Solid pseudopapillary epithelial neoplasm of pancreas in pregnancy: A case report and review of literature.

The solid pseudopapillary epithelial neoplasm (SPEN) of the pancreas is an uncommon tumor that accounts for approximately 1%-2% of exocrine pancreatic neoplasms. It predominantly affects female in their second and third decades of life. In this case report, we present a clinical scenario of a 21-year-old pregnant woman who incidentally discovered a solid cystic lesion in her pancreas, exhibiting features suggestive of SPEN. The patient underwent surgery during the second trimester. Management of pregnant females with SPEN poses challenges due to the absence of definitive treatment guidelines, particularly in determining the ideal timing for surgical intervention. Notably, during pregnancy, the presence of a small SPEN does not necessarily require immediate resection. However, if the tumor is of significant size, it can give rise to complications such as tumor rupture, multivisceral resection, recurrence, spontaneous abortion, intrauterine growth restriction, or premature delivery if not addressed. In the existing literature, a common finding is that approximately two-thirds of pregnant females with SPEN underwent surgery in the second trimester, often without complications for the mother or fetus. All these tumors were larger than 8 cm. The decision to operate before or after birth can be individualized based on team discussion. However, delay in surgery may lead to larger tumors and higher risks like bleeding, rupture, multivisceral resection, and recurrence. Therefore, second-trimester surgery seems safer, and lessens dangers, emergency surgery, and tumor recurrence.

Determination of 73 multi-class pesticides in okra (Abelmoschus esculentus L.) fruits using LC-MS/MS and GC-MS/MS and estimation of analytical uncertainty of measurement.

This study developed a method to simultaneously determine 73 multi-class pesticides in okra fruit using LC-MS/MS and GC-MS/MS. The sample was extracted with acetonitrile and subsequent clean-up through dispersive-SPE method. The quantification level of the technique was 0.01 µg g-1 and compliance to the MRLs fixed by the regulatory bodies like EU and FSSAI. The recovery at 10, 50, and 100 µg kg-1 spiked levels; intra and inter-day precision at 50 µg kg-1 were found within 70-120% with RSD less than 15% with LC-MS/MS and GC-MS/MS. Measurement uncertainty was in the range of 1.81 to 12.91 µg kg-1 estimated at 50 µg kg-1. The matrix effects were slightly higher for LC than GC-compatible pesticides. Risk assessment for pesticides detected in the field and market samples found no hazardous to the consumers except profenofos. The proposed method is highly sensitive, reproducible for the complex matrix like okra, and meets the regulatory standards.

Randomized Controlled Trial of Isha Kriya versus Observation to Improve Quality of Life in Hematopoietic Cell Transplantation Recipients.

