Pancreatic cancer cachexia: a review of mechanisms and therapeutics.

Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions

Diabetes mellitus and risk of plasma cell and lymphoproliferative disorders in 94,579 cases and 368,348 matched controls

this research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 (UAS) and supported by grants from Swedish Cancer Society (MB), Parker Institute of Cancer Immunotherapy Career Development Award (YD, UAS), International Myeloma Society Career Development Award, Paula and Rodger Riney Foundation, American Society of Hematology Clinical Research Training Institute Award and TREC Training Workshop R25CA203650 (PI: Melinda Irwin) (UAS). Copyright & Usage Copyright (c) 2022 Ferrata Storti Foundation Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.Peer reviewe

Pancreatic cancer cachexia: a review of mechanisms and therapeutics.

Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions

Feasibility study on the development of a 50-hectare Board of Investments (BOI) registered industrial estate with special export processing zone features in Liloan, Cebu

This project feasibility study, as the title implies, is on the development of an Industrial Estate with a Special Export Processing Zone (SEPZ) feature. This proposal is intended to be located in Liloan, a municipality in the island of Cebu. The SEPZ is expected to heed the needs of both the foreign and local investors in finding a venue for their businesses, specifically those engaged in the export of goods. The proposed site is approximately 50 hectares or 500,000 square meters with 35 hectares or 350,000 square meters available for locators.The study on the development of a SEPZ was inspired by the government\u27s long sought goal of industrialization. This project would not only help in the realization of this objective, but this could also contribute to another government thrust-industry dispersion. There is a number of existing Export Processing Zones (EPZs) and SEPZs in the country, but majority of them are located in Luzon.Cebu seems to be a very good place to establish a zone, not only because it is a fast developing/industrializing city due to the presence of numerous facilities and labor force, but also because of the place and order situation in the area. These three are considered as basic determinants of a good business location, specially for exporters. This plan would help disperse or spread the industrial zones throughout the country. Project\u27s Long Term Objectives as earlier mentioned, this project is aimed to contribute to the government\u27s long-sought goal of industrialization, and consequently, industry dispersion by encouraging the entry of local and foreign investments and emergence of linkage industries around the area. But these are only some of the objectives it really seeks to achieve. We expect the 35-hectares allotted for locators be filled in 10 years, at which time, at least 17,500 Filipinos could be directly employed, and 52,500 to 87,500 individuals indirectly benefiting. This undertaking will also encourage the transfer of technology to the country. Economic and social benefits are also anticipated, resulting from the operations of the SEPZ, and these are expected to have a tremendous impact on the country as a whole. The feasibility of this study could be measured in terms of its profitability and socio-economic benefits. Profitability could be viewed in two ways, namely the internal rate of return for the developer, and the length of time for the recovery of the investment. The former is necessary so that the developer would be able to assess the viability of his venture, to determine whether his investment was a good one or not. The latter should also be determined, so that the developer could be assured of his investment -- his security.The socio-economic benefits of this study are outstanding. Because of the hugeness of this project, its effect are also expected to create the same impact. The SEPZ would surely turn out to be a great asset not only to the government, but to the whole country as well. It is expected to augment the state\u27s income, provide direct and indirect employment, promote tourism, develop other industries, and permit the transfer of technology

Diabetes Mellitus and Risk of Plasma Cell and Lymphoproliferative Disorders: A Population Based Study Including 94,579 Cases and 368,348 Matched Controls

