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.

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.

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.

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.