The potential role of collagen type VII in breast cancer proliferation.

BACKGROUND: Breast cancer is the most common cancer in women. Cancer cells can persist in a prolonged dormant state for years without any clinical evidence of disease creating an urgent need to better understand the molecular mechanisms leading to relapse. This study aimed to identify extracellular matrix (ECM) components associated with hypoxia-induced breast cancer dormancy. The effects of selected ECM proteins on breast cancer cell proliferation were analyzed, along with their correlation with established prognostic markers in human breast cancer tissue. MATERIALS AND METHODS: Screening of extracellular matrix proteins was performed in hypoxia-induced dormant MCF-7 breast cancer cells. Proliferation of MCF-7 cells in vitro was subsequently determined in the presence of recombinant ColVII. Adipose tissue-derived mesenchymal stem cells (AdMSCs) subpopulation overexpressing ColVII were indirectly isolated by ColVII receptor integrin-α6 specific antibodies. AdMSCs- MCF-7 3D spheroid cultures were generated to model solid tumour conditions. In addition, the association between ColVII and various prognostic markers was evaluated in clinical samples of human breast cancer tissue. RESULTS: Dormant MCF-7 cells showed an elevated expression of ColVII while MCF-7 cells cultured on ColVII exhibited reduced proliferation in vitro. In AdMSCs-MCF-7 3D spheroids, a reduced proliferation of MCF-7 cells was observed in Int-α6+/ ColVIIhigh compared with Int-α6-/ ColVIIlow AdMSCs spheroids. In human tissue, high ColVII expression correlated to several positive prognostic markers. Staining for Cytokeratin-5 revealed that ColVIIhigh-expressing cells were predominantly myoepithelial cells. CONCLUSION: ColVII is associated with reduced proliferation of breast cancer cells in vitro. ColVII is strongly expressed in myoepithelial cells and in breast cancer tissue the high ColVII expression correlates with several well-known positive prognostic markers, highlighting its potential as a prognostic marker in breast cancer.

Anastomotic Leakage in Relation to Type of Mesorectal Excision and Defunctioning Stoma Use in Anterior Resection for Rectal Cancer.

