Identification of diverticular disease in Swedish healthcare registers: a validation study.

PURPOSE: The Swedish National Patient Register (SNPR) is frequently used in studies of colonic diverticular disease (DD). Despite this, the validity of the coding for this specific disease in the register has not been studied. METHODS: From SNPR, 650 admissions were randomly identified encoded with ICD 10, K572-K579. From the years 2002 and 2010, 323 and 327 patients respectively were included in the validation study. Patients were excluded prior to, or up to 2 years after a diagnosis with IBD, Celiac disease, IBS, all forms of colorectal cancer (primary and secondary), and anal cancer. Medical records were collected and data on clinical findings with assessments, X-ray examinations, endoscopies and laboratory results were reviewed. The basis of coding was compared with internationally accepted definitions for colonic diverticular disease. Positive predictive values (PPV) were calculated. RESULTS: The overall PPV for all diagnoses and both years was 95% (95% CI: 93-96). The PPV for the year 2010 was slightly higher 98% (95% CI: 95-99) than in the year 2002, 91% (95% CI: (87-94) which may be due to the increasing use of computed tomography (CT). CONCLUSION: The validity of DD in SNPR is high, making the SNPR a good source for population-based studies on DD.

A Randomized Controlled Clinical Trial of Transanal Irrigation Versus Conservative Treatment in Patients With Low Anterior Resection Syndrome After Rectal Cancer Surgery.

OBJECTIVE: The aim of the study was to evaluate transanal irrigation (TAI) as a treatment for low anterior resection syndrome (LARS). BACKGROUND: LARS is a bowel disorder that is common after sphincter preserving rectal cancer surgery. Despite symptomatic medical treatment of LARS many patients still experience bowel symptoms that may have a negative impact on quality of life (QoL). TAI is a treatment strategy, of which the clinical experience is promising but scientific evidence is limited. MATERIALS AND METHODS: A multicenter randomized trial comparing TAI (intervention) with conservative treatment (control) was performed. Inclusion criteria were major LARS, age above 18 years, low anterior resection with anastomosis and a defunctioning stoma as primary surgery, >6 months since stoma reversal, anastomosis without signs of leakage or stricture, and no signs of recurrence at 1-year follow-up. The primary endpoint was differences in bowel function at 12-month follow-up measured by LARS score, Cleveland Clinic Florida Fecal Incontinence Score, and 4 study-specific questions. The secondary outcome was QoL. RESULTS: A total of 45 patients were included, 22 in the TAI group and 23 in the control group. Follow-up was available for 16 and 22 patients, respectively. At 12 months, patients in the TAI group reported significantly lower LARS scores (22.9 vs 32.4; P =0.002) and Cleveland Clinic Florida Fecal Incontinence Score (6.4 vs 9.2; P =0.050). In addition, patients in the TAI group also scored significantly higher QoL [8 of 16 European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) QoL aspects] compared with the control group. CONCLUSIONS: The results confirm our clinical experience that TAI reduces symptoms included in LARS and improves QoL.

Survival and chance of reversal after intestinal stoma formation during cytoreductive surgery for advanced ovarian cancer; a population-based cohort study.

OBJECTIVE: Our objective was to examine oncologic outcome in women with advanced epithelial ovarian cancer (aEOC) receiving an intestinal stoma (IS) at the time of cytoreductive surgery (CRS), probability of stoma reversal (SR) and variables affecting odds of SR. METHODS: This population-based cohort study included all women diagnosed with aEOC between 2009 and 2018 in the Stockholm/Gotland Region of Sweden. The association between IS formation at CRS and survival was analyzed with proportional hazards regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for predefined confounders. Cumulative incidence functions, with death or recurrence as competing risk, were used to estimate chance of SR. The association between clinical factors and SR was analyzed with logistic regression yielding odds ratios (OR) with 95% CI. RESULTS: The final analysis included 888 women undergoing CRS for aEOC. Of these, 129 (14,5%) received an IS of which 74% (n = 95) were defunctioning and 26% (n = 34) permanent. IS was associated with an increased hazard of death (HR 1.30, CI 95%, 1.05-1.61; p = 0.02) in the univariate analysis, however not in the adjusted analysis. The probability of SR of defunctioning IS within 2 years was 48% (95% CI, 38-58). Median time to SR was 10 months. High surgical complexity score (SCS) was associated with increased odds of reversal (OR 3.43, 95% CI, 1.06-11.05; p = 0.04). CONCLUSIONS: IS formation does not seem to affect prognosis in women with aEOC. We could not identify any factor, known at time of CRS, that may predict the odds of SR except a high SCS.

