Development of a Predictive Nomogram for Circumferential Resection Margin in Rectal Cancer Surgery.

INTRODUCTION: Circumferential resection margin (CRM) is a key quality metric and predictor of oncologic outcomes and overall survival following surgery for rectal cancer. We aimed to develop a nomogram to identify patients at risk for a positive CRM in the preoperative setting. METHODS: We performed a retrospective evaluation of the National Cancer Database from 2010 to 2014 for patients with clinical stage I-III rectal cancer who underwent total mesorectal excision. Patients were excluded for emergency operation, resection for cancer recurrence, palliative resection, transanal resection, and missing CRM status. The primary outcome was positive CRM. Secondary outcomes included overall survival. RESULTS: There were 28,790 patients included. 2245 (7.8%) had a positive CRM. Higher tumor grade, lack of neoadjuvant chemotherapy, mucinous/signet tumor histology, open approach, abdominoperineal resection, higher T stage, lymphovascular invasion, and perineural invasion were all significantly associated with positive CRM (P < 0.05) and were included in the nomogram. The C-statistic was 0.703, suggesting a good predictive model. CONCLUSIONS: Positive CRM is associated with specific patient demographics and tumor characteristics. These factors can be used along with preoperative MRI to predict CRM positivity in the preoperative period and plan accordingly.

Prophylactic defunctioning stomas improve clinical outcomes of anastomotic leak following rectal cancer resections: An analysis of the US Rectal Cancer Consortium.

PURPOSE: Anastomotic leak (AL) is a complication of low anterior resection (LAR) that results in substantial morbidity. There is immense interest in evaluating immediate postoperative and long-term oncologic outcomes in patients who undergo diverting loop ileostomies (DLI). The purpose of this study is to understand the relationship between fecal diversion, AL, and oncologic outcomes. METHODS: This is a retrospective multicenter cohort study using patient data obtained from the US Rectal Cancer Consortium database compiled from six academic institutions. The study population included patients with rectal adenocarcinoma undergoing LAR. The primary outcome was the incidence of AL among patients who did or did not receive DLI during LAR. Secondary outcomes included risk factors for AL, receipt of adjuvant therapy, 3-year overall survival, and 3-year recurrence. RESULTS: Of 815 patients, 38 (4.7%) suffered AL after LAR. Patients with AL were more likely to be male, have unintentional preoperative weight loss, and are less likely to undergo DLI. On multivariable analysis, DLI remained protective against AL (p < 0.001). Diverted patients were less likely to undergo future surgical procedures including additional ostomy creation, completion proctectomy, or pelvic washout for AL. Subgroup analysis of 456 patients with locally advanced disease showed that DLI was correlated with increased receipt of adjuvant therapy for patients with and without AL on univariate analysis (SHR:1.59; [95% CI 1.19-2.14]; p = 0.002), but significance was not met in multivariate models. CONCLUSION: Lack of DLI and preoperative weight loss was associated with anastomotic leak. Fecal diversion may improve the timely initiation of adjuvant oncologic therapy. The long-term outcomes following routine diverting stomas warrant further study.

Opioid Utilization in Outpatient Anorectal Surgery: An Opportunity for Improvement.

INTRODUCTION: The opioid epidemic has resulted in close examination of postsurgical prescribing patterns. Little is known about postoperative opioid use in outpatient anorectal procedures. This study evaluated patient opioid use and created prescribing recommendations for these procedures. METHODS: One hundred and four patients undergoing outpatient anorectal procedures from January to May 2018 were surveyed on opioid consumption, surgical experience, and pain satisfaction. Patients were grouped into three tiers based on opioid usage. Multivariable models were used to determine factors associated with poor pain control. RESULTS: Patient satisfaction with pain control was 85.6%. Twenty five percent of patients reported leftover medication and 9.6% of patients requested opioid refills. Opioid prescribing recommendations were generated for each tier using 50th percentile with interquartile ranges. On multivariable modeling, the high-tier group was associated with poorer pain control. CONCLUSIONS: We created opioid quantity prescribing guidelines for common outpatient anorectal procedures. A multimodal approach to pain control utilizing nonopioids may reduce healthcare utilization.

