Juha M. Grönroos

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.

Roles of secretory phospholipases A2 in inflammatory diseases and trauma

Six distinct secretory small molecular weight phospholipases A(2) (PLA(2)) have been cloned and characterized from human tissues. Two of them, pancreatic group IB PLA(2) (PLA(2)-IB) and synovial-type group IIA PLA(2) (PLA(2)-IIA) have been studied as to their association to various inflammatory diseases. PLA(2)-IB is a digestive enzyme synthesized by pancreatic acinar cells. In acute pancreatitis, which is characterized by destruction of pancreatic tissue, PLA(2)-IB is released into the circulation, but its role in pancreatic and other tissue damage is still hypothetical. The concentration of PLA(2)-IIA increases in blood plasma in generalized inflammatory response resulting from infections, chronic inflammatory diseases, acute pancreatitis, trauma and surgical operations. PLA(2)-IIA is synthesized in a number of gland cells and is present in cellular secretions on mucosal surfaces including Paneth cells of intestinal mucosa, prostatic gland cells and seminal plasma, and lacrimal glands and tears. PLA(2)-IIA is expressed in hepatoma-derived cells in vitro and hepatocytes in vivo. PLA(2)-IIA is regarded as an acute phase protein and seems to function as an antibacterial agent especially effective against Gram-positive bacteria. Other putative functions in the inflammatory reaction include hydrolysis of cell membrane phospholipids and release of arachidonic acid for prostanoid synthesis.

Bile duct injuries during laparoscopic cholecystectomy: primary and long-term results from a single institution

BackgroundIatrogenic bile duct injury carries high morbidity. After the introduction of laparoscopic cholecystectomy the incidence of these injuries has at least doubled, and even after the learning curve, the incidence has plateaued at the level of 0.5%.MethodsA total of 32 patients sustained biliary tract injuries of the 3736 laparoscopic cholecystectomies performed in and around Turku University Central Hospital between January 1995 and April 2002. The data concerning primary treatment and long-term results were collected and analyzed retrospectively.ResultsThe overall incidence for bile duct injuries, including all the minor injuries (cystic duct leaks and bile duct strictures), was 0.86%; for major injuries alone the incidence was 0.38%. Nineteen percent of the injuries were detected intraoperatively. All the cystic duct leaks were treated endoscopically with a 90% success rate. Of the bile duct strictures 88% were treated successfully with endoscopic techniques. Ninety-three percent of the major injuries, including tangential lesions of common bile duct and total transections, were treated operatively. The operation of choice was either hepaticojejunostomy or cholangiojejunostomy in 69% of the cases; the rest were treated with simple suturing over a T-tube or an endoscopically placed stent. The long-term results, with a median follow-up period of 7.5 years, are good in 79% of the operated patients and in 84% of the whole study population. Mortality rate was 3% and acute or chronic cholangitis was seen in 13% of the patients during follow-up.ConclusionMost of the minor bile duct injuries, including cystic duct leaks and bile duct strictures, are well treatable with endoscopic techniques, whereas most of the major injuries require operative treatment, which at optimal circumstances gives good results.

Increased Concentrations of Synovial-Type Phospholipase A2 in Serum and Pulmonary and Renal Complications in Acute Pancreatitis

The most important fatal complications of acute pancreatitis are respiratory dysfunction and anuria. Phospholipase A2 has been postulated to be associated with pathologies of various diseases, such as acute pancreatitis, septic shock and multiple injuries. We have recently developed immunoassays for the measurement of pancreatic and nonpancreatic synovial-type phospholipase A2. The present prospective study on 35 consecutive patients with acute pancreatitis indicated that the concentration of synovial-type phospholipase A2, the catalytic activity of phospholipase A2 and the concentration of C-reactive protein in serum were significantly higher in those patients suffering from acute pancreatitis who needed respirator treatment than in those who managed with spontaneous breathing, while there was no difference between these groups in the concentration of pancreatic phospholipase A2. The only significant difference between patients whose highest creatinine concentration rose up to 140 mumol/l and those whose highest creatinine concentration remained below this cutoff value was in their synovial-type phospholipase A2 values. The increased concentration of nonpancreatic synovial-type phospholipase A2 in serum was associated with pulmonary and renal complications. These results emphasize the role of synovial-type phospholipase A2 in the pathophysiology of acute pancreatitis.

