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1.
Radiographics ; 42(1): 106-124, 2022.
Article in English | MEDLINE | ID: mdl-34990325

ABSTRACT

Complete resection is the only potentially curative treatment for primary or metastatic liver tumors. Improvements in surgical techniques such as conventional two-stage hepatectomy (TSH) with portal vein embolization and ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) promote hypertrophy of the future liver remnant (FLR), expanding resection criteria to include patients with widespread hepatic disease who were formerly not considered candidates for resection. Radiologists are essential in the multidisciplinary approach required for TSH. In particular, multidetector CT has a critical role throughout the various stages of this surgical process. The aims of CT before the first stage of TSH are to define the feasibility of surgery, assess the number and location of liver tumors in relation to relevant anatomy, and provide a detailed anatomic evaluation, including vascular and biliary variants. Volume calculation with CT is also essential to determine if the FLR is sufficient to avoid posthepatectomy liver failure. The objectives of CT between the first and second stages of TSH are to recalculate liver volumes (ie, assess FLR hypertrophy) and depict expected liver changes and complications that could modify the surgical plan or preclude the second stage of definitive resection. In this review, the importance of CT throughout different stages of TSH is discussed and key observations that contribute to surgical planning are highlighted. In addition, the advantages and limitations of MRI for detection of liver metastases and assessment of complications are briefly described. ©RSNA, 2022.


Subject(s)
Hepatectomy , Liver Neoplasms , Hepatectomy/methods , Humans , Liver/blood supply , Liver/diagnostic imaging , Liver/surgery , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Portal Vein , Tomography, X-Ray Computed , Treatment Outcome
2.
Ann Surg ; 272(5): 715-722, 2020 11.
Article in English | MEDLINE | ID: mdl-32833764

ABSTRACT

OBJECTIVE: To test the degree of agreement in selecting therapeutic options for patients suffering from colorectal liver metastasis (CRLM) among surgical experts around the globe. SUMMARY/BACKGROUND: Only few areas in medicine have seen so many novel therapeutic options over the past decades as for liver tumors. Significant variations may therefore exist regarding the choices of treatment, even among experts, which may confuse both the medical community and patients. METHODS: Ten cases of CRLM with different levels of complexity were presented to 43 expert liver surgeons from 23 countries and 4 continents. Experts were defined as experienced surgeons with academic contributions to the field of liver tumors. Experts provided information on their medical education and current practice in liver surgery and transplantation. Using an online platform, they chose their strategy in treating each case from defined multiple choices with added comments. Inter-rater agreement among experts and cases was calculated using free-marginal multirater kappa methodology. A similar, but adjusted survey was presented to 60 general surgeons from Asia, Europe, and North America to test their attitude in treating or referring complex patients to expert centers. RESULTS: Thirty-eight (88%) experts completed the evaluation. Most of them are in leading positions (92%) with a median clinical experience of 25 years. Agreement on therapeutic strategies among them was none to minimal in more than half of the cases with kappa varying from 0.00 to 0.39. Many general surgeons may not refer the complex cases to expert centers, including in Europe, where they also engage in complex liver surgeries. CONCLUSIONS: Considerable inconsistencies of decision-making exist among expert surgeons when choosing a therapeutic strategy for CRLM. This might confuse both patients and referring physicians and indicate that an international high-level consensus statements and widely accepted guidelines are needed.


Subject(s)
Colorectal Neoplasms/pathology , Decision Making , Hepatectomy/methods , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Practice Patterns, Physicians'/statistics & numerical data , Adult , Consensus , Female , Humans , Male , Middle Aged
3.
Future Oncol ; 15(27): 3149-3157, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31426677

ABSTRACT

Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10-1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1-R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Adult , Aged , Colorectal Neoplasms/mortality , Combined Modality Therapy , Female , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Neoplasm Staging , Prognosis , Survival Analysis
4.
Oncotarget ; 8(46): 80235-80248, 2017 Oct 06.
Article in English | MEDLINE | ID: mdl-29113298

