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{{Pancreatic cancer}}
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==Overview==
==Overview==
Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor, with few victims still alive five years after diagnosis, and complete [[remission (medicine)|remission]] still extremely rare.<ref name=Ghaneh>{{cite journal |author=Ghaneh P, Costello E, Neoptolemos JP |title=Biology and management of pancreatic cancer |journal=Gut |volume=56 |issue=8 |pages=1134-52 |year=2007 |pmid=17625148 |doi=10.1136/gut.2006.103333}}</ref>
Patients with [[pancreatic cancer]] present with [[Symptom|symptoms]] such as [[jaundice]], [[Acholic stools|light-colored stools]], [[Urine|dark urine]], and [[epigastric]] [[pain]] in the sixth decade of life. If left untreated, [[Patient|patients]] with [[pancreatic cancer]] may progress to develop [[Exocrine gland|exocrine]] [[pancreatic insufficiency]] arising from [[pancreatic duct]] [[obstruction]] leading to [[malabsorption]], [[malnutrition]] and [[cachexia]].  Common complications of [[pancreatic cancer]] include intractable [[pain]] and [[Jaundice|obstructive jaundice]] that develop as a result of [[Surgery|surgical intervention]]. Depending on the extent of the [[tumor]] at the time of [[diagnosis]], the [[prognosis]] is generally regarded as poor, with complete [[remission (medicine)|remission]] being extremely rare.


===5-Year Survival===
==Natural History==
The natural history of [[pancreatic cancer]] is as follows:<ref name="pmid27931833">{{cite journal |vauthors=Chang SC, Yang WV |title=Hyperglycemia, tumorigenesis, and chronic inflammation |journal=Crit. Rev. Oncol. Hematol. |volume=108 |issue= |pages=146–153 |year=2016 |pmid=27931833 |doi=10.1016/j.critrevonc.2016.11.003 |url=}}</ref><ref name="pmid27247222">{{cite journal |vauthors=Sohal DP, Mangu PB, Khorana AA, Shah MA, Philip PA, O'Reilly EM, Uronis HE, Ramanathan RK, Crane CH, Engebretson A, Ruggiero JT, Copur MS, Lau M, Urba S, Laheru D |title=Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline |journal=J. Clin. Oncol. |volume=34 |issue=23 |pages=2784–96 |year=2016 |pmid=27247222 |pmc=5019760 |doi=10.1200/JCO.2016.67.1412 |url=}}</ref><ref name="pmid27120389">{{cite journal |vauthors=Frič P, Škrha J, Šedo A, Bušek P, Kmochová K, Laclav M, Solař S, Bunganič B, Zavoral M |title=Early pancreatic carcinogenesis - risk factors, early symptoms, and the impact of antidiabetic drugs |journal=Eur J Gastroenterol Hepatol |volume=28 |issue=7 |pages=e19–25 |year=2016 |pmid=27120389 |doi=10.1097/MEG.0000000000000646 |url=}}</ref>
*The [[symptoms]] of [[pancreatic cancer]] usually develop in the sixth decade of life, and start with symptoms such as [[jaundice]], [[Acholic stools|light-colored stools]], [[Urine|dark urine]], [[pain]] in the upper or middle [[abdomen]] and back, unexplained [[weight loss]], [[anorexia]] and [[fatigue]].
*The [[symptoms]] of [[pancreatic cancer]] typically develop about 20-30 years after exposure to [[Risk factor|risk factors]] such as [[smoking]] and [[alcohol]]. [[Genetic|Genetic factors]] such as alterations in [[Tumor suppressor gene|tumor suppressor genes]], [[Oncogene|oncogenes]] and different [[Signal transduction|signaling pathways]] may also be responsible.
*If left untreated, patients with [[pancreatic cancer]] may progress to develop [[Exocrine gland|exocrine]] [[pancreatic insufficiency]] arising from [[pancreatic duct]] [[obstruction]] leading to [[malabsorption]], [[malnutrition]] and [[cachexia]]. Dudodenal [[obstruction]] and [[Bile duct|biliary]] [[obstruction]] may cause symptoms of [[Intestine|bowel]] [[obstruction]] and [[jaundice]]. [[Metastasis]] may occur to different sites.


