AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch.

Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in ILC22 cells that resulted in less secretion of IL-22 and inadequate protection against intestinal bacterial infection. Ahr(-/-) mice also lacked postnatally 'imprinted' cryptopatches and isolated lymphoid follicles (ILFs), but not embryonically 'imprinted' Peyer's patches. AHR induced the transcription factor Notch, which was required for NKp46(+) ILCs, whereas LTi-like ILCs, cryptopatches and ILFs were partially dependent on Notch signaling. Thus, AHR was essential for ILC22 cells and postnatal intestinal lymphoid tissues. Moreover, ILC22 subsets were heterogeneous in their requirement for Notch and their effect on the generation of intestinal lymphoid tissues.

Disparities in Surgical Timing and Guideline-Adherent Staging Work-Up for Colon Cancer.

BACKGROUND: Expedited or delayed surgery for colon cancer without appropriate work-up increases mortality risk. We sought to identify what patient, social, and hospital factors were associated with timely, guideline-adherent work-up for colon cancer. METHODS: Retrospective analysis of 19,046 patients in the Surveillance, Epidemiology, and End Results (SEER) database linked with Medicare administrative claims who underwent elective surgery for colon cancer between 2010 and 2015 was performed. Primary outcome was receipt of complete preoperative work-up (colonoscopy, imaging, tumor marker evaluation) and timely surgery within 60 days of diagnosis. Patients were stratified into four groups: (1) adherent; (2) early surgery (< 30 days) with incomplete work-up; (3) surgery between 30 and 60 days with incomplete work-up; and (4) late surgery (> 60 days) with/without work-up. Characteristics were compared and multinomial logistic regression was performed. RESULTS: Overall, 46.2% of patients received adherent care, 33.1% had early surgery and inadequate work-up, 10.3% had appropriately timed surgery but incomplete work-up, and 10.4% underwent late surgery. Multivariable analysis demonstrated that older, female, Black, and unmarried patients as well as patients living in areas with higher rates of poverty were more likely to receive non-adherent care. A greater proportion of patients at teaching hospitals received complete work-up (57.6% vs. 49.5%) but also underwent late surgery (12.4% vs. 8.6%) compared with non-teaching hospitals. CONCLUSIONS: Patient, societal, and hospital factors impact whether patients receive guideline-adherent colon cancer care. Interventions are needed to improve access to timely and guideline-adherent cancer care as a possible mechanism to combat surgical disparities.

Early Elective Surgery After Colon Cancer Diagnosis has Higher Risk of Readmission and Death.

OBJECTIVE: We hypothesized colon resection within 30 days of diagnosis of cancer would have higher rates of readmission and cancer specific mortality, unless there was demonstrated evidence of preoperative workup. SUMMARY BACKGROUND DATA: Few studies have examined if negative consequences exist with expedited elective surgery after diagnosis of colon cancer. Surgery in a shorter time frame may result in a lack of appropriate preoperative care. METHODS: Retrospective analysis of 25,407 patients in the Surveillance Epidemiology and End Results registry who underwent elective surgical resection for colon cancer from 2010 to 2015. Cohort stratified by age (66-75 vs >75 years). Primary outcomes of interest were 30-day readmission and 5-year colon cancer specific mortality. Relationships between timing of surgery and outcomes were assessed. RESULTS: On unadjusted analysis, surgery before 20 days of diagnosis was associated with higher risk of 30-day readmission and colon cancer specific mortality in both age groups. Among those age 66 to 75 years old, adjusting for patient factors and preoperative workup eliminated the risk of 30-day readmission (risk ratio 1.5-0.9 for 0-10 days, risk ratio 1.3-0.9 for 11-20 days). However, the risk for colon cancer specific mortality, although reduced, persisted (hazard ratio 2.2-1.3 for 0-10 days, hazard ratio 2.0-1.2 for 11-20 days). In the cohort older than 75 years, adjusting for patient level factors and preoperative workup eliminated risk of surgery 20 days postop or sooner. CONCLUSIONS: The risk associated with short time to surgery (within 30 days) may be mitigated if full oncologic workups are provided.

Preoperative Tamsulosin to Prevent Postoperative Urinary Retention: A Randomized Controlled Trial.

