Published online Jul 28, 2016. doi: 10.3748/wjg.v22.i28.6424
Peer-review started: March 25, 2016
First decision: May 12, 2016
Revised: May 24, 2016
Accepted: June 15, 2016
Article in press: June 15, 2016
Published online: July 28, 2016
Processing time: 119 Days and 19.3 Hours
Pancreatic ductal adenocarcinoma carries a poor prognosis with annual deaths almost matching the reported incidence rates. Surgical resection offers the only potential cure. Yet, even among patients that undergo tumor resection, recurrence rates are high and long-term survival is scarce. Various tumor-related factors have been identified as predictors of survival after potentially curative resection. These factors include tumor size, lymph node disease, tumor grade, vascular invasion, perineural invasion and surgical resection margin. This article will re-evaluate the importance of these factors based on recent publications on the topic, with potential implications for treatment and outcome in patients with pancreatic cancer.
Core tip: Many studies have investigated morphological indicators of survival in patients with resectable pancreatic cancer. This article scrutinizes the recent literature related to these classical prognostic factors and examines whether these factors still are able to influence patients’ outcomes in the era of multimodal treatment.
- Citation: Åkerberg D, Ansari D, Andersson R. Re-evaluation of classical prognostic factors in resectable ductal adenocarcinoma of the pancreas. World J Gastroenterol 2016; 22(28): 6424-6433
- URL: https://www.wjgnet.com/1007-9327/full/v22/i28/6424.htm
- DOI: https://dx.doi.org/10.3748/wjg.v22.i28.6424
Pancreatic cancer has a devastatingly poor prognosis. The overall survival remains unchanged over a wide period of time with at a 5-year survival of 5%-10%[1]. Furthermore, according to recent data, the incidence of pancreatic cancer is increasing[2-4]. Pancreatic ductal adenocarcinoma constitutes the most common histopathological subtype of pancreatic cancer originating from the ductal cells of the exocrine pancreas. Surgery remains the only cure for pancreatic cancer, but long-term survival is uncommon despite the addition of oncological treatments.
Over the years, several important prognostic factors for resectable pancreatic cancer have been identified. Among these prognostic factors are tumor size, presence or absence of lymph node metastases (loco-regional and/or distant), vascular tumor involvement (e.g., portal vein, mesenteric vein and/or artery), perineural tumor growth and resection margin status (from tumor to resection line)[5-9].
Many studies have been conducted to elucidate the relative importance of these prognostic factors in terms of recurrence-free survival and long-term cure. Despite this information, limited progress has been made regarding survival aspects. Pancreatic surgery is associated with high morbidity and potentially also immune suppression. Therefore, it is of vital importance to accurately determine which patients that really derive benefit from surgery in order to avoid unnecessary surgical intervention, as well as facilitate treatment planning and guide neo- and adjuvant treatments. The aim of this review was to re-investigate classical morphological prognostic factors in resectable pancreatic cancer by summarizing the recent literature on the topic published since the year 2000.
Tumor size is a morphological variable that can be determined preoperatively and as such as carries much important information for treatment planning. Being part of the current TNM staging system of pancreatic cancer, tumor size is the only discriminant between T1 and T2 tumors (cut-off 2 cm). However, the size at which point a pancreatic tumor becomes associated with aggressive features remains undetermined. This is why most studies that have evaluated the effects of tumor size on survival have not used uniform definitions (Table 1). In general, larger tumors > 2-3 cm have worse prognosis compared to smaller tumors. Tumor size has also been linked to other adverse prognostic factors. For example, tumors with a diameter above 2 cm have been found to have an increased risk of lymph node metastases[10].
Ref. | Year | n | Tumor size, cut-off | Median OS | Statistical model | HR (95%CI) | P value |
Matsumoto et al[38] | 2015 | 968 | ≥ 3 cm | NR | Multivariable | 1.72 (1.16-2.56) | 0.006 |
Jeong et al[39] | 2015 | 276 | ≤ 2.5 cm | 13 mo | Multivariable | 1.65 (1.17–2.32) | 0.004 |
> 2.5 cm | 25 mo | ||||||
Hur et al[17] | 2015 | 18338 | In situ | 120 mo | Multivariable | 1 | |
≤ 1.0 cm | 27 mo | 3.09 (2.35-4.07) | < 0.001 | ||||
1.1-2.0 cm | 17 mo | 4.35 (3.42-5.53) | < 0.001 | ||||
> 2.0 cm | 11 mo | 5.69 (4.49-7.21) | < 0.001 | ||||
Yamamoto et al[40] | 2015 | 195 | ≤ 2 cm | 29 mo (mean) | Multivariable | 0.40 (0.17-0.83) | 0.012 |
Elberm et al[41] | 2015 | 1070 | < 2 cm | 19 mo | Multivariable | 0.63 (0.50-0.78) | < 0.001 |
Liu et al[31] | 2015 | 411 | > 2 cm | NR | Univariable | 1.46 (1.14-1.88) | 0.003 |
Okada et al[42] | 2014 | 200 | ≥ 3 cm | NR | Multivariable | 3.26 (1.52–7.00) | 0.002 |
Dusch et al[21] | 2014 | 415 | < 3 cm | 16 mo | Univariable | - | < 0.03 |
Shin et al[15] | 2014 | 537 | ≤ 3 cm | 22 mo | Multivariable | 1.4 (1.13-1.73) | 0.002 |
> 3 cm | 14 mo | ||||||
Kooby et al[37] | 2014 | 1399 | Continuous | 20 mo | Multivariable | 1.12 (1.06-1.18) | < 0.001 |
Petermann et al[10] | 2013 | 114 | ≤ 2 cm | 35 mo | Multivariable | 0.52 (0.25–1.05) | 0.071 |
2.1–3.4 cm | 16 mo | ||||||
3.5–4.5 cm | 20 mo | ||||||
> 4.5 cm | 8 mo | ||||||
Jamieson et al[43] | 2013 | 217 | ≤ 3 cm | 23 mo | Multivariable | 1.28 (0.93–1.76) | 0.13 |
> 3 cm | 16 mo | ||||||
Franko et al[14] | 2013 | 7135 | ≤ 1 cm | N0/N1: 38/18 mo | Multivariable | 1 | |
1.1–2 cm | N0/N1: 26/19 mo | 1.18 (0.94-1.48) | 0.152 | ||||
> 2 cm | N0/N1: 19/14 mo | 1.67 (1.34-2.07) | < 0.001 | ||||
Lad et al[44] | 2013 | 382 | Continuous | 16 mo | Multivariable | 1.23 (1.07–1.41) | 0.003 |
Sugiura et al[45] | 2013 | 208 | ≥ 3 cm | NR | Univariable | NR | 0.014 |
Hong et al[18] | 2012 | 209 | < 3 cm | 20 mo | Univariable | NR | 0.06 |
≥ 3 cm | 15 mo | ||||||
Bhatti et al[46] | 2010 | 84 | ≤ 2 cm | 34 mo | Univariable | NR | 0.017 |
> 2 cm, invasion- | 27 mo | ||||||
> 2 cm, invasion+ | 11 mo | ||||||
Yamada et al[47] | 2009 | 335 | > 4 cm | NR | Multivariable | 2.69 (1.30-5.56) | < 0.05 |
Ueda et al[48] | 2009 | 140 | < 3 cm | 22 mo | Multivariable | 1.85 (1.14-3.10) | 0.013 |
≥ 3 cm | 11 mo | ||||||
Kaneoka et al[49] | 2009 | 84 | < 2 cm | NR | Multivariable | 1 | |
2–4 cm | 20 mo | 1.7 (1.0–3.1) | 0.031 | ||||
> 4 cm | 11 mo | 2.3 (1.3–4.5) | 0.003 | ||||
Campbell et al[50] | 2009 | 163 | Continuous | 14 mo | Multivariable | 1.02 (1.00-1.03) | 0.049 |
Doi et al[51] | 2007 | 133 | ≤ 4 cm | 45% dead within 1 yr | Univariable | 1.55 (1.06–2.24) | 0.02 |
> 4 cm | 67% dead within 1 yr | ||||||
Zacharias et al[52] | 2007 | 81 | ≤ 3 cm | 28 mo | Multivariable | 1.9 (1.1–3.1) | 0.018 |
> 3 cm | 14 mo | ||||||
Pawlik et al[6] | 2007 | 905 | ≥ 2 cm | 17 mo | Multivariable | 1.24 (1.01-0.51) | 0.04 |
Moon et al[53] | 2006 | 94 | < 3 cm | 25 mo | Multivariable | 0.46 (0.27-0.78) | 0.004 |
Cleary et al[20] | 2004 | 123 | Continuous | 14 mo | Univariable | 1.2 (1.0–1.4) | 0.01 |
Ahmad et al[54] | 2001 | 125 | < 2 cm | 16 mo | Univariable | 1 | |
2-4 cm | 1.05 (0.58-1.89) | 0.87 | |||||
> 4 cm | 1.15 (0.61-2.15) | 0.66 | |||||
Sohn et al[55] | 2000 | 616 | < 3 cm | 21 mo | Multivariable | 0.72 (0.57-0.90) | 0.004 |
≥ 3 cm | 14 mo | ||||||
Meyer et al[56] | 2000 | 113 | ≤ 2 cm | 28 mo | Multivariable | 2.27 | < 0.006 |
> 2 cm | 13 mo |
Tumor size may also affect the rates of margin positivity following pancreatic surgery. It has been found that larger tumors increase the risk of tumor deposits being harbored in the resection line[11]. Larger tumors generally have a greater malignant potential, increasing the risk of tumor involvement of peripancreatic structures[12,13].
