Pancreatic cancer surgery

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Sudarshana Datta, MD [2]

## Overview

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The mainstay of therapy for pancreatic cancer is surgery. The different surgical techniques that may be used for resectable pancreatic cancer include pancreaticoduodenectomy (Whipple Procedure), pylorus sparing Whipple procedure, distal pancreatectomy and total pancreatectomy. The method of surgical resection depends on the locally invasive characteristics and size of the neoplasm. The National Comprehensive Cancer Network (NCCN) has recommended certain guidelines on resectability of pancreatic neoplasms based on resection margins, probability of cure, age, and comorbidities. Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients. CA19-9 levels help predict the likelihood of complete resection, the prognosis of patients with resectable disease and the presence of occult metastasis.

## Surgery

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* In patients with pancreatic cancer, surgery is the primary modality of treatment.
* Various methods of surgical resection may be employed and each of these has its own sets of risks and perioperative complications.
* The benefits, risks and complications are discussed by the patient and surgical team before arriving at a well-informed decision. The method of surgical resection depends on the following features:[1][2][3]
* Locally invasive characteristics of the neoplasm
* Size

#### Criteria for Unresectability

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* Tumor larger than 5 cm
* Tumor invading adjacent tissue of organs (excluding duodenum)
* Encasement, stenosis, or occlusion of the celiac artery, celiac artery branches, and/or SMA
* Portal vein(PV) and/or Superior Mesenteric Vein (SMV) encasement (some centers will operate with venous invasion)
* Hepatic metastasis
* Distant metastasis (i.e. non regional lymph nodes)
* Peritoneal carcinomatosis

Surgical methods of curative resection include:

* Distal pancreatectomy
* Total pancreatectomy
* Pancreaticoduodenectomy, where pylorus may or may not be spared on an individual basis

The National Comprehensive Cancer Network (NCCN) has recommended certain guidelines on resectability of pancreatic neoplasms based on a statement passed by the American pancreatic association:[4][5][6][7][8]

* Patient selection is based on:
* Resection margins
* High probability of cure
* Age of the patient
* Comorbidities
* Curative resection is not contraindicated in all patients with vascular invasion:[9][10][11][12][13]
* Involvement of the portal or superior mesenteric vein can be resected and reconstructed with the help of splenic, saphenous or internal jugular veins.[14][15][16][17]
* The involvement of arteries such as the hepatic, celiac or superior mesenteric are contraindications to resection.[18]
* Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients.
* The European Society for Medical Oncology (ESMO) has certain guidelines on the treatment of pancreatic cancer:[19][20][21]
* The only curative therapy for pancreatic cancer is surgical resection.
* The five year survival of patients with pancreatic cancer is 10 percent.
* Patients with node-positive tumors have very poor long term survival.
* Chemotherapy is not preferred metastatic cancer.
* Gemcitabine is preferred over 5 FU in case of metastasis.
* Treatment in case of metastatic cancer is symptomatic with bypass surgery or stent placement for gastric outlet obstruction or obstructive jaundice.
* In case of locally advanced disease which is unresectable, the following methods of treatment are preferred:[22]
* Microwave ablation
* Photodynamic therapy
* Irreversible electroporation
* Photodynamic therapy
* High-intensity focused ultrasound (HIFU)
* Iodine-125–cryosurgery
* Iodine-125
* Stereotactic body radiation therapy (SBRT)
* Radiofrequency ablation (RFA)

* Treatment of pancreatic cancer depends on the stage of the cancer.[23]
* There are different surgical techniques that may be used for resectable pancreatic cancer and their prognosis has been extensively studied: [1][6][7][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]

#### Pancreaticoduodenectomy (Whipple Procedure)

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Various features of Whipple procedure are as follows:[19][6][39][40][41][42][43][44]

* Whipple procedure is mainly performed for tumors located in:[45][40][46]
* Periampullary region
* Duodenum
* Bile duct (cholangiocarcinoma)
* Pancreatic duct
* Head of pancreas
* Whipple procedure involves removal of the following components due to common blood supply:
* Stomach antrum
* Gallbladder
* Duodenum
* Head of pancreas
* After removal of the above structures, the biliary and distal pancreatic ducts are anastomosed to the jejunum to facilitate surgical drainage.
* Biliary drainage may also be performed preoperatively to decrease chances of infection.[47]

* Whipple procedure is associated with several morbidities that may increase patient mortality:[48][49][50][51][52][53][54][55][56][57][58][59][60]
* Postoperative abscess
* Wound infection[61]
* Anastomotic leak
* Delay in gastric emptying[62]

#### Pylorus sparing Whipple procedure

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* The pylorus may be spared as a modification of Whipple procedure to decrease gastric emptying due to antrectomy.[63][64]
* Pylorus sparing surgery significantly reduces the incidence of nutritional deficiencies arising from this surgery.

