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Pancreatic Cancer Treatment & Management

  • Author: Tomislav Dragovich, MD, PhD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
 
Updated: Jan 11, 2016
 

Approach Considerations

There is consensus that surgery is the primary mode of treatment for pancreatic cancer. However, an important role exists for chemotherapy and/or radiation therapy in an adjuvant or neoadjuvant setting, and in the treatment of patients with unresectable disease.

Typically, extrapancreatic disease precludes curative resection, and surgical treatment may be palliative at best.

Historically, vascular involvement has been considered a contraindication to resective cure. However, the invasion of the superior mesenteric or portal vein is no longer an absolute contraindication.[55] These veins can be resected partially with as much as 50% narrowing of the lumen. In addition, complete reconstruction is possible, especially using native veins as replacement (ie, internal jugular, greater saphenous, or splenic).

Nonetheless, invasion of the superior mesenteric, celiac, and hepatic arteries still presents a barrier to resection. No evidence indicates that a vascular reconstruction, which permits an attempt at surgical resection, improves or contributes to survival.

After a thorough preoperative workup, the surgical approach can be tailored to the location, size, and locally invasive characteristics of the tumor. Curative resection options include pancreaticoduodenectomy, with or without sparing of the pylorus; total pancreatectomy; and distal pancreatectomy. Each procedure is associated with its own set of perioperative complications and risks, and these points should be taken into consideration by the surgical team and discussed with the patient when considering the goal of resection.

Guidelines from the National Comprehensive Cancer Network (NCCN) recommend that decisions about resectability involve input from a multidisciplinary group of specialists at a high-volume center. The NCCN panel also agreed that selecting patients for surgery should be based on the probability of cure as determined by resection margins. Other factors include comorbidities, overall performance, and age.[1]

Guidelines on pancreatic cancer from the European Society for Medical Oncology (ESMO) advise that complete surgical resection is the only potentially curative treatment available; however, 5-yr overall survival is only 10-20%, and long-term survival in patients with node-positive disease is rare. ESMO recommendations include the following[56] :

  • Optimal symptomatic treatment has a prime role in the management of metastatic disease; patients may require stenting or bypass surgery for obstructive jaundice or gastric outlet obstruction
  • The role of chemotherapy is limited
  • Gemcitabine has been associated with a small survival benefit compared with bolus 5-fluorouracil

In patients with unresectable locally advanced pancreatic cancer, local ablation has been explored as a treatment option. A systematic review concluded that the following strategies appear to be feasible and safe[57] :

  • Radiofrequency ablation (RFA)
  • Irreversible electroporation
  • Stereotactic body radiation therapy (SBRT)
  • High-intensity focused ultrasound (HIFU)
  • Iodine-125
  • Iodine-125–cryosurgery
  • Photodynamic therapy
  • Microwave ablation

Several of these ablative techniques have been shown to provide pain relief and improved survival. For example, medial survival of up to 25.6 months with RFA and 24.0 months with SBRT has been reported. Promising quality-of-life outcomes have been reported for SBRT.[57]

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Chemotherapy

In patients with metastatic disease, the combination of gemcitabine and erlotinib has led to a significantly higher median survival and 1-year survival than has the use of gemcitabine alone.[58] This has led to US Food and Drug Administration (FDA) approval of erlotinib for use in combination with gemcitabine in advanced, unresectable pancreatic cancer. The recommendation that this combination should now constitute standard therapy for metastatic or unresectable local disease is premature and problematic. The improvements in response rates seen, although significant, were not great and were obtained with no small amount of patient toxicity.

The combination should be used with considerable care, and the use of gemcitabine alone should still be considered as appropriate therapy for patients with metastatic disease. Gemcitabine alone should also be considered as appropriate therapy for patients with unresectable disease; there is no meaningful significant benefit obtained to adding radiotherapy in this situation. Such an addition simply increases toxicity.[59]

The combination of gemcitabine and capecitabine in advanced pancreatic cancer has been investigated by several groups. A randomized, multicenter, phase III clinical trial in 319 patients by the Central European Cooperative Oncology Group found that clinical response or quality of life was no better with the combination than with gemcitabine alone.[60]

This finding contrasts with the results of the phase III United Kingdom National Cancer Research Institute GEMCAP trial, an open-label, randomized study of gemcitabine alone versus gemcitabine combined with capecitabine in 533 patients. Compared with gemcitabine alone, treatment with the gemcitabine-capecitabine combination produced a significantly higher objective response rate (12.4% vs 19.1%, respectively) and progression-free survival and was associated with a trend toward improved overall survival.

In addition, a meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of the gemcitabine-capecitabine combination. Accordingly, these researchers recommended considering gemcitabine-capecitabine as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.[61]

Results of the phase 3 Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) show that the addition of nanoparticle albumin-bound (nab)-paclitaxel to gemcitabine significantly improves overall survival in treatment-naive patients with metastatic pancreatic cancer compared with gemcitabine alone.[3] Overall survival was approximately 2 months longer in patients treated with combination therapy (8.5 vs 6.7 months). One-year and 2-year survival rates were also higher in the combination therapy group (35% vs 22% and 9% vs 4%, respectively).

