Androgen receptor status predicts response to chemotherapy, not risk of breast cancer in Indian women.

BACKGROUND: Considerably little is known about the biological role and clinical significance of androgen receptor expression in breast cancer. The objectives of this study were to characterize AR-CAG repeat genotypes in a cohort of women with breast cancer and to determine the influence of AR on response to neoadjuvant chemotherapy and clinical outcome. MATERIALS AND METHODS: Genotyping of the AR CAG repeat region was done on 70 patients and 80 healthy aged- matched female controls. To assess response to NACT, tissue samples from 30 LABC cases were evaluated quantitatively by real time for AR mRNA expression. The clinical response was correlated with both the pre and post chemotherapy AR expression. The CAG alleles did not show differences between cases and controls when the mean of short, long and average length of both CAG alleles was considered. However, analysis when done defining short allele as CAGn < 20 (AR1) and the long as CAGn ≥ 20 (AR2), risk was found associated with AR2 allele with marginal significance (P = 0.09). Stratification by age of onset, FH, stage, grade ER and AR status failed to reveal any association with breast cancer risk. Genotype carriers with ≥ 20 CAGn showed decrease of AR mRNA expression although significance could not be established (P = 0.47). Tumours in responders had the higher AR mRNA expression levels in pre neo-adjuvant chemotherapy condition (p < 0.02) which got reduced after neoadjuvant chemotherapy and the difference was found to be significant (P = 0.014). CONCLUSIONS: Although, expansion of the CAGn in the AR gene doesn't show any major effect on breast cancer risk, patients with positive AR expression, pre neoadjuvant chemotherapy, were found to be good responders and a decrease in mRNA level of AR gene related to the chemotherapy-induced apoptosis could serve as an important independent predictor of response to NACT.

Is an aggressive approach justified in the management of an aggressive cancer--the squamous cell carcinoma of thyroid?

BACKGROUND: Primary squamous cell carcinoma of the thyroid is an extremely rare neoplasm, with less than 50 cases reported in the world literature. The prognosis is poor with a median survival of less than six months. The death is usually secondary to progression of local disease as distant metastases are rare. CASE REPORTS: Three cases, two males and one female presenting with sudden increase in the size of long standing thyroid swellings and associated pressure effects on the aero-digestive tract are reported. Exhaustive clinical, endoscopic, and radiological examinations did not reveal any primary site of squamous-cell carcinoma as the likely source of the metastases, or of any contiguous spread from neighboring structures. Two cases were managed by combined modality therapy including curative surgery with radiotherapy and one by radiotherapy alone. CONCLUSION: Primary squamous cell carcinoma is a rare malignancy with a poor outcome inspite of combined modality therapy. Out of three reported cases, two succumbed to their disease within less than one year. Aggressive surgery in the form of curative resection along with adjuvant radiotherapy is recommended, the tumor being chemo resistant.

Role of p-glycoprotein expression in predicting response to neoadjuvant chemotherapy in breast cancer--a prospective clinical study.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is an integral part of multi-modality approach in the management of locally advanced breast cancer. It is vital to predict response to chemotherapy in order to tailor the regime for a particular patient. The prediction would help in avoiding the toxicity induced by an ineffective chemotherapeutic regime in a non-responder and would also help in the planning of an alternate regime. Development of resistance to chemotherapeutic agents is a major problem and one of the mechanisms considered responsible is the expression of 170-k Da membrane glycoprotein (usually referred to as p-170 or p-glycoprotein), which is encoded by multidrug resistance (MDR1) gene. This glycoprotein acts as an energy dependent pump, which actively extrudes certain families of chemotherapeutic agents from the cells. The expression of p-glycoprotein at initial presentation has been found to be associated with refractoriness to chemotherapy and a poor outcome. Against this background a prospective study was conducted using C219 mouse monoclonal antibody specific for p-glycoprotein to ascertain whether pretreatment detection of p-glycoprotein expression could be utilized as a reliable predictor of response to neoadjuvant chemotherapy in patients with breast cancer. PATIENTS AND METHODS: Fifty cases of locally advanced breast cancer were subjected to trucut biopsy and the tissue samples were evaluated immunohistochemically for p-glycoprotein expression and ER, PR status. The response to neoadjuvant chemotherapy was assessed clinically and by using ultrasound after three cycles of FAC regime (cyclophosphamide 600 mg/m2, Adriamycin 50 mg/m2, 5-fluorourail 600 mg/m2 at an interval of three weeks). The clinical response was correlated with both the pre and post chemotherapy p-glycoprotein expression. Descriptive studies were performed with SPSS version 10. The significance of correlation between tumor response and p-glycoprotein expression was determined with chi square test. RESULTS: A significant relationship was found between the pretreatment p-glycoprotein expression and clinical response. The positive p-glycoprotein expression was associated with poor clinical response rates. When the clinical response was correlated with p-glycoprotein expression, a statistically significant negative correlation was observed between the clinical response and p-glycoprotein expression (p < 0.05). There was another significant observation in terms of development of post NACT p-glycoprotein positivity. Before initiation of NACT, 26 patients (52%) were p-glycoprotein positive and after three cycles of NACT, the positivity increased to 73.5% patients. CONCLUSION: The study concluded that pretreatment p-glycoprotein expression predicts and indicates a poor clinical response to NACT. Patients with positive p-glycoprotein expression before initiation of NACT were found to be poor responders. Thus pretreatment detection of p-glycoprotein expression may be utilized, as a reliable predictor of response to NACT in patients with breast cancer The chemotherapy induced p-glycoprotein positivity observed in the study could possibly explain the phenomenon of acquired chemoresistance and may also serve as an intermediate end point in evaluating drug response particularly if the adjuvant therapy is planned with the same regime.

