M Health Fairview: An aligned academic health system.

BACKGROUND: The aim of this article is to familiarize the reader with one system's approach to creating an aligned academic health system that facilitates delivery of academic health care in community hospitals. METHODS: A wide variety of approaches to this challenge include viewing the community facilities as strictly feeders to the academic centers with no shared governance, to viewing them as branding opportunities with aligned governance, to a more integrated model such as ours, and to creating exclusive centers of excellence in the community facilities by consolidating services initially dispersed across competing hospitals into one center. RESULTS: We leveraged service lines and domains to standardize care across all hospital settings which facilitated delivery of complex tertiary care in community hospitals, thus increasing capacity in the Academic Medical Center for complex quarternary care. CONCLUSION: Through creating a more completely integrated, patient centric health system that leverages the community partners we minimized the need for people to travel from their community hospitals to the Academic Medical Center while still ensuring they received the expertise of a leading academic institution.

The Efficacy of a Novel Surgical Device in Preventing Intraoperative Wound Contamination in an In Vivo Porcine Model.

BACKGROUND: Surgical site infections (SSIs) remain a morbid and costly complication in abdominal surgery. Topical antibiotic delivery via intraoperative irrigation and barrier wound protection are strategies for preventing SSI. We tested the safety and efficacy of a novel wound protector device with an integrated fluid irrigation platform in a porcine model. METHODS: A simulated colorectal resection model was designed and performed on adult female pigs with a standardized concentration of 109 colony-forming units (CFU) of Escherichia coli administered to the wound site in 10 mL of normal saline (n = 7). The device was tested intraoperatively with and without irrigation with gentamicin-containing irrigant solution. Swab and tissue samples were obtained in addition to peripheral blood samples. Quantitative culture analysis was performed in addition to histological and immunohistochemical analysis and gentamicin concentration measurements. RESULTS: There were no adverse events observed in the animals. Tissue protected by the device yielded exponentially lower levels of E. coli growth compared to exposed tissue, with a mean 1 × 102 CFU/swab. Use of the device, both with and without irrigation, was associated with an exponential reduction in quantitative bacterial load compared to the control wounds with no device, with limited growth after wound closure in the pigs receiving irrigation. Histology and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining analysis revealed no significant damage to tissue. Serum gentamicin levels remained below the clinical threshold and decreased over time. CONCLUSIONS: This in vivo study suggests safety and efficacy of a novel device for the prevention of intraoperative wound contamination.

The Prognostic Significance of Pretreatment Hematologic Parameters in Patients Undergoing Resection for Colorectal Cancer.

OBJECTIVES: The prognostic value of several hematologic parameters, including platelet, lymphocyte, and neutrophil counts, has been studied in a variety of solid tumors. In this study, we examined the significance of inflammatory markers and their prognostic implications in patients with colorectal cancer (CRC). MATERIALS AND METHODS: Patients with stage I-III CRC who underwent surgical resection at the Stanford Cancer Institute between 2005 and 2009 were included. Patients were excluded if they did not have preoperative complete blood counts performed within 1 month of surgical resection, underwent preoperative chemotherapy or radiation, had metastatic disease at diagnosis, or had another previous malignancy. We included 129 eligible patients with available preoperative complete blood counts in the final analysis. RESULTS: A preoperative neutrophil-to-lymphocyte ratio of>3.3 was significantly associated with worse disease-free (DFS) and overall survival (OS) (P=0.009, 0.003), as was a preoperative lymphocyte-to-monocyte ratio of ≤2.6 (P=0.01, 0.002). Preoperative lymphopenia (P=0.002) was associated with worse OS but not DFS (P=0.09). In addition, preoperative thrombocytosis was associated with worse DFS (P=0.006) and OS (P=0.010). Preoperative leukocytosis was associated with worse OS (P=0.048) but not DFS (P=0.49). Preoperative hemoglobin was neither associated with OS (P=0.24) or DFS (P=0.15). CONCLUSIONS: Pretreatment lymphopenia, thrombocytosis, a decreased lymphocyte-to-monocyte ratio, and an elevated neutrophil-to-lymphocyte ratio independently predict for worse OS in patients with CRC.

