Secondary Logo

Share this article on:

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial

Keck, Tobias MD, MBA, FACS; Wellner, U. F. MD; Bahra, M. MD; Klein, F. MD; Sick, O. MSc; Niedergethmann, M. MD; Wilhelm, T. J. MD; Farkas, S. A. MD; Börner, T. MD; Bruns, C. MD; Kleespies, A. MD; Kleeff, J. MD; Mihaljevic, A. L. MD; Uhl, W. MD; Chromik, A. MD; Fendrich, V. MD; Heeger, K. MD; Padberg, W. MD; Hecker, A. MD; Neumann, U. P. MD; Junge, K. MD; Kalff, J. C. MD; Glowka, T. R. MD; Werner, J. MD; Knebel, P. MD; Piso, P. MD; Mayr, M. MD; Izbicki, J. MD; Vashist, Y. MD; Bronsert, P. MD; Bruckner, T. PhD; Limprecht, R. MSc; Diener, M. K. MD; Rossion, I. MD; Wegener, I. MD; Hopt, U. T. MD

doi: 10.1097/SLA.0000000000001240

Objectives: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial.

Background: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications.

Methods: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up.

Results: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters.

Conclusions: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

Supplemental Digital Content is available in the text

*Klinik für Chirurgie, UKSH Campus Lübeck, Lübeck, Germany

Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg, Freiburg, Germany

Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Charité - Universitätsmedizin Berlin - Campus Virchow-Klinikum, Berlin, Germany

§Chirurgische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany

Klinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Germany

||Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Klinikum der Universität München, Munich, Germany

**Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München und CHIR-Net München, Munich, Germany

††Chirurgische Klinik, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Bochum, Germany

‡‡Klinik für Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Marburg, Marburg, Germany

§§Klinik für Allgemein-, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie des Universitätsklinikums Gießen, Gießen, Germany

¶¶Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Aachen, Aachen, Germany

||||Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Germany

***Abteilung für Allgemeine, Viszerale und Transplantationschirurgie, Universität Heidelberg, Heidelberg, Germany

†††Klinik für Allgemein- und Viszeralchirurgie, Krankenhaus Barmherzige Brüder, Regensburg, Germany

‡‡‡Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

§§§Institut für Pathologie, Universitätsklinikum Freiburg, Freiburg, Germany

¶¶¶Comprehensive Cancer Center Freiburg, Freiburg Germany

||||||Institut für Medizinische Biometrie und Informatik (IMBI), Universität Heidelberg, Heidelberg, Germany

****Studienzentrum der Deutschen Gesellschaft für Chirurgie (SDGC), Heidelberg, Germany.

Reprints: Tobias Keck, MD, MBA, FACS, Klinik für Chirurgie, University Hospital Schleswig Holstein, Campus Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. E-mail:

Disclosure: Supported by the German Research Council fund (Deutsche Forschungsgemeinschaft, DFG-Ke 763/7-1). The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

The first successful pancreatoduodenectomy was performed as a 2-stage procedure by Walter Kausch in 1909.1 Later, Allen O. Whipple popularized the procedure by a series of 37 pancreatoduodenectomies during his career.2 Because of high mortality, the operation was nearly abandoned in the 1970s.2 In the 1990s, large retrospective series from specialized centers around the world set a benchmark for operative mortality of below 5%.2 Nevertheless, morbidity remains substantial after pancreatoduodenectomy.3–10 The main contributing factor is postoperative pancreatic fistula (POPF), involving leakage of pancreatic juice from the pancreatic anastomosis, which can lead to severe secondary complications such as intra-abdominal abscesses and erosion bleeding.9,11,12 Data regarding the prevention of POPF by application of somatostatin analogues have been controversial thus far,13,14 but a recent randomized trial strongly suggests that pasireotide successfully reduces POPF rates.15 Numerous attempts at improving pancreatic anastomosis techniques to lower POPF rates have been proposed.2,16,17 The hypothesis of this trial dates back to Walter Kausch, who discussed the possibility of anastomosis of the pancreatic remnant to the jejunum (pancreatojejunostomy, PJ) or the stomach (pancreatogastrostomy, PG) in his 1912 original publication of the first successful pancreatoduodenectomy.1

