Global Distribution and Outcomes for<Emphasis Type="Italic"> Candida</Emphasis> Species Causing Invasive Candidiasis: Results from an International Randomized Double-Blind Study of Caspofungin Versus Amphotericin B for the Treatment of Invasive Candidiasis

In a randomized study, caspofungin was compared with amphotericin B for the treatment of invasive candidiasis in a total of 239 adults from 56 sites in 20 countries. This study provided a unique opportunity to assess the frequency and outcome of invasive candidiasis caused by different Candida species worldwide, and the results are presented here. Efficacy was primarily assessed at the end of intravenous therapy using a modified intent-to-treat (MITT) analysis. This analysis was performed on 224 of the 239 patients enrolled in the study. Attempts were made to collect baseline Candida isolates from all patients for species identification at a central laboratory. Yeasts were identified to the species level using two commercial systems and microscopic examination. Viable baseline isolates were recovered from 210 of the 224 (94%) patients included in the MITT analysis. Candida albicans was the most frequently isolated species in all regions and was responsible for 45% of cases overall. Nevertheless, the majority of cases of infection were caused by non-albicans Candida species. In the USA and Canada, Candida glabrata was the second most commonly isolated pathogen (18%). In contrast, Candida parapsilosis and Candida tropicalis accounted for 55% of cases in Latin America. Outcomes were comparable for patients treated with caspofungin (74% overall; 64% and 80% for infections due to Candida albicans and non-albicans species) and amphotericin B (62% overall; 58% and 68% for infections due to Candida albicans and non-albicans species), and were generally similar across continents. The distribution of Candida species isolated from patients enrolled in a clinical trial may not be representative of pathogens causing invasive candidiasis in the general population. Nevertheless, our findings may affect the regional choice of empirical antifungal therapy for seriously ill patients with suspected or documented invasive candidiasis since different Candida species have varying susceptibility to conventional antifungal drugs.     

Restoration of intestinal continuity after colectomy for non-occlusive ischemic colitis

Background

Non-occlusive ischemic colitis (IC) is a rare and life-threatening abdominal disease associated with high rates of postoperative mortality. When surgery is performed, in patients with IC, either a Hartmann’s procedure (HP) or a total colectomy and ileostomy is required. The possibility of restoration of intestinal continuity in surviving patients is an important issue. The aim of the present study was to report the outcome of surgically managed IC patients and to identify predictive factors for restoration of intestinal continuity and to assess the results of this procedure.

Methods

Between January 1997 and May 2011, 96 IC patients underwent total colectomy and 68 underwent left colectomy. IC was spontaneous in 62 patients and occurred after prior surgery in 102. Eighty patients died during the postoperative period and nine died during the follow-up from an unrelated disease. Fifteen patients were lost to follow-up. The remaining 60 surviving patients were our study population.

Results

There were 44 men and 16 women with a mean age of 67 years ± 12 SD. Restoration of bowel continuity was performed in 24 patients (40 %). There were no predictive factors for restoration of intestinal continuity in terms of sex, age, IC etiology, and the extent of colon resection at primary surgery. The median interval between first surgery and restoration of bowel continuity was 7.9 months (range 0.2–35 months). There were no postoperative deaths and the overall morbidity rate was 45 % (11/24). No patients developed anastomotic leak or underwent unplanned reoperation.

Conclusions

Reversal of HP after IC is feasible in 40 % of surviving patients with acceptable mortality and morbidity rates. This restoration of intestinal continuity should therefore be discussed for every surviving IC patient.     

Tumor growth pattern as predictor of colorectal liver metastasis recurrence

Background

Surgical resection is the gold standard therapy for the treatment of colorectal liver metastases (CRM). The aim of this study was to investigate the impact of tumor growth patterns on disease recurrence.

Methods

We enrolled 91 patients who underwent CRM resection. Pathological specimens were prospectively evaluated, with particular attention given to tumor growth patterns (infiltrative vs pushing).

Results

Tumor recurrence was observed in 65 patients (71.4%). According to multivariate analysis, 3 or more lesions (P = .05) and the infiltrative tumor margin type (P = .05) were unique independent risk factors for recurrence. Patients with infiltrative margins had a 5-year disease-free survival rate significantly inferior to patients with pushing margins (20.2% vs 40.5%, P = .05).

Conclusions

CRM patients with pushing margins presented superior disease-free survival rates compared with patients with infiltrative margins. Thus, the adoption of the margin pattern can represent a tool for improved selection of patients for adjuvant treatment.     

Multicentre retrospective study on endoscopic ultrasound complications

BACKGROUND: Endoscopic ultrasonography, both conventional and interventional, has been used increasingly during the past 20 years and is deemed a safe technique. Its complication rate, however, has been studied to only a limited extent. This multicentre investigation sought to establish the complication rate for a large number of endoscopic ultrasonography procedures. METHODS: By means of a questionnaire, we collected data from six centres on the number of endoscopic ultrasonography examinations performed and divided them into conventional and interventional examinations of the upper and lower gastrointestinal tract. Information was obtained on technical modalities such as instruments and sedation and, for interventional endoscopic ultrasonography, indications, pre-procedural exams and technical details (needle calibre, number of passes) had to be specified. Complications were classified as mild, moderate, severe or fatal and their onset as immediate, early or late. Variables that entered into the analysis of complication rate included type of endoscopic ultrasonography instrument used, type and site of lesion biopsied, number of needle passes and operator experience. RESULTS: Eleven thousand five hundred thirty nine endoscopic ultrasonographic procedures were reported, of which 10,731 were conventional and 808 interventional. No deaths occurred; there were 14 (0.12%) complications, 5 (0.046%) of them following conventional endoscopic ultrasonography and 9 (1.11%) after interventional endoscopic ultrasonography. Seven complications were mild, four moderate and three severe. CONCLUSIONS: Both conventional and interventional endoscopic ultrasonography were confirmed to be acceptably safe techniques.     

