Menopausal hormone therapy and biliary tract cancer: a population-based matched cohort study in Sweden.

BACKGROUND: This study tested the hypothesis that contemporary menopausal hormonal therapy (MHT) increases the risk of biliary tract cancer. The risk of cancer of the biliary tract (gallbladder and extra-hepatic bile ducts) may be increased following estrogen exposure. MATERIAL AND METHODS: This was a nationwide population-based matched cohort study in Sweden. Data from the Swedish Prescribed Drug Register identified all women exposed to systemic MHT in 2005-2012. Group-level matching (1:3 ratio) was used to select women unexposed to MHT from the same study base, matched for history of delivery, thrombotic events, hysterectomy, age, smoking- and alcohol related diseases, obesity, and diabetes. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Comparing 290,186 women exposed to MHT with 870,165 unexposed, MHT did not increase the OR of biliary tract cancer. The OR of gallbladder cancer was rather decreased in MHT users (OR 0.58, 95% CI 0.43-0.79), but this association became attenuated and statistically non-significant after adjusting for gallstone disease (OR 0.84, 95% CI 0.60-1.15). The OR of extra-hepatic bile duct cancers was 0.83 (95% CI 0.61-1.15). There were no clear differences when the analyses were stratified for estrogen or estrogen/progestogen combinations. MHT increased the risk of gallstone disease (OR 6.95, 95% CI 6.64-7.28). CONCLUSIONS: Contemporary MHT does not seem to increase the risk of biliary tract cancer. The decreased risk of gallbladder cancer may be explained by the increased use of surgery for symptomatic gallstones in MHT users.

Incidence and risk factors for symptomatic venous thromboembolism following cholecystectomy.

BACKGROUND: The benefit of thromboembolism prophylaxis in cholecystectomy is controversial. This population-based study report on the incidence of and risk factors for symptomatic venous thromboembolism (VTE) after cholecystectomy. METHOD: All cholecystectomies registered in the Swedish Register of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) between 2006 and 2011 were reviewed. By linking patient data to the Swedish National Patient Register (NPR), the 30-day postoperative incidence of VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]) was identified. Age- and gender-standardized incidence ratio (SIR) for deep venous thrombosis (DVT) and pulmonary embolism (PE) were calculated. Multivariable analysis determined risk factors for VTE by calculating odds ratio (OR). RESULTS: Altogether 62,488 procedures were registered and postoperative VTE was seen in 154 (0.25%) patients. DVT was seen in 36 (0.06%) patients and PE in 25 (0.04%) patients within 30 days after surgery. The SIR for DVT was 22.2 (95% confidence interval (CI) 13.1-31.3) and for PE 5.6 (95% CI 2.3-8.9). Risk factors for VTE within 30 days after cholecystectomy were age >70 years (odds ratio [OR] = 2.69; 95% confidence interval [CI] 1.68-4.30), open cholecystectomy (OR = 1.95; CI 1.31-2.92), operation time >120 min (OR = 1.66; CI 1.18-2.35), acute cholecystitis (OR = 1.69; CI 1.18-2.42), and previous history of VTE (OR = 50.5; CI 27.3-92.8). Thromboembolism prophylaxis (TP) increased the risk for postoperative bleeding (OR = 1.72; 1.44-2.05). CONCLUSION: The incidence of VTE after cholecystectomy is low and thromboembolism prophylaxis (TP) increases the risk for postoperative bleeding. Patients with previous VTE events should be given TP when undergoing cholecystectomy.

Hospital teaching status and volume related to mortality after pancreatic cancer surgery in a national cohort.

