术前肌少症与恶性肿瘤胰十二指肠切除术后并发症及生存的相关性

摘要

胰十二指肠切除术（PD）是治疗胰头及壶腹周围恶性肿瘤最常规的外科手段，虽然目前外科技术日趋成熟，但是术后并发症仍然居高不下。肌肉减少症（简称肌少症）是一种全身性骨骼肌质量和功能下降的综合性疾病，在PD患者中患病率较高（30%~60%）。肌少症已成为评估外科风险的重要生物学指标。目前发现术前肌少症不仅与Clavien-Dindo III级及以上严重并发症的发生风险相关，还是导致患者总生存期（OS）缩短的危险因素，可能是由于肌细胞因子分泌减少导致免疫功能下降和慢性炎症反应引起的恶病质循环。目前肌少症对术后并发症影响的结论尚存争议，针对性干预措施（营养支持和结构化运动）的临床获益还需验证。系统综述肌少症对因恶性肿瘤行PD患者短期并发症及长期生存影响的研究现状，能够为临床术前风险分层及个体化预康复策略的制定提供参考。

关键词

肌肉减少症 / 胰十二指肠切除术 / 并发症 / 生存期 / 相关性 / 恶性肿瘤

参考文献

[1] De Rooij T , Lu MZ , Steen MW , et al. Minimally invasive versus open pancreatoduodenectomy: systematic review and meta—analysis of comparative cohort and registry studies[J]. Ann Surg, 2016, 264(2): 257-267. DOI: 10.1097/SLA.0000000000001660.

[2] Carroll JE , Smith JK , Simons JP , et al. Redefining mortality after pancreatic cancer resection[J]. J Gastrointest Surg, 2010, 14(11): 1701-1708. DOI: 10.1007/s11605—010—1326—4.

[3] Yoshioka R , Yasunaga H , Hasegawa K , et al. Impact of hospital volume on hospital mortality, length of stay and total costs after pancreaticoduodenectomy[J]. Br J Surg, 2014, 101(5): 523-529. DOI: 10.1002/bjs.9420.

[4] Jiang J , Upfill—Brown A , Dann AM , et al. Association of hospital length of stay and complications with readmission after open pancreaticoduodenectomy[J]. JAMA Surg, 2019, 154(1): 88. DOI: 10.1001/jamasurg.2018.3213.

[5] Yuan F , Essaji Y , Belley—Cote EP , et al. Postoperative complications in elderly patients following pancreaticoduodenectomy lead to increased postoperative mortality and costs: a retrospective cohort study[J]. Int J Surg, 2018, 60: 204-209. DOI: 10.1016/j.ijsu.2018.11.016.

[6] Lenk K , Schuler G , Adams V . Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training[J]. J Cachexia Sarcopenia Muscle, 2010, 1(1): 9-21. DOI: 10.1007/s13539—010—0007—1.

[7] Becchetti C , Dajti E , Su GL , et al. The impact of sarcopenia and frailty on decompensation in compensated cirrhosis: a systematic review[J/OL]. Hepatol Commun, 2025, 9(11)[ 2025—12—22]. https://journals.lww.com/10.1097/HC9.0000000000000811. DOI: 10.1097/HC9.0000000000000811.

[8] Yang L , Wu H , Chen J , et al. Muscle oxygen saturation stratification by photoacoustic imaging in diabetic sarcopenia: Association with disease status[J]. Photoacoustics, 2025, 46: 100771. DOI: 10.1016/j.pacs.2025.100771.

[9] Xu Y , Xu JW , Wu Y , et al. Prevalence and prognosis of sarcopenia in acute COVID—19 and long COVID: A systematic review and meta—analysis[J]. Ann Med, 2025, 57(1): 2519678. DOI: 10.1080/07853890.2025.2519678.

[10] Shachar SS , Williams GR , Muss HB , et al. Prognostic value of sarcopenia in adults with solid tumours: A meta—analysis and systematic review[J]. Eur J Cancer, 2016, 57: 58-67. DOI: 10.1016/j.ejca.2015.12.030.

[11] Wu Y , Xu X , Jin X . Regarding: 'prognostic value of sarcopenia in patients with nasopharyngeal carcinoma: a meta—analysis'[J]. Ann Med, 2025, 57(1): 2547095. DOI: 10.1080/07853890.2025.2547095.

[12] Bucheeri MAGA , Khalaf K , Li H , et al. Prevalence and impact of sarcopenia in chronic pancreatitis: A systematic review and meta—analysis[J]. Pancreatology, 2025, 25(7): 1062-1070. DOI: 10.1016/j.pan.2025.09.026.

[13] Stretch C , Aubin JM , Mickiewicz B , et al. Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas[J]. PLoS One, 2018, 13(5): e0196235. DOI: 10.1371/journal.pone.0196235.

[14] Farquhar R , Matthews S , Baxter N , et al. Sarcopenia and sarcopenic obesity on body composition analysis is a significant predictor of mortality in severe acute pancreatitis: a longitudinal observational study[J]. World J Surg, 2023, 47(11): 2825-2833. DOI: 10.1007/s00268—023—07122—1.

[15] Mir O , Coriat R , Blanchet B , et al. Sarcopenia predicts early dose—limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma[J]. PLoS One, 2012, 7(5): e37563. DOI: 10.1371/journal.pone.0037563.

[16] Choi Y , Oh DY , Kim TY , et al. Skeletal muscle depletion predicts the prognosis of patients with advanced pancreatic cancer undergoing palliative chemotherapy, independent of body mass index[J]. PLoS One, 2015, 10(10): e0139749. DOI: 10.1371/journal.pone.0139749.

[17] 冯福明， 韦京科， 黄鑫 . 结肠癌根治术后肌少症的影响因素分析[J]. 中国现代普通外科进展， 2025， 28（6）： 494-497. DOI: 10.3969/j.issn.1009—9905.2025.06.013.

[18] Shen XD , Wang X , Zheng ZJ , et al. The differential effects of sarcopenia and cachexia on overall survival for pancreatic ductal adenocarcinoma patients following pancreatectomy: A retrospective study based on a large population[J]. Cancer Med, 2023, 12(9): 10438-10448. DOI: 10.1002/cam4.5779.

[19] Choi MH , Yoon SB , Lee K , et al. Preoperative sarcopenia and postoperative accelerated muscle loss negatively impact survival after resection of pancreatic cancer[J]. J Cachexia Sarcopenia Muscle, 2018, 9(2): 326-334. DOI: 10.1002/jcsm.12274.

[20] Liang H , Peng H , Chen L . Prognostic value of sarcopenia and systemic inflammation markers in patients undergoing definitive radiotherapy for esophageal cancer[J]. Cancer Manag Res, 2021, 13: 181-192. DOI: 10.2147/CMAR.S288522.

[21] Lee J , Liu SH , Dai KY , et al. Sarcopenia and systemic inflammation synergistically impact survival in oral cavity cancer[J]. Laryngoscope, 2021, 131(5): E1530-E1538. DOI: 10.1002/lary.29221.

[22] Tankel J , Dagan A , Vainberg E , et al. Sarcopenia is associated with a greater incidence of delayed gastric emptying following pancreaticoduodenectomy[J]. Clin Nutr ESPEN, 2018, 27: 105-109. DOI: 10.1016/j.clnesp.2018.05.011.

[23] Harris T , Woteki C , Briefel RR , et al. NHANES Ⅲ for older persons: nutrition content and methodological considerations[J]. Am J Clin Nutr, 1989, 50(5): 1145-1149. DOI: 10.1093/ajcn/50.5.1145.

[24] Rosenberg IH , Roubenoff R . Stalking sarcopenia[J]. Ann Intern Med, 1995, 123(9): 727-728. DOI: 10.7326/0003—4819—123—9—199511010—00014.

[25] Chen LK , Woo J , Assantachai P , et al. Asian working group for sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment[J]. J Am Med Dir Assoc, 2020, 21(3): 300-307.e2. DOI: 10.1016/j.jamda.2019.12.012.

[26] Cruz—Jentoft AJ , Baeyens JP , Bauer JM , et al. Sarcopenia: european consensus on definition and diagnosis[J]. Age Ageing, 2010, 39(4): 412-423. DOI: 10.1093/ageing/afq034.

