Nearly a Third of High-Grade Dysplasia and Colorectal Cancer Is Undetected in Patients with Inflammatory Bowel Disease.

BACKGROUND: It is unclear whether intensive surveillance protocols have resulted in a decreased incidence of colorectal cancer (CRC) in inflammatory bowel disease (IBD). AIMS: To determine the prevalence and characteristics of IBD associated high-grade dysplasia (HGD) or CRC that was undetected on prior colonoscopy. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Long-term quality of life and risk factors for recurrence after laparoscopic repair of paraesophageal hernia.

IMPORTANCE: Laparoscopic repair of paraesophageal hernia (PEH) has been shown to result in excellent relief of symptoms and improved quality of life (QOL) despite a relatively high radiographically identified recurrence rate. OBJECTIVE: To assess potential risk factors for recurrence and long-term change in QOL after laparoscopic repair of PEH. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective study of 111 patients who underwent elective laparoscopic repair of type III PEH with biological mesh buttressed over a primary cruroplasty from April 3, 2009, through July 31, 2014, at the Department of Surgery, Johns Hopkins University of Medicine. We administered a modified version of a validated gastroesophageal reflux disease-specific QOL tool to patients before and at 2, 12, and 36 months after the procedure. Higher QOL scores represent greater severity of symptoms. An upper gastrointestinal tract barium-contrast radiographic examination was performed at 1 year to assess for recurrence. Demographic factors, comorbidities, and preoperative radiographic findings were analyzed as possible indicators for recurrence using logistic regression. MAIN OUTCOMES AND MEASURES: Quality of life, measured by the gastroesophageal reflux disease-specific QOL tool, and recurrence, defined as a PEH of greater than 2 cm. RESULTS: Median patient age was 61 years, 63.1% of patients were women, and 81.1% of patients were white. Four patients required reoperation, of which only 1 was for symptomatic recurrent PEH. The mean follow-up time for the 36-month QOL assessment was 43.5 months. The overall preoperative and 2-, 12-, and 36-month QOL scores were 28.50, 10.18, 9.74, and 10.58, respectively (P < .001). Recurrences were found in 19 of the 70 patients (27%) who completed the 1-year radiographic examination. Compared with baseline, all individual symptoms improved significantly except for early satiety (mean [SD] score, 3.18 [1.88] at baseline vs 2.07 [1.70] at the 36-month follow-up; P = .07), nausea (1.69 [1.63] vs 0.77 [1.25]; P = .08), pain with swallowing (1.06 [1.50] vs 0.53 [0.90]; P = .73), and bloating/gas (3.28 [1.71] vs 2.23 [1.72]; P = .05) at the 36-month QOL assessment. Although not statistically significant, preoperative hernias containing most of the stomach were more likely to recur after repair when compared with those involving gastric cardia and fundus (odds ratio, 3.74 [95% CI, 0.93-15.14]; P = .06). CONCLUSIONS AND RELEVANCE: Overall, laparoscopic repair of PEH with biological mesh results in excellent long-term QOL. The cause of recurrence is likely multifactorial and individualized to each patient. Further evaluation of novel techniques and unidentified patient factors is needed.

Perioperative glucocorticoid prescribing habits in patients with inflammatory bowel disease: a call for standardization.

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.

Comparative assessment of physical and cognitive ergonomics associated with robotic and traditional laparoscopic surgeries.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Defining recurrence after paraesophageal hernia repair: correlating symptoms and radiographic findings.

BACKGROUND: Laparoscopic repair of paraesophageal hernia (PEH) has been shown to result in excellent relief of symptoms and improved quality of life (QOL) despite a high radiographically identified recurrence rate. Because there is no uniform definition of PEH recurrence, it is difficult to compare studies reporting on this. This study attempts to introduce consistency to the definition of PEH recurrence based on correlation of symptoms and radiographic findings. METHODS: This is an analysis of data derived from an ongoing prospective study. From April 2009 to December 2012, we enrolled 101 patients who underwent elective laparoscopic PEH repair with bioprosthesis buttressed over a primary cruroplasty. A validated gastroesophageal reflux disease-specific QOL tool was administered to patients before, and at 2 and 12 months postoperatively. Upper gastrointestinal barium contrast examination (UGI) was performed at 1 year. RESULTS: Of 101 patients, 13 were not available for follow-up, 58 reached the 1-year milestone for interval UGI, and 1 patient required reoperation for symptomatic recurrent PEH. There was no relationship between total QOL score and radiographic recurrent hernia (RRH); however, significant deterioration in many symptoms was seen in RRH > 2 cm. Based on these findings, we defined recurrence as RRH > 2 cm and calculated our recurrence rate as 28% (n = 16). CONCLUSION: Our analysis of symptom scores after laparoscopic PEH repair suggests that significant worsening occurs with RRH > 2 cm. Given that there is no consistent description of recurrent PEH, we suggest this as a possible standardized definition. Overall, patients with recurrent PEHs continue to experience excellent QOL and rarely require reoperation.

