Mahesh Kumar Mittal

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

BackgroundNeoadjuvant 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 methodsFifty 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.ResultsA 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.ConclusionThe 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.

Variations of celiac axis, common hepatic artery and its branches in 600 patients

Purpose: To evaluate the spectrum of celiac axis, common hepatic artery (CHA), right, left, middle hepatic artery and gastroduodenal artery variations by using spiral computed tomography (CT). Materials and Methods: A retrospective review of Multidetector CT (MDCT) abdominal angiography scans was performed in patients sent for various liver and other abdominal pathologies between January 2012 and February 2013. A total of 600 patients were evaluated. Definitions of CHA, ambiguous celiac axis, course and division patterns of CHA, replaced hepatic artery, accessory hepatic artery and middle hepatic artery were used as proposed by Song et al., Covey et al., and Wang et al. The pattern of the aortic origin of branches of celiac axis, common hepatic artery and its branches was analyzed. Results: Six types of celiac axis anatomic variations were identified in our study. A total of 546 of the 600 patients had a normal celiac axis anatomy. Anatomic variations were seen in 5.5% of patients. Ambiguous anatomy was seen in 3.5% of the patients. CHA originated from celiac axis in 95.83% of the patients. Variations in anatomic origin of CHA were seen in 8 patients. Ambiguous dual pathway was seen in 4 patients. Normal Sp-preportal course of CHA was identified in 97.78% of cases, Sp-retroportal course in 7 patients, Tp-preportal course in 2, Tp-retroportal in 1, Ip-preportal in 1 and through Ligamentum venosum in 2 patients. Normal origin of RHA from HAP was seen in 79.6% patients. Replaced origin of RHA was seen in 15.16% cases and Accessory origin of RHA was seen in 5.16% cases. LHA originated from HAP in 81.5% patients. Replaced LHA origin was seen in 10.8% cases and Accessory LHA origin seen in 7.6% cases. MHA originated from RHA in 41.3% patients, LHA in 27.83% and from CHA in 4.5% cases. Origin of MHA could not be defined in 26.3% of patients. GDA originated from CHA in 97.6% of patients, from celiac axis in 1.6%, from RHA in 0.33% in patients. Trifurcation of CHA was seen in 7.16% and quadrifurcation of CHA in 2.16%. Conclusion: CT Angiography is a safe and highly sensitive and accurate modality for evaluation of arterial anatomy and its variants.

Radiological review of pleural tumors

Tumors of the pleura are not uncommon and diagnosis is clinched by combined imaging and clinical correlation. Malignant tumors are more common than benign tumors. Initial imaging modalities are chest radiography and Computed Tomography (CT). Further characterization may be required using Ultrasoundgraphy (USG), Magnetic resonance Imaging (MRI) and PET-CT. Biopsy remains gold standard. This article highlights various common and uncommon tumors of pleura and characteristic imaging findings.

Predictors of early neurological deterioration in patients with acute ischaemic stroke with special reference to blood urea nitrogen (BUN)/creatinine ratio & urine specific gravity.

Background & objectives: Early neurological deterioration (END) occurs in about 20 to 40 per cent of patients with acute ischaemic stroke and results in increased mortality and functional disability. In recent studies relative dehydration has been found to be associated with END in patients with acute ischaemic stroke. This study was conducted to identify factors useful for predicting END and to assess the role of blood urea nitrogen/creatinine ratio (BUN/creatinine) and urine specific gravity (USG) as predictors of END in patients with acute ischaemic stroke. Methods: The present study was an observational prospective study. Various parameters comprising demographic, clinical, laboratory and radiological variables along with stroke severity were assessed and studied as predictors of early neurological deterioration in 114 consecutive patients presenting to the Emergency department during 2012. BUN/creatinine >15 and USG >1.010 were studied as markers of relative dehydration contributing to END. Results: Of the 114 patients enrolled in the study, END was observed in 25 (21.9%) patients. National Institutes Health Stroke Scale score (NIHSS) ≥ 12 at admission was found to be an independent risk factor for END. Amongst markers of relative dehydration, BUN/creatinine >15 at admission was found to be an independent risk factor for END, as also USG >1.010. Also, cerebral oedema and size of hypodensity >1/3rd of the middle cerebral artery territory on cranial CT were observed to be independent risk factors for END. Interpretation & conclusions: Our study findings highlighted a possible association of relative dehydration, as indicated by BUN/creatinine ratio >15, with END along with other parameters like stroke severity at presentation, extent of hypodensity >1/3rd of the middle cerebral artery (MCA) territory and cerebral oedema. Dehydration being a treatable condition, the use of BUN/creatinine >15 as a marker of relative dehydration, can be helpful in detecting patients with dehydration early and thus play a role in preventing END.

