Antibiotics versus placebo in adults with CT-confirmed uncomplicated acute appendicitis (APPAC III): randomized double-blind superiority trial.

BACKGROUND: Non-operative management of uncomplicated acute appendicitis is an option, but omission of antibiotics from the regimen has not been tested. METHODS: A double-blind, placebo-controlled, superiority RCT in adults with CT-confirmed uncomplicated acute appendicitis was designed to compare placebo with antibiotics (intravenous ertapenem followed by oral levofloxacin and metronidazole). The primary endpoint was treatment success (resolution resulting in discharge without appendicectomy within 10 days); secondary outcomes included pain scores, complications, hospital stay, and return to work. RESULTS: From May 2017 to September 2020, 72 patients with a mean(s.d.) age of 37.5 (11.1) years were recruited at five hospitals. Six were excluded after randomization (5 early consent withdrawals, 1 randomization protocol violation), 35 were assigned to receive antibiotics, and 31 to receive placebo. Enrolment challenges (including hospital pharmacy resources in an acute-care surgery setting) meant that only the lowest sample size of three predefined scenarios was achieved. The 10-day treatment success rate was 87 (95 per cent c.i. 75 to 99) per cent for placebo and 97 (92 to 100) per cent for antibiotics. This clinical difference of 10 (90 per cent c.i. -0.9 to 21) per cent was not statistically different for the primary outcome (1-sided P = 0.142), and secondary outcomes were similar. CONCLUSION: The lack of antibiotic superiority statistically suggests that a non-inferiority trial against placebo is warranted in adults with CT-confirmed mild appendicitis. Registration number: EudraCT 2015-003634-26 (https://eudract.ema.europa.eu/eudract-web/index.faces), NCT03234296 (http://www.clinicaltrials.gov).

Appendicitis was the most common reason for emergency surgery, but we now know that mild and severe acute appendicitis are two different diseases. Severe appendicitis still necessitates removal of the appendix but antibiotics alone are an option for mild disease. This small study found that most cases of mild appendicitis to resolve even without antibiotics. Larger studies (more patients) would be needed to show that omitting antibiotics is safe and no worse than antibiotic therapy for milder acute appendicitis.

The association between appendicitis severity and patient age with appendiceal neoplasm histology-a population-based study.

PURPOSE: Recent studies have reported alarming appendiceal tumor rates associated with complicated acute appendicitis, especially in patients presenting with a periappendicular abscess. However, the data on histology of appendiceal tumors among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. We have previously reported the association of increased appendiceal tumor prevalence with complicated acute appendicitis in this population-based study. The objective of this secondary analysis was to evaluate the association of both appendicitis severity and patient age with appendiceal tumor histology. METHODS: This nationwide population-based registry study (The Finnish Cancer Registry) was conducted from 2007 to 2013. All appendiceal tumors (n = 840) and available medical reports (n = 504) of these patients at eight study hospitals were previously evaluated, identifying altogether 250 patients with both acute appendicitis and appendiceal tumor. RESULTS: The severity of acute appendicitis was significantly associated with more malignant tumor histology. The risk of adenocarcinoma or pseudomyxoma was significantly higher among patients with periappendicular abscess (OR 15.05, CI 95% 6.98-32.49, p < 0.001) and patients presenting with perforated acute appendicitis (OR 4.09, CI 95% 1.69-9.90, p = 0.0018) compared to patients with uncomplicated acute appendicitis. Similarly, patient age over 40 years was significantly associated with the risk of adenocarcinoma and pseudomyxoma (OR 26.46, Cl 95% 7.95-88.09, p < 0.001). Patient sex was not associated with a more malignant appendiceal tumor histology (p = 0.67). CONCLUSION: More malignant appendiceal tumor histology of adenocarcinoma or pseudomyxoma was significantly associated with patient age over 40 years and complicated acute appendicitis, especially periappendicular abscess.

Parastomal Hernia: A Retrospective Nationwide Cohort Study Comparing Different Techniques with Long-Term Follow-Up.

