Intraoperative distensibility measurement in POEM for achalasia: impact on patient outcome and associations with other outcome variables at 1-year follow-up.

BACKGROUND AND AIMS: The functional luminal imaging probe (FLIP) can provide measurements of lower esophageal sphincter (LES) distensibility. Studies report that use of intraoperative FLIP examination during peroral endoscopic myotomy (POEM) for achalasia is associated with treatment success, but evidence is limited and inconsistent. The main aim of the present study was to assess associations between intraoperative FLIP values and 1-year outcomes. Additionally, associations between 1-year FLIP measurements and other 1-year outcome variables were studied. METHODS: We performed a single-center prospective study of consecutive achalasia patients treated with POEM with a standardized 1-year follow-up. The inclusion period was from June 2017 to January 2020. We compared 1-year outcomes (FLIP measurement values, Eckardt score (ES), reflux esophagitis, timed barium esophagogram (TBE), and lower esophageal sphincter resting pressure (LES-rp)) in patients with and without intraoperative FLIP examination. We also assessed associations between intraoperative FLIP values, 1-year FLIP values, and other 1-year outcomes. Results are given as median (IQR), and non-parametrical statistical analyses were applied. RESULTS: Sixty-two patients (27 females) with median age 45 years (35-54) were included. Baseline characteristics were similar in patients with (n = 32) and without (n = 30) intraoperative FLIP examination. In patients with intraoperative FLIP, ES was 2 (1-3) and LES distensibility index (DI) 3.7 (2.6-5.4) after 1 year, compared with ES 2 (1-3) and DI 4.0 (3.1-6.8)) in patients without intraoperative FLIP (ns). Intraoperative DI was not correlated with 1-year ES or DI. One-year DI correlated significantly with 1-year ES (rs - 0.42), TBE (rs - 0.34), and LES-rp (rs - 0.29). CONCLUSIONS: Use of intraoperative FLIP measurements in POEM for achalasia is not associated with improved 1-year outcome, and the clinical value of intraoperative FLIP in POEM for achalasia is questioned. Follow-up FLIP measurements are moderately associated with symptomatic outcome, and may serve as an additional diagnostic modality in post-treatment evaluation.

Quality of life in patients with achalasia: Associations with Eckardt score and objective treatment outcomes after peroral endoscopic myotomy.

Background and study aims Knowledge on self-reported quality of life (QoL) in achalasia and QoL improvements after peroral endoscopic myotomy (POEM) is limited. Furthermore, the clinical role of QoL in achalasia follow-up has not been evaluated. The present study aimed to examine QoL in achalasia patients before and after POEM and assess associations between QoL, Eckardt score (ES) and objective results. Patients and methods This was a single-center prospective study of treatment-naïve achalasia patients with 12-month follow-up after POEM including manometry, upper endoscopy, 24-hour pH registration, and timed barium esophagogram. QoL data were registered using European Organisation for Research and Treatment of Cancer core questionnaire (QLQ-C30) and esophageal module (QLQ-OES18). Comparison with a reference population was performed to assess impact of achalasia on QoL and effect of therapy. Mixed models for repeated measures were applied. Results Fifty patients (26 females) with a median age of 47 years (18-76) were included. Before treatment, all QoL domains were significantly impaired compared with an age- and gender-adjusted reference population ( P  < 0.05). No significant QoL-differences were found after POEM, except for fatigue and nausea/vomiting. Clinically relevant QoL improvement was observed in ≥ 50 % of the patients in all QoL domains, except for physical and role functioning. QoL was significantly associated with ES ( P  < 0.05) but not with objective results. Conclusions Achalasia is associated with severe QoL impairment. Following POEM, a significant and clinically relevant QoL improvement is observed. QoL is associated with ES, but not with objective results after POEM.

Tailored surgery in chronic pancreatitis after implementation of a multidisciplinary team assessment; a prospective observational study.