Low Anterior Resection Syndrome and Quality of Life After Sphincter-Sparing Rectal Cancer Surgery: A Long-term Longitudinal Follow-up.

BACKGROUND: Despite low anterior resection syndrome being a well-known consequence of sphincter-preserving rectal cancer surgery, the long-term effect on bowel function and quality of life is not fully understood. OBJECTIVE: This study aimed to elucidate whether symptoms of low anterior resection syndrome change over time and if the correlation to quality of life is equivalent when measured at 2 time points. DESIGN: This prospective cohort study included measurements at 2 time points (5 years between; range, 7.1-16.1 years from surgery to second follow-up). SETTINGS: This multicenter study included patients from Sweden and Denmark. PATIENTS: Patients were included if they were ≥18 years of age and underwent curative rectal cancer surgery with either total or partial mesorectal excision. MAIN OUTCOME MEASURES: Outcomes were measured with the low anterior resection syndrome questionnaire including a question assessing the impact of bowel function on quality of life and with the validated quality-of-life questionnaire EORTC QLQ-C30. RESULTS: In total, 282 patients were included and there were no statistically significant differences in the distribution among the 3 groups (no, minor, and major low anterior resection syndrome) when comparing time points follow-up 1 with follow-up 2 (p = 0.455). At follow-up 2, 138 patients (49%) still experienced major impairment. No both statistically and clinically significant differences were seen in the mean score of EORTC QLQ-C30 when comparing the same low anterior resection syndrome group at follow-up 1 and follow-up 2, and the impact on quality of life was comparable. Global health status/quality of life was impaired in the major low anterior resection syndrome group at both follow-up 1 (p < 0.001) and follow-up 2 (p < 0.001). LIMITATIONS: The study design prevents an evaluation of causality. CONCLUSIONS: Difficulties with low anterior resection syndrome and the impact on patients' quality of life persist over time. See Video Abstract at http://links.lww.com/DCR/A762.

High intake of dietary fibre from fruit and vegetables reduces the risk of hospitalisation for diverticular disease.

BACKGROUNDS AND AIMS: High intake of dietary fibres has been associated with a reduced risk of DD. However, reports on which type of dietary fibre intake that is most beneficial have been conflicting. The aim of this study was to investigate the association between different dietary fibres and hospitalisation due to diverticular disease (DD) of the colon. METHODS: This was a major cohort study. The Swedish Mammography Cohort and the Cohort of Swedish Men were linked to the Swedish Inpatient Register and the Causes of Death Register. Data on the intake of dietary fibre were collected through questionnaires. The effect of intake (in quartiles) of different types of dietary fibre on the incidence of hospitalisation due to DD was investigated using multivariable Cox regression. Estimates were adjusted according to age, BMI, physical activity, co-morbidity, intake of corticosteroids, smoking, alcohol intake and education level. RESULTS: Women with intake of fruit and vegetable fibres in the highest quartile (median 12.6 g/day) had a 30% decreased risk of hospitalisation compared to those with the lowest intake (4.1 g/day). Men within the highest quartile (10.3 g/day) had a 32% decreased risk compared to those with a low intake (2.9 g/day). High intake of fibres from cereals did not affect the risk. CONCLUSION: A high intake of fruits and vegetables may reduce the risk of hospitalisation due to DD. Intake of cereals did not influence the risk.

Perineal Wound Closure Using Biological Mesh Following Extralevator Abdominoperineal Excision.

AIMS: This study aimed to describe the short-term perineal healing rates in patients with perineal reconstruction using a biological mesh following extralevator abdominoperineal excision (elAPE). METHODS: In a retrospective, descriptive single-centre cohort study, 88 consecutive patients treated with elAPE and perineal closure using a biological mesh between January 2011 and December 2015 were reviewed. All available data from electronic hospital records was collected. Patients were followed for 1 year following surgery and perineal wound status assessed at 3 months and at 1 year. RESULTS: In total, 63 patients were male and all but 8 patients were treated for primary rectal cancer. All patients but 3 had received radiotherapy prior to surgery. Multivisceral excisions were performed in 19 patients. Omentoplasty was performed in 55 patients and 3 different types of meshes were used during the study period. At 3 months, 58 patients (66%) had a healed perineum. No association was detected between patient, tumour or perioperative characteristics and perineal wound status at 3 months. At 1 year, 4 patients were deceased and among the remaining 84, the perineal wound was healed in 77 patients (92%). CONCLUSION: The use of biological meshes in perineal reconstruction following elAPE is feasible and safe, and the perineal wound is healed in the majority of the patients within 3 months.

