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1.
Int J Obstet Anesth ; : 103974, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38508961

ABSTRACT

BACKGROUND: Neuraxial anesthesia with reactivation of a labor epidural catheter is commonly utilized for postpartum tubal ligations (PPTL), although the optimal anesthetic approach is unknown. We assessed institutional anesthesia practices for PPTL, and evaluated the failure rates of reactivation of labor epidural catheters, de novo spinal anesthesia, and spinal anesthesia after failed blocks. METHODS: We conducted a single-center retrospective cohort analysis of 300 consecutive patients who underwent a PPTL and 100 having spinal anesthesia for cesarean delivery. Anesthetic management data (existing labor epidural catheter reactivation, de novo spinal anesthesia or general anesthesia) were collected from electronic medical records. Anesthetic block failure rates were determined for each anesthetic technique. RESULTS: The failure rate was 15% for de novo spinal anesthesia and 23% after failed reactivation of a labor epidural catheter or spinal anesthesia. The epidural catheter reactivation failure rate was 35%. The failure rate of spinal anesthesia for cesarean delivery was 4%. Drug dosage, epidural catheter use in labor, time since epidural catheter placement or delivery, labor neuraxial technique (combined spinal-epidural, epidural), supplemental top-up doses during labor, and anesthesiologist experience did not predict neuraxial anesthesia failures. CONCLUSIONS: Our analysis revealed an unexpectedly high neuraxial anesthesia failure rate even when de novo spinal anesthesia was used for PPTL. The results are consistent with other institutions' recent findings, and are higher than spinal anesthesia failure rates associated with cesarean delivery. Further studies are required to determine optimal anesthesia dosing strategies, and to understand the mechanisms behind high neuraxial anesthesia failures for PPTL.

2.
Int J Obstet Anesth ; 51: 103256, 2022 08.
Article in English | MEDLINE | ID: mdl-35636143

ABSTRACT

BACKGROUND: Peripartum quantitative blood loss (QBL) measurement is recommended over visual estimation. However, QBL measurement after vaginal delivery has been inadequately evaluated. The primary aim of this study was to determine the characteristics of QBL measurements from a large, multicenter cohort of patients having vaginal deliveries. We also determined the incidence of postpartum hemorrhage (PPH) and the relationship between gravimetric QBL from weighed sponges vs. volumetric QBL from liquid drape or suction cannister contents. METHODS: Data were collected from 41 institutions in the United States of America that use an automated QBL device after vaginal delivery as part of routine care. The QBL device tracks cumulative blood loss based on gravimetry and volumetric V-drape assessment, automatically subtracting the dry weights of all blood-containing sponges, towels, pads and other supplies as well as the amniotic fluid volume. RESULTS: Between January 2017 and April 2020, 104 079 QBL values were obtained from patients having vaginal deliveries. Total median [IQR] QBL was 171 [61-362] mL. The PPH incidence, stratified by QBL, was 15.2% (>500 mL), 3.4% (>1000 mL), and 1.0% (>1500 mL). The contribution of QBL from V-drapes was 60.6±26.3% of total QBL. CONCLUSION: Results from this large set of QBL measurements and the PPH incidence provide normative "real-world" clinical care values that can be expected as hospitals transition from estimated blood loss to QBL to assess the blood loss at vaginal delivery.


Subject(s)
Delivery, Obstetric , Postpartum Hemorrhage , Delivery, Obstetric/methods , Female , Humans , Incidence , Postpartum Hemorrhage/epidemiology , Pregnancy , Retrospective Studies
3.
Clin Transl Oncol ; 21(8): 1093-1103, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30739242

