Clinical outcomes of atypical extra-esophageal reflux symptoms following laparoscopic antireflux surgery.

INTRODUCTION: While it is well established that antireflux surgery is effective in relieving typical gastroesophageal reflux disease (GERD) symptoms such as heartburn and regurgitation, it is currently unclear whether atypical symptoms (cough, hoarseness, wheeze) foreshadow a less satisfactory outcome following laparoscopic antireflux surgery (LARS). The purpose of this study is to critically analyze the clinical outcomes of atypical symptoms in patients undergoing LARS. METHODS: Patients scheduled for LARS for GERD were prospectively enrolled over a 7-year period; all subjects underwent preoperative high-resolution manometry (HRM) and had evidence of GERD on ambulatory pH study. Cough, wheeze, and hoarseness were considered atypical symptoms. During preoperative and postoperative examinations, patients completed detailed foregut symptomatology questionnaires, using both 5-point Likert and 10-point visual analog scales (VAS) to document typical as well as atypical symptoms. Atypical symptom burden was calculated as a sum of VAS for the three atypical symptoms, termed the atypical score (ATS). HRM patterns were grouped into normal, spastic, and hypomotile. Statistical significance (p < 0.05) was determined using paired t-test, and analysis of variance with post hoc least significant difference (LSD). RESULTS: One hundred thirteen patients (age 49 ± 1.26 years, range 20-84 years, M:F 47:66) with mean follow-up of 28 ± 2.31 months (range 1-92 months) fulfilled inclusion criteria, having mean modified DeMeester score of 45.5 ± 2.78. Heartburn was noted in 84.1%, while atypical symptoms of some degree were reported by 92.0% (104 patients). Heartburn improved from a preoperative score of 7.1 ± 0.54 to 0.9 ± 0.24 after LARS, and ATS improved from 8.9 ± 0.71 to 2.2 ± 0.42. Significant improvements were noted for all atypical symptoms analyzed (p < 0.0001 for each). Improvement in atypical symptoms was least in the presence of hypomotility features on HRM (21.7% improvement), compared with normal motility (72.4%) and spastic features (83.9%). Preoperative atypical score (p < 0.0001) and esophageal hypomotility (p = 0.04) demonstrated a linear relationship with postoperative atypical score. CONCLUSIONS: In an unselected cohort of patients undergoing LARS, atypical GERD symptoms improved as significantly as typical symptoms. Symptom improvement was significantly lower in the presence of esophageal hypomotility and with higher symptomatic state. Therefore, patients with severe atypical symptoms or hypomotile esophagus may not achieve the same clinical satisfaction from LARS.

Laparoscopic fixation of biologic mesh at the hiatus with fibrin or polyethylene glycol sealant in a porcine model.

BACKGROUND: The objective of this study was to determine the acute and chronic fixation strengths achieved by fibrin or polyethylene glycol (PEG) sealants to secure biologic mesh at the esophageal hiatus in a porcine model. METHODS: For this study, 32 female domestic pigs were divided into four groups of 8 each. The four groups respectively received acute fibrin sealant, acute PEG sealant, chronic fibrin sealant, and chronic PEG sealant. Laparoscopically, a 5.5 × 8.5-cm piece of Biodesign Surgisis Hiatal Hernia Graft (porcine small intestine submucosa) was oriented with the U-shaped cutout around the gastroesophageal junction and the short axis in the craniocaudal direction to simulate hiatal reinforcement with a biologic mesh. The mesh then was secured with 2 ml of either fibrin sealant or PEG sealant. The pigs in the acute groups were maintained alive for 2 h to allow for complete polymerization of the sealants, and the pigs in the chronic group were maintained alive for 14 days. After the pigs were euthanized, specimens of the mesh-tissue interface were subjected to lap shear testing to determine fixation strength, and hematoxylin and eosin (H&E) stained slides were evaluated for evidence of remodeling. RESULTS: No significant differences were observed between the acute and chronic fixation strengths or the remodeling characteristics of the two sealants. However, fixation strength increased significantly over time for both types of sealant. Evidence of remodeling also was significantly more pronounced in the chronic specimens than in the acute specimens. CONCLUSIONS: This study demonstrated the feasibility of using fibrin or PEG sealants to secure biologic mesh at the hiatus in a porcine model.

Biomechanical and histologic evaluation of fenestrated and nonfenestrated biologic mesh in a porcine model of ventral hernia repair.