Almost all retrospective studies suggest superiority of PG over PJ in terms of reduced POPF and other complications.18 To date, however, conflicting results have been reported from 8 prospective randomized controlled trials (RCTs) published from 1995 to 201419–26 (see Supplemental Digital Content Table S1, available at Only 3 RCTs22,24,25 have demonstrated a reduced rate of POPF after PG, and 4 RCTs20,22,24,25 found advantages of PG over PJ in terms of postoperative complications. Soft pancreatic texture was identified as a risk factor for POPF and other complications in 4 RCTs.19,21,23,25 However, the available RCTs have some limitations. With the exception of the recent Belgian multicenter RCT24 including 329 patients, total case numbers of the RCTs are relatively low (n = 90–151) and only 2 RCTs are multicenter trials. Definitions of perioperative outcomes vary as early trials did not use the current consensus definitions of specific complications in pancreatic surgery established by the International Study Group for Pancreatic Surgery (ISGPS). Although many technical variations of PG and PJ have been reported,16,17 all 8 RCTs were restricted to specific subtypes of PG and PJ. Only 2 RCTs with contradictory results report on postoperative pancreatic function measured during follow-up of 3 to 12 months: the Egyptian trial26 reports worse and the Spanish trial25 reports better pancreatic function. None of the RCTs report on quality of life during follow-up.

Here we present data collected at 14 high-volume centers for pancreatic surgery in Germany from the currently largest multicenter randomized trial comparing PG with PJ with respect to perioperative complications and long-term pancreatic function and quality of life.

Back to Top | Article Outline


Study Design, Hypothesis, and Inclusion Criteria

The RECOnstruction after PANCreatoduodenectomy Study (RECOPANC) was designed as a randomized, controlled, observer- and patient-blinded multicenter trial with 2 parallel treatment arms (PG and PJ) (see Supplemental Digital Content, available at The hypothesis was that the rate of clinically relevant POPF is lower after PG. Inclusion criteria were planned pancreatoduodenectomy at one of the participating academic centers and age more than 18 years. Exclusion criteria were participation in interfering clinical trials and expected lack of compliance. With the rationale to increase willingness of participating surgeons to recruit patients and to achieve greater generalizability of the results, we did not restrict PG or PJ to a special technique. Fourteen German academic centers (RECOPANC Trial Group27) with a median case load of 78 major pancreatic resections per year (range: 29–499, figures for year 2012 from the Association of German University Clinics, participated in the trial.

Back to Top | Article Outline

Primary Endpoint and Sample Size

POPF is defined by ISGPS as the occurrence of amylase activity in abdominal drain fluid of 3 times the upper serum limit on postoperative day 3 or later.28,29 In brief, grade A fistula is self-limited and does not need specific treatment, grade B requires medical or invasive interventional treatment, and grade C leads to reoperation and/or severe secondary complications. The primary endpoint chosen for this trial was clinically relevant POPF, that is, ISGPS grade B or C, with the modification that application of somatostatin analogues was not considered a criterion for grading. The primary endpoint was assessed on postoperative day 3 at hospital discharge and on postoperative day 30 to detect all POPFs.

Based on the prior assumption of a POPF B/C rate of 6% and 16% with PG and PJ, respectively, α = 5% and β = 20%, a sample size of 153 per treatment arm (PG vs PJ) was calculated with the 2-sided χ2 test. An adaptive interim analysis of the primary endpoint according to Bauer and Koehne30 was planned after recruitment of 152 patients to allow for premature trial termination (with 1-sided stopping boundaries of P < 0.0038) and sample size recalculation.

Back to Top | Article Outline

Secondary Endpoints and Follow-up

Secondary surgical endpoints were death, relaparotomy, completion pancreatectomy, anastomotic leak other than pancreatic fistula, wound infection, delayed gastric emptying, postpancreatectomy hemorrhage according to the ISGPS definitions,31,32 intra-abdominal abscess requiring invasive treatment, operation time (skin incision to skin closure), and postoperative hospital stay. Further secondary endpoints included septic shock, respiratory failure, deep venous thrombosis, lung embolism, myocardial infarction, and stroke. Pancreatic endocrine and exocrine functions and quality of life were evaluated in long-term follow-up at baseline, 6 and 12 months after the operation by the validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ) C30 and the pancreatic cancer module PAN26.33,34

Back to Top | Article Outline

Randomization and Blinding

Center-based block randomization was performed by the participating centers using a centralized Web-based tool (Randomizer Software, Institute for Medical Informatics, Statistics and Documentation of the Medical University of Graz, with allocation concealment. To avoid a possible intraoperative selection of low-risk patients,23 randomization was performed preoperatively. Obviously, the surgeons were not blinded concerning the intervention. Therefore, blinded observers at the participating centers assessed the primary endpoint. Patients were kept blinded regarding the intervention and unblinded only in the case of emergencies where necessary.

