Saija Hurme

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.

Significance of site-specific prognosis of cancer stem cell marker CD44 in head and neck squamous-cell carcinoma

In several recent studies, CD44 expression has been associated with aggressive behavior in cancers of different types. CD44 expression is also linked to cancer stem cells, which have been shown to play a significant role in tumor progression and poor prognosis in head and neck squamous cell carcinoma (HNSCC), as well as in other cancers. Although CD44 is a potential prognostic marker, it has not been adopted to wider clinical use as a part of treatment planning in HNSCC patients. The aim of this research was to study whether CD44 overexpression is associated with 5year overall survival in HNSCC. We also studied site-specific associations between increased CD44 expression and 5year overall survival. Associations between relative tumor CD44 expressions and smoking, heavy alcohol consumption, histological grade of cancer, TNM staging and HNSCC staging were also studied. In total, 135 paraffin-embedded blocks from HNSCC patients were stained immunohistochemically with a CD44 antibody and were classified by the anatomic location of the tumor. CD44 overexpression had statistically significant association with decreased 5year survival rates when all HNSCC samples were studied (p<0.001). Significant association between intense CD44 expression and poor 5year survival rates was found in the patients with SCC of the oro- and hypopharynx (p<0.001) and the larynx (p=0.042). In patients suffering from HNSCC in the oral cavity, CD44 overexpression did not have a significant effect on overall 5year survival rates. Heavy smoking of over 10 pack years had a significant association with tumor CD44 overexpression (p=0.009). Only pharyngeal (p=0.046) and laryngeal (p=0.047) SCC, but not oral-cavity SCC, had statistically significant associations between heavy smoking and CD44 overexpression when HNSCC was studied in regional groups. Alcohol consumption and tumor grade did not have a significant association with the tumors CD44 expression. Our results suggest that CD44 overexpression could be used as a sign of aggressiveness, in addition to the HNSCC staging, as a prognostic factor in pharyngeal and laryngeal HNSCC and to assist in treatment selection.

Cesarean delivery in Finland: maternal complications and obstetric risk factors

Objective. To assess the rate of maternal complications related to cesarean section (CS) and to compare morbidity between elective, emergency and crash‐emergency CS. To establish risk factors associated with maternal CS morbidity. Design. A prospective multicenter cohort study. Setting. Twelve delivery units in Finland. Population. Women delivering by CS (n = 2,496) during a 6 months period in the study hospitals. Methods. Data on pregnant women, CS, and maternal recovery during the hospital stay was collected prospectively on report forms. The complication rates by different CSs were calculated, and factors associated with morbidity were analyzed by odds ratios (OR). Main outcome measures. Maternal complication rates in different types of CS. The association of risk factors with morbidity. Results. About 27% of women delivering by CS had complications; 10% had severe complications. The complication rate was higher in emergency CS than in elective CS, and highest in crash‐emergency CS. Significant independent risk factors for maternal morbidity were emergency CS and crash‐emergency CS compared to elective CS (OR 1.8; 95% confidence interval (CI) 1.5–2.2), pre‐eclampsia (OR 1.5; CI 1.1–2.0), maternal obesity (OR 1.4; CI 1.1–1.8) and maternal increasing age (OR 1.1; CI 1.03–1.2 per each 5 years). Conclusions. Maternal complications are frequent in CS, and although performing CS electively reduces the occurrence of complications, the frequency is still high. The complication rate depends on the degree of emergency, and increases with maternal obesity, older age and pre‐eclampsia.

Long-term outcome of infective endocarditis: a study on patients surviving over one year after the initial episode treated in a Finnish teaching hospital during 25 years.

BackgroundOnly a few previous studies have focused on the long-term prognosis of the patients with infective endocarditis (IE). Our purpose was to delineate factors potentially associated with the long-term outcome of IE, recurrences of IE and requirement for late valve surgery.MethodsA total of 326 episodes of IE in 303 patients were treated during 1980–2004 in the Turku University Hospital. We evaluated the long-term outcome and requirement for late valve surgery for 243 of these episodes in 226 patients who survived longer than 1 year after the initial admission. Factors associated with recurrences were analysed both for the 1-year survivors and for all 303 patients.ResultsThe mean (SD) follow-up time for the 1-year survivors was 11.5 (7.3) years (range 25 days to 25.5 years). The overall survival was 95%, 82%, 66%, 51% and 45% at 2, 5, 10, 15 and 20 years. In age and sex adjusted multivariate analyses, significant predictors for long-term overall mortality were heart failure within 3 months of admission (HR 1.97, 95% CI 1.27 to 3.06; p = 0.003) and collagen disease (HR 2.54, 95% CI 1.25 to 5.19; p = 0.010) or alcohol abuse (HR 2.39, 95% CI 1.30 to 4.40; p = 0.005) as underlying conditions, while early surgery was significantly associated with lower overall mortality rates (HR 0.31, 95% CI 0.17 to 0.58; p < 0.001). Heart failure was also significantly associated with the long-term cardiac mortality (p = 0.032). Of all 303 patients, 20 had more than 1 disease episode. Chronic dialysis (p = 0.002), intravenous drug use (p = 0.002) and diabetes (p = 0.015) were significant risk factors for recurrent episodes of IE, but when analysed separately for the 1-year survivors, only chronic dialysis remained significant (p = 0.017). Recurrences and late valve surgery did not confer a poor prognosis.ConclusionHeart failure during the index episode of IE was the complication, which significantly predicted a poor long-term outcome. Patients who underwent surgery during the initial hospitalisation for IE faired significantly better than those who did not.

Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial

Importance Laparoscopic sleeve gastrectomy for treatment of morbid obesity has increased substantially despite the lack of long-term results compared with laparoscopic Roux-en-Y gastric bypass. Objective To determine whether laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are equivalent for weight loss at 5 years in patients with morbid obesity. Design, Setting, and Participants The Sleeve vs Bypass (SLEEVEPASS) multicenter, multisurgeon, open-label, randomized clinical equivalence trial was conducted from March 2008 until June 2010 in Finland. The trial enrolled 240 morbidly obese patients aged 18 to 60 years, who were randomly assigned to sleeve gastrectomy or gastric bypass with a 5-year follow-up period (last follow-up, October 14, 2015). Interventions Laparoscopic sleeve gastrectomy (n = 121) or laparoscopic Roux-en-Y gastric bypass (n = 119). Main Outcomes and Measures The primary end point was weight loss evaluated by percentage excess weight loss. Prespecified equivalence margins for the clinical significance of weight loss differences between gastric bypass and sleeve gastrectomy were −9% to +9% excess weight loss. Secondary end points included resolution of comorbidities, improvement of quality of life (QOL), all adverse events (overall morbidity), and mortality. Results Among 240 patients randomized (mean age, 48 [SD, 9] years; mean baseline body mass index, 45.9, [SD, 6.0]; 69.6% women), 80.4% completed the 5-year follow-up. At baseline, 42.1% had type 2 diabetes, 34.6% dyslipidemia, and 70.8% hypertension. The estimated mean percentage excess weight loss at 5 years was 49% (95% CI, 45%-52%) after sleeve gastrectomy and 57% (95% CI, 53%-61%) after gastric bypass (difference, 8.2 percentage units [95% CI, 3.2%-13.2%], higher in the gastric bypass group) and did not meet criteria for equivalence. Complete or partial remission of type 2 diabetes was seen in 37% (n = 15/41) after sleeve gastrectomy and in 45% (n = 18/40) after gastric bypass (P > .99). Medication for dyslipidemia was discontinued in 47% (n = 14/30) after sleeve gastrectomy and 60% (n = 24/40) after gastric bypass (P = .15) and for hypertension in 29% (n = 20/68) and 51% (n = 37/73) (P = .02), respectively. There was no statistically significant difference in QOL between groups (P = .85) and no treatment-related mortality. At 5 years the overall morbidity rate was 19% (n = 23) for sleeve gastrectomy and 26% (n = 31) for gastric bypass (P = .19). Conclusions and Relevance Among patients with morbid obesity, use of laparoscopic sleeve gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not meet criteria for equivalence in terms of percentage excess weight loss at 5 years. Although gastric bypass compared with sleeve gastrectomy was associated with greater percentage excess weight loss at 5 years, the difference was not statistically significant, based on the prespecified equivalence margins. Trial Registration clinicaltrials.gov Identifier: NCT00793143

Quality of life after surgery for rectal cancer with special reference to pelvic floor dysfunction.

Aim  Conventional outcomes such as survival, tumour recurrence and complication rates after surgery for rectal cancer have been rigorously assessed, but the importance of maintaining quality of life (QOL) after surgery for rectal cancer has received less attention. The aim of the current study was to analyse QOL and the occurrence of pelvic dysfunction after the surgical treatment of rectal cancer.