* Between 2007 and 2010, the 5-year relative survival of patients with pancreatic cancer was 7.2%.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
==Complications==
 
Common [[Complication (medicine)|complications]] of [[pancreatic cancer]] may arise as a result of the [[disease]] or [[therapy]]:<ref name="pmid28229252">{{cite journal |vauthors=Koulouris AI, Banim P, Hart AR |title=Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments |journal=Dig. Dis. Sci. |volume=62 |issue=4 |pages=861–870 |year=2017 |pmid=28229252 |doi=10.1007/s10620-017-4488-z |url=}}</ref><ref name="pmid28281169">{{cite journal |vauthors=Ramsey ML, Conwell DL, Hart PA |title=Complications of Chronic Pancreatitis |journal=Dig. Dis. Sci. |volume=62 |issue=7 |pages=1745–1750 |year=2017 |pmid=28281169 |pmc=5667546 |doi=10.1007/s10620-017-4518-x |url=}}</ref><ref name="pmid28241470">{{cite journal |vauthors=Vujasinovic M, Valente R, Del Chiaro M, Permert J, Löhr JM |title=Pancreatic Exocrine Insufficiency in Pancreatic Cancer |journal=Nutrients |volume=9 |issue=3 |pages= |year=2017 |pmid=28241470 |pmc=5372846 |doi=10.3390/nu9030183 |url=}}</ref><ref name="pmid27013367">{{cite journal |vauthors=Poruk KE, Wolfgang CL |title=Palliative Management of Unresectable Pancreas Cancer |journal=Surg. Oncol. Clin. N. Am. |volume=25 |issue=2 |pages=327–37 |year=2016 |pmid=27013367 |doi=10.1016/j.soc.2015.11.005 |url=}}</ref><ref name="pmid27008166">{{cite journal |vauthors=Kapoor VK |title=Complications of pancreato-duodenectomy |journal=Rozhl Chir |volume=95 |issue=2 |pages=53–9 |year=2016 |pmid=27008166 |doi= |url=}}</ref><ref name="pmid26898789">{{cite journal |vauthors=Hucl T |title=[Malignant biliary obstruction] |language=Czech |journal=Cas. Lek. Cesk. |volume=155 |issue=1 |pages=30–7 |year=2016 |pmid=26898789 |doi= |url=}}</ref><ref name="pmid26818541">{{cite journal |vauthors=Dong J, Cong L, Zhang TP, Zhao YP |title=Pancreatic metastasis of renal cell carcinoma |journal=HBPD INT |volume=15 |issue=1 |pages=30–8 |year=2016 |pmid=26818541 |doi= |url=}}</ref>
* When stratified by age, the 5-year relative survival of patients with pancreatic cancer was 10% and 4.6% for patients <65 and ≥ 65 years of age respectively.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
* [[Malabsorption]]
 
** [[Pancreatic insufficiency|Exocrine pancreatic insufficiency]] due to [[pancreatic duct]] [[obstruction]] by the [[tumor]] may lead to [[malabsorption]]. [[Malabsorption]] in patients presents with [[anorexia]], [[weight loss]], and [[diarrhea]].
* The survival of patients with pancreatic cancer varies with the stage of the disease.  Shown below is a table depicting the 5-year relative survival by the stage of pancreatic cancer:<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
* Intractable [[pain]]
 
