Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles.

Risk factors for invasive mold diseases in allogeneic hematopoietic cell transplant recipients.

BACKGROUND: The epidemiology of and risk factors for invasive mold disease (IMD) among allogeneic hematopoietic cell transplant (HCT) recipients may vary according to the region. In this study, we sought to evaluate risk factors for IMD in our patient population. METHODS: Between May 2007 and July 2009, all HCT recipients from 8 Brazilian centers were followed prospectively until 1 year post transplant. Cases of IMD were classified as early (before day +40) or late (after day +40). Patients with IMD (cases) were compared with controls (patients without IMD) using univariate and multivariate Cox regression analysis. RESULTS: Among 345 HCT recipients, 28 IMDs were diagnosed. Risk factors for early IMD were acute myeloid leukemia (hazard ratio [HR] 2.95, 95% confidence interval [95% CI] 1.13-7.68, P = 0.03) and transplant with a human leukocyte antigen-mismatched donor (HR 3.38, 95% CI 1.18-9.68, P = 0.02), and for late IMD risk factors were lymphoma (HR 8.49, 95% CI 2.35-30.68, P = 0.001), cytomegalovirus reactivation (HR 5.51, 95% CI 1.15-26.47, P = 0.03), and neutropenia (HR 3.49, 95% CI 1.01-12.13, P = 0.049). CONCLUSION: The variables identified in this study may help to define risk groups, and to tailor special preventive measures to patients at higher risk to develop IMD.

Correlation of tumor size with other prognostic factors in uterine serous carcinoma: a large multi-institutional study.

OBJECTIVE: Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but ~40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor. METHODS: Clinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan-Meier method; multivariate analysis was performed via cox-regression. RESULTS: The patients' mean age was 67.2 years (range 40-91). Survival ranged from 0 to 184 months (mean 42.8). We used a tumor size cut-off of 1cm and noted significant associations with myometrial invasion (p<0.0001), angiolymphatic invasion (p<0.0001), peritoneal washings (p=0.03), stage (p=0.015) and positive lymph nodes (p=0.05). Furthermore, recurrence was associated with larger tumors (p=0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors <1cm in both univariate and multivariate analysis. CONCLUSIONS: Treatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The 1cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging.

Epidemiology of candidemia in patients with hematologic malignancies and solid tumours in Brazil.

Candidemia in cancer patients may differ according to the type of cancer. To characterise the epidemiology and outcome of candidemia in cancer patients from Brazilian hospitals, we compared the characteristics of patients with hematologic malignancies (HM) and solid tumours (ST). A retrospective study was performed, based on data collected from laboratory-based surveillance studies in 18 tertiary care hospitals between March/2003 and December/2007. The characteristics of patients with HM (n = 117) were compared with patients with ST (n = 248). Predictors of 30-day mortality were identified by uni- and multivariate analyses. Candidemia in HM was more likely to occur in the setting of chemotherapy, corticosteroids, neutropenia, mucositis and tunnelled central venous catheter (CVC), whereas surgery, intensive care unit admission and invasive procedures (mechanical ventilation, parenteral nutrition and CVC) were more frequent in ST. The 30-day mortality rate was higher in the ST group (65% vs. 46%, P = 0.001). Factors significantly associated with 30-day mortality were older age and intensive care unit admission. Important differences in the epidemiology and outcome of candidemia in HM and ST were observed. The characterisation of the epidemiology is important to drive preventive measures and to select appropriate therapies.

[Role of vaginal infection in fetal and neonatal mortality]. / Ruolo delle infezioni vaginali nella mortalità fetale e neonetale.

Preterm delivery is the chief problem in obstetrics today and the main determinant of infant mortality and morbidity. Despite the dramatic decrease in infant mortality rate during the past several years, the percentage of preterm (<37 weeks gestation) and low birth weight (LBW) (<2500) rates remain elevated. Approximately 10% of all births are preterm, with a rate of 1-2% of infant born before the end of the 32 weeks of gestation and with a weight <1500 g. Despite the importance of the problem, the majority of preterm live births remain unexplained, and programmatic attempts at reversing the high level of preterm births have not been successful. Numerous studies have linked bacterial vaginosis, chorioamniotitis and endometritis with preterm birth and LBW, especially among African women. The number of preterm live births among African women is twice the one among Caucasians. Bacterial vaginosis is an independent risk factor for preterm and LBW births and the mechanism by which bacterial vaginosis causes the preterm birth of an infant with LBW is unknown. The aim of this article was to underline the importance of the treatment and early identification of vaginal infection, in particular if due to bacterial vaginosis, as it can have a substantial affect on the incidence of preterm delivery with LBW.

