Risk of Persistent Opioid Use following Major Surgery in Matched Samples of Patients with and without Cancer.

BACKGROUND: The opioid crisis has reached epidemic proportions, yet risk of persistent opioid use following curative intent surgery for cancer and factors influencing this risk are not well understood. METHODS: We used electronic health record data from 3,901 adult patients who received a prescription for an opioid analgesic related to hysterectomy or large bowel surgery from January 1, 2013, through June 30, 2018. Patients with and without a cancer diagnosis were matched on the basis of demographic, clinical, and procedural variables and compared for persistent opioid use. RESULTS: Cancer diagnosis was associated with greater risk for persistent opioid use after hysterectomy [18.9% vs. 9.6%; adjusted OR (aOR), 2.26; 95% confidence interval (CI), 1.38-3.69; P = 0.001], but not after large bowel surgery (28.3% vs. 24.1%; aOR 1.25; 95% CI, 0.97-1.59; P = 0.09). In the cancer hysterectomy cohort, persistent opioid use was associated with cancer stage (increased rates among those with stage III cancer compared with stage I) and use of neoadjuvant or adjuvant chemotherapy; however, these factors were not associated with persistent opioid use in the large bowel cohort. CONCLUSIONS: Patients with cancer may have an increased risk of persistent opioid use following hysterectomy. IMPACT: Risks and benefits of opioid analgesia for surgical pain among patients with cancer undergoing hysterectomy should be carefully considered.

An RCT of Fecal Immunochemical Test Colorectal Cancer Screening in Veterans Without Recent Primary Care.

INTRODUCTION: The use of screening can prevent death from colorectal cancer, yet people without regular healthcare visits may not realize the benefits of this preventive intervention. The objective of this study was to determine the effectiveness of a mailed screening invitation or mailed fecal immunochemical test in increasing colorectal cancer screening uptake in veterans without recent primary care encounters. STUDY DESIGN: Three-arm pragmatic randomized trial. SETTING/PARTICIPANTS: Participants were screening-eligible veterans aged 50-75 years, without a recent primary care visit who accessed medical services at the Corporal Michael J. Crescenz Veteran Affairs Medical Center between January 1, 2017, and July 31, 2017. All data were analyzed from March 1, 2018, to July 31, 2018. INTERVENTION: Participants were randomized to (1) usual opportunistic screening during a healthcare visit (n=260), (2) mailed invitation to screen and reminder phone calls (n=261), or (3) mailed fecal immunochemical test outreach plus reminder calls (n=61). MAIN OUTCOME MEASURES: The main outcome under investigation was the completion of colorectal cancer screening within 6 months after randomization. RESULTS: Of 782 participants in the trial, 53.9% were aged 60-75 years and 59.7% were African American. The screening rate was higher in the mailed fecal immunochemical test group (26.1%) compared with usual care (5.8%) (rate difference=20.3%, 95% CI=14.3%, 26.3%; RR=4.52, 95% CI=2.7, 7.7) or screening invitation (7.7%) (rate difference=18.4%, 95% CI=12.2%, 24.6%; RR=3.4, 95% CI=2.1, 5.4). Screening completion rates were similar between invitation and usual care (rate difference=1.9%, 95% CI= -2.4%, 6.2%; RR=1.3, 95% CI=0.7, 2.5). CONCLUSIONS: Mailed fecal immunochemical test screening promotes colorectal cancer screening participation among veterans without a recent primary care encounter. Despite the addition of reminder calls, an invitation letter was no more effective in screening participation than screening during outpatient appointments. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov NCT02584998.

The volume-outcome relationship in robotic protectectomy: does center volume matter? Results of a national cohort study.