The results of a European phase III trial (ACCORD/PRODIGE) that compared the nongemcitabine regimen FOLFIRINOX (leucovorin plus 5-lfuorouracil [LV5-FU] plus oxaliplatin plus irinotecan) to gemcitabine were reported in May 2011.[2] The median survival on the FOLFIRINOX arm was 11.1 months, versus 6.8 months on the gemcitabine arm. Of note, the incidence of adverse events and febrile neutropenia was significantly higher on the FOLFIRINOX arm, despite the fact that only patients with ECOG performance status of 0-1 were included in this trial.

It remains to be seen how well this regimen will be integrated into the care of patients with pancreatic cancer and good performance status worldwide. The NCCN recommends FOLFIRINOX as a preferred first-line treatment for patients with metastatic or locally advanced unresectable disease with good performance status.[1]

Paclitaxel protein bound was approved by the FDA in September 2013 for metastatic pancreatic cancer.[4] The treatment regimen includes paclitaxel protein bound 125 mg/m2 plus gemcitabine 1000 mg/m2 IV over 30-40 min on days 1, 8, and 15 of each 28-day cycle. The NCCN also recommends the combination as a preferred first-line treatment for patients with metastatic or locally advanced unresectable disease with good performance status.[1] This regimen may be considered instead of FOLFIRINOX in patients unlikely to tolerate toxicities associated with FOLIRINOX.[3]

For patients with metastatic or locally advanced unresectable disease who have poor performance status, the NCCN recommends gemcitabine monotherapy.[1]

Capecitabine alone or capecitabine plus erlotinib may provide second-line therapy benefit in patient's refractory to gemcitabine.[5] There is no advantage to giving gemcitabine in any dose or time of infusion other than 1000 mg/m² over 30 minutes intravenously.

Combinations of gemcitabine with cisplatin, oxaliplatin, irinotecan, or docetaxel have in phase III trials not shown superior benefit over gemcitabine alone.

A new encapsulated form of irinotecan in a long-circulating nanoliposome (Onivyde) was approved by the FDA in October 2015 for patients with advanced pancreatic cancer who have been previously treatment with gemcitabine-based chemotherapy. Irinotecan liposomal is indicated for use in combination with fluorouracil and leucovorin.

Approval of irinotecan liposomal was based on a 3-arm, randomized, open-label study (NAPOLI-1 trial), which was conducted in 417 patients with metastatic pancreatic adenocarcinoma whose cancer had progressed after treatment with gemcitabine alone or in combination with other agents. The regimen used in the trial was a combination of liposomal irinotecan (70 mg/m² IV infused over 90 min [dosage for free-base irinotecan]) administered prior to fluorouracil (2400 mg/m² infused over 46 h) and racemic leucovorin (400 mg/m² infused over 30 min) every 2 weeks.

Patients treated with this combination of liposomal irinotecan plus fluorouracil/leucovorin lived for an average of 6.1 months, compared with 4.2 months for those treated with only fluorouracil/leucovorin or 4.2 months for patients treated with irinotecan liposomal alone. Improvement in progression-free survival was also observed, to a median of 3.1 months with irinotecan liposomal plus fluorouracil/leucovorin compared with 1.5 months for fluorouracil/leucovorin alone.[85]

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Adjuvant Therapy

Several studies (including the GITSG, ESPAC, CONKO) suggested the possibility that chemotherapy, with or without radiation therapy, would significantly improve median survivals following surgical resection of operable disease.[62, 63] These studies were not definitive and not widely accepted as justification for offering either modality for adjuvant therapy.

However, a large, retrospective study supported the use of adjuvant chemoradiotherapy. Yang et al analyzed a registry of 2,877 patients who underwent surgical resection with curative intent for pancreatic adenocarcinoma; approximately half received no adjuvant therapy, and approximately a quarter received postoperative chemoradiotherapy. A significant survival benefit was found for the chemoradiotherapy patients.[64] In 2011, the NCCN panel recommended the measurement of serum CA 19-9 levels after surgery and before adjuvant therapy.[1]

A study by Neuhaus et al in 368 patients with resected pancreatic cancer found that adjuvant gemcitabine prolongs survival when compared with surgery alone.[65] The 3-year survival rates were 36.5% and 19.5% for the gemcitabine and surgery-only arms of the study, respectively. The 5-year survival rates were 21% and 9% for the gemcitabine and surgery-only arms, respectively.

This trial was definitive and transformative. Adjuvant therapy with gemcitabine is now accepted as standard therapy for surgically resected pancreatic cancer.[6]

Postoperative adjuvant chemotherapy with the oral agent S-1 (Taiho Pharmaceutical) significantly increased overall survival compared with gemcitabine in a randomized study of 385 Japanese patients with stages I-III pancreatic cancer. The 2-year survival rate for S-1 was 70%, compared with 53% for gemcitabine, and the 2-year relapse-free survival rates for S-1 and gemcitabine were 49% and 29%, respectively.[66]

Neoadjuvant therapy

The use of chemotherapy and/or radiation therapy in the neoadjuvant setting has been a source of controversy. The rationale for using neoadjuvant therapy includes the assertions that (1) pancreatic cancer is a systemic disease and should be treated systemically from the start, (2) patients will be able to tolerate the toxic effects of chemotherapy more readily before undergoing major pancreatic resection than after, and (3) the tumor will shrink with neoadjuvant therapy, and the resection will be less cumbersome, leading to an improved overall survival.

