Phagoburst Response Level of Neutrophils to Septic and Non-Septic Acinetobacter baumannii Isolates

Background: Acinetobacter baumannii is an opportunistic pathogen causing community-acquired and nosocomial infections. Dissemination of infection to blood causes septicemia associated with serious morbidity and mortality of patients. Neutrophils are essential for the control of A. baumannii infections by different mechanisms, including oxidative burst. Aims: This study was conducted as an attempt to determine the effect of septicemic and non-septicemic A. baumannii isolates on the phagoburst response of neutrophils. Methods: Neutrophils were isolated from an immunocompetent individual; chronic myeloid leukemia (CML) and lung solid tumor (ST) patients. The phagoburst response of these neutrophils to various strains of A. baumannii isolated from septic and non-septic patients was investigated by flow cytometer. Results: The presence of this pathogen lowered the phagoburst response in the different types of neutrophils compared to their response to the opsonized Escherichia coli. The phagoburst response of the neutrophils from the immunocompetent individual was significantly higher than that of neutrophils from the immunodeficient patients when stimulated by the septicemic or nonsepticemic A. baumannii isolates. The isolate type (septicemic or non-septicemic) had no significant effect on the neutrophil phagoburst response of the immunocompetent individual and a significant effect on the phagoburst response of neutrophils from the immunodeficient patients. The phagoburst response of the neutrophils from the immunodeficient patients stimulated by septicemic A. baumannii isolates was significantly lower than that when neutrophils stimulated by the nonsepticemic isolates. Also, there was a significant difference in the phagoburst response of neutrophils from the CML and ST patients when stimulated by the septicemic and non-septicemic isolates. This observation might be due to the combined effect of virulent A. baumannii isolates and the chemotherapy regime the patient was undertaking. Conclusion: The results suggest that both the isolate type and the source of neutrophils have a significant effect on the neutrophil phagoburst response. The potential virulence of the septicemic A. baumannii isolates and dissemination to blood may be dependent on the host’s immune status and the neutrophils phagoburst response.

Unclassifiable lymphoma in pregnancy

A 28-year-old woman, 15 weeks pregnant, consulted for cervical ache and left laterocervical mass. Imaging scans revealed a large mediastinal mass that had spread to supraclavicular and left axillar spaces, including cervicobrachial plexus. Pathological anatomy confirmed an unclassifiable lymphoma, with intermediate features between diffuse large B-cell lymphoma and classical Hodgkin’s lymphoma. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy was started with partial response. But due to disease progression, an elective caesarean section was performed (30th week of pregnancy) to begin a chemotherapy regime incompatible with pregnancy. Despite acute complications related to prematurity, the newborn could be discharged from hospital at 45 days of life. The patient did not respond to the second treatment line and she is currently undergoing a third chemotherapy regime. Given the unusual occurrence of lymphoma during pregnancy, multidisciplinary teamwork between haematologists, neonatologists and obstetricians is essential to achieve the best maternal–fetal outcome.

Systemic inflammation, adjuvant chemotherapy, and survival in stage III colorectal cancer: Results from the ScotScan Colorectal Cancer Collaborative.

228 Background: The systemic inflammatory response (SIR) is a poor prognostic marker in patients with colorectal cancer (CRC), and predicts poor outcome following adjuvant chemotherapy. Whether this may be influenced by chemotherapy regime is not known. The present study examined the relationship between the pre-operative SIR, adjuvant therapy regime, and survival of patients with stage III CRC in the ScotScan cohort. Methods: Patients with stage III CRC in Scotland (1997-2015, n= 317) and Norway (2000-17, n= 312) were included. The pre-operative SIR was measured using C-reactive protein (CRP≤10mg/L or > 10mg/L). Adjuvant status was categorised as none, 5-fluorouracil-only (5FU or capecitabine), or oxaliplatin-combination (Ox). Relationship with 3 year overall (OS) and cancer-specific survival (CSS) was examined. Results: Rates of Ox were comparable between cohorts (Scotland – 26% vs. Norway 28%), although more patients from Norway received single 5FU (4% vs. 19%, P= 0.005). 36% of each cohort were systemically inflamed. Ox was associated with superior OS (90%) and CSS (92%) when compared to 5FU (77% and 84%) and no therapy (61% and 72%, both P< 0.001). Stratified by SIR, patients with CRP≤10mg/L receiving Ox or 5FU had comparable 3yr OS greater than those receiving none (90% vs. 88% vs. 67%), whereas those with CRP > 10mg/L receiving Ox had superior survival than those receiving 5FU or no therapy (89% vs. 64% vs. 53%, P-for interaction = 0.101). Results were similar for CSS (CRP≤10mg/L: 91% vs. 94% vs. 79%; CRP > 10mg/L: 94% vs. 72% vs. 62%, P-for interaction= 0.01). Although patients receiving Ox were younger and less comorbid, both use of Ox and SIR remained independently associated with OS and CSS. Conclusions: Although selection bias in the choice of adjuvant therapy may confound analysis, this study suggests the SIR may aid in determining response to adjuvant therapy. Whereas non-inflamed patients with stage III CRC may benefit from single 5FU, those with an elevated SIR may benefit greater from more intensive, Ox-based regimes. These results remain to be validated, however support the use of the SIR as a prognostic and predictive biomarker in patients with stage III CRC.