Hematopoietic cell transplantation (HCT) impacts recipients' quality of life (QoL). Few mindfulness-based interventions (MBI) in HCT recipients have shown feasibility, but heterogeneous practices and outcome measures have called into question the actual benefit. We hypothesized that self-guided isha kriya, a 12-minute guided meditation based on the principles of yoga focusing on breathing, awareness, and thought, as a mobile app would improve QoL in the acute HCT setting. This single-center, open-label, randomized controlled trial was conducted in 2021 to 2022. Autologous and allogeneic HCT recipients age ≥18 years were included. The study was approved by our Institutional Ethics Committee and registered at the Clinical Trial Registry of India, and all participants provided written informed consent. HCT recipients without access to smartphones or regular practitioners of yoga, meditation, or other mind-body practices were excluded. Participants were randomized to the control arm or the isha kriya arm at a 1:1 ratio stratified by type of transplantation. Patients in the isha kriya arm were instructed to perform the kriya twice daily from pre-HCT to day +30 post-HCT. The primary endpoint was QoL summary scores as assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) questionnaires. The secondary endpoints were the differences in QoL domain scores. The validated questionnaires were self-administered before the intervention and at days +30 and +100 post-HCT. The analysis of endpoints was done on an intention-to-treat basis. Domain and summary scores were calculated for each instrument as recommended by the developers. A P value < .05 was considered to indicate statistical significance, and Cohen's d effect size was used to determine clinical significance. A total of 72 HCT recipients were randomized to the isha kriya and control arms. Patients in the 2 arms were matched for age, sex, diagnosis, and type of HCT. The 2 arms showed no differences in pre-HCT QoL domain, summary, and global scores. At day +30 post-HCT, there was no difference between the arms in the mean FACT-BMT total score (112.9 ± 16.8 for the isha kriya arm versus 101.2 ± 13.9 for the control arm; P = .2) or the mean global health score (global mental health, 45.1 ± 8.6 versus 42.5 ± 7.2 [P = .5]; global physical health, 44.1 ± 6.3 versus 44.1 ± 8.3 [P = .4]) in the 2 groups. Similarly, there were no differences in physical, social, emotional, and functional domain scores. However, the mean bone marrow transplantation (BMT) subscale scores, which addresses BMT-specific QoL concerns, were statistically and clinically significantly higher in the isha kriya arm (27.9 ± 5.1 versus 24.4 ± 9.2; P = .03; Cohen's d = .5; medium effect size). This effect was transient; mean day +100 scores showed no difference (28.3 ± 5.9 versus 26.2 ± 9.4; P = .3). Our data indicate that the isha kriya intervention did not improve the FACT-BMT total and global health scores in the acute HCT setting. However, practicing isha kriya for 1 month was associated with transient improvement in the FACT-BMT subscale scores on day +30 but not on day +100 post-HCT.

Effect of Different Zinc Sources and Concentrations on the Biomass Yield of Saccharomyces cerevisiae Yeast.

Zinc incorporation and the growth of Saccharomyces cerevisiae were investigated in a culture supplemented with three inorganic zinc salts, i.e. zinc sulphate, zinc chloride and zinc nitrate. The cultivation was performed on a yeast extract peptone dextrose (YEPD) broth medium. The growth of yeast was carried out at different concentrations of zinc, i.e. 0, 30, 60, 90 and 120 mg 100 ml-1. It was found that the addition of different zinc sources at 30 mg 100 ml-1 concentration produced higher biomass yield ranging 1.00-1.03 g from 100 ml-1 of cultivation medium, while higher zinc concentration in the medium caused significantly lower yields of yeast biomass. The amount of zinc in yeast cells was determined by an atomic absorption spectrometer (AAS). The highest amount of zinc in yeast cells was achieved when added in the form of zinc sulphate at a concentration of 120 mg 100 ml-1. The increment of intracellular zinc was up to 9889.67 mg kg-1 of biomass.

Simultaneous determination of 79 pesticides in pigeonpea grains using GC-MS/MS and LC-MS/MS.

Pigeonpea grains are important sources of vegetarian proteins. It is the paramount importance to check the pesticide residues due to their frequent use during production. The LC-MS/MS and GC-MS/MS analytical method was developed and validated for the simultaneous determination of 79 pesticide residues in pigeonpea. The LOD and LOQ of the analytical method were in the range of 0.53 to 3.97 and 1.60 to 10.05 µg kg-1, respectively, with a correlation coefficient of more than 0.997. Average recoveries were in the range of 80 to 118.8%, with the RSD of less than 15%. Measurement uncertainty (Ux) for pesticides was in the range of 3.42 to 12.76 µg kg-1 evaluated at 50 µg kg-1. The method was applied to analyze the sample collected from the farmer's field. This method could be useful for routine analysis of selected pesticide residue for monitoring purposes.

Toxicokinetic analysis of commonly used pesticides using data on acute poisoning cases from Hyderabad, South India.

