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Purpose: Although fine-needle aspiration biopsy is the most useful diagnostic tool in evaluating a thyroid nodule, preoperative diagnosis of thyroid nodules is frequently imprecise, with up to 30% of fine-needle aspiration biopsy cytology samples reported as “suspicious” or “indeterminate.” Therefore, other adjuncts, such as molecular-based diagnostic approaches are needed in the preoperative distinction of these lesions.Experimental Design: In an attempt to identify diagnostic markers for the preoperative distinction of these lesions, we chose to study by microarray analysis the eight different thyroid tumor subtypes that can present a diagnostic challenge to the clinician.Results: Our microarray-based analysis of 94 thyroid tumors identified 75 genes that are differentially expressed between benign and malignant tumor subtypes. Of these, 33 were overexpressed and 42 were underexpressed in malignant compared with benign thyroid tumors. Statistical analysis of these genes, using nearest-neighbor classification, showed a 73% sensitivity and 82% specificity in predicting malignancy. Real-time reverse transcription–PCR validation for 12 of these genes was confirmatory. Western blot and immunohistochemical analyses of one of the genes, high mobility group AT-hook 2, further validated the microarray and real-time reverse transcription–PCR data.Conclusions: Our results suggest that these 12 genes could be useful in the development of a panel of markers to differentiate benign from malignant tumors and thus serve as an important first step in solving the clinical problem associated with suspicious thyroid lesions.

Supplementary Figure 1 from Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

Supplementary Table 1 from Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

Supplementary Table 2 from Identification of Genes Differentially Expressed in Benign versus Malignant Thyroid Tumors

Background In inflammatory bowel disease (IBD), many scenarios call for fecal diversion, leaving behind defunctionalized bowel. The theoretical risk of colorectal cancer (CRC) in this segment is frequently cited as a reason for resection. To date, no studies have characterized the incidence of neoplasia in the diverted colorectal segments of IBD patients. Methods A retrospective cohort analysis was conducted for IBD patients identified through a tertiary care center pathology database. Patients that had undergone colorectal diversion and were diverted for ≥ 1 year were included. Incidence of diverted dysplasia/CRC was calculated for Crohn’s disease (CD) and ulcerative colitis (UC) with respect to diverted patient-years (dpy) and patient-years of disease (pyd). Results In total, 154 patients comprising 754 dpy and 1984 pyd were analyzed. Only 2 cases of diverted colorectal dysplasia (CD 1, UC 1) and 1 case of diverted CRC (UC) were observed. In the UC cohort (n = 75), the rate of diversion-associated CRC was 4.5 cases/1000 dpy (95% CI 0.11–25/1000) or 1.5 cases/1000 pyd (95% CI 0.04–8.2/1000). In the CD cohort (n = 79), no patients developed CRC, although a dysplasia rate of 1.9 cases/1000 dpy (95% CI 0.05–11/1000) or 0.77 cases/1000 pyd (95% CI 0.02–4.3/1000) was observed. All patients developing neoplasia had disease duration > 10 years and microscopic inflammation. Conclusions Diverted dysplasia occurred infrequently with rates overlapping those reported in registries for IBD-based rectal cancers. Neoplasia was undetected in patients with < 10 pyd, regardless of diversion duration, suggesting low yield for endoscopic surveillance before this time.

The demonstration of competency in endoscopy is required prior to obtaining American Board of Surgery Certification. To demonstrate competency, the resident must pass a national high-stakes cognitive test and a technical skills exam on a virtual reality simulator. The purpose of this preliminary study was to design a proficiency-based endoscopy simulation curriculum to meet this competency requirement. This is a mixed methods prospective cohort study at a single academic medical institution. Prior to taking the national exam, surgery residents were required to participate in a skills lab and demonstrate proficiency on 10 simulation tasks. Proficiency was based on time and percent of objects targeted/mucosa seen. Simulation practice time, number of task repetitions to proficiency, and prior endoscopic experience were recorded. Resident’s self-reported confidence scores in endoscopic skills prior to and following simulation lab training were obtained. From January 1, 2016 through August 1, 2017, 20 surgical residents (8 PGY2, 8 PGY3, 4 PGY4) completed both a faculty-supervised endoscopy skills lab and independent learning with train-to-proficiency simulation tasks. Median overall simulator time per resident was 306 min (IQR: 247–405 min). Median overall time to proficiency in all tasks was 235 min (IQR: 208–283 min). The median time to proficiency decreased with increasing PGY status (r = 0.4, P = 0.05). There was no correlation between prior real-time endoscopic experience and time to proficiency. Reported confidence in endoscopic skills increased significantly from mean of 5.75 prior to 7.30 following the faculty-supervised endoscopy skills lab (P = 0.0002). All 20 residents passed the national exam. In this preliminary study, a train-to-proficiency curriculum in endoscopy improved surgical resident’s confidence in their endoscopic skills and 100% of residents passed the FES technical skills test on their first attempt. Our findings also indicate that uniform proficiency was not achieved by real-time experience alone.

Background: Creation of a J pouch is the gold standard surgical intervention in the treatment of chronic ulcerative colitis (UC). Pouchoscopy prior to ileostomy takedown is commonly performed. We describe the frequency, indication, and findings on pouchoscopy, and determine if pouchoscopy affects rates of complications after takedown. Methods: All UC or indeterminate inflammatory bowel disease patients with a J pouch were retrospectively evaluated from January 1994 to December 2014. Cases were defined as having routine (asymptomatic) pouchoscopy after pouch creation but before ileostomy takedown. Controls were defined as having no pouchoscopy or pouchoscopy on the same day as that of takedown. Results: The study included 178 patients (81.5% cases, 18.5% controls). Fifty two percent of pouchoscopies were reported as normal. Common abnormal endoscopy findings included stricture (35%), pouchitis (7%), and cuffitis (0.7%). Length of stay during takedown hospitalization was shorter for cases than controls (3 vs. 5 days; p = 0.001), but neither short- nor long-term complications were statistically different between cases and controls. Abnormalities on pouchoscopy were not predictive for short-term complications (p = 0.73) or long-term complications (p = 0.55). Routine pouchoscopy did not delay takedown surgery in any of the included patients. Conclusions: Routine pouchoscopy may not be necessary prior to ileostomy takedown; its greatest utility is in patients with suspected pouch complications.

