Risk of pre-eclampsia after gastric bypass: a matched cohort study.

OBJECTIVE: To investigate whether gastric bypass before pregnancy is associated with reduced risk of pre-eclampsia. DESIGN: Nationwide matched cohort study. SETTING: Swedish national health care. POPULATION: A total of 843 667 singleton pregnancies without pre-pregnancy hypertension were identified in the Swedish Medical Birth Register between 2007 and 2014, of which 2930 had a history of gastric bypass and a pre-surgery weight available from the Scandinavian Obesity Surgery Registry. Two matched control groups (pre-surgery and early-pregnancy body mass index [BMI]) were propensity score matched separately for nulliparous and parous births, to post-gastric bypass pregnancies (npre-surgery-BMI = 2634:2634/nearly-pregnancy-BMI = 2766:2766) on pre-surgery/early-pregnancy BMI, diabetes status (pre-surgery/pre-conception), maternal age, early-pregnancy smoking status, educational level, height, country of birth, delivery year and history of pre-eclampsia. MAIN OUTCOME MEASURES: Pre-eclampsia categorised into any, preterm onset (<37+0 weeks) and term onset (≥37+0 weeks). RESULTS: In post-gastric bypass pregnancies, mean pre-surgery BMI was 42.9 kg/m2 and mean BMI loss between surgery and early pregnancy was 14.0 kg/m2 (39 kg). Post-gastric bypass pregnancies had lower risk of pre-eclampsia compared with pre-surgery BMI-matched controls (1.7 versus 9.7 per 100 pregnancies; hazard ratio [HR] 0.21, 95% CI 0.15-0.28) and early-pregnancy BMI-matched controls (1.9 versus 5.0 per 100 pregnancies; HR 0.44, 95% CI 0.33-0.60). Although relative risks for pre-eclampsia for post-gastric bypass pregnancies versus pre-surgery matched controls was similar, absolute risk differences (RD) were significantly greater for nulliparous women (RD -13.6 per 100 pregnancies, 95% CI -16.1 to -11.2) versus parous women (RD -4.4 per 100 pregnancies, 95% CI -5.7 to -3.1). CONCLUSION: We found that gastric bypass was associated with lower risk of pre-eclampsia, with the largest absolute risk reduction among nulliparous women. TWEETABLE ABSTRACT: In this large study including two comparison groups matched for pre-surgery or early-pregnancy BMI, gastric bypass was associated with lower risk of pre-eclampsia.

Fracture risk after three bariatric surgery procedures in Swedish obese subjects: up to 26 years follow-up of a controlled intervention study.

BACKGROUND: Previous studies have reported an increased fracture risk after bariatric surgery. OBJECTIVE: To investigate the association between different bariatric surgery procedures and fracture risk. METHODS: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups. RESULTS: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02-3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41-2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66-2.79; P < 0.001). CONCLUSIONS: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment.

Outcomes of laparoscopic gastric bypass in a randomized clinical trial compared with a concurrent national database.

BACKGROUND: RCTs are the standard for assessing medical interventions, but they may not be feasible and their external validity is sometimes questioned. This study aimed to compare results from an RCT on mesenteric defect closure during laparoscopic gastric bypass with those from a national database containing data on the same procedure, to shed light on the external validity of the RCT. METHODS: Patients undergoing laparoscopic gastric bypass surgery within an RCT conducted between 1 May 2010 and 14 November 2011 were compared with those who underwent the same procedure in Sweden outside the RCT over the same time interval. Primary endpoints were severe complications within 30 days and surgery for small bowel obstruction within 4 years. RESULTS: Some 2507 patients in the RCT were compared with 8485 patients in the non-RCT group. There were no differences in severe complications within 30 days in the group without closure of the mesenteric defect (odds ratio (OR) for RCT versus non-RCT 0·94, 95 per cent c.i. 0·64 to 1·36; P = 0·728) or in the group with closure of the defect (OR 1·34, 0·96 to 1·86; P = 0·087). There were no differences between the RCT and non-RCT cohorts in reoperation rates for small bowel obstruction in the mesenteric defect non-closure (cumulative incidence 10·9 versus 9·4 per cent respectively; hazard ratio (HR) 1·20, 95 per cent c.i. 0·99 to 1·46; P = 0·065) and closure (cumulative incidence 5·7 versus 7·0 per cent; HR 0·82, 0·62 to 1·07; P = 0·137) groups. The relative risk for small bowel obstruction without mesenteric defect closure compared with closure was 1·91 in the RCT group and 1·39 in the non-RCT group. CONCLUSION: The efficacy of mesenteric defect closure was similar in the RCT and national registry, providing evidence for the external validity of the RCT.