INTRODUCTION: Optimal management of chronic pancreatitis involves several specialties. Selection of patients for surgery may benefit from evaluation by a multidisciplinary team (MDT), similar to cancer care. The aim of this study was to evaluate outcomes in patients selected for surgery after MDT decision. METHODS: A prospective, observational study of consecutive patients operated for pain due to chronic pancreatitis after implementation of a MDT. The main outcome was Quality of life (QoL) assessed by EORTC-QLQ C30 and pain relief in patients followed >3 months. Complications were registered and predictive factors for pain relief analyzed. RESULTS: Of 269 patients evaluated by the MDT, 60 (22%) underwent surgery. Postoperative surgical complications occurred in five patients (8.3%) and reoperation within 30 days in two. There was no 90-days mortality. Complete or partial pain relief was achieved in 44 of 50 patients followed >3 months (88%). Preoperative duration of pain predicted lower probability of success. Postoperative improvement in QoL was most prominent for pain, appetite and nausea. CONCLUSIONS: After MDT evaluation, one in five patients was selected for surgery. Pain relief was obtained in a majority of patients with improved QoL. A tailored approach through a MDT seems warranted and efficient.

Targeted genetic and epigenetic profiling of esophageal adenocarcinomas and non-dysplastic Barrett's esophagus.

BACKGROUND: Despite the efforts to describe the molecular landscape of esophageal adenocarcinoma (EAC) and its precursor lesion Barrett's esophagus (BE), discrepant findings are reported. Here, we investigated the prevalence of selected genetic (TP53 mutations and microsatellite instability (MSI) status) and epigenetic (DNA promoter hypermethylation of APC, CDKN2A, MGMT, TIMP3 and MLH1) modifications in a series of 19 non-dysplastic BE and 145 EAC samples. Additional biopsies from adjacent normal tissue were also evaluated. State-of-the-art methodologies and well-defined scoring criteria were applied in all molecular analyses. RESULTS: Overall, we confirmed frequent TP53 mutations among EAC (28%) in contrast to BE, which harbored no mutations. We demonstrated that MSI and MLH1 promoter hypermethylation are rare events, both in EAC and in BE. Our findings further support that APC, CDKN2A, MGMT and TIMP3 promoter hypermethylation is frequently seen in both lesions (21-89%), as well as in a subset of adjacent normal samples (up to 12%). CONCLUSIONS: Our study further enlightens the molecular background of BE and EAC. To the best of our knowledge, this is one of the largest studies addressing a targeted analysis of genetic and epigenetic modifications simultaneously across a combined series of non-dysplastic BE and EAC samples.

Structural imaging findings are related to clinical complications in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Structural pancreatic changes and complications related to chronic pancreatitis are well described, but little is known about their relationship. We aimed to explore the associations between pancreatic morphology and clinical complications in a large chronic pancreatitis cohort. METHODS: The Scandinavian Baltic Pancreatic Club database collects registrations on patients with definite or probable chronic pancreatitis according to the M-ANNHEIM diagnostic criteria. In this cross-sectional study, we used multivariate logistic regression analyses to evaluate whether imaging-based structural pancreatic changes were associated with common clinical complications. We adjusted for sex, age, disease duration, current alcohol abuse and current smoking. RESULTS: We included 742 patients with a mean age of 55 years. Among these, 68% were males, 69% had pancreatic exocrine insufficiency, 35% had diabetes, 12% were underweighted and 68% reported abdominal pain. Main pancreatic duct obstruction, severe (i.e. more than 14) calcifications, pancreatic atrophy and parenchymal changes throughout the entire pancreas (continuous organ involvement) were positively associated with pancreatic exocrine insufficiency. Continuous organ involvement and pseudocysts were positively and negatively associated with diabetes, respectively. Pancreatic atrophy and severe calcifications were positively associated with underweight, and severe calcifications were negatively associated with pain. CONCLUSIONS: This study shows independent associations between distinct structural changes on pancreatic imaging and clinical complications in chronic pancreatitis. Pancreatic atrophy, severe calcifications and continuous organ involvement may be of particular clinical relevance, and these findings should motivate monitoring of pancreatic function and nutritional status.

Exocrine pancreas insufficiency in chronic pancreatitis - Risk factors and associations with complications. A multicentre study of 1869 patients.

