Preoperative Biliary Drainage in Malignant Biliary Obstruction

Pancreatic Cancer Clinical Trial

— PEAR  

Official title:

Preoperative Biliary Drainage in Malignant Biliary Obstruction - an Observational Cohort Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04847297
• Other study ID #: 40393-10/2020/EÜIG
• Status: Not yet recruiting
• Start date: September 1, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2021
• Source: University of Pecs
• Contact: Ákos Szucs
• Phone: 06305359443
• Email: szucs.akos[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The first alarming symptom of a malignancy of the pancreas or periampullary tumor can be obstructive jaundice (OJ). Pancreato-duodenectomy (PD) combined with oncological treatment can provide long disease-free survival in resectable cases. The literature regarding the preoperative biliary drainage is controversial. The aim of this multicenter, prospective observational cohort study is to investigate the role of preoperative drainage, and to compare it with surgery alone.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 353
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients = 18 years

2. OJ of malignant origin (pancreatic head or periampullary tumor)

3. Total bilirubin level = 40 µmol per liter

4. Signed written informed consent

Exclusion Criteria:

1. Proved metastasis

2. Irresectable tumor

3. Neo-adjuvant chemotherapy

4. Co-existing malignancy

5. Pregnancy

6. Patients not fit for resection

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Procedure:
• Preoperative drainage and pancreatoduodenectomy
Preoperative biliary drainage before surgical removal of the tumor
• Pancreatoduodenectomy
Pancreatic tumor resection without previous preoperative biliary drainage

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Pecs

References & Publications (34)

Abdeldayem H, Ghoneim E, Refaei AA, Abou-Gabal A. Obstructive jaundice promotes intestinal-barrier dysfunction and bacterial translocation: experimental study. Hepatol Int. 2007 Dec;1(4):444-8. doi: 10.1007/s12072-007-9018-1. Epub 2007 Sep 20. — View Citation

Abrahám S, Szabó A, Kaszaki J, Varga R, Eder K, Duda E, Lázár G, Tiszlavicz L, Boros M, Lázár G Jr. Kupffer cell blockade improves the endotoxin-induced microcirculatory inflammatory response in obstructive jaundice. Shock. 2008 Jul;30(1):69-74. doi: 10.1097/SHK.0b013e31815dceea. — View Citation

Assimakopoulos SF, Scopa CD, Vagianos CE. Pathophysiology of increased intestinal permeability in obstructive jaundice. World J Gastroenterol. 2007 Dec 28;13(48):6458-64. Review. — View Citation

Betjes MG, Bajema I. The pathology of jaundice-related renal insufficiency: cholemic nephrosis revisited. J Nephrol. 2006 Mar-Apr;19(2):229-33. — View Citation

Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krle A-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, Dore CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 Statement: defining standard protocol items for clinical trials. Rev Panam Salud Publica. 2015 Dec;38(6):506-14. — View Citation

Dubravcsik Z, Farkas G, Hegyi P, Hritz I, Kelemen D, Lásztity N, Morvay Z, Oláh A, Pap Á, Párniczky A, Sahin-Tóth M, Szentkereszti Z, Szmola R, Takács T, Tiszlavicz L, Szücs Á, Czakó L; Magyar Hasnyálmirigy Munkacsoport, Hungarian Pancreatic Study Group. [Autoimmune pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group]. Orv Hetil. 2015 Feb 22;156(8):292-307. doi: 10.1556/OH.2015.30061. Review. Hungarian. — View Citation

Dubravcsik Z, Madácsy L, Gyökeres T, Vincze Á, Szepes Z, Hegyi P, Hritz I, Szepes A; Hungarian Pancreatic Study Group. Preventive pancreatic stents in the management of acute biliary pancreatitis (PREPAST trial): pre-study protocol for a multicenter, prospective, randomized, interventional, controlled trial. Pancreatology. 2015 Mar-Apr;15(2):115-23. doi: 10.1016/j.pan.2015.02.007. Epub 2015 Feb 25. — View Citation

Fang Y, Gurusamy KS, Wang Q, Davidson BR, Lin H, Xie X, Wang C. Pre-operative biliary drainage for obstructive jaundice. Cochrane Database Syst Rev. 2012 Sep 12;(9):CD005444. doi: 10.1002/14651858.CD005444.pub3. Review. — View Citation

