Hedgehog-interacting protein acts in the habenula to regulate nicotine intake.

Hedgehog-interacting protein (HHIP) sequesters Hedgehog ligands to repress Smoothened (SMO)-mediated recruitment of the GLI family of transcription factors. Allelic variation in HHIP confers risk of chronic obstructive pulmonary disease and other smoking-related lung diseases, but underlying mechanisms are unclear. Using single-cell and cell-type-specific translational profiling, we show that HHIP expression is highly enriched in medial habenula (MHb) neurons, particularly MHb cholinergic neurons that regulate aversive behavioral responses to nicotine. HHIP deficiency dysregulated the expression of genes involved in cholinergic signaling in the MHb and disrupted the function of nicotinic acetylcholine receptors (nAChRs) through a PTCH-1/cholesterol-dependent mechanism. Further, CRISPR/Cas9-mediated genomic cleavage of the Hhip gene in MHb neurons enhanced the motivational properties of nicotine in mice. These findings suggest that HHIP influences vulnerability to smoking-related lung diseases in part by regulating the actions of nicotine on habenular aversion circuits.

Wide variation in surgical techniques to repair incisional hernias: a survey of practice patterns among general surgeons.

BACKGROUND: The purpose of this research was to examine the self-reported practice patterns of Canadian general surgeons regarding the elective repair of incisional hernias. METHODS: A mail survey was sent to all general surgeons in Canada. Data were collected regarding surgeon training, years in practice, practice setting and management of incisional hernias. Surgeons were asked to describe their usual surgical approach for a patient with a midline incisional hernia and a 10 × 6 cm fascial defect. RESULTS: Of the 1876 surveys mailed out 555 (30%) were returned and 483 surgeons indicated that they perform incisional hernia repair. The majority (62%) have been in practice > 10 years and 73% regularly repair incisional hernias. In response to the clinical scenario of a patient with an incisional hernia, 74% indicated that they would perform an open repair and 18% would perform a laparoscopic repair. Ninety eight percent of surgeons would use mesh, 73% would perform primary fascial closure and 47% would perform a component separation. The most common locations for mesh placement were intraperitoneal (46%) and retrorectus/preperitoneal (48%). The most common repair, which was reported by 37% of surgeons, was an open operation, with mesh, with primary fascial closure and a component separation. CONCLUSIONS: While almost all surgeons who perform incisional hernia repairs would use permanent mesh, there was substantial variation reported in surgical approach, mesh location, fascial closure and use of component separation techniques. It is unclear how this variability may impact healthcare resources and patient outcomes.

Timing of recurrences of TEM resected rectal neoplasms is variable as per the surveillance practices of one tertiary care institution.

Transanal endoscopic microsurgery (TEM) is widely used for the excision of rectal adenomas and early rectal adenocarcinoma. Few recommendations currently exist for surveillance of lesions excised by TEM. The purpose of this study was to review the surveillance practices and the patterns of recurrence among TEM resected lesions at a tertiary care hospital. A retrospective chart review was performed on all patients who underwent TEM for rectal adenoma or adenocarcinoma before June 2017. In our study population of 114 patients, the final pathology included 78 (68%) adenomas and 36 (32%) adenocarcinomas. Of the adenocarcinomas 23, 9, and 4 were T1, T2, T3 lesions, respectively. Of those, 25 patients opted for surveillance instead of further treatment. The most commonly recommended endoscopic surveillance strategy by our group for both adenomas and adenocarcinomas excised by TEM was flexible sigmoidoscopy every 6 months for 2 years. Recurrences occurred in 4/78 (5.1%) adenoma patients, all found within 16.9 months of surgery, and in 4/25 (16%) adenocarcinoma patients, found between 7.4 and 38.5 months post-surgery. Our data highlights the fact that the timing of recurrences post TEM surgery is variable. Further studies looking at recurrence patterns are needed in order to create comprehensive guidelines for surveillance of these patients.

Non-invasive molecularly-specific millimeter-resolution manipulation of brain circuits by ultrasound-mediated aggregation and uncaging of drug carriers.

Non-invasive, molecularly-specific, focal modulation of brain circuits with low off-target effects can lead to breakthroughs in treatments of brain disorders. We systemically inject engineered ultrasound-controllable drug carriers and subsequently apply a novel two-component Aggregation and Uncaging Focused Ultrasound Sequence (AU-FUS) at the desired targets inside the brain. The first sequence aggregates drug carriers with millimeter-precision by orders of magnitude. The second sequence uncages the carrier's cargo locally to achieve high target specificity without compromising the blood-brain barrier (BBB). Upon release from the carriers, drugs locally cross the intact BBB. We show circuit-specific manipulation of sensory signaling in motor cortex in rats by locally concentrating and releasing a GABAA receptor agonist from ultrasound-controlled carriers. Our approach uses orders of magnitude (1300x) less drug than is otherwise required by systemic injection and requires very low ultrasound pressures (20-fold below FDA safety limits for diagnostic imaging). We show that the BBB remains intact using passive cavitation detection (PCD), MRI-contrast agents and, importantly, also by sensitive fluorescent dye extravasation and immunohistochemistry.

