Margaret M. Frisella

Lethality of Multiple Endocrine Neoplasia Type I

Abstract. The lethality of the endocrine tumors associated with multiple endocrine neoplasia type I (MEN-I), particularly the pancreatic islet cell tumors, has been controversial. We evaluated the cause and age of death in MEN-I kindreds. Our database contains 34 distinct kindreds with 1838 members. Reliable death data are available for 103 people (excluding accidents and age < 18 years). We compared survival curves of MEN-I patients who died from causes related to MEN-I with those from MEN-I carriers who died from a nonendocrine cause and unaffected kindred members. We also compared ages of death between affected and unaffected members of MEN-I kindreds. Of 59 MEN-I-affected patients, 27 died directly of MEN-I-specific illness and 32 of non-MEN-I causes. The MEN-I-specific deaths occurred at a younger age (median 47 years) than either MEN-I patients whose death was from some nonendocrine cause (median 60 years,p < 0.02) or than all kindred members who did not die of MEN-I disease (median 55 years,p < 0.05). The causes of death of the MEN-I patients included islet cell tumor (n= 12), ulcer disease (n= 6), hypercalcemia/uremia (n= 3), carcinoid tumor (n= 6), and nonendocrine malignancies (n= 9). There was no difference in survival between MEN-I carriers and unaffected kindred members. Of our MEN-I patients, 46% died from causes related to their endocrine tumors after a median age of 47 years, which was younger than family members who did not die from these tumors. Pancreatic islet cell tumors were the most common cause of death of MEN-I patients. Management of kindreds with MEN-I should include an aggressive screening program with early therapeutic intervention when a tumor is identified.

Pooled Data Analysis of Laparoscopic vs. Open Ventral Hernia Repair: 14 Years of Patient Data Accrual

BackgroundThe purpose of this study was to analyze the published perioperative results and outcomes of laparoscopic (LVHR) and open (OVHR) ventral hernia repair focusing on complications and hernia recurrences.MethodsData were compiled from all English-language reports of LVHR published from 1996 through January 2006. Series with fewer than 20 cases of LVHR, insufficient details of complications, or those part of a larger series were excluded. Data were derived from 31 reports of LVHR alone (unpaired studies) and 14 that directly compared LVHR to OVHR (paired sudies). Chi-squared analysis, Fisher’s exact test, and two-tailed t-test analysis were used.ResultsForty-five published series were included, representing 5340 patients (4582 LVHR, 758 OVHR). In the pooled analysis (combined paired and unpaired studies), LVHR was associated with significantly fewer wound complications (3.8% vs. 16.8%, p < 0.0001), total complications (22.7% vs. 41.7%, p < 0.0001), hernia recurrences (4.3% vs. 12.1%, p < 0.0001), and a shorter length of stay (2.4 vs. 4.3 days, p = 0.0004). These outcomes maintained statistical significance when only the paired studies were analyzed. In the pooled analysis, LVHR was associated with fewer gastrointestinal (2.6% vs. 5.9%, p < 0.0001), pulmonary (0.6% vs. 1.7%, p = 0.0013), and miscellaneous (0.7% vs. 1.9%, p = 0.0011) complications, but a higher incidence of prolonged procedure site pain (1.96% vs. 0.92%, p = 0.0469); none of these outcomes was significant in the paired study analysis. No differences in cardiac, neurologic, septic, genitourinary, or thromboembolic complications were found. The mortality rate was 0.13% with LVHR and 0.26% with OVHR (p = NS). Trends toward larger hernia defects and larger mesh sizes were observed for LVHR.ConclusionsThe published literature indicates fewer wound-related and overall complications and a lower rate of hernia recurrence for LVHR compared to OVHR. Further controlled trials are necessary to substantiate these findings and to assess the health care economic impact of this approach.

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 Fishers 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.

