The clinical course of common bile duct stone clearance with endoscopic retrograde cholangio-pancreaticography.

Objectives: Two-stage treatment of common bile duct stones by Endoscopic Retrograde Cholangio-Pancreatography and subsequent laparoscopic cholecystectomy is well established. In many cases multiple procedures are needed before clearance of the common bile duct is obtained. This study aimed to describe the clinical course from common bile duct stone diagnosis to successful clearance. Materials and Methods: A prospective observational study from 2011 to 2014 of consecutive patients diagnosed with common bile duct stones undergoing Endoscopic Retrograde Cholangio-Pancreatography at a public university hospital. Results: In this study 297 patients with common bile duct stones were identified. More than one Endoscopic Retrograde Cholangio-Pancreatography was performed in 174 (59%) patients and more than two in 51(17%) before clearance. A sphincterotomy was performed in 269 (91%) patients and 189 (64%) had a stent inserted. Bleeding occurred in 17 (6%) requiring injection treatment and post procedure complications occurred in 38 (13%). Subsequent laparoscopic cholecystectomy was performed in 180 (61%) patients. Overall, the patients were hospitalized for 11 (8.5) days and the length of treatment from diagnose to stone clearance was 49 (84.5) days. Overweight, pancreatitis at admission, universal anesthesia, and expert level endoscopist inversely determined common bile duct clearance failure. Conclusions: Common bile duct clearance by Endoscopic Retrograde Cholangio-Pancreatography requires multiple procedures and complications are frequent leading to prolonged treatment and hospitalization suggesting a limited efficacy.

Association Between Screen-Detected Gallstone Disease and Cancer in a Cohort Study.

BACKGROUND & AIMS: Knowledge of temporal associations between screen-detected gallstone disease and specific cancers is limited. The objective of this study was to determine if screen-detected gallstones or cholecystectomy are associated with occurrence of gastrointestinal and nongastrointestinal cancers. METHODS: We performed a cohort study of 3 randomly selected groups from the general population of Copenhagen. Participants (N = 5928) were examined from 1982 through 1992 and underwent abdominal ultrasound examination to detect gallstone disease, but were not informed of their gallstone status. Participants were followed for the occurrence of cancers through national registers until December 2014. We performed multivariable Cox regression analyses to identify factors associated with development of cancer. RESULTS: Gallstone disease was identified in 10% of participants (591 of 5928); of these, 6.8% had gallstones and 3.2% had cholecystectomy at baseline. The population was followed for a median of 24.7 years (interquartile range, 18.9-32.4 years) with 1% lost. Pooled gastrointestinal cancers were associated with gallstone disease (11.2% of patients with gallstone disease vs 6.64% without; hazard ratio, 1.50; 95% confidence interval, 1.12-2.01). Right-side colon cancer was also associated with gallstone disease (2.57% of patients with gallstone disease vs 0.96% without; hazard ratio, 2.04; 95% confidence interval, 1.10-3.78). Pancreatic, esophageal, gastric, pooled colorectal, left-side colon, sigmoid colon, and rectal cancers were not associated with gallstone disease. Breast cancer had a weak association with gallstone disease depending on other factors (10.6% of patients with gallstone disease vs 7.41% without; hazard ratio, 1.44; 95% confidence interval, 0.99-2.11). Pooled nongastrointestinal and prostate cancers were not associated with gallstone disease. CONCLUSIONS: Screen-detected gallstone disease in the general population is associated with pooled gastrointestinal and right-side colon cancers. These associations are not due to detection bias or cholecystectomy. Further studies are needed to determine the mechanism of this association.

A Prediction Rule for Risk Stratification of Incidentally Discovered Gallstones: Results From a Large Cohort Study.

