Overview of surgery in the treatment of exocrine pancreatic cancer and prognosis
- Carlos Fernandez-del Castillo, MD
Carlos Fernandez-del Castillo, MD
- Professor of Surgery
- Harvard Medical School
- Ramon E Jimenez, MD
Ramon E Jimenez, MD
- Assistant Professor of Surgery
- University of Connecticut Medical School
- Michael L Steer, MD
Michael L Steer, MD
- Emeritus Professor of Surgery
- Harvard Medical School
- Section Editors
- Stanley W Ashley, MD
Stanley W Ashley, MD
- Section Editor — Pancreatic and Hepatobiliary Surgery
- Chief Medical Officer and Senior Vice President for Clinical Affairs
- Brigham and Women’s Hospital
- Frank Sawyer Professor of Surgery
- Harvard Medical School
- Kenneth K Tanabe, MD
Kenneth K Tanabe, MD
- Section Editor — Gastrointestinal Malignancies
- Professor of Surgery
- Harvard Medical School
Approximately 53,070 people develop exocrine pancreatic cancer each year in the United States, and almost all are expected to die from their disease . Global, country-specific incidence and mortality rates are available from the World Health Organization Globocan database.
The majority of exocrine pancreatic cancers (85 percent) are adenocarcinomas arising from the ductal epithelium. Surgical resection is the only potentially curative treatment.
An overview of the surgical management of cancers of the exocrine pancreas will be reviewed here. The clinical manifestations, diagnosis, and surgical and nonsurgical therapy are discussed separately. (See "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer" and "Surgical resection of lesions of the head of the pancreas" and "Surgical resection of lesions of the body and tail of the pancreas" and "Treatment for potentially resectable exocrine pancreatic cancer".)
CANDIDATES FOR RESECTION
Surgical resection is the only potentially curative treatment. Unfortunately, because of the late presentation of the disease, only 15 to 20 percent of patients are candidates for pancreatectomy. The prognosis of pancreatic cancer is poor even in those with potentially resectable disease, and despite progress in surgical techniques and adjuvant therapy, the evidence that outcomes are improving over time is equivocal. (See 'Outcomes of pancreaticoduodenectomy' below and "Treatment for potentially resectable exocrine pancreatic cancer".)
However, in a study of the National Cancer Database, among those who were candidates for resection of pancreatic cancer, 38 percent were not offered surgery . Underutilization of surgery for early stage pancreatic cancer may be related to socioeconomic factors as well as physician pessimism regarding the prognosis of the disease.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66:7.
- Bilimoria KY, Bentrem DJ, Ko CY, et al. National failure to operate on early stage pancreatic cancer. Ann Surg 2007; 246:173.
- AJCC (American Joint Committee on Cancer) Cancer Staging Manual, 7th ed, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York Vol 2010, p.241.
- Seiler CA, Wagner M, Bachmann T, et al. Randomized clinical trial of pylorus-preserving duodenopancreatectomy versus classical Whipple resection-long term results. Br J Surg 2005; 92:547.
- Fujii T, Kanda M, Kodera Y, et al. Preservation of the pyloric ring has little value in surgery for pancreatic head cancer: a comparative study comparing three surgical procedures. Ann Surg Oncol 2012; 19:176.
- Zeh HJ, Zureikat AH, Secrest A, et al. Outcomes after robot-assisted pancreaticoduodenectomy for periampullary lesions. Ann Surg Oncol 2012; 19:864.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- Sanjay P, Takaori K, Govil S, et al. 'Artery-first' approaches to pancreatoduodenectomy. Br J Surg 2012; 99:1027.
- Evans DB, Farnell MB, Lillemoe KD, et al. Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 2009; 16:1736.
- Gurusamy KS, Kumar S, Davidson BR, Fusai G. Resection versus other treatments for locally advanced pancreatic cancer. Cochrane Database Syst Rev 2014; :CD010244.
- Doi R, Imamura M, Hosotani R, et al. Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial. Surg Today 2008; 38:1021.