Several trials conducted at M.D. Anderson Cancer Center have shown median survival as high as 25 months.[67, 68] No form of neoadjuvant therapy in pancreatic carcinoma should be regarded as a standard form of therapy; this remains an area for clinical trial study. The NCCN agrees with this recommendation.[1]

The optimal treatment plan for patients with locally advanced, unresectable pancreatic cancer is controversial. Commonly used approaches involve chemotherapy, as for metastatic disease, or chemoradiation.

In a retrospective study of 49 stage III locally advanced/borderline resectable patients who were initially unresectable, were downstaged through chemotherapy, and subsequently underwent surgical resection, prolonged preoperative chemotherapy was associated with excellent overall survival and high rates of lymph node – negative disease.[69, 70] A study by Loeherer et al found an improvement in overall survival from 9.2 months to 11.4 months with the addition of concurrent external beam radiation therapy to gemcitabine alone.[71]

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Pancreaticoduodenectomy (Whipple Procedure)

Patients who will most likely benefit from this procedure have a tumor located in the head of the pancreas or the periampullary region. The Whipple procedure is not strictly the surgical approach for pancreatic head tumors. Pancreatic ductal tumors, cholangiocarcinoma (bile duct cancer), and duodenal masses will all require this resection. The operation traditionally involves the following: removal of the pancreatic head, duodenum, gallbladder, and the antrum of the stomach, with surgical drainage of the distal pancreatic duct and biliary system, usually accomplished through anastomosis to the jejunum. The primary reason for removing so much of the intraabdominal structures is that they all share a common blood supply.

Pancreaticoduodenectomy has been shown to have an overall mortality rate of 6.6%.[72] Many forms of morbidity are associated with the operation. One of these is delayed gastric emptying. This occurs in approximately 25% of patients. This condition may require nasogastric decompression and will lead to a longer hospital stay.[73] Other morbidities include pancreatic anastomotic leak. This can be treated with adequate drainage. Postoperative abscesses are not uncommon.

Although preoperative biliary drainage was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by tumors of the pancreatic head, van der Gaag et al found that routine use of this maneuver increases the rate of complications. In a multicenter, randomized trial, 202 patients with obstructive jaundice and a bilirubin level of 40–250 mmol/L (2.3-4.6 mg/dL) were assigned to undergo either preoperative biliary drainage for 4-6 weeks, followed by surgery, or surgery alone within 1 week after diagnosis. The rate of serious complications was higher in the biliary drainage group than in the early surgery group (74% vs 39%, respectively). No significant difference was noted in mortality or length of hospital stay between the 2 groups.[74]

Similarly, Limongelli et al found that preoperative biliary drainage predisposes patients to a positive intraoperative biliary culture, which in turn is associated with an increased risk of postoperative infectious complications and wound infection.[75]

The standard Whipple operation may be altered in order to include a pylorus-sparing procedure. This modification was previously incorporated to increase nutritional strength in these patients, because the increased-gastric emptying associated with antrectomy caused nutritional deficiencies. Although many believe that delayed gastric emptying is worsened by this modification, studies have proven both resections to be equivalent in that regard.

Another source of controversy is the extent of lymphadenectomy that is necessary in a Whipple operation. In an elegant study, Pawlik et al found the ratio of positive nodes to total nodes removed was an important prognostic factor.[76] This was even more significant than margin positivity.[77]

Guidelines on pancreatic cancer from the European Society for Medical Oncology include the following treatment recommendations[56] :

  • Complete surgical resection is the only potentially curative treatment available. However, 5-yr overall survival is only 10-20%; long-term survival in node-positive tumors is rare
  • Optimal symptomatic treatment has a prime role in the management of metastatic disease; these patients may require stenting or bypass surgery for obstructive jaundice or gastric outlet obstruction
  • The role of chemotherapy is limited; gemcitabine has been associated with a small survival benefit compared with bolus 5-fluorouracil
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Distal Pancreatectomy

This procedure possesses a lower mortality rate than the standard Whipple procedure does, at 3.5%, but its use in curative resection remains limited.[72] Essentially, a distal pancreatectomy may be an effective procedure for tumors located in the body and tail of the pancreas. Unfortunately, masses located in this area present later than the periampullary tumors and hence have a higher unresectability rate.

The procedure involves isolation of the distal portion of the pancreas containing the tumor, followed by resection of that segment, with oversewing of the distal pancreatic duct. The main complications for distal pancreatectomy involve pancreatic stump leak, hemorrhage, and endocrine insufficiency.[78] Once again, the best treatment for the pancreatic leak is adequate drainage.