Respiratory specimens and the diagnostic accuracy of Aspergillus lateral flow assays (LFA-IMMY™): real-life data from a multicentre study.

OBJECTIVES: Proper diagnosis of invasive aspergillosis is challenging because conventional methods lack sensitivity and are complicated by time-consuming incubation processes. To meet the requirement for early diagnosis the new Aspergillus-specific point-of-care test LFA-IMMY™ was evaluated with respect to the ability to accurately detect Aspergillus in bronchoalveolar fluids and sputa, and to clarify the potential of cross-reactivity with other fungal pathogens. METHODS: Respiratory specimens (n = 398) from non-selected patients (n = 390) underwent either fungal microscopy, culture or both before Aspergillus lateral flow assay (LFA-IMMY) testing. RESULTS: For Aspergillus culture- and microscopy-positive samples, sensitivity (48/52) and specificity (44/48) were 92% (95% CI 8.0%-9.7%) and 91% (95% CI 7.9%-9.7%), respectively; cross-reactivity was documented with non-Aspergillus pathogens. CONCLUSION: LFA-IMMY is a reliable diagnostic tool for the detection of Aspergillus in respiratory samples.

Evaluation of a Bead-Based Salmonella Molecular Serotyping Method for Salmonella Isolated from Food and Environmental Samples.

Salmonella is a leading cause of foodborne illness worldwide, and foods containing Salmonella (except raw meat and poultry products) are considered adulterated. Serotyping of Salmonella is an essential part of surveillance and investigation of outbreaks. This study evaluated a bead-based Salmonella molecular serotyping (SMS) method, which included the O-group 1, H-antigen, alternate target, and O-group 2 assays, compared with traditional serotyping. Salmonella was isolated from food, pet food, and environmental samples or were reference strains. A total of 572 isolates were analyzed by using two formats of the SMS method in comparison with traditional methods: 485 were analyzed by using Radix SMS (a custom user-mixed format), 218 were analyzed by using Luminex SMS (a commercial kit format), and 131 of the total isolates were analyzed by both formats for comparison. The SMS method was evaluated on the basis of the successful identification of antigens by the probes included in the method. The method identified 550 (96.2%) isolates as expected, 6 (1.0%) isolates were not identified as initially expected but were shown to be correctly identified by SMS after reanalysis by traditional serotyping, and 16 (2.8%) isolates not identified as expected possessed an antigen that should have been detected by the method but was not. Among the isolates considered correctly identified, 255 (44.6%) were identified to a single serovar, 44 (7.7%) required additional biochemical testing to differentiate variants or subspecies, and 251 (43.9%) were partially serotyped because probes for some antigens were not in the assay or had allelic variation for known serovars. Whole genome sequencing, SeqSero, and the Salmonella In Silico Typing Resource gave added confirmation for three isolates. Addition of the O-group 2 assay enabled the identification of 55 (9.6%) of 572 isolates. The SMS method could fully or partially serotype most isolates within a day. The SMS method should be a valuable tool when faster screening methods are needed, such as outbreaks and screening large numbers of environmental isolates.

Acute disseminated candidiasis with skin lesions: a systematic review.

