Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes.

BACKGROUND: Teriflunomide 14 mg (Aubagio®) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting. METHODS: Teri-LIFE was a prospective, open label, non-interventional, observational, multi-centre study that enrolled 200 teriflunomide-treated patients from three Nordic countries. The primary outcome measure changes in patient-reported QoL over 24 months as measured by the Short Form-36 (SF-36) questionnaire. Secondary endpoints included clinical efficacy, fatigue, safety, treatment satisfaction (Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM-1.4)), treatment adherence, and health economic outcomes. Most assessments were made at baseline and then at 6-monthly intervals. RESULTS: Overall, changes in SF-36 scores from baseline to last visit indicated a stable QoL during treatment with teriflunomide for up to 24 months. Relapse activity decreased during the study compared to the pre-baseline period (p<0.001), patient-reported disability increased marginally, and no substantial change was seen in fatigue scores. The mean scores for TSQM domains increased nominally though not significantly from Month 6 to Month 24. The convenience and side effects TSQM domains recorded the highest median scores, indicating the acceptability of oral teriflunomide in this cohort. This was reflected in a generally high treatment adherence and decreased healthcare utilization during the study period. Some differences were seen between treatment-naïve and previously treated patients, likely reflecting different patient demographics and disease status at study entry, along with different treatment expectations. CONCLUSION: Teri-LIFE offers a reliable snapshot of QoL, efficacy, safety, and health economic outcomes in persons with relapsing MS treated with teriflunomide in routine clinical practice in Nordic countries The results were consistent with previous clinical trials and real-world studies.

A comparative study of teriflunomide and dimethyl fumarate within the Swedish MS Registry.

BACKGROUND: Teriflunomide and dimethyl fumarate (DMF) are first-line disease-modifying treatments for multiple sclerosis with similar labels that are used in comparable populations. OBJECTIVES: The objective of this study was to compare the effectiveness and persistence of teriflunomide and DMF in a Swedish real-world setting. METHODS: All relapsing-remitting multiple sclerosis (RRMS) patients in the Swedish MS registry initiating teriflunomide or DMF were included in the analysis. The primary endpoint was treatment persistence. Propensity score matching was used to adjust comparisons for baseline confounders. RESULTS: A total of 353 teriflunomide patients were successfully matched to 353 DMF. There was no difference in the rate of overall treatment discontinuation by treatment group across the entire observation period (hazard ratio (HR) = 1.12; 95% confidence interval (CI) = 0.91-1.39; p = 0.277; reference = teriflunomide). Annualised relapse rate (ARR) was comparable (p = 0.237) between DMF (0.07; 95% CI = 0.05-0.10) and teriflunomide (0.09; 95% CI = 0.07-0.12). There was no difference in time to first on-treatment relapse (HR = 0.78; 95% CI = 0.50-1.21), disability progression (HR = 0.55; 95% CI = 0.27-1.12) or confirmed improvement (HR = 1.17; 95% CI = 0.57-2.36). CONCLUSION: This population-based real-world study reports similarities in treatment persistence, clinical effectiveness and quality of life outcomes between teriflunomide and dimethyl fumarate.

Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta-analysis.

BACKGROUND: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave's syndrome (BS). METHODS: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. RESULTS: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8-5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2-7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2-6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1-3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1-3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD. CONCLUSIONS: This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.

Preoperative detection of sentinel lymph nodes with hybrid SPECT/computed tomography imaging may improve the accuracy of sentinel lymph node biopsies in patients with early stages of cancer of the oesophagus or gastro-oesophageal junction.

