Incidence of Deep Venous Thrombosis and Sickle Cell Disease in Patients Undergoing Spinal Surgery in South Gujarat, India: A Prospective Observational Study.

Introduction: Our objective of this study was to assess the incidence of Deep Venous Thrombosis in patients including those with sickle cell disease who underwent spine surgery, and also to determine the association of Sickle Cell Disease as a clinical predictor for Deep Venous Thrombosis in spinal surgery patients. Materials and methods: All patients who underwent spinal surgery from January 2016 to October 2016 were included in this study. Detailed history, demographic data, physical findings, pre-operative haematological and radiological investigations were documented. All the patients underwent daily clinical evaluation for clinical signs of Deep Venous Thrombosis and also underwent a post-operative venous Doppler and D-dimer test. Results: Seventy-nine consecutive patients were included in the study with the mean age of 41 years. All patients had normal venous Doppler pre-operatively. A total of 2.5% patients had deep vein thrombosis in bilateral lower limbs while 2 patients (2.5%) had evidence of venous stasis but no thrombosis on Doppler ultrasound done post-operatively. Nine patients (11.4%) were sickle cell positive from which 4 patients showed evidence of Deep Venous Thrombosis or Venous Stasis. D-dimer was positive in 5 (8.3%) patients which included 4 patients with Sickle Cell Disease. Conclusion: This study concludes that Sickle Cell Disease is a risk factor for developing Deep Venous Thrombosis in patients undergoing spinal surgery. The study also concludes the effectiveness of mechanical prophylaxis in preventing Deep Venous Thrombosis and recommends pharmacological prophylaxis after assessing the risk profile or positive D-dimer test.

Cubic, hexagonal and tetragonal FeGe x phases (x = 1, 1.5, 2): Raman spectroscopy and magnetic properties.

There is currently an emerging drive towards computational materials design and fabrication of predicted novel materials. One of the keys to developing appropriate fabrication methods is determination of the composition and phase. Here we explore the FeGe system and establish reference Raman signatures for the distinction between FeGe hexagonal and cubic structures, as well as FeGe2 and Fe2Ge3 phases. The experimental results are substantiated by first principles lattice dynamics calculations as well as by complementary structural characterization such as transmission electron microscopy and X-ray diffraction, along with magnetic measurements.

Treatment results in advanced stage Hodgkin's lymphoma: a retrospective study.

BACKGROUND: Hodgkin's lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. AIM: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. MATERIALS AND METHODS: This retrospective study included de-novo advanced stage HL patients (≥15 years) registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS) and progression-free survival (PFS). Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. RESULTS: There were 125 patients (males 77%) who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years). Stage IV disease was seen in (46 patients) 37%; 75% (94 patients) patients had B symptoms. International prognostic score (IPS) ≤4 was seen in 95/112 (85%) patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients). Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4) were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. CONCLUSIONS: The treatment outcomes in this study are comparable with the published literature with limited follow-up data.

Sunitinib in metastatic renal cell carcimoma: a single-center experience.

INTRODUCTION: Historically, metastatic renal cell carcinoma (RCC) has had poor prognosis; the outcomes have improved with the introduction of tyrosine-kinase inhibitors, such as sunitinib. There is no reported literature from India on the use of sunitinib in metastatic RCC. We present an analysis of sunitinib at our institute over 4 years. MATERIALS AND METHODS: An unselected population of patients with metastatic or relapsed metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS: Fifty-nine patients (51 males, 8 females) with a median age of 55 years were included in the study. Lungs and bones were the most common site of metastases. The patients received a median number of 4 cycles, with 23 patients requiring dose-modification and 12 discontinuing therapy due to toxicity. Overall, 38 patients (65%) had CR, PR, or standard deviation while 14 had progression or death at initial evaluation. The median progression-free survival (PFS) was 11.4 months and overall survival was 22.6 months. Hand-foot syndrome, fatigue, mucositis, skin rash, and vomiting were seen more often among our patients, whereas hypertension was not as common compared with previously published reports. CONCLUSION: Sunitinib is a viable option for the treatment of metastatic RCC and shows a comparable PFS in Indian patients. Although toxicity remains a concern, most of the adverse effects can be managed conservatively. Careful patient selection, tailoring the dose of therapy, adequate counseling, and careful follow-up is essential for optimum therapy.

