|Year : 2019 | Volume
| Issue : 1 | Page : 9-14
Indian council of medical research consensus document for the management of pancreatic cancer
Shailesh V Shrikhande1, Savio G Barreto1, Bhawna Sirohi2, Munita Bal1, Raj Kumar Shrimali3, Raju T Chacko4, Vikram Chaudhari1, Vikram Bhatia5, Suyash Kulkarni1, Tanvir Kaur6, RS Dhaliwal6, Goura Kishor Rath6
1 Tata Memorial Centre, Mumbai, Maharashtra, India
2 Max Institute of Cancer Care, New Delhi, India
3 Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
4 Department of Medical Oncology, Division of Non-Communicable Diseases, Christian Medical College, Vellore, Tamil Nadu, India
5 Department of Radiation Oncology, Institute of Liver and Biliary Sciences, New Delhi, India
6 Department of Gatroenterology, Indian Council of Medical Research, New Delhi, India
|Date of Web Publication||16-Apr-2019|
Shailesh V Shrikhande
Chief, Gastrointestinal and Hepato-Pancreato-Biliary Service, Deputy Director, Tata Memorial Hospital, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Shrikhande SV, Barreto SG, Sirohi B, Bal M, Shrimali RK, Chacko RT, Chaudhari V, Bhatia V, Kulkarni S, Kaur T, Dhaliwal R S, Rath GK. Indian council of medical research consensus document for the management of pancreatic cancer. Indian J Med Paediatr Oncol 2019;40:9-14
|How to cite this URL:|
Shrikhande SV, Barreto SG, Sirohi B, Bal M, Shrimali RK, Chacko RT, Chaudhari V, Bhatia V, Kulkarni S, Kaur T, Dhaliwal R S, Rath GK. Indian council of medical research consensus document for the management of pancreatic cancer. Indian J Med Paediatr Oncol [serial online] 2019 [cited 2019 Jul 17];40:9-14. Available from: http://www.ijmpo.org/text.asp?2019/40/1/9/256169
| Executive Summary|| |
This consensus document may be used as framework for more focused and planned research programs to carry forward the process. The aim of the Indian Council of Medical Research (ICMR) Guidelines is to assist oncologists in making major clinical decisions encountered while managing their patients and while realizing the fact that some patients may require treatment strategies other than those suggested in these guidelines.
- Histological confirmation is mandatory before the commencement of definitive treatment
- All patients should be staged according to the tumor, node, and metastasis staging system, and risk should be assessed at diagnosis. A baseline contrast-enhanced computed tomography (CT) scan of the chest, abdomen, and pelvis should be considered
- Patients should receive multidisciplinary care under the care of a surgical, medical, and radiation oncologist
- The indication for endobiliary stenting in patients with obstructive jaundice includes symptoms of cholangitis and/or sepsis, resultant coagulopathy and/or renal insufficiency, or if significant delays in surgery are anticipated
- The patient's malignancy should be classified as resectable, borderline resectable, or locally advanced on the basis of radiologic criteria at diagnosis and treatment plan discussed accordingly
- Resectable pancreatic cancer – Primary surgery remains the standard of care. Neoadjuvant therapy (NAT) (chemotherapy ± radiotherapy) should be considered in locally advanced and borderline resectable tumors to downstage the disease followed by reassessment for surgery in those with stable or partial regression radiological criteria. This may be followed by adjuvant chemotherapy
- Patients with metastatic disease that has spread beyond regional lymph nodes should be assessed for chemotherapy versus best supportive care on an individual basis
- Preferred first-line regimens for chemotherapy include Gemcitabine nab-paclitaxel and FOLFIRINOX
- Patients should be offered regular surveillance after completion of curative resection or treatment of advanced disease
- Encourage participation in institutional and ethical review board-approved, registered clinical trials
- Refer for early palliative care, if indicated.
| Incidence|| |
Pancreatic cancer currently ranks as the 12th most common cancer in the world but has the notorious distinction of being the 4th leading cause of cancer-related deaths.,,, There exists considerable regional variation in the age-standardized incidence rates of pancreatic cancer in the world. Places in Asia report incidences as low as 0.6/100,000 persons per year, while incidence rates as high as 12.6/100,000 have been reported from the West. The age-standardized incidence rates for pancreatic cancer on an average are 8.2 and 2.7/100,000 among males in the developed and developing countries, respectively, and 5.4 and 2.1/100,000 among females in the developed and developing countries, respectively.
