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

Not Applicable

Not yet recruiting

• Conditions: Carcinoma, Hepatocellular; Metabolic Syndrome
• Interventions: Procedure: Liver resection for HCC induced by metabolic syndrome; Procedure: Liver resection and simultaneous sleeve gastrectomy for HCC induced by metabolic syndrome

• Registration Number: NCT06060847
• Lead Sponsor: Ospedale V. Fazzi

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2023-09-08
• Study First Submitted QC: 2023-09-23
• Study First Posted: 2023-09-29
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-18
• Last Update Posted: 2023-12-19
• Study Start: 2024-03-06
• Primary Completion: 2029-03-06
• Study Completion: 2032-03-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with HCC related to metabolic syndrome as unique risk factor	Liver resection for HCC induced by metabolic syndrome	Patients aged 18 years old and older, affected by HCC (hepatocellular carcinoma) with MS (metabolic syndrome) as unique risk factor who will undergo liver resection only
Patients affected by HCC induced by metabolic syndrome as unique risk factor	Liver resection and simultaneous sleeve gastrectomy for HCC induced by metabolic syndrome	Patients aged 18 years old and older, affected by HCC with MS (metabolic syndrome) as unique risk factor who comply with the criteria for bariatric surgery, will undergo liver resection and sleeve gastrectomy with minimally-invasive technique in the same surgical procedure

Primary Outcome Measures

Name	Time	Method
Recurrence-free Survival	1 year, 3 years, 5 years	Calculated from the date of surgery to the date of recurrence
Comprehensive Complication Index	90 post-operative days	Any deviation from the normal postoperative course measured on a scale from 0 (no complication) to 100 (death)
90-day mortality	90 post-operative days	Mortality from any cause
Overall Survival	1 year, 3 years, 5 years	Calculated from the date of diagnosis to the date of death from any cause

Secondary Outcome Measures

Name	Time	Method
Control of obesity-induced comorbidities	After 3 months, up to 5 years	change of insulin therapy or oral hypoglycemics assessed by medical history questionnaire
Percent excess weight loss	After 3 months, up to 5 years	Percent excess weight loss (%EWL) is calculated as follows: \[(initial weight - current weight) / (initial weight - ideal weight)\] × 100
Fibrosis-4 Index for Liver Fibrosis score	After 6 months, up to 5 years	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)/\[platelet count (109/L)×√alanine aminotransferase (ALT) (U/L)\]
Control of obesity-induced hypertension	After 3 months, up to 5 years	Change of antihypertensive therapy assessed by medical history questionnaire
Fibroscan stiffness	After 6 months, up to 5 years	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).
Weight loss	After 3 months, up to 5 years	Weight loss expressed in Kg
Non-Alcoholic Fatty Liver Disease Fibrosis Score	After 6 months, up to 5 years	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).
Body Mass Index	After 3 months, up to 5 years	Body Mass Index (BMI) is combination of bodyweight and body height and presented as kg/m\^2

Trial Locations

Locations (1)

Ospedale Vito Fazzi; 🇮🇹 Lecce, Italy