BACKGROUND: Neutropenic patients developing acute disseminated candidiasis may present with skin lesions. AIMS: To evaluate the epidemiology of acute disseminated candidiasis with skin lesions in neutropenic patients, taking into consideration changes caused by different prophylactic strategies. SOURCES: A systematic review of English-language articles found via PubMed (1963-2016) was performed. We asked the following questions: (a) What Candida species are more frequently involved in this syndrome? (b) Has antifungal prophylaxis changed the species causing skin lesions? (c) What are the typical patterns of skin lesions? (d) What is the frequency of skin lesions in neutropenic patients with candidaemia or acute disseminated candidiasis? (e) Has antifungal prophylaxis decreased the incidence of acute disseminated candidiasis with skin lesions? CONTENT: Among 183 studies, 33 were selected, reporting 100 cases of acute disseminated candidiasis with skin lesions in neutropenic patients. It occurred more frequently in the setting of induction therapy for de novo or relapsed acute leukaemia, and the most frequent Candida species were C. tropicalis (68%) and C. krusei (15%). Diffuse maculopapular lesions predominated in cases caused by C. tropicalis and nodular and papular lesions in cases caused by C. krusei. Prophylaxis with fluconazole was reported in six cases, C. krusei in five and C. ciferrii in one. The death rate was 45.4%. IMPLICATIONS: Two patterns were recognized: disseminated maculopapular lesions caused by C. tropicalis in patients not receiving fluconazole prophylaxis, occurring in 39% to 44% of neutropenic patients with acute disseminated candidiasis, and nodular lesions caused by C. krusei in patients receiving fluconazole prophylaxis, occurring less frequently.

Invasive mould disease in haematologic patients: comparison between fusariosis and aspergillosis.

OBJECTIVES: To compare the epidemiology, clinical presentation, diagnosis, treatment, and outcome of haematologic patients with invasive aspergillosis (IA) or invasive fusariosis (IF). METHODS: We retrospectively reviewed the charts of 36 patients with IA and 26 with IF diagnosed between 2006 and 2017 in haematologic patients, and compared baseline characteristics, coexisting exposures, clinical manifestations, treatment, and the outcome. RESULTS: Fever was more frequent in IF (96.2% vs. 63.9%, p 0.003), whereas pneumonia (88.9% vs. 50.0%, p 0.001) and sinusitis (63.9% vs. 38.5%, p 0.048) were more frequent in IA. Skin lesions and positive blood cultures occurred exclusively in patients with IF. Among patients with pneumonia, the halo sign was more frequent in IA (62.5% vs. 23.1%, p 0.02). Serum galactomannan was positive in 88.6% of patients with IA and in 73.3% with IF (p 0.18), with no differences in the median number of positive tests and galactomannan values. Positive serum galactomannan plus lung infiltrates was the predominant clinical presentation in IA and occurred in four of 13 patients with IF and lung involvement. The 30-day survival was 77.7% in IA and 46.1% in IF (p 0.01). CONCLUSIONS: IA and IF share the same epidemiologic scenario but different clinical presentations in the majority of cases, with disease in the airways in IA, and fever, metastatic skin lesions, and positive blood cultures in IF. However, a substantial proportion of patients with IF present with a clinical picture similar to IA, with fever, lung infiltrates, and positive serum galactomannan.

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Epidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients.

The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.

Breakthrough candidaemia in the era of broad-spectrum antifungal therapies.

We aimed to assess the characteristics, treatment, risk factors and outcome of patients with breakthrough candidaemia (BrC) in the era of broad-spectrum antifungal therapies. We carried out a multicentre study of hospitalized adults with candidaemia at six hospitals in three countries. BrC episodes were compared with the remaining episodes (non-BrC). Of 409 episodes of candidaemia, 37 (9%) were BrC. Among them, antifungal treatment was administered as prophylaxis in 26 severely immunosuppressed patients (70%) and as a fever-driven approach in 11 (30%). Candida albicans was significantly less common in patients with BrC (24% versus 46%, p 0.010) whereas Candida krusei was more frequent (16% versus 2.4%, p < 0.001). BrC was associated with infections caused by fluconazole non-susceptible isolates (50% versus 18%, p < 0.001). Candida albicans BrC was associated with previous fluconazole treatment whereas Candida parapsilosis candidaemia was mostly catheter-related and/or associated with previous echinocandin therapy. The empirical antifungal therapy was more often appropriate in the non-BrC group (57% versus 74%, p 0.055). No significant differences were found in outcomes (early and overall mortality: 11% versus 13% p 0.802 and 40% versus 40% p 0.954, respectively). Fluconazole non-susceptibility was independently associated with the risk of BrC (adjusted OR 5.57; 95% CI 1.45-21.37). In conclusion, BrC accounted for 9% of the episodes in our multicentre cohort. The Candida spp. isolated were different depending on the previous antifungal therapy: previous azole treatment was associated with fluconazole non-susceptible strains and previous echinocandin treatment was associated with BrC caused by C. parapsilosis. These results should be taken into account to improve the empirical treatment of BrC.