BACKGROUND: The purpose of this study was to evaluate the efficacy of tamsulosin, administered preoperatively, for the prevention of postoperative urinary retention (POUR). POUR is a common complication of abdominal surgery, leading to the use of urinary catheters, which are a risk factor for urinary tract infection. Tamsulosin is a uroselective alpha-1a blocker used for the treatment of lower urinary tract symptoms. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was undertaken from August 2015 to May 2018. Adults undergoing elective inpatient abdominal surgery were randomized to receive either tamsulosin 0.4 mg or placebo daily for 7 d before surgery and continuing for up to 7 d postoperatively. The primary outcome was need for at least a single intermittent catheterization postoperatively. Secondary outcomes included first postvoid residual volume, number of catheterizations, need for replacement of an indwelling catheter, hospital length of stay, and urinary tract infection within 30 d of surgery. RESULTS: A total of 158 participants were enrolled, with a final analytic cohort of 141 participants. The two groups had similar baseline characteristics, operative characteristics, and timing of catheter removal. There was no difference in the incidence of POUR between the two groups (26% in tamsulosin versus 31% in placebo, P = 0.49). There was also no difference in any of the secondary outcomes between the two groups. Epidural usage, open surgery, and age <50 were identified as risk factors for POUR. CONCLUSIONS: Perioperative prophylaxis with tamsulosin is not effective in reducing the incidence of POUR in patients undergoing elective abdominal surgery.

The Association of Enhanced Recovery Pathway and Acute Kidney Injury in Patients Undergoing Colorectal Surgery.

BACKGROUND: Acute kidney injury is associated with increased postoperative length of hospital stay and increases the risk of postoperative mortality. The association between the development of postoperative acute kidney injury and the implementation of an enhanced recovery after surgery protocol remains unclear. OBJECTIVE: This study aimed to examine the relationship between the implementation of an enhanced recovery pathway and the development of postoperative acute kidney injury. DESIGN: In this retrospective cohort study, a prospectively maintained database of patients who underwent elective colorectal surgery in an enhanced recovery pathway were compared to a hospital historical National Surgical Quality Improvement Program colorectal registry of patients. SETTINGS: This study was conducted at the University of Alabama at Birmingham, a tertiary referral center. PATIENTS: A total of 1052 patients undergoing elective colorectal surgery from 2012 through 2016 were included. MAIN OUTCOME MEASURES: The development of postoperative acute kidney injury was the primary outcome measured. RESULTS: Patients undergoing an enhanced recovery pathway had significantly greater rates of postoperative acute kidney injury than patients not undergoing an enhanced recovery pathway (13.64% vs 7.08%; p < 0.01). Our adjusted model indicated that patients who underwent an enhanced recovery pathway (OR, 2.31; 95% CI, 1.48-3.59; p < 0.01) had an increased risk of acute kidney injury. Patients who developed acute kidney injury in the enhanced recovery cohort had a significantly longer median length of stay than those who did not (median 4 (interquartile range, 4-9) vs 3 (interquartile range, 2-5) days; p=0.04). LIMITATIONS: This study did not utilize urine output as a modality for detecting acute kidney injury. Data are limited to a sample of patients from a large academic medical center participating in the National Surgical Quality Improvement Program. Interventions or programs in place at our institution that aimed at infection reduction or other initiatives with the goal of improving quality were not accounted for in this study. CONCLUSION: The implementation of an enhanced recovery after surgery protocol is independently associated with the development of postoperative acute kidney injury.See Video Abstract at http://links.lww.com/DCR/B69. LA ASOCIACIÓN DE VÍA DE RECUPERACIÓN MEJORADA Y LESIÓN RENAL AGUDA EN PACIENTES DE CIRUGÍA COLORRECTAL: La lesión renal aguda se asocia con una mayor duración en la estancia hospitalaria y aumenta el riesgo de la mortalidad postoperatoria. La asociación entre el desarrollo de la lesión renal aguda postoperatoria y la implementación de un protocolo de Recuperación Mejorada después de la cirugía, sigue sin ser clara.Examinar la relación entre la implementación de una vía de Recuperación Mejorada y el desarrollo de lesión renal aguda postoperatoria.Estudio de cohorte retrospectivo, de una base de datos mantenida prospectivamente, de pacientes que se sometieron a cirugía colorrectal electiva, en una vía de Recuperación Mejorada, se comparó con el registro histórico de los pacientes colorrectales del Programa Nacional de Mejora de la Calidad Quirúrgica.Universidad de Alabama en Birmingham, un centro de referencia terciario.Un total de 1052 pacientes sometidos a cirugía colorrectal electiva desde 2012 hasta 2016.Desarrollo de lesión renal aguda postoperatoria.Los pacientes sometidos a una vía de Recuperación Mejorada, tuvieron tasas significativamente mayores de lesiones renales agudas postoperatorias, en comparación con los pacientes de Recuperación no Mejorada (13.64% vs 7.08%; p < 0.01). Nuestro modelo ajustado indicó que los pacientes que se sometieron a una vía de Recuperación Mejorada (OR, 2.31; IC, 1.48-3.59; p < 0.01) tuvieron un mayor riesgo de lesión renal aguda. Los pacientes que desarrollaron daño renal agudo en la cohorte de Recuperación Mejorada, tuvieron una estadía mediana significativamente más larga en comparación con aquellos que no [mediana 4 (rango intercuartil (RIC) 4-9) versus 3 (RIC 2-5) días; p = 0.04].Este estudio no utilizó la producción de orina como una modalidad para detectar daño renal agudo. Los datos se limitan a una muestra de pacientes de un gran centro médico académico, que participa en el Programa Nacional de Mejora de la Calidad Quirúrgica. Las intervenciones o programas implementados en nuestra institución, destinados a la reducción de infecciones u otras iniciativas, con el objetivo de mejorar la calidad, no se tomaron en cuenta para este estudio.La implementación de una Recuperación Mejorada después del protocolo de cirugía, se asocia independientemente con el desarrollo de lesión renal aguda postoperatoria.Consulte Video Resumen en http://links.lww.com/DCR/B69. (Traducción-Dr. Fidel Ruiz-Healy).

