Papers by Anurag Srivastava
MCQs emphasize recall of factual information rather than conceptual understanding and integration... more MCQs emphasize recall of factual information rather than conceptual understanding and integration of concepts. We do not need medical students who are encyclopedia of scientific trivia and memorize information that can be stored and retrieved in seconds using palmtops. We do need students skilled in data analysis, critical thinking and clinical problem solving. Based on concept of free recall the questions may be structured as open ended. The authors hope that this suggestion would provoke healthy criticism in the arena of Medical Education.
PLOS ONE, 2017
Introduction Duct ectasia (DE) and periductal mastitis (PDM) are the most common benign breast co... more Introduction Duct ectasia (DE) and periductal mastitis (PDM) are the most common benign breast conditions seen in women. The etiopathogenesis of these entities is still not clear and most of the theories regarding the causation are based on the histological features as seen on light microscopy. The ultramicroscopic features associated with these conditions that may give more insight to the etiopathogenesis are unknown. Aim To study the ultrastructural changes occurring in mammary duct cones in patients with DE and PDM using Transmission Electron Microscopic (TEM). Method Major ducts removed by radical duct excision from 21 patients with final histopathological diagnosis of DE and PDM were subjected to TEM study with 2 normal duct samples as controls. Results The TEM features of DE were denudation of the epithelial cells with focal loss of microvilli, widening of the inter-epithelial junctions with focal disruption of the T bars, periductal collagenisation without inflammation, and features suggestive of Epithelial Mesenchymal Transition (EMT). PDM features are intact epithelial lining with proliferative epithelium and periductal collagenisation with inflammation. Conclusions Based on the TEM findings, we suggest that DE and PDM are two different entities. EMT a novel finding observed in DE in this study.
PLoS ONE, 2012
Tumor hypoxia is a known driver of angiogenesis that also facilitates tumor growth. Moreover, poo... more Tumor hypoxia is a known driver of angiogenesis that also facilitates tumor growth. Moreover, poorly oxygenated central tumor area remains relatively radio or chemo resistant. HBO therapy is known to elevate the levels of dissolved oxygen and eliminates tumor hypoxia. It has been one of the modalities in cancer treatment; therefore its optimization is important. In this experimental study, no cancer enhancing effect was seen during the course of HBO therapy; however, post therapy there was an accelerated growth and progression of tumor. HBO treated mice lived shorter and the response to therapy was dose & tumor volume dependent. HBO therapy probably exert its effect on the cancer proliferating cells through multiple pathways such as increased DNA damage, apoptosis & geno-toxicity leading to slow cancer progression while post therapy tumorigenic effect could be due to impaired DNA repair mechanism, mutagenic effect & aneuploidy as well as altered blood supply & nutrients. Tumor growth reached plateau with time and this finding validated theoretical model predicting tumor reaching an asymptotic limit. While, marked asymmetry observed in tumor volume progression or cancer cell proliferation rate in each of the experimental C3H mouse suggested a need for an alternate small animal pre-clinical cancer therapeutic model.
Proceedings of the 3rd International Conference on Photonics, Optics and Laser Technology, 2015
A new technique of identifying tumour containing sentinel lymph node has been developed. Sentinel... more A new technique of identifying tumour containing sentinel lymph node has been developed. Sentinel node biopsy is the current standard of care practice for assessing axillary nodal status in ladies with early breast cancer. Sentinel node biopsy is performed by using a combination of a blue dye and an isotope tagged to a large particulate matter like sulphur colloid or albumin. These tracers are injected in the breast tissue or skin over the breast. We describe a new method of "dual route of injection" of tracers both in the breast as well as in the systemic circulation through a peripheral vein. This method of dual route injection is expected to detect the axillary nodes containing tumour metastasis and reduce the probability of missing a "false negative sentinel lymph node".