The value of preoperative computed tomography combined with ultrasound in the investigation of small indeterminate liver lesions in patients with colorectal cancer.

Background Computed tomography (CT) is used routinely for the preoperative detection of colorectal cancer (CRC) metastases. When small indeterminate focal liver lesions are detected that are too small to characterize (TSTC) on CT, additional imaging is usually needed, resulting in a potential delay in obtaining a complete diagnostic work-up. Purpose To determine the diagnostic accuracy of ultrasound (US) of the liver performed in direct conjunction to CT in the preoperative investigation among patients with newly diagnosed CRC when indeterminate liver lesions were found on CT. Material and Methods Preoperative investigations with CT and consecutive US where CT had shown at least one focal liver lesion in 74 patients diagnosed with CRC between June 2009 and February 2012 were retrospectively reviewed. Either histopathological findings or a combination of imaging and clinical follow-up one to three years after surgery was used as the reference. Results Liver metastases were diagnosed with CT/US in 13 out of 74 patients (17.6%). In one patient, a liver cyst was preoperatively regarded as liver metastasis by a combined CT/US. The sensitivity and specificity for the CT with consecutive US procedure was 100% (13/13) and 98.4% (60/61). Conclusion US performed in conjunction with CT in patients with indeterminate focal liver lesions on CT is an accurate work-up for detection of liver metastases in patients with newly diagnosed CRC. Although our results are promising, they cannot be considered safely generalizable to all hospitals.

The expression of microvesicles in the blood of patients with Graves' disease and its relationship to treatment.

OBJECTIVE: Graves' disease (GD) is an autoimmune disease characterized by the presence of circulating autoantibodies against thyroid-stimulating hormone (TSH) receptor. Despite extensive research, the pathogenic mechanisms remain unclear. Immune responses associated with the disease may lead to cell activation/apoptosis and the release of microvesicles (MVs) into the circulation. MVs can display biological activities which may aggravate GD further. We studied immune mechanisms in GD by investigating the numbers and phenotype of circulating MVs in patients before and after antithyroid therapy with thiamazole. PATIENTS AND MEASUREMENTS: Samples were obtained from 15 patients with GD in the acute phase of hyperthyroidism and following 17-26 months treatment and 14 healthy controls. MVs from platelets, endothelial cells and monocytes exposing inflammation/activation markers (P-selectin, CD40 ligand, E-selectin and HMGB1) and MVs containing nuclear molecules were measured with flow cytometry. RESULTS: Patients had elevated baseline values of MVs (P < 0·001 for all types of MVs), while the levels decreased during thiamazole treatment (P < 0·05 for all types of MVs). The majority of MV populations remained, however, significantly higher in patients after treatment compared to levels in controls. CONCLUSIONS: GD patients have elevated levels of MVs that carry molecules with potential biological activities. MVs are significantly reduced after antithyroid treatment with thiamazole but still higher compared to levels in healthy controls. Assessment of MV levels and pattern may therefore provide additional information on underlying immune disturbances not obtained by measurements of hormone levels alone.

Emergency management with resection versus proximal stoma or stent treatment and planned resection in malignant left-sided colon obstruction.

BACKGROUND: Emergency surgery for colon cancer, as a result of obstruction, has been vitiated by a high frequency of complications and poor survival. The concept of "bridge to surgery" includes either placement of self-expanding metallic stents (SEMS) or diverting stoma of an obstructing tumour and subsequent planned resection. The aim of this study was to compare acute resection with stoma or stent and later resection regarding surgical and oncological outcomes and total hospital stay. METHODS: This is a retrospective cohort study. All 2424 patients diagnosed with colorectal cancer during 1997-2013 were reviewed. All whom underwent acute surgery with curative intention for left-sided malignant obstruction were included in the study. RESULTS: One hundred patients fulfilled the inclusion criteria. Among them, 57 patients were treated with acute resection and 43 with planned resection after either acute diverting colostomy (n = 23) or stent placement (n = 20). The number of harvested lymph nodes in the resected specimen was higher in the planned resection group compared with acute resection group (21 vs. 8.7; p = 0.001). Fewer patients were treated with adjuvant chemotherapy in the acute resection group than in the stoma group (14 % (8/57 patients) vs. 43 %, (10/23 patients; p = 0.024)). Patients operated with acute resection had a higher 30-day mortality rate and were more frequently left with a permanent stoma. CONCLUSIONS: Decompression of emergency obstructive left colon cancer with stent or stoma and subsequent curative resection appears safer and results in a higher yield of lymph node harvest, and fewer patients are left with a permanent stoma.