Introduction The incidence of lymphoproliferative disorders (including plasma cell disorders) (LPD) and diabetes mellitus (DM) increase with age. The metabolic link between DM and multiple myeloma (MM) or LPD has been researched in other epidemiologic studies with a small number of cases suggesting an increased risk (Dankner et al Am J Epi 2016, Castillo et al Blood 2012). However, this link has not yet been studied in patients with related disorders such as monoclonal gammopathy of unknown significance (MGUS), AL amyloidosis (AL), or Waldenstrom macroglobulinemia (WM). This is the first study to evaluate the risk of DM on LPD in a large Swedish population-based case-control study. Methods We conducted a large population-based matched case-control study to evaluate the impact of a preceding diagnosis of DM on the development of a LPD. We included all cases of MM, WM, AL and other LPs (OLP) in the nationwide Swedish Cancer Registry and cases of AL and chronic lymphocytic leukemia (CLL) in the Swedish patient registry from 1987-2013. MGUS was acquired from a network of oncology and hematology clinics in Sweden. OLPs included the diagnoses of Hodgkin lymphoma, non-Hodgkin lymphoma, CLL, T cell lymphoma and other lymphocytic leukemias. For each case, up to four controls matched by age, gender, and county of residence from the general population were included. Cases with no controls were excluded. Diagnoses of DM were acquired from the Swedish patient registry where they were coded using ICD 9 and 10 codes. Conditional logistic regression was then performed controlling for the matching variables estimating the odds ratio (OR) of each LPD for a diagnosis of DM before the diagnosis of the LPD. OR of each LPD for the diagnosis of DM greater than one year and less than one year prior to the diagnosis of LPD was also calculated. For MGUS cases, we also assessed the risk of progression to LPD. To avoid immortal time bias we include DM as a time dependent covariate in a Cox-model adjusting for age, sex, and year of MGUS diagnosis. All analyses were performed in R using the survival, and survminer packages. Results Patients with a diagnosis of MGUS (OR: 1.58; p 1 year prior to the diagnosis were included (Table 1). However, patients with (vs. without) a diagnosis of DM are not more likely to progress from MGUS to MM, WM, AL or OLP (HR 0.89; p=0.11) (Table 2). Discussion The strength of our study lies in its large sample size and the availability of 4 matched controls for each case. The diagnosis of DM is associated with an increased risk of MGUS, MM, AL and OLP. This risk is greatest for DM diagnosis in the year prior to LPD diagnosis. This may be due to DM induced hyperglycemia leading to epigenetic changes that increase the odds of developing/accelerating early stage cancer given that they may have prediabetes/undiagnosed DM for many years prior (Huang et al Diabetologia 2014). It is also plausible that patients with DM for >1 year have been on metformin which has been shown to have a protective effect and are less likely to progress suggesting the role of hyperglycemia in its progression (Chang et al Lancet Haematol 2015). Alternatively, patients are likely to have DM diagnosed in the year prior due to similar symptoms of fatigue or weight loss, or a detection bias due to increased physician visits and laboratory testing. This lack of increased progression from MGUS in DM may be explained by the small numbers of patients that progressed in this dataset or the inability to control for factors such as DM treatment. Some other limitations include the lack of granular information related to DM, body mass index as well as prognostic information for the LPD. Conclusions Although, smaller prior studies have suggested a link between DM and cancer including MM and LPD, this is the largest study in patients with LPD. This is also the first epidemiologic study establishing a link between DM and MGUS as well as AL. Research into further understanding this association would enable us to provide patients with better treatment options in the future. Disclosures Shah: Physicians Education Resource: Honoraria; Celgene/BMS: Research Funding. Hultcrantz:Intellisphere LLC: Consultancy; Amgen: Research Funding; Daiichi Sankyo: Research Funding; GSK: Research Funding. Hassoun:Takeda: Research Funding; Celgene: Research Funding; Novartis: Consultancy. Korde:Astra Zeneca: Other: Advisory Board; Amgen: Research Funding. Lesokhin:BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GenMab: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; Janssen: Research Funding; Genentech: Research Funding; Juno: Consultancy, Honoraria. Mailankody:Physician Education Resource: Honoraria; PleXus Communications: Honoraria; Takeda Oncology: Research Funding; Janssen Oncology: Research Funding; Allogene Therapeutics: Research Funding; Juno Therapeutics, a Bristol-Myers Squibb Company: Research Funding. Landgren:Adaptive: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Seattle Genetics: Research Funding; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Seattle Genetics: Research Funding; Pfizer: Consultancy, Honoraria; Merck: Other; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Merck: Other; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding