Clinical trial NCT02753517: Hepato Biliary Scintigraphy to Assess the Risk of Postoperative Liver Failure Hepatectomies
Official title: Predictive Value of Hepato Biliary Scintigraphy to Assess the Risk of Postoperative Liver Failure Hepatectomies Stretches of 4 or More Segments on Non-cirrhotic Liver
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hepatic Insufficiency
Keywords: hepatobiliary scintigraphy
extended hepatectomy
volumetry
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2016-04-28
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: Extended hepatectomies of 4 or more segments are complicated by high rates of morbidity and mortality, mainly related to hepatic liver failure. Nowadays, preoperative assessment of the future remnant liver is just performed through its volumetric measurement by computed tomography. Nevertheless, this volumetric assessment does not reflect the hepatocellular function of the future remnant liver that can be disturbed in case of vascular and/or biliary obstruction, chemotherapy-induced liver injuries or steatosis in overweight patients. Literature data (albeit originating from a single centre in Europe) have suggested that (99m)Tc-mebrofenin hepatobiliary scintigraphy could be useful in evaluating the function of the future remnant liver. The aim of this prospective multicentric study is to determine the predictive value of hepatobiliary scintigraphy in assessing the risk of postoperative liver failure of extended hepatectomies of 4 or more segments in noncirrhotic liver.

Detailed description: The main aim of the study is to determine the predictive value of (99m)Tc-mebrofenin hepatobiliary scintigraphy in assessing the postoperative risk of liver failure within 3 months of extended hepatectomy of 4 or more segments in noncirrhotic liver. The main endpoint is the three-months postoperative liver failure, defined as an increased International Normalized Ratio (INR) and concomitant hyperbilirubinemia (according to the normal limits of the local laboratory) on or after postoperative day 5 according to the international classification of the ISGLS (International Study Group of Liver Surgery) and classified according to its severity in grade A (no change of the patient's clinical management), grade B (deviation from the regular course but without invasive therapy) and grade C (invasive treatment)

Secondary objectives are:

To determine the predictive value of (99m)Tc-mebrofenin hepatobiliary scintigraphy in assessing the risk of postoperative morbi-mortality (according to Clavien-Dindo classification) within 3 months of extended hepatectomy of 4 or more segments in noncirrhotic liver, and the duration of intensive care unit stay and of hospitalization.

* To assess the correlation between the results of the hepatobiliary scintigraphy and the presence of parenchymal abnormalities such as steatosis, fibrosis or chemotherapy-induced injuries (sinusoidal obstruction syndrome, steatohepatitis) at the histological analysis of the non tumoral liver parenchyma.
* To assess the sensitivity of hepatobiliary scintigraphy in jaundiced patients who had a preoperative biliary endoscopic or radiologic drainage, considering the existing competition between mebrofenin and bilirubin on hepatic receptors.
* To analyse the inter-centre reproducibility of the hepatobiliary scintigraphy (Central review by the principal investigator of 25 scintigraphy examinations per centre)

Eligibility criteria: Inclusion Criteria:

* Noncirrhotic liver
* Benign or malignant liver tumor
* Anatomic hepatic resection ≥ 4 segments
* Aged ≥18
* ASA Score ≤3
* Signed informed consent
* Presence of contraception in non-menopausal women

Exclusion Criteria:

* Cirrhosis
* Absence of preoperative biliary drainage in case of preoperative jaundice
* Patient refusal
* Absence of affiliation to Social Security
* Body weight above 230kg
* Known allergy to Hida derivatives

Primary outcomes:
measure: Hepatic insufficiency
timeFrame: at 3 months
Secondary outcomes:
measure: Postoperative morbi-mortality
timeFrame: at 3 months
measure: Duration of intensive care unit stay and of hospitalization
timeFrame: 3 months
measure: Histological analysis of the non tumoral liver parenchyma
timeFrame: at 3 months
measure: Inter-centre reproducibility of the hepatobiliary scintigraphy
timeFrame: at 3 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Hôpital Nord, CHU
city: Bordeaux
country: France
facility: CHU
city: Clermont-Ferrand
country: France
facility: Hopital Estaing - Chu63 - Clermont Ferrand
city: Grenoble
country: France
facility: CHU
city: Lille
country: France
facility: CHRU, Hôpital Claude Huriez
city: Lyon
country: France
facility: Centre Leon Berard - Lyon 08
city: Lyon
country: France
facility: Hopital Croix-Rousse - Hcl - Lyon 04
city: Marseille
country: France
facility: CHU
city: Nancy
country: France
facility: Chru Nancy - Hopitaux de Brabois
city: Paris
country: France
facility: AP-HPHôpital Beaujon,
city: Rouen
country: France
facility: CHU
city: Toulouse
country: France
facility: CHU
Study officials:
affiliation: University Hospital, Lille
name: Stéphanie Truant, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bennink RJ, Tulchinsky M, de Graaf W, Kadry Z, van Gulik TM. Liver function testing with nuclear medicine techniques is coming of age. Semin Nucl Med. 2012 Mar;42(2):124-37. doi: 10.1053/j.semnuclmed.2011.10.003.
citation: de Graaf W, Heger M, Spruijt O, Maas A, de Bruin K, Hoekstra R, Bennink RJ, van Gulik TM. Quantitative assessment of liver function after ischemia-reperfusion injury and partial hepatectomy in rats. J Surg Res. 2012 Jan;172(1):85-94. doi: 10.1016/j.jss.2010.06.038. Epub 2010 Jul 21.
citation: de Graaf W, Bennink RJ, Vetelainen R, van Gulik TM. Nuclear imaging techniques for the assessment of hepatic function in liver surgery and transplantation. J Nucl Med. 2010 May;51(5):742-52. doi: 10.2967/jnumed.109.069435. Epub 2010 Apr 15.
citation: de Graaf W, Hausler S, Heger M, van Ginhoven TM, van Cappellen G, Bennink RJ, Kullak-Ublick GA, Hesselmann R, van Gulik TM, Stieger B. Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011 Apr;54(4):738-45. doi: 10.1016/j.jhep.2010.07.047. Epub 2010 Oct 1.
citation: de Graaf W, van Lienden KP, van den Esschert JW, Bennink RJ, van Gulik TM. Increase in future remnant liver function after preoperative portal vein embolization. Br J Surg. 2011 Jun;98(6):825-34. doi: 10.1002/bjs.7456. Epub 2011 Apr 11.