Applicability of a single 5 color cytoplasmic markers tube as primary panel for immunophenotyping of acute leukemia: A Gujarat Cancer and Research Institute experience.

INTRODUCTION: Flow cytometry is highly sensitive for detection and quantitative analysis of surface and intracellular antigens in malignant hemopoietic cells. Immunophenotyping is a routine practice for classification and lineage assignment of acute leukemia. In the present study, our aim is to identify the role of a single 5 color, CD45, myeloperoxidase (MPO), cCD79a, cCD3, and Tdt, cytoplasmic markers combination as a primary tube. We compared with final diagnosis on the basis of morphology, cytochemistry, and primary and secondary panels of immunophenotyping and also with other study. MATERIALS AND METHODS: We have included 455 new cases of acute leukemias with applied primary and secondary panels of markers for immunophenotyping. We analyzed sensitivity and specificity of different subsets with combination of positive and negative markers. RESULTS: MPO was positive in 61.4% of acute myeloid leukemia (AML) cases. All 184 (100%) cases of the AML were negative for cCD3 and cCD79a co-expression. cCD79a expression was highly sensitive as 98.5% B-acute lymphoblastic leukemia (B-ALL) expressed it. cCD3 expression was detected in 100% cases of T-ALL, and its co-expression was not seen in B-ALL and AML. CONCLUSION: Our study indicates that there was very good correlation of 5-color cytoplasmic tube-based diagnosis versus final diagnosis based on morphology, cytochemistry, and flow cytometry. We can use this 5-color cytoplasmic tube method to make immunophenotyping cost-effective.

Intercity deceased donor renal transplantation: a single-center experience from a developing country.

In a developing country such as India, deceased donor renal transplantation (DDRTx) accounts for only about 1% of all renal transplants (RTx). Our institute initiated an intercity DDRTx in the year 2006, which significantly increased the number of RTx. We retrieved 74 kidneys from 37 deceased donors from various cities of Gujarat from January 2006 to December 2009. We transplanted the allografts in 66 recipients and a retrospective analysis of the donor profile and management and recipient outcome was performed. The mean age of the donors was 43.3 ± 18.8 years. The causes of death included road traffic accident in 51.35% of the donors and cerebrovascular stroke in 48.65% of the donors; 83.78% of the donors required ionotropes for hemodynamic stability in addition to vigorous intravenous fluid replacement. The average urine output of the donors was 350 ± 150 mL. The organs were perfused and stored in HTK solution. The mean cold ischemia time (CIT) was 9.12 ± 5.25 h. The mean anastomosis time in the recipient was 30.8 ± 8.7 min. 57.6% of the recipients established urine output on the operating table and 42.4% developed delayed graft function. At the end of 1 month after transplantation, the mean serum creatinine was comparable to the Ahmadabad city DDRTx, although the CIT was significantly longer in the intercity patients. Intercity organ harvesting is a viable option to increase the donor pool. Distance may not be an impediment, and good recipient outcome is possible in spite of prolonged CIT in case of proper harvesting and preservation.

Gemcitabine in brief versus prolonged low-dose infusion, both combined with carboplatin for advanced non-small cell lung cancer.

PURPOSE: Gemcitabine in low-dose prolonged infusion is a treatment with documented activity against a variety of tumors. The present study was conducted to evaluate the efficacy and safety of the combination of gemcitabine at a low-dose prolonged infusion in comparison with standard dose gemcitabine with carboplatin in chemonaive patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Sixty chemonaive patients with stage IIIB or IV NSCLC were included. Patients were randomly assigned 1:1 to receive 350 mg/m 2 gemcitabine in a 6-h infusion on days 1 and 8 and carboplatin area under the serum concentration time curve (AUC) 5 on day 1 versus gemcitabine 1,000 mg/m 2 on days 1 and 8 and carboplatin AUC 5 on day 1 (3-week cycle both). A total of 118 chemotherapy cycles, with a median of 4 cycles per patient (range 2-6), and 134 chemotherapy cycles, with a median of 4.47 cycles per patient (range 3-6) were administered in standard and low infusional dose arm, respectively. RESULTS: Among patients in the standard arm, 40% had overall response rate (ORR), 33.3% had stable disease and 26.6% had progressive disease, while in low-dose infusional arm, 36.6% had ORR, 36.3% had stable disease and 26.6% had progressive disease (P = 0.992). Median progression-free survival was 5.5 months and 5.4 months, median overall survival was 9.7 months and 10.7 months, and 1-year survival was 33.7% and 36.6% in standard arm and low-dose infusion arm, respectively. Grade 3/4 toxicity was rare. CONCLUSION: In NSCLC, gemcitabine low-dose prolonged infusion with carboplatin has low toxicity, especially thrombocytopenia, and has an activity comparable with gemcitabine given in higher dose in standard infusion.

