Acute perioperative hyperlactatemia in oncoplastic reconstructive surgeries: What is the significance?

BACKGROUND AND AIMS: We aim to study the significance of intraoperative hyperlactatemia in reconstructive oncoplastic surgery. MATERIAL AND METHODS: A retrospective observational study was conducted on a cohort of patients who underwent reconstructive oncoplastic surgery with free flap for oral cancer over a 6-month period. The study population was divided into two groups based on peak lactate levels. Group N with peak lactate level less than 2 mmol/L and Group H peak lactate level more than 2 mmol/L. The various parameter studied were patient's comorbidities; intraoperative events (vasopressor requirement, blood transfusion, and duration of surgery); postoperative parameters including the need for re- exploration and duration of stay in hospital and intensive care unit. RESULTS: The study demonstrates that intraoperative rise of lactate was not influenced by comorbidities. None of the intraoperative parameters studied influenced the lactate levels. Baseline lactate level was found to correlate with peak lactate level intraoperatively. But it was observed that there was normalization of lactate level within 24 hours postoperatively in both the groups. There was no difference in outcome parameters in the two groups. CONCLUSION: Intraoperative hyperlactatemia is not a significant prognostic factor for outcome in oncoplastic reconstructive surgery.

Indian patient use of cancer euphemisms: Association with psychological outcomes and health behaviours.

OBJECTIVE: Euphemisms may be used to reduce the threat associated with the word "cancer." Cancer may be particularly threatening in Indian culture due to the myths surrounding its cause and prognosis. This study explored the prevalence of euphemism use by Indian patients and the relationship among euphemism use and illness cognitions, affect, health behaviour, and spontaneous self-affirmation (a behaviour associated with dealing with threat). METHODS: In total, 350 cancer patients in India were recruited to take part in a study exploring patients' experiences of, and thoughts about, having an illness. They responded to a questionnaire measuring illness perceptions, coping strategies, anxiety, depression, health behaviours, and spontaneous self-affirmation. Patients were asked what words they used to describe their illness; euphemism users were those who used a euphemism (ie, non-medical term) as a first word. RESULTS: About 51% of patients used a euphemism as a first word. Those with less education, unskilled employment, a lower income, and more children were more likely to be euphemism users. Euphemism users reported (a) weaker illness perceptions (less personal control, greater reporting of symptoms, and less understanding of their condition), (b) less use of 3 of 14 coping strategies, (c) less likelihood of spontaneously self-affirming, and (d) fewer healthy eating days. CONCLUSIONS: Euphemism use in patients was not related to distress but was related to negative illness perceptions and use of fewer coping strategies, suggesting that we need further study about the extent to which euphemisms signal issues in psychological adaptation to cancer diagnosis.

A health care labyrinth: perspectives of caregivers on the journey to accessing timely cancer diagnosis and treatment for children in India.

BACKGROUND: Cure rates for children with cancer in India lag behind that of high-income countries. Various disease, treatment and socio-economic related factors contribute to this gap including barriers in timely access of diagnostic and therapeutic care. This study investigated barriers to accessing care from symptom onset to beginning of treatment, from perspectives of caregivers of children with cancer in India. METHODS: Semi-structured in-depth interviews were conducted with caregivers of children (< 18 years) diagnosed with cancer in seven tertiary care hospitals across New Delhi and Hyderabad. Purposive sampling to saturation was used to ensure adequate representation of the child's gender, age, cancer type, geographical location and socioeconomic status. Interviews were audio recorded after obtaining informed consent. Thematic content analysis was conducted and organised using NVivo 11. RESULTS: Thirty-nine caregivers were interviewed, where three key themes emerged from the narratives: time intervals to definitive diagnosis and treatment, the importance of social supportive care and the overall accumulative impacts of the journey. There were two phases encapsulating the experiences of the family: referral pathways taken to reach the hospital and after reaching the hospital. Most caregivers, especially those from distant geographical areas had variable and inconsistent referral pathways partly due to poor availability of specialist doctors and diagnostic facilities outside major cities, influence from family or friends, and long travel times. Upon reaching the hospital, families mostly from public hospitals faced challenges navigating the hospital facilities, finding accommodation, and comprehending the diagnosis and treatment pathway. Throughout both phases, financial constraint was a recurring issue amongst low-income families. The caregiver's knowledge and awareness of the disease and health system, religious and social factors were also common barriers. CONCLUSION: This qualitative study highlights and explores some of the barriers to childhood cancer care in India. Our findings show that referral pathways are intrinsically linked to the treatment experience and there should be better recognition of the financial and emotional challenges faced by the family that occur prior to definitive diagnosis and treatment. This information would help inform various stakeholders and contribute to improved interventions addressing these barriers.