Outcomes analysis of laparoscopic resection of pancreatic neoplasms

BackgroundExperience with laparoscopic resection of pancreatic neoplasms remains limited. The purpose of this study is to critically analyze the indications for and outcomes after laparoscopic resection of pancreatic neoplasms.MethodsThe medical records of all patients undergoing laparoscopic resection of pancreatic neoplasms from July 2000 to February 2006 were reviewed. Data are expressed as mean ± standard deviation.ResultsLaparoscopic pancreatic resection was performed in 22 patients (M:F, 8:14) with a mean age of 56.3 ± 15.1 years and mean body mass index (BMI) of 26.3 ± 4.5 kg/m2. Nine patients had undergone previous intra-abdominal surgery. Indications for pancreatic resection were cyst (1), glucagonoma (1), gastrinoma (2), insulinoma (3), metastatic tumor (2), IPMT (4), nonfunctioning neuroendocrine tumor (3), and mucinous/serous cystadenoma (6). Mean tumor size was 2.4 ± 1.6 cm. Laparoscopic distal pancreatectomy was attempted in 18 patients and completed in 17, and enucleation was performed in 4 patients. Laparoscopic ultrasound (n = 10) and a hand-assisted technique (n = 4) were utilized selectively. Mean operative time was 236 ± 60 min and mean blood loss was 244 ± 516 ml. There was one conversion to an open procedure because of bleeding from the splenic vein. The mean postoperative LOS was 4.5 ± 2.0 days. Seven patients experienced a total of ten postoperative complications, including a urinary tract infection (UTI) (1), lower-extremity deep venous thrombosis (DVT) and pulmonary embolus (1), infected peripancreatic fluid collection (1), pancreatic pseudocyst (1), and pancreatic fistula (6). Five pancreatic fistulas were managed by percutaneous drainage. The reoperation rate was 4.5% and the overall pancreatic-related complication rate was 36.4%. One patient developed pancreatitis and a pseudocyst 5 months postoperatively, which was managed successfully with a pancreatic duct stent. There was no 30-day mortality.ConclusionsLaparoscopic pancreatic resection is safe and feasible in selected patients with pancreatic neoplasms. With a pancreatic duct leak rate of 27%, this problem remains an area of development for the minimally invasive technique.

Physicomechanical Evaluation of Polypropylene, Polyester, and Polytetrafluoroethylene Meshes for Inguinal Hernia Repair

BACKGROUND For meshes to be used effectively for hernia repair, it is imperative that engineers and surgeons standardize the terminology and techniques related to physicomechanical evaluation of these materials. The objectives of this study were to propose standard techniques, perform physicomechanical testing, and classify materials commonly used for inguinal hernia repair. STUDY DESIGN Nine meshes were evaluated: 4 polypropylene, 1 polyester, 1 polytetrafluoroethylene, and 3 partially absorbable. Physical properties were determined through image analysis, laser micrometry, and density measurements. Biomechanical properties were determined through suture retention, tear resistance, uniaxial, and ball burst testing with specimens tested in 2 different orientations. A 1-way ANOVA with Tukeys post-test or a t-test were performed, with p < 0.05. RESULTS Significant differences were observed due to both mesh type and orientation. Areas of interstices ranged from 0.33 ± 0.01 mm² for ProLite (Atrium Medical Corp) and C-QUR Lite (Atrium Medical Corp) Large to 4.10 ± 0.06 mm² for ULTRAPRO (Ethicon), and filament diameters ranged from 99.00 ±8.1 μm for ProLite Ultra (Atrium Medical Corp) and C-QUR Lite Small to 338.8 ± 3.7 μm for Parietex Flat Sheet TEC (Covidien). These structural characteristics influenced biomechanical properties such as tear resistance and tensile strength. ProLite Ultra, C-QUR Lite Small, ULTRAPRO and INFINIT (WL Gore & Associates) did not resist tearing as effectively as the others. All meshes exhibited supraphysiologic burst strengths except INFINIT and ULTRAPRO. CONCLUSIONS Significant differences exist between the physicomechanical properties of polypropylene, polyester, polytetrafluoroethylene, and partially absorbable mesh prostheses commonly used for inguinal hernia repair. Orientation of the mesh was also shown to be critical for the success of meshes, particularly those demonstrating anisotropy.