- Lygidakis NJ, Singh G, Bardaxoglou E, et al. Mono-bloc total spleno-pancreaticoduodenectomy for pancreatic head carcinoma with portal-mesenteric venous invasion. A prospective randomized study. Hepatogastroenterology 2004; 51:427.
- Yamada S, Fujii T, Sugimoto H, et al. Aggressive surgery for borderline resectable pancreatic cancer: evaluation of National Comprehensive Cancer Network guidelines. Pancreas 2013; 42:1004.
- Mollberg N, Rahbari NN, Koch M, et al. Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg 2011; 254:882.
- Leach SD, Lee JE, Charnsangavej C, et al. Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head. Br J Surg 1998; 85:611.
- Fuhrman GM, Leach SD, Staley CA, et al. Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group. Ann Surg 1996; 223:154.
- Murakami Y, Uemura K, Sudo T, et al. Benefit of portal or superior mesenteric vein resection with adjuvant chemotherapy for patients with pancreatic head carcinoma. J Surg Oncol 2013; 107:414.
- Tseng JF, Raut CP, Lee JE, et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 2004; 8:935.
- Raut CP, Tseng JF, Sun CC, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg 2007; 246:52.
- Martin RC 2nd, Scoggins CR, Egnatashvili V, et al. Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes. Arch Surg 2009; 144:154.
- Ramacciato G, Mercantini P, Petrucciani N, et al. Does portal-superior mesenteric vein invasion still indicate irresectability for pancreatic carcinoma? Ann Surg Oncol 2009; 16:817.
- Castleberry AW, White RR, De La Fuente SG, et al. The impact of vascular resection on early postoperative outcomes after pancreaticoduodenectomy: an analysis of the American College of Surgeons National Surgical Quality Improvement Program database. Ann Surg Oncol 2012; 19:4068.
- Fortner JG, Klimstra DS, Senie RT, Maclean BJ. Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy. Ann Surg 1996; 223:147.
- Sindelar WF. Clinical experience with regional pancreatectomy for adenocarcinoma of the pancreas. Arch Surg 1989; 124:127.
- Fortner JG. Regional pancreatectomy for cancer of the pancreas, ampulla, and other related sites. Tumor staging and results. Ann Surg 1984; 199:418.
- Tol JA, Gouma DJ, Bassi C, et al. Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery 2014; 156:591.
- Ishikawa O, Ohhigashi H, Sasaki Y, et al. Practical usefulness of lymphatic and connective tissue clearance for the carcinoma of the pancreas head. Ann Surg 1988; 208:215.
- Tsuchiya R, Tsunoda T, Yamaguchi T. Operation of choice for resectable carcinoma of the head of the pancreas. Int J Pancreatol 1990; 6:295.
- Pedrazzoli S, DiCarlo V, Dionigi R, et al. Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg 1998; 228:508.
- Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 2002; 236:355.
- Farnell MB, Pearson RK, Sarr MG, et al. A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery 2005; 138:618.
- Jang JY, Kang MJ, Heo JS, et al. A prospective randomized controlled study comparing outcomes of standard resection and extended resection, including dissection of the nerve plexus and various lymph nodes, in patients with pancreatic head cancer. Ann Surg 2014; 259:656.
- Nimura Y, Nagino M, Takao S, et al. Standard versus extended lymphadenectomy in radical pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas: long-term results of a Japanese multicenter randomized controlled trial. J Hepatobiliary Pancreat Sci 2012; 19:230.
- Sun J, Yang Y, Wang X, et al. Meta-analysis of the efficacies of extended and standard pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas. World J Surg 2014; 38:2708.
- Yeo CJ, Cameron JL, Sohn TA, et al. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg 1997; 226:248.
- Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg 1993; 165:68.
- Benassai G, Mastrorilli M, Quarto G, et al. Survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas. Chir Ital 2000; 52:263.
- Millikan KW, Deziel DJ, Silverstein JC, et al. Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas. Am Surg 1999; 65:618.
- Bakkevold KE, Arnesjø B, Dahl O, Kambestad B. Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study. Eur J Cancer 1993; 29A:698.
