Sections

Treatment

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, tumor invasion of the superior mesenteric or portal vein is no longer an absolute contraindication.^[74]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. In qualified high-volume centers, pancreatic surgery (especially distal pancreatectomy, but including pancreaticoduodenectomy) can often be performed laparoscopically.^[75]

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.^[30]

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 following assertions:

Pancreatic cancer is a systemic disease and should be treated systemically from the start.
Patients will be able to tolerate the toxic effects of chemotherapy more readily before undergoing major pancreatic resection than after.
The tumor will shrink with neoadjuvant therapy so resection will be less cumbersome, leading to improved overall survival.

Trials of preoperative chemoradiotherapy conducted at M.D. Anderson Cancer Center have shown median survival as high as 25 months.^{[76, 77]}However, 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 finds there is limited evidence to recommend specific neoadjuvant regimens off-study for patients with resectable or borderline resectable tumor, and practices vary with regard to the use of chemotherapy and radiation. The guidelines prefer consultation at a high-volume center when considering neoadjuvant therapy. If recommended, treatment should be at or coordinated through a high-volume center when possible. Participation in a clinical trial is encouraged.^[30]

Possible neoadjuvant regimens include the following^[30]:

FOLFIRINOX (folinic acid [leucovorin], 5-fluorouracil, irinotecan, oxaliplatin)/modified FOLFIRINOX, with or without subsequent chemoradiation
Gemcitabine + albumin-bound paclitaxel, with or without subsequent chemoradiation
Gemcitabine + cisplatin (≥2–6 cycles) followed by chemoradiation (only for known BRCA1/2 or PALB2 mutations)

A study by Dhir et al in 193 patients with resectable or borderline resectable pancreatic ductal carcinoma concluded that FOLFIRINOX and gemcitabine plus albumin-bound paclitaxel are viable options for neoadjuvant treatment. After adusting for covariates, however, overall survival was found to be 4.9 months longer with FOLFIRINOX than with gemcitabine-paclitaxel.^[78]

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.^{[79, 80]}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.^[81]

A phase 2 randomized clinical trial of preoperative and postoperative chemotherapy with modified FOLFIRINOX or gemcitabine/albumin-bound paclitaxel in patients with resectable pancreatic cancer found that 2-year overall survival was not significantly improved with either regimen, compared with historical data from trials of adjuvant therapy in resectable pancreatic cancer.^[82]

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 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 intra-abdominal structures is that they all share a common blood supply.

Pancreaticoduodenectomy has been shown to have an overall mortality rate of 6.6%.^[83]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.^[84]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.^[85]

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.^[86]

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 that the ratio of positive nodes to total nodes removed was an important prognostic factor.^[87]This was even more significant than margin positivity.^[88]

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.^[83]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.^[89]Once again, the best treatment for pancreatic leak is adequate drainage.

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.^[83]

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.^[90]

Adjuvant Therapy

Several studies suggested the possibility that postoperative chemotherapy, with or without radiation therapy, would significantly improve median survivals following surgical resection of operable disease. These included the Gastrointestinal Tumor Study Group (GITSG), European Study Group for Pancreatic Cancer (ESPAC), and Charité Onkologie (CONKO) trials.^{[91, 92, 93, 94, 95]}

The first well-powered study to establish the role of adjuvant chemotherapy in pancreatic cancer, conducted by Neuhaus et al in 368 patients with resected pancreatic cancer, found that adjuvant gemcitabine prolongs survival when compared with surgery alone. 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.^[95]

Based on encouraging efficacy shown in the metastatic setting, the PRODIGE Group tested FOLFIRINOX in the adjuvant setting, in 493 patients who had undergone curative resection of the pancreas. Median overall survival was 54.4 months in the FOLFIRINOX arm, compared with 35 months in patients randomized to gemcitabine (the control arm).^[96]This study established modified FOLFIRINOX as a main choice for adjuvant chemotherapy in patients with resected pancreatic cancer.

