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      Diabetic Ketoacidosis as the Initial Presenting Symptom of Pancreatic Adenocarcinoma: A Discussion about Screening Utilizing ENDPAC Scoring Coupled with CT Scans and Endoscopic Ultrasound

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          Abstract

          Pancreatic adenocarcinoma is often discovered at an advanced stage due to a lack of early symptomology, resulting in this being the fourth leading cause of cancer-related death in the USA. The relationship between diabetes mellitus and pancreatic cancer has been known for many years; however, it is not well understood. Studies have suggested that long-standing type 2 diabetes mellitus can increase the risk of pancreatic cancer by 1.5–2.0-fold. However, patients with new-onset diabetes over 50 years of age have an 8-fold higher risk of pancreatic cancer. Evidence has shown that pancreatic cancer causes diabetes, with the majority being new onset. Diabetic ketoacidosis, which occurs in long-term hyperglycemia, as an initial presentation of pancreatic adenocarcinoma is rare, and only a few cases have been reported. It is postulated that pancreatic cancer prevents insulin-producing cells of the pancreas from responding to insulin resistance. The enriching new-onset diabetes for pancreatic cancer (ENDPAC) score may be utilized as a screening tool for pancreatic carcinomas as an early diagnosis may lead to cure by surgery instead of the grave prognosis associated with it. In this case report, we discuss a 52-year-old female presenting with symptoms of diabetic ketoacidosis who was then subsequently found to have stage-4 pancreatic adenocarcinoma. We concluded that if a patient presents with new-onset diabetes, abdominal imaging with CT scans and endoscopic ultrasound may be warranted to rule out pancreatic carcinoma.

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          Most cited references15

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          Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies.

          Diabetes mellitus (DM) is widely considered to be associated with risk of pancreatic cancer (PaC), however, whether DM is a cause or a consequence of PaC is still controversial. We examined this association by conducting a detailed meta-analysis of cohort studies. Studies were identified by searching Medline and Embase through November 30, 2010. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. A total of thirty-five cohort studies were included in this meta-analysis. DM was associated with an increased risk of PaC (the summary RRs=1.94; 95% CI, 1.66-2.27), with significant evidence of heterogeneity among these studies (p<0.001, I²=93.6%). Subgroup analyses revealed that the increased risk of PaC was independent of geographic locations, sex, study design, alcohol consumption, body mass index (BMI) and smoking status. In addition, the relative risk of PaC was correlated negatively with the duration of DM, with the highest risk of PaC found among patients diagnosed within less than 1 year. There was no significant publication bias (p=0.136 for Egger's regression asymmetry test). Findings from this meta-analysis strongly support that diabetes is associated with an increased risk of PaC in both males and females and that DM is both an early manifestation and an etiologic factor of pancreatic cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Trends in pancreatic adenocarcinoma incidence and mortality in the United States in the last four decades; a SEER-based study

            Background Pancreatic cancer is the fourth-leading cause of cancer deaths in the United States. The silent nature of the disease and its poor prognosis, the need for further research, along with the need to assess the outcomes of current approaches necessitate an ongoing evaluation of the epidemiology and mortality-trends of this malignancy. Continuous monitoring of disease-patterns, on population-levels, may help scientists assess the quality of healthcare delivery, boost their understanding of diseases' characteristics and risk factors, and detect gaps whereby further research is needed. None of the previous reports shed light on pancreatic adenocarcinomas (PAC), the most common type of Pancreatic Cancer, as the primary outcome. In this study we aim to investigate PAC’s incidence and mortality trends over the last four decades in the United States. Methods We used SEER 9 database to study PAC cases during 1974-2014. Incidence and mortality rates were calculated by sex, age, race, state and stage of PAC. Annual percent change (APC) was calculated using joinpoint regression software. Results We reviewed 67,878 PAC cases; most of these cases were in the head of pancreas. Overall PAC incidence rates increased 1.03% (95% CI, 0.86-1.21, p <.001) per year over the study period. Rates of adenocarcinoma of the head of pancreas increased 0.87% (95% CI, 0.68-1.07, p <.001), and rates of adenocarcinoma of the body and tail of pancreas increased 3.42% (95% CI, 3.06-3.79, p <.001) per year during 1973-2014. PAC incidence-based mortality increased 2.22% (95% CI, 1.93-2.51, p <.001) per year. However, during 2012-2014 there was a statistically significant decrease in PAC incidence-based mortality; APC, -24.70% (95% CI, -31.78 - -16.88, p <.001). Conclusion PAC’s incidence and mortality rates have been increasing for decades. However, the last few years have shown a promising decrease in mortality. We believe that further advances in healthcare delivery and research can lead to a further mortality decrease. Future studies can use this paper as a baseline to keep monitoring the outcomes of PAC's therapy. Electronic supplementary material The online version of this article (10.1186/s12885-018-4610-4) contains supplementary material, which is available to authorized users.
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              Model to Determine Risk of Pancreatic Cancer in Patients with New-onset Diabetes