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review.

Acute myeloid leukemia (AML) in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. Over the last decade, metronomic chemotherapy has emerged as a potential strategy to control advanced/refractory cancer. Here, we report a case of a 68-year-old gentleman having AML with high-risk cytogenetic features, who achieved complete remission on our oral metronomic PrET (PrET: Prednisolone, etoposide, thioguanine) protocol on an outpatient basis. He was later treated with standard high-dose (HD) cytosine arabinoside (Ara-C) consolidation followed by maintenance with etoposide, thioguanine, and sodium valproate. Presently, the patient is nearly 35 months since diagnosis and 21 months off treatment. This case report and review highlights that the combination of oral low-intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy may be well tolerated by elderly patients especially with less proliferative, high (cytogenetic)-risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. References for this review were identified through searches of Pubmed for recent publications on the subject as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

A randomized comparative trial evaluating the safety and efficacy of liposomal amphotericin B (Fungisome) versus conventional amphotericin B in the empirical treatment of febrile neutropenia in India.

BACKGROUND: In patients with persistent fever and netropenia, amphotericin B is administered empirically for early treatment and prevention of systemic fungal infections. Despite this treatment, there are chances of breakthrough fungal infections and drug is also toxic. MATERIALS AND METHODS: A multicentric, randomized, controlled clinical trial was conducted to compare liposomal amphotericin B two doses with conventional amphotericin B as empirical antifungal therapy. RESULTS: The average body weight of patients was 26.4 ± 14.8 (n=22), 32.9 ± 19.4 (n=23) and 37.9 ± 20.0 (n=20) kg in 1 mg, 3 mg Fungisome (liposomal amphotericin B) and 1 mg/kg/day conventional amphotericin B group, respectively. The mean age was 16.2 ± 13.4, 16.0 ± 10.9 and 22.7 ± 16.2 yrs in 1 and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional AMP B group, respectively. The average duration of treatment with 1 mg and 3 mg/kg/day Fungisome and 1 mg/kg/day conventional amphotericin B was 17 ± 9.8, 16.2 ± 8.3, and 14.7 ± 10.7 days, respectively. The time to resolve fever was 13.3 ± 10.2, 10.9 ± 7.1, 10.1 ± 6.7 days, and for absolute neutrophil count (ANC) to be above 500 cells per microliter, it took 13.4 ± 9.6, 10.6 ± 7.6 and 7.3 ± 3.4 days, respectively. Liposomal formulations were well-tolerated compared to conventional amphotericin B. CONCLUSIONS: This small randomized study showed that the indigenous liposomal formulation Fungisome appears to be equally efficacious and safer than conventional amphotericin B. Also, the lower dose Fungisome (1 mg/kg/day) appears to be equally efficacious and was well-tolerated as compared to higher dose Fungisome (3 mg/kg/day). Treatment cost would be a major factor for limiting use of higher dose of Fungisome.

Histopathological audit of splenectomies received at a cancer hospital.

BACKGROUND: There are few studies in the literature studying the yield of the diagnostic splenectomy in a suspicious lymphoma case. Moreover, their relevance is limited owing to low number of cases, the use of selection criteria, and the lack of modern ancillary studies. We present a histopathological review of splenectomy specimens referred as a case of lymphoma to our center. MATERIALS AND METHODS: The medical charts and laboratory data on all patients of all splenectomy specimens between the years 2003 and 2008 were reviewed. Morphological and immunohistochemical features were analyzed and the lymphomas were sub-typed in accordance to 2008 WHO Classification of Hematolymphoid Neoplasms. Flow cytometry immunophenotyping available in few cases was correlated. RESULTS: A total of 46 cases studied included splenic marginal zone lymphoma (SMZL) (19 cases), splenic diffuse large B-cell lymphoma (DLBCL) (14 cases), splenic diffuse red pulp B-cell lymphoma (DRP) (five cases), follicular lymphoma (three cases), hairy cell leukemia (HCL) (two cases), HCL variant (HCLv) (1 case), 1 case of hepatosplenic gamma delta T-cell lymphoma (TCL), and 1 cases of TCL (not otherwise specified). CONCLUSIONS: Predominantly splenic lymphoma is a biologically heterogeneous entity, ranging from low-grade SMZL to high-grade DLBCLs. TCLs constituted only 4% of all our cases. DRP, HCL, and HCLv have similar diffuse red pulp patterns of splenic involvement and are differentiated based on flow cytometric immunophenotyping. We had a large number of splenic DLBCL and none of these involved bone marrow (BM), while all other lymphoma subtypes had BM involvement (stage IV disease). Morphological and immunophenotypic (immunohistochemistry and flow cytometry) features of BM and splenectomy specimen need to be correlated to differentiate these rare though similar-looking entities with overlapping features.