BACKGROUND: The purpose of this study was to compare tissue incorporation and adhesion characteristics of a novel fenestrated versus nonfenestrated crosslinked porcine dermal matrix (CPDM) (Bard CollaMend) in a porcine model of ventral hernia repair. STUDY DESIGN: Bilateral abdominal wall defects were created in 24 Yucatan minipigs, resulting in 48 defects, which were allowed to mature for 21 days. Twelve defects were repaired with fenestrated CPDM using a preperitoneal technique, 12 with fenestrated CPDM using an intraperitoneal technique, 12 with nonfenestrated CPDM using a preperitoneal technique, and 12 with nonfenestrated CPDM using an intraperitoneal technique. Half of the animals in the intraperitoneal group were euthanized after 1 month, and the other half after 3 months. Similarly, half of the animals in the preperitoneal group were euthanized after 1 month, and the other half after 6 months. Biomechanical testing and histologic evaluation were performed. RESULTS: Intraperitoneal placement of the CPDM products resulted in significantly greater adhesed area compared with preperitoneal placement (p < 0.05). Tissue ingrowth into preperitoneal fenestrated and nonfenestrated CPDM resulted in significantly greater incorporation strengths after 6 months compared with 1 month (p = 0.03 and p < 0.0001). Histologic analysis showed significantly greater cellular infiltration, extracellular matrix deposition, and neovascularization, with less fibrous encapsulation through the center of the fenestrations compared with all other sites evaluated, including nonfenestrated grafts. CONCLUSIONS: Histologic findings revealed increased tissue incorporation at fenestration sites compared with nonfenestrated grafts regardless of implant location or time in vivo. However, preperitoneal placement resulted in greater incorporation strength, less adhesed area, and lower adhesion scores compared with intraperitoneal placement for both fenestrated and nonfenestrated CPDM.

Histologic and biomechanical evaluation of crosslinked and non-crosslinked biologic meshes in a porcine model of ventral incisional hernia repair.

BACKGROUND: The objective of this study was to evaluate the biomechanical characteristics and histologic remodeling of crosslinked (Peri-Guard, Permacol) and non-crosslinked (AlloDerm, Veritas) biologic meshes over a 12 month period using a porcine model of incisional hernia repair. STUDY DESIGN: Bilateral incisional hernias were created in 48 Yucatan minipigs and repaired after 21 days using an underlay technique. Samples were harvested at 1, 6, and 12 months and analyzed for biomechanical and histologic properties. The same biomechanical tests were conducted with de novo (time 0) meshes as well as samples of native abdominal wall. Statistical significance (p < 0.05) was determined using 1-way analysis of variance with a Fisher's least significant difference post-test. RESULTS: All repair sites demonstrated similar tensile strengths at 1, 6, and 12 months and no significant differences were observed between mesh materials (p > 0.05 in all cases). The strength of the native porcine abdominal wall was not augmented by the presence of the mesh at any of the time points, regardless of de novo tensile strength of the mesh. Histologically, non-crosslinked materials showed earlier cell infiltration (p < 0.01), extracellular matrix deposition (p < 0.02), scaffold degradation (p < 0.05), and neovascularization (p < 0.02) compared with crosslinked materials. However, by 12 months, crosslinked materials showed similar results compared with the non-crosslinked materials for many of the features evaluated. CONCLUSIONS: The tensile strengths of sites repaired with biologic mesh were not impacted by very high de novo tensile strength/stiffness or mesh-specific variables such as crosslinking. Although crosslinking distinguishes biologic meshes in the short-term for histologic features, such as cellular infiltration and neovascularization, many differences diminish during longer periods of time. Characteristics other than crosslinking, such as tissue type and processing conditions, are likely responsible for these differences.

Collagen type I:III ratio of the gastroesophageal junction in patients with paraesophageal hernias.

BACKGROUND: The purpose of this study was to examine the biological environment of the esophageal hiatus through analysis of the collagen content within the gastrohepatic ligament (GHL), gastrophrenic ligament (GPL), and phrenoesophageal ligament (PEL) in patients with type I hiatal hernias (HH) and type III paraesophageal hernias (PEH). METHODS: A control group (N=10) and patients with type I HH (N=10) and type III PEH (N=10) were included in the analysis. Specimens of the GHL, PEL, and GPL were collected intraoperatively. Slides stained with sirius red/fast green were created and ten photos at 400×magnification were taken of each specimen. Axiovision 4.7 (Zeiss) photo analysis software was employed for quantification of collagen I (red) and III (green) by calculating color area (µm2). Statistical significance (p<0.05) was determined using a one-way ANOVA and Fisher's LSD post-test. RESULTS: Cross-polarization microscopy revealed that the collagen I content was similar in the three study groups for the GHL, greater in the type III PEH group and in the control group compared to the type I HH group for the PEL, and greater in the type III PEH group compared to control group for the GPL. Collagen III quantity was greater in the control group than in the type I HH group for each ligament, and greater in the GHL and PEL when compared to the type III PEH group. Type III PEH patients had greater collagen III quantity than did type I HH patients for each ligament. Collagen type I:III ratio of the GHL was greater in both hernia groups compared to the control group. Type III PEH patients contained a higher I:III ratio than both the control and type I HH groups with respect to the PEL. There was no difference in the ratio with evaluation of the GPL for the three groups. CONCLUSION: Evaluation of the esophageal hiatus revealed that patients with PEH have a different biological environment with regard to collagen content compared to control patients. The collagen I:III ratio of the study groups was equal to or greater than the control group. Collagen deficiency in the GE junction supporting ligaments does not appear to be an etiology of PEH formation.