BACKGROUND & AIMS: No one knows exactly what proportion of gallstones cause clinical events among subjects unaware of their gallstone status. We investigated the long-term occurrence of clinical events of gallstones and associations between ultrasound observations and clinical events. METHODS: We analyzed data from 3 randomly selected groups in the general population of urban Copenhagen (age, 30-70 y) participating in an international study of cardiovascular risk factors (the Multinational mONItoring of trends and determinants in CArdiovascular disease study). In this study, participants (n = 6037) were examined from 1982 through 1994, and underwent abdominal ultrasound examinations to detect gallstones. Our study population comprised 664 subjects with gallstones; subjects were not informed of their gallstone status. Participants were followed up for clinical events through central registers until December 31, 2011. Independent variables included ultrasound characteristics, age, sex, comorbidity, and female-associated factors, which were analyzed using Cox regression. RESULTS: Study participants were followed up for a median of 17.4 years (range, 0.1-29.1 y); 99.7% of participants completed the study. A total of 19.6% participants developed events (8.0% complicated and 11.6% uncomplicated). Ten percent had awareness of their gallstones; awareness was associated with uncomplicated and complicated events. Stones larger than 10 mm were associated with all events (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.45-3.69), acute cholecystitis (HR, 9.49; 95% CI, 2.05-43.92), and uncomplicated events (HR, 2.55; 95% CI, 1.38-4.71), including cholecystectomy (HR, 2.69; 95% CI, 1.29-5.60). Multiple stones were associated with all events (HR, 1.68; 95% CI, 1.00-2.81), complicated events (HR, 2.52; 95% CI, 1.05-6.04), and common bile duct stones (HR, 11.83; 95% CI, 1.54-91). There was an association between gallstones more than 5 years old and acute cholecystitis. Female sex was associated with all and uncomplicated events. We found a negative association between participant age and all events, uncomplicated events, and acute cholecystitis. Comorbidities and female-associated factors (intake of birth control pills or estrogens and number of births) were not associated with events. Compared with men with a single stone of 10 mm or smaller (reference), women with multiple stones greater than 10 mm had the highest risk for events (HR, 11.05; 95% CI, 3.76-32.44; unadjusted absolute risk, 0.0235 events/person-years). CONCLUSIONS: Fewer than 20% of subjects with gallstones develop clinical events. Larger, multiple, and older gallstones are associated with events. Further studies are needed to confirm the prediction rules.

Metabolic biomarkers and gallstone disease - a population-based study.

OBJECTIVES: The objectives for this study were to examine the associations between metabolic biomarkers of obesity including insulin resistance, vascular dysfunction, systemic inflammation, genetic susceptibility and ultrasound proven gallstone disease or cholecystectomy in a population-based cross-sectional study. MATERIAL AND METHODS: A total of 2650 participants were included, of whom 422 had gallstone disease. Associations between selected metabolic biomarkers and gallstone disease were estimated by multivariable logistic regression models and expressed as odds ratio (OR) and 95% confidence interval (CI). RESULTS: Gallstone disease was associated with fasting glucose (OR 1.14, 95% CI [1.05;1.24]), fasting insulin (OR 1.03, 95% CI [1.01;1.05]), homeostasis model assessment insulin resistance (OR 1.18, 95% CI [1.02;1.36]), the metabolic syndrome (OR 1.51, 95% CI [1.16;1.96]), white blood cell count (OR 1.07, 95% CI [1.00;1.15]) and C-reactive protein (OR 1.03, 95% CI [1.01;1.05]). A tendency towards an association for soluble urokinase plasminogen activator receptor was also found (OR 1.08, 95% CI [0.99;1.18]). The MC4R(rs17782313) (OR 1.27, 95% CI [1.02;1.58]), MAP2K5(rs2241423) (OR 1.80, 95% CI [1.04;3.41]), NRXN3(rs10146997) (OR 1.26, 95% CI [1.01;1.57]), HHEX(rs1111875) (OR 1.29, 95% CI [1.03;1.62]), FAIM2(rs7138803) (OR 0.66, 95% CI [0.48;0.91]), and apolipoprotein E4 allele (OR 0.76, 95% CI [0.59;0.98]) were associated with gallstone disease. Urinary albumin was not associated with gallstone disease. The association between BMI and gallstone disease was explained by insulin resistance. CONCLUSIONS: Biomarkers of insulin resistance, systemic inflammation and genetic obesity or type 2 diabetes risk alleles seem to be associated with gallstone disease. Future studies should explore temporal associations and genetic associations in other populations in order to clarify targets for prevention or intervention.

Screen-detected gallstone disease and cardiovascular disease.