Obesity does not adversely affect the outcome of laparoscopic antireflux surgery (LARS)

Background: Because it has been suggested that obesity adversely affects the outcome of LARS, it is unclear how surgeons should counsel obese patients referred for antireflux surgery. Methods: A prospective database of patients undergoing LARS from 1992 to 2001 was used to compare obese and nonobese patients. Patients were surveyed preoperatively and annually thereafter. Questionnaires were completed regarding global symptoms and overall satisfaction. Results: Of the 505 patients, the body mass index (BMI) was <25 (normal) in 16%, 25–29 (overweight) in 42%, and >30 (obese) in 42%. Although the operative time was longer in the obese group than in the normal weight group (137 ± 55 min vs 115 ± 42 min, p = 0.003), the time to discharge and rate of complications did not differ. At a mean follow-up of 35 ± 25 months, there were no differences in symptoms, overall improvement, or patient satisfaction. Further, the rates of anatomic failure were similar among the obese, overweight, and normal weight groups. Conclusions: Although the operative time is longer in the obese, complication and anatomic failure rates are similar to those in the nonobese at long-term follow-up. Obese patients have equivalent symptom relief and are equally satisfied postoperatively. Therefore, obesity should not be a contraindication to LARS.

Differentiation of biologic scaffold materials through physicomechanical, thermal, and enzymatic degradation techniques.

Objective:The objective of this study was to characterize the physicomechanical, thermal, and degradation properties of several types of biologic scaffold materials to differentiate between the various materials. Background:As more biologic scaffold materials arrive on the market, it is critical that surgeons understand the properties of each material and are provided with resources to determine the suitability of these products for specific applications such as hernia repair. Methods:Twelve biologic scaffold materials were evaluated, including crosslinked and non-crosslinked; those of bovine, human, and porcine origin; and derivatives of pericardium, dermis, and small intestine submucosa. Physicomechanical, thermal, and degradation properties were evaluated through biomechanical testing, modulated differential scanning calorimetry, and collagenase digestion assays, respectively. Biomechanical testing included suture retention, tear strength, uniaxial tensile, and ball burst techniques. Results:All scaffolds exhibited suture retention strengths greater than 20 N, but only half of the scaffolds exhibited tear resistance greater than 20 N, indicating that some scaffolds may not provide adequate resistance to tearing. A wide range of burst strengths were observed ranging from 66.2 ± 10.8 N/cm for Permacol to 1,028.0 ± 199.1 N/cm for X-Thick AlloDerm, and all scaffolds except SurgiMend, Strattice, and CollaMend exhibited strains in the physiological range of 10% to 30% (at a stress of 16 N/cm). Thermal analysis revealed differences between crosslinked and non-crosslinked materials with crosslinked bovine pericardium and porcine dermis materials exhibiting a higher melting temperature than their non-crosslinked counterparts. Similarly, the collagenase digestion assay revealed that crosslinked bovine pericardium materials resisted enzymatic degradation significantly longer than non-crosslinked bovine pericardium. Conclusions:Although differences were observed because of cross-linking, some crosslinked and non-crosslinked materials exhibited very similar properties. Variables other than cross-linking, such as decellularization/sterilization treatments or species/tissue type also contribute to the properties of the scaffolds.

120-Day Comparative Analysis of Adhesion Grade and Quantity, Mesh Contraction, and Tissue Response to a Novel Omega-3 Fatty Acid Bioabsorbable Barrier Macroporous Mesh After Intraperitoneal Placement:

Purpose. This study aimed to evaluate adhesion formation, mesh contraction, and tissue response to an omega-3 fatty acid barrier—coated lightweight polypropylene mesh (C-Qur) after intra-abdominal placement, and compare these properties to those of other commercially available meshes. Materials and methods. After randomization, 3 × 3 cm pieces of Atrium C-Qur, Mesh ProLite Ultra, Composix, Parietex, Proceed, Sepramesh, and DualMesh were sewn to the intact peritoneum on either side of a midline incision in 41 New Zealand white rabbits. Necropsy was performed at 120 days, and explants were evaluated for adhesion grade, adhesion amount, and mesh contraction. Histologic evaluation included extent of capsule formation, abdominal wall tissue ingrowth, degrees of inflammation and vascularization of the surrounding tissue, and the presence of mesothelialization. Results. There were no significant differences between the C-Qur mesh and the commercially available meshes tested with regard to adhesion grade or amount, although percentage adhesion coverage for the C-Qur mesh was much less than for Composix and Proceed. The C-Qur mesh contracted less than all meshes, significantly less (P < .05) than DualMesh or Proceed. DualMesh exhibited the greatest amount of capsule formation and inflammation on its parietal side as compared with the other meshes. Conclusions. Placing lightweight polypropylene mesh with an omega-3 fatty acid barrier coating intraperitoneally results in more favorable adhesion characteristics compared with Composix and Proceed meshes at 120-day explantation after intraperitoneal placement. The minimal amount of contraction and favorable tissue response in comparison to other commercially available meshes makes C-Qur mesh a practical alternative for laparoscopic and open ventral hernia repair.