ABSTRACT

New therapies are needed for advanced hepatocellular carcinoma (HCC) and the use of mesenchymal stromal cells (MSCs) carrying therapeutic genes is a promising strategy. HCC produce cytokines recruiting MSCs to the tumor milieu and modifying its biological properties. Our aim was to study changes generated on human MSCs exposed to conditioned media (CM) derived from human HCC fresh samples and xenografts. All CM shared similar cytokines expression pattern including CXCL1-2-3/GRO, CCL2/MCP-1 and CXCL8/IL-8 being the latter with the highest concentration. Neutralizing and knockdown experiments of CCL2/MCP-1, CXCL8/IL-8, CXCR1 and CXCR2 reduced in vitro MSC migration of ≥20%. Simultaneous CXCR1 and CXCR2 neutralization resulted in 50% of MSC migration inhibition. MSC stimulated with CM (sMSC) from HuH7 or HC-PT-5 showed a 2-fold increase of migration towards the CM compared with unstimulated MSC (usMSC). Gene expression profile of sMSC showed ~500 genes differentially expressed compared with usMSC, being 46 genes related with cell migration and invasion. sMSC increased fibroblasts and endothelial cells chemotaxis. Finally, sMSC with HuH7 CM and then inoculated in HCC tumor bearing-mice did not modify tumor growth. In this work we characterized factors produced by HCC responsible for the changes in MSC chemotactic capacity with would have an impact on therapeutic use of MSCs for human HCC.

5.
Eur J Gastroenterol Hepatol ; 28(4): 421-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26684693

ABSTRACT

BACKGROUND AND AIM: The Up-to-7 criteria on the basis of the explanted liver features categorize patients at higher risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). The aim of this study was to propose a novel pretransplant scoring system to predict recurrence including pre-LT data. PATIENTS AND METHODS: From 763 consecutive adult patients who underwent transplantation in four LT centers from Argentina, 124 patients with HCC were included. A scoring system was developed in 87 patients from pre-LT risk factors for recurrence as determined by hazard ratios (HRs) from a multivariate Cox regression analysis. RESULTS: Overall survival and recurrence rates at 5 years were 63.3 and 13.7%, respectively, during a follow-up period of 3.5±2.2 years. Variables associated with HCC recurrence on multivariate analysis were α-fetoprotein more than 100 ng/ml (HR=5.6, P=0.001) and tumor beyond Up-to-7 imaging criteria (HR=6.3, P=0.001). Bootstrap validation showed that overfitting was negligible. Scoring points were assigned as follows (0-2 points): pre-LT α-fetoprotein more than 100 ng/ml (presence=1 point, absence=0 point), and tumor beyond Up-to-7 imaging criteria (presence=1 point, absence=0 point). AUROC curve indicated a c-statistic of 0.74 (0.58-0.88, P=0.003). Two distinct subgroups of patients were identified with a cut-off more than or equal to 1 point (62% sensitivity and 82% specificity): low risk (0 point) and high risk (1-2 points). The 5-year recurrence rate was 9.4 and 44.5% (P=0.0001) and the 5-year overall survival was 78.1 and 34.8% (P=0.0001) in the low-risk and high-risk groups, respectively. CONCLUSION: This scoring model may be a useful additional tool for HCC recurrence risk stratification before LT. Prospective studies are needed to evaluate our model.


Subject(s)
Carcinoma, Hepatocellular/surgery , Decision Support Techniques , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Neoplasm Recurrence, Local , Aged , Area Under Curve , Argentina , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/blood , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Transplantation/mortality , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Predictive Value of Tests , Proportional Hazards Models , ROC Curve , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , alpha-Fetoproteins/analysis
6.
Ann Hepatol ; 14(6): 845-55, 2015.
Article in English | MEDLINE | ID: mdl-26436356

