Magnetic resonance imaging of anal cancer: tumor characteristics and early prediction of treatment outcome.

PURPOSE: To analyze tumor characteristics derived from pelvic magnetic resonance imaging (MRI) of patients with squamous cell carcinoma of the anus (SCCA) before and during chemoradiotherapy (CRT), and to compare the changes in these characteristics between scans of responders vs. nonresponders to CRT. METHODS: We included 52 patients with a pelvic 3T MRI scan prior to CRT (baseline scan); 39 of these patients received an additional scan during week 2 of CRT (second scan). Volume, diameter, extramural tumor depth (EMTD), and external anal sphincter infiltration (EASI) of the tumor were assessed. Mean, kurtosis, skewness, standard deviation (SD), and entropy values were extracted from apparent diffusion coefficient (ADC) histograms. The main outcome was locoregional treatment failure. Correlations were evaluated with Wilcoxon's signed rank-sum test and Pearson's correlation coefficient, quantile regression, univariate logistic regression, and area under the ROC curve (AUC) analyses. RESULTS: In isolated analyses of the baseline and second MRI scans, none of the characteristics were associated with outcome. Comparison between the scans showed significant changes in several characteristics: volume, diameter, EMTD, and ADC skewness decreased in the second scan, although the mean ADC increased. Small decreases in volume and diameter were associated with treatment failure, and these variables had the highest AUC values (0.73 and 0.76, respectively) among the analyzed characteristics. CONCLUSION: Changes in tumor volume and diameter in an early scan during CRT could represent easily assessable imaging-based biomarkers to eliminate the need for analysis of more complex MRI characteristics.

"No association between disease modifying treatment and fatigue in multiple sclerosis".

BACKGROUND: Fatigue affects 60-90% of people with multiple sclerosis (MS). It reduces quality of life and the ability to work. The cause of fatigue in MS remains unknown. Several disease-modifying treatments (DMTs) slow the disease process in relapsing MS by suppressing neuroinflammation. We aimed to investigate if treatment with a DMT is associated with lower rates of fatigue. METHODS: In this cross-sectional study of the MS population in three counties in Norway, we used the Fatigue Scale for Motor and Cognitive Functions (FSMC) and the Hospital Anxiety and Depression Scale (HADS) to assess patient-reported fatigue, anxiety and depression. Clinical data were retrieved from the electronic patient record system. We categorized DMTs as high-efficacy therapy or moderate-efficacy therapy. High-efficacy drugs included fingolimod, natalizumab, ocrelizumab, rituximab, alemtuzumab, daclizumab, and autologous hematopoietic stem cell transplantation. Moderate-efficacy drugs included interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. We included persons with relapsing MS only. RESULTS: Of 1142 patients, 80% had fatigue. Fifty-six percent of the patients were on DMTs (25% on moderate-efficacy treatment and 30% on high-efficacy treatment), 18% had discontinued treatment and 26% had never received any DMT. Sex, level of disability as measured by the Multiple Sclerosis Severity Score, anxiety and depression were independently associated with fatigue. Moderate-efficacy treatment was associated with less fatigue, but not after adjustment for other variables. There was no association between high-efficacy treatment and fatigue. CONCLUSION: We found no independent relationship between the use of disease-modifying treatment and fatigue in MS.

Factors associated with discharge destination from acute care after moderate-to-severe traumatic injuries in Norway: a prospective population-based study.

BACKGROUND: Previous studies have demonstrated that the trauma population has needs for rehabilitation services that are best provided in a continuous and coordinated way. The discharge destination after acute care is the second step to ensuring quality of care. There is a lack of knowledge regarding the factors associated with the discharge destination for the overall trauma population. This paper aims to identify sociodemographic, geographical, and injury-related factors associated with discharge destination following acute care at trauma centers for patients with moderate-to-severe traumatic injuries. METHODS: A multicenter, population-based, prospective study was conducted with patients of all ages with traumatic injury [New Injury Severity Score (NISS) > 9] admitted within 72 h after the injury to regional trauma centers in southeastern and northern Norway over a 1-year period (2020). RESULTS: In total, 601 patients were included; a majority (76%) sustained severe injuries, and 22% were discharged directly to specialized rehabilitation. Children were primarily discharged home, and most of the patients ≥ 65 years to their local hospital. Depending on the centrality of their residence [Norwegian Centrality Index (NCI) 1-6, where 1 is most central], we found that patients residing in NCI 3-4 and 5-6 areas sustained more severe injuries than patients residing in NCI 1-2 areas. An increase in the NISS, number of injuries, or a spinal injury with an Abbreviated Injury Scale (AIS) ≥ 3 was associated with discharge to local hospitals and specialized rehabilitation than to home. Patients with an AIS ≥ 3 head injury (RRR 6.1, 95% Confidence interval 2.80-13.38) were significantly more likely to be discharged to specialized rehabilitation than patients with a less severe head injury. Age < 18 years was negatively associated with discharge to a local hospital, while NCI 3-4, preinjury comorbidity, and increased severity of injuries in the lower extremities were positively associated. CONCLUSIONS: Two-thirds of the patients sustained severe traumatic injury, and 22% were discharged directly to specialized rehabilitation. Age, centrality of the residence, preinjury comorbidity, injury severity, length of hospital stay, and the number and specific types of injuries were factors that had the greatest influence on discharge destination.