OBJECTIVES: The aim of this study was to investigate the sentinel lymph node biopsy (SLNB) method in patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) guided by preoperative hybrid single-photon emission tomography/computed tomography (SPECT/CT) lymphoscintigraphy. METHODS: Thirty-nine patients with stage T1-T3, any N-stage, M0 cancer of the oesophagus or GOJ planned for curatively intended esophagectomy underwent preoperative SPECT/CT lymphoscintigraphy following endoscopically guided submucosal injection of radiocolloid and intraoperative radio-guided SLNB using a hand-held gamma scintillation device. RESULTS: The detection rate in preoperative SPECT/CT imaging was 88%. The median number of detected SLN stations in preoperative imaging was 1 (range 0-4). At least one suspected SLN was identified in all intraoperative SLNP procedures. In six cases, no lymph nodes were identified in the SLNB. In six cases, the SLNB was false negative. The sensitivity for successful SLNB procedures was 20%, the specificity was 100% and the accuracy was 75%. CONCLUSIONS: Preoperative SLN mapping using SPECT/CT yields a high number of detected SLN stations compared to previous studies using planar imaging. The accuracy of the SLNB method in patients with predominantly ≥T3-stage tumours and with a history of previous neoadjuvant treatment is poor, and the method is not recommended in these patient groups.

Blood neurofilament light levels segregate treatment effects in multiple sclerosis.

OBJECTIVE: To determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS). METHODS: Data including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide). RESULTS: The baseline pNfL concentration was positively associated with relapse rate, Expanded Disability Status Scale score, Age-Related MS Severity Score, and MS Impact Score (MSIS-29), and negatively associated with Symbol Digit Modalities Test performance and the number of previously used DMTs. All analyses, which used inverse propensity score weighting to correct for differences in baseline factors at DMT start, highlighted that both the reduction in pNfL concentration from baseline to on-treatment measurement and the on-treatment pNfL level differed across DMTs. Patients starting alemtuzumab displayed the highest reduction in pNfL concentration and lowest on-treatment pNfL concentrations, while those starting teriflunomide had the smallest decrease and highest on-treatment levels, but also starting from lower values. Both on-treatment pNfL and decrease in pNfL concentrations were highly dependent on baseline concentrations. CONCLUSION: Choice of DMT in RRMS is significantly associated with degree of reduction in pNfL, which supports a role for pNfL as a drug response marker.

"Sentinel lymph node imaging with sequential SPECT/CT lymphoscintigraphy before and after neoadjuvant chemoradiotherapy in patients with cancer of the oesophagus or gastro-oesophageal junction - a pilot study".

BACKGROUND: In current best practise, curatively intended treatment for oesophageal cancer usually consists of neoadjuvant chemo-radiotherapy (nCRT) or perioperative chemotherapy, and oesophagectomy. Sentinel Lymph Node Biopsy (SLNB) has the potential to identify patients without lymph node metastases and thus improve the staging accuracy and influence treatment. The impact of neoadjuvant treatment on the lymphatic drainage of oesophageal cancers and subsequently the SLNB procedure in this tumour type has previously not been well studied. PURPOSE: To evaluate changes in lymphatic drainage patterns of the tumour in patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) using Sentinel Lymph Node (SLN) hybrid SPECT/CT lymphoscintigraphy before and after nCRT. METHODS: Patients with clinical stage T2-T3, any N-stage, M0 cancer of the oesophagus or GOJ underwent endoscopically guided peri-/intratumoral injection of radio-colloid followed by hybrid SPECT/CT lymphoscintigraphy prior to, and once again following, nCRT. SPECT/CT images were evaluated to number and location of SLNs and compared between the two examinations. RESULTS: Ten patients were included in this pilot trial. SPECT/CT lymphoscintigraphy was performed in twenty procedures. The same Sentinel Lymph Node station before and after nCRT was observed in one single patient. In two patients, no SLN was detected before nCRT. In three patients no SLN was detected following nCRT. In four patients, the SLN stations were not the same station at baseline compared to follow-up examination. CONCLUSIONS: The reproducibility SLN detection in patients with cancer of the oesophagus/GOJ following nCRT was very poor. nCRT appears to alter lymphatic drainage patterns and thus may affect detection of SLNs and potentially also the accuracy of an SLNB in these patients. On the basis of these initial results, we abort further patient recruitment in our institution. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR). Identifier ACTRN12618001433291 . Date registered: 27/08/2018. Retrospectively registered.