BACKGROUND: Utilization of robotic proctectomy (RP) for rectal cancer has steadily increased since the inception of robotic surgery in 2002. Randomized control trials evaluating the safety of RP are in process to better understand the role of robotic assistance in proctectomy. This study aimed to characterize the trends in the use of RP for rectal cancer, and to compare oncologic outcomes with center-level RP volume. MATERIALS AND METHODS: 8107 patients with rectal adenocarcinoma who underwent RP were identified in the National Cancer Database (2010-2015). Logistic regression was used to evaluate associations between center-level volume and conversion to open proctectomy, margin status, lymph node yield, 30- and 90-day post-operative mortality, and overall survival. RESULTS: The utilization of RP increased from 2010 to 2015. On multivariate regression, lower center-level volume of RP was associated with significantly higher rates of conversion to open, positive margins, inadequate lymph node harvest (≥ 12), and lower overall survival. The present study was limited by its retrospective design and lack of information regarding disease-specific survival. CONCLUSIONS: This series suggests a volume-outcome relationship association; patients who have robot-assisted proctectomies performed at low-volume centers are more likely to have poorer overall survival, positive margins, inadequate lymph node harvest, and require conversion to open surgery. While these data demonstrate the increased adoption of robot-assisted proctectomy, an understanding of the appropriateness of this intervention is still lacking. As with any new intervention, further information from ongoing randomized controlled trials is needed to better clarify the role of RP in order to optimize patient outcomes.

Operative Management of Anastomotic Leaks after Colorectal Surgery.

Anastomotic leak is associated with increased morbidity and mortality after colorectal surgery. Although surgical techniques have improved over time, anastomotic leak is still a reality in colorectal surgery with rates ranging from as low as 1% for low-risk anastomoses, such as enteroenteric or ileocolic, to 19% for high-risk coloanal anastomoses. There are many varied risk factors for anastomotic leak. However, many of the risk factors have not been definitively proven in high-quality studies. Presumably, risk factors are cumulative and every effort should be made to optimize modifiable risk factors in the perioperative period. Treatment of anastomotic leak should start with the determination of patient stability followed by resuscitation and diagnostic imaging or operative exploration. Operative findings will dictate surgical approach with the goal of controlling sepsis and stabilizing the patient. If nonoperative treatment is undertaken, close patient monitoring is necessary to ensure control of sepsis and that intervention is undertaken if the clinical picture changes. Early intervention at each stage is key to decreasing the morbidity of anastomotic leak.

Predictors of Metastases in Rectal Neuroendocrine Tumors: Results of a National Cohort Study.

BACKGROUND: Rectal neuroendocrine tumors are often found incidentally. Local excision alone has been advocated for lesions ≤2 cm; however, the evidence base for this approach is limited. OBJECTIVE: Associations among tumor size, degree of differentiation, and presence of distant metastatic disease were examined. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted using a nationwide cohort. PATIENTS: A total of 4893 patients with rectal neuroendocrine tumors were identified in the National Cancer Database (2006-2015). MAIN OUTCOME MEASURES: Logistic regression analyses were used to evaluate associations among tumor size, degree of differentiation, and presence of regional and distant metastatic disease. Cut point analysis was performed to identify an optimal size threshold predictive of distant metastatic disease. RESULTS: Of patients included for analysis, 3880 (79.3%) had well-differentiated tumors, 540 (11.0%) had moderately differentiated tumors, and 473 (9.7%) had poorly differentiated tumors. On logistic regression, increasing size was associated with a higher likelihood of pathologically confirmed lymph node involvement (among patients undergoing proctectomy), and both size and degree of differentiation were independently associated with a higher likelihood of distant metastatic disease. The association between tumor size and distant metastatic disease was stronger for well-differentiated and moderately differentiated tumors (OR = 1.4; p < 0.001 for both) than for poorly differentiated tumors (OR = 1.1; p = 0.010). For well-differentiated tumors, the optimal cut point for the presence of distant metastatic disease was 1.15 cm (area under the curve = 0.88; 88% sensitive and 88% specific). Tumors ≥1.15 cm in diameter were associated with a substantially increased incidence of distant metastatic disease (72/449 (13.8%)). For moderately differentiated tumors, the optimal cut point was also 1.15 cm (area under the curve = 0.87, 100% sensitive and 75% specific). LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Tumor size and degree of differentiation are predictive of regional and distant metastatic disease in rectal neuroendocrine tumors. Patients with tumors >1.15 cm are at substantial risk of distant metastasis and should be staged and managed accordingly. See Video Abstract at http://links.lww.com/DCR/A778.