A Multidisciplinary Initiative to Increase Inpatient Discharges Before Noon.

OBJECTIVE: The aim of this study is to evaluate the effect of 2 hospital-wide interventions on achieving a discharge-before-noon rate of 40%. BACKGROUND: A multidisciplinary team led by administrative and physician leadership developed a plan to diminish capacity constraints by minimizing late afternoon hospital discharges using 2 patient flow management techniques. METHODS: The study was a preintervention/postintervention retrospective analysis observing all inpatients discharged across 19 inpatient units in a 484-bed, academic teaching hospital measuring calendar month discharge-before-noon percentage, patient satisfaction, and readmission rates. Patient satisfaction and readmission rates were used as baseline metrics. RESULTS: The discharge-before-noon percentage increased from 14% in the 11-month preintervention period to an average of 24% over the 11-month postintervention period, whereas patient satisfaction scores and readmission rates remained stable. CONCLUSIONS: Implementation of the 2 interventions successfully increased the percentage of discharges before noon yet did not achieve the goal of 40%. Patient satisfaction and readmission rates were not negatively impacted by the program.

Prevalence of Anal Dysplasia in Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Although the prevalence of anal dysplasia is higher in some immunosuppressed populations, the prevalence in patients with inflammatory bowel disease (IBD) is unknown. We examined the prevalence of abnormal anal cytology among IBD patients, and its relation to the human papilloma virus (HPV). METHODS: Adults with IBD and age-matched healthy controls (HC) were recruited. IBD patients were categorized as nonimmunosuppressed (IBD-N) or immunosuppressed (IBD-I). Anal Papanicolaou tests were performed for HPV testing and classification by a cytopathologist as follows: negative, atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, cancer, or unsatisfactory. RESULTS: A total of 270 subjects (100 IBD-I, 94 IBD-N, and 76 HC) were recruited. ASC-US were detected in 19 subjects, with a trend toward a higher prevalence among IBD subjects compared with HC (8.8% vs 2.6%; P = .10). The prevalence did not differ with respect to immunosuppression. Crohn's disease (CD) subjects had a higher prevalence of ASC-US compared with others with IBD (P = .02). Among those with CD, female sex and disease duration longer than 10 years were risk factors. There were no cases of low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, or anal cancer in the cohort. HPV was present in 5.3% and 1.5% of subjects with and without ASC-US, respectively (P = .26). CONCLUSIONS: Although there was a trend toward abnormal anal Papanicolaou tests in IBD subjects compared with HC, there was no difference based on immunosuppression. The presence of HPV did not correlate with abnormal anal cytology. Risk factors associated with this increased trend include female CD subjects and those with a longer duration of CD. ClinicalTrials.gov number: NCT01860963; https://clinicaltrials.gov/ct2/show/NCT01860963.

Screening for Anal Cancer in Women.

OBJECTIVE: The incidence of anal cancer is higher in women than men in the general population and has been increasing for several decades. Similar to cervical cancer, most anal cancers are associated with human papillomavirus (HPV), and it is believed that anal cancers are preceded by anal high-grade squamous intraepithelial lesions (HSIL). Our goals were to summarize the literature on anal cancer, HSIL, and HPV infection in women and to provide screening recommendations in women. METHODS: A group of experts convened by the American Society for Colposcopy and Cervical Pathology and the International Anal Neoplasia Society reviewed the literature on anal HPV infection, anal SIL, and anal cancer in women. RESULTS: Anal HPV infection is common in women but is relatively transient in most. The risk of anal HSIL and cancer varies considerably by risk group, with human immunodeficiency virus-infected women and those with a history of lower genital tract neoplasia at highest risk compared with the general population. CONCLUSIONS: While there are no data yet to demonstrate that identification and treatment of anal HSIL leads to reduced risk of anal cancer, women in groups at the highest risk should be queried for anal cancer symptoms and required to have digital anorectal examinations to detect anal cancers. Human immunodeficiency virus-infected women and women with lower genital tract neoplasia may be considered for screening with anal cytology with triage to treatment if HSIL is diagnosed. Healthy women with no known risk factors or anal cancer symptoms do not need to be routinely screened for anal cancer or anal HSIL.

