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__NOTOC__
{{Pancreatic cancer}}
{{CMG}}; {{AE}} {{Cherry}}
In patients with pancreatic cancer, surgery is the primary modality of treatment.
In patients with pancreatic cancer, surgery is the primary modality of treatment.
Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients.Patients with unresectable disease are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy.
Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients.Patients with unresectable disease are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy.

Revision as of 14:23, 13 November 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2] In patients with pancreatic cancer, surgery is the primary modality of treatment. Extrapancreatic disease requires palliative therapy and curative resection is not performed in such patients.Patients with unresectable disease are treated with chemotherapy and/or radiation therapy as a part of adjuvant or neoadjuvant therapy. Curative resection is not contraindicated in all patients with vascular invasion.[1] Involvement of the portal or superior mesenteric vein can be resected and reconstructed with the help of splenic, saphenous or internal jugular veins. However, the involvement of arteries such as the hepatic, celiac or superior mesenteric are contraindications to resection. Various methods of surgical resection may be employed and each of these has its own sets of risks and perioperative complications. The facts 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:[2]

  • Locally invasive characteristics of the neoplasm
  • Size
  • Location

Methods of curative resection options 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:[3][4][5][6][7]

  • Patient selection is based on:
    • Resection margins
    • High probability of cure
    • Patient's age
    • Comorbidities

European Society for Medical Oncology (ESMO) has certain guidelines on the treatment of metastatic pancreatic cancer:[8][9][10][9][9]

  • Chemotherapy not preferred
  • Gemcitabine is preferred over 5 FU
  • Treatment 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:[11][11] 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)

CHEMOTHERAPY

Metastatic disease/ Advanced pancreatic cancer which is unresectable:[12][13][14][15][16][17][18] The National Comprehensive Cancer Network (NCCN) has recommended guidelines for treatment in patients based on their performance status. In order to predict survival of patients in various stages of pancreatic cancer, the performance status of a patient is a major prognostic factor. Patients with poor prognostic factors have poor performance status. This includes-[19] Metastatic disease Large tumor Severe weight loss In patients with locally advanced unresectable or metastatic disease with good performance status Preferred treatment: FOLFIRINOX[20] In patients with locally advanced unresectable or metastatic disease with good performance status with intolerance to FOLFIRINOX Preferred treatment:Paclitaxel protein bound+ Gemcitabine In patients with locally advanced unresectable or metastatic disease with poor performance status Preferred treatment: Gemcitabine monotherapy[21][22][23][24] In patients with locally advanced unresectable or metastatic disease with poor performance status refractory to Gemcitabine: Preferred treatment: Capecitabine or capecitabine+erlotinib[25] One year survival of FOLFIRINOX (leucovorin+5-lfuorouracil [LV5-FU]+oxaliplatin+irinotecan)>Gemcitabine[26][27][28][29] One year survival of Gemcitabine+ Erlotinib> Gemcitabine[30][31][17] One year survival of Gemcitabine+ Capecitabine≥Gemcitabine [32][33] One year survival of Gemcitabine+ nanoparticle albumin-bound (nab)-paclitaxel> Gemcitabine[34][35]


NEW TREATMENTS 

Irinotecan in an encapsulated form inside a nanoliposome is being used in advanced pancreatic cancer patients who have been earlier been treated using gemcitabine-based chemotherapy. [36]

Liposomal Irinotecan is used along with leucovorin and fluorouracil.[37]


ADJUVANT THERAPY The use of gemcitabine as adjuvant therapy is considered a standard form of therapy following surgical resection in pancreatic cancer patients.[38][39][40][41] NEOADJUVANT THERAPY Neoadjuvant therapy may be used as a form of therapy due to the following reasons:[42][43][44][45] Toxic effects of chemotherapy can be tolerated more easily before surgery as compared to after resection Shrinkage of tumor with neoadjuvant therapy makes resection easier and improves patient prognosis Systemic treatment for cancer involving various systems improves prognosis No therapy is considered as first line therapy under this category.Decisions for treatment are made on an individual basis.