** Patients with advanced [[pancreatic cancer]] may develop intractable [[pain]] requiring [[Narcotic|narcotic analgesics]] and surgical [[Intervention (counseling)|intervention]] such as [[neurolysis]] of [[celiac ganglia]].<ref name="pmid28229252">{{cite journal |vauthors=Koulouris AI, Banim P, Hart AR |title=Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments |journal=Dig. Dis. Sci. |volume=62 |issue=4 |pages=861–870 |year=2017 |pmid=28229252 |doi=10.1007/s10620-017-4488-z |url=}}</ref><ref name="pmid27111447">{{cite journal |vauthors=Dobosz Ł, Kaczor M, Stefaniak TJ |title=Pain in pancreatic cancer: review of medical and surgical remedies |journal=ANZ J Surg |volume=86 |issue=10 |pages=756–761 |year=2016 |pmid=27111447 |doi=10.1111/ans.13609 |url=}}</ref>  
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
* [[Jaundice]]
** [[Jaundice|Obstructive jaundice]] can present with features of [[cholangitis]]:
***[[Fever]] and [[Rigor|chills]]
***[[Nausea and vomiting|Nausea]], [[Nausea and vomiting|vomiting]]
***[[Acholic stools|Clay-colored stools]]
***Dark [[urine]]
***Yellowish discoloration of [[skin]]
***[[Itch|Pruritus]]
***[[Abdominal pain|Right upper quadrant pain]]
***[[Anorexia]]
*Patients may require [[Endoscopy|Endoscopic]] [[decompression]] with [[stent]] placement in patients due to [[Cholestasis|biliary obstruction]].
*[[Duodenum|Duodenal]] [[obstruction]]
**Patients may develop [[Duodenum|duodenal]] [[obstruction]] as a result of complications of [[surgery]].
**[[Duodenum|Duodenal]] [[obstruction]] may be treated with [[Endoscopy|endoscopic]] [[Stent|stenting]] or [[gastrojejunostomy]].
==Prognosis==
*The primary factors that influence [[prognosis]] are:
**Whether the [[tumor]] is localized and can be completely [[Resection|resected]]
**Whether the [[tumor]] has spread to [[Lymph node|lymph nodes]] or elsewhere
'''Staging and TNM (tumour, lymph node, metastasis) classification related to incidence, treatment, and prognosis:'''<ref name="pmid22592847">{{cite journal| author=Bond-Smith G, Banga N, Hammond TM, Imber CJ| title=Pancreatic adenocarcinoma. | journal=BMJ | year= 2012 | volume= 344 | issue=  | pages= e2476 | pmid=22592847 | doi=10.1136/bmj.e2476 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22592847  }} </ref>
{|
! colspan="5" rowspan="1" style="background:#4479BA; color: #FFFFFF;" align="center" + | '''Staging and TNM Classification related to Incidence, Treatment, and Prognosis'''
|+
| colspan="1" rowspan="1" style="background:#4479BA; color: #FFFFFF;" + | '''Stage'''
| colspan="1" rowspan="1" style="background:#4479BA; color: #FFFFFF;" + | '''TNM Classification'''
| colspan="1" rowspan="1" style="background:#4479BA; color: #FFFFFF;" + | '''Clinical Classification'''
| colspan="1" rowspan="1" style="background:#4479BA; color: #FFFFFF;" + | '''Incidence at diagnosis (%)'''
| colspan="1" rowspan="1" style="background:#4479BA; color: #FFFFFF;" + | '''5-year survival rate (%)'''
|-
| style="background:#DCDCDC; + " | '''0'''
| style="background:#F5F5F5; + " | '''Tis, N0, M0'''
| style="background:#F5F5F5; + " | Resectable
| style="background:#F5F5F5; + " | 7.5
| style="background:#F5F5F5; + " | 15
|-
| style="background:#DCDCDC; + " | '''IA'''
| style="background:#F5F5F5; + " | '''T1, N0, M0'''
| style="background:#F5F5F5; + " | —
| style="background:#F5F5F5; + " | —
| style="background:#F5F5F5; + " | 14
|-
|-
|style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align=center |'''Stage'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align=center | '''5-year relative survival (%), (2004-2010)'''
| style="background:#DCDCDC; + " | '''IB'''
| style="background:#F5F5F5; + " | '''T2, N0, M0'''
| style="background:#F5F5F5; + " | —
| style="background:#F5F5F5; + " | —
| style="background:#F5F5F5; + " | 12
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |'''All stages'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |6.7%
| style="background:#DCDCDC; + " | '''IIA'''
| style="background:#F5F5F5; + " | '''T3, N0, M0'''
| style="background:#F5F5F5; + " | —
| style="background:#F5F5F5; + " | —
| style="background:#F5F5F5; + " | 7
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |'''Localized'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left  |25.8%
| style="background:#DCDCDC; + " | '''IIB'''
| style="background:#F5F5F5; + " | '''T1-3, N1, M0'''
| style="background:#F5F5F5; + " | Locally advanced
| style="background:#F5F5F5; + " | 29.3
| style="background:#F5F5F5; + " | 5
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |'''Regional'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |9.9%
| style="background:#DCDCDC; + " | '''III'''
| style="background:#F5F5F5; + " | '''T4, any N, M0'''
| style="background:#F5F5F5; + " | —
| style="background:#F5F5F5; + " | —
| style="background:#F5F5F5; + " | 3
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left  |'''Distant'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left  |2.3%
| style="background:#DCDCDC; + " | '''IV'''
| style="background:#F5F5F5; + " | '''Any T, any N, M1'''
| style="background:#F5F5F5; + " | Metastatic
| style="background:#F5F5F5; + " | 47.2
| style="background:#F5F5F5; + " | 1
|-
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left  |'''Unstaged'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left |4.4%
|}
|}