ABSTRACT

BACKGROUND & RATIONALE: Limited information related to Liver Transplantation (LT) costs in South America exists. Additionally, costs analysis from developed countries may not provide comparable models for those in emerging economies. We sought to evaluate a predictive model of Early Discharge from Hospital after LT (ERDALT = length of hospital stay ≤ 8 days). A predictive model was assessed based on the odds ratios (OR) from a multivariate regression analysis in a cohort of consecutively transplanted adult patients in a single center from Argentina and internally validated with bootstrapping technique. RESULTS: ERDALT was applicable in 34 of 289 patients (11.8%). Variables independently associated with ERDALT were MELD exception points OR 1.9 (P = 0.04), surgery time < 4 h OR 3.8 (P = 0.013), < 5 units of blood products consumption (BPC) OR 3.5 (P = 0.001) and early weaning from mechanical intubation OR 6.3 (P = 0.006). Points in the predictive scoring model were allocated as follows: MELD exception points (absence = 0 points, presence = 1 point), surgery time < 4 h (0-2 points), < 5 units of BPC (0-2 points), and early weaning (0-3 points). Final scores ranged from 0 to 8 points with a c-statistic of 0.83 (95% CI 0.77-0.90; P < 0.0001). Transplant costs were significantly lower in patients with ERDALT (median $23,078 vs. $28,986; P < 0.0001). Neither lower patient and graft survival, nor higher rates of short-term re-hospitalization and acute rejection events after discharge were observed in patients with ERDALT. In conclusion, the ERDALT score identifies patients suitable for early discharge with excellent outcomes after transplantation. This score may provide applicable models particularly for emerging economies.


Subject(s)
Decision Support Techniques , Length of Stay , Liver Transplantation , Patient Discharge , Adult , Aged , Argentina , Chi-Square Distribution , Cost-Benefit Analysis , Female , Graft Survival , Hospital Costs , Humans , Kaplan-Meier Estimate , Length of Stay/economics , Liver Transplantation/adverse effects , Liver Transplantation/economics , Liver Transplantation/mortality , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Operative Time , Patient Discharge/economics , Patient Selection , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Ventilator Weaning
7.
Eur J Gastroenterol Hepatol ; 27(3): 355-60, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25563142

ABSTRACT

BACKGROUND AND AIMS: Surveillance during liver transplantation (LT) waiting list has scarcely been reported in South America. We aimed to describe hepatocellular carcinoma (HCC) surveillance during the LT waiting list in the daily practice. PATIENTS AND METHODS: A multicenter retrospective analysis in cirrhotic patients was carried out. All patients underwent an ultrasound (US) every 6 months and the last pre-LT US was compared with explanted liver findings. A false-negative case was considered when incidentally found HCC (iHCC) was detected, whereas a false-positive case was considered when HCC diagnosed before LT (cHCC) was not confirmed in the explanted liver. US performance was assessed after excluding cHCC patients referred to transplant evaluation. RESULTS: Of 643 patients, 129 had HCC, of whom 92 had cHCC (71.3%) and 37 had iHCC (28.7%). Five patients (5.4%) had nonconfirmed cHCC (n=3 regenerative nodules, n=1 biliary hamartoma, and n=1 cholangiocarcinoma). Patients with iHCC had a higher MELD score (23±10 vs. 15±10; P<0.0001), and were more frequently Child-Pugh C (62.2 vs. 36.6%; P=0.006) compared with patients with cHCC. The number of US performed during waiting list was 1.7±1.6 (median 1.0). During transplant waiting list, the sensitivity and specificity of US were 33 and 99%, with positive and negative predictive values of 0.89 and 0.93, respectively. Multivariate analysis showed that the strongest variable related to iHCC finding was pre-LT Child-Pugh C status (OR 3.5; P=0.004). CONCLUSION: Screening for liver cancer remains an important issue during transplant waiting list. However, the US screening method should be reviewed particularly for Child-Pugh C patients.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Early Detection of Cancer/methods , Liver Neoplasms/diagnostic imaging , Liver Transplantation , Waiting Lists , Adolescent , Adult , Aged , Argentina/epidemiology , Carcinoma, Hepatocellular/epidemiology , Humans , Liver Neoplasms/epidemiology , Middle Aged , Population Surveillance/methods , Predictive Value of Tests , Retrospective Studies , Ultrasonography , Young Adult
8.
PLoS One ; 9(9): e107944, 2014.
Article in English | MEDLINE | ID: mdl-25238610

