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Desmoid disease is a leading cause of morbidity and mortality in patients with familial adenomatous polyposis. Abdominal desmoid disease usually follows total proctocolectomy with IPAA or total abdominal colectomy with ileorectal anastomosis. Sex, extraintestinal manifestations, and a 3'-mutation location have been identified as risk factors, but surgical risk factors are poorly understood. We hypothesized that pouch construction creates a higher risk of desmoid formation due to the increased stretch of the small-bowel mesentery.This study aimed to investigate the surgical risk factors for desmoid formation.This was a retrospective, single-center, registry-based cohort study.This study was conducted at a single academic institution with a prospectively maintained hereditary colorectal cancer database between 1995 and 2015.All patients with familial polyposis (total 345) who underwent either proctocolectomy with a pouch or colectomy with an ileorectal anastomosis during the study period and met inclusion criteria were selected.The development of symptomatic abdominal desmoid disease was the primary end point. Associations between desmoid formation and resection type, surgical approach, and other patient factors were analyzed.A total of 172 (49%) patients underwent proctocolectomy/ileoanal pouch, whereas 173 (51%) underwent total colectomy/ileorectal anastomosis. Overall, 100 (28.9%) developed symptomatic desmoids after surgery. On univariable analysis, open surgery and pouch surgery were associated with desmoid development, along with extracolonic manifestations, family history of desmoids, mutation location, and a high desmoid risk score. On multivarible analysis, proctocolectomy with pouch was most strongly associated with desmoid disease ( p0.01).This study was limited by its retrospective nature, the lack of uniform desmoid screening, and the variable duration of follow-up. Unanalyzed confounding factors include polyposis severity and number of surgeries.Patients with polyposis who underwent total proctocolectomy with pouch by any approach had significantly greater risk of developing desmoid disease than total colectomy with ileorectal anastomosis, even when accounting for other risk factors. See Video Abstract at http://links.lww.com/DCR/B822 .RESULTADOS DE LOS PACIENTES SOMETIDOS A RESECCIÓN INTESTINAL ELECTIVA ANTES Y DESPUÉS DE LA IMPLEMENTACIÓN DE UN PROGRAMA DE DETECCIÓN Y TRATAMIENTO DE ANEMIA.Se sabe que los pacientes anémicos que se someten a una cirugía electiva de cáncer colorrectal tienen tasas significativamente más altas de complicaciones posoperatorias y peores resultados.Mejorar las tasas de detección y tratamiento de la anemia en pacientes sometidos a resecciones electivas de colon y recto a través de una iniciativa de mejora de calidad.Comparamos una cohorte histórica de pacientes antes de la implementación de nuestro programa de detección de anemia y mejora de la calidad del tratamiento con una cohorte prospectiva después de la implementación.Hospital de atención terciaria.Todos los pacientes adultos con un nuevo diagnóstico de cáncer de colon o recto sin evidencia de enfermedad metastásica entre 2017 y 2019.Detección de anemia y programa de mejora de la calidad del tratamiento.El resultado primario fue el costo hospitalario por ingreso.Un total de 84 pacientes se sometieron a resección electiva de colon o recto antes de la implementación de nuestro proyecto de mejora de calidad de la anemia y 88 pacientes se sometieron a cirugía después. En la cohorte previa a la implementación, 44/84 (55,9 %) presentaban anemia en comparación con 47/99 (54,7 %) en la cohorte posterior a la implementación. Las tasas de detección (25 % a 86,4 %) y tratamiento (27,8 % a 63,8 %) aumentaron significativamente en la cohorte posterior a la implementación. El costo total medio por admisión se redujo significativamente en la cohorte posterior a la implementación (costo medio $16 827 vs. $25 796, p = 0,004); esta reducción significativa se observó incluso después de ajustar los factores de confusión relevantes (proporción de medias: 0,74, IC del 95 %: 0,65 a 0,85). El vínculo mecánico entre el tratamiento de la anemia y la reducción de costos sigue siendo desconocido. No hubo diferencias significativas en las tasas de transfusión de sangre, complicaciones o mortalidad entre los grupos.El diseño de antes y después está sujeto a sesgos temporales y de selección.Demostramos la implementación exitosa de un programa de detección y tratamiento de anemia. Este programa se asoció con un costo por admisión significativamente reducido. Este trabajo demuestra el valor y los beneficios posibles de la implementación de un programa de detección y tratamiento de la anemia. Consulte Video Resumen en http://links.lww.com/DCR/C15 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