However, although most studies indicate impaired survival for larger tumors, a small tumor diameter does not exclude poor prognosis[14,15]. Interestingly, it has been found that tumors with a diameter less than 1 cm may also be associated with malignant potential and rapid disease progression[16,17]. Histopathological data obtained from analysis of “early” pancreatic cancer show that small tumor may display the same microvascular invasiveness pattern (i.e., a poor prognostic factor) as larger tumors[18,19].
This, somewhat, unclear relationship between tumor size and prognosis may reflect different tumor biology and invasiveness, independent of tumor size[20], regulating outcome.
Dissemination into the lymphatic system is a major route for pancreatic cancer metastasis. Lymph node status has been demonstrated to be one of the most potent predictors of survival. Several recent studies (Table 2) have proposed that the ratio of metastatic to examined lymph nodes (LNR) may be more powerful predictors of survival than the mere dichotomization into positive or negative lymph nodes. LNR also seems to have negative impact on the long-term survival (≥ 60 mo)[21]. Poor prognosis has been observed with an LNR over 0.3-0.4.
Ref. | Year | n | Cut-off | Detection rate (%) | Median OS with highest LNR (mo) | Survival model | HR (95%CI) | P value |
Fouquet et al[34] | 2014 | 166 | 0.2 | 76 (46) | NR | Multivariable | 2.38 (1.4-4.0) | 0.001 |
Dusch et al[21] | 2014 | 415 | Continuous | 0.10 (0-0.81)1 | NR | Multivariable | 1.73 (NR) | 0.002 |
Valsangkar et al[57] | 2013 | 14907 | 0.3 | 4038 (27) | NR | Multivariable | 2.27 (1.67-3.08) | < 0.001 |
Lewis et al[58] | 2013 | 424 | 0.3 | 83 (20) | 16 | Multivariable | 1.97 (NR) | < 0.001 |
Robinson et al[59] | 2012 | 131 | 0.15 | 70 (53) | NR | Multivariable | 4.14 (NR) | < 0.010 |
La Torre et al[60] | 2011 | 101 | 0.2 | 30 (30) | 13 | Multivariable | 4.88 (1.07-22.2) | 0.008 |
Bhatti et al[46] | 2010 | 84 | 0.3 | 26 (31) | 6 | Multivariable | 2.7 (1.6–4.4) | 0.010 |
Riediger et al[61] | 2009 | 182 | 0.3 | 32 (18) | NR | Multivariable | 2.2 (1.4-3.6) | < 0.001 |
Slidell et al[22] | 2008 | 3868 | 0.4 | 602 (16) | 10 | Multivariable | 1.82 (1.59-2.07) | < 0.001 |
Pawlik et al[6] | 2007 | 905 | 0.4 | 154 (17) | 12 | Multivariable | 2.55 (1.75-2.70) | 0.001 |
There is a wide time span in terms of median survival between studies evaluating the impact of lymph node status on survival after resection for pancreatic cancer. Patients with N0 tumors displayed a superior median survival of up to 40 mo and patients with LNR > 0.3 displayed a median survival of 6 mo at the lowest. The wide range in median survival may reflect different biology in those tumors that spread to lymph nodes and those that do not. It may also be speculated that there is a biological difference in the tumor invasiveness both regarding loco-regional and distant lymph node metastases. In general, lymph node metastases can be correlated to increasing tumor size but not in all of the cases.
It is recommended to sample at least 12 lymph nodes for histopathological diagnosis and staging[22]. Standard lymphadenectomy for pancreatic head tumors include resection of lymph node stations 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a and 17b, while tumors of the body and tail of the pancreas require removal of stations 10, 11, and 18. Extended lymphadenectomy during Whipple’s procedure include resection of lymph nodes along the left side of the superior mesenteric artery and around the celiac trunk, splenic artery or left gastric artery. There is no convincing evidence that extensive lymph node resection in conjunction to pancreatic surgery increases the overall survival and is therefore not recommended[23].
Lymph node status may also be defined based on the location of the lymph nodes involved. Several studies describe lymph node involvement as N1 (metastases in loco-regional lymph nodes) or N2-3 (metastases in distant lymph nodes). A few studies evaluated para-aortic lymph denoted as N3. There is a clear survival difference between local or distant lymph nodes metastases (e.g., para-aortic lymph node metastases). Most studies, but not all, report that para-aortic lymph node involvement is associated with a poor prognosis, being an independent factor of adverse outcome (Table 3). Frozen-section examination of para-aortic nodes accurately detects distant lymphatic involvement reliably and should be routinely performed[24]. The presence of metastases is considered a contraindication to proceed with pancreatic resection.
Ref. | Year | n | Detection rate (%) | Median OS with PALN (mo) | Survival model | HR (95%CI) | P value |
Sho et al[62] | 2015 | 882 | 102 (12) | 17 | Multivariable | 1.15 (0.87-1.50) | 0.335 |
Schwarz et al[24] | 2014 | 111 | 17 (15) | 16 | Univariable | NR | 0.038 |
Kanda et al[63] | 2011 | 429 | 49 (11) | 8 | Univariable | NR | 0.006 |
Murakami et al[64] | 2010 | 103 | 18 (17) | 12 | Multivariable | 1.84 (0.28-1.07) | 0.078 |
Doi et al[51] | 2007 | 133 | 19 (14) | 5 | Multivariable | 2.90 (1.60-5.02) | 0.001 |
Shimada et al[65] | 2006 | 133 | 29 (22) | 13 | Univariable | NR | < 0.001 |
The WHO classification of tumor grade in pancreatic cancer is based on the original proposal of Klöppel et al[25] and takes into consideration mucin production, glandular differentiation, mitotic activity and nuclear atypia. Several studies have shown that tumor grade is an important prognostic indicator after resection of pancreatic cancer[26-28]. Wasif et al[29] analyzed 8082 patients with resected pancreatic cancer. This study found that high tumor grade had a larger impact on survival than both tumor size and lymph node metastases, both of which are part of the current TNM staging system. This observation lead the authors to conclude that the inclusion of tumor grade into the TNM staging for pancreatic cancer would improve prognostic stratification and better reflect the aggressive prognosis of poorly differentiated tumors.