BACKGROUND: Anastomotic leakage after anterior resection for rectal cancer is more common after total mesorectal excision compared to partial mesorectal excision but might be mitigated by a defunctioning stoma. OBJECTIVE: The aim is to assess how anastomotic leakage is affected by type of mesorectal excision and defunctioning stoma use. DESIGN: This is a retrospective multicenter cohort study evaluating anastomotic leakage after anterior resection. Multivariable Cox regression with HRs and 95% CIs was used to contrast mesorectal excision types and defunctioning stoma use with respect to anastomotic leakage, with adjustment for confounding. SETTINGS: This multicenter study included patients from 11 Swedish hospitals between 2014 and 2018. PATIENTS: Patients who underwent anterior resection for rectal cancer were included. MAIN OUTCOMES MEASURES: Anastomotic leakage rates within and after 30 days of surgery are described up to 1 year after surgery. RESULTS: Anastomotic leakage occurred in 24.2% and 9.0% of 1126 patients operated with total and partial mesorectal excision, respectively. Partial compared to total mesorectal excision was associated with a reduction in leakage, with an adjusted HR of 0.46 (95% CI, 0.29-0.74). Early leak rates within 30 days were 14.9% with and 12.5% without a stoma, whereas late leak rates after 30 days were 7.5% with and 1.9% without a stoma. After adjustment, defunctioning stoma was associated with a lower early leak rate (HR 0.47; 95% CI, 0.28-0.77). However, the late leak rate was nonsignificantly higher in patients with defunctioning stomas (HR 1.69; 95% CI, 0.59-4.85). LIMITATIONS: This study was limited by its retrospective observational study design. CONCLUSIONS: Anastomotic leakage is common up to 1 year after anterior resection for rectal cancer, where partial mesorectal excision is associated with a lower leak rate. Defunctioning stomas seem to decrease the occurrence of leakage, although partially by only delaying the diagnosis. See Video Abstract . FUGA ANASTOMTICA SEGN EL TIPO DE EXCISIN MESORRECTAL Y LA CONFECCIN DE OSTOMA DE PROTECCIN EN LA RESECCIN ANTERIOR POR CNCER DE RECTO: ANTECEDENTES:La fuga anastomótica después de una resección anterior por cáncer de recto es más frecuente después de la excisión total del mesorrecto comparada con la excisión parcial del mismo, pero podría mitigarse con la confección de ostomías de protección.OBJETIVO:El objetivo es evaluar cómo la fuga anastomótica se ve afectada según el tipo de excisión mesorrectal y la confección de una ostomía de protección.DISEÑO:Estudio de cohortes multicéntrico y retrospectivo que evalúa la fuga anastomótica después de la resección anterior. Se aplicó la regresión multivariada de Cox con los índices de riesgo (HR) y los intervalos de confianza (IC) al 95% para contrastar los tipos de excisión mesorrectal y el uso de otomías de protección con respecto a la fuga anastomótica, realizando ajustes respecto a las variables de confusión.AJUSTES:El presente estudio multicéntrico incluyó pacientes de 11 hospitales suecos entre 2014 y 2018.PACIENTES:Se incluyeron todos aquellos sometidos a resección anterior por cáncer de recto.PRINCIPALES MEDIDAS DE RESULTADOS:Las tasas de fuga anastomótica dentro y después de los 30 días de la cirugía fueron descritos hasta un año mas tarde al acto quirúrgico.RESULTADOS:La fuga anastomótica ocurrió en el 24,2% y el 9,0% de 1126 pacientes operados por excisión total y parcial del mesorrecto respectivamente.La excisión parcial del mesorrecto en comparación con la total se asoció con una reducción de la fuga, HR ajustado de 0,46 (IC del 95 %: 0,29 a 0,74). Las tasas de fuga temprana dentro de los 30 días fueron del 14,9 % con y el 12,5 % sin estoma, mientras que las tasas de fuga tardía después de 30 días fueron del 7,5 % con y el 1,9 % sin estoma.Después del ajuste de variables de confusión, las ostomías de protección se asociaron con una tasa de fuga temprana más baja (HR 0,47; IC 95 %: 0,28-0,77). Sin embargo, la tasa de fuga tardía no fue significativamente mayor en pacientes ostomizados (HR 1,69; IC 95%: 0,59-4,85).LIMITACIONES:Las limitaciones del presente estudio estuvieron vinculadas con el diseño de tipo observacional y retrospectivo.CONCLUSIONES:La fuga anastomótica es común hasta un año después de la resección anterior por cáncer de recto, donde la excisión parcial del mesorrecto se asocia con una menor tasa de fuga. La confección de ostomías de protección parece disminuir la aparición de fuga anastomótica, aunque en parte sólo retrasen el diagnóstico. (Traducción-Dr. Xavier Delgadillo ).

A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.

Trait-environment interactions of saproxylic beetles as a guide to biodiversity conservation strategies.

Conservation of biodiversity requires in-depth knowledge of trait-environment interactions to understand the influence the environment has on species assemblages. Saproxylic beetles exhibit a wide range of traits and functions in the forest ecosystems. Understanding their responses to surrounding environment thus improves our capacity to identify habitats that should be restored or protected. We investigated potential interactions between ecological traits in saproxylic beetles (feeding guilds and habitat preferences) and environmental variables (deadwood, type and age of surrounding forest). We sampled beetles from 78 plots containing newly created high stumps of Scots pine and Silver birch in boreal forest landscapes in Sweden for three consecutive years. Using a model based approach, our aim was to explore potential interactions between ecological traits and the surrounding environment at close and distant scale (20 m and 500 m radius). We found that broadleaf-preferring beetle species are positively associated with the local broadleaf-originated deadwood and broadleaf-rich forests in the surrounding landscapes. Conifer-preferring species are positively associated with the local amount of coniferous deadwood and young and old forests in the surrounding landscape. Fungivorous and predatory beetles are positively associated with old forests in the surrounding landscapes. Our results indicate that both local amounts of deadwood and types of forests in the landscape are important in shaping saproxylic beetle communities. We particularly highlight the need to increase deadwood amounts of various qualities in the landscape, exempt older forests from production and to increase broadleaf-rich habitats in order to meet different beetle species' habitat requirements. Trait responses among saproxylic beetles provide insights into the significance of broadleaf forest and dead wood as essential attributes in boreal forest restoration, which helps conservation planning and management in forest landscapes.

Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia: A pilot study.

OBJECTIVES: Intraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs. METHODS: This is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis. RESULTS: In total, 46 patients, 48% females, mean age (range) 67 years (45-82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas. CONCLUSION: Intraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.

Defunctioning stoma before neoadjuvant treatment or resection of endoscopically obstructing rectal cancer.

AIM: To investigate whether patients with endoscopically untraversable rectal cancer may benefit from a defunctioning stoma created before neoadjuvant therapy or resectional surgery. METHODS: This retrospective study comprise patients diagnosed with rectal cancer during 2007-2020 in Region Västerbotten, Sweden. The primary outcome was time between diagnosis and any treatment, while survival and the incidence of complications were secondary outcomes. Excluded were patients without endoscopic obstruction, patients already having a stoma, patients with recurrent disease, palliative patients, and patients receiving a stoma shortly after diagnosis due to any urgent bowel-related complication. Data were obtained from the Swedish Colorectal Cancer Registry and medical records. Kaplan-Meier failure curves were drawn, and a multivariable Cox regression model was employed for confounding adjustment. RESULTS: Out of 843 patients, 57 remained after applying exclusion criteria. Some 12/57 (21%) patients received a planned stoma before treatment, and the remainder received upfront neoadjuvant therapy or surgery. Median time to any treatment was 51 days for the planned stoma group and 36 days for the control group, with an adjusted hazard ratio of 0.28 (95% confidence interval: 0.12-0.64). Complications occurred at a rate of 5/12 (42%) and 7/45 (16%) in the planned stoma group and control group, respectively. Survival was similar between groups. CONCLUSION: A planned stoma results in treatment delay, but it remains unclear whether this is clinically relevant. Complications were more common in the planned stoma group, although the data are limited. While larger studies are needed, it seems feasible to avoid defunctioning stomas even in endoscopically obstructing rectal cancers.

Parents' drinking, childhood hangover? Parental alcohol use, subjective health complaints and perceived stress among Swedish adolescents aged 10-18 years.

BACKGROUND: Alcohol abuse is not only harmful to the consumer but may also negatively impact individuals in the drinker's social environment. Alcohol's harm to others is vital to consider when calculating the true societal cost of alcohol use. Children of parents who have alcohol use disorder tend to have an elevated risk of negative outcomes regarding, e.g., health, education, and social relationships. Research on the general youth population has established a link between parental drinking and offspring alcohol use. However, there is a lack of knowledge regarding other outcomes, such as health. The current study aimed to investigate the associations between parental drinking and children's psychological and somatic complaints, and perceived stress. METHODS: Data were derived from a nationally representative sample, obtained from the 2010 Swedish Level-of-Living survey (LNU). Parents and adolescents (ages 10-18) living in the same households were interviewed independently. The final study sample included 909 adolescents from 629 households. The three outcomes, psychological and somatic complaints and perceived stress, were derived from adolescents' self-reports. Parents' self-reports of alcohol use, both frequency and quantity, were used to categorise adolescents as having abstaining, low-consuming, moderate-drinking, or heavy-drinking parents. Control variables included adolescents' gender, age, family structure, and household socioeconomic status. Linear and binary logistic regression analyses were performed. RESULTS: Parental heavy drinking was more common among adolescents living in more socioeconomically advantaged households and among adolescents living with two custodial parents or in reconstituted families. Adolescents with heavy-drinking parents reported higher levels of psychological and somatic complaints and had an increased likelihood of reporting stress, compared with those having moderate-drinking parents. These associations remained statistically significant when adjusting for all control variables. CONCLUSION: The current study's results show that parental alcohol consumption is associated with poorer offspring adolescent health. Public health policies that aim to reduce parental drinking or provide support to these adolescents may be beneficial. Further studies investigating the health-related outcomes among young people living with heavy-drinking parents in the general population are needed to gain more knowledge about these individuals and to implement adequate public health measures.

Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke-A Prospective Observational Study.

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4-8.5 and OR 5.7, 95% CI: 2.5-12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1-3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.