              Background & Aims Of subjects with new-onset diabetes (based on glycemia) over the age of 50 years, approximately 1% are diagnosed with pancreatic cancer within 3 years. We aimed to develop and validate a model to determine risk of pancreatic cancer in individuals with new-onset diabetes. Methods We retrospectively collected data from 4 independent, non-overlapping cohorts of patients (n=1561) with new-onset diabetes (based on glycemia; data collected at date of diagnosis and 12 months before) in the Rochester Epidemiology Project, from January 1, 2000 through December 31, 2015 to create our model. The model weighed scores for the 3 factors identified in the discovery cohort to be most strongly associated with pancreatic cancer (64 patients with pancreatic cancer and 192 with type-2 diabetes): change in weight, change in blood glucose, and age at onset of diabetes. We called our model enriching new-onset diabetes for pancreatic cancer (END-PAC). We validated the locked-down model and cutoff score in an independent population-based cohort of 1096 patients with diabetes; of these 9 patients (.82%) had pancreatic within 3 years of meeting the criteria for new-onset diabetes. Results In the discovery cohort the END-PAC model identified patients who developed pancreatic cancer within 3 years of onset of diabetes with an area under the receiver operating characteristic curve value of 0.87; a score of ≥3 identified patients who developed pancreatic cancer with 80% sensitivity and specificity. In the validation cohort, a score of ≥3 identified 7/9 patients with pancreatic cancer (78%), with 85% specificity; the prevalence of pancreatic cancer in subjects with score of ≥3 (3.6%) was 4.4-fold more than in patients with new-onset diabetes. A high END-PAC score in subjects who did not have pancreatic cancer (false positives) was often due to such factors as recent steroid use or different malignancy. An END-PAC score <0 (in 49% of subjects) meant that patients had an extremely low-risk for pancreatic cancer. An END-PAC score ≥3 identified 75% of subjects in the discovery cohort >6 months before a diagnosis of pancreatic cancer. Conclusions Based on change in weight, change in blood glucose, and age at onset of diabetes, we developed and validated a model to determine risk of pancreatic cancer in patients with new-onset diabetes, based on glycemia (the END-PAC model). An independent, prospective study is needed to further validate this model, which could contribute to early detection of pancreatic cancer.
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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                Case Reports in Oncology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1662-6575
                Sep-Dec 2022
                8 November 2022
                8 November 2022
                : 15
                : 3
                : 942-949
                Affiliations
                Internal medicine, Indiana University Health, Ball Memorial Hospital, Muncie, Indiana, USA
                Author notes
                *Sasmith R. Menakuru, smenakuru@ 123456iuhealth.org
                Article
                cro-0015-0942
                10.1159/000526198
                9830293
                36636678
                69d5c7b9-33ad-49c8-b450-06370e6f6b19
                Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 13 May 2022
                : 6 July 2022
                : 2022
                Page count
                Figures: 2, Tables: 1, References: 15, Pages: 8
                Funding
                No funding was required for the case report.
                Categories
                Case Report

                Oncology & Radiotherapy
                diabetic ketoacidosis,pancreatic adenocarcinoma,computed tomography scan,enriching new-onset diabetes for pancreatic cancer score

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