Disparities in resection of hepatic metastases in colon cancer.

BACKGROUND: Evidence suggests that resection of synchronous hepatic metastases (SHM) in stage IV colon cancer is safe and can improve survival in select patients. Little is known, however, about the use of hepatic resection in this setting on a population level. The aim of this study was to describe trends in resection rates of SHM in patients with stage IV colon cancer using a large national cohort database. METHODS: A retrospective cohort study was performed of stage IV colon cancer patients during 2000-2011 in Surveillance, Epidemiology and End Results (SEER) Medicare data who had diagnosis codes confirming SHM. Univariate and multivariate logistic regression were used to identify patient factors related to receipt of hepatic resection. RESULTS: There were 11,351 patients with colon cancer and SHM. Of these patients, 465 (4.1%) underwent surgical hepatic resection. The proportion increased steadily over time from 2000-2002 (3.5%) to 2009-2011 (5.1%) (P=0.03). Patients who were older with higher comorbidity burden were less likely to undergo hepatic resection. Additionally, the odds of hepatic resection were 30% lower for African-American patients than for white patients (OR 0.70, P=0.05). Odds of hepatic resection were 44% lower for patients from ZIP Codes with >20% poverty than for patients from areas with <5% poverty (OR 0.56, P<0.001). Interestingly, among patients who underwent no surgical treatment at all, only 25% saw a surgeon after diagnosis. This number increased over time from 21.6% in 2000 to 29.1% in 2011 (P<0.001). Similar disparities noted above were seen with surgical evaluation for hepatic resection. CONCLUSIONS: Despite evidence supporting the safety and efficacy of hepatic resection in the setting of SHM, few patients are seen by surgeons and go onto receive hepatic surgery. Additionally, access to hepatic resection is notably lower for African Americans and patients from areas with higher poverty rates.

Surgical Site Infection and Colorectal Surgical Procedures: A Prospective Analysis of Risk Factors.

BACKGROUND: Colorectal surgical procedures (CRS) are associated with the highest surgical site infection (SSI) rate among elective operations. A wide range of patient and surgical characteristics have been identified as risk factors for SSI. Most studies are limited by reliance on retrospective data or subset analysis of data that includes CRS. This study reflects analysis of SSI risk factors using prospectively collected data in an elective CRS population. PATIENTS AND METHODS: We analyzed data prospectively collected as part of a randomized, blinded trial of skin anti-sepsis in elective CRS to identify risk factors associated with SSI, including superficial or deep SSI or cellulitis within 30 days post-discharge. Photodocumentation, patient questionnaires, and blinded review by an attending surgeon were used to identify SSI. Multi-variable logistic regression was used to identify factors significantly associated with SSI and to calculate predicted risks of SSI. RESULTS: From 2011 to 2015, 787 patients undergoing clean-contaminated procedures by colorectal surgeons were analyzed as part of a randomized clinical trial. The overall SSI rate was 21.5%. Four variables-incision length, surgical indication, body mass index, and surgical approach-were significantly associated with SSI. Based on these four variables, the predicted risk of SSI ranges from <5% to >60%. CONCLUSION: This study represents the largest prospective investigation of SSI in elective CRS. There is a very wide range of SSI risk after CRS based on both modifiable and non-modifiable factors. Identification of those at the extreme ends of risk may help us both identify and mitigate contributors to infection.

A Nomogram to Predict Lymph Node Positivity Following Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer.