Effects of a palaeolithic diet on obstructive sleep apnoea occurring in females who are overweight after menopause-a randomised controlled trial.

BACKGROUND/OBJECTIVES: Obesity is the main risk factor for obstructive sleep apnoea, commonly occurring in females who are overweight after menopause. We aimed to study the effect of a palaeolithic diet on sleep apnoea in females with overweight after menopause from the population. METHODS: Seventy healthy, non-smoking females with a mean age of 60 years and a mean BMI of 33 kg/m2 were randomised to a palaeolithic diet or to a control low-fat diet according to Nordic Nutritional Recommendations, for 2 years. The apnoea-hypopnoea index was measured and daytime sleepiness was estimated during the intervention. RESULTS: The mean apnoea-hypopnoea index at baseline was 11.6 (95% CI 8.6-14.5). The mean weight loss was 7.2 kg (95% CI 5.3-9.2 kg) in the palaeolithic diet group and 3.9 kg in the control group (95% CI 1.9-5.9 kg); p < 0.021 for the group difference. The reduction in weight corresponded to a reduction in the apnoea-hypopnoea index in the palaeolithic diet group (r = 0.38, p = 0.034) but not in the control group (r = 0.08, p = 0.69). The apnoea-hypopnoea index was reduced in the palaeolithic diet group when the weight was reduced by more than 8 kg. Daytime sleepiness according to the Epworth Sleepiness Scale score and the Karolinska Sleepiness Scale score was unaffected by dietary group allocation. CONCLUSIONS: A substantial decrease in body weight of 8 kg was needed to achieve a reduction in sleep apnoea in this small trial of women who are overweight after menopause. The palaeolithic diet was more effective for weight reduction than a control low-fat diet and the reduction in sleep apnoea was related to the degree of weight decrement within this diet group. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00692536.

Gambling among 16-year-olds and associated covariates: A Nordic comparison.

Aims: This study aimed to compare the prevalence in different gambling types as well as problem gambling in the Nordic countries, examining gambling, leisure activities, school truancy, parental relations and consumption of alcohol and other substances as covariates for problem gambling. Methods: Cross-country data were provided by the European Survey Project on Alcohol and Other Drugs (ESPAD) 2015. Prevalence of gambling and potential covariates were analysed for Denmark, Finland, Iceland Norway and Sweden (N=13,172 respondents aged 16 years), while analyses regarding problem gambling only included countries that participated in the optional questions on gambling problems (Denmark, Finland and Sweden; N=8108). We tested variables for problem gambling by bivariate logistic regression and multivariate logistic regression. Results: Cross-country differences were found in gambling and problem gambling, as well as differences in covariates for problem gambling. Sweden had the lowest rate of problem gambling. No significant difference was found between Denmark and Finland. Reports of too much gaming, inhalants, slots, betting and online gambling were positively associated with problem gambling, while parental monitoring and parental caring had a negative association. The relevance of the covariates varied across countries. Conclusions: Results indicate that although gambling regulation and its implementation have an important impact on gambling behaviour, we need more research on social, economic and cultural factors and how youth understand and interact with them. Contexts and regulations in other related fields should inform gambling research, policies and interventions.

Monocytes and pyrophosphate promote mesenchymal stem cell viability and early osteogenic differentiation.

Pyrophosphate-containing calcium phosphate implants promote osteoinduction and bone regeneration. The role of pyrophosphate for inflammatory cell-mesenchymal stem cell (MSC) cross-talk during osteogenesis is not known. In the present work, the effects of lipopolysaccharide (LPS) and pyrophosphate (PPi) on primary human monocytes and on osteogenic gene expression in human adipose-derived MSCs were evaluated in vitro, using conditioned media transfer as well as direct effect systems. Direct exposure to pyrophosphate increased nonadherent monocyte survival (by 120% without LPS and 235% with LPS) and MSC viability (LDH) (by 16-19% with and without LPS). Conditioned media from LPS-primed monocytes significantly upregulated osteogenic genes (ALP and RUNX2) and downregulated adipogenic (PPAR-γ) and chondrogenic (SOX9) genes in recipient MSCs. Moreover, the inclusion of PPi (250 µM) resulted in a 1.2- to 2-fold significant downregulation of SOX9 in the recipient MSCs, irrespective of LPS stimulation or culture media type. These results indicate that conditioned media from LPS-stimulated inflammatory monocytes potentiates the early MSCs commitment towards the osteogenic lineage and that direct pyrophosphate exposure to MSCs can promote their viability and reduce their chondrogenic gene expression. These results are the first to show that pyrophosphate can act as a survival factor for both human MSCs and primary monocytes and can influence the early MSC gene expression. Graphical abstract.

