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Influence of the Retrocolic Versus Antecolic Route for Alimentary Tract Reconstruction on Delayed Gastric Emptying After Pancreatoduodenectomy: A Multicenter, Noninferiority Randomized Controlled Trial.
Toyama, H, Matsumoto, I, Mizumoto, T, Fujita, H, Tsuchida, S, Kanbara, Y, Kadowaki, Y, Maeda, H, Okano, K, Fukuoka, M, et al
Annals of surgery. 2021;(6):935-944
Abstract
OBJECTIVE This study aimed to determine whether retrocolic alimentary tract reconstruction is noninferior to antecolic reconstruction in terms of DGE incidence after pancreatoduodenectomy (PD) and investigated patients' postoperative nutritional status. SUMMARY OF BACKGROUND DATA The influence of the route of alimentary tract reconstruction on DGE after PD is controversial. METHODS Patients from 9 participating institutions scheduled for PD were randomly allocated to the retrocolic or antecolic reconstruction groups. The primary outcome was incidence of DGE, defined according to the 2007 version of the International Study Group for Pancreatic Surgery definition. Noninferiority would be indicated if the incidence of DGE in the retrocolic group did not exceed that in the antecolic group by a margin of 10%. Patients' postoperative nutrition data were compared as secondary outcomes. RESULTS Total, 109 and 103 patients were allocated to the retrocolic and antecolic reconstruction group, respectively (n = 212). Baseline characteristics were similar between both groups. DGE occurred in 17 (15.6%) and 13 (12.6%) patients in the retrocolic and antecolic group, respectively (risk difference; 2.97%, 95% confidence interval; -6.3% to 12.6%, which exceeded the specified margin of 10%). There were no differences in the incidence of other postoperative complications and in the duration of hospitalization. Postoperative nutritional indices were similar between both groups. CONCLUSIONS This trial could not demonstrate the noninferiority of retrocolic to antecolic alimentary tract reconstruction in terms of DGE incidence. The alimentary tract should not be reconstructed via the retrocolic route after PD, to prevent DGE.
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Early dose reduction/delay and the efficacy of liposomal irinotecan with fluorouracil and leucovorin in metastatic pancreatic ductal adenocarcinoma (mPDAC): A post hoc analysis of NAPOLI-1.
Chen, LT, Macarulla, T, Blanc, JF, Mirakhur, B, de Jong, FA, Belanger, B, Bekaii-Saab, T, Siveke, JT
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2021;(1):192-199
Abstract
BACKGROUND Chemotherapy dose modification to manage adverse events is commonplace in clinical practice. This exploratory analysis evaluates the impact of liposomal irinotecan dose modification on overall survival (OS) and progression-free survival (PFS) in the NAPOLI-1 clinical trial (NCT01494506). METHODS Analysis includes only patients enrolled under protocol version 2 who received at least the first 2 scheduled doses of study drug. Within the liposomal irinotecan +5 fluorouracil/leucovorin (5 FU/LV) arm, patients were grouped according to whether or not they had a dose modification within the first 6 weeks. Dose reduction was defined as any decrease from initial dose; dose delay was any dosing delay >3 days from target date. OS and PFS (Kaplan-Meier estimates) were compared within the liposomal irinotecan+5-FU/LV arm and between treatment arms. Unstratified hazard ratios (HRs) were calculated using Cox regression analysis. RESULTS Of the 93 patients from the liposomal irinotecan+5 FU/LV arm included in the analysis, 53 experienced a dose modification (both delay and reduction, n = 30; delay only, n = 19; reduction only, n = 4). No apparent difference in median OS or PFS was observed between patients who did versus patients who did not have a dose modification (OS: 8.4 vs 6.7 months; HR, 0.89; PFS: 4.2 vs 3.1 months; HR, 0.74). CONCLUSION An early dose reduction or delay of liposomal irinotecan+5-FU/LV in the first 6 weeks does not significantly impact OS or PFS compared to patients without dose modifications. This finding suggests that tolerability-guided dose modification of liposomal irinotecan does not adversely affect efficacy outcomes.
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Multicenter, randomized, double-blind, controlled trial of transcutaneous electrical nerve stimulation for pancreatic cancer related pain.
