Ian M. Paquette

Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer.

Importance Hereditary cancer syndromes infer high cancer risks and require intensive cancer surveillance, yet the prevalence and spectrum of these conditions among unselected patients with early-onset colorectal cancer (CRC) is largely undetermined. Objective To determine the frequency and spectrum of cancer susceptibility gene mutations among patients with early-onset CRC. Design, Setting, and Participants Overall, 450 patients diagnosed with colorectal cancer younger than 50 years were prospectively accrued from 51 hospitals into the Ohio Colorectal Cancer Prevention Initiative from January 1, 2013, to June 20, 2016. Mismatch repair (MMR) deficiency was determined by microsatellite instability and/or immunohistochemistry. Germline DNA was tested for mutations in 25 cancer susceptibility genes using next-generation sequencing. Main Outcomes and Measures Mutation prevalence and spectrum in patients with early-onset CRC was determined. Clinical characteristics were assessed by mutation status. Results In total 450 patients younger than 50 years were included in the study, and 75 gene mutations were found in 72 patients (16%). Forty-eight patients (10.7%) had MMR-deficient tumors, and 40 patients (83.3%) had at least 1 gene mutation: 37 had Lynch syndrome (13, MLH1 [including one with constitutional MLH1 methylation]; 16, MSH2; 1, MSH2/monoallelic MUTYH; 2, MSH6; 5, PMS2); 1 patient had the APC c.3920T>A, p.I1307K mutation and a PMS2 variant; 9 patients (18.8%) had double somatic MMR mutations (including 2 with germline biallelic MUTYH mutations); and 1 patient had somatic MLH1 methylation. Four hundred two patients (89.3%) had MMR-proficient tumors, and 32 patients (8%) had at least 1 gene mutation: 9 had mutations in high-penetrance CRC genes (5, APC; 1, APC/PMS2; 2, biallelic MUTYH; 1, SMAD4); 13 patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC (3, ATM; 1, ATM/CHEK2; 2, BRCA1; 4, BRCA2; 1, CDKN2A; 2, PALB2); 10 patients had mutations in low-penetrance CRC genes (3, APC c.3920T>A, p.I1307K; 7, monoallelic MUTYH). Importantly, 24 of 72 patients (33.3%) who were mutation positive did not meet established genetic testing criteria for the gene(s) in which they had a mutation. Conclusions and Relevance Of 450 patients with early-onset CRC, 72 (16%) had gene mutations. Given the high frequency and wide spectrum of mutations, genetic counseling and testing with a multigene panel could be considered for all patients with early-onset CRC.

Risk factors and consequences of anastomotic leak after colectomy: a national analysis.

BACKGROUND: Previous research has identified a number of patient and operative factors associated with anastomotic leak after colectomy; however, a study that examines these factors on a national level with direct coding for anastomotic leak is lacking. OBJECTIVE: The purpose of this work was to identify risk factors associated with anastomotic leak on a national level and quantify the additional morbidity and mortality experienced by these patients. DESIGN: We performed a retrospective analysis of patients who underwent segmental colectomy with anastomosis from the 2012 American College of Surgeons National Surgical Quality Improvement Program colectomy procedure-targeted database. Anastomotic leak was defined as minor leak requiring percutaneous intervention or major leak requiring laparotomy. Multivariate logistic regression was used to determine predictors of anastomotic leak and its impact on postoperative outcomes. SETTINGS: This study was conducted at a tertiary university department. PATIENTS: This study includes 13,684 patients who underwent segmental colectomy with anastomosis at American College of Surgeons National Surgical Quality Improvement Program–affiliated hospitals in 2012. MAIN OUTCOME MEASURES: The primary outcome studied was anastomotic leak. RESULTS: The overall leak rate was 3.8%. Male sex, steroid use, smoking, open approach, operative time, and preoperative chemotherapy were associated with increased anastomotic leaks and diverting ileostomy with decreased incidence of leaks on multivariate analysis. Increased length of stay (13 vs 5 days; p < 0.001) and increased 30-day mortality (6.8% vs 1.6%; p < 0.001) were also seen in patients who experienced leaks. These patients also experienced increased readmission rates (43.5% vs 8.3%; p < 0.001) and were 37 times more likely to require reoperation as a complication of their primary procedure (p < 0.001). LIMITATIONS: The main limitations of this study include its retrospective nature and the limited 30-day outcomes recorded in the American College of Surgeons National Surgical Quality Improvement Program database. CONCLUSIONS: This study identified patient and operative risk factors for anastomotic leak on a national scale. It also demonstrates that these patients have increased morbidity and 30-day mortality rates, experience multiple readmissions to the hospital, and have a higher likelihood of requiring further operative intervention.

