Brant K. Oelschlager

Biologic Prosthesis Reduces Recurrence After Laparoscopic Paraesophageal Hernia Repair: A Multicenter, Prospective, Randomized Trial

Objective:Laparoscopic paraesophageal hernia repair (LPEHR) is associated with a high recurrence rate. Repair with synthetic mesh lowers recurrence but can cause dysphagia and visceral erosions. This trial was designed to study the value of a biologic prosthesis, small intestinal submucosa (SIS), in LPEHR. Methods:Patients undergoing LPEHR (n = 108) at 4 institutions were randomized to primary repair −1° (n = 57) or primary repair buttressed with SIS (n = 51) using a standardized technique. The primary outcome measure was evidence of recurrent hernia (≥2 cm) on UGI, read by a study radiologist blinded to the randomization status, 6 months after operation. Results:At 6 months, 99 (93%) patients completed clinical symptomatic follow-up and 95 (90%) patients had an UGI. The groups had similar clinical presentations (symptom profile, quality of life, type and size of hernia, esophageal length, and BMI). Operative times (SIS 202 minutes vs. 1° 183 minutes, P = 0.15) and perioperative complications did not differ. There were no operations for recurrent hernia nor mesh-related complications. At 6 months, 4 patients (9%) developed a recurrent hernia >2 cm in the SIS group and 12 patients (24%) in the 1° group (P = 0.04). Both groups experienced a significant reduction in all measured symptoms (heartburn, regurgitation, dysphagia, chest pain, early satiety, and postprandial pain) and improved QOL (SF-36) after operation. There was no difference between groups in either pre or postoperative symptom severity. Patients with a recurrent hernia had more chest pain (2.7 vs. 1.0, P = 0.03) and early satiety (2.8 vs. 1.3, P = 0.02) and worse physical functioning (63 vs. 72, P = 0.03 per SF-36). Conclusions:Adding a biologic prosthesis during LPEHR reduces the likelihood of recurrence at 6 months, without mesh-related complications or side effects.

Biologic Prosthesis to Prevent Recurrence after Laparoscopic Paraesophageal Hernia Repair: Long-term Follow-up from a Multicenter, Prospective, Randomized Trial

BACKGROUND In 2006, we reported results of a randomized trial of laparoscopic paraesophageal hernia repair (LPEHR), comparing primary diaphragm repair (PR) with primary repair buttressed with a biologic prosthesis (small intestinal submucosa [SIS]). The primary endpoint, radiologic hiatal hernia (HH) recurrence, was higher with PR (24%) than with SIS buttressed repair (9%) after 6 months. The second phase of this trial was designed to determine the long-term durability of biologic mesh-buttressed repair. METHODS We systematically searched for the 108 patients in phase I of this study to assess current clinical symptoms, quality of life (QOL) and determine ongoing durability of the repair by obtaining a follow-up upper gastrointestinal series (UGI) read by 2 radiologists blinded to treatment received. HH recurrence was defined as the greatest measured vertical height of stomach being at least 2 cm above the diaphragm. RESULTS At median follow-up of 58 months (range 42 to 78 mo), 10 patients had died, 26 patients were not found, 72 completed clinical follow-up (PR, n = 39; SIS, n = 33), and 60 repeated a UGI (PR, n = 34; SIS, n = 26). There were 20 patients (59%) with recurrent HH in the PR group and 14 patients (54%) with recurrent HH in the SIS group (p = 0.7). There was no statistically significant difference in relevant symptoms or QOL between patients undergoing PR and SIS buttressed repair. There were no strictures, erosions, dysphagia, or other complications related to the use of SIS mesh. CONCLUSIONS LPEHR results in long and durable relief of symptoms and improvement in QOL with PR or SIS. There does not appear to be a higher rate of complications or side effects with biologic mesh, but its benefit in reducing HH recurrence diminishes at long-term follow-up (more than 5 years postoperatively) or earlier.

Esophageal sphincter device for gastroesophageal reflux disease.