SURGERY

Pancreaticoduodenectomy (Whipple Procedure)[8] It is mainly performed for tumors located in: 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.[46][46] 

This procedure is associated with several morbidities:[47][48][49]

Postoperative abcess Wound infection[50] Anastomotic leak Delay in gastric emptying[51]

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


The European Society for Medical Oncology states that the only curative therapy is surgical resection. Ten percent is the five year survival of patients with pancreatic cancer. Patients with node-positive tumors have very poor long term survival.

Distal Pancreatectomy [47] This procedure has a limited use in curative resection of pancreatic cancer. It is mainly performed for tumors located in: Body of pancreas Tail of pancreas This form of surgery has fewer morbidities than the Whipple procedure.


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 procedure is associated with several morbidities:[52][53][54][55]

Pancreatic endocrine insufficiency Bleeding Leakage of pancreatic stump

Total Pancreatectomy[47][56]


It is the least preferred due to high mortality rate. It is mainly performed for tumors located in: Neck of the pancreas. Due to involvement of neck, patients develop insulin dependent DM.

PALLIATIVE THERAPY

Pain There are various techniques for pain management as palliative therapy in patients:

Narcotic analgesics Narcotic analgesics+ tricyclic antidepressants/ antiemetics Endoscopic decompression with stent placement in patients with biliary or pancreatic duct obstruction Radiation therapy Neurolysis of the celiac ganglia by many approaches Intraoperative Transgastric Transthoracic Transabdominal

Jaundice 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: 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 Preferred treatment: Endoscopic stenting of duodenal obstruction Gastrojejunostomy

