Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors.

BACKGROUND: Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs. PATIENTS AND METHODS: Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome. RESULTS: None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including ≥3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression. CONCLUSIONS: In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs.

Selecting first-line bevacizumab-containing therapy for advanced breast cancer: TURANDOT risk factor analyses.

BACKGROUND: The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV-PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen. METHODS: Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV-PAC (bevacizumab 10 mg kg(-1) days 1 and 15 plus paclitaxel 90 mg m(-2) days 1, 8 and 15 q4w) or BEV-CAP (bevacizumab 15 mg kg(-1) day 1 plus capecitabine 1000 mg m(-2) bid days 1-14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High- and low-risk HR+ were defined, respectively, as having ⩾2 vs ⩽1 of the following four risk factors: disease-free interval ⩽24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ⩾3 organs. RESULTS: The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV-PAC in the TNBC cohort and BEV-CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV-PAC. Grade ⩾3 adverse events were consistently less common with BEV-CAP. CONCLUSIONS: A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340).

[Surgical treatment of metastases and its impact on prognosis in patients with metastatic colorectal carcinoma]. / Chirurgická liecba metastáz a jej vplyv na prognózu u pacientov s metastatickým kolorektálnym karcinómom.

BACKGROUND: Approximately one quarter of patients with colorectal carcinoma (CRC) have distant metastases at initial dia-gnosis and almost 50% will develop them during the disease course. Only radical surgical resection of metastases improves clinical outcome and offers a chance of longterm survival. Initially unresectable metastases can become resectable after downsizing with systemic therapy. MATERIALS AND METHODS: Retrospective analysis included 21 patients with metastatic colorectal carcinoma (mCRC) who were treated from 2006 to 2012 and underwent resection/ ablation of metastases. Fourteen patients had resection at initial dia-gnosis of metastatic disease and seven patients achieved operability of metastases after systemic treatment. The aim of the analysis was to evaluate surgical treatment of metastases and its impact on prognosis in patients with mCRC in correlation with clinical pathological  genetic factors. RESULTS: The median age of patients was 59 years. Fourteen patients had metastases in the liver, one patient had metastases in the lungs, two patients had combination of hepatic and extrahepatic metastases and four patients had metastases in other regions. During median followup of 47 months, 17 patients experienced disease progression and 13 patients died. Median progression free survival (PFS) after surgical resection/ ablation of metastases was 17 months (95% CI 13.8820.12), and median overall survival (OS) was 48 months (95% CI 38.7757.23). KRAS mutation was detected in 47.6% of patients and BRAF mutation in 9.5% of patients. Patients with BRAF mutation had worse PFS (median = 10 months vs 17 months; p = 0.523) and OS (median = 22 months vs 51 months; p = 0.05) compared to patients with BRAF wildtype. No difference was observed in PFS and OS between the patients with one or more metastatic lesions and between the patients who underwent resection/ ablation of metastases initially or after systemic treatment. CONCLUSION: These data suggest that resection/ ablation of metastases significantly improves prognosis of patients with mCRC and support the notion that mutated BRAF has a strong negative prognostic significance also in the group of patients, who undergo surgical resection/ ablation of metastatic lesions.

Bevacizumab in combination with chemotherapy in the first-line treatment of metastatic colorectal carcinoma.

Colorectal carcinoma (CRC) is a malignancy of worldwide increased incidence. The vast majority of all CRC cases occur in patients older than age 50. The initial stage at the time of diagnosis has a strong influence on the overall survival (OS). According to AJCC sixth edition system, 5-year stage-specific survivals are over 90% in stage I, but only approximately 8% in stage IV [1]. Chemotherapy in combination with biological treatment has improved response rates (RR), with prolongation of progression free survival (PFS) and OS. Important role in treatment of metastatic colorectal carcinoma (mCRC) plays surgical resection of metastases. Multidisciplinary cooperation between medical oncologist, surgeon, radiologist and radiotherapist is necessary to achieve the best therapeutic results. The aim of our analysis was to describe the efficacy of bevacizumab used in combination with chemotherapy in the first-line setting and to evaluate frequency of thromboembolic complications during the treatment. The analysis included 58 patients with mCRC, who have been treated with first-line chemotherapy in combination with bevacizumab at the St. Elizabeth Cancer Institute in Bratislava since 2006 and first assessed for the first therapeutic results in October 2010. The clinical benefit after the treatment represented by overall response rate (ORR) and stable disease (SD) was achieved in 87.93% of patients, and surgical resection of metastases after therapy underwent 12.07% of patients. Median time to progression (TTP) was 8 months and median OS evaluated in October 2011 was 27 months. Mutation status of KRAS gene had no influence on the effectiveness of treatment and BRAF mutations exhibited a strong negative prognostic significance. Thromboembolic complications were present in 17.24%.

