Advances in para-aortic nodal dissection in gastric cancer surgery: A review of research progress over the last decade

Table 1 Analysis of clinicopathologic characteristics relevant to para-aortic lymph node metastasis

Ref.	Year	Article type	Clinicopathologic characteristics relevant to para-aortic lymph node metastasis
			Perigastric nodal status	Tumor site (located in the U)	Tumor size ≥ 5 cm	Depth of tumor invasion	N stage of N2 and N3	Macroscopic type Borrmann III/IV	Diffuse/mixed histology
Takashima et al[11]	2005	Review	—	Yes	—	Yes	—	—	—
Lee et al[54]	2006	Article	—	—	—	Yes	—	—	Yes
Nomura et al[24]	2007	Article	No. 7	—	Yes	—	Yes	—	Yes
Chen et al[42]	2009	Meta-analysis	No. 7, 8	—	—	Yes	—	—	—
Hu et al[44]	2009	Article	No. 8a, 9	—	—	—	—	—	—
Fujimura et al[34]	2009	Article	—	Yes	—	—	—	—	—
Tokunaga et al[31]	2010	Article	—	—	—	—	Yes	Yes	—
Roviello et al[21]	2010	Article	—	Yes	—	—	—	—	—
de Manzoni et al[28]	2011	Article	No. 1, 3, 7, 8a, 9	Yes	—	Yes	—	—	Yes
Wang et al[43]	2013	Article	No. 9	Yes	—	—	Yes	Yes	—
Zhou et al[42]	2013	Meta-analysis	No. 1, 3, 7, 9	Yes	Yes	Yes	Yes	Yes	Yes
Zhang et al[53]	2014	Article	—	—	—	Yes	Yes	—	—
Liang et al[45]	2016	Review	No. 9	Yes	—	—	Yes	Yes	—
Douridas et al[47]	2018	Mini review	—	Yes	Yes	Yes	—	Yes	Yes

U: the upper third of the stomach.

Table 2 Some reported series of gastrectomy and a comparison of morbidity, mortality and survival between D2 and D2 + PAND

Ref.	Year	Countries and continents	Number of patients registered	Number of patients underwent D2 + PAND or D2+	Incidence of PAN (%)	Prognosis differences between D2 vs D2 + PADN (D2+)
						Morbidity			Mortality			Recurrence rate			5-yr survival rate
						D2 (%)	D2 + PAND (%)	P value	D2 (%)	D2 + PAND (%)	P value	D2 (%)	D2 + PAND (%)	P value	D2 (%)	D2 + PAND (%)	P value
Günther et al[18]	2000	Turkey	459	75	—	31.5	34.2	—	6.8	1.3	—	—	—	—	—	—	—
Bostanci et al[19]	2004	Turkey	134	34	—	10	35.3	< 0.05	1	8.8	< 0.05	—	—	—	—	—	—
Sano et al[30]	2004	Japan	523	260	—	20.9	28.1	0.067	0.8	0.8	—	—	—	—	—	—	—
Marrelli et al[17]	2007	Italy	330	79	13.9	27	27	0.929	4	4	0.82	—	—	—	—	—	—
Kunisaki et al[55]	2006	Japan	580	150	—	—	—	—	—	—	—	40	50	0.3538	56.0	50.4	0.9899
Kulig et al[20]	2007	Poland	275	134	—	27.7	21.6	0.24	4.9	2.2	0.37	—	—	—	—	—	—
Sasako et al[37]	2008	Japan	523	260	8.5	—	—	—	—	—	—	—	—	—	69.2	70.3	—
Yonemura et al[40]	2008	Japan	293	134	9.0	—	—	—	—	3.7	0.12	46.7	38.8	—	52.6	55.0	0.801
Hu et al[44]	2009	China	117	62	8.1	27.3	24.2	0.703	1.8	0	0.470	—	—	—	66.1	65.8	0.946
Roviello et al[21]	2010	Italy	286	286	12.9	—	28	—	—	2.1	—	—	—	—	—	52.2	—
Tokunaga et al[31]	2010	Japan	178	178	-	—	30	—	—	2	—	—	—	—	—	13	—
de Manzoni et al[28]	2011	Italy	294	294	16	—	—	—	—	—	—	—	—	—	—	—	—
Zhang et al[53]	2014	China	157	69	40.6	—	—	—	12.5	21.7	0.122	43.2	39.1	0.628	31.8	43.7	0.044
de Manzoni et al[78]	2015	Italy	568	294	11.6	—	—	—	4	2.4	0.340	45.3	46.3	0.866	—	—	—

PAN: Para-aortic lymph node; PAND: Para-aortic lymph node dissection.