BACKGROUND: Parastomal hernia repair is a complex surgical procedure with high recurrence and complication rates. This retrospective nationwide cohort study presents the results of different parastomal hernia repair techniques in Finland. METHODS: All patients who underwent a primary end ostomy parastomal hernia repair in the nine participating hospitals during 2007-2017 were included in the study. The primary outcome measure was recurrence rate. Secondary outcomes were complications and re-operation rate. RESULTS: In total, 235 primary elective parastomal hernia repairs were performed in five university hospitals and four central hospitals in Finland during 2007-2017. The major techniques used were the Sugarbaker (38.8%), keyhole (16.3%), and sandwich techniques (15.4%). In addition, a specific intra-abdominal keyhole technique with a funnel-shaped mesh was utilized in 8.3% of the techniques; other parastomal hernia repair techniques were used in 21.3% of the cases. The median follow-up time was 39.0 months (0-146, SD 35.3). The recurrence rates after the keyhole, Sugarbaker, sandwich, specific funnel-shaped mesh, and other techniques were 35.9%, 21.5%, 13.5%, 15%, and 35.3%, respectively. The overall re-operation rate was 20.4%, while complications occurred in 26.3% of patients. CONCLUSION: The recurrence rate after parastomal hernia repair is unacceptable in this nationwide cohort study. As PSH repair volumes are low, further multinational, randomized controlled trials and hernia registry data are needed to improve the results.

Keyhole versus Sugarbaker techniques in parastomal hernia repair following ileal conduit urinary diversion: a retrospective nationwide cohort study.

BACKGROUND: Previous research on parastomal hernia repair following ileal conduit urinary diversion is limited. This nationwide cohort study aims to present the results of keyhole and Sugarbaker techniques in parastomal hernia repair in the setting of ileal conduit urinary diversion. METHOD: All patients in this cohort underwent primary elective parastomal hernia repair following ileal conduit urinary diversion in four university hospitals and one central hospital in Finland in 2007-2017. Retrospective clinical data were collected from patient registries to compare keyhole and Sugarbaker parastomal hernia repair techniques. The primary outcome was parastomal hernia recurrence during the follow-up from primary surgery to the last confirmed follow-up date of the patient. The secondary outcomes were reoperations during the follow-up and complication rate at 30 days' follow-up. RESULTS: The results of 28 hernioplasties were evaluated. The overall parastomal hernia recurrence rate was 18%, the re-operation rate was 14%, and the complication rate was 14% during the median follow-up time of 30 (21-64) months. Recurrence rates were 22% (4/18) after keyhole repair and 10% (1/10) after Sugarbaker repair. Re-operation rates referred to keyhole repair were 22% and Sugarbaker repair 0% during follow-up. The majority of reoperations were indicated by recurrence. Complication rates were 17% after keyhole and 10% after Sugarbaker repair during the 30 days' follow-up. CONCLUSION: The results of parastomal hernia repair in the setting of ileal conduits are below optimal in this nationwide cohort comparing keyhole to Sugarbaker repair in elective parastomal hernia repair. Nonetheless, the Sugarbaker technique should be further studied to confirm the encouraging results of this cohort in terms of recurrence.

Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis: The APPAC II Randomized Clinical Trial.

Importance: Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known. Objective: To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography-confirmed uncomplicated acute appendicitis. Design, Setting, and Participants: The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019. Interventions: Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days. Main Outcomes and Measures: The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference. Results: Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was -3.6% ([1-sided 95% CI, -9.7% to ∞]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin. Conclusion and Relevance: Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics. Trial Registration: ClinicalTrials.gov Identifier: NCT03236961; EudraCT Identifier: 2015-003633-10.

Appendiceal neoplasm risk associated with complicated acute appendicitis-a population based study.