BACKGROUND/OBJECTIVES: There is scarce information about risk factors for exocrine pancreas insufficiency (EPI) in chronic pancreatitis (CP), and how it associates with other complications. The aim of the present study was to examine risk factors for EPI and associations to procedures and other CP related complications in a large, Northern European cohort. PATIENTS AND METHODS: We retrieved cross-sectional data on demographics, status on EPI, aetiological risk factors for CP, CP related complications as well as surgical and endoscopic treatment from the Scandinavian Baltic Pancreatic Club Database. Associations were assessed by univariate and multivariate logistic regression analyses. Results are presented as odds ratios (OR) with 95% confidence intervals. RESULTS: We included 1869 patients with probable or definitive CP in the study. Exocrine pancreas insufficiency was present in 849 (45.4%) of patients. In multivariate analyses, EPI associated with smoking aetiology (OR 1.47 (1.20-1.79), p < 0.001), and nutritional/metabolic aetiology (OR 0.52 (0.31-0.87), p = 0.01) to CP. Pancreatic or common bile duct stenting procedure and pancreatic resection were both associated with EPI (ORs 1.44 (1.15-1.80), p = 0.002 and 1.54 (1.02-2.33), p = 0.04, respectively). The presence of diabetes mellitus (OR 2.45 (1.92-3.15), p < 0.001), bile duct stenosis (OR 1.48 (1.09-2.00), p = 0.02) and underweight (2.05 (OR 1.40-3.02), p < 0.001) were all associated with presence of EPI. CONCLUSIONS: Smoking, bile duct stenosis, previous stenting and resection procedures are all associated with EPI in patients with CP. Presence of EPI were also associated with malnutrition and diabetes mellitus. Hence, intensive nutritional surveillance is needed in these patients.

One year comprehensive prospective follow-up of achalasia patients after peroral endoscopic myotomy.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) is an established therapy for achalasia, but outcome evaluation has often been limited to Eckardt score (ES). The present study was aimed to improve knowledge about outcome evaluation and predictive outcome factors by performing a comprehensive objective evaluation of achalasia patients treated by POEM. METHODS: This single centre prospective study reports outcome data 12 months after POEM in treatment-naive achalasia patients. A predefined follow-up protocol included ES, high resolution manometry, 24-h pH measurement, upper endoscopy and timed barium esophagogram (TBE). Univariate and multivariate regression analyses were performed to analyze association between post-POEM variables and identify predictive factors for objective outcome. RESULTS: Fifty patients were included with a drop-out rate of <5%. ES, lower oesophageal sphincter pressures, TBE heights and maximal oesophageal diameter were all reduced after POEM (p < .001), and 28% (13/47) of the patients had a positive 24-h pH registration. An oesophageal diameter >3 cm after POEM was associated with treatment failure assessed by ES (p = .04) and TBE (p = .03). Advanced achalasia stage (p = .02) and long symptom duration (p = .04) were identified as independent predictive factors for poor outcome assessed by TBE. CONCLUSIONS: The present study confirms that POEM is an efficient therapy for achalasia. The comprehensive objective evaluation after POEM demonstrates that long symptom duration and major changes in oesophageal anatomy at diagnosis imply poor treatment outcome, and a post-POEM dilated oesophagus is associated with treatment failure.Key messagesPeroral endoscopic myotomy (POEM) is established as a safe and effective therapy for achalasia.Timed barium esophagogram offers objective variables that are valuable in treatment response evaluation. Advanced achalasia stage and long symptom duration are predictive factors for poor objective treatment response after POEM.

Aetiological risk factors are associated with distinct imaging findings in patients with chronic pancreatitis: A study of 959 cases from the Scandinavian Baltic Pancreatic Club (SBPC) imaging database.