Evaluation of intraperitoneal placement of absorbable and nonabsorbable barrier coated mesh secured with fibrin sealant in a New Zealand white rabbit model.

BACKGROUND: This study aimed to evaluate the acute and chronic fixation strength of fibrin sealant (FS) as an alternative method of fixation for laparoscopic ventral hernia repair (LVHR). METHODS: Representative mesh types for LVHR included one nonabsorbable barrier mesh (Composix) and three absorbable barrier meshes (Sepramesh, Proceed, and Parietex composite). Macroporous polypropylene mesh (Prolite Ultra) served as the control mesh. Three methods of fixation were used, namely, 0-polypropylene suture+FS (ARTISS 4 IU), FS alone (ARTISS), and tacks alone, to secure 3×4-cm pieces of mesh (10 of each combination) to the peritoneal surface of New Zealand white rabbit abdominal wall. After 2 h of incubation at 37 °C, specimens underwent acute testing. Subsequently, a chronic phase was completed using the aforementioned fixation methods (10 of each combination), in which two 4×4-cm pieces of mesh were secured intraperitoneally in each of 75 New Zealand white rabbits, which survived 8 weeks until they were sacrificed. A transparent grid overlay was used to measure the mesh and adhesion area. Adhesion tenacity was characterized using the Garrard adhesion scale. In both the acute and chronic samples, a 3×3-cm area of mesh-tissue interface underwent lap shear testing at a rate of 0.42 mm/s using a tensiometer (Instron 5542). The maximum load sustained by the mesh-tissue construct was recorded as the acute fixation strength in newtons (N). Data are given as means±standard error of the mean. Statistical significance (p<0.05) was determined using a one-way analysis of variance (ANOVA) with Fisher's least significant difference (LSD) posttest or a nonparametric Kruskal-Wallis test (adhesion scores). RESULTS: The acute fixation strength was significantly greater for all the meshes secured with either suture+FS or tacks alone than for FS alone (p<0.001 for all comparisons). All the meshes except Proceed demonstrated greater acute fixation strength with suture+FS than with tacks alone (p≤0.016). Composix achieved greater acute fixation with suture+FS than all the other meshes (p≤0.022). Acute fixation with suture + FS was greater for Parietex Composite and ProLite Ultra than for Proceed (p≤0.015). When the animals were sacrificed, 48 of 50 meshes fixed with FS alone were insufficiently affixed to the abdominal wall, which may have resulted in hernia recurrence in a hernia model. The chronic fixation strength was greater for all the mesh types with either suture+FS or tacks only than with FS alone (p≤0.0005). The chronic fixation strength was greater with suture+FS than with tacks for Proceed and ProLite Ultra (p≤0.013). Neither mesh area nor adhesion tenacity differed significantly with any mesh/fixation method combination. CONCLUSIONS: In a chronic rabbit model of LVHR, fixation strength with FS alone was inadequate for selected nonabsorbable and absorbable barrier-coated meshes. The acute and chronic fixation strengths of suture+FS were equivalent or superior to the fixation strength of tacks alone. Using a combination of suture and FS for mesh fixation in LVHR may provide adequate fixation while decreasing postoperative pain due to spiral titanium tacks. In this preclinical series, mesh secured to the peritoneal surface by FS alone may have led to early recurrence.

Evaluation of acute fixation strength for mechanical tacking devices and fibrin sealant versus polypropylene suture for laparoscopic ventral hernia repair.

BACKGROUND: The purpose of this comparative study is to evaluate the acute fixation strength of mechanical tacking devices and fibrin sealant against polypropylene suture for laparoscopic ventral hernia repair. METHODS: Three metallic mechanical tacking devices (ProTack, Salute, EndoANCHOR), 4 absorbable tacking devices (AbsorbaTack, PermaSorb, I-Clip, and SorbaFix), and 2 types of fibrin sealant (Tisseel, Artiss) were compared with 0-polypropylene suture. Three constructs from each device or an amount of sealant sufficient to cover a 3 × 3 cm(2) area were used to affix a 4 × 3 cm piece of absorbable barrier-coated mesh (Proceed, Ethicon, Inc) to the peritoneal surface of porcine abdominal wall. Ten samples were completed for each fixation modality. Acute fixation strength was measured via a lap shear test on an Instron tensiometer. RESULTS: Acute fixation strength was significantly greater for suture (59.7 7.2 N) compared with all laparoscopic tacking devices and to fibrin sealant (P < .001 for all comparisons). Protack (29.5 ± 2.8 N) was stronger than Absorbatack (13.2 ± 3.7 N; P = .029). Protack, Permasorb, SorbaFix, and I-clip were stronger than fibrin sealant (P < .05 for all comparisons). CONCLUSIONS: The acute fixation strengths of metallic or absorbable tacks as well as fibrin sealant are all significantly less than that achieved with polypropylene suture. These factors should be considered in selecting the type of mechanical fixation for patients undergoing laparoscopic ventral hernia repair.