Fatigue in multiple sclerosis is associated with socioeconomic factors.

OBJECTIVES: Fatigue is one of the leading causes of reduced quality of life and inability to work in people with multiple sclerosis (pwMS). Currently, no treatment effectively ameliorates fatigue. We still know little about what causes fatigue and which factors may contribute to fatigue. Knowledge about socioeconomic factors' role in fatigue might help us recognize strategies for the management of fatigue. Our aim was to explore whether socioeconomic factors are associated with the presence or level of perceived fatigue. METHODS: This is a cross-sectional study of the MS population in three Norwegian counties. We used the Fatigue Scale for Motor and Cognitive Functions to assess self-reported fatigue, and obtained socioeconomic data from Statistics Norway and questionnaires. To assess self-reported anxiety and depression, we employed the Hospital Anxiety and Depression Scale. Clinical data were gathered from the hospital record system. RESULTS: The response rate was 64% (1599/2512). Seventy percent of the respondents were female, and the mean age was 52 years. Higher levels of education were associated with lower levels of fatigue. Receiving a disability pension, being divorced and having children were all factors associated with higher levels of fatigue, as were low parental education, low income, current smoking, and autoimmune comorbidities. We found a higher prevalence of anxiety and depression in pwMS with fatigue compared to those without fatigue CONCLUSION: Female sex, high level of disability, anxiety, depression and socioeconomic factors were independently associated with fatigue in contemporary patients with MS. These factors should be considered when devising management strategies.

Association of respiratory symptoms with body mass index and occupational exposure comparing sexes and subjects with and without asthma: follow-up of a Norwegian population study (the Telemark study).

BACKGROUND: Occupational exposure and increased body mass index (BMI) are associated with respiratory symptoms. This study investigated whether the association of a respiratory burden score with changes in BMI as well as changes in occupational exposure to vapours, gas, dust and fumes (VGDF) varied in subjects with and without asthma and in both sexes over a 5-year period. METHODS: In a 5-year follow-up of a population-based study, 6350 subjects completed a postal questionnaire in 2013 and 2018. A respiratory burden score based on self-reported respiratory symptoms, BMI and frequency of occupational exposure to VGDF were calculated at both times. The association between change in respiratory burden score and change in BMI or VGDF exposure was assessed using stratified regression models. RESULTS: Changes in respiratory burden score and BMI were associated with a ß-coefficient of 0.05 (95% CI 0.04 to 0.07). This association did not vary significantly by sex, with 0.05 (0.03 to 0.07) for women and 0.06 (0.04 to 0.09) for men. The association was stronger among those with asthma (0.12; 0.06 to 0.18) compared with those without asthma (0.05; 0.03 to 0.06) (p=0.011). The association of change in respiratory burden score with change in VGDF exposure gave a ß-coefficient of 0.15 (0.05 to 0.19). This association was somewhat greater for men versus women, with coefficients of 0.18 (0.12 to 0.24) and 0.13 (0.07 to 0.19), respectively (p=0.064). The estimate was similar among subjects with asthma (0.18; -0.02 to 0.38) and those without asthma (0.15; 0.11 to 0.19). CONCLUSIONS: Increased BMI and exposure to VGDF were associated with increased respiratory burden scores. The change due to increased BMI was not affected by sex, but subjects with asthma had a significantly larger change than those without. Increased frequency of VGDF exposure was associated with increased respiratory burden score but without statistically significant differences with respect to sex or asthma status.