Hatfield AR, Tobias R, Terblanche J, Girdwood AH, Fataar S, Harries-Jones R, Kernoff L, Marks IN. Preoperative external biliary drainage in obstructive jaundice. A prospective controlled clinical trial. Lancet. 1982 Oct 23;2(8304):896-9. — View Citation

Hritz I, Czakó L, Dubravcsik Z, Farkas G, Kelemen D, Lásztity N, Morvay Z, Oláh A, Pap Á, Párniczky A, Sahin-Tóth M, Szentkereszti Z, Szmola R, Szücs Á, Takács T, Tiszlavicz L, Hegyi P; Magyar Hasnyálmirigy Munkacsoport, Hungarian Pancreatic Study Group. [Acute pancreatitis. Evidence-based practice guidelines, prepared by the Hungarian Pancreatic Study Group]. Orv Hetil. 2015 Feb 15;156(7):244-61. doi: 10.1556/OH.2015.30059. Review. Hungarian. — View Citation

Hritz I, Hegyi P. Early Achievable Severity (EASY) index for simple and accurate expedite risk stratification in acute pancreatitis. J Gastrointestin Liver Dis. 2015 Jun;24(2):177-82. doi: 10.15403/jgld.2014.1121.242.easy. — View Citation

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Kennedy JA, Clements WD, Kirk SJ, McCaigue MD, Campbell GR, Erwin PJ, Halliday MI, Rowlands BJ. Characterization of the Kupffer cell response to exogenous endotoxin in a rodent model of obstructive jaundice. Br J Surg. 1999 May;86(5):628-33. — View Citation

Kimmings AN, van Deventer SJ, Obertop H, Rauws EA, Huibregtse K, Gouma DJ. Endotoxin, cytokines, and endotoxin binding proteins in obstructive jaundice and after preoperative biliary drainage. Gut. 2000 May;46(5):725-31. — View Citation

Klinkenbijl JH, Jeekel J, Schmitz PI, Rombout PA, Nix GA, Bruining HA, van Blankenstein M. Carcinoma of the pancreas and periampullary region: palliation versus cure. Br J Surg. 1993 Dec;80(12):1575-8. — View Citation

Kloek JJ, Heger M, van der Gaag NA, Beuers U, van Gulik TM, Gouma DJ, Levi M. Effect of preoperative biliary drainage on coagulation and fibrinolysis in severe obstructive cholestasis. J Clin Gastroenterol. 2010 Oct;44(9):646-52. doi: 10.1097/MCG.0b013e3181ce5b36. — View Citation

Kuzu MA, Kale IT, Cöl C, Tekeli A, Tanik A, Köksoy C. Obstructive jaundice promotes bacterial translocation in humans. Hepatogastroenterology. 1999 Jul-Aug;46(28):2159-64. — View Citation

Márta K, Szabó AN, Pécsi D, Varjú P, Bajor J, Gódi S, Sarlós P, Mikó A, Szemes K, Papp M, Tornai T, Vincze Á, Márton Z, Vincze PA, Lankó E, Szentesi A, Molnár T, Hágendorn R, Faluhelyi N, Battyáni I, Kelemen D, Papp R, Miseta A, Verzár Z, Lerch MM, Neoptolemos JP, Sahin-Tóth M, Petersen OH, Hegyi P; Hungarian Pancreatic Study Group. High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial. BMJ Open. 2017 Sep 14;7(9):e015874. doi: 10.1136/bmjopen-2017-015874. — View Citation

Minter RM, Fan MH, Sun J, Niederbichler A, Ipaktchi K, Arbabi S, Hemmila MR, Remick DG, Wang SC, Su GL. Altered Kupffer cell function in biliary obstruction. Surgery. 2005 Aug;138(2):236-45. — View Citation

N Shachiri DK, D Tonev, M Shishenkov. Hemostasiologic Changes during Hepatobiliary Surgery in Patients with Obstructive Jaundice: Pathophysiology and Clinical Considerations. The Internet Journal of Anesthesiology. 2010;28(1).