Validity assessment of the POLARS score tool in the prediction of post rectal cancer surgery LARS score in a population-based Swedish cohort.

OBJECTIVE: Low anterior resection syndrome (LARS) is one of the most common functional impairments after rectal cancer surgery with a high impact on quality of life. The Pre-Operative LARS score (POLARS) nomogram and its online tool has been developed to predict the degree of postoperative LARS. The aim of this study was to analyse how accurately the POLARS score could predict LARS scores when compared with actual patient-reported LARS (PR-LARS) scores in a population-based Swedish cohort. DESIGN: This retrospective cohort study included patients who underwent curative rectal cancer surgery between 2007 and 2013 in Stockholm County and were identified using the Swedish Colorectal Cancer Registry (SCRCR). Information regarding preoperative risk factors, patient and treatment characteristics, and presence of LARS postoperatively were collected from patient charts, SCRCR and patient questionnaires. The POLARS model formula was used to predict LARS scores, which then were compared with the actual PR-LARS scores. Individual LARS score differences between the two estimates were shown with a modified Bland-Altman plot of difference. RESULTS: The cohort included 477 patients, of whom 359 (75%) of patients were categorised as having no/minor LARS based on the POLARS score. The correctly identified patients by the POLARS score were 80/255 (31%) in the major LARS group and 184/222 (83%) no/minor LARS group. The sensitivity was 31% for major LARS and the positive predictive value was 68%. CONCLUSION: The POLARS score has a low sensitivity for major LARS in this Swedish cohort. Other methods to predict the risk of LARS need to be developed.

Cancer and diverticulitis of the sigmoid colon. Differentiation with computed tomography versus magnetic resonance imaging: preliminary experiences.

BACKGROUND: Both colon cancer and diverticular disease are common in the Western world. A challenge when patients present with clinical findings is that both diseases can present with symptoms that may mimic the other. PURPOSE: To determine whether magnetic resonance imaging (MRI) could be helpful to differentiate between diverticulitis and cancer of the sigmoid colon compared to the differentiation offered by evaluation of multidetector computed tomography (CT) in a clinical situation. MATERIAL AND METHODS: Thirty patients were consecutively included. Fifteen patients were under work-up for a recently diagnosed sigmoid cancer and 15 patients had recently been treated in hospital due to first-time acute sigmoid diverticulitis. All patients underwent CT, T2- weighted MRI and diffusion-weighted MRI. Anonymized examinations were retrospectively presented in random order to one experienced radiologist. RESULTS: With contrast-enhanced CT, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 66.7% (10/15) and 93.3% (14/15), respectively. Using T2-weighted and diffusion-weighted MR images, the sensitivity and specificity for diagnosis of cancer and diverticulitis were 100% (14/14) and 100% (14/14), respectively. CONCLUSION: MRI provides information that may contribute to improve the differentiation between sigmoid cancer and diverticulitis that is offered by CT. These encouraging results need to be confirmed in a larger study.

Morphological predictors for lymph node metastases on computed tomography in colon cancer.

