AIM: To establish the prognosis and feasibility of en-bloc vascular resection of stage II pancreatic adenocarcinoma of the head and uncinate process.

METHODS: We retrospectively analyzed 87 patients with stage II pancreatic adenocarcinoma, who were subjected to pancreaticoduodenectomy (PD) and pylorus-preserving PD (PPPD) between 1996 and 2006 in Chang Gung Memorial Hospital, Taiwan. Twelve and 75 patients underwent PD/PPPD with and without resection of portal vein/superior mesenteric vein (PV/SMV), respectively.

RESULTS: The overall 1- and 3-year survival rates of patients undergoing PD/PPPD with and without vascular resection were 50.0% and 16.7%, and 44.4% and 12.2%, respectively. Morbidity and mortality rates in the PV/SMV resection vs non-resection group were 50.0% and 0.0%, and 40.0% and 2.7%, respectively. In multivariate analysis, serum bilirubin, histological differentiation and adjuvant chemotherapy were independent prognostic factors that influenced survival.

CONCLUSION: In stage II adenocarcinoma of the pancreatic head and uncinate process, serum bilirubin, histological differentiation and adjuvant chemotherapy were independent prognostic factors, and en-bloc vascular resection is a feasible option in carefully selected patients.

Pancreaticoduodenectomy (PD) combined with vascular resection in locally advanced pancreatic malignancies was initially associated with high morbidity and mortality rates[1]. However, with improvement in surgical techniques and postoperative care, more aggressive en-bloc resection of pancreatic malignancies, along with portal vein/superior mesenteric vein (PV/SMV) is being carried out at present, without any increase in surgical complications[2]. Unexpected tumor invasion to the lateral or posterolateral wall of the confluence of the PV/SMV is a common finding during PD for pancreatic malignancies[3]. The 5-year survival rate following PD or pylorus-preserving PD (PPPD) is 10%-15%, and the reported survival for > 5 years is less[4-6]. Mortality associated with PD has decreased dramatically to 0%-5% over the past two decades, but morbidity remains as high as 35%-60%[7-11]. Few studies are available regarding stage II pancreatic adenocarcinoma with special attention to adenocarcinoma located in the pancreatic head and uncinate process, which is more likely to invade the PV/SMV because of its close proximity to these vessels. The aim of the present study was to establish the prognostic factors and feasibility of en-bloc vascular resection in patients with stage II adenocarcinoma of the pancreatic head and uncinate process following PD/PPPD.

In our study, the overall 1- and 3-year survival was comparable to that in the study by Fukuda et al[12], which had a survival rate of 47% and 26.8%, respectively, in group I, and 63.4% and 28.4% in group II patients. However, van Geenen et al[13] have reported 55% and 6%, respectively, Ye et al[14] have reported 37.7% and 5.6%, respectively, and Launois et al[15] have reported 42.4% and 11.9% in group I, which is slightly less than the survival rates in our study. The 3-year survival in the studies of Aramaki et al[16] and Carrère et al[17] was 21.3% and 20.0%, and 22.0% and 25.0%, in group I and II, respectively. All the above studies included all stages of pancreatic cancer, irrespective of location in the pancreas. This differs from our study, in which we focused only on stage II adenocarcinoma localized in the pancreatic head and uncinate process, where there is more probability of vascular encasement.

In our study, the mean survival time in patients undergoing curative PV/SMV resection was 16.28 mo. There was not much difference in the mortality rate in PD/PPPD with or without vascular resection, but the associated morbidity was higher in the vascular resection group. This is in contrast to earlier studies that have found that PV/SMV resection does not greatly influence morbidity and mortality in PD[12,18]. In our study, all 12 patients in group I had negative resection margins. Previous studies have reported that the resectability rate is high in PD with vascular resection[14]. PD/PPD with en-bloc vascular resection potentially provides an opportunity to achieve negative resection margins, and thus might be beneficial in achieving better survival rates in carefully selected patients with pancreatic adenocarcinoma[19,20]. Hence, in patients who were subjected to palliative treatment alone, based on their preoperative evaluation that showed PV/SMV encasement, some carefully selected patients, as determined by preoperative CT [length and severity (complete vs partial circumference) of vascular involvement], may be suitable candidates for en-bloc resection of PV/SMV, thus achieving better survival rates. Earlier studies have suggested that encasement of PV or SMV is a function of tumor location rather than more aggressive behavior, and almost equal or even better survival rates can be achieved by en-bloc resection of PV/SMV[12,19]. Our study shows that en-bloc vascular resection in stage II pancreatic adenocarcinoma is a feasible option in carefully selected patients. Hence, vascular encasement should not be considered as a contraindication for surgery; risk must be balanced against the benefit by case to case evaluation.

Serum bilirubin, histological differentiation and adjuvant chemotherapy were significant prognostic factors in our series. Previous studies have focused on the significance of depth of PV invasion[18], lymph node metastasis[21], tumor size[22], negative resection margin[23], and adjuvant chemotherapy[24] in pancreatic adenocarcinoma. These preoperative and intraoperative factors help in deciding the extent of resection, proper planning of adjuvant therapy, and predicting the survival outcome in these patients. In our study, preoperative biliary drainage has no statistical significance in the outcome of stage II pancreatic adenocarcinoma, similar to an earlier study[25]. Few studies have reported the potential advantages of preoperative biliary drainage, which include improved nutritional, metabolic and immune function, and the possibility of reduced postoperative morbidity and mortality[26,27]. In contrast, one study has reported that the biliary stents induce bacterial contamination and enhance the risk of cholangitis because of clogging. Biliary stenting also generates a severe inflammatory response adjacent to the wall of the bile duct, which is probably a factor that is responsible for increased risk of bile leakage and infection after biliodigestive reconstruction[28]. An experimental study has indicated that a period of 4-6 wk is necessary to recover metabolic and immune functions so that some benefit may be achieved by preoperative biliary drainage[29].

Histological differentiation was found to be significant in our study in determining survival outcome. Patients with well-differentiated adenocarcinoma had better survival than those with moderately well and poorly differentiated adenocarcinoma. Earlier studies by Sohn et al[22], Riediger et al[23] and Yamaguchi et al[30] have highlighted the significance of histological differentiation as a prognostic factor in pancreatic adenocarcinoma.

Adjuvant chemotherapy was also found to be statistically significant. In our study, patients who received adjuvant chemotherapy had better survival than those without chemotherapy. Adjuvant chemotherapy in pancreatic cancer substantially improved the disease-free survival and overall increase in survival rate, as shown by our study and an earlier one[31]. The drawback of our study is that it was a retrospective analysis. However, it still gives information about the prognostic factors and feasibility of en-bloc vascular resection in stage II adenocarcinoma of the pancreatic head and uncinate process.

In summary, our study concludes that serum bilirubin, histological differentiation and adjuvant chemotherapy are independent prognostic factors that influence survival in patients with stage II adenocarcinoma of the pancreatic head and uncinate process. PD/PPPD along with en-bloc vascular resection is a technically feasible option in carefully selected patients.