Organophosphorus pesticides (OPs) interfere with the activity of acetylcholinesterase (AChE), a vital enzyme that regulates the functioning of the nervous system, resulting in acetylcholine (Ach) accumulation at the synapses and myoneural junctions. It remains unknown whether the commonly used OPs in South India also interfere with the AChE activity and their toxicokinetics in humans remains poorly understood. We collected peripheral blood samples from OP-associated suicide cases (hospitalised) and analysed the pesticide concentration and AChE activity, and the toxicokinetics of six commonly used pesticides. LC-MS/MS was used for the estimation of pesticide concentration. Based on a comparison of six pesticide kinetic profiles and toxicokinetic parameters, we concluded that chlorpyrifos ingestion resulted in the highest concentration of chlopyrifos among the identified pesticides, followed by acephate, triazophos, propanil, while dimethoate exhibited the lowest concentration. Based on a time-course analysis, we observed a faster elimination phase for monocrotophos and dimethoate. We observed that there was a significant decrease in the mean concentration of monocrotophos (64 ng/mL) (P = 0.015), while the mean value of AChE (1.08 unit/mL) increased over time. While monocrotophos and dimethoate elimination phases were remarkable in human subjects, the other pesticides did notdemonstrate similar elimination phases owing to their low rate of metabolism and high stability.

Calvarial involvement in disseminated rhinosporidiosis - A case report and literature review.

Rhinosporidiosis is a chronic granulomatous infection caused by Rhinosporidium seeberi and mainly involves nasal and ocular mucosa. Bony involvement in rhinosporidiosis is very rare. A young male, previously operated for nasal rhinosporidiosis, presented with two bony swellings on the forehead and multiple subcutaneous lesions on the right lower limb. The diagnosis of disseminated cutaneous rhinosporidiosis with frontal bone involvement was made with the help of fine needle aspiration cytology (FNAC), histopathology, and computed tomography (CT) scan head. Wide excision of the bony lesion was performed. To the best of our knowledge, this is the first radiologically proven case of frontal bone involvement in disseminated rhinosporidiosis. Early diagnosis can be established with a good clinicopathological and radiological correlation. It also emphasizes the importance of CT scan for the evaluation of any subcutaneous skull lesion.

Collaborations in gynecologic oncology education and research in low- and middle- income countries: Current status, barriers and opportunities.

Eighty-five percent of the incidents and deaths from cervical cancer occur in low and middle income countries. In many of these countries, this is the most common cancer in women. The survivals of the women with gynecologic cancers are hampered by the paucity of prevention, screening, treatment facilities and gynecologic oncology providers. Increasing efforts dedicated to improving education and research in these countries have been provided by international organizations. We describe here the existing educational and research programs that are offered by major international organizations, the barriers and opportunities provided by these collaborations and hope to improve the outcomes of cervical cancer through these efforts.

Recurrence of vulval intraepithelial neoplasia following treatment with cidofovir or imiquimod: results from a multicentre, randomised, phase II trial (RT3VIN).

OBJECTIVE: To compare the recurrence rates after complete response to topical treatment with either cidofovir or imiquimod for vulval intraepithelial neoplasia (VIN) 3. DESIGN: A prospective, open, randomised multicentre trial. SETTING: 32 general hospitals located in Wales and England. POPULATION OR SAMPLE: 180 patients were randomised consecutively between 21 October 2009 and 11 January 2013, 89 to cidofoovir (of whom 41 completely responded to treatment) and 91 to imiquimod (of whom 42 completely responded to treatment). METHODS: After 24 weeks of treatment, complete responders were followed up at 6-monthly intervals for 24 months. At each visit, the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was assessed and any new lesions were biopsied for histology. MAIN OUTCOME MEASURES: Time to histologically confirmed disease recurrence (any grade of VIN). RESULTS: The median length of follow up was 18.4 months. At 18 months, more participants were VIN-free in the cidofovir arm: 94% (95% CI 78.2-98.5) versus 71.6% (95% CI 52.0-84.3) [univariable hazard ratio (HR) 3.46, 95% CI 0.95-12.60, P = 0.059; multivariable HR 3.53, 95% CI 0.96-12.98, P = 0.057). The number of grade 2+ events was similar between treatment arms (imiquimod: 24/42 (57%) versus cidofovir: 27/41 (66%), χ2 = 0.665, P = 0.415), with no grade 4+. CONCLUSIONS: Long-term data indicates a trend towards response being maintained for longer following treatment with cidofovir than with imiquimod, with similar low rates of adverse events for each drug. Adverse event rates indicated acceptable safety of both drugs TWEETABLE ABSTRACT: Long-term follow up in the RT3VIN trial suggests cidofovir may maintain response for longer than imiquimod.

