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1.
Curr Oncol ; 27(Suppl 3): S144-S151, 2020 11.
Article in English | MEDLINE | ID: mdl-33343208

ABSTRACT

Locoregional therapies (lrts) play an important role in the treatment of hepatocellular carcinoma (hcc), with the aim of increasing overall survival while preserving liver function. Various forms of lrt are available, and choosing the best one depends on technical aspects, liver morphology, tumour biology, and the patient's symptoms. The purpose of the present review article is to provide an overview of the current evidence relating to the use of percutaneous ablation, transarterial chemoembolization, and transarterial radioembolization for the curative or palliative treatment of hcc. Special situations are also reviewed, including the combined use of systemic therapy and lrt, indications and techniques for bridging to transplant and downstaging, and the use of lrt to treat patients with hcc and macrovascular invasion.


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Chemoembolization, Therapeutic , Liver Neoplasms , Carcinoma, Hepatocellular/surgery , Combined Modality Therapy , Humans , Liver Neoplasms/surgery
2.
Hepatology ; 64(4): 1178-88, 2016 10.
Article in English | MEDLINE | ID: mdl-27481548

ABSTRACT

UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).


Subject(s)
Bile Duct Neoplasms/surgery , Carcinoma, Hepatocellular/surgery , Cholangiocarcinoma/surgery , Liver Neoplasms/surgery , Liver Transplantation , Aged , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prospective Studies , Retrospective Studies , Survival Rate
3.
Br J Surg ; 100(11): 1516-22, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24037575

ABSTRACT

BACKGROUND: The role of liver resection in patients with multifocal hepatocellular carcinoma (HCC) with well preserved liver function is controversial. This study was conducted to evaluate the outcomes of such patients. METHODS: This was a retrospective analysis of patients who underwent liver resection for multifocal HCC between 1992 and 2011. Postoperative outcomes, survival and predictors of outcomes were analysed. RESULTS: Of 46 patients who underwent hepatic resection for multifocal HCC, 38 had Barcelona Clinic Liver Cancer stage B disease. Major hepatectomy was performed in 27 patients, and major complications occurred in nine (20 per cent). The 90-day postoperative mortality rate was 7 per cent. Overall 1-, 2-, 3- and 5-year survival rates were 78, 64, 59 and 53 per cent respectively (median 70 months), whereas corresponding recurrence-free survival rates were 53, 32, 30 and 27 per cent (median 14 months). Recurrence developed in 28 (61 per cent) of the 46 patients, affecting the liver only in 22. Three-quarters of patients with recurrence underwent further therapy. Major hepatectomy (hazard ratio (HR) 0.37, 95 per cent confidence interval 0.14 to 0·95; P = 0·038), microvascular (HR 3·44, 1·35 to 8·74; P = 0·009) and macrovascular (HR 2·68, 1·11 to 6·43; P = 0·028) invasion, and cirrhosis (HR 3·15, 1·12 to 8·86; P = 0·029) were associated with overall survival. Microvascular invasion (HR 2·81, 1·06 to 7·40; P = 0·037), cirrhosis (HR 3·12, 1·41 to 6·88; P < 0·001) and bilobar disease (HR 2·93, 1·09 to 7·88; P = 0·033) were associated with recurrence-free survival. CONCLUSION: In selected patients with multifocal HCC and well preserved liver function, long-term survival is possible after liver resection and subsequent aggressive treatment of recurrence.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/pathology , Combined Modality Therapy , Disease-Free Survival , Female , Hepatectomy/mortality , Hepatitis B, Chronic/complications , Hepatitis C, Chronic , Humans , Liver Cirrhosis/complications , Liver Neoplasms/pathology , Liver Transplantation/statistics & numerical data , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness/pathology , Postoperative Complications , Retrospective Studies , Treatment Outcome , Tumor Burden
4.
Br J Surg ; 100(10): 1349-56, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23939847