Specialized Palliative Care and the Quality of Life for Hospitalized Cancer Patients at a Low-Resource Hospital in India.

AIM: This study aimed to compare the quality of life (QoL) of cancer patients, with an Eastern Cooperative Oncology Group (ECOG) performance of 3-4, in contact with or without contact, with a specialized palliative care unit (PCU) at a low-resource governmental cancer hospital, as well as studying the impact of this contact on the QoL in their caregivers. MATERIALS AND METHODS: Hospitalized patients with an ECOG performance of 3 or 4 and their primary caregiver were asked to participate in this observational study. Patients in contact with the specialized PCU and their closest caregivers formed Group A, while patients and families without this contact formed Group B. Contact was mainly one consultation. The patients were asked to complete the Palliative Care Outcome Scale (POS), and the caregivers were asked to complete the Hospital Anxiety and Depression Scale (HADS) and the distress thermometer (DT). RESULTS: There was no statistically significant difference between the median POS values of the patient groups, neither regarding the total sum nor per any item. There were also no statistically significant differences between the median HADS values and median DT values when comparing the caregivers to Group A and B. CONCLUSION: Consultation with a specialized PCU at this tertiary referral center did not alter the QoL of patients with an ECOG performance of 3-4 nor did it affect the psychological well-being of their caregivers. We argue that monitoring prescribed treatment and follow-up is a necessary component of PC.

Recommendations to Support Nurses and Improve the Delivery of Oncology and Palliative Care in India.

CONTEXT: Nurses in India often practice in resource-constrained settings and care for cancer patients with high symptom burden yet receive little oncology or palliative care training. AIM: The aim of this study is to explore challenges encountered by nurses in India and offer recommendations to improve the delivery of oncology and palliative care. METHODS: Qualitative ethnography. SETTING: The study was conducted at a government cancer hospital in urban South India. SAMPLE: Thirty-seven oncology/palliative care nurses and 22 others (physicians, social workers, pharmacists, patients/family members) who interact closely with nurses were included in the study. DATA COLLECTION: Data were collected over 9 months (September 2011- June 2012). Key data sources included over 400 hours of participant observation and 54 audio-recorded semi-structured interviews. ANALYSIS: Systematic qualitative analysis of field notes and interview transcripts identified key themes and patterns. RESULTS: Key concerns of nurses included safety related to chemotherapy administration, workload and clerical responsibilities, patients who died on the wards, monitoring family attendants, and lack of supplies. Many participants verbalized distress that they received no formal oncology training. CONCLUSIONS: Recommendations to support nurses in India include: prioritize safety, optimize role of the nurse and explore innovative models of care delivery, empower staff nurses, strengthen nurse leadership, offer relevant educational programs, enhance teamwork, improve cancer pain management, and engage in research and quality improvement projects. Strong institutional commitment and leadership are required to implement interventions to support nurses. Successful interventions must account for existing cultural and professional norms and first address safety needs of nurses. Positive aspects from existing models of care delivery can be adapted and integrated into general nursing practice.

Influence of BCL2-938C>A and BAX-248G>A promoter polymorphisms in the development of AML: case-control study from South India.

