Kapil Kumar

Kras Gene Mutation and RASSF1A, FHIT and MGMT Gene Promoter Hypermethylation: Indicators of Tumor Staging and Metastasis in Adenocarcinomatous Sporadic Colorectal Cancer in Indian Population

Objective Colorectal cancer (CRC) development involves underlying modifications at genetic/epigenetic level. This study evaluated the role of Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation together/independently in sporadic CRC in Indian population and correlation with clinicopathological variables of the disease. Methods One hundred and twenty four consecutive surgically resected tissues (62 tumor and equal number of normal adjacent controls) of primary sporadic CRC were included and patient details including demographic characteristics, lifestyle/food or drinking habits, clinical and histopathological profiles were recorded. Polymerase chain reaction - Restriction fragment length polymorphism and direct sequencing for Kras gene mutation and Methylation Specific-PCR for RASSF1A, FHIT and MGMT genes was performed. Results Kras gene mutation at codon 12 & 13 and methylated RASSF1A, FHIT and MGMT gene was observed in 47%, 19%, 47%, 37% and 47% cases, respectively. Alcohol intake and smoking were significantly associated with presence of Kras mutation (codon 12) and MGMT methylation (p-value <0.049). Tumor stage and metastasis correlated with presence of mutant Kras codon 12 (p-values 0.018, 0.044) and methylated RASSF1A (p-values 0.034, 0.044), FHIT (p-values 0.001, 0.047) and MGMT (p-values 0.018, 0.044) genes. Combinatorial effect of gene mutation/methylation was also observed (p-value <0.025). Overall, tumor stage 3, moderately differentiated tumors, presence of lymphatic invasion and absence of metastasis was more frequently observed in tumors with mutated Kras and/or methylated RASSF1A, FHIT and MGMT genes. Conclusion Synergistic interrelationship between these genes in sporadic CRC may be used as diagnostic/prognostic markers in assessing the overall pathological status of CRC.

Immunohistochemical Profile of Breast Cancer Patients at a Tertiary Care Hospital in New Delhi, India

BACKGROUNDnTo assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associations with various clinicopathological characteristics.nnnMATERIALS AND METHODSnThis is a retrospective analysis of women who presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Data were retrieved from the medical records of the hospital including both early and locally advanced cancer cases. ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified. Associations of triple negative and non-triple negative groups with clinicopathological characteristics were also evaluated.nnnRESULTSnA total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in the analysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors were triple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive. ER and PgR positivity was significantly associated with negative HER2 status (p-value<0.0001). Younger age, premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumor were strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinoma in situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01).nnnCONCLUSIONSnThe present analysis is one of the largest studies from India. The majority of the Indian breast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patients tended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodes status and lower frequency of ductal carcinoma in situ.

A Report of Sarcomatoid Carcinoma of the Gallbladder Treated with Palliative Deocetaxel and Gemcitabine Chemotherapy

Gallbladder carcinoma (GBC) is a disease common in the northern part of India, Chile, and Japan [1]. The commonest histological type of this neoplasm is adenocarcinoma, while sarcomatoid histology is rare [2]. There are a few reports available in the literature on sarcomatoid GBC where it was detected in a surgically resectable stage [3, 4]. The prognosis of this type of neoplasm is very poor [2]. We report a case of metastatic sarcomatoid carcinoma along with its outcome who received palliative deocetaxel and gemcitabine chemotherapy.