Another landmark trial, conducted by ESPAC, compared adjuvant therapy with gemcitabine only and gemcitabine plus capecitabine (GemCap) in 732 patients who had undergone R0 or R1 resection for pancreatic ductal adenocarcinoma (PDAC). Median overall survival was 28 months in the gemcitabine plus capecitabine arm versus 25.5 months for gemcitabine arm, suggesting a benefit from adding capecitabine to gemcitabine in the postoperative setting.^[97]

Although GemCap has never been compared with modified FOLFIRINOX in a randomized trial, GemCap can be still considered as an option for patients too old or too frail to receive FOLFIRINOX (see Chemotherapy for Unresectable and Metastatic Pancreatic Cancer).^{[98, 30]}

Combining gemcitabine with nab-paclitaxel for adjuvant therapy was explored in the phase 3 APACT trial, which included 8666 patients who had undergone complete resection of pancreatic cancer. While there was a suggestion of benefit from gemcitabine plus nab-paclitaxel compared with gemcitabine alone, the study did not meet its primary endpoint of longer disease-free survival or its secondary endpoint of improved overall survival.^[99]Consequently, this combination cannot be currently recommended in the adjuvant setting.

Current European Society for Medical Oncology (ESMO) guidelines include the following recommendations for adjuvant therapy^[100]:

mFOLFIRINOX should be the first adjuvant therapeutic option after resection of pancreatic cancer in selected and fit patients, in view of survival outcomes and associated toxicity profile.
In more frail patients (age > 70, Eastern Cooperative Oncology Group performance status 2, or patients who have any contraindication to the drugs used in FOLFIRINOX), GemCap could be an option.
Gemcitabine alone should be used only in frail patients.

A systematic review and meta-analysis by Wan et al found that adjuvant therapy with metformin signficantly reduced the risk of death in Asian patients with pancreatic cancer, but not in Whites. Mortality risk was reduced in Asian patients with stage I-II disease treated with metformin (hazard ratio [HR]=0.76, 95% CI=0.68-0.86) as well as in those with stage I-IV disease (HR=0.88, 95% CI=0.79-0.99), but not in those with stage III-IV disease.^[101]

Acinar cell adenocarcinoma

The existing literature on treatment of acinar cell adenocarcinoma (ACC) consists largely of retrospective cohorts and case reviews; there are almost no prospective randomized trials to provide high-level evidence to treat ACC differently than PDAC. As first-line therapy in fit patients, there appears to be a slight preference for using fluoropyrimidine-based combinations (FOLFIRINOX or FOLFOX) versus gemcitabine plus nab-paclitaxel. Regardless of regimen, the disease control rate in ACC seems to be higher than is seen in PDAC. Also based on some small studies, ACC appears to be more radiosensitive than PDAC, thus warranting consideration of radiotherapy or stereotactic brachytherapy in the neoadjuvant or palliative setting. Overall, the stage-based treatment paradigm is similar to the one for PDAC.

Adenosquamous carcinoma of the pancreas

Due to the rarity of adenosquamous carcinoma of the pancreas (ASCP), no randomized trials have addressed treatment strategy for it. Based on small case cohorts and the molecular profile of ASCP, there is a sense that ASCP may have sensitivity to regimens comprising a fluoropyrimidine plus platinum (eg, FOLFIRINOX, XELOX). As expected for a squamous variant, ASCPs tend to be radiosensitive. Although ASCP tends to have higher expression of PDL-1 than PDAC, the efficacy of immune checkpoint inhibitors in these patients has not been studied.