Evaluation of resection of the gastroesophageal junction and jejunal interposition (Merendino procedure) as a rescue procedure in patients with a failed redo antireflux procedure. A single-center experience.

BACKGROUND: Primary antireflux surgery has high success rates but 5 to 20% of patients undergoing antireflux operations can experience recurrent reflux and dysphagia, requiring reoperation. Different surgical approaches after failed fundoplication have been described in the literature. The aim of this study was to evaluate resection of the gastroesophageal junction with jejunal interposition (Merendino procedure) as a rescue procedure after failed fundoplication. METHODS: All patients who underwent a Merendino procedure at the Karolinska University Hospital between 2004 and 2012 after a failed antireflux fundoplication were identified. Data regarding previous surgical history, preoperative workup, postoperative complications, subsequent investigations and re-interventions were collected retrospectively. The follow-up also included questionnaires regarding quality of life, gastrointestinal function and the dumping syndrome. RESULTS: Twelve patients had a Merendino reconstruction. Ten patients had undergone at least two previous fundoplications, of which one patient had four such procedures. The main indication for surgery was epigastric and radiating back pain, with or without dysphagia. Postoperative complications occurred in 8/12 patients (67%). During a median follow-up of 35 months (range 20-61), four (25%) patients had an additional redo procedure with conversion to a Roux-en-Y esophagojejunostomy within 12 months, mainly due to obstructive symptoms that could not be managed conservatively or with endoscopic techniques. Questionnaires scores were generally poor in all dimensions. CONCLUSIONS: In our experience, the Merendino procedure seems to be an unsuitable surgical option for patients who require an alternative surgical reconstruction due to a failed fundoplication. However, the small number of patients included in this study as well as the small number of participants who completed the postoperative workout limits this study.

Pulse oximetric assessment of anatomical vascular contribution to tissue perfusion in the gastric conduit.

BACKGROUND: Tubularized stomach is a common substitute used after oesophageal resection. The risk for gastric conduit ischemia, as well as the mechanisms and dynamics for the occurrence of deficient tissue perfusion during the critical construction of a gastric tube, is poorly understood. METHODS: Twenty-nine patients that underwent oesophagectomy were studied with transmural pulse oximetry of different parts of the stomach, and at predefined preparatory steps during the construction of the gastric conduit. RESULTS: After ligation of the left gastric artery (LGA), a reduction to 83.5% in tissue saturation was observed. Three patients (10.3%) had a sustained saturation despite ligation at this point. During final preparation of the gastric tube, and after stapling of the minor curvature, saturation fell to 76.5%. Saturation increased significantly to 80.0% 2 h after the stapling, just before construction of the anastomosis (P = 0.021). There was no association between the level of oxygen saturation and the risk of anastomotic dehiscence. CONCLUSION: During gastric tube construction for oesophageal replacement, conduit perfusion, measured as oxygen saturation with pulse oximetry, decreases significantly. The main cause of this reduction seems to be ligation of the LGA and the final stapling of the gastric tube. Future studies are needed to establish the clinical implications of this finding.

Extent of lymphadenectomy has no impact on postoperative complications after gastric cancer surgery in Sweden.