Prospective evaluation of adhesion characteristics to intraperitoneal mesh and adhesiolysis-related complications during laparoscopic re-exploration after prior ventral hernia repair.

BACKGROUND: The purpose of this study was to characterize the adhesion characteristics of absorbable- and nonabsorbable-barrier-coated meshes and to report adhesiolysis-related complications during laparoscopic re-exploration after prior ventral hernia repair. METHODS: Under an IRB-approved protocol, patients undergoing laparoscopic re-exploration after prior intraperitoneal mesh placement were prospectively graded intraoperatively for adhesion tenacity (0-4), adhesion surface area (0 = 0%, 10 = 100%), and ratio of adhesiolysis time to mesh surface area (min/cm(2)). Adhesiolysis-related complications were also recorded. Data are given as mean ± SD. Statistical significance (P < 0.05) was determined using the t test and Fisher's exact test. RESULTS: From March 2006 to March 2009, 69 patients underwent laparoscopic surgery after prior intraperitoneal mesh placement for ventral hernia repair. Previous meshes were absorbable-barrier-coated mesh (n = 18), permanent-barrier composite mesh [Composix® (n = 17)], permanent-barrier noncomposite mesh [DualMesh® (n = 14)], uncoated polypropylene mesh (n = 12), and biologic mesh (n = 8). Indications for laparoscopic re-exploration were recurrent ventral hernia (n = 58), chronic pain (n = 3), cholecystectomy (n = 3), parastomal hernia (n = 2), small bowel obstruction (n = 1), nephrectomy (n = 1), and Nissen fundoplication (n = 1). Adhesions to DualMesh were less tenacious (P < 0.05) compared to all other meshes. Surface area of adhesions to DualMesh were less (P < 0.05) than to Composix and to uncoated polypropylene mesh, but not to absorbable-barrier-coated and biologic meshes. Adhesiolysis time:mesh surface area was less (P < 0.05) for DualMesh compared to Composix, uncoated polypropylene, and biologic mesh, but not to absorbable-barrier-coated mesh. Adhesiolysis-related complications occurred in two (16.7%) (P = ns) patients with uncoated polypropylene mesh, one cystotomy and one enterotomy; both were repaired laparoscopically. There were two (16.7%) (P = ns) conversions to an open procedure: one converted patient had Composix (6.7%) and one had absorbable-barrier-coated mesh (5.9%). There were no adhesiolysis-related complications with these meshes. There were no adhesiolysis-related complications or conversions to open in the DualMesh or biologic mesh groups. CONCLUSIONS: Adhesion characteristics of mesh placed intraperitoneally and adhesiolysis-related complications during laparoscopic re-exploration after ventral hernia repair are associated with unique properties of the mesh and/or barrier.

Informed consent: cultural and religious issues associated with the use of allogeneic and xenogeneic mesh products.

BACKGROUND: Our aim was to investigate the views of major religions and cultural groups regarding the use of allogeneic and xenogeneic mesh for soft tissue repair. STUDY DESIGN: We contacted representatives from Judaism, Islam, Buddhism, Hinduism, Scientology, and Christianity (Baptists, Methodists, Seventh-Day Adventists, Catholics, Lutherans, Church of Jesus Christ of Latter-Day Saints, Evangelical, and Jehovah's Witnesses). We also contacted American Vegan and People for the Ethical Treatment of Animals (PETA). Standardized questionnaires were distributed to the religious and cultural authorities. Questions solicited views on the consumption of beef and pork products and the acceptability of human-, bovine-, or porcine-derived acellular grafts. RESULTS: Dietary restrictions among Jews and Muslims do not translate to tissue implantation restriction. Approximately 50% of Seventh-day Adventists and 40% of Buddhists practice vegetarianism, which may translate into a refusal of the use of xenogeneic tissue. Some Hindus categorically prohibit the use of human tissue and animal products; others allow the donation and receipt of human organs and tissues. PETA is opposed to all uses of animals, but not to human acellular grafts or organ transplantation. Some vegans prefer allogeneic to xenogeneic tissue. Allogeneic and xenogeneic acellular grafts are acceptable among Scientologists, Baptists, Lutherans, Evangelicals, and Catholics. Methodists, Jehovah's Witnesses, and The Church of Jesus Christ of Latter-Day Saints leave the decision up to the individual. CONCLUSIONS: Knowledge of religious and cultural preferences regarding biologic mesh assists the surgeon in obtaining a culturally sensitive informed consent for procedures involving acellular allogeneic or xenogeneic grafts.

