Maria Del Pilar Estevez Diz

Transfusion Requirements in Surgical Oncology Patients A Prospective, Randomized Controlled Trial

Background:Several studies have indicated that a restrictive erythrocyte transfusion strategy is as safe as a liberal one in critically ill patients, but there is no clear evidence to support the superiority of any perioperative transfusion strategy in patients with cancer. Methods:In a randomized, controlled, parallel-group, double-blind (patients and outcome assessors) superiority trial in the intensive care unit of a tertiary oncology hospital, the authors evaluated whether a restrictive strategy of erythrocyte transfusion (transfusion when hemoglobin concentration <7 g/dl) was superior to a liberal one (transfusion when hemoglobin concentration <9 g/dl) for reducing mortality and severe clinical complications among patients having major cancer surgery. All adult patients with cancer having major abdominal surgery who required postoperative intensive care were included and randomly allocated to treatment with the liberal or the restrictive erythrocyte transfusion strategy. The primary outcome was a composite endpoint of mortality and morbidity. Results:A total of 198 patients were included as follows: 101 in the restrictive group and 97 in the liberal group. The primary composite endpoint occurred in 19.6% (95% CI, 12.9 to 28.6%) of patients in the liberal-strategy group and in 35.6% (27.0 to 45.4%) of patients in the restrictive-strategy group (P = 0.012). Compared with the restrictive strategy, the liberal transfusion strategy was associated with an absolute risk reduction for the composite outcome of 16% (3.8 to 28.2%) and a number needed to treat of 6.2 (3.5 to 26.5). Conclusion:A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy.

Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness

OBJECTIVE Three cycles of neoadjuvant chemotherapy (NACT) followed by interval debulking (ID) surgery is an alternative for patients with advanced ovarian cancer unresectable disease. This study aimed to determine the efficacy and safety of six cycles of NACT followed by cytoreduction. METHODS Retrospective analysis of all patients with advanced epithelial ovarian cancer, tubal carcinoma, or primary peritoneal carcinoma treated with platinum based NACT between January 2008 and February 2012. RESULTS Eighty-two patients underwent NACT; 78% and 18.2% had extensive stage IIIC or IV disease at diagnosis, respectively. Their median age was 60 years (41-82). On histology, serous adenocarcinoma was found in 90.2%. Patients did not receive chemotherapy after debulking surgery. 35.4% suffered grade 3/4 toxicity; the most commonly observed toxicities were hematologic and nausea. After NACT, 23.1% experienced clinical complete response, 57.4% partial response, and 12.1% disease progression. Complete resection of all macroscopic and microscopic disease (R0) was performed in 63.7%. Surgical complications were uncommon; however, four (6.2%) patients needed a second procedure due to operative complications and 18 (27.3%) needed blood transfusion after debulking. Over a median follow-up period of 19.2 months, median overall survival and chemotherapy-free interval were 37.5 months (confidence interval not reached) and 16 months, respectively. CONCLUSION Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective and did not increase perioperative or postoperative complications in patients with stage IIIC/IV disease who were unsuitable for optimal PDS. The overall survival of this cohort was higher than that of those treated with ID surgery.

Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial*

Objective: To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock. Design: Single center, randomized, double-blind controlled trial. Setting: Teaching hospital. Patients: Adult cancer patients with septic shock in the first 6 hours of ICU admission. Interventions: Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay. Measurements and Main Results: Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0–3] vs 0 [0–2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53–1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53–0.97; p = 0.03). Conclusions: We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.

Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy

Background: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is extremely controversial. In the era of neoadjuvant chemotherapy (NACT), endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease. Objectives: To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC submitted to NACT. Methods: This is a pilot observational study on initially unresectable, high-grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2). The inclusion criteria were clinical complete response, CA-125 normalization, imaging without disease in critical areas, and optimal cytoreduction. Results: From January 2011 to March 2014, 21 patients were included. Ten women underwent laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were observed between the groups. No surgery-related casualties, intraoperative complications, conversion to laparotomy, or excessive blood loss or transfusion was detected in the laparoscopic procedures. The mean time of operation was 292 min. The length of hospital stay averaged 3.6 days. Two women in group 1 developed relevant complications. After a mean follow-up of 20 months, the recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2. Although statistical significance was not reached, the mortality related to cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapy-free interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288). Conclusion: Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients. Nevertheless, laparoscopy was substantially associated with inferior oncologic results. Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospective trials confirm the observed results.