Noninvasive Detection of Colorectal Carcinomas Using Serum Protein Biomarkers.

BACKGROUND: A major roadblock to reducing the mortality of colorectal cancer (CRC) is prompt detection and treatment, and a simple blood test is likely to have higher compliance than all of the current methods. The purpose of this report is to examine the utility of a mass spectrometry-based blood serum protein biomarker test for detection of CRC. MATERIALS AND METHODS: Blood was drawn from individuals (n = 213) before colonoscopy or from patients with nonmetastatic CRC (n = 50) before surgery. Proteins were isolated from the serum of patients using targeted liquid chromatography-tandem mass spectrometry. We designed a machine-learning statistical model to assess these proteins. RESULTS: When considered individually, over 70% of the selected biomarkers showed significance by Mann-Whitney testing for distinguishing cancer-bearing cases from cancer-free cases. Using machine-learning methods, peptides derived from epidermal growth factor receptor and leucine-rich alpha-2-glycoprotein 1 were consistently identified as highly predictive for detecting CRC from cancer-free cases. A five-marker panel consisting of leucine-rich alpha-2-glycoprotein 1, epidermal growth factor receptor, inter-alpha-trypsin inhibitor heavy-chain family member 4, hemopexin, and superoxide dismutase 3 performed the best with 70% specificity at over 89% sensitivity (area under the curve = 0.86) in the validation set. For distinguishing regional from localized cancers, cross-validation within the training set showed that a panel of four proteins consisting of CD44 molecule, GC-vitamin D-binding protein, C-reactive protein, and inter-alpha-trypsin inhibitor heavy-chain family member 3 yielded the highest performance (area under the curve = 0.75). CONCLUSIONS: The minimally invasive blood biomarker panels identified here could serve as screening/detection alternatives for CRC in a human population and potentially useful for staging of existing cancer.

Postoperative Complications After Colorectal Surgery: Where Are We in the Era of Enhanced Recovery?