ABSTRACT

We have shown that ex vivo pre-conditioning of bone marrow-derived dendritic cells (DC) with low molecular weight hyaluronan (LMW HA) induces antitumor immunity against colorectal carcinoma (CRC) in mice. In the present study we investigated the effects of LMW HA priming on human-tumor-pulsed monocytes-derived dendritic cells (DC/TL) obtained from healthy donors and patients with CRC. LMW HA treatment resulted in an improved maturation state of DC/TL and an enhanced mixed leucocyte reaction activity in vivo. Importantly, pre-conditioning of DC/TL with LMW HA increased their ability to migrate and reduced their attraction to human tumor derived supernatants. These effects were associated with increased CCR7 expression levels in DC. Indeed, a significant increase in migratory response toward CCL21 was observed in LMW HA primed tumor-pulsed monocyte-derived dendritic cells (DC/TL/LMW HA) when compared to LWM HA untreated cells (DC/TL). Moreover, LMW HA priming modulated other mechanisms implicated in DC migration toward lymph nodes such as the metalloproteinase activity. Furthermore, it also resulted in a significant reduction in DC migratory capacity toward tumor supernatant and IL8 in vitro. Consistently, LMW HA dramatically enhanced in vivo DC recruitment to tumor-regional lymph nodes and reduced DC migration toward tumor tissue. This study shows that LMW HA--a poorly immunogenic molecule--represents a promising candidate to improve human DC maturation protocols in the context of DC-based vaccines development, due to its ability to enhance their immunogenic properties as well as their migratory capacity toward lymph nodes instead of tumors.


Subject(s)
Cell Movement/drug effects , Colorectal Neoplasms/immunology , Dendritic Cells/drug effects , Hyaluronic Acid/pharmacology , Culture Media , Humans , Tumor Cells, Cultured , Tumor Microenvironment
9.
Mol Clin Oncol ; 2(5): 673-684, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25054030

ABSTRACT

Neuroendocrine tumors (NET) include a spectrum of malignancies arising from neuroendocrine cells throughout the body. The objective of this clinical investigation of retrospectively and prospectively collected data was to describe the prevalence, demographic data, clinical symptoms and methods of diagnosis of NET and the treatment and long-term follow-up of patients with NET. Data were provided by the participating centers and assessed for consistency by internal reviewers. All the cases were centrally evaluated (when necessary) by the pathologists in our group. The tissue samples were reviewed by hematoxylin and eosin and immunohistochemical staining techniques to confirm the diagnosis of NET. In total, 532 cases were documented: 461 gastroenteropancreatic-NET (GEP-NET) and 71 bronchial NET (BNET). All the tumors were immunohistochemically defined according to the World Health Organization (WHO) and European Neuroendocrine Tumor Society criteria. The most common initial symptoms in GEP-NET were abdominal pain, diarrhea, bowel obstruction, flushing, gastrointestinal bleeding and weight loss. The most common tumor types were carcinoid (58.0%), non-functional pancreatic tumor (23.0%), metastatic NET of unknown primary (16.0%) and functional pancreatic tumor (3.0%). Of the BNET, 89.0% were typical and 11.0% atypical carcinoids. Of the patients with GEP-NET, 59.2% had distant metastasis at diagnosis. The locations of the primary tumors in GEP-NET were the small bowel (26.9%), pancreas (25.2%), colon-rectum (12.4%), appendix (7.6%), stomach (6.9%), esophagus (2.8%), duodenum (2.0%) and unknown primary (16.3%). The histological subtypes based on the WHO classification were well-differentiated NET (20.1%), well-differentiated neuroendocrine carcinomas (66.5%) and poorly differentiated neuroendocrine carcinomas (10.3%). Overall, 67.3% of the patients underwent surgery, 41.2% with curative intent and 26.1% for palliative purposes. The 5-year survival rates were 65.1% (95% confidence interval, 58.0-71.4%) in GEP-NET and 100.0% in typical carcinoid of the lung. This observational, non-interventional, longitudinal study aimed to accumulate relevant information regarding the epidemiology, clinical presentation and current practices in the treatment of NET patients in Argentina, providing insight into regional differences and patterns of care in this heterogeneous disease.