PURPOSE: Appendiceal tumors are rare, but high neoplasm rates have been reported at interval appendectomy after periappendicular abscess. Non-operative management of uncomplicated acute appendicitis has shown promising results. The data on appendiceal tumor incidence and presentation among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. Objective was to assess appendiceal tumor incidence and tumor association to appendicitis in patients with uncomplicated and complicated acute appendicitis. METHODS: This nationwide population-based registry study was conducted from 2007 to 2013. The Finnish Cancer Registry and the National Institute for Health Registry were used to combine data on all appendiceal tumors and acute appendicitis diagnosis with medical reports evaluated at eight study hospitals. RESULTS: Altogether, 840 appendiceal tumors were identified, and out of these, 504 patient reports were reviewed, including 472 patients in this study. Tumor was diagnosed at appendectomy for suspected acute appendicitis in 276 patients (58%). In the whole study, histologically acute appendicitis and tumor were both present in 53% (n = 250), and out of these, 41% (n = 102) were complicated and 59% (n = 148) uncomplicated acute appendicitis. The associated tumor risk was significantly higher in complicated acute appendicitis compared with uncomplicated cases (3.24% vs. 0.87%, p < 0.001). Overall tumor prevalence among acute appendicitis patients was 1.24%. CONCLUSIONS: Appendiceal tumor prevalence in acute appendicitis was low. Tumor risk was significantly higher in complicated acute appendicitis compared with uncomplicated acute appendicitis. The risk of missed appendiceal tumors related to antibiotic therapy of uncomplicated acute appendicitis is very low.

Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial.

Importance: Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known. Objective: To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis. Design, Setting, and Participants: Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland; last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone. Interventions: Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole. Main Outcomes and Measures: In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave. Results: Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group). Conclusions and Relevance: Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis. Trial Registration: ClinicalTrials.gov Identifier: NCT01022567.

Clinical and laboratory findings in the diagnosis of right lower quadrant abdominal pain: outcome analysis of the APPAC trial.

BACKGROUND: The current research on acute appendicitis aims to improve the diagnostics and to clarify to whom antibiotic treatment might be the treatment of choice. METHODS: The present study is a retrospective analysis of a prospectively collected data in our randomized multicenter trial comparing surgery and antibiotic treatment for acute uncomplicated appendicitis (APPAC trial, NCTO1022567). We evaluated 1321 patients with a clinical suspicion of acute appendicitis, who underwent computed tomography (CT). Age, gender, body temperature, pain scores, the duration of symptoms, white blood cell count (WBC) and C-reactive protein (CRP) were recorded on admission. RESULTS: CT confirmed the diagnosis of acute appendicitis in 73% (n=970) and in 27% (n=351) it revealed no or other diagnosis. Acute appendicitis patients had significantly higher WBC levels than patients without appendicitis (median 12.2 and 10.0, respectively, p<0.0001), whereas CRP levels did not differ between the two groups. Ideal cut-off points were assessed with receiver operating characteristic (ROC) curves, but neither these markers or neither their combination nor any clinical characteristic could accurately differentiate between patients with acute appendicitis and those without. The proportion of patients with normal WBC count and CRP was significantly (p=0.0007) lower in patients with acute appendicitis than in patients without appendicitis. CONCLUSIONS: Both clinical findings and laboratory tests are unable to reliably distinguish between patients with acute appendicitis and those without. If both WBC count and CRP are normal, acute appendicitis is very unlikely. The current results emphasize the role of CT imaging in patients with suspected acute appendicitis.

Can Laparoscopic Cholecystectomy Prevent Recurrent Idiopathic Acute Pancreatitis?: A Prospective Randomized Multicenter Trial.