PURPOSE OF REVIEW: Individual elements in enhanced recovery pathways may be associated with specific complication risks. In this review, we highlight three areas of controversy surrounding complications in enhanced recovery: (1) whether enhanced recovery is associated with increased rates of acute kidney injury, (2) whether NSAID use is associated with anastomotic leaks, and (3) whether early urinary catheter removal is justified following colorectal surgery. RECENT FINDINGS: Acute kidney injury has been reported at several institutions following implementation of enhanced recovery pathways highlighting the importance of institutional data tracking. NSAID use has been implicated in anastomotic leak rates for non-elective colorectal procedures, and criteria for its use should be implemented. Early urinary catheter removal has been supported despite increased urinary retention rates in order to decrease urinary tract infections. Enhanced recovery protocols will continue to evolve, and risk profiles associated with individual elements should continue to be evaluated.

Panitumumab-IRDye800CW for Fluorescence-Guided Surgical Resection of Colorectal Cancer.

BACKGROUND: Fluorescence-guided surgery (FGS) is a rapidly advancing field that may improve outcomes in several cancer types. Although screening has decreased colorectal cancer (CRC) mortality, it remains a common and often fatal malignancy. In this study, we sought to identify an optical imaging agent for the application of FGS technology to CRC. METHODS: We compared a panitumumab-IRDye800CW conjugate to an IgG-IRDye800CW isotype control. Mice were implanted with one of three CRC cell lines (LS174T, Colo205, and SW948) and imaged with open- and closed-filed fluorescence imaging systems. Fluorescent contrast was quantified by calculating the ratio between tumor and background fluorescence. After 10 d, the mice were sacrificed, and their tumors stained for microscopic imaging. RESULTS: Panitumumab-IRDye800CW produced significantly greater (P < 0.05) fluorescent contrast in all three cell lines. Average tumor to background ratio was 6.00 versus 2.60 for LS174T, 5.78 versus 2.52 for Colo205, and 4.31 versus 1.70 for SW948. A 1-mg tumor fragment produced significantly greater fluorescent contrast in the Colo205 and SW948 cell lines in the panitumumab-IRDye800CW group. Western blotting for epidermal growth factor receptor (EGFR) and a semiquantitative analysis of EGFR expression noted strong expression in all three cell lines; however, EGFR expression did not directly correlate to tumor to background ratio. CONCLUSIONS: Panitumumab-IRDye800CW produces significantly greater fluorescent contrast than IgG-IRDye800CW in a murine model of CRC and is a suitable agent for the application of FGS technology to CRC.

Enhanced Recovery After Surgery (ERAS) Eliminates Racial Disparities in Postoperative Length of Stay After Colorectal Surgery.

OBJECTIVE: To investigate the effects of enhanced recovery after surgery (ERAS) on racial disparities in postoperative length of stay (pLOS) after colorectal surgery. BACKGROUND: Racial disparities in surgical outcomes exist. We hypothesized that ERAS would reduce disparities in pLOS between black and white patients. METHODS: Patients undergoing ERAS in 2015 were 1:1 matched by race/ethnicity, age, sex, and procedure to a pre-ERAS group from 2010 to 2014. After stratification by race/ethnicity, expected pLOS was calculated using the American College of Surgeons National Surgical Quality Improvement Project Risk Calculator. Primary outcome was the observed pLOS and observed-to-expected difference in pLOS. Secondary outcomes were National Surgical Quality Improvement Project postoperative complications including 30-day readmissions and mortality. Adjusted sensitivity analyses on pLOS were also performed. RESULTS: Of 420 patients (210 ERAS and 210 pre-ERAS) examined, 28.3% were black. Black and white patients were similar in age, body mass index, sex, American Anesthesia Association class, and minimally invasive approaches. Within the pre-ERAS group, black patients stayed a mean of 2.7 days longer than expected compared with white patients (P < 0.05). Overall, ERAS patients had a significantly shorter pLOS (5.7 vs 8 days) and observed-to-expected difference (-0.7 vs 1.4 days) compared with pre-ERAS patients (P < 0.01). In the ERAS group, disparities in pLOS were reduced with no differences in readmissions or mortality between black and white patients. On sensitivity analyses, race/ethnicity remained a significant predictor of pLOS among pre-ERAS patients, but not for ERAS patients. CONCLUSIONS: ERAS eliminated racial differences in pLOS between black and white patients undergoing colorectal surgery. Reduced pLOS occurred without increases in mortality, readmissions, and most postoperative complications. ERAS may provide a practical approach to reducing disparities in surgical outcomes.

The aryl hydrocarbon receptor as an antitumor target of synthetic curcuminoids in colorectal cancer.