Equivocal effect of intraoperative fluorescence angiography on colorectal anastomotic leaks.

BACKGROUND: Intraoperative fluorescence angiography is beneficial in several surgical settings to assess tissue perfusion. It is also used to assess bowel perfusion, but its role in improving outcomes in colorectal surgery has not been studied. OBJECTIVE: The purpose of this work was to determine whether intraoperative angiography decreases colorectal anastomotic leaks. DESIGN: This was a case-matched retrospective study in which patients were matched 1:1 with respect to sex, age, level of anastomosis, presence of a diverting loop ileostomy, and preoperative pelvic radiation therapy. SETTINGS: The study was conducted at an academic medical center. PATIENTS: Patients who underwent colectomy or proctectomy with primary anastomoses were included. INTERVENTIONS: The intraoperative use of fluorescence angiography to assess perfusion of the colon for anastomosis was studied. MAIN OUTCOME MEASURES: Anastomotic leak within 60 days and whether angiography changed surgical management were the main outcomes measured. RESULTS: Case matching produced 173 pairs. The groups were also comparable with respect to BMI, smoking status, diabetes mellitus, surgical indications, and type of resection. In patients who had intraoperative angiography, 7.5% developed anastomotic leak, whereas 6.4% of those without angiography did (p value not significant). Univariate analysis revealed that preoperative pelvic radiation, more distal anastomosis, surgeon, and diverting loop ileostomy were positively associated with anastomotic leak. Multivariate analysis demonstrated that level of anastomosis and surgeon were associated with leaks. Poor perfusion of the proximal colon seen on angiography led to additional colon resection before anastomosis in 5% of patients who underwent intraoperative angiography. LIMITATIONS: The retrospective study design with the use of historical control subjects, selection bias, and small sample size were limitations to this study. CONCLUSIONS: Intraoperative fluorescence angiography to assess the perfusion of the colon conduit for anastomosis was not associated with colorectal anastomotic leak. Perfusion is but one of multiple factors contributing to anastomotic leaks. Additional studies are necessary to determine whether this technology is beneficial for colorectal surgery.

Progression of anal high-grade squamous intraepithelial lesions to invasive anal cancer among HIV-infected men who have sex with men.

The incidence of anal cancer is elevated in human immunodeficiency virus (HIV)-infected men-who-have-sex-with-men (MSM) compared to the general population. Anal high-grade squamous intraepithelial lesions (HSIL) are common in HIV-infected MSM and the presumed precursors to anal squamous cell cancer; however, direct progression of HSIL to anal cancer has not been previously demonstrated. The medical records were reviewed of 138 HIV-infected MSM followed up at the University of California, San Francisco, who developed anal canal or perianal squamous cancer between 1997 and 2011. Men were followed up regularly with digital anorectal examination (DARE), high-resolution anoscopy (HRA) and HRA-guided biopsy. Although treatment for HSIL and follow-up were recommended, not all were treated and some were lost to follow-up. Prevalent cancer was found in 66 men. Seventy-two HIV-infected MSM developed anal cancer while under observation. In 27 men, anal cancer developed at a previously biopsied site of HSIL. An additional 45 men were not analyzed in this analysis due to inadequate documentation of HSIL in relation to cancer location. Of the 27 men with documented progression to cancer at the site of biopsy-proven HSIL, 20 men progressed from prevalent HSIL identified when first examined and seven men from incident HSIL. Prevalent HSIL progressed to cancer over an average of 57 months compared to 64 months for incident HSIL. Most men were asymptomatic, and cancers were detected by DARE. Anal HSIL has clear potential to progress to anal cancer in HIV-infected MSM. Early diagnosis is facilitated by careful follow-up. Carefully controlled studies evaluating efficacy of screening for and treatment of HSIL to prevent anal cancer are needed.

Do hospitals that serve a high percentage of Medicaid patients perform well on evidence-based guidelines for colon cancer care?