Clinical predictors of operative complexity in laparoscopic ventral hernia repair: a prospective study.

BACKGROUND: Because of uncertainties about the complexity of laparoscopic ventral hernia repair for varying patient populations, surgeons may be reluctant to perform this procedure. This study aimed to delineate the risk factors that can be identified in the preoperative setting predictive of longer operative times and complexity in laparoscopic ventral hernia repair. METHODS: Patient demographics including body mass index (BMI), comorbidities, previous laparoscopic and open surgical procedures, ventral hernia repairs, and hernia characteristics (defect size and location, adhesions, incarceration) were recorded prospectively. Data are given as mean +/- standard deviation. Times (min) required for abdominal access, adhesiolysis, and mesh placement as well as the total operative time were recorded during each case as outcome measures of operative difficulty. Univariate analyses were performed with the t-test or the Mann-Whitney U test as well as multivariate analyses using the stepwise analysis of covariance model to determine demographic and clinical variables influencing operative times. RESULT: The study enrolled 180 patients (78 men and 102 women) with a mean age of 54.8 +/- 12.2 years and a mean BMI of 33.3 +/- 13.0 kg/m(2). Multivariate analysis demonstrated significantly longer (p < 0.05) adhesiolysis and total operative times for patients with prior ventral hernia repairs, suprapubic hernia, bowel adhesion to the abdominal wall or hernia sac, and larger hernia defect. The total operative time also was increased (p < 0.05) with incarcerated hernia contents. Mesh placement time was increased (p < 0.05) with incarcerated hernia contents, suprapubic hernia location, hernias requiring larger mesh for repair, and decreased postgraduate year of the surgical assistant. The time required to obtain abdominal access was longer (p < 0.05) with a greater BMI and a higher American Society of Anesthesiology (ASA) classification. The operative times were not increased with a history of peritonitis, diabetes, immunosuppression, cancer, or with higher numbers of previous open or laparoscopic surgeries. CONCLUSIONS: At least 10 preoperatively identifiable patient variables, either alone or in combination, are predictive of prolonged operative times during laparoscopic ventral hernia repair and may be used as surrogates to determine the complexity of a minimally invasive approach.

Differential regulation of MMP-2 in the gastrohepatic ligament of the gastroesophageal junction.

INTRODUCTION: Ligamentous attachments maintain the normal anatomic position of the gastroesophageal (GE) junction. Failure of these elastic ligaments through an alteration in collagen synthesis, deposition, and metabolism may be a primary etiology of hiatal hernia formation. Differential expression of zinc-dependent matrix metalloproteinases (MMPs) is largely responsible for collagen remodeling. The purpose of this study was to survey baseline levels of MMPs in supporting ligaments of the GE junction from patients without hiatal hernia. METHODS: Following an institutional review board-approved protocol, plasma and tissue biopsies of the gastrohepatic ligament (GHL), gastrophrenic ligament (GPL), and phrenoesophageal ligament (PEL) were obtained in six patients without a hiatal hernia during laparoscopic anterior esophageal myotomy for achalasia. Total protein extracts from tissue biopsies were analyzed for elastases MMP-2, -9, and -12 and collagenases MMP-1, -3, -7, -8, and -13 using a multiplex profiling kit (R&D Systems, Minneapolis, MN). Data are reported as mean +/- standard deviation. Statistical significance (p < 0.05) was determined using Tukey's test and analysis of variance. RESULTS: In control patients without hiatal hernias, increased levels of MMP-2 (p < 0.02) were detected in the GHL compared with the GPL and PEL, respectively. Tissue levels of MMP-1, -12, and -13 were not detectable. CONCLUSIONS: Gelatinase-A (MMP-2) is present in the GHL and plasma of control patients. The GHL may provide the primary GE junction supporting ligament to compare tissue from patients with type I (sliding) and type III (paraesophageal) hiatal hernias to examine the role of altered collagen metabolism in hiatal hernia formation.

Primary and overall success rates for clinical outcomes after laparoscopic, endoscopic, and open pancreatic cystgastrostomy for pancreatic pseudocysts.

