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3.  Indian Council of Medical Research consensus document for the management of gastric cancer 
EXECUTIVE SUMMARY
The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India.Evaluation of a patient with newly diagnosed gastric cancer should include essential tests: A standard white light endoscopy with multiple biopsies from the tumor for confirmation of the diagnosis, a computed tomography (CT) scan (multi-detector or helical) of the abdomen and pelvis for staging with a CT chest or chest X-ray, and complete blood counts, renal and liver function tests. Endoscopic ultrasonography/ magnetic resonance imaging/positron emission tomography-CT is not recommended for all patients.For early stage disease (IA/B, N0), surgery alone is recommended. The need for adjuvant treatment would be guided by the histopathological analysis of the resected specimen.For locally advanced stage (IB, N+ to IIIC), neoadjuvant chemotherapy may be considered to downstage the disease followed by surgery. This may be followed by adjuvant chemotherapy (as part of the peri-operative chemotherapy regimen)Patients with stage IV/metastatic disease must be assessed for chemotherapy versus best supportive care on an individual basis.Clinical examination including history and physical examination are recommended at each follow-up visit, with a yearly CT scan of the chest, abdomen, and pelvis.HER2 testing should be considered in patients with metastatic disease.5-FU may be replaced with capecitabine if patients do not have gastric outlet obstruction. Cisplatin may be replaced with oxaliplatin in the regimens.
doi:10.4103/0971-5851.144970
PMCID: PMC4264267  PMID: 25538398
Diagnosis; gastric cancer; guidelines; Indian Council of Medical Research; treatment
4.  Indian Council of Medical Research consensus document for the management of gastrointestinal stromal tumors 
EXECUTIVE SUMMARY
This consensus statement was produced along with the gastric cancer discussions as stomach is the most common site for gastrointestinal stromal tumor (GIST). The recommendations apply to treatment of GIST.Evaluation of a patient with newly diagnosed GIST should include essential tests: A standard white light endoscopy with 6-8 biopsies (c-KIT testing on immunohistochemistry) from the tumor for confirmation of the diagnosis, a computed tomography (CT) scan (multi-detector or helical) of the abdomen and pelvis for staging with a CT chest or chest X-ray, and complete blood counts, renal function tests and liver function tests. Endoscopic ultrasonography (EUS)/magnetic resonance imaging (MRI)/positron emission tomography (PET)-CT are not recommended for all patients.For localized and resectable disease, surgery is recommended. The need for adjuvant treatment with imatinib would be guided by the risk stratification on the histopathological analysis of the resected specimen.For localized but borderline resectable tumors, upfront surgery may be considered only if complications due to the tumor are present such as major bleeding or gastric outlet obstruction. In all other patients, neoadjuvant imatinib should be considered to downstage the disease followed by surgery (with a curative intent, if feasible) in those with stable or partial response. This may be followed by adjuvant imatinib. In those patients with a poor response, further imatinib with dose escalation or sunitinib may be considered.Patients with metastatic disease must be assessed for treatment with imatinib as first-line therapy followed by sunitinib as second-line therapy versus best supportive care on an individual basis.
doi:10.4103/0971-5851.144983
PMCID: PMC4264268  PMID: 25538399
Diagnosis; GIST; guidelines; ICMR; treatment
5.  Lung cancer screening: Is there a future? 
Lung cancer is the leading cause of cancer death worldwide with an average rate of 40-100/100,000 depending on the level of deprivation, and the rates are higher in smokers. The National Lung Screening Trial using three consecutive annual low-dose computed tomography scans is the first and largest screening study to show clear evidence of a significant reduction in lung cancer mortality in selected high-risk subjects. The many on-going European screening studies will generate information on the groups of subjects that may or may not benefit from screening (demographics, pack-years smoked, length of smoking, number of years from quitting etc.) and the required frequency and duration of the intervention. Smoking cessation remains the most important tool for general improvement in health outcomes and in particular lung cancer prevention. Early intervention for investigations of symptoms that are considered mild or common could also change the outcome. Doctors and patients must become increasingly aware that these common symptoms are also potentially symptoms of lung cancer and are not ‘normal’ even in smokers.