Serum markers of cardiac complications in a systemic sclerosis cohort.

Primary cardiac involvement is one of the leading causes of mortality in systemic sclerosis (SSc), but little is known regarding circulating biomarkers for cardiac SSc. Here, we aimed to investigate potential associations between cardiac SSc and candidate serum markers. Serum samples from patients of the Oslo University SSc cohort and 100 healthy controls were screened against two custom-made candidate marker panels containing molecules deemed relevant for cardiopulmonary and/or fibrotic diseases. Left (LV) and right ventricular (RV) dysfunction was assessed by protocol echocardiography, performed within three years from serum sampling. Patients suspected of pulmonary hypertension underwent right heart catheterization. Vital status at study end was available for all patients. Descriptive analyses, logistic and Cox regressions were conducted to assess associations between cardiac SSc and candidate serum markers. The 371 patients presented an average age of 57.2 (± 13.9) years. Female sex (84%) and limited cutaneous SSc (73%) were predominant. Association between LV diastolic dysfunction and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (OR 0.41, 95% CI 0.21-0.78, p = 0.007) was identified. LV systolic dysfunction defined by global longitudinal strain was associated with angiopoietin 2 (ANGPT2) (OR 3.42, 95% CI 1.52-7.71, p = 0.003) and osteopontin (OPN) (OR 1.95, 95% CI 1.08-3.52, p = 0.026). RV systolic dysfunction, measured by tricuspid annular plane systolic excursion, was associated to markers of LV dysfunction (ANGPT2, OPN, and TRAIL) (OR 1.67, 95% CI 1.11-2.50, p = 0.014, OR 1.86, 95% CI 1.25-2.77, p = 0.002, OR 0.32, 95% CI 0.15-0.66, p = 0.002, respectively) and endostatin (OR 1.86, 95% CI 1.22-2.84, p = 0.004). In conclusion, ANGPT2, OPN and TRAIL seem to be circulating biomarkers associated with both LV and RV dysfunction in SSc.

Gastrointestinal symptom severity and progression in systemic sclerosis.

OBJECTIVES: To evaluate the severity and evolution of patient-reported gastrointestinal tract (GIT) symptoms in systemic sclerosis (SSc) patients, assess predictive factors for progression and determine the impact of standard of care treatment. METHODS: SSc patients from the Leiden and Oslo cohorts were included. We assessed clinical data and patient-reported GIT symptoms measured by the validated University of California, Los-Angeles Gastrointestinal-tract (UCLA-GIT) score at baseline and annually. GIT severity and progression was determined. Logistic regression was applied to identify risk factors associated with baseline GIT symptom severity. Linear mixed-effect models were applied to assess progression in GIT symptom burden and to identify predictive factors. We repeated all analysis in patients with early disease (inception cohort) to exclude the effect of longstanding disease and increase insights in development of GIT symptom burden early in the disease course. RESULTS: We included 834 SSc patients with baseline UCLA GIT scores, 454 from Leiden and 380 from Oslo. In the total cohort, 28% reported moderate-severe GIT symptoms at baseline, with increased risk for severity conferred by ACA, smoking and corticosteroid use, while use of calcium channel blockers appeared protective. In the inception cohort, 23% reported moderate-severe GIT symptoms at baseline, with increased risk for females and with smoking. Over time, symptom burden increased mainly for reflux/bloating. Female sex and ACA predicted GIT symptom progression. CONCLUSION: High GIT symptom burden is present early in SSc disease course. Both for prevalence and for progression of GIT symptom burden, female sex and smoking were identified as risk factors.

The impact of body mass index and height on risk for primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves in 1.7 million norwegian women and men: a prospective cohort study.