  1. ↑ 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.
  2. ↑ Ryan DP, Hong TS, Bardeesy N (2014). "Pancreatic adenocarcinoma". N. Engl. J. Med. 371 (11): 1039–49. doi:10.1056/NEJMra1404198. PMID 25207767.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 8.0 8.1 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.
  9. ↑ 9.0 9.1 9.2 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.
  10. ↑ 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.
  11. ↑ 11.0 11.1 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.
  12. ↑ Irigoyen A, Gallego J, Guillén Ponce C, Vera R, Iranzo V, Ales I, Arévalo S, Pisa A, Martín M, Salud A, Falcó E, Sáenz A, Manzano Mozo JL, Pulido G, Martínez Galán J, Pazo-Cid R, Rivera F, García García T, Serra O, Fernández Parra EM, Hurtado A, Gómez Reina MJ, López Gomez LJ, Martínez Ortega E, Benavides M, Aranda E (2017). "Gemcitabine-erlotinib versus gemcitabine-erlotinib-capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group". Eur. J. Cancer. 75: 73–82. doi:10.1016/j.ejca.2016.12.032. PMID 28222309.
  13. ↑ Middleton G, Palmer DH, Greenhalf W, Ghaneh P, Jackson R, Cox T, Evans A, Shaw VE, Wadsley J, Valle JW, Propper D, Wasan H, Falk S, Cunningham D, Coxon F, Ross P, Madhusudan S, Wadd N, Corrie P, Hickish T, Costello E, Campbell F, Rawcliffe C, Neoptolemos JP (2017). "Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial". Lancet Oncol. 18 (4): 486–499. doi:10.1016/S1470-2045(17)30084-0. PMID 28259610.
  14. ↑ Xia BT, Fu B, Wang J, Kim Y, Ahmad SA, Dhar VK, Levinsky NC, Hanseman DJ, Habib DA, Wilson GC, Smith M, Olowokure OO, Kharofa J, Al Humaidi AH, Choe KA, Abbott DE, Ahmad SA (2017). "Does radiologic response correlate to pathologic response in patients undergoing neoadjuvant therapy for borderline resectable pancreatic malignancy?". J Surg Oncol. 115 (4): 376–383. doi:10.1002/jso.24538. PMID 28105634.
  15. ↑ Choi SJ, Kim HJ, Kim JS, Bak YT, Kim JS (2016). "Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report". BMC Cancer. 16: 588. doi:10.1186/s12885-016-2616-3. PMC 4971692. PMID 27484349.
  16. ↑ Wang Y, Hu GF, Zhang QQ, Tang N, Guo J, Liu LY, Han X, Wang X, Wang ZH (2016). "Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis". Drug Des Devel Ther. 10: 1961–72. doi:10.2147/DDDT.S105442. PMC 4912328. PMID 27358556.
  17. ↑ 17.0 17.1 Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C (2016). "Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial". JAMA. 315 (17): 1844–53. doi:10.1001/jama.2016.4324. PMID 27139057.
  18. ↑ Chen J, Kaley K, Garcon MC, Rodriguez T, Saif MW (2016). "A novel schedule of erlotinib/capecitabine (7/7) as salvage therapy in previously treated advanced pancreatic adenocarcinoma: a case series". Therap Adv Gastroenterol. 9 (2): 162–8. doi:10.1177/1756283X15622779. PMC 4749861. PMID 26929778.
  19. ↑ Tas F, Sen F, Odabas H, Kılıc L, Keskın S, Yıldız I (2013). "Performance status of patients is the major prognostic factor at all stages of pancreatic cancer". Int. J. Clin. Oncol. 18 (5): 839–46. doi:10.1007/s10147-012-0474-9. PMID 22996141.
  20. ↑ Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C, Bennouna J, Bachet JB, Khemissa-Akouz F, Péré-Vergé D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M (2011). "FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer". N. Engl. J. Med. 364 (19): 1817–25. doi:10.1056/NEJMoa1011923. PMID 21561347.
  21. ↑ Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A (2005). "Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial". J. Clin. Oncol. 23 (15): 3509–16. doi:10.1200/JCO.2005.06.023. PMID 15908661.
  22. ↑ Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D (2004). "Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer". J. Clin. Oncol. 22 (8): 1430–8. doi:10.1200/JCO.2004.10.112. PMID 15084616.
  23. ↑ Rocha Lima CM, Green MR, Rotche R, Miller WH, Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL (2004). "Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate". J. Clin. Oncol. 22 (18): 3776–83. doi:10.1200/JCO.2004.12.082. PMID 15365074.
