Cancer has become the second most serious disease threatening human health, followed by cardiovascular diseases. This study aimed to quantitatively estimate the mortality, morbidity, and analyze the trends of 29 cancer groups in 195 countries/regions between 1990 and 2017. Detailed information of 29 cancer groups were collected from the Global Burden of Disease (GBD) study in 2017 and age-standardized incidence rates (ASIR) and age-standardized death rates (ASDR) of 29 cancer groups were calculated based on gender, age, region, and country. Trend analyses were conducted for major cancer types. In 2017, the global death population caused by cancer reached 9 million, which was nearly twice the number in 1990. The ASDR and ASIR of cancer in males were about 1.5 times those of females. Breast cancer showed the highest mortality rate in females in 2017. Individuals aged over 50 are at high risk of developing cancer and the number of cases and deaths in this age group accounted for more than 80% of all cancers in all age groups. Asia has the heaviest cancer burden due to its large population density. Different cancers in varied countries globally have their own characteristics. The ASDR and ASIR of some major cancers demonstrated changes from 1990 to 2017. Analyses of these data provided basis for future investigations to the common etiological factors, leading to the occurrence of different cancers, the development of prevention strategies based on local characteristics, socioeconomic and other conditions, and the formulation of more targeted interventions.

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Incidence and death in 29 cancer groups in 2017 and trend analysis from 1990 to 2017 from the Global Burden of Disease Study

The role of LncRNA ADAMTS9-AS2 in the regulation of chemoresistance of gastric cancer (GC) is largely unknown. Here we found that LncRNA ADAMTS9-AS2 was low-expressed in GC tissues and cells compared to their normal counterparts. In addition, LncRNA ADAMTS9-AS2 inhibited miR-223-3p expressions in GC cells by acting as competing endogenous RNA, and the levels of LncRNA ADAMTS9-AS2 and miR-223-3p showed negative correlations in GC tissues. Of note, overexpression of LncRNA ADAMTS9-AS2 inhibited GC cell viability and motility by sponging miR-223-3p. In addition, the levels of LncRNA ADAMTS9-AS2 were lower, and miR-223-3p was higher in cisplatin-resistant GC (CR-GC) cells than their parental cisplatin-sensitive GC (CS-GC) cells. LncRNA ADAMTS9-AS2 overexpression enhanced the cytotoxic effects of cisplatin on CR-GC cells, which were reversed by overexpressing miR-223-3p. Furthermore, LncRNA ADAMTS9-AS2 increased NLRP3 expressions by targeting miR-223-3p, and upregulation of LncRNA ADAMTS9-AS2 triggered pyroptotic cell death in cisplatin treated CR-GC cells by activating NLRP3 inflammasome through downregulating miR-223-3p. Finally, the promoting effects of LncRNA ADAMTS9-AS2 overexpression on CR-GC cell death were abrogated by pyroptosis inhibitor Necrosulfonamide (NSA). Collectively, LncRNA ADAMTS9-AS2 acted as a tumor suppressor and enhanced cisplatin sensitivity in GC cells by activating NLRP3 mediated pyroptotic cell death through sponging miR-223-3p.

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LncRNA ADAMTS9-AS2 inhibits gastric cancer (GC) development and sensitizes chemoresistant GC cells to cisplatin by regulating miR-223-3p/NLRP3 axis.

The systemic treatment options for advanced gastric cancer (GC) have evolved rapidly in recent years. We have reviewed the recent data of clinical trial incorporating targeted agents, including inhibitors of angiogenesis, human epidermal growth factor receptor 2 (HER2), mesenchymal–epithelial transition, epidermal growth factor receptor, mammalian target of rapamycin, claudin-18.2, programmed death-1 and DNA. Addition of trastuzumab to platinum-based chemotherapy has become standard of care as front-line therapy in advanced GC overexpressing HER2. In the second-line setting, ramucirumab with paclitaxel significantly improves overall survival compared to paclitaxel alone. For patients with refractory disease, apatinib, nivolumab, ramucirumab and TAS-102 have demonstrated single-agent activity with improved overall survival compared to placebo alone. Pembrolizumab has demonstrated more than 50% response rate in microsatellite instability-high tumors, 15% response rate in tumors expressing programmed death ligand 1, and non-inferior outcome in first-line treatment compared to chemotherapy. This review summarizes the current state and progress of research on targeted therapy for advanced GC.

/pdf/targeted-and-novel-therapy-in-advanced-gastric-cancer-2bpxsq0n32.pdf

Targeted and novel therapy in advanced gastric cancer.

HER2 expression remains an important biomarker to guide the addition of the monoclonal antibody trastuzumab to first-line systemic chemotherapy in unresectable, metastatic gastroesophageal adenocarcinomas (GEA). However, in contrast to breast cancer, other HER2-targeted strategies to date have not improved outcomes in this molecular subtype of GEA. Since the initial development of HER2 biomarker testing guidelines, significant spatial intratumoral heterogeneity of HER2 overexpression has been recognized as a major characteristic of this disease. In this review, we aim to survey the seminal positive and negative trials investigating HER2-targeted agents for GEA. We also highlight emerging data on the genomic and temporal heterogeneity of molecular resistance alterations that have yielded further insight into the heterogeneity of therapeutic responses. We conclude with an overview of promising novel agents and strategies which may refine the therapeutic landscape.

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Progress and challenges in HER2-positive gastroesophageal adenocarcinoma

Health Policy Section, Department of Nursing, Faculty of Medical Technology, Teikyo University, Tokyo, Japan Correspondence to: Chisato Hamashima, MD, DrMedSc. Health Policy Section, Department of Nursing, Faculty of Medical Technology, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-1211, Japan. Email: chamashi@med.teikyo-u.ac.jp. Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Translational Medicine. The article did not undergo external peer review. Comment on: Solanki S, Chakinala RC, Haq KF, et al. Inpatient burden of gastric cancer in the United States. Ann Transl Med 2019;7:772.

https://atm.amegroups.com/article/download/39921/pdf

The burden of gastric cancer

There is no convincing data on the trends of hospitalizations, mortality, cost, and demographic variations associated with inpatient admissions for gastric cancer in the USA. The aim of this study was to use a national database of US hospitals to evaluate the trends associated with gastric cancer. We analyzed the National Inpatient Sample (NIS) database for all patients in whom gastric cancer (ICD-9 code: 151.0, 151.1, 151.2, 151.3, 151.4, 151.5, 151.6, 151.8, 151.9) was the principal discharge diagnosis during the period, 2003–2014. The NIS is the largest publicly available all-payer inpatient care database in the US. It contains data from approximately eight million hospital stays each year. The statistical significance of the difference in the number of hospital discharges, length of stay, and hospital costs over the study period was determined by regression analysis. In 2003, there were 23,921 admissions with a principal discharge diagnosis of gastric cancer as compared to 21,540 in 2014 (P < 0.01). The mean length of stay for gastric cancer decreased by 17% between 2003 and 2014 from 10.9 days to 8.95 days (P < 0.01). However, during this period, the mean hospital charges increased significantly by 21% from $ 75,341 per patient in 2003 to $ 91,385 per patient in 2014 (P < 0.001). There was a more significant reduction in mortality over a period of 11 years from 2428 (10.15%) in 2003 to 1345 (6.24%) in 2014 (P < 0.01). The aggregate charges (i.e., “national bill”) for gastric cancer increased significantly from 1.79 bn $ to 1. 96 bn $ (P < 0.001), despite decrease in hospitalization (inflation adjusted). Although the number of inpatient admissions for gastric cancer have decreased over the past decade, the healthcare burden and cost related to it has increased significantly. Inpatient mortality is decreasing which is consistent with overall decrease in gastric cancer-related deaths. Cost increase associated with gastric cancer contributed significantly to the national healthcare bill.

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Decreasing mortality and hospitalizations with rising costs related to gastric cancer in the USA: an epidemiological perspective.