doi:10.4103/0971-5851.144984
PMCID: PMC4264269  PMID: 25538400
Lung cancer; low dose computed tomography scan; screening
6.  Anti-angiogenic therapies for advanced esophago-gastric cancer 
Neo-vascularization is a vital process for tumor growth and development which involves the interaction between tumor cells and stromal endothelial cells through several growth factors and membranous receptors which ultimately activate pro-angiogenic intracellular signaling pathways. Inhibition of angiogenesis has become a standard treatment option for several tumor types including colorectal cancer, glioblastoma and ovarian cancer. In gastric cancer, the therapeutic role of anti-angiogenic agents is more controversial. Bevacizumab and ramucirumab, two monoclonal antibodies, which target vascular endothelial growth factor-A and vascular endothelial growth factor receptor-2, respectively, have been demonstrated antitumor activity in patients with tumors of the stomach or esophagogastric junction. However, especially for bevacizumab, this antitumor activity has not consistently translated into a survival advantage over standard treatment in randomized trials. In this article, we provide an overview of the role of angiogenesis in gastric cancer and discuss the results of clinical trials that investigated safety and effectiveness of antiangiogenic therapies in this disease. A review of the literature has been done using PubMed, ClinicalTrials.gov website and the ASCO Annual Meeting Library.
doi:10.4103/0971-5851.144985
PMCID: PMC4264270  PMID: 25538401
Angiogenesis; bevacizumab; gastric cancer; esophageal cancer; ramucirumab
7.  Down-staging following neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: Does timing of surgery really matter? 
Background:
Neoadjuvant chemoradiotherapy (NACTRT) improves local recurrence rate in locally advanced (LA) rectal cancer with no survival benefit. Pathological complete response (pCR) post-NACTRT is associated with improved outcome. Debate is ongoing as to when would be the opportune time to operate.
Aim:
To determine if greater down-staging can be achieved by a longer time interval from NACTRT to surgery (tumor regression score [TRS]) and whether this would impact sphincter saving surgery rates and early relapse rates.
Materials and Methods:
A retrospective analysis of a prospectively maintained database of patients with LA rectal adenocarcinoma treated from January 2012 to August 2013 was carried out. One hundred and ten patients who completed NACTRT (50 Gy/25 fractions with capecitabine 825 mg/m2 twice daily) followed by surgical resection were included. For response evaluation patients were divided into two groups, Group 1 (TRS ≤60 days, n = 42) and 2 (TRS >60 days, n = 68). Tumor down-staging, pCR rate, tumor regression grade (TRG) post-NACTRT and relapse rates were correlated with TRS.
Results:
Of 110 patients (median age: 49 years (21-73), 71% males; 18 (16.5%) with signet ring histology) 96% patients underwent an R0 resection. Post-NACTRT, CR was attained in 5 (4.5%), partial response in 98 (89%) and stable disease in 7 (6.4%) patients. Median time from completion of NACTRT to surgery was 64.5 days (6-474). Median lymph nodes harvested were 10 (1-50). Overall, 22 (20%) patients achieved pCR. 26 (62%) patients in Group 1 compared to 36 (53%) in Group 2 underwent sphincter sparing surgery (SSS) (P = 0.357). Six patients (14%) in Group 1 and 16 (24%) in Group 2 achieved pCR (P = 0.24). Median TRG in both groups was three.