OBJECTIVE: The aim of the present trial was to ascertain whether laparoscopic cholecystectomy (LCC) can prevent recurrent attacks of idiopathic acute pancreatitis (IAP). SUMMARY: Up to 50% to 75% of IAP may be due to microlithiasis, which is undetectable by conventional imaging methods. METHODS: This randomized, prospective trial included 85 patients (39 in the LCC and 46 in the control group) in 8 hospitals in Finland. We included adult patients (over 18 years) with their first attack of IAP. The diagnosis of IAP was based on the exclusion of common etiological reasons for acute pancreatitis (AP), whereafter the patients were randomized into conservative watchful waiting (controls) or LCC group. The primary end point was the number of patients with recurrent AP during the follow-up. All recurrent attacks of AP after an initial IAP episode were registered. RESULTS: During a median follow-up of 36 (5-58) months, the recurrence of IAP was significantly higher in the control group than in LCC group (14/46 vs. 4/39, P = 0.016), as was also the number of recurrences (23/46 vs. 8/39, P = 0.003). In the subgroup of patients with at least 24 months' follow-up, the recurrence was still higher among controls (14/37 vs. 4/35, P = 0.008). In patients with normal liver function, recurrence was also significantly higher in the control than in the LCC group (13/46 vs. 4/39, P = 0.026). During surgery, 23/39 (59%) of the gallbladders were found to contain biliary stones or sludge. CONCLUSIONS: LCC can effectively prevent the recurrence of IAP when all other possible etiologies of pancreatitis are carefully excluded. A total of 5 patients needed to be treated (NNT-value) to prevent 1 IAP.

Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial.

IMPORTANCE: An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. OBJECTIVE: To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). DESIGN, SETTING, AND PARTICIPANTS: The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. INTERVENTIONS: Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy. MAIN OUTCOMES AND MEASURES: The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. RESULTS: There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of -27.0% (95% CI, -31.6% to ∞) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment. CONCLUSIONS AND RELEVANCE: Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01022567.

Three-Year Outcomes of Oral Antibiotics vs Intravenous and Oral Antibiotics for Uncomplicated Acute Appendicitis: A Secondary Analysis of the APPAC II Randomized Clinical Trial.

Importance: Current short-term evidence has shown that uncomplicated acute appendicitis can be treated successfully with oral antibiotics alone, but longer-term results are lacking. Objective: To assess the treatment effectiveness of oral antibiotic monotherapy compared with combined intravenous (IV) and oral antibiotics in computed tomography-confirmed uncomplicated acute appendicitis at a longer-term follow-up. Design, Setting, and Participants: This secondary analysis of a predefined year 3 follow-up of the Appendicitis Acuta II (APPAC II) noninferiority, multicenter randomized clinical trial compared oral moxifloxacin with combined IV ertapenem plus oral levofloxacin and metronidazole for the treatment of uncomplicated acute appendicitis. The trial was conducted at 9 university and central hospitals in Finland from April 2017 to November 2018, with the last follow-up in November 2022. Participants included patients aged 18 to 60 years, who were randomized to receive either oral antibiotics monotherapy (n = 301) or combined IV and oral antibiotics (n = 298). Interventions: Antibiotics monotherapy consisted of oral moxifloxacin, 400 mg/d, for 7 days. Combined IV and oral antibiotics consisted of IV ertapenem sodium, 1 g/d, for 2 days plus oral levofloxacin, 500 mg/d, and metronidazole, 500 mg 3 times/d, for 5 days. Main Outcomes and Measures: The primary end point was treatment success, defined as the resolution of acute appendicitis and discharge from hospital without the need for surgical intervention and no appendicitis recurrence at the year 3 follow-up evaluated using a noninferiority design. The secondary end points included late (after 1 year) appendicitis recurrence as well as treatment-related adverse events, quality of life, length of hospital stay, and length of sick leave, which were evaluated using a superiority design. Results: After exclusions, 599 patients (mean [SD] age, 36 [12] years; 336 males [56.1%]) were randomized; after withdrawal and loss to follow-up, 582 patients (99.8%) were available for the year 3 follow-up. The treatment success at year 3 was 63.4% (1-sided 95% CI, 58.8% to ∞) in the oral antibiotic monotherapy group and 65.2% (1-sided 95% CI, 60.5% to ∞) in the combined IV and oral antibiotics group. The difference in treatment success rate between the groups at year 3 was -1.8 percentage points (1-sided 95% CI, -8.3 percentage points to ∞; P = .14 for noninferiority), with the CI limit exceeding the noninferiority margin. There were no significant differences between groups in treatment-related adverse events, quality of life, length of hospital stay, or length of sick leave. Conclusions and Relevance: This secondary analysis of the APPAC II trial found a slightly higher appendectomy rate in patients who received oral antibiotic monotherapy; however, noninferiority of oral antibiotic monotherapy compared with combined IV and oral antibiotics could not be demonstrated. The results encourage future studies to assess oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis. Trial Registration: ClinicalTrials.gov Identifier: NCT03236961.