In comparison to the West, India has a relatively lower incidence of pancreatic cancer. The rates in India vary from 0.5 to 2.4/100,000 persons per year among women to 0.2 to 1.8/100,000 persons per year among men. The National Cancer Registry Programme (ICMR, Bengaluru) has estimated that by 2020, there will be 8440 and 6090 new cases of pancreatic cancer afflicting Indian men and women, respectively.
| Purpose|| |
Although International Guidelines are available for the management of pancreatic cancer, it is not entirely feasible to apply these guidelines to the Indian population owing to differences in incidence of the disease in different parts of India, socioeconomic factors, and availability of resources. Therefore, it is essential to analyze the evidence pertaining to pancreatic cancer from India and the rest of the world, with an aim to formulate evidence-based guidelines that could be applicable to Indian patients. Taking into consideration peripheral oncology centers, regional cancer centers, and tertiary cancer centers in major cities, the set of recommendations includes two categories, namely desirable/ideal and essential.
Tests and treatments that may not be available at all centers but the centers should aspire to have them in the near future
Bare minimum that should be offered to all the patients by all the centers treating cancer patients.
| Diagnosis and Staging|| |
In India, like most countries in the world, there is no screening program for the early detection of pancreatic cancer. Furthermore, symptoms related to pancreatic cancer tend to be nonspecific including weight loss, abdominal pain, nausea, and dyspepsia. Both of the above contribute to the late presentation of the cancer and its notoriously poor outcomes. Thus, clinicians must be aware of specific clinical presentations linked with pancreatic cancer. Around 60%–70% of cancers arise in the head of pancreas, and these patients present with jaundice, pale stools, and itching. New-onset diabetes mellitus after 40 years or unexplained thrombophlebitis merits investigation. Acute pancreatitis may be a manifestation of pancreatic cancer, especially when it occurs for the first time in an older adult without any obvious reason (such as gallstones or alcohol ingestion). Patients with chronic pancreatitis with super-added carcinoma may present with worsening pain, weight loss, and worsening diabetes control. In a long-standing diabetic patient, sudden unexplained weight loss or loss of blood sugar control may be features of pancreatic cancer.
Recognizing these symptoms and initiating early investigation may help in the early detection of the cancer with corresponding improvement in outcomes.
Evaluation of a patient presenting with a pancreatic cancer should be aimed at pathological confirmation of the diagnosis and an accurate staging of the disease.
| Diagnosis of Pancreatic Cancer|| |
A CT scan of the abdomen and pelvis is essential in every patient suspected to have pancreatic cancer along with either a chest X-ray or inclusion of the chest in the same CT scan. Ideally, the scan of the abdomen should be carried out as per the pancreas protocol. While obtaining a tissue diagnosis of a suspected pancreatic cancer is not mandatory in a medically fit patient with disease amenable to a curative resection, a biopsy is required for any patient who is a candidate for neoadjuvant treatment, including borderline resectable patients. Endoscopic ultrasound (EUS)-guided biopsy is preferred over percutaneous image-guided biopsy in these patients because of better diagnostic yield, safety, and potentially lower risk of peritoneal seeding., In patients with locally advanced or metastatic disease, a percutaneous biopsy from an easily accessible site is preferred over EUS-guided sampling on account of its lower cost, wider availability in India, and wider applicability among sicker patients where sedation may be hazardous.
Initial biochemical evaluation of suspected or proven patients with pancreatic cancer should include the liver function tests, fasting blood sugars, HbA1c, and tumor markers such as serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen levels. CA19-9 levels may be elevated in conditions other than cancer, including benign or malignant biliary obstruction and cholangitis. For an accurate baseline, the CA19.9 levels should be measured after the bilirubin levels have normalized. CA19.9 may be undetectable in Lewis antigen-negative patients with pancreatic cancer. Preoperative CA19-9 levels correlate with both American Joint Cancer Committee (AJCC) staging and resectability. A preoperative serum CA19-9 level ≥500 UI/ml indicates a worse prognosis after surgery.
| Staging of Pancreatic Cancer|| |
Pancreatic cancer is staged as per the AJCC system. However, a more clinically relevant way to classify pancreatic cancer is into the following categories:
- Potentially curable
- Borderline resectable.