Kathmandu University medical journal (KUMJ)
To compare transvaginal sonography (TVS), sonohysterography (SHG), hysteroscopy and endometrial a... more To compare transvaginal sonography (TVS), sonohysterography (SHG), hysteroscopy and endometrial aspiration (EA) and p53 expression in assessing endometrial abnormalities in women on tamoxifen. In a cross sectional study of 50 pre- and post-menopausal women receiving tamoxifen for > 2 years, all participants underwent TVS and EA. Those with endometrial thickness > 4 mm on TVS underwent hysteroscopy and SHG. Serum p53 antibody and p53 immunohistochemistry were tested in all women. The sensitivity and specificity when compared with histopathology as the reference standard were as follows: TVS 100% and 33.3%, SHG 85.7% and 50%, hysteroscopy 92.8% and 80.8%, serum p53 50% and 83.3%, and p53 immunohistochemistry 57.1% and 61.1%. Prevalence of endometrial abnormalities was not significantly different in asymptomatic and symptomatic women. Tamoxifen-users require routine testing for endometrial evaluation. TVS followed by hysteroscopy and biopsy is an effective option. p53 expression ...
Clinical cancer research : an official journal of the American Association for Cancer Research, 2000
The cyclin-dependent kinase inhibitor gene p21(Waf1/Cip1) plays a central role in inducing cellul... more The cyclin-dependent kinase inhibitor gene p21(Waf1/Cip1) plays a central role in inducing cellular growth arrest, terminal differentiation, and apoptosis. Alterations in this gene may adversely affect regulation of these processes and increase susceptibility for cancer. We have recently reported a novel polymorphism in the p21(Waf1/Cip1) gene in the Indian population and its association with esophageal cancer. An A-->G transition at codon 149 resulted in amino acid substitution from aspartate to glycine in the proliferating cell nuclear antigen binding COOH-terminal domain of p21(Waf1/Cip1) that may affect PCNA-p21(Waf1/Cip1) interactions, thereby affecting regulation of cellular proliferation, and may increase susceptibility for development of cancer. In a parallel study in our laboratory, we searched for putative p21(Waf1/Cip1) mutations in oral premalignant and malignant lesions. No somatic mutation was detected in exon 2 of p21(Waf1/Cip1). Interestingly, a codon 149 polymorp...
Annals of Surgery, 1993
ABSTRACT
BMC Cancer, 2010
Background We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme ... more Background We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure. Methods Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems. Results Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was signi...
Indian Journal of Surgery, 2010
Deep vein thrombosis [DVT] is one of the most dreaded complications in post-operative patients as... more Deep vein thrombosis [DVT] is one of the most dreaded complications in post-operative patients as it is associated with considerable morbidity and mortality. Majority of patients with postoperative DVT are asymptomatic. The pulmonary embolism, which is seen in 10% of the cases with proximal DVT, may be fatal. Therefore it becomes imperative to prevent DVT rather than to diagnose and treat. Only one randomized trial has been reported from India to assess the effectiveness of low molecular weight heparin in preventing post-operative DVT. To assess the risk of DVT in North Indian patients following major abdominal operations and to evaluate the effectiveness of Nadroparin, A Low Molecular Weight Heparin (LMWH) therapy in preventing post-operative DVT. Sixty five patients were randomised preoperatively into Group-I; Nadroparin prophylaxis and Group-II: No prophylaxis. The primary outcome was the occurrence of DVT, diagnosed by bilateral lower limb venogram performed, seven to ten days after operation. Secondary outcome measures included adverse effects of radio-opaque dye, intra-operative blood loss, operating time, postoperative platelet count, intraoperative blood transfusion requirements and the total duration of postoperative bed rest. No case of DVT occurred in either group. There was no statistical difference in the risk of secondary outcome measures in the two groups. DVT was not observed in any of the patients, even with several high risk factors indicating a possible protective mechanism in the North Indian population.