BACKGROUND: Primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves comprise a heterogenous group of pathology, dominantly represented by meningioma, nerve sheath tumours (NST) and glioma. Body height and body mass index (BMI) are risk factors for certain brain tumour subgroups, but no other study has specifically assessed height and BMI in relation to primary tumours of the spine and peripheral nerves in women and men. METHODS: In this prospective population-based cohort study height and weight were measured in 1.7 million adult Norwegian women and men at baseline. Incident cases of primary tumours arising from the spinal cord, spinal meninges, spinal and peripheral nerves during follow-up were identified by linkage to the National Cancer Registry. Tumour risk was assessed by Cox regression analyses in relation to height and BMI. RESULTS: During 49 million person-years of follow-up, 857 primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves were identified. Overweight and obesity were not associated with risk for all tumours or any tumour subgroup. Height was positively associated with risk for all tumours (HR per 10 cm increase: 1.30, 95% CI 1.16-1.46). The association between height and tumour risk varied between tumour subgroups: while height was not significantly associated with NST, height increased the risk for meningioma (HR 1.42, 95% CI 1.13-1.78) and glioma (HR 1.56, 95% CI 1.06-2.28). The strongest association between height and tumour risk was found for the glioma subgroup of ependymoma in women (HR 3.38, 95% CI 1.64-6.94). CONCLUSION: This study could not identify overweight and obesity as risk factors for primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves in women or men. Increasing body height was associated with increased tumour risk overall, but not universal for all tumour subgroups.Importance of the studyPrimary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves have received little focus in epidemiologic studies, although the incidence and histo-pathological tumour subgroups differ significantly from primary brain tumours. Risk factors for these tumours have hardly been assessed in previous studies. Height, overweight and obesity are known risk factors for several cancers, including certain brain tumour subgroups, such as meningioma.This is the first study to report the association between height, overweight and obesity and primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves. This includes tumour subgroups of meningioma, nerve sheath tumour, glioma and the most common spinal glioma subgroup of ependymoma. While overweight and obesity were not associated with either of the tumour subgroups, an association between increasing body height and risk for spinal meningioma and glioma, including ependymoma, was found. Nerve sheath tumour risk was not associated with increasing body height.

Effects of ischaemic postconditioning in aortic valve replacement: a multicenter randomized controlled trial.

OBJECTIVES: The effect of ischaemic postconditioning (IPost) on postcardioplegic cardiac function is not known. We hypothesized that IPost was cardioprotective in adult patients undergoing elective aortic valve replacement. METHODS: In a multicentre, prospective, randomized trial, patients (n = 209) were randomized to either a standard operation (controls) or postconditioning. Immediately before the cross-clamp was released, patients in the postconditioning group underwent 3 cycles of flow/non-flow (2 min each) of normothermic blood via the antegrade cardioplegia line. The primary end point was cardiac index. Secondary end points included additional haemodynamic measurements, biomarkers of cardiomyocyte injury, renal function parameters, intra- and postoperative arrhythmias and use of inotropic agents. RESULTS: There was no significant difference between the groups regarding cardiac index [mean between-group difference, 95% confidence interval (CI), 0.11 (-0.1 to 0.3), P = 0.27]. Postconditioning had no effect on other haemodynamic parametres. There was no between-group difference regarding troponin T or creatine kinase MB. Postconditioning reduced the relative risk for arrhythmias by 45% (P = 0.03) when postoperative atrial fibrillation and intraoperative ventricular fibrillation were combined. There were no differences in patients with/without diabetes, patients above/below 70 years of age or between the centres. However, after postconditioning, the cardiac index [95% CI, 0.46 (0.2-0.7), P = 0.001], cardiac output (P < 0.001), mean arterial pressure (P < 0.001) and left ventricular stroke work index (P < 0.001) were higher in males compared to females. CONCLUSIONS: IPost had no overall cardioprotective effects in patients undergoing aortic valve replacement but improved postoperative cardiac performance in men compared to women.

Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series.

During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1-2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate.

Maternal education has significant influence on progression in multiple sclerosis.

OBJECTIVE: The identification of potential risk factors for disease severity is of great importance in the treatment of multiple sclerosis. The influence of socioeconomic status on progression in multiple sclerosis (MS) is sparsely investigated. Our aim was to investigate how socioeconomic status in adolescence influences disease progression in later life. METHODS: A total of 1598 patients with multiple sclerosis from a well-defined population in Norway were included. Detailed information on disease progression, measured by expanded disability status scale (EDSS) and multiple sclerosis severity score (MSSS), were combined with data on socioeconomic factors. We used residency and parental level of education at patients' age 16 and exposure to second-hand smoking as a measure of socioeconomic status in adolescence, adjusting for the same variables as well as use of disease modifying treatments at prevalence date 01.01.18. RESULTS: High maternal level of education at patients' age 16 was significantly associated with less pronounced disease progression measured by MSSS (ß-coefficient -0.58, p = 0.015), younger age and lower EDSS at disease onset, and shorter time from onset to diagnosis. No significant associations were found for paternal education level and MSSS. The use of any disease modifying treatment before prevalence date was significantly associated with disease progression (ß-coefficient -0.49, p=0.004), while residence, current and second-hand smoking were not. CONCLUSION: This study on a population-based, real-world cohort shows that the parental level of education has a significant impact on a timely diagnosis of MS. In addition to disease modifying treatment, maternal level of education also had an impact on disease progression in later life.

