Liver Resection and Simultaneous Sleeve Gastrectomy for MS-HCC (LIRESS)

Metabolic Syndrome Clinical Trial

— LIRESS  

Official title:

Liver Resection and Simultaneous Sleeve Gastrectomy for HCC Related to Metabolic Syndrome (LIRESS)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06060847
• Other study ID #: 3/2023
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 6, 2024
• Est. completion date: March 6, 2032

Study information

• Verified date: December 2023
• Source: Ospedale V. Fazzi
• Contact: Annarita Libia
• Phone: 0039 0833335284
• Email: libiamd[@]me.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hepatocellular carcinoma (HCC) related to metabolic syndrome (MS) as unique risk factor is gradually overpassing the more common viral and alcohol etiology, becoming a global health issue. Liver surgery for metabolic syndrome-related HCC in this frail subset of patients constitute a challenge, due to high morbidity and mortality rate reported in literature, and contrasting results in term of oncologic outcome. The present multicentric prospective study aims to ascertain if the combination of sleeve gastrectomy and liver surgery in the same surgical procedure may have benefit in terms of reduced perioperative morbidity and prolonged Overall Survival and Recurrence Free Survival. Secondary outcome will be the evaluation of the consequences induced by sleeve gastrectomy on liver disease, in particular liver fibrosis evaluated in term of NFS score (Non-Alcoholic Fatty Liver Disease Fibrosis score), FIB-4 (Fibrosis-4 Index for Liver Fibrosis) score and Fibroscan transient elastography.

Description:

Obesity is a worldwide epidemic, with more than 2 billion people currently overweight and an additional 1.12 billion projected to be overweight by 2030. HCC (hepatocellular carcinoma) associated to obesity and its comorbidity is overcoming Hepatitis C Virus (HCV) related cancer and is already the leading cause of liver transplant in USA. HCC remains the sixth most common cancer in the world and the third cause of cancer-related death. Considering these epidemiological evidence, the incidence of MS-HCC (metabolic syndrome-related hepatocellular carcinoma) is expected to increase with huge cost efforts for the global healthcare system. The impaired performance status of patients with HCC and metabolic syndrome seems to explain high perioperative morbidity rate reported in literature. Literature reports several experiences of bariatric surgery combined to liver transplant for chronic liver disease related induced by non alcoholic steatohepatitis (NASH), performed before or after liver surgery, or even at the same time. Even if evidences are weak, outcomes reported seem to be promising. Since sleeve gastrectomy is not only a mere restrictive bariatric procedure, but it produces hormonal and metabolic changes, with the present study the investigators want to ascertain if sleeve gastrectomy at time of liver resection for MS-HCC (metabolic syndrome-related hepatocellular carcinoma) can modify short perioperative outcomes and long-term oncologic results.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: March 6, 2032
• Est. primary completion date: March 6, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Be willing and able to provide written informed consent/assent for the trial

2. Be = 18 years of age on day of signing informed consent.

3. Have hepatocellular carcinoma with metabolic syndrome as unique risk factor

4. Have an overall Child-Pugh score = A

5. Be eligible for liver resection with laparoscopic or robotic technique

6. Be eligible for bariatric surgery as defined below

• BMI = 40 kg/m2

• BMI = 35-40 kg/m2 with associated comorbidities

• BMI 30-35 kg/m2 and type 2 diabetes

• BMI 30-35 kg/m2 and arterial hypertension with poor control despite optimal medical therapy.

Exclusion Criteria:

1. Have hepatocellular carcinoma related to other etiology, even in case of coexisting metabolic syndrome

2. Denial of the patient to undergo bariatric procedure

3. Have BMI < 30

4. Have negative opinion of psychologic consultant

5. Have an overall Child-Pugh score > 7

6. Evidence of clinical significant portal hypertension as followed:

• esophageal varices

• gastric varices

• portal hypertensive gastropathy

• gastric vascular ectasia

Of note: 1) Conversion to open surgery for any reason does not represent a reason of data exclusion from the analysis; 2) any type of hepatic resection, according to Brisbane classification, is included, also major hepatectomy requiring preoperative intervention to achieve adequate volume remnant

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Metabolic Syndrome
• Syndrome