Is newer always better?: comparing cost and short-term outcomes between laparoscopic and robotic right hemicolectomy.

BACKGROUND: Enthusiasm is high for expansion of robotic assisted surgery into right hemicolectomy. But data on outcomes and cost is lacking. Our objective was to determine the association between surgical approach and cost for minimally invasive right hemicolectomy. We hypothesized that a robot approach would have increased costs (both economic and opportunity) while achieving similar short-term outcomes. METHODS: We performed a retrospective cohort analysis with a simulation of operating room utilization at a quaternary care, academic institution. We enrolled patients undergoing minimally invasive right hemicolectomy from November 2017 to August 2019. Patients were categorized by the intended approach- laparoscopic or robotic. The primary outcome was the technical variable direct cost. Secondary outcomes included total cost, supply cost, operating room utilization, operative time, conversion, length of stay and 30-day post-operative outcomes. RESULTS: 79 patients were included in the study. A robotic approach was used in 22% of the cohort. The groups differed significantly only in etiology of surgery. Robotic surgery was associated with a 1.5 times increase in the technical variable direct cost (p < 0.001), increased supply cost (2.6 times; p < 0.001) and increased total cost (1.3 times; p < 0.001). Significant differences were observed in median room time (Robotic: 285 min vs. Laparoscopic: 170 min; p < 0.001) and procedure time (Robotic: 203 min vs. Laparoscopic: 118 min; p < 0.001). There were no differences observed in post-operative outcomes including length of stay or readmission. In a simulation of OR utilization, 45 laparoscopic right hemicolectomies could be performed in an OR in a month compared to 31 robotic cases. CONCLUSIONS: Robotic right hemicolectomy was associated with increased costs with no improvement in post-operative outcomes. In a simulation of operating room efficiency, a robotic approach was associated with 14 fewer cases per month. Practitioners and administrators should be aware of the increased cost of a robotic approach.

Benchmarking patient satisfaction scores in a colorectal patient population.

BACKGROUND: Healthcare reimbursement is rapidly moving away from a fee-for-service model toward value-based purchasing. An integral component of this new focus on quality is patient-centered outcomes. One metric used to define patient satisfaction is the Press Ganey Patient Satisfaction Survey. Data are lacking to accurately benchmark these scores based on diagnosis. We sought to identify if different colorectal disease processes affected a patient's perception of their healthcare experience. METHODS: Adult colorectal patients seen between July 2015 and September 2016 in a tertiary hospital colorectal clinic were mailed a Press Ganey survey. Patients were stratified based on diagnosis: neoplasia, IBD, anorectal and benign colorectal disease. Survey scores were compared across the groups with adjustment for confounding variables. RESULTS: 312 patients responded and formed the cohort. The mean age was 61 (range 18-93) and 56% were women. The cohort breakdown was 38% neoplasia, 32% anorectal, 21% benign, and 9% IBD. In a multivariable model, there was a difference in PG scores by diagnosis; patients with neoplasia had higher Overall scores (ß 10.2; Std Error 4.0; p = 0.01), Care Provider scores (ß 8.5; Std Error 4.2; p = 0.04), Nurse Assistant scores (ß 15.0; Std Error 5.7; p = 0.01), and Personal Issues scores (ß 11.8; Std Error 5/0; p = 0.01). CONCLUSION: Press Ganey scores were found to vary significantly. Patients with a neoplasia diagnosis reported higher overall satisfaction, Care Provider, Nurse Assistant, and Personal Issues scores. Adjustment for disease condition is important when assessing patient satisfaction as an indicator of quality and as a metric for reimbursement. This study adds to increasing evidence about bias in these scores.

Improving understanding of type 2 diabetes remission: research recommendations from Diabetes UK's 2019 remission workshop.