#### Distal Pancreatectomy

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* This procedure has a limited use in curative resection of pancreatic cancer. [48][65][66]
* It is mainly performed for tumors located in:[67][68]
* Body of pancreas
* Tail of pancreas
* Distal Pancreatectomy involves the following components:
* Separation of the distal pancreas bearing the tumor from the normal tissue.
* Resection of the affected portion.
* Oversewing of the distal pancreatic duct.
* This form of surgery has fewer morbidities than the Whipple procedure.
* This procedure is associated with the following morbidities:[69][70][71][72]
* Pancreatic endocrine insufficiency
* Bleeding
* Leakage of pancreatic stump

#### Total Pancreatectomy

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Various features of total pancreatectomy are as follows:[48][73][74][75][76][77][78][79]

* Total pancreatectomy is the least preferred surgery due to high mortality rate.
* Total pancreatectomy is mainly performed for tumors located in:
* Neck of the pancreas
* Involvement of the neck of pancreas may lead to the development of insulin dependent DM.

#### Lymphadnectomy

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* Removal of positive nodes is preferrable, but some surgeons prefer extended as opposed to standard lymphadenectomy.[33][34][80][81][82][83][84][85][86]

#### CA 19-9 level

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* Elevated levels of CA19-9 can help in the following ways:[87]
* Predict the likelihood of complete resection
* Predict prognosis of patients with resectable pancreatic cancer
* Predict the presence of occult metastasis
* CA19-9 levels are not used to dictate the initial strategy for treatment of pancreatic cancer.

###  Palliative Therapy

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Palliative therapy in patients with pancreatic cancer mainly involves the management of symptoms arising as a result of complications of surgery:[88][89][90][91][92][93][94][95]

#### Pain:

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* There are various techniques for pain management as palliative therapy in patients.

* Surgical techniques used to treat pain in advanced pancreatic cancer include:
* Endoscopic decompression with stent placement in patients with biliary or pancreatic duct obstruction
* Neurolysis of the celiac ganglia by approaches, such as:
* Intraoperative
* Transgastric
* Transthoracic
* Transabdominal

#### Jaundice:

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* Obstructive jaundice can present with features of cholangitis:
* Fever and chills
* Nausea, vomiting
* Clay-colored stools
* Dark urine
* Yellowish discoloration of skin
* Pruritus
* Right upper quadrant pain
* Anorexia
* Preferred treatment in patients with obstructive jaundice:
* Endoscopic decompression with stent placement in patients with biliary obstruction.
* Techniques of biliary decompression:
* Cholecystojejunostomy
* Choledochojejunostomy

* Types of stents:
* Metal- costly, longer lifespan
* Plastic- cheaper, need replacement every three months

#### Duodenal obstruction

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* Preferred treatment:
* Endoscopic stenting of duodenal obstruction
* Gastrojejunostomy