BACKGROUND: Internal drainage of pancreatic pseudocysts can be accomplished by traditional open or minimally invasive laparoscopic or endoscopic approaches. This study aimed to evaluate the primary and overall success rates and clinical outcomes after laparoscopic, endoscopic, and open pancreatic cystgastrostomy for pancreatic pseudocysts. METHODS: Records of 83 patients undergoing laparoscopic (n = 16), endoscopic (n = 45), and open (n = 22) pancreatic cystgastrostomy were analyzed on an intention-to-treat basis. RESULTS: There were no significant differences (p < 0.05) in the mean patient age (years), gender, body mass index (BMI) (kg/m(2)), etiology of pancreatitis (% gallstone), or size (cm) of pancreatic pseudocyst between the groups. Grade 2 or greater complications occurred within 30 days of the primary procedure for 31.5% of the laparoscopic patients, 15.6% of the endoscopic patients, and 22.7% of the open patients (nonsignificant differences). The follow-up evaluation for 75 patients (90.4%) was performed at a mean interval of 9.5 months (range, 1-40 months). The primary compared with the overall success rate, defined as cyst resolution, was 51.1% vs. 84.6% for the endoscopic group, 87.5% vs. 93.8% for the laparoscopic group, and 81.2% vs. 90.9% for the open group. The primary success rate was significantly higher (p < 0.01) for laparoscopic and open groups than for the endoscopic group, but the overall success rate was equivalent across the groups (nonsignificant differences). Primary endoscopic failures were salvaged by open pancreatic cystgastrostomy (n = 13), percutaneous drainage (n = 3), and repeat endoscopic drainage (n = 6). CONCLUSIONS: Laparoscopic and open pancreatic cystgastrostomy both have a higher primary success rate than endoscopic internal drainage, although repeat endoscopic cystgastrostomy provides overall success for selected patients.

Clinical utility of routine barium esophagram after laparoscopic anterior esophageal myotomy for achalasia.

BACKGROUND: This study aimed to evaluate the clinical utility of routine barium esophagram after laparoscopic anterior esophageal myotomy for achalasia. METHODS: The records of 260 consecutive patients who underwent laparoscopic anterior esophageal myotomy for achalasia from May 1996 to August 2007 were reviewed from a prospective institutional review board-approved database. Data are given as mean +/- standard deviation. Statistical significance (p \ 0.05) was determined using a two-tailed t-test and Fisher's exact test. RESULTS: Routine protocol barium esophagrams performed for 236 patients a mean of 1 +/- 0.3 days postoperatively were interpreted for 145 (61.4%) of the patients as normal flow of contrast after esophageal myotomy. There were no false-negative studies in this group, and diet was initiated without incident at a mean of 1 +/- 0.2 days. The time to the goal diet was 1.3 +/- 0.7 postoperative days, and the mean postoperative time to discharge was 1.5 +/- 1 days. Of the 236 patients, 91 (38.6%) had an abnormal barium esophagram (contrast retention or pooling, delayed emptying). For this group, initiation of a diet was delayed for only six (6.6%) patients. Two barium esophagrams (0.9%) interpreted as an esophageal leak were determined to be false-positives after the one patient underwent negative exploratory laparoscopy and the other was observed clinically. In this group, diet was initiated at a mean of 1.1 +/- 0.3 days. The time to the goal diet was 1.4 +/- 0.7 days, and the mean postoperative time to discharge was 1.8 +/- 1.9 days. The mean times to diet initiation, goal diet, and discharge were not significantly different (p >or= 0.14) between the normal and the abnormal barium esophagram groups. The sensitivity and specificity of an abnormal routine barium esophagram after laparoscopic esophageal myotomy were, respectively, 100% and 62.0%, and the positive and negative predictive values were 2.2% and 100%. CONCLUSIONS: Because of its poor positive predictive value, routine barium esophagram after laparoscopic anterior esophageal myotomy should be used selectively in the immediate postoperative period after an uncomplicated procedure.

Esophageal manometric characteristics and outcomes for laparoscopic esophageal diverticulectomy, myotomy, and partial fundoplication for epiphrenic diverticula.

