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   Table of Contents - Current issue
Coverpage
October-December 2019
Volume 56 | Issue 4
Page Nos. 291-383

Online since Friday, October 11, 2019

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EDITORIAL  

Will health marketplace apps improve laboratories? Highly accessed article p. 291
Jacob McKnight, Ken Fleming
DOI:10.4103/ijc.IJC_673_19  PMID:31607694
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BREAST CANCER Top

Revisiting adjuvant ovarian suppression in premenopausal breast cancer patients Highly accessed article p. 293
Waseem Abbas, Ranga Raju Rao
DOI:10.4103/ijc.IJC_697_18  
Adjuvant ovarian suppression, on addition to chemotherapy, reduces the risk of breast cancer in pre-menopausal women after surgery and adjuvant hormonal therapy. Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) showed greater benefit with exemestane in high risk females in comparison to Tamoxifen. Ovarian Function Suppression (OFS) and exemestane became the standard of care, with 30% patients experiencing grade 3 and more side effects. Much higher benefit was seen in high risk group. But there are concerns about incomplete OFS (estrogen escape) with exemestane plus OFS. Updated analysis of TEXT AND SOFT showed better survival benefit with OFS plus Tamoxifen as compared to OFS plus exemestane. Overall survival is a better end point. Should preference be given to Tamoxifen over exemestane? Further research is required to get the final answer.
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GI TRACT Top

