The American Cancer Society has estimated that as many as 43,920 citizens will be diagnosed with pancreatic cancer in 2012 and an additional 37,390 will die of the disease this year alone 1. Pancreatic cancer represents the tenth most common cancer among American’s and is the sixth most common cause of death. Patients suffering from various forms of pancreatic pathology such as neoplasms in the head of the pancreas and in the periampullary region, benign neoplasms, and even chronically symptomatic pancreatitis refractive to medical treatment can benefit from pancreaticoduodenectomy (PD)2. Despite continual improvements to techniques of reconstituting pancreatoenteric continuity, surgical morbidity remains at 40-50%, with the most common complications being post-operative pancreatic fistula (POPF), delayed gastric emptying, and wound infection 3.

Anastomotic failure remains one of the most serious and dreaded complications. POPF is believed to be a consequence of pancreatic exocrine secretion seepage across a compromised anastomotic site. The primary mechanism is likely autodigestion and destruction of the tissue surrounding the PJ anastomotic site leading to dehiscence and seepage into the abdominal cavity. The release of these activated pancreatic juices then cause peripancreatic collections, intraabdominal abscesses, hemorrhage, and POPF4.

The additional association of POPF with increased overall morbidity, increased hospital stay and readmission, and increased hospital cost 5 have led to development of many techniques and varied opinion between surgeons regarding the overall efficacy of pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) in the pancreatoenteric reconstruction following PD 6.

Several retrospective studies 7, 8, 9, a randomized control trial 10, and a meta analysis 11 have all suggested a decreased rate of POPF with PG over PJ. However, a more recent meta analysis 12 and several randomized control trials 13-17 have shown data suggesting that there is in fact no significant difference in the incidence of POPF and overall morbidity between the two modes of pancreatoenteric reconstruction. Thus, after considering the outcomes of different reconstructions, we decided to conduct a meta-analysis of five randomized control trials to evaluate and compare the following morbidities associated with PG and PJ after PD: POPF, delayed gastric emptying (DGE), biliary leak (BL), fluid collection (FC), and overall morbidity and mortality.

The process of identifying relevant trials from all 86 trials retrieved from the initial manual electronic searches is described in Figure 1. Sixty-five studies were excluded from the initial group because the study was irrelevant or the study design was not congruent with our search criteria. This left eighteen studies as potentially appropriate for the meta- analysis. Seven studies were further eliminated because there was inadequate randomization. Six more studies were removed from the remaining studies due to retrospective examination of data and for reporting other methods of reconstruction which were not being included in the meta-analysis. This left five randomized controlled trials 12-17 which examined the relevant outcomes being considered in the meta-analysis. Among the five studies, there were a total of 669 patients, of whom 335 underwent PG; the remaining 334 patients underwent reconstruction using PJ. The main characteristics examined are delineated individually below.

Figure 1: Forest Plot for fluid collection.

The primary endpoint examined was formation of POPF which was reported by all studies 12-17 and there was found to have no significant difference in the overall incidence (OR 0.1, 95% CI = 0.45 to 1.10, p = 0.13). Examination of four studies 14-17 comprising of 524 patients with the endpoint of mortality, was found to have no statistically significant difference in incidence with either method of reconstruction (OR 1.07, 95% CI = 0.43 to 2.66, p = 0.88). A similar finding was reached for the endpoint of Delayed Gastric Emptying utilizing four studies 13-16 which reported the outcome for 520 patients (OR 0.77, 95% CI = 0.47 to 1.26, p = 0.29). When considering the four studies 13-16, examining the outcome of incidence of overall morbidity in the cohort of 553 patients, there was found to be no statistically significant difference (OR 0.79, 95% CI = 0.56 to 1.12, p = 0.18). There was also found to be no significant difference in the incidence of bile leak in the four studies 13-16 examining the outcome in 553 patients (OR 0.55, 95% CI = 0.22 to 1.35, p = 0.19). Finally, the only outcome examined in which there was found to be a statistically significant difference of incidence was Fluid Collection. PG was found to have a smaller risk of incidence of fluid collection as was reported by the four studies 14-17 which evaluated the outcome in 524 patients (OR 0.51 95% CI = 0.31 to 0.83, p = 0.006).