Lipoadenoma of the parathyroid gland - a rare cause of hyperparathyroidism.

Lipoadenoma of parathyroid gland is an unusual morphologic variant of parathyroid adenoma in which the glandular elements are associated with abundant mature adipose tissue. The lesion has also been reported as parathyroid lipohyperplasia, parathyroid hamartoma, and parathyroid adenoma with myxoid stroma. Most cases are functioning and are associated with hyperparathyroidism. Lipoadenoma of parathyroid gland are difficult to diagnose as a cause of hyperparathyroidism because of rarity of these lesions and overlap with normal parathyroid tissue on microscopic evaluation. Only few cases have been documented in the literature so far. The lesion may be overlooked by both surgeon and pathologists alike, if they are not aware of this specific clinicopathologic entity.

Management of primary and metastatic triple negative breast cancer: perceptions of oncologists from India.

BACKGROUND: In order to document the understanding of current evidence for the management of triple negative breast cancer and application of this knowledge in daily practice, we conducted an interactive survey of practicing Indian oncologists. MATERIALS AND METHODS: A core group of academic oncologists devised two hypothetical triple negative cases (metastatic and early breast cancer, respectively) and multiple choice options under different clinical circumstances. The respondents were practicing oncologists in different Indian cities who participated in either an online survey or a meeting. The participants electronically chose their preferred option based on their everyday practice. RESULTS: A total of 152 oncologists participated. Just over half (53.8%) preferred taxane based chemotherapy as first-line chemotherapy in the metastatic setting. In the adjuvant setting, a taxane regimen was chosen by 61%. Over half of respondents (52.6%) underestimated the baseline survival of a patient with node positive triple-negative tumor and 18.9% overestimated this survival compared to the estimate of the Adjuvant! program. DISCUSSION: This data offers insight into the perceptions and practice of a diverse cross-section of practicing oncologists in India with respect to their therapeutic choices in metastatic and adjuvant settings in triple negative breast cancer.

Titanium ossicular chain replacement prostheses: prognostic factors and preliminary functional results.

OBJECTIVE: To assess the efficiency of ossiculoplasty procedures with the Kurz titanium ossicular prosthesis and evaluate prognostic factors for the functional results. METHODS: Retrospective chart reviews were performed for ossiculoplasty involving Kurz titanium prostheses between 2006 and 2009 in the ENT Head and Neck Department of the hôpital Nord, Marseille, France. RESULTS: The population studied was 70 patients, with 37 procedures using the partial (PORP) and 33 the total ossicular replacement prosthesis (TORP). Mean follow-up was 9 months. Pre- and postoperative audiological parameters on four frequency averages (0.5, 1, 2, and 3kHz) were compared according to AAO-HNS guidelines. A postoperative air-bone gap (ABG)≤20dB was obtained in 71.43% of the patients (86.49% for PORP, and 54.55% for TORP). The mean change in ABG was 12.45dB in cholesteatomatous otitis versus 13.41dB in non-cholesteatomatous otitis. CONCLUSION: Increasing the length of the ossicular prosthesis, especially TORP, may improve postoperative functional results.

Combined epidural and general anesthesia for paediatric renal transplantation-a single center experience.