Antibiotic use among older adults on an acute care general surgery service.

BACKGROUND: Antibiotics play an important role in the treatment of many surgical diseases that affect older adults, and the potential for inappropriate use of these drugs is high. Our objective was to describe antibiotic use among older adults admitted to an acute care surgery service at a tertiary care teaching hospital. METHODS: Detailed data regarding diagnosis, comorbidities, surgery and antibiotic use were retrospectively collected for patients 70 years and older admitted to an acute care surgery service. We evaluated antibiotic use (perioperative prophylaxis and treatment) for appropriateness based on published guidelines. RESULTS: During the study period 453 patients were admitted to the acute care surgery service, and 229 underwent surgery. The most common diagnoses were small bowel obstruction (27.2%) and acute cholecystitis (11.0%). In total 251 nonelective abdominal operations were performed, and perioperative antibiotic prophylaxis was appropriate in 49.5% of cases. The most common prophylaxis errors were incorrect timing (15.5%) and incorrect dose (12.4%). Overall 206 patients received treatment with antibiotics for their underlying disease process, and 44.2% received appropriate first-line drug therapy. The most common therapeutic errors were administration of second- or third-line antibiotics without indication (37.9%) and use of antibiotics when not indicated (12.1%). There was considerable variation in the duration of treatment for patients with the same diagnoses. CONCLUSION: Inappropriate antibiotic use was common among older patients admitted to an acute care surgery service. Quality improvement initiatives are needed to ensure patients receive optimal care in this complex hospital environment.

CONTEXTE: Les antibiotiques jouent un rôle important dans de nombreux cas de chirurgie chez les adultes âgés, et le risque d'utilisation inappropriée de ces médicaments est élevé. Notre objectif était de décrire l'utilisation des antibiotiques chez les patients âgés admis au service chirurgical d'urgence d'un centre hospitalier universitaire de soins tertiaires. MÉTHODES: Nous avons recueilli de manière rétrospective les données détaillées sur le diagnostic, les comorbidités, la chirurgie et l'utilisation d'antibiotiques chez les patients de 70 ans et plus admis dans un service chirurgical d'urgence. Nous avons évalué le bien-fondé du recours aux antibiotiques (prophylaxie et traitement périopératoire) en fonction des lignes directrices publiées. RÉSULTATS: Durant la période de l'étude, 453 patients ont été admis au service chirurgical d'urgence et 229 ont subi une chirurgie. Les diagnostics les plus fréquents étaient : occlusion de l'intestin grêle (27,2 %) et cholécystite aigüe (11,0 %). En tout, 251 interventions abdominales urgentes ont été effectuées et l'antibioprophylaxie périopératoire était justifiée dans 49,5 % des cas. Les erreurs les plus fréquentes en matière de prophylaxie ont été : moment mal choisi (15,5 %) et dose incorrecte (12,4 %). En tout, 206 patients ont reçu une antibiothérapie pour un processus pathologique sous-jacent et 44,2 % ont reçu un traitement antibiotique de première intention approprié. Les erreurs thérapeutiques les plus fréquentes concernaient l'administration d'antibiotiques de deuxième ou de troisième intention sans indication (37,9 %) et l'utilisation d'antibiotiques lorsque cela n'était pas indiqué (12,1 %). On a noté une variation considérable de la durée des traitements chez des patients porteurs de diagnostics semblables. CONCLUSION: L'utilisation inappropriée des antibiotiques a été fréquente chez les patients adultes admis dans un service chirurgical d'urgence. Des initiatives s'imposent sur le plan de l'amélioration de la qualité pour s'assurer ainsi que les patients reçoivent des soins optimaux dans cet environnement hospitalier complexe.

Angiographic severity does not correlate with fractional flow reserve in heavily calcified coronary arteries.