It is commonly believed that robotic surgery systems provide surgeons with an ergonomically sound work environment; however, the actual experience of surgeons practicing robotic surgery (RS) has not been thoroughly researched. In this ergonomics survey study, we investigated surgeons’ physical symptom reports and their association with factors including demographics, specialties, and robotic systems. Four hundred and thirty-two surgeons regularly practicing RS completed this comprehensive survey comprising 20 questions in four categories: demographics, systems, ergonomics, and physical symptoms. Chi-square and multinomial logistic regression analyses were used for statistical analysis. Two hundred and thirty-six surgeons (56.1 %) reported physical symptoms or discomfort. Among those symptoms, neck stiffness, finger, and eye fatigues were the most common. With the newest robot, eye symptom rate was considerably reduced, while neck and finger symptoms did not improve significantly. A high rate of lower back stiffness was correlated with higher annual robotic case volume, and eye symptoms were more common with longer years practicing robotic surgery (p

It is unclear whether intensive surveillance protocols have resulted in a decreased incidence of colorectal cancer (CRC) in inflammatory bowel disease (IBD). To determine the prevalence and characteristics of IBD associated high-grade dysplasia (HGD) or CRC that was undetected on prior colonoscopy. This is a single-center, retrospective study from 1994 to 2013. All participants had a confirmed IBD diagnosis and underwent a colectomy with either HGD or CRC found in the colectomy specimen.The undetected group had no HGD or CRC on prior colonoscopies. The detected group had HGD or CRC identified on previous biopsies. Of 70 participants, with ulcerative colitis (UC) (n = 47), Crohn’s disease (CD) (n = 21), and indeterminate colitis (n = 2), 29% (n = 20) had undetected HGD/CRC at colectomy (15 HGD and 5 CRC). In the undetected group, 75% had prior LGD, 15% had indefinite dysplasia, and 10% had no dysplasia (HGD was found in colonic strictures). Patients in the undetected group were more likely to have pancolitis (55 vs. 20%) and multifocal dysplasia (35 vs. 8%). The undetected group was less likely to have CRC at colectomy (25 vs. 62%). There was a trend toward right-sided HGD/CRC at colectomy (40 vs. 20%; p = 0.08). In addition, 84% of the lesions found in the rectum at colectomy were not seen on prior colonoscopy in the undetected group. The prevalence of previously undetected HGD/CRC in IBD found at colectomy was 29%. The high proportion of undetected rectal and right-sided HGD/CRC suggests that these areas may need greater attention during surveillance.

Recent gene-profiling analyses showed significant upregulation of the folate hydrolase (FOLH1) gene in the affected intestinal mucosa of patients with inflammatory bowel disease (IBD). The FOLH1 gene encodes a type II transmembrane glycoprotein termed glutamate carboxypeptidase II (GCPII). To establish that the previously reported increased gene expression was functional, we quantified the glutamate carboxypeptidase enzymatic activity in 31 surgical specimens and report a robust 2.8- to 41-fold increase in enzymatic activity in the affected intestinal mucosa of IBD patients compared with an uninvolved area in the same patients or intestinal mucosa from healthy controls. Using a human-to-mouse approach, we next showed a similar enzymatic increase in two well-validated IBD murine models and evaluated the therapeutic effect of the potent FOLH1/ GCPII inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) (IC50 = 300 pM). In the dextran sodium sulfate (DSS) colitis model, 2-PMPA inhibited the GCPII activity in the colonic mucosa by over 90% and substantially reduced the disease activity. The significance of the target was confirmed in FOLH1-/- mice who exhibited resistance to DSS treatment. In the murine IL-10-/- model of spontaneous colitis, daily 2-PMPA treatment also significantly reduced both macroscopic and microscopic disease severity. These results provide the first evidence of FOLH1/GCPII enzymatic inhibition as a therapeutic option for IBD.

DNA hypermethylation is a common epigenetic abnormality in colorectal cancers (CRCs) and a promising class of CRC screening biomarkers. We conducted a genome-wide search for novel neoplasia-specific hypermethylation events in the colon. We applied methylation microarray analysis to identify loci hypermethylated in 17 primary CRCs relative to eight non-neoplastic colonic mucosae (NCs) from neoplasia-free subjects. These CRC-associated hypermethylation events were then individually evaluated for their ability to discriminate neoplastic from non-neoplastic cases, based on real-time quantitative methylation-specific PCR (qMSP) assays in 113 colonic tissues: 51 CRCs, nine adenomas, 19 NCs from CRC patients (CRC–NCs), and 34 NCs from neoplasia-free subjects (control NCs). A strict microarray data filtering identified 169 candidate CRC-associated hypermethylation events. Fourteen of these 169 loci were evaluated using qMSP assays. Ten of these 14 methylation events significantly distinguished CRCs from age-matched control NCs (PP−6), followed by BEN domain containing 4 (BEND4), neuronal pentraxin I (NPTX1), ALX homeobox 3 (ALX3), miR-34b, glucagon-like peptide 1 receptor (GLP1R), BTG4, homer homolog 2 (HOMER2), zinc finger protein 583 (ZNF583), and gap junction protein, gamma 1 (GJC1). Adenomas were significantly discriminated from control NCs by hypermethylation of VSX2, BEND4, NPTX1, miR-34b, GLP1R, and HOMER2 (PP−4). In conclusion, systematic methylome-wide analysis has identified ten novel methylation events in neoplastic and non-neoplastic colonic mucosae from CRC patients. These potential biomarkers significantly discriminate CRC patients from controls. Thus, they merit further evaluation in stool- and circulating DNA-based CRC detection studies.

Background: Crohn's disease (CD) and ulcerative colitis (UC) result from pathophysiologically distinct dysregulated immune responses, as evidenced by the preponderance of differing immune cell mediators and circulating cytokine expression profiles. MicroRNAs (miRNAs) are small, noncoding RNAs that act as negative regulators of gene expression and have an increasingly recognized role in immune regulation. We hypothesized that differences in circulating immune cells in CD and UC patients are reflected by altered miRNA expression and that miRNA expression patterns can distinguish CD and UC from normal healthy individuals. Methods: Peripheral blood was obtained from patients with active CD, inactive CD, active UC, inactive UC, and normal healthy adults. Total RNA was isolated and miRNA expression assessed using miRNA microarray and validated by mature miRNA quantitative reverse-transcription polymerase chain reaction. Results: Five miRNAs were significantly increased and two miRNAs (149* and miRplus-F1065) were significantly decreased in the blood of active CD patients as compared to healthy controls. Twelve miRNAs were significantly increased and miRNA-505* was significantly decreased in the blood of active UC patients as compared to healthy controls. Ten miRNAs were significantly increased and one miRNA was significantly decreased in the blood of active UC patients as compared to active CD patients. Conclusions: Peripheral blood miRNAs can be used to distinguish active CD and UC from healthy controls. The data support the evidence that CD and UC are associated with different circulating immune cells types and that the differential expression of peripheral blood miRNAs may form the basis of future diagnostic tests for inflammatory bowel disease. (Inflamm Bowel Dis 2011;)

Introduction: Lasers 2-microm in wavelength offer efficient tissue cutting with limited thermal damage in biological tissue. Objective: To evaluate the dissection capabilities of a 2-microm continuous-wave laser for NOTES procedures. Methods and procedures: We conducted 18 acute animal experiments. Group 1 (three animals): transcolonic access to the peritoneal cavity (15-W transcolonic laser puncture, balloon dilation over the laser probe). Group 2 (six animals): transcolonic access with needle-knife puncture and balloon dilation. Group 3 (three animals): transgastric access to the peritoneal cavity (similar technique as group 1) followed by laser-assisted dissection of the kidney. In one animal of group 3, a therapeutic target (hematoma) was created by percutaneous puncture of the kidney. Group 4 (six animals): transgastric access (similar to the technique of group 2). Results: Translumenal access to the peritoneal cavity was achieved in 2-3 min in group 1 (significantly shorter than with the needle-knife-assisted technique, 4-5 min, p=0.02) and in 7-10 min in group 3 (compared to 6-17 min in group 4, p=0.88). In group 3, laser dissection of the parietal peritoneum and of perinephric connective tissue allowed access to the retroperitoneum with complete removal of a blood collection in the animal with puncture trauma. Laser dissection demonstrated good maneuverability, clean and rapid cutting, and excellent hemostasis. Peritoneoscopy and necropsy showed no damage of targeted tissue and surrounding organs. Conclusions: The 2-microm continuous-wave laser system showed promising capabilities for highly precise and safe dissection during NOTES procedures.