BACKGROUND: The association between hospital teaching status and mortality after pancreatic resection is not well explored. Although hospital volume is related to short-term mortality, the effect on long-term survival needs investigation, taking into account hospital teaching status and selective referral patterns. METHODS: This was a nationwide retrospective register-based cohort study of patients undergoing pancreatic resection between 1990 and 2010. Follow-up for survival was carried out until 31 December 2011. The associations between hospital teaching status and annual hospital volume and short-, intermediate- and long-term mortality were determined by use of multivariable Cox regression models, which provided hazard ratios (HRs) with 95 per cent c.i. The analyses were mutually adjusted for hospital teaching status and volume, as well as for patients' sex, age, education, co-morbidity, type of resection, tumour site and histology, time interval, referral and hospital clustering. RESULTS: A total of 3298 patients were identified during the study interval. Hospital teaching status was associated with a decrease in overall mortality during the latest interval (years 2005-2010) (university versus non-university hospitals: HR 0·72, 95 per cent c.i. 0·56 to 0·91; P = 0·007). During all time periods, hospital teaching status was associated with decreased mortality more than 2 years after surgery (university versus non-university hospitals: HR 0·86, 0·75 to 0·98; P = 0·026). Lower annual hospital volume increased the risk of short-term mortality (HR for 3 or fewer compared with 4-6 pancreatic cancer resections annually: 1·60, 1·04 to 2·48; P = 0·034), but not long-term mortality. Sensitivity analyses with adjustment for tumour stage did not change the results. CONCLUSION: Hospital teaching status was strongly related to decreased mortality in both the short and long term. This may relate to processes of care rather than volume per se. Very low-volume hospitals had the highest short-term mortality risk.

Obesity and abdominal aortic aneurysm.

BACKGROUND: The relationship between obesity and abdominal aortic aneurysm (AAA) is unclear. An observational cohort study was undertaken to examine the associations between waist circumference as a measure of abdominal adiposity, and between body mass index (BMI) as a measure of total adiposity, and risk of AAA. METHODS: Data were used from the population-based Swedish Mammography Cohort and the Cohort of Swedish Men, involving 63,655 men and women, aged 46-84 years. Between 1998 and 2009, 597 patients with incident AAA defined by relevant clinical events were identified by linkage to the Swedish Inpatient Register and the Swedish Vascular Registry. Cox proportional hazards models were used to estimate relative risks (RRs) with 95 per cent confidence intervals. RESULTS: In multivariable analysis, individuals with an increased waist circumference had a 30 per cent higher risk of AAA (RR 1·30, 95 per cent confidence interval 1·05 to 1·60) compared with those with a normal waist circumference. The risk of AAA increased by 15 per cent (RR 1·15, 1·05 to 1·26) per 5-cm increment of waist circumference up to the level 100 cm for men and 88 cm for women. There was no association between BMI and risk of AAA. CONCLUSION: Abdominal, but not total, adiposity was associated with an increased risk of incident AAA. A threshold was observed at a waist circumference of 100 cm for men and 88 cm for women.

Abdominal and total adiposity and the risk of acute pancreatitis: a population-based prospective cohort study.

OBJECTIVES: Previous research has indicated that obesity may be linked to the severity of acute pancreatitis. However, the association between abdominal and total adiposity as risk factors in the development of acute pancreatitis in a general population has not been studied. METHODS: A follow-up study was conducted, using the Swedish Mammography Cohort and the Cohort of Swedish Men, to examine the association between waist circumference and body mass index (BMI) and the risk of first-time acute pancreatitis. Severe acute pancreatitis was defined as hospital stay of >14 days, in-hospital death, or mortality within 30 days of discharge. Cox proportional hazards models were used to estimate rate ratios (RRs) with 95% confidence intervals (CIs), adjusted for confounders. RESULTS: In total, 68,158 individuals, aged 46-84 years, were studied for a median of 12 years. During this time, 424 persons developed first-time acute pancreatitis. The risk of acute pancreatitis among those with a waist circumference of >105 cm was twofold increased (RR=2.37; 95% CI: 1.50-3.74) compared with individuals with a waist circumference of 75.1-85.0 cm, when adjusted for confounders. This association was seen in patients with non-gallstone-related and gallstone-related acute pancreatitis. The results remained unchanged when stratifying the analyses with regards to sex or the severity of acute pancreatitis. There was no association between BMI and the risk of acute pancreatitis. CONCLUSIONS: Abdominal adiposity, but not total adiposity, is an independent risk factor for the development of acute pancreatitis.

Cigarette smoking, smoking cessation and acute pancreatitis: a prospective population-based study.

BACKGROUND: Several studies have shown that smoking increases the risk of chronic pancreatitis. However, the impact of smoking on the development of acute pancreatitis has not been fully studied. OBJECTIVE: To clarify the association between cigarette smoking, smoking cessation and the risk of acute pancreatitis. DESIGN: A follow-up study was conducted of 84,667 Swedish women and men, aged 46-84, during 12 years to study the association between smoking status, smoking intensity and duration, duration of smoking cessation and the risk of acute pancreatitis. Only those with the first event of the disease and no previous history of acute pancreatitis were included. Cox proportional hazards models were used to estimate rate ratios (RRs) with 95% CI for different smoking-related variables, adjusted for age, gender, body mass index, diabetes, educational level and alcohol consumption. RESULTS: In total, 307 cases with non-gallstone-related and 234 cases with gallstone-related acute pancreatitis were identified. The risk of non-gallstone-related acute pancreatitis was more than double (RR=2.29; 95% CI 1.63 to 3.22, p<0.01) among current smokers with ≥20 pack-years of smoking as compared with never-smokers. The corresponding risk among individuals with ≥400 g monthly consumption of alcohol was increased more than fourfold (RR=4.12; 95% CI 1.98 to 8.60, p<0.01). The duration of smoking rather than smoking intensity increased the risk of non-gallstone-related acute pancreatitis. After two decades of smoking cessation the risk of non-gallstone-related acute pancreatitis was reduced to a level comparable to that of non-smokers. There was no association between smoking and gallstone-related acute pancreatitis. CONCLUSION: Smoking is an important risk factor for non-gallstone-related acute pancreatitis. Early smoking cessation should be recommended as a part of the clinical management of patients with acute pancreatitis.

Validation of the harmless acute pancreatitis score in predicting nonsevere course of acute pancreatitis.

BACKGROUND: The Harmless Acute Pancreatitis Score (HAPS) is a scoring algorithm to identify patients with nonsevere acute pancreatitis. The aim of this study was to evaluate the reproducibility of HAPS outside its original study setting. METHOD: Baseline information of all hospitalized patients with acute pancreatitis at Karolinska University Hospital, Stockholm, Sweden, between 2004 and 2009 was collected. The parameters constituting HAPS were signs of peritonitis, hematocrit and serum creatinine levels. Since hematocrit was not available in all patients, complete sample analysis was performed by replacing hematocrit with hemoglobin (strongly correlated with hematocrit; r = 0.86). RESULTS: In total, 531 patients with a first-time or a recurrent attack of acute pancreatitis were included. Among 353 patients with complete information on parameters constituting HAPS, 79 patients were predicted to have a nonsevere course, of whom 1 patient developed severe acute pancreatitis. The specificity of HAPS in predicting a nonsevere course of acute pancreatitis was 96.3% (95% CI: 81.0-99.9) with a corresponding positive predictive value of 98.7% (95% CI: 93.1-100). Complete sample analysis replacing hematocrit with hemoglobin level predicted a nonsevere course in 182 patients, of whom 2 patients had severe acute pancreatitis (94.3% specificity and 98.9% positive predictive value). CONCLUSION: HAPS is a highly specific scoring algorithm that predicts a nonsevere course of acute pancreatitis. Therefore, HAPS might be an additional tool in the clinical assessment of acute pancreatitis where early screening is important to treat the patients at an optimal level of care.

Effect of type of alcoholic beverage in causing acute pancreatitis.