Indian Journal of Surgery, 2010
We conducted a randomized trial to evaluate effectiveness of Centchroman in control of mastalgia ... more We conducted a randomized trial to evaluate effectiveness of Centchroman in control of mastalgia and compared it with Danazol. Research Question-Is proportion of pain relief achieved by Centchroman similar to or inferior to that achieved by Danazol? In a randomized controlled trial of Centchroman vs. Danazol in mastalgia, 81 patients with mastalgia were studied. Thirty-nine patients were randomized to Danazol arm and 42 in Centchroman arm. The treatment was given for 12 weeks, followed by observation for 12 weeks. The pain was measured by visual analogue scale (VAS) of 0-10. At 12 weeks 89.7% women achieved reduction in pain score to ≤3 in Centchroman group (pvalue 0.001). In Danazol group 69.44% women achieved reduction in pain score to ≤ 3 (p=0.001). Three months after stopping therapy, Centchroman was more effective in pain score reduction at 24 weeks as compared to Danazol (p=0.019). Centchroman is an effective, safe and inexpensive alternative to Danazol for treatment of mastalgia.
Indian Journal of Surgery, 2010
We conducted a randomized trial to evaluate effectiveness of Centchroman in control of mastalgia ... more We conducted a randomized trial to evaluate effectiveness of Centchroman in control of mastalgia and compared it with Danazol. Research Question-Is proportion of pain relief achieved by Centchroman similar to or inferior to that achieved by Danazol? In a randomized controlled trial of Centchroman vs. Danazol in mastalgia, 81 patients with mastalgia were studied. Thirty-nine patients were randomized to Danazol arm and 42 in Centchroman arm. The treatment was given for 12 weeks, followed by observation for 12 weeks. The pain was measured by visual analogue scale (VAS) of 0-10. At 12 weeks 89.7% women achieved reduction in pain score to ≤3 in Centchroman group (pvalue 0.001). In Danazol group 69.44% women achieved reduction in pain score to ≤ 3 (p=0.001). Three months after stopping therapy, Centchroman was more effective in pain score reduction at 24 weeks as compared to Danazol (p=0.019). Centchroman is an effective, safe and inexpensive alternative to Danazol for treatment of mastalgia.
Indian journal of surgical oncology, 2010
The axillary lymph node status is the most important determinant of prognosis in patients with br... more The axillary lymph node status is the most important determinant of prognosis in patients with breast cancer. Sentinel lymph node (SLN) biopsy is a safe alternative for axillary clearance with an equal efficacy limiting the morbidity caused by axillary clearance. From May 1996 till September 2009, 523 clinically node negative, early breast cancer patients attending our clinic at All India Institute of Medical Sciences were included in the study. They underwent sentinel lymph node biopsy by either combined technique or blue dye alone. All patients irrespective of the axillary status underwent axillary lymph node dissection (ALND). Of 523 patients, 267 underwent combined technique of sentinel node mapping and 256 underwent blue dye technique alone. The identification rate of sentinel lymph node was 94.3% (253/267) for combined technique and 87.8% (225/256) for blue dye alone. Of 523 patients SLN was identified in 478 patients. The identification rate was 91.3%. The sensitivity = 91.5%...
Indian journal of surgical oncology, 2010
The axillary lymph node status is the most important determinant of prognosis in patients with br... more The axillary lymph node status is the most important determinant of prognosis in patients with breast cancer. Sentinel lymph node (SLN) biopsy is a safe alternative for axillary clearance with an equal efficacy limiting the morbidity caused by axillary clearance. From May 1996 till September 2009, 523 clinically node negative, early breast cancer patients attending our clinic at All India Institute of Medical Sciences were included in the study. They underwent sentinel lymph node biopsy by either combined technique or blue dye alone. All patients irrespective of the axillary status underwent axillary lymph node dissection (ALND). Of 523 patients, 267 underwent combined technique of sentinel node mapping and 256 underwent blue dye technique alone. The identification rate of sentinel lymph node was 94.3% (253/267) for combined technique and 87.8% (225/256) for blue dye alone. Of 523 patients SLN was identified in 478 patients. The identification rate was 91.3%. The sensitivity = 91.5%...