Pancreatic tumors may occlude peripancreatic vascular structures, either partly or totally, and in the latter case are categorized as unresectable. The extent of vessel wall involvement, i.e., involvement of tunica adventitia, media or intima, has been correlated with outcome[30]. Invasion of major retroperitoneal blood vessels has been found to be an independent predictor of poor survival[11,30,31]. Vascular resections should be performed if it is possible to obtain R0 resections, which is supported by previous histopathological data[32]. In the situation with positive para-aortic lymph nodes, however, venous and arterial tumor involvement may not be a prognostic factor for survival. It has been speculated that para-aortic lymph node involvement might be a stronger prognostic factor than vascular involvement.
Portal vein and superior mesenteric vein invasion often occurs due to the anatomic location of the tumor. Venous invasion was for a long time considered a contraindication to surgery. Today, vascular resection has become more common. Most studies indicate that vascular resection has similar survival rates as standard resection (Table 4), but it should be performed in carefully selected cases, given the slightly increased perioperative mortality rate and some reports that indicate worse survival, likely due to more advanced disease. Arterial resection during pancreatic resection is associated with poor short- and long-term outcome and is not recommended outside of clinical trials[33].
Ref. | Year | n | VR rate (%) | Median OS without VR/with VR (mo) | Survival model | HR (95%CI) | P value |
Jeong et al[39] | 2015 | 276 | 46 (17) | 16/12 | Multivariable | 1.15 (0.78–1.71) | 0.474 |
Murakami et al[66] | 2015 | 937 | 435 (46) | 26/19 | Multivariable | 1.16 (0.89-1.53) | 0.268 |
Wang et al[67] | 2014 | 122 | 64 (53) | 31/18 | Multivariable | NR | NS |
Kelly et al[68] | 2013 | 492 | 70 (14) | 19/12 | Multivariable | 1.14 (0.83-1.57) | 0.410 |
Gong et al[69] | 2013 | 566 | 119 (21) | 20/13 | Univariable | NR | < 0.050 |
Castleberry et al[70] | 2012 | 3582 | 281 (8) | Increased 30-d postoperative mortality, 2.9% vs 5.7% | Multivariable | 2.1 (1.22-3.73) | 0.008 |
Chakravarty et al[71] | 2010 | 87 | 12 (14) | 10/9 | Multivariable | NR | 0.591 |
Ouaissi et al[72] | 2010 | 149 | 59 (40) | 19/18 | Multivariable | DFS: 0.43 (0.22-0.82) | 0.011 |
Kaneoka et al[49] | 2009 | 84 | 42 (50) | 26/12 | Multivariable | NR | NS |
Kurosaki et al[73] | 2008 | 77 | 35 (45) | 20/20 | Univariable | NR | 0.330 |
Fukuda et al[30] | 2007 | 121 | 37 (31) | NR | Univariable | NR | 0.550 |
Carrère et al[74] | 2006 | 133 | 45 (34) | 19/15 | Univariable | NR | 0.690 |
Shimada et al[75] | 2006 | 149 | 86 (58) | 35/14 | Multivariable | 2.25 (1.09–3.62) | NR |
Tseng et al[76] | 2004 | 291 | 110 (38) | 27/23 | Multivariable | 1.13 (0.79-1.63) | 0.500 |
Poon et al[77] | 2004 | 50 | 12 (24) | 21/20 | Univariable | NR | 0.769 |
Nakagohri et al[78] | 2003 | 81 | 33 (41) | 10/15 | Univariable | NR | NS |
Bachellier et al[79] | 2001 | 87 | 31 (36) | 12/12 | Univariable | NR | 0.480 |
Perineural invasion (PNI) is a common way of pancreatic tumor growth. Several studies have revealed that PNI in specimens from patients who underwent surgical resection was associated with worse survival (Table 5). Data also indicate that perineural involvement is a predictor for early cancer recurrence[34]. The lack of perineural involvement may be a good prognostic marker of disease free survival[35]. However, various criteria for the diagnosis of PNI have been used, and the frequency of PNI in pancreatic cancer varies widely among the previous reports, between 30%-96%. According to a recent study the severity of PNI can be correlated with survival[36]. This study demonstrated that the number of PNIs was a potent predictor of survival in patients with resectable pancreatic cancer.
Ref. | Year | n | Detection rate (%) | Median OS with PNI (mo) | Survival model | HR (95%CI) | P value |
Kondo et al[36] | 2015 | 209 | 197 (94) | 15 | Multivariable | No of PNIs: | < 0.001 |
< 14: 1 | |||||||
14-40: 1.96 (1.01-3.93) | |||||||
> 40: 5.81 (3.17-11.35) | |||||||
Fouquet et al[34] | 2014 | 166 | 133 (81) | NR | Multivariable | 2.77 (1.40-5.26) | 0.001 |
Chatterjee et al[80] | 2012 | 212 | 123 (58) | 29 | Multivariable | 1.70 (1.18-2.45) | 0.005 |
Takahashi et al[81] | 2012 | 110 | 56 (51) | NR | Multivariable | 2.48 (1.11-5.52) | 0.026 |
Sahin et al[82] | 2012 | 544 | 473 (87) | 29 | Multivariable | 1.60 (1.08-2.36) | 0.019 |
Robinson et al[59] | 2012 | 134 | 128 (96) | NR | Multivariable | 5.52 (NR) | < 0.050 |
Kanda et al[63] | 2011 | 429 | 148 (34) | NR | Multivariable | 1.72 (1.15-2.58) | < 0.001 |
Shimada et al[35] | 2011 | 153 | 146 (94) | 7 (DFS) | Multivariable | 2.19 (1.36-3.52) | 0.001 |
Murakami et al[64] | 2010 | 103 | 31 (30) | NR | Multivariable | 1.93 (1.03–3.62) | 0.041 |
Kazanjan et al[83] | 2008 | 182 | 112 (62) | 20 | Multivariable | 2.66 (1.74-4.06) | < 0.001 |
The R classification for pancreatic cancer entails estimation of the radicality of resection. R0 denotes complete microscopic tumor removal. R1 indicates microscopic residual tumor, while R2 indicates macroscopic residual tumor. The influence of margin status on outcomes in pancreatic cancer remains controversial (Table 6). This is largely due to lack of standardization of margin definitions and reporting. Most studies show a worsened prognosis of R1 compared to R0 resection.