Venous Thromboembolism Prophylaxis

Venous thromboembolism (VTE) is a common and sometimes fatal complication in patients with pancreatic cancer.^[53]Primary prophylaxis with low molecular weight heparin (LMWH) or direct oral anticoagulants (DOAC) has been shown to significantly reduce the rate of VTE, without increasing the risk of major bleeding. Consequently, most clinical practice guidelines recommend thromboprophylaxis for ambulatory cancer patients at high risk of VTE, in the absence of contraindications.^[102]

Risk for VTE can be determined by calculating the Khorana score (see the Khorana risk score calculator). However, the Khorana score assigns +2 points for pancreatic cancer and so classifies all patients with pancreatic cancer at at least intermediate risk of VTE; thus, some guidelines recommend considering primary VTE prophylaxis in all patients with pancreatic cancer who are undergoing chemotherapy.^[102]

Systemic Therapy for Unresectable and Metastatic Pancreatic Cancer

In the phase 3 Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), the addition of nanoparticle albumin–bound (nab)-paclitaxel to gemcitabine significantly improved overall survival in treatment-naive patients with metastatic pancreatic cancer compared with gemcitabine alone. 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).^[3]

FOLFIRINOX demonstrated a survival advantage compared with gemcitabine, but increased toxicity, in the European phase III ACCORD/PRODIGE trial, conducted in 342 patients with metastatic pancreatic cancer. Median survival in the FOLFIRINOX arm was 11.1 months, versus 6.8 months on the gemcitabine arm, but 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.^[103]

The NCCN currently recommends FOLFIRINOX or modified FOLFIRINOX as a preferred first-line treatment for patients with metastatic or locally advanced unresectable disease who have good performance status. The alternative first-line option is gemcitabine plus nab-paclitaxel. For patients with poor performance status, the NCCN recommends gemcitabine monotherapy.^[30]Capecitabine alone may provide second-line therapy benefit in patients whose cancer is refractory to gemcitabine.^[104]

Another recommended second-line regimen in patients with metastatic pancreatic cancer that has failed to respond to gemcitabine-based therapy is liposomal irinotecan (Onivyde) in combination with fluorouracil and leucovorin. US Food and Drug Administration (FDA) approval for this was based on a 3-arm, randomized, open-label study (NAPOLI-1 trial) in which median overall survival with liposomal irinotecan/fluorouracil/leucovorin was 6.1 months, compared with 4.2 months for patients treated with fluorouracil/leucovorin or liposomal irinotecan 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.^[105]

In the 5-9% of pancreatic cancer patients with BRCA1/2 or PALB2 germline mutations, or those rare patients with somatic (tumor) BRCA mutations, platinum-based chemotherapy combinations such as FOLFIRINOX or gemcitabine plus cisplatin should be considered as first-line options for unresectable or metastatic disease.^{[106, 107]}For patients with borderline performance status, carboplatin can be considered as an alternative to cisplatin. Mitomycin C is another DNA intercalating agent that has shown activity in BRCA2-associated pancreatic cancer.^[108]

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is indicated for first-line maintenance treatment of adults with deleterious or suspected deleterious germline BRCA1/2 mutations whose metastatic pancreatic adenocarcinoma has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. FDA approval for this indication was based on the POLO trial, in which patients on olaparib maintenance arm had superior progression-free survival (7.4 months, vs 3.8 months in the placebo arm).^[8]

Rucaparib, another selective PARP inhibitor, also demonstrated efficacy in a phase 2 trial, with overall response rate of 25% and disease control rate of 32%.^[109]Unfortunately, adding the PARP inhibitor veliparib to gemcitabine plus cisplatin chemotherapy, or to modified FOLFIRI, did not demonstrate additive benefit.^{[110, 111]}

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.

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.

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.