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Total Pancreatectomy

Although this procedure is the least commonly performed and has the highest associated mortality rate (8.3%), it may still be a valuable instrument in the surgical cure of pancreatic cancer.[72]

The indication for the use of total pancreatectomy is in cases in which the tumor involves the neck of the pancreas. This can either be a situation in which the tumor originates from the neck or is growing into the neck. These patients obviously get insulin-dependent diabetes. In some cases, the diabetes can be hard to control. Despite this, the morbidity of a total pancreatectomy is comparable to that of a Whipple procedure.[79]

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Palliative Therapy

Pain

Patients not undergoing resection for pancreatic cancer should have therapy focused on palliating their major symptoms. Pain relief is crucial in these patients. Narcotic analgesics should be used early and in adequate dosages. Combining narcotic analgesics with tricyclic antidepressants or antiemetics can sometimes potentiate their analgesic effects. In some patients, narcotics are insufficient and other approaches must be considered.

Neurolysis of the celiac ganglia may provide significant, long-term pain relief in patients with refractory abdominal pain. This can be performed transthoracically or transabdominally by invasive radiology or anesthesiology, transgastrically using EUS-guided fine-needle injection, or intraoperatively when assessing the patient's potential for resection.

Radiation therapy for pancreatic cancer can palliate pain but does not affect the patient's survival.

Some patients may experience pain from the obstruction of the pancreatic or biliary ducts, especially if the pain significantly worsens after eating. These patients may benefit from endoscopic decompression with stents.

Jaundice

Obstructive jaundice warrants palliation if the patient has pruritus or right upper quadrant pain or has developed cholangitis. Some patients’ anorexia also seems to improve after relief of biliary obstruction.

Biliary obstruction from pancreatic cancer is usually best palliated by the endoscopic placement of plastic or metal stents. The more expensive and permanent metallic stents appear to have a longer period of patency and are preferable in patients with an estimated lifespan of more than 3 months. Plastic stents usually need to be replaced every 3-4 months.

Patients can also undergo operative biliary decompression, either by choledochojejunostomy or cholecystojejunostomy, at the time of an operation for resectability assessment.

Duodenal obstruction

Approximately 5% of patients develop duodenal obstruction secondary to pancreatic carcinoma. These patients can be palliated operatively with a gastrojejunostomy or an endoscopic procedure.

Endoscopic stenting of duodenal obstruction is usually reserved for patients who are poor operative candidates. Some surgeons empirically palliate patients with a gastrojejunostomy at the time of an unsuccessful attempt at pancreatic resection in an effort to prevent the later need for this operation.

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Diet

As with most patients with advanced cancer, patients with pancreatic carcinoma are often anorexic. Pharmacologic stimulation of appetite is usually unsuccessful, but it may be tried.

Patients may have some degree of malabsorption secondary to exocrine pancreatic insufficiency caused by the cancer obstructing the pancreatic duct. Patients with malabsorption diarrhea and weight loss may benefit from pancreatic enzyme supplementation. Their diarrhea may also be improved by avoidance of high-fat or high-protein diets.

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Consultations

The management of pancreatic carcinoma is a multidisciplinary process. Typically, the management of pancreatic cancer entails consultations with a gastroenterologist, medical oncologist, general surgeon or surgical oncologist, and, possibly, a radiation oncologist.

A gastroenterologist is usually involved either for evaluation of the cause of the patient's presenting symptoms (eg, abdominal pain, nausea, weight loss, diarrhea) or for a definitive diagnosis of the cause of jaundice by EUS and/or ERCP. Consultation with a gastroenterologist is also needed if an endoscopically placed stent is needed for palliation of obstructive jaundice.

Consultation with a medical oncologist is often needed to select and administer neoadjuvant, adjuvant, or primary chemotherapy for the disease. Consultation with a medical oncologist is also useful for the management of other common cancer symptoms, such as pain and nausea.

Consultation with a surgeon is needed when the patient's imaging studies suggest that operative resection may be feasible. The surgeon may perform diagnostic laparoscopy or even laparoscopic ultrasonography prior to an attempt at definitive resection.

If curative resection is not possible, consultation with a surgeon may still be useful to consider operative palliation of biliary and/or duodenal obstruction. Consult with a surgeon or surgical oncologist who is very experienced in performing pancreaticoduodenectomies.

Consultation with a radiologist may be needed for special issues, such as obstructive jaundice that is difficult to manage where percutaneous transhepatic cholangiography may be needed.

Consultation with a radiation oncologist is usually considered at the discretion of a medical oncologist when combined chemoradiation may be beneficial. This approach is only indicated when this combination therapy is the subject of a clinical trial.

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Contributor Information and Disclosures
Author

Tomislav Dragovich, MD, PhD Chief, Section of Hematology and Oncology, Banner MD Anderson Cancer Center

Tomislav Dragovich, MD, PhD is a member of the following medical societies: American Association for Cancer Research, SWOG, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Richard A Erickson, MD, FACP, FACG Professor of Medicine, Division of Gastroenterology, Department of Internal Medicine, Texas A&M University Health Science Center; Director, Scott and White Clinic and Hospital

Richard A Erickson, MD, FACP, FACG is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Mohsen Shabahang, MD, PhD, FACS Assistant Professor of Surgery, Division of Surgical Oncology, Director of Surgical Residency, Texas A&M Health Science Center, Scott and White Clinic

Mohsen Shabahang, MD, PhD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, Association for Academic Surgery, Society of Surgical Oncology, Texas Medical Association, Western Surgical Association

Disclosure: Nothing to disclose.

