Adjuvant role of traditional Chinese medicine in postoperative gastric cancer

Table 1 Clinical studies of traditional Chinese medicine for the treatment of postoperative gastric cancer

TCM	Compounds/constituents	Intervention	Intervention time	Postoperative condition	Study design	Outcome	Ref.
Sijunzi decoction	Radix Codonopsis (Dangshen), Poria cocos (Fuling), Rhizoma Atractylodis Macrocephalae (Baizhu), and Radix Glycyrrhizae (Gancao)	Sijunzi decoction + enteral nutrition vs enteral nutrition alone	8-10 days after operation	POCs after gastrectomy, Postoperative nutritional therapy	10 RCTs (688 participants), meta	Enhancing immune function, reducing the incidence of postoperative complications, and improving body nutrition status	[9]
Jianpi Yangzheng decoction	15 g Dangshen, 10 g Baizhu, 10 g Fuling, 15 g Shengyiren, 10 g Danggui, 15 g Shanyao, 10 g Muxiang, 10 g Baishao, 6 g Chenpi, 10 g Baqia, 15 g Shijianchuan and 3 g Zhigancao	TCM nursing intervention group (n = 520) vs the routine nursing intervention group (n = 512)	Every day after gastrectomy for at least 6 months	POCs after gastrectomy	Prospective, randomized controlled study	Improving POCs, mental status, long-term survival and reduces the recurrence	[25]
Yiqi Huayu Jiedu decoction	Astragalus membranaceus, 15 g; Codonopsis pilosula, 15 g; Atractylodes macrocephala, 10 g; Angelica, 10 g; Radices paeoniae alba, 10 g; Pericarpium citri reticulatae, 6 g; Pinellia, 10 g; Rhizoma sparganii, 10 g; Curcuma zedoary, 10 g; Chinese sage herb, 30 g; Hedyotis diffusa, 30 g; and Radix glycyrrhizae preparata, 5 g	Chemotherapy alone (n = 238) vs chemotherapy combined with Yiqi Huayu Jiedu decoction (n = 251)	More than 6 months	Stage II or III GC after radical gastrectomy	Multicenter, prospective, cohort study	Improve DFS rate in patients with GC stage III after radical gastrectomy and reduce the risk of recurrence and metastasis and improve the quality of life in patients with stage II or III GC after radical gastrectomy	[21]
Weifuchun	Radix Ginseng Rubra (Red Ginseng), Rabdosia amethystoides H. Hara (Xiangchacai), and fried Fructus Aurantii (Zhike)	Standard chemotherapy supplemented with Weifuchun tablets (n = 32) vs chemotherapy alone (n = 31)	6 months	Stages II and III GC and having undergonecurative resection within 8 weeks	Randomized, controlled, single-blind study	Reduce the 2-year recurrence and metastasis rates	[26]
TCM therapy	TCM therapies such as TCM decoction, moxibustion therapy, auricular-plaster therapy, hot ironing therapy, personalized food therapy, etc.	N/A	N/A	After the GC surgery	Meta-analysis (32 RCTs)	Reduce the risks of postoperative Wound infections and help shorten the time of wound healing; help patients rebuild a normal immune system and nutritional state	[38]
TCM therapy	The most common single herb prescriptions are Hwang-Chyi (Radix Hedysari; 11.8%), Dan-Shen (Radix Salviae Miltiorrhizae; 9.8%), Yan-Hu-Suo (Rhizoma Corydalis; 9.4%), Bai-Hua-She-She-Cao (Herba Hedyotidis Diffusae; 9.2%), and Hou-Pu (Cortex Magnoliae; 9.0%). The most common herbal formula prescriptions are Xiang-Sha-Liu-Jun-Zi-Tang (15.5%), Ping-Wei-San (12.6%), Ban-Xia-Xie-Xin-Tang (11.8%), Bu-Zhong-Yi-Qi-Tang (10.3%), and Shen-Lin-Bai-Zhu-San (10.2%)	Short-term TCM users (TCM use 30-179 days) (n = 1178) vs long-term TCM users (TCM use ≥ 180 days) (n = 523) vs nonusers (n = 5103)	N/A	Patients with GC following surgery and adjuvant chemotherapy	Nationwide matched cohort study	Short-term and long-term TCM users were independently associated with a decreased risk of death with HRs of 0.59 (95%CI: 0.55-0.65) in TCM users and 0.41 (95%CI: 0.36-0.47) in TCM nonusers	[100]
Zhipu Liujunzi decoction	Ginseng, solomonseal rhizome, figwort root, Ganoderma sinense, glabrous greenbrier rhizome, appendiculate cremastra pseudobulb and bamboo shavings (15 g each), 30 g of Mongolian milkvetch root, 20 g of large-head atractylodes rhizome, 6 g of villous amomum fruit, 6 g of finger citron, 12 g of dried tangerine peel, and 12 g of ginger processed pinellia	Early chemotherapy (oxaliplatin + capecitabine) (n = 50) vs Zhipu Liujunzi decoction + early chemotherapy (n = 50)	2 weeks	After radical gastrectomy	Retrospective analysis	Improve the immune function and quality of life for GC patients with higher safety	[15]