OBJECTIVE: Curative gastric cancer surgery entails removal of the primary tumor with adequate margins including regional lymph nodes. European randomized controlled trials with recruitment in the 1990's reported increased morbidity and mortality for D2 compared to D1. Here, we examined the extent of lymphadenectomy during gastric cancer surgery and the associated risk for postoperative complications and mortality using the strengths of a population-based study. METHODS: A prospective nationwide study conducted within the National Register of Esophageal and Gastric Cancer. All patients in Sweden from 2006 to 2013 who underwent gastric cancer resections with curative intent were included. Patients were categorized into D0, D1, or D1+/D2, and analyzed regarding postoperative morbidity and mortality using multivariable logistic regression. RESULTS: In total, 349 (31.7%) patients had a D0, 494 (44.9%) D1, and 258 (23.4%) D1+/D2 lymphadenectomy. The 30-d postoperative complication rates were 25.5%, 25.1% and 32.2% (D0, D1 and D1+/D2, respectively), and 90-d mortality rates were 8.3%, 4.3% and 5.8%. After adjustment for confounders, in multivariable analysis, there were no significant differences in risk for postoperative complications between the lymphadenectomy groups. For 90-d mortality, there was a lower risk for D1 vs. D0. CONCLUSIONS: The majority of gastric cancer resections in Sweden have included only a limited lymphadenectomy (D0 and D1). More extensive lymphadenectomy (D1+/D2) seemed to have no impact on postoperative morbidity or mortality.

Effects of neoadjuvant chemo or chemoradiotherapy for oesophageal cancer on perioperative haemodynamics: A prospective cohort study within a randomised clinical trial.

BACKGROUND: Neoadjuvant chemoradiotherapy might improve oncological outcome compared with chemotherapy after surgery for oesophagus or gastrooesophageal junction cancer. However, radiotherapy may induce cardiovascular side-effects that could increase the risk of perioperative adverse effects and postoperative morbidity. OBJECTIVES: The aim of this study was to compare the perioperative haemodynamics in patients undergoing oesophagectomy following neoadjuvant chemotherapy or chemoradiotherapy for cancer. DESIGN: A prospective single-centre cohort study within a randomised multi-centre trial. SETTING: A Swedish University Hospital from January 2009 to March 2013. PATIENTS: A total of 31 patients (chemotherapy 17, chemoradiotherapy 14) included in a multi-centre trial randomising chemotherapy vs. chemoradiotherapy and operated at Karolinska University Hospital, Huddinge. INTERVENTIONS: Cisplatin and 5-fluorouracil, either with or without concurrent radiotherapy (40 Gy), were given prior to surgery. Cardiac function was assessed with LiDCOplus (LiDCO Ltd, London, United Kingdom), echocardiography, troponin T and N-terminal pro-B-type natriuretic peptide, before, during and after surgery. MAIN OUTCOME MEASURES: The primary outcome was the interaction effect of the neoadjuvant treatment on stroke volume index during the perioperative period. Secondary outcomes were the interaction effects of oxygen delivery index, cardiac index, echocardiography and biochemical markers. RESULTS: The groups were matched regarding comorbidities, but patients in the chemoradiotherapy group were older (66 vs. 60 years P = 0.03). Haemodynamic values changed in a similar way in both groups during the study period. The chemoradiotherapy group had a lower cardiac index before surgery (2.9 vs. 3.4 l min m, P = 0.03). On the third postoperative day, both groups displayed a hyperdynamic state compared with baseline, with no increase in troponin T, and a similar increase in N-terminal pro-B-type natriuretic peptide. CONCLUSION: Neoadjuvant chemoradiotherapy for oesophageal or gastrooesophageal junction cancer seems to induce only a marginal negative effect on cardiac function compared with neoadjuvant chemotherapy. This difference did not remain when patients' haemodynamics were challenged by surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01362127.

A systematic review and meta-analysis comparing partial stomach partitioning gastrojejunostomy versus conventional gastrojejunostomy for malignant gastroduodenal obstruction.