BACKGROUND: Patients with locally advanced rectal cancer typically receive neoadjuvant chemoradiation followed by total mesorectal excision. Other treatment approaches, including transanal techniques and close surveillance, are becoming increasingly common following positive responses to chemoradiation. Lack of pathologic lymph node staging is one major disadvantage of these novel strategies. OBJECTIVE: The purposes of this study were to determine clinicopathologic factors associated with positive lymph nodes following neoadjuvant chemoradiation for rectal cancer and to create a nomogram using these factors to predict rates of lymph node positivity. DESIGN: This is a retrospective cohort analysis. SETTINGS: This study used the National Cancer Database. PATIENTS: Patients aged 18 to 90 with clinical stage T3/T4, N0, M0 or Tany, N1-2, M0 adenocarcinoma of the rectum who underwent neoadjuvant chemoradiation before total mesorectal excision from 2010 to 2012 were identified. MAIN OUTCOME MEASURES: The primary outcome measure was lymph node positivity after neoadjuvant chemoradiation for locally advanced rectal cancer. Bivariate and multivariate analyses were used to determine the associations of clinicopathologic variables with lymph node positivity. RESULTS: Eight thousand nine hundred eighty-four patients were included. Young age, lower Charlson score, mucinous histology, poorly differentiated and undifferentiated tumors, the presence of lymphovascular invasion, elevated CEA level, and clinical lymph node positivity were significantly predictive of pathologic lymph node positivity following neoadjuvant chemoradiation. The predictive accuracy of the nomogram is 70.9%, with a c index of 0.71. There was minimal deviation between the predicted and observed outcomes. LIMITATIONS: This study is retrospective, and it cannot be determined when in the course of treatment the data were collected. CONCLUSIONS: We created a nomogram to predict lymph node positivity following neoadjuvant chemoradiation for locally advanced rectal cancer that can serve as a valuable complement to imaging to aid clinicians and patients in determining the best treatment strategy.

Trends in the Use of (18)F-Fluorodeoxyglucose PET Imaging in Surveillance of Non-Small-Cell Lung and Colorectal Cancer.

PURPOSE: Surveillance PET after curative-intent treatment of non-small-cell lung cancer (NSCLC) or colorectal cancer (CRC) is not clearly supported by available evidence or the Choosing Wisely campaign. However, the frequency of PET imaging during the surveillance period is relatively unknown. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, 65,748 patients aged 66 years or older who were diagnosed with stage I to IIIA NSCLC or stage I to III CRC from 2001 through 2009 and who underwent surgical resection were identified. Trends in "any PET" or "PET-only" use 6 to 18 months postoperatively were assessed. RESULTS: Any PET use more than doubled over the study period. Eleven percent of patients with NSCLC and 4% of those with CRC diagnosed in 2001 received any PET, compared with 25% of patients with NSCLC and 13% of those with CRC in 2009 (P < .001 for both). Higher stage disease was correlated with higher PET utilization and faster growth in use over the study period. PET-only use also increased over the study period, especially in higher stage disease. Fewer than 2% of patients diagnosed with stage IIIA NSCLC in 2001 received PET only, compared with 15% of patients diagnosed in 2009 (P = .014). Similarly, 1% of patients diagnosed with stage III CRC in 2001 received PET only, compared with 8% of patients diagnosed in 2009 (P < .001). CONCLUSIONS: PET utilization during the surveillance period increased between 2001 and 2009. Further research is needed to determine the factors driving use of surveillance PET and to examine relationships between PET and patient outcomes.

Trends in surveillance for resected colorectal cancer, 2001-2009.