Claire R Larson, MD Resident Physician, Department of General Surgery, Scott and White Hospital, Texas A&M Health Science Center College of Medicine

Claire R Larson, MD is a member of the following medical societies: American College of Surgeons, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

N Joseph Espat, MD, MS, FACS Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center

N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, Surgical Infection Society

Disclosure: Nothing to disclose.

Additional Contributors

Lodovico Balducci, MD Professor, Oncology Fellowship Director, Department of Internal Medicine, Division of Adult Oncology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida Morsani College of Medicine

Lodovico Balducci, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American College of Physicians, American Geriatrics Society, American Society of Hematology, New York Academy of Sciences, American Society of Clinical Oncology, Southern Society for Clinical Investigation, International Society for Experimental Hematology, American Federation for Clinical Research, American Society of Breast Disease

Disclosure: Nothing to disclose.

References
  1. [Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma, v.2.2015. Available at http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed: October 20, 2015.

  2. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12. 364(19):1817-25. [Medline].

  3. Von Hoff DD, Arena FP, Chiorean EG, Infante JR, Moore MJ, Seay TE, et al. Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT). J Clin Oncol 30: 2012 (suppl 34; abstr LBA148), Presented January 25, 2013 at the 2013 Gastrointestinal Cancers Symposium, San Francisco, CA.

  4. Mulcahy N. FDA Approves Nab-Paclitaxel for Pancreatic Cancer. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/810564. Accessed: September 16, 2013.

  5. Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, et al. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol. 2007 Oct 20. 25(30):4787-92. [Medline].

  6. Neuhaus P, Riess H, Post S. CONKO-001:Final results of the randomized, prospective multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancratic cancer. J Clin Oncol. 2008. 26(15S):204s(abstract LBA4504).

  7. American Cancer Society. Pancreatic Cancer. American Cancer Society. Available at http://www.cancer.org/cancer/pancreaticcancer/. Accessed: October 20, 2015.

  8. Cancer Facts & Figures 2015. American Cancer Society. Available at http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf. Accessed: October 20, 2015.

  9. Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol. 2009 Dec. 6(12):699-708. [Medline].

  10. Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML, et al. Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA. 2009 Jun 24. 301(24):2553-62. [Medline]. [Full Text].

  11. Genkinger JM, Spiegelman D, Anderson KE, et al. A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk. Int J Cancer. 2011 Oct 1. 129(7):1708-17. [Medline]. [Full Text].

  12. Urayama KY, Holcatova I, Janout V, et al. Body mass index and body size in early adulthood and risk of pancreatic cancer in a central European multicenter case-control study. Int J Cancer. 2011 Dec 15. 129(12):2875-84. [Medline]. [Full Text].

  13. Nkondjock A, Ghadirian P, Johnson KC, Krewski D. Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr. 2005 Mar. 135(3):592-7. [Medline].

  14. Risch HA. Etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity. J Natl Cancer Inst. 2003 Jul 2. 95(13):948-60. [Medline].

  15. Nöthlings U, Wilkens LR, Murphy SP, Hankin JH, Henderson BE, Kolonel LN. Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst. 2005 Oct 5. 97(19):1458-65. [Medline].

  16. Lin Y, Tamakoshi A, Kawamura T, et al. Risk of pancreatic cancer in relation to alcohol drinking, coffee consumption and medical history: findings from the Japan collaborative cohort study for evaluation of cancer risk. Int J Cancer. 2002 Jun 10. 99(5):742-6. [Medline].

  17. Lowenfels AB, Maisonneuve P, Cavallini G, Ammann RW, Lankisch PG, Andersen JR, et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993 May 20. 328(20):1433-7. [Medline].

  18. Cowgill SM, Muscarella P. The genetics of pancreatic cancer. Am J Surg. 2003 Sep. 186(3):279-86. [Medline].

  19. Whitcomb DC. Genetics and alcohol: a lethal combination in pancreatic disease?. Alcohol Clin Exp Res. 2011 May. 35(5):838-42. [Medline].

  20. Greer JB, Whitcomb DC, Brand RE. Genetic predisposition to pancreatic cancer: a brief review. Am J Gastroenterol. 2007 Nov. 102(11):2564-9. [Medline].

  21. Soto JL, Barbera VM, Saceda M, Carrato A. Molecular biology of exocrine pancreatic cancer. Clin Transl Oncol. May 2006. 8:306-12. [Medline].

  22. Hahn SA, Kern SE. Molecular genetics of exocrine pancreatic neoplasms. Surg Clin North Am. 1995 Oct. 75(5):857-69. [Medline].

  23. Shi C, Daniels JA, Hruban RH. Molecular characterization of pancreatic neoplasms. Adv Anat Pathol. 2008 Jul. 15(4):185-95. [Medline].