BACKGROUND: Previous work suggests hospitals serving high percentages of patients with Medicaid are associated with worse colon cancer survival. It is unclear if practice patterns in these settings explain differential outcomes. HYPOTHESIS: High Medicaid hospitals (HMH) have lower compliance with evidence-based care processes (examining 12 or more lymph nodes (LN) during surgical staging and providing appropriate chemo-therapy). METHODS: Retrospective analysis of stage I-III colon cancers from California Cancer Registry (1996-2006) linked to discharge abstracts and hospital profiles predicted hospital compliance with guidelines and trends in compliance over time. RESULTS: Cases (N=60,000) in 439 hospitals analyzed. High Medicaid hospital settings had lower odds of compliance with the 12 LN exam (OR(HMH)0.91, CI(HMH)[0.85, 0.98]) and with the delivery of appropriate chemotherapy (OR(HMH)0.76, CI(HMH)[0.67, 0.86]). CONCLUSIONS: High Medicaid hospital status is associated with poor performance on evidence-based colon cancer care. Policies to improve the quality of colon cancer care should target these settings.

Predictors of postoperative urinary retention after colorectal surgery.

BACKGROUND: National quality initiatives have mandated the earlier removal of urinary catheters after surgery to decrease urinary tract infection rates. A potential unintended consequence is an increased postoperative urinary retention rate. OBJECTIVE: The aim of this study was to determine the incidence and risk factors for postoperative urinary retention after colorectal surgery. DESIGN: This was a prospective observational study. SETTINGS: A colorectal unit within a single institution was the setting for this study. PATIENTS: Adults undergoing elective colorectal operations were included. INTERVENTIONS: Urinary catheters were removed on postoperative day 1 for patients undergoing abdominal operations, and on day 3 for patients undergoing pelvic operations. Postvoid residual and retention volumes were measured. MAIN OUTCOME MEASURES: The primary outcomes measured were urinary retention and urinary tract infection. RESULTS: The overall urinary retention rate was 22.4% (22.8% in the abdominal group, 21.9% in the pelvic group) and was associated with longer operative time and increased perioperative fluid administration. Mean operative time for those with retention was 2.8 hours and, for those without retention, the mean operative time 2.2 hours (abdominal group 2 hours vs 1.4 hours, pelvic group 3.9 hours vs 3.1 hours, p ≤ 0.02). Patients with retention received a mean of 2.7L during the operation, whereas patients without retention received 1.8L (abdominal group 1.9L vs 1.4L, pelvic group 3.6L vs 2.2L, p < 0.01). In the abdominal group, patients with and without retention also received different fluid volumes on postoperative days 1 (2.2L vs 1.7L, p = 0.004) and 2 (1.6L vs 1L, p = 0.05). Laparoscopic abdominal group had a 40% retention rate in comparison with 12% in the open abdominal group (p = 0.004). Age, sex, preoperative radiation therapy, preoperative prostatism, preoperative diagnosis, and level of anastomosis were not associated with retention. The urinary tract infection rate was 4.9%. LIMITATION: The lack of documentation of preoperative urinary function was a limitation of this study. CONCLUSIONS: The practice of earlier urinary catheter removal must be balanced with operative time and fluid volume to avoid high urinary retention rates. Also important is increased vigilance for the early detection of retention.

p16 is superior to ProEx C in identifying high-grade squamous intraepithelial lesions (HSIL) of the anal canal.

Although the incidence of human papillomavirus (HPV)-associated anal neoplasia is increasing, interobserver and intraobserver reproducibility in the grading of biopsy specimens from this area remains unacceptably low. Attempts to produce a more reproducible grading scheme have led to the use of biomarkers for the detection of high-risk HPV (HR-HPV). We evaluated the performance of standard morphology and biomarkers p16, ProEx C, and Ki-67 in a set of 75 lesions [17 nondysplastic lesions, 23 low-grade squamous intraepithelial lesions (LSIL)/condyloma, 20 high-grade squamous intraepithelial lesions (HSIL), 15 invasive squamous cell carcinomas] from the anal and perianal region in 65 patients and correlated these findings with HPV subtype on the basis of a type-specific multiplex real-time polymerase chain reaction assay designed to detect HR-HPV. A subset of cases with amplifiable HPV DNA was also sequenced. HSIL was typically flat (15/20), and only a minority (4/20) had koilocytes. In contrast, only 1 LSIL was flat (1/23), and the remainder were exophytic. The majority of LSIL had areas of koilocytic change (20/23). HR-HPV DNA was detected in the majority (89%) of invasive carcinomas and HSIL biopsies, 86% and 97% of which were accurately labeled by strong and diffuse block-positive p16 and ProEx C, respectively. LSIL cases, however, only infrequently harbored HR-HPV (13%); most harbored low-risk HPV (LR-HPV) types 6 and 11. Within the LSIL group, p16 outperformed ProEx C, resulting in fewer false-positive cases (5% vs. 75%). Ki-67 was also increased in HR-HPV-positive lesions, although biopsies with increased inflammation and reactive changes also showed higher Ki-67 indices. These data suggest that strong and diffuse block-positive nuclear and cytoplasmic labeling with p16 is a highly specific biomarker for the presence of HR-HPV in anal biopsies and that this finding correlates with high-grade lesions.