PURPOSE: Partial stomach partitioning gastrojejunostomy (PSPGJ) was introduced as a palliative treatment for malignant gastric outlet obstruction (MGO) caused by unresectable gastric or periampullary cancers and suggested to offer advantages over conventional gastrojejunostomy (CGJ) in reducing the risk for delayed gastric emptying (DGE). However, insufficient evidence is available to allow a comprehensive view of the true value of PSPGJ. The present study aimed to show the advantages of PSPGJ in terms of alleviating DGE and improving postoperative recovery compared to CGJ. METHODS: A systematic literature search was performed, and studies comparing DGE and other perioperative and postoperative data including operation time, blood loss, total postoperative complications, anastomotic leak, postoperative period before oral intake, and/or hospital stay between PSPGJ and CGJ for MGO were incorporated. Risk ratio (RR) for binary variables and weighted mean difference (WMD) for continuous variables were calculated, and meta-analyses were performed. RESULTS: Seven studies containing 207 patients were included. The risk for DGE was significantly lower after PSPGJ (RR 0.32; 95%CI 0.17 to 0.60; P < 0.001). PSPGJ significantly reduced the postoperative hospital stay (WMD -6.1 days; 95%CI -8.9 to -3.3 days; P < 0.001). No significant differences were observed in the other variables between the groups. CONCLUSIONS: PSPGJ for MGO seems to offer significant advantages in terms of alleviating DGE and improving postoperative recovery compared to CGJ.

Treatment of esophageal anastomotic leakage with self-expanding metal stents: analysis of risk factors for treatment failure.

BACKGROUND AND STUDY AIM: The endoscopic placement of self-expandable metallic esophageal stents (SEMS) has become the preferred primary treatment for esophageal anastomotic leakage in many institutions. The aim of this study was to investigate possible risk factors for failure of SEMS-based therapy in patients with esophageal anastomotic leakage. PATIENTS AND METHODS: Beginning in 2003, all patients with an esophageal leak were initially approached and assessed for temporary closure with a SEMS. Until 2014, all patients at the Karolinska University Hospital with a leak from an esophagogastric or esophagojejunal anastomosis were identified. Data regarding the characteristics of the patients and leaks and the treatment outcomes were compiled. Failure of the SEMS treatment strategy was defined as death due to the leak or a major change in management strategy. The risk factors for treatment failure were analyzed with simple and multivariable logistic regression statistics. RESULTS: A total of 447 patients with an esophagogastric or esophagojejunal anastomosis were identified. Of these patients, 80 (18 %) had an anastomotic leak, of whom 46 (58 %) received a stent as first-line treatment. In 29 of these 46 patients, the leak healed without any major change in treatment strategy. Continuous leakage after the application of a stent, decreased physical performance preoperatively, and concomitant esophagotracheal fistula were identified as independent risk factors for failure with multivariable logistic regression analysis. CONCLUSION: Stent treatment for esophageal anastomotic leakage is successful in the majority of cases. Continuous leakage after initial stent insertion, decreased physical performance preoperatively, and the development of an esophagotracheal fistula decrease the probability of successful treatment.

Thoracoscopic side-to-side esophagogastrostomy by use of linear stapler-a simplified technique facilitating a minimally invasive Ivor-Lewis operation.

PURPOSE: Minimally invasive esophagectomy (MIE) has been met with increased interest for the surgical treatment of esophageal cancer. One critical obstacle for the implementation of MIE has been the intrathoracic anastomosis. In this study, we describe a technique of thoracoscopic intrathoracic anastomosis using a linear stapler in prone position and present the short-term outcomes of this procedure. METHODS: This prospective pilot study included 46 consecutive patients with a cancer either of the gastroesophageal junction (GEJ) or the distal esophagus who underwent either total MIE or thoracoscopic-assisted esophagectomy followed by intrathoracic stapled side-to-side anastomosis. The short-term outcomes including postoperative complications were recorded and analyzed. RESULTS: This pilot study included 41 males (89 %) and 5 females (11 %) with a mean age of 65.7 years. The majority had adenocarcinoma (93 %). Before surgery, 4 patients (8.7 %) had an incomplete endoscopic submucosal resection, 5 patients (11 %) received chemotherapy alone, and 33 patients (71 %) had chemoradiotherapy. Mean operation time was 408 minutes. Postoperative complications classified as Clavien-Dindo Grade IIIa or more severe occurred in 7 patients (15 %), of whom 4 patients (8.7 %) developed anastomotic leakages without any need for intensive care. Another 2 patients (4.3 %) required intensive care due to aspiration pneumonia and acute renal failure. No in-hospital mortality was registered. Only one patient (2.2 %) with anastomotic leakage developed postoperative anastomotic stenosis requiring balloon dilatation. CONCLUSIONS: The intrathoracic stapled side-to-side anastomosis technique seems to be feasible, safe, and easy to perform, associated with a limited postsurgical complication rate and a good functional outcome.