## References

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1. ↑ 1.0 1.1 Ryan DP, Hong TS, Bardeesy N (2014). "Pancreatic adenocarcinoma". N. Engl. J. Med. 371 (11): 1039–49. doi:10.1056/NEJMra1404198. PMID 25207767.
2. ↑ Allen PJ, Kuk D, Castillo CF, Basturk O, Wolfgang CL, Cameron JL, Lillemoe KD, Ferrone CR, Morales-Oyarvide V, He J, Weiss MJ, Hruban RH, Gönen M, Klimstra DS, Mino-Kenudson M (2017). "Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for T and N Staging in Patients With Pancreatic Adenocarcinoma". Ann. Surg. 265 (1): 185–191. doi:10.1097/SLA.0000000000001763. PMID 27163957.
3. ↑ Bilimoria KY, Bentrem DJ, Ko CY, Ritchey J, Stewart AK, Winchester DP, Talamonti MS (2007). "Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database". Cancer. 110 (4): 738–44. doi:10.1002/cncr.22852. PMID 17580363.
4. ↑ Fonseca AL, Fleming JB (2017). "Surgery for pancreatic cancer: critical radiologic findings for clinical decision making". Abdom Radiol (NY). doi:10.1007/s00261-017-1332-z. PMID 28948329.
5. ↑ Al-Hawary MM, Francis IR, Chari ST, Fishman EK, Hough DM, Lu DS, Macari M, Megibow AJ, Miller FH, Mortele KJ, Merchant NB, Minter RM, Tamm EP, Sahani DV, Simeone DM (2014). "Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the Society of Abdominal Radiology and the American Pancreatic Association". Radiology. 270 (1): 248–60. doi:10.1148/radiol.13131184. PMID 24354378.
6. ↑ 6.0 6.1 6.2 Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, Mohile SG, Mumber M, Schulick R, Shapiro M, Urba S, Zeh HJ, Katz MH (2016). "Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline". J. Clin. Oncol. 34 (21): 2541–56. doi:10.1200/JCO.2016.67.5553. PMID 27247221.
7. ↑ 7.0 7.1 Yamada S, Fujii T, Sugimoto H, Nomoto S, Takeda S, Kodera Y, Nakao A (2013). "Aggressive surgery for borderline resectable pancreatic cancer: evaluation of National Comprehensive Cancer Network guidelines". Pancreas. 42 (6): 1004–10. doi:10.1097/MPA.0b013e31827b2d7c. PMID 23532000.
8. ↑ Balaban EP, Mangu PB, Khorana AA, Shah MA, Mukherjee S, Crane CH, Javle MM, Eads JR, Allen P, Ko AH, Engebretson A, Herman JM, Strickler JH, Benson AB, Urba S, Yee NS (2016). "Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline". J. Clin. Oncol. 34 (22): 2654–68. doi:10.1200/JCO.2016.67.5561. PMID 27247216.
9. ↑ Al-Haddad M, Martin JK, Nguyen J, Pungpapong S, Raimondo M, Woodward T, Kim G, Noh K, Wallace MB (2007). "Vascular resection and reconstruction for pancreatic malignancy: a single center survival study". J. Gastrointest. Surg. 11 (9): 1168–74. doi:10.1007/s11605-007-0216-x. PMID 17632763.
10. ↑ Donahue TR, Isacoff WH, Hines OJ, Tomlinson JS, Farrell JJ, Bhat YM, Garon E, Clerkin B, Reber HA (2011). "Downstaging chemotherapy and alteration in the classic computed tomography/magnetic resonance imaging signs of vascular involvement in patients with pancreaticobiliary malignant tumors: influence on patient selection for surgery". Arch Surg. 146 (7): 836–43. doi:10.1001/archsurg.2011.152. PMID 21768431.
11. ↑ Tseng JF, Raut CP, Lee JE, Pisters PW, Vauthey JN, Abdalla EK, Gomez HF, Sun CC, Crane CH, Wolff RA, Evans DB (2004). "Pancreaticoduodenectomy with vascular resection: margin status and survival duration". J. Gastrointest. Surg. 8 (8): 935–49, discussion 949–50. doi:10.1016/j.gassur.2004.09.046. PMID 15585381.
12. ↑ Martin RC, Scoggins CR, Egnatashvili V, Staley CA, McMasters KM, Kooby DA (2009). "Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes". Arch Surg. 144 (2): 154–9. doi:10.1001/archsurg.2008.547. PMID 19221327.