Padillo J, Puente J, Gómez M, Dios F, Naranjo A, Vallejo JA, Miño G, Pera C, Sitges-Serra A. Improved cardiac function in patients with obstructive jaundice after internal biliary drainage: hemodynamic and hormonal assessment. Ann Surg. 2001 Nov;234(5):652-6. — View Citation

Párniczky A, Mosztbacher D, Zsoldos F, Tóth A, Lásztity N, Hegyi P; Hungarian Pancreatic Study Group and the International Association of Pancreatology. Analysis of Pediatric Pancreatitis (APPLE Trial): Pre-Study Protocol of a Multinational Prospective Clinical Trial. Digestion. 2016;93(2):105-10. doi: 10.1159/000441353. Epub 2015 Nov 26. — View Citation

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Sewnath ME, Karsten TM, Prins MH, Rauws EJ, Obertop H, Gouma DJ. A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. Ann Surg. 2002 Jul;236(1):17-27. Review. — View Citation

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Szmola R, Farkas G, Hegyi P, Czakó L, Dubravcsik Z, Hritz I, Kelemen D, Lásztity N, Morvay Z, Oláh A, Párniczky A, Rubovszky G, Sahin-Tóth M, Szentkereszti Z, Szücs Á, Takács T, Tiszlavicz L, Pap Á; Magyar Hasnyálmirigy Munkacsoport, Hungarian Pancreatic Study Group. [Pancreatic cancer. Evidence based management guidelines of the Hungarian Pancreatic Study Group]. Orv Hetil. 2015 Feb 22;156(8):326-39. doi: 10.1556/OH.2015.30063. Review. Hungarian. — View Citation

Takács T, Czakó L, Dubravcsik Z, Farkas G, Hegyi P, Hritz I, Kelemen D, Lásztity N, Morvay Z, Oláh A, Pap Á, Párniczky A, Patai Á, Sahin-Tóth M, Szentkereszti Z, Szmola R, Tiszlavicz L, Szücs Á; Magyar Hasnyálmirigy Munkacsoport. [Chronic pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group]. Orv Hetil. 2015 Feb 15;156(7):262-88. doi: 10.1556/OH.2015.30060. Review. Hungarian. — View Citation

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Uslu A, Tasli FA, Nart A, Postaci H, Aykas A, Bati H, Coskun Y. Human kidney histopathology in acute obstructive jaundice: a prospective study. Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1458-65. doi: 10.1097/MEG.0b013e32833f71f6. — View Citation

van der Gaag NA, Kloek JJ, de Castro SM, Busch OR, van Gulik TM, Gouma DJ. Preoperative biliary drainage in patients with obstructive jaundice: history and current status. J Gastrointest Surg. 2009 Apr;13(4):814-20. doi: 10.1007/s11605-008-0618-4. Epub 2008 Aug 23. Review. — View Citation

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Zsoldos F, Párniczky A, Mosztbacher D, Tóth A, Lásztity N, Hegyi P; Hungarian Pancreatic Study Group and the International Association of Pancreatology. Pain in the Early Phase of Pediatric Pancreatitis (PINEAPPLE Trial): Pre-Study Protocol of a Multinational Prospective Clinical Trial. Digestion. 2016;93(2):121-6. doi: 10.1159/000441352. Epub 2015 Dec 4. — View Citation

* Note: There are 34 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rate of serious complications	rate of serious complications after preoperative biliary drainage and surgery; Pancreatitis; New onset of cholecystitis; Cholangitis; Perforation; Hemorrhage after endoscopic retrograde cholangiopancreatography (ERCP); Related to stent; Occlusion; Need for exchange Related to surgery; Pancreas anastomosis leakage	120 days
Primary	rate of serious complications	rate of serious complications after preoperative biliary drainage and surgery defined as: Pancreatitis; New onset of cholecystitis; Cholangitis; Perforation; Hemorrhage after endoscopic retrograde cholangiopancreatography (ERCP); Related to stent; Occlusion; Need for exchange Related to surgery; Pancreas anastomosis leakage	120 days
Secondary	Length of hospitalization	Length of hospitalization after biliary drainage and surgery	120 days
Secondary	Mortality	Rate of mortality among groups	30 days
Secondary	Mortality	Rate of mortality among the groups	120 days