Management of ampullary neoplasms: A tailored approach between endoscopy and surgery

Table 1 Staging classification of the ampullary neoplasms according to the American Joint Committee on Cancer TNM classification, 7^th edition[47]

T = Primary Tumor
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Tis	Carcinoma in situ
T1	Tumor limited to ampulla of Vater or sphincter of Oddi
T2	Tumor invades duodenal wall
T3	Tumor invades pancreas
T4	Tumor invades peripancreatic soft tissue or other adjacent organs or structures other than pancreas
N = Regional Lymph Nodes
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Regional lymph node metastasis
M = Distant Metastasis
MX	Distant metastasis cannot be assessed
M0	No distant metastasis
M1	Distant metastasis
G = Histologic Grade
GX	Grade cannot be assessed
G1	Well differentiated
G2	Moderate differentiated
G3	Poorly differentiated
G4	Undifferentiated
Stage	T	N	M
0	Tis	N0	M0
IA	T1	N0	M0
IB	T2	N0	M0
IIA	T3	N0	M0
IIB	T1	N1	M0
	T2	N1	M0
	T3	N1	M0
III	T4	Any N	M0
IV	Any T	Any N	M1

Table 2 Survival in papillary tumors and predictors of poor prognosis

Ref.	n/resected	Operative mortality (%)	Positive nodes (%)	R0 (%)	Pancreatobil/intestinal, n (%)	Survival-resected		Median survival - resected (mo)	Predictors of worse survival or recurrence
						5 yr	10 yr
Albagli et al[128]	50/50	8.0	36.0	-	-	N0 52%	-	-	None
						N+ 39%
Allema et al[136]	67/67	1.5	52.0	75.0	-	50%	-		R+
Beger et al[50]	171/171	3.1	54.0	79.6	-	N+ 21%	-	-	N+2, Pan+, R, Stage2, G2-3
						N0: 63%
Bettschart et al[18]	88/70	0.0	40.0	97.2		37.91		45.8	Bilirubin2, Age > 70, G3, N+2, Neu+, Pan+
Brown et al[91]	72/51	2.0	47.0	100.0	-	58%			N+2, T, G
Carter et al[137]	157/145	-	33.0	86.0	53 (45)-54 (46)	-	-	-	Pancreatobil2, Bilirubin, Stage2, N+, T, Ly+2, Neu+2
Chareton et al[35]	63/51	7.5	-	-	-	40%	-		Stage, Ampullectomy
Choi et al[129]	78/70	2.6	31.4	95.7	-	59.90%	29%	70	Jaundice, Ulcerated, Pan+, G
						N0 63.5%
						N+ 50.8%
Di Giorgio1 et al[138]	94/64	8.6	28.0	100.0	-	64.4%		54	No resection , Size, G, Depth of infiltration2
Duffy et al[92]	55	0.0	41.8	98.2	-	67.70%	-	-	Neu+2
Falconi et al[19]	90/90	4.0	48.0			61% (disease free)			Stage, T, LNR2
Hornick et al[16]	157/150		59.8			Adenocarcinoma 45%			Jaundice, Stage, N+
	106					Adenoma 82%
	Adenocarcinoma					N+ 47%
						N0 63%
Howe1 et al[28]	123/101	5.0	45.5	96.1	-	46%	-	58.8	No resection, N+2, R+2, G3
Iacono et al[139]	59/59	7.8	37.3	-	-	46%	33%	31	G, T2, N+, Chromosome 17p2, 18q2, Micro satellite instab., Standard PD
Inoue et al[140]	34/34					52.6%			N+2, Pan+, V+2, Neu+2, SMA2
Kawaguchi et al[141]	28/28					56.4%		37	Duo+, Ly+, V+2
Kim et al[34]	104/104		39.4		62 (60)-42 (40)	60.1%	57.6%		T2, CEA, N+2, G32, Pancreatobil2, Neu+, Ly+
Kimura et al[36]	51	-	45.0	-	38 (74)-13 (25)				Pancreatobil
Klempnauer et al[142]	94/94	9.6	38.0	97.0	-	34.5%	28.6%	-	Size2, G3, N+, Stage
Lazaryan et al[20]	72/72	-	34.0	96.0	-	61%	-	-	Neu+2, Ulcerated2, N+2, Stage, Weight loss
Norero et al[143]	50/50					32%		28	N+2
Ohike et al[134]	244/244	-	38.0	95.0	162 (66) other	33%	-	-	Budding2, N+2, T2, R+2
					82 (34) intestinal	Hi budding 24%
						Low budding 68%
Qiao et al[59]	127/127	9.7	35.0	98.4		43.3%	35.7%		N+2, T2, Stage, Pan+
Roder et al[144]	69/66	4.5	42.0	-	-	35%	-	41	N(nr)
Sakata et al[130]	71/71	0.0	48.0	97.2		64%	55%		G, Pan+, Ly+2, V+2, Neu+, R+, N+2, LNR
Shinkawa et al[145]	23/23					52%	32%		Pan+, N+
Talamini1 et al[51]	120/106	3.8	40.0	-	-	38%	-	46	No resection, Transfusion2, N+, G2-3
						N+ 31%
						N0 43%
Todoroki et al[95]	66/59	0.0	60.0	93.2	-	52.6%			R+, CEA, Ulcerated, T2, N+, Stage2, Ly+2, V+
Westgaard et al[25]	114/114	3.5	57.0	65.0	67 (59)-47 (41.2)	-			Pancreatobil2, N+2, V+2
	41 ampullary								Size2
Winter et al[127]	450/450	2.0	54.5	96.1		Adenocarcinoma 45%		N+ 23.4	N+2, Neu+2, Transfusion2
	Adenoca: 347					Adenoma 86%		N0 79
						N+ 35%
						N0 56%
Yokoyama et al[15]	74/59	-	53.5	100.0	-	61.0%	53%	-	Pan+2, N+2, Jaundice, V+, Ly+2, Neu+, G
Zhao et al[146]	105/105	8.6	37.1			42.8%			Pan+, Size2, T, TNM stage, N(nr)2