- Tsao JI, Rossi RL, Lowell JA. Pylorus-preserving pancreatoduodenectomy. Is it an adequate cancer operation. Arch Surg 1994; 129:405.
- Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg 1995; 221:721.
- Cameron JL, Pitt HA, Yeo CJ, et al. One hundred and forty-five consecutive pancreaticoduodenectomies without mortality. Ann Surg 1993; 217:430.
- Balcom JH 4th, Rattner DW, Warshaw AL, et al. Ten-year experience with 733 pancreatic resections: changing indications, older patients, and decreasing length of hospitalization. Arch Surg 2001; 136:391.
- Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg 1990; 211:447.
- Pellegrini CA, Heck CF, Raper S, Way LW. An analysis of the reduced morbidity and mortality rates after pancreaticoduodenectomy. Arch Surg 1989; 124:778.
- Crist DW, Sitzmann JV, Cameron JL. Improved hospital morbidity, mortality, and survival after the Whipple procedure. Ann Surg 1987; 206:358.
- Kneuertz PJ, Pitt HA, Bilimoria KY, et al. Risk of morbidity and mortality following hepato-pancreato-biliary surgery. J Gastrointest Surg 2012; 16:1727.
- Birkmeyer JD, Siewers AE, Finlayson EV, et al. Hospital volume and surgical mortality in the United States. N Engl J Med 2002; 346:1128.
- Birkmeyer JD, Warshaw AL, Finlayson SR, et al. Relationship between hospital volume and late survival after pancreaticoduodenectomy. Surgery 1999; 126:178.
- Bilimoria KY, Talamonti MS, Sener SF, et al. Effect of hospital volume on margin status after pancreaticoduodenectomy for cancer. J Am Coll Surg 2008; 207:510.
- Birkmeyer JD, Stukel TA, Siewers AE, et al. Surgeon volume and operative mortality in the United States. N Engl J Med 2003; 349:2117.
- Gooiker GA, van Gijn W, Wouters MW, et al. Systematic review and meta-analysis of the volume-outcome relationship in pancreatic surgery. Br J Surg 2011; 98:485.
- Hartwig W, Werner J, Jäger D, et al. Improvement of surgical results for pancreatic cancer. Lancet Oncol 2013; 14:e476.
- Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg 2003; 237:74.
- Serrano PE, Cleary SP, Dhani N, et al. Improved long-term outcomes after resection of pancreatic adenocarcinoma: a comparison between two time periods. Ann Surg Oncol 2015; 22:1160.
- Winter JM, Brennan MF, Tang LH, et al. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol 2012; 19:169.
- Johnson CD, Schwall G, Flechtenmacher J, Trede M. Resection for adenocarcinoma of the body and tail of the pancreas. Br J Surg 1993; 80:1177.
- Dalton RR, Sarr MG, van Heerden JA, Colby TV. Carcinoma of the body and tail of the pancreas: is curative resection justified? Surgery 1992; 111:489.
- Brennan MF, Moccia RD, Klimstra D. Management of adenocarcinoma of the body and tail of the pancreas. Ann Surg 1996; 223:506.
- Winter JM, Cameron JL, Campbell KA, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg 2006; 10:1199.
- Schmidt CM, Powell ES, Yiannoutsos CT, et al. Pancreaticoduodenectomy: a 20-year experience in 516 patients. Arch Surg 2004; 139:718.
- Schmidt CM, Glant J, Winter JM, et al. Total pancreatectomy (R0 resection) improves survival over subtotal pancreatectomy in isolated neck margin positive pancreatic adenocarcinoma. Surgery 2007; 142:572.
- Brooks JR, Brooks DC, Levine JD. Total pancreatectomy for ductal cell carcinoma of the pancreas. An update. Ann Surg 1989; 209:405.
- Dresler CM, Fortner JG, McDermott K, Bajorunas DR. Metabolic consequences of (regional) total pancreatectomy. Ann Surg 1991; 214:131.
- Andrén-Sandberg A, Ihse I. Factors influencing survival after total pancreatectomy in patients with pancreatic cancer. Ann Surg 1983; 198:605.