BACKGROUND: The effect of different alcoholic beverages and drinking behaviour on the risk of acute pancreatitis has rarely been studied. The aim of this study was to investigate the effect of different types of alcoholic beverage in causing acute pancreatitis. METHODS: A follow-up study was conducted, using the Swedish Mammography Cohort and Cohort of Swedish Men, to study the association between consumption of spirits, wine and beer and the risk of acute pancreatitis. No patient with a history of chronic pancreatitis was included and those who developed pancreatic cancer during follow-up were excluded. Multivariable Cox proportional hazards models were used to estimate rate ratios. RESULTS: In total, 84,601 individuals, aged 46-84 years, were followed for a median of 10 years, of whom 513 developed acute pancreatitis. There was a dose-response association between the amount of spirits consumed on a single occasion and the risk of acute pancreatitis. After multivariable adjustments, there was a 52 per cent (risk ratio 1·52, 95 per cent confidence interval 1·12 to 2·06) increased risk of acute pancreatitis for every increment of five standard drinks of spirits consumed on a single occasion. The association weakened slightly when those with gallstone-related pancreatitis were excluded. There was no association between consumption of wine or beer, frequency of alcoholic beverage consumption including spirits, or average total monthly consumption of alcohol (ethanol) and the risk of acute pancreatitis. CONCLUSION: The risk of acute pancreatitis was associated with the amount of spirits consumed on a single occasion but not with wine or beer consumption.

Stress radiography for osteoarthritis of the knee: a new technique.

Stress radiographs have been used for several years to detect the amount of varus/valgus knee laxity and to evaluate the degree of compartmental involvement in degenerative osteoarthritis. However, the popularity of these radiographic methods has been affected by their technical limits due to the x-ray exposure for the personnel involved and the variability of the stress forces applied. A device was developed with the aim to create a constant varus or valgus stress force to the knee with the patient in a supine position. The device does not require personal assistance during the actual film taking. Sixty consecutive patients where included in the study and measured prior to their total knee replacement. All patients had standard weight-bearing AP and lateral views as well as stress views in varus and valgus. Both knees were examined in full extension and 30° of flexion. The joint space width in both the lateral and medial compartments were measured and subsequently compared with the standard weight-bearing films. A significant decrease in joint space distance in the affected compartment was found in the stress radiographs compared with the standard weight-bearing views. The medial compartment was best examined with the knee extended and varus stress force (P < 0.001) and for the lateral compartment 30° of flexion proved to be more efficient (P < 0.01). In conclusion, this stress radiographic device offers a possibility to enhance the varus/valgus force in a standardized way compared to standard weight-bearing views of the knee. The reliability and reproducibility is high. It is suitable for clinical practice and a valuable tool in research.

The quality of randomized clinical trials in the field of surgery: studies on laparoscopic versus open appendectomy as an example.

BACKGROUND: The field of surgery undergoes rapid renewal and introduction of surgical techniques and instruments. Thus, the quality of the randomized clinical trials in this field should be evaluated. We assessed the quality of randomized trials comparing laparoscopic versus open appendectomy as a model. METHOD: Using MEDLINE and EMBASE, 42 first-time published randomized clinical trials in the English language met the inclusion criteria. Factors related to the methodological quality, e.g. blinding, sample size calculation and intention-to-treat analysis, were reviewed. RESULTS: Method of random number generation was described in only 15 (36%) of the studies, i.e., it was not clear if the remaining two thirds of the studies were actually randomized or not. Although not using blocking, the trials often reported similar sample size in the intervention and control groups. Proper concealment of the allocation status was reported in almost half of the studies. None of the trials was judged to use proper double-blinding measures. Sample size calculation was present in one of five trials and half of the studies performed analysis according to intention-to-treat. CONCLUSIONS: It seems that surgical trials do not always follow the basic methodological guidelines to maintain the high quality of randomized clinical trials. Compliance with the CONSORT statement and transparency in result reporting is strongly recommended to improve the quality of randomized trials in the field of surgery.

