Oncological problems in pancreatic cancer surgery

Table 1 Comparative studies of extended versus standard operation for pancreatic cancer

Author	Yr	Results
Ishikawa et al[24]	1988	Retrospective study	standard (n = 37): 9%, 5-Y-S
			extended (n = 22): 28%, 5-Y-S
Mukaiya et al[25]	1998	Retrospective study 77 institutions, 501 patients: NS
Henne-Bruns et al[26]	2000	Retrospective study	standard (n = 26)	NS
			extended (n = 46)
Pedrazzoli et al[27]	1998	RCT	standard (n = 40)	overall survival: NS
			extended (n = 41)	survival of node positive patients: extended > standard
Yeo et al[28]	2002	RCT	standard (n = 146)	mortality: NS, morbidity: extended > standard,
			extended (n = 148)	survival: NS

RCT: Randomized controlled test; NS: Not significant.

Table 2 Incidence of postoperative recurrence in pancreatic cancer

Author	Yr	Cases (n)	Liver (%)	Local (%)	Peritoneal (%)	Bone (%)	Lung (%)	Other (%)
Westerdahl et al[53]	1993	74	92	86.5
Kayahara et al[54]	1993	30	60	83.3	40
Takahashi et al[55]	1995	25	80	100	56	24	56
Sperti et al[56]	1997	78	62	72	6
Nakao et al[57]	1997	76	57	34	41	3	1	1

Table 3 Randomised controlled trials of adjuvant treatment for pancreatic ductal adenocarcima

Trial	Comparison	Adjuvant treatment	Number of patients	Conclusions
GITSG, 1985[58], 1987[59]	CRT vs OBS	2 × (20 Gy in 10 fractions + 500 mgm-2 5FU d 1-3) + weekly 5FU to recurrence	49 pancreatic patients randomised	Significant increase in median survival (20 vs 11 mo, P = 0.035) in 43 eligible patients
Norway, 1993[60]	CT vs OBS	AMF (40 mgm-2 doxorubicin, 6 mgm-2 mytomycin C, 500 mgm-2 5FU) once every 3 wk for six courses	61 patients (47 pancreatic, 14 ampullary) randomised 46 additional nonrandomised patients	Significant increase in median survival (23 vs 11 mo, P = 0.02) in 60 pancreatic and ampullary patients combined
EORTC, 1999[61]	CRT vs OBS	2 × (20 Gy in 10 fractions + 25 mgkg-1 5FU/FA d 1-5)	218 patients (120 pancreatic, 93 ampullary) randomised	NS increase in median survival (25 vs 19 mo, P = 0.21) in 207 eligible patients NS increase in median survival in 114 eligible pancreatic patients (17 vs 13 mo, P = 0.099)
Japan, 2002[62]	CT vs OBS	6 mgm-2 mytomycin C d 1 + 310 mgm-2 5FU d 1-5 and d 15-20 followed by 100 mgm-2 oral 5FU daily until recurrence	508 patients (173 pancreatic, 335 bile duct/gallbladder/ampullary) randomised	Significant survival benefit in gallbladder No difference in 158 eligible pancreatic patients No difference in 48 eligible ampullary patients
ESPAC1, 2001[63], 2004[64]	CRT vs no CRT CT vs no CT	2 × (20 Gy in 10 fractions + 500 mgm-2 5FU/FA d 1-3)(20 mgm-2 FA + 425 mgm-2 5FU d 1-5) × six cycles	289 pancreatic patients randomised	NS decrease in survival for CRT (P = 0.05) in 289 patients Significant increase in survival for CT (P = 0.009) in 289 eligible patients
CONKO-001, 2005[65]	CT vs OBS	1 gm-2 GEM, d 1, 8, 15, every 4 wk for 6 mo	368 pancreatic patients randomised	Significant increase in median DFS (14.2 vs 7.5 mo, P < 0.05) in 356 eligible patients

CRT: Chemoradiotherapy; CT: Chemotherapy; OBS: Observation; NS: Not significant; DFS: Disease-free survival.

Table 4 Incidence of pancreatic cancer cells in peripheral blood, bone marrow, and liver tissue

Author	Yr	Incidence
Tada et al[71]	1993	Peripheral blood, K-ras 2/6 (33%)
Juhl et al[72]	1994	Bone marrow, immunostaining: 15/26 (58%)
Inoue et al[73]	1995	Liver tissue, K-ras: 13/17 (76%)
Nomoto et al[74]	1996	Peripheral blood, K–ras: postoperative period10/10 (100%)
Funaki et al[75]	1996	Peripheral blood, CEAmRNA: 3/9 (33%)
Aihara et al[76]	1997	Peripheral blood, Keratin 19m RNA: 2/38 (5%)
Miyazono et al[77]	1999	Peripheral blood, CEAmRNA: 13-21 (61.9%)
Uemura et al[78]	2004	Peripheral blood, K-ras: 9/26 (35%)

Table 5 Reports of occult lymph node metastasis

Author	Yr	Results
Tian et al[79]	1992	HE: 8/56 (14%) Cytokeratin: 17/56 = (30%)
Ando et al[80]	1997	K-ras: paraaortic lymph nodes: 42/101 (42%)
Demeure et al[81]	1998	K-ras: Stage I (T1-2, N0, M0) 16/22 (73%)
Yamada et al[82]	2000	K-ras (-) has a better prognosis than K-ras (+)
Bogoevski et al[83]	2004	Ber–EP4: immunostaining 56/148 (37.8%)

Table 6 Incidence of occult peritoneal dissemination

Author	Yr	Results
Lei et al[84]	1994	Peritoneal washings, conventional cytology, 3/36 (8%), 1/11 (9%) with ascites
Juhl et al[72]	1994	Immunostaining (CEA, CA19-9,…, cytokeratin bone marrow 58%, peritoneal washings 58%
Vogel et al[85]	1999	Peritoneal washings 39%, bone marrow 38%, one of them positive: died within 19 mo, both negative: 5 y.s. 30% (P < 0.0001)
Castillo et al[86]	1995	Laparoscopy 16/94 (17%)
Leach et al[87]	1996	4/60 (7%)
Nomoto et al[88]	1997	Conventional: 0/18 (0%), immunostaining (CEA, CA19-9): 2/18 (11%)
Nakao et al[89]	1999	Conventional: 5/66 (8%), immunostaining 14/66 (22%) prognosis between cytology positive and negative: NS