- Karpoff HM, Klimstra DS, Brennan MF, Conlon KC. Results of total pancreatectomy for adenocarcinoma of the pancreas. Arch Surg 2001; 136:44.
- Müller MW, Friess H, Kleeff J, et al. Is there still a role for total pancreatectomy? Ann Surg 2007; 246:966.
- Reddy S, Wolfgang CL, Cameron JL, et al. Total pancreatectomy for pancreatic adenocarcinoma: evaluation of morbidity and long-term survival. Ann Surg 2009; 250:282.
- Grace PA, Pitt HA, Tompkins RK, et al. Decreased morbidity and mortality after pancreatoduodenectomy. Am J Surg 1986; 151:141.
- Nathan H, Wolfgang CL, Edil BH, et al. Peri-operative mortality and long-term survival after total pancreatectomy for pancreatic adenocarcinoma: a population-based perspective. J Surg Oncol 2009; 99:87.
- Kang MJ, Jang JY, Chang YR, et al. Revisiting the concept of lymph node metastases of pancreatic head cancer: number of metastatic lymph nodes and lymph node ratio according to N stage. Ann Surg Oncol 2014; 21:1545.
- Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg 2006; 244:10.
- Bilimoria KY, Bentrem DJ, Ko CY, et al. Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database. Cancer 2007; 110:738.
- Mayo SC, Nathan H, Cameron JL, et al. Conditional survival in patients with pancreatic ductal adenocarcinoma resected with curative intent. Cancer 2012; 118:2674.
- Meyer W, Jurowich C, Reichel M, et al. Pathomorphological and histological prognostic factors in curatively resected ductal adenocarcinoma of the pancreas. Surg Today 2000; 30:582.
- Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 2000; 4:567.
- Chang DK, Johns AL, Merrett ND, et al. Margin clearance and outcome in resected pancreatic cancer. J Clin Oncol 2009; 27:2855.
- Helm J, Centeno BA, Coppola D, et al. Histologic characteristics enhance predictive value of American Joint Committee on Cancer staging in resectable pancreas cancer. Cancer 2009; 115:4080.
- Kinsella TJ, Seo Y, Willis J, et al. The impact of resection margin status and postoperative CA19-9 levels on survival and patterns of recurrence after postoperative high-dose radiotherapy with 5-FU-based concurrent chemotherapy for resectable pancreatic cancer. Am J Clin Oncol 2008; 31:446.
- Franko J, Hugec V, Lopes TL, Goldman CD. Survival among pancreaticoduodenectomy patients treated for pancreatic head cancer <1 or 2 cm. Ann Surg Oncol 2013; 20:357.
- Sinn M, Striefler JK, Sinn BV, et al. Does long-term survival in patients with pancreatic cancer really exist? Results from the CONKO-001 study. J Surg Oncol 2013; 108:398.
- Ferrone CR, Kattan MW, Tomlinson JS, et al. Validation of a postresection pancreatic adenocarcinoma nomogram for disease-specific survival. J Clin Oncol 2005; 23:7529.
- Tomlinson JS, Jain S, Bentrem DJ, et al. Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg 2007; 142:767.
- Brennan MF, Kattan MW, Klimstra D, Conlon K. Prognostic nomogram for patients undergoing resection for adenocarcinoma of the pancreas. Ann Surg 2004; 240:293.
- CANDIDATES FOR RESECTION
- PREOPERATIVE CONSIDERATIONS
- Staging laparoscopy
- Role of preoperative biliary drainage
- TUMORS IN THE HEAD OF THE PANCREAS
- - Vascular resection
- - Regional pancreatectomy
- - Extent of lymphadenectomy
- Outcomes of pancreaticoduodenectomy
- TUMORS IN THE BODY OR TAIL
- Outcomes of distal pancreas resection
- TUMORS INVOLVING THE ENTIRE GLAND
- PROGNOSIS AND PROGNOSTIC FACTORS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS
- Tumors in the head/uncinate process
- Tumors of the tail/body
- Tumors involving the entire gland