The influence of anaesthetic technique upon the immune response to hysterectomy. A comparison of propofol infusion and isoflurane.

Earlier studies on propofol have shown increased percentages of T helper cells after minor surgery. In this study, the effects of propofol infusion anaesthesia on the immune response were compared with those of combined isoflurane anaesthesia in 30patients (median age 47 years, ASA 1–2) undergoing major surgery. The total dose of propofol in the propofol infusion group of 15 women was 860 mg (range 540–1520 mg) and the median end‐expiratory isoflurane concentration in the combined isoflurane group of 15 women was 0.6% (range 0.5–0.8). The following were measured; leucocyte and differential counts; percentages of lymphocyte subpopulations (CDS, CD4, CD8, CD 19, CD 16 and HLA‐DR + CD3); phytohaemagglutinin‐, concanavalin A‐, and pokeweed mitogen‐induced and unstimulated lymphocyte proliferation; plasma interleukin‐6; serum group II phospholipase A2, C‐reactive protein and cortisol concentrations. Measurements were made pre‐operatively, at the end of the operation and on the first and fifth postoperative days. No statistically significant overall differences were observed in the immune response between the groups. The serum cortisol response was weaker in the propofol group than in the isoflurane group (p < 0.05). Time‐related changes were seen within the groups.

Risk of serious upper gastrointestinal events with concurrent use of NSAIDs and SSRIs: a case-control study in the general population

ObjectivesTo study the risk of serious upper gastrointestinal (GI) events associated with the concurrent use of selective serotonin re-uptake inhibitors (SSRIs) and different types of non-steroidal anti-inflammatory drugs (NSAIDs).MethodsThis was a nationwide, register-based matched case-control study on non-institutionalized residents of Finland during the period 2000–2004. Patient-cases with serious upper GI events (n = 9191) were drawn from the Hospital Discharge Register, and individually matched controls (n = 41,780) were drawn from the Population Register. Logistic regression was applied in the data analysis, and adjustments were made for various co-morbidities and the use of other drugs associated with the risk of serious upper GI event.ResultsThe adjusted odds ratio (AOR) of serious upper GI events for SSRI use compared to non-use of SSRIs or NSAIDs was 1.30 [95% confidence interval (95%CI: 1.13–1.50)], and the AOR for concurrent SSRI and NSAID use compared to the non-use of either drug was 4.19 (95%CI: 3.30–5.31). The AOR of upper GI events for the concurrent use of SSRIs with NSAIDs compared to patients using NSAIDs only was 1.57 (95%CI: 1.24–1.99). The respective AOR for traditional, non-selective NSAIDs was 1.77 (95%CI: 1.31–2.38), for semi-selective NSAIDs (nimesulide, nabumetone, meloxicam, and etodolac) 1.30 (95%CI: 0.76–2.24) and for COX-2 selective NSAIDs 1.33 (95%CI: 0.70–2.50).ConclusionsThe concurrent use of SSRIs and NSAIDs is associated with a moderate excess relative risk of a serious upper GI event when compared with NSAID use alone.

Gene expression of group II phospholipase A2 in intestine in Crohn's disease.