OBJECTIVES: To determine the relationship between severity of stenosis and hemodynamic significance in calcified coronary arteries. BACKGROUND: Severity of stenosis is widely used to determine the need for revascularization but the effect of lesion calcification on hemodynamic significance is not well understood. METHODS: Two hundred consecutive patients undergoing fractional flow reserve (FFR) testing of an intermediate coronary lesion with a pressure wire and intravenous infusion of adenosine were studied. Coronary calcium was quantified based upon radiopacities at the site of the stenosis on cineangiography using the method of Mintz et al. (0 = none or mild calcium, 1 = moderate calcium, 2 = severe calcium). RESULTS: Mean age was 61 ± 11 years, 66% were males, 87.5% had hypertension, 44.5% had diabetes, and 20.5% were current smokers. The mean coronary stenosis by quantitative coronary angiography was 60 ± 12% and the mean FFR was 0.83 ± 0.08. There were 109, 45, and 46 patients classified as Calcium Score of 0, 1, or 2, respectively. Compared to those with no/mild or moderate calcification, patients with severe coronary calcium were older and more likely to have chronic kidney disease and pulmonary disease. The correlation between angiographic severity and FFR decreased as lesion calcification increased [calcium score = 0 (R2 = 0.25, P < 0.005); calcium score = 1 (R2 = 0.11, P < 0.005); calcium score = 2 (R2 = 0.02, P = 0.35)]. CONCLUSIONS: In patients with heavily calcified coronary lesions, there was no association between angiographic stenosis and hemodynamic significance and FFR is needed to determine hemodynamic significance of intermediate lesions. © 2016 Wiley Periodicals, Inc.

The impact of adverse events on health care costs for older adults undergoing nonelective abdominal surgery.

BACKGROUND: Postoperative complications have been identified as an important and potentially preventable cause of increased hospital costs. While older adults are at increased risk of experiencing complications and other adverse events, very little research has specifically examined how these events impact inpatient costs. We sought to examine the association between postoperative complications, hospital mortality and loss of independence and direct inpatient health care costs in patients 70 years or older who underwent nonelective abdominal surgery. METHODS: We prospectively enrolled consecutive patients 70 years or older who underwent nonelective abdominal surgery between July 1, 2011, and Sept. 30, 2012. Detailed patient-level data were collected regarding demographics, diagnosis, treatment and outcomes. Patient-level resource tracking was used to calculate direct hospital costs (2012 $CDN). We examined the association between complications, hospital mortality and loss of independence cost using multiple linear regression. RESULTS: During the study period 212 patients underwent surgery. Overall, 51.9% of patients experienced a nonfatal complication (32.5% minor and 19.4% major), 6.6% died in hospital and 22.6% experienced a loss of independence. On multivariate analysis nonfatal complications (p < 0.001), hospital mortality (p = 0.021) and loss of independence at discharge (p < 0.001) were independently associated with health care costs. These adverse events respectively accounted for 30%, 4% and 10% of the total costs of hospital care. CONCLUSION: Adverse events were common after abdominal surgery in older adults and accounted for 44% of overall costs. This represents a substantial opportunity for better patient outcomes and cost savings with quality improvement strategies tailored to the needs of this high-risk surgical population.

CONTEXTE: Les complications postopératoires sont une cause évitable qui contribue grandement aux coûts hospitaliers élevés. Malgré le fait que les personnes âgées courent un risque accru de subir des complications ou des événements indésirables, peu de recherches ont étudié l'incidence de ces éléments sur les coûts d'hospitalisation. Nous nous sommes penchés sur la relation entre les coûts des soins de santé assumés par les malades hospitalisés et les complications postopératoires, la mortalité hospitalière et la perte d'autonomie auprès d'une population de patients de 70 ans et plus ayant subi une intervention chirurgicale abdominale non facultative. MÉTHODES: La cohorte prospective a été formée de patients consécutifs âgés de 70 ans et plus ayant subi une intervention chirurgicale abdominale non facultative entre le 1er juillet 2011 et le 30 septembre 2012. Des données détaillées concernant leur profil démographique, leur diagnostic, leur traitement et leurs résultats ont été recueillies. Le calcul des coûts hospitaliers directs est basé sur un suivi des ressources utilisées par les patients (en dollars canadiens, 2012). Au moyen d'une régression linéaire multiple, nous avons analysé la relation entre les complications, la mortalité hospitalière et la perte d'autonomie. RÉSULTATS: Pendant la période à l'étude, 212 patients ont subi une intervention chirurgicale. Parmi eux, 51,9 % ont subi une complication non mortelle (mineure dans 32,5 % des cas; majeure dans 19,4 % des cas), 6,6 % sont décédés à l'hôpital, et 22,6 % ont subi une perte d'autonomie. Une analyse multivariable a permis de conclure que les complications non mortelles (p < 0,001), la mortalité hospitalière (p = 0,021) et la perte d'autonomie à la sortie de l'hôpital (p < 0,001) étaient indépendamment associées aux coûts des soins de santé et qu'elles représentaient respectivement 30 %, 4 % et 10 % des coûts d'hospitalisation totaux. CONCLUSION: Les événements indésirables étaient fréquents dans le contexte des interventions chirurgicales abdominales réalisées sur des personnes âgées et représentaient 44 % des coûts totaux. Nous devons saisir cette occasion et nous doter de stratégies d'amélioration de la qualité adaptées aux besoins de cette population, à risque élevé sur le plan chirurgical, afin d'améliorer les résultats pour les patients et de diminuer les coûts.