Guidelines

Cancer Facts & Figures 2022. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf. Accessed: May 27, 2022.
PDQ Adult Treatment Editorial Board. Pancreatic Cancer Treatment (PDQ®): Health Professional Version. February 3, 2021. [QxMD MEDLINE Link]. [Full Text].
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.
Mulcahy N. FDA Approves Nab-Paclitaxel for Pancreatic Cancer. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/810564. September 06, 2013; Accessed: September 09, 2018.
Yang ZY, Yuan JQ, Di MY, Zheng DY, Chen JZ, Ding H, et al. Gemcitabine plus erlotinib for advanced pancreatic cancer: a systematic review with meta-analysis. PLoS One. 2013. 8 (3):e57528. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Sohal DPS, Kennedy EB, Cinar P, Conroy T, Copur MS, Crane CH, et al. Metastatic Pancreatic Cancer: ASCO Guideline Update. J Clin Oncol. 2020 Aug 5. JCO2001364. [QxMD MEDLINE Link]. [Full Text].
Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28. 357 (6349):409-413. [QxMD MEDLINE Link]. [Full Text].
Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019 Jul 25. 381 (4):317-327. [QxMD MEDLINE Link].
Glazer ES, Neill KG, Frakes JM, Coppola D, Hodul PJ, Hoffe SE, et al. Systematic Review and Case Series Report of Acinar Cell Carcinoma of the Pancreas. Cancer Control. 2016 Oct. 23 (4):446-454. [QxMD MEDLINE Link]. [Full Text].
Hackeng WM, Hruban RH, Offerhaus GJ, Brosens LA. Surgical and molecular pathology of pancreatic neoplasms. Diagn Pathol. 2016 Jun 7. 11 (1):47. [QxMD MEDLINE Link]. [Full Text].
Abraham SC, Wu TT, Hruban RH, Lee JH, Yeo CJ, Conlon K, et al. Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway. Am J Pathol. 2002 Mar. 160 (3):953-62. [QxMD MEDLINE Link]. [Full Text].
Chmielecki J, Hutchinson KE, Frampton GM, Chalmers ZR, Johnson A, Shi C, et al. Comprehensive genomic profiling of pancreatic acinar cell carcinomas identifies recurrent RAF fusions and frequent inactivation of DNA repair genes. Cancer Discov. 2014 Dec. 4 (12):1398-405. [QxMD MEDLINE Link]. [Full Text].
Jiao Y, Yonescu R, Offerhaus GJ, Klimstra DS, Maitra A, Eshleman JR, et al. Whole-exome sequencing of pancreatic neoplasms with acinar differentiation. J Pathol. 2014 Mar. 232 (4):428-35. [QxMD MEDLINE Link]. [Full Text].
Hsu JT, Yeh CN, Chen YR, Chen HM, Hwang TL, Jan YY, et al. Adenosquamous carcinoma of the pancreas. Digestion. 2005. 72 (2-3):104-8. [QxMD MEDLINE Link].
Borazanci E, Millis SZ, Korn R, Han H, Whatcott CJ, Gatalica Z, et al. Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review. World J Gastrointest Oncol. 2015 Sep 15. 7 (9):132-40. [QxMD MEDLINE Link]. [Full Text].
Katz MH, Taylor TH, Al-Refaie WB, Hanna MH, Imagawa DK, Anton-Culver H, et al. Adenosquamous versus adenocarcinoma of the pancreas: a population-based outcomes analysis. J Gastrointest Surg. 2011 Jan. 15 (1):165-74. [QxMD MEDLINE Link]. [Full Text].
Molina-Montes E, et al; PanGenEU Study Investigators. Pancreatic Cancer Risk in Relation to Lifetime Smoking Patterns, Tobacco Type, and Dose-Response Relationships. Cancer Epidemiol Biomarkers Prev. 2020 May. 29 (5):1009-1018. [QxMD MEDLINE Link]. [Full Text].
Raimondi S, Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol. 2009 Dec. 6(12):699-708. [QxMD MEDLINE Link].
Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an update. Dig Dis. 2010. 28 (4-5):645-56. [QxMD MEDLINE Link].
Kirkegård J, Mortensen FV, Cronin-Fenton D. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis. Am J Gastroenterol. 2017 Sep. 112 (9):1366-1372. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Ben Q, Xu M, Ning X, Liu J, Hong S, Huang W, et al. Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies. Eur J Cancer. 2011 Sep. 47 (13):1928-37. [QxMD MEDLINE Link].
Bosetti C, Rosato V, Li D, Silverman D, Petersen GM, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol. 2014 Oct. 25 (10):2065-72. [QxMD MEDLINE Link]. [Full Text].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Pancreatic Adenocarcinoma. NCCN. Available at http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Version 1.2022 — February 24, 2022; Accessed: June 3, 2022.