Ref. | Year | n | R1 definition | R1 rate (%) | Median OS | Survival model | HR (95% CI) | P value |
R0/R1 (mo) | ||||||||
Kooby et al[37] | 2014 | 1399 | 1 mm | R0 (86) | 21 | Multivariable | 1 | 0.009 |
R1→R0 (5) | 12 | 1.55 (1.11-2.16) | 0.004 | |||||
R1 (9) | 14 | 1.46 (1.13-1.90) | ||||||
Konstantinidis et al[84] | 2013 | 554 | 1 mm | 157 (28) | 35/14 | Univariable | NR | < 0.001 |
Kimbrough et al[85] | 2013 | 283 | 0 mm | 76 (27) | 22/15 | Multivariable | NR | NS |
Gnerlich et al[86] | 2012 | 285 | 1 mm | 97 (34) | 22/16 | Univariable | NR | 0.010 |
Jamieson et al[11] | 2010 | 148 | 1 mm | 110 (74) | 27/15 | Multivariable | 1.76 (1.15–2.28) | 0.009 |
Van den Broeck et al[87] | 2009 | 144 | 1 mm | 48 (33) | 24/12 | Univariable | NR | < 0.001 |
Chang et al[88] | 2009 | 365 | 0 mm | 131 (36) | 20/13 | Multivariable | 1.48 (1.15–1.89) | 0.002 |
Campbell et al[50] | 2009 | 163 | 1 mm | 128 (79) | 25/13 | Multivariable | 1.44 (0.90-2.32) | 0.132 |
Westgaard et al[89] | 2008 | 40 | 1 mm | 18 (45) | 16/11 | Univariable | NR | 0.300 |
Esposito et al[90] | 2008 | 111 | 1 mm | 84 (76) | NR | Univariable | NR | 0.370 |
Raut et al[91] | 2007 | 360 | 0 mm | 61 (17) | 28/22 | Multivariable | NR | NS |
Verbeke et al[92] | 2006 | 26 | 1 mm | 22 (85) | 37/11 | Multivariable | NR | 0.790 |
Howard et al[93] | 2006 | 226 | 0 mm | 68 (30) | NR | Multivariable | 1.39 (1.02-1.90) | 0.030 |
The poor prognosis in R1 resections is underscored by the observation that once tumor cell deposits have reached beyond the resected pancreatic surface area, it is difficult to improve survival by trying to convert R1 to R0 resections. Data show that the overall survival of turning R1 to R0 resections is still not convincingly high and once a positive intraoperative resection margin is discovered on frozen section it is doubtful whether the conversion to R0 resection is a “true R0” since the overall survival is not changed[37].
The definition of margin clearance is still under debate. However, nowadays most studies now use a margin clearance over 1 mm to define R1 resection.
Despite technical advances in the field of pancreatic surgery, the long-term prognosis of pancreatic cancer still remains dismal. This article updates the role of established prognostic factors after curatively intended surgery for pancreatic cancer.
Tumor size is a prognostic factor, with survival decreasing in parallel to increased tumor size. However, small tumors (< 2 cm) may still metastasize and be associated with a poor outcome.
Lymph node involvement is associated with poor survival. A LNR of > 0.3 is a strong prognostic determinant. Para-aortic node sampling with frozen-section examination detects distant lymphatic involvement reliably and should be performed routinely. Metastatic deposits in para-aortic lymph nodes indicate distant disease, and should be considered a contraindication for surgical resection.
Tumor grade may be as powerful a prognostic factor as tumor size and lymph node status.
Invasion of major retroperitoneal blood vessels predicts poor outcome. The extent of vessel wall involvement is correlated with survival. Patients undergoing portal vein resection for pancreatic cancer have a similar long-term prognosis to patients undergoing standard resection.
PNI is present in most pancreatic tumors. The severity of PNI is a novel prognostic factor.
Tumor cells in the resection margin increase the risk of early deaths. A margin clearance over 1 mm should be achieved. However, additional resection to achieve a negative neck margin after positive frozen section is not recommended due to lack of survival advantage.
Manuscript Source: Invited manuscript
Specialty Type: Gastroenterology and Hepatology
Country of Origin: Sweden
Peer-Review Report Classification
Grade A (Excellent): 0
Grade B (Very good): B, B, B
Grade C (Good): 0
Grade D (Fair): 0
Grade E (Poor): 0
P- Reviewer: Kleeff J, Yang F, Zhang ZM S- Editor: Ma YJ L- Editor: A E- Editor: Ma S
1. | Kos FT, Yazici O, Civelek B, Seker M, Arik Z, Aksoy S, Uncu D, Ozdemir N, Zengin N. Evaluation of the effect of comorbidity on survival in pancreatic cancer by using “Charlson Comorbidity Index” and “Cumulative Illness Rating Scale”. Wien Klin Wochenschr. 2014;126:36-41. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 13] [Cited by in F6Publishing: 14] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
2. | Akhtar-Danesh GG, Finley C, Akhtar-Danesh N. Long-term trends in the incidence and relative survival of pancreatic cancer in Canada: A population-based study. Pancreatology. 2016;16:259-265. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 13] [Cited by in F6Publishing: 12] [Article Influence: 1.5] [Reference Citation Analysis (0)] |
3. | Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69-90. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 23762] [Cited by in F6Publishing: 25273] [Article Influence: 1944.1] [Reference Citation Analysis (6)] |
4. | Nitecki SS, Sarr MG, Colby TV, van Heerden JA. Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving? Ann Surg. 1995;221:59-66. [PubMed] [Cited in This Article: ] |
5. | Yeo CJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt HA, Talamini MA, Hruban RH, Ord SE, Sauter PK, Coleman J. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg. 1997;226:248-257; discussion 257-260. [PubMed] [Cited in This Article: ] |
6. | Pawlik TM, Gleisner AL, Cameron JL, Winter JM, Assumpcao L, Lillemoe KD, Wolfgang C, Hruban RH, Schulick RD, Yeo CJ. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007;141:610-618. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 334] [Cited by in F6Publishing: 341] [Article Influence: 20.1] [Reference Citation Analysis (0)] |
7. | Fortner JG, Klimstra DS, Senie RT, Maclean BJ. Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy. Ann Surg. 1996;223:147-153. [PubMed] [Cited in This Article: ] |
8. | Paniccia A, Hosokawa P, Henderson W, Schulick RD, Edil BH, McCarter MD, Gajdos C. Characteristics of 10-Year Survivors of Pancreatic Ductal Adenocarcinoma. JAMA Surg. 2015;150:701-710. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 110] [Cited by in F6Publishing: 118] [Article Influence: 13.1] [Reference Citation Analysis (0)] |
9. | Ferrone CR, Pieretti-Vanmarcke R, Bloom JP, Zheng H, Szymonifka J, Wargo JA, Thayer SP, Lauwers GY, Deshpande V, Mino-Kenudson M. Pancreatic ductal adenocarcinoma: long-term survival does not equal cure. Surgery. 2012;152:S43-S49. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 152] [Cited by in F6Publishing: 152] [Article Influence: 12.7] [Reference Citation Analysis (0)] |
10. | Petermann D, Demartines N, Schäfer M. Is tumour size an underestimated feature in the current TNM system for malignancies of the pancreatic head? HPB (Oxford). 2013;15:872-881. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 14] [Cited by in F6Publishing: 14] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
11. | Jamieson NB, Foulis AK, Oien KA, Dickson EJ, Imrie CW, Carter R, McKay CJ. Peripancreatic fat invasion is an independent predictor of poor outcome following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. J Gastrointest Surg. 2011;15:512-524. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 20] [Cited by in F6Publishing: 21] [Article Influence: 1.6] [Reference Citation Analysis (0)] |