Bone mineral density in early breast cancer patients.

PURPOSE: Recent data indicate that women with breast cancer receiving aromatase inhibitors (AIs) are at increase risk of osteoporosis. PATIENTS AND METHODS: We evaluated 263 patients in our study, 42 receiving AI (22 - Arimidex, 20 - Femara), 69 selective estrogen receptor modulater (SERM - Tamoxifen), in 72 the therapy with SERM was changed for AI and 80 were in follow-up without hormonal therapy. We measured BMD by whole-body densitometer Hologic explorer. BMD of proximal femur and L spine was measured and evaluated and in case of degenerative changes also the region of distal forearm. We evaluated T-score. 43. RESULTS: 35% of the patients had decline of BMD to T-score of osteoporosis and only 13.31% of patients had normal bone density. 53.13% of the treated patients had BMD level of osteoporosis versus 40.2% of untreated patients or patients treated for less than one year. 3.13% of treated patients had normal BMD versus 16.58% of untreated patients (p = 0.015). CONCLUSIONS: We confirm the influence of adjuvant AI therapy on decline of BMD in early breast cancer patients in our study. The bone loss was statistically significant in patients whose therapy lasted at least one year (Fig. 6, Ref. 20). Full Text (Free, PDF) www.bmj.sk.

Circulating tumour cells in breast cancer--review.

Disseminated malignancies are responsible for the majority of cancer-related deaths. During the metastatic process, circulating tumour cells (CTCs) are generated. The presence of CTCs, epithelial cells found in the peripheral blood, is an essential step in establishing distant metastases. Circulating epithelial cells have the morphology of malignant cells and their number in the blood correlates with tumour burden. To identify CTCs in peripheral blood, two major approaches are used involving additional antibodies and nucleic acid-based techniques. Tumour cells with HER-2 overexpression are frequently resistant to cytotoxic drugs and radiotherapy. Wider clinical application of the detection of minimal residual disease is partly limited by the lack of standardized methods for detection. Recent studies suggest that in addition to the prognostic significance of tumour cells, determination of CTCs may be important in therapy monitoring or as potential targets for targeted therapy. Persistence of minimal residual disease after primary treatment may be an indication for extensive adjuvant treatment in order to prevent relapse of the disease. Detection of CTCs and the use of prognostic markers such as HER-2 overexpression may help us to better understand the biology and clinical significance of the presence of CTCs in breast cancer patients.

[Treatment of recurrent ovarian cancer--a retrospective study]. / Liecba rekurentného karcinómu ovária--retrospektívna analýza.

BACKGROUNDS: Treatment of recurrent ovarian cancer is not standardized. Pre-clinical tests have confirmed the synergistic effect of gemcitabine and platinum, which can break through drug resistance to platinum. Therefore, efficacy of a combined gemcitabine and platinum-based regimen can be expected not only in therapy platinum-sensitive but also in platinum-resistant disease. Surgery--so-called secondary (eventually tertiary) cytoreductive surgery, should be considered in recurrent disease before planning the chemotherapy. PATIENTS AND METHODS: This is a retrospective analysis of 58 patients with recurrent ovarian cancer treated with a gemcitabine and platinum-based regimen (GP) as the second or third-line chemotherapy. Some of the patients underwent secondary cytoreductive surgery before starting the systemic treatment. The aim of the study was to detect the response rate, progression-free survival and overall survival in the whole group of patients and in subgroups with platinum-sensitive and platinum-resistant disease. Another aim was to detect the correlation between secondary cytoreductive surgery and the efficacy of chemotherapy. RESULTS: Systemic treatment (GP) has helped to achieve a response rate of 53.5%, with time to progression 10 months and overall survival 23.5 months. A better response rate, progression free survival and overall survival were achieved in the group of patients with platinum-sensitive disease compared to patients with platinum-resistant disease, but this difference was not statistically significant. 20 patients underwent effective secondary cytoreductive surgery before the systemic treatment. Patients who underwent effective secondary cytoreductive surgery had a statistically better response rate (RR: 80% vs 39.5%), longer progression-free survival (PFS: 13.5 m vs 9 m, p = 0.006) and longer overall survival (OS: 40 m vs 16.9 m, p = 0.006) when compared to patients without secondary cytoreductive surgery. CONCLUSION: We have confirmed the efficacy of a gemcitabine and platinum-based regimen in the therapy of recurrent ovarian cancer, in both platinum-sensitive and platinum-resistant disease. An important prognostic factor in the whole group of patients was the realization of effective secondary cytoreductive surgery.