Component analysis of enhanced recovery pathways for esophagectomy.

The objective of this systematic review is to identify key components of enhanced recovery protocols (ERP) that lead to improved length of hospital stay (LOS) following esophagectomy. Relevant electronic databases were searched for studies comparing clinical outcome from esophagectomy followed by a conventional pathway versus ERP. Relevant outcome measures were compared and metaregression was performed to identify the key ERP components associated with reduced in LOS. Thirteen publications were included, ERP was associated with no changes in in-hospital mortality, total complications, anastomotic leak, or pulmonary complications compared with a conventional pathway, however LOS was reduced in the ERP group. Metaregression identified that immediate extubation was associated with reduced LOS (OR = -0.51, 95%CI -0.77 to -0.25; P < 0.01). Several postoperative factors were associated with a significant reduction in length of hospital stay, and in order of most important were (i) gastrograffin swallow ≤5 days (OR = -4.27, 95%CI -4.50 to -4.03); (ii) mobilization on postoperative day ≤1 (OR = -2.49, 95%CI -2.63 to -2.34); (iii) removal of urinary catheter ≤2 days (OR = -0.99, 95%CI -1.15 to -0.84); (iv) oral intake with at least sips of fluid ≤1 day (OR = -0.96, 95%CI -1.24 to -0.68); (v) enteral diet with feeding jejunostomy or gastrostomy ≤ 1 day (OR = -0.57, 95%CI -0.80 to -0.35) and (vi) epidural removal ≤ 4 days (OR = -0.17, 95%CI -0.27 to -0.07). Several core ERP components and principles appear to be associated with LOS reduction. These elements should form a part of the core ERP for the specialty, while surgical teams incorporate other elements through an iterative process.

Survival effect of laparoscopic para-aortic staging in locally advanced cervical cancer: a retrospective cohort analysis.

OBJECTIVE: This study compares two methods of evaluating para-aortic node involvement in locally advanced cervical cancer (LACC) in order to define external radiotherapy treatment fields: laparoscopic surgical para-aortic lymphadenectomy or PET-CT imaging. POPULATION: We selected 187 patients with LACC who had been treated by chemoradiation therapy in two comprehensive cancer centres from January 2001 to December 2013. A total of 98 underwent para-aortic evaluation by PET-CT (Centre 1) and 89 received surgical laparoscopic excision (Centre 2). METHODS: All patients with LACC were retrospectively collected in each centre. OS and DFS were calculated using the Kaplan-Meier's method and survival curves were compared using log-rank test. MAIN OUTCOME MEASURES: Outcomes were the comparison of patients' disease-free (DFS) and overall survival (OS) between the two centres. RESULTS: Patients had a significantly better disease-free survival in cohort 1 than in cohort 2, at 2 years [80.9% (71.7-87.5) versus 57.1% (46.1-67.3)] and at 5 years [70.5% (58.8-79.9) versus 49.2% (38.2-60.4)] (P = 0.009). These results are confirmed by multivariate analysis model [hazard ratio (HR) 1.93; 95% CI 1.03-3.61; P = 0.04]. The overall survival was also better in cohort 1, both at 2 and 5 years [93.5% (86.5-97.0) versus 78.5% (68.5-86.0) and 85.1% (73.2-92.2) versus 63.8% (51.9-74.2), respectively; P = 0.006]. The multivariate analysis model found concordant results with an increased relative risk of death for patients treated in cohort 2 (HR 2.55; 95% CI 1.09-5.99; P = 0.01). CONCLUSION: In this retrospective cohort analysis, para-aortic surgical staging in LACC is more deleterious for patients than is radiological staging in terms of OS and DFS. TWEETABLE ABSTRACT: Para-aortic surgical staging in LACC is more deleterious for patients than clinical staging.