A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer.

BACKGROUND: This phase II study estimated the difference in objective response rate (ORR) among patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) receiving paclitaxel-carboplatin (CP) plus motesanib or bevacizumab. PATIENTS AND METHODS: Chemotherapy-naive patients (N = 186) were randomized 1:1:1 to receive CP plus motesanib 125 mg once daily (qd) (arm A), motesanib 75 mg twice daily (b.i.d.) 5 days on/2 days off (arm B), or bevacizumab 15 mg/kg every 3 weeks (q3w) (arm C). The primary end point was ORR (per RECIST). Other end points included progression-free survival (PFS), overall survival (OS), motesanib pharmacokinetics, and adverse events (AEs). RESULTS: ORRs in the three arms were as follows: arm A, 30% (95% confidence interval 18% to 43%); arm B, 23% (13% to 36%); and arm C, 37% (25% to 50%). Median PFS in arm A was 7.7 months, arm B 5.8 months, and arm C 8.3 months; median OS for arm A was 14.0 months, arm B 12.8 months, and arm C 14.0 months. Incidence of AEs was greater in arms A and B than in arm C. More grade 5 AEs not attributable to disease progression occurred in arm B (n = 10) than in arms A (n = 4) and C (n = 4). Motesanib plasma C(max) and C(min) values were consistent with its pharmacokinetic properties observed in previous studies. CONCLUSIONS: The efficacy of 125 mg qd motesanib or bevacizumab plus CP was estimated to be comparable. Toxicity was higher but manageable in both motesanib arms. Efficacy and tolerability of motesanib 125 mg qd plus CP in advanced nonsquamous NSCLC are being further investigated in a phase III study.

A retrospective audit of clinicopathological attributes and treatment outcomes of adolescent and young adult non-Hodgkin lymphomas from a tertiary care center.

BACKGROUND: The uniqueness of adolescent and young adult (AYA) non-Hodgkin lymphomas (NHL) with respect to biology and treatment have largely remained unanswered due to marked heterogeneity in treatment, paucity of prospective, or retrospective studies and poor representation of AYA in clinical trials. This audit attempts to put forward the clinicopathological attributes and treatment outcomes of AYA NHL treated with both pediatric and adult protocols from a single centre in a developing country. PATIENTS AND METHODS: Hospital records of all consecutive NHL patients registered in lymphoma clinic from January 2007 to May 2010 were reviewed for information on demography, clinical features, histology subtype, staging, treatment regimen, response rates, toxicities, and follow up. Two-year progression-free (PFS) and overall survival (OS) were calculated with Kaplan-Meier method. RESULTS: AYA NHL constituted 4% of all lymphomas. Diffuse large B-cell (DLBL) was the most frequent subtype. Following were the 2-year PFS and OS - DLBL 64%, 76.9%, Burkitt's lymphoma: 56%, 56%, lymphoblastic lymphoma: 33.2%, 44%. Our results did not show any improvement in outcome of DLBL with the use of Burkitt's lymphoma like regimen. CONCLUSIONS: This study highlights some of the key features of AYA NHL occurring in developing world.

Validation of recursive partitioning analysis classification in patients with brain metastases from non-small cell lung cancer treated with short-course accelerated radiotherapy.