Genetic analysis of KRAS mutation status in metastatic colorectal cancer patients.

Colorectal carcinoma (CRC) represents a serious problem worldwide: in the Slovak republic are diagnosed about 2600 new CRC cases annually and its incidence is increasing. Colorectal cancer patients may succumb to the disease because of local recurrence or local formation of metastasis. Therefore, it is necessary to modulate therapeutic algorithm with new methods, leading to early diagnostic of CRC or changing the existing therapeutic procedures. Recent progresses have been made in understanding of EGFR pathway involved in CRC carcinogenesis, especially the role of Ras protein. Mutations in KRAS oncogene are frequently found in human cancers, particularly colorectal, pancreatic, billiary tract and lung tumors. The presence of the KRAS mutations in metastatic colorectal cancer patients correlates with lack of response to the certain epidemal growth factor receptor (EGFR) inhibitor therapies, such as Panitumumab and Cetuximab. Consequently, screening for KRAS mutations status may be used as a prognostic marker, because the CRC patients with KRAS positive tumors have a worse prognosis. The aim of our study was to establish the methods for rapid and sensitive detection of KRAS mutation status in formalin fixed paraffin embedded (FFPE) tissues DNA. We applied Real Time PCR analysis (TheraScreen KRAS Mutation Test Kit) and sequencing analysis (optimised for the analysis of FFPE tissues) to detect somatic mutations in codon 12 and 13 of KRAS gene. Both methods were used concurrently in the panel of DNA isolated from 25 colorectal FFPE tissues tumor. The positive or negative results from all 25 samples were identified by both methods independently. The KRAS mutations were presented in 8 of 25 patients (32%). Our results demonstrate that the Real Time PCR analysis can be used for detection of somatic KRAS mutations in FFPE clinical samples. However, we also recognize that the sequencing analysis of approximately 200bp amplicons may be used for mutations status screening, but with care of method sensitivity.

[Neo-adjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer treatment--a retrospective study]. / Neo-adjuvantná chemoterapia s následnou IDS (interval debulking surgery) v liecbe pokrocilého karcinómu ovária--retrospektívna analýza.

BACKGROUNDS: Primary debulking surgery and chemotherapy (paclitaxel and carboplatin) remain the standard treatment for advanced ovarian cancer. The size of the residual tumour after primary debulking surgery has proved to be an important prognostic determinant. Complete tumour debulking without any macroscopic residual disease is considered the optimal primary debulking surgery. It is not possible to perform such an aggressive operation in patients with advanced ovarian cancer due to the bad performance status and extensive disease. Neo-adjuvant chemotherapy and interval debulking surgery seem to be an effective treatment strategy in this group of patients. MATERIAL AND METHODS: The retrospective analysis evaluated the efficiency of interval debulking surgery in correlation with progression-free and overall survival in patients with advanced ovarian cancer. 38 patients were treated with standard chemotherapy: paclitaxel 175 mg/m2 and carboplatin 5-6 AUC every three weeks. According to the clinical response, surgical debulking was considered, after which postoperative chemotherapy was given. Ineligible patients for interval debulking were treated with 2nd line chemotherapy. RESULTS: After neo-adjuvant chemotherapy, 24 patients of the group of 38 achieved partial remission and interval debulking surgery was indicated. Optimal interval debulking surgery was performed in 12 patients, suboptimal debulking surgery in 12 patients. Of the entire group, 14 patients did not show any adequate response to the primary treatment, they did not have interval debulking surgery indicated and they were treated with 2nd line chemotherapy. Progression-free survival in patients after optimal debulking was 11 months, median overall survival was not achieved (OS > 42.5 months). Progression-free survival in patients after suboptimal debulking was 6 months and median overall survival was 33 months. Median overall survival in patients without surgical treatment was 21.5 months. CONCLUSION: The results of the study confirm that neo-adjuvant chemotherapy with subsequent interval debulking surgery is a suitable therapeutic approach in primary inoperable patients with advanced ovarian cancer.