Neoadjuvant chemoradiotherapy may increase the risk of severe anastomotic complications after esophagectomy with cervical anastomosis.

PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) improves long-term survival for patients with esophageal cancer. On the other hand, there are indications that nCRT may increase the risk for postoperative morbidity. The aims of this study were to estimate the radiation exposure to the site of anastomosis on the gastric fundus and to assess whether nCRT affected the incidence or severity of cervical anastomotic complications. METHODS: A retrospective cohort of patients with cancer of the esophagus or gastroesophageal junction, who were reconstructed with cervical anastomosis. The planned radiation dose to the site of the cervical anastomosis on the gastric fundus was estimated for each patient. RESULTS: The analysis of the dose plans showed that 20 out of 22 (93 %) available patients received radiotherapy toward the planned site of the anastomosis in the region of the gastric fundus with doses ranging from 6 to 40 Gy. In the nCRT group, 12 out of 28 patients (43 %) had anastomotic complications compared to 16 out of 42 (38 %) in the non-RT group (p = 0.69). In the nCRT group, 39 % had anastomotic complications that led to a Clavien-Dindo grade of IVa or higher compared to 17 % in the non-RT group (p = 0.03). The OR for Clavien-Dindo grade IVa or worse was 6.0 (95 % CI 1.52-23.50). CONCLUSION: This small retrospective study suggests that nCRT exposes the future anastomotic site to doses of radiation that may impair healing of the subsequent cervical anastomosis. Our data further suggest that nCRT may increase the severity of cervical anastomotic complications, and this hypothesis needs to be tested in a large prospective study.

The Added Value of Partial Stomach-partitioning to a Conventional Gastrojejunostomy in the Treatment of Gastric Outlet Obstruction.

INTRODUCTION: Poor results have been reported after conventional gastrojejunostomy (CGJ) as palliative surgical bypass treatment of gastric outlet obstruction (GOO). Partial stomach-partitioning gastrojejunostomy (PSPGJ) has been introduced as an alternative surgical treatment of GOO to reduce the risk of postoperative delayed gastric emptying (DGE). AIM: The aim was to study PSPGJ as an alternative to CGJ in the treatment of GOO, with respect to DGE. PATIENTS AND METHODS: A retrospective cohort study was completed in all patients who underwent a bypass of the duodenum via PSPGJ or CGJ due to GOO. Cases where concomitant biliary or bariatric procedures were performed were excluded. RESULTS: Twenty-four patients met the inclusion criteria for the study; ten cases underwent PSPGJ and 14 CGJ. The incidence of DGE grade B-C was significantly lower in the PSPGJ group (0 %) compared with the CGJ group (42.9 %, p = 0.024). Oral nutrition only was recorded more often at follow-up in the PSPGJ group (9/9, 100 %) than in the CGJ group (4/13, 30.8 %) (p = 0.002). CONCLUSION: PSPGJ seems to be followed by a lower rate of DGE compared to CGJ.

Per-oral endoscopic myotomy for achalasia. Are results comparable to laparoscopic Heller myotomy?