[27] Chen LK , Liu LK , Woo J , et al. Sarcopenia in Asia: consensus report of the asian working group for sarcopenia[J]. J Am Med Dir Assoc, 2014, 15(2): 95-101. DOI: 10.1016/j.jamda.2013.11.025.

[28] Cruz—Jentoft AJ , Bahat G , Bauer J , et al. Sarcopenia: revised european consensus on definition and diagnosis[J]. Age Ageing, 2019, 48(4): 601— 601. DOI: 10.1093/ageing/afz046.

[29] Liguori I , Russo G , Aran L , et al. Sarcopenia: assessment of disease burden and strategies to improve outcomes[J]. Clin Interv Aging, 2018, 13: 913-927. DOI: 10.2147/CIA.S149232.

[30] Porter MM , Vandervoort AA , Lexell J . Aging of human muscle: structure, function and adaptability[J]. Scand J Med Sci Sports, 1995, 5(3): 129-142. DOI: 10.1111/j.1600—0838.1995.tb00026.x.

[31] Balcer K , Garnier J , Richa Y , et al. Impact on survival of sarcopenia, systemic inflammatory response and anthropometric factors after pancreatectomy for resectable pancreatic adenocarcinoma[J]. World J Surg Oncol, 2024, 22(1): 232. DOI: 10.1186/s12957—024—03510—6.

[32] Sendil AM , Gündogdu E . Comparative analysis of the sarcopenia and HALP score on postoperative outcomes in pancreatic cancer patients after pancreatoduodenectomy[J]. Pancreatology, 2024, 24(3): 504. DOI: 10.1016/j.pan.2024.03.009.

[33] Jang M , Park HW , Huh J , et al. Predictive value of sarcopenia and visceral obesity for postoperative pancreatic fistula after pancreaticoduodenectomy analyzed on clinically acquired CT and MRI[J]. Eur Radiol, 2019, 29(5): 2417-2425. DOI: 10.1007/s00330—018—5790—7.

[34] Prado CM , Lieffers JR , McCargar LJ , et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population—based study[J]. Lancet Oncol, 2008, 9(7): 629-635. DOI: 10.1016/S1470—2045(08)70153—0.

[35] Xu Z , Chen J , Mou Y , et al. Effects of nutritional status on short—term prognosis after minimally invasive pancreaticoduodenectomy[J]. Sci Rep, 2024, 14(1): 29549. DOI: 10.1038/s41598—024—81016—7.

[36] Martin L , Birdsell L , MacDonald N , et al. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index[J]. J Clin Oncol, 2013, 31(12): 1539-1547. DOI: 10.1200/JCO.2012.45.2722.

[37] Qu G , Zhou C , Zhang Y , et al. Influence of sarcopenia on postoperative complications and long—term survival in pancreatic cancer patients undergone pancreaticoduodenectomy[J]. Front Nutr, 2024, 11: 1434630. DOI: 10.3389/fnut.2024.1434630.

[38] Nishikawa H , Shiraki M , Hiramatsu A , et al. Japan society of hepatology guidelines for sarcopenia in liver disease (1st edition): recommendation from the working group for creation of sarcopenia assessment criteria[J]. Hepatol Res, 2016, 46(10): 951-963. DOI: 10.1111/hepr.12774.

[39] Fujiwara N , Nakagawa H , Kudo Y , et al. Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma[J]. J Hepatol, 2015, 63(1): 131-140. DOI: 10.1016/j.jhep.2015.02.031.

[40] Guarneri G , Pecorelli N , Bettinelli A , et al. Prognostic value of preoperative CT scan derived body composition measures in resected pancreatic cancer[J]. Eur J Surg Oncol, 2024, 50(5): 106848. DOI: 10.1016/j.ejso.2023.02.005.

[41] La Vaccara V , Cascone C , Coppola A , et al. Role of preoperative sarcopenia in predicting postoperative complications and survival after pancreatoduodenectomy for pancreatic cancer[J]. Ann Ital Chir, 2023, 94: 45-51.

[42] Mourtzakis M , Prado CM M, Lieffers JR , et al. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care[J]. Appl Physiol Nutr Metab, 2008, 33(5): 997-1006. DOI: 10.1139/H08—075.