Back to Top | Article Outline

Ethical Approval, Safety, and Registration

The study protocol was approved by the local ethics committees of the participating centers and carried out according to the rules of Good Clinical Practice and the Declaration of Helsinki.35 Written informed consent was obtained from each patient. An independent institution served as the Data Safety Monitoring Board and was responsible for on-site clinical monitoring, source data verification, and management of severe adverse event reports (Center for Clinical Studies, Freiburg, Germany). The trial was assigned a Universal Trial Number (UTN U1111-1117-9588) and registered in the German Trials Register (DRKS 00000767) on March 23, 2011. The study protocol was published in Trials.27

Back to Top | Article Outline

Statistical Analysis

The primary endpoint was analyzed according to the intention-to-treat principle (see Supplemental Digital Content, available at A multivariate logistic regression model adjusting a priori for age, center, surgeon volume/experience, and pancreatic texture was applied to compare POPF rates in both treatment groups. Missing values for the primary endpoint were replaced by imputed case analysis according to Higgins et al.36 Exploratory analysis was planned for secondary endpoints. SAS software 9.1 (SAS 9.1 software, SAS, Cary NC) and 2-sided tests were used for all calculations.

Back to Top | Article Outline


Trial Flow

A total of 618 patients were screened and 440 patients were randomized from May 31, 2011, through December 5, 2012. The number of patients randomized per center is shown in Supplemental Digital Content Fig. S1, available at, and ranged from 6 to 84, with 5 centers recruiting less than 20 patients and 2 centers recruiting more than 50 patients. After the interim analysis of the first 152 included patients, the Data Safety and Monitoring Board advised continuation of the trial. A total of 120 randomized patients were excluded from the final analysis: 3 patients were randomized by mistake (randomized but not eligible), 5 did not undergo laparotomy, and 112 did not receive pancreatoduodenectomy and were, therefore, excluded from further analysis. Fifteen patients randomized to PG received PJ and 12 patients randomized to PG received PJ because of the surgeon's technical preference. Reasons given for PJ instead of PG included technical problems with PG: short pancreatic remnant (n = 9), difficult pancreatic remnant mobilization (n = 2), and gastric ulcer (n = 1); reasons for PG instead of PJ were soft pancreas with small duct (n = 11) and pancreas divisum (n = 1). In total, 320 patients were included in the intention-to-treat analysis of the primary endpoint: 149 patients randomized for PJ and 171 randomized for PG. Ninety-six patients did not finish the whole 12-month follow-up because of prior death (n = 75), loss to follow-up (n = 10), withdrawal of consent (n = 5), and other reasons (n = 6) (Fig. 1).



Back to Top | Article Outline

Patient Baseline Characteristics and Operations

Patient baseline parameters are shown in Table 1 . The treatment groups were balanced in terms of age, sex, body mass index, indications, symptoms, preoperative biliary drainage, comorbidities, American Society of Anesthesiologists (ASA) Classification, medication, and standard laboratory parameters. The treatment groups were also comparable in terms of operation technique, surgeon experience/volume, and blood loss/intraoperative transfusion requirement. In particular, the rates of soft pancreata (PG vs PJ, 59% vs 57%) and nondilated pancreatic ducts (PG vs PJ, 58% vs 55%), which are indicators for increased risk of fistula formation,5,37–40 were not significantly different between the 2 groups (Table 1 ).





Supplemental Digital Content Table S2, available at, shows the technical varieties used for PG and PJ at the trial centers. According to the ISGPS classification for pancreatic anastomoses,16 the most commonly performed techniques were nonstented duct-mucosa anastomosis (ISGPS type I-A-S0) with 2 interrupted monofilament resorbable suture rows for PJ and nonstented dunking PG (ISGPS type II-B-S0) anastomosis with purse-string plus interrupted monofilament resorbable suture.

Back to Top | Article Outline

Primary Endpoint Analysis

The rate of clinically relevant POPF was 20% after PG and 22% after PJ in the control group (P = 0.62, 2-sided χ2 test, Table 2). In a multivariate logistic regression model (Table 2), including anastomotic technique (PG vs PJ), age, center (north vs south), pancreatic texture (soft vs hard) and surgeon volume (pancreatic resections per year), and soft pancreatic texture was the only significant factor affecting POPF B/C, with an odds ratio estimate of 2.1 (P = 0.016) (Table 2).