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. [QxMD MEDLINE Link].
Cowgill SM, Muscarella P. The genetics of pancreatic cancer. Am J Surg. 2003 Sep. 186(3):279-86. [QxMD MEDLINE Link].
Whitcomb DC. Genetics and alcohol: a lethal combination in pancreatic disease?. Alcohol Clin Exp Res. 2011 May. 35(5):838-42. [QxMD MEDLINE Link].
Mintziras I, Bartsch DK. Progress report: familial pancreatic cancer. Fam Cancer. 2019 Feb 22. 102(11):2564-9. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Lynch HT, Fusaro RM, Lynch JF, Brand R. Pancreatic cancer and the FAMMM syndrome. Fam Cancer. 2008. 7(1):103-12. [QxMD MEDLINE Link].
[Guideline] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. National Comprehensive Cancer Network. Available at https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf. Version 2.2022 — March 9, 2022; Accessed: June 1, 2022.
Cancer Stat Facts: Pancreatic Cancer. National Cancer Institute. Available at https://seer.cancer.gov/statfacts/html/pancreas.html. Accessed: May 31, 2022.
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. [QxMD MEDLINE Link].
Rawla P, Sunkara T, Gaduputi V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol. 2019 Feb. 10 (1):10-27. [QxMD MEDLINE Link]. [Full Text].
Key Statistics for Pancreatic Cancer. American Cancer Society. Available at https://www.cancer.org/cancer/pancreatic-cancer/about/key-statistics.html. January 21, 2022; Accessed: May 27, 2022.
Tingle SJ, Severs GR, Goodfellow M, Moir JA, White SA. NARCA: A novel prognostic scoring system using neutrophil-albumin ratio and Ca19-9 to predict overall survival in palliative pancreatic cancer. J Surg Oncol. 2018 Sep 9. [QxMD MEDLINE Link].
Can Pancreatic Cancer Be Prevented?. American Cancer Society. Available at https://www.cancer.org/cancer/pancreatic-cancer/causes-risks-prevention/prevention.html. June 9, 2020; Accessed: June 2, 2022.
Ferreira M, Moreira H, Esperto H, Carvalho A. Depression preceding the diagnosis of pancreatic cancer. BMJ Case Rep. 2021 Feb 4. 14 (2):[QxMD MEDLINE Link].
Jarrin Jara MD, Gautam AS, Peesapati VSR, Sadik M, Khan S. The Role of Interleukin-6 and Inflammatory Cytokines in Pancreatic Cancer-Associated Depression. Cureus. 2020 Aug 23. 12 (8):e9969. [QxMD MEDLINE Link]. [Full Text].
Turaga KK, Malafa MP, Jacobsen PB, Schell MJ, Sarr MG. Suicide in patients with pancreatic cancer. Cancer. 2011 Feb 1. 117(3):642-7. [QxMD MEDLINE Link].
Epstein AS, O'Reilly EM. Exocrine pancreas cancer and thromboembolic events: a systematic literature review. J Natl Compr Canc Netw. 2012 Jul 1. 10 (7):835-46. [QxMD MEDLINE Link].
[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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Boone BA, Steve J, Zenati MS, Hogg ME, Singhi AD, Bartlett DL, et al. Serum CA 19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol. 2014 Dec. 21 (13):4351-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Horton KM, Fishman EK. Adenocarcinoma of the pancreas: CT imaging. Radiol Clin North Am. 2002 Dec. 40(6):1263-72. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Louden K. New risk factors proposed for pancreatic cancer. Medscape Medical News. September 26, 2013. [Full Text].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Neuroendocrine Tumors. Available at http://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Version 3.2021 — August 13, 2021; Accessed: October 6, 2021.
Tempero MA. NCCN Guidelines Updates: Pancreatic Cancer. J Natl Compr Canc Netw. 2019 May 1. 17 (5.5):603-605. [QxMD MEDLINE Link]. [Full Text].
