Clinical trial NCT06060847: Liver Resection and Simultaneous Sleeve Gastrectomy for MS-HCC (LIRESS)
Official title: Liver Resection and Simultaneous Sleeve Gastrectomy for HCC Related to Metabolic Syndrome (LIRESS)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Carcinoma, Hepatocellular
Metabolic Syndrome
Keywords: hepatocellular carcinoma
sleeve gastrectomy
morbid obesity
Lead sponsor: Ospedale V. Fazzi
Sponsor class: OTHER
First posted: 2023-09-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients 18 years old and older, affected by hepatocellular carcinoma (HCC) with metabolic syndrome (MS) as unique risk factor, with compensated liver function (Child A) who are deemed suitable for liver resection and comply with the criteria for bariatric surgery, will undergo liver resection of HCC and simultaneous sleeve gastrectomy for morbid obesity during the same surgical procedure.

Patients affected by HCC related to metabolic syndrome who fall within exclusion criteria, will undergo liver resection for HCC without sleeve gastrectomy.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: 1 year, 3 years, 5 years
measure: Recurrence-free Survival
timeFrame: 1 year, 3 years, 5 years
measure: 90-day mortality
timeFrame: 90 post-operative days
measure: Comprehensive Complication Index
timeFrame: 90 post-operative days
Secondary outcomes:
measure: Fibrosis-4 Index for Liver Fibrosis score
timeFrame: After 6 months, up to 5 years
measure: Non-Alcoholic Fatty Liver Disease Fibrosis Score
timeFrame: After 6 months, up to 5 years
measure: Fibroscan stiffness
timeFrame: After 6 months, up to 5 years
measure: Body Mass Index
timeFrame: After 3 months, up to 5 years
measure: Weight loss
timeFrame: After 3 months, up to 5 years
measure: Percent excess weight loss
timeFrame: After 3 months, up to 5 years
measure: Control of obesity-induced hypertension
timeFrame: After 3 months, up to 5 years
measure: Control of obesity-induced comorbidities
timeFrame: After 3 months, up to 5 years
Other outcomes:
Locations:
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi
Study officials:
affiliation: Ospedale Vito Fazzi, Lecce
name: Annarita Libia
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.