The Impact of Nonelective Abdominal Surgery on the Residential Status of Older Adult Patients.

OBJECTIVE: To describe the change in residential status at discharge and 6 months after hospitalization among older adults who have undergone nonelective abdominal surgery and to identify risk factors associated with discharge to institution. BACKGROUND: Surgery in older adults may lead to a loss of independence that prevents them from returning to their preadmission residential status. Understanding the impact of surgery on residential status and risk factors for institutionalization is important for patient counseling, discharge planning, and resource allocation. METHODS: Community-dwelling patients aged 70 years and older who underwent nonelective abdominal surgery over a 15-month period were prospectively enrolled. Residential status before admission, at discharge, and 6 months after admission was assessed. Multiple logistic regression was used to identify factors associated with discharge to institution. RESULTS: Of the 197 patients who underwent surgery and survived to discharge, 30% were living alone before admission and 70% were living with others. At discharge, 72% of patients returned to their preadmission residential status and 22% were institutionalized. Six months after hospitalization, 55% of institutionalized patients had returned to community-living, and 79% of all patients had returned to their preadmission residential status. Change in residential status was associated with decreased quality of life. Increasing American Society of Anesthesiologists score, frailty, surgery for malignancy, and postoperative complications were associated with discharge to institution. CONCLUSIONS: The majority of older patients, including those who were discharged to an institution, returned to their preadmission residential status 6 months after nonelective abdominal surgery.

Management and outcomes of small bowel obstruction in older adult patients: a prospective cohort study.

BACKGROUND: The purpose of this research was to examine the morbidity, mortality and rate of recurrent bowel obstruction associated with the treatment of small bowel obstruction (SBO) in older adults. METHODS: We prospectively enrolled all patients 70 years or older with an SBO who were admitted to a tertiary care teaching centre between Jul. 1, 2011, and Sept. 30, 2012. Data regarding presentation, investigations, treatment and outcomes were collected. RESULTS: Of the 104 patients admitted with an SBO, 49% were managed nonoperatively and 51% underwent surgery. Patients who underwent surgery experienced more complications (64% v. 27%, p = 0.002) and stayed in hospital longer (10 v. 3 d, p < 0.001) than patients managed nonoperatively. Nonoperative management was associated with a high rate of recurrent SBO: 31% after a median follow-up of 17 months. Of the patients managed operatively, 60% underwent immediate surgery and 40% underwent surgery after attempted nonoperative management. Patients in whom nonoperative management failed underwent surgery after a median of 2 days, and 89% underwent surgery within 5 days. The rate of bowel resection was high (29%) among those who underwent delayed surgery. Surgery after failed nonoperative management was associated with a mortality of 14% versus 3% for those who underwent immediate surgery; however, this difference was not significant. CONCLUSION: These data suggest that some elderly patients with SBO may be waiting too long for surgery.

CONTEXTE: Le but de cette recherche était d'analyser la morbidité, la mortalité et le taux de récurrence de l'occlusion intestinale associés au traitement de l'occlusion intestinale grêle (OIG) chez des adultes âgés. MÉTHODES: Nous avons inscrit de manière prospective tous les patients de 70 ans ou plus présentant une OIG qui ont été admis dans un établissement de soins tertiaires entre le 1er juillet 2011 et le 30 septembre 2012. Nous avons recueilli les données concernant les tableaux cliniques, les épreuves diagnostiques, les traitements et leurs résultats. RÉSULTATS: Parmi les 104 patients admis pour OIG, 49 % ont été traités non chirurgicalement et 51 % ont subi une intervention chirurgicale. Les patients soumis à la chirurgie ont présenté davantage de complications (64 % c. 27 %, p = 0,002) et ont séjourné plus longtemps à l'hôpital (10 j. c. 3 j., p < 0,001) comparativement aux patients qui n'ont pas été opérés. La prise en charge non chirurgicale a été associée à un taux élevé de récurrences de l'OIG : 31 % après un suivi médian de 17 mois. Parmi les patients opérés, 60 % ont subi une chirurgie immédiate et 40 % ont subi leur chirurgie après une tentative de prise en charge non chirurgicale. Les patients chez qui la prise en charge non chirurgicale a échoué ont subi leur chirurgie après une période médiane de 2 jours et 89 % en l'espace de 5 jours. Le taux de résection intestinale a été élevé (29 %) chez ceux dont la chirurgie a été retardée. La chirurgie après une intervention non chirurgicale infructueuse a été associée à un taux de mortalité de 14 %, contre 3 % chez les patients immédiatement soumis à la chirurgie. Toutefois, cette différence s'est révélée non significative. CONCLUSION: Ces données laissent penser que certains patients âgés présentant une OIG attendent peut-être trop longtemps pour leur chirurgie.