A prospective randomized controlled multicenter trial comparing antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis (APPAC trial).

BACKGROUND: Although the standard treatment of acute appendicitis (AA) consists of an early appendectomy, there has recently been both an interest and an increase in the use of antibiotic therapy as the primary treatment for uncomplicated AA. However, the use of antibiotic therapy in the treatment of uncomplicated AA is still controversial. METHODS/DESIGN: The APPAC trial is a randomized prospective controlled, open label, non-inferiority multicenter trial designed to compare antibiotic therapy (ertapenem) with emergency appendectomy in the treatment of uncomplicated AA. The primary endpoint of the study is the success of the randomized treatment. In the antibiotic treatment arm successful treatment is defined as being discharged from the hospital without the need for surgical intervention and no recurrent appendicitis during a minimum follow-up of one-year (treatment efficacy). Treatment efficacy in the operative treatment arm is defined as successful appendectomy evaluated to be 100%. Secondary endpoints are post-intervention complications, overall morbidity and mortality, the length of hospital stay and sick leave, treatment costs and pain scores (VAS, visual analoque scale). A maximum of 610 adult patients (aged 18-60 years) with a CT scan confirmed uncomplicated AA will be enrolled from six hospitals and randomized by a closed envelope method in a 1:1 ratio either to undergo emergency appendectomy or to receive ertapenem (1 g per day) for three days continued by oral levofloxacin (500 mg per day) plus metronidazole (1.5 g per day) for seven days. Follow-up by a telephone interview will be at 1 week, 2 months and 1, 3, 5 and 10 years; the primary and secondary endpoints of the trial will be evaluated at each time point. DISCUSSION: The APPAC trial aims to provide level I evidence to support the hypothesis that approximately 75-85% of patients with uncomplicated AA can be treated with effective antibiotic therapy avoiding unnecessary appendectomies and the related operative morbidity, also resulting in major cost savings.

Laparoscopic versus open cholecystectomy in diabetic patients and postoperative outcome.

BACKGROUND: Diabetes mellitus is associated with an increased risk of complications after abdominal surgery. We evaluated retrospectively the impact of preoperative risk factors and outcome of diabetic patients after laparoscopic cholecystectomy (LC) compared with open cholecystectomy (OC) for symptomatic gallstones. METHODS: Altogether 2,548 consecutive patients (1,581 LC, 967 OC) with symptomatic gallstones underwent cholecystectomy at our secondary referral center, being the only operative unit in the catchment area. Between the years 1995 and 2008, we operated 227 (9%) patients with diabetes, of whom 45 (20%) had type 1 diabetes. Preoperative data and operative outcome of the diabetic patients undergoing LC (n = 102) and OC (n = 125) were compared. The effect of comorbidities of diabetes on the risk for postoperative complications was analyzed by multiple logistic regression analysis. RESULTS: The percentage of morbidly obese diabetic patients did not change during the study period. Almost half of the cholecystectomies (n = 111) in diabetics were performed as acute surgery due to cholecystitis. Conversion to open surgery was required in 16% of the diabetic patients undergoing LC compared with 7% in the nondiabetic controls (p < 0.0001). Mortality rate was zero and nine patients (7.2%), respectively, in the LC and OC groups (p < 0.01). Other complications were also more frequently observed in the OC than LC groups. This outcome difference was unchanged during time. On multivariate analysis, comorbidities of diabetes were associated with an elevated risk for complications, but obesity or acute surgery was not independently associated with postoperative complications. CONCLUSIONS: When feasible, LC was a safe procedure in diabetes. Open surgery with comorbidities increased the operative risks. Our study was not randomized, and therefore selection bias to type of procedure may affect the results.

Laparoscopic and open cholecystectomy in surgical training.