OBJECTIVES: The relation between aetiology and structural changes of the pancreas in patients with chronic pancreatitis (CP) is not fully understood. Earlier studies are limited by focusing on selected factors in studies of limited sample size. We aimed to use a large dataset to explore associations between aetiology and pancreatic morphology in CP. METHODS: Subjects with definite or probable CP according to the M-ANNHEIM diagnostic criteria were included in this multicentre cross-sectional observational study and assessed using a standardized and validated CP imaging system. We performed multivariate logistic regression to analyse if aetiological factors adjusted for covariates were independently associated with morphological pancreatic features. RESULTS: We included 959 patients (66% males). Mean (SD) age was 55 (14) years. Pancreatic structural changes were found in 94% of the subjects: 67% had calcifications, 59% main pancreatic duct dilatation, 33% pseudo-cysts and 22% pancreatic atrophy. Alcohol abuse was independently associated with pancreatic calcifications (odds ratio (OR, [95% CI]); 1.61, [1.09, 2.37]) and focal acute pancreatitis (OR; 2.13, [1.27, 3.56]), whereas smoking was independently associated with more severe calcifications (OR; 2.09, [1.34, 3.27]) and involvement of the whole gland (OR; 2.29, [1.61, 3.28]). Disease duration was positively associated with calcifications (OR; (per year) 1.05 [1.02, 1.08]) and pancreatic atrophy (OR; 1.05 [1.02, 1.08]) and negatively associated with focal acute pancreatitis (OR 0.91, [0.87, 0.95] and pseudo cysts (OR; 0.96, [0.93, 0.98]). CONCLUSION: In this large-scale study, etiological risk factors and disease duration in CP were independently associated with specific structural pancreatic imaging changes.

Pain and aetiological risk factors determine quality of life in patients with chronic pancreatitis, but a brick in the puzzle is missing.

BACKGROUND AND OBJECTIVES: Chronic pancreatitis (CP) is a debilitating fibro-inflammatory disease with a profound impact on patients' quality of life (QOL). We investigated determinants of QOL in a large cohort of CP patients. METHODS: This was a multicentre study including 517 patients with CP. All patients fulfilled the EORTC QLQ-C30 questionnaire. Questionnaire responses were compared to results obtained from a general reference population (n = 11,343). Demographic characteristics, risk factors (smoking and alcohol consumption), pain symptoms, disease phenotype (complications) and treatments were recorded. A multivariable regression model was used to identify factors independently associated with QOL scores. RESULTS: Included patients had a mean age of 56.3 ± 12.8 years, 355 (69%) were men and 309 (60%) had alcohol aetiology. Compared to the reference population, patients with CP had lower global health status (50.5 vs. 66.1; p < 0.001) as well as reduced scores for all functional scales (all p < 0.001). Additionally, CP patients reported a higher burden for all symptom items, with pain being the most prominent complaint (all p < 0.001). Constant pain (coefficient -11.3; p = 0.02), opioid based pain treatment (coefficient -19.7; p < 0.001) and alcoholic aetiology (coefficient -5.1; p = 0.03) were independently associated with lowered global health status. The final multivariable model explained 18% of the variance in global health status. CONCLUSIONS: Patients with CP have significantly lower QOL compared to a population-based reference population. Factors independently associated with a lowered QOL are constant pain, opioid based pain treatment and alcohol aetiology. However, these factors only explain a fraction of QOL and additional factors need identification.

Outcome after endoscopic treatment for dysplasia and superficial esophageal cancer - a cohort study.

BACKGROUND: Dysplasia and superficial esophageal cancer should initially be treated endoscopically. Little is known about post-procedural health-related quality of life (HRQL). The aim of this study was to present our results with endoscopic treatment and post-procedural HRQL. MATERIALS AND METHODS: From June 2014 to December 2018, all patients treated with endoscopic mucosal resection (EMR) and/or radiofrequency ablation (RFA) for low-grade dysplasia (LGD), high-grade dysplasia (HGD), T1a and a minority of patients with T1b at Oslo University Hospital were prospectively included. In June 2019, all patients alive were scored according to the Ogilvie dysphagia score as well as the QLQ-C30 and QLQ-OG25 for assessment of HRQL. RESULTS: Eighty-six patients were treated out of whom 22 (26%) had LGD, 44 (51%) HGD, 13 (15%) T1a, and six patients (7%) T1b. Histology revealed adenocarcinoma in 18 (21%) and squamous cell carcinoma in one (1%), respectively. The mean follow-up was 22.9 months. Tumor regression or downstaging was archived in 78% of the patients with LGD, 66% of patients with HGD and in 89% of patients with T1a/b. Five patients (6%) had esophagectomy. There were few and no serious complications. The 90-days mortality was 1%. Fifty-two patients (88%) experienced no dysphagia (Ogilvie score 0). There was no difference in 11 out of the 15 variables in QLQ-C30 when compared to a non-cancerous reference population. CONCLUSIONS: Endoscopic treatment is safe and efficient for treatment of dysplasia and superficial esophageal cancer. The two-years post-procedural level of HRQL and dysphagia was satisfactory.