Background Currently reported natural orifice transluminal endoscopic surgery (NOTES) procedures in animals have been done in heterogeneous milieus ranging from nonsterile to sterile procedures, with mixed results, including no infection in those performed in nonsterile settings. Objective To establish the potential frequency of infection during NOTES, comparing sterile to nonsterile approaches. Setting Survival experiments on sixteen 50-kg pigs. Design and Interventions From pilot data (100% infection frequency after nonsterile procedures), sample size (8 animals in each group) was calculated by using a power of 95% and an alpha risk of 0.05. The animals were randomly assigned to two groups: In the transgastric peritoneoscopy study group, liver and ovarian biopsies were performed with sterile overtubes, endoscopes, and accessories and the use of preoperative intravenous antibiotics and antiseptic gastric lavage. In the nonsterile (control) group, the same procedures were performed with nonsterile endoscopes and accessories without the use of gastric lavage and preoperative antibiotics. Complete transmural closure of the transgastric access site was made in all animals. After a 1-week survival time, all animals were killed for necropsy, which included Gram staining and peritoneal cultures. Main Outcome Measurements Intraperitoneal infection on necropsy. Results All necropsies revealed intraperitoneal infection (abscesses, fibrinopurulent exudates, and adhesions) in the control group (frequency of infection 100%). Peritoneal bacterial culture grew various aerobic and anaerobic organisms. No gross or bacteriological evidence of infection was seen in the sterile group (frequency of infection 0%, P value= Limitations Animal experiments. Conclusion Nonsterile conditions invariably lead to intraperitoneal infection. Aseptic techniques during NOTES can prevent intra-abdominal infection. Future studies will determine which infection prevention steps are mandatory and which can be omitted during NOTES procedures.

Introduction The utility of the greater omentum has not been assessed in transluminal access closure after natural orifice transluminal endoscopic surgery (NOTES) procedures. Objective Our purpose was to evaluate the feasibility, efficacy, and safety of omentoplasty for gastrotomy closure. Methods and Procedures Survival experiments in 9 female 40-kg pigs were randomly assigned to 3 groups: group A, endoscopic full-thickness resection (EFTR) for transgastric access and peritoneoscopy without closure; group B, ETFR and peritoneoscopy with omentoplasty (flap of omentum is pulled into the stomach and attached to the gastric mucosa with clips but no clips are used for gastrotomy closure itself); group C, balloon dilation for opening and peritoneoscopy followed by omentoplasty for closure. The animals were observed for 2 weeks and then underwent endoscopy and necropsy with histologic evaluation. Results Transgastric opening and peritoneoscopy were achieved in all pigs. In groups B and C, a flap of omentum was easily placed to seal the gastrotomy and then attached to the gastric mucosa with 2 to 5 clips (median 4) in 7 to 20 minutes (median 15 minutes). In group A, peritonitis developed in all animals. In both groups B and C, all animals survived 15 days with no peritonitis and minimal adhesions outside the gastrotomy site. In addition, all achieved complete healing (transmural, n=4; mucosal ulceration, n=2) of the gastrotomy site. One animal in group B had an 18-mm abscess in the omental flap. Limitations Animal model, small sample size, lack of appropriate controls for group C. Conclusions Omentoplasty of the gastrotomy site is a technically feasible method to seal balloon-created transgastric access to the peritoneal cavity after NOTES procedures.

Leak-resistant closure of transluminal access is a major challenge facing natural orifice transluminal endoscopic surgery (NOTES).To evaluate a hydrogen (H(2))-based leak test for assessment of transluminal-access closure integrity after NOTES procedures.Nine acute porcine experiments.After gastric-wall puncture and balloon dilation, peritoneoscopy was performed, followed by transmural closure of the gastric opening. The animals were randomly assigned to complete or incomplete closure groups. The H(2) leak test was performed by using 1000 mL of 4% H(2) gas mixture and the Hydrogen Leak Detector H2000+. The animals were then euthanized for a methylene blue (MB) test of gastric closure integrity.Intraperitoneal H(2) concentration after gastric insufflation with H(2).The H(2) leak test was quick and easy. Intraperitoneal H(2) concentrations in parts per million in both groups were similar at baseline (mean +/- SD, 0.18 +/- 0.29 parts per million [ppm] vs 0.22 +/- 0.35 ppm, P = .97) and after balloon dilation (414.8 +/- 198.5 ppm vs 601.3 +/- 116.1 ppm, P.99). Postclosure intraperitoneal H(2) concentrations dropped to 0.01 +/- 0.77 ppm in the complete-closure group, similar (P = .81) to matched-pairs preopening levels and significantly lower than in the incomplete-closure group (162.0 +/- 83.0 ppm, P.02). On necropsy, the MB test was negative in all 5 animals of the complete-closure group and positive in all 4 animals of the incomplete-closure group. A cutoff of 25 ppm in intraperitoneal H(2) concentration after closure gave 100% sensitivity, specificity, and positive and negative predictive values for MB leakage.Nonsurvival animal experiments.The H(2) leak test is highly accurate for detection of leakage after NOTES procedures and could become a substitute for currently used MB leak tests.

Transluminal access site closure remains a major challenge in natural orifice transluminal endoscopic surgery (NOTES).Our purpose was to develop in vivo leak tests for evaluation of the integrity of transgastric access closure.Survival experiments on 12 50-kg pigs.After a standardized transgastric approach to the peritoneal cavity and peritoneoscopy, the gastric wall incision was closed with T-bars (Wilson-Cook Medical, Winston-Salem, NC) deployed on both sides of the incision and then cinched together. Gastrotomy closure was assessed with air and fluid leak tests. The animals were observed for 1 week and then underwent endoscopic evaluation and necropsy.(1) Leak-proof closure of the gastric wall incision. (2) Gastric incision healing 1 week after the procedure.The mean intraperitoneal pressure increased 10.7 +/- 3.7 mm Hg during gastric insufflation when the air leak test was performed before closure compared with 0.9 +/- 0.8 mm Hg after transmural closure of the transgastric access site with T-bars (P.001). Fluid leak tests demonstrated no leakage of liquid contrast from the stomach into the peritoneal cavity after closure. Necropsy in 1 week confirmed completeness of the gastric closure in all animals with full-thickness healing and no spillage of the gastric contents into the peritoneal cavity.Leak tests were only evaluated on an animal model.Fluid and air leak tests are simple techniques to evaluate in vivo the adequacy of the transluminal access site closure after NOTES procedures. Leak-proof gastric closure resulted in adequate tissue approximation and full-thickness healing of the gastric wall incision.