Reasons Not to Drink Alcohol among 9th Graders in Sweden.

AIM: Alcohol is one of the leading contributors to the disease burden among young people. Drinking motives are one of the strongest factors influencing drinking behaviors among youth, yet we know little about reasons for why young people do not drink. The aim of the present study is to examine reasons for not drinking in a nationally representative sample of Swedish youth. DATA AND METHODS: Data from a survey of a nationally representative sample of students in year 9 (15-16 years old) was used. Data was collected in 2017 and the total sample comprise 5549 respondents. Ten items measured reasons not to drink alcohol. Comparisons were made between drinkers and nondrinkers in endorsement of the reasons for not drinking. A multivariable logistic regression model was fitted to examine the relative importance of the different reasons. RESULTS: That alcohol is bad for health and parents disapproval of drinking was the most commonly endorsed reasons both among drinkers and nondrinkers. The multivariable analysis showed that the strongest association with being a nondrinker was found for "Alcohol tastes horrible" (OR 2.995), "I have religious reasons for not drinking" (OR 2.775), "People who drink lose control in an unpleasant way" (OR 2.460) and "Drinking is too likely to lead to serious accidents" (OR 2.458). DISCUSSION AND CONCLUSIONS: Harm avoidance and religious reasons are the most important reasons not to drink among Swedish youth. Future research should examine how different reasons predict abstinence.

Hyperglycemia as a risk factor in pancreatic cancer: A nested case-control study using prediagnostic blood glucose levels.

OBJECTIVE: To determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples. METHODS: Prospective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test. RESULTS: The unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05-1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05-2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26-12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08-8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04-2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival. CONCLUSIONS: High fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.

Early postoperative pain as a marker of anastomotic leakage in colorectal cancer surgery.

PURPOSE: Even though anastomotic leakage after colorectal surgery is a major clinical problem in need of a timely diagnosis, early indicators of leakage have been insufficiently studied. We therefore conducted a population-based observational study to determine whether the patient's early postoperative pain is an independent marker of anastomotic leakage. METHODS: By combining the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry, we retrieved prospectively collected data on 3084 patients who underwent anastomotic colorectal surgery for cancer in 2014-2017. Postoperative pain, measured with the numerical rating scale (NRS), was considered exposure, while anastomotic leakage and reoperation due to leakage were outcomes. We performed logistic regression to evaluate associations, estimating odds ratios (ORs) and 95% confidence intervals (CIs), while multiple imputation was used to handle missing data. RESULTS: In total, 189 patients suffered from anastomotic leakage, of whom 121 patients also needed a reoperation due to leakage. Moderate or severe postoperative pain (NRS 4-10) was associated with an increased risk of anastomotic leakage (OR 1.69, 95% CI 1.21-2.38), as well as reoperation (OR 2.17, 95% CI 1.41-3.32). Severe pain (NRS 8-10) was more strongly related to leakage (OR 2.38, 95% CI 1.44-3.93). These associations were confirmed in multivariable analyses and when reoperation due to leakage was used as an outcome. CONCLUSION: In this population-based retrospective study on prospectively collected data, increased pain in the post-anaesthesia care unit is an independent marker of anastomotic leakage, possibly indicating a need for further diagnostic measures.

Mucosal blood flow in the remaining rectal stump is more affected by total than partial mesorectal excision in patients undergoing anterior resection: a key to understanding differing rates of anastomotic leakage?