Patient reported exposure to smoking and alcohol abuse are associated with pain and other complications in patients with chronic pancreatitis.

BACKGROUND/OBJECTIVES: Smoking and alcohol abuse are established risk factors for chronic pancreatitis (CP). Few studies have examined how exposure to smoking and alcohol abuse act as risk factors for complications in CP. Our aim was to examine associations between patient reported exposure to smoking and alcohol abuse and complications in CP in a large cohort of patients from the Scandinavian and Baltic countries. METHODS: We retrieved data on demographics, CP related complications and patients' histories of exposure to smoking and alcohol abuse from the Scandinavian Baltic Pancreatic Club database. Associations were investigated by univariate and multivariate logistic regression analyses. Results are presented as odds ratios (OR) with 95% confidence intervals. RESULTS: A complete history of smoking and alcohol exposure was available for 932 patients. In multivariate regression analyses, the presence of pain and exocrine pancreatic insufficiency were both significantly associated with history of smoking (OR 1.94 (1.40-2.68), p < 0.001 and OR 1.89 (1.36-2.62), p < 0.001, respectively) and alcohol abuse (OR 1.66 (1.21-2.26), p = 0.001 and 1.55 (1.14-2.11), p = 0.005, respectively). Smoking was associated with calcifications (OR 2.89 (2.09-3.96), p < 0.001), moderate to severe ductal changes (OR 1.42 (1.05-1.92), p = 0.02), and underweight (OR 4.73 (2.23-10.02), p < 0.001). History of alcohol abuse was associated with pseudocysts (OR 1.38 (1.00-1.90) p = 0.05) and diabetes mellitus (OR 1.44 (1.03-2.01), p = 0.03). There were significantly increased odds-ratios for several complications with increasing exposure to smoking and alcohol abuse. CONCLUSION: Smoking and alcohol abuse are both independently associated with development of complications in patients with CP. There seems to be a dose-dependent relationship between smoking and alcohol abuse and complications in CP.

Pancreatic calcifications associate with diverse aetiological risk factors in patients with chronic pancreatitis: A multicentre study of 1500 cases.

BACKGROUND: Pancreatic calcifications is a common finding in patients with chronic pancreatitis (CP), but the underlying pathophysiology is incompletely understood. Past studies for risk factors of calcifications have generally been focused on single parameters or limited by small sample sizes. The aim of this study was to explore several patient and disease characteristics and their associations with pancreatic calcifications in a large cohort of CP patients with diverse aetiological risk factors. METHODS: This was a multicentre, cross-sectional study including 1509 patients with CP. Patient and disease characteristics were compared for patients with calcifications (n = 912) vs. without calcifications (n = 597). Multivariable logistic regression was performed to assess the parameters independently associated with calcifications. RESULTS: The mean age of patients was 53.9 ±â€¯14.5 years and 1006 (67%) were men. The prevalence of calcifications was 60.4% in the overall patient cohort, but highly variable between patients with different aetiological risk factors (range: 2-69%). On multivariate analysis, alcoholic aetiology (OR 1.76 [95% CI, 1.39-2.24]; p < 0.001) and smoking aetiology (OR 1.77 [95% CI, 1.39-2.26], p < 0.001) were positively associated with the presence of calcifications, while an autoimmune aetiology was negatively associated with calcifications (OR 0.15 [95% CI, 0.08-0.27], p < 0.001). Patients with pancreatic calcifications were more likely to have undergone pancreatic duct stenting (OR 1.59 [95%CI, 1.16-2.19], p = 0.004). CONCLUSION: The presence of pancreatic calcifications is associated with diverse aetiological risk factors in patients with CP. This observation attest to the understanding of CP as a complex disease and may have implications for disease classification.