[43] Nishida Y , Kato Y , Kudo M , et al. Preoperative sarcopenia strongly influences the risk of postoperative pancreatic fistula formation after pancreaticoduodenectomy[J]. J Gastrointest Surg, 2016, 20(9): 1586-1594. DOI: 10.1007/s11605—016—3146—7.

[44] Allen PJ , Gönen M , Brennan MF , et al. Pasireotide for postoperative pancreatic fistula[J]. N Engl J Med, 2014, 370(21): 2014-2022. DOI: 10.1056/NEJMoa1313688.

[45] Aoki Y , Furukawa K , Suzuki D , et al. Influence of sarcopenia as defined by EWGSOP2 on complications after pancreaticoduodenectomy and on the prognosis of pancreatic head cancer: A prospective cohort study[J]. Nutrition, 2022, 99—100: 111660. DOI: 10.1016/j.nut.2022.111660.

[46] Lutz CT , Quinn LS . Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism[J]. Aging, 2012, 4(8): 535-546. DOI: 10.18632/aging.100482.

[47] Arends J , Bachmann P , Baracos V , et al. ESPEN guidelines on nutrition in cancer patients[J]. Clin Nutr, 2017, 36(1): 11-48. DOI: 10.1016/j.clnu.2016.07.015.

[48] Tazeoglu D , Benli S , Colak T , et al. Comparative analysis of the sarcopenia and HALP score on postoperative outcomes in pancreatic cancer patients after pancreatoduodenectomy[J]. Pancreatology, 2023, 23(5): 530-536. DOI: 10.1016/j.pan.2023.05.006.

[49] Sui K , Okabayshi T , Iwata J , et al. Correlation between the skeletal muscle index and surgical outcomes of pancreaticoduodenectomy[J]. Surg Today, 2018, 48(5): 545-551. DOI: 10.1007/s00595—017—1622—7.

[50] Peng YC , Wu CH , Tien YW , et al. Preoperative sarcopenia is associated with poor overall survival in pancreatic cancer patients following pancreaticoduodenectomy[J]. Eur Radiol, 2021, 31(4): 2472-2481. DOI: 10.1007/s00330—020—07294—7.

[51] Utsumi M , Inagaki M , Kitada K , et al. Combination of sarcopenia and systemic inflammation—based markers for predicting the prognosis of patients undergoing pancreaticoduodenectomy for pancreatic cancer[J]. PLoS One, 2024, 19(6): e0305844. DOI: 10.1371/journal.pone.0305844.

[52] Aversa Z , Costelli P , Muscaritoli M . Cancer—induced muscle wasting: latest findings in prevention and treatment[J]. Ther Adv Med Oncol, 2017, 9(5): 369-382. DOI: 10.1177/1758834017698643.

[53] Takagi K , Inoue Y , Oba A , et al. Impact of sarcopenia on S1 adjuvant chemotherapy and prognosis in pancreatic cancer patients[J]. Biosci Trends, 2023, 17(4): 310-317. DOI: 10.5582/bst.2023.01209.

[54] Lutz CT , Quinn LS . Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism[J]. Aging, 2012, 4(8): 535-546. DOI: 10.18632/aging.100482.

[55] Pedersen BK . Edward F. Adolph distinguished lecture: muscle as an endocrine organ: IL—6 and other myokines[J]. J Appl Physiol, 2009, 107(4): 1006-1014. DOI: 10.1152/japplphysiol.00734.2009.

[56] Peng H , Tan X . The prognostic significance of sarcopenia and the neutrophil—to—lymphocyte ratio in elderly patients with esophageal squamous cell carcinoma[J]. Cancer Manag Res, 2021, 13: 3209-3218. DOI: 10.2147/CMAR.S302274.

[57] Quinn LS . Interleukin—15: A muscle—derived cytokine regulating fat—to—lean body composition1, 2[J]. J Anim Sci, 2008, 86(suppl_14): E75-E83. DOI: 10.2527/jas.2007—0458.

[58] Kim JW , Kim R , Choi H , et al. Understanding of sarcopenia: from definition to therapeutic strategies[J]. Arch Pharm Res, 2021, 44(9—10): 876-889. DOI: 10.1007/s12272—021—01349—z.