INTRODUCTION/BACKGROUND: The aim of the study was to assess morphological predictors for lymph node metastases (Stage III disease) in colon cancer on computed tomography. METHODS AND MATERIALS: Ninety-four patients with histology-proven colon cancer (adenocarcinoma) who underwent elective primary curative resection between the years 2012 and 2014 were included. Contrast-enhanced CT examinations were independently reviewed by two blinded observers regarding tumor location, depth of tumor invasion, and presence of lymph node metastases. Ocular presence of internal heterogeneity and presence of irregular outer border were used as morphological criteria for lymph node involvement. Protocol-based histopathology after curative surgery served as reference standard. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy for each morphological criterion for prediction of stage III disease were calculated. Inter-observer agreement was compared using Kappa statistics. RESULTS: According to histopathology, 59 patients were staged as I-II disease and 35 patients were staged as stage III disease. The presence of internal heterogeneity in a lymph node on CT resulted in moderate sensitivity (66-77%) but high specificity (95-95%) for prediction of Stage III disease by both observers. The presence of irregular outer border also resulted in poor sensitivity (49-54%) but high specificity (97-97%). The combination of either internal heterogeneity and/or irregular outer border per patient resulted in a moderate sensitivity (67-77%) and high specificity (95-95%), PPV (89-96%), and NPV (84-88%). Inter-observer agreement (Cohens Kappa) was 0.72. Consensus reading for the combined criteria resulted in sensitivity and specificity of 69% and 100%, respectively. CONCLUSION: Using morphological criteria for lymph node metastases on CT examination in patients with colon cancer results in high specificity but moderate sensitivity in predicting stage III disease.

Impaired Quality of Life After Radioiodine Therapy Compared to Antithyroid Drugs or Surgical Treatment for Graves' Hyperthyroidism: A Long-Term Follow-Up with the Thyroid-Related Patient-Reported Outcome Questionnaire and 36-Item Short Form Health Status Survey.

BACKGROUND: Hyperthyroidism is known to have a significant impact on quality of life (QoL), at least in the short term. The purpose of the present study was to assess QoL in patients 6-10 years after treatment for Graves' disease (GD) with radioiodine (RAI) compared to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) questionnaire and general (36-item Short Form Health Status) QoL survey. METHODS: The study evaluated 1186 GD patients in a sub-cohort from an incidence study 2003-2005 who had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n = 975) and/or the 36-item Short Form Health Status survey questionnaire (n = 964) and informed consent at follow-up. Scores from ThyPRO were compared to scores from a general population sample (n = 712) using multiple linear regression adjusting for age and sex as well as multiple testing. Treatment-related QoL outcome for ATD, RAI, and surgery were compared, including adjustment for the number of treatments received, sex, age, and comorbidity. RESULTS: Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6-10 years after diagnosis compared to the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism. CONCLUSIONS: GD is associated with a lower QoL many years after treatment compared to the general population. In a previous small randomized controlled trial, no difference was found in patient satisfaction years after ATD, RAI, or surgery. Now, it is reported that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and 36-item Short Form Health Status survey. These findings in a Swedish population are limited by comparison to normative data from Denmark, older age, and possibly a more prolonged course in those patients who received RAI, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown, but since the results may be important for future considerations regarding treatment options for GD, they need to be substantiated in further studies.

The Long-Term Outcome of Treatment for Graves' Hyperthyroidism.

Background: The treatment efficacy of antithyroid drug (ATD) therapy, radioactive iodine (131I), or surgery for Graves' hyperthyroidism is well described. However, there are a few reports on the long-term total outcome of each treatment modality regarding how many require levothyroxine supplementation, the need of thyroid ablation, or the individual patient's estimation of their recovery. Methods: We conducted a pragmatic trial to determine the effectiveness and adverse outcome in a patient cohort newly diagnosed with Graves' hyperthyroidism between 2003 and 2005 (n = 2430). The patients were invited to participate in a longitudinal study spanning 8 ± 0.9 years (mean ± standard deviation) after diagnosis. We were able to follow 1186 (60%) patients who had been treated with ATD, 131I, or surgery. We determined the mode of treatment, remission rate, recurrence, quality of life, demographic data, comorbidities, and lifestyle factors through questionnaires and a review of the individual's medical history records. Results: At follow-up, the remission rate after first-line treatment choice with ATD was 45.3% (351/774), with 131I therapy 81.5% (324/264), and with surgery 96.3% (52/54). Among those patients who had a second course of ATD, 29.4% achieved remission (vs. the 45.3% after the first course of ATD). The total number of patients who had undergone ablative treatment was 64.3% (763/1186), of whom 23% (278/1186) had received surgery, 43% (505/1186) had received 131I therapy, including 2% (20/1186) who had received both surgery and 131I. Patients who received ATD as first-line treatment and possibly additional ATD had 49.7% risk (385/774) of having undergone ablative treatment at follow-up. Levothyroxine replacement was needed in 23% (81/351) of the initially ATD treated in remission, in 77.3% (204/264) of the 131I treated, and in 96.2% (50/52) of the surgically treated patients. Taken together after 6-10 years, and all treatment considered, normal thyroid hormone status without thyroxine supplementation was only achieved in 35.7% (423/1186) of all patients and in only 40.3% of those initially treated with ATD. The proportion of patients that did not feel fully recovered at follow-up was 25.3%. Conclusion: A patient selecting ATD therapy as the initial approach in the treatment of Graves' hyperthyroidism should be informed that they have only a 50.3% chance of ultimately avoiding ablative treatment and only a 40% chance of eventually being euthyroid without thyroid medication. Surprisingly, 1 in 4 patients did not feel fully recovered after 6-10 years. The treatment for Graves' hyperthyroidism, thus, has unexpected long-term consequences for many patients.