B-cell lymphoma 2 (BCL2) and BCL2-associated X protein (BAX) proteins are anti-apoptotic and pro-apoptotic determinants of mitochondrial-mediated apoptosis, and their relative expression determines the cell fate. The promoter polymorphisms in these genes were shown to alter the protein function or expression and exert an impact on apoptosis regulation. Deregulation in the expression of any of these genes leads to disruption of cellular homeostasis and malignant transformation. The present study was aimed to determine the association of BCL2-938C>A and BAX-248G>A promoter polymorphisms with origin and progression of acute myeloid leukemia (AML). We also have performed combined genotype analysis to evaluate the cumulative effect of risk genotypes in the AML development. These polymorphisms were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) in 221 AML patients and 305 age- and sex-matched healthy controls. Our study revealed that BCL2-938CA (p = 0.018) and BAX-248GG (0.043) genotypes were significantly associated with increased risk for AML occurrence. BAX-248A allele had shown decreased risk for AML. The combined analysis had shown that BCL2-938CA+AA-BAX-248GG group had a 1.63-fold (95 % CI: 1.08-2.45, p = 0.02) increased risk for AML. None of the clinical variables had shown any significant association with both polymorphisms. With respect to complete remission (CR) rate, BAX-248GG genotype (p = 0.002) and G allele (p = 0.009) had conferred significant risk for complete remission failure. Although the log rank test was not significant, survival analysis had shown a trend where BCL2-938CA genotype, and BAX-248GG had reduced median disease-free survival (DFS) of 9 and 10 months, respectively. In conclusion, BCL2-938C>A and BAX-248G>A gene polymorphisms might contribute to the origin of AML. Moreover, influence of BAX-248GG genotype on CR and DFS rate suggests that the BAX-248G>A polymorphism can serve as marker for poor prognosis in AML.

Association of caspase9 promoter polymorphisms with the susceptibility of AML in south Indian subjects.

Abnormal apoptosis is one of the hallmarks of cancers including acute myeloid leukemia (AML), as it plays a pivotal role in precisely maintaining self-renewal, proliferation, and differentiation properties of hematopoietic stem cells (HSCs). Caspase9 (CASP9), an initiator caspase activated by mitochondrial-mediated apoptotic pathway (intrinsic pathway), triggers cascade of effector caspases and executes apoptosis. Functional SNPs in CASP9 might influence the gene expression leading to altered apoptosis which confer the risk to AML. To test this hypothesis, we have analyzed four CASP9 gene polymorphisms [CASP9 - 1263A > G (rs4645978), CASP9 - 712C > T (rs4645981), CASP9 - 293_275del CGTGAGGTC AGTGCGGGGA (-293del) (rs4645982), and CASP9 Ex5 + 32G > A (rs1052576)] in 180 AML cases and 304 age- and sex-matched healthy controls. We performed various statistical analyses to determine the potential interactions between these SNPs and AML. The study revealed that presence of G allele at CASP9 - 1263 position elevates the risk of AML 1.53-fold and CT/TT genotype at CASP9 - 712 position by 2.60-fold under dominant model of inheritance. Two CASP9 haplotypes, G-del(+)-C-A and G-del(+)-T-A, were found to be significantly associated with increased AML risk by 2.19- (95 % confidence interval (CI), 1.09-4.39; p = 0.028) and 11.75-fold (95 % CI, 1.01-136.57; p = 0.05), respectively. Further, multidimensionality reduction (MDR) analysis had revealed single locus CASP9 - 712C > T SNP and four loci CASP9 - 1263A > G, CASP9 - 293del, CASP9 - 712C > T, and CASP9 Ex5 + 32G > A SNPs as highest predicting models for AML development. Our results revealed a significant association of two SNPs in CASP9 (-1263A > G and -712C > T) and two haplotypes of the four SNP combinations with AML susceptibility.

Gelatinase B (-1562C/T) polymorphism in tumor progression and invasion of breast cancer.