BACKGROUND Patients with gastroesophageal reflux disease who have a partial response to proton-pump inhibitors often seek alternative therapy. We evaluated the safety and effectiveness of a new magnetic device to augment the lower esophageal sphincter. METHODS We prospectively assessed 100 patients with gastroesophageal reflux disease before and after sphincter augmentation. The study did not include a concurrent control group. The primary outcome measure was normalization of esophageal acid exposure or a 50% or greater reduction in exposure at 1 year. Secondary outcomes were 50% or greater improvement in quality of life related to gastroesophageal reflux disease and a 50% or greater reduction in the use of proton-pump inhibitors at 1 year. For each outcome, the prespecified definition of successful treatment was achievement of the outcome in at least 60% of the patients. The 3-year results of a 5-year study are reported. RESULTS The primary outcome was achieved in 64% of patients (95% confidence interval [CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed. CONCLUSIONS In this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety. (Funded by Torax Medical; ClinicalTrials.gov number, NCT00776997.).

Characterization of a Recurrent Germ Line Mutation of the E-Cadherin Gene: Implications for Genetic Testing and Clinical Management

Purpose: To identify germ line CDH1 mutations in hereditary diffuse gastric cancer (HDGC) families and develop guidelines for management of at risk individuals. Experimental Design: We ascertained 31 HDGC previously unreported families, including 10 isolated early-onset diffuse gastric cancer (DGC) cases. Screening for CDH1 germ line mutations was done by denaturing high-performance liquid chromatography and automated DNA sequencing. Results: We identified eight inactivating and one missense CDH1 germ line mutation. The missense mutation conferred in vitro loss of protein function. Two families had the previously described 1003C>T nonsense mutation. Haplotype analysis revealed this to be a recurrent and not a founder mutation. Thirty-six percent (5 of 14) of the families with a documented DGC diagnosed before the age of 50 and other cases of gastric cancer carried CDH1 germ line mutations. Two of 10 isolated cases of DGC in individuals ages <35 years harbored CDH1 germ line mutations. One mutation positive family was ascertained through a family history of lobular breast cancer (LBC) and another through an individual with both DGC and LBC. Occult DGC was identified in five of six prophylactic gastrectomies done on asymptomatic, endoscopically negative 1003C>T mutation carriers. Conclusions: In addition to families with a strong history of early-onset DGC, CDH1 mutation screening should be offered to isolated cases of DGC in individuals ages <35 years and for families with multiple cases of LBC, with any history of DGC or unspecified GI malignancies. Prophylactic gastrectomy is potentially a lifesaving procedure and clinical breast screening is recommended for asymptomatic mutation carriers.

The use of small intestine submucosa in the repair of paraesophageal hernias: Initial observations of a new technique

BACKGROUND Recent reports suggest that when laparoscopy is used to repair paraesophageal hernias recurrence rates reach 20% to 40%. Tension-free hernia closure with synthetic mesh reduces recurrence but occasionally results in esophageal injury. We hypothesized that reinforcement of the hiatal closure with small intestine submucosa (SIS) mesh, in some unusually large hernias, might reduce recurrence rates without causing injury to the esophagus. METHODS From January 2001 to March 2002 we treated 18 large paraesophageal hernias via a laparoscopic approach. In 9 of the largest hernias (one type II and 8 type III, of which 1 was recurrent) the repair was reinforced with SIS mesh (Surgisis, Cook Surgical) and represent the subjects of this study. Nissen fundoplication with gastropexy was performed in all patients. Clinical follow-up ranged from 3 to 16 months (median 8). Every patient was evaluated with barium esophagram or endoscopy or both 1 to 8 months (median 2) postoperatively. RESULTS The presenting symptoms were postprandial pain/fullness (9 of 9), heartburn (4 of 9), anemia (4 of 9), dysphagia (3 of 9), regurgitation (3 of 9), and chest pain (3 of 9). One patient died of a hemorrhagic stroke within 30 days of the operation. Postoperatively, presenting symptoms resolved (83%) or improved (17%) in each of the remaining 8 patients. One patient required endoscopic dilation for mild dysphagia. Seven of 8 patients had a normal barium esophagram without evidence of hernia. One morbidly obese (body mass index = 47) patient had a small (2 cm) sliding hiatal hernia postoperatively. There were no other complications, and specifically no perforations or mesh erosions. CONCLUSIONS These observations suggest that the use of SIS in the repair of paraesophageal hernias is safe and may reduce recurrence. Longer follow-up and a randomized study are needed to validate these results.