Unresectable, locally advancedMetastatic.
Magnetic resonance imaging and MR cholangiopancreatography should be used to improve the characterization of indeterminate liver lesions on CT-scan or in patient who report severe allergy to intravenous iodinated contrast material. EUS is complementary to CT scans and is used selectively. It is most useful when a pancreatic cancer is suspected but CT and/or MR cannot demonstrate the tumor. These situations include unexplained dilatation or stricture of pancreatic and/or bile duct, raised CA19.9 levels, unexplained acute pancreatitis in an older adult, or sudden unexplained worsening in a patient with diabetes or chronic pancreatitis. In CT-demonstrable lesions, EUS may be indicated to evaluate vascular involvement, especially when the cancer is staged as borderline resectable. While the routine performance of a positron emission tomography-CT scan is not indicated, it may be considered after formal pancreatic CT protocol in high-risk patients to detect extrapancreatic metastases. These include patients with borderline resectable disease or those patients with a markedly elevated CA19-9, large primary tumors, or large regional lymph nodes. Staging laparoscopy may be considered in patients with resectable disease on preoperative imaging who harbor features suspicious for disseminated disease (high CA19-9, large primary tumors, large regional lymph nodes, body-tail tumors) as it can permit identification of peritoneal, capsular, or serosal implants that are radiologically inapparent even with conventional imaging, thereby avoiding morbid incisions in inoperable patients.
Staging should be performed as per the AJCC staging manual (8th edition, updated in 2016), and patients should be assigned a TNM stage.
| Treatment Plan|| |
Treatment of each patient should ideally be undertaken by a multidisciplinary team. The intent of treatment is “curative” for patients deemed to have resectable disease (as discussed above) and “palliative” for patients with unresectable, locally advanced disease or metastases. The treatment paradigms in the management of borderline resectable tumors are evolving and will be discussed in more detail.
| Biliary Stenting|| |
Biliary stenting should not be routinely performed in patients with pancreatic cancer except in selected indications such as in patients with obstructive jaundice in a pancreatic head or periampullary cancer who are symptomatic (with a serum bilirubin level of >15 mg/dl), septic, coagulopathic, patients who have renal insufficiency, or in whom surgical resection is significantly delayed.
Biliary decompression is mandatory in jaundiced patients undergoing NAT before resection or who are receiving chemotherapy for advanced disease. Usually, bilirubin levels <3 mg/dL are prerequisite for chemotherapy. A self-expanding metal stent (SEMS) of short length is preferred to plastic stent(s) for this indication. Biliary stenting also relieves pruritus and improves the quality of life. Uncovered SEMS should never be placed before confirmatory tissue diagnosis of malignancy.
Endoscopically placed biliary stents are preferred to surgical hepaticojejunostomy for relief of biliary obstruction., SEMS has an advantage over plastic stents in terms of wider diameter, faster resolution of jaundice, and less need for reinterventions.