AIM: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of remission of type 2 diabetes, and provide recommendations to researchers and research funders on how best to address them. With the ultimate aim of enabling the remission of type 2 diabetes to become a possibility for more people. METHODS: A 1-day research workshop was conducted, bringing together 31 researchers, people living with diabetes, healthcare professionals and members of staff from Diabetes UK to identify and prioritize recommendations for future research into remission of type 2 diabetes. RESULTS: Workshop attendees identified 10 key themes for further research. Four of these themes were prioritized for further focus: (i) understanding how to personalize lifestyle approaches based on biology, patient choice and subtypes; (ii) understanding the biology of remission; (iii) understanding the most effective approaches to implementation of lifestyle interventions; and (iv) understanding the best approaches to combining therapies (gut hormones, other drugs, lifestyle approaches and bariatric surgery). CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to remission of type 2 diabetes.

The effects of ketamine on typical and atypical depressive symptoms.

OBJECTIVE: Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery-Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5), and atypical symptoms (measured using the Scale for Atypical Symptoms (SAS)). METHODS: Data from 68 participants with treatment-resistant major depressive disorder (MDD) or bipolar depression were pooled from three separate, double-blind, placebo-controlled, crossover studies investigating ketamine's efficacy in depression. MDD participants were unmedicated; bipolar participants received therapeutic-dose lithium or valproate. Clinical symptoms were collected preinfusion and up to 14 days postinfusion. Effect sizes were calculated for days 1 and 3 postinfusion. The primary measures of interest for this exploratory analysis were total MADRS, MADRS5, and SAS scores. Individual symptoms were also analyzed in an exploratory manner. RESULTS: Scores improved significantly at Day 1 postinfusion (MADRS: Cohen's d = 0.64; MADRS5: Cohen's d = 0.61; SAS: Cohen's d = 0.41) and continued to be significantly improved over placebo at Day 3 (MADRS: Cohen's d = 0.49; MADRS5: Cohen's d = 0.43; SAS: Cohen's d = 0.39). Effect sizes were greater for typical/melancholic than atypical symptoms at Day 1 postinfusion. CONCLUSION: Ketamine appears to effectively treat both the typical/melancholic and atypical symptoms of depression, but may have early preferential effects for the former.

Comparing pathologic outcomes for robotic versus laparoscopic Surgery in rectal cancer resection: a propensity adjusted analysis of 7616 patients.

BACKGROUND: Margin negative resection of rectal cancer with minimally invasive techniques remains technically challenging. Robotic surgery has potential advantages over traditional laparoscopy. We hypothesize that the difference in the rate of negative margin status will be < 6% between laparoscopic and robotic approach. METHODS: The National Cancer Database (2010-2014) was queried for adults with locally advanced rectal cancer who underwent neoadjuvant chemoradiation and curative resection to conduct an observational retrospective cohort study of a prospectively maintained database. Patients were grouped by either robotic (ROB) or laparoscopic (LAP) approach in an intent-to-treat analysis. Primary outcome was negative margin status, defined as a composite of circumferential resection margin and distal margin. Secondary outcomes included length of stay (LOS), readmission, 90-day mortality, and overall survival. RESULTS: 7616 patients with locally advanced rectal cancer who underwent minimally invasive resection were identified. 2472 (32%) underwent attempted robotic approach. The overall conversion rate was 13% and was increased in the laparoscopic group [LAP: 15% vs. ROB: 8%; OR 0.47; 95% CI (0.39, 0.57)]. Differences in margin negative resection rate were within the prespecified range of practical equivalence (LAP: 93% vs.: ROB 94%; 95% CI (0.69, 1.06); [Formula: see text] = 1). For secondary outcomes, there was no difference in 30-day readmission [LAP: 9% vs.: ROB 8%; 95% CI (0.84, 1.24)] and 90-day mortality [LAP: 1% vs.: ROB 1%; 95% CI (0.38, 1.24)]. While the median LOS was 5 days in both groups, the mean LOS was 0.6 (95% CI: 0.24, 0.89) days shorter in the robotic group. CONCLUSION: This robust analysis supports either robotic or laparoscopic approach for resection of locally advanced rectal cancer from a margin perspective. Both have similar readmission and 5-year overall survival rates. Patients undergoing robotic surgery have a 0.6-day decrease in LOS and decreased conversion rate.