13. ↑ Castleberry AW, White RR, De La Fuente SG, Clary BM, Blazer DG, McCann RL, Pappas TN, Tyler DS, Scarborough JE (2012). "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. 19 (13): 4068–77. doi:10.1245/s10434-012-2585-y. PMID 22932857.
14. ↑ Leach SD, Lee JE, Charnsangavej C, Cleary KR, Lowy AM, Fenoglio CJ, Pisters PW, Evans DB (1998). "Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head". Br J Surg. 85 (5): 611–7. doi:10.1046/j.1365-2168.1998.00641.x. PMID 9635805.
15. ↑ Fuhrman GM, Leach SD, Staley CA, Cusack JC, Charnsangavej C, Cleary KR, El-Naggar AK, Fenoglio CJ, Lee JE, Evans DB (1996). "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. 223 (2): 154–62. PMC 1235091. PMID 8597509.
16. ↑ Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Nakagawa N, Sueda T (2013). "Benefit of portal or superior mesenteric vein resection with adjuvant chemotherapy for patients with pancreatic head carcinoma". J Surg Oncol. 107 (4): 414–21. doi:10.1002/jso.23229. PMID 22886567.
17. ↑ Ramacciato G, Mercantini P, Petrucciani N, Giaccaglia V, Nigri G, Ravaioli M, Cescon M, Cucchetti A, Del Gaudio M (2009). "Does portal-superior mesenteric vein invasion still indicate irresectability for pancreatic carcinoma?". Ann. Surg. Oncol. 16 (4): 817–25. doi:10.1245/s10434-008-0281-8. PMID 19156463.
18. ↑ Mollberg N, Rahbari NN, Koch M, Hartwig W, Hoeger Y, Büchler MW, Weitz J (2011). "Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis". Ann. Surg. 254 (6): 882–93. doi:10.1097/SLA.0b013e31823ac299. PMID 22064622.
19. ↑ 19.0 19.1 Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goéré D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T, Arnold D (2015). "Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up". Ann. Oncol. 26 Suppl 5: v56–68. doi:10.1093/annonc/mdv295. PMID 26314780.
20. ↑ Seufferlein T, Bachet JB, Van Cutsem E, Rougier P (2012). "Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Ann. Oncol. 23 Suppl 7: vii33–40. doi:10.1093/annonc/mds224. PMID 22997452.
21. ↑ Evans DB, George B, Tsai S (2015). "Non-metastatic Pancreatic Cancer: Resectable, Borderline Resectable, and Locally Advanced-Definitions of Increasing Importance for the Optimal Delivery of Multimodality Therapy". Ann. Surg. Oncol. 22 (11): 3409–13. doi:10.1245/s10434-015-4649-2. PMID 26122369.
22. ↑ Rombouts SJ, Vogel JA, van Santvoort HC, van Lienden KP, van Hillegersberg R, Busch OR, Besselink MG, Molenaar IQ (2015). "Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer". Br J Surg. 102 (3): 182–93. doi:10.1002/bjs.9716. PMID 25524417.
23. ↑ Pancreatic Cancer - Johns Hopkins Medicine: Surgical Treatment of Pancreatic Cancer
24. ↑ Krzyzanowska MK, Weeks JC, Earle CC (2003). "Treatment of locally advanced pancreatic cancer in the real world: population-based practices and effectiveness". J. Clin. Oncol. 21 (18): 3409–14. doi:10.1200/JCO.2003.03.007. PMID 12972517.
25. ↑ Aristu J, Cañón R, Pardo F, Martínez-Monge R, Martin-Algarra S, Manuel Ordoñez J, Villafranca E, Moreno M, Cambeiro M, Azinovic I (2003). "Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer". Am. J. Clin. Oncol. 26 (1): 30–6. PMID 12576921.
26. ↑ Turrini O, Viret F, Moureau-Zabotto L, Guiramand J, Moutardier V, Lelong B, Giovannini M, Delpero JR (2009). "Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma". Eur J Surg Oncol. 35 (12): 1306–11. doi:10.1016/j.ejso.2009.06.005. PMID 19576722.
27. ↑ Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, Mohile SG, Mumber M, Schulick R, Shapiro M, Urba S, Zeh HJ, Katz M (2017). "Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update". J. Clin. Oncol. 35 (20): 2324–2328. doi:10.1200/JCO.2017.72.4948. PMID 28398845. Vancouver style error: initials (help)