| Resectable Pancreatic Cancer|| |
Surgery remains the only option for cure in patients with resectable pancreatic cancer, so long as a complete resection with microscopically negative margins (an R0 resection) can be achieved. The optimal surgical resection for malignancies of the head and/or neck of pancreas is a pancreatoduodenectomy (PD). A distal or subtotal pancreatectomy is performed for malignancies involving distal neck and body, or the body and/or tail of the pancreas. Left pancreatic resections for cancer must include a splenectomy. All patients must undergo a standard lymphadenectomy, that entails harvesting of lymph nodes situated to the right side of the hepatoduodenal ligament (12b1, 12b1, 12c), the posterior pancreaticoduodenal nodes (13a, 13b), lymph nodes situated along the right side of the superior mesenteric artery extending from the origin of the superior mesenteric artery down to the inferior pancreaticoduodenal artery (14a, 14b) as well as anterior pancreaticoduodenal nodes (17a, 17b).,
There is no evidence in literature to suggest the superiority of the pylorus-preserving PD over the Classic Whipple's procedure in terms of oncological outcomes., A critical evaluation of the literature indicates that there exists no difference in the rates of POPF between PJ and PG, as well as their individual variations, except in a high-risk anastomoses where performing a PJ has its benefits. The performance of an antecolic gastro-/duodeno-jejunostomy is likely to yield a significantly lower rate of delayed gastric emptying.,,, Multivisceral resections for pancreatic cancer are technically feasible., Based on the limited data available, these resections are associated with a high morbidity and even mortality but an improved survival (5-year survival rates of 16%–22%), when compared to no resection. Thus, such resections should only be performed if there exists a clear and objective possibility of achieving a complete resection (R0). Current evidence does not support the routine performance of intraoperative frozen section of the resection margin. Laparoscopic resections for pancreatic tumors are technically feasible.,,, At the present time, the necessary evidence to suggest an advantage, or even comparability, of laparoscopic PD to open surgery in terms of overall survival is lacking.
| Borderline Resectable Pancreatic Cancer|| |
Borderline resectable pancreatic cancers are those tumor “that have limited involvement of the mesenteric vessels such that resection is technically possible, but which carry a high risk of margin-positive resection unless NAT is employed before surgery.” There are currently numerous definitions of “borderline resectable” pancreatic cancer.,,,,, The ideal management strategy for these patients needs to be established., The choice of management of these patients varies between neoadjuvant chemoradiotherapy followed by surgery versus upfront surgery., In patients diagnosed with borderline resectable disease based on radiological features, the next plan of action would entail the performance of a staging laparoscopy to determine the intent of treatment. The absence of distant metastatic disease would suggest an attempt at cure that would involve neoadjuvant chemoradiotherapy followed by reassessment. If the disease is stable or demonstrates regression on restaging, a trial of resection with the possibility of a synchronous venous resection and reconstruction would seem prudent. Synchronous arterial resections for pancreatic cancer should not be performed as they are associated with increased morbidity and mortality and have a survival rate comparable to nonresected patients.,
| Locally Advanced Pancreatic Cancer|| |
Outstanding results with FOLFIRINOX in terms of downstaging of locally advanced tumors, – even rendering a proportion of them (30%–46%) amenable to resection – have prompted a more aggressive approach in this subclass of tumors, so long as the patient is medically fit for management. Chemotherapy with or without radiotherapy is the first line of management of locally advanced pancreatic cancer. In tumors that show a response to therapy (as has been seen with FOLFIRINOX-based therapy), a trial of surgery may be considered.
| Metastatic Pancreatic Cancer|| |
There is no role for surgery in the management of metastatic pancreatic cancer. These patients should be considered for palliative therapies based on their functional status.
| Palliative Surgery|| |
Routine performance of palliative surgeries should be discouraged as they lead to increased morbidity with no survival benefit compared to aborted laparotomies. Additionally, should the patient develop complications following the surgery - these complications have been shown to significantly impact survival. Thus, in patients deemed clearly unresectable on preoperative staging, nonsurgical alternatives for palliation of biliary and gastroduodenal obstruction include SEMS. In patients with a reasonable life expectancy (>6 months) and a good performance status (ECOG = 0-2) in whom nonsurgical methods of palliation have been unsuccessful, and/or in patients who were following NAT underwent a surgically exploration (as part of the trial of resection) and were found to harbor nonmetastatic, but unresectable disease, performance of a prophylactic GJ, despite the absence of features of gastric outlet obstruction,, is supported by evidence in literature.
| Adjuvant Therapy|| |
While the ESPAC-1 trial laid the foundation for the beneficial role of adjuvant chemotherapy in terms of a survival benefit, the findings of the ESPAC-3 trial demonstrated a lack of benefit of gemcitabine over 5-fluorouracil. Despite this, gemcitabine remains the preferred (single agent) drug in the adjuvant setting. At the recent meeting of the American Society of Clinical Oncology, the oncologists involved in the PRODIGE24 trial presented their results from the 30.5-month median follow-up. mFOLFIRINOX (FOL – folinic acid (also called leucovorin, calcium folinate or FA) F – fluorouracil (also called 5FU), IRIN - irinotecan and OX-oxaliplatin) is safe and has a significantly better disease-free and overall survival compared to Gemcitabine when used in patients aged 18–79 years, with a WHO performance status ≤1, 21–84 days after a surgical (R0 or R1) resection, and in whom there were no hematologic, renal, or cardiac issues to preclude the use of the therapy.