Matrix metalloproteinases (MMPs) play an important role in breast cancer tumor invasion and progression. MMP-9 is a member of the MMP family and is also known as Gelatinase B or type IV collagenases (92 kDa) and possesses proteolytic activity against type IV collagen, a major component of the basement membrane. Our study aims to examine the association of Gelatinase B (-1562C > T) promoter polymorphism with breast cancer invasion and progression. The study involves 200 breast cancer patients and age-matched 191 healthy controls. The SNP-1562C > T (rs3918242) in MMP-9 promoter region was examined by allele-specific polymerase chain reaction and gel electrophoresis. The genotypes were determined and compared between patients and controls, and the influence of the polymorphism on clinicopathological data was analyzed. The T allele of the -1562C > T MMP-9 polymorphism was detected more frequently in breast cancer patients than controls (p < 0.001). Our results suggest the clinical importance of MMP-9 gene polymorphism (-1562C > T) in breast cancer patients. The study may also help in identifying individuals at risk of developing breast cancer.

Low-Dose Oral Ketamine for Procedural Analgesia in Pediatric Cancer Patients Undergoing Lumbar Puncture at a Resource-Limited Cancer Hospital in India.

Aim: The aim of this study was to evaluate the therapeutic efficacy and safety profile of orally administered low-dose ketamine for procedural pain management in pediatric cancer patients undergoing lumbar puncture (LP) in a resource-limited hospital setting. Methods: Patients between 4 and 15 years of age, with leukemia, undergoing LP were asked to participate. The study was designed as a two-armed blinded placebo-controlled trial where 0.8 mg/kg (bodyweight) of ketamine mixed in juice was given 30 minutes before the procedure to Group K (ketamine) compared with placebo, only juice, to Group P (placebo). In addition, topical analgesia (EMLA®) was given according to established standard of care. Patients and caregivers assessed the pain using the Wong-Baker Faces Pain Rating Scale. Results: A total number of 52 patients, equally distributed between Group K and Group P, were included in the study. The placebo-controlled group had significantly higher self-reported pain score than the group receiving ketamine (p = 0.046), as well as in caregiver-assessed pain (p = 0.033). Only three incidents of mild adverse effects were reported. Conclusion: Low-dose oral ketamine can be safely administered for procedural analgesia in pediatric cancer patients undergoing LP in a resource-limited hospital setting and have significant pain-reducing effect compared with placebo.

Cancer Treatment and End-of-Life Care.

AIM: To study to what extent tumor-specific treatment (chemo- or radiotherapy) was given during the last 30 days in life and to examine how many of the patients were referred to a specialized palliative care unit (PCU), at a low-resource governmental hospital in India. PATIENTS AND METHODS: Medical records of adult cancer patients deceased between April 1 and May 31 in 2016, and pediatric cancer patients deceased between April 1 and September 30 in 2016 were collected. Data regarding gender, age at admission, cancer diagnosis, tumor-specific treatment received, referral to the PCU, and date of death, were sampled. RESULTS: A total of 96 patients (52 adults and 44 pediatric patients) were included in the study. In the last 30 days of life, tumor-specific treatment was given to 39 adult patients and 38 pediatric patients. During the last week in life, 26 adult and 25 pediatric patients, respectively, received tumor-specific treatment. Twenty-six adult and 25 pediatric patients, respectively, were referred to the PCU. End-of-life (EoL) tumor therapy was given to a lesser extent among referred patients. CONCLUSIONS: Eighty percent of the patients were given tumor-specific treatment near EoL. Half of the patients had been referred for specialized palliative care (SPC).

End-of-Life Treatments in Pediatric Patients at a Government Tertiary Cancer Center in India.

AIM: The primary objective of this study was to describe demographics and end-of-life treatments of children with cancer at a government tertiary cancer center in India. METHODS: A retrospective review was undertaken of medical charts of all children younger than 18 years, who died as inpatients while undergoing treatment at the pediatric oncology department between April and September 2016. Data were collected on demographics, diagnosis, treatments, survival, palliative care involvement, and symptoms at end of life. RESULTS: There were 44 pediatric oncology patients who died in the hospital during the study period. The most frequent diagnoses were hematological malignancies (n = 29). Tumor-specific treatment was given to 38/44 (86%) patients in the last 30 days of life, and 13 patients in the last day of life or 1 day before. Of all deaths, 23/44 (52%) occurred within 30 days of admission to the pediatric ward and 34/44 (77%) within 90 days. Of the 44 patients, 25 (57%) were referred to palliative care. The median number of days between referral and death was 14 (0-78) days. Frequent symptoms documented were bleeding (11/44), dyspnea (10/44), pain (7/44), seizures (7/44), and delirium (5/44), with each patient having one or more of these symptoms. Only patients with a palliative care referral received opioid analgesics or benzodiazepines at the end of life. CONCLUSIONS: This study highlights the demographics of suffering, death, and end-of-life care in children with cancer at a government tertiary cancer center in India.

