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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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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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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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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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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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The utility of nutritional supportive care with an eicosapentaenoic acid (EPA)-enriched nutrition agent during pre-operative chemoradiotherapy for pancreatic cancer: Prospective randomized control study.
Akita, H, Takahashi, H, Asukai, K, Tomokuni, A, Wada, H, Marukawa, S, Yamasaki, T, Yanagimoto, Y, Takahashi, Y, Sugimura, K, et al
Clinical nutrition ESPEN. 2019;:148-153
Abstract
BACKGROUND & AIMS Neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer (PC) is potentially associated with various toxicities, which can lead to impaired nutritional status. Eicosapentaenoic acid (EPA) can reduce proinflammatory cytokines and positively influence cancer cachexia syndrome. The aim of this study is to clarify the utility of EPA enriched nutrition support during NACRT for PC. METHODS We randomly assigned 62 patients with PC that received NACRT to either a nutrition intervention (NI) or a normal diet (ND). Patients in the NI group received 2 bottles/day (550 kcal/day) of an EPA-enriched nutrition supplement during NACRT. The primary endpoints were the before-to-after NACRT ratios (post/pre ratios) of skeletal muscle mass and psoas major muscle area (PMA). The secondary endpoints were the post/pre ratios of other nutritional parameters and treatment-related toxicities. RESULTS Only 14 patients (45.2%) in the NI group consumed more than 50% of the EPA-enriched supplement provided. The post/pre ratio of skeletal muscle mass in the NI group (0.99 ± 0.060) was not significantly different from that of the ND group (0.96 ± 0.079, p = 0.102). However, patients that consumed ≥50% of the EPA-enriched supplement (the good intake group) had significantly higher skeletal muscle mass ratios than patients in the ND group (p = 0.042). The PMA ratio was significantly higher in the NI group (0.96 ± 0.081) than in the ND group (0.89 ± 0.072, p = 0.001). The NI and ND groups were not significantly different in other nutritional parameters or in NACRT-related toxicity. CONCLUSIONS We found that EPA-enriched intake could potentially improve the nutritional status of patients with PC that received NACRT, but it was difficult for many patients to drink, due to its disagreeable taste. University Hospital Medical Information Network (http://www.umin.ac.jp), registration number UMIN000033589, https://upload.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000038300.
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The Impact of Preoperative Enteral Nutrition Enriched with Eicosapentaenoic Acid on Postoperative Hypercytokinemia after Pancreatoduodenectomy: The Results of a Double-Blinded Randomized Controlled Trial.
Ashida, R, Okamura, Y, Wakabayashi-Nakao, K, Mizuno, T, Aoki, S, Uesaka, K
Digestive surgery. 2019;(4):348-356
Abstract
AIMS: To investigate whether preoperative enteral diets -enriched in eicosapentaenoic acid (EPA) supplements could reduce the incidence of hypercytokinemia after pancreatoduodenectomy (PD) in a double-blinded randomized -controlled trial. METHODS Patients with resectable periampullary cancer were randomized into either the control group or the treatment group. Patients in the treatment group received oral supplementation (600 kcal/day) containing EPA for 7 days before surgery. Patients in the control group received isocaloric isonitrogenous standard nutrition (600 kcal/day) without EPA for 7 days before surgery. The primary endpoint was postoperative serum concentrations of interleukin-6 (IL-6). The secondary endpoints were the postoperative nutritional status and the incidence of postoperative infectious complications. RESULTS Twenty-four patients were enrolled in the present study. After exclusion, 20 patients (control group, n = 9; treatment group, n = 11) were analyzed. There were no significant differences in the curves for the serum concentration of IL-6 (p = 0.68) or the incidence of infectious complications between the 2 groups (control group: 78%, treatment group: 55%, p = 0.37). CONCLUSIONS The results of a double-blinded randomized controlled trial indicated that preoperative immunonutrition had no marked impact on the rates of postoperative hypercytokinemia or infectious complications after PD.
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Efficacy of prolonged elemental diet therapy after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: A pilot prospective randomized trial (UMIN000004108).