| Follow-up and Rehabilitation|| |
Patients should be encouraged to maintain lead a healthy lifestyle and abstain from tobacco and alcohol. The aim of follow-up is to detect recurrences early as well as to assess any complication due to surgery/radiotherapy. Postsurgery, the follow-up is done every 3–4 months for the 1st year with each visit comprised of clinical examination (including history and physical examination). The follow-up in years 2–3 is every 6 months and annually, thereafter till year 5. At the end of each of the first 3 years, a CT scan of the chest, abdomen, and pelvis is recommended. For patients with advanced pancreatic cancer, the scans are symptom driven or for response assessment.
| References|| |
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al.
Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer 2013;49:1374-403.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7-30.
Shrikhande SV, Barreto SG, Somashekar BA, Suradkar K, Shetty GS, Talole S, et al.
Evolution of pancreatoduodenectomy in a tertiary cancer center in India: Improved results from service reconfiguration. Pancreatology 2013;13:63-71.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, et al.
Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
Dhir V, Mohandas KM. Epidemiology of digestive tract cancers in India IV. Gall bladder and pancreas. Indian J Gastroenterol 1999;18:24-8.
Takiar R, Nadayil D, Nandakumar A. Projections of number of cancer cases in India (2010-2020) by cancer groups. Asian Pac J Cancer Prev 2010;11:1045-9.
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;26 Suppl 5:v56-68.
Tempero MA, Malafa MP, Al-Hawary M, Asbun H, Bain A, Behrman SW, et al.
Pancreatic adenocarcinoma, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2017;15:1028-61.
Watanabe H, Kanematsu M, Tanaka K, Osada S, Tomita H, Hara A, et al.
Fibrosis and postoperative fistula of the pancreas: Correlation with MR imaging findings – Preliminary results. Radiology 2014;270:791-9.
Yardimci S, Kara YB, Tuney D, Attaallah W, Ugurlu MU, Dulundu E, et al.
A simple method to evaluate whether pancreas texture can be used to predict pancreatic fistula risk after pancreatoduodenectomy. J Gastrointest Surg 2015;19:1625-31.
Lee SE, Jang JY, Lim CS, Kang MJ, Kim SH, Kim MA, et al.
Measurement of pancreatic fat by magnetic resonance imaging: Predicting the occurrence of pancreatic fistula after pancreatoduodenectomy. Ann Surg 2010;251:932-6.
Kakar S, Pawlik T, Allen P. Exocrine pancreas. Pancreatic adenocarcinoma. In: Amin M, editor. AJCC Cancer Staging Manual. 8th
ed. New York: Springer-Verlag; 2016.
Barreto S, Windsor J. Palliation of extra-hepatic biliary malignancies: Diminishing role for surgery. Clin Oncol 2017;2:1229.
Buettner S, Wilson A, Margonis GA, Gani F, Ethun CG, Poultsides GA, et al.
Assessing trends in palliative surgery for extrahepatic biliary malignancies: A 15-year multicenter study. J Gastrointest Surg 2016;20:1444-52.
Shoup M, Brennan MF, McWhite K, Leung DH, Klimstra D, Conlon KC, et al.
The value of splenic preservation with distal pancreatectomy. Arch Surg 2002;137:164-8.
Iqbal N, Lovegrove RE, Tilney HS, Abraham AT, Bhattacharya S, Tekkis PP, et al.
A comparison of pancreaticoduodenectomy with extended pancreaticoduodenectomy: A meta-analysis of 1909 patients. Eur J Surg Oncol 2009;35:79-86.
Michalski CW, Kleeff J, Wente MN, Diener MK, Büchler MW, Friess H, et al.
Systematic review and meta-analysis of standard and extended lymphadenectomy in pancreaticoduodenectomy for pancreatic cancer. Br J Surg 2007;94:265-73.