Assessing Hereditary Colorectal Cancer Referral Patterns to a Tertiary Care Center: A Novel Approach Using Geographic Information System Mapping.

BACKGROUND: Patients and their family members with hereditary colorectal cancer require longitudinal follow-up that is best achieved through a dedicated program with a registry. However, referrals for these conditions remain poor. Geographic information systems technology is a novel method to evaluate geographic variation in multiple realms but is being used more in health care. OBJECTIVE: The purpose of this study was to evaluate referral patterns with geographic information systems technology to better target efforts for improving overall referrals. We hypothesized that marked variation would exist as to the geospatial locations of referrals and that gastroenterologists would be the dominant referral source. DESIGN: This was a retrospective cross-sectional study. SETTINGS: The study was conducted at Vanderbilt University Medical Center. PATIENTS: The hereditary colorectal cancer registry was queried from June 2007 to August 2016 for demographics, distance to center, genetic mutations, and the specialty of the referring providers. Geospatial data on both patient and referring specialist were collected. MAIN OUTCOME MEASURES: We analyzed patient and referral data with geographic information systems technology to look for gaps and patterns. RESULTS: A total of 676 patients were entered into the registry during this period. Fifty-six percent were women, and the median age was 50 years (interquartile range, 42-60 y). The median distance from the center was 60 miles (interquartile range, 22-120 miles), and 31% carried an identified germline mutation. Gastroenterology represented the overall largest source of referrals and, when broken down by syndrome, they represented the top referral specialty for familial adenomatous polyposis. Surgeons were the largest referral source for Lynch syndrome. LIMITATIONS: The study was limited by covariates in the database. CONCLUSIONS: Our hereditary colorectal cancer registry serves a large geographic area, with the largest group of referrals coming from gastroenterologists. Performing this analysis with geographic information systems technology mapping allowed us to identify clustering of patients and providers throughout the region as well as gaps. This information will help to target outreach and distribution of educational materials for providers and their patients to increase registry enrollment. See Video Abstract at http://links.lww.com/DCR/A950.

An enhanced recovery program in colorectal surgery is associated with decreased organ level rates of complications: a difference-in-differences analysis.

BACKGROUND: Perioperative care has lacked coordination and standardization. Enhanced recovery programs (ERPs) have been shown to decrease aggregate complications across surgical specialties. We hypothesize that the sustained implementation of an ERP will be associated with a decrease in a broad range of complications at the organ system level. STUDY DESIGN: Adult patients undergoing elective colorectal procedures between 1/2011 and 10/2016 were included. Patients were stratified based on exposure to a sustained ERP (7/2014-10/2016) after an 18-month wash-in period in a pre-post analysis. The primary outcome was 30-day complication rate by organ category as collected by National Surgical Quality Improvement Program (NSQIP) abstractors. Demographic and other patient level data were collected. Complication rates were compared using multivariable regression employing a differences-in-differences (DiD) approach using the national NSQIP PUF file to account for secular trends. RESULTS: A total of 1182 patients were included in this study, with 47% treated in an ERP. The two groups were similar in age, gender, race, BMI, comorbidity index, and procedure type. In a multivariable DiD analysis, significant reductions were seen in surgical site infection (OR 0.30; 95% CI 0.20-0.43), postoperative pulmonary complications (OR 0.46; 95% CI 0.24-0.90), transfusion (OR 0.27; 95% CI 0.15-0.51), urinary tract infections (OR 0.34; 95% CI 0.18-0.66), sepsis (OR 0.35; 95% CI 0.20-0.61), and cardiac complications (OR 0.10; 95% CI 0.01-0.84). A reduction in return to the operating room and 30-day readmission was also observed. Median length of stay (LOS) decreased from 5.2 to 3.5 days (p < 0.001). No significant changes occurred for acute kidney injury and hematologic complications. CONCLUSION: An ERP was associated with reduced complication rates across a wide range of organ categories and > 1.5-day reduction in LOS in a colorectal surgery population.

Correction to: Progression of anal intraepithelial neoplasia in HIV-positive individuals: predisposing factors.

Unfortunately, the "Informed consent" statement was incorrectly published in the original version. The complete correct reference should read as follows.

