B. Dousset

Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial

BACKGROUND Researchers have suggested that antibiotics could cure acute appendicitis. We assessed the efficacy of amoxicillin plus clavulanic acid by comparison with emergency appendicectomy for treatment of patients with uncomplicated acute appendicitis. METHODS In this open-label, non-inferiority, randomised trial, adult patients (aged 18-68 years) with uncomplicated acute appendicitis, as assessed by CT scan, were enrolled at six university hospitals in France. A computer-generated randomisation sequence was used to allocate patients randomly in a 1:1 ratio to receive amoxicillin plus clavulanic acid (3 g per day) for 8-15 days or emergency appendicectomy. The primary endpoint was occurrence of postintervention peritonitis within 30 days of treatment initiation. Non-inferiority was shown if the upper limit of the two-sided 95% CI for the difference in rates was lower than 10 percentage points. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT00135603. FINDINGS Of 243 patients randomised, 123 were allocated to the antibiotic group and 120 to the appendicectomy group. Four were excluded from analysis because of early dropout before receiving the intervention, leaving 239 (antibiotic group, 120; appendicectomy group, 119) patients for intention-to-treat analysis. 30-day postintervention peritonitis was significantly more frequent in the antibiotic group (8%, n=9) than in the appendicectomy group (2%, n=2; treatment difference 5·8; 95% CI 0·3-12·1). In the appendicectomy group, despite CT-scan assessment, 21 (18%) of 119 patients were unexpectedly identified at surgery to have complicated appendicitis with peritonitis. In the antibiotic group, 14 (12% [7·1-18·6]) of 120 underwent an appendicectomy during the first 30 days and 30 (29% [21·4-38·9]) of 102 underwent appendicectomy between 1 month and 1 year, 26 of whom had acute appendicitis (recurrence rate 26%; 18·0-34·7). INTERPRETATION Amoxicillin plus clavulanic acid was not non-inferior to emergency appendicectomy for treatment of acute appendicitis. Identification of predictive markers on CT scans might enable improved targeting of antibiotic treatment. FUNDING French Ministry of Health, Programme Hospitalier de Recherche Clinique 2002.

Treatment of Stage IVA Hepatocellular Carcinoma: Should We Reappraise the Role of Surgery?

HYPOTHESIS A subset of patients with stage IVA hepatocellular carcinoma (HCC) and preserved liver function may benefit from hepatic resection. DESIGN Retrospective review of a prospectively collected database. SETTING An academic tertiary care hepatobiliary unit. PATIENTS Twenty patients who underwent surgical treatment for stage IVA HCC between July 1998 and October 2004 were identified from the database. INTERVENTION Intraoperative ablation of HCC nodules was combined with resection in 6 patients (30%) to increase resectability. Three patients also underwent resection of extrahepatic tumors. Five patients (25%) had macroscopic invasion of the portal vein and 2 patients (10%) underwent thrombectomy of the vena cava. MAIN OUTCOME MEASURES Intraoperative data, recurrence, and long-term survival rates were analyzed. RESULTS Postoperative mortality and morbidity were 5% and 30%, respectively. The median number of resected tumors per patient was 3, and the median diameter of the largest tumor was 60 mm. With a median follow-up of 23 months, 14 patients (70%) developed recurrence. Treatment of recurrence was possible in 10 patients and included transarterial chemoembolization in 7 patients (35%), of whom 2 (10%) had radiofrequency ablation first, and systemic chemotherapy in 3 patients (15%). Median survival time was 32 months, and the actuarial 1-, 3-, and 5-year survival rates were 73%, 56%, and 45%, respectively. CONCLUSIONS Long-term survival can be achieved using an aggressive surgical approach in select patients with advanced HCC. Patients with stage IVA HCC should be followed up by a multidisciplinary team because recurrence is common and sequential treatments may prolong survival.

Unusual case of digestive bleeding nine months after a cephalic pancreaticoduodenectomy (CPD)

Graphical abstract

Correlation between daily cyclosporine dose and allograft injury in liver recipients with and without recurrent hepatitis C.

BACKGROUND: After liver transplantation, the daily cyclosporine dose is adjusted to maintain the blood level in a chosen range. The aim of this study was to assess the influence of liver graft injury on cyclosporine dose. METHODS: The parameters of liver function were investigated in 145 patients. Ninety-two patients took part in a longitudinal study. RESULTS: The cyclosporine dose correlated with the MEGX test (r=0.38, P=0.01) and with the ICG (r=0.38, P=0.0001) and BSP (r=0.37, P=0.0002) clearances; it had an inverse correlation with transaminases (AST: r=0.38, P=0.0001) and histological lesions (r=-0.29, P=0.005). The cyclosporine dose was lower in patients with recurrent hepatitis C (179+/-9 mg/day) than in those without (241+/-10 mg/day), and was lower in patients with chronic hepatitis (154+/-9 mg/day) than in those without (207+/-16 mg/day). In the longitudinal study, the percent variation of AST correlated inversely with that of cyclosporine dose (r=-0.62, P=0.0002). CONCLUSION: Progressive graft injury leads to a reduction in the cyclosporine dose, particularly in patients with recurrent hepatitis C.