Abhishek Mahajan

Utility of serum pancreatic enzyme levels in diagnosing blunt trauma to the pancreas: a prospective study with systematic review.

INTRODUCTION Reliability of serum pancreatic enzyme levels in predicting pancreatic injuries has been a parameter of interest and the present recommendations on its utility are based primarily on anecdotal observations. The aim of this study was to evaluate the utility of serum pancreatic enzyme assessment in predicting blunt pancreatic injury with imaging and surgical correlation and compare our results with a systematic review of literature till date. METHODS A prospective cohort study conducted over 4 years in a tertiary care referral centre with 164 consecutive patients who presented to the emergency department with a history of blunt abdominal trauma and had serum pancreatic enzyme assessment, USG and subsequent diagnostic CECT were analyzed. The CT findings and AAST grade of pancreatic injury, various intra-abdominal injuries and time elapsed since injury and other associated factors were correlated with serum pancreatic enzyme levels. For systematic review of literature MEDLINE database was searched between 1940 and 2012, also the related citations and bibliographies of relevant articles were analyzed and 40 articles were included for review. We compared our results with the systematic critique of literature till date to formulate recommendations. RESULTS 33(21%) patients had pancreatic injury documented on CT and were graded according to AAST. Statistically significant elevated serum amylase levels were observed in patients with pancreatic and bowel injuries. However, elevated serum lipase was observed specifically in patients with pancreatic injury with or without bowel injury. Combined serum amylase and lipase showed 100% specificity, 85% sensitivity in predicting pancreatic injury. Elevated (n=28, 85%) vs. normal (n=5, 15%) serum amylase and lipase levels showed sole statistically significant association with time elapse since injury to admission, with a cutoff of 3h. CONCLUSIONS Based on our results and the systematic review of the literature till date we conclude, persistently elevated or rising combined estimation of serum amylase and lipase levels are reliable indicators of pancreatic injury and is time dependent, nondiagnostic within 6h or less after trauma. In resource constrained countries where CT is not available everywhere it may support a clinical suspicion of pancreatic injury and can be reliable and cost-effective as a screening tool.

Osteoradionecrosis of the mandible: through a radiologist's eyes.

Head and neck malignancies constitute a major cause of morbidity and mortality all over the world. Radiotherapy plays a pivotal role in the management of these tumours; however, it has associated complications, with mandibular osteoradionecrosis (ORN) being one of the gravest orofacial complications. Early diagnosis, extent evaluation, and detection of complications of ORN are imperative for instituting an appropriate management protocol. ORN can closely mimic tumour recurrence, the differentiation of which has obvious clinical implications. The purpose of the present review is to acquaint the radiologist with the imaging features of mandibular ORN and the ways to differentiate ORN from tumour recurrence.

Emerging clinical applications of PET based molecular imaging in oncology: the promising future potential for evolving personalized cancer care

This review focuses on the potential of advanced applications of functional molecular imaging in assessing tumor biology and cellular characteristics with emphasis on positron emission tomography (PET) applications with both 18-fluorodeoxyglucose (FDG) and non-FDG tracers. The inherent heterogeneity of cancer cells with their varied cellular biology and metabolic and receptor phenotypic expression in each individual patient and also intra-and inter-lesionally in the same individual mandates for transitioning from a generalized “same-size-fits-all” approach to personalized medicine in oncology. The past two decades have witnessed improvement of oncological imaging through CT, MR imaging, PET, subsequent movement through hybrid or fusion imaging with PET/CT and single-photon emission computerized tomography (SPECT-CT), and now toward the evolving PET/MR imaging. These recent developments have proven invaluable in enhancing oncology care and have the potential to help image the tumor biology at the cellular level, followed by providing a tailored treatment. Molecular imaging, integrated diagnostics or Radiomics, biology-driven interventional radiology and theranostics, all hold immense potential to serve as a guide to give “start and stop” treatment for a patient on an individual basis. This will likely have substantial impact on both treatment costs and outcomes. In this review, we bring forth the current trends in molecular imaging with established techniques (PET/CT), with particular emphasis on newer molecules (such as amino acid metabolism and hypoxia imaging, somatostatin receptor based imaging, and hormone receptor imaging) and further potential for FDG. An introductory discussion on the novel hybrid imaging techniques such as PET/MR is also made to understand the futuristic trends.

EGFR mutation in squamous cell carcinoma of the lung: does it carry the same connotation as in adenocarcinomas?