Conclusion:
Timing of surgery following NACTRT for LA rectal cancer does not influence pathological response, ability to perform SSS or disease-free survival. There is no incremental benefit of delaying the surgery though this needs to be confirmed in a prospective randomized trial.
doi:10.4103/0971-5851.144986
PMCID: PMC4264271  PMID: 25538402
Adverse events; neoadjuvant chemoradiotherapy; rectal cancer; surgery; treatment
8.  Morphometric evaluation and clinical correlations in pediatric malignant small round cell tumors 
Aims:
Nuclear size increases in malignant tumors and reflects DNA content, ploidy and proliferation index. Present study investigated if the nuclear morphometry could differentiate histomorphologically similar paediatric malignant small round cell tumors on hematoxylin and eosin stained sections for diagnostics in a resource poor setting.
Settings and Design:
All the consecutive malignant pediatric tumors received in Pathology Department from other faculties of King George's Medical University and also those referred directly to Pathology Department from other hospitals of city/other cities during 3 years period were recorded.
Materials and Methods:
Morphometric analysis was done in 22 confirmed (by higher ancillary techniques) but histomorphologically difficult to differentiate round cell tumors. All sections were analyzed by cell images from six different areas, using Leica Q win 500 images software.
Results:
Nuclear measurements were obtained for retinoblastoma (RB) (nine cases), neuroblastoma (five cases), Wilms tumor (WT) (three cases), rhabdomyosarcoma (three cases), malignant hemangiopericytoma (one case) and non-Hodgkin lymphoma (one case). Among the RBs, maximum mean nuclear area percent (24.93) was seen in a case with nerve involvement and metastasis, followed by cases with only nerve involvement (21.60) and smallest area (16.57) was in non-nerve involving, nonmetastatic cases. All five cases of neuroblastoma had almost similar mean nuclear area percent (18.05-18.29). WT case with metastasis had higher nuclear area (21.25) than nonmetastatic (19.47). Amongst all the tumors, minimum value (14.93) was seen in malignant hemangiopericytoma.
Conclusion:
Morphometric evaluation in paediatric malignant round cell tumors have generated useful data, and needs further multicentric confirmation for implementation.
doi:10.4103/0971-5851.144987
PMCID: PMC4264272  PMID: 25538403
Histopathology; morphometry; pediatric; small round cell tumors
9.  Hairy cell leukemia: A decade long experience of North Indian Hematology Center 
Introduction:
Hairy cell leukemia is a rare chronic B-cell disorder that follows an indolent but progressive course. This disorder is characterized by pancytopenia, splenomegaly, bone marrow fibrosis and the presence of atypical lymphoid cells with hairy projections in peripheral blood, bone marrow and spleen. Treatment is mainly with nucleoside analog cladribine, which induces complete remission in up to 85% cases.
Materials and Methods:
This is a retrospective analysis of Hairy cell Leukemia cases diagnosed and treated in the Department of Hematology, All India Institute of Medical Sciences, New Delhi between 2002 and 2013. Various parameters such as clinical features, laboratory parameters including complete blood cell count, bone marrow findings, cytochemistry, immunophenotyping by flowcytometry or immunohistochemistry, treatment protocol and complications secondary to treatment and relapse were reviewed.
Results:
A total of 35 cases were diagnosed during this period of 12 years of which 27 received cladribine and went in to remission. Median follow-up duration was 26 months. 5 (18%) cases had a relapse and all relapsed cases achieved second remission with cladribine; however, there was no case of second malignancy in our cohort.
Conclusion:
Cladribine has emerged as the treatment of choice for hairy cell leukemia given that the overwhelming majority of patients achieve long-lasting complete remissions. Upon relapse, these patients could be successfully salvaged with cladribine retreatment.
doi:10.4103/0971-5851.144988
PMCID: PMC4264273  PMID: 25538404
Cladribine; Hairy cell leukemia; relapse; remission
10.  Thiopurine methyltransferase polymorphisms in children with acute lymphoblastic leukemia 
Introduction:
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. 6-mercaptopurine (6-MP) and methotrexate are backbone drugs for maintenance phase of treatment. Purine Analogs 6-MP/6-thioguanine/azathiopurine are metabolized to its inactive form by the enzyme thiopurine methyltransferase (TPMT). Ninety percent of the population harbor wild type on both alleles (TPMT wild/wild), 10% are heterozygous, that is, one allele is mutant (TPMT wild/mutant) and 0.3% are homozygous, that is, both allele are mutant (TPMT mutant/mutant). In heterozygous and homozygous variant, activity of enzyme is low, leading to a higher incidence of toxicity (myelosuppression).