Hüttner FJ, Fitzmaurice C, Schwarzer G, Seiler CM, Antes G, Büchler MW, et al.
Pylorus-preserving pancreaticoduodenectomy (pp whipple) versus pancreaticoduodenectomy (classic whipple) for surgical treatment of periampullary and pancreatic carcinoma. Cochrane Database Syst Rev 2016;2:CD006053.
Barreto SG. Classical or pylorus-preserving pancreatoduodenectomy in pancreatic and periampullary cancer: “The jury is still out!” Indian J Med Paediatr Oncol 2016;37:209-10.
Barreto SG, Shukla PJ. Different types of pancreatico-enteric anastomosis. Transl Gastroenterol Hepatol 2017;2:89.
Imamura M, Kimura Y, Ito T, Kyuno T, Nobuoka T, Mizuguchi T, et al.
Effects of antecolic versus retrocolic reconstruction for gastro/duodenojejunostomy on delayed gastric emptying after pancreatoduodenectomy: A systematic review and meta-analysis. J Surg Res 2016;200:147-57.
Qu H, Sun GR, Zhou SQ, He QS. Clinical risk factors of delayed gastric emptying in patients after pancreaticoduodenectomy: A systematic review and meta-analysis. Eur J Surg Oncol 2013;39:213-23.
Su AP, Cao SS, Zhang Y, Zhang ZD, Hu WM, Tian BL, et al.
Does antecolic reconstruction for duodenojejunostomy improve delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy? A systematic review and meta-analysis. World J Gastroenterol 2012;18:6315-23.
Barreto SG, Windsor JA. Does the ileal brake contribute to delayed gastric emptying after pancreatoduodenectomy? Dig Dis Sci 2017;62:319-35.
Mitra A, Pai E, Dusane R, Ranganathan P, DeSouza A, Goel M, et al.
Extended pancreatectomy as defined by the ISGPS: Useful in selected cases of pancreatic cancer but invaluable in other complex pancreatic tumors. Langenbecks Arch Surg 2018;403:203-12.
Shrikhande SV, Barreto SG. Extended pancreatic resections and lymphadenectomy: An appraisal of the current evidence. World J Gastrointest Surg 2010;2:39-46.
Sasson AR, Hoffman JP, Ross EA, Kagan SA, Pingpank JF, Eisenberg BL, et al.
En bloc resection for locally advanced cancer of the pancreas: Is it worthwhile? J Gastrointest Surg 2002;6:147-57.
Shoup M, Conlon KC, Klimstra D, Brennan MF. Is extended resection for adenocarcinoma of the body or tail of the pancreas justified? J Gastrointest Surg 2003;7:946-52.
Barreto SG, Pandanaboyana S, Ironside N, Windsor JA. Does revision of resection margins based on frozen section improve overall survival following pancreatoduodenectomy for pancreatic ductal adenocarcinoma? A meta-analysis. HPB (Oxford) 2017;19:573-9.
Kendrick ML, Cusati D. Total laparoscopic pancreaticoduodenectomy: Feasibility and outcome in an early experience. Arch Surg 2010;145:19-23.
Palanivelu C, Rajan PS, Rangarajan M, Vaithiswaran V, Senthilnathan P, Parthasarathi R, et al.
Evolution in techniques of laparoscopic pancreaticoduodenectomy: A decade long experience from a tertiary center. J Hepatobiliary Pancreat Surg 2009;16:731-40.
Ammori BJ. Laparoscopic hand-assisted pancreaticoduodenectomy: Initial UK experience. Surg Endosc 2004;18:717-8.
Staudacher C, Orsenigo E, Baccari P, Di Palo S, Crippa S. Laparoscopic assisted duodenopancreatectomy. Surg Endosc 2005;19:352-6.
Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, et al.
Borderline resectable pancreatic cancer: The importance of this emerging stage of disease. J Am Coll Surg 2008;206:833-46.
Al-Hawary MM, Francis IR, Chari ST, Fishman EK, Hough DM, Lu DS, et al.
Pancreatic ductal adenocarcinoma radiology reporting template: Consensus statement of the society of abdominal radiology and the American Pancreatic Association. Gastroenterology 2014;146:291-3040.
Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC, et al.
