Acute appendicitis: A block-randomized study on active observation with or without antibiotic treatment.

BACKGROUND: Antibiotic treatment of unselected patients with acute appendicitis is safe and effective. However, it is unknown to what extent early provision of antibiotic treatment may represent overtreatment due to spontaneous healing of appendix inflammation. The aim of the present study was to evaluate the role of antibiotic treatment versus active in-hospital observation on spontaneous regression of acute appendicitis. METHOD: Patients who sought acute medical care at Sahlgrenska University Hospital were block-randomized according to age (18-60 years) and systemic inflammation (C-reactive protein <60 mg/L, white blood cell <13,000/µL), in combination with clinical and abdominal characteristics of acute appendicitis. Study patients received antibiotic treatment and active observation, while control patients were allocated to classic active "wait and see observation" for either disease regression or the need for surgical exploration. According to our standard surgical care, certified surgeons in charge decided whether and when appendectomy was necessary. In total, 1,019 patients were screened for eligibility; 203 patients met inclusion criteria, 126 were accepted to participate, 29 declined, and 48 were missed for inclusion. RESULTS: The antibiotic group (n = 69) and the control group (n = 57) were comparable at inclusion. Appendectomy at first hospital stay was 28% and 53% for study and control patients (χ2, P < .004). Life table analysis indicated a time-dependent difference in the need for appendectomy during follow-up (P < .03). Antibiotics prevented surgical exploration and appendectomy by 72% to 50% compared to 47% to 37% in the control group across the time course follow-ups between 5 and 1,200 days. CONCLUSION: Early antibiotic treatment is superior to traditional "wait and see observation" to avoid surgical exploration and appendectomy.

Improved survival after laparoscopic compared to open gastrectomy for advanced gastric cancer: a Swedish population-based cohort study.

BACKGROUND: Laparoscopic gastrectomy is increasingly used for the treatment of locally advanced gastric cancer but concerns remain whether similar results can be obtained compared to open gastrectomy, especially in Western populations. This study compared the short-term postoperative, oncological and survival outcomes following laparoscopic versus open gastrectomy based on data from the Swedish National Register for Esophageal and Gastric Cancer. METHODS: Patients who underwent surgery with curative intent for adenocarcinoma of the stomach or gastroesophageal junction Siewert type III from 2015 to 2020 were identified, and 622 patients with cT2-4aN0-3M0 tumors were included. The impact of surgical approach on short-term outcomes was assessed using multivariable logistic regression. Long-term survival was compared using multivariable Cox regression. RESULTS: In total, 350 patients underwent open and 272 laparoscopic gastrectomy, of which 12.9% were converted to open surgery. The groups were similar regarding distribution of clinical disease stage (27.6% stage I, 46.0% stage II, and 26.4% stage III). Neoadjuvant chemotherapy was administered to 52.7% of the patients. There was no difference in the rate of postoperative complications, but laparoscopic approach was associated with lower 90 day mortality (1.8 vs 4.9%, p = 0.043). The median number of resected lymph nodes was higher after laparoscopic surgery (32 vs 26, p < 0.001), while no difference was found in the rate of tumor-free resection margins. Better overall survival was observed after laparoscopic gastrectomy (HR 0.63, p < 0.001). CONCLUSIONS: Laparoscopic gastrectomy can be safely preformed for advanced gastric cancer and is associated with improved overall survival compared to open surgery.

Laparoscopic Heller myotomy or pneumatic dilatation in achalasia: results of a prospective, randomized study with at least a decade of follow-up.

BACKGROUND AND OBJECTIVES: The most efficient long-term treatment strategy for achalasia has yet to be established. This study compared the long-term results (≥ 10 years) after either pneumatic dilatations or laparoscopic myotomy using treatment failure as the primary outcome. Secondary objectives were; the frequency and degree of dysphagia and effects on health-related quality of life (QoL). PATIENTS AND METHODS: Out of the 53 patients with achalasia who were initially randomized to either laparoscopic myotomy with a posterior partial fundoplication (LM) or repetitive pneumatic dilatation (PD), 43 remained for scrutiny after a median observation period of 170 months (LM; n = 20 and PD; n = 23). RESULTS: At the follow-up of 60 months, 10 patients (36%) in the PD group and two patients (8%) in the LM group were classified as treatment failures (p = 0.016). At the latest follow-up time point (≥ 10 years), the corresponding numbers were 13 (57%) and 4 (20%), respectively. The Kaplan-Meier analysis of the cumulative incidence of treatment failure revealed a significant advantage of LM over the dilatation strategy (p = 0.036)). QoL assessed by the generic instrument PGWB and the more disease-specific instrument GSRS revealed scores which were similar in the two study groups with no obvious changes over time. Reflux was better controlled in the LM group (p = 0.02 regarding PPI consumption). CONCLUSIONS: After more than a decade of follow-up, laparoscopic myotomy reinforces its superiority over repetitive pneumatic dilatation treatment strategy in the management of newly diagnosed achalasia.