He, L, Tan, K, Lin, X, Yi, H, Wang, X, Zhang, J, Lin, J, Lin, L
Medicine. 2021;(5):e23748
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Abstract
BACKGROUND Up to 80% of patients with pancreatic cancer experience abdominal and back pain. Although pharmacologic medications provide some relief, many report inadequate analgesia and adverse effects. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive physical modality and had been widely applied for pain relieving, yet no study has investigated the effectiveness of TENS for pain in pancreatic cancer. METHODS Eligible patients were randomly assigned in a 1:1 ratio to TENS group or control group. The primary outcome was percentage change of numerous rating scale (NRS) after treatment. Secondary outcomes included percentage change of analgesic medication consumption and effect on constipation and poor appetite. RESULTS One hundred seventy-one patients were recruited (84 to control group and 87 to TENS group). NRS in TENS group has been largely decreased 77.9% right after treatment and 27.1% in 2 hours, before applying any analgesic medication, while that in control group was slightly downregulated right after treatment but gave a trend to increase at 1, 2, and 3 hours. When comparing both groups, pain was significantly well controlled without analgesic medication supplement in TENS group at 0 hour (difference in mean percent change in NRS = 50.0 [95% CI, 50-51.4], P < .01) and 3 hours (difference in mean percent change in NRS = 134.0 [95% CI, 130.0-142.7], P < .01) after treatment, and this analgesic effect last to 3 weeks after treatment cycle (difference in mean percent change in NRS = 22.5 [95% CI, 17.6-27.3], P < .01) without increase of analgesic medication consumption. CONCLUSIONS TENS reduces pain without increase analgesic medication consumption in patients with pancreatic cancer pain. It provides an alternative therapy for pain in pancreatic cancer. CLINICAL TRIAL REGISTRATION This study was registered at ClinicalTrials.gov, identifier NCT03331055.
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Case Report: Unmasking Hypercalcemia in Patients With Neuroendocrine Neoplasms. Experience From Six Italian Referral Centers.
Giannetta, E, Sesti, F, Modica, R, Grossrubatscher, EM, Guarnotta, V, Ragni, A, Zanata, I, Colao, A, Faggiano, A
Frontiers in endocrinology. 2021;:665698
Abstract
BACKGROUND Hypercalcemia is a common paraneoplastic syndrome which can occur in up to 10% of patients with advanced neoplasms. Paraneoplastic parathyroid hormone-related protein (PTHrP) represents the most frequent cause of this syndrome. In neuroendocrine neoplasms (NENs) paraneoplastic hypercalcemia is rare. CASE SERIES The present series includes all patients with NENs and paraneoplastic hypercalcemia from four Italian centres: (I) A 40-year-old man was hospitalized for repeated episodes of falls, hyposthenia and drowsiness. Severe hypercalcemia was found. Metastatic pancreatic G2 NEN and PTHrP-related hypercalcemia were diagnosed. The patient started therapy with somatostatin analogs (SSA) and Denosumab. After disease progression peptide receptor radionuclide therapy (PRRT) was started with an objective response associated with PTHrP reduction and normocalcemia. (II) A 45-year-old man was referred for pancreatic G2 NEN. SSA and subsequently everolimus were administered for metastases occurrence. Hypercalcemia occurred and PRRT and Denosumab were started for disease progression with the onset of bone metastases. Despite disease stability after four cycles of PRRT the patient's performance status worsened until death. (III) A 49-year-old woman was hospitalized for psychic slowdown, confusional state, sensory dullness. A severe hypercalcemia, associated with a pancreatic G1 NEN was diagnosed and treated with haemodialysis, bisphosphonates injections and continuous infusion of calcitonin. 1,25-dihydroxyvitamin D was high, PTHrP was undetectable. After surgery serum calcium levels and 1,25-dihydroxyvitamin D were normalized. (IV) A 69-year-old man was hospitalized after the onset of shortness of breath and dyspnea, asthenia and weight loss. Computed Tomography (CT) and 68Ga DOTATOC Positron Emission Tomography (PET)-CT revealed a left pulmonary nodule. Hypercalcemia and markedly elevated PTHrP levels were detected. The histological examination revealed an atypical carcinoid. After surgery, calcium levels were normalized, PTHrP was significantly reduced with an improvement of general conditions. CONCLUSION In our series, paraneoplastic PTHrP-related hypercalcemia occurred in pancreatic NEN and in one bronchial carcinoid representing the third case in the literature. Our case associated with 1,25-dihydroxyvitamin D secretion represents the fourth case in the literature. PTHrP secretion should be considered in NENs' patients with hypercalcemia. Acute treatment should be focused on lowering calcium levels, and long-term control can be achieved by tumor cytoreduction inhibiting PTHrP release.
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FOLFIRINEC: a randomized phase II trial of mFOLFIRINOX vs platinum-etoposide for metastatic neuroendocrine carcinoma of gastroenteropancreatic or unknown origin.