Progression of anal intraepithelial neoplasia in HIV-positive individuals: predisposing factors.

BACKGROUND: The aim of the present study was to evaluate patient factors that affect the progression of anal dysplasia in human immunodeficiency virus (HIV)-positive individuals. METHODS: A retrospective cohort study of HIV-positive adults with human papilloma virus related anal lesions was performed from 2012 to 2017. All patients underwent surgical excision or biopsy and fulguration of lesions in the operating room without using high resolution anoscopy. Patients with initial presentation of squamous cell carcinoma were excluded. The study was designed to investigate progression between the first available histology and either the follow up histology or a negative examination. Patient files were reviewed and data was collected. A bivariate analysis of continuous and categorical variables was performed. RESULTS: One hundred and sixty-one patients met the inclusion criteria. Ninety-seven percent were male. Mean age was 41 years. Thirty-five percent were African American and 47% were Caucasian. After a median follow-up interval of 331 days (IQR 120-615 days) 14 (9%) of patients had progression of disease. Visible lesions on initial presentation, as opposed to lesions found  in patients undergoing examination under anesthesia because of HSIL on anal pap smear, was associated with progression (p = 0.0.2). A lower initial CD4 count (p = 0.01) and initial surgical pathology of anal condylomata (p = 0.01) were also associated with progression. High-risk serotype was associated with no change or regression (p = 0.01). CONCLUSIONS: In our large cohort of HIV-positive patients treated without high resolution anoscopy the rate of progression was low.  Most notably, visible lesions at initial presentation and CD4 count when lower were associated with progression. Initial surgical pathology of anal condylomata was associated with progression, while high-risk serotypes correlated with regression or stability. Identification of risk factors has important implications concerning postoperative surveillance and counseling of HIV-positive patients with anal condylomata/ anal dysplasia.

Ketorolac Use and Anastomotic Leak in Elective Colorectal Surgery: A Detailed Analysis.

BACKGROUND: Recent population-level analyses have linked ketorolac use to adverse outcomes. However, its use is also associated with decreased opioids and faster return of bowel function. OBJECTIVE: This study aims to assess the association between ketorolac and anastomotic leak. We hypothesize that receiving at least 1 dose of ketorolac will not be associated with anastomotic leak in elective colorectal surgery. DESIGN: This is a retrospective, observational cohort study of a prospectively collected data base. Anastomotic leak rates and other patient outcomes were adjusted for patient-level factors and then compared via a multivariable logistic regression. A secondary analysis assessed a dose-response association with anastomotic leak. SETTING: This study was conducted at a tertiary care colorectal surgery service. PATIENTS: Consecutive patients undergoing elective colorectal surgery with a nondiverted anastomosis were identified from 2012 to 2016. INTERVENTION: Exposure was defined as any administration of ketorolac during the perioperative time period. MAIN OUTCOME MEASURES: The primary outcome measured was anastomotic leak. RESULTS: A total of 877 patients met inclusion criteria. Of these, 479 (54.6%) were women, and the median age was 55 years. Overall, 566 (64.5%) patients were exposed to ketorolac. In the cohort, 27 (3.1%) patients experienced an anastomotic leak. In an unadjusted analysis, there was no association between ketorolac exposure and anastomotic leak (ketorolac: 3.1% vs no ketorolac: 3.3%; p = 0.84). This persisted in a multivariable model (OR, 0.98; 95% CI, 0.38-2.57; p = 0.98). Neither AKI (OR, 3.24; 95% CI, 0.51-20.6; p = 0.21), return to the operating room (OR, 1.07; 95% CI, 0.40-2.85; p = 0.88), nor readmission (OR, 1.03; 95% CI, 0.59-1.80; p = 0.93) was associated with ketorolac use. In a secondary analysis of patients receiving ketorolac, there was no association between total ketorolac dosing and anastomotic leak (OR, 0.99; 95% CI, 0.99-1.00; p = 0.20). LIMITATIONS: This study was a retrospective review, and there was a low incidence of anastomotic leak. CONCLUSION: Ketorolac exposure was associated with neither anastomotic leak nor other important postoperative outcomes. See Video Abstract at http://links.lww.com/DCR/A784.