BACKGROUND: Appropriate anesthesia for pediatric renal transplantation requires stable intraoperative hemodynamics, optimal perfusion of the newly transplanted kidney and good analgesia during recovery. The aim of this study was to assess the preliminary application, success and safety of combined epidural and general anesthesia in pediatric renal transplantation in a small cohort. METHODS: We retrospectively reviewed the anesthesia records of 46 consecutive pediatric patients who received renal transplantation under combined epidural and general anesthesia from January 2003-2007. RESULTS: The mean patient age and weight were 13.2 +/- 2.4 years and 25.7 +/- 5.46 kg, respectively. The infused crystalloids, 20% albumin and red blood cell concentrates were 120 +/- 2 mL/kg to achieve a CVP of 13 to 15 mm Hg. Brisk diuresis was observed in all patients. Epidural tramadol (2 mg/kg) provided good postoperative analgesia in 89% patients. 15% patients developed radiological evidence of pulmonary edema, only one required mechanical ventilation for hypoxemia. Minor adverse effects were nausea and vomiting (17.5%) and convulsions (8.5%). No perioperative mortality or major morbidity was recorded. CONCLUSION: Epidural anesthesia is a useful adjunct to general anesthesia due to stable intraoperative haemodynamics and good postoperative analgesia.

Liposarcoma of the breast--a case report.

Sarcoma of the breast constitutes less than 1% of all malignant breast tumors and liposarcoma of the breast has an incidence of 0.3% of all the mammary sarcomas. A 90-year-old woman presented with a mass in the upper outer quadrant of the right breast measuring 25 x 15 x 7 cm. Mammography was performed and the mass was diagnosed as a liposarcoma. A wide excision was performed with a 2 cm margin of healthy tissue. The tumor was diagnosed histologically as a fibrous liposarcoma. The patient was discharged and her postoperative recovery was uneventful. We report a case of liposarcoma of the breast and discuss this rare malignant tumor together with the various diagnostic and therapeutic modalities used.

Predictors of ovarian reserve in young women with breast cancer.

Ovarian reserve can be diminished following treatment for breast cancer. This study evaluated biochemical and biophysical parameters of ovarian reserve in these patients. Biochemical and biophysical tests of ovarian reserve were performed simultaneously in young (age 22-42 years), regularly menstruating women with breast cancer (n=22) and age-matched controls (n=24). All tests were performed before (baseline) and after transient ovarian stimulation in the early follicular phase. Patients were recruited both before and after completion of chemotherapy, with some patients being followed up prospectively. Serum samples were analysed for follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol (E(2)), inhibins A and B, and antimullerian hormone (AMH). Biophysical (ultrasound) tests included ovarian volume, antral follicle count (AFC), ovarian stromal blood flow and uterine dimensions. Significant differences were revealed (when compared with the controls) for basal FSH (11.32+/-1.48 vs 6.62+/-0.42 mIU ml(-1), P<0.001), basal AMH (0.95+/-0.34 vs 7.89+/-1.62 ng ml(-1), P<0.001) and basal inhibin B (19.24+/-4.56 vs 83.61+/-13.45 pg ml(-1), P<0.001). Following transient ovarian stimulation, there were significant differences in the increment change (Delta) for inhibin B (3.02+/-2.3 vs 96.82+/-16.38 pg ml(-1), P<0.001) and E(2) (107.8+/-23.95 vs 283.2+/-40.34 pg ml(-1), P<0.01). AFC was the only biophysical parameter that was significantly different between patients and the controls (7.80+/-0.85 vs 16.77+/-1.11, P<0.001). Basal and stimulated biochemical (serum AMH, FSH, inhibin B and E(2)) and biophysical (AFC) tests may be potential markers of ovarian reserve in young women with breast cancer.

Outcome after autologous and allogeneic stem cell transplantation for patients with multiple myeloma: impact of graft-versus-myeloma effect.