As there were 12 patients allocated to PG receiving PJ instead and 15 patients with PG instead of PJ, we also performed an as-treated analysis of the primary endpoint (see Supplemental Digital Content Table S3, available at The results did not differ from those of the intention-to-treat analysis.

Back to Top | Article Outline

Assessment of Learning Effects

The odds ratio estimate for fistula rate in surgeons with less than 10 pancreatoduodenectomies was 1.2 to 6.8 (95% confidence interval) but did not reach the significance level (P = 0.064 in multivariate analysis, see Table 2). Surgeons with less than 10 pancreatoduodenectomies per year had a higher fistula rate with PJ (46%) than with PG (27%), and this effect was gradually lost with increasing individual case load (see Supplemental Digital Content Table S4, available at; however, these differences did not reach statistical significance. There was also no significant center effect as to the preferred type of anastomosis in the participating centers (see Supplemental Digital Content Table S4, available at

Back to Top | Article Outline

Perioperative Secondary Endpoint Analysis

Operation time did not differ between PG and PJ. There were no significant differences between PG and PJ with regard to the frequency of surgical complications such as delayed gastric emptying, intra-abdominal abscesses, relaparotomy, completion pancreatectomy, anastomotic leaks, and surgical site infection. There was also no difference in the incidence of systemic complications such as septic shock, respiratory failure, deep vein thrombosis, lung embolism, and myocardial infarction. There were more (n = 5) stroke events in the PG group but none in the PJ group (P = 0.035) and significantly more postpancreatectomy hemorrhage events in the PG group (P = 0.023), the latter due to more grade A (5% vs 1%) and B (9% vs 4%) hemorrhages. Stroke and grade A/B bleeding were not associated, however (P = 0.998). Perioperative in-house mortality in the treatment groups (PG vs PJ, 6% vs 5%, P = 0.963) and 90-day mortality (PG vs PJ, 10% vs 5%, P = 0.167) were not statistically different. Postoperative hospital stay was equal with a median of 16 days (Table 3).



Back to Top | Article Outline

Survival During Follow-up

Overall survival curves are given in Supplemental Digital Content Fig. S2, available at One-year (365 days) Kaplan-Meier survival estimates (±standard error) were 77% ± 3% in PG and 76% ± 4% in PJ and thus comparable (P = 0.675 in 2-sided log-rank test) (see Supplemental Digital Content Fig. S2, available at

Back to Top | Article Outline

Pancreatic Function and Long-term Follow-up

The percentage of patients receiving oral enzyme replacement rose from 8% preoperatively to around 80% during 6- and 12-month follow-up. Exploratory analysis also suggested a significantly reduced rate of oral enzyme replacement therapy in patients with PG at 6 months after the operation (PG vs PJ, 72% vs 89%, P < 0.001). This difference did not persist at 12-month follow-up because of a slightly decreasing percentage of PJ patients using oral enzyme supplementation (PG vs PJ, 72% vs 81%, P = 0.11). However, simultaneously the rate of patients reporting steatorrhea in the PJ group increased (from 17% at 6 months to 22% at 12 months), suggesting now insufficient enzyme supplementation in some patients. This was not the case with PG, where reported steatorrhea decreased from 20% to 13%. The amount of enzyme units taken per day was comparable in both treatment groups.

The prevalence of diabetes mellitus rose only slightly after pancreatoduodenectomy (from 25% at operation to 31% at 12-month follow-up) and was comparable after PG and PJ. Among diabetic patients, there was an increase of insulin dependence from around 50% to around 70% after pancreatoduodenectomy, whereas the percentage of patients with dietary therapy dropped only from 23% preoperatively to 13% and 9% at 6 and 12 months, respectively. There was no significant difference between both treatment arms (Table 4).



Back to Top | Article Outline

Quality of Life and Long-term Follow-up

At the time of operation, EORTC QLQ-C30 and PAN26 scores were balanced between the treatment groups except for the physical functioning scale scores, which were higher in the PG group (P = 0.002). The patients assigned the lowest scores to role functioning and body image. Other major reported problems were fatigue, insomnia, pain, and digestive symptoms such as altered bowel habit. At 6 and 12 months after the operation, the most severe impairments were observed in role functioning, altered bowel habit, and fatigue. On the contrary, appetite, nausea, and hepatic symptoms improved. At 6 months, a reduced score on the financial problems scale could be observed (P = 0.044) in PG compared with PJ, which persisted at 12-month follow-up. Furthermore, emotional and social functioning scale scores were significantly better after PG than after PJ (P = 0.039 and 0.019) (see Supplemental Digital Content Table S5, available at