Serum anti-glycan antibody biomarkers for inflammatory bowel disease diagnosis and progression: a systematic review and meta-analysis.

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.

Staple versus fibrin glue fixation in laparoscopic total extraperitoneal repair of inguinal hernia: a systematic review and meta-analysis.

BACKGROUND: Fixation of mesh is typically performed to minimize risk of recurrence in laparoscopic inguinal hernia repair. Mesh fixation with staples has been implicated as a cause of chronic inguinal pain. Our study aim is to compare mesh fixation using a fibrin sealant versus staple fixation in laparoscopic inguinal hernia and compare outcomes for hernia recurrence and chronic inguinal pain. METHODS AND PROCEDURES: PubMed was searched through December 2010 by use of specific search terms. Inclusion criteria were laparoscopic total extraperitoneal repair inguinal hernia repair, and comparison of both mesh fibrin glue fixation and mesh staple fixation. Primary outcomes were inguinal hernia recurrence and chronic inguinal pain. Secondary outcomes were operative time, seroma formation, hospital stay, and time to return to normal activity. Pooled odds ratios (OR) were calculated assuming random-effects models. RESULTS: Four studies were included in the review. A total of 662 repairs were included, of which 394 were mesh fixed by staples or tacks, versus 268 with mesh fixed by fibrin glue. There was no difference in inguinal hernia recurrence with fixation of mesh by staples/tacks versus fibrin glue [OR 2.13; 95% confidence interval (CI) 0.60-7.63]. Chronic inguinal pain (at 3 months) incidence was significantly higher with staple/tack fixation (OR 3.25; 95% CI 1.62-6.49). There was no significant difference in operative time, seroma formation, hospital stay, or time to return to normal activities. CONCLUSIONS: The meta-analysis does not show an advantage of staple fixation of mesh over fibrin glue fixation in laparoscopic total extraperitoneal inguinal hernia repair. Because fibrin glue mesh fixation with laparoscopic inguinal hernia repair achieves similar hernia recurrence rates compared with staple/tack fixation, but decreased incidence of chronic inguinal pain, it may be the preferred technique.

Unique patterns of CpG island methylation in inflammatory bowel disease-associated colorectal cancers.

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.

Novel candidate colorectal cancer biomarkers identified by methylation microarray-based scanning.

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 (P<0.05 by receiver operator characteristic curve analysis); methylation of visual system homeobox 2 (VSX2) achieved the highest discriminative accuracy (83.3% sensitivity and 92.3% specificity, P<1×10(-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 (P<0.05). CRC-NCs were significantly distinguished from control NCs by methylation of ALX3 (P<1×10(-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.

Gastric wall healing after NOTES procedures: closure with endoscopic clips provides superior histological outcome compared with threaded tags closure.

BACKGROUND: Closure of the transgastric access to the peritoneal cavity is a critical step in natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To perform a direct comparison of the histological healing post clips and threaded tags (T-tags) closure after transgastric NOTES procedures. DESIGN AND INTERVENTION: Twelve survival porcine experiments. After standardized endoscopic gastric wall puncture, balloon-dilation, and transgastric peritoneoscopy, closure of the gastric wall was performed with either clips or T-tags. Necropsy at 14 days was performed for histological evaluation of 2-mm interval transversal cross sections of the gastrotomy site. MAIN OUTCOME MEASUREMENTS: Histological healing of the gastric wall opening. RESULTS: Endoscopic closure of the gastrotomy was successfully achieved in all 12 animals, followed by an uneventful 2-week clinical follow-up. Transmural healing was seen in 3 (75%) animals after clip closure compared with only 1 (12.5%) in the group with T-tag closure (P = .06). Gastric wall muscular bridging was observed in 4 (100%) animals with clip closure compared with only 1 (12.5%) in the group with T-tag closure (P = .01). LIMITATIONS: Animal model with short-term follow-up. CONCLUSIONS: Endoscopic clip closure results in a layer-to-layer transmural healing of the gastric wall. In contrast, T-tag gastric wall plication impairs gastric layer bridging. These findings might guide the future design of new endoscopic devices and techniques for gastrotomy closure after NOTES procedures.