Trends in management and outcome of cystic pancreatic lesions - analysis of 322 cases undergoing surgical resection.

Background: Several guidelines for the management of cystic pancreatic lesions (CPL) exists. From 2013, Oslo University Hospital adapted the European consensus guidelines (ECG) in the decision-making as to whether patients should be advised to have resection or observation for CPL. The aims of the study were to assess changes over time in the workup and diagnostic accuracy of resected CPL, and the short-term surgical outcome. Methods: Preoperative radiological workup, clinicopathological characteristics, and perioperative outcomes were retrospectively reviewed in three consecutive time periods (early: 2004-2008, intermediate: 2009-2012, late: 2013-2016). The rate of concordance between the ECG recommendations for resection (ECG+) or observation (ECG-) and the final histological diagnosis were assessed. Results: A total of 322 consecutive patients underwent resection for CPL (early: n = 89, intermediate: n = 108, late: n = 125). The most common diagnoses were intraductal papillary mucinous neoplasia (IPMN, 36.0%), serous cystic neoplasm (SCN, 23.9%), mucinous cystic neoplasm (10.6%), pseudocyst (9.6%), solid pseudopapillary neoplasm (7.8%), and cystic pancreatic neuroendocrine tumour (5.3%). The proportion of ECG+ CPL undergoing surgery increased significantly (42.7% vs. 60.7% vs. 70.4%, p < .001). The relative proportion of patients undergoing resection for SCN decreased (38.2% vs. 21.3% vs. 16.0%), whereas it increased for IPMN (31.5% vs. 30.6% vs. 44.0%). The use of magnetic resonance imaging and endoscopic ultrasound increased. There were no differences in postoperative severe complications (23.0% vs. 23.6%) or 90-day mortality (2.3% vs. 0.8%) between ECG+ and ECG- patients. Conclusion: Several changes in the management of CPL were revealed during time. Adherence to guidelines is important in order to avoid unnecessary surgery for CPL.

Chronic Pancreatitis Is Characterized by Distinct Complication Clusters That Associate With Etiological Risk Factors.

OBJECTIVES: Chronic pancreatitis (CP) is characterized by several disease-related complications and multiple etiological risk factors. Past studies of associations between complications and risk factors have mostly been limited to single complications or highly focused on single etiologies. Using an objective data-driven approach (cluster analysis), we characterized complication clusters and their associations with etiological risk factors in a large cohort of patients with CP. METHODS: This was a multicenter, cross-sectional study including 1,071 patients with CP from the Scandinavian and Baltic countries. Complications to CP were classified according to the M-ANNHEIM system, and treelet transform was used to derive complication clusters. Cluster complication frequencies were analyzed for their association with main etiological risk factors (smoking and alcohol). RESULTS: The mean age of participants was 57 years and 66% were men. Alcohol (55%) and smoking (53%) were the most common etiological risk factors and seen in combination in 36% of patients. Cluster analysis identified 3 distinct complication clusters characterized by inflammation, fibrosis, and pancreatic insufficiencies. An independent association between inflammatory complications and alcoholic etiology was seen (odds ratio [OR] 2.00 [95% CI [confidence interval], 1.38-2.90], P < 0.001), whereas smoking was associated with fibrosis-related complications (OR 2.23 [95% CI, 1.56-2.3.20], P < 0.001) and pancreatic insufficiencies (OR 1.42 [95% CI, 1.00-2.01], P = 0.046). DISCUSSION: Three distinctive clusters of complications to CP were identified. Their differing associations with alcoholic and smoking etiology indicate distinct underlying disease mechanisms.

Outcome of peroral endoscopic myotomy (POEM) in treatment-naive patients. A systematic review.