Table 3 Main studies that reported clinical data including survival outcomes following chemotherapy and surgery in patients with pathological positivity of para-aortic lymph nodes

Ref.	Registration number	Types of clinical trials (Phase I/II/III)	Published year	Time of accrual	Chemotherapy regimens	Followed by surgery	Extent of lymphadenectomy	Number of patients registered	Incidence of PAN (%)	Primary endpoint	R0 resection rate	Response rate		Survival rate			TRD
												Clinical	Pathological	Relapse-free survival	3-yr (%)	5-yr (%)
Yoshikaw et al[61]	JCOG0001	II	2009	2000-2003	CPT-11/CDDP	Yes	D2 + PAND	55	54.5	3-yr survival rate TRD rate	65 (95%CI 51-78)	56	15	—	27	NA	3/55
Oyama et al[60]	—	—	2012	1990-2008	S-1/CDDP/docetaxel	Yes	D2 + PAND	44	100	—	—	—	87.5	75 (2-yr)	—	—	0/44
Wang et al[64]	—	II	2014	2008-2013	XELOX (capecitabine and oxaliplatin)	Yes	D2	48	100	Response rate of NAC	50%	85.1	49	—	—	—	—
Tsuburayaet al[33]	JCOG0405	II	2014	2005-2007	S-1/CDDP	Yes	D2 + PAND	51	51	R0 resection rate	82(95%CI 69-92)	65	51	—	59	53	0/51
Ito et al[62]	JCOG1002	II	2017	2011-2013	S-1/CDDP/docetaxel	Yes	D2 + PAND	52	43.4	Response rate (RECISTver.1.0)	84.6	57.7	50	—	—	—	0/52
Takahari et al[63]	JCOG1002	II	2019	2011-2013	S-1/CDDP/docetaxel	Yes	D2 + PAND	52	43.4	Clinical RR	—	—	34.6	47.7 (5-yr)	62.7	54.9	0/52

PAN: Para-aortic lymph node; PAND: Para-aortic lymph node dissection; CI: Confidence interval; TRD, treatment-related death .

Table 4 Adverse effects in three Japanese prospective randomized trials exploring neoadjuvant chemotherapy plus surgery for patients with extensive lymph node metastasis (Para-aortic lymph nodes metastasis or bulky lymph nodes)

Adverse effect	JCOG0001[61]	JCOG0405[33]	JCOG1002[62,63]
Grade 3/4 toxicity from chemotherapy
Leucopenia	31%	4%	18.9%
Neutropenia	55%	19%	39.6%
Anemia	24%	13%	7.5%
Febrile neutropenia	16%	2%	5.7%
Thrombocytopenia	—	4%	1.9%
Hyponatremia	—	—	15.1%
Hypokalemia	—	—	5.7%
Anorexia	—	10%	9.4%
Vomiting	13%	—	—
Chemotherapy-related mortality	2/55	0/51	0/52
Surgical complications
Leakage	1/49	3/49	2/49
Pancreatic fistula	6/49	11/49	9/49
Abdominal abscess	2/49	8/49	—
Pneumonia	2/49	2/49	4/49
Wound infection	2/49	0/49	2/49
Anastomotic stenosis	1/49	0/49	1/49
Intestinal obstruction	0/49	0/49	2/49
Cardiac failure	1/49	—	—
Renal dysfunction	1/49	—	—
Atelectasis	—	3/49	—
Abdominal infection	—	—	5/49
Pleural effusion	—	—	6/49
Chylous ascites	—	—	3/49
Delayed gastric emptying	—	—	1/49
Thromboembolic event	—	2/49	2/49
Other	6/49	11/49	—
Postoperative mortality	1/49	0/49	0/49