall allotransplantation to provide a potential solution for end stage abdominal wall failure. Based on the model set forth, future work will evaluate the biomechanical properties of the composite allograft to provide a suitable dynamic abdominal wall replacement.

A Two-step Technique for Neo-umbilicoplasty in the Abdominal Reconstructive Population.

The umbilicus is the centerpiece of the abdomen and an important cosmetic landmark. Secondary intention healing can be used to create the illusion of an umbilicus in reconstructive surgery. However, there is a sparsity of literature on the role of neo-umbilicoplasty in this subset of patients and how they perceive their new umbilicus. We conducted a retrospective review of patients who received a neo-umbilicus during an abdominal reconstructive operation in 2016-2018. The umbilicus was amputated intraoperatively and tacking sutures were placed to create an indentation in the soft tissue; an inverted-V incision was sutured to create the illusion of an umbilicus. Postoperatively, patients were asked to rate their satisfaction with umbilicus appearance on a 5-point Likert scale. Of the 10 patients included; the majority were female (9:1), with a mean age of 37 years (range: 26-50) and mean BMI 29 (range: 21-38). The most common procedure performed at time of neo-umbilicoplasty was hernia repair (80%). There were no wound complications associated with the neo-umbilicus. Satisfaction was high (median 5, range: 1-5) and independent of time since surgery. Three patients gave scores below 5 and cited reasons of "lack of indentation" (n = 3, scores 4, 4, and 1), and "insufficiently notable scar" (n = 1, score 1). We hereby describe a simple surgical technique for neo-umbilicoplasty in patients undergoing reconstructive abdominal surgery that leads to long-lasting cosmetic satisfaction. Further studies of patient-reported outcomes and refinement of the technique will maximize the aesthetically pleasing results.

Hybrid surgery: combined laparoscopy and natural orifice surgery.

Hybrid procedures combine laparoscopy and natural orifice surgery techniques. Some groups are currently using hybrid procedures to investigate the concepts of pure natural orifice surgery. Thus far, hybrid procedures have validated the safety of transgastric peritoneoscopy, although improved instrumentation is imperative before widespread clinical applications. As technical improvements develop from hybrid surgery, gastrointestinal endoscopy and abdominal surgery could be revolutionized.

Management of colorectal injuries during operation iraqi freedom: patterns of stoma usage.

BACKGROUND: Management of penetrating colorectal injuries in the civilian trauma population has evolved away from diversionary stoma into primary repair or resection and primary anastomosis. With this in mind, we evaluated how injuries to the colon and rectum were managed in the ongoing war in Iraq. METHODS: The records of Operation Iraqi Freedom patients evacuated to National Naval Medical Center (NNMC) from March 2004 until November 2005 were retrospectively reviewed. Patients with colorectal injuries were identified and characterized by the following: (1) injury type; (2) mechanism; (3) associated injuries; (4) Injury Severity Score; (5) levels of medical care involved in patient treatment; (6) time interval(s) between levels of care; (7) management; and (8) outcomes. RESULTS: Twenty-three patients were identified as having either colon or rectal injury. The average ISS was 24.4 (range, 9-54; median 24). On average, patients were evaluated and treated at 2.5 levels of surgically capable medical care (range, 2-3; median 2) between time of injury and arrival at NNMC, with a median of 6 days from initial injury until presentation at NNMC (range, 3-11). Management of colorectal injuries included 7 primary repairs (30.4%), 3 resections with anastomoses (13.0%), and 13 colostomies (56.6%). There was one death (4.3%) and three anastomotic leaks (30%). Total complication rate was 48%. CONCLUSIONS: Based upon injury severity, the complex nature of triage and medical evacuation, and the multiple levels of care involved for injured military personnel, temporary stoma usage should play a greater role in military casualties than in the civilian environment for penetrating colorectal injuries.

Preparing for the American Board of Surgery Flexible Endoscopy Curriculum: Development of multi-institutional proficiency-based training standards and pilot testing of a simulation-based mastery learning curriculum for the Endoscopy Training System.

BACKGROUND: The Fundamentals of Endoscopic Surgery (FES) exam is required for American Board of Surgery certification. The purpose of this study was to develop performance standards for a simulation-based mastery learning (SBML) curriculum for the FES performance exam using the Endoscopy Training System (ETS). METHODS: Experienced endoscopists from multiple institutions and specialties performed each ETS task (scope manipulation (SM), tool targeting (TT), retroflexion (RF), loop management (LM), and mucosal inspection (MI)) with scores used to develop performance standards for a SBML training curriculum. Trainees completed the curriculum to determine feasibility, and effect on FES performance. RESULTS: Task specific training standards were determined (SM-121sec, TT-243sec, RF-159sec, LM-261sec, MI-180-480sec, 7 polyps). Trainees required 29.5 ± 3.7 training trials over 2.75 ± 0.5 training sessions to complete the SBML curriculum. Despite high baseline FES performance, scores improved (pre 73.4 ± 7, post 78.1 ± 5.2; effect size = 0.76, p > 0.1), but this was not statistically discernable. CONCLUSIONS: This SBML curriculum was feasible and improved FES scores in a group of high performers. This curriculum should be applied to novice endoscopists to determine effectiveness for FES exam preparation.

CD154 blockade, sirolimus, and donor-specific transfusion prevents renal allograft rejection in cynomolgus monkeys despite homeostatic T-cell activation.