Aim:
The primary objective was to access the polymorphism of the enzyme, TPMT, in Children with ALL. Secondary objective was to correlate TPMT genotype with 6-MP toxicities.
Materials and Methods:
Seventy-two children with newly diagnosed ALL during first maintenance phase were serially enrolled after obtaining consent. Five ml of peripheral blood was drawn and DNA extracted. TPMT 2 polymorphisms were performed using Allele specific polymerase chain reaction (PCR) and TPMT 3B and 3C are performed by PCR-restriction fragment length polymorphism.
Results:
Sixty-nine children of 72 (95.8%) were wild for TPMT polymorphism and 3 (4.2%) were heterozygous for TPMT. Among the heterozygous variant one each (33.3%) were heterozygous for 2A, 3A, 3C. Febrile neutropenia was the most common toxicity in both wild and heterozygous group.
Conclusion:
The frequency of TPMT polymorphisms in children with ALL is 4.2%. Heterozygous variant is this study are one each (33%) of 2A, 3A, 3C.
doi:10.4103/0971-5851.144989
PMCID: PMC4264274  PMID: 25538405
Acute lymphoblastic leukemia; thiopurine methyltransferase; myelosuppression
11.  Immediate treatment effects of high-dose methotrexate and cranial irradiation on neuropsychological functions of children treated for acute lymphoblastic leukemia at a regional cancer center 
Context:
Overall cure rates for pediatric acute lymphoblastic leukemia (ALL) have improved; however, the neuropsychological sequelae of ALL treatment have not been adequately documented in India.
Aims:
The present study assesses the immediate effects of ALL treatment on neuropsychological functioning, at the Regional Cancer Center in Chennai, South India.
Materials and Methods:
Newly diagnosed with ALL patients (n = 24) (aged 6–15 years; 13M:11F) registered between March 2008 and February 2009 were included. Patients who had received high-dose methotrexate (HD-MTX) and cranial radiotherapy (CRT) as part of their treatment were enrolled for the study. Neurocognitive assessments were done to assess various functions such as performance intelligence, visuo-perception, visuo-spatial, perceptual organization, processing speed, planning, working memory, and immediate verbal memory (IVM) (Malin's intelligence scale); verbal fluency (ideation fluency test) and verbal attention (vigilance test). Three assessments were done during induction (baseline), after re-induction phase (second) and during the maintenance phase (third).
Results:
The patients performed significantly worse in the third assessment (mean duration from diagnosis 17.48 months) on performance intelligence quotient (PIQ), visuo-perception, visuo-spatial, processing speed, planning, IVM, verbal attention, and verbal fluency (P < 0.05), there were no significant changes observed in visuo-perceptual organization and working memory (P > 0.05). Significant difference was observed between age groups 6 and 10 (41.7%) and 11–15 years (58.3%) in perceptual organization, verbal fluency, and verbal attention (P < 0.05) and no gender difference was observed across the three assessments (P > 0.05).