Fully covered stents are similar to semi-covered stents with regard to migration in palliative treatment of malignant strictures of the esophagus and gastric cardia: results of a randomized controlled trial.

INTRODUCTION: Stent migration is a significant clinical problem in palliation of malignant strictures in the esophagus and gastro-esophageal junction (GEJ). We have compared a newer design of a fully-covered stent to a widely used semi-covered stent using migration >20 mm as the primary outcome variable. Effects on dysphagia, quality of life (QoL) and re-intervention frequency were also investigated. METHODS: Patients with dysphagia due to non-curable esophagus/GEJ cancer were randomized to receive either a more recent design of a fully-covered stent (n = 48) or a conventional semi-covered stent (n = 47). Chest x-ray, dysphagia and QoL were studied at baseline, one week, four weeks and three months thereafter. RESULTS: There were no significant differences either in stent migration distance or in the migration frequency. Stent migration during the total study period occurred in 37.2 % in the semi-covered group compared to 20.0 % for the fully-covered group. Dysphagia was measured with Watson and Ogilvie scores and with the dysphagia module in the QoL scale (QLQ-OG25). On average, there was a tendency to better dysphagia relief for the fully-covered design as scored with the two latter dysphagia instruments (p= 0.081 and p= 0.067) at three months and towards more re-interventions in the semi-covered group (p= 0.083). CONCLUSION: In spite of its somewhat lower intrinsic radial force, the fully-covered stent was comparable to the conventional semi-covered stent with regard to stent migration. The data further suggest a potential benefit of the fully-covered stent in improving dysphagia in patients with longer life expectancy.

Treatment of achalasia with laparoscopic myotomy or pneumatic dilatation: long-term results of a prospective, randomized study.

BACKGROUND: This study compares the long-term results of pneumatic dilatations versus laparoscopic myotomy using treatment failure as the primary outcome. The frequency and degree of dysphagia, the effects on quality of life (QoL), and health economy were also examined. METHODS: Fifty-three patients with achalasia were randomized to laparoscopic myotomy with a posterior partial fundoplication [laparoscopic myotomy (LM) n = 25] or repetitive pneumatic dilatation [pneumatic dilatation (PD) n = 28]. The median observation period was 81.5 months (range 12-131). RESULTS: At the minimal follow-up of 5 years, ten patients (36%) in the dilatation group and two patients (8%) in the myotomy group, including two patients lost to follow-up (one in each arm), were classified as failures (p = 0.016). The cumulative incidence of treatment failures was analyzed by survival statistics. Taking the entire follow-up period into account, a significant difference was observed in favor of the LM strategy (p = 0.02). Although both treatments resulted in significant improvements in dysphagia scores, LM was significantly favored over PD after 1 and 3 years, but not after 5 years. Health-related QoL assessed by the personal general well being score was higher in the LM group after 3 years, but the difference was not fully statistically significant at 5 years. Direct medical costs during the entire follow-up period were in median $13,421 for LM as compared to $5,558 for PD (p = 0.001). CONCLUSIONS: This long-term follow-up of a randomized clinical study shows that LM is superior to repetitive PD treatment of newly diagnosed achalasia, albeit that this surgical strategy is burdened by high initial direct medical costs. www.ClinicalTrials.gov NCT 02086669.

Multiple-Band Imaging Provides Better Value Than White-light Endoscopy in Detection of Dysplasia in Patients With Barrett's Esophagus.

