Too Much Water Drowned the Miller—Does Extended Pancreaticoduodenectomy Benefit the Long-term Survival Outcomes in the Treatment of Pancreatic Cancer?

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To the Editor:
We read with interest the article by Jang et al1 prospectively evaluating the survival benefit of dissection of the nerve plexus and lymphadenectomy in patients with pancreatic head cancer. In that randomized controlled trial (RCT), they concluded that compared with extended pancreaticoduodenectomy (EPD), standard Whipple operation could be performed safely and efficiently, without negatively affecting oncologic efficacy or long-term survival. Considering that in the past decades in the field of surgical management of pancreatic cancer attempts have been made to perform more extended resections by various medical centers, we systematically reviewed the clinical evidence of published RCTs up to now to explore the long-term oncologic combined outcomes of EPD versus standard pancreaticoduodenectomy (SPD).
Literatures comparing outcomes after EPD and SPD for pancreatic tumors were retrieved through searches of PubMed and EMBASE for RCTs published up to September 2014, supplemented by manual searches and reference backtracking. The following words or terms were adopted as key words or key terms: pancreatic cancer/adenocarcinoma, pancreatoduodenectomy, extended, radical, and standard. Two review authors (Z.Y. and T.T.M.) independently screened the titles and abstracts of the citations and the methodological quality of the considered trials. Any discrepancies were resolved by consensus. The hazard ratio (HR) was used as a summary statistic for long-term survival analysis as described by Parmar et al.2 Survival rates were extracted from Kaplan-Meier curves in each trial to reconstruct the HR estimate and its variance, with the assumption that patients were censored at a constant rate during the study follow-up.3 Forest plots were generated by Review Manager software (RevMan software, version 5.3; The Nordic Cochrane Centre, Copenhagen, The Cochrane Collaboration, 2012). A total of 704 patients from 5 RCTs1,4–7 were finally included for analysis. As demonstrated by Figure 1, 5-year overall survival of EPD compared with SPD did not indicate a significant difference, and the HR was 1.04 (95% confidence interval, 0.88–1.23). As for the postoperative 3- and 1-year overall survival, the HR was 1.06 (95% confidence interval, 0.89–1.27) and 1.14 (95% confidence interval, 0.87–1.50), respectively. Likewise, there was no significant difference in the long-term disease-free survival between the patients who underwent SPD and those who underwent EPD.
We focused on long-term survival analysis in the current study because lifetime is the most important observational index to assess an operation. In the EPD group, an extended lymph node dissection and soft-tissue clearance were performed, and distal gastrectomy and dissection of the nerve plexus were reported by 2 RCTs.1,5 The present survival analysis failed to show any benefit with EPD. In addition, previous systematic reviews on the postoperative mortality and the overall morbidity revealed no significant differences between the 2 groups.8,9 Thus, the quality of life might become the critical factor in comparing the 2 surgical procedures. Because of retroperitoneal lymph nodes and nerve plexus dissection, diarrhea was observed more in the EPD group in these trials. Also, in a prospective study concerning the quality of life before and 24 months after surgery by the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, poor quality of life was associated with EPD in the early postsurgical stages.10 Together with the newly published study by Jang et al, EPD does not have an advantage over SPD in the long-term survival outcomes and should not be generally recommended for patients with adenocarcinoma of the head of the pancreas.

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