Intervention

Procedure:
• Liver resection and simultaneous sleeve gastrectomy for HCC induced by metabolic syndrome
Patients in the experimental arm will undergo liver resection for HCC and sleeve gastrectomy for MS during the same surgical procedure.
• Liver resection for HCC induced by metabolic syndrome
Patients in the active comparator arm will undergo liver resection for HCC

Locations

Country	Name	City	State
Italy	Ospedale Vito Fazzi	Lecce

Sponsors (1)

Lead Sponsor	Collaborator
Ospedale V. Fazzi

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Cauchy F, Zalinski S, Dokmak S, Fuks D, Farges O, Castera L, Paradis V, Belghiti J. Surgical treatment of hepatocellular carcinoma associated with the metabolic syndrome. Br J Surg. 2013 Jan;100(1):113-21. doi: 10.1002/bjs.8963. Epub 2012 Nov 12. — View Citation

de Barros F, Cardoso Faleiro Uba PH. Liver transplantation and bariatric surgery: a new surgical reality: a systematic review of the best time for bariatric surgery. Updates Surg. 2021 Oct;73(5):1615-1622. doi: 10.1007/s13304-021-01106-3. Epub 2021 Jun 12. — View Citation

Hobeika C, Ronot M, Beaufrere A, Paradis V, Soubrane O, Cauchy F. Metabolic syndrome and hepatic surgery. J Visc Surg. 2020 Jun;157(3):231-238. doi: 10.1016/j.jviscsurg.2019.11.004. Epub 2019 Dec 19. — View Citation

Yang T, Hu LY, Li ZL, Liu K, Wu H, Xing H, Lau WY, Pawlik TM, Zeng YY, Zhou YH, Gu WM, Wang H, Chen TH, Han J, Li C, Wang MD, Wu MC, Shen F. Liver Resection for Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease: a Multicenter Propensity Matching Analysis with HBV-HCC. J Gastrointest Surg. 2020 Feb;24(2):320-329. doi: 10.1007/s11605-018-04071-2. Epub 2019 Jan 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Calculated from the date of diagnosis to the date of death from any cause	1 year, 3 years, 5 years
Primary	Recurrence-free Survival	Calculated from the date of surgery to the date of recurrence	1 year, 3 years, 5 years
Primary	90-day mortality	Mortality from any cause	90 post-operative days
Primary	Comprehensive Complication Index	Any deviation from the normal postoperative course measured on a scale from 0 (no complication) to 100 (death)	90 post-operative days
Secondary	Fibrosis-4 Index for Liver Fibrosis score	Fibrosis-4 Index for Liver Fibrosis score (FIB-4 score) will be calculated using the following formula: FIB-4 score= Age (years)× aspartate aminotransferase (AST) (U/L)/[platelet count (109/L)×valanine aminotransferase (ALT) (U/L)]	After 6 months, up to 5 years
Secondary	Non-Alcoholic Fatty Liver Disease Fibrosis Score	Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS score) will be calculated using the following formula: NFS = -1.675 + 0.037 - age (years) + 0.094 - BMI (kg/m2) + 1.13 × impaired fasting glucose/diabetes (yes = 1, no = 0) + 0.99 × aspartate aminotransferase/ alanine aminotransferase (AST/ALT) ratio - 0.013 × platelet count (×109/l) - 0.66 × albumin (g/dl).	After 6 months, up to 5 years
Secondary	Fibroscan stiffness	The Fibroscan stiffness measurement relies on the propagation of elastic waves to assess the stiffness of the liver: the faster elastic waves propagates within the liver, the stiffer the organ is. The final liver stiffness value is the median of individual liver stiffness values using the valid measurements and is expressed in kilo Pascal (kPa).	After 6 months, up to 5 years
Secondary	Body Mass Index	Body Mass Index (BMI) is combination of bodyweight and body height and presented as kg/m^2	After 3 months, up to 5 years
Secondary	Weight loss	Weight loss expressed in Kg	After 3 months, up to 5 years
Secondary	Percent excess weight loss	Percent excess weight loss (%EWL) is calculated as follows: [(initial weight - current weight) / (initial weight - ideal weight)] × 100	After 3 months, up to 5 years
Secondary	Control of obesity-induced hypertension	Change of antihypertensive therapy assessed by medical history questionnaire	After 3 months, up to 5 years
Secondary	Control of obesity-induced comorbidities	change of insulin therapy or oral hypoglycemics assessed by medical history questionnaire	After 3 months, up to 5 years