BACKGROUND: Curcumin has proven to be a potent antitumor agent in both preclinical and clinical models of colorectal cancer (CRC). It has also been identified as a ligand of the transcription factor known as the aryl hydrocarbon receptor (AHR). Our laboratory has identified the AHR as a mechanism which contributes to both tumorigenesis in a mouse model of inflammatory CRC as well an apoptotic target in vitro. Curcumin's role as an AHR ligand may modulate its effects to induce colon cancer cell death, and this role may be enhanced via structural modification of the curcumin backbone. We sought to determine if the two piperidone analogs of curcumin, RL66 and RL118, exhibit more robust antitumor actions than their parent compound in the context of colorectal cancer in vitro. Moreover, to ascertain the ability of curcumin, RL66 and RL118 to activate the AHR and evaluate if this activation has any effect on CRC cell death. MATERIALS AND METHODS: DLD1, HCT116, LS513, and RKO colon cell lines were propagated in vitro. Natural curcumin was obtained commercially, whereas RL66 and RL118 were synthesized and characterized de novo. Multiwell fluorescent/luminescent signal detection was used to simultaneously ascertain cell viability, cell cytonecrosis, and relative amounts of apoptotic activity. AHR activity was measured with a dual luciferase reporter gene system. Stable expression of small interfering RNA interference was established in the HCT116 cell lines to create AHR "knock down" cell lines. RESULTS: Both RL66 and RL118 proved to be more potent antitumor agents than their parent compound curcumin in all cell lines tested. The majority of this cell death was due to induction of apoptosis, which occurred earlier and to a greater degree following RL66 and RL118 treatment as opposed to curcumin. Also, RL66 and RL118 were found to be activators of AHR, and a portion of their ability to cause cell death was dependent on this induction. Curcumin was found unable to activate the AHR, and levels of AHR messenger RNA did not change their effects on cell death. CONCLUSIONS: Piperidone analogs of curcumin exhibited enhanced antitumor effects in vitro as opposed to their parent compound. Even more, this enhanced cell death profile may be partially attributed to the ability of these compounds to activate the AHR. Further study of synthetic curcumin analogs as chemopreventives and chemoadjuncts in CRC is warranted. Also, more generally, the AHR may represent a potential putative target for novel anticancer agents for CRC.

Incorporation of Leadership Rounds in CAUTI Prevention Efforts.

Leadership engagement is an important aspect of integrating best practices at the bedside. The catheter-associated urinary tract infection (CAUTI) prevention workgroup at our academic medical center implemented leadership rounding in partnership with clinical staff to increase participation in CAUTI prevention initiatives on inpatient units. There was an associated decrease in urinary catheter utilization and CAUTI rates. Implementation of leadership rounds should be considered as a part of comprehensive CAUTI prevention efforts in health care settings.

Implications of Multiple Complications on the Postoperative Recovery of General Surgery Patients.

OBJECTIVES: To evaluate the association between multiple complications and postoperative outcomes and to assess which complications occur together in patients with multiple complications. BACKGROUND: Patients who suffer multiple complications have increased risk of prolonged hospital stay and mortality. However, little is known about what places patients at risk for multiple complications or which complications tend to occur in these patients. METHODS: Surgical patients were identified from the American College of Surgeons National Quality Improvement Program (ACS NSQIP) database from 2005 to 2011. The frequency of postoperative complications was assessed. Patients with less than two complications were compared with patients who had multiple complications using χ and logistic regression analysis. Relationships among postoperative complications were explored by learning a Bayesian network model. RESULTS: The study population consisted of 470,108 general surgery patients. The overall complication rate was 15% with multiple complications in 27,032 (6%) patients. Patients with multiple complications had worse postoperative outcomes (P < 0.001). The strongest predictors for developing multiple complications were admission from chronic care facility or nursing home, dependent functional status, and higher American Society of Anesthesiologist Physical Status classification. In patients with multiple complications, the most common complication was sepsis (42%), followed by failure to wean ventilator (31%), and organ space surgical site infection (27%). We found that severe complications were most strongly associated with development of multiple complications. Using a Bayesian network, we were able to identify how strongly associated specific complications were in patients who developed multiple complications. CONCLUSIONS: Almost half (40%) of patients with complications suffer multiple complications. Patient factors such as frailty and comorbidity strongly predict the development of multiple complications. The results of our Bayesian analysis identify targets for interventions aimed at disrupting the cascade of multiple complications in high-risk patients.