Readmission for dehydration or renal failure after ileostomy creation.

BACKGROUND: Ileostomy creation is a commonly performed operation in colorectal surgery; however, many patients develop complications such as dehydration postoperatively. Dehydration is often severe enough to warrant hospital readmission and may result in renal failure. The true incidence of this complication has not been well described. OBJECTIVE: The aim of this study was to identify the rate of hospital readmission secondary to dehydration or renal failure within 30 days of ileostomy creation. DESIGN: Retrospective review of all patients undergoing ileostomy creation from 2007 to 2011 in a single colorectal practice of 4 surgeons was performed. Charts were reviewed to identify patients readmitted for dehydration or renal failure within 30 days of operation. Data were then analyzed to identify predictors of readmission, dehydration, and renal failure. Subset analysis compared patients readmitted with simple dehydration versus patients with renal failure. PATIENTS: Two hundred one patients undergoing colorectal operations that included ileostomy creation within a 4-year period at a single institution for a variety of indications were included. MAIN OUTCOME MEASURES: The primary outcome measured was readmission for dehydration or renal failure. RESULTS: We observed a 17% 30-day readmission rate for dehydration or renal failure following ileostomy creation. Age greater than 50 was identified as an independent predictor of readmission with renal failure, whereas IPAA was predictive of readmission for simple dehydration, but not renal failure. Patients admitted with renal failure had significantly longer hospital stays and median hospital charges after readmission in comparison with patients admitted with simple dehydration. LIMITATIONS: This study was limited by its retrospective nature and its limited sample size. CONCLUSION: Hospital readmission due to dehydration or renal failure following ileostomy creation is common, with age >50 being the strongest predictor for renal failure. Appropriate strategies to decrease dehydration and renal failure following ileostomy creation need to be investigated.

The American Society of Colon and Rectal Surgeons' Clinical Practice Guideline for the Treatment of Fecal Incontinence.

623 Diseases of the Colon & ReCtum Volume 58: 7 (2015) the american society of Colon and Rectal surgeons is dedicated to assuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. the Clinical Practice Guidelines Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. this Committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus. this is accompanied by developing Clinical Practice Guidelines based on the best available evidence. these guidelines are inclusive and not prescriptive. their purpose is to provide information based on which decisions can be made, rather than to dictate a specific form of treatment. these guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. it should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. the ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient.

Patient and hospital factors associated with use of sphincter-sparing surgery for rectal cancer.

PURPOSE: Sphincter-sparing surgery for rectal cancer is associated with higher patient satisfaction, equivalent oncologic outcomes, and less morbidity than abdominoperineal resection. No national studies have explored trends in the use of sphincter-preserving rectal resection, while accounting for both hospital and patient factors. METHODS: This is a retrospective cohort study of 47,713 patients from the Nationwide Inpatient Sample who underwent surgery for rectal cancer from 1988 to 2006. Univariate analysis was used to identify patient and hospital factors associated with sphincter preservation. Logistic regression was performed to control for confounding variables. Trends in use of sphincter-sparing surgery over time were examined to identify hospital factors associated with higher rates of adoption. RESULTS: Patient demographics associated with sphincter preservation in multivariate analysis were age <60, female gender, and white race. Among hospital factors associated with sphincter preservation, the most important predictors were high procedural volume (odds ratio 1.55; 95% CI 1.33–1.79; P < .001), and urban location (odds ratio 1.26; 95% CI 1.33–1.40; P < .001). Although sphincter preservation increased over time in the entire cohort (35.4% in 1988 vs 60.5% in 2006), high-volume hospitals had significantly higher rates of sphincter preservation compared with the lowest-volume hospitals. CONCLUSIONS: Although rates of adoption of sphincter-sparing surgery were similar across hospital volume strata, overall rates of sphincter preservation were consistently higher in high-volume and urban hospitals, and among patients who are female, white, and younger. Further research is needed to determine whether these differences reflect disparities in quality of surgical care, or differences in referral patterns or case mix.

Perforated appendicitis among rural and urban patients: implications of access to care.