BACKGROUND & AIMS: Surveillance of patients with Barrett's esophagus usually is performed with standard white-light endoscopy (SDWLE) and the collection of 4 biopsy specimens (every 1-2 cm of the metaplastic segment), based on Seattle protocol. New endoscopic techniques are used routinely, but have been validated based only on low-grade evidence. We aimed to validate the use of high-definition magnifying endoscopy with multiple-band imaging (HDMEMBI) with a targeted biopsy collection for the detection of dysplasia, using SDWLE with quadrant biopsy collection as the reference. METHODS: In a cross-over study, patients with suspected or histologically verified BE (without known neoplasia) seen at a tertiary referral high-volume endoscopy center in Sweden, from November 2009 through November 2012, were assigned randomly to undergo HDMEMBI (n = 63) or SDWLE (n = 47) as the initial procedure, followed by the other procedure in 1 to 4 months. The primary end point was the total number of subjects found to have low-grade dysplasia or high-grade dysplasia (HGD) by each technique. Secondary end points included the number of biopsy specimens taken and the duration of each procedure. RESULTS: There was no significant difference between groups in diagnostic yield for low-grade dysplasia (14 in HDMEMBI vs. 13 in SDWLE) or HGD. Four HGDs were found: 3 using HDMEMBI and 1 using SDWLE. Significantly fewer biopsy specimens were collected during the HDMEMBI procedure (P < .001). The diagnostic yield for the detection of dysplasia per biopsy specimen collected therefore was significantly higher for HDMEMBI than SDWLE (0.25 vs. 0.07; P = .018). There was no significant difference in the duration of procedures. CONCLUSIONS: There is no significant difference in the detection of dysplastic lesions using HDMEMBI with targeted collection of biopsy specimens vs SDWLE with 4-quadrant biopsy specimen collection. However, HDMEMBI requires the collection of significantly fewer biopsy specimens, providing better value for health care providers. ClinicalTrials.gov number: NCT01694511.

Covered and uncovered self-expandable metallic Hanarostents are equally efficacious in the drainage of extrahepatic malignant strictures. Results of a double-blind randomized study.

BACKGROUND: Self-expandable metallic stents (SEMS) placement is a standard treatment for inoperable malignant bile duct strictures. Covered SEMS have been introduced to avoid stent occlusion by tumor ingrowth. The aims were to compare covered and uncovered stents in terms of patency, efficacy and complication rate. MATERIAL AND METHODS: Consecutive patients with inoperable malignant distal biliary strictures were included in the study and randomized to receive a covered (n = 34) or uncovered (n = 34) Hanaro SEMS. Follow-up was performed by nurses after 18 h, 48 h, 2 weeks and thereafter every month until stent dysfunction or the patient died. Outcomes were measured as follows: the patients reported urine and stool color, presence of fever and abdominal pain. Liver function tests and CRP were analyzed each time. The procedure time and complications were monitored. The follow-up was blinded to stent type. RESULTS: The median patient age was 79 years (IQR: 66-83, R: 54-92), 59% were female and 85% had the gallbladder in situ. There was no difference between covered and uncovered stents in terms of procedure time (median: 30 min (20-38, R: 12-90) vs. 30 min (IQR: 20-42, R: 12-70)), stent patency (median: 153 days (IQR: 65-217; R: 20-609) vs. median of 127 days (IQR: 70-196; R: 18-486)) or patient survival (median: 154 days (IQR: 65-217; R: 21-609) vs 157 days (IQR: 70-273, R: 20-690)). Eighty-seven percent died with a patent covered and 83% with an uncovered stent (n.s.). Two early complications occurred (sepsis; pancreatitis), both with covered stents. CONCLUSION: There is no clinical difference between covered and uncovered biliary Hanaro SEMS. Both types are easily inserted with low complication rate and have long-term patency.

Tailored vs. standardized internet-based cognitive behavior therapy for depression and comorbid symptoms: a randomized controlled trial.