Management of colon cancer at a tertiary referral center in India - Patterns of presentation, treatment, and survival outcomes p. 297
Jarin Noronha, Ashwin deSouza, Prachi Patil, Shaesta Mehta, Reena Engineer, Vikas Ostwal, Anant Ramaswamy, Suman K Ankathi, Mukta Ramadwar, Avanish Saklani
DOI:10.4103/ijc.IJC_379_18  PMID:31607696
AIM: To define the patterns of disease presentation, treatment strategies, and outcomes for patients with colon cancer at a tertiary referral center in India over 1 year period. MATERIALS AND METHODS: This is a retrospective analysis of a prospectively maintained database. All consecutive patients with proven or suspected colonic adenocarcinoma between July 2013 and July 2014 were evaluated in a dedicated analysed multidisciplinary clinic at the Tata Memorial Hospital, Mumbai. The demography, treatment plan, pathology, stage, and survival data were examined. RESULTS: The median age of presentation was 49 years with 60.1% male patients. In total, 151 cases (57.4%) underwent treatment with curative intent consisting of surgery with adjuvant chemotherapy as indicated. The rest were offered either palliative chemotherapy (36.9%) or best supportive care (5.7%). Approximately, 70% patients had advanced stage disease (Stage III/IV) at presentation and 41.8% presented with metastatic disease with the liver being the most common site of disease dissemination. With a median follow-up of 29 months, the estimated 3-year disease free survival for patients treated with curative intent was 67.1%. The median progression free survival was 12.3 months for patients treated with palliative intent. The estimated 3-year overall survival was 89.7%, 65.5%, and 22.8% for Stage I/II, Stage III, and Stage IV, respectively. CONCLUSION: Indian patients with colon cancer, at a tertiary referral center, tend to present at more advanced stages of the disease as compared to the West. However, curative treatment with surgery and chemotherapy offers similar survival outcomes when compared stage for stage.
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Prognostic and predictive significance of microsatellite instability in stage II colorectal carcinoma: An 8-year study from a tertiary center in South India p. 302
Roopa R Paulose, Divya A Ail, Shital Biradar, Anu Vasudevan, KR Sundaram
DOI:10.4103/ijc.IJC_365_18  
BACKGROUND: Microsatellite instability (MSI) accounts for 15–20% of colorectal cancer (CRC) and is considered to have favorable stage-adjusted prognosis compared to Microsatellite stable (MSS) CRCs. Determination of MSI in stage II CRC is important for management decisions regarding adjuvant chemotherapy administration. The aim of this study was to determine the prognostic and predictive significance of MSI in stage 2 CRC in the Indian scenario. MATERIALS AND METHODS: A total of 195 patients who underwent curative surgery for stage II CRC from 2010 to 2017 were included. MSI testing by immunohistochemistry (DNA MisMatch Repair proteins) was performed in all. Various clinicopathological factors and disease-free survival and overall survival were assessed between MSI and MSS groups. The effect of treatment in terms of survival benefits with adjuvant therapy in the MSI group was also assessed. RESULTS: 27.1% of the CRCs' showed MSI. Younger age (<50 years), family history of cancer, synchronous/metachronous malignancies, proximal (right sided) location, poor morphological tumour differentiation, mucin production, and presence of peritumoral (Crohn's-like) lymphocytic response showed statistically significant association with MSI. Majority (56%) of our patients showed combined loss of MLH1 and PMS2. Overall, survival among the MSI patients was significantly higher (76.6 ± 4.149 months) than the MSS patients (65.05 ± 3.555)P= 0.04. MSI patients did not show any differences in survival with or without treatment. CONCLUSION: This study highlights the distinct clinicopathological features of MSI-related CRC and the relevance of MSI testing of stage II CRC for management decisions and prognostication.
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Microsatellite instability in young patients with mucinous colorectal cancers – characterization using molecular testing, immunohistochemistry, and histological features p. 309
Nitty Skariah Mathews, Dipti Masih, Rohin Mittal, Benjamin Perakath, Dhananjayan Sakthi, Grace Rebekah, Rekha Pai, Anna B Pulimood
DOI:10.4103/ijc.IJC_224_18  
CONTEXT: The incidence of colorectal cancers (CRCs) in young Indian patients is higher than the international average. CRCs in young patients are commonly of mucinous type and show microsatellite instability (MSI). AIMS: To ascertain the MSI status of mucinous CRCs in patients ≤40 years of age by molecular testing and to correlate this with immunohistochemical (IHC) analysis and tumor histology. SUBJECTS AND METHODS: Archived formalin-fixed paraffin embedded tissue blocks of 30 young mucinous CRC patients were retrieved. MSI testing was done using two mononucleotide markers – BAT26 and NR24. IHC analysis was done using MLH1, MSH2, and MSH6. Histological features of all cases were studied. Data were analyzed using the SPSS software and the Pearson's chi-square test and Fisher's exact test. RESULTS: Eight out of 30 cases (26.7%) showed MSI by molecular testing. IHC identified seven of these cases. Histological features showing a statistically significant association with MSI were the presence of a well-differentiated adenocarcinoma component (P = 0.003), peritumoral lymphocytes (P = 0.002) and tumor budding (P = 0.021). CONCLUSION: The detection of defective mismatch repair (MMR) proteins using IHC for MLH1, MSH2, and MSH6 and molecular testing using BAT26 and NR24 appears to be a good protocol to detect CRCs with MSI. Histology could be useful in identifying cases that require screening for presence of MMR protein defects.
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LUNG CANCER Top

An observational single-center study of nivolumab in Indian patients with recurrent advanced non-small cell lung cancer p. 315
Naresh Somani, Pawan Agarwal, Harish Singhal, Abhishek K Singh, Abhilasha Sinha, Rajshri Somani, Jia Agarwal, Shaurya Dugar
DOI:10.4103/ijc.IJC_298_18  PMID:31607699
Purpose: Limited treatment options are available for patients with advanced non-small cell lung cancer (NSCLC) after failure of first-line platinum-based chemotherapy. The treatment of recurrent advanced NSCLC progressed with the arrival of nivolumab and other immunotherapeutic agents. Our single-center prospective study aimed to present the effectiveness and safety of nivolumab in second-line setting after first-line platinum doublet in Indian patients with advanced NSCLC. Patients and Methods: Twenty-nine adult patients with stage IV NSCLC treated with nivolumab after failure of first-line platinum-based chemotherapy at Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, India, between October 2016 and January 2018, were included in the study. Overall survival (OS), hematological, and nonhematological toxicities were evaluated. Results: A total of 29 patients (mean age of 59.6 years at enrollment) were evaluated. Histological evaluation revealed adenocarcinoma (44.8%) and squamous (55.2%) type of cancer. The Eastern Cooperative Oncology Group performance score was II in 7 patients (24.1%) and I in 22 (75.9%) patients. Patients received an average of four cycles of nivolumab. The median survival duration was 101 days, and OS rate in the study was 51.7%. Six patients (20.7%) had stable disease response, five patients (17.2%) had partial response, and three patients (10.3%) were lost to follow-up. Asthenia and cough were the most common nonhematological toxicities. Only three patients developed hematological toxicities (anemia and thrombocytopenia). Conclusion: Data from our study suggest nivolumab is well-tolerated and effective in Indian patients with recurrent advanced NSCLC after failure of the multiple first lines of platinum-based combination chemotherapy.
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PEDIATRIC ONCOLOGY Top