An unusual presentation of testicular cancer.

We report two rare cases of patients presenting with unusual symptoms, which led to the diagnosis of a germ cell tumor. Metastatic germ cell tumor of testis involving the gastrointestinal tract and causing the occult gastrointestinal bleeding is described in the first case. The second patient is reported to have limbic encephalitis with positive serum for Ma2 antibodies (antibodies against neuronal proteins) and parallel malignant germ cell tumor diagnosis (Fig. 4, Scheme 2, Ref. 12). Full Text (Free, PDF) www.bmj.sk.

Nosocomial meningitis caused by Staphylococcus other than S. aureus in children: multicentre study.

Analysing 101 cases of nosocomial meningitis due to staphylococci other than S. aureus within last 15 years, coagulase negative staphylococci represented the commonest pathogen. Major risk factor for staphylococcal meningitis was prior neurosurgery, mainly ventriculoperitoneal shunt insertion. Ten of 101 cases were caused by glycopeptide intermediate resistant strains in patients pretreated with multiple combination of antibiotics including vancomycin and shunt exchanges: 76% of strains were also oxacillin resistant.

Predictors of inferior outcome in community acquired bacterial meningitis.

The aim of this study was to assess mortality and sequellae within cases from Nationwide survey of community acquired meningitis and identify risk factors for inferior outcome. Risk factors such as underlying disease (diabetes mellitus, cancer, trauma, neonatal age, splenectomy, alcoholism, sepsis, other infections), etiology, clinical symptoms and outcome (death, improvement and cured after modifications of ATB therapy, cured without change of therapy, cured with neurologic sequellae) were recorded and analysed with univariate analysis (chi2 or t test for trends, CDC Atlanta 2004). Analysing risk factors for inferior outcome (death or cured with neurologic sequellae), we compared patients who died or survived with neurologic sequellae to all patients with community acquired bacterial meningitis. Univariate analysis showed that trauma (p<0.05), alcohol abuse (p<0.05), diabetes, S. aureus (p<0.05) and gram-negative etiology (A. baumannii, Ps. aeruginosa or Enterobacteriaceae) (36% vs. 11,9%, p<0.05) were predicting inferior outcome. Analysing risk factors for treatment failure (death or failed but cured after change of antibiotic treatment) prior sepsis (34.1% vs. 13.9%, p<0.01) and gram-negative etiology (25% vs. 11.9%, p<0.02) were statistically significant predictors of treatment failure. Neisseria meningitis had less failures (p<0.05). Concerning infection associated mortality again diabetes mellitus (p<0.05), alcoholism (p<0.05) staphylococcal and gram-negative etiology (p<0.05) were significant predictors of death. N. meningitis had surprisingly less treatment failures (appropriate and rapid initial therapy). Neurologic sequellae were more common in patients with alcohol abuse (p<0.05), craniocerbral trauma (p<0.05) and less common in meningitis with pneumococcal etiology (p<0.05).

Treatment of metastatic head and neck cancer with mesenchymal stem cells combined with prodrug gene therapy.

This is a clinical observation of a patient treated for metastatic head and neck cancer with mesenchymal stem cells mediated prodrug gene therapy. The cells were applied intravenously. We did not observe any therapeutic effect. However, a temporal bicytopenia was observed.

Eight-year surveillance of non-albicans Candida spp. in an oncology department prior to and after fluconazole had been introduced into antifungal prophylaxis.