Clinical and Pathologic Response of Barrett's Esophagus to Laparoscopic Antireflux Surgery

Summary Background Data: Patients with Barretts esophagus (BE) are frequently offered laparoscopic antireflux surgery (LARS) to treat symptoms. The effectiveness of this operation with regards to symptoms and to the evolution of the columnar-lined epithelium remains controversial. Methods: We analyzed the course of 106 consecutive patients with BE who underwent LARS between 1994 and 2000, representing 14% of all LARS (754) performed in our institution during that period. All 106 patients agreed to clinical follow-up in 2002 at 40 months (median; range, 12–95 months). Fifty-three patients (50%) agreed to functional evaluation (manometry and 24-hour pH monitoring); 90 patients (85%) to thorough endoscopy, with appropriate biopsies and histologic evaluation to determine the status of BE. Results: Heartburn improved in 94 (96%) of 98 and resolved in 69 patients (70%) after LARS. Regurgitation improved in 58 (84%) of 69 and dysphagia improved in 27 (82%) of 33. Distal esophageal acid exposure improved in 48 (91%) of 53 patients tested and returned to normal in 39 patients (74%). One patient underwent reoperation 2 days after fundoplication (gastric perforation). Preoperatively, biopsy revealed BE without dysplasia in 91 patients, BE indefinite for dysplasia in 12 patients, and low-grade dysplasia in 3 patients. Fifty-four of the 90 patients with endoscopic follow-up had short-segment BE (<3cm), and 36 had long-segment BE (>3cm) preoperatively. Postoperatively, endoscopy and pathology revealed complete regression of intestinal metaplasia (absence of any sign suggestive of BE) in 30 (55%) of 54 patients with short-segment BE but in 0 of 36 of those with long-segment BE. Among patients with complete regression, 89% of those tested with pH monitoring had normal esophageal acid exposure. This was observed in 69% of those who failed to have complete regression. One patient developed adenocarcinoma within 10 months of LARS. Conclusions: In patients with BE, LARS provides excellent control of symptoms and esophageal acid exposure. Moreover, intestinal metaplasia regressed in the majority of patients who had short-segment BE and normal pH monitoring following LARS, a fact that was, heretofore, not appreciated. LARS should be recommended to patients with BE to quell symptoms and to prevent the development of cancer.

Complications of PTFE Mesh at the Diaphragmatic Hiatus

Paraesophageal hernia repair has been associated with a recurrence rate of up to 42%. Thus, in the last decade, there has been increasing interest in the use of mesh reinforcement of the hiatal repair. Polytetrafluoroethylene (PTFE) is one of the materials that have been used for this purpose, as it is thought to induce minimal tissue reaction. We report two cases in which complications specific to the use of PTFE mesh in this location developed over time. In the first patient, a gastrectomy was required to remove a large PTFE mesh which had eroded into the esophagogastric junction and gastric cardia. The second patient experienced severe dysphagia resulting from a stricture caused by the implant, requiring removal of the mesh. Although such complications have only rarely been reported, the severity and consequences of these incidents, as reported in the literature and in light of our observations, suggest that an alternative to PTFE should be considered for crural reinforcement during paraesophageal hernia repair.

Long-term outcomes after laparoscopic antireflux surgery.

OBJECTIVES:We studied the long-term outcomes of laparoscopic antireflux surgery (LARS) and the factors that determine it, as neither has been previously well established.METHODS:From September 1993 (start of our program) to September 1999, 441 patients underwent LARS. Preoperative symptoms and the results of esophageal functional studies as well as details of the operation and follow-up were recorded prospectively in our database. In 2004, with the help of a private investigator, we were able to contact 288 (65%). There were no differences in presentation profiles of those patients contacted and those we could not.RESULTS:At a median follow-up of 69 months, individual symptoms, among those who had it preoperatively, were as follows: heartburn (N = 282) improved in 254 (90%) and resolved in 188 (67%); regurgitation (N = 258) improved in 238 (92%) and resolved 199 (70%); dysphagia (N = 123) improved in 96 (78%) and resolved in 76 (62%); cough (N = 119) improved in 82 (69%) and resolved in 48 (40%); and hoarseness (N = 106) improved in 73 (69%) and resolved in 50 (47%). Univariate regression analysis showed that the presence of heartburn (P = 0.02), male gender (P = 0.03), and younger age (P = 0.04) predicted symptom resolution, whereas preoperative dysphagia (P = 0.03), airway manifestations (P = 0.03), bloating (P = 0.04), and defective esophageal motility (P = 0.08) were negative predictive factors. By multivariate analysis, male gender, dysphagia, and age remained significant (P < 0.05). Seven patients (2%) developed a new onset of dysphagia; 32 patients (11%) developed new or increased diarrhea and 27 patients (9%) developed bloating postoperatively. One hundred nineteen patients (41%) were taking some form of antacid medication; 66 (23%) patients were using PPIs and 10 (3%) had undergone reoperation.CONCLUSION:LARS provides effective long-term relief of GERD. Younger patients, men, and those without dysphagia are predictors of superior outcomes.