Limb salvage surgery for osteosarcoma- Early results in Indian patients

Background: While limb salvage surgery has long been established as the standard of care for osteosarcoma, large studies from Indian centers are few. Given the diverse socio economic milieu of our patients, it becomes significant to determine the feasibility and outcome of management of osteosarcoma in our population. We analyzed the early outcome of limb salvage surgery with multimodality treatment of osteosarcoma of the extremity/girdle bones at a tertiary North Indian Cancer Centre. Materials and Methods: A total of 51 limb salvage surgeries performed during the months between November 2008 and November 2012 were studied. Neoadjuvant/adjuvant chemotherapy was given by the pediatric/adult medical oncology teams as applicable. The mean followup was 19.45 months (range 2-50 months). The oncological outcome was correlated with age, sex, size of tumor, stage at presentation, site, histological subtype, type of chemotherapy protocol followed and necrosis seen on postoperative examination of resected specimen. The functional outcome of the patients was evaluated using the musculoskeletal tumor society (MSTS) scoring system. Results: Out of a total of 37 males and 14 females with an average age of 18.8 years, the 3 year overall survival was 66% and 3 year event free survival was 61.8%. In this group of patients with a short followup, a better oncological outcome was associated with good postoperative tumor necrosis, nonchondroblastic histology and age <14 years. The average MSTS score was highest in patients with proximal or distal femur prosthesis and the lowest in patients undergoing a knee arthrodesis. Conclusion: The present study shows oncological and functional outcomes of limb salvage combined with chemotherapy in Indian patients with osteosarcoma comparable to those in world literature. Larger studies on Indian population with longer followup are recommended.

Cervical Cord Compression as Initial Presentation of Papillary Thyroid Carcinoma: a Case Report

Cervical cord compression secondary to extension of a long standing papillary thyroid carcinoma as well as multiple cases of distal cord compression from occult follicular thyroid carcinoma have been reported. But cervical cord compression from Papillary Thyroid Carcinoma has not been reported so far. Forty eight year old lady presented with progressive quadriparesis of 2xa0months duration. MRI of the cervical spine showed destructive lesion with soft tissue component in vertebral bodies and posterior elements of C4-C6 vertebrae with cord compression along with a large thyroid mass extending to retrosternal region likely malignant. USG guided FNAC & Biopsy of thyroid lesion was inconclusive. She underwent Preoperative Selective angioembolisation for vertebral metastasis followed by total thyroidectomy with cervical cord decompression, bone grafting and plating. HPE reported follicular variant of Papillary Thyroid carcinoma. Four weeks postoperatively she underwent radioiodine ablation by 263xa0mci of I 131. She then received palliative EBRT to cervical and dorsal spine 30xa0Gy/10 fractions. She is alive and neurologically stable at 6xa0months follow up. Papillary thyroid carcinoma has an excellent prognosis. Hence a prompt management of primary disease and aggressive approach to metastatic lesion may prolong survival and allow favorable prognosis.

Lifestyle and Sporadic Colorectal Cancer in India.

BACKGROUNDnThe study evaluated the patient, lifestyle and tumor profile in patients undergoing upfront surgery for sporadic colorectal cancer (CRC) in Indian population.nnnMATERIALS AND METHODSnOne hundred consecutive patients were included. Details related to their demographic profile, habits, signs and symptoms, tumor profile, further treatment and follow up were recorded.nnnRESULTSnThe majority of the patients had colonic cancer (68%), advanced tumor stage 3 and 4 (46%), moderately differentiated tumors (70%) with absence of lymphatic invasion (60%) and metastasis (90%). Correlations between tumor location and abdominal pain (p-value 0.002), bleeding per rectum (p-value <0.001), difficulty in micturition (p-value 0.012) and constipation (p-value 0.007) were found to be statistically significant. Abdominal pain was more frequently reported in patients with metastasis (p-value 0.031). Loss of weight statistically correlated with absence of lymphatic invasion (p-value 0.047). Associations between tumor stage and alcohol intake (p-value 0.050) and non vegetarian diet (p-value 0.006); lymphatic invasion and intake of spicy food (p-value 0.040) and non vegetarian diet (p-value 0.001) and metastasis and alcohol intake (p-value 0.041) were also observed. Age and tumor grade were also correlated (p-value 0.020).nnnCONCLUSIONSnMinimizing the adverse lifestyle factors can help in reducing the overall incidence of CRC in the Indian population.