  24. ↑ Ishii H, Furuse J, Boku N, Okusaka T, Ikeda M, Ohkawa S, Fukutomi A, Hamamoto Y, Nakamura K, Fukuda H (2010). "Phase II study of gemcitabine chemotherapy alone for locally advanced pancreatic carcinoma: JCOG0506". Jpn. J. Clin. Oncol. 40 (6): 573–9. doi:10.1093/jjco/hyq011. PMID 20185458.
  25. ↑ Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS (2007). "Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer". J. Clin. Oncol. 25 (30): 4787–92. doi:10.1200/JCO.2007.11.8521. PMID 17947726.
  26. ↑ Conroy T, Gavoille C, Samalin E, Ychou M, Ducreux M (2013). "The role of the FOLFIRINOX regimen for advanced pancreatic cancer". Curr Oncol Rep. 15 (2): 182–9. doi:10.1007/s11912-012-0290-4. PMID 23341367.
  27. ↑ Boone BA, Steve J, Krasinskas AM, Zureikat AH, Lembersky BC, Gibson MK, Stoller RG, Zeh HJ, Bahary N (2013). "Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer". J Surg Oncol. 108 (4): 236–41. doi:10.1002/jso.23392. PMC 3816713. PMID 23955427.
  28. ↑ Conroy T, Paillot B, François E, Bugat R, Jacob JH, Stein U, Nasca S, Metges JP, Rixe O, Michel P, Magherini E, Hua A, Deplanque G (2005). "Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer--a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study". J. Clin. Oncol. 23 (6): 1228–36. doi:10.1200/JCO.2005.06.050. PMID 15718320.
  29. ↑ Peddi PF, Lubner S, McWilliams R, Tan BR, Picus J, Sorscher SM, Suresh R, Lockhart AC, Wang J, Menias C, Gao F, Linehan D, Wang-Gillam A (2012). "Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma". JOP. 13 (5): 497–501. PMID 22964956.
  30. ↑ Furuse J, Gemma A, Ichikawa W, Okusaka T, Seki A, Ishii T (2017). "Postmarketing surveillance study of erlotinib plus gemcitabine for pancreatic cancer in Japan: POLARIS final analysis". Jpn. J. Clin. Oncol. 47 (9): 832–839. doi:10.1093/jjco/hyx075. PMID 28541474.
  31. ↑ Fountzilas C, Chhatrala R, Khushalani N, Tan W, LeVea C, Hutson A, Tucker C, Ma WW, Warren G, Boland P, Iyer R (2017). "A phase II trial of erlotinib monotherapy in advanced pancreatic cancer as a first- or second-line agent". Cancer Chemother. Pharmacol. doi:10.1007/s00280-017-3375-9. PMID 28702772.
  32. ↑ Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R (2008). "Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001". J. Clin. Oncol. 26 (22): 3695–701. doi:10.1200/JCO.2007.15.6240. PMID 18669454.
  33. ↑ Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP (2009). "Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer". J. Clin. Oncol. 27 (33): 5513–8. doi:10.1200/JCO.2009.24.2446. PMID 19858379.
  34. ↑ Passero FC, Saif MW (2017). "Second line treatment options for pancreatic cancer". Expert Opin Pharmacother. 18 (15): 1607–1617. doi:10.1080/14656566.2017.1369955. PMID 28820270.
  35. ↑ Saif MW (2014). "Advanced stage pancreatic cancer: novel therapeutic options". Expert Rev Clin Pharmacol. 7 (4): 487–98. doi:10.1586/17512433.2014.910451. PMID 24939470.
  36. ↑ Chiang NJ, Chang JY, Shan YS, Chen LT (2016). "Development of nanoliposomal irinotecan (nal-IRI, MM-398, PEP02) in the management of metastatic pancreatic cancer". Expert Opin Pharmacother. 17 (10): 1413–20. doi:10.1080/14656566.2016.1183646. PMID 27140876.
  37. ↑ Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT (2016). "Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial". Lancet. 387 (10018): 545–57. doi:10.1016/S0140-6736(15)00986-1. PMID 26615328.
  38. ↑ Kalser MH, Ellenberg SS (1985). "Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection". Arch Surg. 120 (8): 899–903. PMID 4015380.
  39. ↑ Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW (2004). "A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer". N. Engl. J. Med. 350 (12): 1200–10. doi:10.1056/NEJMoa032295. PMID 15028824.
  40. ↑ Yang R, Cheung MC, Byrne MM, Jin X, Montero AJ, Jones C, Koniaris LG (2010). "Survival effects of adjuvant chemoradiotherapy after resection for pancreatic carcinoma". Arch Surg. 145 (1): 49–56. doi:10.1001/archsurg.2009.244. PMID 20083754.