BACKGROUND: Little is known about recent trends in surveillance among the more than 1 million US colorectal cancer (CRC) survivors. Moreover, for stage I disease, which accounts for more than 30% of survivors, the guidelines are limited, and the use of surveillance has not been well studied. Guidelines were changed in 2005 to include recommendations for computed tomography (CT) surveillance in select patients, but the impact of these changes has not been explored. METHODS: A retrospective analysis of patients who were identified in the Survival, Epidemiology, and End Results-Medicare database and underwent resection of stage I to III CRC between 2001 and 2009 was performed. The receipt of guideline-determined sufficient surveillance, including office visits, colonoscopy, carcinoembryonic antigen (CEA) testing, and CT imaging, in the 3 years after resection was evaluated. RESULTS: The study included 23,990 colon cancer patients and 5665 rectal cancer patients. Rates of office visits and colonoscopy were high and stable over the study period. Rates of CEA surveillance increased over the study period but remained low, even for stage III disease. Rates of CT imaging increased gradually during the study period, but the 2005 guideline change had no effect. Stage II patients, including high-risk patients, received surveillance at significantly lower rates than stage III patients despite similar recommendations. Conversely, up to 30% of stage I patients received nonrecommended CEA testing and CT imaging. CONCLUSIONS: There continues to be substantial underuse of surveillance for CRC survivors and particularly for stage II patients, who constitute almost 40% of survivors. The 2005 guideline change had a negligible impact on CT surveillance. Conversely, although guidelines are limited, many stage I patients are receiving intensive surveillance.

Surveillance after neoadjuvant therapy in advanced rectal cancer with complete clinical response can have comparable outcomes to total mesorectal excision.

PURPOSE: While the standard of care for patients with rectal cancer who sustain a complete clinical response (cCR) to chemoradiotherapy (CRT) remains proctectomy with total mesorectal excision, data suggests that non-operative management may be a safe alternative. The purpose of this study is to compare outcomes between patients treated with CRT that attained a cCR and opted for a vigilant surveillance to those of the patients who had a complete pathologic response (cPR) following proctectomy. METHOD: This is a retrospective review of patients treated for adenocarcinoma of the rectum who achieved either a cCR or a cPR following CRT. Patients with a cCR were enrolled in an active surveillance program which included regularly scheduled exams, proctoscopy, serum carcinoembryonic antigen (CEA), endorectal ultrasound, and cross-sectional imaging. Outcomes were compared to those patients who underwent proctectomy with a cPR. Our primary outcome measures were post-treatment complications, recurrence, and survival. RESULTS: We reviewed 18 patients who opted for surveillance after cCR and 30 patients who underwent proctectomy after a cPR. No non-operative patients had a documented treatment complication, while 17 patients with cPR suffered significant morbidity. There were two recurrences in the active surveillance group, one local and once distant, both treated by salvage resection with no associated mortality at 54 and 62 months. In the cPR group, one patient had a distant recurrence 24 months after surgery which was managed non-operatively. This patient died of unrelated causes 35 months after surgery. CONCLUSIONS: Active surveillance can be a safe option that avoids the morbidity associated with proctectomy and preserves oncologic outcomes.

Local excision for early stage rectal cancer in patients over age 65 years: 2000-2009.

BACKGROUND: Local excision of rectal cancer is an attractive option because it avoids the morbidity of radical resection. Concerns have arisen during the past decade, however, regarding substandard oncologic results. OBJECTIVE: Using the most recent Survey of Epidemiology and End Results-Medicare data, we examined the change in the use of local excision for rectal cancer from 2000 to 2009 and examined patient, surgeon, and hospital factors related to its use. DESIGN: This study is a retrospective cohort study. SETTINGS: This study was conducted at a tertiary care medical center using Survey of Epidemiology and End Results-Medicare data. PATIENTS: Patients with pathologic Tis, T1, or T2 rectal cancer who were >65 years of age and underwent primary radical resection or local excision between 2000 and 2009 were included in this study. MAIN OUTCOME MEASURES: The change in the use of local excision for rectal cancer from 2000 to 2009 was the main outcome measured. RESULTS: A total of 8966 patients were identified. The use of local excision decreased significantly between 2000 and 2009. Women and patients who were older and had more comorbidities were significantly more likely to undergo local excision. Having a colorectal surgeon perform the surgery increased the odds of local excision by 1.5 times (p < 0.001). Similar trends were seen in patients operated on at the National Cancer Institute (OR, 1.7; p <0.001) and teaching hospitals (OR, 1.2; p = 0.003). Younger surgeons were more likely to perform local excisions. For surgeons graduating in 1980-1989 or 1990 and after, the odds of local excision were 1.40 (p = 0.001) and 2.1 (p <0.001) compared with surgeons graduating before 1970. LIMITATIONS: The study was limited by the retrospective design, and the data were collected by multiple healthcare officials in their representative institutions. CONCLUSIONS: In patient >65 years of age, the odds of undergoing local excision for early stage rectal cancer decreased significantly between 2000 and 2009, coincident with evidence of oncologic inferiority. However, there was still significant variation in its use. More studies are needed to better understand these variations in an attempt to bring more uniformity to the use of local excision in early stage rectal cancer.