The management of patients with thyroid fine-needle aspiration (FNA) specimens that are neither benign nor malignant still remains problematic. Efforts to improve their management have focused on identifying risk factors that predict malignancy. This study seeks to identify clinical and tumor characteristics that predict thyroid malignancy among patients with indeterminate or suspicious FNA and to develop a diagnostic predictor model.The records of 639 patients with an indeterminate or suspicious thyroid FNA between January 1995 and April 2005 were reviewed. Patient and tumor characteristics were evaluated for their potential to predict malignancy in the final surgical histopathology. A diagnostic predictor model was designed based on statistically significant predictors. Patients seen between April 2005 and April 2007 were used to validate the model.Patient age, nodule size, and FNA cytopathology were identified as risk factors. Patients at extremes of age were at increased risk. Patients 50 years of age had the lowest risk of malignancy. For patients less than age 50, the risk increased 3% for each year decrease in age (p = 0.001). After 50, the risk increased 3.4% for each year increase in age (p = 0.016). Nodules 2.5 cm had the lowest likelihood of malignancy. For smaller nodules, the risk increased 53% per cm decrease in size (p0.001). For larger nodules, the risk increased 39% per cm increase (p0.001). Patients with FNA cytology suspicious for papillary thyroid carcinoma had the greatest risk of malignancy (p0.001).A predictor model was created using the variables age, nodule size, and FNA cytology to predict thyroid malignancy.

Reliable closure of the translumenal incision is one of the main challenges facing natural orifice translumenal endoscopic surgery (NOTES). This study aimed to evaluate the use of an automated flexible stapling device (SurgASSIST) for closure of the gastrotomy incision in a porcine model. A double-channel gastroscope was advanced into the stomach. A gastric wall incision was made, and the endoscope was advanced into the peritoneal cavity. After peritoneoscopy, the endoscope was withdrawn into the stomach. The SurgASSIST stapler was advanced orally into the stomach. The gastrotomy edges were positioned between the opened stapler arms using two endoscopic grasping forceps. Stapler loads with and without a cutting blade were used for gastric closure. After firing of the stapler to close the gastric wall incision, x-ray with contrast was performed to assess for gastric leakage. At the end of the procedure, the animals were killed for a study of closure adequacy. Four acute animal experiments were performed. The delivery and positioning of the stapler were achieved, with technical difficulties mostly due to a short working length (60 cm) of the device. Firing of the staple delivered four rows of staples. Postmortem examination of pig 1 (when a cutting blade was used) demonstrated full-thickness closure of the gastric wall incision, but the cutting blade caused a transmural hole right at the end of the staple line. For this reason, we stopped using stapler loads with a cutting blade. In the three remaining animals (pigs 2–4), we were able to achieve a full-thickness closure of the gastric wall incision without any complications. The flexible stapling device may provide a simple and reliable technique for lumenal closure after NOTES procedures. Further survival studies are currently under way to evaluate the long-term efficacy of gastric closure with the stapler after intraperitoneal interventions.

BACKGROUND AND STUDY AIMS: Reliable closure of the translumenal incision is the crucial step for natural orifice translumenal endoscopic surgery (NOTES) procedures. The aim of this study was to evaluate the feasibility and effectiveness of transgastric access closure with a flexible stapling device in a porcine survival model. PATIENTS AND METHODS: We carried out four experiments (two sterile and two nonsterile) on 50 kg pigs. The endoscope was passed through a gastrotomy made with a needle knife and an 18-mm controlled radial expansion dilating balloon. After peritoneoscopy, a flexible linear stapling device (NOLC60, Power Medical Interventions®, Langhorne, Pennsylvania, USA) was perorally advanced over a guide wire into the stomach, positioned under endoscopic guidance, and opened to include the site of gastrotomy between its two arms; four rows of staples were fired. One animal was sacrificed 24 hours after the procedure (progression of pre-existing pneumonia). The remaining animals were survived for 1 week and then underwent repeat endoscopy and postmortem examination. RESULTS: Peroral delivery and positioning of the stapling device involved some technical difficulties, mostly due to the short length (60 cm) of the stapling device. The stapler provided complete leak-resistant gastric closure in all pigs. None of the surviving animals had any clinical signs of infection. Necropsy demonstrated an intact staple line with full-thickness healing of the gastrotomy in all animals. Histologic examination confirmed healing, but also revealed intramural micro-abscesses within the gastric wall after nonsterile procedure. CONCLUSIONS: Gastrotomy closure with a perorally delivered flexible stapling device created a leak-resistant transmural line of staples followed by full-thickness healing of the gastric wall incision. Increasing the length of the instrument and adding device articulation will further facilitate its use for NOTES procedures.

We have shown previously that abdominal insufflation with CO(2) increases serum levels of IL-10 and TNFalpha and increases survival among animals with lipopolysaccharide (LPS)-induced sepsis, even after a laparotomy. We demonstrated previously that the effect of CO(2) is not from changes in systemic pH, although the peritoneum is locally acidotic during abdominal insufflation with CO(2) even when systemic pH is corrected. We hypothesized that acidification of the peritoneum via means other than CO(2) insufflation would produce alterations in the inflammatory response similar to those associated with CO(2) pneumoperitoneum.In total, 42 rats were randomized into 7 groups (n = 6): 1) LPS only, 2) anesthesia control, 3) helium pneumoperitoneum, 4) CO(2) pneumoperitoneum, 5) buffered mild acid lavage, 6) buffered strong acid lavage, and 7) buffered strong acid lavage + helium pneumoperitoneum. Animals received anesthesia with vaporized isoflurane (except the LPS-only group) and their respective abdominal treatment (pneumoperitoneum and/or lavage) for 30 min followed immediately by stimulation with systemic LPS (1 mg/kg, IV). Blood was harvested via cardiac puncture 60 min after LPS injection, and serum levels of IL-10 and TNFalpha levels were determined by enzyme-linked immunosorbent assay.Mean peritoneal pH decreased (P.05) after CO(2) pneumoperitoneum, buffered strong acid lavage, and buffered strong acid lavage + helium pneumoperitoneum, and it decreased (P = .1) after helium pneumoperitoneum alone and buffered mild acid lavage. IL-10 levels were increased (P.01), and TNFalpha levels decreased (P.001) among animals with acidic peritoneal cavities compared with animals with pH-normal peritoneal cavities. Decreasing peritoneal pH correlated with both increasing IL-10 levels (r = -.465, P.01) and decreasing TNFalpha levels (r = 0.448, P.01). Among animals with peritoneal acidosis, there were no differences in levels of IL-10 or TNFalpha regardless of insufflation status (P.05 for both cytokines).Acidification of the peritoneal cavity whether by abdominal insufflation or by peritoneal acid lavage increases serum IL-10 and decreases serum TNFalpha levels in response to systemic LPS challenge. The degree of peritoneal acidification correlates with the degree of inflammatory response reduction. These results support the hypothesis that pneumoperitoneum-mediated attenuation of the inflammatory response after laparoscopic surgery occurs via a mechanism of peritoneal cell acidification.