Knowledge about temporal associations for screen-detected gallstone disease and cardiovascular disease is limited. The objective of this study was to determine if screen-detected gallstones or cholecystectomy was associated with development of cardiovascular disease. A cohort study of three randomly selected groups from the general population of Copenhagen was performed. Participants (n = 5928) were examined 1982-1992 and underwent abdominal ultrasound examination to detect gallstone disease and were not informed of their gallstone status. Participants were followed up for occurrence of cardiovascular disease through nationwide registers until December 2014. Multivariable Cox regression analyses were performed including traditional cardiovascular disease risk factors and apolipoprotein E genotype. Gallstone disease was identified in 10% (591/5928) of participants at baseline of whom 6.8% had gallstones and 3.2% had cholecystectomy. The study population was followed for a period of 32 years with only 1% lost to follow-up. Gallstone disease was associated with all cardiovascular disease (hazard ratio (HR) 1.36, 95% confidence interval (CI) [1.17;1.59]) and to the subgroups coronary artery (HR 1.34, 95% CI [1.10;1.64]), cerebrovascular (HR 1.22, 95% CI [0.97;1.52]), and peripheral artery disease (HR 1.57, 95% CI [1.15;2.13]). No differences in estimates were identified for gallstones detected at ultrasound or cholecystectomy. Adjustment did not change estimates substantially. Gallstone disease seems to be independently associated to cardiovascular disease. Associations cannot be explained through traditional cardiovascular disease risk factors, apolipoprotein E4 allele, or detection bias. Future studies should explore the link between gallstone and cardiovascular disease further and gut microbiota may be a candidate mechanism.

Determinants for clinical events in gallstone carriers unaware of their gallstones.

BACKGROUND AND AIM: Knowledge about determinants for clinical events in gallstone carriers is missing. The aim of this cohort study was to identify determinants of clinical gallstone events during long-term follow-up of a population unaware of their gallstones. METHODS: Three randomly selected groups from the general population of Copenhagen (n = 6 037) underwent ultrasound examinations to detect gallstones in the period 1982-1994. Participants unaware of gallstone (n = 595) were followed up for clinical gallstone events through central registers until December 31, 2011. Follow-up length was median 17.5 years and 99.8% complete. Cox regression analyses were performed. RESULTS: Gallstone events occurred in 16.6% participants of whom 7.2% were complicated and 9.4% were uncomplicated. Total events were associated with body mass index. Complicated events were associated with coffee consumption, vocational training, and inversely association to a higher physical activity level when compared with being sedentary. Multiple adjusted models confirmed association for total events and body mass index and for complicated events and physical activity. No significant associations were identified for alcohol, coffee, diet, smoking, or visits to general practitioner and clinical events. CONCLUSIONS: Body mass index, vocational training, and physical activity level were associated with clinical events in long-term follow-up of unaware gallstone carriers. Future trials should investigate clinical effects of lifestyle and medical interventions in gallstone carriers.

Plasma suPAR is lowered by smoking cessation: a randomized controlled study.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a stable inflammatory biomarker. In patients, suPAR is a marker of disease presence, severity and prognosis. In the general population, suPAR is predictive of disease development, such as diabetes and cardiovascular disease and, in smokers, predictive of long-term lung cancer development. Whether smoking cessation impacts the suPAR level is unknown. MATERIALS AND METHODS: Forty-eight smokers were randomized into three groups of 16: (i) continued to smoke 20 cigarettes per day, (ii) refrained from smoking and used transdermal nicotine patches and (iii) refrained from smoking and used placebo patches. Nonsmokers were included for comparison. suPAR and C-reactive protein (CRP) levels were measured by ELISA. RESULTS: At baseline, the suPAR level was significantly higher in the 48 smokers (median 3·2 ng mL, IQR (2·5-3·9)) than in 46 never smokers (1·9 ng/mL (1·7-2·2)). In smokers randomized to smoking cessation, suPAR levels after 4 weeks of stopping were decreased and no longer significantly different from the never smokers values. SuPAR decreased in both those who received a placebo as well as nicotine patch. Interestingly, those with the highest suPAR level at time of smoking were also those with the highest level of suPAR after smoking cessation. In contrast, smoking or smoking cessation had no influence on CRP levels. CONCLUSION: Our study suggests that the suPAR level may aid to personalize the risk of smoking by identifying those smokers with the highest risk of developing disease and who may have the most benefit of smoking cessation.