PURPOSE: The purpose of this study is to characterize the esophageal motor and lower esophageal sphincter (LES) abnormalities associated with epiphrenic esophageal diverticula and analyze outcomes for laparoscopic esophageal diverticulectomy, myotomy, and partial fundoplication. METHODS: The endoscopic, radiographic, manometric, and perioperative records for patients undergoing laparoscopic esophageal diverticulectomy, anterior esophageal myotomy, and partial fundoplication from 8/99 until 9/06 were reviewed from an Institutional Review Board (IRB)-approved outcomes database. Data are given as mean +/- standard deviation (SD). RESULTS: An esophageal body motor disorder and/or LES abnormalities were present in 11 patients with epiphrenic diverticula; three patients were characterized as achalasia, one had vigorous achalasia, two had diffuse esophageal spasm, and five had a nonspecific motor disorder. Presenting symptoms included dysphagia (13/13), regurgitation (7/13), and chest pain (4/13). Three patients had previous Botox injections and three patients had esophageal dilatations. Laparoscopic epiphrenic diverticulectomy with an anterior esophageal myotomy was completed in 13 patients (M:F; 3:10) with a mean age of 67.6 +/- 4.2 years, body mass index (BMI) of 28.1 +/- 1.9 kg/m2 and American Society of Anesthesiologists (ASA) 2.2 +/- 0.1. Partial fundoplication was performed in 12/13 patients (Dor, n = 2; Toupet, n = 10). Four patients had a type I and one patient had a type III hiatal hernia requiring repair. Mean operative time was 210 +/- 15.1 min and mean length of stay (LOS) was 2.8 +/- 0.4 days. Two grade II or higher complications occurred, including one patient who was readmitted on postoperative day 4 with a leak requiring a thoracotomy. After a mean follow-up of 13.6 +/- 3.0 months (range 3-36 months), two patients complained of mild solid food dysphagia and one patient required proton pump inhibitor (PPI) for gastroesophageal reflux disease (GERD) symptoms. CONCLUSION: The majority of patients with epiphrenic esophageal diverticula have esophageal body motor disorders and/or LES abnormalities. Laparoscopic esophageal diverticulectomy and anterior esophageal myotomy with partial fundoplication is an appropriate alternative with acceptable short-term outcomes in symptomatic patients.

Current trends in laparoscopic solid organ surgery: spleen, adrenal, pancreas, and liver.

Laparoscopic procedures are becoming increasingly preferred by both surgeons and patients owing to decreased pain, reduced perioperative morbidity, and an earlier return to self-reliance. Laparoscopy for solid organ surgery has been slower to evolve when compared with procedures such as laparoscopic cholecystectomy owing to factors involving lower case volume and refinement of technologies specific to operations involving the spleen, adrenal, pancreas, and liver. Future integration of technology will allow surgeons to offer increasingly less morbid therapies aimed at the patient's best clinical outcome.

Elastic fiber depletion in the supporting ligaments of the gastroesophageal junction: a structural basis for the development of hiatal hernia.

BACKGROUND: The position of the gastroesophageal junction is maintained by a complex of fibroelastic ligaments. The purpose of this study was to characterize and compare the histology of these ligaments in patients with gastroesophageal reflux disease (GERD) and hiatal hernia (HH) versus GERD alone, with emphasis on the elastin morphology. STUDY DESIGN: Thirteen patients were examined at the time of laparoscopic fundoplication for symptomatic GERD; nine had no significant HH and four had large diaphragmatic hernias (GERD/HH). Tissue biopsies were obtained from the gastrohepatic ligament (GHL, n=5 and n=3, GERD and GERD/HH, respectively), the phrenoesophageal ligament (n=7 and n=4, respectively), and the gastrophrenic ligament (n=6 and n=4, respectively). Sections of fixed tissue were stained with hematoxylin and eosin, Masson's trichrome, and resorcin-fuchsin for analysis of elastic fibers by light microscopy, and elastin area was quantified and expressed as a percentage of the imaged tissue. RESULTS: Elastin and collagen fibers were prominent in all ligaments in patients with GERD alone. In patients with GERD/HH, there was fragmentation and distortion of elastin in the phrenoesophageal ligament and gastrohepatic ligament, and to a lesser degree, in the gastrophrenic ligament. Compared with patients with GERD alone, the presence of hiatal hernia was associated with a reduction in elastin area by more than 50% in the phrenoesophageal ligament ([mean +/- SEM] 31.0%+/-3.3% versus 15.1%+/-1.3%, p < 0.01) and gastrohepatic ligament (26.9% +/- 0.5% versus 12.5%+/-0.1%, p < 0.008). There was no decrease with respect to elastin in the gastrophrenic ligament. CONCLUSIONS: The periesophageal ligaments in patients with GERD are characterized by prominent elastic fibers. In contrast, GERD/HH is associated with depletion of elastic fibers in two of three ligaments supporting the gastroesophageal junction. Elastic fiber depletion in the periesophageal ligaments thereby provides a structural basis for the development of HH. It remains unclear if this represents a primary (etiologic) alteration or if it is a secondary phenomenon.

Intramuscular cavernous hemangioma.

Intramuscular cavernous hemagiomas represent <1% of all hemangiomas and consist of benign proliferations of blood vessels. Typical presentation is an enlarging painful soft-tissue mass without cutaneous changes. Intramuscular cavernous hemangiomas do not undergo spontaneous regression and may be locally destructive because pressure is exerted on neighboring structures. Phleboliths on radiograph are a specific finding for cavernous hemangioma. Definitive treatment of this condition is surgical excision.