Genetic and environmental influences on the risk of acute appendicitis in twins.

BACKGROUND: Acute appendicitis is common but the aetiology is unclear. This study examined the heritability of acute appendicitis. METHODS: The study included twin pairs with known zygosity born between 1959 and 1985. Individuals with acute appendicitis were found by record linkage with the Swedish Inpatient Register. Comparing monodizygotic and dizygotic twins, the similarity and relative proportions of phenotypic variance resulting from genetic and environmental factors were analysed. Risks of acute appendicitis explained by heritability and environmental effects were estimated. RESULTS: Some 3441 monozygotic and 2429 dizygotic twins were identified. Almost no genetic effects were found in males (8 (95 per cent confidence interval 0 to 50) per cent), but shared (31 (0 to 49) per cent) and non-shared (61 (47 to 74) per cent) environmental factors accounted for this risk. In females, the heritability was estimated as 20 (0 to 36) per cent and the remaining variation was due to non-shared environmental factors (80 (64 to 98) per cent). For the sexes combined, genetic effects accounted for 30 (5 to 40) per cent and non-shared environmental effects for 70 (60 to 81) per cent of the risk. CONCLUSION: Acute appendicitis has a complex aetiology with sex differences in heritability and environmental factors.

The efficacy of a smoking cessation programme in patients undergoing elective surgery: a randomised clinical trial.

It is known that smokers constitute an important risk group of patients undergoing surgery. It is unknown how smoking cessation intervention initiated 4 weeks prior to elective surgery affects the probability of permanent cessation. We randomly assigned 117 patients, scheduled to undergo elective orthopaedic and general surgery, to smoking cessation intervention and control group. The intervention group underwent a programme initiated, on average, 4 weeks prior to surgery with weekly meetings or telephone counselling and were provided with free nicotine replacement therapy (NRT). The control group received standard care. As a result, 20/55 (36%) patients the intervention group vs 1/62 (2%) in the control group became completely abstinent throughout the peri-operative period (p < 0.001). After 1 year, those in the intervention group was most likely to be abstinent (18/55 (33%) vs 9/62 (15%) of the controls (p = 0.03). Level of nicotine dependence and obesity seemed to be a predictor of long-term abstinence (p = 0.02).

Impact of body mass index and tobacco smoking on outcome after open appendicectomy.

BACKGROUND: The effect of body mass index (BMI) and smoking on the risk of perforated appendix and postoperative complications in patients undergoing open appendicectomy for acute appendicitis was studied. METHODS: Record linkage was used to identify 6676 male construction workers who underwent open appendicectomy for acute appendicitis between 1971 and 2004. Multivariable binomial logistic regression analyses were performed. RESULTS: After adjustment for age, calendar period and BMI, smoking was significantly associated with an increased risk of perforated appendicitis (PA) (P = 0.004). The relative risk was 1.29 (95 per cent confidence interval 1.11 to 1.50) among current smokers with more than 10 pack-years of tobacco use. In patients with non-perforated appendicitis (NPA), the relative risk of overall postoperative complications was significantly associated with BMI (P < 0.001), and was 2.60 (1.71 to 3.95) in obese patients and 1.51 (1.03 to 2.22) in current smokers with more than 10 pack-years of tobacco use. In patients with PA, overweight, obesity and smoking status were not associated with an increased risk of overall postoperative complications. CONCLUSION: Perforation due to acute appendicitis was associated with current tobacco smoking. A BMI of 27.5 kg/m(2) or more and current smoking were associated with overall postoperative complications in patients with NPA.

The effect of tobacco consumption and body mass index on complications and hospital stay after inguinal hernia surgery.