BACKGROUND: Open cholecystectomy (OC) may still be necessary in surgical training to perform safe conversions of laparoscopic cholecystectomy (LC). Our aim was to study the outcome of LCs and OCs performed by surgical trainees. METHODS: All consecutive cholecystectomies (1,581 LCs and 984 OCs) were retrospectively analyzed from 1995 until 2008. Operative complications were compared between the cholecystectomies performed by 20 trainees alone (n = 822), assisted operations (n = 754, trainees/specialist surgeons) and 9 specialists alone (n = 989). RESULTS: Surgical trainees performed 787 (50%) LCs and 789 (80%) OCs either alone or assisted. The conversion rate of LC for trainees and specialist surgeons were 34 (7.0%) and 44 (5.5%), respectively. Complication rates and mortality were similar between the trainees and specialist surgeons. No bile duct injuries were associated with LCs or OCs performed by trainees alone. LCs were associated with 9 (0.57%) cases of bile leakage from cystic stump and 2 (0.13%) other bile duct injuries. CONCLUSION: Surgical trainees performed over half of our cholecystectomies with good results. The patient selection for LC versus OC was good, because no total transection of the common bile duct was observed in over 1,500 LC operations.

Quality of Life and Patient Satisfaction at 7-Year Follow-up of Antibiotic Therapy vs Appendectomy for Uncomplicated Acute Appendicitis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Long-term results support antibiotics for uncomplicated acute appendicitis as an alternative to appendectomy. To our knowledge, treatment-related long-term patient satisfaction and quality of life (QOL) are not known. Objective: To determine patient satisfaction and QOL after antibiotic therapy and appendectomy for treating uncomplicated acute appendicitis. Interventions: Open appendectomy vs antibiotics with intravenous ertapenem, 1 g once daily, for 3 days followed by 7 days of oral levofloxacin, 500 mg once daily, and metronidazole, 500 mg 3 times per day. Design, Setting, and Participants: This observational follow-up of the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotics included 530 patients age 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis who were randomized to undergo appendectomy (273 [52%]) or receive antibiotics (257 [49%]). The trial was conducted from November 2009 to June 2012; the last follow-up was May 9, 2018. The data were analyzed in February 2019. Main Outcomes and Measures: In this analysis, post hoc secondary end points of postintervention QOL (EQ-5D-5L) and patient satisfaction and treatment preference were evaluated. Results: Of the 530 patients enrolled in the trial (appendectomy group: 273 [174 men (64%)] with a median age of 35 years; (antibiotic group: 257 [155 men (60%)] with a median age of 33 years), 423 patients (80%) were available for phone interview at a median follow-up of 7 years; 206 patients (80%) took antibiotics and 217 (79%) underwent appendectomy. Of the 206 patients taking antibiotics, 81 (39%) had undergone appendectomy. The QOL between appendectomy and antibiotic group patients was similar (median health index value, 1.0 in both groups; 95% CI, 0.86-1.0; P = .96). Patients who underwent appendectomy were more satisfied in the treatment than patients taking antibiotics (68% very satisfied, 21% satisfied, 6% indifferent, 4% unsatisfied, and 1% very unsatisfied in the appendectomy group and 53% very satisfied, 21% satisfied, 13% indifferent, 7% unsatisfied, and 6% very unsatisfied in the antibiotic group; P < .001) and in a subgroup analysis this difference was based on the antibiotic group patients undergoing appendectomy. There was no difference in patient satisfaction after successful antibiotic treatment compared with appendectomy (cumulative odds ratio [COR], 7.8; 95% CI, 0.5-1.3; P < .36). Patients with appendectomy or with successful antibiotic therapy were more satisfied than antibiotic group patients who later underwent appendectomy (COR, 7.7; 95% CI, 4.6-12.9; P < .001; COR, 9.7; 95% CI, 5.4-15.3; P < .001, respectively). Of the 81 patients taking antibiotics who underwent appendectomy, 27 (33%) would again choose antibiotics as their primary treatment. Conclusions and Relevance: In this analysis, long-term QOL was similar after appendectomy and antibiotic therapy for the treatment of uncomplicated acute appendicitis. Patients taking antibiotics who later underwent appendectomy were less satisfied than patients with successful antibiotics or appendectomy. Trial Registration: Clinicaltrials.gov Identifier: NCT01022567.