Determinants for gallstone formation - a new data cohort study and a systematic review with meta-analysis.

OBJECTIVE: Only few determinants of gallstone formation have been identified in cohort studies. The aim was to identify further determinants for gallstones in a Danish cohort and to perform a meta-analysis of results from existing cohorts. MATERIAL AND METHODS: Data from a cohort study was used. Gallstone incidence was assessed through repeated ultrasound examinations. Body mass index (BMI), blood pressure, self-rated health, lifestyle variables, blood lipids, and use of female sex hormones were measured at the baseline examination. Statistical analyses included logistic regression. Based on a prospective protocol, a systematic review of the literature was performed identifying all articles dealing with determinants of incident gallstones. Meta-analyses of comparable determinants were performed through fixed effect models. RESULTS: Participants with no gallstones at baseline and with at least one re-examination were followed-up completely (mean 11.6 years, N = 2848). The overall cumulative incidence of gallstones was 0.60% per year. Independent positive determinants for incident gallstones were age, female sex, non-high density lipoprotein (non-HDL) cholesterol, and gallbladder polyps. In addition, BMI was positively associated in men. The systematic review additionally identified associations for comorbidities, parity, and dietary factors. Meta-analysis confirmed the significant associations for incident gallstones and age, female sex, BMI, and non-HDL cholesterol. No significant associations were found for blood pressure, smoking, alcohol consumption, HDL cholesterol, or triglycerides in meta-analyses. CONCLUSIONS: Age, female sex, BMI, non-HDL cholesterol, and polyps are independent determinants for gallstone formation. Incident gallstones and the metabolic syndrome share common risk factors. More studies are needed for further exploration.

Re-resection Rates and Disease Recurrence in Crohn's Disease - A Population-Based Study Using Individual-Level Patient Data.

BACKGROUND AND AIMS: Despite advances in the medical treatment of Crohn's disease (CD), many patients will still need bowel resections and face the subsequent risk of recurrence and re-resection. We describe contemporary re-resection rates and identify disease-modifying factors and risk factors for re-resection. METHODS: We conducted a retrospective, population-based, individual patient data cohort study covering 47.4% of the Danish population, including all CD patients who underwent a primary resection between 2010 and 2020. RESULTS: Among 631 primary resected patients, 24.5% underwent a second resection, and 5.3% a third. Re-resection rates after one, five, and 10 years were 12.6%, 22.4%, and 32.2%, respectively. Reasons for additional resections were mainly disease activity (57%) and stoma reversal (40%). Disease activity-driven re-resection rates after one, five, and 10 years were 3.6%, 10.1%, and 14.1%, respectively. Most stoma reversals occurred within one year (80%). The median time to recurrence was 11.0 months. Biologics started within one year of the first resection revealed protective effect against re-resection for stenotic and penetrating phenotypes. Prophylactic biologic therapy at primary ileocecal resection reduced disease recurrence and re-resection risk (HR 0.58, 95% CI (0.34-0.99), p=0.047). Risk factors for re-resection were location of resected bowel segments at the primary resection, disease location, disease behavior, smoking, and perianal disease. CONCLUSION: Re-resection rates, categorized by disease activity, are lower than those reported in other studies and are closely associated with disease phenotype and localization. Biological therapy may be disease-modifying for certain subgroups when initiated within one year of resection.

One-step laparoscopic cholecystectomy with common bile duct exploration and stone extraction versus two-step endoscopic retrograde cholangiography with stone extraction plus laparoscopic cholecystectomy for patients with common bile duct stones: a randomised feasibility and pilot clinical trial-the preGallStep trial.