Survival analysis of osteosarcoma patients: A 15-year experience

Introduction: Management of osteosarcoma has evolved considerably for the past two decades and there have been changes of practices especially pertaining to chemotherapy regime. This is a review of our cases in the past 15 years. Method: This is a retrospective survival analysis study of 128 patients treated at University Malaya Medical Centre (UMMC) from 1997 to 2011. Results: There were 80 (62.5%) male and 48 (37.5%) female patients with the median age being 15 (5–59). Majority had osteosarcoma of extremities (94.5%). More than 60% patients developed metastasis throughout the course of treatment with 39% presenting with lung metastasis. Osteoblastic osteosarcoma was the commonest subtype (65.6%). Of the 109 patients treated surgically, 84 patients (65.6%) underwent limb salvage surgery while the rest underwent amputation. Seventy-one per cent of patients completed treatment with local recurrence rate of 22.7%. The 5-year and 10-year survival rates were 56.31% (95% CI: 46.20, 65.24) and 22.33% (95% CI: 14.86, 30.76), respectively. The 5-year event-free survival was 52.94% (95% CI: 41.83, 62.87). In multivariate analysis, the independent prognostic factors were presence of metastasis and completion of treatment for both 5-year and 10-year overall survival. Good histological response was only significant for multivariate analysis at 5 years. Patients with metastasis had a hazard ratio of 20.4 at 5 years and 3.26 at 10 years. Conclusion: Overall survival rate for osteosarcoma patients at our centre was comparably higher than other centres in the region. Two independent risk factors for survival are metastatic status and completion of treatment. A standardized chemotherapy regime is essential for long-term survival.

Pure Immature Teratoma of the Ovary in Adults: Thirty-Year Experience of a Single Tertiary Care Center

ObjectiveThe aim of this study was to evaluate clinicopathologic characteristics, treatment outcome, and reproductive function in women diagnosed with ovarian immature teratoma (IT). Our standard chemotherapy regime is currently etoposide/cisplatin (EP), creating a unique opportunity to evaluate this protocol in ovarian ITs.Materials and MethodsThis study is a retrospective analysis. Twenty-seven women older than 18 years with ovarian IT stages IA to IIIC were identified and included in this study. Patients were treated at 1 institution, Health Sciences Center, Women’s Hospital, Winnipeg, Manitoba, Canada, between 1983 and 2013.ResultsThe median age at diagnosis was 27.0 years (range, 18–36 years). Twenty-two (82%) presented with an International Federation of Gynecology and Obstetrics stage I disease, 3 (11%) had stage II, and 2 patients (7%) had stage III disease. The histologic grade distribution was grade I in 9 patients (33%), grade II in 3 patients (11%), and grade III in 15 patients (56%). Initial management was surgical for all patients: 3 (11%) hysterectomy and bilateral salpingo-oophorectomy, 1 (4%) cystectomy only, and 23 (85%) unilateral salpingo-oophorectomy. Twenty-one patients (78%) received adjuvant therapy. The median follow-up was 60 months (range, 36–72 months). One patient recurred (histological grade III) 6 months after surgery and had a complete clinical response to 4 cycles of EP chemotherapy. Twelve patients reported an attempt to conceive resulting in 10 pregnancies (8 after chemotherapy).ConclusionsOvarian IT is a curable disease. Fertility-sparing surgery should be offered. Adjuvant treatment with cisplatinum-based chemotherapy, typically with bleomycin, etoposide, and cisplatin, is still considered the standard in stages greater than stage IA grade I. Etoposide/cisplatin as a primary chemotherapy regime for early- or advanced-stage disease is an effective treatment with minimal adverse effects and high tolerability. This is the first published study examining EP as a primary treatment modality for IT. Further studies are needed to strengthen these findings.

Assessment of adherence to the guidelines for the management of nausea and vomiting induced by chemotherapy

ABSTRACT Objective: To assess adherence of the prescribing physicians in a private cancer care center to the American Society of Clinical Oncology guideline for antiemetic prophylaxis, in the first cycle of antineoplastic chemotherapy. Methods: A total of 139 chemotherapy regimens, of 105 patients, were evaluated retrospectively from 2011 to 2013. Results: We observed 78% of non-adherence to the guideline rate. The main disagreements with the directive were the prescription of higher doses of dexamethasone and excessive use of 5-HT3 antagonist for low risk emetogenic chemotherapy regimens. On univariate analysis, hematological malignancies (p=0.005), the use of two or more chemotherapy (p=0.05) and high emetogenic risk regimes (p=0.012) were factors statistically associated with greater adherence to guidelines. Treatment based on paclitaxel was the only significant risk factor for non-adherence (p=0.02). By multivariate analysis, the chemotherapy of high emetogenic risk most correlated with adherence to guideline (p=0.05). Conclusion: We concluded that the adherence to guidelines is greater if the chemotherapy regime has high emetogenic risk. Educational efforts should focus more intensely on the management of chemotherapy regimens with low and moderate emetogenic potential. Perhaps the development of a computer generated reminder may improve the adherence to guidelines.