A total of 228 patients with multiple myeloma (MM), 166 patients receiving autologous transplantation (124 PBSC and 38 BM) and 66 patients receiving T-cell-depleted allogeneic transplantation were analyzed to compare overall survival (OS), progression-free survival (PFS) and risk of relapse. Patients receiving autologous transplantation had a significantly improved OS (P=0.006) and PFS (P=0.002) at 2 years with OS and PFS for autologous transplant 74% and 48%, respectively, compared with 51% and 28% for allogeneic transplantation. By 4 years after transplantation, outcome was similar with OS and PFS for autologous transplantation 41% and 23%, respectively, compared with 39% and 18% for allogeneic transplantation. The 4-year cumulative incidence of nonrelapse mortality was significantly higher in patients receiving allogeneic transplantation (24% vs 13%) (P=0.004). Relapse was the principle cause of treatment failure for both groups; however, there was a significantly reduced risk of relapse associated with allogeneic transplantation at 4 years: 46% for allograft vs 56% for autograft (P=0.02). Despite a lower risk of relapse after allogeneic transplantation, autologous transplantation is associated with improved OS and PFS compared with allogeneic transplantation in patients with MM. Strategies focused on reducing nonrelapse mortality in allogeneic transplantation may translate into an improved outcome for patients receiving allogeneic transplantation.

T-cell--depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect.

Previous trials of allogeneic bone marrow transplantation (BMT) in patients with multiple myeloma (MM) have demonstrated high response rates but also high transplantation-related mortality (TRM) and high relapse rates. Exploitation of this strategy remains of interest because donor lymphocyte infusions (DLIs) can induce a potent graft-versus-myeloma (GVM) effect. CD6 T-cell--depleted allogeneic BMT was combined with prophylactic CD4(+) DLI administered 6 to 9 months after BMT in an effort to reduce TRM and to induce a GVM response after BMT. Twenty-four patients with matched sibling donors and chemotherapy-sensitive disease underwent BMT. CD6 T-cell depletion of donor bone marrow was the sole method of graft-versus-host disease (GVHD) prophylaxis. GVHD after BMT was minimal, 1 (4%) grade III and 4 (17%) grade II GVHD. Fourteen patients received DLI, 3 in complete response and 11 with persistent disease after BMT. Significant GVM responses were noted after DLI in 10 patients with persistent disease, resulting in 6 complete responses and 4 partial responses. After DLI, 50% of patients developed acute (> or = II) or extensive chronic GVHD. Two-year estimated overall survival and current progression-free survival (PFS) for all 24 patients is 55% and 42%, respectively. The 14 patients receiving DLI had an improved 2-year current PFS (65%) when compared with a historical cohort of MM patients who underwent CD6-depleted BMT survived 6 months with no GVHD and did not receive DLI (41%) (P =.13). Although this study suggests that prophylactic DLI induces significant GVM responses after allogeneic BMT, only 58% of patients were able to receive DLI despite T-cell--depleted BMT. Therefore, less toxic transplantation strategies are needed to allow a higher proportion of patients to receive DLI and the benefit from the GVM effect after transplantation. (Blood. 2001;98:934-939)

Tuberculosis of the sternum and clavicle: imaging findings in 15 patients.

OBJECTIVE: To describe the imaging findings in sterno-clavicular tubercular involvement. DESIGN AND PATIENTS: Fifteen patients with pathologically proven tuberculosis of the sternum and clavicle were retrospectively evaluated. Routine radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were used in some or all of the patients. Clinical information and imaging features were evaluated in each case. RESULTS: Eight patients had sternoclavicular joint (SCJ) involvement, five had isolated sternal involvement and two had isolated clavicular involvement. Seven patients were evaluated with only CT, six with only MRI and two with both. There were eight male and seven female patients, varying in age between 16 and 78 years. Fever, swelling and pain were common presenting symptoms. Two patients were HIV positive. Radiographs were positive in only eight patients. Destruction and signal intensity (SI) changes of the sternum and clavicle, destruction of the cartilage, soft tissue changes representing granulation tissue/abscess, displacement of the adjacent structures (vessels, trachea, etc.) and inflammatory changes in the adjacent structures in the form of cellulitis and myositis were common imaging features. CONCLUSIONS: All imaging methods can provide complementary information regarding sterno-clavicular tubercular involvement that is helpful for determination of the therapy. MRI is useful in determining the extent of the lesion, particularly marrow involvement and soft tissue extent.

Directly measured tissue pH is an earlier indicator of splanchnic acidosis than tonometric parameters during hemorrhagic shock in swine.