OBJECTIVE: Per-oral endoscopic myotomy (POEM) has recently been introduced as a minimal invasive alternative to conventional treatment for achalasia. This study aimed to clarify the feasibility and the short-term clinical efficacy of POEM as compared to laparoscopic Heller myotomy (LHM). METHODS: Treatment outcomes were prospectively recorded and compared between the procedures in a nonrandomized fashion. Reduction rate (RR) in timed barium esophagogram (TBE) was calculated at 1, 2 and 5 min after barium ingestion as: RR = 1- postoperative barium height/preoperative barium height. Risk factors for treatment failure defined as the proportion of patients with RR <0.5 (1 min) and gastroesophageal reflux (GER) after POEM were analyzed. RESULTS: Forty-two consecutive patients who underwent POEM were compared to 41 patients who had a LHM during the immediate time period prior to the introduction of POEM. Ninety percent of the cases reported complete symptom relief after POEM. The percentage of esophageal emptying and RR in TBE improved dramatically by both procedures without significant difference. A longer operation time (odds ratio [OR] 32.80, 95%CI 2.99-359.82, p = 0.004) and younger age (OR 26.81, 95%CI 2.09-344.03, p = 0.012) were the independent predictors of treatment failure after POEM. GER was observed in seven patients where previous dilatation (OR 8.59, 95%CI 1.16-63.45, p = 0.035) and higher body mass index (OR 8.69, 95%CI 1.13-66.63, p = 0.037) were the independent predictors for symptomatic GER after POEM. CONCLUSION: POEM seems to be a safe and effective treatment option for achalasia in the short-term perspective; an effect well comparable to LHM.

Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction - a prospective cohort pilot study within a randomized clinical trial.

BACKGROUND: Neoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy. METHODS: Patients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups. RESULTS: 40 patients participated (chemoradiotherapy, n=17; chemotherapy, n=23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p=0.02, p=0.01, and p=0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p=0.09 and p=0.09). NT-proBNP increased following chemoradiotherapy (p=0.05) but not after chemotherapy (p>0.99), and there was a trend towards an interaction effect (p=0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p=0.03) and was more pronounced after chemoradiotherapy with a trend towards an interaction effect (p=0.10). CONCLUSIONS: Neoadjuvant chemoradiotherapy but not chemotherapy before surgery for cancer of the esophagus or GE-junction seems to induce an acute negative effect on both systolic and diastolic left ventricular function. Future studies on neoadjuvant treatment for esophageal cancer are suggested to add measurements of cardiac function. TRIAL REGISTRATION: Clinical Trials.gov NCT01362127 .

Predictors for failure of stent treatment for benign esophageal perforations - a single center 10-year experience.

AIM: To investigate possible predictors for failed self-expandable metallic stent (SEMS) therapy in consecutive patients with benign esophageal perforation-rupture (EPR). METHODS: All patients between 2003-2013 treated for EPR at the Karolinska University Hospital, a tertiary referral center, were studied with regard to initial management with SEMS. Patients with malignancy as an underlying cause and those with anastomotic leakages were excluded. Sealing of the perforation with a covered SEMS was the primary strategy whenever feasible. Stent therapy failure was defined as a radical change of treatment strategy due to uncontrolled mediastinitis, which in this setting consisted of emergency esophagectomy with end-esophagostomy or death as a consequence of the perforation and subsequent uncontrolled sepsis. Patient and lesion characteristics were analyzed and are presented as median and interquartile range. Possible predictors for failed stent therapy were analyzed with uni-variate logistic regression, while variables with P < 0.2 were further analyzed with multi-variate logistic regression. RESULTS: Of the total number of 48 patients presenting with EPR, 40 patients (83.3%) were treated with SEMS at the time of admission, with an intention to heal the perforation. Twenty-three patients had Boerhaave's syndrome (58%), 16 had an iatrogenic perforation (40%) and 1 had external trauma to the esophagus (3%). The total in-hospital mortality, including the cases that had other initial treatments (n = 8), was 10.4% and 7.5% among those who were subjected to the SEMS-based strategy. In 33 of the 40 patients (82.5%) who were treated with stent, the EPR healed without further change in treatment strategy. Patients classified as treatment success received a SEMS at a median time of 1 (1-1) d after the actual EPR, compared to 3 (1-10) d among those where the initial treatment failed, P = 0.039 in uni-variate analysis and P = 0.052 in multi-variate analysis. No other significant factors emerged, indicating an increased risk for failure. Six of 7 patients, where stent treatment of the defect failed, underwent an emergency esophagectomy with end esophagostomy and one patient died. CONCLUSION: SEMS as an upfront therapeutic strategy seems to be a successful concept, when applied to an unselected group of patients with EPR.