Invasive Fungal Disease in Renal Transplant Recipients at a Brazilian Center: Local Epidemiology Matters.

INTRODUCTION: Invasive fungal disease (IFD) is an important complication after solid organ transplantation (SOT). A marked geographic variation in the epidemiology of IFD after kidney transplantation (KT) has been suggested by the results of previous studies. Nevertheless, data from Latin American centers are scarce. OBJECTIVE: This study sought to describe the epidemiology of IFD at a Brazilian KT center. METHODS: This study was a retrospective single-center cohort study that included patients who underwent KT between 1998 and 2009 and were followed up until July 2015. Cases of simultaneous kidney-pancreas transplantation were excluded. The primary study outcome was the occurrence of proven or probable IFD. RESULTS: Among 908 KT recipients, 44 cases of IFD occurred in 42 patients (4.6%). Cryptococcus spp. infection, diagnosed in 16 cases (36.3%), was the leading cause of IFD, followed by histoplasmosis in 10 cases (22.7%) and invasive candidiasis in 10 (22.7%). Sporotrichosis, mucormycosis, invasive aspergillosis, pulmonary Cladophialophora sp. infection, trichosporonosis and Saccharomyces cerevisiae fungemia occurred in 1 recipient each (2.3%). Two additional (4.5%) cases of unspecified mold infections were identified by histopathological analysis. Most cases of IFD (67%) occurred later than 6 months after transplantation. Previous use of antilymphocyte antibodies (P = .008) and corticosteroid pulse therapy (P < .001) were more frequent among cases of IFD occurring within the first 6 months after transplantation. CONCLUSIONS: The epidemiology of IFD in this Brazilian cohort was characterized by a large predominance of late infections and a high proportion of cases of cryptococcosis and histoplasmosis. These results highlight the considerable geographic variability of IFD epidemiology after KT.

Predictors of choice of initial antifungal treatment in intraabdominal candidiasis.

Intraabdominal candidiasis (IAC) is the second most frequent form of invasive candidiasis, and is associated with high mortality rates. This study aims to identify current practices in initial antifungal treatment (IAT) in a real-world scenario and to define the predictors of the choice of echinocandins or azoles in IAC episodes. Secondary analysis was performed of a multinational retrospective cohort at 13 teaching hospitals in four countries (Italy, Greece, Spain and Brazil), over a 3-year period (2011-2013). IAC was identified in 481 patients, 323 of whom received antifungal therapy (classified as the treatment group). After excluding 13 patients given amphotericin B, the treatment group was further divided into the echinocandin group (209 patients; 64.7%) and the azole group (101 patients; 32.3%). Median APACHE II scores were significantly higher in the echinocandin group (p 0.013), but IAT did not differ significantly with regard to the Candida species involved. Logistic multivariate stepwise regression analysis, adjusted for centre effect, identified septic shock (adjusted OR (aOR) 1.54), APACHE II >15 (aOR 1.16) and presence in surgical ward at diagnosis (aOR 1.16) as the top three independent variables associated with an empirical echinocandin regimen. No differences in 30-day mortality were observed between groups. Echinocandin regimen was the first choice for IAT in patients with IAC. No statistical differences in mortality were observed between regimens, but echinocandins were administered to patients with more severe disease. Some disagreements were identified between current clinical guidelines and prescription of antifungals for IAC at the bedside, so further educational measures are required to optimize therapies.

A simple prediction score for estimating the risk of candidaemia caused by fluconazole non-susceptible strains.