Back to Top | Article Outline


We report the currently largest RCT to compare PG and PJ in terms of POPF and perioperative complications and long-term outcome including quality of life. Of note, this multicenter trial was independently monitored. In contrast to previous RCTs, PG or PJ was not restricted to a specific subtype. The results of this trial have several implications for clinical practice. First, although it was designed to confirm the hypothesis of a reduction of clinically relevant POPF in patients with PG, the results show similar rates of grade B/C POPF regardless of the reconstruction method with an overall rate of 21%. This is higher than the reported range of 4% to 18% from large retrospective benchmark series (see Supplemental Digital Content Table S1, available at The previous RCTs report fistula rates between 12% and 24% (see Supplemental Digital Content Table S1, available at In comparison with the other RCTs, RECOPANC included the oldest patients (average 68 years vs 56–67 years in other RCTs) with the highest body mass index (average 25 vs 21–25 in other RCTs). Of note, RECOPANC is also the first RCT to report independent monitoring. Taken together, the observed POPF rate must be considered valid in view of an ageing general population with increased operative risk.

Also, overall in-hospital mortality of 6% and the 90-day mortality of 7% in this trial do not meet the usually cited 5% benchmark for pancreatoduodenectomy. It is above the reported range of 0.7% to 3.7% from current large-scale retrospective series (see Supplemental Digital Content Table S1, available at, whereas some RCTs report comparable perioperative mortality rates of 0% to 11% (see Supplemental Digital Content Table S1, available at In agreement with a current study,41 our data highlight the relevance of 90-day mortality figures in pancreatic surgery. It seems appropriate to accept that clinically relevant fistula rates of 20% and perioperative mortality of more than 5% mirror clinical reality even in high-volume pancreatic surgery. A similar effect was observed in the distal pancreatectomy trial, which reported a pancreatic fistula rate after distal pancreatic resection more than twice as high as previously reported in several retrospective series.42,43

Meta-analysis of the available RCTs19–26 incorporating data from this trial suggests no significant reduction in POPF rates (odds ratio: 0.66; 95% confidence interval: 0.43–1.01; P = 0.056) (see Supplemental Digital Content Table S6, available at for details). This stands in contrast to current meta-analysis.44

In a multivariate analysis, the single most important factor influencing POPF rates was the quality and texture of the organ. Soft pancreatic texture, as judged intraoperatively by the surgeon, has been demonstrated to bear a higher risk for secondary complications, erosion bleeding, and mortality in previous studies.6,9,11,24,37,38,40 It has been shown that subjective evaluation of the pancreatic hardness and texture strongly correlates with the histopathological degree of fibrosis.40 On the one hand, pancreatic cancer and chronic pancreatitis are usually associated with hardening of the whole organ including the pancreatic remnant; on the other hand, prophylactic surgery for benign lesions such as cystic neoplasms or small tumors such as ampullary cancer is usually associated with soft pancreatic tissue.9,19,40

As outlined, all participating clinics were high-volume academic centers for pancreatic surgery, and there was no statistically significant center effect regarding POPF rate. Nevertheless, a high odds ratio for POPF in the low-volume surgeons indicates that besides center volume, individual surgeon volume is a relevant factor influencing complication rates in pancreatoduodenectomy.

Furthermore, from our data, it might be speculated that PG offers an easier-to-learn technique suited for less experienced surgeons, but this effect did not reach statistical significance. This opinion has also been expressed by other authors of previous RCTs19,20,24,26 on the basis of the assumption that it is technically easier to achieve secure invagination of the pancreatic remnant with PG, especially in case of a bulky soft pancreas. Reasons given for conversion to PG instead of PJ (soft pancreas in 11 of 12 cases) in the current trial may reflect this assumption. However, operation time was not reduced with PG in the current trial, and only 2 previous RCTs23,26 found a shorter operation time with PG.

The incidence of grade A and B postpancreatectomy hemorrhages was increased after PG. By ISGPS definition, grade A bleeding has no therapeutic consequence, but grade B events require conservative or even invasive therapy and may be sentinels of later grade C hemorrhage. The feared life-threatening (grade C) bleeding events were not increased with PG. These findings confirm previous retrospective and prospective observations, which showed increased bleeding events from PGs.23,45,46 Meticulous hemostatic measures at the pancreatic cut surface are, therefore, advised. There was a higher rate of perioperative stroke events in patients with PGs that were not associated with the bleeding events, however. For lack of a rational explanation, this might be interpreted as an artifact of exploratory data analysis.