Thermal growth performance of juvenile brown trout Salmo trutta: no support for thermal adaptation hypotheses.

Using thermal growth data from eight populations of anadromous and lake-feeding brown trout Salmo trutta, hypotheses of adaptation to local optima and countergradient variation in growth were tested. The adaptation to local optima hypothesis suggests that natural selection can shift optimal performance temperatures to match the prevailing temperature in a new or changed thermal niche. In contradiction, the countergradient variation hypothesis suggests that populations from hostile environments perform better than conspecifics from benign environments at all temperatures. In this study, growth capacity varied between populations but there was no significant correlation between any of the estimated thermal performance parameters (e.g. lower and upper thermal growth limits, optimal temperature for growth and maximum growth capacity) and natural climatic conditions among populations. Hence, S. trutta growth response to temperature lends no support for either of the two suggested thermal adaptation hypotheses. Instead, growth capacity among populations tended to correlate positively with female size at maturity.

Body composition through adult life: Swedish reference data on body composition.

BACKGROUND/OBJECTIVES: The prevalence of obesity, defined as body mass index (BMI) ⩾30 kg/m(2), differs between populations; however, there is a need for data on description on body composition in reference populations of different ages and from different countries. The objective of this study was to pool dual-energy X-ray absorptiometry (DXA) body composition reference data from population-based Swedish cohorts. SUBJECTS/METHODS: Four population-based cross-sectional cohort studies including 1424 adult Swedes were divided into five age groups (20-29, 30-39, 40-49, 50-61 and 75 years of age); BMI 24.6±3.9 kg/m(2) were pooled. Body composition was measured with DXA. RESULTS: The difference in BMI from the youngest to the oldest age group was 3.2 and 4.3 kg/m(2) in men and women, respectively (P<0.001, both sexes), and fat mass (FM) was 9.9 and 9.1% higher in the oldest compared with the youngest men and women (P<0.001, both sexes). Fat-free mass (FFM) remained stable up to 60 years of age in men (P=0.83) and was lower at 75 years of age compared with the younger ages. In women, FFM was lower from age 60. From youngest to oldest age groups, height-adjusted FM differed from 4.6 to 7.8 kg/m(2) in men and from 6.8 to 10.8 kg/m(2) in women (P<0.001, both sexes). CONCLUSIONS: Our results provide reference data on body composition in Swedish populations. BMI and FM were higher among older age groups compared with the younger ones. FFM remained stable up to 60 years of age and was lower first among the 75 years of age.

Formation of the Scandinavian Obesity Surgery Registry, SOReg.