Higher incidence of syndrome of inappropriate antidiuretic hormone secretion during induction chemotherapy of acute lymphoblastic leukemia in indian children p. 320
Shwetha Seetharam, Priyakumari Thankamony, Kaduveettil Gopinathan Gopakumar, K M Jagathnath Krishna
DOI:10.4103/ijc.IJC_737_18  
BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a well-known adverse effect of vincristine (VCR). Literature suggests that Asians are predisposed to develop SIADH following VCR administration. However, data regarding the occurrence of SIADH in children with malignancy are limited. This study aims to analyze the incidence, clinical picture, risk factors, management, and outcome of SIADH during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A prospective study was conducted among the 166 newly diagnosed pediatric ALL patients who were treated at a tertiary cancer center in India between January 2015 and December 2015. Patients who developed hyponatremia during induction chemotherapy were further investigated for SIADH. RESULTS: The incidence of SIADH was 10.8% (n = 18) with a mean sodium level of 125 mEq/L (114–129 mEq/L). In the preceding 2 weeks, 72% of episodes were associated with the administration of two (n = 6) or three (n = 7) doses of VCR. One child presented with seizures. All the patients were managed with fluid restriction and only two patients required sodium correction with 3% saline. Girls older than 10 years of age showed a marginally significant correlation to develop SIADH (P-value = 0.059). CONCLUSION: We report a higher incidence of SIADH (10.8%) in Indian children, compared to that described in the literature, during induction chemotherapy for ALL. Regular monitoring of sodium levels during this period of chemotherapy is hence essential for the timely diagnosis and appropriate management of SIADH, which in turn will avert complications, including neurological symptoms secondary to SIADH.
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HEAD AND NECK CANCER Top