PURPOSE: Anterior resection is the procedure of choice for tumours in the mid and upper rectum. Depending on tumour height, a total mesorectal excision (TME) or partial mesorectal excision (PME) can be performed. Low anastomoses in particular have a high risk of developing anastomotic leakage, which might be explained by blood perfusion compromise. A pilot study indicated a worse blood flow in TME patients in an open setting. The aim of this study was to further evaluate perianastomotic blood perfusion changes in relation to TME and PME in a predominantly laparoscopic context. METHOD: In this prospective cohort study, laser Doppler flowmetry was used to evaluate the perianastomotic colonic and rectal perfusion before and after surgery. The two surgical techniques were compared in terms of mean differences of perfusion units using a repeated measures ANOVA design, which also enabled interaction analyses between type of mesorectal excision and location of measurement. Anastomotic leakage until 90 days after surgery was reported for descriptive purposes. RESULTS: Some 28 patients were available for analysis: 17 TME and 11 PME patients. TME patients had a reduced blood perfusion postoperatively compared to PME patients in the aboral posterior area (mean difference: -57 vs 18 perfusion units; p = 0.010). An interaction between mesorectal excision type and anterior/posterior location was detected at the aboral level (p = 0.007). Two patients developed a minor leakage, diagnosed after discharge. CONCLUSION: Patients operated on using TME have a decreased blood flow in the aboral posterior quadrant of the rectum postoperatively compared to patients operated on using PME. This might explain differing rates of anastomotic leakage. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02401100.

Prophylactic Mastectomy: Postoperative Skin Flap Thickness Evaluated by MRT, Ultrasound and Clinical Examination.

BACKGROUND: Women with an increased hereditary risk of breast cancer can undergo prophylactic mastectomy (PM), which provides a significant, but not total, risk reduction. There is an ongoing discussion about how much skin and subcutaneous tissue should be resected to perform an adequate PM while leaving viable skin flaps. METHODS: Forty-five women who had undergone PM were examined with magnetic resonance tomography (MRT), ultrasound (US) and clinical examination (CE) by a plastic surgeon and a general surgeon to estimate skin flap thickness. RESULTS: The estimated mean skin flap thickness after PM was 13.3 (± 9.6), 7.0 (± 3.3), 6.9 (± 2.8) and 7.4 (± 2.8) mm following MRT, US, and CE performed by a plastic surgeon and a general surgeon, respectively. The mean difference in estimated skin flap thickness was significant between MRT and the other measuring methods, while there was no significant difference between US and CE, nor between CE performed by the surgeons. The mean skin flap thickness was significantly affected by the age at PM. Following PM, necrosis was detected in 7/23 (30.4%) of the breasts in skin flaps ≤ 5 mm and in 5/46 (10.9%) of the breasts in skin flaps > 5 mm (OR 6.29; CI 1.20-32.94; p = 0.03). CONCLUSION: The odds of getting postoperative necrosis was > 6 times higher in skin flaps ≤ 5 mm. Thus, if the degree of remaining glandular tissue is acceptably low, it is desirable to create skin flaps thicker than 5 mm to prevent wound healing problems after the PM procedure.

The Impact of Anastomotic Leakage on Long-term Function After Anterior Resection for Rectal Cancer.