BACKGROUND: Obesity surgery is expanding, the quality of care is ever more important, and learning curve assessment should be established. A large registry cohort can show long-term effects on obesity and its comorbidities, complications, and long-term side effects of surgery, as well as changes in health-related quality of life (QoL). Sweden is ideally suited to the task of data collection and audit, with universal use of personal identification numbers, nation-wide registries permitting cross-matching to analyze causes of death, in-hospital care, and health-related absenteeism. METHOD: In 2004, the Scandinavian Obesity Surgery Registry (SOReg) was initiated and government financing secured. A project group created a national database covering all public as well as private hospitals. Data entry was to be made online, operative definitions of comorbidity were formed, and complication severity scored. Several forms of audit were devised. RESULTS: After pilot studies, the system has been running in its present form since 2007. Since 15 January 2013, SOReg covers all bariatric surgery centers in Sweden. The number of operations in the database exceeded 40,000 (March 2014), with a median follow-up of 2.94 years. Audit shows that >98% of data are correct. All results are publicized annually on the Internet. COMMENTS: Using this systematic approach, it has been possible to cover >99% of all bariatric surgery, cross-matching our data with nation-wide registries for in-hospital care, cause of death, and permitting regular nation-wide audit. Several scientific studies have used, or are using, what seems to be the most comprehensive database in obesity surgery.

Reduced incidence of bone metastases in irradiated areas after external radiation therapy of prostatic carcinoma.

Fourteen males, out of 380 patients, treated with radiation to the central pelvis and lumbar spine for poorly differentiated prostatic carcinoma were analyzed in retrospect. The dose of radiation to the bones of the target area was 5,000 cGy. The patients showed no signs of metastases at bone scintigraphy performed in connection with the treatment. In an average of 34 months after finishing radiotherapy, the patients developed metastases at bone scintigraphy. The pattern was similar in all patients. The treated target area appeared as a "cold zone" surrounded by more or less homogenously and strongly increased activity of the axial skeleton, characteristic of bone metastases. Radiography, which was performed in 11 patients, confirmed widespread metastatic disease sparing the target area. This was interpretated as bone metastasis being precluded by the irradiation. The most probable explanation of this finding is eradication in situ of distant micrometastases already present in the bone marrow at the time of treatment. An alternate explanation is a reduced implantation of later seeded blood-born metastases as an effect of the irradiation. The characteristic pattern of this phenomenon must be recognized at bone scintigraphy.

Can 8-oxo-dG be used as a predictor for individual radiosensitivity?

PURPOSE: To develop predictive tests for individual radiosensitivity of tumor patients. METHODS AND MATERIALS: Acute skin reactions were clinically scored among 40 women after 46 Gy, given with 2 Gy fractions to breast and regional lymph nodes, adjuvant after surgery. The acute skin reactions were compared to the excretion of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) in urine, determined by high-performance liquid chromatography (HPLC) with electrochemical detector. Specimens of urine were collected before and during postoperative radiation treatment at given intervals. We compared a group of 9 patients with the most pronounced skin reactions with another group of 8 patients with almost no skin reactions at 46 Gy. RESULTS: The level of 8-oxo-dG excreted in urine during 8 h was measured. After normalizing the excretion to irradiated volumes, dose per volume and excretion before irradiation, the 8-oxo-dG level in urine was significantly (p < 0.001) lower for the patients with pronounced skin reactions as compared to patients with minor skin reactions, at an accumulated dose of 12 Gy. In addition, the background level of 8-oxo-dG excreted before treatment started, was significantly (p = 0.043) lower for patients with minor skin reactions as compared to patients with pronounced skin reactions. The background level of 8-oxo-dG was corrected for body weight and normalized to BMI. CONCLUSION: We suggest that the excretion of 8-oxo-dG into urine of breast cancer patients is a possible marker for acute radiosensitivity.

NO and de novo mammalian angiogenesis: further evidence that NO inhibits bFGF-induced angiogenesis while not influencing VEGF165-induced angiogenesis.

