Difference of Risk of Pancreatic Cancer in New-Onset Diabetes and Long-standing Diabetes: A Population-based Cohort Study.

CONTEXT: Considering the absence of methods to find pancreatic cancer early, surveillance of high-risk groups is needed for early diagnosis. OBJECTIVE: The study aimed to investigate the effect in the incidence of pancreatic cancer and the differences between new-onset diabetes mellitus (NODM) and long-standing DM (LSDM) since NODM group is a representative high-risk group. METHODS: The Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013 data were used. Regarding 88 396 people with DM (case group), we conducted a 1:1 propensity score matching to select a matched non-DM population (control group). To investigate the interaction between DM and the time variable distinguishing NODM and LSDM, we performed a multivariate time-dependent Cox regression analysis. RESULTS: The incidence of pancreatic cancer was higher in the DM group compared to the non-DM group (0.52% vs 0.16%; P < .001). The DM group had shown different risk of pancreatic cancer development according to the duration since the DM diagnosis (NODM hazard ratio (HR): 3.81; 95% CI, 2.97-4.88; P < .001; LSDM HR: 1.53; 95% CI, 1.11-2.11; P < .001). When the NODM and the LSDM groups were compared, the risk of pancreatic cancer was higher in the NODM group than in the LSDM group (HR: 1.55; P = .020). In subgroup analysis, NODM group showed that men (HR = 4.42; 95% CI, 3.15-6.19; P < .001) and patients who were in their 50 seconds (HR = 7.54; 95% CI, 3.24-17.56; P < .001) were at a higher risk of developing pancreatic cancer than matched same sex or age control group (non-DM population), respectively. CONCLUSION: The risk of pancreatic cancer was greater in people with DM than in a non-DM population. Among people with DM, NODM showed a higher risk of pancreatic cancer than LSDM.

Impact of UGT1A1 Polymorphisms on Febrile Neutropenia in Pancreatic Cancer Patients Receiving FOLFIRINOX: A Single-Center Cohort Study.

FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and 5-fluorouracil) is a first-line chemotherapy for metastatic pancreatic cancer (PC). Chemotherapy-induced neutropenia is one of the most serious adverse events associated with advanced PC. Although UGT1A1 polymorphisms are associated with the metabolism of irinotecan, their role as surrogate markers for FOLFIRINOX-induced neutropenia has not been confirmed. We investigated risk factors for FN-in particular, UGT1A1 polymorphisms-in PC patients receiving FOLFIRINOX, using a single-center cohort registry. To investigate the association between UGT1A1 polymorphisms and FN, we divided patients into three groups based on the predicted UGT1A1 phenotype: extensive metabolizer (EM) vs. intermediate metabolizer (IM) vs. poor metabolizer (PM). A total of 154 patients (FN group (n = 31) vs. non-FN group (n = 123)) receiving first-line FOLFIRINOX were identified between December 2017 and July 2020. The Cox regression analysis showed that female sex (HR: 2.20; p = 0.031), Eastern Cooperative Oncology Group performance status = 1 (HR: 2.83; p = 0.008), UGT1A1 IM (HR: 4.30; p = 0.004), and UGT1A1 PM (HR: 4.03; p = 0.028) were statistically significant risk factors for FN. We propose that UGT1A1 is the strongest predictive factor for FN and that this gene should be screened prior to the administration of chemotherapy.

Response to Neoadjuvant Therapy and Prognosis in Patients with Resectable Pancreatic Cancer: A Propensity Score Matching Analysis.

BACKGROUND/AIMS: : Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. METHODS: We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. RESULTS: Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. CONCLUSIONS: We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

Usefulness of Smartphone Apps for Improving Nutritional Status of Pancreatic Cancer Patients: Randomized Controlled Trial.