Toupet versus Dor as a procedure to prevent reflux after cardiomyotomy for achalasia: results of a randomised clinical trial.

BACKGROUND: The optimal anti-reflux procedure after Heller cardiomyotomy for oesophageal achalasia remains unclear. The most commonly used procedure is the anterior partial fundoplication according to Dor, although during recent years the posterior counterpart (Toupet) has become popular. METHODS: Patients with newly diagnosed achalasia and referred for cardiomyotomy were randomised to receive either an anterior or partial posterior fundoplication following a classical cardiomyotomy. The effect of surgery was assessed during the first postoperative year by Eckardt scores, EORTC QLQ-OES18 scores and HRQL questionnaires. Timed barium oesophagogram (TBO) and ambulatory 24-h pH monitoring were performed to determine oesophageal emptying and the degree of reflux control, respectively. RESULTS: Forty-two patients were randomised into Dor (n = 20) and Toupet (n = 22) groups. Eckardt scores improved dramatically with both procedures, but the EORTC QLQ-OES18 (functional scales) scores revealed significantly better relative improvements in the Toupet group compared to the Dor repair (P = 0.044). Corresponding advantages in favour of Toupet were observed postoperatively in the percentage of oesophageal emptying at TBO (P = 0.011 in height and P = 0.018 in area), an effect not observed in the Dor group. There were no other significant differences recorded between the study groups concerning HRQL evaluations and objective assessment of gastro-oesophageal acid reflux. CONCLUSIONS: A partial posterior fundoplication after cardiomyotomy seems to achieve more improvement in oesophageal emptying and EORTC QLQ-OES18 functional scale scores than the anterior fundoplication. Otherwise no differences between the two anti-reflux repairs were noted. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01933373.

Postoperative pancreatic fistula formation according to ISGPF criteria after D2 gastrectomy in Western patients.

BACKGROUND: Limited information is available on the incidence of postoperative pancreatic fistula (POPF) after D2 gastrectomy with the strict use of the International Study Group of Pancreatic Fistula (ISGPF) criteria, particularly so in Western patients. METHODS: All patients who underwent gastrectomy for adenocarcinoma at the Karolinska University Hospital Huddinge from 2006 until June 2012 were identified via hospital records and reviewed for type of surgical procedure, postoperative morbidity, incidence, and risk factors for POPF. RESULTS: Ninety-two of 107 cases had a D2 gastrectomy eligible for evaluation of POPF, of which 83 (90 %) also underwent bursectomy. Seven patients fulfilled the criteria for POPF grade A (7.6 %), 5 met the criteria for POPF grade B (5.4 %), and 6 the criteria for POPF grade C (6.5 %). The incidence of POPF grade B or C was 4.9 % among the 82 patients for whom no pancreatic resection was performed and 70 % among 10 cases with concomitant pancreatic resection. The latter (OR 156.2, 95 % CI 8.00-3046.93) and age (OR 1.2, 95 % CI 1.02-1.35) were found to be the only risk factors for POPF after gastrectomy upon a multivariate analysis. CONCLUSIONS: In this series of Western patients, POPF grade B or C according to the ISGPF criteria was uncommon after D2 gastrectomy without pancreatic resection. Bursectomy was not a risk factor for POPF.