Thyroid hormone state and quality of life at long-term follow-up after randomized treatment of Graves' disease.

OBJECTIVE: In a 14-21 year follow-up of health-related quality of life (HRQL) outcome of 179 patients after randomized treatment of Graves' disease (GD) with surgical, medical or radioiodine, we found no differences. The HRQL for Graves' patients, however, was lower compared with a large age- and sex-matched Swedish reference population. We have now studied whether the reported HRQL-scores by Medical Outcome Study 36-item Short-Form Health Status Survey (SF36) and quality of life 2004 (QoL2004) answers were related to the thyroid hormone state of the patient. METHODS: This report comprises 91 of the original patients in which both the results of SF36 and QoL2004 questionnaire as well as serum thyroid hormones and current use of l-thyroxine treatment were available. RESULTS: A large number of the patients had low or undetectable serum TSH concentrations. SF36 scores and answers to QoL2004 questionnaires were not correlated to TSH levels or associated with suppressed TSH. A low free triiodothyronine was weakly associated with a low GH score (P < 0.02) and elevated thyrotropin receptor antibody with a low physical component summary (P < 0.02). CONCLUSION: HRQL do not seem to be influenced by the thyroid hormone state of the patient including subclinical thyrotoxicosis. It is possible that the personality of GD patients as such may have resulted both in the development of GD and lower HQRL scores later on in life. Alternatively, the generic SF36 may not be a proper instrument to detect relevant differences in HRQL related to the thyroid state.

Assessment and diagnostic accuracy of lymph node status to predict stage III colon cancer using computed tomography.

BACKGROUND: To study different imaging criteria for prediction of lymph node metastases (Stage III disease) in colon cancer using CT. METHODS: In a retrospective setting, 483 consecutive patients with histology proven colon cancer underwent elective primary resection during 2008-2011, a cohort of 119 patients were included. Contrast enhanced CT examinations, in portal-venous phase, were reviewed with assessment of the number of lymph nodes, their anatomical distribution, size, size ratio, internal heterogeneity, presence of irregular outer border and attenuation values. Sensitivity, specificity, PPV and NPV for each studied criteria for prediction of stage III disease was calculated. RESULTS: According to histopathology 80 patients were stage I-II and 39 were stage III. Of the studied CT-criteria for lymph node metastases per patient, internal heterogeneity in at least one lymph node resulted in the best performance with sensitivity, specificity, PPV and NPV of 79, 84, 70 and 89%, Odds ratio (OR) 20. Presence of irregular outer border resulted in a sensitivity, specificity, PPV and NPV of 59, 81, 61 and 82%, OR 6.2. If both internal heterogeneity and/or irregular outer border was used as a criterion this resulted in a sensitivity, specificity, PPV and NPV of 85, 75, 62 and 91%, OR 16.5. None of the size criteria used were predictive for stage III disease. CONCLUSIONS: When performing preoperative CT in patients with colon cancer, the imaging criteria that allow best prediction of stage III disease on CT are either presence of at least one lymph node with internal heterogeneity or internal heterogeneity and/or irregular outer border. These criteria have to be validated in a prospective study.

Graves' disease: a long-term quality-of-life follow up of patients randomized to treatment with antithyroid drugs, radioiodine, or surgery.

The effects of treatment modality for Graves' disease (GD) were studied with respect to long-term quality of life and present health status. A total of 179 patients with GD were randomized during the period 1983-1990 for treatment with antithyroid drugs, radioiodine, or surgery. A 36-item Short Form Health Status Survey questionnaire and specific questions for GD were sent to patients 14-21 years after randomization. Present medical records, and clinical and laboratory status were recorded. No major significant differences in quality of life among the three treatments were observed. Compared to a large Swedish reference group, all treatment groups had significantly lower scores for vitality (p < 0.05). The Mental Component Summary was lower for both the young medical, young surgical, and the older medical group (p < 0.05). Radioiodine-treated patients had a lower General Health score. Young medical patients (<35 years) had lower Mental Health scores (p < 0.05). There was also a strong trend, which barely met statistically significance, for older surgical and radioiodine groups for lower Mental Component Summary. GD patients have, compared with a large Swedish reference population, diminished vital and mental quality of life aspects even many years after treatment. The quality-of-life scores were not different among the three treatment modalities.

