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Clinical presentation and outcomes of esophageal candidiasis (EC) in cancer patients are scarcely studied in the azole era, as is the correlation between clinical, endoscopic, and histopathological EC manifestations. We retrospectively reviewed the risk factors, clinical features, and outcomes of pathology-documented EC cases at MD Anderson Cancer Center. We further assessed associations between presence of symptoms, standardized 4-stage endoscopic grade (Kodsi classification), histopathological data, and fluconazole treatment failure. Among 323 cancer patients with EC, 89% had solid tumors, most commonly esophageal cancer (29%). Thirty-three percent of EC patients were asymptomatic. The proportion of symptomatic EC patients significantly increased with endoscopic grade (P = 0.005). Among 202 patients receiving oral fluconazole, 27 (13%) had treatment failure. Underlying esophageal disease was the only independent predictor of fluconazole treatment failure (odds ratio: 3.88, P = 0.005). Endoscopic grade correlated significantly with Candida organism burden (Correlation coefficient [ρ] = 0.21, P < 0.01) and neutrophilic inflammation (ρ = 0.18, P < 0.01). Candida invasion of the squamous mucosal layer was associated with treatment failure (P = 0.049). EC was predominantly encountered in patients with solid tumors. One-third of EC patients were asymptomatic, challenging traditional symptom-based diagnosis. The development of integrated clinicopathological scoring systems could further guide the therapeutic management of cancer patients with EC. [ABSTRACT FROM AUTHOR]

Objectives: Fungal empyema thoracis (FET) is a rare life-threatening infection. We sought to describe the clinical characteristics of FET in a large academic cancer center.Methods: We conducted a retrospective chart review of all cancer patients who had a fungal isolate from the pleural fluid culture between 1/2005 and 8/2013.Results: A total of 106 fungal isolates were identified in 97 patients. Yeasts accounted for 62% of the isolates whereas 38% were identified as molds. The most frequent pathogens were Candida spp. (58%) and Aspergillus spp. (12%). All patients with Aspergillus and 83% with Candida met criteria for proven fungal disease. Compared to the Aspergillus group, Candida FET was associated with recent abdominal or thoracic surgical procedures (44% vs. 0%, p = 0.01). Overall, 6-week mortality was high, with no significant differences between Candida and Aspergillus (31% vs. 45%, respectively [p = 0.48]). Only 1 out of 11 patients with uncommon molds died at 6 weeks, despite only 2 of them received appropriate antifungal therapy.Conclusions: Development of FET carries a high mortality in cancer patients. A history of a recent surgical procedure is a risk factor for FET due to Candida. Isolation of uncommon molds is likely to represent a contamination of the pleural fluid. [ABSTRACT FROM AUTHOR]

Background & Aims: Data on acute exacerbation and reactivation of chronic hepatitis C virus (HCV) infection following chemotherapy are very limited. We sought to characterize the episodes of acute exacerbation and viral reactivation of HCV infection in cancer patients. Methods: The medical records of HCV-infected patients seen at our institution (2008–2009) were analyzed retrospectively. Acute exacerbation was defined as greater than 3-fold increase in serum level of alanine aminotransferase, and viral reactivation as ⩾1log10 IU/ml increase of HCV viral load following chemotherapy. Results: Acute exacerbation occurred in 33 (11%) of 308 patients with proven HCV infection. Patients with acute exacerbation more often had underlying hematological malignancies (73% vs. 29%; p <0.001) and lymphopenia (6% vs. 0%; p = 0.01) than patients without it. In multivariate analysis, underlying hematological malignancies (p= 0.02; odds ratio, 3.2; 95% confidence interval, 1.2–8.7) and use of rituximab (p = 0.004; odds ratio, 4.2; 95% confidence interval, 1.6–10.9) were associated with acute exacerbation. Patients with acute exacerbation received higher median cumulative dose of rituximab than those without exacerbation. Discontinuation of chemotherapy due to liver dysfunction was more common in patients with acute exacerbation than in patients without it (45% vs. 11%; p <0.001). Eight (36%) of 22 patients with known pre- and post-chemotherapy viral load had viral reactivation. Conclusions: Acute exacerbation and reactivation of chronic HCV infection occur often after chemotherapy. Liver dysfunction can lead to discontinuation of potentially life-saving chemotherapy in nearly one-half of the patients with exacerbation of HCV infection. [ABSTRACT FROM AUTHOR]

