Gianotti Luca, Paiella Salvatore, Capretti Giovanni, Pecorelli Nicolò, Frigerio Isabella, Sandini Marta, Fogliati Alessandro, Vico Eleonora, Braga Marco, Cotsoglou Christian, Pedalino Alfonso, Malleo Giuseppe, Ricchitelli Simone, Caspani Sabrina, Guarneri Giovanni, Vallorani Alessia, Giardino Alessandro, Pasqualoni Elettra, Salvia Roberto, Zerbi Alessandro, Falconi Massimo, Butturini Giovanni, Bernasconi Davide Paolo
School of Medicine and Surgery, Milano-Bicocca University, Pancreas Surgery Unit, IRCCS San Gerardo, Monza, Italy.
University of Verona, Italy.
EClinicalMedicine. 2025 Aug 21;87:103455. doi: 10.1016/j.eclinm.2025.103455. eCollection 2025 Sep.
The role of supplemental parenteral nutrition (SPN) following pancreatoduodenectomy (PD) in the context of an enhanced recovery program is unexplored. This study aimed to determine whether SPN is superior to early oral feeding alone in reducing postoperative complications.
This pragmatic, multicenter, randomized controlled, trial, across five centers in Italy, enrolled patients aged 18-89 years undergoing open PD for cancer. We excluded patients with an American Society of Anaesthesiology physical status >3 and a preoperative body weight loss of ≥15%. Patients were randomly assigned (1:1) postoperatively to either SPN from day 1 to 5 or no-SPN. All patients were free to begin oral feeding after the operation as desired in the context of a full enhanced recovery after surgery (ERAS) program. The primary outcome was morbidity burden, measured using the comprehensive complication index (CCI). Secondary outcomes included the overall rate of morbidity. Outcomes were assessed up to 90 days postoperatively. Overall, 120 patients per group were required to achieve 80% power and detect at least 30% reduction in the CCI in the SPN group, which was expected to be 23 (median) (interquartile range 21-31). The expected complication rate was 60%, and the type I error rate was set at 5%. Registration at ClinicalTrials.gov (#NCT04438447).
From June 1, 2022, to December 20, 2023, 405 patients were screened for eligibility and 254 patients were randomly allocated to control (no-SPN; n = 129) or treatment (SPN; n = 125) group. All patients were included in the primary and secondary outcome analysis according to the intent-to-treat principle. The median CCI was 20.9 in both arms (median difference 0 [95% CI: -1.07 to 1.7]). The proportion of patients with at least one complication (CCI >0) was similar in both groups [(29.6% vs 29.2%; risk difference 0.4 (95% CI -11.1 to 7.0)]. The overall 90-day morbidity was 67.4% and 63.2% in the no-SPN arm and SPN arm groups, respectively [risk difference -4.2 (95% CI -16.7 to 8.2)]. In high nutritional risk patients (nutritional risk score ≥3), SPN was not protective against the primary outcome when compared with low-risk patients [OR 1.16 (95% CI 0.71-1.91)].
In an ERAS program emphasizing early postoperative oral feeding, SPN does not affect outcome measures, even in patients at high nutritional risk. However, these results do not apply to severely malnourished patients or with critical comorbidities.
The Italian Society for Artificial Nutrition and Metabolism (SINPE) and Baxter Italia S.p.A (Rome, Italy).
在强化康复计划背景下，胰十二指肠切除术（PD）后补充肠外营养（SPN）的作用尚未得到探索。本研究旨在确定SPN在降低术后并发症方面是否优于单纯早期口服喂养。
这项务实的、多中心、随机对照试验在意大利的五个中心进行，纳入年龄在18 - 89岁、因癌症接受开放性PD手术的患者。我们排除了美国麻醉医师协会身体状况评分>3以及术前体重减轻≥15%的患者。患者术后被随机分配（1:1），从第1天到第5天接受SPN或不接受SPN。所有患者在手术后可根据全面的术后加速康复（ERAS）计划的要求自由开始口服喂养。主要结局是发病负担，采用综合并发症指数（CCI）进行测量。次要结局包括总体发病率。结局评估至术后90天。总体而言，每组需要120名患者才能达到80%的检验效能，并检测出SPN组的CCI至少降低30%，预计该组CCI中位数为23（四分位间距21 - 31）。预期并发症发生率为60%，I型错误率设定为5%。在ClinicalTrials.gov注册（#NCT04438447）。
从2022年6月1日至2023年12月20日，405名患者接受资格筛查，254名患者被随机分配至对照组（不接受SPN；n = 129）或治疗组（接受SPN；n = 125）。所有患者均根据意向性分析原则纳入主要和次要结局分析。两组的CCI中位数均为20.9（中位数差值为0 [95% CI：-1.07至1.7]）。两组中至少发生一种并发症（CCI>0）的患者比例相似[（29.6%对29.2%；风险差值0.4（95% CI -11.1至7.0）]。不接受SPN组和接受SPN组的90天总体发病率分别为67.4%和63.2%[风险差值-4.2（95% CI -16.7至8.2）]。在高营养风险患者（营养风险评分≥3）中，与低风险患者相比，SPN对主要结局无保护作用[OR 1.16（95% CI 0.71 - 1.91）]。
在强调术后早期口服喂养的ERAS计划中，SPN不影响结局指标，即使在高营养风险患者中也是如此。然而，这些结果不适用于严重营养不良或伴有严重合并症的患者。
意大利人工营养与代谢学会（SINPE）和百特意大利股份公司（意大利罗马）。