ABSTRACT

AIMS: The primary standard treatment for classic Hodgkin's lymphoma (cHL) is chemotherapy and radiation therapy. However, some patients get relapsed, or their diseases become resistant. PD1 blocking antibodies have been used to increase the response of treatment in solid tumors, and led to potentially stable responses that are acceptable. Our purpose in this study is to investigate the effect of nivolumab as a PD1 blocking antibody on the survival rate of patients with Hodgkin's cancer. METHODS: Databases were found in International Medical Sciences, Web of Science, Medline, Scopus, Index Copernicus, PubMed, DOAJ, Google Scholar, EBSCO-CINAHL, and Persian databases containing SID and Magiran using keywords such as: "checkpoint inhibitor", "nivolumab", "Hodgkin lymphoma", and "PD1 Blockade". The risk of bias was determined by two external observers using the Cochrane checklists. After the search, the data provided in 51 documents was independently evaluated. Duplicate papers were excluded. Assessing the full texts of the remaining papers, 7 papers were approved. RESULTS: Pooled data of these seven studies revealed that the overall objective response rate was 68% (CI 64.1% to 72.1%; heterogeneity; I2 = 40.19%; p = 0.123) with partial remission (52%; CI 46.5% to 57.6%; heterogeneity; I2 = 28.36%; p = 0.212). In the pooled analysis, complete remission was 16.8 (CI 11.1% to 26.4%). Pooled data of six studies showed that stable disease was averaged to 19% (CI 16% to 23%; heterogeneity; I2 = 30%; p = 0.209; fixed-effect model). CONCLUSIONS: The results of the study indicate that nivolumab as a PD1 pathway inhibitor can be effective in treating relapsed and refractory cHL patients compared to other therapies, and lead to more effective treatment over the long term. Furthermore, the adverse effects of nivolumab are controllable and have a good safety profile.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Drug Resistance, Neoplasm/drug effects , Hodgkin Disease/mortality , Neoplasm Recurrence, Local/mortality , Nivolumab/therapeutic use , Salvage Therapy , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Humans , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Prospective Studies , Remission Induction , Survival Rate
4.
Andrologia ; 50(2)2018 Mar.
Article in English | MEDLINE | ID: mdl-28730645

ABSTRACT

The study was designed to evaluate the effects of metformin on apoptosis and epididymal sperm quality in a rat testicular ischaemia/reperfusion (I/R) injury model. A total of 72 male rats were divided into four groups (n = 18 for each group): group 1 (sham-operated group), group 2 (metformin group), group 3 (torsion/detorsion [T/D] + saline) and group 4 (T/D + 300 mg kg-1 metformin). Testicular torsion was achieved by rotating the right testis 720° in a clockwise direction for 1 hr. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in comparison with sham-operated group 4 hr after detorsion (p < .001). In six rats of each group 24 hr after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubule diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in six animals per group. Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4 hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved. Reduction in oxidative stress and apoptosis may have a major role in cytoprotective effects of metformin.


Subject(s)
Apoptosis/drug effects , Enzyme Activators/pharmacology , Metformin/pharmacology , Reperfusion Injury/physiopathology , Spermatozoa/physiology , AMP-Activated Protein Kinases/metabolism , Animals , Caspase 3/metabolism , Catalase/metabolism , Disease Models, Animal , Enzyme Activators/therapeutic use , Epididymis/cytology , Epididymis/drug effects , Epididymis/pathology , Humans , In Situ Nick-End Labeling , Male , Malondialdehyde/metabolism , Metformin/therapeutic use , Oxidative Stress/drug effects , Rats , Rats, Wistar , Reperfusion Injury/drug therapy , Reperfusion Injury/etiology , Sperm Count , Spermatic Cord Torsion/complications , Spermatozoa/drug effects , Testis/pathology
5.
Case Rep Oncol ; 10(2): 438-441, 2017.
Article in English | MEDLINE | ID: mdl-28626403

ABSTRACT

A 24-year-old woman presented with a 5-month history of a left flank mass that was painful on palpation. Magnetic resonance imaging revealed a 10.0 × 6.0 × 2.5 cm mass consistent with lipoma. A fatty lobulated mass was excised and subjected to H&E staining and immunohistochemical analyses. The specimen consisted of mature univacuolated adipocytic cells, with intermixed multivacuolated eosinophilic granular cells. No atypia or hyperchromasia was identified. Most of the cells were S100 positive and Ki-67 immunonegative. A diagnosis of a lipoma-like hibernoma was rendered. Hibernomas are rare benign lipomatous tumors that show differentiation toward brown fat. The lipoma-like hibernoma subtype is rare and can be misdiagnosed as atypical lipoma or well-differentiated liposarcoma. Here we describe an example of this rare tumor.