28. ↑ Gurusamy KS, Kumar S, Davidson BR, Fusai G (2014). "Resection versus other treatments for locally advanced pancreatic cancer". Cochrane Database Syst Rev (2): CD010244. doi:10.1002/14651858.CD010244.pub2. PMID 24578248.
29. ↑ Doi R, Imamura M, Hosotani R, Imaizumi T, Hatori T, Takasaki K, Funakoshi A, Wakasugi H, Asano T, Hishinuma S, Ogata Y, Sunamura M, Yamaguchi K, Tanaka M, Takao S, Aikou T, Hirata K, Maguchi H, Aiura K, Aoki T, Kakita A, Sasaki M, Ozaki M, Matsusue S, Higashide S, Noda H, Ikeda S, Maetani S, Yoshida S (2008). "Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial". Surg. Today. 38 (11): 1021–8. doi:10.1007/s00595-007-3745-8. PMID 18958561.
30. ↑ Lygidakis NJ, Singh G, Bardaxoglou E, Dedemadi G, Sgourakis G, Nestoridis J, Malliotakis A, Pedonomou M, Solomou EK, Safioleas M, Alamani M, Grigorakos L, Merikas EM (2004). "Mono-bloc total spleno-pancreaticoduodenectomy for pancreatic head carcinoma with portal-mesenteric venous invasion. A prospective randomized study". Hepatogastroenterology. 51 (56): 427–33. PMID 15086174.
31. ↑ Fortner JG, Klimstra DS, Senie RT, Maclean BJ (1996). "Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy". Ann. Surg. 223 (2): 147–53. PMC 1235090. PMID 8597508.
32. ↑ Fortner JG (1984). "Regional pancreatectomy for cancer of the pancreas, ampulla, and other related sites. Tumor staging and results". Ann. Surg. 199 (4): 418–25. PMC 1353360. PMID 6712317.
33. ↑ 33.0 33.1 Yeo CJ, Cameron JL, Lillemoe KD, Sohn TA, Campbell KA, Sauter PK, Coleman J, Abrams RA, Hruban RH (2002). "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. 236 (3): 355–66, discussion 366–8. doi:10.1097/01.SLA.0000027272.08464.0B. PMC 1422589. PMID 12192322.
34. ↑ 34.0 34.1 Farnell MB, Pearson RK, Sarr MG, DiMagno EP, Burgart LJ, Dahl TR, Foster N, Sargent DJ (2005). "A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma". Surgery. 138 (4): 618–28, discussion 628–30. doi:10.1016/j.surg.2005.06.044. PMID 16269290.
35. ↑ Balcom JH, Rattner DW, Warshaw AL, Chang Y, Fernandez-del Castillo C (2001). "Ten-year experience with 733 pancreatic resections: changing indications, older patients, and decreasing length of hospitalization". Arch Surg. 136 (4): 391–8. PMID 11296108.
36. ↑ Serrano PE, Cleary SP, Dhani N, Kim PT, Greig PD, Leung K, Moulton CA, Gallinger S, Wei AC (2015). "Improved long-term outcomes after resection of pancreatic adenocarcinoma: a comparison between two time periods". Ann. Surg. Oncol. 22 (4): 1160–7. doi:10.1245/s10434-014-4196-2. PMID 25348784.
37. ↑ Mayo SC, Nathan H, Cameron JL, Olino K, Edil BH, Herman JM, Hirose K, Schulick RD, Choti MA, Wolfgang CL, Pawlik TM (2012). "Conditional survival in patients with pancreatic ductal adenocarcinoma resected with curative intent". Cancer. 118 (10): 2674–81. doi:10.1002/cncr.26553. PMC 3578343. PMID 21935914.
38. ↑ Sinn M, Striefler JK, Sinn BV, Sallmon D, Bischoff S, Stieler JM, Pelzer U, Bahra M, Neuhaus P, Dörken B, Denkert C, Riess H, Oettle H (2013). "Does long-term survival in patients with pancreatic cancer really exist? Results from the CONKO-001 study". J Surg Oncol. 108 (6): 398–402. doi:10.1002/jso.23409. PMID 24038103.
39. ↑ Evans DB, Farnell MB, Lillemoe KD, Vollmer C, Strasberg SM, Schulick RD (2009). "Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement". Ann. Surg. Oncol. 16 (7): 1736–44. doi:10.1245/s10434-009-0416-6. PMID 19387741.
40. ↑ 40.0 40.1 Yeo CJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt HA, Talamini MA, Hruban RH, Ord SE, Sauter PK, Coleman J, Zahurak ML, Grochow LB, Abrams RA (1997). "Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes". Ann. Surg. 226 (3): 248–57, discussion 257–60. PMC 1191017. PMID 9339931.