[59] Jeyaraman M , Jeyaraman N , Nallakumarasamy A , et al. Sarcopenia in aging: pathogenesis, diagnosis, and emerging therapeutic frontiers[J/OL]. Mol Imaging Biol, https://link.springer.com/10.1007/s11307—025—02071—8. 2025[ 2025—12—22]. DOI: 10.1007/s11307—025—02071—8.

[60] Papadopoulou SK , Papadimitriou K , Voulgaridou G , et al. Exercise and nutrition impact on osteoporosis and sarcopenia—the incidence of osteosarcopenia: a narrative review[J]. Nutrients, 2021, 13(12): 4499. DOI: 10.3390/nu13124499.

[61] Liu X , Chen X , Cui J . Therapeutic advances in sarcopenia management: from traditional interventions to personalized medicine[J]. Clin Nutr, 2025, 51: 187-197. DOI: 10.1016/j.clnu.2025.06.007.

[62] Cognetti DJ , Sheean AJ , Owens JG . Blood flow restriction therapy and its use for rehabilitation and return to sport: physiology, application, and guidelines for implementation[J]. Arthrosc Sports Med Rehabil, 2022, 4(1): e71-e76. DOI: 10.1016/j.asmr.2021.09.025.

[63] Ackermann PW , Juthberg R , Flodin J . Unlocking the potential of neuromuscular electrical stimulation: achieving physical activity benefits for all abilities[J]. Front Sports Act Living, 2024, 6: 1507402. DOI: 10.3389/fspor.2024.1507402.

[64] Rondanelli M , Klersy C , Terracol G , et al. Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat—free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly[J]. Am J Clin Nutr, 2016, 103(3): 830-840. DOI: 10.3945/ajcn.115.113357.

[65] Kawahara T , Suzuki G , Mizuno S , et al. Active vitamin D treatment in the prevention of sarcopenia in adults with prediabetes (DPVD ancillary study): A randomised controlled trial[J]. Lancet Healthy Longev, 2024, 5(4): e255-e263. DOI: 10.1016/S2666—7568(24)00009—6.

[66] Morvan F , Rondeau JM , Zou C , et al. Blockade of activin type II receptors with a dual anti—ActRⅡA/ⅡB antibody is critical to promote maximal skeletal muscle hypertrophy[J]. Proc Natl Acad Sci USA, 2017, 114(47): 12448-12453. DOI: 10.1073/pnas.1707925114.

[67] Neil D , Clark RV , Magee M , et al. GSK2881078, a SARM, produces dose—dependent increases in lean mass in healthy older men and women[J]. J Clin Endocrinol Metab, 2018, 103(9): 3215-3224. DOI: 10.1210/jc.2017—02644.

[68] Drummond MJ , McCarthy JJ , Sinha M , et al. Aging and microRNA expression in human skeletal muscle: a microarray and bioinformatics analysis[J]. Physiol Genomics, 2011, 43(10): 595-603. DOI: 10.1152/physiolgenomics.00148.2010.

[69] Dalton JT , Barnette KG , Bohl CE , et al. The selective androgen receptor modulator GTx—024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double—blind, placebo—controlled phase II trial[J]. J Cachexia Sarcopenia Muscle, 2011, 2(3): 153-161. DOI: 10.1007/s13539—011—0034—6.

[70] Popescu GA , Minca DG , Jafal NM , et al. Multimodal prehabilitation in major abdominal surgery: rationale, modalities, results and limitations[J]. Medicina, 2025, 61(5): 908. DOI: 10.3390/medicina61050908.

[71] Yamamoto K , Nagatsuma Y , Fukuda Y , et al. Effectiveness of a preoperative exercise and nutritional support program for elderly sarcopenic patients with gastric cancer[J]. Gastric Cancer, 2017, 20(5): 913-918. DOI: 10.1007/s10120—016—0683—4.

[72] Du L , Liu X , Zhu Q , et al. Sarcopenia as a prognostic factor and multimodal interventions in breast cancer[J]. Int J Gen Med, 2024, 17: 6605-6616. DOI: 10.2147/IJGM.S497897.

基金资助

重庆市教委科学技术研究项目(KJQN202300105)

秀山县医学科研项目(2022XSKY04)