Hong SB, Lee SS, Kim JH, Kim HJ, Byun JH, Hong SM, et al. Pancreatic Cancer CT: Prediction of Resectability according to NCCN Criteria. Radiology. 2018 Dec. 289 (3):710-718. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Evans DB, George B, Tsai S. Non-metastatic Pancreatic Cancer: Resectable, Borderline Resectable, and Locally Advanced-Definitions of Increasing Importance for the Optimal Delivery of Multimodality Therapy. Ann Surg Oncol. 2015 Oct. 22 (11):3409-13. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
de Rooij T, Klompmaker S, Abu Hilal M, Kendrick ML, Busch OR, Besselink MG. Laparoscopic pancreatic surgery for benign and malignant disease. Nat Rev Gastroenterol Hepatol. 2016 Apr. 13 (4):227-38. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Dhir M, Zenati MS, Hamad A, Singhi AD, Bahary N, Hogg ME, et al. FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel for Neoadjuvant Treatment of Resectable and Borderline Resectable Pancreatic Head Adenocarcinoma. Ann Surg Oncol. 2018 Jul. 25 (7):1896-1903. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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.
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. [QxMD MEDLINE Link].
Sohal DPS, Duong M, Ahmad SA, Gandhi NS, Beg MS, Wang-Gillam A, et al. Efficacy of Perioperative Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Mar 1. 7 (3):421-427. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Gallagher S, Zervos E, Murr M. Distal Pancreatectomy. Von Hoff, Evans, Hruban. Pancreatic Cancer. Sudbury, Mass: Jones and Bartlett; 2005. 20.
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. [QxMD MEDLINE Link].
Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985 Aug. 120(8):899-903. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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).
Conroy T, Hammel P, Hebbar M, et al, Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018 Dec 20. 379 (25):2395-2406. [QxMD MEDLINE Link]. [Full Text].
Neoptolemos JP, et al; European Study Group for Pancreatic Cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017 Mar 11. 389 (10073):1011-1024. [QxMD MEDLINE Link]. [Full Text].
Nelson R. Best Survival Ever in Resectable Pancreatic Cancer. Medscape Medical News. Available at https://www.medscape.com/viewarticle/897600. June 04, 2018; Accessed: January 10, 2020.
Tempero M, O'Reilly E, Van Cutsem E, et al. LBA-1 Phase 3 APACT trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P + Gem) vs gemcitabine (Gem) alone in patients with resected pancreatic cancer (PC): Updated 5-year overall survival. Ann Oncol. July 01, 2021. 32 (suppl 3):S226. [Full Text].
[Guideline] eUpdate – Cancer of the Pancreas Treatment Recommendations. European Society for Medical Oncology. Available at https://www.esmo.org/guidelines/guidelines-by-topic/gastrointestinal-cancers/pancreatic-cancer/eupdate-cancer-of-the-pancreas-treatment-recommendations. March 15, 2019; Accessed: June 3, 2022.
Wan G, Sun X, Li F, Wang X, Li C, Li H, et al. Survival Benefit of Metformin Adjuvant Treatment For Pancreatic Cancer Patients: a Systematic Review and Meta-Analysis. Cell Physiol Biochem. 2018 Sep 5. 49 (3):I. [QxMD MEDLINE Link]. [Full Text].
Frere C, Crichi B, Bournet B, Canivet C, Abdallah NA, Buscail L, et al. Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cancers (Basel). 2020 Jul 24. 12 (8):[QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Jameson GS, Borazanci E, Babiker HM, Poplin E, Niewiarowska AA, Gordon MS, et al. Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment Among Patients With Advanced Pancreatic Cancer: A Phase 1b/2 Pilot Clinical Trial. JAMA Oncol. 2019 Oct 3. [QxMD MEDLINE Link]. [Full Text].
O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, et al. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol. 2020 May 1. 38 (13):1378-1388. [QxMD MEDLINE Link]. [Full Text].
Chalasani P, Kurtin S, Dragovich T. Response to a third-line mitomycin C (MMC)-based chemotherapy in a patient with metastatic pancreatic adenocarcinoma carrying germline BRCA2 mutation. JOP. 2008 May 8. 9 (3):305-8. [QxMD MEDLINE Link].