Hadoux, J, Afchain, P, Walter, T, Tougeron, D, Hautefeuille, V, Monterymard, C, Lorgis, V, Thuillier, F, Baudin, E, Scoazec, JY, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2021;(7):824-829
Abstract
BACKGROUND Poorly differentiated neuroendocrine carcinomas (NEC) are rare diseases with a poor prognosis. Platinum-etoposide (PE) has been the recommended first-line treatment for decades. FOLFIRINEC (NCT04325425) is a national multicenter randomized phase II study which aims to challenge this standard regimen. METHODS The primary objective is to compare the median progression-free survival (PFS) under mFOLFIRINOX versus PE. The secondary objectives are to evaluate the objective response rates (ORR), median overall survival (OS), safety and quality of life. The associated real-time translational study will establish a molecular profile for each patient enrolled. MAIN INCLUSION CRITERIA ARE NEC of gastroenteropancreatic (GEP) or unknown origin, metastatic and RECIST 1.1 evaluable disease, tumor sample available and no contraindication to chemotherapy. Patients will be randomized 1:1 between PE every 21 days for 6-8 cycles and mFOLFIRINOX every 14 days for up to 12 cycles and stratified according to center, performance status, Ki67 and pathological subtype. This trial will randomize 218 patients (24 months of follow-up) to have 80% power to detect an improvement of the median PFS from 5 months under PE to 7.5 months under mFOLFIRINOX (HR of 0.67, α =5%, two-sided). An intermediate analysis is planned at 50% of events. Recruitment started on October 20, 2020.
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Dietary Acid Load and the Risk of Pancreatic Cancer: A Prospective Cohort Study.
Shi, LW, Wu, YL, Hu, JJ, Yang, PF, Sun, WP, Gao, J, Wang, K, Peng, Y, Wu, JJ, Zhong, GC
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021;(5):1009-1019
Abstract
BACKGROUND Modern Western diets are rich in acidogenic foods. Human and in vitro studies suggest a potential link between dietary acid load and cancer risk. However, no epidemiologic studies have investigated the association of dietary acid load with the risk of pancreatic cancer. Therefore, we conducted a prospective cohort study to fill this gap. METHODS A population-based cohort of 95,708 American adults was identified. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were used to assess dietary acid load of each subject, with greater values indicating greater dietary acid load. Cox regression was used to estimate risk estimates for pancreatic cancer incidence. Predefined subgroup analysis was used to identify the potential effect modifiers. RESULTS A total of 337 pancreatic cancer cases were observed during 848,534.0 person-years of follow-up. PRAL score was found to be positively associated with the risk of pancreatic cancer [fully adjusted HRquartile 4 vs. 1: 1.73; 95% confidence interval (95% CI), 1.21-2.48; P trend = 0.001] in a nonlinear dose-response pattern (P nonlinearity = 0.012). Subgroup analysis found that the positive association of PRAL score with the risk of pancreatic cancer was more pronounced in subjects aged <65 years than in those ≥65 years (P interaction = 0.018). Similar results were obtained for NEAP score. CONCLUSIONS Higher dietary acid load is associated with a higher risk of pancreatic cancer. Future studies should validate our findings in other populations and settings. IMPACTS This is the first epidemiologic study suggesting that reducing dietary acid load may be useful in primary prevention of pancreatic cancer.
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FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer: A subset analysis of data from a nationwide multicenter observational study in Japan.
Kobayashi, N, Omae, K, Horita, Y, Ueno, H, Mizuno, N, Uesugi, K, Sudo, K, Ozaka, M, Hayashi, H, Okano, N, et al
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2020;(7):1519-1525
Abstract
BACKGROUND Data on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study-a nationwide, multicenter, observational study-FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice. METHODS We performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings. RESULTS Of the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients' characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2-19.1) months and 6 cycles (range, 1-13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2-13.3), 4.1 (95% CI, 2.6-5.5) months, and 30%, respectively. CONCLUSION Our findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.
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Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study.
Bang, YJ, Li, CP, Lee, KH, Chiu, CF, Park, JO, Shan, YS, Kim, JS, Chen, JS, Shim, HJ, Rau, KM, et al
Cancer science. 2020;(2):513-527
Abstract
The global, randomized NAPOLI-1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine-based therapy. Median overall survival (OS) with nal-IRI+5-FU/LV was 6.1 vs 4.2 months with 5-FU/LV alone (unstratified hazard ratio [HR] = 0.67, P = .012). Herein, we report efficacy and safety results from a post-hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal-IRI+5-FU/LV (n = 34) had significantly longer median OS versus 5-FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P = .025). Patients had significantly increased median PFS with nal-IRI+5-FU/LV versus 5-FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P = .011), and increased ORR (8.8% vs 0; P = .114). nal-IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5-FU/LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P = .423) and median PFS was 2.8 versus 1.4 months (HR = 0.69, P = .155). Grade ≥3 neutropenia was reported more frequently with nal-IRI+5-FU/LV versus 5-FU/LV (54.5% vs 3.4%), and incidence of grade ≥3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal-IRI+5-FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine-based therapy, with a safety profile agreeing with previous findings. The nal-IRI+5-FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials.gov: NCT01494506).