BACKGROUND: Endoscopic retrograde cholangiography (ERC) with stone extraction and papillotomy with subsequent laparoscopic cholecystectomy-the two-step approach-is the standard treatment of common bile duct stones in many countries. However, ERC is associated with a high risk of complications and more than half of patients require multiple ERCs. Meta-analyses of randomised clinical trials find no major differences of the two-step approach in comparison with laparoscopic cholecystectomy with intraoperative laparoscopic stone clearance-the one-step approach. Currently, there are insufficient data to ascertain superiority. METHODS: The preGallstep trial is an investigator-initiated, multicentre randomised feasibility and pilot clinical trial with blinded outcome assessment. Eligible patients are patients with common bile duct stones (identified by magnetic resonance cholagiopancreatography), age 18 years or above with the possibility to perform both interventions within a reasonable time. We intent to randomise 150 participants allocated 1:1. The experimental intervention is the one-step approach. This consists of laparoscopic common bile duct exploration plus laparoscopic cholecystectomy. The control intervention is the two-step approach which consists of ERC plus sphincterotomy (first step) and subsequent laparoscopic cholecystectomy (second step). Feasibility outcomes include the proportion of eligible patients not wanting to participate, reasons for rejection to participate, difficulties during the informed consent procedure, difficulties with randomisation, difficulties with data management, difficulties with blinding patient charts and forms and difficulties with maintaining blinding for the outcome assessors. The primary pilot outcome is the proportion of participants with at least one postoperative complication according to the Clavien-Dindo score grade II and above until 90 days after randomisation. This outcome will be used for a future sample size calculation of a larger pragmatic trial. Further, a range of clinical explorative outcomes will be assessed. DISCUSSION: As no sample size is estimated in this trial, there is a risk of wrongly assessing the effect on the patient-related outcome. The surgical procedures cannot be blinded. However, blinding will be employed in all other aspects of the trial, including the establishment of a blinded outcome adjudication committee with three independent assessors. Heterogeneity in screening, randomisation, diagnostics, treatment procedures, interventions and follow-up across trial sites may cause challenges in conducting a larger pragmatic trial. To monitor inter-site differences, we have implemented a central data monitoring scheme. TRIAL REGISTRATION: ClinicalTrials.gov identification: NCT04801238 , Registered on 16 March 2021.

Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review.

OBJECTIVE: The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved. BACKGROUND: Smoking is a recognized risk factor for healing complications after surgery, but the pathophysiological mechanisms remain largely unknown. METHODS: Pathophysiological studies addressing smoking and wound healing were identified through electronic databases (PubMed, EMBASE) and by hand-search of articles' bibliography. Of the 1460 citations identified, 325 articles were retained following title and abstract reviews. In total, 177 articles were included and systematically reviewed. RESULTS: Smoking decreases tissue oxygenation and aerobe metabolism temporarily. The inflammatory healing response is attenuated by a reduced inflammatory cell chemotactic responsiveness, migratory function, and oxidative bactericidal mechanisms. In addition, the release of proteolytic enzymes and inhibitors is imbalanced. The proliferative response is impaired by a reduced fibroblast migration and proliferation in addition to a downregulated collagen synthesis and deposition. Smoking cessation restores tissue oxygenation and metabolism rapidly. Inflammatory cell response is reversed in part within 4 weeks, whereas the proliferative response remains impaired. Nicotine does not affect tissue microenvironment, but appears to impair inflammation and stimulate proliferation. CONCLUSIONS: Smoking has a transient effect on the tissue microenvironment and a prolonged effect on inflammatory and reparative cell functions leading to delayed healing and complications. Smoking cessation restores the tissue microenvironment rapidly and the inflammatory cellular functions within 4 weeks, but the proliferative response remain impaired. Nicotine and nicotine replacement drugs seem to attenuate inflammation and enhance proliferation but the effect appears to be marginal.

National clinical practice guidelines for the treatment of symptomatic gallstone disease: 2021 recommendations from the Danish Surgical Society.