A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis

BACKGROUND: Candida esophagitis remains an important cause of morbidity in patients with advanced human immunodeficiency virus (HIV) infection. Fluconazole is widely regarded as the treatment of choice for this condition. METHODS: The efficacy and safety of caspofungin were compared with fluconazole in adult patients with Candida esophagitis in a double-blind randomized trial. Eligible patients had symptoms compatible with esophagitis, endoscopic demonstration of mucosal plaques, and microscopic demonstration of Candida from the esophageal lesions. Patients were randomly assigned to receive caspofungin (50 mg) or fluconazole (200 mg) intravenously once daily for 7 to 21 days. The primary endpoint was the combined response of symptom resolution and significant endoscopic improvement 5 to 7 days after discontinuation of treatment. Data were analyzed with a modified intention-to-treat analysis, which excluded 2 ineligible patients. RESULTS: Most patients (154/177; 87%) had HIV infection, with a median CD4 count of 30 cells/mm(3). Candida albicans was the predominant isolate. Favorable response rates were achieved in 66 (81%) of the 81 patients in the caspofungin arm and in 80 (85%) of the 94 patients in the fluconazole arm (difference = -4%; 95% confidence interval: -15% to +8%). Symptoms had resolved in >50% of patients in both groups by the fifth day of treatment. No patient in the caspofungin group developed a serious drug-related adverse event; therapy was only discontinued in 1 patient (receiving fluconazole) due to a drug-related adverse experience. Four weeks after stopping study drug, symptoms had recurred in 18 (28%) of 64 patients given caspofungin and in 12 (17%) of 72 patients given fluconazole (P = 0.19). CONCLUSIONS: In this study, caspofungin appeared to be as efficacious and generally as well tolerated as fluconazole in patients with advanced HIV infection and documented Candida esophagitis.     

Benign obstruction of the common hepatic duct (Mirizzi syndrome): diagnosis and operative management

BACKGROUND: Mirizzi syndrome is a rare complication of prolonged cholelithiasis, characterized by narrowing of the common hepatic duct due to mechanical compression and/or inflammation due to biliary calculus impacted in the infundibula of the gallbladder or in the cystic duct. OBJECTIVES: To describe a series of eight consecutive patients with Mirizzi syndrome, at a single institution, submitted to surgical treatment and to comment on their aspects with emphasis on the diagnosis and treatment. METHODS: Four women and four men, with a mean age of 61.6 years (42 to 82 years), presenting Mirizzi syndrome were operated between 1997 and 2003. The following items were evaluated: clinical presentation, laboratory results, preoperative evaluation, operative findings, presence of choledocholithiasis, type of Mirizzi syndrome according to the classification by Csendes, choice of operative procedures, and complications. RESULTS: The most frequent symptoms were abdominal pain (87.5%) and jaundice (87.5%). All the patients presented altered hepatic function tests. The diagnosis of Mirizzi syndrome was intra-operative in seven (87.5%) patients, and preoperative in one (12.5%). Cholecystocholedochal fistula associated with choledocholithiasis was observed in three (37.5%) cases. Mirizzi syndrome was classified as Csendes type I in five (62.5%) patients, type II in one (12.5%), type III in one (12,5%) and type IV in another (12.5%). Cholecystectomy, as an isolated surgical procedure, was performed in four (50.0%) patients. One (12.5%) patient was submitted to partial cholecystectomy and closure of the fistulous orifice with the central part of the infundibula. Two (25.0%) patients were submitted to cholecystectomy and side-to-side choledochoduodenostomy and another (12.5%) to side-to-side choledochoduodenostomy remaining the gallbladder in situ. Seven (87.5%) patients had an uneventful recovery and were discharged in good conditions. One (12.5%) patient presented a postoperative sepsis due to a sub-hepatic abscess, and was reoperated. There was no operative mortality. CONCLUSION: The preoperative diagnosis of Mirizzi syndrome is difficult and an awarded suspicion is necessary to avoid lesions of the biliary tree. The problem may only become evident during the operation due to firm adherences around Calot's triangle. The success of the treatment is related to a precocious recognition of the condition, even at the time of surgery, and adapting the management considering to the individual characteristics of each case.     

Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine

BACKGROUND: The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory. METHODS: A total of 552, 16-23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years' follow-up. A subset of 241 subjects (n=114 in the quadrivalent HPV vaccine group and n=127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series. RESULTS: Serum anti-HPV levels declined post-vaccination, but reached a plateau at month 24 that remained stable through month 60. Administration of a challenge dose of vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post-challenge reaching levels observed 1 month following the completion of the three-dose primary series. At 1 month post-challenge, anti-HPV responses were higher than those observed 1-month post-dose 3. DISCUSSION: A three-dose regimen of quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at least 5 years. Vaccination also induces robust immune memory. These findings suggest that the efficacy of this vaccine will be long lasting.     

HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine

The efficacy of the quadrivalent Human Papillomavirus (HPV) vaccine is thought to be mediated by humoral immunity. We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy. 17,622 women were vaccinated at day 1, and months 2 and 6. At day 1 and at 6-12 months intervals for up to 48 months, subjects underwent Papanicolaou and genital HPV testing. No immune correlate of protection could be found due to low number of cases. Although 40% of vaccine subjects were anti-HPV 18 seronegative at end-of-study, efficacy against HPV 18-related disease remained high (98.4%; 95% CI: 90.5-100.0) despite high attack rates in the placebo group. These results suggest vaccine-induced protection via immune memory, or lower than detectable HPV 18 antibody titers.