Myeloid translocation genes differentially regulate colorectal cancer programs.

Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1-/- mice have progressive depletion of all intestinal secretory cells, and Mtg16-/- mice have a decrease in goblet cells. Furthermore, both Mtgr1-/- and Mtg16-/- mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc1638/+-dependent intestinal tumorigenesis. Mtgr1-/- mice, but not Mtg16-/- mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of chromatin immunoprecipitation sequencing data sets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1-/- tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context-dependent effect on intestinal tumorigenesis.

Association between occupational history of exposure to tobacco dust and risk of carcinoma cervix: A case-control study.

CONTEXT: Cervical cancer is the second most common malignancy among women in India. There is thus a need to identify unexplored risk factors such as occupational exposure to tobacco dust to justify its increasing trend so as to recommend suitable preventive measures. AIMS: The aim was to study the association between occupational exposure to tobacco dust with development of carcinoma cervix. SETTINGS AND DESIGN: Case-control study done in two tertiary care hospitals in Mangalore. METHODOLOGY: 239 histologically confirmed new cases of cervical cancer and the equivalent number of age-matched controls from 2011 to 2012 were interviewed about occupational history of beedi rolling and related factors. STATISTICAL ANALYSIS: Chi-square test, unpaired t-test, logistic regression. RESULTS: Exposure rate to tobacco dust following beedi rolling was 63 (26.4%) among cases and 38 (15.9%) among controls (P = 0.005, odds ratio [OR] =1.893). The latent period from occupational exposure of tobacco dust subsequent to beedi rolling and development of cervical cancer was found to be 26.5 ± 8.5 years. Adjusted OR of beedi rolling with development of cervical cancer was found to be 1.913 (P = 0.005) after controlling the confounding effect of tobacco usage and was 1.618 (P = 0.225) after controlling the effects of all confounders. Three-quarters of beedi rollers were working in conditions of inadequate ventilation and hardy anybody used face mask during work. About a quarter of participants underwent voluntary screening for cervical cancer. CONCLUSION: Occupational exposure to tobacco dust was found to be associated with risk of developing cervical cancer. Measures to promote awareness, timely screening of this disease along with the improvement in working conditions is required for improving the health status of beedi rollers and to minimize the incidence of carcinoma cervix in the community.

Practical recommendation for rash and diarrhea management in Indian patients treated with tyrosine kinase inhibitors for the treatment of non-small cell lung cancer.

Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) in patients with mutations in the epidermal growth factor receptor (EGFR). The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to these tyrosine kinase inhibitors (TKIs). Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGFR tyrosine kinase inhibitor therapy and are most impactful on the patient's quality of life. Dermatologic side effects are also relatively common among patients treated with EGFR inhibitors. Evidence has emerged in recent years to suggest that the incidence and severity of rash, positively correlated with response to treatment.These skin disorders are generally mild or moderate in severity and can be managed by appropriate interventions or by reducing or interrupting the dose. Appropriate and timely management make it possible to continue a patient's quality of life and maintain compliance; however if these adverse events (AEs) are not managed appropriately, and become more severe, treatment cessation may be warranted compromising clinical outcome. Strategies to improve the assessment and management of TKI related skin AEs are therefore essential to ensure compliance with TKI therapy, thereby enabling patients to achieve optimal benefits. This article provides a consensus on practical recommendation for the prevention and management of diarrhoea and rash in Non-Small Cell Lung Cancer (NSCLC) patients receiving TKIs.

The microbial etiology and antimicrobial susceptibility of bloodstream infections in patients with cancer at a private tertiary care hospital in Mumbai, India.