6.
Asian Pac J Cancer Prev ; 18(2): 431-435, 2017 02 01.
Article in English | MEDLINE | ID: mdl-28345826

ABSTRACT

Background: Lymphadenectomy, as part of the initial surgical staging of patients with endometrial carcinoma, remains a controversial topic in gynecologic oncology. Sentinel lymph node (SLN) mapping has become a well-accepted procedure for melanomas and breast cancer; a number of investigators have begun to explore the utility and accuracy of this technique with regard to endometrial cancer. Aim: This study was conducted to evaluate SLN mapping of early stage endometrial cancer with blue dye in conjunction with a radioactive tracer. Subjects and methods: In this prospective cross-sectional study, patients with stage I and II endometrial cancer who were candidates for systemic lymph node dissection during surgery were enrolled, some underwent lymph node mapping and SLN biopsy using combined intra cervical radiotracer and blue dye injections and some applying only an intra cervical radiotracer. SLNs and other lymph nodes were sent for pathological assessment. Sensitivity, specificity, the positive predictive value, and the negative predictive value were calculated as predictive values for the radiotracer and blue dye. Results: Pre-operative lymph node mapping showed SLN in 29 out of 30 patients. Intra operations in 29/30 patients, SLNs were harvested by gamma probe; in 13 out of 19 patients SLNs were detected by blue dye. The median number of SLNs per patient was 3 and the total number of SLNs detected was 81. Four patients had positive pelvic lymph nodes. All of the positive nodes were SLNs. Using this technique (radiotracer and blue dye) an overall detection rate of 96.7%, an NPV of 100%, a sensitivity of 100% and a specificity of 3.85% were achieved. Conclusion: Results of SLN research for endometrial cancer are promising and make feasible the possibility of avoiding unnecessary aggressive surgical procedures in near future by advances in SLN mapping.

7.
J La State Med Soc ; 168(1): 6-7, 2016.
Article in English | MEDLINE | ID: mdl-26986859

ABSTRACT

A seven-year-old African-American male presented with a history of hematuria, proteinuria, jaundice, and anemia occasionally treated with transfusions since early childhood. The family history included a father and sister with similar symptoms of anemia, both of which had been diagnosed with hereditary pyropoikilocytosis. Due to the patient's family history and symptoms indicating a possible hematologic problem, a blood draw was performed. Laboratory studies showed an elevated alkaline phosphatase and bilirubin, and hemolytic anemia with unusual erythrocyte indices. The patient's vital signs and abdominal ultrasound were normal, and he had no known allergies. Examination of the patient's peripheral blood smear revealed extreme erythrocyte poikilocytosis with bizarre forms resembling the erythrocyte morphology sometimes seen in individuals with severe thermal burns.


Subject(s)
Elliptocytosis, Hereditary/diagnosis , Erythrocytes, Abnormal , Anemia, Hemolytic, Congenital , Burns/diagnosis , Child , Erythrocytes , Humans , Male
8.
Transplant Proc ; 47(2): 394-8, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25769580

ABSTRACT

BK virus-associated nephropathy (BKVN) can cause clinically significant viral infection in renal transplant recipients, leading to allograft dysfunction and loss. The usual management of BKVN involves the reduction of immunosuppression and the addition of leflunomide, quinolones, and cidofovir, but the rate of graft loss remains high. The aim of this study was to assess the impact of treatment with intravenous human immunoglobulin (IVIG) on the outcome of BKVN in renal transplant recipients. Upon diagnosis of BKVN, patients remained on anti-polyomavirus treatment, consisting of the reduction of immunosuppression and the use of leflunomide therapy. Treatment with IVIG was given only to patients who did not respond to 8 weeks of the adjustment of immunosuppression and leflunomide. All 30 patients had persistent BKV viremia and BKVN with their mean BK viral loads higher than the baseline (range, 15,000-2 million copies/mL). Mean peak BK load was 205,314 copies/mL compared with 697 copies/mL after 1 year of follow-up. Twenty-seven patients (90%) had a positive response in clearing viremia. The actuarial patient and graft survival rates after 12 months were 100% and 96.7%, respectively. IVIG administration appeared to be safe and effective in treating BKV viremia and BKVN and preventing graft loss in patients who had inadequate response to immunosuppression reduction and leflunomide therapy.


Subject(s)
BK Virus/isolation & purification , Immunoglobulins, Intravenous/therapeutic use , Kidney Transplantation/adverse effects , Kidney/virology , Transplant Recipients , Tumor Virus Infections/drug therapy , Viremia/drug therapy , Female , Humans , Immunologic Factors/therapeutic use , Immunosuppression Therapy/adverse effects , Male , Middle Aged , Polyomavirus Infections/virology , Tumor Virus Infections/virology , Viral Load , Viremia/virology
9.
Transpl Infect Dis ; 16(5): 724-32, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25208755