BACKGROUND: Approximately 80% of pancreatic ductal adenocarcinoma (PDAC) patients suffer from anorexia, weight loss, and asthenia. Most PDAC patients receive chemotherapy, which often worsens their nutritional status owing to the adverse effects of chemotherapy. Malnutrition of PDAC patients is known to be associated with poor prognosis; therefore, nutritional management during chemotherapy is a key factor influencing the outcome of the treatment. Mobile apps have the potential to provide readily accessible nutritional support for patients with PDAC. OBJECTIVE: We aimed to evaluate the efficacy of a mobile app-based program, Noom, in patients receiving chemotherapy for PDAC. METHODS: We prospectively enrolled 40 patients who were newly diagnosed with unresectable PDAC from a single university-affiliated hospital in South Korea, and randomly assigned them into a Noom user group (n=20) and a non-Noom user group (n=20). The 12-week in-app interventions included meal and physical activity logging as well as nutritional education feedback from dietitians. The non-Noom user group did not receive any nutrition intervention. The primary outcomes were the changes in the nutritional status and quality of life (QoL) from the baseline to 12 weeks. The secondary outcomes included the changes in the skeletal muscle index (SMI) from the baseline to 12 weeks. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and the Patient-Generated Subjective Global Assessment (PG-SGA) were used as paper questionnaires to assess the QoL and nutritional status of the patients. Intention-to-treat and per-protocol analyses were conducted. Regarding the study data collection time points, we assessed the nutritional status and QoL at the baseline (T0), and at 4 (T1), 8 (T2), and 12 (T3) weeks. Abdominal computed tomography (CT) imaging was conducted at the baseline and after 8 weeks for tumor response and SMI evaluation. The skeletal muscle area (cm2) was calculated using routine CT images. The cross-sectional areas (cm2) of the L3 skeletal muscles were analyzed. RESULTS: Between February 2017 and January 2018, 48 patients were assessed for eligibility. Totally 40 patients with pancreatic cancer were included by random allocation. Only 17 participants in the Noom user group and 16 in the non-Noom user group completed all follow-ups. All the study participants showed a significant improvement in the nutritional status according to the PG-SGA score regardless of Noom app usage. Noom users showed statistically significant improvements on the global health status (GHS) and QoL scales compared to non-Noom users, based on the EORTC QLQ (P=.004). The SMI decreased in both groups during chemotherapy (Noom users, 49.08±12.27 cm2/m2 to 46.08±10.55 cm2/m2; non-Noom users, 50.60±9.05 cm2/m2 to 42.97±8.12 cm2/m2). The decrement was higher in the non-Noom user group than in the Noom user group, but it was not statistically significant (-13.96% vs. -3.27%; P=.11). CONCLUSIONS: This pilot study demonstrates that a mobile app-based approach is beneficial for nutritional and psychological support for PDAC patients receiving chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04109495; https://clinicaltrials.gov/ct2/show/NCT04109495.

Single-center risk factor analysis for FOLFIRINOX associated febrile neutropenia in patients with pancreatic cancer.

PURPOSE: FOLFIRINOX is the standard therapy in patients with unresectable pancreatic cancer (PC). However, FOLFIRINOX frequently induces febrile neutropenia (FN) and neutropenia. The purpose of this study was to explore risk factors for FN and grade 4 neutropenia (NP G4) in patients receiving FOLFIRINOX for PC. METHODS: We collected data on 106 patients with PC treated with first-line FOLFIRINOX between 2015 and 2017 using the Pancreatic Cancer Cohort Registry of Severance Hospital in Seoul, Korea. RESULTS: Multivariate logistic regression analysis showed that female (OR, 3.24; P = 0.023), Eastern Cooperative Oncology Group performance status (OR, 3.70; P = 0.024), overweight (OR, 4.25; P = 0.022), and initial biliary stent insertion (OR, 4.22; P = 0.008) were significantly related to a high risk of FN. Time-dependent bias was reduced using Cox regression analysis, which revealed that female (OR, 2.29; P = 0.041), overweight (OR, 2.67; P = 0.022), and initial biliary stent insertion (OR, 2.59; P = 0.016) were statistically significant predictors. Regarding NP G4, female sex (OR, 2.90; P = 0.016) and overweight (OR, 4.07; P = 0.033) were identified as risk factors in multivariate analysis; however, in Cox regression analysis, tumor in the head of the pancreas (OR, 1.96; P = 0.027) and hemoglobin (g/dL < 12) (OR, 1.87; P = 0.049) were also identified as risk factors. CONCLUSION: Female sex, overweight, and initial biliary stent insertion were independent risk factors for the occurrence of FN in patients with unresectable PC treated with FOLFIRINOX.