While neoadjuvant chemoradiation therapy (nCRT) is accepted as standard of care for locally advanced rectal cancer, the approach to treatment of patients with clinically staged T3N0 disease has been increasingly debated. This study examines the accuracy of clinical staging for cT3N0 rectal cancer as recorded in the National Cancer Data Base and evaluates the role of nCRT in treating these patients.Total of 15,843 patients with clinically staged T3N0M0 rectal cancer who either received nCRT or proceeded to surgery-first met inclusion criteria. Propensity score matching was employed to balance the groups.23% of cT3N0 patients undergoing surgery-first were found to have pathologically positive nodes. Another 16% turned out to have stage II disease on surgical pathology. Survival curves for matched nCRT and surgery-first groups demonstrated a survival advantage for cT3N0 patients treated with nCRT.Poor clinical staging accuracy can result in both undertreatment and overtreatment of cT3N0 rectal cancer.

Robotic surgery is increasingly used for proctectomy, but the cost-effectiveness of this approach is uncertain. Robotic surgery is considered more expensive than open or laparoscopic approaches, but in certain situations has been demonstrated to be cost-effective. We examined the cost-effectiveness of open, laparoscopic, and robotic approaches to proctectomy from societal and healthcare system perspectives. We developed a decision-analytic model to evaluate one-year costs and outcomes of robotic, laparoscopic, and open proctectomy based on data from the available literature. The robustness of our results was tested with one-way and multi-way sensitivity analyses. Open proctectomy had increased cost and lower quality of life (QOL) compared with laparoscopy and robotic approaches. In the societal perspective, robotic proctectomy costs $497/case more than laparoscopy, with minimal QOL improvements, resulting in an incremental cost-effectiveness ratio (ICER) of $751,056 per quality-adjusted life year (QALY). In the healthcare sector perspective, robotic proctectomy resulted in $983/case more and an ICER of $1,485,139/QALY. One-way sensitivity analyses demonstrated factors influencing cost-effectiveness primarily pertained to the operative cost and the postoperative length of stay (LOS). In a probabilistic sensitivity analysis, the cost-effective approach to proctectomy was laparoscopic in 42% of cases, robotic in 39%, and open in 19% at a willingness-to-pay (WTP) of $100,000/QALY. Laparoscopic and robotic proctectomy cost less and have higher QALY than the open approach. Based on current data, laparoscopy is the most cost-effective approach. Robotic proctectomy can be cost-effective if modest differences in costs or postoperative LOS can be achieved.