"Sense of Control": Patients' Experiences of Multimodal Pain Rehabilitation and its Impact in their Everyday Lives.

OBJECTIVE: Long-lasting pain is a challenge for pa-tients' everyday lives. The aim of this study was to examine how women and men who have participa-ted in multimodal pain rehabilitation experience its impact in their everyday lives. PATIENTS AND METHODS: Individual semi-structured interviews with 5 women and 3 men who had parti-cipated in multimodal pain rehabilitation at a clinic in Sweden, analysed using qualitative content ana-lysis. RESULTS: Participants perceived that their "sense of control" increased, which had a positive impact in their everyday life. Sense of control consisted of 3 categories: importance of the patient-provider re-lationship, knowledge gained (especially on body functions and medication), and pain in a social con-text. Three results were discussed in particular: (i) a trustful patient-provider relationship based on confidence in the provider's expertise was a pre-requisite for pain acceptance; (ii) patients were aware of gender norms in healthcare; (iii) social support was not stressed as important to cope with pain. CONCLUSION: The importance of patients' confidence in the provider's expertise and patients' awareness about gender norms need consideration in terms of the patient-provider encounter. The value of social support for pain rehabilitation was found to be less important compared with previous research; this should be explored further.

Risk of Appendiceal Neoplasm in Periappendicular Abscess in Patients Treated With Interval Appendectomy vs Follow-up With Magnetic Resonance Imaging: 1-Year Outcomes of the Peri-Appendicitis Acuta Randomized Clinical Trial.

Importance: The step after conservative treatment of periappendicular abscess arouses controversy, ranging from recommendations to abandon interval appendectomy based on low recurrence rates of the precipitating diagnosis to performing routine interval appendectomy owing to novel findings of increased neoplasm risk at interval appendectomy. To our knowledge, there are no randomized clinical trials with sufficient patient numbers comparing these treatments. Objective: To compare interval appendectomy and follow-up with magnetic resonance imaging after initial successful nonoperative treatment of periappendicular abscess. Design, Setting, and Participants: The Peri-Appendicitis Acuta randomized clinical trial was a multicenter, noninferiority trial conducted in 5 hospitals in Finland. All patients between age 18 and 60 years with periappendicular abscess diagnosed by computed tomography and successful initial nonoperative treatment from January 2013 to April 2016 were included. Data analysis occurred from April 2016 to September 2017. Interventions: Patients were randomized either to interval appendectomy or follow-up with magnetic resonance imaging; all patients underwent colonoscopy. Main Outcomes and Measures: The primary end point was treatment success, defined as an absence of postoperative morbidity in the appendectomy group and appendicitis recurrence in the follow-up group. Secondary predefined end points included neoplasm incidence, inflammatory bowel disease, length of hospital stay, and days of sick leave. Results: A total of 60 patients were included (36 men [60%]; median [interquartile range] age: interval appendectomy group, 49 [18-60] years; follow-up group, 47 [22-61] years). An interim analysis in April 2016 showed a high rate of neoplasm (10 of 60 [17%]), with all neoplasms in patients older than 40 years. The trial was prematurely terminated owing to ethical concerns. Two more neoplasms were diagnosed after study termination, resulting in an overall neoplasm incidence of 20% (12 of 60). On study termination, the overall morbidity rate of interval appendectomy was 10% (3 of 30), and 10 of the patients in the follow-up group (33%) had undergone appendectomy. Conclusions and Relevance: The neoplasm rate after periappendicular abscess in this small study population was high, especially in patients older than 40 years. If this considerable rate of neoplasms after periappendicular abscess is validated by future studies, it would argue for routine interval appendectomy in this setting. Trial Registration: ClinicalTrials.gov identifier: NCT03013686.