Barriers to laparoscopic colon resection for cancer: a national analysis.

BACKGROUND: Level one evidence has shown that minimally invasive surgery (MIS) for colon cancer improves short-term outcomes with equivalent long-term oncologic results when compared to open surgery. However, the adoption of MIS for patients with colon cancer has not been universal. The goal of this study is to identify barriers to the use of MIS surgery in colon cancer resection across the United States. METHODS: The National Cancer Database was queried for all cases of colonic adenocarcinoma resection from 2010 to 2012. Patients undergoing an MIS approach were compared with those undergoing open surgery (OS). MIS was defined as either robotic or laparoscopic surgery. Patients with metastatic disease, surgery for palliation, or tumors >8 cm were excluded. Multivariable modeling was used to identify variables associated with the use of open surgery. RESULTS: After applying exclusion criteria, 124,205 cases were identified. An MIS approach was used in only 54,621 (44%) patients. In a multivariable model adjusting for stage and tumor size, a number of important factors were associated with decreased odds of a MIS approach including black race (OR .91; p < .0001), lack of insurance (OR .51; p < .0001), lower education (OR .88; p < .0001), lower income (OR .83; p < .0001), treatment at a community program (OR .86; p < .0001), and treatment at a low-volume center (OR .79; p < .0001). Utilization of MIS increased over the study period (2010: 38.7%, 2011: 44.0%, 2012: 49.1%; p < .0001). CONCLUSIONS: MIS approach is utilized in less than half of all colon resections in this national database, which accounts for over 70% of all diagnosed cancers in the US. Significant variability exists among age, race, insurance status, socioeconomic status, region, and facility type. In light of the recognized benefits of the MIS approach, local and national policy should focus on narrowing these disparities and continuing the upward trend of MIS utilization.

Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States.

BACKGROUND: Short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT) are accepted neoadjuvant treatments of rectal cancer. In the current study, the authors surveyed US radiation oncologists to assess practice patterns and attitudes regarding SC-RT and LC-CRT for patients with rectal cancer. METHODS: The authors distributed a survey to 1701 radiation oncologists regarding treatment of neoadjuvant rectal cancer. Respondents were asked questions regarding the number of patients with rectal cancer treated, preference for SC-RT versus LC-CRT, and factors influencing regimen choice. RESULTS: Of 1659 contactable physicians, 182 responses (11%) were received. Approximately 83% treated at least 5 patients with rectal cancer annually. The majority of responding radiation oncologists (96%) preferred neoadjuvant LC-CRT for the treatment of patients with locally advanced rectal cancer and 44% never used SC-RT. Among radiation oncologists using SC-RT, respondents indicated they would not recommend this regimen for patients with low (74%) or bulky tumors (70%) and/or concern for a positive circumferential surgical resection margin (69%). The most frequent reasons for not offering SC-RT were insufficient downstaging for sphincter preservation (53%) and a desire for longer follow-up (45%). Many radiation oncologists indicated they would prescribe SC-RT for patients not receiving chemotherapy (62%) or patients with a geographic barrier to receiving LC-CRT (82%). Patient comorbidities appeared to influence regimen preferences for 79% of respondents. Approximately 20% of respondents indicated that altered oncology care reimbursement using capitated payment by diagnosis would impact their consideration of SC-RT. CONCLUSIONS: US radiation oncologists rarely use neoadjuvant SC-RT despite 3 randomized controlled trials demonstrating no significant differences in outcome compared with LC-CRT. Further research is necessary to determine whether longer follow-up coupled with the benefits of lower cost, increased patient convenience, and lower acute toxicity will increase the adoption of SC-RT by radiation oncologists in the United States. Cancer 2017;123:1434-1441. © 2016 American Cancer Society.

Nodal Disease in Rectal Cancer Patients With Complete Tumor Response After Neoadjuvant Chemoradiation: Danger Below Calm Waters.