Does Anastomotic Leak Contribute to High Failure-to-rescue Rates?

OBJECTIVE: Our aim was to evaluate failure-to-rescue (FTR) after anastomotic leak (AL) in colectomy patients. BACKGROUND: In the era of pay for performance, it is imperative that we understand the quality measures under which we are scrutinized. FTR has been proposed as a marker of surgical quality. We investigated the role of complications in FTR rates in colectomy patients. METHODS: Patients who underwent nonemergent colectomy from 2012 to 2013 were identified from the The American College of Surgeons National Quality Improvement Program (ACS NSQIP database). Mortality after AL was assessed and stratified in relation to mortality after other postoperative complications. χ and logistic regression analysis were used to assess the effect of AL on mortality. RESULTS: We identified 30,101 patients who met inclusion criteria, 1127 suffered an AL (3.7%). FTR was increased in patients with AL compared with those without AL (6% vs 1%, P < 0.001). The mortality rate after leak was similar to mortality after other major complications. Independent risk factors for death after AL included older age (odds ratio [OR] 3.140; 95% confidence interval [CI], 1.744-5.651), cancer diagnosis (OR 2.032; 95% CI, 1.177-3.507), and open approach (OR 2.124; 95% CI, 1.194-3.776) while preoperative bowel preparation was protective (OR 0.563; 95% CI, 0.328-0.969). CONCLUSIONS: AL is a common complication after colectomy with a relatively high FTR rate. As hospitals are penalized for not reaching specific rates of FTR, we must better understand these complex relationships to improve quality and safety of patient care.

The Aryl Hydrocarbon Receptor is a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse.

OBJECTIVE: To determine the role of the aryl hydrocarbon receptor (AHR) in colitis-associated colorectal tumorigenesis. BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in United States. Chronic intestinal inflammation increases the risk for the development of CRC. We investigated the involvement of AHR, a ligand-activated transcriptional regulator, in colitis-associated colorectal tumorigenesis. METHODS: We used a mouse model of colitis-associated colorectal tumorigenesis that employs treatment with azoxymethane and dextran sodium sulfate. We examined the role of AHR using both an Ahr-deletion mouse model (Ahr) and treatment with the AHR pro-agonist indole-3-carbinol (I3C). Incidence, multiplicity, and location of tumors were visually counted. Tumors were defined as neoplasms. Intestinal inflammation was assessed by quantitative PCR for proinflammatory markers and colon length. Data were evaluated and compared using GraphPad Prism software (version 6, La Jolla, CA). RESULTS: Tumor incidence was increased 32% in Ahr null mice and tumor multiplicity was approximately increased 3-fold compared with wild-type mice (2.4 vs 7; P < 0.05). Furthermore, tumor multiplicity was reduced 92% by treatment of I3C in wild-type mice, whereas the suppressor effect of I3C was not observed in Ahr null mice (P < 0.05). CONCLUSIONS: We found that AHR plays a protective role in colitis-associated colorectal tumorigenesis. This conclusion is based on the observations that Ahr null mice showed increased number of colorectal tumors, and mice treated with I3C exhibited fewer tumors. This study supports the use of AHR agonists such as I3C as a chemopreventive therapy for IBD-associated CRC in human patients.

The Log Odds of Positive Lymph Nodes Stratifies and Predicts Survival of High-Risk Individuals Among Stage III Rectal Cancer Patients.