The peroral transgastric endoscopic approach for intraabdominal procedures appears to be feasible, although multiple aspects of this approach remain unclear. This study aimed to measure intraperitoneal pressure in a porcine model during the peroral transgastric endoscopic approach, comparing an endoscopic on-demand insufflator/light source with a standard autoregulated laparoscopic insufflator.All experiments were performed with 50-kg female pigs under general anesthesia. A standard upper endoscope was advanced perorally through a gastric wall incision into the peritoneal cavity. The peritoneal cavity was insufflated with operating room air from an endoscopic light source/insufflator. Intraperitoneal pressure was measured by three routes: (1) through the endoscope biopsy channel, (2) through a 5-mm transabdominal laparoscopic port, and (3) through a 16-gauge Veress needle inserted into the peritoneal cavity through the anterior abdominal wall. The source of insufflation alternated between on-demand manual insufflation through the endoscopic light source/insufflator using room air and a standard autoregulated laparoscopic insufflator using carbon dioxide (CO(2)).Six acute experiments were performed. Intraperitoneal pressure measurements showed good correlation regardless of measurement route and were independent of the type of insufflation gas, whether room air or CO(2). On-demand insufflation with the endoscopic light source/insufflator resulted in a wide variation in pressures (range, 4-32 mmHg; mean, 16.0 +/- 11.7). Intraabdominal pressures using a standard autoregulated laparoscopic insufflator demonstrated minimal fluctuation (range, 8-15 mmHg; mean, 11.0 +/- 2.2 mmHg) around a predetermined value.Use of an on-demand unregulated endoscopic light source/insufflator for translumenal surgery can cause large variation in intraperitoneal pressures and intraabdominal hypertension, leading to the risk of hemodynamic and respiratory compromise. Safety may favor well-controlled intraabdominal pressures achieved with a standard autoregulated laparoscopic insufflator.

Pancreatic duct stenting remains an attractive strategy to reduce the incidence of pancreatic fistulas following pancreaticoduodenectomy (PD) with encouraging results in both retrospective and prospective studies. We performed a prospective randomized trial to test the hypothesis that internal pancreatic duct stenting reduces the development of pancreatic fistulas following PD. Two hundred thirty-eight patients were randomized to either receive a pancreatic stent (S) or no stent (NS), and stratified according to the texture of the pancreatic remnant (soft/normal versus hard). Four patients were excluded from the study; in three instances due to a pancreatic duct that was too small to cannulate and in the other instance because a total pancreatectomy was performed. Patients who randomized to the S group had a 6-cm-long segment of a plastic pediatric feeding tube used to stent the pancreaticojejunostomy anastomosis. In patients with a soft pancreas, 57 randomized to the S group and 56 randomized to the NS group. In patients with a hard pancreas, 58 randomized to the S group and 63 randomized to the NS group. The S and NS groups for the entire study population, as well as for the subgroup of high-risk patients with soft pancreata, were similar as regard to demographics, past medical history, preoperative symptoms, preoperative procedures, and intraoperative data. The pancreatic fistula rate for the entire study population was 9.4%. The fistula rates in the S and NS subgroups with hard pancreata were similar, at 1.7% and 4.8% (P = 0.4), respectively. The fistula rates in the S and NS subgroups with soft pancreata were also similar, at 21.1% and 10.7% (P = 0.1), respectively. A nonstatistically significant increase in the pancreatic fistula rate in the S group persisted after adjusting for the operating surgeon and technical details of the operation (e.g., anastomotic technique, anastomotic orientation, pancreatic duct size, and number of intra-abdominal drains placed). In patients with soft pancreata, 63% percent of the pancreatic fistulas in stented patients required adjustment to the clinical pathway (including two deaths), compared to 47% of the pancreatic fistulas in patients in the NS group (P = 0.3). Internal pancreatic duct stenting does not decrease the frequency or the severity of postoperative pancreatic fistulas.

Laparoscopic surgery preserves the immune system and has anti-inflammatory properties. CO2 pneumoperitoneum attenuates lipopolysaccharide (LPS)-induced cytokine production and increases survival. We tested the hypothesis that CO2 pneumoperitoneum mediates its immunomodulatory properties via stimulation of the cholinergic pathway.In the first experiment, rats (n = 68) received atropine 1 mg/kg or saline injection 10 min prior to LPS injection and were randomization into four 30-min treatment subgroups: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. In a second experiment, rats (n = 40) received atropine 2 mg/kg or saline 10 min prior to randomization into the same four subgroups described previously. In a third experiment, rats (n = 96) received atropine 2 mg/kg or saline 10 min prior to randomization into eight 30-min treatment subgroups followed by LPS injection: LPS only control; anesthesia control; and CO2 or helium pneumoperitoneum at 4, 8, and 12 mmHg. In a fourth experiment, rats (n = 58) were subjected to bilateral subdiaphragmatic truncal vagotomy or sham operation. Two weeks postoperatively, animals were randomized into four 30-min treatment subgroups followed by LPS injection: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. Blood samples were collected from all animals 1.5 h after LPS injection, and cytokine levels were determined by enzyme-linked immunosorbent assay.Serum tumor necrosis factor-alpha (TNF-alpha) levels were consistently suppressed among the saline-CO2 pneumoperitoneum groups compared to saline-LPS only control groups (p0.05 for all four experiments). All chemically vagotomized animals had significantly reduced TNF-alpha levels compared to their saline-treated counterparts (p0.05 for all), except among the CO2 pneumoperitoneum-treated animals. Increasing insufflation pressure with helium eliminated differences (p0.05) in TNF-alpha production between saline- and atropine-treated groups but had no effect among CO2 pneumoperitoneum-treated animals. Finally, vagotomy (whether chemical or surgical) independently decreased LPS-stimulated TNF-alpha production in all four experiments.CO2 pneumoperitoneum modulates the immune system independent of the vagus nerve and the cholinergic pathway.

Carbon dioxide (CO2) pneumoperitoneum has been shown to attenuate the inflammatory response after laparoscopy. This study tested the hypothesis that abdominal insufflation with CO2 improves survival in an animal model of sepsis and investigated the associated mechanism. The effect of CO2, helium, and air pneumoperitoneum on mortality was studied by inducing sepsis in 143 rats via intravenous injection of lipopolysaccharide (LPS). To test the protective effect of CO2 in the setting of a laparotomy, an additional 65 animals were subjected to CO2 pneumoperitoneum, helium pneumoperitoneum, or the control condition after laparotomy and intraperitoneal LPS injection. The mechanism of CO2 protection was investigated in another 84 animals. Statistical significance was determined via Kaplan– Meier analysis for survival and analysis of variance (ANOVA) for serum cytokines. Among rats with LPS-induced sepsis, CO2 pneumoperitoneum increased survival to 78%, as compared with using helium pneumoperitoneum (52%; p < 0.05), air pneumoperitoneum (55%; p = 0.09), anesthesia control (50%; p < 0.05), and LPS-only control (42%; p < 0.01). Carbon dioxide insufflation also significantly increased survival over the control condition (85% vs 25%; p < 0.05) among laparotomized septic animals, whereas helium insufflation did not (65% survival). Carbon dioxide insufflation increased plasma interleukin-10 (IL-10) levels by 35% compared with helium pneumoperitoneum (p < 0.05), and by 34% compared with anesthesia control (p < 0.05) 90 min after LPS stimulation. Carbon dioxide pneumoperitoneum resulted in a threefold reduction in tumor necrosis factor-α (TNF-α) compared with helium pneumoperitoneum (p < 0.05), and a sixfold reduction with anesthesia control (p < 0.001). Abdominal insufflation with CO2, but not helium or air, significantly reduces mortality among animals with LPS-induced sepsis. Furthermore, CO2 pneumoperitoneum rescues animals from abdominal sepsis after a laparotomy. Because IL-10 is known to downregulate TNF-α, the increase in IL-10 and the decrease in TNF-α found among the CO2-insufflated animals in our study provide evidence for a mechanism whereby CO2 pneumoperitoneum reduces mortality via IL-10-mediated downregulation of TNF-α.

