Tuomo Rantanen

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

IMPORTANCEnAn increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis.nnnOBJECTIVEnTo compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT).nnnDESIGN, SETTING, AND PARTICIPANTSnThe 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.nnnINTERVENTIONSnPatients 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.nnnMAIN OUTCOMES AND MEASURESnThe 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.nnnRESULTSnThere 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 ∞) (Pu2009=u2009.89). 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.nnnCONCLUSIONS AND RELEVANCEnAmong 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.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT01022567.

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

BackgroundAlthough 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/designThe 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.DiscussionThe 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.Trial registrationClinicaltrials.govhttp://NCT01022567

Endovascular Therapy as a Primary Revascularization Modality in Acute Mesenteric Ischemia.

PurposeTo evaluate endovascular therapy (EVT) as the primary revascularization method for acute mesenteric ischemia (AMI).MethodsA retrospective review was performed on all consecutive patients treated for AMI during a 5-year period (January 2009 to December 2013). EVT was attempted in all patients referred for emergent revascularization. Surgical revascularization was performed selectively after failure of EVT. Patient characteristics, clinical presentation, and outcomes were studied. Failures and complications of EVT were recorded.ResultsFifty patients, aged 79xa0±xa09xa0years (meanxa0±xa0SD), out of 66 consecutive patients with AMI secondary to embolic or thrombotic obstruction of the superior mesenteric artery were referred for revascularization. The etiology of AMI was embolism in 18 (36xa0%) and thrombosis in 32 (64xa0%) patients. EVT was technically successful in 44 (88xa0%) patients. Mortality after successful or failed EVT was 32xa0%. The rates of emergency laparotomy, bowel resection, and EVT-related complication were 40, 34, and 10xa0%, respectively. Three out of six patients with failure of EVT were treated with surgical bypass. EVT failure did not significantly affect survival.ConclusionsEVT is feasible in most cases of AMI, with favorable patient outcome and acceptable complication rate.

Is preoperative distinction between complicated and uncomplicated acute appendicitis feasible without imaging

BACKGROUNDnOne of the main aims of appendicitis research is the differential diagnostics between complicated and uncomplicated acute appendicitis that enable provision of the optimal treatment for each patient.nnnMETHODSnData in the present study were collected prospectively in our randomized antibiotic treatment for uncomplicated acute appendicitis trial (APPAC) comparing surgery and antibiotic treatment for uncomplicated acute appendicitis (NCT01022567). We evaluated 705 patients who had acute appendicitis on computed tomography. Patients with uncomplicated acute appendicitis (nxa0=xa0368) were compared with all complicated acute appendicitis patients (nxa0=xa0337), and subgroup analyses were performed between uncomplicated acute appendicitis and an appendicolith appendicitis (CA1; nxa0=xa0256) and uncomplicated acute appendicitis and perforation and/or abscess (CA2; nxa0=xa078). Age, sex, body temperature (°C), duration of symptoms, white blood cell count (E9/L), and C-reactive protein (mg/L) were recorded on admission. Receiver operating characteristic curves were calculated for white blood cell count, C-reactive protein, and temperature.nnnRESULTSnCA2 patients had significantly greater C-reactive protein levels (mean 122 and 47, respectively, Pxa0<xa0.001) and longer duration of symptoms than uncomplicated acute appendicitis patients; 81% of CA2 patients and 38% of uncomplicated acute appendicitis patients had symptoms >24xa0hours before admission (Pxa0<xa0.001). In receiver operating characteristic analysis, C-reactive protein and temperature had clinically significant results only in comparison with uncomplicated acute appendicitis and CA2 (area under the curve >0.7), but no optimum cutoff points could be identified.nnnCONCLUSIONnIn clinical decision making, neither clinical findings nor laboratory markers are reliable enough to estimate the severity of the acute appendicitis accurately or to determine the presence of an appendicolith. The current results emphasize the role of computed tomography in thexa0differential diagnosis of complicated and uncomplicated acute appendicitis.

Emergency Abdominal Operations in the Elderly: A Multivariate Regression Analysis of 430 Consecutive Patients with Acute Abdomen

BackgroundThis study is intended to ascertain if outcome of acute abdominal surgery among elderly patients with acute abdominal pain have improved.MethodsAltogether 456 patients aged >65xa0years underwent emergency abdominal surgery between the years 2007 and 2009 in our hospital. After excluding emergency reoperations of elective surgery, a total of 430 consecutive patients were included in this retrospective audit. The key factors under analysis in this study were the occurrence of major complications and death from any cause within 30xa0days after the operation. In addition, we compared our results to our previously published data some 20xa0years ago.ResultsThe most common diagnoses were cholecystitis (nxa0=xa0139, 32.3xa0%, incidence of 125 per 100,000 elderly persons), incarcerated hernia (nxa0=xa060, 13.9xa0%, 54/100,000), malignancy related (nxa0=xa050, 11.6xa0%, 45/100,000), or acute appendicitis (nxa0=xa046, 10.7xa0%, 41/100,000). The majority of operations (80.7xa0%) were performed using open technique. Of all 112 laparoscopic procedures, 25.9xa0% were converted to open surgery. Reoperations were rare and postoperative surgical complications were not associated with statistically significant increase in mortality, even if reoperation was needed. The 30-day mortality and morbidity rates were 14.2 and 31.9xa0%, respectively. Logistic regression analysis showed that patient’s age (pxa0=xa00.014), atrial fibrillation (pxa0=xa00.017), low body mass index (pxa0=xa00.001), open surgery (pxa0=xa00.029), ASA grade III or more (pxa0<xa00.001), and previous history of malignancies (pxa0=xa00.010) were likely to increase mortality.ConclusionsDespite modern diagnostics and improved surgical techniques, the results of emergency abdominal surgery still have relatively high morbidity and mortality as reported in earlier studies.