BACKGROUND AND AIMS: Major depression can be treated by means of cognitive behavior therapy, delivered via the Internet as guided self-help. Individually tailored guided self-help treatments have shown promising results in the treatment of anxiety disorders. This randomized controlled trial tested the efficacy of an Internet-based individually tailored guided self-help treatment which specifically targeted depression with comorbid symptoms. The treatment was compared both to standardized (non-tailored) Internet-based treatment and to an active control group in the form of a monitored online discussion group. Both guided self-help treatments were based on cognitive behavior therapy and lasted for 10 weeks. The discussion group consisted of weekly discussion themes related to depression and the treatment of depression. METHODS: A total of 121 participants with diagnosed major depressive disorder and with a range of comorbid symptoms were randomized to three groups. The tailored treatment consisted of a prescribed set of modules targeting depression as well as comorbid problems. The standardized treatment was a previously tested guided self-help program for depression. RESULTS: From pre-treatment to post-treatment, both treatment groups improved on measures of depression, anxiety and quality of life. The results were maintained at a 6-month follow-up. Subgroup analyses showed that the tailored treatment was more effective than the standardized treatment among participants with higher levels of depression at baseline and more comorbidity, both in terms of reduction of depressive symptoms and on recovery rates. In the subgroup with lower baseline scores of depression, few differences were seen between treatments and the discussion group. CONCLUSIONS: This study shows that tailored Internet-based treatment for depression is effective and that addressing comorbidity by tailoring may be one way of making guided self-help treatments more effective than standardized approaches in the treatment of more severe depression. TRIAL REGISTRATION: Clinicaltrials.gov NCT01181583.

Antibiotics as first-line therapy for acute appendicitis: evidence for a change in clinical practice.

BACKGROUND: Randomized studies have indicated that acute appendicitis may be treated by antibiotics without the need of surgery. However, concerns have been raised about selection bias of patients in such studies. Therefore, the present study was aimed to validate previous findings in randomized studies by a full-scale population-based application. METHODS: All patients with acute appendicitis at Sahlgrenska University Hospital (May 2009 and February 2010) were offered intravenous piperacillin plus tazobactam according to our previous experience, followed by 9 days out-hospital oral ciprofloxacin plus metronidazole. Endpoints were treatment efficacy and complications. Efficient antibiotic treatment was defined as recovery without the need of surgery beyond 1 year of follow-up. RESULTS: A total of 558 consecutive patients were hospitalized and treated due to acute appendicitis. Seventy-nine percent (n = 442) received antibiotics as first-line therapy and 20 % (n = 111) had primary surgery as the second-line therapy. Seventy-seven percent of patients on primary antibiotics recovered while 23 % (n = 100) had subsequent appendectomy due to failed initial treatment on antibiotics. Thirty-eight patients (11 %) of the 342 had experienced recurrent appendicitis at 1-year follow-up. Primary antibiotic treatment had fewer complications compared to primary surgery. CONCLUSIONS: This population-based study confirms previous results of randomized studies. Antibiotic treatment can be offered as the first-line therapy to a majority of unselected patients with acute appendicitis without medical drawbacks other than the unknown risk for long-term relapse, which must be weighed against the unpredicted but well-known risk for serious major complications following surgical intervention.

A randomized controlled trial of Internet-delivered cognitive behavior therapy and acceptance and commitment therapy in the treatment of tinnitus.

OBJECTIVE: Our aim in this randomized controlled trial was to investigate the effects on global tinnitus severity of 2 Internet-delivered psychological treatments, acceptance and commitment therapy (ACT) and cognitive behavior therapy (CBT), in guided self-help format. METHOD: Ninety-nine participants (mean age = 48.5 years; 43% female) who were significantly distressed by tinnitus were recruited from the community. Participants were randomly assigned to CBT (n = 32), ACT (n = 35), or a control condition (monitored Internet discussion forum; n = 32), and they were assessed with standardized self-report measures (Tinnitus Handicap Inventory; Hospital Anxiety and Depression Scale; Quality of Life Inventory; Perceived Stress Scale; Tinnitus Acceptance Questionnaire) at pre-, posttreatment (8 weeks), and 1-year follow-up. RESULTS: Mixed-effects linear regression analysis of all randomized participants showed significant effects on the primary outcome (Tinnitus Handicap Inventory) for CBT and for ACT compared with control at posttreatment (95% CI [-17.03, -2.94], d = 0.70, and 95% CI [-16.29, -2.53], d = 0.68, respectively). Within-group effects were substantial from pretreatment through 1-year-follow-up for both treatments (95% CI [-44.65, -20.45], d = 1.34), with no significant difference between treatments (95% CI [-14.87, 11.21], d = 0.16). CONCLUSIONS: Acceptance-based procedures may be a viable alternative to traditional CBT techniques in the management of tinnitus. The Internet can improve access to psychological interventions for tinnitus.