The third listed randomized trial by Izbicki et al. [ 11 ] in 1998 consisted of 30 patients who underwent ppPD and 31 patients who underwent DPPHR (Frey). The ppPD group had no mortality while one patient (3.2 %) in the DPPHR group died of a myocardial infarction. Overall morbidity was signifi cantly less in the DPPHR group due to the higher rate of delayed gastric emptying in patients undergoing ppPD (p < 0.05). Delayed gastric emptying was defi ned as need for nasogastric tube decompression for more than 7 days postoperatively. After a median follow-up of 24 months, similar relief of symptoms was reported in each group (87 % and 90 % respectively). Additionally, patients were given a pain score that contained the fol­lowing components: a visual analog scale, frequency of pain attacks, pain medica­tions, and inability to work. The median pain score decreased 71 % in the ppPD group and 90 % in the DPPHR group. The postoperative pain scores were signifi ­cantly lower in both groups when compared to their preoperative scores but were not different between groups. Pancreatic endocrine function was assessed by an oral glucose tolerance test, the treatment required (diet, oral agents, or insulin), fasting serum insulin, C-peptide, and HbA1C. Pancreatic exocrine function was assessed by measuring the fecal chymotrypsin concentration and the pancreolauryl test. Although no statistical analysis was provided to compare pancreatic endocrine and exocrine function between ppPD and DPPHR, the outcomes appear to be similar. Overall QoL, using the EORTC QLQ-30, was signifi cantly higher for patients undergoing DPPHR compared to ppPD. Long-term follow-up of this trial was reported by Strate et al. [ 14 ] in 2008 at 84 months and by Bachman et al. [ 15 ] in 2013 at 180 months. Twenty four (80 %) and 14 (47 %) of the patients who under­went PD compared to 23 (74 %) and 21 (68 %) of patients who underwent DPPHR were available to be assessed. Neither follow-up report showed any signifi cant dif­ference in pain relief, pancreatic function or QoL. The study population was bal­anced with proper follow up reporting, adequate defi nition of outcome parameters, sample size calculation, and allocation concealment. Blinding of outcome assess­ment and intention to treat (ITT) analysis were not described. The quality of evi­dence is moderate according to the GRADE system.

The fourth listed randomized trial by Farkas et al. [ 16 ] in 2006 consisted of 20 patients who underwent ppPD and 20 patients who underwent DPPHR (modifi ed Frey) with a median follow-up of 12 months. There was no perioperative mortality . The operative time and hospital LOS were signifi cantly longer in the ppPD group. Additionally, overall morbidity was signifi cantly higher in the ppPD group due to

The fi fth listed randomized trial conducted by Keck et al. [ 17 ] reported short and long-term results comparing 45 patients who underwent ppPD and 47 patients who underwent DPPHR (Beger or Frey). There was no mortality in either group and the overall morbidity was similar (30 % versus 33 %). Pain relief was assessed using a visual analog scale and pain frequency questionnaire. At a median follow-up of 66 months, 67 % of patients in both groups were pain free. Pancreatic endocrine func­tion was assessed preoperatively using the oral glucose tolerance test or a 24-h glucose profi le. Postoperatively, pancreatic endocrine function was assessed using a questionnaire for the presence of diabetes and diabetes medication use. New onset diabetes developed in 19 % of patients in the PD group and 24 % of patients in the DPPHR group (p 0.56). Pancreatic exocrine function was determined by patient reported presence of steatorrhea or use of pancreatic enzyme supplementation. Postoperative de novo pancreatic exocrine insuffi ciency was 21 % in the PD group and 26 % in the DPPHR group (p 0.57). QoL was measured using the EORTC QLQ-30 questionnaire and was also similar in both groups. The study population was balanced with proper follow up reporting and adequate defi nition of outcome parameters. Examiners were blinded to QoL questionnaires but blinding of other outcome assessments was not described. Sample size calculation, allocation con­cealment, and intention to treat (ITT) analysis were not described. The quality of evidence is moderate according to the GRADE system.

The second systematic review and meta-analysis by Yin et al. [ 19 ] reported 541 patients in the PD group and 466 patients in the DPPHR from 15 studies. This review included the four randomized trials reported by Diener et al. as well as a randomized trial by Izbicki et al. that compared the Beger and Frey procedure s. Also included were ten non-randomized or retrospective trials. Perioperative mor­tality was not reported. Pooled data for postoperative morbidity and pain relief were similar between the PD and DPPHR operations. However, subgroup analyses showed that the Beger procedure provided signifi cantly better pain relief than PD while the Frey procedure had signifi cantly lower postoperative morbidity than PD. Pancreatic endocrine insuffi ciency was similar in both groups but exocrine insuffi ciency outcomes signifi cantly favored DPPHR. Pooled data showed that QoL was signifi cantly better after DPPHR compared to PD. The fi ve randomized trials were analyzed using the Cochrane Risk of Bias Tool in the meta-analysis and deemed of moderate quality by the authors. The ten observational studies were eval­uated using the Newcastle-Ottawa Scale but the results were not described. These observational studies are at risk of allocation bias. None of the observational studies adequately described patient fl ow or methods for handling missing data. The quality of evidence is low.

The 2013 report from Lu et al. [ 20 ] included fi ve RCT. Two RCT (Klempa and Farkas) were original trials and two (Strate and Muller) were follow-up reports of the original trials. The fi fth trial included was a retrospective study by McClaine et al. that was incorrectly labeled as a prospective RCT. Perioperative mortality and morbidity were not analyzed. A total of 206 patients were available for meta­analysis: 104 patients in the PD group and 102 patients in the DPPHR group. Pain relief, pancreatic endocrine and exocrine functions were similar in both groups. Only global QoL was found to be signifi cantly better in the DPPHR group. Heterogeneous study quality was reported with sample size, standardization of study interventions, consistency of follow-up and outcome assessment. Small sample size, inadequate allocation concealment, and loss of population during fol­low- up were limitations of the meta-analysis. The quality of evidence is low.