BACKGROUND AND OBJECTIVE: Gallstones are highly prevalent, and more than 9000 cholecystectomies are performed annually in Denmark. The aim of this guideline was to improve the clinical course of patients with gallstone disease including a subgroup of high-risk patients. Outcomes included reduction of complications, readmissions, and need for additional interventions in patients with uncomplicated gallstone disease, acute cholecystitis, and common bile duct stones (CBDS). METHODS: An interdisciplinary group of clinicians developed the guideline according to the GRADE methodology. Randomized controlled trials (RCTs) were primarily included. Non-RCTs were included if RCTs could not answer the clinical questions. Recommendations were strong or weak depending on effect estimates, quality of evidence, and patient preferences. RESULTS: For patients with acute cholecystitis, acute laparoscopic cholecystectomy is recommended (16 RCTs, strong recommendation). Gallbladder drainage may be used as an interval procedure before a delayed laparoscopic cholecystectomy in patients with temporary contraindications to surgery and severe acute cholecystitis (1 RCT and 1 non-RCT, weak recommendation). High-risk patients are suggested to undergo acute laparoscopic cholecystectomy instead of drainage (1 RCT and 1 non-RCT, weak recommendation). For patients with CBDS, a one-step procedure with simultaneous laparoscopic cholecystectomy and CBDS removal by laparoscopy or endoscopy is recommended (22 RCTs, strong recommendation). In high-risk patients with CBDS, laparoscopic cholecystectomy is suggested to be included in the treatment (6 RCTs, weak recommendation). For diagnosis of CBDS, the use of magnetic resonance imaging or endoscopic ultrasound prior to surgical treatment is recommended (8 RCTs, strong recommendation). For patients with uncomplicated symptomatic gallstone disease, observation is suggested as an alternative to laparoscopic cholecystectomy (2 RCTs, weak recommendation). CONCLUSIONS: Seven recommendations, four weak and three strong, for treating patients with symptomatic gallstone disease were developed. Studies for treatment of high-risk patients are few and more are needed. ENDORSEMENT: The Danish Surgical Society.

Smoking attenuates wound inflammation and proliferation while smoking cessation restores inflammation but not proliferation.

Full-thickness 5 mm punch biopsy wounds were made lateral to the sacrum in 48 smokers and 30 never smokers. After 1 week, the wounds were excised and fixed. The smokers were then randomized to continuous smoking or abstinence with a transdermal nicotine patch or a placebo patch. The sequence of wounding and excision was repeated after 4, 8, and 12 weeks. All excised tissue was stained with hematoxylin-eosin and immunohistochemically for macrophages (CD68), procollagen 1 N-terminal propeptide (PINP) in fibroblasts, and endothelial cells (CD31). The cellularity was assessed and scored by two independent histopathologists, and for the analysis, proportional odds models and random effect models for repeated measurements were applied. Macrophages and PINP-stained fibroblasts were reduced in the smokers' wounds (0.28 [0.14-0.58] [OR, 95%CI]; p=0.01 and 0.37[0.19-0.70]; p<0.01, respectively, when compared with never smokers' wounds). Inflammation scores were marginally affected. Following smoking cessation, inflammatory cell infiltration and macrophages in the wounds increased. PINP-stained fibroblasts were unaffected. Neovascularization was not affected by smoking or abstinence. Wound inflammation and fibroblast proliferation were attenuated in smokers, suggesting delayed healing. Abstinence from smoking restores inflammation, but does not affect proliferation. These findings suggest a pathophysiologic mechanism for postoperative wound infection and dehiscence in smokers and why smoking cessation appears to reduce wound infection but not dehiscence.

Acute effects of nicotine and smoking on blood flow, tissue oxygen, and aerobe metabolism of the skin and subcutis.

BACKGROUND: Nicotine released from tobacco smoke causing reduction in blood flow has been suggested as causative for postoperative wound complications in smokers, but the mechanism remains unknown. MATERIALS AND METHODS: In eight healthy male smokers and eight ex-smokers, the cutaneous and subcutaneous blood flow (QBF, SqBF) was assessed by Laser Doppler and 133Xe clearance. Tissue oxygen tension (TO(2)) was measured by a LICOX O(2)-electrode. Tissue glucose and lactate (Tgluc, Tlact) were assessed by microdialysis. The parameters were studied after intravenous infusion of 1.0 mg nicotine, smoking of one cigarette, arterial occlusion, and reperfusion. RESULTS: Nicotine infusion decreased SqBF from 4.2 +/- 2.0 to 3.1 +/- 1.2 mL/100 g tissue/min (P < 0.01), whereas QBF was 21.7 +/- 8.6 and 22.7 +/- 9.6 Arbitrary Units (AU), respectively (P = 0.21). TO(2) increased from 49.3 +/- 12.0 to 53.9 +/- 12.0 mm Hg (P = 0.01). Tgluc and Tlact remained unaffected. Smoking decreased SqBF from 4.2 +/- 2.0 to 2.7 +/- 1.2 mL/100 g tissue/min (P < 0.01). QBF decreased from 23.4 +/- 9.2 to 20.3 +/- 7.4 AU (P < 0.01), and TO(2) decreased from 53.9 +/- 12.0 to 48.4 +/- 11.1 mm Hg (P < 0.01). Following smoking, Tgluc decreased from 0.7 +/- 0.1 to 0.6 +/- 0.1 ng/mL (P < 0.01), and Tlact increased from 0.2 +/- 0.1 to 0.3 +/- 0.2 ng/mL (P < 0.01). The observed alterations were similar in smokers and ex-smokers. CONCLUSIONS: Nicotine has a limited vasoactive effect in the skin and subcutis unlikely to be explained by smoking, which distinctly decreases tissue blood flow, oxygen tension, and aerobe metabolism independent of smoking status.