We aimed to develop a simple prediction score to identify fluconazole non-susceptible (Flu-NS) candidaemia using simple clinical criteria. A derivation cohort was extracted from the CANDIPOP study, a prospective, multicentre, population-based surveillance programme on candidaemia conducted in 29 hospitals in Spain from April 2010 to May 2011. The score was validated with an external, multicentre cohort of adults with candidaemia in six tertiary hospitals in three countries. The prediction score was based on three variables selected by a logistic regression model together with the severity of disease. In total, 617 and 297 cases of candidaemia were included in the derivation and validation cohorts, respectively; of these, 134 (21.7%) and 57 (19.2%) were caused by Flu-NS strains. Factors independently associated with Flu-NS were transplant recipient status (adjusted odds ratio (AOR) 2.13; 95% CI 1.01-4.55; p 0.047), hospitalization in a unit with a high prevalence (≥ 15%) of Flu-NS strains (7.53; 4.68-12.10; p < 0.001), and previous azole therapy for at least 3 days (2.04; 1.16-3.62; p 0.014). The area under the receiver operating characteristics curve (AUC) was 0.76 (0.72-0.81), and using 2 points as the Flu-NS prediction score cut-off gave a sensitivity of 82.1%, a specificity of 65.6%, and a negative predictive value of 93%. The AUC in the validation cohort was 0.72 (95% CI 0.65-0.79). Hence, the Flu-NS prediction score helped to exclude Flu-NS Candida strains. This could improve the selection of empirical treatments for candidaemia in the future.

Revisiting the source of candidemia: skin or gut?

The source of candidemia has been the subject of considerable debate, with some suggesting a origin in the gastrointestinal tract and others suggesting a skin origin. To evaluate the potential sources of candidemia, we performed a computerized search of the MEDLINE database for studies published from January 1966 through September 2000 and we identified relevant abstracts presented at national meetings. We reviewed the literature with special emphasis on studies that used appropriate definitions, evaluated both gut and skin as sources, and conducted molecular-relatedness studies. Among 203 candidemia studies published, we identified 21 that evaluated a specific source for candidemia and only 5 that performed molecular typing. Those studies and additional experimental, epidemiologic, and molecular-relatedness studies strongly suggested that the gut is an important source of candidemia, and studies that supported the skin as a source for this infection were surprisingly incomplete.

Ectopic prostatic tissue in the uterine cervix: a report of four cases and review of ectopic prostatic tissue.

We report four examples of prostatic tissue occurring in the uterine cervix of patients aged 22, 25, 31, and 77 years. Three were incidental findings in loop excisions (two patients) and cone biopsy (one patient) of the cervix for high-grade squamous dysplasia. One presented as a cervical mass, clinically suspected to represent a fibroid. The prostatic tissue consisted of ducts and acini, some of which had papillary or cribriform patterns. Squamous metaplasia was prominent in all cases. No Wolffian duct tissue was present. The glandular epithelium in all cases was positive for prostatic acid phosphatase and prostate-specific antigen. High molecular weight keratin, performed in two cases, highlighted basal cells in a manner similar to the normal prostate. These unusual cases, only one of which is documented previously, further complicate the often-challenging area of interpretation of benign glandular lesions of the cervix. The unusual phenomenon of ectopic prostate tissue in general is reviewed.

Cellular angiofibroma: a benign neoplasm distinct from angiomyofibroblastoma and spindle cell lipoma.

Four cases of a distinctive soft-tissue tumor of the vulva are described. They were characterized by occurrence in middle-aged women (39-50 years), small size (< 3 cm), and a usually well-circumscribed margin. The preoperative clinical diagnosis was that of a labial or Bartholin gland cyst in three of the four cases. The microscopic appearance was remarkably consistent and was characterized by a cellular neoplasm composed of uniform, bland, spindled stromal cells, numerous thick-walled and often hyalinized vessels, and a scarce component of mature adipocytes. Mitotic activity was brisk in three cases (up to 11 mitoses per 10 high power fields). The stromal cells were positive for vimentin and negative for CD34, S-100 protein, actin, desmin, and epithelial membrane antigen, suggesting fibroblastic differentiation. Two patients with follow-up showed no evidence of recurrence. The differential diagnosis of this distinctive tumor includes aggressive angiomyxoma, angiomyofibroblastoma, spindle cell lipoma, solitary fibrous tumor, perineurioma, and leiomyoma. The designation of "cellular angiofibroma" is chosen to emphasize the two principal components of this tumor: the cellular spindle cell component and the prominent blood vessels.