Objective:To determine whether rural patients are more likely to present with perforated appendicitis compared with urban patients. Background:Appendiceal perforation has been associated with increased morbidity, length of hospital stay, and overall health care costs. Recent arguments suggest that high rates of appendiceal rupture may be unrelated to the quality of hospital care, and rather associated with inadequate access to surgical care. Methods:We performed a retrospective cohort study of 122,990 patients with acute appendicitis from the Nationwide Inpatient Sample from 2003 to 2004. International Classification of Diseases diagnosis 9 (ICD-9) codes were used to determine appendiceal perforation. Urban influence codes from the US Department of Agriculture were used to determine rural versus urban status. Univariate and multivariate analyses were used to determine patient and hospital factors associated with perforation. Results:Overall, 32.07% of patients presented with perforation. Rural patients were more likely than urban patients to present with perforation (35.76% vs. 31.48%). Factors associated with perforation in multivariate analysis were age more than 40 years, male gender, transfer from another facility, black race, poorest 25th percentile, Charlson score of 3 or higher, and rural residence. Thirty percent of rural patients were treated in urban hospitals. Rural patients treated at urban hospitals were more likely to present with perforation compared with rural patients treated at rural hospitals (OR = 1.23). Conclusions:Patients from rural areas have higher rates of perforation with acute appendicitis than urban patients. This difference persists when accounting for other factors associated with perforation. These differences in perforation rates suggest disparities in access to timely surgical care.

Neighborhood level effects of socioeconomic status on liver transplant selection and recipient survival.

BACKGROUND & AIMS Previous studies have reported that patients of higher socioeconomic status (SES) have increased access to liver transplantation and reduced waitlist mortality than patients of lower SES. However, little is known about the association between SES and outcomes after liver transplantation. METHODS By using a link between the University HealthSystem Consortium and the Scientific Registry of Transplant Recipients databases, we identified 12,445 patients who underwent liver transplantation from 2007 through 2011. We used a proportional hazards model to assess the effect of SES on patient survival, controlling for characteristics of recipients, donors, geography, and center. RESULTS Compared with liver recipients in the lowest SES quintile, those in the highest quintile were more likely to be male, Caucasian, have private insurance, and undergo transplantation when they had lower Model for End-Stage Liver Disease scores. In proportional hazards model analysis, liver recipients of the lowest SES were at an increased risk for death within a median of 2 years after transplantation (hazard ratio, 1.17; 95% confidence interval, 1.02-1.35). CONCLUSIONS Patients of lower SES appear to face barriers to liver transplantation, but perioperative outcomes (length of stay, in-hospital mortality, or 30-day readmission) do not differ significantly from those of patients of higher SES. However, fewer patients of low SES survive for 2 years after transplantation, independent of features of the recipient, donor, surgery center, or location.

Outpatient Cholecystectomy at Hospitals Versus Freestanding Ambulatory Surgical Centers

BACKGROUND Because of safety concerns, some payers do not reimburse for laparoscopic cholecystectomy performed in freestanding ambulatory surgical centers (ASCs). This policy has been controversial because of increasing competition between ASCs and hospitals for low risk surgical patients. STUDY DESIGN We performed a retrospective cohort study of patients undergoing elective outpatient laparoscopic cholecystectomy in the state of Florida in 2002 and 2003 (n=40,040), using the Agency for Healthcare Research and Quality State Ambulatory Surgery Database. Patients treated in hospitals and ASCs were compared with respect to patient characteristics, charges, outcomes, and processes of care. RESULTS For both hospital-based and ASC-based laparoscopic cholecystectomy patients, greater than 99% were successfully discharged home, and there were no reported deaths. Compared with those treated in hospitals, patients in ASCs had a higher rate of intraoperative cholangiogram (39% versus 36%, p=0.008). There was no difference in the proportion of procedures converted to open cholecystectomy. ASC-based patients were slightly younger (mean age 45 years versus 49 years, p < 0.001), were less often diagnosed with acute cholecystitis (4.8% versus 8.3%, p < 0.001), and had fewer comorbidities on average than hospital-based patients, but both cohorts had few comorbidities overall (99% had Charlson scores of 0 or 1). ASC patients were more likely to be Caucasian (86% versus 75%, p < 0.001) and were more likely to have private insurance (92% versus 67%, p < 0.001). For patients who had ambulatory laparoscopic cholecystectomy as the only procedure, the median charges were

Utilization of laparoscopic and open inguinal hernia repair: a population-based analysis.

6,028 at ASCs, compared with

Is liver transplantation safe and effective in elderly (≥70 years) recipients? A case-controlled analysis

10,876 at hospitals. CONCLUSIONS In a population of slightly younger, healthier patients, laparoscopic cholecystectomy in freestanding ASCs appears to be performed safely and with substantially lower charges than in hospitals.