OBJECTIVES: Achalasia is a primary motility disorder of the esophagus characterized by aperistalsis and failure of lower esophageal sphincter (LES) relaxation. Treatment of achalasia aims at reducing LES pressure. The common treatment modalities are laparoscopic Heller myotomy and pneumatic dilatation, but during the last decade, a promising treatment, per oral endoscopic myotomy (POEM), has been introduced. The aim of the present study was to perform a systematic review of the literature to assess the outcome of POEM in treatment-naive patients. MATERIALS AND METHODS: A systematic literature search in PubMed, Embase and Cochrane databases was performed using the terms 'Achalasia AND (POEM OR peroral endoscopic myotomy OR per-oral endoscopic myotomy)'. Inclusion criteria were: original article; English language; n ≥ 20 with ≥90% treatment-naive patients; follow-up ≥3 months; and outcome evaluation of POEM including symptom score and objective tests. Exclusion criteria were: reviews and meta-analyses; pediatric data; duplicates; and articles with overlapping data material. RESULTS: Of the 1641 articles identified, seven were included. The included studies all reported a short-term clinical success of >90%. Clinical success including post-POEM reflux was mainly estimated by symptom scorings. There were few procedure-related complications. CONCLUSIONS: The studies of treatment-naive patients indicate a high rate of clinical success. Nevertheless, a more systematic and standardized evaluation is recommended to improve the reports on outcome of POEM. The follow-up rate should be high and the evaluation protocol should include both symptom scoring and objective testing with predefined treatment goals.

The effect of corn trypsin inhibitor, anti-tissue factor pathway inhibitor antibodies and phospholipids on microvesicle-associated thrombin generation in patients with pancreatic cancer and healthy controls.

Circulating microvesicles (MVs) are suggested to be important contributors to cancer-associated thrombosis due to the presence of surface-bound procoagulant molecules like tissue factor (TF) and phosphatidylserine (PS). Pancreatic cancer is considered to be one of the most prothrombotic malignancies. The aim of this study was to describe the impact of analytical variables on MV-associated thrombin generation in patients with pancreatic cancer and in healthy controls. MVs were isolated from citrated plasma and added to pooled normal plasma (PNP). Thrombin generation was measured by the calibrated automated thrombogram. The impact of corn trypsin inhibitor (CTI), anti-tissue factor pathway inhibitor (TFPI) antibodies and phospholipids was described. Antibodies against TF were used to assess TF-dependency, and MV-bound PS activity was measured with the Zymuphen MP-activity kit. MVs from the pancreatic cancer patients displayed higher thrombin generation and higher PS-activity than MVs from the healthy control group, while TF-dependency was observed in only 1 out of 13 patient samples. Adequate thrombin generation-curves were only achieved when CTI was omitted and anti-TFPI antibodies were added to PNP prepared in low contact-activating tubes. Addition of phospholipids reduced the significant differences between the two groups, and should be omitted. This modified thrombin generation assay could be useful for measurement of procoagulant circulating MVs, allowing the contribution from MVs affecting both the intrinsic and the extrinsic pathway to be measured.

Analysis of lifestyle factors in patients with concomitant chronic pancreatitis and liver cirrhosis.

BACKGROUND & OBJECTIVES: Chronic pancreatitis (CP) and liver cirrhosis (LC) are common gastroenterological disorders but their co-incidence is considered to be rare. This study was designed to identify lifestyle factors that are associated with the development of concomitant LC in patients with CP. METHODS: In a retrospective case-control study between 2000 and 2005 122 patients with both CP and LC and 223 matched control patients with CP and no known liver disease were identified in 11 European university medical centers. Another 24 patients and 48 CP controls were identified in the period between 2006 and 2012. RESULTS: Alcoholism was most commonly regarded as aetiology for both CP (82.2%; 95% confidence interval (CI): 75.0-88.0%) and LC (79.5%; 95% CI: 72.0-85.7%) as compared to controls with CP only (68.6%; 95% CI: 62.7-74.1%). The preferred type of alcoholic beverage and pattern of alcohol intake were the only significant lifestyle factors in multivariate analysis. Frequency of alcohol intake (p = 0.105) and smoking status (p = 0.099) were not significant in bivariate analysis and dropped out of the multivariate model. Recurrent and chronic pancreatic pain was observed more often in patients with only CP, whereas gallstones were more common in individuals with both chronic disorders. CONCLUSIONS: These findings indicate that certain lifestyle factors might be important for the development of concomitant CP and LC. More studies will be needed to identify additional genetic and environmental factors underlying this association.