Unusual loco-regional presentation in papillary carcinoma of thyroid: A case series p. 325
Prateek V Jain, Rajeev Sharan, Kapila Manikantan, Gautam Biswas, Soumendranath Ray, Pattatheyil Arun
DOI:10.4103/ijc.IJC_368_18  
BACKGROUND: Papillary carcinoma of thyroid (PTC) is usually indolent with good prognosis and excellent long-term survival. However, PTC sometimes presents itself in unusual situations, posing diagnostic and therapeutic challenges. Owing to paucity of data, there is lack of consensus as to what treatment should be prescribed in patients with loco-regional spread other than the usual sites. MATERIALS AND METHODS: Six patients of PTC presenting with involvement of the aero-digestive tract, retropharyngeal, and para-pharyngeal lymph nodes and great vessels of the neck are included in this case series. RESULTS AND CONCLUSION: Though rare, unusual loco-regional presentation of PTC poses challenges in diagnosis and treatment. A keen clinical sense is paramount in effectively diagnosing these cases. Aggressive surgical resection and reconstruction results in good functional and aesthetic outcomes. Further studies are required for establishing specific guidelines on the approach to the treatment of these cases.
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Biological tailoring of adjuvant radiotherapy in head and neck and oral malignancies – The potential role of p53 and eIF4E as predictive parameters p. 330
Bindhu Joseph, Rekha V Kumar, G Champaka, Ashok Shenoy, KS Sabitha, V Lokesh, C Ramesh, CR Vijay
DOI:10.4103/ijc.IJC_56_18  
BACKGROUND: Recent advances in radiation technology has allowed to significantly reduce toxicity and improve the efficacy of radical radiotherapy in head and neck and oral squamous cell cancers. Insights into molecular biology of carcinogenesis has opened a window for identifying aggressive clinical situations that may benefit with larger clinical target volume (CTV ) margin, broader levels of nodal coverage, or alternative radiation sensitizers. AIM: To evaluate the potential role of eukaryotic translation initiation factor 4E (elF4E) and p53 as predictive biomarkers in resected margins of head and neck and oral cancers. MATERIAL AND METHODS: Forty patients with oral cancers and 26 patients with head and neck cancers were evaluated for p53 and eIF4E in their negative surgical margins, for pattern of distribution and outcome. RESULTS: In oral cancers, 27 patients (67.5%) were positive for p53 and 10 (25%) for eIF4E in surgically negative margins. For head and neck cancer, the values were 13 (50%) for p53 and 9 (34.6%) for eIF4E. Twelve patients with oral cancers and 8 patients with head and neck cancers had local failure or death. The association with these biomarkers did not achieve statistical significance. However, adjuvant radiotherapy had a significant protective value. It improved median survival from 15 to 21 months in patients positive for p53 (P = 0.018) and from 12 to 20 months (P = 0.03) in those with eIF4E. There was no predictive association of subsite, tumor size, or nodal status. CONCLUSION: The overexpression of p53 and eIF4E in pathologically negative margins may represent a subset of patients who would benefit from early initiation of adjuvant radiation and tailored intensity-modulated radiotherapy (IMRT).
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FEMALE GENITAL TRACT Top

Utility of YWHAE fluorescent in-situ hybridisation in mesenchymal tumors of uterus- An initial experience from tertiary oncology centre in India p. 335
Anuj Verma, Santosh Menon, Bharat Rekhi, Trupti Pai, Amita Maheshwari, Jaya Ghosh, Sudeep Gupta, Kedar Deodhar
DOI:10.4103/ijc.IJC_722_18  PMID:31607703
Background: Endometrial stromal sarcoma (ESS) is a common uterine mesenchymal malignancy. According to World Health Organisation (WHO) 2014 classification, ESSs are further subdivided into low-grade ESS (LGESS) and high-grade ESS (HGESS). HGESS is defined by the presence of YWHAE gene rearrangement and has a poorer prognosis compared to LGESS. METHODS: Twenty-four cases comprising of 16 endometrial stromal sarcoma and 8 lesions mimicking ESS were retrieved from the archives of the Department of Pathology and subjected to fluorescent in situ hybridization (FISH) analysis for YWHAE gene rearrangement. Immunohistochemistry for CD10, ER, PR, Cyclin D1, SMA, H-Caldesmon, Desmin, Ki-67, and Pan Cytokeratin was performed. RESULTS: Two cases with histological features similar to HGESS were positive for YWHAE gene rearrangement while 1 was indeterminate. No cases of LGESS and histological mimics of ESS were positive for this rearrangement. CONCLUSIONS: HGESSs are defined by the presence of YWHAE rearrangement. These tumors present at higher stage and have poorer prognosis. They may not respond to hormonal therapy and may be treated with chemotherapy. Cyclin D1 though not specific remains a sensitive tool to triage endometrial stromal sarcomas for this FISH study.
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Analysis of postoperative radiotherapy effects within risk groups in patients with FIGO I, II, and III endometrial cancer p. 341
Vladan Popovic, Neda Milosavljevic, Marija Zivkovic Radojevic, Radisa H Vojinovic, Nikola Nedovic, Slobodanka Mitrovic, Jasmina Nedovic, Aleksandar Tomasevic
DOI:10.4103/ijc.IJC_370_18  PMID:31607704
INTRODUCTION: To define indications for adjuvant radiotherapy in patients with endometrial cancer, the risk groups have been established according to clinical and pathological prognostic factors. The purpose was to determine precise criteria for adjuvant radiotherapy and identify patients with increased risk for disease relapse who may benefit from postoperative radiotherapy, with an acceptable level of toxicity. MATERIALS AND METHODS: A retrospective study was conducted at the Department of Oncology and Radiology, Kragujevac, during a 5-year period. A group of 80 patients with endometrial cancer treated with adjuvant radiotherapy were included in the study. Patients were divided into four risk groups according to ESMO-ESGO-ESTRO Consensus Conference classification. The Kaplan-Meier method was used for overall and progression-free survival. A statistical analysis was performed using SPSS 20.0 statistical software. RESULTS: The 5-year survival rate was 80%, and 66.3% patients were progression-free during this period. Fatal outcome occurred in 20% of patients. The results showed survival was shortest in patients from the high-risk group. Factors that had impact on the 5-year survival were comorbidities, FIGO stage, postoperative radiotherapy, organ site of late toxicity, and localization of metastases. The analysis of postoperative radiotherapy effects showed that 72.5% of patients had no complications. The most common symptoms of late irradiation toxicity arose from the gastrointestinal tract. Toxicity was usually moderate. CONCLUSIONS: Adjuvant radiotherapy can potentially prolong survival and prevent recurrence, with acceptable level of toxicity, to preserve patient's quality of life. Patient classification into appropriate risk groups allows for adjuvant treatment individualization.
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MCQS Top