10.
Transpl Int ; 27(12): 1244-52, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25052132

ABSTRACT

The aim of this study was to identify potential risk factors linked to neurologic events (NE) occurring after liver transplantation (LT) and use them to construct a model to predict such events. From odds ratios (OR) of risk factors, a scoring system was assessed using multivariate regression analysis. Forty-one of 307 LT patients presented NE (13.3%), with prolonged hospital stay and decreased post-LT survival. On multivariate analysis, factors associated with NE included: severe pre-LT ascites OR 3.9 (1.80-8.41; P = 0.001), delta sodium ≥12 mEq/l OR 3.5 (1.36-8.67; P = 0.01), and post-LT hypomagnesemia OR 2.9 (1.37-5.98; P = 0.005). Points were assigned depending on ORs as follows: ascites 4 points, and hypomagnesemia and delta sodium ≥12 mEq/l, 3 points each (score range = 0-10 points). ROC curve analysis suggested good discriminative power for the model, with a c-statistic of 0.72 (CI 0.62-0.81; P < 0.0001), best performance for a cutoff value >3 points (71% sensitivity, 60% specificity). NE risk increased progressively from 6.4%, to 10.3%, 12.8%, 31.5% and 71.0% as scores rose from 0 to 3, 4, 6-7 and 10 cumulative points, respectively. The score described helps to identify patients potentially at risk for neurologic events, and its prevention would decrease morbidity and mortality after LT.


Subject(s)
Consciousness Disorders/epidemiology , Delirium/epidemiology , Dysarthria/epidemiology , Liver Transplantation , Movement Disorders/epidemiology , Postoperative Complications/epidemiology , Seizures/epidemiology , Vision Disorders/epidemiology , Adult , Aged , Confidence Intervals , Consciousness Disorders/etiology , Delirium/etiology , Dysarthria/etiology , Female , Humans , Kaplan-Meier Estimate , Length of Stay/statistics & numerical data , Magnesium/blood , Male , Middle Aged , Movement Disorders/etiology , Odds Ratio , Postoperative Complications/blood , Postoperative Complications/etiology , Retrospective Studies , Risk , Seizures/etiology , Sodium/blood , Vision Disorders/etiology
11.
PLoS One ; 9(4): e95171, 2014.
Article in English | MEDLINE | ID: mdl-24736611

ABSTRACT

BACKGROUND AND AIMS: Several reports described the migration of human mesenchymal stromal cells (MSCs) towards tumor-released factors. Autocrine motility factor (AMF) is produced by several tumors including hepatocellular carcinoma (HCC). The aim of this study was to analyze AMF involvement on MSC migration towards human HCC. METHODS: Production of AMF by HCC tumors was evaluated by western analysis. The effects of AMF on MSCs from different sources (bone marrow, adipose tissue and perivascular cells from umbilical cord) were analyzed using in vitro migration assay; metalloproteinase 2 (MMP2) activity and expression of critical genes were studied by zymography and qRT-PCR, respectively. To assess AMF involvement on the in vivo MSC migration, noninvasive fluorescence imaging was performed. To test the effect of AMF-primed MSCs on tumor development, in vitro proliferation and spheroids growth and in vivo tumor volume were evaluated. RESULTS: AMF produced by HCC was found to induce migration of different MSCs in vitro and to enhance their MMP2 activity. Stimulation of MSCs with recombinant AMF (rAMF) also induced the in vitro adhesion to endothelial cells in coincidence with changes in the expression levels of MMP3, AMF receptor, caveolin-1, and -2 and GDI-2. Importantly, stimulation of MSCs with rAMF increased the in vivo migration of MSCs towards experimental HCC tumors. AMF-priming of MSCs did not induce a pro-tumorigenic effect on HCC cells neither in vivo nor in vitro. CONCLUSION: AMF plays a role in MSC recruitment towards HCC. However, its ability to increase MSC migration to HCC for therapeutic purposes merits further evaluation.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Glucose-6-Phosphate Isomerase/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mesenchymal Stem Cells/metabolism , Animals , Carcinoma, Hepatocellular/genetics , Cell Adhesion/drug effects , Cell Adhesion/genetics , Cell Line, Tumor , Cell Movement/drug effects , Chemotaxis/drug effects , Disease Models, Animal , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Enzyme Activation/drug effects , Glucose-6-Phosphate Isomerase/pharmacology , Heterografts , Humans , Liver Neoplasms/genetics , Male , Mesenchymal Stem Cells/drug effects , Metalloendopeptidases/metabolism , Mice , Tumor Burden
12.
Rev. argent. cir ; 106(1): 1-5, mar. 2014. ilus
Article in Spanish | LILACS | ID: biblio-957798
13.
Ann Hepatol ; 13(2): 211-8, 2014.
Article in English | MEDLINE | ID: mdl-24552863