  24. Goggins M, Schutte M, Lu J, et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 1996 Dec 1. 56(23):5360-4. [Medline].

  25. Yan L, McFaul C, Howes N, Leslie J, Lancaster G, Wong T, et al. Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk groups. Gastroenterology. June 2005. 128:2124-30. [Medline].

  26. Kojima K, Vickers SM, Adsay NV, et al. Inactivation of Smad4 accelerates Kras(G12D)-mediated pancreatic neoplasia. Cancer Res. 2007 Sep 1. 67(17):8121-30. [Medline].

  27. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science. 2008 Sep 26. 321(5897):1801-6. [Medline]. [Full Text].

  28. Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010 Oct 28. 467(7319):1114-7. [Medline].

  29. Campbell PJ, Yachida S, Mudie LJ, et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature. 2010 Oct 28. 467(7319):1109-13. [Medline].

  30. Kouvaraki MA, Shapiro SE, Cote GJ, Lee JE, Yao JC, Waguespack SG, et al. Management of pancreatic endocrine tumors in multiple endocrine neoplasia type 1. World J Surg. 2006 May. 30(5):643-53. [Medline].

  31. Blansfield JA, Choyke L, Morita SY, Choyke PL, Pingpank JF, Alexander HR, et al. Clinical, genetic and radiographic analysis of 108 patients with von Hippel-Lindau disease (VHL) manifested by pancreatic neuroendocrine neoplasms (PNETs). Surgery. 2007 Dec. 142(6):814-8; discussion 818.e1-2. [Medline].

  32. Groen EJ, Roos A, Muntinghe FL, Enting RH, de Vries J, Kleibeuker JH, et al. Extra-intestinal manifestations of familial adenomatous polyposis. Ann Surg Oncol. 2008 Sep. 15(9):2439-50. [Medline].

  33. Lynch HT, Fusaro RM, Lynch JF, Brand R. Pancreatic cancer and the FAMMM syndrome. Fam Cancer. 2008. 7(1):103-12. [Medline].

  34. American Cancer Society. Cancer facts and figures for African Americans 2009-2010. Available at http://www.acsevents.org/downloads/STT/cffaa_2009-2010.pdf. Accessed: February 5, 2010.

  35. Arnold LD, Patel AV, Yan Y, Jacobs EJ, Thun MJ, Calle EE, et al. Are racial disparities in pancreatic cancer explained by smoking and overweight/obesity?. Cancer Epidemiol Biomarkers Prev. 2009 Sep. 18(9):2397-405. [Medline].

  36. Anderson KE, Mack T, Silverman D. Cancer of the pancreas. Schottenfeld D, Fraumeni JF Jr. Cancer Epidemiology and Prevention. 3rd Ed. New York: Oxford University Press; 2006.

  37. Chari ST, Leibson CL, Rabe KG, Ransom J, de Andrade M, Petersen GM. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology. Aug 2005. 129:504-11. [Medline].

  38. Turaga KK, Malafa MP, Jacobsen PB, Schell MJ, Sarr MG. Suicide in patients with pancreatic cancer. Cancer. 2011 Feb 1. 117(3):642-7. [Medline].

  39. [Guideline] Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006 Nov 20. 24(33):5313-27. [Medline].

  40. Fujioka S, Misawa T, Okamoto T, Gocho T, Futagawa Y, Ishida Y, et al. Preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels for the evaluation of curability and resectability in patients with pancreatic adenocarcinoma. J Hepatobiliary Pancreat Surg. 2007. 14(6):539-44. [Medline].

  41. Kang CM, Kim JY, Choi GH, Kim KS, Choi JS, Lee WJ. The use of adjusted preoperative CA 19-9 to predict the recurrence of resectable pancreatic cancer. J Surg Res. 2007 Jun 1. 140(1):31-5. [Medline].

  42. Horton KM, Fishman EK. Multidetector CT angiography of pancreatic carcinoma: part I, evaluation of arterial involvement. AJR Am J Roentgenol. 2002 Apr. 178(4):827-31. [Medline].

  43. Horton KM, Fishman EK. Adenocarcinoma of the pancreas: CT imaging. Radiol Clin North Am. 2002 Dec. 40(6):1263-72. [Medline].

  44. Kauhanen SP, Komar G, Seppänen MP, Dean KI, Minn HR, Kajander SA, et al. A prospective diagnostic accuracy study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer. Ann Surg. 2009 Dec. 250(6):957-63. [Medline].

  45. Farma JM, Santillan AA, Melis M, Walters J, Belinc D, Chen DT, et al. PET/CT fusion scan enhances CT staging in patients with pancreatic neoplasms. Ann Surg Oncol. 2008 Sep. 15(9):2465-71. [Medline].

  46. Itani KM, Taylor TV, Green LK. Needle biopsy for suspicious lesions of the head of the pancreas: pitfalls and implications for therapy. J Gastrointest Surg. 1997 Jul-Aug. 1(4):337-41. [Medline].