Cost analysis of antibiotic therapy versus appendectomy for treatment of uncomplicated acute appendicitis: 5-year results of the APPAC randomized clinical trial.

BACKGROUND: The efficacy and safety of antibiotic treatment for uncomplicated acute appendicitis has been established at long-term follow-up with the majority of recurrences shown to occur within the first year. Overall costs of antibiotics are significantly lower compared with appendectomy at short-term follow-up, but long-term durability of these cost savings is unclear. The study objective was to compare the long-term overall costs of antibiotic therapy versus appendectomy in the treatment of uncomplicated acute appendicitis in the APPAC (APPendicitis ACuta) trial at 5 years. METHODS AND FINDINGS: This multicentre, non-inferiority randomized clinical trial randomly assigned 530 adult patients with CT-confirmed uncomplicated acute appendicitis to appendectomy or antibiotic treatment at six Finnish hospitals. All major costs during the 5-year follow-up were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis. Between November 2009 and June 2012, 273 patients were randomized to appendectomy and 257 to antibiotics. The overall costs of appendectomy were 1.4 times higher (p<0.001) (€5716; 95% CI: €5510 to €5925) compared with antibiotic therapy (€4171; 95% CI: €3879 to €4463) resulting in cost savings of €1545 per patient (95% CI: €1193 to €1899; p<0.001) in the antibiotic group. At 5 years, the majority (61%, n = 156) of antibiotic group patients did not undergo appendectomy. CONCLUSIONS: At 5-year follow-up antibiotic treatment resulted in significantly lower overall costs compared with appendectomy. As the majority of appendicitis recurrences occur within the first year after the initial antibiotic treatment, these results suggest that treating uncomplicated acute appendicitis with antibiotics instead of appendectomy results in lower overall costs even at longer-term follow-up.

A randomised placebo-controlled double-blind multicentre trial comparing antibiotic therapy with placebo in the treatment of uncomplicated acute appendicitis: APPAC III trial study protocol.

INTRODUCTION: Recent studies show that antibiotic therapy is safe and feasible for CT-confirmed uncomplicated acute appendicitis. Spontaneous resolution of acute appendicitis has already been observed over a hundred years ago. In CT-confirmed uncomplicated acute diverticulitis (left-sided appendicitis), studies have shown no benefit from antibiotics compared with symptomatic treatment, but this shift from antibiotics to symptomatic treatment has not yet been widely implemented in clinical practice. Recently, symptomatic treatment of uncomplicated acute appendicitis has been demonstrated in a Korean open-label study. However, a double-blinded placebo-controlled study to illustrate the role of antibiotics and spontaneous resolution of uncomplicated acute appendicitis is still lacking. METHODS AND ANALYSIS: The APPAC III (APPendicitis ACuta III) trial is a multicentre, double-blind, placebo-controlled, superiority randomised study comparing antibiotic therapy with placebo in the treatment CT scan-confirmed uncomplicated acute appendicitis aiming to evaluate the role of antibiotics in the resolution of uncomplicated acute appendicitis. Adult patients (18-60 years) with CT scan-confirmed uncomplicated acute appendicitis (the absence of appendicolith, abscess, perforation and tumour) will be enrolled in five Finnish university hospitals.Primary endpoint is success of the randomised treatment, defined as resolution of acute appendicitis resulting in discharge from the hospital without surgical intervention within 10 days after initiating randomised treatment (treatment efficacy). Secondary endpoints include postintervention complications, recurrent symptoms after treatment up to 1 year, late recurrence of acute appendicitis after 1 year, duration of hospital stay, sick leave, treatment costs and quality of life. A decrease of 15 percentage points in success rate is considered clinically important difference. The superiority of antibiotic treatment compared with placebo will be analysed using Fisher's one-sided test and CI will be calculated for proportion difference. ETHICS AND DISSEMINATION: This protocol has been approved by the Ethics Committee of Turku University Hospital and the Finnish Medicines Agency (FIMEA). The findings will be disseminated in peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: NCT03234296; Pre-results.