Improved survival and quality of life in patients undergoing R1 pancreatic resection compared to patients with locally advanced unresectable pancreatic adenocarcinoma.

OBJECTIVE: To prospectively record the clinical consequences of R1 resection of pancreatic adenocarcinoma compared to patients with locally advanced tumours not undergoing surgery. BACKGROUND: Surgery is the only potentially curative treatment of pancreatic cancer, and postoperative safety is increasing. The rate of R1 resections might also increase unintentionally as surgical procedures with curative goal become more comprehensive, and the clinical outcome requires further prospective evaluation. MATERIAL AND METHODS: Prospective observational cohort study from October 2008 to December 2010. Outcome after R1 resection (group 1, surgery, n = 32) and conservative palliative chemoradiation/endoscopy (group 2, no surgery, n = 56) is compared with survival and longitudinal patient-reported quality of life (QoL) as endpoints. QoL was assessed by the Edmonton Symptom Assessment System (ESAS). RESULTS: Demographic characteristics and tumour diameters were similar in both groups: 38.0 (31.3, 49.8) mm in group 1 versus 44.0 (39.6, 49.1) mm in group 2 (p = 0.18). Perioperative morbidity was 25% with no mortality. Disease-specific survival was 18.0 (14.5, 23.8) months in group 1 versus 8.1 (4.8, 10.1) months in group 2 (p < 0.0001). Overall survival was 11 (7.8, 14.4) months. Reduction in fatigue was significantly improved in the surgery group 6, 12, and 19 weeks after baseline, whereas reduction in global health was significantly better in group 2. CONCLUSION: Radical removal (R0 resection) is the primary aim of surgery, but also R1 resection seems to improve survival and QoL, compared to outcome in patients with locally advanced tumours not undergoing surgery.

Opportunities of improvement in the management of pancreatic and periampullary tumors.

Abstract Objective. The first objective of the present study was to identify opportunities of improvement for clinical practice, assessed by local quality indicators, then to analyze possible reasons why we did not reach defined treatment quality measures. The second objective was to characterize patients, considered unresectable according to present criteria, for future arrangement of interventional studies with improved patient selection. Material and methods. Prospective observational cohort study from October 2008 to December 2010 of patients referred to the authors' institution with suspected pancreatic or periampullary neoplasm. Results. Of 330 patients, 135 underwent surgery, 195 did not, 129 due to unresectable malignancies. The rest had benign lesions. Perioperative morbidity rate was 32.6%, mortality 0.7%. Radical resection (R0) was obtained in 23 (41.8%) of 55 patients operated for pancreatic adenocarcinoma and 6.3% underwent reconstructive vascular surgery. Diagnostic failure/delay resulted in unresectable carcinoma, primarily misconceived as serous cystic adenoma in two patients. One resected lesion turned out to be focal autoimmune pancreatitis. One case with misdiagnosed cancer was revised to be a pseudoaneurysm. Palliative treatment was offered to 144 patients with malignant tumors, 62 due to locally advanced disease and all pancreatic adenocarcinomas. Conclusions. Quality improvement opportunities were identified for patient selection and surgical technique: Too few patients underwent reconstructive vascular surgery. The most important quality indicators are those securing resectional, radical (R0) surgery. Altogether 143 patients (57.9%) of those with malignant tumors were found unresectable, most of these patients are eligible for inclusion in future interventional studies with curative and/or palliative intention.

Iatrogenic esophago-tracheal fistula: challenges in diagnosis and management.

Esophageo-tracheal fistula is a rare condition, and in most cases such fistulas are caused by malignant disease or emergency endotracheal intubation. A case where a wrapped tablet produced a fistula between the esophagus and trachea is described. The patient is a male born in 1938 who swallowed a tablet without unwrapping it. The patient was treated with self-expanding metal stents (SEMS), but closure of the fistula was not achieved. Different examinations and treatment options are discussed. Surgical treatment for this condition has demonstrated considerable mortality and morbidity. In some cases closure of the fistula can be achieved by use of SEMS. Although we advise treatment of such cases with SEMS, in some cases treatment with stents will prove troublesome and the risk/benefit analysis will have to be reevaluated.