Role of the MDM2 promoter polymorphism (-309T>G) in acute myeloid leukemia development.

BACKGROUND: The human homologue of the mouse double minute 2 (MDM2) gene is a negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was found to be associated with overexpression thereby attenuation of Tp53 stress response and increased cancer susceptibility. We have planned to evaluate the possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy in AML. MATERIALS AND METHODS: A total of 223 de novo AML cases and 304 age and sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism through the tetra-primer amplification refractory mutation system (ARMS)-PCR method. In order to assess the functional relationship of -309T>G SNP with MDM2 expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were correlated with disease free survival (DFS) rates among patients who have achieved complete remission (CR) after first induction chemotherapy. RESULTS: MDM2-309T>G polymorphism was significantly associated with AML development (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered 1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p=0.003) increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11 months) and TG (9 months) genotype groups. Further, MDM2 expression was also found to be significantly elevated in GG genotype patients (p=0.0039) and among CR+ve cases (p=0.0036). CONCLUSIONS: The MDM2-309T>G polymorphism might be involved in AML development and also serve as a good prognostic indicator.

A novel technique to prevent endobronchial spillage during video assisted thoracoscopic lobectomy.

Endobronchial spillage of fungal material into normal lung can infect it and the spillage of fungal material should be prevented during surgery. We report our experience of a patient who presented for right upper lobectomy with bronchiectasis, tubercular destruction and subsequent aspergilloma. A 4F Fogarty catheter was introduced through the tracheal lumen of the left sided endobronchial double lumen tube (DLT) to occlude the bronchus intermedius to prevent spillage of aspergilloma into the non-infected lower and middle lobes of the right lung. The Fogarty catheter was pulled into the trachea just before stapling the bronchus; thereafter, right upper lobectomy was completed successfully. The patient was extubated uneventfully and transferred to post-operative recovery ward. The endobronchial blockage of the intermediate bronchus of the operative lung by the Fogarty catheter and isolation of the left lung by the DLT prevented spillage of aspergilloma in both the operative right lung and the left lung.

Palliative chemotherapy in head and neck squamous cell cancer - What is best in Indian population? A time without symptoms, treatment toxicity score based study.

BACKGROUND: Patients with recurrent and metastatic head and neck Squamous Cell Cancer (HNSCC) have poor prognosis with limited treatment options. In view of decimal prognosis, the treatment decision should include quality of life (QOL) issues, cost-effectiveness besides the response rates and survival. AIM: Present retrospective analysis was conducted to evaluate efficacy (disease-free survival), pharmacoeconomics, and toxicity profile of four (4) different regimens, viz. gefitinib alone, gefitinib with methotrexate, methotrexate alone, or 5-FU with cisplatin. MATERIALS AND METHODS: Case records between 2007 September and 2008 September were analyzed, 68 patients were found suitable for analysis. Patients received gefitinib (250 mg/day), methotrexate as 50 mg intramuscular weekly or a combination of the same or 5-FU 750 mg/m(2)/day for 4 days along with cisplatin 75 mg/m(2)/day on day 1 in 21-day cycle. RESULTS: A total of 68 patients received therapy. Fifty-one patients have clinically meaningful response (stable disease + complete + partial responses) (75%) and had symptomatic improvement. The median progression-free survival was significantly superior in responders (those who achieved partial or complete response) (8.4 months vs. 3.1 months, P=0.001). Methotrexate with gefitinib had maximum median survival and better overall QOL compared to the other treatment regimens. Weekly methotrexate is relatively cost-effective followed by methotrexate with gefitinib and gefitinib alone. 5-FU with cisplatin in our experience does not appear so attractive in view of high complication rates (when given in full doses) and prolonged hospital stay. CONCLUSION: Based on the results of this retrospective analysis, methotrexate weekly as single agent or in combination with gefitinib appears as an attractive alternative regimen for patients with metastatic HNSCC including those having poor performance status. A prospective study was planned and submitted to the local ethics committee based on above results to validate these results and compare methotrexate and gefitinib arm with 5-FU + cisplatin.