Decoction with Astragalus mongholicus and Semen Cuscutae	Radix Pseudostellariae 45 g, Rhizoma Atractylodis Macrocephalae 45 g, Rhizoma Zingiberis 45 g, Radix Glycyrrhizae Preparata 45 g, Rhizoma Pinellinae Praeparata 15 g, Fructus Amomi 15 g, Rhiizoma Dioscoreae 60 g, Astragalus mongholicus 120 g, Semen Cuscutae 60 g, Lignum Millettiae 60 g	Each N-of-1 trial consisted of two or three cycles with treatment decotion and control decotion assigned randomly	20-30 weeks (3-week standard chemotherapy and then used 3-day treatment periods)	After radical gastrectomy	A series of N-of-1 trials with randomization, double-blind, and controlled treatment	The QoL score after the trial was reported is a little higher than before	[101]
San Jie Pai Shi decoction	10 g of Codonopsis pilosula, 6 g of Radix glycyrrhiza, 12 g of the rhizome of Atrac_x005f tylodis macrocephalae, 9 g of the cortex of Magnoliae officinalis, 12 g of immature bitter orange, 12 g of the endothelium cor neum of Gigeriae galli, and 9 g of Rheum officinale	N/A	2 weeks	Gastric bezoar after Billroth II gastrectomy for GC	Case report	Gastroscopic examination showed that the gastric bezoar had dissolved	[22]
Xuesaitong injection	Extract from the roots of Pannax notoginseng (Sanqi)	Conventional anti-infection and transfusion treatment + 400 mg Xuesaitong Injection (n = 25) vs conventional anti-infection and transfusion treatment (n = 25)	6 days from the first day after surgery	After laparoscopic surgery for gastric cancer	RCT	The occurrence rate of deep vein thrombosis on day 7 after operation in the Xuesaitong group was lower than that in the control group	[41]
Rikkunshito (Liujunzi decoction)	Dried Atractyloidis lanceae rhizoma, Ginseng radix, Pi_x005f nelliae tuber, Hoelen, Zizyphi fructus, Aurantii nobilis percarpium, Glycyrrhizae radix, and Zingiberis rhizome	Rikkunshito and then off treatment (n = 4) vs off treatment and then Rikkunshito (n = 7)	On treatment and off treatment for 4 weeks each	Underwent PPG for early GC more than 5 years ago	Crossover design study	Improved gastric emptying and ameliorated postoperative symptoms of patients who had undergone a PPG	[39]
Dai-kenchu-to (Dajianzhong decotion)	Dried ginger root, ginseng, and zanthoxylum fruit	Dai-kenchu-to and then off treatment (n = 10) vs off treatment and then Dai-kenchu-to (n = 7)	On treatment and off treatment for 2 weeks each	Underwent total gastrectomy with jejunal pouch interposition for GC	Crossover design study	Reduced stasis-related symptoms, accelerated emptying of both liquid and solid meals from the pouch, increased intestinal motility and decreased postoperative symptoms	[42]
Fuzheng Huoxue anticancer prescription	Codonopsis pilosula (Franch.) N annf (15 g), Astragalus membranaceus (Fisch.) Bge (15 g), Atractylodes macrocephala Koidz (12 g), Poria cocos (Schw.) Wolf (12 g), Rehmannia glutinosa (Gaertn.) Lib osch (12 g), Adenophoratetraphylla (Thunb.) Fisch (15 g), Salvia miltiorrhiza Bge (15 g), and Angelica sinensis (Oliv.) Diels (12 g)	Fuzheng Huoxue anticancer prescription (n = 35) vs control prescription (n = 34)	Five days, starting at one month after an operation	Mid- or late-stage (23 cases received palliative surgery and 11 cases radical surgery)	RCT	Replenish vital functions (Zhengqi), correct a hypercoagulatory state, improve immunologic function, and extend patient survival times, directly inhibit gastric tumor growth without producing toxic side effects	[13]
Powder of eight Noble Ingredients and cinnamon twig and Poria pills	Ginseng, white atractylodes rhizome, Poria, Pinellia, 4 g each; tangerine peel and Fructus ZiZiphi Jujubae, 2 g each; liquorice, 1 g; dried ginger, 0.5 g; cinnamon twig, Poria, Moutan bark, peach seed, peony root, 4 g each	FAP regimen (5-fluorouracil, 300 mg/m2 intravenous gutta for five consecutive days; adriamycin, 40 mg/m2 for the first day), or the CODP regimens (cyclophosphamide, vincristine, daunorubicin, prednisone) (n = 31) vs FAP regimen and TCM (n = 32)	6 months	Metastasis formation after surgery for GC	RCT	Metastatic relapse was reduced and the ornithine decarboxylase levels of the gastric mucosa were sharply reduced	[27]