The formation of post-operative pancreatic fistula following pancreaticoduodenectomy remains one of the major causes of morbidity and a factor contributing to mortality. Reconstitution of the flow of exocrine secretions from the pancreas is an important factor in the reconstruction following the procedure and seepage of these fluids across an area of anastomotic failure is the cause of POPF formation.

The two main risk factors reported favoring the formations of POPF have been a texture of the pancreatic remnant 18 and the diameter of the pancreatic stump 19. The most largely used methods for reconstruction have been pancreatogastrostomy and pancreatojejunostomy. This meta-analysis showed a significant difference in the incidence of only one secondary endpoint examined, fluid collection (p = 0.006). The randomized control trials examined showed that the incidence of fluid collection following PD was decreased when PG was used to reinstate pancreatoenteric continuity. The primary endpoint, formation of POPF, showed no significant difference in incidence (p = 0.13). The remaining secondary endpoints examined all showed no significant difference in incidence, DGE (p=0.29), mortality (p = 0.88), overall morbidity (p = 0.18), and bile leak (p = 0.19).

However, in numerous RCT’s, PG has been cited as being the superior method of reconstruction when examining the aforementioned endpoints. This could be due to a number of potential technical advantages of PG. According to Yeo et al., the PG anastomosis can be performed more easily due to the proximity of the transected pancreatic remnant to the mobilized posterior wall of the stomach. In addition, it is postulated that due to the entrance of the pancreatic exocrine secretions into an acidic environment (the gastric contents), digestive damage of the actual anastomosis site by the proteolytic enzymes is avoided. Conversely, the presence of intestinal enterokinases and bile can cause the activation of proteolytic enzymes causing digestion of the mucosa at the anastomosis site leading to POPF after PJ 20. PG avoids the accumulation of secretions in the early postoperative period in the jejunal loop created in the anastomosis, this coupled with decompression of the stomach postoperatively can provide removal of excess secretions, thereby relieving tension on the anastomosis and preventing leakage. Yeo et al proposed that due to these proposed theoretical advantages, published studies may favor PG over PJ in reconstruction following PD.

As mentioned previously, the main physical factors at the anastomotic site contributing to the formation of POPF are texture of the remnant 24, in that a soft remnant will prove to be fragile compared to a fibrotic remnant and will not hold as will in the anastomosis, thereby having a higher rate of leakage 21. Other pancreatic factors influencing patency of the anastomosis include original pathology, blood supply to the pancreatic remnant 22, pancreatic juice output 23, and duct diameter. The most important factors of these were texture, duct diameter, juice output, and remnant blood supply. Other non-pancreatic factors were patient related (age, gender, severity of preoperative jaundice, comorbid illness) and operative factors (operation time, blood loss, type of anastomosis, and stenting of the duct)24, 25.

The results of our meta analysis show all RCTs reporting diverse pancreatic, patient, and operative factors failed to show any significant difference in the postoperative incidence of pancreatic fistula regardless of the method of reconstruction used. Our meta-analysis results show, similar to those found by Wente et al, in their 2007 meta analysis 26, there is in fact no significant difference in the postoperative outcomes between either PG or PJ for reconstruction following PD. Even with the inclusion of the extra RCT, by Wellner et al in 2012, only furthers the conclusion that there is no significant difference in the clinical endpoints following either method of reconstruction. Their study reported the same for all endpoints examined: POPF (p = 0.775), reduced hospital stay (p = 0.155), Delayed gastric emptying (p = 0.246), and intraluminal bleeding (p = 0.364)27.

In conclusion, this meta analysis shows no significant difference in incidence of postoperative complications, especially POPF following either PG or PJ for reconstruction after a Whipple procedure. It seems apparent that more attention must be paid to the basics of constructing the pancreatic anastomosis and the surgeon must pay great attention to the pancreatic, patient, and operative factors mentioned earlier in order to optimize the patency of the pancreatoenteric anastomosis.

