Surgery Versus Surveillance for Well-Differentiated, Nonfunctional Pancreatic Neuroendocrine Tumors: An 11-Year Analysis of the National Cancer Database.

BACKGROUND: Pancreatic neuroendocrine tumors (panNETs) are a rare group of tumors that make up 2%-3% of pancreatic tumors. Recommended treatment for panNETs generally consists of resection for symptomatic or large asymptomatic tumors; however, optimal management for localized disease is still controversial, with conflicting recommendations in established guidelines. Our study aim is to compare surgical intervention versus active surveillance in nonmetastatic panNETs by size of primary tumor. MATERIALS AND METHODS: Using the National Cancer Database, we identified 2,004 patients diagnosed with localized well-differentiated, nonfunctional panNETs (NF-panNETs) between 2004 and 2015. Patients' clinicopathologic characteristics, treatment modalities, and overall survival (OS) were analyzed using frequency statistics, chi-square, and Kaplan-Meier curves. The objective of the study is to assess the outcome of surgical resection versus nonoperative management in patients with panNETs with different tumor sizes. RESULTS: Tumor sizes were divided into three categories: <1 cm, 1-2 cm, and >2 cm. The number of patients with tumor size <1 cm, 1-2 cm, and >2 cm was 220 (11%), 794 (39.6%), and 990 (49.4%), respectively. Overall, 1,781 underwent surgical resection, whereas 223 patients did not. Median follow-up was 25.9 months. After adjusting for covariates, surgical resection was associated with improved OS in patients with tumor size 1-2 cm (hazard ratio [HR] = 0.37) and >2c m (HR = 0.30) but not <1 cm (HR = 2.81). Independent prognostic factors were age at diagnosis, Charlson-Deyo comorbidity score, stage, tumor location, and surgical resection. Higher tumor grade was not associated with worse OS. CONCLUSION: Our findings suggest that active surveillance is potentially a safe approach for NF-panNETs <1 cm. Larger tumors likely need active intervention. Intermediate-grade tumors did not result in worse survival outcome compared with low-grade tumors. Future studies might consider prospective randomized clinical trials to validate our findings. IMPLICATIONS FOR PRACTICE: The present study seeks to address the discrepancy in treatment recommendations in the management of nonfunctional pancreatic neuroendocrine tumors (NF-panNETs) by evaluating whether surgical resection is associated with improved overall survival in different tumor size groups as well as elucidating independent prognostic factors in patients with NF-panNETs. Data from the National Cancer Database were reviewed. This study's findings suggest that active surveillance is potentially a safe approach for NF-panNETs <1 cm. Larger tumors likely need active intervention. Independent prognostic factors include age at diagnosis, Charlson-Deyo comorbidity score, stage, tumor location, and surgical resection. These findings will help guide medical and surgical oncologists when formulating treatment plans for patients with small NF-panNETs.

Emerging treatment for ALK-positive lung cancer.

INTRODUCTION: Lung cancer is associated with poor prognosis and limited benefit from chemotherapy. The treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the discovery of targetable genetic alterations, including the ALK fusion oncogene. AREAS COVERED: Three drugs have been approved for clinical use in ALK-positive patients - crizotinib, ceritinib and alectinib. Unfortunately, treatment resistance inevitably develops. Several mechanisms of acquired resistance are reported. In this review, we will discuss emerging treatment options in ALK-positive advanced NSCLC and strategies to overcome resistance mechanisms, including newer generation of ALK inhibitors, Hsp90 inhibitors and immunotherapy. EXPERT OPINION: Tremendous advances have been made in the treatment of ALK-positive lung cancers, but management hurdles still exist, including universal development of resistance to ALK inhibitors and limited CNS activity. Given that specific treatment strategies target distinct patterns of resistance, re-biopsy at the time of progression appears necessary to optimize management. However, there remain many issues in routine clinical application including the burden placed on the patients by serial biopsies and the risks of repeat invasive procedures. Future studies are needed to validate the usage of non- or minimally invasive tests and to determine the optimal orders of utilizing different ALK inhibitors.

An Observational Study of Clinical, Metabolic and Hormonal Profile of Pediatric Acne.