Summary: Background: Rare opportunistic (non-Candida, non-Cryptococcus) yeast bloodstream infections (ROYBSIs) are rare, even in cancer patients. Methods: We retrospectively reviewed all episodes of ROYBSIs occurring from 1998 to 2010 in our cancer center. Results: Of 2984 blood cultures positive for Candida and non-Candida yeasts, 94 (3.1%) were positive for non-Candida yeasts, representing 41 ROYBSIs (incidence, 2.1 cases/100,000 patient-days). Catheter-associated fungemia occurred in 21 (51%) patients. Breakthrough ROYBSIs occurred in 20 (49%) patients. The yeast species distribution was Rhodotorula in 21 (51%) patients, Trichosporon in 8 (20%) patients, Saccharomyces cerevisiae in 8 (20%) patients, Geotrichum in 2 (5%) patients, Pichia anomala, and Malassezia furfur in 1 patient each. All tested Trichosporon, Geotrichum, and Pichia isolates were azole-susceptible, whereas the Rhodotorula isolates were mostly azole-resistant. We noted echinocandin nonsusceptibility (minimal inhibitory concentration ≥ 2 mg/L) in all but the S. cerevisiae isolates. Most of the isolates (28/33 [85%]) were susceptible to amphotericin B. The mortality rate in all patients at 30 days after ROYBSIs diagnosis was 34%. Multivariate survival analysis revealed increased risk of death in patients with S. cerevisiae infections (hazard ratio, 3.7), Geotrichum infections (hazard ratio, 111.3), or disseminated infections (hazard ratio, 33.4) and reduced risk in patients who had catheter removal (hazard ratio, 0.1). Conclusions: ROYBSIs are uncommon in patients with cancer, and catheters are common sources of them. Half of the ROYBSIs occurred as breakthrough infections, and in vitro species-specific resistance to echinocandins and azoles was common. Disseminated infections resulted in the high mortality rate. [ABSTRACT FROM AUTHOR]

Objectives: Pulmonary mucormycosis (PMM) is an emerging, frequently lethal fungal infection in immunosuppressed cancer patients. We sought to characterize the histopathologic features of PMM in this population.Methods: We identified patients with PMM who underwent autopsy or lung biopsy between 1990 and 2007. Histopathology slides were blindly reviewed by a pathologist and findings were scored on standardized forms. Pathologic findings were correlated with demographic and clinical data abstracted from patient's medical records.Results: Twenty patients with PMM were included in this study. Nineteen patients (95%) had hematologic malignancies. High frequencies of angioinvasion (100%), hemorrhagic infarction (90%), coagulative necrosis (85%), and intra-alveolar hemorrhage (85%) were observed, whereas inflammatory infiltrates were uncommon (30%). Neutropenic patients had more extensive angioinvasion compared with non-neutropenic patients (77% versus 29%, P=0.06). Allogeneic hematopoietic stem cell transplantation (HSCT) recipients, all of whom had graft-versus-host disease, had more inflammatory cell infiltration but less intra-alveolar hemorrhage than non-HSCT patients (67% versus 14%, P=0.04; 50% versus 100%, P=0.02, respectively).Conclusions: PMM in immunocompromised cancer patients is characterized by extensive angioinvasion and coagulative necrosis. The different histopathologic features of PMM in neutropenic, non-neutropnic, and HSCT patients may reflect differences in the pathobiology of PMM in these populations. [ABSTRACT FROM AUTHOR]

Abstract: Although gastrointestinal cytomegalovirus disease (GI-CMVd) is not common in cancer patients, it is associated with high morbidity and mortality. Herein, we review our 2-decade experience with GI-CMVd in such patient population at The University of Texas M.D. Anderson Cancer Center. Forty-seven patients were identified. Thirty-four patients (72%) had an underlying haematological malignancy, and 18 patients (38%) developed GI-CMVd following hematopoietic stem cell transplantation (HSCT). Nine (25%) of the 36 cancer patients with data available had AIDS. Upper-GI tract involvement was more common in patients with haematological malignancies than in those with solid tumours (P =0.02). Patients with AIDS were more likely to have colonic involvement than were those without AIDS (67% vs. 15%, P =0.006), and patients without AIDS were more likely to have gastric involvement (59% vs. 11%, P =0.01). The CMV-attributable mortality rate was 42%. Independent predictors of death by multivariate analysis included disseminated CMV and AIDS (P <0.01). The presentation of GI-CMVd varies according to the type of cancer, and AIDS. GI-CMVd is associated with a high mortality among cancer patients, particularly those with disseminated CMV disease or AIDS. [Copyright &y& Elsevier]

Summary: We retrospectively collected information about 29 cancer patients who underwent measurement of their plasma concentration (PC) of voriconazole (VRC) (2002–2006). Nine patients (31%) had VRC PC <1μg/ml. VRC PC <1μg/ml occurred in 7 of 10 patients who were on VRC >2 months versus only 2 of 19 patients who were on VRC <2 months (P =0.001). VRC PCs were infrequently ordered, did not follow clear indications, and the use of the results was variable. [Copyright &y& Elsevier]