Mori, R, Matsuyama, R, Taniguchi, K, Goto, K, Miyake, K, Hiratani, S, Homma, Y, Ohta, Y, Kumamoto, T, Morioka, D, et al
Clinical nutrition ESPEN. 2019;:116-124
Abstract
BACKGROUNDS AND AIMS This randomized clinical trial examined efficacy of prolonged elemental diet (ED) therapy after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC), which often causes postoperative malnutrition leading to worsened short- and long-term outcomes. METHODS Thirty-nine patients with PDAC receiving PD was randomly assigned to prolonged ED group (PEDG) and control group (CG). Fat-free ED (Elental®, EA Pharma CO., Ltd., Tokyo, Japan) via tube jejunostomy was initiated on postoperative day 1 and increased to maintain with 600 kcal/day in addition to oral intake. ED was discontinued if sufficient oral intake was achieved in CG but continued during 3 postoperative months in PEDG. Primary outcome was complication necessitating readmission. Secondary outcomes were nutritional parameters, relative dose intensity (RDI) in cases of adjuvant chemotherapy, and survival outcomes. RESULTS Twenty patients were assigned to CG and 19 to PEDG. Cumulative post-discharge readmission rate was significantly lower in PEDG than in CG (PEDG vs CG; 12.6% vs 43.7% at 12-post-discharge-month; p = 0.018). Total calorie and ED-derived protein intakes were significantly larger in PEDG than in CG up to 3-postoperative-month but thereafter similar among groups. Lymphocyte counts were significantly increased and neutrophil-to-lymphocyte-ratio (NLR) was significantly reduced in PEDG than in CG at 2-, 3-, and 6-postoperative-month. However, other outcome measures did not differ among groups. CONCLUSION This trial failed to show survival benefit of prolonged ED therapy but demonstrated its favorable effect on increased lymphocyte counts, reduced NLR, and prevention of complications necessitating readmission, those which may lead to survival benefit with some modifications.
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Prehabilitation in patients undergoing pancreaticoduodenectomy: a randomized controlled trial.
Ausania, F, Senra, P, Meléndez, R, Caballeiro, R, Ouviña, R, Casal-Núñez, E
Revista espanola de enfermedades digestivas. 2019;(8):603-608
Abstract
INTRODUCTION prehabilitation has been proposed as an effective tool to prevent postoperative complications in patients undergoing major abdominal surgery. However, no studies have demonstrated its effectiveness in pancreatic surgical patients. The aim of this study was to assess the impact of prehabilitation on postoperative complications in patients undergoing a pancreaticoduodenectomy (PD). METHODS this was a randomized controlled trial. Eligible candidates who accepted to participate were randomized to the control (standard care) or intervention (standard care + prehabilitation) group. All patients with pancreatic or periampullary tumors who were candidates for pancreaticoduodenectomy were included. Patients who received neoadjuvant treatment were excluded. Prehabilitation covered three actions: a) nutritional support; b) control of diabetes and exocrine pancreatic insufficiency; and c) physical and respiratory training. The main study outcome was the proportion of patients who suffered postoperative complications. Secondary outcomes included the occurrence of specific complications (pancreatic leak and delayed gastric emptying) and hospital stay. RESULTS forty patients were included in the analysis. Twenty-two patients were randomized to the control arm and 18, to the intervention group. No statistically significant differences were observed in terms of overall and major complications between the prehabilitation and standard care groups. Pancreatic leak was not statistically different between the groups (11% vs 27%, p = 0.204). However, DGE was significantly lower in the prehabilitation group (5.6% vs 40.9% in the standard care group, p = 0.01). CONCLUSION prehabilitation did not reduce postoperative complications following pancreaticoduodenectomy. However, a reduction in DGE was observed. Further studies are needed to validate the role and the timing of prehabilitation in high-risk patients.
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Survival with nal-IRI (liposomal irinotecan) plus 5-fluorouracil and leucovorin versus 5-fluorouracil and leucovorin in per-protocol and non-per-protocol populations of NAPOLI-1: Expanded analysis of a global phase 3 trial.
Chen, LT, Siveke, JT, Wang-Gillam, A, Li, CP, Bodoky, G, Dean, AP, Shan, YS, Jameson, GS, Macarulla, T, Lee, KH, et al
European journal of cancer (Oxford, England : 1990). 2018;:71-78
Abstract
BACKGROUND In the phase 3 randomised NAPOLI-1 clinical study, a 45% increase in median overall survival (OS) was shown with liposomal irinotecan, 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) versus 5-FU/LV in patients with metastatic pancreatic cancer progressing after gemcitabine-based therapy. Here, we report data from a pre-specified, expanded analysis of outcomes in the per-protocol (PP) population. MATERIALS AND METHODS The PP population comprised patients receiving ≥80% of planned treatment during the first 6 weeks, with no major protocol violations. A post-hoc analysis of the non-PP population was also performed. RESULTS For PP patients, median OS was 8.9 (95% confidence interval: 6.4-10.5) months with nal-IRI+5-FU/LV (n = 66) vs 5.1 (4.0-7.2) months with 5-FU/LV (n = 71; unstratified hazard ratio [HR] 0.57, p = 0.011). For non-PP patients, it was 4.4 (3.3-5.3) months with nal-IRI+5-FU/LV (n = 51) vs 2.8 (1.7-3.2) months with 5-FU/LV (n = 48; unstratified HR 0.64, p = 0.0648). CONCLUSION A statistically significant survival advantage was observed with nal-IRI+5-FU/LV vs 5-FU/LV in the PP patient population.