Thymectomy in Juvenile Myasthenia Gravis Is Safe Regarding Long Term Immunological Effects.

Thymectomy is an established treatment in adult MG and also recommended for the treatment of post-pubertal onset juvenile MG. Whether the youngest children should be thymectomized is still debated. Signs of premature aging of the immune system have been shown in studies on early perioperative thymectomy in children with congenital heart defect. In this retrospective cohort study the objective was to investigate the long-term effects of treatment related thymectomy on T cell subsets and T cell receptor rearrangement excision circles (TRECs) in peripheral blood of juvenile myasthenia gravis (MG) patients, as well as clinical occurrence of autoimmune disorders, malignancies and infectious diseases. Forty-seven patients with onset of myasthenia gravis before the age of 19 years were included; 32 (68.1%) had been thymectomized and 15 (31.8%) had not. They were studied at varying times after thymectomy (7-26 years). We found a significant lower number of naïve helper T cells (CD4+CD45RA+) with an increased proportion of memory helper T cells (CD4+CD45RO+), and a significant lower number of naïve cytotoxic T cells (CD8+CD27+CD28+) in the thymectomized patients. In addition they showed a significant reduction in the number of TRECs and proportion of recent thymic emigrants (RTE) compared to non-thymectomized patients. In none of them an increased frequency of malignancies or infections was found. Our findings indicate a premature aging of the immune system after thymectomy in juvenile MG, but associated clinical consequences could not be verified.

Preoperative CTC-Detection by CellSearch® Is Associated with Early Distant Metastasis and Impaired Survival in Resected Pancreatic Cancer.

In patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of CTCs-presence on the patterns of recurrence and survival in 98 patients resected for PDAC with 5-10 years of follow-up. Preoperative samples were analysed by the CellSearch® system for EpCAM+/DAPI+/CK+/CD45-CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median disease-free survival (DFS) of 3.3 vs. 9.2 months and a median cancer specific survival (CSS)of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 patients developed distant metastases (DM) and 29 developed isolated local recurrence (ILR) as the first sign of cancer relapse. All patients with CTCs experienced DM. pN-status and histological grade >2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. Preoperative parameters did not affect clinical outcome. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. Preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future.

Preoperative inhibitory control predicts weight loss 1 year after bariatric surgery.

OBJECTIVE: Executive function (EF) and, in particular, inhibitory control have been associated with weight loss (WL) in behavioural WL treatment for obesity. Few studies have focused on the relationship between preoperative inhibitory control and post-operative WL following bariatric surgery, and the potential mediating role of maladaptive eating behaviours is unclear. The aim of this study was to investigate preoperative executive function as a predictor of WL at 1 year following bariatric surgery. Additionally, we aimed to explore the mediating role of postoperative compulsive grazing in the relationship between inhibitory control and WL. METHOD: A prospective observational study in which participants completed neuropsychological testing 30 days before and 1 year following surgery (n = 61/80; 76% follow-up). Participants were 80% female, with an average age of 41 years. Approximately 54% underwent gastric bypass, 26% gastric sleeve and 20% had one anastomosis gastric bypass. Regression analyses were employed to examine the relationship between preoperative EF and percentage total weight loss (%TWL), and structural equation modelling was used to examine compulsive grazing as a mediator. RESULTS: After adjusting for control variables, preoperative inhibitory control explained 8% of the variance in %TWL (p ≤ 0.05). Preoperative working memory was not significantly associated with %TWL. Postoperative compulsive grazing was significantly associated with %TWL (p ≤ 0.05), but did not mediate the association between preoperative inhibitory control and %TWL. CONCLUSION: The results suggest that preoperative inhibitory control performance is a relevant predictor of postoperative WL and that compulsive grazing is a maladaptive eating behaviour that warrants clinical attention after surgery.

Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information.

BACKGROUND: Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC). METHODS: Preoperative BM samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis. RESULTS: Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The proportion of patients with detected CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC). CONCLUSIONS: The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed. TRIAL REGISTRATION: clinicaltrials.gov ( NCT01919151 ).