OBJECTIVE: To compare tissue pH in the stomach, bowel, and abdominal wall muscle during hemorrhagic shock and recovery using tissue electrodes; also, to compare tissue electrode pH measurements to gastric intramucosal pH (pHi), gastric luminal PCO2, and PCO2 gap (gastric luminal CO2--arterial CO2) measured with an air-equilibrated tonometer. DESIGN: Prospective animal study. SETTING: University animal research laboratory. SUBJECTS: Eight anesthetized, mechanically ventilated Yorkshire swine. INTERVENTIONS: Hemorrhagic shock was initiated by withdrawing blood over a 15-min period to lower systolic blood pressure to 45 mm Hg. Shock was maintained for 45 mins and was followed by a 5-min resuscitation to normal blood pressure with a blood/lactated Ringer's (1:2) mixture. Recovery was monitored for 60 mins. MEASUREMENTS AND MAIN RESULTS: pH was measured with electrodes in the submucosa of the stomach, the submucosa of the small bowel, and the abdominal wall muscle. Gastric luminal PCO2 was measured with an air-equilibrated tonometer and pHi and PCO2 gap were calculated. Each organ showed a different sensitivity to shock and resuscitation. The bowel pH responded most rapidly to the onset of hemorrhagic shock and had the largest change in tissue pH. The bowel also showed the most rapid recovery during resuscitation. The submucosal pH of the stomach responded more slowly than the bowel, but faster than the abdominal wall muscle pH, gastric PCO2 gap, or pHi. The smallest changes in organ pH as a result of hemorrhagic shock were seen in the abdominal wall muscle and the stomach as assessed by gastric tonometry. CONCLUSIONS: Direct measurement of tissue pH indicates that intra-abdominal organ pH varies during hemorrhagic shock. The small bowel pH changes the most in magnitude and rapidity compared with stomach pH or abdominal wall muscle pH. Tonometrically derived parameters were not as sensitive in the detection of tissue acidosis during shock and resuscitation as pH measured directly in the submucosa of the stomach or small bowel.

Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older.

PURPOSE: The surgical treatment of colorectal cancer (CRC) in elderly patients (age 70 years or older) has improved, but data on adjuvant and palliative chemotherapy tolerability and benefits in this growing population remain scarce. Elderly patients are underrepresented in clinical trials, and results for older patients are seldom reported separately. PATIENTS AND METHODS: Using a prospective database, we analyzed demographics, chemotherapy toxicity, response rates, failure-free survival (FFS), and overall survival (OS) of CRC patients receiving chemotherapy at the Royal Marsden Hospital. The cutoff age was 70 years. RESULTS: A total of 844 patients received first-line chemotherapy with various fluorouracil (5-FU)-containing regimens or raltitrexed for advanced disease, and 543 patients were administered adjuvant, protracted venous infusion 5-FU or bolus 5-FU/folinic acid (FA) chemotherapy. Of the 1,387 patients, 310 were 70 years or older. There was no difference in overall or severe (Common Toxicity Criteria III to IV) toxicity between the two age groups, with the exception of more frequent severe mucositis in older patients receiving adjuvant bolus 5-FU/FA. For patients receiving palliative chemotherapy, no difference in response rates (24% v 29%, P =.19) and median FFS (164 v 168 days) were detected when the elderly were compared with younger patients. Median OS was 292 days for the elderly group and 350 days for the younger patients (P =.04), and 1-year survival was 44% and 48%, respectively. The length of inpatient hospital stay was identical. CONCLUSION: Elderly patients with good performance status tolerated adjuvant and palliative chemotherapy for CRC as well as did younger patients and had similar benefits from palliative chemotherapy.

Translocation (11;14)(q13;q32) and overexpression of cyclin D1 protein in a CD23-positive low-grade B-cell neoplasm.