  47. Turner BG, Cizginer S, Agarwal D, Yang J, Pitman MB, Brugge WR. Diagnosis of pancreatic neoplasia with EUS and FNA: a report of accuracy. Gastrointest Endosc. 2010 Jan. 71(1):91-8. [Medline].

  48. Micames C, Jowell PS, White R, Paulson E, Nelson R, Morse M, et al. Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA. Gastrointest Endosc. 2003 Nov. 58(5):690-5. [Medline].

  49. Louden K. New risk factors proposed for pancreatic cancer. Medscape Medical News. September 26, 2013. [Full Text].

  50. [Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Neuroendocrine Tumors, v.1.2015. Available at http://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Accessed: October 21, 2015.

  51. Katz MH, Hwang R, Fleming JB, Evans DB. Tumor-node-metastasis staging of pancreatic adenocarcinoma. CA Cancer J Clin. 2008 Mar-Apr. 58(2):111-25. [Medline].

  52. Callery MP, Strasberg SM, Doherty GM, Soper NJ, Norton JA. Staging laparoscopy with laparoscopic ultrasonography: optimizing resectability in hepatobiliary and pancreatic malignancy. J Am Coll Surg. 1997 Jul. 185(1):33-9. [Medline].

  53. Vollmer CM, Drebin JA, Middleton WD, Teefey SA, Linehan DC, Soper NJ. Utility of staging laparoscopy in subsets of peripancreatic and biliary malignancies. Ann Surg. 2002 Jan. 235(1):1-7. [Medline].

  54. Jarnagin WR, Bodniewicz J, Dougherty E, Conlon K, Blumgart LH, Fong Y. A prospective analysis of staging laparoscopy in patients with primary and secondary hepatobiliary malignancies. J Gastrointest Surg. 2000 Jan-Feb. 4(1):34-43. [Medline].

  55. Al-Haddad M, Martin JK, Nguyen J, Pungpapong S, Raimondo M, Woodward T. Vascular resection and reconstruction for pancreatic malignancy: a single center survival study. J Gastrointest Surg. 2007 Sep. 11(9):1168-74. [Medline].

  56. [Guideline] Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goéré D, et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2015 Sep. 26 Suppl 5:v56-v68. [Medline]. [Full Text].

  57. Rombouts SJ, Vogel JA, van Santvoort HC, van Lienden KP, van Hillegersberg R, Busch OR, et al. Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer. Br J Surg. 2015 Feb. 102 (3):182-93. [Medline].

  58. Vervenne W, Bennouna J, Humblett Y. A randomized double-blind, placebo (P) controlled, multicenter phase III trial to evaluate the efficacy and safety of adding bevacizumab (B) to erlotinib (E) and gemcitabine (G) in patients (pts) with metastatic pancreatic cancer. J Clin Oncol. 2008. 26(15S):214s(abstract 4507).

  59. Loehrer P, Powell M, Cardenes H. A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer:E4201. J Clin Oncol. 2008. 26(15S):214(abstract 4506).

  60. Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, et al. 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. 2008 Aug 1. 26(22):3695-701. [Medline].

  61. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009 Nov 20. 27(33):5513-8. [Medline].

  62. Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985 Aug. 120(8):899-903. [Medline].

  63. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004 Mar 18. 350(12):1200-10. [Medline].

  64. Yang R, Cheung MC, Byrne MM, Jin X, Montero AJ, Jones C, et al. Survival effects of adjuvant chemoradiotherapy after resection for pancreatic carcinoma. Arch Surg. 2010 Jan. 145(1):49-56. [Medline].

  65. Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007 Jan 17. 297(3):267-77. [Medline].

  66. Mulcahy N. Incredibly Promising' Adjuvant Agent for Pancreatic Cancer. Available at http://www.medscape.com/viewarticle/778018. Accessed: February 20, 2013.

  67. Pisters PW, Abbruzzese JL, Janjan NA, Cleary KR, Charnsangavej C, Goswitz MS. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol. 1998 Dec. 16(12):3843-50. [Medline].

  68. Pisters PW, Wolff RA, Janjan NA, Cleary KR, Charnsangavej C, Crane CN. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol. 2002 May 15. 20(10):2537-44. [Medline].

  69. Kadera BE, Sunjaya DB, Isacoff WH, Li L, Hines OJ, Tomlinson JS, et al. Locally Advanced Pancreatic Cancer: Association Between Prolonged Preoperative Treatment and Lymph-Node Negativity and Overall Survival. JAMA Surg. 2013 Dec 4. [Medline].

  70. Boggs W. Preop Chemo for Locally Advanced Pancreatic Cancer Associated With 'Excellent' Survival. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/817801. Accessed: December 22, 2013.

  71. Loehrer PJ Sr, Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2011 Nov 1. 29(31):4105-12. [Medline].

  72. McPhee JT, Hill JS, Whalen GF, Zayaruzny M, Litwin DE, Sullivan ME. Perioperative mortality for pancreatectomy: a national perspective. Ann Surg. 2007 Aug. 246(2):246-53. [Medline].

  73. Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2007 Nov. 142(5):761-8. [Medline].

  74. van der Gaag NA, Rauws EA, van Eijck CH, Bruno MJ, van der Harst E, Kubben FJ, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010 Jan 14. 362(2):129-37. [Medline].