BACKGROUND: A subset of patients with rectal cancer who undergo neoadjuvant chemoradiation therapy will develop a complete pathologic tumor response. Complete nodal response is not universal in these patients and is difficult to assess clinically. Quantifying the risk of nodal disease would allow for targeted therapy with either radical resection or "watchful waiting." OBJECTIVE: This study aimed to identify risk factors for residual nodal disease in ypT0 rectal adenocarcinoma. DESIGN: This is a retrospective case control study. SETTINGS: The National Cancer Database 2006 to 2014 was used to identify patients for this study. PATIENTS: Patients with stage II/III rectal adenocarcinoma who completed chemoradiation therapy followed by resection and who had ypT0 tumors were included. Patients with metastatic disease and <2 lymph nodes evaluated were excluded. Patients were divided into 2 groups: node positive and node negative. MAIN OUTCOME MEASURES: The main outcome was nodal disease. The secondary outcome was overall survival. RESULTS: A total of 42,257 patients with stage II/III rectal cancer underwent chemoradiation therapy and radical resection; 4170 (9.9%) patients had ypT0 tumors and 395 (9.5%) were node positive. Of patients with clinically node-negative disease (ie, pretreatment imaging), 6.2% were node positive after chemoradiation therapy and resection. In multivariable analysis, factors predictive of nodal disease included increasing (pretreatment) clinical N-stage, high tumor grade (3/4), perineural invasion, and lymphovascular invasion. Higher clinical T-stage was inversely associated with residual nodal disease. Overall 5-year survival was significantly different between patients with ypN0, ypN1, and ypN2 disease (87.4%, 82.2%, and 62.5%, p = 0.002). LIMITATIONS: This study was limited by the lack of clinical detail in the database and the inability to assess recurrence. CONCLUSIONS: Ten percent of patients with ypT0 tumors had positive nodes after chemoradiation therapy and resection. Factors associated with residual nodal disease included clinical nodal disease at diagnosis and poor histologic features. Patients with any of these features should consider radical resection regardless of tumor response. Others could be suitable for "watchful waiting" strategies. See Video Abstract at http://links.lww.com/DCR/A458.

Modelling the associations between fat-free mass, resting metabolic rate and energy intake in the context of total energy balance.

BACKGROUND: The relationship between body composition, energy expenditure and ad libitum energy intake (EI) has rarely been examined under conditions that allow any interplay between these variables to be disclosed. OBJECTIVE: The present study examined the relationships between body composition, energy expenditure and EI under controlled laboratory conditions in which the energy density and macronutrient content of the diet varied freely as a function of food choice. METHODS: Fifty-nine subjects (30 men: mean body mass index=26.7±4.0 kg m(-2); 29 women: mean body mass index=25.4±3.5 kg m(-)(2)) completed a 14-day stay in a residential feeding behaviour suite. During days 1 and 2, subjects consumed a fixed diet designed to maintain energy balance. On days 3-14, food intake was covertly measured in subjects who had ad libitum access to a wide variety of foods typical of their normal diets. Resting metabolic rate (RMR; respiratory exchange), total daily energy expenditure (doubly labelled water) and body composition (total body water estimated from deuterium dilution) were measured on days 3-14. RESULTS: Hierarchical multiple regression indicated that after controlling for age and sex, both fat-free mass (FFM; P<0.001) and RMR (P<0.001) predicted daily EI. However, a mediation model using path analysis indicated that the effect of FFM (and fat mass) on EI was fully mediated by RMR (P<0.001). CONCLUSIONS: These data indicate that RMR is a strong determinant of EI under controlled laboratory conditions where food choice is allowed to freely vary and subjects are close to energy balance. Therefore, the conventional adipocentric model of appetite control should be revised to reflect the influence of RMR.

Constraints on geographic variation in fiddler crabs (Ocypodidae: Uca) from the western Atlantic.