Conclusions:
Combining HD MTX and CRT had an immediate effect on neuropsychological sequelae among the children with ALL, however, long-term evaluation is recommended to study the long-term effects.
doi:10.4103/0971-5851.144990
PMCID: PMC4264275  PMID: 25538406
Acute lymphoblastic leukemia; central nervous system prophylaxis; chemotherapy; cranial radiation; neuro-cognitive functions
15.  Adjuvant therapy for resected high-risk colon cancer: Current standards and controversies 
This evidence-based review will discuss the current standard of adjuvant chemotherapy for resected high-risk colon cancer and address existing controversies including strategies for risk-stratification, the status of targeted therapy, treatment of the elderly and the optimal duration of therapy.
doi:10.4103/0971-5851.142032
PMCID: PMC4202614  PMID: 25336789
Adjuvant therapy; colon cancer; 5-FU; oxaliplatin; stage II
16.  Oligometastatic breast cancer: A mini review 
With few exceptions such as germ cell tumors, trophoblastic neoplasms and colonic cancers, metastatic solid tumors are considered largely incurable. It is increasingly appreciated that oligometaststic cancer differs from multi-metastatic disease in prognosis and survival. Oligometastatic breast cancer (OMBC) is, therefore, sometimes considered as an intermediate biological state between localized and widely metastatic disease. There is no strict definition of OMBC with studies using different criteria. Treatment of OMBC is still controversial in view of sparse data that is retrospective. However, there is an increasing shift toward individualized, multidisciplinary management of OMBC with the intent to cure some patients. This article will concisely review the subject of OMBC from points of view of biology and practical management recommendations.
doi:10.4103/0971-5851.142035
PMCID: PMC4202615  PMID: 25336790
Oligometastastasis; breast cancer; cure
17.  Current status of hematopoietic stem cell transplant in chronic myeloid leukemia 
Indications for hematopoietic stem cell transplant (HSCT) in chronic myeloid leukemia (CML) have changed over time. This change has largely been influenced by the advent of tyrosine kinase inhibitors, increased understanding of the mechanisms underlying disease phase progression as well as drug resistance, refinement of transplant techniques and exploitation of graft versus leukemia effect in this disease. Here, we have discussed the status of HSCT in CML in the present era with regards to the current indications, factors determining outcome and management strategies for posttransplant relapse.
doi:10.4103/0971-5851.142036
PMCID: PMC4202616  PMID: 25336791
Chronic myeloid leukemia; hematopoietic stem cell transplant; posttransplant relapse
18.  Plasma cell leukemia: A case series from South India with emphasis on rarer variants 
Plasma cell leukemia (PCL) is a rare and aggressive variant of plasma cell dyscrasia. They occur de novo (primary) or as a late manifestation of multiple myeloma (secondary). Patients present with anemia, thrombocytopenia, renal failure, organomegaly and extramedullary manifestations. We are presenting this series as it is the second largest series from India (16) with 4 young cases (under 40 years of age), more number of female patients and two having ‘hairy cell’ morphology. It is recommended that techniques like immunophenotyping and protein electrophoresis be performed, whenever the morphology is not characteristic of plasma cells.
doi:10.4103/0971-5851.142037
PMCID: PMC4202617  PMID: 25336792
Immunophenotyping; primary plasma cell leukemia; secondary plasma cell leukemia
19.  Outcome of neoadjuvant chemotherapy in locally advanced breast cancer: A tertiary care centre experience 
Background:
Introduction of neoadjuvant chemotherapy (NACT) has dramatically changed the management of locally advanced breast cancer (LABC). However, very few randomized trials of NACT have been carried out specifically in LABC patients in our country. In this retrospective analysis, we presented our experience with NACT in LABC patients.
Materials and Methods:
Medical records of 148 patients of stage III LABC patients treated with NACT, followed by surgery and radiotherapy from January 2006 to December 2010 were reviewed. Clinical and pathological responses to different chemotherapy regimens were assessed according to World Health Organization criteria. Various factors influencing response to NACT and clinical outcome were identified and analyzed.
Results:
A total of 90 (60.8%) patients received anthracycline-based chemotherapy and 52 (35.1%) patients received mixed anthracycline and taxane-based chemotherapy.119 patients (80.4%) responded to NACT either in the form of complete or partial response (PR). Complete response was seen in 27 (18.2%) patients and 92 (62.2%) patients showed PR after NACT. Pathological complete response was seen in 24 (16.2%) patients-. At a median follow-up period of 44 months 36 patients (24.3%) developed relapse of which six patients developed locoregional recurrence, while 28 (18.9%) patients developed distant metastasis. Nodal status, response to chemotherapy, pathological tumor size <3 cm and extracapsular extension (ECE) came out to be important prognostic factors in this study.