Effect of smoking, abstention, and nicotine patch on epidermal healing and collagenase in skin transudate.

Delayed wound healing may explain postoperative tissue and wound dehiscence in smokers, but the effects of smoking and smoking cessation on the cellular mechanisms remain unclear. Suction blisters were raised in 48 smokers and 30 never smokers. The fluid was retrieved and the epidermal roof was excised. Transepidermal water loss (TEWL) was measured after 2, 4, and 7 days. Then, the smokers were randomized to continuous smoking or abstinence with a transdermal nicotine patch or a placebo by concealed allocation. The sequence was repeated after 4, 8, and 12 weeks in all smokers and abstainers and in 6 never smokers. Matrix metalloproteinase (MMP)-8 and MMP-1 levels in suction blister fluid were assessed by an enzyme-linked immunosorbent assay. Random-effects models for repeated measurements were applied and p< or =0.05 was considered significant. One week after wounding the TEWL was 17.20 (14.47-19.92) g/cm(2) hour (mean, 95% CI) in smokers and 13.89 (9.46-18.33) in never smokers (p<0.01). In abstinent smokers TEWL was 18.95 (15.20-22.70)(p<0.01, when compared with smokers). In smokers, MMP-8 was 36.4 (24.3-48.5) ng/mL (mean, 95% CI) and 15.2 (1.4-30.2) ng/mL in never smokers (p<0.01). Abstinent smokers' MMP-8 level was 21.2 ng/mL (6.6-43.0) (p=0.02, when compared with smokers). MMP-1 was unaffected by smoking and abstention. Transdermal nicotine patch did not affect any parameter. We conclude that smoking attenuates epidermal healing and may enhance extracellular matrix degradation. Three months of abstinence from smoking does not restore epidermal healing, whereas 4 weeks of abstinence normalizes suction blister MMP-8 levels. These findings suggest sustained impaired wound healing in smokers and potential reversibility of extracellular matrix degradation.

Percutaneous Cholecystostomy Versus Conservative Treatment for Acute Cholecystitis: a Cohort Study.

BACKGROUND: Percutaneous cholecystostomy is frequently used as a treatment option for acute calculous cholecystitis in patients unfit for surgery. There is sparse evidence on the long-term impact of cholecystostomy on gallstone-related morbidity and mortality in patients with acute calculous cholecystitis. This study describes the long-term outcome of acute calculous cholecystitis following percutaneous cholecystostomy compared to conservative treatment. METHODS: This was a cohort study of patients admitted at our institution from 2006 to 2015 with acute calculous cholecystitis without early or delayed cholecystectomy. Endpoints were gallstone-related readmissions, recurrent cholecystitis, and overall mortality. RESULTS: The investigation included 201 patients of whom 97 (48.2%) underwent percutaneous cholecystostomy. Patients in the cholecystostomy group had significantly higher age, comorbidity level, and inflammatory response at admission. The median duration of catheter placement in the cholecystostomy group was 6 days. The complication rate of cholecystostomy was 3.1% and the mortality during the index admission was 3.5%. The median follow-up was 1.6 years. The rate of gallstone-related readmissions was 38.6%, and 25.3% had recurrence of cholecystitis. Cox regression analyses revealed no significant differences in gallstone-related readmissions, recurrence of acute calculous cholecystitis, and overall mortality in the two groups. CONCLUSIONS: Percutaneous cholecystostomy in the treatment of acute calculous cholecystitis was neither associated with long-term benefits nor complications. Based on the high gallstone-related readmission rates of this study population and todays perioperative improvements, we suggest rethinking the indications for non-operative management including percutaneous cholecystostomy in acute calculous cholecystitis.