Using the non-surgical rat mesenteric window angiogenesis assay, we studied the systemic effect of (i) the nitric oxide (NO)-releasing vasodilator isosorbide-5-mononitrate (ISMN) and (ii) the NO-synthase inhibitor L-NAME on angiogenesis induced by the intraperitoneal injection of bFGF and VEGF165. The response was assessed objectively and quantitatively by microscopic morphometry and image analysis in terms of the vascularized area (VA; a measurement of microvessel spatial extension), the microvascular length (MVL; a composite measurement of microvessel density), the total microvascular length (TMVL=VA x MVL), the number of microvessel segments per unit tissue volume (No. MS), the length of the microvessel segments (Le. MS) and the degree of microvessel tortuosity (MVT). Additional architectural features of the network were assessed in terms of variables introduced here: the number of microvessel branching points per unit tissue volume (No. BP), the index of interconnecting microvessel loop formation (In. LF), the index of microvessel intersection (In. IS), the number of microvessel sprouts per unit tissue volume (No. SP) and their length (Le. SP). In bFGF-mediated angiogenesis, L-NAME significantly, augmented angiogenesis, whereas ISMN significantly inhibited angiogenesis. By contrast, neither L-NAME nor ISMN affected the angiogenic response to VEGF165.

Staple disruption in vertical banded gastroplasty.

BACKGROUND: In earlier studies of vertical banded gastroplasty (VBG), staple-line disruptions (SD) were only reported in a few per cent or less. Two recent studies have shown a significantly higher frequency of SD. To find the true frequency of SD, all patients must be examined regardless of weight outcome. METHODS: 91 consecutive patients were examined by a standardized radiological method at different postoperative intervals ranging from 6 to 48 months. RESULTS: 41 out of 91 patients developed SD. The average diameter of the disruptions was 6 mm (range 2-16 mm). During the first 2 years of follow-up, when at least 31% of the patients had developed SD, there was no significant difference in weight loss between the group with SD and the group without SD. CONCLUSION: SD is an inherent problem of VBG which has been underestimated for a long period of time. An SD frequency of 45% or more within the first few years is not acceptable and changes in the VBG technique must be considered.

Evaluation of screening for cervical cancer in Sweden: trends in incidence and mortality 1958-1980.

Papanicolaou screening for cancer of the uterine cervix was introduced in Sweden in the late 1950's. Screening programmes covering the age groups 30-49 years were organized in various countries between 1965 and 1973. The approximate number of smears rose from 100 000 in 1960 to one million in 1970, in a female population of four million. Almost 60 000 cases of in situ carcinoma and 17 100 invasive carcinomas of the uterine cervix were registered in Sweden between 1958 and 1980. The age-standardized incidence of invasive carcinoma fell in this period by about 40%. Within the screened cohorts and age groups, the incidence was reduced by two-thirds and there was a parallel fall in mortality from the disease. At least part of these reductions seemed to be explained by the intensity of screening.

Immunological and haematological monitoring in bladder cancer patients receiving adjuvant bestatin treatment following radiation therapy. A prospective randomized trial.

In a prospective randomized trial the clinical value of Bestatin, a low molecular weight immunomodulator, is being examined in patients having completed a full course of local radiation therapy for bladder cancer. At termination of irradiation (64 Gy in eight weeks) the patients are divided into two treatment arms: (i) 10 mg of Bestatin orally three times daily without breaks for at least one year and (ii) no further adjuvant treatment. Routine haematological monitoring of 68 patients for a period of up to two years did not reveal any differences between the two groups. Studies on the blood lymphocyte population, however, showed a significantly elevated frequency of cells forming rosettes with sheep erythrocytes after one month of Bestatin treatment. Upon continuation of treatment, however, this value declined and reached the level of the control patients at three months. The frequencies of lymphocytes with Fc-receptors for IgG or complement were unaffected by Bestatin. Spontaneous cytotoxicity against Chang cells appeared to be increased during the first three months of Bestatin treatment in those patients who survived for more than 18 months. No increase was observed in patients who died earlier. Although the above data seem to indicate that Bestatin should be administered at higher doses and intermittently instead of continuously, our preliminary results on disease-free survival in a limited patient material seem to be in favour of the Bestatin treated patients.

The pulse wash instrument. A new sampling method for uterine cervical cancer detection.