Orthovoltage intraoperative radiotherapy for locally advanced and recurrent colorectal cancer.

BACKGROUND: Locally advanced and recurrent colorectal cancers pose a significant therapeutic challenge. Orthovoltage intraoperative radiotherapy provides one potential means of improving disease control at the time of surgery. OBJECTIVE: This study sought to analyze outcomes and identify prognostic factors of patients treated with orthovoltage intraoperative radiotherapy for locally advanced or recurrent colorectal cancer. DESIGN AND SETTING: This study is a retrospective chart review conducted at a tertiary medical center. PATIENTS: Between January 1990 and July 2009, 55 patients underwent intraoperative radiotherapy to a total of 61 sites for locally advanced (n = 14) or recurrent (n = 41) cancers of colon (n = 18) or rectum/rectosigmoid junction (n = 37). INTERVENTIONS: Median dose was 12 Gy (range, 7.5-20 Gy). Among locally advanced rectal/rectosigmoid cases, surgery included abdominoperineal resection (n = 3) or low anterior resection (n = 9). Seven treated sites had gross residual (R2) disease, 28 had pathologic or clinical microscopic residual disease (R1), and 15 were complete resections (R0). Treated sites included sacrum (n = 22), anterior pelvis/pelvic sidewall (19), sacrum and sidewall (n = 1), aortic bifurcation (n = 2), vaginal cuff (n = 2), psoas (n = 3), perivesicular region (n = 2), and other (n = 10). MAIN OUTCOMES MEASURES: Outcomes measures included in-field local control, locoregional control, overall survival, and grade ≥3 toxicity. RESULTS: At a median follow-up of 27 months (range, 4-237) among living patients, 2-year Kaplan-Meier estimates of in-field local control, locoregional control, and overall survival were 69%, 51%, and 59%. Margin status predicted for improved locoregional control (p = 0.01) and overall survival (p = 0.01). Seventeen patients (31%) developed a grade 3 to 5 toxicity following surgery with intraoperative radiotherapy. LIMITATIONS: This study was limited by its retrospective nature and relatively small sample size. CONCLUSIONS: Local control with intraoperative radiotherapy for locally advanced and recurrent colorectal cancers is good despite the high risk of residual disease. Among carefully selected patients, multimodality regimens including intraoperative radiotherapy may permit long-term survival.

Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features.