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) is the most common cause of viral infection, causing morbidity and mortality among renal transplant recipients (RTRs). Cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and interferon-gamma (IFN-γ) have been shown to possess antiviral properties, and their polymorphisms are associated with disease outcome. The aim was to investigate the association of gene polymorphisms in IL-10, IFN-γ, and TNF-α with CMV infection in RTRs. METHODS: IL-10 -1082 A>G, -592 A>C; TNF-α -308 A>G; and IFN-γ +874 A>T gene polymorphisms were studied in 247 Hispanic RTRs (52 RTRs with CMV infection and 195 without CMV infection), using DNA-based polymerase chain reaction with sequence-specific primers and restriction. RESULTS: Median time to CMV infection was 8 months, with a mean peak CMV viral load of 25,314 copies/mL. Patients with donor-positive/recipient-negative (D+/R-) serostatus were found to be associated with a high risk of CMV infection (P = 0.001). A statistically significant correlation was found between IFN-γ +874 A>T polymorphism and the risk of CMV infection. The IFN-γ +874 AA genotype was associated with a 3.4-fold increased risk for the CMV-infected group compared to the non-CMV group (odds ratio = 3.4, 95% confidence interval = 1.24-9.34, P = 0.01). The association was independently significant in multiple logistic regression (P = 0.01), along with serologic status D+/R-, acute rejection, and anti-thymocyte globulin induction. The allelic as well as genotypic frequencies of TNF-α and IL-10 did not significantly differ between the CMV-infection group and the control group. Individuals with IFN-γ +874 AT and AA genotypes exhibited higher risk of allograft loss. CONCLUSION: This study suggested that RTRs with variant homozygous IFN-γ AA genotype were at risk of CMV infection, whereas the high producer IFN-γ +874 TT genotype appears to be associated with lower risk of CMV infection.


Subject(s)
Antibodies, Viral/blood , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/genetics , Cytomegalovirus/immunology , Hispanic or Latino/genetics , Interferon-gamma/genetics , Kidney Transplantation/adverse effects , Adult , Case-Control Studies , Cytomegalovirus Infections/virology , Female , Gene Frequency , Genotype , Graft Rejection/genetics , Humans , Incidence , Interleukin-10/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide , Retrospective Studies , Risk Factors , Tumor Necrosis Factor-alpha/genetics , Viral Load
10.
Oncol Lett ; 3(4): 855-859, 2012 Apr 01.
Article in English | MEDLINE | ID: mdl-22741006

ABSTRACT

The aim of this study was to investigate the outcome of patients with muscle-invasive bladder cancer (MIBC) receiving neo-adjuvant chemotherapy (neo-CT) using a cisplatin-based regimen fractionated on days 1 and 8 of a 21-day cycle prior to organ-preservation (chemoradiation) or cystectomy. Patients with stage T2-T4, N0, M0, transitional cell carcinoma (TCC) of the bladder with a calculated glomerular filtration rate (GFR) ≥40 ml/min were eligible for inclusion in the study. Neo-CT comprised of gemcitabine (1,000 mg/m(2) d1, d8, q21) plus cisplatin (35 mg/m(2) d1, d8, q21) for four cycles. Following the administration of neo-CT, patients underwent surgery or radiotherapy (RT) with or without concurrent chemotherapy (CRT), based on the response to neo-CT and clinician and patient preference. A total of 23 patients were recruited: 21 males and 2 females; median age, 69 years (range, 49-85); stage T2=11, T3A=7, T3B=5, grade 2=1, grade 3=22. One patient progressed prior to neo-CT. In total, 75 cycles of neo-CT were administered. Treatment was well-tolerated with only one episode of neutropenic sepsis. Three of 22 patients developed early progression and did not receive radical treatment. For the remaining 19 patients, choice of definitive treatment (surgery vs. RT/CRT) was based on response to neo-CT. Eight patients had residual disease at cystoscopy following the completion of neo-CT; six patients underwent surgery and two underwent RT/CRT. A total of 11 patients had a complete response (CR) to neo-CT, nine of whom were treated by RT/CRT, with the remaining two declining radical treatment. Median follow-up for alive patients was 57 months (range, 4.4-68.5). Three-year survival was 37% (95% CI 17-58%) and 5-year survival was 31% (95% CI 15-52%). Neo-CT is effective and well-tolerated in MIBC. This split-dose cisplatin regimen facilitates treatment in an outpatient setting and allows inclusion of patients with compromised GFR.