AIMS: To study various prognostic factors affecting outcome and to validate Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class in non-small cell lung cancer (NSCLC) with brain metastases treated with short-course accelerated radiotherapy (SCAR). MATERIALS AND METHODS: The case records of 100 patients with NSCLC consecutively treated at Tata Memorial Hospital from August 2006 to August 2009 were studied for various patient, tumour and treatment-related prognostic factors. Patients received whole-brain radiotherapy to a dose of 20 Gy/five fractions over 1 week (n=90) or 30 Gy/10 fractions over 2 weeks (n=10). The Kaplan-Meier estimate was used for survival analysis in SPSS v15. RESULTS: The median overall survival was 4.0 months (range 0.5-30.0 months). The 6-, 12-, 18- and 24-month survival rates were 35.8, 18.0, 9.3 and 6.2%, respectively. Of the various prognostic factors, RPA class (II versus III, P value=0.023), Karnofsky performance score (<70 versus ≥70, P value=0.039) and the use of systemic therapy (yes versus no, P value=0.00) emerged as significant on univariate analysis. RPA classification effectively separated the patient population into prognostically distinct subgroups. The median overall survival for RPA class II and RPA class III was 6 and 4 months, respectively. The use of systemic therapy prolonged overall survival by 6 months (3 months versus 9 months). CONCLUSION: The SCAR regimen is an effective and resource-sparing palliative strategy for brain metastases in NSCLC. The results validate the usefulness of RPA classification in this specific subset of patients treated with SCAR.

Case report: Second primary small cell carcinoma of the trachea in a breast cancer survivor: a case report and literature review.

Small cell carcinoma of the trachea is a rare entity and only a few cases have been described, none as a second malignant neoplasm. This is the first report of a metachronous second primary of the trachea with small cell histology in a breast cancer survivor. A 25-year-old woman was diagnosed initially with an infiltrating ductal carcinoma of the breast, and was treated with modified radical mastectomy followed by adjuvant chemo-radiotherapy. 10 years later, she presented with breathlessness and central airway obstruction. Bronchoscopy revealed an intraluminal lesion in the proximal trachea, which was reported as small cell carcinoma on biopsy. There was no evidence of loco-regional recurrence of the previously treated breast cancer. Whole-body positron emission tomography did not show any distant metastases. As it was a small cell carcinoma, she was treated with concurrent chemo-radiotherapy and remains loco-regionally controlled. Decision-making in such instances should take into account prior treatment and needs to be individualized. There is a need for increased awareness amongst primary care physicians regarding second malignant neoplasms in the long-term follow-up of breast cancer patients treated with radiation and chemotherapeutic agents that have carcinogenic potential.

Encouraging experience of concomitant Temozolomide with radiotherapy followed by adjuvant Temozolomide in newly diagnosed glioblastoma multiforme: single institution experience.

The purpose of this study was to report our experience with concomitant and adjuvant temozolomide (TMZ) with radiotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). Forty-two newly diagnosed histopathologically proven patients with GBM underwent maximal safe resection followed by external radiotherapy to a total dose of 60 Gy in 30 fractions over 6 weeks along with concomitant oral TMZ (75 mg/m2) daily followed by adjuvant TMZ for 5 days every 28 days for six cycles (150 mg/m2 for the first cycle and 200 mg/m2 for rest of the cycles). Patients were monitored clinicoradiologically as per standard practice. Patients were 13-69 years of age with a median age of 49.5 years (31 males, 11 females). Fifty per cent of patients underwent a gross total resection of tumour, 43% had partial resection, and 7% an open or stereotactic biopsy only. 53% of the patients had a post-operative Karnofsky Performance Score (KPS) of 60-80%. All patients received concomitant radiation and TMZ with 74% of the patients completing six cycles of adjuvant TMZ. At a median follow-up of 12.5 months, the 1- and 2-year survival was 67 and 29%, respectively. The median overall and progression-free survival was 16.4 and 14.9 months respectively. Patients with pretreatment KPS of >80% had significantly better overall survival as compared with those having KPS

Rituximab (anti-CD20 monoclonal antibody) in lymphoproliferative malignancies: Tata Memorial experience.

Rituximab has been used extensively in lymphoproliferative disorders. We evaluated the results of 64 consecutive patients treated between 2001 and 2004 at our institution. This included 54 males and 10 females. The median age was 54 years (range 17 to 85 years). One-fourth of patients were above 60 years. The histology was aggressive NHL in 35, indolent NHL in 22 and 7 cases were diagnosed as CLL. Among NHL, sixteen were in early stage (I/II) and the remaining forty-one were in advanced stage (III/IV) of disease. B symptoms were present in 47% of cases. A total of 33 were de novo cases and 31 were previously treated. Rituximab monotherapy was used in 17 cases. Rituximab was used in combination with chemotherapy in the other 47 cases. Infusional toxicity included anaphylaxis in one, hypotension in one and minor infusional reactions in four others. The patient who developed anaphylaxis required discontinuation of further Rituximab. Growth factors were used in 25 patients. Febrile neutropenia occurred in 19 patients. The overall RR (CR + PR) was 72%. One patient had stable disease and progressive disease was documented in 17 patients. A total of seven patients died, three due to progressive disease, three due to chemotherapy related toxicity and one due to an unrelated cause. We conclude that Rituximab is a valuable addition to the treatment armamentarium of lymphoproliferative disorders.