Impact of BMI on postoperative outcomes in patients undergoing proctectomy for rectal cancer: a national surgical quality improvement program analysis.

BACKGROUND: There is a mounting body of evidence that suggests worsened postoperative outcomes at the extremes of BMI, yet few studies investigate this relationship in patients undergoing proctectomy for rectal cancer. OBJECTIVE: We aimed to examine the relationship between BMI and short-term outcomes after proctectomy for cancer. DESIGN: This was a retrospective study comparing the outcomes of patients undergoing proctectomy for rectal cancer as they relate to BMI. SETTINGS: The American College of Surgeons-National Surgical Quality Improvement Program database was queried for this study. PATIENTS: Patients included were those who underwent proctectomy for rectal neoplasm between 2005 and 2011. MAIN OUTCOME MEASURES: Study end points included 30-day mortality and overall morbidity, including the receipt of blood transfusion, venous thromboembolic disease, wound dehiscence, renal failure, reintubation, cardiac complications, readmission, reoperation, and infectious complications (surgical site infection, intra-abdominal abscess, pneumonia, and urinary tract infection). Univariate logistic regression was used to analyze differences among patients of varying BMI ranges (kg/m; ≤20, 20-24, 25-29, 30-34, and ≥35). When significant differences were found, multivariable logistic regression, adjusting for preoperative demographic and clinical variables, was performed. RESULTS: A total of 11,995 patients were analyzed in this study. The incidences of overall morbidity, wound infection, urinary tract infection, venous thromboembolic event, and sepsis were highest in those patients with a BMI of ≥35 kg/m (OR, 1.63, 3.42, 1.47, 1.64, and 1.50). Wound dehiscence was also significantly more common in heavier patients. Patients with a BMI <20 kg/m had significantly increased rates of mortality (OR, 1.72) and sepsis (OR, 1.30). LIMITATIONS: This study was limited by its retrospective design. Furthermore, it only includes patients from the American College of Surgeons-National Surgical Quality Improvement Program database, limiting its generalizability to nonparticipating hospitals. CONCLUSIONS: Obese and underweight patients undergoing proctectomy for neoplasm are at a higher risk for postoperative complications and death.

Biologic therapy and surgery for crohn disease.

In 1998, infliximab, an antitumor necrosis factor alpha (anti-TNF-α) antibody, was approved for use in the treatment of Crohn disease (CD). Since then, other biologic therapies, including adalimumab and certolizumab pegol (newer anti-TNF-α antibodies), and natalizumab, an antibody against alpha-4 integrin, have also been approved. Here, we review the published studies that examine the relationship between pre- and postoperative biologic therapy and postoperative complications in patients with CD. This body of literature is composed of numerous small, retrospective, heterogeneous studies that demonstrate conflicting and varied results. Overall, the receipt of biologic therapy in the pre- or postoperative period does not appear to significantly increase the risk of postoperative complications. It is, however, difficult to draw any firm conclusions based on the existing level of data. In the future, larger prospective studies are needed to better elucidate the true risks, if any, that the use of biologic therapy poses to patients with CD requiring operation.

Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction.