Supernumerary kidneys- a rare anatomic variant

Supernumerary kidneys are a rare congenital anomaly with fewer than 100 cases reported over the years. A fused supernumerary kidney is a still rarer entity. We present imaging findings in two cases of supernumerary kidneys—the first case is a spectacular image of four kidneys in one patient seen in an excretory phase of intravenous urogram with only four cases described in the literature. The second case is that of three kidneys (fused supernumerary) seen in another patient.

Role of calf muscle stimulation in the prevention of DVT in Indian patients undergoing surgeries for fractures around the hip

Background: The venous stasis of soleal vein during surgery may be an important factor in the development of deep vein thrombosis (DVT). The stimulation of calf muscle during surgery may help in preventing DVT. The present study is conducted to evaluate the role of peroperative calf muscle electrostimulation in prevention of DVT in patients undergoing surgeries around the hip joint. Materials and Methods: The study comprised 200 patients undergoing surgeries around the hip joint. The patients having risk factors (such as previous myocardial infarction, malignancies, paraplegia or lower limb monoplegia, previous history of DVT or varicose veins, etc.) for the development of DVT were excluded. They were randomized into two groups: 100 cases were given peroperative calf muscle electrostimulation for DVT prophylaxis (Group A) and the remaining 100 patients were taken as controls without any prophylaxis (Group B). The color Doppler ultrasound was performed to exclude pre-existing DVT and on 7th day postoperative to find out the incidence of DVT in both the groups. Results: Two patients among Group A and six patients among Group B demonstrated DVT on ultrasonography, but the difference was not found to be statistically significant (P=0.279). None of the patients had any clinical evidence of DVT. Conclusion: The role of peroperative calf muscle electrostimulation for DVT prophylaxis remains controversial. The risk of developing DVT in patients undergoing surgeries around the hip joint is very less in patients analysed in our series.

Imaging spectrum of gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GISTs) were first described by Clark and Mazur in 1983 for smooth muscle neoplasms of the gastrointestinal tract differentiating them from leiomyoma, leiomyosarcomas and neurogenic tumors. GISTs can arise from the bowel, peritoneum, omentum or retroperitoneum. This article reviews the computed tomography imaging features of primary GISTs, response to treatment and highlights data on predicting the outcome to chemotherapeutic drugs on imaging.

Radiography in the Initial Diagnosis of Biologic Activity or Growth Rate of Primary Bone Tumors

AJR 2013; 201:W770 0361–803X/13/2015–W770

Melorheostosis: Two atypical cases.

Melorheostosis is an uncommon mesenchymal dysplasia that rarely affects the axial skeleton. We describe two atypical cases of melorheostosis with classical imaging findings – the first one involving the cervico-dorsal spine with encroachment of left vertebral artery canal causing attenuation of the left vertebral artery and the second one of mixed sclerosing bony dysplasia (monomelic involvement coexisting with osteopoikilosis).

Unusual Mediastinal Dumbbell Tumor Mimicking an Aggressive Malignancy

Hydatid cyst is known to affect all possible anatomical locations of the human body. However, the mediastinal localization is extremely rare. This benign, commonly asymptomatic and incidentally detected disease, at times may simulate an aggressive malignancy by its potential to cause osseous destruction and intraspinal extension. A young female, farmer by occupation, presented with complaints of left chest pain and monoparesis of the left lower limb. Radiograph followed by computed tomography (CT) of the chest demonstrated a cystic mass within the posterior mediastinum, eroding and scalloping overlying ribs and extending into the spinal canal by causing destruction of adjoining vertebra, and assuming a dumbbell shape. The serology was positive for echinococcosis. The patient underwent surgery and the postoperative histopathology confirmed the diagnosis of hydatid cyst. The patient recovered with no complications or recurrence. Hydatid cyst should always be considered in the differential diagnosis of mediastinal cystic lesions, however aggressive the lessions may appear.