Recent literature suggests an increasing incidence of colorectal carcinoma in young patients. We performed a histologic, molecular, and immunophenotypic analysis of patients with sporadic early-onset (≤40 years of age) colorectal carcinoma seen at our institution from the years 2000-2010 and compared these tumors to a cohort of consecutively resected colorectal carcinomas seen in patients >40 years of age. A total of 1160 primary colorectal adenocarcinomas were surgically resected for the years 2000 through 2010. Of these, 75 (6%) were diagnoses in patients ≤40 years of age of which 13 (17%) demonstrated abnormalities in DNA mismatch repair, 4 (5%) were in patients with known germline genetic disorders (two patients with familial adenomatous polyposis, one patient with juvenile polyposis, and one patient with Li-Fraumeni syndrome), and three patients (4%) had long-standing chronic inflammatory bowel disease. The sporadic early-onset colorectal carcinoma group comprised a total of 55 patients (55/1160, 5%) and were compared with a control group comprising 73 consecutively resected colorectal carcinomas with proficient DNA mismatch repair in patients >40 years of age. For the early-onset colorectal carcinoma group, most cases (33/55, 60%) were diagnosed between the age of 35 and 40 years of age. Compared with the control group, the early-onset colorectal carcinoma group was significantly different with respect to tumor location (P<0.007) with 80% (44/55 cases) identified in either the sigmoid colon (24/55, 44%) or rectum (20/55, 36%). Morphologically, early-onset colorectal carcinomas more frequently displayed adverse histologic features compared with the control colorectal carcinoma group such as signet ring cell differentiation (7/55, 13% vs 1/73, 1%, P=0.021), perineural invasion (16/55, 29% vs 8/73, 11%, P=0.009) and venous invasion (12/55, 22% vs 4/73, 6%, P=0.006). A precursor adenomatous lesion was less frequently identified in the early-onset colorectal carcinoma group compared with the control group (19/55, 35% vs 39/73, 53%, P=0.034). Of the early-onset colorectal carcinomas, only 2/45 cases (4%) demonstrated KRAS mutations compared with 11/73 (15%) of the control group colorectal adenocarcinomas harboring KRAS mutations, although this difference did not reach statistical significance (P=0.13). BRAF V600E mutations were not identified in the early-onset colorectal carcinoma group. No difference was identified between the two groups with regard to tumor stage, tumor size, number of lymph node metastases, lymphatic invasion, tumor budding, mucinous histology, or tumor-infiltrating lymphocytes. Both groups had similar recurrence-free (P=0.28) and overall survival (P=0.73). However, patients in the early-onset colorectal carcinoma group more frequently either presented with or developed metastatic disease during their disease course compared with the control colorectal carcinoma group (25/55, 45% vs 18/73, 25%, P=0.014). In addition, 8/55 patients (15%) in the early-onset colorectal carcinoma group developed local recurrence of their tumor while no patients in the control colorectal carcinoma group developed local recurrence (P<0.001), likely due to the increased incidence of rectal carcinoma in the patients with early-onset colorectal carcinoma. Our study demonstrates that colorectal carcinoma is not infrequently diagnosed in patients ≤40 years of age and is not frequently the result of underlying Lynch syndrome or associated with other cancer-predisposing genetic conditions or chronic inflammatory conditions. These tumors have a striking predilection for the distal colon, particularly the sigmoid colon and rectum and are much more likely to demonstrate adverse histologic factors, including signet ring cell differentiation, venous invasion, and perineural invasion.

Intensity-modulated radiation therapy versus conventional radiation therapy for squamous cell carcinoma of the anal canal.

BACKGROUND: The purpose of this study was to compare outcomes in patients with anal canal squamous cell carcinoma (SCCA) who were treated with definitive chemoradiotherapy by either intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT). METHODS: Forty-six patients who received definitive chemoradiotherapy from January 1993 to August 2009 were included. Forty-five patients received 5-fluorouracil with mitomycin C (n = 39) or cisplatin (n = 6). Seventeen (37%) were treated with CRT and 29 (63%) with IMRT. The median dose was 54 Gy in both groups. Median follow-up was 26 months (CRT) and 32 months (IMRT). T3-T4 stage (P = .18) and lymph node-positive disease (P = .6) were similar between groups. RESULTS: The CRT group required longer treatment duration (57 days vs 40 days, P < .0001), more treatment breaks (88% vs 34.5%, P = .001), and longer breaks (12 days vs 1.5 days, P < .0001) than patients treated with IMRT. Eleven (65%) patients in the CRT group experienced grade >2 nonhematologic toxicity compared with 6 (21%) patients in the IMRT group (P = .003). The 3-year overall survival (OS), locoregional control (LRC), and progression-free survival were 87.8%, 91.9%, and 84.2%, respectively, for the IMRT groups and 51.8%, 56.7%, and 56.7%, respectively, for the CRT group (all P < .01). On multivariate analysis, T stage, use of IMRT, and treatment duration were associated with OS, and T stage and use of IMRT were associated with LRC. CONCLUSIONS: The use of IMRT was associated with less toxicity, reduced need for treatment breaks, and excellent LRC and OS compared with CRT in patients with SCCA of the anal canal.