11.
Iran J Cancer Prev ; 4(4): 170-6, 2011.
Article in English | MEDLINE | ID: mdl-26322194

ABSTRACT

BACKGROUND: Her2/neu is one of the epidermal growth factor receptors families and seems to have prognostic significance of some solid tumors. The objective of this study is to evaluate the possibility of Her2 expression in gastric cancers and the possible relationship of Her2 with tumor's clinicopathologic parameters and also its prognostic role. METHODS: This study was performed on 100 cases of gastric carcinoma with stage I b to III (according to TNM staging). Survival, recurrence date of patients, grade and lymph nodes involvement were assessed. Her2/neu expression was determined by immunohistochemical method on received sample blocks. Survival of patients with or without Her2-neu expression were evaluated by Kaplan- Meier method and compared with the log-rank test followed by multivariate analysis using Cox regression. RESULTS: Seven cases were 3+ membranous Her2 reactivity, 5 cases were 2+ and13 cases were 1+; also 75% of cases demonstrated no reactivity. Regardingrelationship between tumor grade and membranous Her2 , all patients with poorly differentiated tumors were Her2 negative but patients with moderate and well differentiated tumor had 18.1% and 19.6% Her2 reactivity respectively; there were no significant difference between groups statistically(P>0.05). Median overall survival was 27.25 and 46 months in Her2 negative and her2 positive cases respectively; there were no significant difference between groups statistically as well (P>0.05). CONCLUSION: Her2 reactivity has not relationship with tumor grade and lymph node involvement as well as tumor stage. From the other point of view no significant correlation is found between Her2 expression and disease free survival or overall survival of gastric cancer patients.

12.
Oncol Rep ; 24(5): 1121-31, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20878101

ABSTRACT

The use of cytotoxic chemotherapy in both advanced and early stage breast cancer has made significant progress in the last 10 years with several landmark studies identifying clear survival benefits for newer therapies. In spite of these developments the optimal approach for any specific patient can not be determined from a literature review or decision-making algorithm alone. Treatment choices are predominantly based on practice determined by individual or collective experience and the historical development of treatment within a locality. The improvement in the understanding of the molecular biological basis of breast cancer provides possible targets for novel therapies. Personalised therapies for breast cancer based on the molecular characteristics of the tumour could improve the risk: benefit ratio of current therapies. Increased improvements in the use of a panel of biomarkers will thus not only move us towards tailored therapies but will also spare a group of patients that do not benefit from adjuvant chemotherapy. At the same time a better understanding of tumour biology will also streamline the development of new regimens for those who are unlikely to benefit from existing drugs. This review will focus on the evidence for the use of chemotherapy and highlight advances in chemotherapy treatments with the addition of new and novel drugs marching into our clinics as standard treatments based on evidence from clinical trials and from a better understanding of tumour biology that has transformed the outlook in breast cancer in both the adjuvant and metastatic setting.


Subject(s)
Breast Neoplasms/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Female , Humans
13.
Anticancer Agents Med Chem ; 10(3): 225-35, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20184547

ABSTRACT

A better understanding of the molecular biology of renal cell carcinoma (RCC) and the emergence of tyrosine kinase inhibitors (TKIs) have revolutionized the treatment for patients with metastatic RCC (mRCC). Multikinase inhibitors (sunitinib and sorafenib) and the inhibitors of mammalian target of rapamycin (temsirolimus and everolimus) have recently shown superiority over IFN-alpha or placebo; and bevacizumab + IFN-alpha have demonstrated improved activity when compared to IFN-alpha alone in patients with mRCC. Newer anti-vascular endothelial growth factor (VEGF) agents such as axitinib, pazopanib and cediranib are currently under investigation to expand and elucidate future treatment options. Several studies have investigated the synergistic potential of TKIs with a view to blocking multiple signalling pathways simultaneously, but this approach has resulted in a significant increase in toxicity. Sequential TKI administration has demonstrated encouraging results but the optimal sequence of TKIs is yet to be determined. Studies combining TKIs with immunotherapy have resulted in varying degrees of success; with bevacizumab + IFN-alpha being the only studies with positive outcomes. The purpose of this review is to summarize the current evidence supporting the role of TKIs and to discuss potential future directions in the management of mRCC. The role of TKIs as monotherapy, in combination with immunotherapy or other TKIs (combined or sequential approach) will be discussed.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers/blood , Biomarkers/metabolism , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/secondary , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Kidney Neoplasms/diagnosis , Kidney Neoplasms/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/drug effects , Sirolimus/pharmacology , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolism
14.
Anticancer Agents Med Chem ; 9(5): 569-75, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19519298