Self-reported practice patterns and knowledge of rectal cancer care among Canadian general surgeons.

BACKGROUND: Our objective was to examine the knowledge and treatment decision practice patterns of Canadian surgeons who treat patients with rectal cancer. METHODS: A mail survey with 6 questions on staging investigations, management of low rectal cancer, lymph node harvest, surgical margins and use of adjuvant therapies was sent to all general surgeons in Canada. Appropriate responses to survey questions were defined a priori. We compared survey responses according to surgeon training (colorectal/surgical oncology v. others) and geographic region (Atlantic, Central, West). RESULTS: The survey was sent to 2143 general surgeons; of the 1312 respondents, 703 treat patients with rectal cancer. Most surgeons responded appropriately to the questions regarding staging investigations (88%) and management of low rectal cancer (88%). Only 55% of surgeons correctly identified the recommended lymph node harvest as 12 or more nodes, 45% identified 5 cm as the recommended distal margin for upper rectal cancer, and 70% appropriately identified which patients should be referred for adjuvant therapy. Surgeons with subspecialty training were significantly more likely to provide correct responses to all of the survey questions than other surgeons. There was limited variation in responses according to geographic region. Subspecialty-trained surgeons and recent graduates were more likely to answer all of the survey questions correctly than other surgeons. CONCLUSION: Initiatives are needed to ensure that all surgeons who treat patients with rectal cancer, regardless of training, maintain a thorough and accurate knowledge of rectal cancer treatment issues.

CONTEXTE: Notre objectif était d'évaluer les connaissances et les processus décisionnels thérapeutiques des chirurgiens canadiens qui traitent des patients atteints de cancer rectal. MÉTHODES: Un sondage envoyé par la poste comportant 6 questions sur les épreuves de stadification, la prise en charge du cancer du bas rectum, le prélèvement des ganglions lymphatiques, les marges chirurgicales et l'utilisation de traitements adjuvants a été envoyé à tous les chirurgiens généraux au Canada. Les réponses appropriées aux questions du sondage avaient été définies au préalable. Nous avons comparé les réponses au sondage selon la formation des chirurgiens (oncologie colorectale/chirurgicale c. autres) et selon la région (Atlantique, Centre, Ouest). RÉSULTATS: Le sondage a été envoyé à 2143 chirurgiens généraux; parmi les 1312 répondants, 703 traitent des patients atteints de cancer rectal. La plupart des chirurgiens ont répondu de façon appropriée aux questions concernant les épreuves de stadification (88 %) et la prise en charge du cancer du bas rectum (88 %). Seulement 55 % des chirurgiens ont correctement répondu à la question sur le nombre optimal de ganglions lymphatiques à prélever, soit 12 ganglions ou plus, 45 % ont donné 5 cm comme marge distale recommandée pour le cancer du haut rectum et 70 % ont déterminé de manière appropriée quels patients il faut orienter vers un traitement adjuvant. Les chirurgiens qui avaient reçu une formation spécialisée étaient significativement plus susceptibles de fournir des réponses exactes à toutes les questions du sondage comparativement aux autres chirurgiens. On a noté une variation limitée entre les réponses selon les régions. Les chirurgiens spécialisés et les nouveaux diplômés étaient plus susceptibles de répondre correctement à toutes les questions du sondage comparativement aux autres chirurgiens. CONCLUSION: Des initiatives s'imposent pour s'assurer qu'indépendamment de leur formation tous les chirurgiens qui traitent des patients atteints d'un cancer rectal maintiennent des connaissances complètes et exactes sur les enjeux thérapeutiques entourant le cancer rectal.

Population-based use of sphincter-preserving surgery in patients with rectal cancer: is there room for improvement?