MCQs on “Analysis of postoperative radiotherapy effects within risk groups in patients with FIGO I, II, and III endometrial cancer” p. 348
HS Darling, S Jayalakshmi, Pradeep Jaiswal
DOI:10.4103/ijc.IJC_868_19  PMID:31607705
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CASE REPORTS Top

Osteoid osteoma of the calcaneus misdiagnosed as subtalar sprain p. 350
Sandeep Vijayan, Chirag Jain, Monappa Aroor Naik, Sharath Kumar Rao
DOI:10.4103/ijc.IJC_146_18  PMID:31607706
Osteoid osteoma of foot and ankle account for ten percent of benign bone tumors and commonly involve the talus and metatarsals. Its occurrence in calcaneus is extremely rare and can mimic ankle instability, subtalar arthritis, osteochondritis or plantar fasciitis leading to delay in diagnosis. We present the case of a 17 year old boy with periarticular osteoid osteoma in the calcaneum, who presented following an ankle sprain. He was successfully treated with CT guided percutaneous radiofrequency ablation and we feel that it is a safe, precise and effective treatment option for even periarticular osteoid osteoma in the foot and ankle region.
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Atypical chronic myeloid leukemia achieving good response with azacitidine p. 354
Atsushi Marumo, Taro Mizuki, Sakae Tanosaki
DOI:10.4103/ijc.IJC_506_18  PMID:31607707
The prognosis of atypical chronic myeloid leukemia (aCML) patients is poor, but some patients with a suitable donor can be treated with allogeneic hematopoietic stem cell transplantation (HSCT). However, many of these patients cannot be treated with HSCT due to their age. The effectiveness of decitabine was recently indicated in case reports; however, the effectiveness of azacitidine (AZA) has not yet been reported. We report the case of a aCML patient successfully treated with AZA. A 66-year-old man with no remarkable medical history was admitted to our hospital because of leukocytosis. We diagnosed his disease as aCML and administered hydroxyurea (HU) and AZA. After four courses of AZA, his blood cell values improved, and he no longer needed transfusions and was able to stop HU. He continued receiving AZA without any severe complications. This is the first report that AZA is effective for the treatment of aCML.
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Submental nodal metastasis in papillary carcinoma of the thyroid p. 356
Jeyashanth Riju, Shaji Thomas
DOI:10.4103/ijc.IJC_279_18  PMID:31607708
Papillary carcinoma of thyroid (PCT) commonly shows metastasis to central and lateral cervical compartment neck nodes. Submental nodes are rarely involved by PCT. Thus, its management is not clear. We report two young men who presented with submental nodal metastasis from PCT. Both underwent total thyroidectomy with central compartment neck dissection and modified radical neck dissection (MRND). Probable factors which might influence submental nodal metastasis are analyzed. We conclude that physicians should be aware of the possibility of submental nodal metastasis from PCT. A selective approach for neck dissection can be an alternative to MRND, reducing the morbidity in management of such cases.
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VIEW POINT Top