A 2-microm continuous-wave laser system for safe and high-precision dissection during NOTES procedures.

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.

Infection during natural orifice transluminal endoscopic surgery: a randomized, controlled study in a live porcine model.

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 = <.0002). 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.

Omentoplasty for gastrotomy closure after natural orifice transluminal endoscopic surgery procedures (with video).

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.

Hydrogen leak test is minimally invasive and highly specific for assessment of the integrity of the luminal closure after natural orifice transluminal endoscopic surgery procedures (with video).

BACKGROUND: Leak-resistant closure of transluminal access is a major challenge facing natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: To evaluate a hydrogen (H(2))-based leak test for assessment of transluminal-access closure integrity after NOTES procedures. SETTING: Nine acute porcine experiments. DESIGN AND INTERVENTION: 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. MAIN OUTCOME MEASUREMENT: Intraperitoneal H(2) concentration after gastric insufflation with H(2). RESULTS: 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. LIMITATIONS: Nonsurvival animal experiments. CONCLUSIONS: 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.

Transgastric ventral hernia repair: a controlled study in a live porcine model (with videos).

BACKGROUND: Ventral hernia repair is currently performed via open surgery or laparoscopic approach. OBJECTIVE: To develop an alternative ventral hernia repair technique. SETTING: Acute and survival experiments on twelve 50-kg pigs. DESIGN AND INTERVENTIONS: An endoscope was introduced transgastrically into the peritoneal cavity. An abdominal wall hernia was created through a 5-mm skin incision followed by a 5-cm-long incision of the abdominal wall muscles and aponeurosis. A hernia repair technique was developed in 3 acute experiments. Then animals were randomized into 2 groups. In the experimental group (5 animals) Gore-Tex mesh was transgastrically attached to the abdominal wall, repairing the previously created abdominal wall hernia. In the control group (4 animals), the hernia was not repaired. In both groups, the endoscope was then withdrawn into the stomach, and the gastric wall incision was closed with T-bars. The animals survived for 2 weeks and were then euthanized. MAIN OUTCOME MEASUREMENT: The presence of ventral hernia on necropsy. RESULTS: In the control group, the ventral hernia was present on necropsy in all animals. In the experimental group, the ventral hernia was easily repaired, with no evidence of hernia on necropsy. In the first animal in the experimental group, necropsy revealed infected mesh. After this discovery, we used sterilized cover for mesh delivery and did not find any signs of infection in 4 subsequent study animals. LIMITATION: The study was performed in a porcine model. CONCLUSIONS: Transgastric ventral hernia repair is feasible, technically easy, and effective. It can become a less invasive alternative to the currently used laparoscopic and surgical ventral hernia repair.

A diagnostic predictor model for indeterminate or suspicious thyroid FNA samples.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p < 0.001). For larger nodules, the risk increased 39% per cm increase (p < 0.001). Patients with FNA cytology suspicious for papillary thyroid carcinoma had the greatest risk of malignancy (p < 0.001). CONCLUSIONS: A predictor model was created using the variables age, nodule size, and FNA cytology to predict thyroid malignancy.

Identification of genes differentially expressed in benign versus malignant thyroid tumors.

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.

Air and fluid leak tests after NOTES procedures: a pilot study in a live porcine model (with videos).

BACKGROUND: Transluminal access site closure remains a major challenge in natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE: Our purpose was to develop in vivo leak tests for evaluation of the integrity of transgastric access closure. SETTINGS: Survival experiments on 12 50-kg pigs. DESIGN AND INTERVENTIONS: 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. MAIN OUTCOME MEASUREMENTS: (1) Leak-proof closure of the gastric wall incision. (2) Gastric incision healing 1 week after the procedure. RESULTS: 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. LIMITATIONS: Leak tests were only evaluated on an animal model. CONCLUSIONS: 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.

Transcontinental telesurgical nephrectomy using the da Vinci robot in a porcine model.

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.