OBJECTIVE: Microvascular malperfusion after myocardial infarction leads to infarct expansion, adverse remodeling, and functional impairment. Native reparative mechanisms exist but are inadequate to vascularize ischemic myocardium. We hypothesized that a 3-dimensional human fibroblast culture (3DFC) functions as a sustained source of angiogenic cytokines, thereby augmenting native angiogenesis and limiting adverse effects of myocardial ischemia. METHODS: Lewis rats underwent ligation of the left anterior descending coronary artery to induce heart failure; experimental animals received a 3DFC scaffold to the ischemic region. Border-zone tissue was analyzed for the presence of human fibroblast surface protein, vascular endothelial growth factor, and hepatocyte growth factor. Cardiac function was assessed with echocardiography and pressure-volume conductance. Hearts underwent immunohistochemical analysis of angiogenesis by co-localization of platelet endothelial cell adhesion molecule and alpha smooth muscle actin and by digital analysis of ventricular geometry. Microvascular angiography was performed with fluorescein-labeled lectin to assess perfusion. RESULTS: Immunoblotting confirmed the presence of human fibroblast surface protein in rats receiving 3DFC, indicating survival of transplanted cells. Increased expression of vascular endothelial growth factor and hepatocyte growth factor in experimental rats confirmed elution by the 3DFC. Microvasculature expressing platelet endothelial cell adhesion molecule/alpha smooth muscle actin was increased in infarct and border-zone regions of rats receiving 3DFC. Microvascular perfusion was also improved in infarct and border-zone regions in these rats. Rats receiving 3DFC had increased wall thickness, smaller infarct area, and smaller infarct fraction. Echocardiography and pressure-volume measurements showed that cardiac function was preserved in these rats. CONCLUSIONS: Application of a bioengineered 3DFC augments native angiogenesis through delivery of angiogenic cytokines to ischemic myocardium. This yields improved microvascular perfusion, limits infarct progression and adverse remodeling, and improves ventricular function.

Acuity and survival in colon cancer surgery.

PURPOSE: Reports indicate that up to 40% of patients with colon cancer require nonelective resection, which has been shown to portend worse long-term prognosis compared with elective resection. We used a national database to identify specific preoperative, perioperative, and postoperative factors mediating the acuity-survival relationship in an effort to identify areas of medical practice that can serve as targets for improvement in cancer care. METHODS: We used the Surveillance, Epidemiology and End Results-Medicare-linked database to identify non-health maintenance organization-enrolled people aged 66 years and older who were diagnosed with stages I to III colon cancer between 1996 and 2003 (N = 30,685). Using stepwise, multivariate Cox regression, disease-specific survival was compared in patients undergoing elective vs nonelective resection. Adjustment for preoperative, perioperative, and postoperative variables was performed to identify factors contributing to the acuity-survival relationship. RESULTS: Five-year disease-specific survival was 86.3% after elective and 75.4% after nonelective colon resection (hazard ratio, 1.92; P < .001). A significant proportion of this disparity was the result of differences in stage and patient characteristics, particularly age and comorbidity burden, at the time of resection. Differences in adequacy of nodal assessment and the use of surveillance colonoscopy and adjuvant chemotherapy, however, also contributed to the disparity. After adjustment for these factors, the hazard ratio for nonelective resection was 1.30 (P < .001). CONCLUSION: Nonelective resection of colon cancer is associated with poor long-term prognosis compared with elective resection. Disease-specific survival among patients undergoing nonelective surgery may be improved by addressing insufficient nodal assessment, inadequate follow-up care, and underutilization of appropriate, adjuvant chemotherapy.

Gender influences treatment and survival in colorectal cancer surgery.