World Journal of Surgery, 2007
Background: Fibroadenoma is common among women in reproductive age group. Still treatment for thi... more Background: Fibroadenoma is common among women in reproductive age group. Still treatment for this condition is not standardised. Most of the drugs used are expensive and have side effects. Centchroman is a non-steroidal, selective antioestrogen and has the advantages of less frequent administration and is free from side effects of steroidal agents, whereas, the efficacy of commonly used evening primrose oil is still in debate. Aim: To assess the role of Centchroman versus evening primrose oil in the regression of fibroadenoma of breast. Material and Methods: Eighty patients were diagnosed with fibroadenoma and they were divided into two groups. One group was given Centchroman 30mg OD alternate days and the other group was given Evening primrose oil 500 mg BD daily for a period of 3 months and followed up for next 3 months. Patients were followed up with clinical examination and ultrasound breast. Results: 8 (20%) fibroadenomas in Centchroman arm disappeared completely as compared to four (10%) in Evening primrose oil arm over a period of 6 months. There was a decrease in the volume of fibroadenoma in eight (20%) patients in Evening primrose oil arm and 28 (70%) patients in Centchroman arm. Centchroman therapy allowed 20% fibroadenoma to regress completely with scanty menses or amenorrhea as the only side effect. Conclusion: Centchroman at a dosage of 30 mg daily for 3 months allowed complete regression of 20% of fibroadenoma, whereas only 10% of lesions regressed completely with Evening primrose oil.
Indian Journal of Nuclear Medicine, 2013
survival and for deciding systemic and loco regional treatment in breast cancer. [2,3] Axillary l... more survival and for deciding systemic and loco regional treatment in breast cancer. [2,3] Axillary lymph node dissection (ALND) is considered to be the standard procedure to assess axillary lymph node status. It is associated with significant morbidity such as lymphedema and paresthesias (relative risk-0.37) when compared with sentinel lymph node biopsy (SLNB). [4-6] The success of SLNB depends on identification rate and false negative rates. Lymphatic blockage is an important cause for failure to identify sentinel lymph node (SLN) and false negativity is due to skip metastases, which occur in 4-10% of cases. [7,8] Also SLNB requires expertise and special equipment (gamma probe for performing lymphoscintigraphy) which makes it difficult to be performed at all centers. Hence there is a need for less invasive techniques, with good accuracy and lesser complications to identify axillary
Indian Journal of Surgery, 2013
Breast pain or mastalgia is the common symptom in the breast. The two most common concerns of pat... more Breast pain or mastalgia is the common symptom in the breast. The two most common concerns of patients presenting with mastalgia are: the fear that breast pain is a symptom of breast cancer and the presence of severe pain that affects a woman's quality of life. Breast pain requires thorough assessment and should be investigated in the same manner as any other breast symptom. We conducted a systematic review of treatment for breast pain. We searched various reviews, randomized controlled trial, and observational studies over Pubmed and Medline via internet. Searches were carried out on MEDLINE (1950-present), EMBASE (1980-present), and CINAHL (1981-present) using the NHS Evidence Healthcare Databases Advanced Search interface. A further search was also carried out on Cochrane Database of Systematic Reviews (issue 12 of 12, Dec 2011) and Central Register of Controlled Trials (issue 4 of 4, Oct 2011). If no abnormality is found in the breast on assessment, then a combination of reassurance, breast support brassiere, and topical NSAID gel massage are usually effective. Antiestrogen (centchroman/tamoxifen) therapy for 3 to 6 months is the second-line treatment of choice. Danazol may be used in resistant cases. Gamma-linolenic acid or evening primrose oil though commonly prescribed is not effective.