A key question in evolutionary biology is how intraspecific variation biases the evolution of a population and its divergence from other populations. Such constraints potentially limit the extent to which populations respond to selection, but may endure long enough to have macroevolutionary consequences. Previous studies have focused on the association between covariation patterns and divergence among isolated populations. Few have focused on geographic variation among semi-connected populations, however, even though this may be indicative of early selective pressures that could lead to long-term divergence and speciation. Here, we test whether covariation in the shape of the carapace of fiddler crabs (genus Uca Leach, 1814) is important for structuring geographic variation. We find that morphological divergence among populations is associated with evolvability in the direction of divergence in only a few species. The shape of the ancestral covariation matrix in these species differs from other species in having notably more variation concentrated along fewer directions (i.e. higher eccentricity). For most species, there is some evidence that covariation has constrained the range of directions into which populations have diverged but not the degree of divergence. These results suggest that even though fiddler crab populations have diverged morphologically in directions predicted by covariation, constraints on the extent to which divergence has occurred may only be manifested in species where variation patterns are eccentric enough to limit populations' ability to respond effectively in many directions.

Single-item migraine screening tests, self-reported bothersome headache or stripe pattern hypersensitivity?

BACKGROUND: A simple screening tool may potentially help the migraine diagnosis in a primary care setting. The use of single-item tests, such as stripe pattern hypersensitivity test and self-reported bothersome headache (HA) question, as migraine screening tools have not been fully explored. METHODS: Two hundred and fifty-four subjects (patients and companions) were randomly enrolled from an OB/GYN clinic (men 82, women 172; age 38 ± 14). They were instructed to rate the stripe sensitivity level (0-4) and to report any bothersome HA (yes/no). A brief structured HA interview was conducted to describe the HA characteristics and for migraine diagnosis based on the ICHD-IIIß criteria. RESULTS: In a multivariate model, bothersome HA question and stripe pattern hypersensitivity test were both significantly associated with EM+PM+CM (odds ratio: 24.0, P < 0.01 vs 2.6, P = 0.01) or EM (odds ratio: 16.2, P < 0.01 vs 3.0, P < 0.01). Bothersome HA question had a greater screening power than stripe pattern hypersensitivity for screening EM+PM+CM (area under the ROC curve: 0.84 [95% CI 0.78-0.89] vs 0.62 [95% CI 0.55-0.69]) or EM (area under the ROC curve: 0.80 [95% CI 0.73-0.86] vs 0.64 [95% CI 0.56-0.72]). CONCLUSION: When performed in an OB/GYN clinic, self-reported bothersome HA question seemed more powerful than visual stripe pattern test in screening migraine thus could potentially be used as a single-item screening test.

CD56+ T cells are increased in kidney transplant patients following cytomegalovirus infection.

BACKGROUND: CD56+ T cells previously have been identified as potentially cytotoxic lymphocytes, and relative numbers are increased in some infectious diseases. PATIENTS AND METHODS: Relative proportions of CD56+ T cells were measured by flow cytometry in groups of renal transplant patients differing in cytomegalovirus (CMV) status of donor (D) and recipient (R). These measurements were related to episodes of CMV viremia. RESULTS: Patient groups in which recipients (R+) or donors (D+/R-) were CMV+ had significantly higher proportions of CD56+ T cells (5.11 ± 0.69% and 5.42 ± 1.01%, respectively) than the D-/R- group (1.9 ± 0.35%; P = 0.0018 and 0.017, respectively). In the high-risk D+/R- group, it was found that patients who had post-transplant CMV viremia had higher levels than those who remained CMV negative (9.09 ± 2.34% vs. 3.16 ± 1.22%; P = 0.01). CD56+ T cells from R+ and D+/R- groups had higher proportions of both CD4+ and CD8+ cells than the D-/R- group. When activation markers were examined, some CD56+ T cells from both CMV+ groups had a TEM phenotype, with significantly more expressing CD45RO and NKG2C, and less expressing CD28, CD62L, CD127, and CD161 compared to the D-/R- group. Some CD56+ T cells showed specificity for CMV antigens and similar proportions of CD8+ cells were positive for class I HLA-CMV tetramers containing immunodominant CMV peptides compared to the majority CD56- T cells. CONCLUSION: The results show significant increases in proportions of CD56+ T cells in relation to CMV infection in renal transplant patients and suggest that these cells have a cytotoxic function against CMV-infected cells.