Carbon dioxide (CO(2))-pneumoperitoneum is known to favorably modify the systemic immune response during laparoscopic surgery. The presented studies were designed to determine whether treating animals with CO(2) abdominal insufflation before undergoing a lipopolysaccharide (LPS)-contaminated laparotomy would serve as "shock prophylaxis" and thus improve survival and attenuate cytokine production. Rats were randomized into five groups: CO(2)-pneumoperitoneum, helium-pneumoperitoneum, anesthesia control, laparotomy/LPS control, and LPS only control. Animals in the first four groups all received a laparotomy and a lethal dose of LPS. Immediately preceding their laparotomy, animals in the pneumoperitoneum groups received a 30-minute pretreatment of abdominal insufflation with either CO(2) or helium. The anesthesia control group received a 30-minute pretreatment of isoflurane. Animal mortality was then recorded during the ensuing 72 hours. Subsequently, a similar protocol was repeated for measurements of cytokines. CO(2)-pneumoperitoneum increased survival at 48 hours compared with LPS control (P.05), and decreased interleukin-6 plasma levels at 2 hours (P.05). Abdominal insufflation with CO(2) before the performance of a laparotomy contaminated with endotoxin increases survival and attenuates interleukin-6. The beneficial immune-modulating effects of CO(2)-pneumoperitoneum endure after abdominal insufflation. CO(2)-pneumoperitoneum pretreatment may improve outcomes among patients undergoing gastrointestinal surgery who are at high risk for abdominal fecal contamination.

Paragangliomas of the organ of Zuckerkandl are rare tumors with only several case reports noted in the literature. Synchronous paraganglioma occur sporadically, and on occasion, in association with several genetic syndromes. Paraganglioma of the organ of Zuckerkandl with synchronous carotid body paraganglioma is described herein. Traditionally, surgical resection of abdominal paraganglioma involved an exploratory laparotomy. In this manuscript, we describe one of the first reported laparoscopic resections of this tumor and review the literature on multiple paragangliomas and their associated genetic syndromes.

We have shown that the inflammation-attenuating effects of CO2 pneumoperitoneum during laparoscopy are not due to changes in systemic pH. However, acidification of peritoneal macrophages in an in vitro CO2 environment has been shown to reduce LPS-mediated cytokine release. We tested the hypothesis that the peritoneum is locally acidotic during abdominal insufflation with CO2deven when systemic pH is corrected. Rats (n = 20) were anesthetized and randomized into two groups: continued spontaneous ventilation (SV) or intubation and mechanical ventilation (MV). All animals were then subjected to abdominal insufflation with CO2. Mean arterial pH among SV rats decreased significantly from baseline after 15 and 30 minutes of CO2 pneumoperitoneum (7.329→7.210→7.191, P < 0.05), while arterial pH among MV rats remained relatively constant (7.388→7.245→7.316, P = NS). In contrast, peritoneal pH dropped significantly from baseline and remained low for both groups during CO2 abdominal insufflation (SV 6.74 → 6.41 → 6.40, P < 0.05; MV 6.94 → 6.45 → 6.45, P < 0.05). In a second experiment, rats (n = 10) were randomized to receive abdominal insufflation with either CO2 or helium. Abdominal insufflation with helium did not significantly affect peritoneal pH (7.10 → 7.02 →6.95, P = NS), and the decrease in pH among CO2-insufflated animals was significant compared with helium-insufflated animals (P < 0.05). Peritoneal pH returned to baseline levels in all groups within 15 minutes of desufflation in both experiments. A significant local peritoneal acidosis occurs during laparoscopy which is specifically attributable to the use of CO2 and which is independent of systemic pH. These data provide additional evidence that localized peritoneal acidosis is central to the mechanism of CO2-mediated attenuation of the inflammatory response following laparoscopic surgery.

BACKGROUND: The dawn of laparoscopic surgery and the telecommunications revolution have given birth to the field of telesurgery. METHODS: Even now, surgery is being performed over great distances to bring expert surgical care to physically isolated patients with otherwise limited healthcare access. RESULTS: As technical obstacles are eliminated in the future, telesurgery will extend the reach of military surgeons to patients at sea and on the battlefield, and astronauts will undergo procedures performed by earthbound interventionalists. Just as the Internet has revolutionized the way everyday consumers shop, eventually, telesurgery may transform surgical care, as patients may stay in their local hospitals and simply "dial up" the best telesurgeon for their specific operation. Telesurgical teams have now formed to refine technical approaches to telesurgery, study the effects of telesurgery on human task performance, and establish telesurgery networks around the world. CONCLUSIONS: While some legitimate social, political, and economic issues remain as impediments to the routine practice of telesurgery, there is now no question that telesurgery will play a role in the delivery of surgical care in the twenty-first century.

Background Peritoneal absorption of CO2 during abdominal insufflation in laparoscopy may disrupt the acid-base equilibrium and alter the physiological response to stress. Current nonventilated rodent models of laparoscopy do not manage the CO2 load of pneumoperitoneum, but ventilated surgical rodent models are invasive (tracheotomy) and may independently induce the inflammatory response. Materials and methods A comprehensive rodent model of laparoscopy was developed. Rats were randomized to receive anesthesia alone, anesthesia plus CO2 pneumoperitoneum, or anesthesia plus CO2 pneumoperitoneum with videoendoscopic intubation and mechanical ventilation. Arterial blood-gas analysis was performed at baseline and after 30 min of intervention. Results Baseline pH, pCO2, and HCO3− arterial blood gas parameters were normal for all rats. After 30 min, pCO2 and pH changed slightly but remained normal among rats receiving anesthesia alone (pCO2 = 46.5 ± 1.9; pH = 7.365 ± 0.009) whereas animals receiving anesthesia plus CO2 pneumoperitoneum that were dependent on spontaneous respiration for ventilation developed significant hypercarbic acidosis (pCO2 = 53.2 ± 1.9, P Conclusions CO2 pneumoperitoneum induces significant hypercarbic acidosis in nonventilated rats. Noninvasive endotracheal intubation is feasible in the rat with videoendoscopic assistance. Our noninvasive rodent model of laparoscopic surgery controls for anesthesia- and capnoperitoneum-related acid-base changes and provides an environment in which the biological response to pneumoperitoneum can be studied precisely.

Introduction The “Nintendo” surgery revolution, which began in 1987, has impacted every surgical specialty. However, our operating rooms remain isolated worlds where surgeons use awkward, primitive, rigid instruments with suboptimal visualization. We need “smart instruments,” “smart technology,” and “smart imaging.” Is surgical robotics the answer? Methods We provide an analysis of current surgical technology and skills, propose criteria for what the next generation of surgical instruments and technology should achieve, and then examine the evolution and current state of surgical robotic solutions, assessing how they answer future surgical needs. Finally we report on the U.S. Military's early experience with surgical robotics and the lessons learned therein. Results Current surgical robotic technology has made remarkable progress with miniaturization, articulating hand-imitating instruments, precision, scaling, and three-dimensional vision. The specialty-specific early clinical applications reviewed are promising, but they do have limitations. Surgical robotics offers enormous military application potential. Needed future refinements are identified, including haptics, communications, infrastructure, and information integration. Conclusions Laparoscopic surgery is a transition technology, constrained by instrument, equipment, and skill limitations. Surgical robotics or, more properly, computer-assisted surgery may be the key to the future. The operating room of the future will be an integrated environment with global reach. Surgeons will operate with three-dimensional vision, use real-time three-dimensional reconstructions of patient anatomy, use miniaturized minimally invasive robotic technology, and be able to telementor, teleconsult, and even telemanipulate at a distance, thus offering enhanced patient care and safety.