Laryngoscopy and pharyngeal pH are complementary in the diagnosis of gastroesophageal-laryngeal reflux.

Pharyngeal pH monitoring and laryngoscopy are routinely used to diagnose gastroesophageal-laryngeal reflux as a cause of respiratory symptoms. Although their use seems intuitive, their ultimate diagnostic value is yet to be defined. We studied 10 asymptomatic (control) subjects and 76 patients with respiratory symptoms. Both patients and control subjects were given a symptom questionnaire. Each underwent direct laryngoscopy using the reflux finding score (RFS) to grade laryngeal injury, esophageal manometry, and 24-hour esophagopharyngeal pH monitoring. The patients were then classified as RFS+, if the score was greater than 7, and pharyngeal reflux (PR)+, if they had more than one episode of PR detected during pH monitoring. The most common symptoms reported by patients were hoarseness (87%), cough (53%), and heartburn (50%). Control subjects had a significantly lower RFS (2.1 vs. 9.6, P < 0.01) and fewer episodes of PR (0.2 vs. 3.4, P < 0.01), than patients. None of the control subjects had more than one episode of PR during a 24-hour period. Fifty patients (66%) were RFS+ and 26 (34%) were RFS—. Thirty-two patients (42%) were PR+ and 44 (58%) were PR-. Fifteen patients had a normal RFS and no PR (group I = RFS—/PR—). Forty patients had discordance between the laryngoscopic findings and the pH monitoring (group II = RFS—/PR + or RFS+/PR—). Twenty-one patients had both an abnormal RFS and PR (group III = RFS+/PR+). Patients in group III had significantly higher heartburn scores and distal esophageal acid exposure. Eighty-three percent of patients in group III but only 44% in group I improved their respiratory symptoms as a result of antireflux therapy. An abnormal PR or RFS differentiates patients with laryngeal symptoms from control subjects. Agreement between PR and RFS helps establish or refute the diagnosis of gastroesophageal reflux as a cause of laryngeal symptoms. Patients who are RFS+ and PR—may have laryngeal injury from another source, whereas patients who are RFS— and PR+ may not have acid entering the larynx, despite the presence of PR. Patients who are RFS+ and PR+ have more severe gastroesophageal reflux disease and their reflux causes laryngeal damage. Laryngoscopy and pharyngeal pH monitoring should be considered complementary studies in establishing the diagnosis of laryngeal injury induced by gastroesophageal reflux.

Long-term outcome of esophagectomy for high-grade dysplasia or cancer found during surveillance for barrett’s esophagus

Endoscopic surveillance is recommended for patients with Barrett’s esophagus to detect high-grade dys-plasia (HGD) or cancer. We studied the outcome of esophagectomy in a cohort of patients who devel-oped HGD or cancer between 1995 and 2003 while under surveillance for Barrett’s. Outcomes were measured by analysis of clinical records, symptom questionnaire, and SF-36 (version 2). In 34 patients, mean surveillance time was 48 months (range, 4–132); the mean number of endoscopies was 10 (range, 3–30). Preoperative diagnosis was HGD in 9 patients (26.5%), carcinoma in situ in 16 (47%), and ad-enocarcinoma in 9 (26.5%). There was no esophagectomy-related mortality; 10 patients (29%) had com-plications. At mean follow-up of 46 months (range, 13–108), SF-36 (version 2) results showed quality of life scores equal to or better than those of healthy individuals. Incidence and severity scores (VAS 1–10) for postoperative symptoms were reflux, 59% (2.8); dysphagia, 28% (3.7); bloating, 45% (2.6); nausea, 28% (2.1); and diarrhea, 55% (2.5). Twenty-nine patients (85%) have no clinical, radiographic, or en-doscopic evidence of recurrent esophageal cancer or metastasis. One patient has metastatic disease. En-doscopic surveillance in Barrett’s patients yields malignant lesions at an early, generally curable, stage. Esophagectomy is curative in the great majority and can be accomplished with minimal mortality and excellent quality of life.