Screen-detected gallstone disease and autoimmune diseases - A cohort study.

BACKGROUND: Gallstone disease is highly prevalent and is associated with systemic inflammation. AIMS: To determine whether screen-detected gallstones or cholecystectomy are associated with the occurrence of autoimmune and autoinflammatory diseases and the most common subgroups thereof. METHODS: A cohort study of three randomly selected general population samples from Copenhagen was performed. Participants (n = 5928) were examined in the period 1982-1992, underwent abdominal ultrasound examination to detect gallstone disease, and followed through national registers until December 2014 (median 24.7 years) for occurrence of immunological diseases. Multivariable Cox regression analyses were performed. RESULTS: Gallstone disease was identified in 10% (591/5928) of participants, of whom 6.8% had gallstones and 3.2% had cholecystectomy at baseline. Gallstone disease was associated with incidence of autoimmune diseases (12.9% versus 7.92%; hazard ratio 1.46; 95% confidence interval [CI], [1.11;1.91]), diabetes mellitus type 1 (5.95% versus 3.67%; 1.53; [1.02;2.30]), and autoimmune thyroid disease (3.70% versus 1.59%; 2.06; [1.26;3.38]). Rheumatoid arthritis, autoinflammatory diseases, or any subgroups thereof were not associated. CONCLUSIONS: In a large general population sample, screen-detected gallstone disease was associated with the development of autoimmune diseases during long-term follow-up. Future research efforts are needed to further explore common disease mechanisms.

Risk factors for mortality and postoperative complications after gastrointestinal surgery.

BACKGROUND: Predictors of a poor surgical outcome are numerous, of which some are well-defined. We aimed to assess risk factors predictive of poor surgical outcome across different gastrointestinal operations related to the patient, the disease, the treatment, and the organization of care. METHODS: Data from 5,255 unselected patients undergoing open gastrointestinal surgery from 1995 through 1998 was prospectively recorded in a clinical database and validated. The database embraced variables related to patient history, preoperative clinical condition, operative findings and complexity, and the surgeon's training. Variables predictive of mortality and complications occurring within 30 days after surgery were assessed by multiple logistic regression analysis. RESULTS: After elective operation, the 30-day mortality was 2.8% and major complications occurred in 11.5% of the patients. The corresponding figures in emergency surgery were 13.8% and 30.1%. Independent of elective or emergency surgery, dependent functional status, and type of operation were associated with postoperative mortality. Comorbidity, type of operation, blood loss, and reoperation were predictors of complications regardless of elective or emergency operation. In elective surgery, predictors of poor surgical outcome were high age, comorbidity, malignancy, and the surgeons training, whereas abnormal vital signs values and peritonitis were predictors of poor outcome after emergency surgery. CONCLUSION: Premorbid factors, characteristics of the disease, the patients' preoperative condition, operative factors, and the surgeon's training are all associated with surgical outcome across different gastrointestinal operations and should be assessed when auditing surgical outcome.

Which Abdominal Symptoms are Associated with Clinical Events in a Population Unaware of Their Gallstones? a Cohort Study.

BACKGROUND: High rates of persistent symptoms are found following cholecystectomy in patients with gallstones. The aim of this population based cohort study was to determine which symptoms were associated with the development of clinical gallstone events in a population unaware of their gallstones. MATERIAL AND METHODS: Three random population samples from Copenhagen (N = 6037) were examined with ultrasound during 1982-1994. Participants were not informed about gallstone status. Abdominal symptoms were assessed at baseline through a questionnaire. Follow-up for clinical events was performed through central registers until 2011. Multivariable Cox regression analyses were performed. RESULTS: Participants unaware of their gallstones (N = 595) were followed for median 17.5 years. A total of 16.6% participants developed clinical events. Both uncomplicated and complicated events were associated with high pain intensity at baseline. Complicated events were also associated with pain at night. Uncomplicated events were associated with pain localized in the epigastrium, of longer duration, and in need of pain medication. No associations were identified for dyspepsia or irritable bowel syndrome. CONCLUSIONS: In a population of unaware gallstone carriers, it was possible to identify abdominal symptoms associated with later clinical detection of the gallstones. These finding may contribute to a better selection of patients for surgery.