Shown below is an image depicting the 5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between YEAR and YEAR of pancreatic cancer by stage at diagnosis according to [[SEER]]. These graphs are adapted from [[SEER]]: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.<ref name="SEER">Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.</ref>
=== Five year survival rate ===
* The percentage of people who live for a minimum of five years after [[diagnosis]] is called the 5- year [[survival rate]].
* [[Survival rate|Survival rates]] for [[Exocrine gland|exocrine]] [[pancreatic cancer]]:
** Lifespan is found to be longer in [[Patient|patients]] treated with [[surgery]], as opposed to other [[Patient|patients]].
** The 5-year [[survival rate]] for people at various stages of [[pancreatic cancer]] are as follows based on the most recent statistics of the [[American Cancer Society]] are as follows:<ref name="urlPancreatic Cancer Survival Rates, by Stage">{{cite web |url=https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html#references |title=Pancreatic Cancer Survival Rates, by Stage |format= |work= |accessdate=}}</ref><ref name="CarratoFalcone2015">{{cite journal|last1=Carrato|first1=A.|last2=Falcone|first2=A.|last3=Ducreux|first3=M.|last4=Valle|first4=J. W.|last5=Parnaby|first5=A.|last6=Djazouli|first6=K.|last7=Alnwick-Allu|first7=K.|last8=Hutchings|first8=A.|last9=Palaska|first9=C.|last10=Parthenaki|first10=I.|title=A Systematic Review of the Burden of Pancreatic Cancer in Europe: Real-World Impact on Survival, Quality of Life and Costs|journal=Journal of Gastrointestinal Cancer|volume=46|issue=3|year=2015|pages=201–211|issn=1941-6628|doi=10.1007/s12029-015-9724-1}}</ref>


[Insert figure x.5 here]
*** Stage IA: 14%
*** Stage IB: 12%
*** Stage IIA 7%
*** Stage IIB 5%
*** Stage III 3%
*** Stage IV 1%
** Survival rates for [[Neuroendocrine tumors|neuroendocrine pancreatic tumors]] (treated with [[surgery]]) are as follows:
*** Stage I [[Pancreas|pancreatic]] [[Neuroendocrine tumors|NETs]] 61%
*** Stage II [[Neuroendocrine tumors|pancreatic NETs]] 52%
*** Stage III [[Neuroendocrine|pancreatic NETs]] 41%
*** Stage IV [[Neuroendocrine tumors|pancreatic NETs]] 16%
** Five year [[survival rate]] of [[Tumor|tumors]] not removed by [[surgery]] is 16%


==References==
==References==
Line 44: Line 118:


[[Category:Disease]]
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[[Category:Needs content]]
[[Category:Types of cancer]]
[[Category:Types of cancer]]
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[[Category:Mature chapter]]
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[[Category:Primary care]]

Latest revision as of 23:33, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aravind Reddy Kothagadi M.B.B.S[2] Sudarshana Datta, MD [3]

Overview

Patients with pancreatic cancer present with symptoms such as jaundice, light-colored stools, dark urine, and epigastric pain in the sixth decade of life. If left untreated, patients with pancreatic cancer may progress to develop exocrine pancreatic insufficiency arising from pancreatic duct obstruction leading to malabsorption, malnutrition and cachexia. Common complications of pancreatic cancer include intractable pain and obstructive jaundice that develop as a result of surgical intervention. Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor, with complete remission being extremely rare.