  41. ↑ Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H (2007). "Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial". JAMA. 297 (3): 267–77. doi:10.1001/jama.297.3.267. PMID 17227978.
  42. ↑ Pisters PW, Abbruzzese JL, Janjan NA, Cleary KR, Charnsangavej C, Goswitz MS, Rich TA, Raijman I, Wolff RA, Lenzi R, Lee JE, Evans DB (1998). "Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma". J. Clin. Oncol. 16 (12): 3843–50. doi:10.1200/JCO.1998.16.12.3843. PMID 9850029.
  43. ↑ Pisters PW, Wolff RA, Janjan NA, Cleary KR, Charnsangavej C, Crane CN, Lenzi R, Vauthey JN, Lee JE, Abbruzzese JL, Evans DB (2002). "Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome". J. Clin. Oncol. 20 (10): 2537–44. doi:10.1200/JCO.2002.11.064. PMID 12011133.
  44. ↑ Kadera BE, Sunjaya DB, Isacoff WH, Li L, Hines OJ, Tomlinson JS, Dawson DW, Rochefort MM, Donald GW, Clerkin BM, Reber HA, Donahue TR (2014). "Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival". JAMA Surg. 149 (2): 145–53. doi:10.1001/jamasurg.2013.2690. PMID 24306217.
  45. ↑ Loehrer PJ, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB (2011). "Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial". J. Clin. Oncol. 29 (31): 4105–12. doi:10.1200/JCO.2011.34.8904. PMC 3525836. PMID 21969502.
  46. ↑ 46.0 46.1 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.
  47. ↑ 47.0 47.1 47.2 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.
  48. ↑ Pawlik TM, Gleisner AL, Cameron JL, Winter JM, Assumpcao L, Lillemoe KD, Wolfgang C, Hruban RH, Schulick RD, Yeo CJ, Choti MA (2007). "Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer". Surgery. 141 (5): 610–8. doi:10.1016/j.surg.2006.12.013. PMID 17462460.
  49. ↑ House MG, Gönen M, Jarnagin WR, D'Angelica M, DeMatteo RP, Fong Y, Brennan MF, Allen PJ (2007). "Prognostic significance of pathologic nodal status in patients with resected pancreatic cancer". J. Gastrointest. Surg. 11 (11): 1549–55. doi:10.1007/s11605-007-0243-7. PMID 17786531.
  50. ↑ Limongelli P, Pai M, Bansi D, Thiallinagram A, Tait P, Jackson J, Habib NA, Williamson RC, Jiao LR (2007). "Correlation between preoperative biliary drainage, bile duct contamination, and postoperative outcomes for pancreatic surgery". Surgery. 142 (3): 313–8. doi:10.1016/j.surg.2007.04.022. PMID 17723881.
  51. ↑ Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, Neoptolemos JP, Padbury RT, Sarr MG, Traverso LW, Yeo CJ, Büchler MW (2007). "Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS)". Surgery. 142 (5): 761–8. doi:10.1016/j.surg.2007.05.005. PMID 17981197.
  52. ↑ Elliott IA, Epelboym I, Winner M, Allendorf JD, Haigh PI (2017). "Population-Level Incidence and Predictors of Surgically Induced Diabetes and Exocrine Insufficiency after Partial Pancreatic Resection". Perm J. 21. doi:10.7812/TPP/16-095. PMC 5391783. PMID 28406793.
  53. ↑ Liu A, Carmichael KA, Schallom ME, Klinkenberg WD (2017). "Retrospective review of postoperative glycemic control in patients after distal pancreatectomy". Int J Surg. 41: 86–90. doi:10.1016/j.ijsu.2017.03.060. PMID 28347869.
  54. ↑ Gilliland TM, Villafane-Ferriol N, Shah KP, Shah RM, Tran Cao HS, Massarweh NN, Silberfein EJ, Choi EA, Hsu C, McElhany AL, Barakat O, Fisher W, Van Buren G (2017). "Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection". Nutrients. 9 (3). doi:10.3390/nu9030243. PMC 5372906. PMID 28272344.
  55. ↑ Strobel O, Brangs S, Hinz U, Pausch T, Hüttner FJ, Diener MK, Schneider L, Hackert T, Büchler MW (2017). "Incidence, risk factors and clinical implications of chyle leak after pancreatic surgery". Br J Surg. 104 (1): 108–117. doi:10.1002/bjs.10316. PMID 27763684.
  56. ↑ Müller MW, Friess H, Kleeff J, Dahmen R, Wagner M, Hinz U, Breisch-Girbig D, Ceyhan GO, Büchler MW (2007). "Is there still a role for total pancreatectomy?". Ann. Surg. 246 (6): 966–74, discussion 974–5. doi:10.1097/SLA.0b013e31815c2ca3. PMID 18043098.
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