Decreased birth weight, length, and head circumference in children born by women years after treatment for hyperthyroidism.

CONTEXT: Whether hyperthyroidism influences the birth characteristics of children born several years after treatment is unknown. OBJECTIVE: The objective of the study was to compare birth characteristics in singleton newborns delivered by women previously treated for Graves' disease (GD), toxic nodular goiter (TNG), or nontoxic goiter (NTG). DESIGN: This was a nested case-control design within a national cohort registry study from 1950 through 2006. SETTING: The study was conducted at a university and a hospital center in collaboration. PATIENTS: The birth characteristics of newborns (n = 3421) delivered in a cohort of 43 633 women treated for GD or toxic nodular goiter by radioiodine or surgery (exposed group) at least 1 year prior to pregnancy were compared with newborns (n = 2914) of 45 655 mothers, previously operated for NTG (unexposed group). MAIN OUTCOME: The primary outcome was birth weight, length, and head circumference. The secondary outcome was malformations, gestational age, and type of hyperthyroidism. RESULTS: The birth weight of exposed children was 3431 ± 607 g (mean ± SD) compared with the unexposed, 3520 ± 641 g (P < .001). The cumulative odds ratio (OR) for lower birth weight was 1.29 [95% confidence interval (CI) 1.16-1.43]. The average birth length for the exposed children was 50.0 ± 2.7 cm compared with the unexposed of 50.4 cm ± 2.6 cm (P < .01) [cumulative OR 1.25 (95% CI 1.13-1.37)]. The head circumference was 34.5 ± 1.9 cm among exposed and 34.7 ± 1.8 cm, respectively (P < .001), with an OR of 1.24 (95% CI 1.13-1.35). No differences in birth characteristics were observed between children born after maternal GD or toxic nodular goiter. CONCLUSIONS: Previous GD or TNG may influence the birth characteristics several years after radioiodine or surgical treatment.

Colonic amyloidosis, computational analysis of the major amyloidogenic species, Serum Amyloid A.

Amyloidosis is characterized by misfolding of proteins. The clinical gastrointestinal manifestations of amyloidosis may mimic other disease, such as inflammatory bowel disease or colonic cancer. As these patients have a high risk for bleeding and poor wound healing following surgery it is important to diagnose them correctly and do a careful preoperative assessment. The most common form of colonic amyloidosis is caused by Serum Amyloid A (SAA), an acute phase protein of unknown function. It is expressed in response to inflammation and the increased levels may lead to amyloidosis. The main treatment is to suppress the acute phase response and thereby reduce production of SAA. As no structure for SAA is available we aim to perform an in silico assessment of its structural and fibrillation properties. In the paper we propose an ab initio model of the structure of SAA, which consists of a five membered helical bundle with a fold related to the tetratricopeptide repeat domain. As there are uncertainties relating to the packing of the helices, each helical region is subjected to triplicate molecular dynamics simulations to assess the integrity of the structural region. The first helix, stretching from residues 1 to 13, is the least stable according to the simulations; almost all of the helical conformation is lost during the 10 ns simulations, whereas the other helices maintain portions that remain in an helical conformation in at least 80% of the simulations. All helices are also subjected to a single 100 ns simulation to investigate how the secondary structure develops over time. In them helix 1 adopts a ß-hairpin structure similar to other fibril forming proteins. The ß-hairpin can in turn multimerise and form a mature fibril structure. The mechanism behind the conformational transition appears to be driven by interactions of side chains of charged residues, particularly Arginine 1. It exchanges interaction partners in the simulation and stabilizes intermediate conformations on the folding pathway to the final ß-hairpin.

Incidence of hyperthyroidism in Sweden.

INTRODUCTION: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100,000 inhabitants per year. This extended study has evaluated the incidence for ~40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. METHODS: All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows: clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. RESULTS: A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100,000 inhabitants per year. The incidence of GD was 21.0/100,000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100,000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. CONCLUSION: The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.