Modified ShengYangYiwei decoction	30 g ginseng, 9 g atractylodes macrocephala, 9 g poria, 60 g astragalus, 15 g white peony, 30 g pinellia ternata, 6 g rhizoma coptidis, 9 g rhizoma alismatis, 12 g dried tangerine peel, 10 g magnolia officinalis, 9 g rhizoma Notopterygii, 9 g angelica pubescens, 9 g fangfeng, 9 g bupleurum chinense, 5 g ginger, 6 g jujube (denuded), 6 g cohosh, 9 g kudzu, 9 g pueraria lobata, 15 g Shijian Chuan, 12 g divine koji, and 6 g raw licorice	Modified ShengYangYiwei decoction one week before the examination (n = 56) vs routine gastrointestinal endoscopy (n = 50)	One week before the examination	GC patients after painless gastroscopy	Prospective, randomized controlled study	Optimize the anesthesia program during painless gastroscopy, improve the gastrointestinal function of patients after the operation, reduce the occurrence of examination-related complications	[102]
Acupuncture	Bilateral ST-36 (Zusanli), SP-6 (Sanyinjiao), LI-4 (Hegu), TE-6 (Ziagou), LV-3 (Taichong), LI-11 (Quchi), and unilaterally at GV-20 (Baihui), EX-HN3 (Yintang), GV-26 (Shuigou), and CV-24 (Chengjiang)	Acupuncture (n = 18) vs non-acupuncture (n = 18)	Once daily for 5 consecutive days starting at postoperative day 1	Postoperative Ileus after Distal Gastrectomy for GC	Prospective, randomized controlled, phase III study	Promoting the passage of sitz markers in small intestine; reducing the duration of POI after gastric cancer surgery, by earlier recovery of small bowel movement	[45]
	Acupuncture therapy including electroacupuncture, manual acupuncture, moxibustion, TEAS, warm needling, and ear acupressure	Acupuncture therapy vs standard perioperative care or sham/placebo acupuncture	N/A	Postoperative gastrointestinal dysfunction in patients with gastric and colorectal cancer	Umbrella review (six systematic reviews/meta-analyses)	Improve postoperative gastrointestinal function for postoperative GC patients	[44]
	Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Gongsun (SP 4), Sanyinjiao (SP 6)	Acupuncture + routine treatment (n = 40) vs routine treatment (continuous gastrointestinal decompression) (n = 40)	30 minutes each time, once a day, 5 days as a course, 1-3 courses	Functional delayed gastric emptying after GC surgery	RCT	The first exhaust time, remove gastric tube time, liquid food intake time and hospital stay were shortened	[103]
	Baihui (GV 20), Zusanli (ST 36), Neiguan (PC 6), etc.	High-dose acupuncture (n = 19) vs low-dose acupuncture (n = 20) vs control group (n = 19)	Chemotherapy cycle of 21 days, 3 courses	Patients with GC during adjuvant chemotherapy after gastrectomy	RCT	The total score and the scores of feeling of non-well being, pain and shortness of breath of ESAS in the acupuncture group were lower than the control group	[104]
	Bilateral ST 36 (Zusanli), SP 6 (Sanyinjiao), LI 4 (Hegu), TE 6 (Ziagou), LV 3 (Taichong), LI 11 (Quchi), and unilaterally at GV 20 (Baihui), EX HN3 (Yintang), GV 26 (Shuigou), and CV 24 (Chengjiang)	Acupuncture (n = 5) vs nonacupuncture (n = 5)	5 consecutive days starting on postoperative day 1	POI after GC surgery	Prospective, randomized, controlled pilot study	Reduce duration of POI after GC surgery, by earlier recovery of small bowel movement	[105]
Simo decoction + acupuncture	Fructus aurantii (Zhike), Radix aucklandiae (Muxiang), Semen arecae (Binlang), Radix linderae (Wuyao)PC6 (Neiguan), ST36 (Zusanli), LV-3 (Taichong), SP-6 (Sanyinjiao)	Control group (n = 30) vs Simo decoction (n = 30) vs acupuncture + Simo decoction (n = 30)	10 days	After radical surgeries for GC	RCT	Accelerate early air exhaustion and defecation, improve clinical symptoms, bi-directional regulate peripheral white blood cells	[106]
TEAS	Hegu (LI4), Neiguan (PC6), Weishu (BL21), Xiaochangshu (BL27), Zusanli (ST36), Shangjuxu (ST37)	TEAS therapy on postoperative day 1-3 (n = 41) vs usual care (n = 40)	3 days	Patients underwent radical surgery for GC (laparoscopy/robot)	Unblinded randomized controlled trial	Relieve postoperative pain and promote the recovery of gastrointestinal function	[49]