BACKGROUND: Treatment of rectal cancer in North America has been associated with lower rates of sphincter-preserving surgery in comparison with other regions. It is unclear if these lower rates are due to patient, tumor, or treatment factors; thus, the potential to increase the use of sphincter-preserving surgery is unknown. OBJECTIVE: The aim of this study is to identify the factors associated with the use of sphincter-preserving surgery and to quantify the potential for an increase in sphincter preservation. DESIGN: This population-based retrospective cohort study used patient-level data collected through a comprehensive, standardized review of hospital inpatient and outpatient medical records and cancer center charts. SETTINGS: This study was conducted in all hospitals providing rectal cancer surgery in a Canadian province. PATIENTS: All patients with a new diagnosis of rectal cancer from July 1, 2002 to June 30, 2006 who underwent potentially curative radical surgery were included. MAIN OUTCOME MEASURES: Logistic regression was used to identify factors associated with receiving a permanent colostomy. Patients were categorized as having received an appropriate or potentially inappropriate colostomy based on a priori determined patient, tumor, operative, and pathologic criteria. RESULTS: Of 466 patients who underwent radical surgery, 48% received a permanent colostomy. There was significant variation in the rate of sphincter-preserving surgery among the 10 hospitals that provided rectal cancer care (12%-73%, p = 0.0001). On multivariate analysis, male sex, low tumor height, and increasing tumor stage were associated with the receipt of a permanent colostomy. Among patients who received a permanent stoma, 65 of 224 (29%) patients received a potentially inappropriate stoma. On multivariate analysis, male sex and treatment in a medium- or low-volume hospital was associated with the receipt of a potentially inappropriate colostomy. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: These data suggest that the receipt of a permanent colostomy by many patients with rectal cancer may be inappropriate, and there is potential to increase the use of sphincter-preserving surgery in patients with rectal cancer.

Surgeon knowledge contributes to the relationship between surgeon volume and patient outcomes in rectal cancer.

OBJECTIVE: To determine whether surgeon knowledge contributes to the relationship between surgeon procedure volume and patient outcomes in rectal cancer. BACKGROUND: Although previous research has shown that treatment by high-volume surgeons is associated with improved outcomes among patients with rectal cancer, the mechanisms for such an association are not well understood. METHODS: In 2009, a mail survey with 8 questions pertaining to rectal cancer care was created, modified for content validity, and sent to all general surgeons in Nova Scotia, Canada. Patients with rectal cancer, who were treated by the survey respondents between July 1, 2002, and June 30, 2006, were identified retrospectively, and a comprehensive standardized review of medical records was used to collect outcome data for this population-based cohort. The association between surgeon survey score (dichotomized into high- and low-score groups on the basis of the median score), surgeon procedure volume, and patient outcomes was examined. RESULTS: Of 521 patients who underwent treatment with curative intent from July 1, 2002, to June 30, 2006, 377 patients (72%) were treated by 25 surgeons who responded to the survey. After controlling for patient and tumor factors, patients treated by high-volume surgeons were more likely to receive a total mesorectal excision (TME) [odds ratio (OR) = 3.89; 95% confidence interval (CI), 2.20-5.83], more likely to undergo an adequate lymph node harvest (OR = 3.67; 95%CI, 2.36-5.70), less likely to have a permanent colostomy (OR = 0.53; 95%CI, 0.30-0.93), and less likely to develop local recurrence (HR = 0.54; 95%CI, 0.29-0.99). When surgeon survey score was included in the multivariate regression models, the relationship between surgeon procedure volume and permanent colostomy was diminished. There was a significant interaction between surgeon survey score and surgeon volume for the outcomes of use of TME (P < 0.01) and local recurrence (P = 0.01). CONCLUSIONS: These data suggest that surgeon knowledge may, at least in part, explain surgeon volume-associated differences in rectal cancer outcomes.

The impact of intraoperative cholangiography on recurrent pancreatitis and biliary complications in patients with gallstone pancreatitis.

INTRODUCTION: Although gallstone pancreatitis is initiated by the presence of stones in the common bile duct, the benefit associated with routine intraoperative cholangiography at the time of cholecystectomy in these patients is unclear. The purpose of this study, using population-based data, was to determine the impact of cholangiography on clinical outcomes after cholecystectomy for gallstone pancreatitis. METHODS: All patients who were admitted to hospital from January 1, 1997 to December 31, 2001 in Nova Scotia, Canada with pancreatitis who underwent cholecystectomy during the same admission were identified. The rates of recurrent pancreatitis and biliary complications after surgery were compared between patients who underwent cholecystectomy with intraoperative cholangiography ± common bile duct exploration and those who underwent cholecystectomy alone, using three linked administrative databases. RESULTS: Three hundred thirty-two patients were identified, 119 had cholangiography at the time of cholecystectomy and 213 did not. After a median follow-up of after 3.8 years, there was no difference in the rate of recurrent pancreatitis or biliary complications between those who had cholangiography ± common bile duct exploration at the time of surgery and those who did not; 13.4 versus 10.8 %, respectively (p = 0.55). CONCLUSIONS: These data suggest that intraoperative cholangiography does not improve outcomes after cholecystectomy for gallstone pancreatitis.