Our reported length of hospital stay (median, 16 days) is about twice as long as that usually reported from high-volume North American centers (see Supplemental Digital Content Table S1, available at Our explanations are that due to law-enforced universal health care insurance in Germany, patients usually do not experience financial pressure to be discharged early, and the common practice is to discharge patients home after full recovery. Even in a fast-track surgery program applied to major pancreatic resections in a German center,47 patients were discharged at median on day 10, with a 30-day readmission rate of only 3.5%, whereas readmission rates of 15% to 20% after pancreatoduodenectomy are currently reported from the United States.48,49 In consequence, readmission has been highlighted as a significant problem by American scientific studies and is financially penalized in the United States but not in Germany.47–51

The results of long-term pancreatic function follow-up in the current trial may be interpreted as suggestive of better exocrine function in patients with PG. However, pancreatic function was not measured directly but by means of the surrogate parameters oral enzyme supplementation and steatorrhea, and the drawback of exploratory data analysis must be kept in mind. Previous RCTs with smaller case numbers have reported inconsistent outcomes.25,26 The current study represents the largest prospective evaluation of this issue and will be followed by a prospective long-term observation of the included patients. Regarding the usually encountered opinion that pancreatic function is worse after PG compared with PJ, our results suggest that this is not the case.

Only one previous retrospective study compared quality of life after pancreatoduodenectomy with PG and PJ and found no difference, but it was unbalanced with regard to the preoperative patient status.52 Follow-up in the present trial did not reveal differences between the treatment groups in most aspects covered by the EORTC QLQ-C30/PAN26 questionnaires. On the contrary, the few detected that differences are not large enough to be considered clinically relevant. We also interpret these as an artifact of explorative analysis of the many quality-of-life aspects. Our results, however, provide valuable data to identify major problems that impair the quality of life of patients before and after pancreatoduodenectomy: role functioning, altered bowel habit, and fatigue.

Back to Top | Article Outline


In summary, this trial demonstrated several salient findings. Reconstruction by PG, when not restricted to a specific subtype and evaluated in a multicenter setting, did not reduce perioperative complications. Soft pancreatic tissue quality remains the most influential factor for POPF rate. PG may offer a technically less demanding but safe anastomotic technique. However, a higher rate of postoperative grade A/B hemorrhage was observed, advocating increased awareness toward hemostatic measures with PG. The rate of POPF remains substantial and is currently underestimated. Perioperative mortality can surpass the 5% margin even in the high-volume academic pancreatic surgery setting. Both may be attributed to extended indications for pancreatoduodenectomy in an ageing population. Quality of life in pancreatoduodenectomy patients is most severely impaired regarding role functioning and body image. The operation seems to ameliorate gastrointestinal and hepatic symptoms but does not improve fatigue and role functioning. Long-term exocrine pancreatic function after PG does not seem to be inferior to PJ.