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A Chinese Retrospective Multicenter Study of First-Line Chemotherapy for Advanced Pancreatic Cancer.
Cui, H, Guan, J, Deng, G, Yuan, J, Lou, C, Zhang, W, Zhou, A, Zhang, Y, Zhou, J, Dai, G
Medical science monitor : international medical journal of experimental and clinical research. 2020;:e927654
Abstract
BACKGROUND Pancreatic cancer (PC) is a common digestive system tumor. For patients with advanced pancreatic cancer (APC), chemotherapy is still the predominant treatment. However, no large-scale clinical studies have been done of it as first-line therapy for APC. The goal of the present study was to assess real-world outcomes with chemotherapy in that setting. MATERIAL AND METHODS We retrospectively analyzed data from 322 patients with APC who were treated with chemotherapy at 4 hospitals in different cities in China. The first-line regimens used were AS (nab-paclitaxel and S-1), AG (nab-paclitaxel and gemcitabine), and FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin). RESULTS Of the patients, 232 received AS, 79 received AG, and 11 received FOLFIRINOX. The median number of chemotherapy cycles was 5. The median overall survival (mOS) was 9 months and the median progression-free survival (mPFS) was 5 months. The AS, AG, and FOLFIRINOX regimens were associated with mOS rates of 9 months, 9 months, and 10 months, respectively. The mPFS rates for the AS, AG, and FOLFIRINOX regimens were 5, 4, and 5 months, respectively. The differences between the PFS rates for the regimens were statistically significant. The overall response rate (ORR) and overall disease control rate (DCR) for chemotherapy were 38% and 81.8%, respectively. The ORRs for the AS, AG, and FOLFIRINOX regimens were 46.9%, 18.7%, and 0%, respectively. The DCRs for the AS, AG and FOLFIRINOX regimens were 87.2%, 69.3%, and 63.6%, respectively. The differences between the ORRs and DCRs for the regimens were statistically significant. The incidences of grade 3/4 adverse events (AEs) associated with the AS, AG, and FOLFIRINOX regimens were 29.9%, 25%, and 36.4%, respectively. CONCLUSIONS The AS regimen was associated with a higher ORR and DCR than the other 2 regimens, with a lower rate of AEs.
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Treatment sequence in patients with neuroendocrine tumours: a nationwide multicentre, observational analysis of the Swiss neuroendocrine tumour registry.
Kollar, A, Bütikofer, L, Ochsenbein, A, Stettler, C, Trepp, R
Swiss medical weekly. 2020;:w20176
Abstract
BACKGROUND In recent years, several treatment modalities have proved to be effective in the treatment of neuroendocrine tumours (NETs). However, there is currently no consensus on the sequence in which these options are best used. METHODS In this observational study, we analysed the treatment modalities and sequences of all patients included in the Swiss NeuroEndocrine Tumour registry (SwissNET). SwissNET is a national registry, which has prospectively included patients with a NET from all regions of Switzerland since 2008. RESULTS The registry includes 1366 patients; 1063 had documented therapies after the main diagnosis and were included in the analysis. The median follow-up time was 1.86 years. The most common primary site was the small intestine (291 patients, 27%) followed by pancreas (254 patients, 24%), lung (172 patients, 16%) and appendix (163 patients, 15%). A total of 167 different therapy sequences were observed. In 708 (67%) patients, surgery was the only treatment. The sequence of surgery followed by chemotherapy was most frequently documented in poorly (G3) differentiated (24 patients, 60%) and pancreatic (15 patients, 34%) NETs. Tumours treated with surgery followed by biotherapy or followed by peptide receptor radionuclide therapy (PRRT) were predominantly well-differentiated G1 NETs of the small intestine. In patients who were treated with either PRRT or systemic therapy (chemotherapy or molecular therapy) or both, PRRT was used more frequently than systemic therapy in patients with a small intestinal NET (35 patients, 62% vs 30, 54%), whereas the opposite held true in pancreatic (44 patients, 59% vs 56, 70%) and lung NETs (6 patients, 14% vs 40, 97%). If both chemotherapy and molecular therapy were used, chemotherapy was applied prior to molecular therapy in 13 of 19 (68%) patients with a pancreatic NET. CONCLUSION Surgery represents the treatment of choice in most patients with a NET irrespective of tumour stage. In patients receiving additional treatment, an impressive variety of treatment sequences were documented. In small intestinal NETs, patients received PRRT more often than chemotherapy, whereas the opposite holds true for patients with pancreatic and lung NETs.