BACKGROUND: It is still not clear whether anastomotic leakage after anterior resection for rectal cancer affects long-term functional outcome. OBJECTIVE: This study aimed to evaluate how anastomotic leakage following anterior resection for rectal cancer influences defecatory, urinary, and sexual function. DESIGN: In this retrospective population-based cohort study, patients were identified through the Swedish Colorectal Cancer Registry, which was also used for information on the exposure variable anastomotic leakage and covariates. SETTINGS: A nationwide register was used for including patients. PATIENTS: All patients undergoing anterior resection for rectal cancer in Sweden from April 2011 to June 2013 were included. MAIN OUTCOME MEASURES: Outcome was any defecatory, sexual, or urinary dysfunction, assessed 2 years after surgery by a postal questionnaire. The association between anastomotic leakage and function was assessed in multivariable logistic and linear regression models, with adjustment for confounding. RESULTS: Response rate was 82%, resulting in 1180 included patients. Anastomotic leakage occurred in 7.5%. A permanent stoma was more common among patients with leakage (44% vs 9%; p < 0.001). Patients with leakage had an increased risk of aid use for fecal incontinence (OR, 2.27; 95% CI, 1.20-4.30) and reduced sexual activity (90% vs 82%; p = 0.003), whereas the risk of urinary incontinence was decreased (OR, 0.53; 95% CI, 0.31-0.90). A sensitivity analysis assuming that a permanent stoma was created because of anorectal dysfunction strengthened the negative impact of leakage on defecatory dysfunction. LIMITATIONS: Limitations include the use of a questionnaire that had not been previously validated, underreporting of anastomotic leakage in the register, and small patient numbers in the analysis of sexual symptoms. CONCLUSIONS: Anastomotic leakage was found to statistically significantly increase the risk of aid use due to fecal incontinence and reduced sexual activity, although the impact on defecatory dysfunction might be underestimated, because permanent stomas are sometimes fashioned because of anorectal dysfunction. Further research is warranted, especially regarding urogenital function. See Video Abstract at http://links.lww.com/DCR/B157. EL IMPACTO DE LA FUGA ANASTOMÓTICA EN LA FUNCIÓN A LARGO PLAZO DESPUÉS DE LA RESECCIÓN ANTERIOR POR CÁNCER RECTAL: Todavía no está claro si la fuga anastomótica después de la resección anterior por cáncer rectal afecta el resultado funcional a largo plazo.Evaluar cómo la fuga anastomótica después de la resección anterior para el cáncer rectal influye en la función defecatoria, urinaria y sexual.En este estudio de cohorte retrospectivo basado en la población, los pacientes fueron identificados a través del Registro Sueco de cáncer colorrectal, que también se utilizó para obtener información sobre la variable de exposición de fuga anastomótica y las covariables.Se utilizó un registro nacional para incluir pacientes.Se incluyeron todos los pacientes sometidos a resección anterior por cáncer de recto en Suecia desde abril de 2011 hasta junio de 2013.El resultado fue cualquier disfunción defecatoria, sexual o urinaria, evaluada dos años después de la cirugía mediante un cuestionario postal. La asociación entre la fuga anastomótica y la función se evaluó en modelos logísticos multivariables y de regresión lineal, con ajuste por confusión.La tasa de respuesta fue del 82%, lo que resultó en 1180 pacientes incluidos. La fuga anastomótica ocurrió en el 7,5%. Un estoma permanente fue más común entre los pacientes con fugas (44% vs. 9%; p <0.001). Los pacientes con fugas tenían un mayor riesgo de uso de ayuda para la incontinencia fecal (OR 2.27; IC 95% 1.20-4.30) y una menor actividad sexual (90% vs. 82%; p = 0.003), mientras que el riesgo de incontinencia urinaria disminuyó (OR 0.53; IC 95% 0.31-0.90). Un análisis de sensibilidad que supone que se creaba un estoma permanente debido a una disfunción anorrectal fortaleció el impacto negativo de la fuga en la disfunción defecatoria.Las limitaciones incluyen el cuestionario utilizado que no ha sido validado previamente, el subregistro de fugas anastomóticas en el registro y el pequeño número de pacientes en el análisis de síntomas sexuales.Se descubrió que la fuga anastomótica aumentaba estadísticamente de manera significativa el riesgo de uso de ayuda debido a la incontinencia fecal y la actividad sexual reducida, aunque el impacto en la disfunción defecatoria podría estar subestimada, ya que a veces los estomas permanentes se forman debido a la disfunción anorrectal. Se justifica la investigación adicional, especialmente con respecto a la función urogenital. Consulte Video Resumen en http://links.lww.com/DCR/B157. (Traducción-Dr. Gonzalo Hagerman).

Circulating levels of vascular endothelial growth factor and post-stroke long-term functional outcome.