Background Textbook outcome (TO) is a composite measure of quality representing the most ideal result that can be expected from a surgical encounter. TOs for hepatobiliary, bariatric and thoracic procedures have been described in the literature. The purpose of this study was to define and to benchmark the rates of TO for common procedures in patients with Inflammatory Bowel Disease (IBD). Methods The American College of Surgeons National Surgical Quality Improvement Project (NSQIP) participant user files (PUF) from 2011 to 2019 were examined. Adults undergoing surgery for Crohn’s disease or ulcerative colitis were included. Four index procedures were selected for the study using Current Procedural Terminology (CPT) codes: ileocolic resection (ICR), diverting loop ileostomy closure (DLIC), total abdominal colectomy (TAC), and ileal pouch construction (IPAA). Four criteria had to be satisfied completely to achieve TO: 1) no 30-day complications, 2) no unplanned return to operating room, 3) no 30-day readmission, and 4) length of hospital stay (LOS) less than or equal to a predetermined threshold for each procedure. The LOS thresholds were derived by surveying 12 colorectal surgeons at our institution about the ideal length of stay for each of index procedure. Relevant preoperative variables collected in the NSQIP PUF were analyzed with multivariable logistic regression to identify potential predictors of TO for each procedure. Results The study included 15,261 distinct surgical encounters containing 6,862 ICR, 1,149 DLIC, 3,835 TAC and 3,415 IPAA. The survey mean ideal LOS for each procedure was 3 days for ICR, 2 days for DLIC, 4 days for TAC, and 4 days for IPAA. Using the above definition, TO was achieved in 29% of ICR, 20% of DLIC, 46% of TAC, and 35% of IPAA. The rate of achieving TO increased over time for all four procedures studied (Figure 1). Multivariable logistic regression identified several unique positive and negative predictors of achieving TO. For ICR, male sex and ASA class 4 were significant negative predictors of TO (OR 0.73 [0.66–0.82] and 0.23 [0.07–0.86] respectively); while for TAC, older age and presence of wound infection [DL3] made TO less likely (OR 0.51 [0.35–0.75] and 0.45 [0.23–0.88] respectively); for IPAA, laparoscopic approach made TO much more likely [DL4] (OR 2.0; [1.62–2.46]). We identified no statistically significant predictors of TO for DLIC. Satisfying the LOS threshold was the greatest determinant of achieving TO for all four procedures studied. Conclusion In this study, we present the rates of TO for the four most common IBD operations as captured in NSQIP. TO has the advantage of being easy to interpret and can be followed over time to benchmark individual and institutional performance.

BACKGROUND: This an update of the review first published in 2009. Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) administered during the in‐hospital period is well‐documented, but the optimal duration of prophylaxis after surgery remains controversial. Some studies suggest that patients undergoing major abdominopelvic surgery benefit from prolongation of the prophylaxis up to 28 days after surgery. OBJECTIVES: To evaluate the efficacy and safety of prolonged thromboprophylaxis with LMWH for at least 14 days after abdominal or pelvic surgery compared with thromboprophylaxis administered during the in‐hospital period only in preventing late onset VTE. SEARCH METHODS: We performed electronic searches on 28 October 2017 in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS and registered trials (Clinicaltrials.gov October 28, 2017 and World Health Organization International Clinical Trials Registry Platform (ICTRP) 28 October 2017). Abstract books from major congresses addressing thromboembolism were handsearched from 1976 to 28 October 2017, as were reference lists from relevant studies. SELECTION CRITERIA: We assessed randomized controlled clinical trials (RCTs) comparing prolonged thromboprophylaxis (≥ fourteen days) with any LMWH agent to thromboprophylaxis during the admission period only followed by placebo or no thromoprophylaxis after discharge. The population consisted of persons undergoing abdominal or pelvic surgery for both benign and malignant pathology. The outcome measures included VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE)) as assessed by objective means (venography, ultrasonography, pulmonary ventilation/perfusion scintigraphy, spiral computed tomography (CT) scan or autopsy). We excluded studies exclusively reporting on clinical diagnosis of VTE without objective confirmation. DATA COLLECTION AND ANALYSIS: Review authors identified studies and extracted data. Outcomes were VTE (DVT or PE) assessed by objective means. Safety outcomes were defined as bleeding complications and mortality within three months after surgery. Sensitivity analyses were also performed with unpublished studies excluded, and with study participants limited to those undergoing solely open and not laparoscopic surgery. We used a fixed‐effect model for analysis. MAIN RESULTS: We identified seven RCTs (1728 participants) evaluating prolonged thromboprophylaxis with LMWH compared with in‐hospital thromoprophylaxis followed by placebo or no thromboprophylaxis after discharge. The searches resulted in 1632 studies, of which we excluded 1528. One hundred and four abstracts, eligible for inclusion, were assessed of which seven studies met the inclusion criteria. For the primary outcome, the incidence of overall VTE after major abdominal or pelvic surgery was 13.2% in the control group compared to 5.3% in the patients receiving out‐of‐hospital LMWH (Mantel Haentzel (M‐H) odds ratio (OR) 0.38, 95% confidence interval (CI) 0.26 to 0.54; I(2) = 28%; moderate‐quality evidence). For the secondary outcome of all DVT, seven studies, n = 1728, showed prolonged thromboprophylaxis with LMWH to be associated with a statistically significant reduction in the incidence of all DVT (M‐H OR 0.39, 95% CI 0.27 to 0.55; I(2) = 28%; moderate‐quality evidence). We found a similar reduction when analysis was limited to incidence in proximal DVT (M‐H OR 0.22, 95% CI 0.10 to 0.47; I(2) = 0%; moderate‐quality evidence). The incidence of symptomatic VTE was also reduced from 1.0% in the control group to 0.1% in patients receiving prolonged thromboprophylaxis, which approached significance (M‐H OR 0.30, 95% CI 0.08 to 1.11; I(2) = 0%; moderate‐quality evidence). No difference in the incidence of bleeding between the control and LMWH group was found, 2.8% and 3.4%, respectively (M‐H OR 1.10, 95% CI 0.67 to 1.81; I(2) = 0%; moderate‐quality evidence). No difference in mortality between the control and LMWH group was found, 3.8% and 3.9%, respectively (M‐H OR 1.15, 95% CI 0.72 to 1.84; moderate‐quality evidence). Estimates of heterogeneity ranged between 0% and 28% depending on the analysis, suggesting low or unimportant heterogeneity. AUTHORS' CONCLUSIONS: Prolonged thromboprophylaxis with LMWH significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications or mortality after major abdominal or pelvic surgery. This finding also holds true for DVT alone, and for both proximal and symptomatic DVT. The quality of the evidence is moderate and provides moderate support for routine use of prolonged thromboprophylaxis. Given the low heterogeneity between studies and the consistent and moderate evidence of a decrease in risk for VTE, our findings suggest that additional studies may help refine the degree of risk reduction but would be unlikely to significantly influence these findings. This updated review provides additional evidence and supports the previous results reported in the 2009 review.