1. American Cancer Society. What are the key statistics about pancreatic cancer? Available at: http://www.cancer.org/cancer/pancreaticcancer/detailedguide/pancre atic-cancer-key-statistics. Accessed April 15, 2012.
2. Shrikhande S. V., Qureshi S. S., Rajneesh N., and Shukla P. J., “Pancreatic anastomoses after pancreaticoduodenectomy: do we need further studies?” World Journal of Surgery, vol. 29, no.12, pp. 1642–1649, 2005.
3. Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J et al. Pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J GastrointestSurg. 2006;10:1199-1211.
4. Crippa S, Salvia R, Falconi M, Buttirini G, Landoni L, and Bassi C, Anastomotic leakage in pancreatic surgery. HPB (Oxford). 2007;9(1):8-15.
5. Veillette G, Dominguez I, Ferrone C, Thayer SP, McGrath D, Warshaw AL, and Fernandez-del Castillo C. Implications and management of pancreatic fistulas following pancreaticoduodenectomy: The massachusetts general hospital experience. Arch Surg 2008;143:476–481.
6. Wellner U, Sick O, Olschewski M, Adam U, Hopt U, and Keck T. Randomized Controlled Single-Center Trial Comparing Pancreatogastrostomy Versus Pancreatojejunostomy After Partial Pancreatoduodenectomy: The Society for Surgery of the Alimentary Tract. J Gastrointest Surg (2012) 16:1686-1695.
7. Shukla P. J., “The challenges of improving survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma,” Annals of Surgery, vol. 254, no. 2, pp. 385–386, 2011.
8. Schlitt H. J, Schmidt U, Simunec D, Jager M, Aselmann H, Neipp M, and Piso P, “Morbidity and mortality associated with pancreatogastrostomy and pancreatojejunostomy following partial pancreatoduodenectomy,” British Journal of Surgery, vol. 89, no. 10, pp. 1245–1251, 2002.
9. E. Oussoultzoglou, P. Bachellier, J. M. Bigourdan, J. C. Weber, H. Nakano, and D. Jaeck, “Pancreaticogastrostomy decreased relaparotomy caused by pancreatic fistula after pancreaticoduodenectomy compared with pancreaticojejunostomy,” Archives of Surgery, vol. 139, no. 3, pp. 327–335, 2004.
10. Fern’andez-Cruz L., Cosa R., Blanco L., L’opez-Boado M. A., and Astudillo E., “Pancreatogastrostomy with gastric partition after pylorus- preserving pancreatoduodenectomy versus conventional pancreatojejunostomy a prospective randomized study,” Annals of Surgery, vol. 248, no. 6, pp. 930–937, 2008.
11. McKay A., Mackenzie S., Sutherland F. R., Bathe O.F., Doig C., Dort J., Vollmer Jr C.M., and Dixon E., “Metaanalysis of pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy,” British Journal of Surgery, vol. 93, no. 8, pp. 929–936, 2006.
12. Wente M. N., Shrikhande S. V., M ̈uller M. W., Diener M. K., Seiler C. M., and Friess H., “Pancreaticojejunostomy versus pancreaticogastrostomy: systematic review and metaanalysis,” American Journal of Surgery, vol. 193, no. 2, pp. 171– 183, 2007.
13. Yeo C. J., Cameron J. L., Maher M. M., Sauter P.K., Zahurak M.L., Talamini M.A., Lillemoe K.D., and Pitt H.A., “A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy,” Annals of Surgery, vol. 222, no. 4, pp. 580–592, 1995.
14. Bassi C., Falconi M., Molinari E., Salvia R., Buttirini G., Sartori N., et al., “Reconstruction by pancreaticojejunostomy versus pancreaticogastrostomy following pancreatectomy: results of a comparative study,” Annals of Surgery, vol. 242, no. 6, pp. 767–773, 2005.