PO-1091 GTV as prognostic marker in head and neck cancer - Time to redefine GTV beyond contouring

To the Editor: Drug reaction with eosinophilia and systemic symptoms (DRESSs), also called drug-induced hypersensitivity syndrome, is a life-threatening adverse drug reaction with mortality rates of up to 10%–20%.1 The clinical presentation includes mucocutaneous rash, fever, lymphadenopathy, hematologic abnormalities such as eosinophilia and atypical lymphocytes, and multiple organ dysfunction, including liver, kidneys, heart, and lungs.1 Although fever and rash are the most common presentations, the defining characteristic of the syndrome is organ dysfunction. It usually presents 2–8 weeks after the introduction of the causative agent and symptoms may persist for a longer period of time, despite discontinuing the offending drug. Most commonly associated medications are aromatic antiepileptics.2,3 Others include sulfonamides/sulfones, nonsteroidal anti-inflammatory agents, angiotensinogen-converting enzyme inhibitors, and antidepressants. The precise incidence of DRESS is yet to be determined; an estimate is 1/1000 to 1/10,000 new users of antiepileptic therapy may present with this hypersensitivity reaction.4,5 The patient is a 29-year-old woman with a history of chronic pancreatitis and gastric bypass surgery, who initially presented with lower extremity swelling in the setting of hypoalbuminemia and protein-calorie malnutrition. She was started on a high calorie/protein diet and was discharged on furosemide andmultivitamin tablets. Three weeks after discharge, she noticed peri-oral rash, which extended to lower extremities, groin, and trunk. On presentation she had multiple areas of erythema and crusting over body, with small tense vesicles of legs and bilateral lower extremity edema. Blood work showed elevated liver enzymes, elevated International normalized ratio, low vitamin D, macrocytic anemia, and elevated eosinophils. She underwent skin biopsy of the left forearm, which showed spongiotic epidermis with paucicellular intraepidermal vesicle/bullae with scattered eosinophils and neutrophils. Rare necrotic keratinocytes sites were identified within the epidermis. The Naranjo algorithm score was 5 that indicated probable adverse dug reaction to furosemide, and no other offending agents were identified. She was diagnosed with DRESS syndrome secondary to furosemide and was started on oral prednisone therapy in view of liver dysfunction. The rash and liver function improved with oral steroid therapy. Hospital course was complicated by sudden drop in hemoglobin. No source of bleeding was identified. Hemolysis workup came back positive with elevated Lactate Dehydrogenase, low haptoglobin, elevated reticulocyte count, and positive C3 and poly antibody Coombs tests (negative Immunoglobulin G Coombs test). She was diagnosed with autoimmune hemolytic anemia refractory to oral prednisone therapy and received 1 dose of intravenous immunoglobulin therapy. She also received 1 unit of packed red blood cells. Her hemoglobin remained stable, without any further drop. She was discharged on oral prednisone therapy and completed prednisone taper over the next 12 weeks as an outpatient. No recurrence of hemolytic episodes is seen in 6 months outpatient follow-up. DRESS syndrome is a severe delayed type hypersensitivity (type IV hypersensitivity) reaction with a prolonged latency period of 3–8 weeks. The clinical course of the syndrome varies widely. Early in the course it may present with prodromal symptoms (fever, pruritus, dysphagia, or lymphadenopathy) and a mucocutaneous rash.1 Internal organ involvement is the characteristic feature of DRESS syndrome, and the most commonly involved organs are the liver, kidneys, heart, and lungs. Although fever and rash are the most common presenting features, liver damage may develop before the onset of a rash in up to 10% of patients.6 Hematologic abnormalities, including eosinophilia and atypical lymphocytosis may be seen on initial presentation. The most commonly associated drugs are aromatic anticonvulsants (carbamazepine, phenytoin, and phenobarbital). Although cross-sensitivity as high as 75% has been reported among the aromatic anticonvulsants, carbamazepine remains the most widely reported agent.7 There are only a few case reports of DRESS syndrome in association with loop diuretics (furosemide and torsemide). American Journal of Therapeutics 0, 1–3 (2020)

Amirta Devi

Papers

Decreasing mortality and hospitalizations with rising costs related to gastric cancer in the USA: an epidemiological perspective.

PO-1091 GTV as prognostic marker in head and neck cancer - Time to redefine GTV beyond contouring

Furosemide-Associated Drug Reaction With Eosinophilia and Systemic Symptoms.