We describe a case of low-grade B-cell neoplasm with features overlapping between B-chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The patient presented with a 10-year history of stable CLL without any treatment. The peripheral-blood picture was consistent with atypical mixed CLL (French-American-British criteria), whereas the lymph-node histology was more consistent with MCL. Neoplastic cells were strongly positive for surface immunoglobulin M, kappa, CD5, CD20, CD23, and cyclin D1. Expression of CD11c was weak. Translocation (11;14) and der(10)t(10;?)(p11;?) were the primary cytogenetic changes observed in both peripheral blood (47%) and lymph node (7%). Trisomy 12 was absent. Deletion 6q21 and rearrangements involving 1p/q, consistently associated with progression in lymphomas, also were noted in the peripheral blood but were nonclonal. The present case and similar cases with features overlapping between CLL and MCL most likely represent hybrids. In cases with features of typical CLL, t(11;14) is probably associated with gradual progression and may precede clinical and histologic transformation.

The pokeweed antiviral protein specifically inhibits Ty1-directed +1 ribosomal frameshifting and retrotransposition in Saccharomyces cerevisiae.

Programmed ribosomal frameshifting is a molecular mechanism that is used by many RNA viruses to produce Gag-Pol fusion proteins. The efficiency of these frameshift events determines the ratio of viral Gag to Gag-Pol proteins available for viral particle morphogenesis, and changes in ribosomal frameshift efficiencies can severely inhibit virus propagation. Since ribosomal frameshifting occurs during the elongation phase of protein translation, it is reasonable to hypothesize that agents that affect the different steps in this process may also have an impact on programmed ribosomal frameshifting. We examined the molecular mechanisms governing programmed ribosomal frameshifting by using two viruses of the yeast Saccharomyces cerevisiae. Here, we present evidence that pokeweed antiviral protein (PAP), a single-chain ribosomal inhibitory protein that depurinates an adenine residue in the alpha-sarcin loop of 25S rRNA and inhibits translocation, specifically inhibits Ty1-directed +1 ribosomal frameshifting in intact yeast cells and in an in vitro assay system. Using an in vivo assay for Ty1 retrotransposition, we show that PAP specifically inhibits Ty1 retrotransposition, suggesting that Ty1 viral particle morphogenesis is inhibited in infected cells. PAP does not affect programmed -1 ribosomal frameshift efficiencies, nor does it have a noticeable impact on the ability of cells to maintain the M1-dependent killer virus phenotype, suggesting that -1 ribosomal frameshifting does not occur after the peptidyltransferase reaction. These results provide the first evidence that PAP has viral RNA-specific effects in vivo which may be responsible for the mechanism of its antiviral activity.

Diminished myocardial function precedes tissue acidosis during coronary hypoperfusion.

The current study sought to elucidate the relationship between myocardial pH and function during a significant but not absolute reduction in coronary flow. In a canine model, a partial coronary arterial stenosis was created, with the left anterior descending coronary artery (LAD) flow reduced by 50% compared to prestenosis levels, and maintained at that level for the duration of the study. During the experiment, interstitial myocardial pH and regional myocardial function, as assessed by the regional preload recruitable work area (PRWA), were measured. PRWA was depressed to 60% of baseline values, on average, for the entire period of reduced LAD flow. In contrast to the pattern observed with myocardial blood flow and systolic function, metabolic evidence of myocardial ischemia, that is, reduced myocardial pH did not become significantly different from baseline levels until after LAD flow had been reduced for 15 min. Thus, measurable changes in myocardial pH appeared slowly over time despite the fact that regional myocardial blood flow was decreased immediately. Therefore, myocardial pH cannot be used to anticipate alterations in myocardial contractile function.

Pattern of second primary neoplasms following breast cancer.

BACKGROUND: Second primary neoplasms (SPN) have been seen with diseases such as breast cancer and Hodgkin's disease. Therapeutic agents used for their treatment have been found responsible for the development of SPN in some cases. In addition, genetic factors are known to contribute to their development. METHODS: A retrospective study of 15 patients who had primary breast cancer and developed SPN concurrently or sequentially was conducted. RESULTS: Of 15 patients analysed in this study, five had haematological SPN, four had ovarian cancer, and six had different types of non-haematological SPN. Familial clustering was found in two patients. A peculiar abnormality of chromosome 5 and 7 was detected in one patient with haematological SPN, suggesting therapy-related leukaemia. CONCLUSIONS: It is postulated that alkylating agents with or without p53 gene inactivation may predispose to leukaemia, whereas ovarian tumors following breast cancer could be related to BRCA 1 gene inactivation.