More Harm than Good

Despite all the research-driven ‘‘breakthroughs’’ in the management of pancreatic cancer, the one constant for patients to have any chance at achieving long-term survival is that they are able to undergo resection with curative intent. It is also evident from data generated from phase III randomized trials that chemotherapy (with or without radiation) delivered in the adjuvant setting improves survival in this highly lethal cancer. Surgery followed by chemotherapy or chemoradiotherapy is considered the standard of care for most patients. Yet, considering the extent of surgery necessary to achieve a negative margin resection for cancer of the head of the pancreas, initiating or completing this standard treatment sequence is unfortunately not straightforward. Pancreaticoduodenectomy (PD) is known to be associated with one of the highest postoperative complication rates, up to and exceeding 50 % in many series, even in the most experienced surgical hands at high-volume centers. So, this begs the question: what is the impact of surgical complications on the receipt and timing of adjuvant therapy post-PD? In an attempt to answer this very question, Wu et al. have conducted a comprehensive, retrospective review of their extensive experience with PD for adenocarcinoma of the pancreas at Johns Hopkins to analyze the impact of postoperative complications on the receipt of adjuvant therapy, both in the timing and type of treatment. The authors hypothesize that delay in the delivery of adjuvant therapy secondary to postoperative complications would abrogate the potential benefit the patient derives from multimodality therapy and subsequently decrease survival. Although this is a reasonable hypothesis, one needs to further dissect the data presented to determine whether it is supportive of this premise. The authors demonstrate that the presence of a complication was associated with a significant delay in time to adjuvant therapy, but the grade of complication was not. Despite having an overall complication rate of 49.1 %, clinically severe complications (CIIIb) occurred in only 4.2 % of their patients. Clearly, the number of severe complications is too small for a meaningful analysis of severe morbidity, and this may not be as clinically relevant as the patients who had less severe complications (\IIIb). From a clinically relevant standpoint, the patients with these severe complications may never recover to a level that will allow them to ever undergo adjuvant therapy; therefore, the complications we should be focusing on are the less severe complications. 1 It is also likely that a low-severity complication, such as a wound infection, could cause treatment to be significantly prolonged as compared with delayed gastric emptying, but the Clavien–Dindo score is not descriptive enough to decipher these relative differences in their grading system. Thus, it may behoove investigators to find a different way to analyze the complications that will be particularly clinically relevant after a PD. In this review, only 54.3 % of the patients received postoperative therapy, with 41.3 % receiving multimodality adjuvant therapy. On multivariate analysis, age [68 years and length of stay[9 days were associated with a decreased chance of receiving adjuvant therapy. Postoperative complications (both presence and grade) were shown to reduce the intensity of the adjuvant therapy, with patients more likely to receive single-agent chemotherapy or radiation therapy if they had a postoperative complication than if they did not. Here again the numbers are too small to separate out single-agent chemotherapy from radiation treatment alone, and our focus is on multimodality therapy. As expected, receipt of multimodality therapy correlated with a significantly longer median