Shroff RT, Hendifar A, McWilliams RR, Geva R, Epelbaum R, Rolfe L, et al. Rucaparib Monotherapy in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation. JCO Precis Oncol. 2018. 2018:JCO2001364. [QxMD MEDLINE Link]. [Full Text].
O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, et al. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol. 2020 May 1. 38 (13):1378-1388. [QxMD MEDLINE Link]. [Full Text].
Chiorean EG, Guthrie KA, Philip PA, Swisher EM, Jalikis F, Pishvaian MJ, et al. Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513. Clin Cancer Res. 2021 Dec 1. 27 (23):6314-6322. [QxMD MEDLINE Link].
[Guideline] U.S. Preventive Services Task Force. Final Recommendation Statement: Pancreatic Cancer: Screening. Available at https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/pancreatic-cancer-screening1. October 2019; Accessed: January 10, 2020.
American Academy of Family Physicians. Summary of Recommendations for Clinical Preventive Services. Leawood KS: American Academy of Family Physicians; November 2015. [Full Text].
Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 Mar. 62 (3):339-47. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Goggins M, et al; International Cancer of the Pancreas Screening (CAPS) consortium. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020 Jan. 69 (1):7-17. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Aslanian HR, Lee JH, Canto MI. AGA Clinical Practice Update on Pancreas Cancer Screening in High Risk Individuals: Expert Review. Gastroenterology. 2020 May 13. [QxMD MEDLINE Link].
[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. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, et al. Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Jul 20. 34 (21):2541-56. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Khorana AA, McKernin SE, Berlin J, Hong TS, Maitra A, Moravek C, et al. Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2019 Aug 10. 37 (23):2082-2088. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Balaban EP, Mangu PB, Khorana AA, Shah MA, Mukherjee S, Crane CH, et al. Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Aug 1. 34 (22):2654-68. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Sohal DP, Mangu PB, Khorana AA, Shah MA, Philip PA, O'Reilly EM, et al. Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Aug 10. 34 (23):2784-96. [QxMD MEDLINE Link]. [Full Text].
[Guideline] eUpdate – Cancer of the Pancreas Treatment Recommendations. European Society for Medical Oncology. Available at https://www.esmo.org/guidelines/gastrointestinal-cancers/pancreatic-cancer/eupdate-cancer-of-the-pancreas-treatment-recommendations2. June 20, 2017; Accessed: October 6, 2021.
Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV, et al. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2012 Jan-Feb. 62 (1):30-67. [QxMD MEDLINE Link].
Soto JL, Barbera VM, Saceda M, Carrato A. Molecular biology of exocrine pancreatic cancer. Clin Transl Oncol. May 2006. 8:306-12. [QxMD MEDLINE Link].
Hahn SA, Kern SE. Molecular genetics of exocrine pancreatic neoplasms. Surg Clin North Am. 1995 Oct. 75(5):857-69. [QxMD MEDLINE Link].
Shi C, Daniels JA, Hruban RH. Molecular characterization of pancreatic neoplasms. Adv Anat Pathol. 2008 Jul. 15(4):185-95. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Dreyer SB, Upstill-Goddard R, Paulus-Hock V, et al. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer. Gastroenterology. 2020 Oct 8. [QxMD MEDLINE Link].
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).
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).
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].

Media Gallery

Pancreatic cancer. Gross section of an adenocarcinoma of the pancreas measuring 5 × 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.

of 9

Pancreatic Cancer Treatment & Management

Approach Considerations

Neoadjuvant Therapy

Pancreaticoduodenectomy (Whipple Procedure)

Distal Pancreatectomy

Total Pancreatectomy