INTRODUCTION: The log odds of positive lymph nodes (LODDS) is an empiric transform formula that incorporates positive and negative lymph node data into a single ratio for prognostic utility. We sought to determine the value of the log odds ratio as a prognostic indicator compared with established lymph node indices in advanced-stage rectal cancer patients who have undergone curative resection. METHODS: Retrospective analysis of rectal cancer operations from 1995 to 2013 identified all stage III cancer patients who underwent curative resection. Patients were stratified into three groups according to calculated lymph node ratios (LNRs) and log odds ratios (LODDS). The relationship between LNR, LODDS, and 5-year overall survival (OS) were assessed. RESULTS: OS for all patients was 81.4%. Both LNR and LODDS stratifications identified differences in 5-year OS. LODDS stratification was significantly associated with OS (p = .04). Additional significant clinicopathologic demographic variables included sex (p = .02), venous invasion (p = .02), tumor location (p < .001), and receipt of adjuvant chemotherapy (p = .047). LODDS separated survival among patients in the low LNR group (LNR1). CONCLUSION: This study confirms that the measure of lymph node involvement transformed by the log odds ratio is a suitable predictor of 5-year overall survival in stage III rectal cancer. LODDS may be applied to stratify high-risk patients in the management of adjuvant therapy. IMPLICATIONS FOR PRACTICE: Traditionally, clinicians have relied solely on the total number of positive lymph nodes affected when determining patient prognosis in rectal cancer. However, the current staging strategy does not account for "high-risk," biologically aggressive tumors that fall into the same risk categories as less clinically aggressive tumors. The log odds of positive lymph nodes is a logistic transform formula that uses pathologic lymph node data to stratify survival differences among patients within a single stage of disease. This formula allows clinicians to identify whether patients with clinically aggressive tumors fall into higher-risk groups, providing additional insight into how to better counsel patients and manage postoperative therapies.

Preoperative urinary tract infection increases postoperative morbidity.

BACKGROUND: Preoperative urinary tract infection (UTI) may be associated with surgical site infections secondary to hematogenous spread of bacteria. The association between preoperative UTI and postoperative complications has not been evaluated in general surgery populations. MATERIALS AND METHODS: Patients undergoing elective general surgery procedures from 2011 to 2013 were selected from the American College of Surgeons National Surgical Quality Improvement Program database. Patients with UTI present at the time of surgery (PATOS) were identified as cases. Patients without UTI PATOS were selected and matched 2:1 on age, American Society of Anesthesiologists class, and Current Procedural Terminology code with identified cases. Univariate and multivariate analyses compared postoperative outcomes between the two groups. RESULTS: A total of 434,802 patients were identified for inclusion in the study, with an overall preoperative UTI rate of 0.1% (n = 363). On univariate analysis, the UTI group had a significantly higher incidence of overall complications, infectious complications, and noninfectious complications. Multivariate analysis confirmed that patients with UTI had a higher risk of postoperative complications compared with those without preoperative UTI (odds ratio [OR] 1.551, 95% confidence interval [CI] 1.071-2.247). This relationship persisted for both infectious (OR 1.515, 95% CI 1.000-2.296) and noninfectious (OR 1.683, 95% CI 1.012-2.799) complications. CONCLUSIONS: We demonstrated an increased rate of 30-d complications in elective general surgery patients with UTI PATOS. These findings suggest that diligent efforts to diagnose and treat UTI before surgery may result in improved outcomes. Furthermore, surgeons should consider postponing elective procedures to allow for the complete resolution of preoperative UTI.

Independent risk factors for prolonged postoperative ileus development.

BACKGROUND: Postoperative ileus (POI) has a significant impact on patient wellbeing, and with a 15% incidence in colectomy patients costs US hospitals >$1.3 billion per year. Although some causative mechanisms have been identified, little is known about what places patients at risk for ileus. We aimed to identify factors that independently influence the development of POI. MATERIALS AND METHODS: Patients who underwent elective surgery between 2011 and 2012 were identified from the colectomy-specific American College of Surgeons National Surgical Quality Improvement Program database. Descriptive statistics were calculated, and demographics, comorbidities, preoperative treatments, and operative characteristics were evaluated as risk factors using multivariate analyses. RESULTS: A total of 9734 patients were included in this analysis; 1364 (14%) were found to have POI. Patients who developed an ileus were more likely to develop any postoperative complication, to be readmitted, and require reoperation compared with patients without POI. In addition, we identified 13 independent risk factors for POI. CONCLUSIONS: Five modifiable risk factors for development of POI were identified as follows: smoking, weight loss, preoperative oral antibiotics, mechanical bowel preparation, and surgical approach. These identifications provide insight into possible targets for preoperative modification, which may lead to improvements in patients' quality of life and influence outcomes such as postoperative complications, readmission, and reoperation.

Indole-3-carbinol induces tumor cell death: function follows form.