BACKGROUND With increasing public reporting of outcomes and bundled payments, hospitals and providers are scrutinized for morbidity and mortality. The impact of patient transfer before colorectal surgery has not been well characterized in a risk-adjusted fashion. OBJECTIVE We hypothesized that hospital-to-hospital transfer would independently predict morbidity and mortality beyond traditional predictor variables. DESIGN We constructed a retrospective cohort of 158,446 patients who underwent colorectal surgery using the 2009-2013 American College of Surgeons National Surgical Quality Improvement Program database. SETTINGS The study was conducted at a tertiary care hospital. PATIENTS All of the patients who underwent colorectal surgery during the study period were included. Patients were excluded for unknown transfer status or transfer from a chronic care facility. MAIN OUTCOME MEASURES Baseline characteristics were compared by transfer status. Multivariate logistic regression was used to evaluate the impact of transfer on major complications and mortality. RESULTS A total of 7259 operations (4.6%) were performed after transfer. Transferred patients had higher rates of complications (p < 0.0001) with significant differences in unplanned endotracheal reintubation, bleeding, organ-space surgical site infection, wound dehiscence, postoperative sepsis, cardiac arrest requiring cardiopulmonary resuscitation, deep venous thrombosis, and myocardial infarction. Transferred patients also had longer hospital stays (9 vs 6 days; p < 0.0001) and a higher risk of death (13.2% vs 2.6%; p < 0.0001). On multivariate analysis, transferred patients had higher mortality rates despite risk adjustment (OR = 1.13 (95% CI, 1.02-1.25); p = 0.019) and were also more likely to have serious complications (OR = 1.12 (95% CI, 1.06-1.19); p < 0.001). LIMITATIONS We were unable to analyze outcomes beyond 30 days, and we did not have information on preoperative evaluation or the reason for patient transfer. CONCLUSIONS Hospital-to-hospital transfer independently contributed to patient morbidity and mortality in patients undergoing colorectal surgery. The impact of hospital transfer must be considered when evaluating surgeon and hospital performance, because the increased risk of serious complications or death is not fully accounted for by traditional methods.