12. | Warren BF. Resection margins and R1 rates in pancreatic cancer--are we there yet? Histopathology. 2008;53:599; author reply 599. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 3] [Cited by in F6Publishing: 3] [Article Influence: 0.2] [Reference Citation Analysis (0)] |
13. | Michalski CW, Weitz J, Büchler MW. Surgery insight: surgical management of pancreatic cancer. Nat Clin Pract Oncol. 2007;4:526-535. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 51] [Cited by in F6Publishing: 53] [Article Influence: 3.1] [Reference Citation Analysis (0)] |
14. | Franko J, Hugec V, Lopes TL, Goldman CD. Survival among pancreaticoduodenectomy patients treated for pancreatic head cancer & lt; 1 or 2 cm. Ann Surg Oncol. 2013;20:357-361. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 15] [Cited by in F6Publishing: 16] [Article Influence: 1.3] [Reference Citation Analysis (0)] |
15. | Shin SH, Kim SC, Hong SM, Song KB, Lee JH, Park KM, Lee YJ. Can statistically determined prognostic factors predict the long-term survival of patients with pancreatic ductal adenocarcinoma following surgical resection?: Clinicopathological analysis of 82 long-term survivors. Pancreas. 2014;43:571-577. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 16] [Cited by in F6Publishing: 14] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
16. | Izumi S, Nakamura S, Mano S, Onoda Y. Well-differentiated pancreatic ductal adenocarcinomas measuring ≤ 1 cm exhibit early features of tumor progression: a report of five lesions and a comparative study with advanced lesions. Surg Today. 2014;44:2058-2064. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 6] [Cited by in F6Publishing: 6] [Article Influence: 0.5] [Reference Citation Analysis (0)] |
17. | Hur C, Tramontano AC, Dowling EC, Brooks GA, Jeon A, Brugge WR, Gazelle GS, Kong CY, Pandharipande PV. Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size: Positive Implications for Future Targeted Screening. Pancreas. 2015; Epub ahead of print. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 25] [Cited by in F6Publishing: 26] [Article Influence: 3.3] [Reference Citation Analysis (0)] |
18. | Hong SM, Goggins M, Wolfgang CL, Schulick RD, Edil BH, Cameron JL, Handra-Luca A, Herman JM, Hruban RH. Vascular invasion in infiltrating ductal adenocarcinoma of the pancreas can mimic pancreatic intraepithelial neoplasia: a histopathologic study of 209 cases. Am J Surg Pathol. 2012;36:235-241. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 31] [Cited by in F6Publishing: 34] [Article Influence: 2.8] [Reference Citation Analysis (0)] |
19. | Bagci P, Andea AA, Basturk O, Jang KT, Erbarut I, Adsay V. Large duct type invasive adenocarcinoma of the pancreas with microcystic and papillary patterns: a potential microscopic mimic of non-invasive ductal neoplasia. Mod Pathol. 2012;25:439-448. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 34] [Cited by in F6Publishing: 36] [Article Influence: 3.0] [Reference Citation Analysis (0)] |
20. | Cleary SP, Gryfe R, Guindi M, Greig P, Smith L, Mackenzie R, Strasberg S, Hanna S, Taylor B, Langer B. Prognostic factors in resected pancreatic adenocarcinoma: analysis of actual 5-year survivors. J Am Coll Surg. 2004;198:722-731. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 262] [Cited by in F6Publishing: 253] [Article Influence: 12.7] [Reference Citation Analysis (0)] |
21. | Dusch N, Weiss C, Ströbel P, Kienle P, Post S, Niedergethmann M. Factors predicting long-term survival following pancreatic resection for ductal adenocarcinoma of the pancreas: 40 years of experience. J Gastrointest Surg. 2014;18:674-681. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 44] [Cited by in F6Publishing: 46] [Article Influence: 4.6] [Reference Citation Analysis (0)] |
22. | Slidell MB, Chang DC, Cameron JL, Wolfgang C, Herman JM, Schulick RD, Choti MA, Pawlik TM. Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis. Ann Surg Oncol. 2008;15:165-174. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 286] [Cited by in F6Publishing: 297] [Article Influence: 18.6] [Reference Citation Analysis (0)] |
23. | Tol JA, Gouma DJ, Bassi C, Dervenis C, Montorsi M, Adham M, Andrén-Sandberg A, Asbun HJ, Bockhorn M, Büchler MW. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery. 2014;156:591-600. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 458] [Cited by in F6Publishing: 440] [Article Influence: 44.0] [Reference Citation Analysis (0)] |
24. | Schwarz L, Lupinacci RM, Svrcek M, Lesurtel M, Bubenheim M, Vuarnesson H, Balladur P, Paye F. Para-aortic lymph node sampling in pancreatic head adenocarcinoma. Br J Surg. 2014;101:530-538. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 88] [Cited by in F6Publishing: 87] [Article Influence: 8.7] [Reference Citation Analysis (0)] |
25. | Klöppel G, Lingenthal G, von Bülow M, Kern HF. Histological and fine structural features of pancreatic ductal adenocarcinomas in relation to growth and prognosis: studies in xenografted tumours and clinico-histopathological correlation in a series of 75 cases. Histopathology. 1985;9:841-856. [PubMed] [Cited in This Article: ] |
26. | Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg. 2003;237:74-85. [PubMed] [DOI] [Cited in This Article: ] [Cited by in F6Publishing: 11] [Reference Citation Analysis (0)] |
27. | Kuhlmann KF, de Castro SM, Wesseling JG, ten Kate FJ, Offerhaus GJ, Busch OR, van Gulik TM, Obertop H, Gouma DJ. Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients. Eur J Cancer. 2004;40:549-558. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 217] [Cited by in F6Publishing: 196] [Article Influence: 9.8] [Reference Citation Analysis (0)] |
28. | Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, Hodgin MB, Sauter PK, Hruban RH, Riall TS. 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg. 2006;10:1199-1210; discussion 1210-1211. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 1125] [Cited by in F6Publishing: 1090] [Article Influence: 60.6] [Reference Citation Analysis (0)] |
29. | Wasif N, Ko CY, Farrell J, Wainberg Z, Hines OJ, Reber H, Tomlinson JS. Impact of tumor grade on prognosis in pancreatic cancer: should we include grade in AJCC staging? Ann Surg Oncol. 2010;17:2312-2320. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 91] [Cited by in F6Publishing: 102] [Article Influence: 7.3] [Reference Citation Analysis (0)] |
30. | Fukuda S, Oussoultzoglou E, Bachellier P, Rosso E, Nakano H, Audet M, Jaeck D. Significance of the depth of portal vein wall invasion after curative resection for pancreatic adenocarcinoma. Arch Surg. 2007;142:172-179; discussion 180. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 89] [Cited by in F6Publishing: 96] [Article Influence: 5.6] [Reference Citation Analysis (0)] |
31. | Liu L, Katz MH, Lee SM, Fischer LK, Prakash L, Parker N, Wang H, Varadhachary GR, Wolff RA, Lee JE. Superior Mesenteric Artery Margin of Posttherapy Pancreaticoduodenectomy and Prognosis in Patients With Pancreatic Ductal Adenocarcinoma. Am J Surg Pathol. 2015;39:1395-1403. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 45] [Cited by in F6Publishing: 46] [Article Influence: 5.1] [Reference Citation Analysis (0)] |
32. | Rehders A, Stoecklein NH, Güray A, Riediger R, Alexander A, Knoefel WT. Vascular invasion in pancreatic cancer: tumor biology or tumor topography? Surgery. 2012;152:S143-S151. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 33] [Cited by in F6Publishing: 29] [Article Influence: 2.4] [Reference Citation Analysis (0)] |