BACKGROUND: The extent to which lifestyle factors such as tobacco consumption and obesity affect the outcome after inguinal hernia surgery has been poorly studied. This study was undertaken to assess the effect of smoking, smokeless tobacco consumption and obesity on postoperative complications after inguinal hernia surgery. The second aim was to evaluate the effect of tobacco consumption and obesity on the length of hospital stay. METHODS: A cohort of 12,697 Swedish construction workers with prospectively collected exposure data on tobacco consumption and body mass index (BMI) from 1968 onward were linked to the Swedish inpatient register. Information on inguinal hernia procedures was collected from the inpatient register. Any postoperative complication occurring within 30 days was registered. In addition to this, the length of hospitalization was calculated. The risk of postoperative complications due to tobacco exposure and BMI was estimated using a multiple logistic regression model and the length of hospital stay was estimated in a multiple linear regression model. RESULTS: After adjusting for the other covariates in the multivariate analysis, current smokers had a 34% (OR 1.34, 95% CI 1.04, 1.72) increased risk of postoperative complications compared to never smokers. Use of "Swedish oral moist snuff" (snus) and pack-years of tobacco smoking were not found to be significantly associated with an increased risk of postoperative complications. BMI was found to be significantly associated with an increased risk of postoperative complications (P = 0.04). This effect was mediated by the underweighted group (OR 2.94; 95% CI 1.15, 7.51). In a multivariable model, increased BMI was also found to be significantly associated with an increased mean length of hospital stay (P < 0.001). There was no statistically significant association between smoking or using snus, and the mean length of hospitalization after adjusting for the other covariates in the model. CONCLUSION: Smoking increases the risk of postoperative complications even in minor surgery such as inguinal hernia procedures. Obesity increases hospitalization after inguinal hernia surgery. The Swedish version of oral moist tobacco, snus, does not seem to affect the complication rate after hernia surgery at all.

The impact of tobacco use and body mass index on the length of stay in hospital and the risk of post-operative complications among patients undergoing total hip replacement.

We carried out a retrospective cohort study of 3309 patients undergoing primary total hip replacement to examine the impact of tobacco use and body mass index on the length of stay in hospital and the risk of short term post-operative complications. Heavy tobacco use was associated with an increased risk of systemic post-operative complications (p = 0.004). Previous and current smokers had a 43% and 56% increased risk of systemic complications, respectively, when compared with non-smokers. In heavy smokers, the risk increased by 121%. A high body mass index was significantly associated with an increased mean length of stay in hospital of between 4.7% and 7%. The risk of systemic complications was increased by 58% in the obese. Smoking and body mass index were not significantly related to the development of local complications. Greater efforts should be taken to reduce the impact of preventable life style factors, such as smoking and high body mass index, on the post-operative course of total hip replacement.

Coronary angioplasty and cancer risk: a population-based cohort study in Sweden.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) has become the reperfusion method of choice in patients with coronary artery disease. This sometimes complicated and lengthy procedure is performed using fluoroscopy and cineradiography or digital imaging, which may result in considerable exposure to ionizing radiation. Possible cancer risks in PTCA patients have been discussed, but never before examined in a population-based setting. OBJECTIVE: To assess the cancer risks following PTCA. METHODS: A cohort study was carried out based on nationwide registration of all coronary angioplasty procedures in Sweden between 1989 and 1998. The study encompassed a total of 23,097 PTCA patients followed up for cancer outcomes in the Swedish Cancer Register until December 31, 2000. The mean and median follow-up times were 4.8 and 4.5 years, respectively. The main outcome measures were standardized incidence ratios of cancer. RESULTS: Except for a transient excess of lung cancers, observed number of cancers in patients who had undergone coronary angioplasty did not differ from those expected in the general population. If anything, the overall cancer risk was lower in the PTCA group (SIR 0.94; 95% CI 0.88-0.99). In particular, no increased risks were detected for leukemias or thyroid cancer. CONCLUSION: There was no indication of increased risks of leukemia or cancers overall in PTCA patients.