The National Comprehensive Cancer Network recommends that patients who have colorectal cancer receive up to 4 weeks of postoperative out-of-hospital venous thromboembolism prophylaxis. Patients with IBD are at high risk for venous thromboembolism, but there are no recommendations for routine postdischarge prophylaxis.The purpose of this study was to compare the postoperative venous thromboembolism rate in IBD patients versus patients who have colorectal cancer to determine if IBD patients warrant postdischarge thromboembolism prophylaxis.This study is a retrospective review of IBD patients and patients who had colorectal cancer who underwent major abdominal and pelvic surgery.Data were collected from the American College of Surgeons National Surgical Quality Improvement Program (2005-2010).The primary outcome was 30-day postoperative venous thromboembolism in IBD patients and patients who had colorectal cancer. Risk factors for venous thromboembolism were analyzed with the use of univariate testing and stepwise logistic regression.A total of 45,964 patients were identified with IBD (8888) and colorectal cancer (37,076). The 30-day postoperative rate of venous thromboembolism in IBD patients was significantly higher than in patients who had colorectal cancer (2.7% vs 2.1%, p0.001). In a model with 15 significant covariates, the OR for venous thromboembolism was 1.26 (95% CI, 1.021-1.56; p = 0.03) for the IBD patients in comparison with the patients who have colorectal cancer.This study was limited by the retrospective design and the limitations of the data included in the database.Patients with IBD had a significantly increased risk for postoperative venous thromboembolism in comparison with patients who had colorectal cancer. Therefore, postdischarge venous thromboembolism prophylaxis recommendations for IBD patients should mirror that for patients who have colorectal cancer. This would suggest a change in clinical practice to extend out-of-hospital prophylaxis for 4 weeks in postoperative IBD patients.

Background Anastomotic complications, including leaks, strictures/stenoses, and bleeding, cause considerable mortality and morbidity after colorectal surgery. Objective The aim of this study was to assess whether the use of a synthetic, bioabsorbable staple line reinforcement material with circular staplers would reduce postoperative anastomotic leakage in patients with a colorectal, coloanal, or ileoanal anastomosis. Design This was a randomized study that compared outcomes in patients in whom the reinforcement material was used with those in patients who were not given the material. Settings This study was conducted at several centers in the United States. Patients The 258 patients (123 in the reinforcement group and 135 control subjects) underwent surgery for a variety of conditions, but most (n = 200) were treated for rectal cancer. Main outcome measures The main outcome measures were occurrence of anastomotic leaks and other complications according to the study protocol. Results There were no significant differences in the 2 study groups with respect to age, BMI, ASA physical status, operating time, diagnosis, previous chemoradiotherapy, surgical technique, or 30-day complications, except for a higher rate of small-bowel obstruction (p = 0.03) and anastomotic stricture (p = 0.006) in the control group. The overall anastomotic leak rate was 12% (bioabsorbable staple line reinforcement, 11.4%; no bioabsorbable staple line reinforcement, 12.6%). Limitations The study was nonblinded and was terminated at the first planned interim analysis because of insufficient power to detect an intergroup difference in anastomotic leak rate in the time allotted for the investigation. Conclusions Reinforcing the circular staple line in colorectal anastomoses with bioabsorbable material did not significantly affect the anastomotic leak rate but may have reduced anastomotic strictures. Most strictures did not require an anastomotic revision or delay in stoma closure. The bioabsorbable material may positively affect some aspects of the healing of circular stapled colorectal anastomoses; however, additional research on factors associated with anastomotic leakage is needed.