Visual, Verbal and Everyday Memory 2 Years After Bariatric Surgery: Poorer Memory Performance at 1-Year Follow-Up.

Severe obesity has been associated with reduced performance on tests of verbal memory in bariatric surgery candidates. There is also some evidence that bariatric surgery leads to improved verbal memory, yet these findings need further elucidation. Little is known regarding postoperative memory changes in the visual domain and how patients subjectively experience their everyday memory after surgery. The aim of the current study was to repeat and extend prior findings on postoperative memory by investigating visual, verbal, and self-reported everyday memory following surgery, and to examine whether weight loss and somatic comorbidity predict memory performance. The study was a prospective, observational study in which participants (n = 48) underwent cognitive testing at baseline, 1 and 2 years after bariatric surgery. Repeated measures analyses of variance revealed significantly poorer visual and verbal memory performance at the 1-year follow-up, with performance subsequently returning to baseline levels after 2 years. Verbal learning and self-reported everyday memory did not show significant postoperative changes. Memory performance at 1 year was not significantly predicted by weight loss, changes in C-reactive protein levels or postoperative somatic comorbidity (Type 2 diabetes, sleep apnea, and hypertension). The study demonstrated poorer visual and verbal memory performance at 1-year follow-up that returned to baseline levels after 2 years. These findings are in contrast to most previous studies and require further replication, however, the results indicate that postoperative memory improvements following bariatric surgery are not universal. Findings suggest that treatment providers should also be aware of patients potentially having poorer memory at 1 year following surgery.

Circulating Tumor Cells are an Independent Predictor of Shorter Survival in Patients Undergoing Resection for Pancreatic and Periampullary Adenocarcinoma.

OBJECTIVE: We evaluated the prognostic impact of circulating tumor cells (CTCs) for patients with presumed resectable pancreatic and periampullary cancers. SUMMARY OF BACKGROUND DATA: Initial treatment decisions for this group are currently taken without a reliable prognostic marker. The CellSearch system allows standardized CTC-testing and has shown excellent specificity and prognostic value in other applications. METHODS: Preoperative blood samples from 242 patients between September 2009 and December 2014 were analyzed. One hundred seventy-nine patients underwent tumor resection, of whom 30 with stage-I tumors and duodenal cancer were assigned to the low-risk group, and the others to the high-risk group. Further 33 had advanced disease, 30 benign histology. Observation ended in December 2016. Cancer-specific survival (CSS) and disease-free survival (DFS) were calculated by log-rank and Cox regression. RESULTS: CTCs (CTC-positive; ≥1 CTC/7.5 mL) were detected in 6.8% (10/147) of the high-risk patients and 6.2% (2/33) with advanced disease. No CTCs (CTC-negative) were detected in the low-risk patients or benign disease. In high-risk patients, median CSS for CTC-positive versus CTC-negative was 8.1 versus 20.0 months (P < 0.0001), and DFS 4.0 versus 10.5 months (P < 0.001). Median CSS in advanced disease was 7.7 months. Univariate hazard ratio (HR) of CTC-positivity was 3.4 (P < 0.001). In multivariable analysis, CTC-status remained independent (HR: 2.4, P = 0.009) when corrected for histological type (HR: 2.7, P = 0.030), nodal status (HR: 1.7, P = 0.016), and vascular infiltration (HR: 1.7, P = 0.001). CONCLUSION: Patients testing CTC-positive preoperatively showed a detrimental outcome despite successful tumor resections. Although the low CTC-rate seems a limiting factor, results indicate high specificity. Thus, preoperative analysis of CTCs by this test may guide treatment decisions and warrants further testing in clinical trials.

Irritable bowel syndrome-like symptoms and health related quality of life two years after Roux-en-Y gastric bypass - a prospective cohort study.