Conclusion:
Neoadjuvant chemotherapy is a reasonable alternative to upfront surgery in the management of LABC. Clinicopathological variables such as nodal status, response to chemotherapy, pathological tumor size and presence of ECE had significant impact on disease free survival.
doi:10.4103/0971-5851.142038
PMCID: PMC4202618  PMID: 25336793
Locally advanced breast cancer; neoadjuvant chemotherapy; radiotherapy
20.  The seroprevalence of Kaposi's sarcoma associated herpes virus and human herpes virus-6 in pediatric patients with cancer and healthy children in a Turkish pediatric oncology center 
Background:
Many studies have tried to be establish a pathogenic role for human herpesvirus-6 and -8 (HHV-6, HHV-8) in malignant diseases, but whether these viruses plays a role in these pathologies remains unclear. HHV-6 and HHV-8 seropositivity were shown in a healthy population. There is no published data in Turkey about seroprevalence of these viruses. We aimed to determine the seroprevalence of HHV-6 and HHV-8 in pediatric cancer patients and to compare with healthy Turkish children's viral seroprevalence.
Patients and Methods:
Ninety-three pediatric cancer patients and 43 age-matched healthy children were included in the study. All sera were screened for antibodies to HHV-6 and HHV-8 by ELISA.
Results:
HHV-8 immunoglobulin G (IgG) was positive in 3.3% of lymphoma patients, in 4.8% of acute lymphoblastic leukemia (ALL) patients, in 4.8% of retinoblastoma patients and in 7% of healthy children. There was no significant difference in HHV-8 seroprevelance between these groups. HHV-6 seroprevalence was 81% in ALL patients, 70% in lymphoma group, 81% in retinoblastoma patients and 69.8% in healthy children. Although there was no significant difference in HHV-6 prevalence between healthy children and pediatric cancer patients, HHV-6 seropositivity tended to be higher in retinoblastoma patients under age of 4 years (odds ratio: 2.925).
Conclusion:
HHV-6 seroprevalence was higher than HHV-8 seropositivity in our study. Viral studies related HHV-6 seroprevelance in retinoblastoma patients would be useful to clarify if there is any etiological association between HHV-6 and retinoblastoma.
doi:10.4103/0971-5851.142039
PMCID: PMC4202619  PMID: 25336794
Herpesvirus-6; herpesvirus-8; pediatric malignancies
22.  International Federation of Head Neck Oncology Society 5th World Congress/American Head Neck Society 2014 update 
Head neck cancer is an important health problem with high morbidity and mortality. Early detection and adequate treatment improve prognosis significantly. Thus creating awareness among clinicians is an important step toward control of head neck cancer and reducing its overall burden. We here provide an update on the International Federation of Head Neck Oncology Society/American Head Neck Society 2014 held between July 26, 2014 and July 30, 2014 in New York.
doi:10.4103/0971-5851.142041
PMCID: PMC4202621  PMID: 25336796
Head Neck Cancer; IFHNOS; AHNS
23.  Immature teratoma at umbilicus region presenting as exomphalos: A case report with review of literature 
Umbilical cord neoplasms are rare. Teratomas, which are accepted as the only true neoplasms at this site, are exceptional. These tumors are polymorphic in their presentation and are often associated with other abnormalities, with exomphalos being the most common abnormality. Histologically these tumors show mature tissues from all the three-germ layers. Immature elements as seen in our case are rare. Germ cells which have gone astray during embryonic development are thought to be the cells of origin of these tumors.
doi:10.4103/0971-5851.142042
PMCID: PMC4202622  PMID: 25336797
Exomphalos; teratoma; umbilical cord

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