OBJECTIVES: Vascular endothelial growth factor (VEGF) acts in angiogenesis and neuroprotection, although the beneficial effects on experimental ischemic stroke (IS) have not been replicated in clinical studies. We investigated serum VEGF (s-VEGF) in the acute stage (baseline) and 3 months post-stroke in relation to stroke severity and functional outcome. METHODS: The s-VEGF and serum high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in patients enrolled in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) at the acute time-point (median 4 days, N = 492, 36% female; mean age, 57 years) and at 3 months post-stroke (N = 469). Baseline stroke severity was classified according to the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes (3 months and 2 years) were evaluated using the modified Rankin Scale (mRS), dichotomized into good (mRS 0-2), and poor (mRS 3-6) outcomes. Multivariable logistic regression analyses were adjusted for covariates. RESULTS: The baseline s-VEGF did not correlate with stroke severity but correlated moderately with hs-CRP (r = .17, P < .001). The baseline s-VEGF was 39.8% higher in total anterior cerebral infarctions than in lacunar cerebral infarctions. In binary logistic regression analysis, associations with 3-month functional outcome were non-significant. However, an association between the 3-month s-VEGF and poor 2-year outcome withstood adjustments for age, sex, cardiovascular covariates, and stroke severity (per 10-fold increase in s-VEGF, odds ratio [OR], 2.56, 95% confidence interval [CI] 1.12-5.82) or hs-CRP (OR 2.53, CI 1.15-5.55). CONCLUSIONS: High 3-month s-VEGF is independently associated with poor 2-year functional outcome but not with 3-month outcome.

Postoperative pain after colorectal surgery.

PURPOSE: Postoperative pain is a keystone in perioperative programs, as pain negatively impacts recovery. This study aimed to evaluate pain after elective colorectal surgery and to identify risk factors for postoperative pain. METHODS: This prospective cohort study comprised consecutive patients undergoing elective colorectal surgery within the Enhanced Recovery after Surgery (ERAS) perioperative program between March 2013 and April 2017. The numeric rating scale (NRS) was used to estimate maximum pain. Logistic regression was used to model associations with the type of surgery, age, gender, and comorbidities. RESULTS: The cohort comprised 434 of 459 eligible patients. On the day of surgery to postoperative day 3, 50-64% of patients reported moderate to severe pain (NRS 4-10). Postoperative pain was similar for open and minimally invasive rectal surgery, while patients undergoing minimally invasive colonic surgery experienced more pain on the day of surgery and less pain on postoperative days 2 and 3 vs. open colonic surgery. Younger age was associated with more pain every postoperative day and by 0.7 NRS/10 years (95% CI 0.5-0.9, P < 0.001) on the day of surgery, while having diabetes type 2 was associated with less postoperative pain by - 1.3 NRS (95% CI - 2.4 to - 0.2) on the day of surgery. CONCLUSIONS: The majority, and young patients in particular, experience moderate to severe pain after open and minimally invasive colorectal surgery, despite following ERAS perioperative program. There is a need for effective and individualized analgesia after colorectal surgery, since the individual pain response to surgery is difficult to predict.

School ethos and adolescent gambling: a multilevel study of upper secondary schools in Stockholm, Sweden.

BACKGROUND: Gambling is not uncommon among adolescents, and a non-trivial minority has serious problems with gambling. Therefore, enhanced knowledge about factors that may prevent against problematic gambling among youth is needed. Prior research has shown that a strong school ethos, which can be defined as a set of attitudes and values pervading at a school, is associated with a lower inclination among students to engage in various risk behaviours. Knowledge about the link between school ethos and adolescent gambling is however scarce. The aim of the study was to investigate the association between teacher-rated school ethos and student-reported gambling and risk gambling, when controlling also for sociodemographic characteristics at the student- and the school-level. METHODS: Data from two separate cross-sectional surveys were combined. The Stockholm School Survey (SSS) was performed among 5123 students (aged 17-18 years) in 46 upper secondary schools, and the Stockholm Teacher Survey (STS) was carried out among 1061 teachers in the same schools. School ethos was measured by an index based on teachers' ratings of 12 items in the STS. Adolescent gambling and risk gambling were based on a set of single items in the SSS. Sociodemographic characteristics at the student-level were measured by student-reported information from the SSS. Information on sociodemographic characteristics at the school-level was retrieved from administrative registers. The statistical method was multilevel regression analysis. Two-level binary logistic regression models were performed. RESULTS: The analyses showed that higher teacher ratings of the school's ethos were associated with a lower likelihood of gambling and risk gambling among students, when adjusting also for student- and school-level sociodemographic characteristics. CONCLUSIONS: This study showed that school ethos was inversely associated with students' inclination to engage in gambling and in risk gambling. In more general terms, the study provides evidence that schools' values and norms as reflected by the teachers' ratings of their school's ethos have the potential to counteract unwanted behaviours among the students.