Surgical management of ulcerative colitis: a comparison of Canadian and American colorectal surgeons.

BACKGROUND: Ileal pouch anal anastomosis (IPAA) to surgically manage ulcerative colitis may involve multiple separate surgical procedures, impacting treatment costs, length of stay in hospital, complication rates and patient outcomes, and there is currently no accepted standard of care regarding the number of stages that should be performed. The purpose of this study was to compare the practice patterns of Canadian and American colorectal surgeons regarding the surgical management of ulcerative colitis. METHODS: A questionnaire was mailed to all practisng fellows of the American Society of Colon and Rectal Surgeons (ASCRS) in Canada and the United States. Surgeons were asked to describe their typical practices for 3 clinical scenarios. RESULTS: Questionnaires were mailed to 40 Canadian and 873 American ASCRS fellows with response rates of 86% and 62%, respectively. In the case of a patient who has had a prior colectomy, who is not taking steroids and in whom a tension-free IPAA is possible, 44% of Canadian surgeons would perform IPAA alone and 56% would perform IPAA with a loop ileostomy. In contrast, only 26% of American surgeons would perform IPAA alone and 74% would perform IPAA with a loop ileostomy (p = 0.002). In the case of a patient who has not had previous surgery, who is taking 10 mg/day of prednisone and in whom a tension-free IPAA is possible, the majority of both Canadian and American surgeons would perform an IPAA with a loop ileostomy (93% and 89%, respectively, p = 0.06). In the case of a patient who has not had previous surgery, who is taking 40 mg/day of prednisone and in whom a tension-free IPAA is possible, 45% of Canadian surgeons would perform a subtotal colectomy with an end ileostomy compared with 14% of American surgeons (p < 0.001). CONCLUSION: There are significant differences in the surgical management of ulcerative colitis between Canadian and American colorectal surgeons.

Habenular α5 nicotinic receptor subunit signalling controls nicotine intake.

Genetic variation in CHRNA5, the gene encoding the α5 nicotinic acetylcholine receptor subunit, increases vulnerability to tobacco addiction and lung cancer, but the underlying mechanisms are unknown. Here we report markedly increased nicotine intake in mice with a null mutation in Chrna5. This effect was 'rescued' in knockout mice by re-expressing α5 subunits in the medial habenula (MHb), and recapitulated in rats through α5 subunit knockdown in MHb. Remarkably, α5 subunit knockdown in MHb did not alter the rewarding effects of nicotine but abolished the inhibitory effects of higher nicotine doses on brain reward systems. The MHb extends projections almost exclusively to the interpeduncular nucleus (IPN). We found diminished IPN activation in response to nicotine in α5 knockout mice. Further, disruption of IPN signalling increased nicotine intake in rats. Our findings indicate that nicotine activates the habenulo-interpeduncular pathway through α5-containing nAChRs, triggering an inhibitory motivational signal that acts to limit nicotine intake.

Proximal diversion at the time of ileal pouch-anal anastomosis for ulcerative colitis: current practices of North American colorectal surgeons.

PURPOSE: Pelvic sepsis is a serious complication after ileal pouch-anal anastomosis for ulcerative colitis that may lead to pouch failure or poor function. Although a temporary loop ileostomy may be created at the time of ileal pouch-anal anastomosis to prevent or minimize the consequences of an anastomotic leak, research has suggested that an ileostomy can be safely omitted in selected patients. The purpose of this study was to examine the use of proximal diversion by colorectal surgeons at the time of ileal pouch-anal anastomosis for ulcerative colitis. METHODS: A questionnaire was mailed to all practicing fellows of The American Society of Colon and Rectal Surgeons in North America. Surgeons were asked to describe their typical practice for a number of clinical scenarios. RESULTS: Questionnaires were mailed to 913 American Society of Colon and Rectal Surgeons fellows, and 63 percent responded. For a patient who has had a prior colectomy and is not taking steroids, 27 percent of surgeons would perform ileal pouch-anal anastomosis alone, and 73 percent would perform ileal pouch-anal anastomosis with a loop ileostomy. For a patient who has not had previous surgery and is taking prednisone 40 mg/day, 16 percent of surgeons would perform a subtotal colectomy with an end ileostomy, 82 percent would perform a total proctocolectomy and ileal pouch-anal anastomosis with a loop ileostomy, and 2 percent would perform a total proctocolectomy and ileal pouch-anal anastomosis without an ileostomy. There was no relationship between practice setting, annual ileal pouch-anal anastomosis volume, or years in practice and surgeon response for either scenario. CONCLUSIONS: The majority of surgeons create a temporary loop ileostomy at the time of ileal pouch-anal anastomosis for ulcerative colitis.

