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Objectives: Although continuous positive airway pressure (CPAP) effectively prevents sleep apnea and reduces blood pressure, many patients do not use CPAP every night. This trial investigates cardiovascular effects after sleeping five nights without CPAP.

Methods: We randomized 100 patients (67 men and 33 women with a mean age 64±9 years) using CPAP treatment for moderate-to-severe sleep apnea to either withdraw treatment for five nights (n=50) or to continue with CPAP (n=50). The primary outcomes were arterial stiffness and 24h blood pressure.

Results: The 24h SBP increased by a mean of 2.8mmHg [95% confidence interval (CI) 0.2-5.4mmHg] (P=0.035) and DBP increased by a mean of 1.7mmHg (95% CI 0.1-3.3mmHg) (P=0.032) in the group without CPAP compared to the CPAP group. There was a significant effect on blood pressure in women but not in men. In women, SBP increased by 5.1mmHg (95% CI 1.0-9.5mmHg) (P=0.017) and DBP by 2.9mmHg (95% CI 0.4-5.6mmHg) (P=0.029). Arterial stiffness remained unaffected. Secondary outcomes that worsened in patients without CPAP included apnea-hypopnea index, oxygen desaturation index, hemoglobin levels, and daytime sleepiness.

Conclusion: Blood pressure is affected after five nights of CPAP interruption, along with a rapid return of sleep apneas, nocturnal hypoxic events, daytime sleepiness and increased hemoglobin levels, but arterial stiffness was not affected. Blood pressure was affected in women only, suggesting a sex-related CPAP effect on blood pressure.

Background: The 5-year survival rate in muscle-invasive bladder cancer (MIBC) is approximately 50%, cross over computed tomography (CT) stage in chemo-naive patients. Studies indicate lower survival rates in females when compared to males. The theories that explain the sex disparity are hormonal factors and delayed diagnosis for females. New investigations suggest that neoadjuvant chemotherapy (NAC) might be a possible method for bridging the gender survival gap. The aim of this study was to investigate whether complete treatment with NAC (≥3 cycles) prior to cystectomy reduces the gender gap in survival rates for MIBC and improves the surrogate marker of downstaging.

Methods: A multicenter retrospective cohort from five Swedish urological centers, from 1st January 2005 to 17th July 2023 based on NAC-eligible patients divided in NAC-receiving and non-NAC-receiving subgroups and further divided by sex (males and females). Survival was analyzed based on the Kaplan-Meier method, using log-rank test and adjusted analyses were made with the Cox regression model. Outcome measurements were overall survival (OS), disease-free survival (DFS), and downstaging.

Results: In the analysis of the total cohort (n=412), we could not detect any statistically significant differences in OS between NAC and non-NAC, nor between sexes, in the unadjusted analysis. In the adjusted analysis, we did not observe any significant differences in OS between sexes, either in total or within the NAC subgroups. Further analyzing the NAC group, we could see a significant increased downstaging rate in the NAC group compared to the non-NAC group (P<0.001) which indicates an increased survival in those receiving NAC treatment. There was no relationship between sexes and downstaging (P=0.72). Neither could we see any significant difference in downstaging between males and females in the NAC/non-NAC subgroups (P=0.41 and P=0.92, respectively).

Conclusions: NAC-eligible female and male MIBC patients who underwent radical cystectomy (RC) after at least three cycles of NAC, demonstrated similar OS and DFS. NAC seems to obliterate survival differences between genders in MIBC patients.

Background: Postoperative death measured 30 days after surgery is a conventional quality metric, whereas intervals up to 90 days are increasingly used, although data-driven time windows have scarcely been investigated.

Methods: The Swedish Colorectal Cancer Registry was used to identify all patients subjected resection for colorectal cancer between 2007 and 2020. All patients were followed up until 180 days after surgery. A join-point statistical hazard model was used to model a declining hazard to a transition point, followed by a stable death rate. This method was subsequently applied to describe postoperative deaths for the entire cohort and subgroups according to tumour location (colon and rectum).

Results: Some 56 096 patients electively operated on for colorectal cancer during the study interval were included, with a 30-day and 90-day fatality of 805 (1.43%) and 1458 (2.60%) patients respectively. The derived postoperative fatality window, after which the death rate transitioned to a stable rate, was 23.8 (95% c.i. 21.5 to 28.2) days after surgery. There was no significant difference in the time window between rectal cancer (22.9 days; 95% c.i. 15.1 to 28.4) and colon cancer (27.3 days; 95% c.i. 21.4 to 31.8) patients (P = 0.455). However, postoperative fatality time windows were extended in patients aged at least 80 years and with American Society of Anesthesiologists’ grade III or IV.

Conclusion: The traditional postoperative time window of 30 days was confirmed to be an appropriate metric in elective colorectal cancer surgery when evaluated with a hazards-based statistical framework. Importantly, this time window is influenced by older age and advanced co-morbidity, which could prompt increased vigilance for these patient groups.