BACKGROUND: Knowledge of the etiology and antimicrobial susceptibility of blood stream infections in patients with cancer is crucial to design empirical therapy regimes. METHODS: This is a prospective observational study at a tertiary care private hospital in Mumbai, India from Nov 2009 - Dec 2014. RESULTS: A total of 62 episodes of blood stream infections in 57 patients with cancer were recorded during the study period. Analysis was limited to 52 isolates from 49 episodes in 45 patients. Gram negative pathogens caused 77% of these infections; commonest pathogens were E. coli and Klebsiella. High prevalence of antimicrobial resistance was noted. Susceptibility in E. coli, Klebsiella, Acinetobacter and Pseudomonas to 3rd generation cephalosporins, beta lactam beta lactamase inhibitor combinations, carbapenems and amikacin was 4%, 56.5%, 70% and 86% respectively. CONCLUSION: The high rates of antimicrobial resistance in gram negative isolates is alarming.

A tumor deconstruction platform identifies definitive end points in the evaluation of drug responses.

Tumor heterogeneity and the presence of drug-sensitive and refractory populations within the same tumor are almost never assessed in the drug discovery pipeline. Such incomplete assessment of drugs arising from spatial and temporal tumor cell heterogeneity reflects on their failure in the clinic and considerable wasted costs in the drug discovery pipeline. Here we report the derivation of a flow cytometry-based tumor deconstruction platform for resolution of at least 18 discrete tumor cell fractions. This is achieved through concurrent identification, quantification and analysis of components of cancer stem cell hierarchies, genetically instable clones and differentially cycling populations within a tumor. We also demonstrate such resolution of the tumor cytotype to be a potential value addition in drug screening through definitive cell target identification. Additionally, this real-time definition of intra-tumor heterogeneity provides a convenient, incisive and analytical tool for predicting drug efficacies through profiling perturbations within discrete tumor cell subsets in response to different drugs and candidates. Consequently, possible applications in informed therapeutic monitoring and drug repositioning in personalized cancer therapy would complement rational design of new candidates besides achieving a re-evaluation of existing drugs to derive non-obvious combinations that hold better chances of achieving remission.

Outbreak of Burkholderia cepacia complex bacteremia in a chemotherapy day care unit due to intrinsic contamination of an antiemetic drug.

BACKGROUND: In the end of 2009, a large number of patients with cancer undergoing chemotherapy at the day care unit of a private hospital in Mumbai, India developed Burkholderia cepacia complex (BCC) blood stream infection (BSI). OBJECTIVE: The objectives were to identify the source of the outbreak and terminate the outbreak as rapidly as possible. MATERIALS AND METHODS: All infection control protocols and processes were reviewed. Intensive training was started for all nursing staff involved in patient care. Cultures were sent from the environment (surfaces, water, air), intravenous fluids, disinfectants and antiseptics and opened/unopened medication. RESULTS: A total of 13 patients with cancer with tunneled catheters were affected with BCC BSI. The isolates were of similar antimicrobial sensitivity. No significant breach of infection control protocols could be identified. Cultures from the prepared intravenous medication bags grew BCC. Subsequently, culture from unused vials of the antiemetic granisetron grew BCC, whereas those from the unopened IV fluid bag and chemotherapy medication were negative. On review, it was discovered that the outbreak started when a new brand of granisetron was introduced. The result was communicated to the manufacturer and the brand was withdrawn. There were no further cases. CONCLUSIONS: This outbreak was thus linked to intrinsic contamination of medication vials. We acknowledge a delay in identifying the source as we were concentrating more on human errors in medication preparation and less on intrinsic contamination. We recommend that in an event of an outbreak, unopened vials be cultured at the outset.

Genomic profiling in a homogeneous molecular subtype of non-small cell lung cancer: An effort to explore new drug targets.