Fifteen-Year Outcome of Laparoscopic and Open Nissen Fundoplication: A Randomized Clinical Trial

BACKGROUND Laparoscopic Nissen fundoplication (LNF) has become the method of choice in the surgical treatment of gastroesophageal reflux disease (GERD), replacing its open counterpart without confirmation by the long-term results of controlled clinical studies. The goal of the present study was to compare the 15-year outcome of a randomized controlled comparison study of LNF versus open Nissen fundoplication (ONF). METHODS From 1992 to 1995, 110 consecutive patients were randomized to undergo LNF or ONF. The 15-year objective results were evaluated by endoscopy, and the subjective symptomatic outcome was assessed by interviews. RESULTS A total of 86 patients (48 in the LNF [LAP] and 38 in the ONF [OPEN] group) participated in the study. The late long-term symptomatic outcome was similar in the two patient groups. In the LAP group, 91.7% of the patients gave a positive evaluation of their surgical result, as compared with 76.3% of the patients in the OPEN group (p=0.0484). A significantly greater number of disrupted plications (p=0.0115) and incisional hernias (p<0.001) occurred in the OPEN than in the LAP group. Both the subjective outcome and the objective endoscopic and clinical findings in the present study were in accord with our previously reported outcomes at 11-years after laparoscopic versus open fundoplication. The study found a trend toward (p=0.0851) an increasing need for the regular use of a proton pump inhibitor with the passage of time after Nissen fundoplication. CONCLUSIONS The 15-year results obtained in the present study define laparoscopic Nissen fundoplication as the procedure of choice in the surgical management of GERD. The long-term symptomatic outcomes of open and laparoscopic Nissen fundoplication appear to remain unaltered after the first 10 postoperative years.

Utility of C-reactive protein in assessing the disease severity and complications of community-acquired pneumonia

Previous studies on the usefulness of C-reactive protein (CRP) in patients with community-acquired pneumonia (CAP) have yielded somewhat inconsistent results. Our aim was to assess the value of CRP in estimating the severity and complications of CAP. CRP levels during the first 5 days of hospitalization were measured in 384 adult patients with CAP, and the data were evaluated using comprehensive statistical analyses. Significantly higher CRP levels on admission were detected in Pneumonia Severity Index (PSI) classes III-V than in classes I and II (p <0.001). An increment of 50 mg/L CRP on admission was associated with a 1.22-fold odds for a patient to be in PSI classes III-V as compared with classes I and II (OR 1.22, 95% CI 1.11-1.34; p <0.001). CRP levels were significantly higher in bacteraemic pneumonia than in non-bacteraemic pneumonia (p <0.001). An increment of 50 mg/L CRP was associated with a 1.67-fold odds for a patient to be bacteraemic (OR 1.67, 95% CI 1.46-1.92; p <0.001). CRP levels >100 mg/L on day 4 after the admission were significantly associated with complications (p <0.01). There was a trend for an association between the level of CRP on admission and the time to reach clinical stability (p <0.01). In conclusion, CRP may be valuable for revealing the development of complications in CAP. It may also be useful to assess the disease severity, thus being complementary to the assessment of the PSI. In our patients, high CRP levels were associated with a failure to reach clinical stability.

Group IIA phospholipase A2 as a prognostic marker in prostate cancer: relevance to clinicopathological variables and disease-specific mortality

Group IIA Phospholipase A2 (PLA2‐IIA), a key enzyme in arachidonic acid and eicosanoid metabolism, participates in a variety of inflammatory processes but possibly also plays a role in tumor progression in vivo. Our aim was to determine the mRNA and protein expression of PLA2‐IIA during prostate cancer progression in localized and metastatic prostate tumors. We evaluated the prognostic significance of PLA2‐IIA expression in biochemical recurrence, clinical recurrence and disease‐specific survival after surgical treatment. The expression of PLA2‐IIA was examined by immunohistochemistry and chromogenic in situ hybridization in tissue microarrays of radical prostatectomy specimens and advanced/metastatic carcinomas. The expression data were analyzed in conjunction with clinical follow‐up information and clinicopathological variables. The mRNA and protein expression of PLA2‐IIA was significantly increased in Gleason pattern grade 2–4 carcinomas compared with benign prostate (p‐values 0.042–0.001). In metastases, the expression was significantly lower than in local cancers (p=0.001). The PLA2‐IIA expression correlated positively with Ki‐67 and α‐methylacyl CoA racemase (AMACR) expression. The prognostic evaluation revealed decreased PLA2‐IIA protein expression among patients who had died of prostate cancer. In conclusion, PLA2‐IIA expression is increased in carcinoma when compared with benign prostate. However, metastatic carcinoma showed decreased expression of PLA2‐IIA when compared with primary carcinomas. PLA2‐IIA may serve as a marker for highly proliferating, possibly poorly differentiated prostate carcinomas. The protein expression of PLA2‐IIA may be diminished in patients who consequently die of prostate cancer.

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