BACKGROUND: Even with colonoscopy screening and preventive measures becoming more commonplace, colorectal cancer (CRC) remains the third leading cause of oncologic death in the United States as of 2014. Many chemotherapeutics exist for the treatment of colorectal cancer, though they often come with significant side effect profiles or narrow efficacy ranges in terms of patient profile. Dietary phytochemicals such as glucobrassicin and its metabolite indole-3-carbinol (I3C) have been implicated in tumor prevention in many preclinical models across a variety of gastrointestinal tumors and represent an intriguing new class of natural chemotherapeutics for CRC. I3C has been identified as a ligand of the aryl hydrocarbon receptor (AHR), and we aimed to characterize this AHR activation in relation to its cytotoxic properties. METHODS: Human colorectal cancer cell lines DLD1, HCT116, HT-29, LS513, and RKO were treated with indole-3-carbinol or vehicle. Cell viability was assessed via a fluorescent product assay, and apoptotic activity was assessed via a luminescent signal tied to a ratio of caspase-3 and caspase-7 activity. Gene expression of AHR and CYP1A1 messenger ribonucleic acid (mRNA) was measured using quantitative real-time polymerase chain reaction. Small interfering RNA stable expression lines were established on a HCT116 background using a laboratory-developed transfection protocol as published elsewhere. RESULTS: Multiple colorectal cancer cell types express increased CYP1A1 mRNA levels (a specific marker of AHR-driven activity) after treatment with I3C, characterizing I3C treatment as agonistic of this pathway. Also, I3C induced a dose-dependent decrease in cell viability as well as inducing apoptosis. Furthermore, using small interfering RNA interference to knockdown AHR responsiveness generated a significant resistance to the chemotherapeutic actions of indole-3-carbinol regarding both cell viability and apoptotic activity. CONCLUSIONS: Some degree of the cytotoxic and proapoptotic effects of indole-3-carbinol on colon cancer cells is dependent on activation of the aryl hydrocarbon receptor. This represents a novel mechanism for the molecular action of indole-3-carbinol and enhances our understanding of its effects in the context of colorectal cancer. Continued preclinical study of both indole-3-carbinol and the aryl hydrocarbon receptor pathway is warranted, which may one day lead to novel diet-derived colon cancer treatments that enlist the AHR.

Short-term outcomes of minimally invasive versus open colectomy for colon cancer.

BACKGROUND: Laparoscopic and open approaches to colon resection have equivalent long-term outcomes and oncologic integrity for the treatment of colon cancer. Differences in short-term outcomes should therefore help to guide surgeons in their choice of operation. We hypothesized that minimally invasive colectomy is associated with superior short-term outcomes compared to traditional open colectomy in the setting of colon cancer. MATERIALS AND METHODS: Patients undergoing nonemergent colectomy for colon cancer in 2012 and 2013 were selected from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted colectomy participant use file. Patients were divided into two cohorts based on operative approach-open versus minimally invasive surgery (MIS). Univariate, multivariate, and propensity-adjusted multivariate analyses were performed to compare postoperative outcomes between the two groups. RESULTS: A total of 11,031 patients were identified for inclusion in the study, with an overall MIS rate of 65.3% (n = 7200). On both univariate and multivariate analysis, MIS approach was associated with fewer postoperative complications and lower mortality. In the risk-adjusted multivariate analysis, MIS approach was associated with an odds ratio of 0.598 for any postoperative morbidity compared to open (P < 0.001). CONCLUSIONS: This retrospective study of patients undergoing colectomy for colon cancer demonstrates significantly improved outcomes associated with a MIS approach, even when controlling for baseline differences in illness severity. When feasible, minimally invasive colectomy should be considered gold standard for the surgical treatment of colon cancer.

Postoperative Complications: Looking Forward to a Safer Future.

Colorectal surgery patients frequently suffer from postoperative complications. Patients with complications have been shown to be at higher risk for mortality, poor oncologic outcomes, additional complications, and worse quality of life. Complications are increasingly recognized as markers of quality of care with more use of risk-adjusted national surgical databases and increasing transparency in health care. Quality improvement work in colorectal surgery has identified methods to decrease complication rates and improve outcomes in this patient population. Future work will continue to identify best practices and standardized ways to measure quality of care.