Epidermal growth factor receptor (EGFR) mutations as biomarker for head and neck squamous cell carcinomas (HNSCC).

CONTEXT: Mutations in tyrosine kinase domain (TK) of epidermal growth factor receptor (EGFR) lead to signalling interruptions in several cancers. OBJECTIVE: To understand EGFR mutations in head and neck squamous cell carcinomas (HNSCC), and their role as biomarkers. METHODS: Screened 129 HNSCC patients and 150 controls for mutations in the TK domain using polymerase chain reaction (PCR), single strand confirmatory polymorphism (SSCP) and sequencing. RESULTS: 81.39% of HNSCC had four mutations: G2155C, G2176A, C2188G and G2471A among these two mutations were also reported in other cancers where as two novel mutations are being reported for the first time in HNSCC. Mutational frequency was significantly associated with an advanced stage of HNSCC, habits of tobacco/alcohol and ages above 49 years. CONCLUSION: EGFR single nucleotide polymorphisms could be useful biomarkers of HNSCC.

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

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

Hematological profile of HIV patients in relation to immune status - a hospital-based cohort from Varanasi, North India.

OBJECTIVES: To study the spectrum of hematological manifestations and evaluate the relationship between various hematological manifestations and CD4 cell counts in a hospital-based cohort of HIV-infected adults in and around Varanasi, North India. MATERIALS-METHODS: The clinical and hematological profiles of the patients attending the Infectious Disease Clinic, Varanasi, India were recorded. The relationship between CD4 counts and various hematological manifestations was analyzed. RESULTS: A total of 470 HIV-infected individuals were followed for 830 person years of observation (PYO). Rate of hematological episodes was 1047 episodes per 1000 PYO. CD4 counts were significantly lower in individuals with severe anemia and neutropenia compared to those without. However, no relation could be established between thrombocytopenia and CD4 counts. In the above- mentioned population, CD4 levels were significantly lower in those with anemia/neutropenia harboring any particular disease compared to those who had the same disease without anemia/ neutropenia. CONCLUSIONS: There is a strong negative association between CD4 counts and the severity of anemia and neutropenia in this population. They can be considered as good clinical indicators to predict and access the underlying immune status. Though fall in the CD4 levels during neutropenia is observed, it is difficult to comment since the estimations of CD4 rely on the total leukocyte counts. However, the relation between anemia and disease progression is straight forward and quite useful for the treating physician.

Orbital metastasis: a rare presentation of osteosarcoma.

Non-pulmonary metastases in osteosarcoma are increasingly recognized because of improved longevity in patients receiving modern treatment. One rare site of metastasis is the orbit, with only three cases reported so far. This report describes a 16-year-old male patient, who underwent above-knee amputation for right tibial osteosarcoma and later presented with a painful protrusion of the right eyeball and near-normal vision. The uncommon features in the present case are the site of metastasis and near-normal vision.

Malignant myelomatous pleural effusion-Is onset of effusion a new prognostic factor?

Malignant pleural effusion in myeloma (MMPE) is a rare terminal event; with a median survival is four months. All the patients usually have multiple poor prognostic factors and none of them (like beta 2-microglobulin, karyotype, Stage of disease, C-reactive protein etc.) correctly predicts the survival. We are reporting a series of five cases and evaluated the factors influencing the overall survival. All of our patients had a very good response to treatment and had a better survival compared to the reported cases so far. After reviewing the literature carefully we found that timing of development of pleural effusion is probably the most important prognostic factor. Those who develop effusion after some time lag form the initial treatment, will have a poor survival (median four months) compared to those who had effusion at the start of the disease.

Diarrhea, CD4 counts and enteric infections in a hospital - based cohort of HIV-infected patients around Varanasi, India.

BACKGROUND: As most of the studies in HIV patients with diarrhea were cross sectional, focusing on the etiological agents, we are reporting data on the rate of diarrhea, associations between diarrhea and CD4 counts and variation in frequency of identifying a pathogen with consistency of diarrhea and duration in a prospective hospital based study. METHODS: Stool specimens were obtained between Jan 2001 and April 2003 from HIV infected adults with diarrhea presenting to Infectious Disease clinic, Banaras Hindu University, Varanasi. In all patients with diarrhea, specimens were examined by microscopy and cultures to identify pathogens. RESULTS: During the study, 630 person years of observations with diarrhea were analyzed. 140 stool samples were collected representing 43% of episodes of reported diarrhea. Positivity of finding a pathogen from watery stools and formed stools were 40%&24% respectively (p < 0.01) probably due to associated inflammation is more in watery diarrhea. Patients having chronic diarrhea are 2.25 (95%CI 1.52-2.81) times at more risk of developing other opportunistic infections compared to those who don't have. However this is not true with the acute diarrhea where risk of harboring the opportunistic infections remain same. CONCLUSION: Diarrhea was most strongly associated with low CD4 counts. Over two-thirds of diarrheal episodes were undiagnosed, suggesting that unidentified agents or primary HIV enteropathy are important causes of diarrhea in this population. There is a strong negative association between duration of diarrhea and CD4 levels.

A retrospective study of clinico-hematological and cytogenetic profile of erythroleukemia from South India.

Objective of the study is the retrospective evaluation of clinico-hematological and cytogenetic profile of patients with erythroleukemia (EL) in a south Indian population. Case records of all patients with acute myeloid leukemia seen in the Department of Medical Oncology at Kidwai Memorial Institute of Oncology, Bangalore, between January 1997 and December 2004 were reviewed. Clinical details were noted and slides were reviewed. A total of 326 AML patient were diagnosed of whom 14 patients had AML M6. Contribution of EL to all forms of AML was 4.3%. The mean age was 37.1+13.9 yrs (range: 16-65); most patients were in their 4th decade, with a male: female ratio of 3.67: 1. Mean duration of symptoms in the present series was 10.9+6.9 weeks. Cytogenetics were normal in 71% of cases, and minor abnormalities were observed in 21% of cases. As a conclusion relative low incidence of secondary EL, more frequent normal karyotype, and relatively younger age observed in our series makes the picture of EL in our subcontinent different from that in other series reported thus far.

Simultaneous occurrence of multiple myeloma and acute myeloid leukemia.

Multiple myeloma and acute leukemia may sometimes occur in the same patient, usually in patients with myeloma who receive chemotherapy and subsequently develop acute leukemia. However, simultaneous occurrence of myeloma and acute leukemia on presentation is rare, with only a handful of such cases reported in the literature.

Retroperitoneal inflammatory myofibroblastic tumor.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a neoplasm of unknown etiology occurring at various sites. By definition, it is composed of spindle cells (myofibroblasts) with variable inflammatory component, hence the name is IMT. CASE PRESENTATION: The present case is of a 46 years old woman presented with a history of flank pain, abdominal mass and intermittent hematuria for last 6 months. The initial diagnosis was kept as renal cell carcinoma. Finally, it turned out to be a case of retroperitoneal IMT. The patient was managed by complete surgical resection of the tumor. CONCLUSION: IMT is a rare neoplasm of uncertain biological potential. Complete surgical resection remains the mainstay of the treatment.