BACKGROUND: CD154-specific antibodies have been shown to prevent acute rejection in many preclinical models including nonhuman primates (NHPs). However, they have been ineffective in pilot clinical trials, suggesting a need for more robust preclinical analysis. One factor affecting the disparate results may be related to the recipient's immune activation state. Specifically, adult humans have a high percentage of memory-phenotype T cells compared to young animals. Postdepletional homeostatic repopulation has been shown to enrich for memory-phenotype T cells and interfere with CD154-based therapies in rodents. METHODS: We developed a NHP model nonspecifically enriched for peripheral memory-phenotype T cells. Thymectomized cynomolgus macaques underwent depletion with polyclonal anti-thymocyte globulin followed by repopulation. Peripheral phenotype was serially determined using polychromatic flow cytometry. In vitro response to donor and environmental antigens was also confirmed before and after manipulation. We then tested a regimen previously successful in rhesus monkeys combining anti-CD154, sirolimus, and donor-specific blood transfusion (DST), in a second primate species with and without the provocation of increased peripheral homeostatic T-cell activation. RESULTS: Monkeys that were thymectomized (n=3) and depleted recovered via homeostatic repopulation with a repertoire enriched for cells with a memory surface phenotype compared to unmanipulated controls (n=3). Despite a repertoire markedly enriched for memory-phenotype cells, the regimen effectively prevented acute rejection for the duration of therapy. CONCLUSIONS: Cynomolgus monkeys can be rendered memory phenotype enriched using homeostatic repopulation. Despite a generally activated T-cell repertoire, anti-CD154, sirolimus, and DST effectively prevents rejection in cynomolgus monkeys.

PEG "Rescue": a practical NOTES technique.

UNLABELLED: Dislodged percutaneous endoscopic gastrostomy (PEG) tubes occur commonly and may require urgent surgical intervention in a susceptible patient population. Natural orifice translumenal endoscopic surgery (NOTES) may facilitate PEG rescue and avoid the morbidity associated with contemporary surgical techniques. We report a case of a dislodged PEG tube in the early post-operative period with evidence of incomplete gastrocutaneous tract formation and intra-abdominal leakage. Bedside transgastric NOTES exploration facilitated peritoneoscopy, evacuation of intra-abdominal fluid, and re-establishment of the PEG tube through the original gastrotomy tract. Tube feeds were resumed and postoperative contrast fluoroscopy demonstrated no intra-abdominal leakage from the replaced PEG tube. No postoperative complications related to the NOTES procedure were noted at 30 days of follow-up. PEG rescue represents a unique, practical, and empowering application of the burgeoning experience of NOTES. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1007/s464-007-9361-2) contains supplementary material, which is available to authorized users.

Benign pneumoperitoneum after colonoscopy: a prospective pilot study.

Benign pneumoperitoneum is asymptomatic free intraabdominal air and is reported to occur occasionally with colonoscopy. Management of benign pneumoperitoneum after colonoscopy is controversial and may depend on incidence or etiology. No previous studies prospectively investigated the incidence or inciting factors of benign pneumoperitoneum resulting from colonoscopy. In this study, 100 patients underwent colonoscopy and then radiography of the chest and abdomen to detect free air. The average age was 58 +/- 6.2 years, and 48 of the colonoscopies were therapeutic. No cases of benign pneumoperitoneum were detected, estimating the incidence at 0% to 3% for diagnostic and therapeutic colonoscopy. These data indicate that benign pneumoperitoneum attributable to colonoscopy is rare and possibly nonexistent. Given the paucity of data favoring the occurrence of benign pneumoperitoneum after colonoscopy, we advocate treating all cases of free intraabdominal air after colonoscopy as perforations.

Immune profiling: molecular monitoring in renal transplantation.

Molecular techniques have become a mainstay for most biomedical research. In particular, sensitive methods for gene transcript detection and advanced flow cytometry have been crucial in fostering our understanding of the basic mechanisms promoting allosensitization and adaptive immune regulation. These technologies have been validated in vitro, and in pre-clinical settings, and as such their clinical application is now clearly appropriate. It is becoming increasingly clear that these robust techniques hold much promise to better elucidate human transplant biology, and more importantly, guide clinical decision making with mechanistically-based information. This article will discuss our laboratory's use of several novel technologies, including gene polymorphism analysis, real-time polymerase chain reaction transcript quantification, and multi-color flow cytometry in clinical human renal transplantation. Specific technical methodology will be presented outlining keys for effective clinical application. Clinical correlations will be presented as examples of how these techniques may have clinical relevance. Suggestions for the adaptation of these methods for therapeutic intervention will be given. We propose that clinical transplantation should proceed in close step with modern molecular diagnostics.

Nonfunctioning islet cell carcinoma of the pancreas: case report.

Islet cell carcinomas have an incidence of 5 per million per year; 50 per cent of these are nonfunctioning islet cell tumors. The presenting symptoms mimic pancreatic ductal adenocarcinoma. The CT finding of a pancreatic head mass that spares the main duct may distinguish between the two. The treatment of choice is resection. Most nonfunctioning islet cell tumors are not discovered until metastases are present. However, favorable survival rates have been reported in locally advanced tumors that have undergone resection. Liver metastases carry an unfavorable prognosis. Five-year survival over 60 per cent has been reported. Node-negative patients have a median survival of more than 10 years, and node-positive patients who have undergone resection have a median survival of 75 months. Streptozotocin and 5-fluorouracil are used postoperatively in patients with advanced disease. Considering the favorable survival with resection aggressive surgical treatment is mandated in cases of nonfunctioning islet cell tumors.

Tolerance: is it achievable in pediatric solid organ transplantation?

Significant advances have been made in the understanding of allograft rejection. There is growing awareness that allograft acceptance, or tolerance, is also an active process rather than a passive absence of rejection. Mechanistic awareness of this process has spawned many preclinical strategies for the prevention of allograft rejection without the need for chronic immunosuppression. These therapies are currently entering clinical trials. This article reviews the prevailing therapies that hold promise for future clinical application. In particular, their application in children is discussed, as are biologic aspects of childhood immunity that may play a role in the success or failure of these strategies.