From 1989 until 1996, during the last 8 years, the proportion of Candida (C.) krusei, and other non-albicans Candida spp. isolated from surveillance cultures and from sterile body sites, was analyzed among 13,758 admissions in a National Cancer Institute. During these admissions a total of 9,042 isolates were prospectively collected from surveillance cultures, and 126 from blood cultures. The proportion of C. krusei among all organisms was 12.7% to 16.5% in 1989 through 1991, i.e., before fluconazole was introduced into prophylactic protocols. After the introduction of fluconazole into prophylaxis in acute leukemia in 1992 the incidence of C. krusei was 7.9% to 8.6% during 1994 to 1996. After 5 years of using this drug for prophylaxis, the incidence of C. krusei was lower than before this drug was introduced in our institute. Among yeasts, the most frequently isolated pathogen was still Candida albicans (72.2% of all isolated fungal organisms). Among molds, Aspergillus spp. was the most frequently isolated agent. Analyzing the etiology of proven fungal infections (fungemias) confirmed by positive blood cultures, C. albicans was the most common causative organism in 53.8% of cases. The incidence of fungemia due to Torulopsis (C.) glabrata and C. krusei before and after fluconazole introduction did not change. Of 126 organisms isolated from blood cultures, there was no increase in T. (C.) glabrata or C. krusei after introduction of fluconazole for prophylaxis and therapy, and the quoted 6.4% of fungemic episodes remained stable with an incidence of 1 fungemia/year since 1991. The proportion of C. krusei and C. glabrata among Candida spp. was decreasing in our center between 1989 and 1996. Also, the proportion of non-albicans Candida spp. among isolates decreased from 25.7% in 1990 to 11.9% in 1996.

Risk factors, aetiology, therapy and outcome in 123 episodes of breakthrough bacteraemia and fungaemia during antimicrobial prophylaxis and therapy in cancer patients.

One hundred and twenty-three breakthrough bacteraemias (BB) were defined during a 5-year period in a National Cancer Centre, among 9986 admissions and a total of 979 bacteraemic episodes analysed. Of 123 bacteraemias in 103 patients, 77 were polymicrobial and 116 of the 323 organisms isolated were resistant to currently administered antimicrobial agents. Sixty-seven of the bacteraemic episodes were catheter-associated, as confirmed by the isolation of the same organisms from both blood and catheter tip. The strains isolated most frequently were coagulase-negative staphylococci (30.5%), corynebacteria (10%), Pseudomonas aeruginosa (10%), Enterococcus faecalis (9%) and viridans streptococci (8.5%). Gram-positive aerobes accounted for two-thirds of all micro-organisms isolated during breakthrough bacteraemic and fungaemic episodes. Polymicrobial episodes were associated more frequently with vascular catheters and neutropenia, and had a less favourable outcome than monomicrobial infections. Relapse was associated more frequently with catheter-related episodes, but the overall mortality rate was similar and independent of catheter insertion. Breakthrough bacteraemic and fungaemic episodes were associated more frequently with acute leukaemia. Catheter removal, as an independent variable, and modification of antimicrobial therapy were essential for better outcome.

Polymicrobial bacteremia in cancer patients: analysis of risk factors, etiology and outcome in 214 episodes.

Two hundred and fourteen episodes of polymicrobial bacteremia in 182 cancer patients in a period of 6 years in a 360-bed National Cancer Institute were analyzed for etiology, risk factors and outcome. Variables were compared with 187 episodes of monomicrobial bacteremias in 147 cancer patients to find statistical significance among risk factors, etiology and outcome. Urinary catheters and breakthrough bacteremia were the only risk factors associated with polymicrobial in comparison to monomicrobial bacteremia (P < 0.05). Concerning etiology, Enterococcus faecalis, Candida spp., Acinetobacter calcoaceticus and Stenotrophomonas maltophilia were more commonly isolated in polymicrobial than in monomicrobial bacteremic episodes. Polymicrobial bacteremia presented more frequently with septic shock (22.9% vs. 9.0%, P < 0.05) and/or organ complications (25.2% vs. 11.8%, P < 0.05). However, mortality due to bacteremia did not significantly differ between polymicrobial and monomicrobial, but when polymicrobial bacteremia with and without coagulase negative staphylococci were compared, mortality in polymicrobial bacteremia without staphylococci was higher (10% vs. 4.7%, P < 0.04).

Bacteremia due to methicillin-resistant staphylococci occurs more frequently in neutropenic patients who received antimicrobial prophylaxis and is associated with higher mortality in comparison to methicillin-sensitive bacteriemia.