BACKGROUND: It has been observed that survival after colorectal cancer resection is longer in women than men. The majority of these studies are in non-U.S. populations and few use appropriate multivariate adjustment. We used the Surveillance, Epidemiology and End Results- Medicare database to examine disease-specific survival in women and men undergoing colorectal cancer resection in the United States, adjusting for patient, cancer, and hospital characteristics in an effort to identify disparities, not only in survival, but also in patterns of presentation, surgical resection, and treatment. METHODS: With use of the Surveillance, Epidemiology and End Results-Medicare-linked database, we performed a retrospective cohort study of 30,975 patients with colon cancer and 8,350 patients with rectal cancer who underwent surgical resection from 1996 to 2003. Kaplan-Meier curves, the log-rank test, and Cox regression compared survival between genders. Multivariate adjustment was performed by use of patient demographics; cancer variables including stage, medical treatment, and adequacy of nodal harvest; and hospital characteristics. RESULTS: In both cancers, women presented at an older age and more emergently than men. They also underwent less aggressive medical therapy for advanced disease; in particular, in the octogenarian population. In unadjusted analysis, there was no gender difference in survival (colon hazard ratio, 0.98; P = 0.74; rectal hazard ratio, 0.95; P =0.10). After full adjustment, however, women had significantly longer survival, in particular, after rectal resection (colon hazard ratio, 0.91; P< 0.001; rectal hazard ratio, 0.82; P< 0.001). CONCLUSIONS: Women in this cohort have longer adjusted survival compared with men; however, they present more emergently and at an older age, and they receive less aggressive medical treatment. These are noticeable disparities that could serve as targets for continued improvement.

Time-of-day effects on surgical outcomes in the private sector: a retrospective cohort study.

BACKGROUND: Surgical care is delivered around the clock. Elective cases within the Veterans Affairs health system starting after 4 pm appear to have an elevated risk of morbidity, but not mortality, compared with earlier cases. The relationship between operation start time and patient outcomes is not described in private-sector patients or for emergency cases. STUDY DESIGN: We performed a retrospective cohort study of 56,920 general and vascular surgical procedures performed from October 2001 through September 2004, and entered into the National Surgical Quality Improvement Program database. Operation start time was the independent variable of interest. Random effects, hierarchical logistic regression models adjusted for patient, operative, and facility characteristics. Two independent models determined associations between start time and morbidity or mortality. Subset analysis was performed for emergency and nonemergency cases. RESULTS: After adjustment for patient and procedure characteristics, mortality had a moderately strong association with start time, but only for nonemergency cases starting 9:30 pm to 7:30 am (odds ratio = 1.752; p = 0.028; reference 7:30 am to 9:30 am). As for morbidity, after adjustment, operations starting 9:30 am to 1:30 pm and 5:30 pm to 9:30 pm were associated with a weakly elevated risk of morbidity, but those starting 9:30 pm to 7:30 am demonstrated a strong effect on morbidity (odds ratio = 1.32; p < 0.0001). Subgroup analysis showed this effect was largely a result of elevated risk of morbidity in emergency cases from this overnight time period (odds ratio = 1.48; p = 0.001). CONCLUSIONS: Surgical start times are associated with risk-adjusted patient outcomes. In terms of facility operations management and resource allocation, consideration should be given to the capacity to accommodate cases with differences in risk during different time periods.

HER-2/neu overexpression as a predictor for the transition from in situ to invasive breast cancer.

The clinical implications of HER-2/neu (HER2) expression in ductal carcinoma in situ (DCIS) lesions have yet to be clearly elucidated; this despite the more frequent expression of HER2 in high-grade DCIS lesions compared with invasive cancers. We hypothesized that HER2 overexpression in DCIS is associated with more rapid progression to invasive disease. Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 was done on DCIS specimens. Univariate analysis and a multivariate logistic regression were done to determine whether estrogen receptor, progesterone receptor, or HER2 status, comedo necrosis, nuclear grade, lesion size, or patient age predicted the presence of associated invasive disease in patients with DCIS. Invasive foci were found in association with HER2 overexpressing DCIS at a higher frequency than with DCIS that did not overexpress HER2. Although high nuclear grade, large lesion size, and HER2 overexpression were all associated with the presence of invasive disease on univariate analysis, HER2 was the only significant predictor for the presence of invasive disease after multivariate adjustment (odds ratio, 6.4; P = 0.01). These data indicate that HER2 overexpression in DCIS lesions predicts the presence of invasive foci in patients with DCIS and suggest that targeting of HER2 in an early disease setting may forestall or prevent disease progression.