Early tracheostomy in closed head injuries: experience at a tertiary center in a developing country--a prospective study.

BACKGROUND: An important factor contributing to the high mortality in patients with severe head trauma is cerebral hypoxia. The mechanical ventilation helps both by reduction in the intracranial pressure and hypoxia. Ventilatory support is also required in these patients because of patient's inability to protect the airway, persistence of excessive secretions, and inadequacy of spontaneous ventilation. Prolonged endotracheal intubation is however associated with trauma to the larynx, trachea, and patient discomfort in addition to requirement of sedatives. Tracheostomy has been found to play an integral role in the airway management of such patients, but its timing remains subject to considerable practice variation. In a developing country like India where the intensive care facilities are scarce and rarely available, these critical patients have to be managed in high dependency cubicles in the ward, often with inadequately trained nursing staff and equipment to monitor them. An early tracheostomy in the selected group of patients based on Glasgow Coma Score(GCS) may prove to be life saving. Against this background a prospective study was contemplated to assess the role of early tracheostomy in patients with isolated closed head injury. METHODS: The series consisted of a cohort of 50 patients admitted to the surgical emergency with isolated closed head injury, that were not considered for surgery by the neuro-surgeon or shifted to ICU, but had GCS score of less than 8 and SAPS II score of more than 50. First 50 case records from January 2001 that fulfilled the criteria constituted the control group. The patients were managed as per ATLS protocol and intubated if required at any time before decision to perform tracheostomy was taken. These patients were serially assessed for GCS (worst score of the day as calculated by senior surgical resident) and SAPS scores till day 15 to chart any changes in their status of head injuries and predictive mortality. Those patients who continued to have a GCS score of <8 and SAPS score of >50 for more than 24 hours (to rule out concussion or recovery) underwent tracheostomy. All these patients were finally assessed for mortality rate and hospital stay, the statistical analysis was carried out using SPSS10 version. The final outcome (in terms of mortality) was analyzed utilizing chi-square test and p value <0.05 was considered significant. RESULTS: At admission both tracheostomy and non-tracheostomy groups were matched with respect to GCS score and SAPS score. The average day of tracheostomy was 2.18 +/- 1.0038 days. The GCS scores on days 1, 2, 3, 4, 5, 10 between tracheostomy and non-tracheostomized group were comparable. However the difference in the GCS scores was statistically significant on day 15 being higher in the tracheostomy group. Thus early tracheostomy was observed to improve the mortality rate significantly in patients with isolated closed head injury. CONCLUSION: It may be concluded that early tracheostomy is beneficial in patients with isolated closed head injury which is severe enough to affect systemic physiological parameters, in terms of decreased mortality and intubation associated complications in centers where ICU care is not readily available. Also, in a selected group of patients, early tracheostomy may do away with the need for prolonged mechanical ventilation.

Primary mediastinal hemangiopericytoma treated with preoperative embolization and surgery.

Hemangiopericytomas are rare tumors originating from vascular pericytes. The mediastinum is an extremely uncommon site with only a few cases reported. Diagnosis is based on histopathology and immunohistochemistry, which differentiates them from synovial sarcoma and solitary fibrous histiocytoma. They have a variable malignant potential. Treatment is mainly surgical extirpation as the role of adjuvant therapy is controversial. Preoperative embolization has been sparingly used. We report a case of primary mediastinal hemangiopericytoma in a 47-year-old man treated successfully with preoperative embolization and surgery.

Carcinoma developing in a fibroadenoma in a woman with a family history of breast cancer: a case report and review of literature.

INTRODUCTION: Malignant transformation of a fibroadenoma is rare with only about 100 cases reported in the world literature. Fibroadenoma occurring in middle aged woman with a strong family history of breast or ovarian cancer should be investigated with a high suspicion for malignancy. CASE PRESENTATION: A 35-year- old Indian lady operated previously for fibroadenoma of the right breast presented with a recurrent lump at the same site. She had a strong family history of breast carcinoma. Mammography and trucut biopsy was suggestive of infiltrating duct carcinoma. She was managed by lumpectomy and axillary lymph node dissection with a satisfactory outcome. There was no evidence of BRCA-1, BRCA-2 mutation on immunohistochemistry. CONCLUSION: Malignant change in a pre-existing fibroadenoma is rare, however in a middle aged woman with a family history of breast cancer it should be suspected. In the absence of any definite clinical and radiological criteria of diagnosing malignant change in a fibroadenoma, high suspicion index is mandatory. The management and outcome depends on the stage and grade of presentation.