In this study, we examined the prognostic significance of histologic tumor involvement of the resected SMV/PV in 225 consecutive patients with stage II PAC who received neoadjuvant therapy and subsequently underwent PD with or without SMV/PV resection. We found that histologic tumor involvement of the SMV/PV was an independent predictor of both DFS and OS. However, the addition of venous resection to PD itself had no significant impact on either DFS or OS. Our results highlight the clinical importance of careful histologic evaluation of the resected SMV/PV in PD specimens.
The current consensus in patients with borderline resectable PDAC is PD with venous resection if complete gross resection of tumor can be achieved.15
There is also growing evidence that the use of neoadjuvant therapy may be a rational treatment approach for patients with potentially resectable disease because it could potentially downstages the disease and increases the likelihood of a complete resection.8
However, data on the prognostic importance of tumor involvement of the resected vein in patients with PAC who underwent PD with venous resection are conflicting, with some reports demonstrating that histologic evidence of tumor in the vein conferred a worse survival duration by univariate analysis16–19
while other reports found no significant difference in survival between patients who had tumor involvement of the resected vein and those who did not.20–22
In addition, most of the above studies were smaller series with analysis of fewer than 50 patients who underwent SMV/PV resection16, 18, 20, 21, 23–30
and also lacked standardized evaluation of the resected SMV/PV. In this study, we included only patients with stage II PAC who received neoadjuvant therapy and PD with or without SMV/PV resection. The resected portion or segment of SMV/PV in the PD specimen was entirely submitted for histologic evaluation in all patients who underwent SMV/PV resection. Therefore, we not only had complete and accurate histologic evaluation of the tumor involvement in various layers of the resected SMV/PV, but also of the margin status of the resected vein. It is difficult to distinguish fibrosis involving the adventitia of SMV/PV secondary to inflammation or neoadjuvant therapy from fibrosis secondary to tumor involvement with complete response following neoadjuvant therapy. In this study, we defined the tumor involvement of the adventitia of SMV/PV as presence of viable tumor cells to ≤ 1.0 mm from the media with fibrosis extends to the media of the vein. We found tumor involvement of the resected SMV/PV in 67% of our patients who underwent SMV/PV resection. This result is similar to the reported vein involvement of 43% to 100% in a recent meta-analysis reported by Ramacciato et al. which included 12 studies16–18, 20, 21, 23–29
of patients with PDAC who underwent pancreatic resection (PD, distal pancreatectomy and total pancreatectomy) with or without SMV/PV resection published between 2000 and 2008 7,16–18, 20, 21, 23–29
and 78% (86 of 110 patients) reported by Muller et al. However, only 16 of 110 patients in Muller’s study and none of the patients in other 12 studies received neoadjuvant therapy. The average intra-operative blood loss reported by the 12 studies ranged from approximately 700 mL to 3100 mL, which is similar to average blood loss of 900 mL in our study. Among the four studies which included more than 30 patients who underwent SMV/PV resection,16–18, 27
the R1 resection rates were higher (14.3% to 38.4%), compared to 12% in our study. The median OS of 32.2 months in our patient population is better than the 13 to 22 months reported in the previous studies16–18, 21, 24–26
, this difference may be due to the highly selected population of patients reported here, all of whom underwent for PD with or without vein resection following neoadjuvant therapy in our study.
Many studies have shown that the addition of venous resection to PD is safe and feasible in the treatment of patients with PAC.5, 16, 18–21, 25, 26
In this study, we found that addition of SMV/PV resection itself to PD does not affect either DFS or OS when compared to the patients with PAC who underwent PD alone. Our data are in agreement with previous studies that SMV/PV resection can be safely performed with PD in patients with PAC. Patients with PAC invasion into the adventitia, vein wall or lumen of the resected SMV/PV (vein involved) had shorter DFS and OS than those who had no histologic tumor involvement of the resected SMV/PV or those who underwent PD alone. Our results demonstrate that histologic tumor involvement of the resected SMV/PV is an independent prognostic factor for both poorer DFS and OS by multivariate analysis. In addition, our data also demonstrate that tumor involvement of the resected vein is associated with larger tumor size, increased intra-operative blood loss, higher rates of positive margins and local/distant recurrence, which are similar to a previous study.17
These findings suggest that histologic tumor involvement of the resected vein can lead to an increased likelihood of residual tumor being present even after an attempted curative resection. In contrast to prior studies, which found that the depth of invasion into the resected SMV/PV correlated with the prognosis, 31, 32
our data did not show significant differences in either DFS or OS in patients with tumor invasion into the adventitia, wall, or lumen of the resected SMV/PV (p>0.05).
In summary, we found that histologic tumor involvement of the resected SMV/PV is an independent predictor of both DFS and OS in patients with stage II PAC who received neoadjuvant therapy and subsequently underwent PD with or without SMV/PV resection. Patients with tumor involvement of the resected vein were more likely to have larger tumors, higher rates of positive resection margins and increased likelihood of local and distant recurrence. Therefore, complete pathologic evaluation of the resected SMV/PV in PD specimens is a predictor of prognosis in patients with PAC who received neoadjuvant therapy and subsequent PD.