A new sampling method for uterine cervical cancer detection is described. In this method, sampling of cytologic material is done by using a pulse wash instrument. Liquid jets with a diameter of 0.2 mm at a speed of 20 m/s create a successful rinsing effect of cervical epithelial cells due to the high kinetic energy produced. Because cells are suspended in the flushing liquid it is possible to collect material for additional cytochemical, immunocytochemical, and microbiologic diagnostic techniques in addition to a conventional smear technique. Compared to a conventional Papanicolaou smear technique performed in 75 women at two cervical atypia clinics at the Karolinska Hospital, the pulse wash technique is suggested to result in a more representative cellular sample, thus offering a method to decrease false negative diagnoses in uterine cervical cancer detection.

Electrochemical treatment of tumours.

The electrochemical treatment (EChT) of tumours implies that tumour tissue is treated with a continuous direct current through two or more electrodes placed in or near the tumour. The treatment offers considerable promise of a safe, simple and relatively noninvasive anti-tumour therapy for treatment of localised malignant as well as benign tumours. Although more than 10,000 patients have been treated in China during the past 10 years, EChT has not yet been universally accepted. The reason for this is the lack of essential preclinical studies and controlled clinical trials. Uncertainties regarding the destruction mechanism of EChT also hinder the development of an optimised and reliable dose-planning methodology. This article reviews the collected Chinese and occidental experiences of the electrochemical treatment of tumours, alone and in combination with other therapies. The current knowledge of the destruction mechanism underlying EChT is presented along with different approaches towards a dose planning methodology. In addition, we discuss our view of different important parameters that have to be accounted for, if clinical trials are to be initiated outside of China.

Effects of information supply on satisfaction with information and quality of life in cancer patients receiving curative radiation therapy.

In order to test the efficacy of various information inputs, 210 consecutive cancer patients were randomized to one of three information conditions before the start of curative radiation treatment: (1) standard information plus group and repeated individual information (n=70), (2) standard information plus brochure (n=70), and (3) standard information only (n=70). Patients completed questions regarding satisfaction with information, anxiety, depression, subjective distress and quality of life at inclusion, and 1h before the start of the radiation therapy treatment (approximately 4 weeks later). Patients receiving standard information plus group and repeated individual information were significantly more satisfied with the information than were patients in the remaining two groups. There were no differences with respect to any of the other outcome measures. This study has shown that the nurses group and individual information was of significant importance in preparing the patients for the procedure of receiving radiation therapy.

Budget impact analysis of surgical treatment for obesity in Sweden.

BACKGROUND: The recent substantial increase in the number of obese surgeries performed in Sweden has raised concerns about the budget impact. OBJECTIVE: Our aim in this paper is to present an assessment of the budgetary impact of different policies for surgical intervention for obese and overweight subjects from a healthcare perspective in Sweden. METHODS: The model simulates the annual expected treatment costs of obesity related diseases and surgery in patients of different sex, age and Body Mass Index (BMI). Costs evaluated are costs of surgery plus the excess treatment costs that an obese patient has over and above the treatment costs of a normal-weight patient. The diagnoses that are included for costs assessment are diabetes and cardiovascular disease since these diagnoses are the principal diagnoses associated with obesity. Four different scenarios over the number of surgical operations performed each year are simulated and compared: (1) no surgical operation, (2) 3 000 surgical operations in persons with BMI > 40, (3) 4 000 (BMI > 40), and (4) 5 000 (expanded to BMI > 38). RESULTS: Comparing Scenario 2 with Scenario 1 results in a net budget impact of on average SEK 121 million per annum or SEK 40 000 per patient. This implies that 55 percent of the cost of surgery, set equal to SEK 90 000 for each patient, has been offset by a reduction in the excess treatment costs of obesity related diseases. Expanding annual surgery from 3000 to 4000 the cost-offset increased to 58%. By expanding annual surgery further from 4000 to 5000 and at the same time expanding the indication for surgery from BMI > 40 to BMI > 38, no cost-offset is obtained. CONCLUSION: A cost-minimization strategy for bariatric surgery in Sweden should not expand indication, but rather increase the number of surgeries within the currently accepted indication.