Factors influencing progression-free survival in gastrointestinal stromal tumors with special reference to pathologic features, cytogenetics, and radiologic response.

BACKGROUND: Treatment of gastrointestinal stromal tumors (GISTs) changed significantly with the advent of targeted therapy with imatinib. Clear markers predictive of response to imatinib therapy and disease-free survival in patients with GIST have not been identified. Even RECIST criteria are inadequate for predicting response to therapy, especially in patients with stable disease. Data collected at a tertiary care cancer center from 2003 to 2005 in south India were analyzed retrospectively to assess clinical, pathologic, and cytogenetic profiles of patients with GIST. In addition, radiologic responses to therapy were evaluated for correlation with the disease-free survival. METHODS: GIST was defined as a mesenchymal spindle/epitheloid cell lesion arising in the GI tract with CD117 positivity. Only data from patients with locally advanced or metastatic disease were analyzed. Clinical and pathologic details of the patients were noted from case records. NCCN guidelines were followed for the treatment. Radiologic response to therapy was reassessed according to RECIST, and progression-free survival calculated for all analyzed patients using intent-to-treat analysis. RESULTS: The mean age of presentation was 42.8 ± 5.3 years (24-60), with a male-to-female ratio of 1.5:1. Small intestine was the most common disease site (60%), followed by stomach (20%), mesentery (7.2%), colorectal regions (7.2%), and other sites (5.6%). The most frequent pathologic finding in patients having recurrence was high mitotic rate. Initial tumor size (either in the metastatic setting or in local recurrence) had no bearing on progression-free or overall survival, nor did initial anatomic location or site of metastasis. Histologically, however, patients with a mixed-cell morphology had shorter survival compared to the other morphologies. Those patients having any cytogenetic abnormality had worse outcome compared to those with normal karyotype. Similarly, among patients who achieved remission, those who did so within 12 weeks had better overall survival than did those with a delayed time to remission. Overall survival of patients having stable disease and late partial responses (after 3 months) was similar and superior to survival for patients whose disease progressed while on therapy. CONCLUSION: GISTs characterized by a high mitotic rate and mixed-cell morphology and any cytogenetic abnormalities are associated with poorer outcome. Similarly, shorter time to response was more important than the actual response to therapy. Initial disease site, the site of metastasis, and tumor size had no bearing on outcomes to therapy.

Risk-scoring system for predicting mucositis in patients of head and neck cancer receiving concurrent chemoradiotherapy [rssm-hn].

BACKGROUND: One of the most distressing complications of head and neck cancer patients on chemoradiotherapy is mucositis. There is no proper tool to predict its occurrence in these patients. AIM: This study was conducted to develop a risk-scoring system to predict probable incidence and severity of mucositis in head and neck cancer patients on chemoradiotherapy. MATERIALS AND METHODS: This is a retrospective analysis conducted at a tertiary care cancer center with approximately 2,000 new cases of head and neck cancer patients annually. We Hypothesized were age, comorbid conditions, leukocyte count, nutritional status, oral hygiene, tobacco use, erythrocyte sedimentation rate (ESR); Eastern cooperative oncology group (ECOG) performance status (PS) and TNM (tumor, node, metastasis) stage as possible risk factors. Receiver operating characteristic (ROC) curves were drawn to predict the cutoff values for risk factors, and a final scoring system was developed with sensitivity and specificity data. RESULTS: A total of 218 patients on chemoradiation receiving cisplatin 40 mg/m2 /week along with local radiation of 60-70 Gy depending on primary site were analyzed. Based on ROC analysis, the following cutoff values were selected: age > 40 years, ECOG PS > 2, WBC < 3000/µL, elevated ESR, albumin < 3 gm/dL and > stage III disease. The remaining factors were indicated as present or absent. A score of 1 was assigned for the above risk factors. For patients, the final score of 3 or less there is 17% probability of developing grade 3 or 4 mucositis, while patients having score of 6 or more have 76% probability. CONCLUSION: The current tool is fairly accurate in predicting development of mucositis in head and neck cancer patients on chemoradiotherapy. This will further help clinicians to adopt preventive strategies as well as better counseling.