Objectives: To study the biochemical, metabolic and hormonal profile among children presenting with acne and to determine the correlation of these parameters with acne grading. Methods: The observational cross-sectional study was conducted for a duration of 18 months on a total of 50 children between 1 and 12 years of age with clinical features of acne. The detailed information regarding the type of acne, biochemical profile (lipid profile, blood sugar levels), hormonal profile and associated illnesses were recorded. Spearman's rank correlation coefficient was used to find out the correlation of acne grading with hormonal and metabolic changes. Results: The mean age of the children was 11.4 years. Among the various lesions, comedones were seen in 98% cases, papules in 94.00% cases, a scar in 14.00% and pustule in 4.00% cases. As compared to children of age 1-7 years, those in age group 8-12 years had significantly more comedones (48 vs 1, P = 0.04), significantly fewer pustules (0.00% vs 100.00%, P = 0.001), and a comparable number of papules and scars. Most of the children (88.00%) had acne vulgaris grade 1. There was a significant negative correlation of Blood sugar-fasting (r = -0.312, P = 0.0275) and a significant positive correlation of HDL (r = 0.28, P = 0.0491) with acne grading. Conclusion: Comedones and papules are the commonest and the earliest forms of pediatric acne. Severe forms of acne are rarely seen below 12 years, age group. Preadolescent acne is commoner than mid-childhood acne, with no difference between male and females. Blood sugar levels and lipid profile derangements have a weak correlation with acne grading.

Predictors of Outcome in Patients With Fibrolamellar Carcinoma: Analysis of the National Cancer Database.

BACKGROUND: Fibrolamellar carcinoma (FLC) is a very rare liver tumor. We aimed to retrospectively analyze the clinicopathological factors and treatment modalities affecting overall survival (OS) in FLC. The objective of the study was to identify predictors of survival in FLC. PATIENTS AND METHODS: Using the National Cancer Database, we identified 496 patients diagnosed with FLC between 2004 and 2015. Clinicopathological, treatment, and survival data were collected. RESULTS: Hepatic resection was performed on 254 (51.2%) patients, liver-directed therapy on 13 (2.6%) patients, and liver transplantation on 15 (3.0%) patients. Median OS by stage were 142.1, 87.2, 32.3, and 14.1 months for stages 1, 2, 3, and 4, respectively. Metastatectomy was not associated with superior median OS (23.4 vs. 10.5 months, p=0.163). Age ≤40, low Charlson-Deyo comorbidity score, early stage and hepatic resection were independently associated with longer OS. CONCLUSION: Our study reports current trends in FLC management, and identifies independent predictors of OS.

Progress in extracellular vesicle biology and their application in cancer medicine.

Under the broader category of extracellular vesicles (EVs), exosomes are now well recognized for their contribution and potential for biomedical research. During the last ten years, numerous technologies for purification and characterization of EVs have been developed. This enhanced knowledge has resulted in the development of novel applications of EVs. This review is an attempt to capture the exponential growth observed in EV science in the last decade and discuss the future potential to improve our understanding of EVs, develop technologies to overcome current limitations, and advance their utility for human benefit, especially in cancer medicine. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Exosomes as drug delivery vehicle and contributor of resistance to anticancer drugs.

Exosomes are small membranous vesicles implicated in intercellular signalling. Through their uncanny ability to carry and deliver donor cellular cargo (biomolecules) to target cells, they exert a profound effect on the regular functioning of healthy cells and play a significant role in pathogenesis and progression of several diseases, including cancer. The composition and number of endogenously circulating exosomes frequently vary, which is often reflective of the pathophysiological status of the cell. Applicability of exosomes derived from normal cells as a drug carrier with or without modifying their intraluminal and surface components are generally tested. Conversely, exosomes also are reported to contribute to resistance towards several anti-cancer therapies. Therefore, it is necessary to carefully evaluate the role of exosomes in cancer progression, resistance and the potential use of exosomes as a delivery vehicle of cancer therapeutics. In this review, we summarize the recent advancements in the exploitation of exosomes as a drug delivery vehicle. We also discuss the role of exosomes in conferring resistance to anti-cancer therapeutics. While this review is focused on cancer, the exosome-based drug delivery and resistance is also applicable to other human diseases.

Porokeratosis.

This case report describes multiple, hyperpigmented plaques involving the face, trunk, and bilateral upper and lower extremities.

Immune checkpoint blockade in human cancer therapy: lung cancer and hematologic malignancies.

Tumor immune evasion is one of the hallmarks of cancer, and expression of the B7 family of immune checkpoints (PD-L1, PD-L2, B7-H3, B7x and HHLA2) is one mechanism of immune evasion by tumors to suppress T-cell function. Antibodies blocking these interactions of B7-1/B7-2/CTLA-4 and PD-L1/PD-L2/PD-1 have had remarkable clinical success in several cancers and are less toxic than traditional chemotherapy. Even though only a small proportion of patients respond to checkpoint blockade, the duration of such responders due to immunological memory is remarkable and is longer than would be expected with any other agent in refractory disease. In this article, we review the therapeutic trials of blocking these pathways in human lung cancer and hematological malignancies.