Back to Top | Article Outline


T. Keck and U. F. Wellner equally contributed to the manuscript and share primary authorship.

Back to Top | Article Outline


1. Kausch W. Das Carcinom der Papilla Duodeni und seine radikale Entfernung. Beitr Z Clin Chir 1912; 78:439–486.
2. Howard J. History of pancreatic head resection–the evaluation of surgical technique. Am J Surg 2007; 194:S6–S10.
3. Cameron JL, Riall TS, Coleman J, et al. One thousand consecutive pancreaticoduodenectomies. Ann Surg 2006; 244:10–15.
4. Castillo CF, Morales-Oyarvide V, McGrath D, et al. Evolution of the Whipple procedure at the Massachusetts General Hospital. Surgery 2012; 152:S56–S63.
5. Kawai M, Kondo S, Yamaue H, et al. Predictive risk factors for clinically relevant pancreatic fistula analyzed in 1,239 patients with pancreaticoduodenectomy: multicenter data collection as a project study of pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 2011; 18:601–608.
6. Kimura W, Miyata H, Gotoh M, et al. A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: the 30-day and in-hospital mortality rates for pancreaticoduodenectomy. Ann Surg 2014; 259:773–780.
7. Leichtle SW, Kaoutzanis C, Mouawad NJ, et al. Classic Whipple versus pylorus-preserving pancreaticoduodenectomy in the ACS NSQIP. J Surg Res 2013; 183:170–176.
8. Venkat R, Puhan MA, Schulick RD, et al. Predicting the risk of perioperative mortality in patients undergoing pancreaticoduodenectomy: a novel scoring system. Arch Surg 2011; 146:1277–1284.
9. Wellner UF, Kulemann B, Lapshyn H, et al. Postpancreatectomy hemorrhage–incidence, treatment, and risk factors in over 1,000 pancreatic resections. J Gastrointest Surg 2014; 18:464–475.
10. Wu W, He J, Cameron JL, et al. The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy for adenocarcinoma. Ann Surg Oncol 2014; 21:2873–2881.
11. Fuks D, Piessen G, Huet E, et al. Life-threatening postoperative pancreatic fistula (grade C) after pancreaticoduodenectomy: incidence, prognosis, and risk factors. Am J Surg 2009; 197:702–709.
12. Pratt WB, Maithel SK, Vanounou T, et al. Clinical and economic validation of the International Study Group of Pancreatic Fistula (ISGPF) classification scheme. Ann Surg 2007; 245:443–451.
13. Gans SL, van Westreenen HL, Kiewiet JJS, et al. Systematic review and meta-analysis of somatostatin analogues for the treatment of pancreatic fistula. Br J Surg 2012; 99:754–760.
14. Gurusamy KS, Koti R, Fusai G, et al. Somatostatin analogues for pancreatic surgery. Cochrane Database Syst Rev Online 2012; 6:CD008370.
15. Allen PJ, Gönen M, Brennan MF, et al. Pasireotide for postoperative pancreatic fistula. N Engl J Med 2014; 370:2014–2022.
16. Shukla PJ, Barreto SG, Fingerhut A, et al. Toward improving uniformity and standardization in the reporting of pancreatic anastomoses: a new classification system by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2010; 147:144–153.
17. Shrikhande SV, Qureshi SS, Rajneesh N, et al. Pancreatic anastomoses after pancreaticoduodenectomy: do we need further studies? World J Surg 2005; 29:1642–1649.
18. Wente MN, Shrikhande SV, Muller MW, et al. Pancreaticojejunostomy versus pancreaticogastrostomy: systematic review and meta-analysis. Am J Surg 2007; 193:171–183.
19. Yeo CJ, Cameron JL, Maher MM, et al. A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy. Ann Surg 1995; 222:580–592.
20. Bassi C, Falconi M, Molinari E, et al. Reconstruction by pancreaticojejunostomy versus pancreaticogastrostomy following pancreatectomy: results of a comparative study. Ann Surg 2005; 242:767–771.discussion 771–773.
21. Duffas J-P, Suc B, Msika S, et al. A controlled randomized multicenter trial of pancreatogastrostomy or pancreatojejunostomy after pancreatoduodenectomy. Am J Surg 2005; 189:720–729.
22. Fernandez-Cruz L, Cosa R, Blanco L, et al. Pancreatogastrostomy with gastric partition after pylorus-preserving pancreatoduodenectomy versus conventional pancreatojejunostomy: a prospective randomized study. Ann Surg 2008; 248:930–938.
23. Wellner UF, Sick O, Olschewski M, et al. Randomized controlled single-center trial comparing pancreatogastrostomy versus pancreaticojejunostomy after partial pancreatoduodenectomy. J Gastrointest Surg 2012; 16:1686–1695.
24. Topal B, Fieuws S, Aerts R, et al. Pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy for pancreatic or periampullary tumours: a multicentre randomised trial. Lancet Oncol 2013; 14:655–662.
25. Figueras J, Sabater L, Planellas P, et al. Randomized clinical trial of pancreaticogastrostomy versus pancreaticojejunostomy on the rate and severity of pancreatic fistula after pancreaticoduodenectomy. Br J Surg 2013; 100:1597–1605.
26. El Nakeeb A, Hamdy E, Sultan AM, et al. Isolated Roux loop pancreaticojejunostomy versus pancreaticogastrostomy after pancreaticoduodenectomy: a prospective randomized study. HPB 2014; 16:713–722.