ABSTRACT

Protein tyrosine kinases are enzymes which catalyze the phosphorylation of tyrosine residues and activate a downstream cascade of cellular signalling pathways which regulate cell proliferation, differentiation and apoptosis and a wide variety of cellular functions. Clinical developments over the past decade have identified several novel therapeutic agents which inhibit tyrosine kinase activity, either by direct receptor inhibition or indirect inhibition of tyrosine kinase controlled pathways. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI), such as gefitinib and erlotinib have been studied extensively in patients with refractory non-small cell lung cancer (NSCLC). Early studies with gefitinib showed undoubted clinical activity but failed to show a survival benefit, whereas studies with erlotinib showed a small but statistically significant benefit in overall survival. Subsequent studies explored the possibility of synergistic activity between targeted agents (gefitinib or erlotinib) and conventional chemotherapy drugs reporting disappointing results. Clinical trial results with gefitinib and erlotinib, either as monotherapy or in combination with chemotherapy, have failed to match the encouraging results noted in the pre-clinical setting. It is now increasingly recognised that clinical exploration of molecular targeted agents may not conform well to traditional phase I/II/III drug trial designs. Therapeutic responses may be limited to a small subpopulation of patients, therefore diluting the overall therapeutic effect. Hypothesising a genetic basis for the heterogeneity in trial results, biomarkers (such as EGFR gene mutation analysis, EGFR protein expression, and increased EGFR gene copy number) have been studied with a view to identifying a target population most likely to benefit from these drugs. Future clinical trials with targeted agents need to be carefully designed to incorporate correlative translational research elements that will allow selection of appropriate treatment strategies for individual patients. For assessment of phase III trial results in advanced disease, progression free survival may serve as a more appropriate end-point than response rate in an adequately designed trial in the appropriately selected population, although there should be no substitute for the overall survival and quality of life end points. The role of EFGR TKI in NSCLC will be discussed in detail and data from these studies will be used to illustrate the challenges in designing clinical trials and interpreting outcomes.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/drug therapy , Protein-Tyrosine Kinases/antagonists & inhibitors , Quinazolines/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/analysis , Biomarkers, Tumor/antagonists & inhibitors , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/diagnosis , Clinical Trials as Topic , DNA Mutational Analysis , ErbB Receptors/analysis , ErbB Receptors/genetics , ErbB Receptors/metabolism , Erlotinib Hydrochloride , Gefitinib , Humans , Lung Neoplasms/diagnosis , Quinazolines/pharmacology
15.
Int J Gynecol Cancer ; 19(3): 361-6, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19407560

ABSTRACT

BACKGROUND: Epithelial ovarian cancer's response to platinum retreatment depends on the duration of response to first-line platinum therapy. Platinum-free interval predicts subsequent platinum sensitivity and is a prognostic factor. Little has been published on the effect of pegylated liposomal doxorubicin (PLD) in the prolongation of treatment-free interval. METHODS: Patients treated with PLD were reviewed to assess response to platinum retreatment after PLD and to establish the use of cancer antigen 125 (Ca125) trends. All patients treated with PLD had progressed within 12 months of prior platinum therapy. Cancer antigen 125 fluctuations were categorized as the variances from the baseline (+/-10%, +/-10%-25%, and >25%). The response to chemotherapy was defined as Ca125 reduction from the baseline of more than 50%, clinical, or radiological response. RESULTS: Fifty-nine women were identified. The response rate (RR) to PLD was 28.9%, and the median overall survival from PLD initiation was 62 weeks. The number of women demonstrating more than 25% reduction in Ca125 from the baseline increased progressively with each cycle; at cycle 2, 11%; cycle 3, 18%; cycle 4, 22%; and cycle 5, 27% (trend significant between cycles 2 and 4, P = 0.004). Fifteen patients were re-treated with platinum after progression after PLD with 80% (12/15) of the patients responding. The RR to platinum retreatment after PLD compares favorably with the historical data on the response to second-line platinum retreatment. CONCLUSIONS: The sole use of early Ca125 trends in PLD treatment before cycle 4 may result in an erroneous discontinuation of PLD in potential responders. Retreatment with platinum after PLD may yield a good RR in selected patients even those with disease progression within 12 months after prior platinum treatment.


