Does Prior Adjuvant Chemoradiotherapy Lead to a Safer Pancreatoduodenectomy?

Abstract

The article by Cheng et al. is another attempt to compare the effects of preoperative versus postoperative adjuvant chemoradiotherapy (CRT) for presumably localized pancreatic adenocarcinoma by retrospective analysis of two nonrandomized treatment cohorts. Because the only significant differences in morbidity within the preoperative and postoperative cohorts in this study were in pancreatic leak and intra-abdominal abscess formation (favoring the preoperative CRT cohort), the primary focus of this study was the relative incidence of postoperative pancreatic leaks. The authors aver that preoperative CRT reduces the incidence of both pancreatic leaks and leak-associated morbidity and mortality, and they even go so far as to recommend preoperative CRT in those with ampullary cancer to decrease postoperative leaks. Is this information new, true, or relevant? Ishikawa et al. were the first to examine the question. They described two retrospective nonrandomized cohorts: one treated with preoperative radiotherapy (RT) and the other not. Patients with fistulas were defined as those with amylase levels >2000 U/L in their drains for >1 week. Furthermore, a fistula was defined as major if either bile was seen in the drain fluid or the fistulogram showed entry of dye into the jejunum (all patients had pancreatojejunostomy over external pancreatic stents). Minor fistulas were those without either of these findings but with the defined drain amylase levels. One of 22 patients with preoperative RT developed a major fistula, and 1 of 54 patients without preoperative RT had a major fistula; 3 of 54 had minor fistulas that became major, and 6 had minor fistulas. Because the two immediate major fistulas were attributed to premature withdrawal or occlusion of pancreatic stents, these cases were excluded. The 9 of 53 patients with minor or minor changing to major fistulas without RT were compared with the 0 of 21 patients without fistulas in the post-RT cohort: differences were significant (P = .05). Statistical significance here, however, required that the two major leaks be omitted. Clearly, those receiving preoperative RT seemed to do no worse than those without it. Lowy et al. examined pancreatic leak in patients with and without preoperative CRT in a randomized study of perioperative octreotide. Their definition of fistula was either biochemical (defined as increased drain amylase at postoperative day 3) or clinical (requiring reoperation or drainage). Whereas none of the 46 patients with protocol-based preoperative CRT for pancreatic cancer developed clinical pancreatic fistulas, there were enough with biochemical leaks that no difference was shown between those treated with preoperative CRT and those who had surgery first. Again, preoperative CRT seemed not to be a deterrent to safe recovery from pancreatoduodenectomy, but leaks were no less frequent than in those treated without preoperative therapy. Cheng et al. defined a leak as any drainage fluid at any time after surgery with a value three times that of serum amylase. Multivariate analysis showed that preoperative CRT produced a statistically significant decrease in pancreatic leaks (10.1% vs. 43.3%; P < .001). For those with pancreatic head cancer, 3 (4.8%) of 62 of those with preoperative CRT had a fistula, Received October 19, 2005; accepted October 26, 2005; published online January 1, 2006. Address correspondence and reprint requests to: John Hoffman, MD; E-mail: jp_hoffman@fccc.edu