15. Duffas J. P., Suc B., Msika S., Fourtanier G., Muscari F., Hay J.M. et al., “controlled randomized multicenter trial of pancreatogastrostomy or pancreatojejunostomy after pancreatoduodenectomy,” American Journal of Surgery, vol. 189, no. 6, pp. 720–729, 2005.
16. Fernandez-Cruz L., Cosa R., Blanco L., L ́opez-Boado M. A., and Astudillo E., “Pancreatogastrostomy with gastric partition after pylorus- preserving pancreatoduodenectomy versus conventional pancreatojejunostomy a prospective randomized study,” Annals of Surgery, vol. 248, no. 6, pp. 930–937, 2008.
17. Wellner U, Sick O, Olschewski M, Adam U, Hopt U, and Keck T. Randomized Controlled Single-Center Trial Comparing Pancreatogastrostomy Versus Pancreatojejunostomy After Partial Pancreatoduodenectomy: The Society for Surgery of the Alimentary Tract. J Gastrointest Surg (2012) 16:1686-1695.
18. Doll R. Controlled trials: the 1948 watershed. BMJ. 1998;317(7167):1217-20.
19. Lin JW, Cameron JL, Yeo CL, Riall TS, and LIllemoe KD, Risk factors and outcomes in postpancreaticoduodenectomy pancreaticocutaneous fistula. J Gastrointest Surg. 2004;8(8):951-9.
20. Yeo C. J., Cameron J. L., Maher M. M., Sauter P.K., Zahurak M.L., Talamini M.A., Lillemoe K.D., and Pitt H.A., “A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy,” Annals of Surgery, vol. 222, no. 4, pp. 580–592, 1995.
21. Eiji U., Takashi T., Yoshiharu N., Aimoto T., and Naito Z., “Relationship between grade of fibrosis in pancreatic stump and postoperative pancreatic exocrine activity after pancreaticoduodenectomy: with special reference to insuffiency of pancreaticointestinal anastomosis,” Journal of Nippon Medical School, vol. 69, no. 6, pp. 549-556, 2002.
22. Sato N., Yamaguchi K., Chijiiwa K., and Tanaka M., “Risk analysis of pancreatic fistula after pancreatic head resection,” Archives of Surgery, vol. 133, no. 10, pp. 1094–1098, 1998.
23. Hamanaka Y., Nishihara K., Hamasaki T., Kawahata A., Yamamoto S., Tsurunni M., et al., “Pancreatic juice output after pancreatoduodenectomy in relation to pancreatic consistency, duct size, and leakage,” Surgery, vol. 119, no. 3, pp. 281–287, 1996.
24. Y. M. Shyr, C. H. Su, C. W. Wu, and W. Y. Lui, “Does drainage fluid amylase reflect pancreatic leakage after pancreaticoduodenectomy?” World Journal of Surgery, vol. 27, no. 5, pp. 606– 610, 2003.
25. M. I. Van Berge Henegouwen, L. T. De Wit, T. M. Van Gulik, H. Obertop, and D. J. Gouma, “Incidence, risk factors, and treatment of pancreatic leakage after pancreaticoduodenectomy: drainage versus resection of the pancreatic remnant,” Journal of the American College of Surgeons, vol. 185, no. 1, pp. 18–24, 1997.
26. M. N. Wente, S. V. Shrikhande, M. W. M ̈uller, M. K. Diener, C. M. Seiler, and H. Friess, “Pancreaticojejunostomy versus pancreaticogastrostomy: systematic review and meta analysis,” American Journal of Surgery, vol. 193, no. 2, pp. 171– 183, 2007.
27. Wellner U, Sick O, Olschewski M, Adam U, Hopt U, and Keck T. Randomized Controlled Single-Center Trial Comparing Pancreatogastrostomy Versus Pancreatojejunostomy After Partial Pancreatoduodenectomy: The Society for Surgery of the Alimentary Tract. J Gastrointest Surg (2012) 16:1686-1695.