Tailored approach to management of bilateral breast cancer in Indian women

Introduction: Bilateral breast cancer BCC is relatively uncommon with an overall incidence of 5-20% in women with early breast cancer. They are divided into synchronous if cancers are detected simultaneously or within 6 months of each other and metachronous if they are detected more than 6 months apart from each other. Family history and hereditary cancers multicentricity and lobular histology are some of the factors associated with BCC. In this background, we sought to evaluate the incidence, clinicopathological profile, and management of women with bilateral primary breast cancer at our institute. Materials and Methods: We retrospectively reviewed the medical records of women who underwent surgery for BCC at the breast services unit at our institute from October 2010 to April 2015. The clinicopathological profile and outcomes were analyzed using SPSS 22 software and appropriate statistical tests. Results: Out of 1330 women who underwent surgery for early breast cancer between October 2010 and April 2015, 44 were bilateral. Twenty-eight were synchronous and 16 were metachronous. Mean age of the presentation of patients was 53 years (range 30-79 years). The histological type were same in 82.14% of synchronous tumors and 87.5% of metachronous tumors (P = 0.496). The grades were similar in 42.85% of synchronous tumors and 56.25% of metachronous lesions (P = 0.294). The stage concordance among synchronous tumors was 39.28%, whereas it was 60% among metachronous lesions (P = 0.164). Conclusions: The management of BCC is complex and has to be tailored to the individual based on characteristics of index and second tumor, prior therapy, adjuvant treatment, and risk stratification. Moreover, the concordance of receptor expression is higher in synchronous cancers than metachronous cancers.

Radical Esophagectomy After Neoadjuvant Chemoradiation: Single Institutional Experience from Tertiary Cancer Centre in India

Although preoperative chemoradiation has shown to improve surgical outcomes in both loco-regional control and long term survival; it has still not become the standard of care in many centers. There is reluctance in accepting preoperative chemoradiation primarily due to fear of increased perioperative morbidity/mortality or non-availability of infrastructure and expertise. We present a retrospective analysis of our results of radical esophagectomy after neoadjuvant chemoradiation. All patients who underwent Radical Esophagectomy from January 2009 to December 2013 by a single surgical team at our institute were included in the series (nu2009=u2009118). Patients undergoing surgery after chemo-radiation (group Au2009=u200966) were compared with those under going upfront surgery (group Bu2009=u200952) in terms of patient variables (age, sex, comorbidities, tumor location, staging, histology) and postoperative surgical outcomes and complications using Chi square test. Overall and disease free survival was analyzed using Kaplan Meir curve. There was no difference in duration of surgery, postoperative stay and overall morbidity and mortality in both groups. Although group A patients had more of advanced cases clinically, but histopathology showed complete pathological response (pCR) in nearly 40xa0% patients and negative nodes (pN0) in 62.5xa0% patients. OS and DFS showed a trend towards better survival with preoperative chemoradiation. We conclude that radical esophagectomy after preoperative chemoradiation is feasible and safe in developing countries. Moreover pathological complete response correlates well with improved survival. Randomized control trials may be required to further substantiate the results.

Sternal Resection and Reconstruction for Malignant Phylloides Tumor

Malignant phylloides tumor is a locally aggressive breast neoplasm constituting less than 1 % of all breast cancers. It has a tendency for local recurrence and management is multidisciplinary. We hereby report a case of total sternal resection and reconstruction using Biopore HDPE prosthesis for Malignant Phylloides tumor.

Arm lymphedema after treatment of breast cancer: Etiology, diagnosis, and management

Breast cancer related lymphedema (BCRL) is a chronic debilitating condition seen after treatment of breast cancer. The overall incidence varies from 20% to 56% in all patients treated for breast cancer. Every patient is at a lifelong risk for BCRL and the risk goes on increasing as the followup period increases. Locoregional treatment including surgery or radiotherapy is the most common risk factor for development of arm lymphedema. There are two phases of arm lymphedema. There is increased fluid accumulation in the fluid phase of lymphedema which later on goes into the solid phase where fat and fibrotic tissue is deposited in the subcutaneous tissue. The treatment of BCRL is a challenge both for the patient and the treating surgeon and it needs multidisciplinary team work to be successful. Non-surgical treatment modalities include complete decongestive therapy (CDT) and pneumatic compression therapy. Surgery for BCRL is usually undertaken as a salvage modality after failure of conservative approaches. The surgical spectrum for BCRL varies from extensive excisional operations which were commonly done in the past to newer methods like suction assisted protein lipectomy, lymphatic reconstruction and vascular lymph node transfer (VLNT) using super-microsurgical techniques. There is no consensus regarding the preference of one procedure over other due to lack of randomised control trials. It is however suggested to do lymphovenous anastomosis and complete decongestive therapy for early cases in fluid phase; while patients in the solid phase may be treated with a combination of liposuction with CDT or VLNT alone.