Length of stay following elective colorectal surgery is being reported as a quality measure in surgical outcome registries, such as the National Surgical Quality Improvement Program. Regional referral centers with large geographic catchment areas attract patients from significant distances.The aim of this study was to examine the effect of patient distance traveled, from primary residence to a tertiary care hospital, on length of stay in elective colorectal surgery patients.Retrospective population-based cohort study uses data obtained from the National Surgical Quality Improvement Program database.This study was conducted at a tertiary referral hospital.Data on 866 patients undergoing elective colorectal surgery from May 2003 to April 2011 were reviewed.Demographics, surgery-related variables, and distance traveled were analyzed relative to the length of stay.Of the 866 patients, 54% were men, mean age was 57 years, mean distance traveled was 145 miles (range, 2-2984 miles), and mean length of stay was 8.8 days. Univariate analysis showed a significant increase in length of stay with increased distance traveled (p = 0.02). Linear regression analysis revealed a significant association between increased length of stay and male sex (p = 0.006), increasing ASA score (p = 0.000), living alone (p = 0.009), and increased distance traveled (p = 0.028). For each incremental increase in log distance traveled, the length of stay increases by 2.5%.This is a retrospective review that uses National Surgical Quality Improvement Program data. It is not known how many patients left the hospital and did not return to their primary residence.In a model that controlled for variables, increased travel distance from a patient's residence to the surgical hospital was associated with an increase in length of stay. If length of stay is a reportable quality measure in patients undergoing colorectal surgery, significant travel distance should be accounted for in the risk adjustment model calculations.

Postoperative pain management with a continuous preperitoneal infusion (CPI) for locoregional anesthesia has been shown to have improved postoperative outcomes. This is the first direct comparison of CPI versus epidural infusion (EPI), both in conjunction with systemic analgesia.A retrospective review was performed of midline laparotomy cases, comparing the use of CPI with systemic patient-controlled analgesia to EPI with systemic patient-controlled analgesia for postoperative outcomes.A total of 240 cases from 2007 to 2009 were reviewed. There were 41.3% using CPI and 58.7% with EPI. There were no differences with respect to age, body mass index, or American Society of Anesthesiologists score between CPI and EPI cases. In a multivariate model, total hospital stay was 2 days shorter for the CPI group (P.001), and the total admission cost was less for CPI (by $6,164; P.001).The use of CPI results in decreased length of hospital stay, decreased number of days with a Foley catheter, and lower hospital costs, compared with EPI use. These findings show that the routine use of CPI for pain management after laparotomy is a safe alternative to EPI.

Immunosuppression used in transplantation is associated with an increased incidence of various cancers. Although the incidence of colorectal cancer in transplant patients seems to be equal to nontransplant population, the effects of immunosuppression on patients who develop colorectal cancer are not well defined. The purpose of this study was to define the characteristics and survival patterns of transplant patients developing de novo colorectal cancer.The Israel Penn International Transplant Tumor Registry was queried for patients with colorectal cancer. Analysis included patient demographics, age at transplantation and colorectal cancer diagnosis, tumor stage, and survival. Age and survival rates were compared to United States population-based colorectal cancer statistics using the National Cancer Institute Surveillance Epidemiology and End Results database.A total of 150 transplant patients with de novo colorectal cancer were identified: 93 kidney, 29 heart, 27 liver, and 1 lung. Mean age at transplantation was 53 years. Age at transplantation and colorectal cancer diagnosis was not significant for gender, race, or stage of disease. Compared to National Cancer Institute Surveillance Epidemiology and End Results database, transplantation patients had a younger mean age at colorectal cancer diagnosis (58 vs. 70 years; P0.001), and a worse five-year survival (overall, 44 vs. 62 percent, P0.001; Dukes A and B, 74 vs. 90 percent, P0.001; Dukes C, 20 vs. 66 percent, P0.001; and Dukes D, 0 vs. 9 percent, P = 0.08).Transplant patients develop colorectal cancer at a younger age and exhibit worse five-year survival rates than the general population. These data suggest that chronic immunosuppression results in a more aggressive tumor biology. Frequent posttransplantation colorectal cancer screening program may be warranted.

We present a 31-year-old woman who developed ascending colon intussusception several hours after a routine colonoscopy where random mucosal biopsies were obtained. She underwent an ileocolic resection, and pathology did not show an etiology for the intussusception. Colonic intussusception occuring without pathology and after minimal intervention is rare.