33. | Mollberg N, Rahbari NN, Koch M, Hartwig W, Hoeger Y, Büchler MW, Weitz J. Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg. 2011;254:882-893. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 337] [Cited by in F6Publishing: 316] [Article Influence: 26.3] [Reference Citation Analysis (0)] |
34. | Fouquet T, Germain A, Brunaud L, Bresler L, Ayav A. Is perineural invasion more accurate than other factors to predict early recurrence after pancreatoduodenectomy for pancreatic head adenocarcinoma? World J Surg. 2014;38:2132-2137. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 16] [Cited by in F6Publishing: 17] [Article Influence: 1.7] [Reference Citation Analysis (0)] |
35. | Shimada K, Nara S, Esaki M, Sakamoto Y, Kosuge T, Hiraoka N. Intrapancreatic nerve invasion as a predictor for recurrence after pancreaticoduodenectomy in patients with invasive ductal carcinoma of the pancreas. Pancreas. 2011;40:464-468. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 39] [Cited by in F6Publishing: 39] [Article Influence: 3.0] [Reference Citation Analysis (0)] |
36. | Kondo N, Murakami Y, Uemura K, Hashimoto Y, Nakagawa N, Sasaki H, Sueda T. An Increased Number of Perineural Invasions Is Independently Associated With Poor Survival of Patients With Resectable Pancreatic Ductal Adenocarcinoma. Pancreas. 2015;44:1345-1351. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 6] [Cited by in F6Publishing: 4] [Article Influence: 0.4] [Reference Citation Analysis (0)] |
37. | Kooby DA, Lad NL, Squires MH, Maithel SK, Sarmiento JM, Staley CA, Adsay NV, El-Rayes BF, Weber SM, Winslow ER. Value of intraoperative neck margin analysis during Whipple for pancreatic adenocarcinoma: a multicenter analysis of 1399 patients. Ann Surg. 2014;260:494-501; discussion 501-503. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 76] [Cited by in F6Publishing: 77] [Article Influence: 7.7] [Reference Citation Analysis (0)] |
38. | Matsumoto I, Murakami Y, Shinzeki M, Asari S, Goto T, Tani M, Motoi F, Uemura K, Sho M, Satoi S. Proposed preoperative risk factors for early recurrence in patients with resectable pancreatic ductal adenocarcinoma after surgical resection: A multi-center retrospective study. Pancreatology. 2015;15:674-680. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 68] [Cited by in F6Publishing: 86] [Article Influence: 9.6] [Reference Citation Analysis (0)] |
39. | Jeong J, Choi DW, Choi SH, Heo JS, Jang KT. Long-term outcome of portomesenteric vein invasion and prognostic factors in pancreas head adenocarcinoma. ANZ J Surg. 2015;85:264-269. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 22] [Cited by in F6Publishing: 24] [Article Influence: 2.7] [Reference Citation Analysis (0)] |
40. | Yamamoto T, Yagi S, Kinoshita H, Sakamoto Y, Okada K, Uryuhara K, Morimoto T, Kaihara S, Hosotani R. Long-term survival after resection of pancreatic cancer: a single-center retrospective analysis. World J Gastroenterol. 2015;21:262-268. [PubMed] [DOI] [Cited in This Article: ] [Cited by in CrossRef: 80] [Cited by in F6Publishing: 71] [Article Influence: 7.9] [Reference Citation Analysis (0)] |
41. | Elberm H, Ravikumar R, Sabin C, Abu Hilal M, Al-Hilli A, Aroori S, Bond-Smith G, Bramhall S, Coldham C, Hammond J. Outcome after pancreaticoduodenectomy for T3 adenocarcinoma: A multivariable analysis from the UK Vascular Resection for Pancreatic Cancer Study Group. Eur J Surg Oncol. 2015;41:1500-1507. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 29] [Cited by in F6Publishing: 33] [Article Influence: 3.7] [Reference Citation Analysis (0)] |
42. | Okada S, Okusaka T, Ishii H, Kyogoku A, Yoshimori M, Kajimura N, Yamaguchi K, Kakizoe T. Elevated serum interleukin-6 levels in patients with pancreatic cancer. Jpn J Clin Oncol. 1998;28:12-15. [PubMed] [Cited in This Article: ] |
43. | Jamieson NB, Chan NI, Foulis AK, Dickson EJ, McKay CJ, Carter CR. The prognostic influence of resection margin clearance following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. J Gastrointest Surg. 2013;17:511-521. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 66] [Cited by in F6Publishing: 62] [Article Influence: 5.6] [Reference Citation Analysis (0)] |
44. | Lad NL, Squires MH, Maithel SK, Fisher SB, Mehta VV, Cardona K, Russell MC, Staley CA, Adsay NV, Kooby DA. Is it time to stop checking frozen section neck margins during pancreaticoduodenectomy? Ann Surg Oncol. 2013;20:3626-3633. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 38] [Cited by in F6Publishing: 41] [Article Influence: 3.7] [Reference Citation Analysis (0)] |
45. | Sugiura T, Uesaka K, Mihara K, Sasaki K, Kanemoto H, Mizuno T, Okamura Y. Margin status, recurrence pattern, and prognosis after resection of pancreatic cancer. Surgery. 2013;154:1078-1086. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 70] [Cited by in F6Publishing: 70] [Article Influence: 6.4] [Reference Citation Analysis (0)] |
46. | Bhatti I, Peacock O, Awan AK, Semeraro D, Larvin M, Hall RI. Lymph node ratio versus number of affected lymph nodes as predictors of survival for resected pancreatic adenocarcinoma. World J Surg. 2010;34:768-775. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 51] [Cited by in F6Publishing: 56] [Article Influence: 4.0] [Reference Citation Analysis (0)] |
47. | Yamada S, Nakao A, Fujii T, Sugimoto H, Kanazumi N, Nomoto S, Kodera Y, Takeda S. Pancreatic cancer with paraaortic lymph node metastasis: a contraindication for radical surgery? Pancreas. 2009;38:e13-e17. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 54] [Cited by in F6Publishing: 49] [Article Influence: 3.3] [Reference Citation Analysis (0)] |
48. | Ueda M, Endo I, Nakashima M, Minami Y, Takeda K, Matsuo K, Nagano Y, Tanaka K, Ichikawa Y, Togo S. Prognostic factors after resection of pancreatic cancer. World J Surg. 2009;33:104-110. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 67] [Cited by in F6Publishing: 69] [Article Influence: 4.6] [Reference Citation Analysis (0)] |
49. | Kaneoka Y, Yamaguchi A, Isogai M. Portal or superior mesenteric vein resection for pancreatic head adenocarcinoma: prognostic value of the length of venous resection. Surgery. 2009;145:417-425. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 85] [Cited by in F6Publishing: 92] [Article Influence: 6.1] [Reference Citation Analysis (0)] |
50. | Campbell F, Smith RA, Whelan P, Sutton R, Raraty M, Neoptolemos JP, Ghaneh P. Classification of R1 resections for pancreatic cancer: the prognostic relevance of tumour involvement within 1 mm of a resection margin. Histopathology. 2009;55:277-283. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 192] [Cited by in F6Publishing: 195] [Article Influence: 13.0] [Reference Citation Analysis (0)] |
51. | Doi R, Kami K, Ito D, Fujimoto K, Kawaguchi Y, Wada M, Kogire M, Hosotani R, Imamura M, Uemoto S. Prognostic implication of para-aortic lymph node metastasis in resectable pancreatic cancer. World J Surg. 2007;31:147-154. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 65] [Cited by in F6Publishing: 73] [Article Influence: 4.3] [Reference Citation Analysis (0)] |