Evaluation of acellular human dermis reinforcement of the crural closure in patients with difficult hiatal hernias

BackgroundBiologic prosthetics may circumvent mesh-related complications at the esophageal hiatus by becoming remodeled by native cells. We present our experience with acellular human dermal matrix in the repair of difficult hiatal hernias (HH).MethodsRecords of 17 patients who underwent laparoscopic HH repair using acellular human dermis to buttress the crural closure were analyzed. Hernias were paraesophageal (PEH) in 12 patients, large type 1 in 1 patient, and recurrent after prior HH repair in 4 patients. Barium swallow (BAS) was obtained 6–12 months after surgery. (Data are presented as mean ± standard deviation.)ResultsMean patient age was 65 ± 12 years and BMI was 31 ± 4. Mean gastroesophageal (GE) junction distance above the diaphragm in the PEHs was 4.9 ± 1.5 cm; 9 of 12 patients with PEH had more than 50% of the stomach in the chest. Mean operating time was 273 ± 48 min. Average hiatal defect size was 4.7 × 2.7 cm, with 4.2 ± 1.2 sutures used to close the crura. Nissen fundoplication was performed in all patients, esophageal lengthening in four patients, and anterior gastropexy in three patients. Mean hospital length of stay (LOS) was 2.3 ± 0.8 days. Mean followup was 14.4 ± 4.4 months. Postoperatively, only one (6%) patient had heartburn/regurgitation, one (6%) had mild dysphagia, and two (12%) take proton pump inhibitors. Followup BAS at 10.3 ± 4.9 months after surgery showed small recurrent hernias in two patients (12%), but only one was symptomatic. In addition, there was one symptomatic failure of a redo Nissen in an obese patient. Reoperative gastric bypass 15 months later showed an intact crural closure with a remodeled buttress site.ConclusionsAcellular human dermal matrix may be an effective method to buttress the crural closure in patients with large hiatal hernias. Longer followup in larger numbers of patients is needed to assess the validity of this approach.

Clinical outcomes after laparoscopic antireflux surgery in patients with and without preoperative endoscopic esophagitis.

A wide spectrum of endoscopic findings exists in patients with gastroesophageal reflux disease (GERD). This study compared clinical outcomes after laparoscopic antireflux surgery (LARS) in patients who had GERD with and without preoperative endoscopic esophagitis. From 1992 to 2001, a total of 414 patients who underwent LARS with 6 months or more of follow-up were prospectively entered into a database. Among these patients, 84 (20%) had no endoscopic evidence of esophagitis on preoperative endoscopy (group 1), whereas 330 (80%) did have esophagitis (group 2). Perioperative outcomes, GERD symptom relief, and the use of acid-reducing medication were assessed. Preoperative DeMeester scores in groups 1 and 2 were 44 ± 29 and 61 ± 62 (P < 0.05) and mean esophageal peristaltic amplitude was 86 ± 32 mm Hg vs. 60 ± 42 mm Hg, respectively (P < 0.05). Although procedure time was significantly shorter in group 1, other perioperative outcomes were similar. At postoperative follow-up, the use of proton pump inhibitors was reduced in both groups (86% to ≤14%). With the exception of postoperative dysphagia, there was no difference in GERD symptom relief between groups 1 and 2. The presence or absence of preoperative esophagitis has minimal effect on favorable symptomatic outcomes after LARS. Thus LARS is an effective treatment option for patients, irrespective of endoscopic evidence of esophagitis, leading to excellent symptom relief and a marked reduction in the use of proton pump inhibitors.