Background EGFR tyrosine kinase inhibitors (TKIs) have greatly improved the outcomes of EGFR mutation-positive adenocarcinomas of the lung. In contrast, the significance of EGFR mutation in metastatic squamous cell carcinoma (SCC) of the lung has been debated. Methods All patients with metastatic SCC who underwent EGFR mutation testing at our center from 2010 to 2015 were included for analysis. EGFR kinase domain mutations were tested using Taqman-based real-time polymerase chain reaction (PCR). Response assessment was done using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Kaplan–Meier method was used for calculating progression-free survival (PFS) and overall survival (OS). Results EGFR mutation was detected in 29 out of 639 patients with SCC. Furthermore, 19 out of the 29 patients received TKIs at some point during their treatment. TKI therapy led to a partial response in 5 out of 19 patients and stable disease in 4 out of 19 patients. The median PFS of patients treated with TKIs was 5.0 months. The median OS of the whole EGFR-positive SCC cohort was 6.6 months. On univariate analysis, patients having received TKI therapy was the only factor associated with a significantly better OS of 13.48 months versus 2.58 months (P=0.000). On multivariate analysis, patients receiving TKI therapy, Eastern Cooperative Oncology Group–Performance Scale (ECOG-PS) score <2, EGFR exon 19 mutation and nonsmoking status were associated with significantly better OS. Conclusion EGFR mutation in SCC of the lung predicts a better outcome if the patient is given TKI, but it may be inferior to the outcomes seen in EGFR-positive adenocarcinomas treated with TKI.

Molecular functional imaging in personalized clinical oncology: The road less traveled.

Imaging features can quantify the spatial variation in architecture and function of individual tumors and can approximately capture measurements of blood flow, hypoxia, metabolism, cell death, and other phenotypic features.[4-6] This robust identification of genotype and phenotype features and establishing their correlation based on relevant clinical questions is called “radiomics” and it challenges the concept “one size fits all.” This “radiomics” signature analysis not only helps in prognosticating tumors but also captures intratumor heterogeneity associated with underlying gene-expression patterns.[1,4,7] Recent studies have found that it may have a significant impact in clinical practice and will provide an unprecedented opportunity to improve personalized cancer treatment at low-cost.[1,2] For example, there has been a tremendous advancement in breast cancer management with development of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2)/neu therapies, rapamycin which is mammalian target of rapamycin (mTOR) target and other anti-angiogenic therapies. Maximum in vivo success has been seen in the HER2 therapy that has been validated using the in vivo molecular functional imaging.[5] The use of companion targeted delivery known as “theranostics” is also gaining ground few specific examples being molecular interventional oncoradiology using nanoparticles tagged antibodies and PET radionuclide-based molecular targeted therapies.[1,8]

PET Imaging of Skeletal Metastases and Its Role in Personalizing Further Management

In oncology, the skeleton is one of the most frequently encountered sites for metastatic disease and thus early detection not only has an impact on an individual patients management but also on the overall outcome. Multiparametric and multimodal hybrid PET/computed tomography and PET/MR imaging have revolutionized imaging for bone metastases, but irrespective of tumor biology or morphology of the bone lesion it remains unclear which imaging modality is the most clinically relevant to guide individualized cancer care. In this review, we highlight the current clinical challenges of PET imaging in evaluation and quantification of skeletal tumor burden and its impact on personalized cancer management.

Clinical Outcome in Definitive Concurrent Chemoradiation With Weekly Paclitaxel and Carboplatin for Locally Advanced Esophageal and Junctional Cancer.

There are little data on the efficacy and safety of taxane/platinum with definitive radiotherapy (RT) for esophageal/GEJ cancer. This article is a retrospective analysis of patients who received weekly paclitaxel 50 mg/m(2) and carboplatin AUC 2 with radical definitive RT for locally advanced esophageal/GEJ cancer. Between February 2011 and July 2014, 179 patients were included. The median age was 54 years. Ninety-two percent of patients had squamous histology. Mean RT dose was 58.7 Gy in 32 fractions over 53 days, with mean of six chemotherapy cycles. Fifty-six percent of patients developed ≥grade 3 acute toxicities, commonly febrile neutropenia (12%) and infection (11%); ≥grade 3 laboratory abnormalities included hyponatremia (38%), leukopenia (49%), neutropenia (27%), and anemia (16%). Twelve percent of patients developed ≥grade 3 chronic toxicity. Fatal toxicities included six during CRT, eight within 30 days of completing CRT, and three chronic. Radiologic response was 49% (CR 5.6%, PR 43%). Follow-up endoscopy showed remission in 53% and residual disease in 14%. At a median follow-up of 28 months, median PFS was 11 months (95% CI: 8-13.9), median OS was 19 months (95% CI: 15.4-22.6), and estimated 1-year, 2-year, and 3-year survivals were 70%, 47%, and 39%, respectively. Weekly paclitaxel-carboplatin concurrently with definitive RT is efficacious with manageable toxicity. [The trial was registered with the Clinical Trials Registry-India (CTRI), registration number: CTRI/2014/07/004776.].