Bacteriemia due to coagulase-negative staphylococci (CNS) resistant to methicillin and sensitive only to glycopeptides in 220 cancer patients was prospectively analyzed for risk factors and outcome. A group of 33 cases of bacteriemia with CNS-sensitive only to glycopeptides was compared with a group of 187 cases with CNS sensitive to methicillin. All cases appeared in two affiliated major cancer institutes in Bratislava with the same antibiotic policy. Univariate analysis showed differences in recorded risk factors: acute leukemia (48 vs. 33%, P < 0.05), neutropenia (57 vs. 32%, P < 0.045), previous prophylaxis with quinolones (30 vs. 11%, P < 0.01) and penicillin-V (15 vs. 3%, P < 0.02) and previous colonisation with CNS (27 vs. 3%, P < 0.01) were more frequently associated with bacteriemia resistant to methicillin and sensitive only to glycopeptides. Attributable mortality was also higher in this subgroup in comparison to bacteriemias with CNS sensitive to methicillin (12 vs. 3%, P < 0.05) however, overall mortality was similar. Bacteriemias due to CNS caused by sensitivity only to glycopeptides occurred more frequently in neutropenic patients (1), with acute leukemia (2), receiving quinolone and penicillin prophylaxis (3), and previously colonized (4), patients and had worse prognosis in comparison to those with methicillin-sensitive staphylococcal bacteriemias.

Bacteremia due to Enterobacter spp. in cancer patients--analysis of 51 episodes.

Fifty one episodes of bacteremia due to Enterobacter spp. appearing within 7 years among 12 301 admissions in a single cancer institution were studied for risk factors, clinical presentation and outcome. Fifteen episodes were due to Enterobacter aerogenes, 23 due to E. cloacae and 13 due to E. agglomerans. The proportion of bacteremia due to Enterobacter spp. among Gram-negative bacteremias was 10.1% and infection associated mortality was 13.8%. The incidence in 1989-1995 varied from 3.7 to 8.7% and was relatively stable. Most common risk factors were: solid tumors as underlying disease, central venous catheter insertion, prior surgery and prior chemotherapy within 48 h. Neutropenia and urinary catheters were not at high risk in either one of the patients subgroups. Comparing two subgroups of 51 bacteremias, monomicrobial and polymicrobial (when Enterobacter spp. was isolated from blood culture with other microorganism), previous chemotherapy, vascular catheter insertion and prior endoscopy were more frequently associated with polymicrobial Enterobacter spp. bacteremia. There was also differences in infection associated mortality: bacteremias due to Enterobacter spp. only had significantly lower mortality in comparison to polymicrobial Enterobacter spp. bacteremias (3.3 vs. 29.3%; P<0.02). Susceptibility of Enterobacter spp. strains isolated from 51 episodes was stable and showed only two episodes due to quinolone-resistant strains, both in 1992 despite of the use of ofloxacin in prophylaxis of neutropenic patients since 1990 in our institute. Ninety-two to 94% of all strains were susceptible to aminoglycosides, 96-98% to ofloxacin and ciprofloxacin, respectively and 94.9% to meropenem but only 75.5% to ceftazidime.

Fungaemia due to Fusarium spp. in cancer patients.

Five cases of fungaemia due to Fusarium spp. in cancer patients are described. Two were breakthrough cases, despite ongoing therapy with amphotericin B. Three were caused by Fusarium solani, one by F. oxysporum and one by F. dimerum. Four patients died, three of them despite therapy with amphotericin B for between 5-37 days. We describe only the second reported case of F. dimerum fungaemia. Since 1972, 93 cases of systemic infection with Fusarium spp. have been described: 43 had positive blood cultures and the overall mortality was 72%.

Growth factors and hematopoietic recovery.

Availability of hematopoietic growth factors (GC-SF, GM-CSF, erythropoietin, etc.) has started a new arena of dose-intensification. The use of such growth factors has resulted in faster hematopoietic recovery of cancer patients and now offers several new treatment modifications. These include: (1)dose-intensification without hematopoietic stem cell support, (2) speedier hematopoietic recovery after hematoablative therapy and stem cell transplantation (allogeneic or autologous); (3) use of combination of growth factors, and (4) improvement in the delivery of anti-microbial drugs which are toxic towards hematopoietic cells (Gancyclovir, Bactrim, etc.). The above treatment strategies are under active clinical trials and can provide improved, cost-effective methods of treating patients with cancer.