First report of a clinical isolate of Candida haemulonii in Brazil

The spectrum of Candida species associated with invasive fungal infections is evolving. New microbiology diagnostic tools, the increasing number of immunosuppressed patients with invasive devices and the use of prophylaxis with fluconazole could contribute to this phenomenon (1). In recent years, an increasing number of rare species with reduced susceptibility to antifungal molecules have been described, including C. ciferrii, C. inconspicua, C. guilliermondii, C. humicola, C. lambica, C. lipolytica, C. norvegensis, C. palmioleophila, C. rugosa, C. valida, C. fermentati, and C. lusitaniae (2)-(5). Data from the SENTRY Antimicrobial Surveillance Program-Fungal Objective (5) concerning bloodstream infections from 2008 and 2009 show that 4.5% of 348 episodes from 10 centers in Latin America were caused by species other than C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei. In 1984, Lavarde et al. (6) reported the first clinical isolate of C. haemulonii from a blood culture. Since then, rare cases of human infections with C. haemulonii have been reported worldwide, including central venous catheter (CVC)-related bloodstream infections in patients from Argentina, Korea, and China (7)-(11); in preterm neonates receiving parenteral nutrition in Kuwait (12); and in a 37-year-old French patient with osteomyelitis of the left hallux (13). This pathogen has not been identified in previous reports of candidemia from Brazil (14)-(17). The present paper reports for the first time a case of fungemia caused by C. haemulonii in a tertiary hospital in the city of Sao Paulo. Clinical features and laboratory analyses, including phenotypic and molecular identification and antifungal susceptibility testing (AST), are described.

Infection Related to Implantable Central Venous Access Devices in Cancer Patients: Epidemiology and Risk Factors

OBJECTIVE To describe the epidemiology of infections related to the use of implantable central venous access devices (CVADs) in cancer patients and to evaluate measures aimed at reducing the rates of such infections. DESIGN Prospective cohort study. SETTING Referral hospital for cancer in São Paulo, Brazil. PATIENTS We prospectively evaluated all implantable CVADs employed between January 2009 and December 2011. Inpatients and outpatients were followed until catheter removal, transfer to another facility, or death. METHODS Outcome measures were bloodstream infection and pocket infection. We also evaluated the effects that the creation of a multidisciplinary team for CVAD care, avoiding in-hospital implantation of CVADs, and limiting CVAD insertion in neutropenic patients have on the rates of such infections. RESULTS During the study period, 966 CVADs (mostly venous ports) were implanted in 933 patients, for a combined total of 243,792 catheter-days. We identified 184 episodes of infection: 154 (84%) were bloodstream infections, 21 (11%) were pocket infections, and 9 (5%) were surgical site infections. During the study period, the rate of CVAD-related infection dropped from 2.2 to 0.24 per 1,000 catheter-days ([Formula: see text]). Multivariate analysis revealed that relevant risk factors for such infection include surgical reintervention, implantation in a neutropenic patient, in-hospital implantation, use of a cuffed catheter, and nonchemotherapy indication for catheter use. CONCLUSIONS Establishing a multidisciplinary team specifically focused on CVAD care, together with systematic reporting of infections, appears to reduce the rates of infection related to the use of these devices.

A phase II trial with anti-Lewis-Y monoclonal antibody (hu3S193) for the treatment of platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma

OBJECTIVES The primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics. METHODS This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20mg/m(2) intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). RESULTS 26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24+weeks [clinical benefit rate 23% (95% CI=9.77%-46.71%)]. Median PFS was 8.4 weeks (95% CI=6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p=0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3). CONCLUSIONS Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.

Primary Ovary Choriocarcinoma: Individual DNA Polymorphic Analysis as a Strategy to Confirm Diagnosis and Treatment:

Abstract Primary choriocarcinoma of the ovary is rare. Furthermore, this tumor can arise from gestational tissue or pure germ cells of the ovary, with the latter resulting in non-gestational choriocarcinoma. While the clinical characteristics and histology of both tumor types are identical, differentiation of these tumors is necessary for effective treatment. One strategy for the differentiation of these tumors types is to assay for the presence of paternal DNA. Accordingly, in the present case, a patient with primary choriocarcinoma of the ovary with a non-gestational origin was confirmed by DNA analysis. The patient subsequently exhibited an excellent response to chemotherapy, and following surgery, achieved complete remission. A pathological analysis of surgical specimens further confirmed the absence of tumor.

Hereditary cancer risk assessment: essential tools for a better approach

Hereditary cancer risk assessment (HCRA) is a multidisciplinary process of estimating probabilities of germline mutations in cancer susceptibility genes and assessing empiric risks of cancer, based on personal and family history. It includes genetic counseling, testing and management of at-risk individuals so that they can make well-informed choices about cancer surveillance, surgical treatment and chemopreventive measures, including biomolecular cancer therapies. Providing patients and family members with an appropriate HCRA will contribute to a better process of making decisions about their personal and family risks of cancer. Following individuals at high risk through screening protocols, reassuring those at low risk, and referring those at increased risk of hereditary cancer to a cancer genetics center may be the best suitable approach of HCRA.

Immature Uterine Teratoma Associated with Uterine Inversion

Teratomas are the most commonly diagnosed germ cell tumors and occur primarily in testes and ovaries. Platinum-based therapy followed by surgical resection of the residual lesion is generally the recommended treatment. In contrast, immature uterine teratomas are rare, with few cases reported in the literature. Moreover, there is no standard treatment for these tumors. Non-puerperal uterine inversion is also rare in women younger than 45 years of age, and neoplastic lesions are responsible for this condition. Here, we report a case of an immature uterine teratoma associated with uterine inversion. The patient underwent surgery followed by adjuvant chemotherapy and continues to be monitored.