Psoas muscle metastasis from cervical carcinoma: Correlation and comparison of diagnostic features on FDG-PET/CT and diffusion-weighted MRI

Psoas muscle metastasis, though rare, is the commonest site of skeletal muscle involvement in cervical carcinoma. The appropriate clinical management of this condition, particularly of the pain related to malignant psoas syndrome, is still evolving and the diagnostic features on conventional morphological imaging modalities are often non specific, with the differential diagnosis lying between sarcoma, hematoma, and abscess. In this report, a comparison of various morphofunctional imaging modalities was made. Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) was the first to suspect disease involvement of the psoas muscle, demonstrating intense FDG uptake (compared with the contralateral muscle), while ultrasound showed heterogeneous echotexture, and magnetic resonance imaging (MRI) showed subtle altered signal intensity in the right psoas muscle. Both anatomical imaging modalities and non contrast CT of the PET-CT examination demonstrated a bulky psoas muscle, without any focal abnormality. On diffusion-weighted imaging of MRI (DWI-MRI), restricted diffusion of the involved muscle was an important observation. The psoas muscle metastatic involvement was proven histopathologically. Thus, enhanced glucose metabolism and restricted diffusion in the newer non-invasive molecular imaging modalities (e.g., PET/CT and DWI-MRI) could serve as valuable adjunctive parameters in diagnosing this entity in the absence of a focal abnormality in the anatomical modalities. In the treatment response monitoring scenario, FDG-PET/CT demonstrated near complete resolution following administration of 3 cycles of systemic chemotherapy and local external radiotherapy.

ALK Positive Lung Cancer: Clinical Profile, Practice and Outcomes in a Developing Country

Objectives To evaluate the performance and treatment profile of advanced EML4—ALK positive Non-small cell lung cancer (NSCLC) patients in a developing country with potentially restricted access to Crizotinib. Materials and Methods A retrospective analysis of advanced ALK positive NSCLC patients who were treated from June 2012 to September 2015 was conducted. The primary goal was to evaluate outcomes of advanced ALK positive NSCLC in our practice and examine the logistic constraints in procuring Crizotinib. Results 94 patients were available for analysis. 21 (22.3%) patients were started on Crizotinib upfront, 60 (63.8%) on chemotherapy, 10 (10.6%) on Tyrosine kinase inhibitors (in view of poor PS) and 3 (3.2%) patients were offered best supportive care. Reasons for not starting Crizotinib upfront included symptomatic patients needing early initiation of therapy (23.3%), ALK not tested upfront (23.3%) and financial constraints (21.9%). 69 patients (73.4%) received Crizotinib at some stage during treatment. Dose interruptions (> 1 week) with Crizotinib were seen in 20 patients (29%), with drug toxicity being the commonest reason (85%). Median Progression free survival (PFS) on first line therapy for the entire cohort was 10 months, with a significant difference between patients receiving Crizotinib and those who did not ever receive Crizotinib (10 months vs. 2 months, p = 0.028). Median Overall Survival (OS) was not reached for the entire cohort, with 1 year survival being 81.2%. Patients with an ECOG Performance Status (PS) of >2 had a significantly reduced PFS compared to patients with PS < = 2 (1.5 months vs. 11 months, p< 0.001). 47 patients with financial constraints (68.1%) received Crizotinib completely free via various extramural support schemes. Conclusion A majority of our ALK positive NSCLC patients were exposed to Crizotinib through the help of various support mechanisms and these patients had similar outcomes to that reported from previously published literature.

Diffusion magnetic resonance imaging: A molecular imaging tool caught between hope, hype and the real world of “personalized oncology”

“Personalized oncology” is a multi-disciplinary science, which requires inputs from various streams for optimal patient management. Humongous progress in the treatment modalities available and the increasing need to provide functional information in addition to the morphological data; has led to leaping progress in the field of imaging. Magnetic resonance imaging has undergone tremendous progress with various newer MR techniques providing vital functional information and is becoming the cornerstone of “radiomics/radiogenomics”. Diffusion-weighted imaging is one such technique which capitalizes on the tendency of water protons to diffuse randomly in a given system. This technique has revolutionized oncological imaging, by giving vital qualitative and quantitative information regarding tumor biology which helps in detection, characterization and post treatment surveillance of the lesions and challenging the notion that “one size fits all”. It has been applied at various sites with different clinical experience. We hereby present a brief review of this novel functional imaging tool, with its application in “personalized oncology”.