The aim of the study was to assess the association inflammation with symptom burden in patients with acute myeloid leukemia (AML), assessed before and during remission induction chemotherapy (IC). Patients with AML (n = 95) were followed from baseline (before IC) to the third week of IC for severity of self-reported somatic symptoms (assessed with the MD Anderson Symptom Inventory) and plasma levels of 13 inflammation-related biomarkers (n = 64). A composite symptom burden severity score was computed as the average score of the six most severe somatic symptoms i.e., fatigue, disturbed sleep, drowsiness, dry mouth, lack of appetite, and pain. Results from cross-sectional analyses showed that inflammation was weakly associated with symptom burden before IC (multiple regression model, explained variance = 10%) but this association grew stronger during IC (week 3 explained variance = 35%). About half of the sample showed a change over time in symptom severity. These changes were not reflected in similar changes over time in inflammatory markers, suggesting that it is the absolute concentration of a given inflammatory marker at a given time point rather than its relative change over time that is of importance. In conclusion, inflammation was strongly associated with symptom burden only during IC, possibly because expression of cytokines only then becomes relevant for regulation of symptom burden. While the current study does not allow for determination of causality, the results suggest that AML patients might benefit from anti-inflammatory interventions during treatment to alleviate somatic symptom experience. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hepatitis C virus (HCV) is a known carcinogen with considerable genetic heterogeneity: six different genotypes have been identified. HCV genotype distribution varies from country to country. In the United States, the most prevalent genotypes are 1a, and 1b followed by genotypes 2, and 3. Objectives: To examine whether the distribution of HCV genotypes differed by cancer status among patients in the same area. Study design: We reviewed epidemiologic and virological data of 636 patients with HCV infection evaluated at 3 institutions in Houston, Texas, in 2008 and 2009. Results: We included 129 cancer patients (53 with hematologic malignancies and 76 with solid tumors), 333 immunocompetent patients, and 102 HIV-co-infected patients. The prevalence of genotype 1 (G-1) was 66% among cancer patients, 84% among immunocompetents (P =0.00004), and 99% among HIV-co-infected patients (P <0.00001). G-2 and G-3 were more common in cancer patients than other patients. Demographics, risk factors, and duration of HCV infection were similar between cancer and immunocompetent patients. G-1 was more prevalent in immunocompetents (84%) than in patients with hepatocellular carcinoma (74%, P =0.08) or lymphoma (59%, P =0.001). G-2 was more prevalent in lymphoma patients (24%) than in immunocompetents (8%, P =0.003); cancer risk was 3 times as great with G-2 as with other genotypes (OR 3.72, 95% CI 1.38–9.76). Conclusions: This multicenter retrospective study provides evidence of differences in HCV genotype distribution by underlying disease among geographically related patients and suggests a possible greater carcinogenic potential of some variants. Large-scale prospective studies are warranted to investigate HCV genotype distribution in other regions. [Copyright &y& Elsevier]

Among cancer patients with Candida glabrata (the Candida species with the slowest in-vitro growth) fungemia, time-to-positive blood culture reporting (TTR) was shorter in catheter-associated candidemia (mean±standard deviation: 67±35 h) than in candidemia from other sources (79±31, P <.01). TTR<48 h was 92% specific for catheter-associated C. glabrata fungemia. [ABSTRACT FROM AUTHOR]

Abstract: This study was performed to evaluate retrospectively the efficacy and safety of caspofungin monotherapy for candidaemia in patients with cancer. The medical records were reviewed of 63 consecutive adult patients with cancer who had candidaemia treated with caspofungin alone for at least 3 consecutive days at The University of Texas M.D. Anderson Cancer Center (March 2001–February 2007). Twenty patients (32%) had haematological malignancies. Most of the candidaemia cases (54%) were caused by non-albicans Candida spp. The most frequent isolates were C. albicans (38%) followed by Candida parapsilosis (21%), Candida tropicalis (16%) and Candida glabrata (10%). In vitro susceptibility studies showed that of 30 Candida isolates tested, only one C. parapsilosis isolate had a caspofungin minimum inhibitory concentration >1μg/mL. The clinical and mycological response rates after 7 days of treatment with caspofungin were 78% and 77%, respectively. The overall mortality rate was 5% on Day 7, 12% on Day 14 and 21% on Day 30. The 30-day Candida-attributable mortality rate was 11% and was significantly higher in patients with fluconazole-resistant or susceptible-dose-dependent Candida isolates. Caspofungin was well tolerated in all patients. Although selection of candidaemic patients with cancer who received caspofungin monotherapy may have accounted for the favourable outcomes, it was observed that caspofungin had efficacy and safety comparable with those in candidaemic patients without malignancy. [Copyright &y& Elsevier]