Natural History

The natural history of pancreatic cancer is as follows:[1][2][3]

Complications

Common complications of pancreatic cancer may arise as a result of the disease or therapy:[4][5][6][7][8][9][10]

Prognosis

Staging and TNM (tumour, lymph node, metastasis) classification related to incidence, treatment, and prognosis:[12]

Staging and TNM Classification related to Incidence, Treatment, and Prognosis
Stage TNM Classification Clinical Classification Incidence at diagnosis (%) 5-year survival rate (%)
0 Tis, N0, M0 Resectable 7.5 15
IA T1, N0, M0 — — 14
IB T2, N0, M0 — — 12
IIA T3, N0, M0 — — 7
IIB T1-3, N1, M0 Locally advanced 29.3 5
III T4, any N, M0 — — 3
IV Any T, any N, M1 Metastatic 47.2 1

Five year survival rate

References

  1. ↑ Chang SC, Yang WV (2016). "Hyperglycemia, tumorigenesis, and chronic inflammation". Crit. Rev. Oncol. Hematol. 108: 146–153. doi:10.1016/j.critrevonc.2016.11.003. PMID 27931833.
  2. ↑ Sohal DP, Mangu PB, Khorana AA, Shah MA, Philip PA, O'Reilly EM, Uronis HE, Ramanathan RK, Crane CH, Engebretson A, Ruggiero JT, Copur MS, Lau M, Urba S, Laheru D (2016). "Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline". J. Clin. Oncol. 34 (23): 2784–96. doi:10.1200/JCO.2016.67.1412. PMC 5019760. PMID 27247222.
  3. ↑ Frič P, Škrha J, Šedo A, Bušek P, Kmochová K, Laclav M, Solař S, Bunganič B, Zavoral M (2016). "Early pancreatic carcinogenesis - risk factors, early symptoms, and the impact of antidiabetic drugs". Eur J Gastroenterol Hepatol. 28 (7): e19–25. doi:10.1097/MEG.0000000000000646. PMID 27120389.
  4. ↑ 4.0 4.1 Koulouris AI, Banim P, Hart AR (2017). "Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments". Dig. Dis. Sci. 62 (4): 861–870. doi:10.1007/s10620-017-4488-z. PMID 28229252.
  5. ↑ Ramsey ML, Conwell DL, Hart PA (2017). "Complications of Chronic Pancreatitis". Dig. Dis. Sci. 62 (7): 1745–1750. doi:10.1007/s10620-017-4518-x. PMC 5667546. PMID 28281169.
  6. ↑ Vujasinovic M, Valente R, Del Chiaro M, Permert J, Löhr JM (2017). "Pancreatic Exocrine Insufficiency in Pancreatic Cancer". Nutrients. 9 (3). doi:10.3390/nu9030183. PMC 5372846. PMID 28241470.
  7. ↑ Poruk KE, Wolfgang CL (2016). "Palliative Management of Unresectable Pancreas Cancer". Surg. Oncol. Clin. N. Am. 25 (2): 327–37. doi:10.1016/j.soc.2015.11.005. PMID 27013367.
  8. ↑ Kapoor VK (2016). "Complications of pancreato-duodenectomy". Rozhl Chir. 95 (2): 53–9. PMID 27008166.
  9. ↑ Hucl T (2016). "[Malignant biliary obstruction]". Cas. Lek. Cesk. (in Czech). 155 (1): 30–7. PMID 26898789.
  10. ↑ Dong J, Cong L, Zhang TP, Zhao YP (2016). "Pancreatic metastasis of renal cell carcinoma". HBPD INT. 15 (1): 30–8. PMID 26818541.
  11. ↑ Dobosz Ł, Kaczor M, Stefaniak TJ (2016). "Pain in pancreatic cancer: review of medical and surgical remedies". ANZ J Surg. 86 (10): 756–761. doi:10.1111/ans.13609. PMID 27111447.
  12. ↑ Bond-Smith G, Banga N, Hammond TM, Imber CJ (2012). "Pancreatic adenocarcinoma". BMJ. 344: e2476. doi:10.1136/bmj.e2476. PMID 22592847.
  13. ↑ "Pancreatic Cancer Survival Rates, by Stage".
  14. ↑ Carrato, A.; Falcone, A.; Ducreux, M.; Valle, J. W.; Parnaby, A.; Djazouli, K.; Alnwick-Allu, K.; Hutchings, A.; Palaska, C.; Parthenaki, I. (2015). "A Systematic Review of the Burden of Pancreatic Cancer in Europe: Real-World Impact on Survival, Quality of Life and Costs". Journal of Gastrointestinal Cancer. 46 (3): 201–211. doi:10.1007/s12029-015-9724-1. ISSN 1941-6628.



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