Subject(s)
CA-125 Antigen/metabolism , Doxorubicin/analogs & derivatives , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Platinum/therapeutic use , Polyethylene Glycols/therapeutic use , Carcinoma, Papillary/drug therapy , Carcinoma, Papillary/metabolism , Carcinoma, Papillary/secondary , Cohort Studies , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/metabolism , Cystadenocarcinoma, Serous/secondary , Doxorubicin/therapeutic use , Drug Resistance, Neoplasm , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/secondary , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Prognosis , Retrospective Studies , Survival Rate , Treatment Outcome
16.
Kathmandu Univ Med J (KUMJ) ; 5(1): 48-59, 2007.
Article in English | MEDLINE | ID: mdl-18603986

ABSTRACT

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is one of the potentially lethal complications of cirrhosis and is defined as infected ascites in the absence of any recognizable secondary cause of infection. Objective was to study the occurrence of SBP, clinical and laboratory characteristics and the response to antibiotics. METHODS: We had prospectively evaluated 81 cirrhotic patients with ascites during one-year period. All SBP patients were treated with cefotaxime, 2gm IV, every 12h for 5days. RESULTS: Of these 81 patients, 24.67% of patients (n=20) had SBP and its variants (classical SBP n= 4, CNNA n=13 and bacterascites n=3). There were thirteen males and 7 females in the study.85% of the cases had Child;s class C cirrhosis. UGI bleeding and abdominal pain were the most common presenting symptoms of SBP. Culture positives were 35% (n=7). The most frequent organisms were Escherichia coli (n=3) and Streptococcus pneumoniae (n=2). 94% of the patients responded to therapy after 48 hours of treatment. Total resolution after 5 days of therapy was 73% and in-hospital mortality was 15% (n=3). CONCLUSION: SBP, if diagnosed early can be treated with very good success rate up to 73%. Appropriate treatment of SBP with cefotaxime can help in reducing mortality and morbidity in patients with chronic liver disease.


Subject(s)
Ascites/complications , Bacterial Infections/epidemiology , Liver Cirrhosis/complications , Peritonitis/epidemiology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Cefotaxime/therapeutic use , Female , Humans , Male , Middle Aged , Nepal/epidemiology , Peritonitis/drug therapy , Peritonitis/microbiology , Prospective Studies , Treatment Outcome
17.
Singapore Med J ; 45(8): 385-9, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15284933

ABSTRACT

INTRODUCTION: To study the extent, frequency and pathogenesis of the cardiac and electrocardiographical manifestations of acute organophosphate poisoning. METHODS: 37 adult patients admitted over a three-year period with a diagnosis of acute organophosphate or carbamate poisoning were studied prospectively. The clinical features and electrocardiographical finding were recorded. RESULTS: Cardiac complications developed in 23 patients (62.2 percent). These were: non-cardiogenic pulmonary oedema in eight cases (21.6 percent), electrocardiographical abnormalities including prolonged Q-Tc interval in 14 cases (37.8 percent), ST-T changes in 11 cases (29.7 percent), and conduction defects in two cases (5.4 percent). Sinus tachycardia occurred in 15 patients (40.5 percent) and sinus bradycardia in seven patients (18.9 percent). Hypertension developed in five patients (13.5 percent) and hypotension in four patients (10.8 percent). Five patients (13.5 percent) needed respiratory support because of respiratory depression of which two patients developed intermediate syndrome. Out of 14 patients with prolonged Q-Tc interval, only one had polymorphic ventricular tachycardia of the torsade de pointes type. Two patients died from non-cardiogenic pulmonary oedema and one from ventricular fibrillation, giving a hospital mortality of 8.1 percent. CONCLUSION: Cardiac complications usually occur during the first hour after exposure. Hypoxemia, electrolyte derangements and acidosis are major predisposing factors for the development of these complications. Intensive supportive treatment, meticulous respiratory care and administration of atropine in adequate doses vary early in the course of the illness will reduce the mortality.


Subject(s)
Carbamates/poisoning , Electrocardiography , Heart Diseases/chemically induced , Insecticides/poisoning , Organophosphorus Compounds , Acute Disease , Adolescent , Adult , Arrhythmias, Cardiac/chemically induced , Critical Care , Emergencies , Female , Heart Diseases/diagnosis , Heart Diseases/therapy , Humans , Hypertension/chemically induced , Hypotension/chemically induced , Male , Poisoning/therapy , Prospective Studies
18.
Clin Oncol (R Coll Radiol) ; 16(1): 71-6, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14768759

ABSTRACT

A 53-year-old man presented with an 8-week history of upper and lower limb paraesthesia. Neurological examination revealed a glove and stocking distribution of sensory loss. Sural nerve biopsy showed severe axonal neuropathy associated with microvasculitis. Positron-emission tomography and thoracic computed tomography helped in localising the underlying malignancy. A transbronchial biopsy confirmed the diagnosis of small cell lung carcinoma (SCLC). Neuroimmunological studies identified anti-Hu antibodies and confirmed a paraneoplastic aetiology for his neuropathy. Treatment of small cell lung cancer with carboplatin and etoposide resulted in significant improvement of neurological symptoms. We report a case of a patient with SCLC and anti-Hu paraneoplastic sensory neuropathy with microvasculitis, and discuss the literature on prognosis of patients with SCLC with paraneoplastic neurological syndromes compared with patients with SCLC only.