OBJECTIVE:Phospholipase A2 (PLA2) has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases. Our aim was to identify cells that express group II phospholipase A2 (PLA2-II) at the mRNA and enzyme protein levels in the intestine in Crohns disease.METHODS:Tissue samples were obtained from the intestine of 20 patients with Crohns disease (seven operated and 13 colonoscopied) and from eight control patients without inflammatory diseases. The samples were studied by immunohistochemistry for PLA2-II enzyme protein and in situ hybridization for PLA2-II mRNA.RESULTS:PLA2-II protein and mRNA were detected in the Paneth cells of the small intestinal mucosa in all patients and controls. PLA2-II protein and mRNA were found in the columnar epithelial cells of the small intestinal mucosa in six of eight and eight of eight patients with Crohns ileitis, respectively. In the eight control patients PLA2-II protein and mRNA were not found in these cells (p= 0.007 and p < 0.001, respectively). Metaplastic Paneth cells, which consistently contained PLA2-II mRNA, were found in the colonic mucosa in five of six patients with Crohns colitis and of one of eight control patients (p= 0.026). The columnar epithelial cells of the colonic mucosa contained PLA2-II protein in three of six and PLA2-II mRNA in six of six patients with Crohns colitis, whereas the protein was found in these cells in none of eight of the controls (p= 0.055) and the mRNA in only one of eight (p= 0.005) controls.CONCLUSIONS:In Crohns disease, Paneth cells and columnar epithelial cells of the small and large intestinal mucosa synthesize PLA2-II at the site of active inflammation.

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.

Randomized multicenter study of multiple plastic stents vs. covered self-expandable metallic stent in the treatment of biliary stricture in chronic pancreatitis

BACKGROUND AND STUDY AIMS The use of covered self-expandable metallic stents (cSEMS) in benign biliary indications is evolving. The aim of the study was to assess the safety and feasibility of cSEMS compared with multiple plastic stents in the treatment of benign biliary stricture (BBS) caused by chronic pancreatitis. PATIENTS AND METHODS This was a prospective, multicenter, randomized study of 60 patients with BBS caused by chronic pancreatitis. All patients received an initial plastic stent before randomization. At randomization, the stent was replaced either with a single cSEMS or three plastic stents. After 3 months, the position of the cSEMS was checked or another three plastic stents were added. At 6 months after randomization, all stents were removed. Clinical follow-up including abdominal ultrasound and laboratory tests were performed at 6 months and 2 years after stent removal. RESULTS Two patients dropped out of the cSEMS group before stent removal. In April 2014, the median follow-up was 40 months (range 1 - 66 months). The 2-year, stricture-free success rate was 90 % (95 % confidence interval [CI] 72 % - 97 %) in the plastic stent group and 92 % (95 %CI 70 % - 98 %) in the cSEMS group (P = 0.405). There was one late recurrence in the plastic stent group 50 months after stent removal. Stent migration occurred three times (10 %) in the plastic stent group and twice in the cSEMS group (7 %; P = 1.000). CONCLUSION A 6-month treatment with either six 10-Fr plastic stents or with one 10-mm cSEMS produced good long-term relief of biliary stricture caused by chronic pancreatitis.Study registered at ClinicalTrials.gov (NCT01085747).

Phospholipase A2 in serum and colonic mucosa in ulcerative colitis

Group II phospholipase A2 is involved in the pathogenesis of various inflammatory diseases and in the host defence against bacteria. The enzyme is expressed in the epithelial cells of colonic mucosa in ulcerative colitis. In this study, we measured the concentration of group II phospholipase A2 in serum and colonic mucosa of patients with ulcerative colitis of different severity and of control patients without any inflammatory disease. The activity of ulcerative colitis was assessed by endoscopy. The concentration of group II phospholipase A2 was measured with an immunoassay. The concentrations of group II phospholipase A2 in serum and colonic mucosa were significantly higher in patients with active and inactive ulcerative colitis than in controls. However, the group II phospholipase A2 levels did not separate patients with different disease activity. The concentration of group II phospholipase A2 in colonic mucosa corresponded with the mucosal inflammatory activity (higher in active colonic areas) intra-individually, but not between different patients with ulcerative colitis. Serum group II phospholipase A2 values were above the normal reference range more often than the values of 11 standard laboratory blood tests widely used for the follow-up of inflammatory activity in ulcerative colitis. These results indicate that the concentration of group II phospholipase A2 is increased in serum and colonic mucosa of patients with ulcerative colitis. The clinical value of the measurement of group II phospholipase A2 in the follow-up of ulcerative colitis remains to be clarified.