BACKGROUND: Patients' who are positive for kinase domain activating mutations in epidermal growth factor receptor (EGFR) gene, constitute 30-40% of non-small cell lung cancer (NSCLC), and are suitable candidates for Tyrosine Kinase Inhibitor based targeted/personalized therapy. In EGFR non-mutated subset, 8-10% that show molecular abnormalities such as EML4-ALK, ROS1-ALK, KIP4-ALK, may also derive the benefit of targeted therapy. However, 40% of NSCLC belong to a grey zone of tumours that are negative for the clinically approved biomarkers for personalized therapy. This pilot study aims to identify and classify molecular subtypes of this group to address the un-met need for new drug targets in this category. Here we screened for known/novel oncogenic driver mutations using a 46 gene Ampliseq Panel V1.0 that includes Ser/Thr/Tyr kinases, transcription factors and tumor suppressors. METHODS: NSCLC with tumor burden of at least 40% on histopathology were screened for 29 somatic mutations in the EGFR kinase domain by real-time polymerase chain reaction methods. 20 cases which were EGFR non-mutated for TK domain mutations were included in this study. DNA Quality was verified from each of the 20 cases by fluorimeter, pooled and subjected to targeted re-sequencing in the Ion Torrent platform. Torrent Suite software was used for next generation sequencing raw data processing and variant calling. RESULTS: The clinical relevance and pathological role of all the mutations/variants that include SNPs and Indels was assessed using polyphen-2/SIFT/PROVEAN/mutation assessor structure function prediction programs. There were 10 pathogenic mutations in six different oncogenes for which annotation was available in the COSMIC database; C420R mutation in PIK3CA, Q472H mutation in vascular endothelial growth factor receptor 2 (VEGFR2) (KDR), C630W and C634R in RET, K367M mutation in fibroblast growth factor receptor 2 (FGFR2), G12C in KRAS and 4 pathogenic mutations in TP53 in the DNA binding domain (E285K, R213L, R175H, V173G). CONCLUSION: Results suggest, a potential role for PIK3CA, VEGFR2, RET and FGFR2 as therapeutic targets in EGFR non-mutated NSCLC that requires further clinical validation.

Lobed spleen: an autopsy case report with emphasis on surgical anatomy.

During the medico-legal autopsy of a male aged 45 years, a bilobed morphology of the spleen was observed. An oblique fissure was located longitudinally at the mid-region of the diaphragmatic surface of the spleen. The fissure was partially deep and observed throughout the diaphragmatic surface. The clinician should be aware of the developmental anomalies of the spleen; as such anomalies may cause confusion during the procedures like splenic biopsy and splenectomy. We believe that, the present case report is important to the radiologists and clinicians involved in the diagnosis and management of splenic pathology. The knowledge is also enlightening to the morphologists and embryologists. The radiologist and clinician should make sure that the fissure in a spleen is not misinterpreted as a laceration or rupture.

The impact of cerebral embolization during infant cardiac surgery on neurodevelopmental outcomes at intermediate follow-up.

Cerebral embolization during pediatric cardiac surgery may be an underappreciated source of subsequent neurodevelopmental impairment. Transcranial Doppler ultrasound is a neuromonitoring tool that can provide intraoperative surveillance for cerebral embolization. We hypothesized that increased cerebral embolic signals detected during infant cardiac surgery would be associated with worse neurodevelopmental outcomes at follow-up. A study group of 24 children who underwent infant cardiac surgery with transcranial Doppler detection of cerebral embolic signals returned at intermediate follow-up for standardized neurodevelopmental assessment. The children were evaluated using two neurocognitive tests and the parents completed two questionnaires regarding observed behavior. Statistical analysis assessed for correlation between the number of cerebral embolic signals at surgery and the results of the neurodevelopmental assessment. Of the 67 test parameters analyzed, five showed a significant association with the number of embolic signals, yet, all in the contrary direction of the clinical hypothesis, likely representing a Type I error. Thus, in this small cohort of patients, the number of cerebral embolic signals detected during infant cardiac surgery was not shown to be associated with worse neurodevelopmental outcomes at intermediate follow-up. A larger study is probably necessary to ascertain the potential influence of cerebral embolic signals on eventual neurologic outcomes in children. The clinical relevance of cerebral embolic signals during pediatric cardiac surgery remains undetermined and deserves further investigation.