Brain metastasis--evidence based management.

Advances in cancer management have resulted in a significant increase in median survival of number of diseases. Consequently we are seeing more patients living long enough to develop symptomatic brain metastases. The management of such patients will be discussed here. The most important definitive investigation is contrast enhanced MRI scan of brain. Management consists of supportive care and disease directed treatment. Surgical resection remains the gold standard for the treatment of solitary brain metastases. Whole brain radiotherapy is considered standard treatment for all patients with brain metastases. The role of chemotherapy was limited in the past. Recently several new agents have been identified as potentially useful. Preliminary results indicate that drugs like temozolomide and topotecan have antitumor activity against the brain metastases as well as the primary systemic malignancies. The goal of multimodality treatment for brain metastases is to palliate local symptoms and prevent consequences of neurological involvement.

High dose chemotherapy followed by autologous haemopoietic stem cell transplant in multiple myeloma.

BACKGROUND: High dose chemotherapy followed by autologous stem cell transplant is currently used for the treatment of patients with advanced multiple myeloma. However, there are no reports of the results of this treatment modality in Indian patients. METHODS: Fifty patients with advanced multiple myeloma underwent treatment with high dose melphalan followed by autologous stem cell transplant (bone marrow: 7; peripheral blood stem cells: 43). The patients' ages ranged from 26 to 65 years (median: 52 years) and 35 were men. All patients had received chemotherapy initially with a mean of 9.4 cycles (range: 1-36). Thirty patients had evidence of chemosensitive disease at the time of transplant. The mean interval from diagnosis to transplant was 17.5 months (range: 3-129 months) and the median number of mononuclear cells infused was 4.86 x 10(8) per kg (range: 2-10.48). RESULTS: Post-transplant, 43 of 50 patients engrafted. The median number of days to engraftment (absolute neutrophil count > 500/cmm) was 12 (range: 9-24) and to achieve platelet transfusion independence (> 20,000/cmm) was 13 (range: 8-36). Seven patients died prior to engraftment. Grade III-IV oral mucositis was the major non-haematological toxicity. Excluding the 4 patients who had complete response prior to the transplant and continued in the same status post-transplant, 31/46 patients (67%) responded; complete response was achieved in 25 (54%) and partial response in 6 (13%). Patients with chemosensitive disease had higher rates of complete response; 20 of 26 patients with partial response at transplant achieved complete response compared to 5 of 20 patients with persistent/refractory disease (p < 0.01). Currently, 34 of 50 (68%) patients are alive, 17 (34%) disease-free, 6 with disease are on salvage therapy, 11 (22%) with positive monoclonal protein but asymptomatic are under observation. Nine (18%) patients have died; 8 due to progressive disease and 1 of an unrelated cause. The median follow up for the entire group is 26 months (range: 1-144 months). The Kaplan-Meier probability of overall and progression-free survival for the whole group at 30 months is 62% +/- 8.11% (SE) and 42% +/- 9.54% (SE), respectively. A haemoglobin level < or = 10 g/dl (p < 0.003) affected the survival adversely. Chemosensitive disease (p < 0.008) at transplant and complete response post-transplant (p < 0.0001) were associated with significantly longer survival. CONCLUSION: High dose melphalan followed by autologous stem cell transplantation is an effective treatment for patients with advanced multiple myeloma and achievement of complete response is associated with improved survival.

Avascular necrosis of head of femur in a patient with acute promyelocytic leukemia.

Avascular necrosis (AVN) of head of the femur is associated with various pathological conditions and treatment modalities. We present a case of acute promyelocytic leukemia who was treated with all-transretinoic acid (ATRA), daunomycin, cytarabine and a short course of dexamethasone. He developed AVN of bone after 2 years of treatment. Whether this is related to ATRA is dealt with in the discussion.