Objectives: Sleep apnea is suggested to be associated with cancer risk, but results are heterogenous, and few studies are population-based. We aimed to assess risk associations between self-reported witnessed apnea during sleep and specific cancers in a population-based cohort.

Methods: This retrospective cohort study analyzed questions on witnessed sleep apnea in relation to incident cancer in the Northern Sweden Health and Disease Study. Cancer diagnoses were derived from the Swedish Cancer Registry and characterized as 12 different cancer types. Cox regression models adjusted for age, sex, ever smoking, body mass index, and education were used to assess risk associations.

Results: In total, 82,059 participants were included, and 10,668 (13 %) reported witnessed sleep apnea. They were followed for 9.0 (SD 4.7) years and 4030 incident cancers were diagnosed. Self-reported witnessed sleep apnea was independently associated with incident lung cancer with an adjusted hazard ratio (aHR), 1.78 (95 %CI 1.16, 2.73) p = 0.008 and breast cancer aHR, 1.39 (95 %CI 1.04, 1.84) p = 0.023. The risk for lung cancer was driven by an association with lung adenocarcinoma aHR, 2.16 (95 %CI 1.19, 3.91) p = 0.01. There was a multiplicative effect on ever smoking and reporting witnessed apnea for lung cancer with an aHR, 5.27 (95 %CI 3.07, 9.05) p < 0.001.

Conclusions: Self-reported witnessed sleep apnea is associated with an increased risk of developing lung- and breast cancer. There is a multiplicative effect of reporting witnessed sleep apnea and ever-smoking with an over 5 times increase on the hazard for lung cancer.

Background: Large bowel obstruction is a possible complication in patients undergoing neoadjuvant treatment for rectal cancer; however, it may be prevented by placing a pretreatment defunctioning stoma. The aim of this retrospective study was to investigate complication rates in patients with rectal cancer undergoing long-course neoadjuvant therapy, comparing those with and without a prophylactic stoma.

Methods: All patients with rectal cancer undergoing neoadjuvant therapy between 2007 and 2022 in Region Västerbotten, Sweden, were identified using the Swedish Colorectal Cancer Registry. Patients not planned for curative long-course neoadjuvant therapy and those requiring a stoma due to urgent bowel-related issues before treatment were excluded. The primary outcome was the incidence of complications between diagnosis and resection surgery or end of follow-up. The secondary outcomes were 30-day complications following resection, time to treatment (neoadjuvant therapy and surgery), and overall survival. Multivariable regression analysis was used, with adjustment for age, sex, American Society of Anesthesiologists fitness grade, and clinical tumour stage.

Results: Of 482 identified patients, 105 were analysed after exclusion. Among these, 22.9% (24 of 105) received a pretreatment stoma, whereas 77.1% (81 of 105) received upfront neoadjuvant therapy. The complication incidence before resection in the group with a defunctioning stoma and in the group without a defunctioning stoma was 75.0% (18 of 24) and 29.6% (24 of 81) respectively. A considerable number of complications were directly caused by the stoma surgery. Patients in the stoma group had an adjusted OR of 6.71 (95% c.i. 2.17 to 20.76) for any complication. However, for 30-day complications following resection, an adjusted non-significant OR of 2.05 (95% c.i. 0.62 to 6.81) was documented for the stoma group, in comparison with the control group. Neoadjuvant treatment was also delayed for the stoma group (adjusted mean time difference: 21 (95% c.i. 14 to 27) days), whereas the difference was not significant for the time to resection surgery. The median survival after diagnosis was 4.7 years in the stoma group and 12.2 years in the control group (P = 0.015); however, adjustment in the multivariable analysis rendered the estimate non-significant (HR 1.71 (95% c.i. 0.93 to 3.14)).

Conclusion: Patients with rectal cancer who receive a stoma before long-course neoadjuvant therapy, in the absence of urgent symptoms, experience more complications than those without a stoma and a delay with regard to the start of neoadjuvant treatment.

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.

Background: Without evidence, positive expiratory pressure therapy is a part of rehabilitation worldwide to prevent postoperative hypoxia. Reading aloud could be used as an alternative therapy as lung volumes increases while speaking. We aimed to investigate whether reading aloud is superior to positive expiratory pressure therapy for improving oxygen saturation after abdominal surgery.

Material and Methods: This crossover randomized controlled trial compared reading a text aloud with positive expiratory pressure therapy in patients on postoperative day 1 or 2 after upper gastrointestinal, colorectal, urological, or gynecological abdominal surgery at Umeå University Hospital, Sweden. The primary outcome was the change in peripheral oxygen saturation compared with baseline at 7 min after the intervention. The secondary outcome was transcutaneous carbon dioxide partial pressure change.

