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.

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.

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.

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.

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.

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.

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.

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.

Hybrid SPECT/CT imaging of sentinel nodes in esophageal cancer: first results.

BACKGROUND: Sentinel node (SN) biopsy in esophageal cancer has the potential of becoming an important tool for ruling out the presence of lymph node metastases in patients opted for less extensive surgery without neoadjuvant treatment. PURPOSE: To investigate preoperative SN imaging in esophageal cancer using hybrid single photon emission computed tomography (SPECT)/CT. MATERIAL AND METHODS: Eight patients with esophageal cancer scheduled for thoracoabdominal esophagectomy after neoadjuvant treatment, underwent endoscopic submucosal injection of (99m)Tc-nanocoll the day before surgery, followed by imaging with SPECT/CT for preoperative detection. Intraoperative detection of SNs was performed with a gamma probe. RESULTS: SNs were identified by SPECT/CT in 7/8 cases (88%) and by gamma probe in all cases. The median number of identified lymph node stations with SN in the operating field was 1 (range 0-2) for SPECT/CT and 1 (range 1-3) for gamma probe. The median distance between the perceived location of the respective SN according to SPECT/CT and the location identified with the gamma probe was <5 mm (range <5-15 mm). In one patient who had a complete histologic response to neoadjuvant treatment in the primary tumor, there was one single metastasis that was not contained in one of the SNs. CONCLUSION: Preoperative identification of sentinel nodes with hybrid SPECT/CT after endoscopic injection of radiocolloid is a technique with obvious potential for SN mapping in esophageal cancer.

Management of alcohol use disorders in patients with chronic pancreatitis.

CONTEXT: The outcome of treatment for patients with chronic pancreatitis may be improved by multidisciplinary management. OBJECTIVE: To study patients with chronic pancreatitis, especially regarding alcohol use, within a multi disciplinary program. MAIN OUTCOME MEASURES: Prospective assessment at baseline and follow-up of alcohol use disorders using DSM-IV criteria, AUDIT score, interview-based quantification of alcohol intake and the biomarker for alcohol use s-CDT in patients referred because of chronic pancreatitis together with retrospective classification with the M-ANNHEIM risk factor analysis and severity scoring for chronic pancreatitis. RESULTS: Sixty patients (95%) of 63 consecutively included patients were classified as having chronic pancreatitis. Forty-four of these (73%) were available for follow-up evaluation, which took place after a minimum of 1 year (median 3 years). Alcohol consumption decreased at follow-up and no patients had ongoing alcohol dependence (P<0.001) as compared to 10 (23%) at initial evaluation. Patients with harmful alcohol use (AUDIT score ≥8 points) and pathological s-CDT had a reduction in both parameters (P=0.004 and P=0.060, respectively). Pain score according to M-ANNHEIM was unchanged, whereas use of analgesics decreased (P=0.005). CONCLUSIONS: This feasibility study of patients with chronic pancreatitis demonstrated that multidisciplinary management seems to give a positive and sustainable effect on alcohol abuse and may be a useful concept for optimal classification, selection and treatment of patients with chronic pancreatitis.

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.

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.

One-lung ventilation during thoracoabdominal esophagectomy elicits complement activation.

BACKGROUND: One-lung ventilation (OLV) during thoracoabdominal esophagectomy may induce an inflammatory response that can contribute to the induction and propagation of frequently occurring postoperative respiratory distress. Markers of such a response might be detected in the pulmonary as well as in the systemic circulation. Inflammation and tissue damage may be key pathogenetic pathways and we hypothesized that 1-lung ventilation may induce an inflammatory cascade reflected by markers for such a response. MATERIALS AND METHODS: Thirty patients with esophageal cancer were randomized to OLV (n = 16) or 2-lung ventilation (TLV; n = 14) during the thoracic part of the operation. Compounds involved in inflammation and coagulation were measured perioperatively and during the 1st, 2nd, 3rd, and 10th postoperative d. RESULTS: During the perioperative phase, the proinflammatory cytokine interleukin-6 and thrombin, measured as thrombin-antithrombin complexes, started to increase. Thrombin, which can induce complement activation, peaked at the end of surgery and interleukin-6 at the 1st to 2nd postoperative d, but there were no differences between the OLV and TLV groups. C3a and terminal complement complex (TCC) started to increase on the 2nd postoperative d and continued to do so for the rest of the study period. The increase of TCC was significantly higher in the OLV group compared to the TLV group, whereas C3a attained similar levels in the 2 groups. CONCLUSIONS: OLV is associated with an augmented inflammatory response as reflected by the activation of the TCC. This may induce pulmonary tissue damage and recruitment of inflammatory cells.

Effects of synovial fluid from aseptic prosthesis loosening on collagen production in osteoblasts.

Synovial fluid from a loose prosthesis may act as a vehicle for factors that regulate bone turnover. The effect of such synovial fluid on osteoblasts has been studied. Synovial fluid obtained from patients who underwent revision hip arthroplasty because of aseptic prosthesis loosening was studied regarding the effect on protein synthesis, procollagen I mRNA expression, the secretion of procollagen I carboxyterminal propeptide (PICP) and osteocalcin in MG63 osteoblasts. Protein synthesis was increased and procollagen I mRNA expression was decreased by synovial fluid from patients with prosthesis loosening. Synovial fluid stimulated the total PICP in cell medium, but there was no change after correction for cell protein content in the cells. Synovial fluid in patients with prosthesis loosening has a general stimulatory effect on collagen formation and osteoblast proliferation because of a stimulatory effect on cell growth. Aseptic prosthesis loosening may be associated with an increase in bone formation.

Local inflammatory and metabolic response in the knee synovium after arthroscopy or arthroscopic anterior cruciate ligament reconstruction.

PURPOSE: The aim of this study was to study local synovial metabolism and inflammation after arthroscopy and arthroscopic anterior cruciate ligament (ACL) reconstruction. METHODS: Microdialysis in the synovial membrane was performed during 4 hours postoperatively in 20 patients undergoing a minor arthroscopy procedure (e.g., meniscus surgery and 10 patients undergoing ACL reconstruction with a quadruple hamstring graft). Contralateral thigh adipose tissue served as a reference. Lactate, glucose, glycerol, and prostaglandin E(2) (PGE(2)) were monitored. The ACL group received intra-articular morphine preoperatively, and a cooling and compression device was applied postoperatively according to local clinical routines. RESULTS: The synovial lactate levels and the consumption of synovial glucose was increased postoperatively in the arthroscopy group compared to the reference adipose tissue. There were no significant differences regarding synovial levels of glycerol, lactate, or glucose compared to the reference tissue in the ACL group. PGE(2) levels were significantly lower in the ACL group compared to the arthroscopy group. CONCLUSIONS: A major arthroscopic surgical procedure (ACL reconstruction) did not increase the local synovial metabolism or induce a detectable inflammatory response compared to a minor arthroscopic surgical procedure (e.g., meniscal surgery) in our clinical setting. Intra-articular injection of morphine and or the use of a combined cooling and compression device in the ACL group showed a modulation of the response in tissue chemistry as measured by synovial microdialysis. LEVEL OF EVIDENCE: Level III, therapeutic case-control 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.

"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.