Subject(s)
Carcinoma, Small Cell/complications , Carcinoma, Small Cell/immunology , Lung Neoplasms/complications , Lung Neoplasms/immunology , Nerve Tissue Proteins/immunology , Paraneoplastic Polyneuropathy/etiology , Paraneoplastic Polyneuropathy/immunology , RNA-Binding Proteins/immunology , Autoantibodies , ELAV Proteins , Humans , Male , Middle Aged , Prognosis
19.
East Mediterr Health J ; 10(1-2): 19-26, 2004.
Article in English | MEDLINE | ID: mdl-16201705

ABSTRACT

From November 2001 to March 2002, the National Institute of Health, Islamabad, Pakistan, received 230 samples from 194 different sources for analysis for anthrax spores. These samples were taken from letters/packages suspected of containing anthrax and from individuals exposed to them. When cultured on sheep blood agar, 141 samples yielded growth suggestive of Bacillus species. On the basis of growth characteristics, absence of beta-haemolysis, absent or doubtful motility and morphological characters of the isolates on Gram stain, 62 isolates were considered suspicious and were inoculated into guinea-pigs. Inoculated animals remained healthy well beyond the required observation period of 5 days. All the samples were therefore reported as negative for B. anthracis. Systems for handling and analysing suspected anthrax-contaminated materials are discussed.


Subject(s)
Anthrax/microbiology , Anthrax/prevention & control , Bioterrorism/prevention & control , Correspondence as Topic , Disaster Planning/methods , Environmental Monitoring/methods , Anthrax/diagnosis , Biological Assay/methods , Developing Countries , Humans , Inhalation Exposure/analysis , Occupational Exposure/analysis , Pakistan , Postal Service , Public Health Practice , Specimen Handling/methods , Spores, Bacterial/growth & development , Spores, Bacterial/isolation & purification
20.
Article in English | MEDLINE | ID: mdl-15691150

ABSTRACT

Thirty-six consecutive cases of liver abscess seen at the BP Koirala Institute of Health Sciences Hospital, Dharan, Nepal, from 1995 to 1998, were reviewed. Twenty-one cases were male and 15 female, with a mean age of 42 years. Twenty-four cases (66.7%) were amebic, 7 (19.4%) pyogenic, 3 (8.3%) indeterminate and 2 (5.5%) tuberculous. The most frequent clinical features included fever (88%), leukocytosis (66.7%), abnormal level of serum albumin (44.4%) and alkaline phosphatase (38.9%). The liver abscess was single in 61.1%, multiple in 27.8%, and in 66.7% of cases the abscess was present in the right lobe of the liver. Ultrasonography was diagnostic in all cases. A positive culture of the abscess was obtained in 7 cases (19.4%). The most frequent bacteria found were Klebsiella pneumoniae (4;11.1%), followed by Escherichia coli (3;8.3%). Two cases were due to Mycobacterium tuberculosis and none had malignancy. Percutaneous drainage was performed in 27 patients (75%). Mortality attributable to the abscess was 5.5%. We found percutaneous needle aspiration of liver abscess helpful in confirming diagnosis, as it provides a better bacteriological culture yield, gives a good outcome, and may uncover clinically unsuspected conditions like malignancy and tuberculosis. These two conditions should certainly be considered possible causes in our part of the world when an abscess fails to respond to standard treatment. In developing countries like Nepal, the clinical presentation of liver abscess has not varied over time. At present, rapid diagnosis and image-guided percutaneous drainage offer a better prognosis for liver abscess. We also recommend routine cytological examination of aspirated abscess materials, as well as stains and cultures for acid-fast bacilli.


Subject(s)
Escherichia coli/isolation & purification , Klebsiella pneumoniae/isolation & purification , Liver Abscess/diagnosis , Mycobacterium tuberculosis/isolation & purification , Adolescent , Adult , Biopsy, Needle , Female , Humans , Liver Abscess/classification , Liver Abscess/epidemiology , Liver Abscess/microbiology , Male , Middle Aged , Nepal/epidemiology , Tropical Climate
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