  75. Limongelli P, Pai M, Bansi D, Thiallinagram A, Tait P, Jackson J. Correlation between preoperative biliary drainage, bile duct contamination, and postoperative outcomes for pancreatic surgery. Surgery. 2007 Sep. 142(3):313-8. [Medline].

  76. Pawlik TM, Gleisner AL, Cameron JL, Winter JM, Assumpcao L, Lillemoe KD. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007 May. 141(5):610-8. [Medline].

  77. House MG, Gonen M, Jarnagin WR, DAngelica M, DeMatteo RP, Fong Y. Prognostic significance of pathologic nodal status in patients with resected pancreatic cancer. J Gastrointest Surg. 2007 Nov. 11(11):1549-55. [Medline].

  78. Gallagher S, Zervos E, Murr M. Distal Pancreatectomy. Von Hoff, Evans, Hruban. Pancreatic Cancer. Sudbury, Mass: Jones and Bartlett; 2005. 20.

  79. Muller MW, Friess H, Kleeff J, Dahmen R, Wagner M, Hinz U, et al. Is there still a role for total pancreatectomy?. Ann Surg. 2007 Dec. 246(6):966-74; discussion 974-5. [Medline].

  80. Rothwell PM, Fowkes GR, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials. Lancet. Dec 7/2010; Early online publication. [Full Text].

  81. Bekaii-Saab T, Phelps MA, Li X, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol. 2011 Jun 10. 29(17):2357-63. [Medline]. [Full Text].

  82. Asbun HJ, Conlon K, Fernandez-Cruz L, et al. When to perform a pancreatoduodenectomy in the absence of positive histology? A consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2014 Jan 6. [Epub ahead of print].

  83. Barone JE. When is it OK to do a pancreaticoduodenectomy without a histologic diagnosis of cancer?. Medscape Medical News. January 22, 2014. [Full Text].

  84. Girelli R, Frigerio I, Giardino A, Regi P, Gobbo S, Malleo G, et al. Results of 100 pancreatic radiofrequency ablations in the context of a multimodal strategy for stage III ductal adenocarcinoma. Langenbecks Arch Surg. 2013 Jan. 398(1):63-9. [Medline].

  85. Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, et al. 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. 2015 Nov 29. [Medline].

 
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Pancreatic cancer. Gross section of an adenocarcinoma of the pancreas measuring 5 X 6 cm resected from the pancreatic body and tail. Although the tumor was considered to have been fully resected and had not spread to any nodes, the patient died of recurrent cancer within 1 year.
Pancreatic cancer. Hematoxylin and eosin stain of a pancreatic carcinoma. Note the intense desmoplastic response around the neoplastic cells. The large amount of fibrotic reaction in these tumors can make obtaining adequate tissue by fine-needle aspiration difficult.
Pancreatic cancer. T staging for pancreatic carcinoma. T1 and T2 stages are confined to the pancreatic parenchyma. T3 lesions invade local structures such as the duodenum, bile duct, and/or major peripancreatic veins, and T4 lesions invade surrounding organs (eg, stomach, colon, liver) or invade major arteries such as the superior mesenteric or celiac arteries.
Pancreatic cancer. Computerized tomographic scan showing a pancreatic adenocarcinoma of the pancreatic head. The gallbladder (gb) is distended because of biliary obstruction. The superior mesenteric artery (sma) is surrounded by tumor, making this an unresectable T4 lesion.
Pancreatic cancer. Abdominal CT scan of a small, vaguely seen, 2-cm pancreatic adenocarcinoma (mass) causing obstruction of both the common bile duct (cbd) and pancreatic duct (pd).
Pancreatic cancer. Endoscopic ultrasound of a 2.2-cm pancreatic adenocarcinoma of the head of the pancreas obstructing the common bile duct (CBD) but not invading the portal vein (PV) or superior mesenteric vein (SMV). Findings from endoscopic ultrasound–guided fine-needle aspiration revealed a moderately to poorly differentiated adenocarcinoma. Abdominal CT findings did not show this mass, and an attempt at endoscopic retrograde cholangiopancreatography at another institution was unsuccessful.
Algorithm for evaluation of a patient with suspected pancreatic cancer. CT scanning for definitive diagnosis and staging must be with thin-cut, multidetector, spiral CT scanning using dual-phase contrast imaging to allow for maximal information. This schema varies among institutions depending on local expertise, research interest, and therapeutic protocols for pancreatic carcinoma.
Pancreatic cancer. Tip of linear array echoendoscope (Pentax FG 36UX) with 22-gauge aspiration needle exiting from biopsy channel. Insert shows magnification of aspiration needle tip. Note that the needle exits from the biopsy channel such that it appears continuously in the view of the ultrasonic transducer on the tip of the echoendoscope.
Pancreatic cancer. Cytologic samples from fine-needle aspirations (rapid Papanicolaou stain) of pancreatic adenocarcinomas. (A) Well differentiated, (B) moderately differentiated, (C) moderate to poorly differentiated, (D) poorly differentiated tumor.
 
 
 
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