Electro-acupuncture	Bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points	High-dose EA (seven times each chemotherapy cycle for three cycles) + adjuvant chemotherapy vs low-dose EA (three times each chemotherapy cycle) + adjuvant chemotherapy vs or adjuvant chemotherapy	3 chemotherapy cycles	During adjuvant chemotherapy following gastrectomy	Open-label, multicenter, parallel controlled trial	Improve HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in GC patients	[107]
Fu’s subcutaneous needling	Erector spinae muscle and rectus abdominis muscle	N/A	Once a day for three days	Progressive nausea, vomiting and stomach fullness, with a bloating abdomen ten days after laparoscopic radical gastrectomy for GC	Case report	Gastrointestinal motility enhancement and gastric drainage volume decrement	[46]
Acupuncture and moxibustion	N/A	Experimental group (n = 638) vs control group (n = 621)	N/A	Undergone any type of surgical treatment (e.g., partial gastrectomy, and total gastrectomy) and/or any chemotherapy regimen	Meta-analysis (fifteen RCTs)	Aid in gastrointestinal function recovery, reduce the incidence of AEs of surgery and chemotherapy, and improve immune function	[47]
Acupoint injection	Zusanli (ST36) acupoint injection with Neostigmine	ST36 acupoint injection with neostigmine 05 mg per side (n = 67) vs gluteal intramuscular injection with 1.0 mg neostigmine (n = 67) vs ST36 acupuncture alone (n = 67) vs standard therapy (n = 67)	Once a day until recovery of peristalsis	Patients with paralytic POI following gastrectomy for GC	RCT	Shorter time to bowel sound recovery, shorter time to first flatus and first defecation	[48]
Auricular point-pressing with bean	Acupoints of the stomach, spleen, large intestine, endocrine, subcortex, and small intestine	Auricular point-pressing with bean plus 20 mg EM tablets (n = 41) vs routine EM tablets (n = 37)	The therapist conducted compression once every 6 hours	Gastrointestinal dysfunction after ESD	Retrospective study	Alleviate the gastrointestinal dysfunction of early GC patients after ESD and help them to maintain normal gastrointestinal function	[57]
	Spleen acupoint, large intestine acupoint, and gastrointestinal pain point	Acupoint patch combined with ear acupoint bean pressing burrowing (n = 41) vs conventional nursing methods (n = 41)	Postoperative until 1 day before patient discharge	After laparoscopic surgery for gastric cancer	Retrospective study	Better adapt to the treatment process, reduce anxiety, and improve the treatment effect and quality of life	[108]
Auricular acupuncture	Shenmen, sympathetic nerve, thalamus, point zero, and omega 2	Sham auricular acupuncture (n = 20) vs auricular acupuncture (n = 20)	6 days	Postoperative movement-evoked pain after open radical gastrectomy	Single-blind randomized controlled pilot trial	Have a certain relief effect on mild postoperative pain at rest with pain score below 3	[62]
Traditional Chinese medicine nursing	(1) TCM psychological care; (2) Syndrome differentiation nursing; (3) Dietetic nursing; and (4) Nursing of auricular-plaster therapy of TCM: Auricular points: Spleen, stomach, sympathy, endocrine, large and small intestines	TCM nursing (n = 52) vs routine nursing (n = 51)	Until the patient was discharged from hospital	Postoperative patients with GC after radical gastrectomy	Prospective, randomized controlled study	Improve postoperative gastrointestinal dysfunction, alleviate acute inflammation, improve postoperative unhealthy mental state, reduce the occurrence of postoperative complications	[58]

TCM: Traditional Chinese medicine; POI: Postoperative ileus; POC: Postoperative complication; GC: Gastric cancer; N/A: Not applicable; HRs: Hazard ratios; CI: Confidence interval; QoL: Quality of life; PPG: Pylorus-preserving gastrectomy; EA: Electro-acupuncture; EM: Esomeprazole magnesium; ESD: Endoscopic submucosal dissection; DFS: Disease-free survival; RCT: Randomized controlled trial; TEAS: Transcutaneous electrical acupoint stimulation; ESAS: Edmonton symptom assessment system; HRQOL: Health-related quality of life; FAP regimens: 5-fluorouracil, adriamycin, cisplatin; CODP regimens: Cyclophosphamide, vincristine, daunorubicin, prednisone; EA: Electro-acupuncture.