Results: This study included 50 patients of which 48 patients were analyzed. Peripheral oxygen saturation rapidly decreased to minimum values below baseline immediately after both interventions and then increased to values above baseline after reading aloud (1%, 95% confidence interval 0.2% to 1%, P = 0.004), but not after positive expiratory pressure therapy (−0.2%, 95% confidence interval −1% to 0.4%, P = 0.436). The difference in oxygen saturation was 1% (95% confidence interval 0.1% to 2%, P = 0.039) at 7 min after termination of the interventions. The interventions reduced transcutaneous carbon dioxide partial pressure by similar amounts.

Conclusions: This trial adds to the evidence against the use of positive expiratory pressure therapy after abdominal surgery. It is even slightly better to read aloud.

Introduction: Fibrillar collagens accumulate in the breast cancer stroma and appear as poorly defined spiculated masses in mammography imaging. The prognostic value of tissue type I collagen remains elusive in treatment-naïve and chemotherapy-treated breast cancer patients. Here, type I collagen mRNA and protein expression were analysed in 2 large independent breast cancer cohorts. Levels were related to clinicopathological parameters, prognostic biomarkers, and outcome.

Method: COL1A1 mRNA expression was analysed in 2509 patients with breast cancer obtained from the cBioPortal database. Type I collagen protein expression was studied by immunohistochemistry in 1395 women diagnosed with early invasive breast cancer.

Results: Low COL1A1 mRNA and protein levels correlated with poor prognosis features, such as hormone receptor negativity, high histological grade, triple-negative subtype, node positivity, and tumour size. In unadjusted analysis, high stromal type I collagen protein expression was associated with improved overall survival (OS) (HR = 0.78, 95% CI = 0.61-0.99, p = .043) and trended towards improved breast cancer–specific survival (BCSS) (HR = 0.65, 95% CI = 0.42-1.01, P = 0.053), although these findings were lost after adjustment for other clinical variables. In unadjusted analysis, high expression of type I collagen was associated with better OS (HR = 0.70, 95% CI = 0.55-0.90, P = .006) and BCSS (HR = 0.55, 95% CI = 0.34-0.88, P = .014) among patients not receiving chemotherapy. Strikingly, the opposite was observed among patients receiving chemotherapy. There, high expression of type I collagen was instead associated with worse OS (HR = 1.83, 95% CI = 0.65-5.14, P = .25) and BCSS (HR = 1.72, 95% CI = 0.54-5.50, P = .357).

Conclusion: Low stromal type I collagen mRNA and protein expression are associated with unfavourable tumour characteristics in breast cancer. Stromal type I collagen might predict chemotherapy response.

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.

Background: A previously published study at Norrland University Hospital, Umeå, Sweden, found that in 29.5% of patients with urinary bladder cancer (UBC) who underwent cystectomy, incorrect cT-stage (clinical T-stage) was registered in the Swedish National Register of Urinary Bladder Cancer (SNRUBC). Tumor in bladder diverticulum (TIBD) and tumor-associated hydronephrosis (TAH) were common causes for misclassification. Our aim was to further investigate cT-staging, as well as pathoanatomical markers, in the SNRUBC, compared to detailed data from medical records in a larger, retrospective multicenter cohort. Our secondary objective was to describe the frequency of pathoanatomical markers in pathology reports (PAD) after transurethral resection of the bladder (TURb): variant histology (VH), concomitant carcinoma in situ (CIS), lymphovascular invasion (LVI) and perineural invasion (PNI).

Methods: Medical records of 630 patients planned for radical cystectomy in the years 2009-2022 in the Northern Healthcare Region, Region of Gävleborg and Region of Västmanland were reviewed. Factors impacting risk of misclassification of cT-staging were identified through logistic regression. In TURb pathology reports, all comments on pathoanatomical markers were identified. For each pathoanatomical marker, respectively, comments were then registered as positive or negative. The absence of a comment on a marker was registered as "not commented".

Results: A total discrepancy rate of 36.5% was found between validated cT-staging and the SNRUBC, of which 13.3% were upstaged from <T2 to ≥T2. The results are presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Registrations with discrepancy were significantly associated with TIBD (OR: 10.28, 95% CI: 5.20-20.34), TAH (OR: 9.60, 95% CI: 6.12-15.10) and year of cystectomy 2009-2011 (OR: 3.38, 95% CI: 2.13-5.36). Incorrect CIS registration: 134 (35.8%); incorrect histology registration: 98 (25.6%). Total frequencies of recorded pathoanatomical markers in TURb-reports were for VH =23.8%, concomitant CIS =36.9%, LVI =30.4%, PNI =2.3%.

Conclusions: The SNRUBC has a significant prevalence of misclassification of cT-staging with a large proportion due to TAH and TIBD. Misclassification of VH and CIS is also common. Improved guidelines could increase consistency. Total rates of recorded pathoanatomical markers in TURb-reports are low.