ABSTRACT

BACKGROUND: Incidental hepatocellular carcinoma (iHCC) generates uncertainty over risk of recurrence after liver transplantation (LT). AIM: To compare recurrence between iHCC and confirmed HCC diagnosed prior to transplant based on imaging criteria (cHCC). MATERIAL AND METHODS: Fifty-four HCC patients were analyzed from a series of 309 consecutive adult transplanted patients. We developed a recurrence predicting score (RPS) applying ORs based on pathologic risk variables. RESULTS: Incidence of iHCC was 4.8% (n = 15) and overall recurrence 12.9% (cHCC 15.4% and iHCC 7%; P = 0.39). Variables included in the RPS were: microvascular invasion OR 17.8 (1.78-178.97; P = 0.014: 2 points), neural invasion OR 15.5 (1.13-212.17; P = 0.04: 1.5 points), nuclear grade > II OR 9.3 (1.17-74.84; P = 0.035: 1 point), and beyond Up-to 7 criteria OR 13.1 (1.66-103.67; P = 0.015: 1.5 points). Two risk groups were identified: low risk for recurrence (0-1 point) and intermediate-high risk groups (2-6 points). Low risk category remained an independent predictor of recurrence: OR 0.11 (0.01-0.67; P = 0.017); AUROC of 0.75 (0.54-0.96). A tendency towards more patients categorized as low risk group among iHCC patients was observed (69.2%; P = 0.13). CONCLUSIONS: In this series iHCC was not associated to lower risk of recurrence when compared to cHCC. We propose application of an RPS as a clinical tool for recurrence risk estimation.


Subject(s)
Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/surgery , Incidental Findings , Liver Neoplasms/diagnosis , Liver Neoplasms/surgery , Liver Transplantation , Models, Statistical , Neoplasm Recurrence, Local/epidemiology , Adult , Aged , Biopsy , Carcinoma, Hepatocellular/epidemiology , Female , Follow-Up Studies , Humans , Incidence , Kaplan-Meier Estimate , Liver/pathology , Liver Neoplasms/epidemiology , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Retrospective Studies , Risk Factors , Survival Rate , Time Factors , Treatment Outcome
14.
Ann Hepatol ; 13(2): 288-92, 2014.
Article in English | MEDLINE | ID: mdl-24552872

ABSTRACT

Severe liver dysfunction during pregnancy implies a serious risk for both mother and fetus, and represents a technical and ethical challenge for treating physicians. We report a case of a previously healthy 32-year old woman who was admitted to our hospital with idiopathic fulminant hepatic failure and underwent successful orthotopic liver transplantation (OLT) at gestation week 21. Patient's and fetus' immediate postoperative course were relatively uneventful until week six after OLT, when the mother developed oligohydramnios and preeclampsia. At pregnancy week 27, after inducing baby's lung maturation, a cesarean section was performed with the delivery of an otherwise healthy girl. After 3 years of follow-up, mother and child are leading normal lives with no complications related either to pregnancy or to OLT. We describe the case of a successful emergency liver transplant in a woman during the second trimester of pregnancy, demonstrating that OLT can be a viable option to preserve the life of the mother and an otherwise unviable fetus. Intrauterine baby's growths until the attainment of a viable gestational age was feasible despite the mother's fulminant hepatic failure and liver transplant surgery.


Subject(s)
Liver Failure, Acute/surgery , Liver Transplantation , Pregnancy Complications/surgery , Pregnancy Outcome , Pregnancy Trimester, Second , Adult , Cesarean Section , Female , Follow-Up Studies , Humans , Infant, Newborn , Pregnancy , Risk Factors , Time Factors , Treatment Outcome
17.
Mol Pharm ; 8(5): 1538-48, 2011 Oct 03.
Article in English | MEDLINE | ID: mdl-21770423