International Journal of Cancer, 2005
Background: Perturbations in cell adhesion molecules are linked to alterations in cadherin-cateni... more Background: Perturbations in cell adhesion molecules are linked to alterations in cadherin-catenin complexes and likely play major roles in invasion and metastasis; their impact on early precancerous stages remains yet unknown. We showed ALCAM overexpression in early oral lesions and its cytoplasmic accumulation in oral squamous cell carcinoma (OSCC) to be a predictor of disease progression and poor prognosis. This study tested the hypothesis that alterations in E-cadherin and b-catenin expressions are early events in oral tumorigenesis, associated with disease prognosis, and correlate with perturbations in ALCAM expression. Methods: Expressions of E-cadherin and b-catenin were analyzed in the same cohort of 105 OSCCs, 76 oral lesions and 30 normal oral tissues by immunohistochemistry and correlated with clinicopathological parameters and prognosis. The effect of siRNA mediated ALCAM knockdown on E-cadherin and b-catenin was determined using western blot, confocal microscopy and RT-PCR analysis in oral cancer cells. Results: Significant loss of membranous E-cadherin and b-catenin expression was observed from normal, hyperplasia, dysplasia to OSCCs (p trend ,0.001); and correlated with cytoplasmic ALCAM accumulation in OSCCs (p = 0.006). Multivariate analysis revealed b-catenin membrane loss and ALCAM/b-catenin nuclear/cytoplasmic accumulation to be significant predictors for late clinical stage (p,0.001, OR = 8.7; p = 0.006, OR = 9.9, respectively) and nodal metastasis (p = 0.003, OR = 3.8; p = 0.025, OR = 3.4 respectively). Cox's regression showed E-cadherin membrane loss/ALCAM cytoplasmic expression [p,0.001; HR = 4.8] to be independent adverse prognosticators in OSCCs. siRNA mediated silencing of ALCAM resulted in concurrent increase in E-cadherin and b-catenin both at the transcript and protein levels. Conclusions: Losses of E-cadherin and b-catenin expressions are early events in oral tumorigenesis; their associations with aggressive tumor behavior and disease recurrence underscore their potential as prognostic markers. Correlation of loss of Ecadherin and b-catenin with cytoplasmic ALCAM accumulation both in vitro and in in vivo suggests that these dynamic changes in cell adhesion system may play pivotal role in oral cancer.
Indian Journal of Surgery
Breast cancer in India is becoming the leading cause of cancer-related mortality in urban women. ... more Breast cancer in India is becoming the leading cause of cancer-related mortality in urban women. In developed countries, the mortality from breast cancer has decreased in the past few years attributable to better awareness of disease, screening programs, early detection and more effective treatment available. Although widely used, the screening programs running in the western countries have been a point of criticism in the recent years as they lead to increased healthcare cost and detection of otherwise benign and clinically insignificant breast lesion (both benign and malignant). Also in a developing country like ours where the awareness about breast cancer among the ladies is itself poor, whether screening is feasible and cost-effective is a matter of ongoing debate. We conducted this literature review to ascertain the importance of breast cancer awareness, breast self-examination, and clinical breast examination as effective screening tools in a resource deficient country like India.
Indian Journal of Surgery, 2016
Mastalgia is the commonest affliction of mammary gland among ladies of the reproductive age group... more Mastalgia is the commonest affliction of mammary gland among ladies of the reproductive age group. Since etiopathogenesis and therapy are different for cyclical and noncyclical pain, it is imperative to ascertain the exact type correctly. This is usually done in the breast clinics by advising the patient to fill a pain diary over a period of 2 months over two menstrual cycles. The Cardiff pain chart records the severity of pain in the form of a triangle for mild to moderate pain and a square for severe pain. Moreover, Cardiff pain chart does not allow a patient to record the severity of pain on days of menses, as she has to put the letter BP^in the box. These problems have been resolved in the new breast pain chart. In the new pain chart, the lady records pain severity in the form of visual linear analogue scale score on every day of menstrual cycle. She enters her menstrual experience on a separate part of chart, which allows us to visualize the full month's pain severity in an uncluttered way.
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Papers by Anurag Srivastava