¹Including not resected pts;

²Independent predictor; duo+: Duodenal invasion; G: Histologic grade of differentiation; LNR : Lymph nodes ratio; Ly+: Lymphatic vessel invasion; N+: pOsitive lymph nodes; N(nr): Number of metastatic lymph nodes; Neu+: Perineural invasion; Pan+: Pancreatic invasion; Pancreatobil: Pancreatobiliary histological subtype; R+: Positive resection margins; No resection: Patients not resected vs those who underwent surgical resection; SMA: Lymphadenectomy around the superior mesenteric artery; V+: Blood vessel invasion.

Table 3 Accuracy of various methods in indenfying and staging papillary tumors

Ref.	n	Test	Tumor detection			T	N			Resectability
			Sens	Spec	Acc	Acc	Sens	Spec	Acc	Sens	Spec	Acc
Artifon et al[147]	27	CT	-	-	-	51.8%	40.0%	65.0%	55.5%	-	-	-
		EUS	-	-	-	74.1%	70.0%	88.0%	81.4%	-	-	-
Buscail et al[148]	6	EUS	-	-	-	83.0%	-	-	100.0%	100.0%	100%	100%
Cannon et al[79]	50	CT	-	-	-	24.0%	-	-	59.0%	-	-	-
		MRI	-	-	-	46.0%	-	-	77.0%	-	-	-
		EUS	-	-	-	78.0%	-	-	68.0%	-	-	-
Chen et al[61]	19	US	5.0%	-	-	11.0%	7.0%	-	-	-	-	-
		CT	21.0%	-	-	22.0%	33.0%	-	-	-	-	-
		EUS	95.0%	-	-	72.0%	47.0%	-	-	-	-	-
Chen et al[5]	41	US	-	-	12.2%	-	-	-	-	-	-	-
		CT	-	-	28.6%	26.1%	0.0%	-	44.0%	-	-	-
		MRI	-	-	81.3%	53.8%	25.0%	-	77.0%	-	-	-
		EUS	-	-	97.6%	72.7%	47.0%	-	67.0%	-	-	-
Heinzow et al[84]	72	IDUS	87.5%	92.5%	90.2%	-	-	-	75.0%	-	-	-
		ETP	68.7%	100.0%	86.0%	-	-	-	-	-	-	-
		IDUS +ETP	97.0%	100.0%	94.5%	-	-	-	-	-	-	-
Howard et al[149]	21	CT	-	-	-	-	-	-	-	63.0%	100%	86%
		EUS	-	-	-	-	-	-	-	75.0%	77%	76%
Kubo et al[85]	35	EUS	-	-	-	74.0%	-	-	63.0%	-	-	-
Manta et al[82]	24	MRI	75.0%	-	-	-	-	-	-	-	-	-
		EUS	100.0%	-	-	-	-	-	-	-	-	-
Midwinter et al[63]	34	CT	76.0%	-	-	-	33.0%	86.0%	-	-	-	-
		EUS	97.0%	-	-	-	44.0%	93.0%	-	-	-	-
Mukai et al[83]	23	EUS	96.0%	-	-	78.0%	-	-	-	-	-	-
Qiao et al[59]	127	US	7.9%	-	-	-	-	-	-	-	-	-
		CT	19.0%	-	-	-	-	-	-	-	-	-
Rösch et al[64]	28	US	7.0%	-	-	-	-	-	-	-	-	-
		CT	29.0%	-	-	-	-	-	-	-	-	-
		EUS	93.0%	-	-	-	-	-	-	-	-	-
Skordilis et al[60]	20	US	15.0%	-	-	-	-	-	-	-	-	-
		CT	20.0%	-	-	-	-	-	-	-	-	-
		EUS	100.0%	-	-	82.0%	-	-	71.0%	-	-	-
Tio et al[150]	32	EUS	-	-	-	84.4%	68.8%	37.5%	53.1%	-	-	-

Acc: Accuracy; CT: Computerized tomography; ETP: Endoscopic transpapillary forceps biopsies; EUS: Endoscopic ultrasonography; IDUS: Transpapillary intraductal ultrasonography; MRI: Magnetic resonance imaging; Sens: sensitivity; Spec: Specificity.