Surgical site infections following colorectal surgery in patients with diabetes: association with postoperative hyperglycemia.

INTRODUCTION: Postoperative glycemic control reduces sternal infections following cardiac surgery in patients with diabetes mellitus (DM). The objective of this study was to examine the relationship between postoperative glycemic control and surgical site infections (SSI) in patients with DM undergoing colorectal resection. DISCUSSION: A cohort of patients with DM who underwent colorectal resection (April 2001-May 2006) at our institution were reviewed. SSI were defined by Centers for Disease Control criteria. From a study cohort of 149 patients, 24% had poor postoperative glycemic control (defined as a mean 48-h postoperative capillary glucose (MCG) >11.0 mmol/L or 200 mg/dL), and these patients developed SSI at a significantly higher rate than those with a 48-h MCG < or =11.0 mmol/L (29.7% vs. 14.3%; odds ratio (OR) 2.5, p = 0.03). On multivariate logistic regression, 48-h MCG >11.0 mmol/L was significantly associated with SSI (OR 3.6, p = 0.02), independent of the dose and regimen of postoperative insulin administration. In conclusion, 48-h MCG >11.0 mmol/L (200 mg/dL) was independently associated with increased SSI following colorectal resection in patients with DM. Prospective studies are required to validate this relationship, address the role of preoperative glycemic control, and examine strategies to improve glycemic control following colorectal resection.

Decreased brain reward function during nicotine withdrawal in C57BL6 mice: evidence from intracranial self-stimulation (ICSS) studies.

Deficits in brain reward function during nicotine withdrawal may serve as an important substrate for negative reinforcement that contributes to the persistence of the tobacco habit in human smokers. The ability to assess withdrawal-associated reward deficits in genetically modified mice may facilitate understanding of the neurobiological mechanisms of nicotine dependence. Here, we assessed the effects of nicotine withdrawal on brain reward function in mice, as measured by intracranial self-stimulation (ICSS) thresholds. Male C57BL6 mice were trained in a discrete-trial current-threshold ICSS procedure until stable reward thresholds were obtained. Mice then received experimenter-administered saline or nicotine (2 mg/kg/injection salt; x4 daily) injections for 7 consecutive days, and ICSS thresholds assessed for 3 days after cessation of injections. Thresholds were unaltered in nicotine- and saline-treated mice after cessation of injections, indicating that this treatment regimen was not sufficient to induce withdrawal-associated reward deficits. Next, mice were implanted subcutaneously with osmotic minipumps delivering a constant daily amount of saline or nicotine (24 mg/kg/day; free-base), with pumps surgically removed 13 days later. The nicotinic receptor antagonist mecamylamine (2 mg/kg) elevated ICSS thresholds in nicotine- but not saline-treated mice when administered 8-10 days after pump implantation. Similarly, reward thresholds were elevated in nicotine-treated mice 12-72 h after minipump removal. These data demonstrate that antagonist-precipitated or spontaneous withdrawal from nicotine delivered via osmotic minipumps induced reward deficits in mice. Further, these findings highlight the potential utility of the ICSS procedure for assessing this important affective component of nicotine withdrawal in genetically modified mice.

Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer.

PURPOSE: The purpose of this study was to examine the impact of the number of negative lymph nodes on survival in patients with stage III colon cancer. PATIENTS AND METHODS: Patients who underwent surgery for stage III colon cancer between January 1988 and December 1997 were identified from the Surveillance, Epidemiology and End Results cancer registry. The number of negative and positive nodes was determined for 20,702 eligible patients. Disease-specific survival was examined by substage according to the number of negative nodes identified. A proportional hazards model was constructed to determine the effect of the number of negative nodes on survival. RESULTS: For stage IIIB and IIIC patients, there was a significant decrease in disease-specific mortality as the number of negative nodes increased; cumulative 5-year cancer mortality was 27% in stage IIIB patients with 13 or more negative nodes identified versus 45% in those with three or fewer negative lymph nodes evaluated (P < .0001). In patients with stage IIIC cancer, those with 13 or more negative nodes had a 5-year mortality of 42% versus 65% in those with three or fewer negative lymph nodes evaluated (P < .0001). There was no association between the number of negative nodes identified and disease-specific survival for patients with stage IIIA disease. After controlling for the number of positive nodes, a higher number of negative nodes was found to be independently associated with improved disease-specific survival. CONCLUSION: The number of negative nodes is an important independent prognostic factor for patients with stage IIIB and IIIC colon cancer.