BACKGROUND: Irritable bowel syndrome (IBS) is prevalent in patients with morbid obesity. After Roux-en-Y gastric bypass (RYGB) chronic abdominal pain is common, however the etiology is largely unknown. We aimed to study the change in the prevalence of IBS-like symptoms 2 years after RYGB and possible preoperative predictors of such symptoms. Secondly, to evaluate changes in symptoms of constipation and diarrhea, and Health related quality of life (HRQoL). METHODS: Patients with morbid obesity were included at two obesity centers in South-Eastern Norway. IBS was diagnosed according to the Rome III criteria. Predictors were evaluated in a multivariable logistic regression analysis. RESULTS: Of 307 participants operated with RYGB, 233 (76%) completed the study questionnaires. Preoperatively 27/233 participants (12%) had IBS, 2 years after RYGB 61/233 (26%) had IBS-like symptoms (p < 0.001). Eleven participants with IBS preoperatively (41%) did not report such symptoms after RYGB. New onset IBS-like symptoms was identified in 45/206 (22%) after RYGB. Fibromyalgia, low LDL levels, high vitamin B1 levels and IBS before RYGB were independent preoperative predictors of IBS-like symptoms at the follow-up visit. Symptom scores for constipation preoperatively and 2 year after RYGB were 1.5 (0.9) and 1.8 (1.2), and for diarrhea 1.4 (0.9) and 1.8 (1.1), respectively (p < 0.001). We observed a significant improvement in the physical component score for all participants. However, participants with new onset IBS-like symptoms had a significant worsening of the mental component score. CONCLUSIONS: The prevalence of IBS-like symptoms doubled 2 years after RYGB, and these symptoms were associated with reduced HRQoL. Preoperative IBS and fibromyalgia were strong predictors of postoperative IBS-like symptoms.

Bone metabolism, bone mineral density and low-energy fractures 10 years after Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is a common surgical procedure for treatment of morbid obesity. RYGB induces considerable and sustained weight loss, and remission of obesity related-comorbidities. While studies have suggested negative effects of RYGB on bone health, long-term data are lacking. We aimed to evaluate the prevalence of aBMD below the expected range for age, osteopenia, osteoporosis and low-energy fractures in a defined patient cohort 10 years after RYGB. Secondly, we wanted to identify factors associated with increased risk of aBMD z-score or t-score of -1.1 or lower 10 years after RYGB. METHODS: Patients undergoing RYGB surgery from June 2004 to December 2006 at the Department of Morbid Obesity and Bariatric Surgery, Oslo University Hospital, a tertiary referral centre for treatment of morbid obesity, were invited to a 10 year follow-up. Follow-up visits included morning fasting blood samples, clinical examination, anthropometric measures and dual energy X-ray absorptiometry (DXA). RESULTS: Out of 194 patients eligible for the study, 124 attended the 10 year follow-up and 122 (63%) were examined with DXA. Mean (SD) age was 50.3 (9.0) years, 118 (97%) were of Caucasian ethnicity, 94 were females (77%), of whom 41 (44%) were postmenopausal. Secondary hyperparathyroidism (SHPT) was noted in 37 participants (31%) and vitamin D deficiency (value below 50 nmol/L) and insufficiency (value below 75 nmol/L) in 40 (33%) and 91 (75%), respectively. Among the 63 participants who were premenopausal females or males 49 years or younger the prevalence of areal bone mineral density (aBMD) in the lower range of normal (z-score -1.1- to -1.9) was 30% (n = 19) and aBMD below the expected range for age (z-score ≤ -2.0) was noted in 8% (n = 5). Among the 59 participants who were postmenopausal females or males 50 years or older, the prevalence of osteopenia (t-score -1.1 to -2.4) was 51% (n = 30) and osteoporosis (t-score ≤ -2.5) was 27% (n = 16). The bone resorption markers CTX-1 and PINP were higher in participants with aBMD z-score or t-score of -1.1 or lower compared to participants with aBMD z-score or t-score of -1.0 or higher. Preoperative hypothyroidism, or higher age, postmenopausal status, BMI < 35 kg/m2, SHPT or higher PINP levels at 10 year follow-up were independently associated with aBMD z-score or t-score of -1.1 or lower 10 years after RYGB. Eighteen participants (15%) reported a clinical low-energy fracture after RYGB. In addition, vertebral fracture assessment by DXA revealed that 10 participants (8%) had experienced at least one moderate to severe morphometric vertebral fracture. CONCLUSION: Ten years after RYGB 27% of postmenopausal females and males 50 years or older were osteoporotic, and 8% of premenopausal females and males 49 years or younger exhibited aBMD below the expected range for age. The prevalence of fragility fractures was high. SHPT, higher age, postmenopausal status or higher PINP levels at 10 years and preoperative hypothyroidism were all independent risk factors for aBMD z-score or t-score of -1.1 or lower 10 years after RYGB.