Incidence of residual choledocholithiasis detected by intraoperative cholangiography at the time of laparoscopic cholecystectomy in patients having undergone preoperative ERCP.

INTRODUCTION: The purpose of this study is to determine the incidence of residual common bile duct (CBD) stones after preoperative ERCP for choledocholithiasis and to evaluate the utility of routine intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC) in this patient population. METHODS: All patients who underwent preoperative ERCP and interval LC with IOC from 5/96 to 12/05 were reviewed under an Institutional Review Board (IRB)-approved protocol. Data collected included all radiologic imaging, laboratory values, clinical and pathologic diagnoses, and results of preoperative ERCP and LC with IOC. Standard statistical analyses were used with significance set at p < 0.05. RESULTS: A total of 227 patients (male:female 72:155, mean age 51.9 years) underwent preoperative ERCP for suspicion of choledocholithiasis. One hundred and eighteen patients were found to have CBD stones on preoperative ERCP, and of these, 22 had choledocholithiasis diagnosed on IOC during LC. However, two patients had residual stones on completion cholangiogram after ERCP and were considered to have retained stones. Therefore, 20 patients overall were diagnosed with either interval passage of stones into the CBD or a false-negative preoperative ERCP. In the 109 patients without CBD stones on preoperative ERCP, nine patients had CBD stones on IOC during LC, an 8.3% incidence of interval passage of stones or false-negative preoperative ERCP. In both groups, there was no correlation (p > 0.05) between an increased incidence of CBD stones on IOC and a longer time interval between ERCP and LC, performance of sphincterotomy, incidence of cystic duct stones, or pathologic diagnosis of cholelithiasis. CONCLUSIONS: The overall incidence of retained or newly passed CBD stones on IOC during LC after a preoperative ERCP is 12.9%. Although the natural history of residual CBD stones after preoperative ERCP is not known, the routine use of IOC should be considered in patients with CBD stones on preoperative ERCP undergoing an interval LC.

Oral 1-O-octadecyl-2-O-benzyl-sn-glycero-3-cidofovir targets the lung and is effective against a lethal respiratory challenge with ectromelia virus in mice.

Hexadecyloxypropyl-cidofovir (HDP-CDV) has been shown to be orally active against lethal infection with orthopoxviruses including, mousepox, cowpox, vaccinia and rabbitpox. The alkoxyalkyl group provides oral absorption and reduces greatly the amount of drug reaching the kidney, the site of CDV's dose limiting toxicity. However, the amount of HDP-CDV detected in lung, an important site of early poxvirus replication, is low and the reduction of viral titers in surviving animals is reduced moderately compared with the liver where poxvirus titers are virtually undetectable. We synthesized a novel glycerol ester of CDV, 1-O-octadecyl-2-O-benzyl-sn-glycero-3-CDV (ODBG-CDV), and compared its oral pharmacokinetics with that of HDP-CDV. Surprisingly, ODBG-CDV levels in lung are much higher and liver levels are reduced, suggesting that the compound is transported in small intestinal lymph instead the portal vein. ODBG-CDV has excellent in vitro activity in cells infected with ectromelia virus (ECTV). In mice infected with a lethal aerosol or intranasal challenge of ECTV, HDP-CDV and ODBG-CDV are equally effective in preventing death from disease. Other drugs esterified to 1-O-octadecyl-2-O-benzyl-sn-glycerol or 1-O-octadecyl-2-O-benzyl-sn-glycerol-3-phosphate may provide lung targeting for treatment of microbial or neoplastic diseases while reducing first pass removal by the liver during oral absorption.

Efficacy of oral active ether lipid analogs of cidofovir in a lethal mousepox model.

Cidofovir (CDV) is a highly effective inhibitor of orthopoxvirus replication and may be used intravenously to treat smallpox or complications arising from the smallpox vaccine under an investigational new drug application (IND). However, CDV is absorbed poorly following oral administration and is inactive orally. To improve the bioavailability of CDV, others synthesized alkoxyalkanol esters of CDV and observed >100-fold more activity than unmodified CDV against cowpox, vaccinia, and variola virus (VARV) replication. These ether lipid analogs of CDV have high oral bioavailability in mice. In this study, we compared the oral activity of CDV with the hexadecyloxypropyl (HDP)-, octadecyloxyethyl-, oleyloxypropyl-, and oleyloxyethyl-esters of CDV in a lethal, aerosol ectromelia virus (ECTV) challenge model in A/NCR mice. Octadecyloxyethyl-CDV appeared to be the most potent CDV analog as a dose regimen of 5 mg/kg started 4 h following challenge completely blocked virus replication in spleen and liver, and protected 100% of A/NCR mice, although oral, unmodified CDV was inactive. These results suggest that this family of compounds deserves further evaluation as poxvirus antiviral.