Apocrine carcinoma (AC) is an extremely rare skin appendage tumor, which is located at lower dermal and subcutaneous tissue. We report a case of an anal AC arising from an apocrine adenoma in the anal region, which is only the second case reported in this region. A 71-year-old male presented to clinic with soreness in the anal region for 6 weeks. An excisional biopsy was performed. Histologically, the lesion was poorly circumscribed, infiltrative, and was composed of small to medium sized glands extending to the surgical margins. There were centrally dilated large glands with duct-like openings into the mucosal surface. The larger central glands contain periodic acid-Schiff-positive eosinophilic acellular secretions. At the periphery, there were smaller glands with significant cytologic atypia and numerous mitoses. A diagnosis of AC was made making it the second case report of this very rare malignancy in this region. Although ACs usually do not have a fatal outcome, there have been case reports of distant metastases and even death from this disease, making histologic distinction of this malignancy from a benign apocrine adenoma important. Wide local excision is typically the treatment of choice, although Mohs micrographic surgery has also been used with similar success.

Locomotor stepping can be elicited by brain stimulation at various diencephalic sites under moderate levels of Nembutal. This study determined if locomotor initiation measured under anesthesia provides a valid measure of the intersite factors which determine initiation in the awake condition. We compared the latencies to initiate locomotor stepping elicited by electrical stimulation (50 microA, 0.5-msec pulses, 10 to 160 Hz) by rats tested while awake and unrestrained in a rotary runway or anesthetized and held in a stereotaxic apparatus. In the latter tests, initial anesthesia was provided by Nembutal (25 mg/kg) and 2% halothane and maintenance anesthesia was provided by 7 mg/kg as needed and local injections of lidocaine. For 30 sites in 16 rats, average locomotor initiation latency in the awake condition and the shortest latencies in the anesthetized condition were positively correlated (r = .78). Locomotion at sites with long latencies in the awake condition was frequently blocked in the anesthetized condition, but sites with short latencies were rarely blocked. The results indicate that the shortest locomotor latencies in the anesthetized condition approximate the latencies measured in the awake condition. It is concluded that the anesthetized condition can provide valid initiation measures, but sites with long latencies in the awake condition are prone to depression under anesthesia.

Mutations in the human adenomatous polyposis coli (APC) gene are thought to initiate colorectal tumorigenesis. The tumor suppressor function of APC is attributed primarily to its ability to regulate the WNT pathway by targeting the destruction of beta-catenin. We report here a novel role for APC in regulating degradation of the transcriptional co-repressor C-terminal-binding protein-1 (CtBP1) through a proteasome-dependent process. Further, CtBP1 suppresses the expression of intestinal retinol dehydrogenases, which are required for retinoic acid production and intestinal differentiation. In support of a role for CtBP1 in initiation of colorectal cancer, adenomas taken from individuals with familial adenomatous polyposis contain high levels of CtBP1 protein in comparison with matched, uninvolved tissue. The relationship between APC and CtBP1 is conserved between humans and zebrafish and provides a mechanistic model explaining APC control of intestinal retinoic acid biosynthesis.

At moderate levels of Nembutal, within the anesthetic range, locomotor stepping can be elicited by brain stimulation. We determined if Nembutal (7, 14 and 28 mg/kg) had different effects on locomotion elicited by stimulation at different brain regions. Two regions were compared: the medial forebrain bundle (MFB, 13 sites) and the areas medial and dorsal to it (MED/DORSAL, 20 sites). Locomotion was produced by electrical stimulation (50 μA, 0.5 msec pulses, 10 to 160 Hz) of unrestrained rats in a rotary runway. The latency to initiate locomotion and the time to complete 1 revolution of the rotary were measured. With no drug, MFB locomotion was initiated sooner but took longer to complete than MED/DORSAL locomotion. Nembutal at 7 mg/kg did not affect initiation of MFB or MED/DORSAL locomotion. Nembutal at 14 mg/kg shortened MFB initiations, but this dose prolonged MED/DORSAL initiations. Initiations with both types of sites were blocked with 28 mg/kg. The 7 and 14 mg/kg doses prolonged the locomotor completion times of the MFB sites but not of the MED/DORSAL sites. The results indicate that the response to Nembutal differs qualitatively for locomotion elicited by stimulation of the MFB and locomotion elicited by stimulation of the medial and dorsal hypothalamus. The mechanisms underlying the difference remain to be elucidated; they may relate to nonlocomotor behaviors also elicited by stimulation or to the motivational states reflected in those behaviors.