Health-related quality of life among children with cancer in Hyderabad, India.

OBJECTIVE: Health-related quality of life (HRQL) experienced by children with cancer is more important than ever before as survival rates are increasing. The aim of this study was to assess the HRQL of children with cancer in a developing country, using physician proxy assessments. METHODS: The Health Utilities Index (HUI) was chosen as the measurement tool and physicians' assessments were obtained using an HUI proxy-respondent interview-administered questionnaire. RESULTS: A total of 45 patients and their physicians (n=6) were recruited from 2 hospitals in Andhra Pradesh, India. Most of the children had acute lymphoblastic leukaemia. There were no differences in patterns observed between cancer types for the child's HRQL, but there was wide variation in the total HRQL scores among the children. This variation was more evident in certain aspects of children's life such as emotion and pain. CONCLUSION: This study has shown that HRQL as determined by physician proxy assessments in children with cancer in India is compromised, matching results in similar populations elsewhere.

Emp is a component of the nuclear matrix of mammalian cells and undergoes dynamic rearrangements during cell division.

Emp, originally detected in erythroblastic islands, is expressed in numerous cell types and tissues suggesting a functionality not limited to hematopoiesis. To study the function of Emp in non-hematopoietic cells, an epitope-tagged recombinant human Emp was expressed in HEK cells. Preliminary studies revealed that Emp partitioned into both the nuclear and Triton X-100-insoluble cytoskeletal fractions in approximately a 4:1 ratio. In this study, we report investigations of Emp in the nucleus. Sequential extractions of interphase nuclei showed that recombinant Emp was present predominantly in the nuclear matrix. Immunofluorescence microscopy showed that Emp was present in typical nuclear speckles enriched with the spliceosome assembly factor SC35 and partially co-localized with actin staining. Coimmunoprecipitation and GST-pull-down assays confirmed the apparent close association of Emp with nuclear actin. During mitosis, Emp was detected at the mitotic spindle/spindle poles, as well as in the contractile ring during cytokinesis. These results suggest that Emp undergoes dynamic rearrangements within the nuclear architecture that are correlated with cell division.

Safety and efficacy of peripheral blood progenitor cell mobilization and collection in patients with advanced coronary heart disease.

Information on the safety of mobilization and collection of peripheral blood progenitor cells (PBPC) in patients with advanced coronary heart disease (CHD) is limited. We report herein our early experience with patients participating in a Phase I trial of injection of autologous CD 34(+) cells into threatened, ischemic myocardium for neovascularization and symptom relief in patients with chronic refractory myocardial ischemia. All patients had advanced inoperable CHD despite the best medical therapy. Granulocyte colony stimulating factor (G-CSF, 5 microg/kg/day) was administered subcutaneously for 5 days for mobilization of CD34(+) cells into the peripheral blood. PBPCs were collected in the outpatient apheresis suite on day 5. Nine patients from our institution were evaluable. Adverse effects of mobilization included: increase in frequency and/or intensity of angina in 8 patients (88.8%); bone pain in 7 patients (77.7%); headaches in 4 patients (44.4%); 2 patients (22%) were hospitalized. Collection phase toxicities included: tingling in 5 patients (55.5%) and angina in 3 patients (33%). All procedures were completed without new myocardial infarction, congestive heart failure, or death. The median peripheral blood CD34(+) cell count on day 5 of G-CSF was 21 cells/microl (range 10-40 cells/microl). A median of 1.65 x 10(6) CD34(+) cells/kg (range: 0.13-3.0 x 10(6)/kg) were harvested. We conclude that mobilization and collection of PBPC in patients with advanced CHD can be safely performed as an outpatient procedure. Apheresis professionals should be aware of the intensity and frequency of angina in this patient population.