ABSTRACT

BACKGROUND: The management of portal vein (PV) involvement by pancreatic adenocarcinoma during pancreaticoduodenectomy (PD) is controversial. The aim of this study was to compare the outcomes of unplanned and planned PV resections as part of PD. METHODS: An analysis of PD over 11 years was performed. Patients who had undergone PV resection (PV-PD) were identified, and categorized into those who had undergone planned or unplanned resection. Postoperative and oncological outcomes were compared. RESULTS: Of 249 patients who underwent PD for pancreatic adenocarcinoma, 66 (26·5 per cent) had PV-PD, including 27 (41 per cent) planned and 39 (59 per cent) unplanned PV resections. Twenty-five of 27 planned PV resections were circumferential PV-PD, whereas 25 of 39 unplanned PV resections were partial PV-PD. Planned PV resections were performed in slightly younger patients (mean(s.d.) 60(9) versus 65(10) years; P = 0·031), and associated with longer operating times (mean(s.d.) 602(131) versus 458(83) min; P < 0·001) and more major complications (26 versus 5 per cent; P = 0·026). Planned PV resections were associated with a lower rate of positive margins (4 versus 44 per cent; P < 0·001) despite being carried out for larger tumours (mean(s.d.) 3·9(1·4) versus 2·9(1·0) cm; P = 0·002). There was no difference in survival between the two groups (P = 0·998). On multivariable analysis, margin status was a significant predictor of survival. CONCLUSION: Although planned PV resections for pancreatic adenocarcinoma were associated with higher rates of postoperative morbidity than unplanned resections, R0 resection rates were better.


Subject(s)
Adenocarcinoma/surgery , Mesenteric Veins/surgery , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Portal Vein/surgery , Blood Loss, Surgical , Blood Vessel Prosthesis Implantation/methods , Female , Humans , Length of Stay , Male , Middle Aged , Neoplasm Invasiveness , Operative Time , Patient Care Planning , Portal Vein/injuries , Postoperative Complications/etiology , Treatment Outcome , Vascular Neoplasms/surgery
5.
Diabetologia ; 50(2): 395-403, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17195063

ABSTRACT

AIMS/HYPOTHESIS: Insulin controls glucose metabolism via multiple signalling pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway in muscle and adipose tissue. The protein/lipid phosphatase Pten (phosphatase and tensin homologue deleted on chromosome 10) attenuates PI3K signalling by dephosphorylating the phosphatidylinositol 3,4,5-trisphosphate generated by PI3K. The current study was aimed at investigating the effect of haploinsufficiency for Pten on insulin-stimulated glucose uptake. MATERIALS AND METHODS: Insulin sensitivity in Pten heterozygous (Pten(+/-)) mice was investigated in i.p. insulin challenge and glucose tolerance tests. Glucose uptake was monitored in vitro in primary cultures of myocytes from Pten(+/-) mice, and in vivo by positron emission tomography. The phosphorylation status of protein kinase B (PKB/Akt), a downstream signalling protein in the PI3K pathway, and glycogen synthase kinase 3beta (GSK3beta), a substrate of PKB/Akt, was determined by western immunoblotting. RESULTS: Following i.p. insulin challenge, blood glucose levels in Pten(+/-) mice remained depressed for up to 120 min, whereas glucose levels in wild-type mice began to recover after approximately 30 min. After glucose challenge, blood glucose returned to normal about twice as rapidly in Pten(+/-) mice. Enhanced glucose uptake was observed both in Pten(+/-) myocytes and in skeletal muscle of Pten(+/-) mice by PET. PKB and GSK3beta phosphorylation was enhanced and prolonged in Pten(+/-) myocytes. CONCLUSIONS/INTERPRETATION: Pten is a key negative regulator of insulin-stimulated glucose uptake in vitro and in vivo. The partial reduction of Pten due to Pten haploinsufficiency is enough to elicit enhanced insulin sensitivity and glucose tolerance in Pten(+/-) mice.


Subject(s)
Insulin/pharmacology , PTEN Phosphohydrolase/genetics , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Crosses, Genetic , Deoxyglucose/metabolism , Diabetes Mellitus, Type 2/genetics , Fluorodeoxyglucose F18 , Genetic Carrier Screening , Glucose/pharmacology , Glucose Tolerance Test , Glucose Transporter Type 1/metabolism , Glucose Transporter Type 4/metabolism , Insulin/blood , Insulin-Secreting Cells/metabolism , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Mice , PTEN Phosphohydrolase/deficiency , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Positron-Emission Tomography
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