Economic evaluation of antibiotic therapy versus appendicectomy for the treatment of uncomplicated acute appendicitis from the APPAC randomized clinical trial

An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial.

Severe Sepsis in Elderly Patients Undergoing Gastrointestinal Surgery—a Prospective Multicenter Follow-up Study of Finnish Intensive Care Units

BackgroundWe aimed to evaluate the outcome of elderly patients with severe sepsis after alimentary tract surgery.MethodsA prospective study was conducted in 24 intensive care units (ICU) in Finland. Four thousand five hundred consecutive patients were admitted to ICUs and 470 patients fulfilled the criteria for severe sepsis. All patients who had undergone gastrointestinal surgery were included. The outcomes of elderly (≥65xa0years) and younger patients were compared. The key factor under analysis was death from any cause during the hospitalization or within 1xa0year after the surgery.ResultsA total of 73 elderly patients (and 81 younger patients) were found to have severexa0alimentary tract surgery-related sepsis. The mean age of the elderly patients was 76.4xa0years, and 56.2xa0% were female. The most common indication for surgery was acute cholecystitis (21.9xa0%), followed by acute diverticulitis (13.7xa0%), and gastroduodenal ulcer (13.7xa0%). The anatomic site of the infection was intra-abdominal in 86.3xa0% of cases, the second most common being pulmonary (13.7xa0%). In-hospital mortality was 47.9xa0% and 1-year mortality 64.4xa0%. Of the discharged patients, 31.6xa0% died within 1xa0year. Patients who died were older and more frequently had concomitant conditions. The ICU scoring systems (APACHE, SAPS, and SOFA) and elevated lactate levels were predictive of increased mortality.ConclusionSevere sepsis among the elderly is a rare but often-fatal infectious event. In addition to high in-hospital mortality, it is also associated with significant 1-year mortality.

Alcohol Abuse Increases Rebleeding Risk and Mortality in Patients with Non-variceal Upper Gastrointestinal Bleeding

BackgroundNo current data are available on rebleeding and mortality risk in patients who use alcohol excessively and are admitted for non-variceal upper gastrointestinal bleeding (NVUGIB). This information could help in planning interventions and follow-up protocols for these patients.AimThis study provides contemporary data on the long-term outcome after first-time NVUGIB in alcohol abusers (AAs) compared to non-abusers (NAs).MethodsConsecutive patients hospitalized for their first acute gastrointestinal bleeding from 2009 through 2011 were retrospectively recorded and categorized as AA or NA. Risk factors for one-year mortality and rebleeding were identified, and patients were further monitored for long-term mortality until 2015.ResultsAlcohol abuse was identified in 19.7xa0% of patients with NVUGIB (nxa0=xa0518). The one-year rebleeding rate was 16.7xa0% in AAs versus 9.1xa0% in NAs (Pxa0=xa00.027). Alcohol abuse was associated with a twofold increase in rebleeding risk (Pxa0=xa00.025); the risk especially increased 6xa0months after the initial bleeding. The study groups did not differ significantly in 30-day (6.0xa0%) or one-year mortality rates (20.5xa0%). However, there was a tendency for higher overall mortality in AAs than NAs after adjustment of comorbidities.ConclusionAAs with NVUGIB are at high risk of rebleeding, and mortality is increased in AA patients. A close follow-up strategy and long-term proton pump inhibitor therapy are recommended for AA patients with peptic ulcer or esophagitis.

The Accuracy of the Computed Tomography Diagnosis of Acute Appendicitis: Does the Experience of the Radiologist Matter?:

Background and Aims: To assess the accuracy of computed tomography in diagnosing acute appendicitis with a special reference to radiologist experience. Material and Methods: Data were collected prospectively in our randomized controlled trial comparing surgery and antibiotic treatment for uncomplicated acute appendicitis (APPAC trial, NCT01022567). We evaluated 1065 patients who underwent computed tomography for suspected appendicitis. The on-call radiologist preoperatively analyzed these computed tomography images. In this study, the radiologists were divided into experienced (consultants) and inexperienced (residents) ones, and the comparison of interpretations was made between these two radiologist groups. Results: Out of the 1065 patients, 714 had acute appendicitis and 351 had other or no diagnosis on computed tomography. There were 700 true-positive, 327 true-negative, 14 false-positive, and 24 false-negative cases. The sensitivity and the specificity of computed tomography were 96.7% (95% confidence interval, 95.1–97.8) and 95.9% (95% confidence interval, 93.2–97.5), respectively. The rate of false computed tomography diagnosis was 4.2% for experienced consultant radiologists and 2.2% for inexperienced resident radiologists (pu2009=u20090.071). Thus, the experience of the radiologist had no effect on the accuracy of computed tomography diagnosis. Conclusion: The accuracy of computed tomography in diagnosing acute appendicitis was high. The experience of the radiologist did not improve the diagnostic accuracy. The results emphasize the role of computed tomography as an accurate modality in daily routine diagnostics for acute appendicitis in all clinical emergency settings.

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 (nu2009=u2009273) or receive antibiotic therapy (nu2009=u2009257). 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%) (nu2009=u200960/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (nu2009=u200916/246) in antibiotic group (Pu2009<u2009.001), 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