52. | Zacharias T, Jaeck D, Oussoultzoglou E, Neuville A, Bachellier P. Impact of lymph node involvement on long-term survival after R0 pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas. J Gastrointest Surg. 2007;11:350-356. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 57] [Cited by in F6Publishing: 57] [Article Influence: 3.4] [Reference Citation Analysis (0)] |
53. | Moon HJ, An JY, Heo JS, Choi SH, Joh JW, Kim YI. Predicting survival after surgical resection for pancreatic ductal adenocarcinoma. Pancreas. 2006;32:37-43. [PubMed] [Cited in This Article: ] |
54. | Ahmad NA, Lewis JD, Ginsberg GG, Haller DG, Morris JB, Williams NN, Rosato EF, Kochman ML. Long term survival after pancreatic resection for pancreatic adenocarcinoma. Am J Gastroenterol. 2001;96:2609-2615. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 75] [Cited by in F6Publishing: 81] [Article Influence: 3.5] [Reference Citation Analysis (0)] |
55. | Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, Sauter PK, Coleman J, Hruban RH, Lillemoe KD. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4:567-579. [PubMed] [Cited in This Article: ] |
56. | Meyer W, Jurowich C, Reichel M, Steinhäuser B, Wünsch PH, Gebhardt C. Pathomorphological and histological prognostic factors in curatively resected ductal adenocarcinoma of the pancreas. Surg Today. 2000;30:582-587. [PubMed] [Cited in This Article: ] |
57. | Valsangkar NP, Bush DM, Michaelson JS, Ferrone CR, Wargo JA, Lillemoe KD, Fernández-del Castillo C, Warshaw AL, Thayer SP. N0/N1, PNL, or LNR? The effect of lymph node number on accurate survival prediction in pancreatic ductal adenocarcinoma. J Gastrointest Surg. 2013;17:257-266. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 104] [Cited by in F6Publishing: 107] [Article Influence: 9.7] [Reference Citation Analysis (0)] |
58. | Lewis R, Drebin JA, Callery MP, Fraker D, Kent TS, Gates J, Vollmer CM. A contemporary analysis of survival for resected pancreatic ductal adenocarcinoma. HPB (Oxford). 2013;15:49-60. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 80] [Cited by in F6Publishing: 80] [Article Influence: 7.3] [Reference Citation Analysis (0)] |
59. | Robinson SM, Rahman A, Haugk B, French JJ, Manas DM, Jaques BC, Charnley RM, White SA. Metastatic lymph node ratio as an important prognostic factor in pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2012;38:333-339. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 52] [Cited by in F6Publishing: 51] [Article Influence: 4.3] [Reference Citation Analysis (0)] |
60. | La Torre M, Cavallini M, Ramacciato G, Cosenza G, Rossi Del Monte S, Nigri G, Ferri M, Mercantini P, Ziparo V. Role of the lymph node ratio in pancreatic ductal adenocarcinoma. Impact on patient stratification and prognosis. J Surg Oncol. 2011;104:629-633. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 43] [Cited by in F6Publishing: 44] [Article Influence: 3.4] [Reference Citation Analysis (0)] |
61. | Riediger H, Keck T, Wellner U, zur Hausen A, Adam U, Hopt UT, Makowiec F. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg. 2009;13:1337-1344. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 267] [Cited by in F6Publishing: 276] [Article Influence: 18.4] [Reference Citation Analysis (0)] |
62. | Sho M, Murakami Y, Motoi F, Satoi S, Matsumoto I, Kawai M, Honda G, Uemura K, Yanagimoto H, Kurata M. Postoperative prognosis of pancreatic cancer with para-aortic lymph node metastasis: a multicenter study on 822 patients. J Gastroenterol. 2015;50:694-702. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 52] [Cited by in F6Publishing: 56] [Article Influence: 6.2] [Reference Citation Analysis (0)] |
63. | Kanda M, Fujii T, Nagai S, Kodera Y, Kanzaki A, Sahin TT, Hayashi M, Yamada S, Sugimoto H, Nomoto S. Pattern of lymph node metastasis spread in pancreatic cancer. Pancreas. 2011;40:951-955. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 74] [Cited by in F6Publishing: 77] [Article Influence: 5.9] [Reference Citation Analysis (0)] |
64. | Murakami Y, Uemura K, Sudo T, Hashimoto Y, Yuasa Y, Sueda T. Prognostic impact of para-aortic lymph node metastasis in pancreatic ductal adenocarcinoma. World J Surg. 2010;34:1900-1907. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 56] [Cited by in F6Publishing: 57] [Article Influence: 4.1] [Reference Citation Analysis (0)] |
65. | Shimada K, Sakamoto Y, Sano T, Kosuge T. The role of paraaortic lymph node involvement on early recurrence and survival after macroscopic curative resection with extended lymphadenectomy for pancreatic carcinoma. J Am Coll Surg. 2006;203:345-352. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 75] [Cited by in F6Publishing: 80] [Article Influence: 4.4] [Reference Citation Analysis (0)] |
66. | Murakami Y, Satoi S, Motoi F, Sho M, Kawai M, Matsumoto I, Honda G; Multicentre Study Group of Pancreatobiliary Surgery (MSG-PBS). Portal or superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head carcinoma. Br J Surg. 2015;102:837-846. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 85] [Cited by in F6Publishing: 87] [Article Influence: 9.7] [Reference Citation Analysis (0)] |
67. | Wang F, Gill AJ, Neale M, Puttaswamy V, Gananadha S, Pavlakis N, Clarke S, Hugh TJ, Samra JS. Adverse tumor biology associated with mesenterico-portal vein resection influences survival in patients with pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2014;21:1937-1947. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 32] [Cited by in F6Publishing: 32] [Article Influence: 3.2] [Reference Citation Analysis (0)] |
68. | Kelly KJ, Winslow E, Kooby D, Lad NL, Parikh AA, Scoggins CR, Ahmad S, Martin RC, Maithel SK, Kim HJ. Vein involvement during pancreaticoduodenectomy: is there a need for redefinition of “borderline resectable disease”? J Gastrointest Surg. 2013;17:1209-1217; discussion 1217. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 60] [Cited by in F6Publishing: 63] [Article Influence: 5.7] [Reference Citation Analysis (0)] |
69. | Gong Y, Zhang L, He T, Ding J, Zhang H, Chen G, Zhang D, Wu Z, Chen Q, Fan H. Pancreaticoduodenectomy combined with vascular resection and reconstruction for patients with locally advanced pancreatic cancer: a multicenter, retrospective analysis. PLoS One. 2013;8:e70340. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 42] [Cited by in F6Publishing: 44] [Article Influence: 4.0] [Reference Citation Analysis (0)] |
70. | Castleberry AW, White RR, De La Fuente SG, Clary BM, Blazer DG, McCann RL, Pappas TN, Tyler DS, Scarborough JE. The impact of vascular resection on early postoperative outcomes after pancreaticoduodenectomy: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database. Ann Surg Oncol. 2012;19:4068-4077. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 101] [Cited by in F6Publishing: 93] [Article Influence: 7.8] [Reference Citation Analysis (0)] |
71. | Chakravarty KD, Hsu JT, Liu KH, Yeh CN, Yeh TS, Hwang TL, Jan YY, Chen MF. Prognosis and feasibility of en-bloc vascular resection in stage II pancreatic adenocarcinoma. World J Gastroenterol. 2010;16:997-1002. [PubMed] [Cited in This Article: ] |
72. | Ouaissi M, Hubert C, Verhelst R, Astarci P, Sempoux C, Jouret-Mourin A, Loundou A, Gigot JF; Multidisciplary HPB Group of Center of Cancer. Vascular reconstruction during pancreatoduodenectomy for ductal adenocarcinoma of the pancreas improves resectability but does not achieve cure. World J Surg. 2010;34:2648-2661. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 50] [Cited by in F6Publishing: 45] [Article Influence: 3.2] [Reference Citation Analysis (0)] |