Pretreatment assessment of resectable and borderline resectable pancreatic cancer: Expert consensus statement. Ann Surg Oncol 2009;16:1727-33.
Katz MH, Marsh R, Herman JM, Shi Q, Collison E, Venook AP, et al.
Borderline resectable pancreatic cancer: Need for standardization and methods for optimal clinical trial design. Ann Surg Oncol 2013;20:2787-95.
Tempero MA, Arnoletti JP, Behrman SW, Ben-Josef E, Benson AB 3rd
, Casper ES, et al.
Pancreatic adenocarcinoma, version 2.2012: Featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2012;10:703-13.
Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, et al.
Borderline resectable pancreatic cancer: Definitions, management, and role of preoperative therapy. Ann Surg Oncol 2006;13:1035-46.
Barreto SG, Windsor JA. Justifying vein resection with pancreatoduodenectomy. Lancet Oncol 2016;17:e118-24.
Windsor JA, Barreto SG. The concept of 'borderline resectable' pancreatic cancer: Limited foundations and limited future? J Gastrointest Oncol 2017;8:189-93.
Tucker ON, Rela M. Controversies in the management of borderline resectable proximal pancreatic adenocarcinoma with vascular involvement. HPB Surg 2008;2008:839503.
Shrikhande SV, Arya S, Barreto SG, Ingle S, D'Souza MA, Hawaldar R, et al.
Borderline resectable pancreatic tumors: Is there a need for further refinement of this stage? Hepatobiliary Pancreat Dis Int 2011;10:319-24.
Barreto SG, Loveday B, Windsor JA, Pandanaboyana S. Detecting tumour response and predicting resectability after neoadjuvant therapy for borderline resectable and locally advanced pancreatic cancer. ANZ J Surg. 2018. doi: 10.1111/ans.14764. [Epub ahead of print].
Kato H, Usui M, Isaji S, Nagakawa T, Wada K, Unno M, et al.
Clinical features and treatment outcome of borderline resectable pancreatic head/body cancer: A multi-institutional survey by the Japanese Society of Pancreatic Surgery. J Hepatobiliary Pancreat Sci 2013;20:601-10.
Ravikumar R, Holroyd D, Fusai G. Is there a role for arterial reconstruction in surgery for pancreatic cancer? World J Gastrointest Surg 2013;5:27-9.
Petrelli F, Coinu A, Borgonovo K, Cabiddu M, Ghilardi M, Lonati V, et al.
FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable pancreatic cancer: A meta-analytical review of published studies. Pancreas 2015;44:515-21.
Hackert T, Sachsenmaier M, Hinz U, Schneider L, Michalski CW, Springfeld C, et al.
Locally advanced pancreatic cancer: Neoadjuvant therapy with folfirinox results in resectability in 60% of the patients. Ann Surg 2016;264:457-63.
Ausania F, Vallance AE, Manas DM, Prentis JM, Snowden CP, White SA, et al.
Double bypass for inoperable pancreatic malignancy at laparotomy: Postoperative complications and long-term outcome. Ann R Coll Surg Engl 2012;94:563-8.
Gurusamy KS, Kumar S, Davidson BR. Prophylactic gastrojejunostomy for unresectable periampullary carcinoma. Cochrane Database Syst Rev 2013;(2):CD008533. doi: 10.1002/14651858.CD008533.pub3.
Hüser N, Michalski CW, Schuster T, Friess H, Kleeff J. Systematic review and meta-analysis of prophylactic gastroenterostomy for unresectable advanced pancreatic cancer. Br J Surg 2009;96:711-9.
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al.
A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350:1200-10.
Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, et al.
Adjuvant chemotherapy with fluorouracil plus folinic acid vs. gemcitabine following pancreatic cancer resection: A randomized controlled trial. JAMA 2010;304:1073-81.
Antoniou G, Kountourakis P, Papadimitriou K, Vassiliou V, Papamichael D. Adjuvant therapy for resectable pancreatic adenocarcinoma: Review of the current treatment approaches and future directions. Cancer Treat Rev 2014;40:78-85.
Conroy T, Hammel P, Hebbar M. Unicancer GI PRODIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas. J Clin Oncol 2018;36:18_suppl, LBA4001.