OBJECTIVES Robotic telesurgery has been demonstrated over long distances and offers theoretical benefits to urologic training and the care of patients in remote regions. The multiple arms and three-dimensional vision of the da Vinci robotic system provide a platform conducive to long-distance telementoring and telesurgery. Whereas prior telesurgical efforts have used dedicated lines for information transmission, the public Internet offers a less expensive alternative. It was the intent of this study to test the validity of using the da Vinci system in urologic telesurgery, and to conduct telerobotic nephrectomies using the public Internet. METHODS We performed four right nephrectomies in porcine models using the da Vinci robotic system. Telementoring and telesurgical approaches were used, with resident surgeons operating a console adjacent to the swine, while attending surgeons simultaneously operated a second console at distances of 1300 and 2400 miles from the operating room. RESULTS All four procedures and both telementoring and telesurgical models were successful. Round-trip delays from 450 to 900 ms were demonstrated. Blood loss was minimal, and there were no intraoperative complications. CONCLUSIONS This study represents the first use of the da Vinci Surgical System in urologic telesurgery and the first successful telesurgical nephrectomy in an animal model.

Importance High-dose glucocorticoids (GCs) are routinely given to surgical patients with a history of GC exposure to prevent perioperative acute adrenal insufficiency, but this practice is not well supported. Objective To evaluate the variability of perioperative GC dosing among patients with inflammatory bowel disease (IBD) undergoing major abdominal surgery. Design, Setting, and Participants This was a retrospective study of 49 patients with IBD undergoing colorectal surgery at a single institution between July 2010 and August 2011. Data on patient comorbidities, intraoperative risk factors, surgical site infections, and 30-day readmission rates were prospectively collected from the National Surgical Quality Improvement Program. Preoperative GC exposure at the time of the index admission and perioperative GC therapy during admission were collected by review of the medical records. Patients were divided into 3 groups at the time of surgery: (1) 1 week or more of prior GC exposure, not receiving maintenance therapy (n = 15); (2) currently receiving budesonide (n = 10); and (3) currently receiving oral prednisone (n = 24). Main Outcomes and Measures Perioperative GC exposure was the main outcome. Qualitative comparisons of perioperative exposure stratified by preoperative GC exposure were done. A multivariate logistic regression analysis was performed to determine significant differences in surgical site infection and 30-day readmission rates among patients with and without perioperative GC exposure. Results Overall, 38 of 49 patients (78%) received perioperative GCs; intraoperative GCs were administered to 35 of 49 patients (71%), and 33 of 49 patients (67%) received postoperative GCs. Patients received intraoperative and postoperative GCs, respectively, as follows: 8 patients (53%) and 7 (47%) in group 1, 7 (70%) and 3 (30%) in group 2, and 20 (83%) and 23 (96%) in group 3. The median intraoperative GC dose was 100 mg (range, 50-267 mg of hydrocortisone or hydrocortisone equivalent for dexamethasone); the median total postoperative GC dose for the first 5 days after surgery was 485 mg (range, 50-890 mg of hydrocortisone or hydrocortisone equivalent for prednisone). The median duration of postoperative GC administration was 3 days for group 1, 6 days for group 2, and 7 days for group 3. No statistically significant difference in surgical site infection and 30-day readmission rates was detected in the GC exposure vs no-exposure groups. Conclusions and Relevance Perioperative GC dosing among patients with IBD undergoing colorectal surgery is highly variable even within a single center. Additional studies are needed to define the risk of postoperative adrenal insufficiency and establish standardized practices for perioperative GC therapy, which may have the benefit of reducing GC overuse.

We conducted this study to investigate how physical and cognitive ergonomic workloads would differ between robotic and laparoscopic surgeries and whether any ergonomic differences would be related to surgeons' robotic surgery skill level. Our hypothesis is that the unique features in robotic surgery will demonstrate skill-related results both in substantially less physical and cognitive workload and uncompromised task performance.Thirteen MIS surgeons were recruited for this institutional review board-approved study and divided into three groups based on their robotic surgery experiences: laparoscopy experts with no robotic experience, novices with no or little robotic experience, and robotic experts. Each participant performed six surgical training tasks using traditional laparoscopy and robotic surgery. Physical workload was assessed by using surface electromyography from eight muscles (biceps, triceps, deltoid, trapezius, flexor carpi ulnaris, extensor digitorum, thenar compartment, and erector spinae). Mental workload assessment was conducted using the NASA-TLX.The cumulative muscular workload (CMW) from the biceps and the flexor carpi ulnaris with robotic surgery was significantly lower than with laparoscopy (p 0.05). Interestingly, the CMW from the trapezius was significantly higher with robotic surgery than with laparoscopy (p 0.05), but this difference was only observed in laparoscopic experts (LEs) and robotic surgery novices. NASA-TLX analysis showed that both robotic surgery novices and experts expressed lower global workloads with robotic surgery than with laparoscopy, whereas LEs showed higher global workload with robotic surgery (p 0.05). Robotic surgery experts and novices had significantly higher performance scores with robotic surgery than with laparoscopy (p 0.05).This study demonstrated that the physical and cognitive ergonomics with robotic surgery were significantly less challenging. Additionally, several ergonomic components were skill-related. Robotic experts could benefit the most from the ergonomic advantages in robotic surgery. These results emphasize the need for well-structured training and well-defined ergonomics guidelines to maximize the benefits utilizing the robotic surgery.

Objective This study provides the first objective assessment of a complete patient population undergoing laparoscopic cholecystectomy in the steady state. The authors determined the frequency of complications, particularly bile duct, bowel, vascular injuries, and deaths. Summary Background Data This retrospective study, conducted for the Department of Defense healthcare system by the Civilian External Peer Review Program, is the second complete audit of laparoscopic cholecystectomy. Data were collected on 9130 patients undergoing laparoscopic cholecystectomy between January 1993 and May 1994. Methods The study sample consisted of clinical data abstracted from the complete records of 9054 (99.2%) of the 9130 laparoscopic cholecystectomies performed at 94 military medical treatment facilities. Results Of 10,458 cholecystectomies performed in the Military Health Services System, 9130 (87.3%) were laparoscopic and 1328 (12.7%) were traditional open procedures. Seventy-six medical records were incomplete; however, there was sufficient data to determine mortality and bile duct injury rates. Of the remaining 9054 cases, 6.09% experienced complications, including bile duct (0.41%), bowel (0.32%), and vascular injuries (0.10 percent). The mortality rate was 0.13%. Access via Veress technique was used in 57.6% and Hasson technique in 42.4% of patients. Intraoperative cholangiograms were performed in 42.7% of the cases with a success rate of 86.2%. Eight hundred ninety-two (9.8%) patients were converted to open cholecystectomies. Conclusions In the steady state, despite an increase in the percentage of laparoscopic cholecystectomies performed for nonmalignant gallbladder disease, there continues to be minimal complications and low mortality.