27. Wellner UF, Brett S, Bruckner T, et al. Pancreatogastrostomy versus pancreatojejunostomy for RECOnstruction after partial PANCreatoduodenectomy (RECOPANC): study protocol of a randomized controlled trial UTN U1111-1117-9588. Trials 2012; 13:45.
28. Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005; 138:8–13.
29. Hashimoto Y, Traverso LW. Incidence of pancreatic anastomotic failure and delayed gastric emptying after pancreatoduodenectomy in 507 consecutive patients: use of a web-based calculator to improve homogeneity of definition. Surgery 2010; 147:503–515.
30. Bauer P, Koehne K. Evaluation of experiments with adaptive interim analyses. Biometrics 1994; 50:1029–1041.
31. Wente MN, Veit JA, Bassi C, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery 2007; 142:20–25.
32. Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2007; 142:761–768.
33. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85:365–376.
34. Fitzsimmons D, Johnson CD, George S, et al. Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study Group on Quality of Life. Eur J Cancer 1999; 35:939–941.
35. Ethical principles for medical research involving human subjects. Available at: Published 2008. Accessed January 15, 2011.
36. Higgins JP, White IR, Wood AM. Imputation methods for missing outcome data in meta-analysis of clinical trials. Clin Trials 2008; 5:225–239.
37. Belyaev O, Munding J, Herzog T, et al. Histomorphological features of the pancreatic remnant as independent risk factors for postoperative pancreatic fistula: a matched-pairs analysis. Pancreatology 2011; 11:516–524.
38. Belyaev O, Herden H, Meier JJ, et al. Assessment of pancreatic hardness-surgeon versus durometer. J Surg Res 2010; 158:53–60.
39. Pratt WB, Callery MP, Vollmer CM. Risk prediction for development of pancreatic fistula using the ISGPF classification scheme. World J Surg 2008; 32:419–428.
40. Wellner UF, Kayser G, Lapshyn H, et al. A simple scoring system based on clinical factors related to pancreatic texture predicts postoperative pancreatic fistula preoperatively. HPB 2010; 12:696–702.
41. Mise Y, Vauthey J-N, Zimmitti G, et al. Ninety-day postoperative mortality is a legitimate measure of hepatopancreatobiliary surgical quality. Ann Surg 2015; 262:1071–1078.
42. Diener MK, Seiler CM, Rossion I, et al. Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial. Lancet 2011; 377:1514–1522.
43. Knaebel HP, Diener MK, Wente MN, et al. Systematic review and meta-analysis of technique for closure of the pancreatic remnant after distal pancreatectomy. Br J Surg 2005; 92:539–546.
44. Menahem B, Guittet L, Mulliri A, et al. Pancreaticogastrostomy is superior to pancreaticojejunostomy for prevention of pancreatic fistula after pancreaticoduodenectomy: an updated meta-analysis of randomized controlled trials. Ann Surg 2015; 261:882–887.
45. Clerveus M, Morandeira-Rivas A, Picazo-Yeste J, et al. Pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy: a systematic review and meta-analysis of randomized controlled trials. J Gastrointest Surg 2014; 18:1693–1704.
46. Wellner U, Makowiec F, Fischer E, et al. Reduced postoperative pancreatic fistula rate after pancreatogastrostomy versus pancreaticojejunostomy. J Gastrointest Surg 2009; 13:745–751.
47. Berberat PO, Ingold H, Gulbinas A, et al. Fast track-different implications in pancreatic surgery. J Gastrointest Surg 2007; 11:880–887.
48. Fong ZV, Ferrone CR, Thayer SP, et al. Understanding hospital readmissions after pancreaticoduodenectomy: can we prevent them?: a 10-year contemporary experience with 1,173 patients at the Massachusetts General Hospital. J Gastrointest Surg 2014; 18:137–144.discussion 144–145.
49. Hyder O, Dodson RM, Nathan H, et al. Influence of patient, physician, and hospital factors on 30-day readmission following pancreatoduodenectomy in the United States. JAMA Surg 2013; 148:1095–1102.
50. Ahmad SA, Edwards MJ, Sutton JM, et al. Factors influencing readmission after pancreaticoduodenectomy: a multi-institutional study of 1302 patients. Ann Surg 2012; 256:529–537.
51. Kristensen SR, Bech M, Quentin W. A roadmap for comparing readmission policies with application to Denmark, England and the United States. Health Policy 2015; 119:264–273.
52. Schmidt U, Simunec D, Piso P, et al. Quality of life and functional long-term outcome after partial pancreatoduodenectomy: pancreatogastrostomy versus pancreatojejunostomy. Ann Surg Oncol 2005; 12:467–472.

pancreatoduodenectomy; pancreatogastrostomy; pancreatojejunostomy; postoperative pancreatic fistula; postoperative pancreatic function

Supplemental Digital Content

Back to Top | Article Outline
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.