Radiotherapy in India: History, current scenario and proposed solutions p. 359
Anusheel Munshi, Tharmarnadar Ganesh, Bidhu K Mohanti
DOI:10.4103/ijc.IJC_82_19  PMID:31607709
The history and current status of a biomedical discipline in a country or region provide important health system indicators. During the last one hundred years, radiotherapy has established its position as a vital specialty in cancer management. It has proved to be one of the most cost effective ways of treating cancer providing both radical and palliative treatments depending on patient stage and performance status. However, access to radiotherapy for cancer patients in India is limited by several factors including physical proximity of centre, cost and availability of required technology. This article gives an outline of the history, existing radiotherapy facilities and future trends related to radiotherapy practice in India.
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HISTORY OF CANCER Top

V. R. Khanolkar and the Indian Cancer Research Centre, 1952–1962 p. 364
Shirish N Kavadi
DOI:10.4103/ijc.IJC_14_19  
This note presents a brief account of the ideas and efforts of V.R. Khanolkar in the period 1952–1962 to develop the Indian Cancer Research Centre into a “center of excellence”. Khanolkar, who is recognized as a pioneer in cancer research in India, focused on developing multidisciplinary medical research and mentored and trained young medical researchers. He sought and received aid from the Rockefeller Foundation, which was keen to support him in this task.
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IMAGE Top

Phyllodes-like focus in prostatic hyperplasia p. 368
John D Coyne
DOI:10.4103/ijc.IJC_477_18  PMID:31464200
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LETTERS TO THE EDITOR Top

Breast metastasis as initial presentation of asymptomatic gastroesophageal carcinoma: A case report p. 370
Rashmi Sudhir, Veeriah K Chaudhary, Faiq Ahmed, K VVN Raju
DOI:10.4103/ijc.IJC_159_19  PMID:31607711
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Linking of national health protection mission data to national cancer registry program of india for estimating cancer incidence p. 371
Manoj Kalita, Manigreeva Krishnatreya
DOI:10.4103/ijc.IJC_247_19  
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Adult ALK-positive diffuse large B-cell lymphoma: A limited institutional experience p. 373
Ilavarasi Vanidassane, Ajay Gogia, Saumyaranjan Mallick
DOI:10.4103/ijc.IJC_705_18  
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Gastric perforation due to nivolumab related tumor flare p. 374
Basawantrao Malipatil, Adarsh Palleti, Namita Sinha Verma, Sanjeev V Katti
DOI:10.4103/ijc.IJC_776_18  PMID:31464201
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The impact of clinicopathological aspects on the recurrence of oral leukoplakia: A retrospective study in a cohort of 83 patients from the north of Spain p. 375
Sergio Pineiro-Donis, Manuel Torres-López, Abel García-García, Xavier Marichalar-Mendía, Pilar Gándara-Vila, Alejandro-Ismael Lorenzo-Pouso, Andrés Blanco-Carrión, Mario Pérez-Sáyans
DOI:10.4103/ijc.IJC_230_18  PMID:31607714
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False positive helmet sign on radioactive iodine-131 scintigraphy p. 379
Ramachandran Krishna Kumar, Arvind Krishnamurthy, Gomadam Kuppusamy Rangarajan, Nagarathinam Anandi, Namasivayam Parvathnathan
DOI:10.4103/ijc.IJC_55_19  PMID:31607715
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NEWS Top

News from the world of oncology p. 381

DOI:10.4103/ijc.IJC_861_19  
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