73. | Kurosaki I, Hatakeyama K, Minagawa M, Sato D. Portal vein resection in surgery for cancer of biliary tract and pancreas: special reference to the relationship between the surgical outcome and site of primary tumor. J Gastrointest Surg. 2008;12:907-918. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 41] [Cited by in F6Publishing: 42] [Article Influence: 2.6] [Reference Citation Analysis (0)] |
74. | Carrère N, Sauvanet A, Goere D, Kianmanesh R, Vullierme MP, Couvelard A, Ruszniewski P, Belghiti J. Pancreaticoduodenectomy with mesentericoportal vein resection for adenocarcinoma of the pancreatic head. World J Surg. 2006;30:1526-1535. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 93] [Cited by in F6Publishing: 87] [Article Influence: 4.8] [Reference Citation Analysis (0)] |
75. | Shimada K, Sano T, Sakamoto Y, Kosuge T. Clinical implications of combined portal vein resection as a palliative procedure in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma. Ann Surg Oncol. 2006;13:1569-1578. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 66] [Cited by in F6Publishing: 71] [Article Influence: 3.9] [Reference Citation Analysis (0)] |
76. | Tseng JF, Raut CP, Lee JE, Pisters PW, Vauthey JN, Abdalla EK, Gomez HF, Sun CC, Crane CH, Wolff RA. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg. 2004;8:935-949; discussion 949-950. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 418] [Cited by in F6Publishing: 392] [Article Influence: 19.6] [Reference Citation Analysis (0)] |
77. | Poon RT, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C, Wong J. Pancreaticoduodenectomy with en bloc portal vein resection for pancreatic carcinoma with suspected portal vein involvement. World J Surg. 2004;28:602-608. [PubMed] [Cited in This Article: ] |
78. | Nakagohri T, Kinoshita T, Konishi M, Inoue K, Takahashi S. Survival benefits of portal vein resection for pancreatic cancer. Am J Surg. 2003;186:149-153. [PubMed] [Cited in This Article: ] |
79. | Bachellier P, Nakano H, Oussoultzoglou PD, Weber JC, Boudjema K, Wolf PD, Jaeck D. Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile? Am J Surg. 2001;182:120-129. [PubMed] [Cited in This Article: ] |
80. | Chatterjee D, Katz MH, Rashid A, Wang H, Iuga AC, Varadhachary GR, Wolff RA, Lee JE, Pisters PW, Crane CH. Perineural and intraneural invasion in posttherapy pancreaticoduodenectomy specimens predicts poor prognosis in patients with pancreatic ductal adenocarcinoma. Am J Surg Pathol. 2012;36:409-417. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 127] [Cited by in F6Publishing: 144] [Article Influence: 12.0] [Reference Citation Analysis (0)] |
81. | Takahashi H, Ohigashi H, Ishikawa O, Gotoh K, Yamada T, Nagata S, Tomita Y, Eguchi H, Doki Y, Yano M. Perineural invasion and lymph node involvement as indicators of surgical outcome and pattern of recurrence in the setting of preoperative gemcitabine-based chemoradiation therapy for resectable pancreatic cancer. Ann Surg. 2012;255:95-102. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 89] [Cited by in F6Publishing: 97] [Article Influence: 8.1] [Reference Citation Analysis (0)] |
82. | Sahin IH, Shama MA, Tanaka M, Abbruzzese JL, Curley SA, Hassan M, Li D. Association of diabetes and perineural invasion in pancreatic cancer. Cancer Med. 2012;1:357-362. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 24] [Cited by in F6Publishing: 23] [Article Influence: 1.9] [Reference Citation Analysis (0)] |
83. | Kazanjian KK, Hines OJ, Duffy JP, Yoon DY, Cortina G, Reber HA. Improved survival following pancreaticoduodenectomy to treat adenocarcinoma of the pancreas: the influence of operative blood loss. Arch Surg. 2008;143:1166-1171. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 68] [Cited by in F6Publishing: 71] [Article Influence: 4.7] [Reference Citation Analysis (0)] |
84. | Konstantinidis IT, Warshaw AL, Allen JN, Blaszkowsky LS, Castillo CF, Deshpande V, Hong TS, Kwak EL, Lauwers GY, Ryan DP. Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a “true” R0 resection? Ann Surg. 2013;257:731-736. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 281] [Cited by in F6Publishing: 284] [Article Influence: 25.8] [Reference Citation Analysis (0)] |
85. | Kimbrough CW, St Hill CR, Martin RC, McMasters KM, Scoggins CR. Tumor-positive resection margins reflect an aggressive tumor biology in pancreatic cancer. J Surg Oncol. 2013;107:602-607. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 36] [Cited by in F6Publishing: 42] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
86. | Gnerlich JL, Luka SR, Deshpande AD, Dubray BJ, Weir JS, Carpenter DH, Brunt EM, Strasberg SM, Hawkins WG, Linehan DC. Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch Surg. 2012;147:753-760. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 107] [Cited by in F6Publishing: 110] [Article Influence: 9.2] [Reference Citation Analysis (0)] |
87. | Van den Broeck A, Sergeant G, Ectors N, Van Steenbergen W, Aerts R, Topal B. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2009;35:600-604. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 217] [Cited by in F6Publishing: 217] [Article Influence: 14.5] [Reference Citation Analysis (0)] |
88. | Chang DK, Johns AL, Merrett ND, Gill AJ, Colvin EK, Scarlett CJ, Nguyen NQ, Leong RW, Cosman PH, Kelly MI. Margin clearance and outcome in resected pancreatic cancer. J Clin Oncol. 2009;27:2855-2862. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 245] [Cited by in F6Publishing: 240] [Article Influence: 16.0] [Reference Citation Analysis (0)] |
89. | Westgaard A, Tafjord S, Farstad IN, Cvancarova M, Eide TJ, Mathisen O, Clausen OP, Gladhaug IP. Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor. BMC Cancer. 2008;8:5. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 97] [Cited by in F6Publishing: 97] [Article Influence: 6.1] [Reference Citation Analysis (0)] |
90. | Esposito I, Kleeff J, Bergmann F, Reiser C, Herpel E, Friess H, Schirmacher P, Büchler MW. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651-1660. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 454] [Cited by in F6Publishing: 547] [Article Influence: 34.2] [Reference Citation Analysis (0)] |
91. | Raut CP, Tseng JF, Sun CC, Wang H, Wolff RA, Crane CH, Hwang R, Vauthey JN, Abdalla EK, Lee JE. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007;246:52-60. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 449] [Cited by in F6Publishing: 437] [Article Influence: 25.7] [Reference Citation Analysis (0)] |
92. | Verbeke CS, Leitch D, Menon KV, McMahon MJ, Guillou PJ, Anthoney A. Redefining the R1 resection in pancreatic cancer. Br J Surg. 2006;93:1232-1237. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 419] [Cited by in F6Publishing: 427] [Article Influence: 23.7] [Reference Citation Analysis (0)] |
93. | Howard TJ, Krug JE, Yu J, Zyromski NJ, Schmidt CM, Jacobson LE, Madura JA, Wiebke EA, Lillemoe KD. A margin-negative R0 resection accomplished with minimal postoperative complications is the surgeon’s contribution to long-term survival in pancreatic cancer. J Gastrointest Surg. 2006;10:1338-1345; discussion 1345-1346. [PubMed] [DOI] [Cited in This Article: ] [Cited by in Crossref: 246] [Cited by in F6Publishing: 253] [Article Influence: 14.1] [Reference Citation Analysis (0)] |