41. ↑ Massucco P, Capussotti L, Magnino A, Sperti E, Gatti M, Muratore A, Sgotto E, Gabriele P, Aglietta M (2006). "Pancreatic resections after chemoradiotherapy for locally advanced ductal adenocarcinoma: analysis of perioperative outcome and survival". Ann. Surg. Oncol. 13 (9): 1201–8. doi:10.1245/s10434-006-9032-x. PMID 16955382.
42. ↑ Sanjay P, Takaori K, Govil S, Shrikhande SV, Windsor JA (2012). "'Artery-first' approaches to pancreatoduodenectomy". Br J Surg. 99 (8): 1027–35. doi:10.1002/bjs.8763. PMID 22569924.
43. ↑ Sun J, Yang Y, Wang X, Yu Z, Zhang T, Song J, Zhao H, Wen J, Du Y, Lau WY, Zhang Y (2014). "Meta-analysis of the efficacies of extended and standard pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas". World J Surg. 38 (10): 2708–15. doi:10.1007/s00268-014-2633-9. PMID 24912627.
44. ↑ Millikan KW, Deziel DJ, Silverstein JC, Kanjo TM, Christein JD, Doolas A, Prinz RA (1999). "Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas". Am Surg. 65 (7): 618–23, discussion 623–4. PMID 10399969.
45. ↑ Yeo CJ, Cameron JL, Lillemoe KD, Sitzmann JV, Hruban RH, Goodman SN, Dooley WC, Coleman J, Pitt HA (1995). "Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients". Ann. Surg. 221 (6): 721–31, discussion 731–3. PMC 1234702. PMID 7794076.
46. ↑ Cameron JL, Pitt HA, Yeo CJ, Lillemoe KD, Kaufman HS, Coleman J (1993). "One hundred and forty-five consecutive pancreaticoduodenectomies without mortality". Ann. Surg. 217 (5): 430–5, discussion 435–8. PMC 1242815. PMID 8098202.
47. ↑ van der Gaag NA, Rauws EA, van Eijck CH, Bruno MJ, van der Harst E, Kubben FJ, Gerritsen JJ, Greve JW, Gerhards MF, de Hingh IH, Klinkenbijl JH, Nio CY, de Castro SM, Busch OR, van Gulik TM, Bossuyt PM, Gouma DJ (2010). "Preoperative biliary drainage for cancer of the head of the pancreas". N. Engl. J. Med. 362 (2): 129–37. doi:10.1056/NEJMoa0903230. PMID 20071702.
48. ↑ 48.0 48.1 48.2 McPhee JT, Hill JS, Whalen GF, Zayaruzny M, Litwin DE, Sullivan ME, Anderson FA, Tseng JF (2007). "Perioperative mortality for pancreatectomy: a national perspective". Ann. Surg. 246 (2): 246–53. doi:10.1097/01.sla.0000259993.17350.3a. PMC 1933570. PMID 17667503.
49. ↑ Raut CP, Tseng JF, Sun CC, Wang H, Wolff RA, Crane CH, Hwang R, Vauthey JN, Abdalla EK, Lee JE, Pisters PW, Evans DB (2007). "Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma". Ann. Surg. 246 (1): 52–60. doi:10.1097/01.sla.0000259391.84304.2b. PMC 1899216. PMID 17592291.
50. ↑ Geer RJ, Brennan MF (1993). "Prognostic indicators for survival after resection of pancreatic adenocarcinoma". Am. J. Surg. 165 (1): 68–72, discussion 72–3. PMID 8380315.
51. ↑ Benassai G, Mastrorilli M, Quarto G, Cappiello A, Giani U, Mosella G (2000). "Survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas". Chir Ital. 52 (3): 263–70. PMID 10932371.
52. ↑ Trede M, Schwall G, Saeger HD (1990). "Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality". Ann. Surg. 211 (4): 447–58. PMC 1358031. PMID 2322039.
53. ↑ Pellegrini CA, Heck CF, Raper S, Way LW (1989). "An analysis of the reduced morbidity and mortality rates after pancreaticoduodenectomy". Arch Surg. 124 (7): 778–81. PMID 2742478.
54. ↑ Crist DW, Sitzmann JV, Cameron JL (1987). "Improved hospital morbidity, mortality, and survival after the Whipple procedure". Ann. Surg. 206 (3): 358–65. PMC 1493175. PMID 3632096.
55. ↑ Kneuertz PJ, Pitt HA, Bilimoria KY, Smiley JP, Cohen ME, Ko CY, Pawlik TM (2012). "Risk of morbidity and mortality following hepato-pancreato-biliary surgery". J. Gastrointest. Surg. 16 (9): 1727–35. doi:10.1007/s11605-012-1938-y. PMID 22760965.
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