Background and aims NLRP3 inflammasome is known to be involved in inflammatory bowel diseases. However, it is controversial whether it is pathogenic or beneficial. This study evaluated the roles of NLRP3 inflammasome in the pathogenesis of inflammatory bowel disease in IL-10-/- mice and humans. Methods NLRP3 inflammasome in colonic mucosa, macrophages, and colonic epithelial cells were analysed by western blotting. The NLRP3 inflammasome components were studied by sucrose density gradient fractionation, chemical cross-linking, and co-immunoprecipitation. The role of NLPR3 inflammasome in the pathogenesis of colitis was extensively evaluated in IL-10-/- mice, using a specific NLPR3 inflammasome inhibitor glyburide. Results NLRP3 inflammasome was upregulated in colonic mucosa of both IL-10-/- mice and Crohn's patients. NLRP3 inflammasome activity in IL-10-/- mice was elevated prior to colitis onset; it progressively increased as disease worsened and peaked as macroscopic disease emerged. NLRP3 inflammasome was found in both intestinal epithelial cells and colonic macrophages, as a large complex with a molecular weight of ≥ 360 kDa in size. In the absence of IL-10, NLRP3 inflammasome was spontaneously active and more robustly responsive when activated by LPS and nigericin. Glyburide markedly suppressed NLRP3 inflammasome expression/activation in IL-10-/- mice, leading to not only alleviation of ongoing colitis but also prevention/delay of disease onset. Glyburide also effectively inhibited the release of proinflammatory cytokines/chemokines by mucosal explants from Crohn's patients. Conclusions Abnormal activation of NLRP3 inflammasome plays a major pathogenic role in the development of chronic colitis in IL-10-/- mice and humans. Glyburide, an FDA-approved drug, may have great potential in the management of inflammatory bowel diseases.

OBJECTIVE: This study provided an objective survey by an outside auditing group of a large, complete patient population undergoing laparoscopic cholecystectomies, determined the frequency of complications, especially bile duct injuries, and presented a system for classifying and comparing the severity of bile duct injuries. SUMMARY BACKGROUND DATA: This is the first study of laparoscopic cholecystectomy to encompass a large and complete patient population and to be based on objectively collected data rather than self-reported data. The Civilian External Peer Review Program (CEPRP) of the Department of Defense health care system conducted a retrospective study of 5642 patients who underwent laparoscopic cholecystectomies at 89 military medical treatment facilities from July 1990 through May 1992. METHODS: The study sample consisted of the complete records of 5607 (99.38%) of the 5642 laparoscopic cholecystectomy patients. RESULTS: Of the sample, 6.87% of patients experienced complications within 30 days of surgery, 0.57% sustained bile duct injuries, and 0.5% sustained bowel injuries. Among 5154 patients whose procedures were completed laparoscopically, 5.47% experienced complications. Laparoscopic procedures were converted to open cholecystectomies in 8.08% of cases. Intraoperative cholangiograms were attempted in 46.5% of cases and completed in 80.59% of those attempts. There were no intraoperative deaths; 0.04% of the patients died within 30 days of surgery. CONCLUSIONS: The frequency of complications found in this study is comparable to the frequency of complications reported in recent large civilian studies and earlier, smaller studies. The authors present a system for classifying bile duct injuries, which is designed to standardize references to such injuries and allow for accurate comparison of bile duct injuries in the future.

Background: Anti-glycan antibody serologic markers may serve as a useful adjunct in the diagnosis/prognosis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis/systemic review aimed to evaluate the diagnostic value, as well as the association of anti-glycan biomarkers with IBD susceptible gene variants, disease complications, and the need for surgery in IBD. Methods: The diagnostic odds ratio (DOR), 95% confidence interval (CI), and sensitivity/specificity were used to compare the diagnostic value of individual and combinations of anti-glycan markers and their association with disease course (complication and/or need for surgery). Results: Fourteen studies were included in the systemic review and nine in the meta-analysis. Individually, anti-Saccharomyces cervisiae antibodies (ASCA) had the highest DOR for differentiating IBD from healthy (DOR 21.1; 1.8–247.3; two studies), and CD from UC (DOR 10.2; CI 7.7–13.7; seven studies). For combination of ≥2 markers, the DOR was 2.8 (CI 2.2–3.6; two studies) for CD-related surgery, higher than any individual marker, while the DOR for differentiating CD from UC was 10.2 (CI 5.6–18.5; three studies) and for complication was 2.8 (CI 2.2–3.7; two studies), similar to individual markers. Conclusions: ASCA had the highest diagnostic value among individual anti-glycan markers. While anti-chitobioside carbohydrate antibody (ACCA) had the highest association with complications, ASCA and ACCA associated equally with the need for surgery. Although in most individual studies the combination of ≥2 markers had a better diagnostic value as well as higher association with complications and need for surgery, we found the combination performing slightly better than any individual marker in our meta-analysis. (Inflamm Bowel Dis 2012)

Background: CpG island (CGI) hypermethylation at discrete loci is a prevalent cancer-promoting abnormality in sporadic colorectal carcinomas (S-CRCs). We investigated genome-wide CGI methylation in inflammatory bowel disease (IBD)-associated CRCs (IBD-CRCs). Methods: Methylation microarray analyses were conducted on seven IBD-CRCs, 17 S-CRCs, and eight normal control colonic tissues from patients without CRC or IBD. CGI methylator phenotype (CIMP), a surrogate marker for widespread cancer-specific CGI hypermethylation, was examined in 30 IBD-CRCs and 43 S-CRCs. Results: The genome-wide CGI methylation pattern of IBD-CRCs was CIMP status-dependent. Based on methylation array data profiling of all autosomal loci, CIMP+ IBD-CRCs grouped together with S-CRCs, while CIMP− IBD-CRCs grouped together with control tissues. CIMP− IBD-CRCs demonstrated less methylation than did age-matched CIMP− S-CRCs at autosomal CGIs (z-score −0.17 vs. 0.09, P = 3 × 10−3) and CRC-associated hypermethylation target CGIs (z-score −0.43 vs. 0.68, P = 1 × 10−4). Age-associated hypermethylation target CGIs were significantly overrepresented in CGIs that were hypermethylated in S-CRCs (P = 1 × 10−192), but not in CGIs that were hypermethylated in IBD-CRCs (P = 0.11). In contrast, KRAS mutation prevalence was similar between IBD-CRCs and S-CRCs. Notably, CIMP+ prevalence was significantly higher in older than in younger IBD-CRC cases (50.0 vs. 4.2, P = 0.02), but not in S-CRC cases (9.7 vs. 16.7, P = 0.92). Conclusions: Cancer-specific CGI hypermethylation and age-associated CGI hypermethylation are diminished in IBD-CRCs relative to S-CRCs, while the KRAS mutation rate is comparable between these cancers. CGI hypermethylation appears to play only a minor role in IBD-associated carcinogenesis. We speculate that aging, rather than inflammation per se, promotes CIMP+ CRCs in IBD patients. (Inflamm Bowel Dis 2011;)