ABSTRACT

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third cause of cancer-related death. Fibrogenesis is an active process characterized by the production of several proinflammatory cytokines, chemokines and growth factors. It involves the activation of hepatic stellate cells (HSCs) which accumulate at the site of injury and are the main source of the extracellular matrix deposits. There are no curative treatments for advanced HCC, thus, new therapies are urgently needed. Mesenchymal stromal cells (MSCs) have the ability to migrate to sites of injury or to remodeling tissues after in vivo administration; however, in several cancer models they demonstrated limited efficacy to eradicate experimental tumors partially due to poor engraftment. Thus, the aim of this work was to analyze the capacity of human MSCs (hMSCs) to migrate and anchor to HCC tumors. We observed that HCC and HSCs, but not nontumoral stroma, produce factors that induce hMSC migration in vitro. Conditioned media (CM) generated from established HCC cell lines were found to induce higher levels of hMSC migration than CM derived from fresh patient tumor samples. In addition, after exposure to CM from HCC cells or HSCs, hMSCs demonstrated adhesion and invasion capability to endothelial cells, type IV collagen and fibrinogen. Consistently, these cells were found to increase metalloproteinase-2 activity. In vivo studies with subcutaneous and orthotopic HCC models indicated that intravenously infused hMSCs migrated to lungs, spleen and liver. Seven days post-hMSC infusion cells were located also in the tumor in both models, but the signal intensity was significantly higher in orthotopic than in subcutaneous model. Interestingly, when orthotopic HCC tumors where established in noncirrhotic or cirrhotic livers, the amount of hMSCs localized in the liver was higher in comparison with healthy animals. A very low signal was found in lungs and spleens, indicating that liver tumors are able to recruit them at high efficiency. Taken together our results indicate that HCC and HSC cells produce factors that efficiently induce hMSC migration toward tumor microenvironment in vitro and in vivo and make MSCs candidates for cell-based therapeutic strategies to hepatocellular carcinoma associated with fibrosis.


Subject(s)
Bone Marrow Cells/metabolism , Carcinoma, Hepatocellular/pathology , Cell Movement , Liver Cirrhosis/metabolism , Liver Neoplasms/pathology , Mesenchymal Stem Cells/pathology , Tumor Microenvironment , Animals , Bone Marrow Cells/pathology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/physiopathology , Carcinoma, Hepatocellular/therapy , Cell Adhesion , Cell Line , Cell Line, Tumor , Culture Media, Conditioned , Endothelium, Vascular/metabolism , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/pathology , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Liver Cirrhosis/therapy , Liver Neoplasms/metabolism , Liver Neoplasms/physiopathology , Liver Neoplasms/therapy , Male , Matrix Metalloproteinase 2/metabolism , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Mice , Mice, Nude , Neoplasm Proteins/metabolism , Spheroids, Cellular/metabolism , Spheroids, Cellular/pathology , Tumor Cells, Cultured , Up-Regulation , Xenograft Model Antitumor Assays
18.
HPB (Oxford) ; 12(8): 531-7, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20887320

ABSTRACT

BACKGROUND: In 2005, the model of end-stage liver disease (MELD)-based allocation system was adopted to assess potential liver transplant (LT) recipients in Argentina. The aim of the present study was to revise the activity of the MELD Exception Experts Committee. METHODS: Between 2005 and 2009, 1623 patients were listed for LT. Regulation provides extra-MELD points for amyloidosis, hepatopulmonary syndrome (HPS) and T(2) hepatocellular carcinoma (T(2) HCC). Centres could also request priority for other situations. Using a prospective database, we identified patients in whom priority points were requested. Pathology reports of explanted livers were analysed for patients with T(2) HCC. RESULTS: From 234 out of 1623 (14.4%) requests, the overall approval rate was 60.2% including: 2 amyloidosis, 6 HPS, 111 T(2) HCC and 22 non-regulated situations. Of the 111 patients with T(2) HCC, 6 died (5.4%), 8 had tumour progression (7.2%), 94 were transplanted (84.2%) and 3 are still waiting. An explants correlation showed that presumed diagnosis of T(2) HCC was incorrect in 20/94 (22%) and was correct in only 41/94 (43%) cases being T(1) HCC in 9 and T(3) HCC in 23. CONCLUSIONS: MELD exceptions are frequently requested in Argentina. Unfortunately, most receiving priority points for T(2) HCC benefited by medical error or imaging limitations. An intense review process is urgently needed to maintain equity and justice in the allocation system.


Subject(s)
Advisory Committees , Health Care Rationing , Health Status Indicators , Healthcare Disparities , Liver Diseases/surgery , Liver Transplantation , Tissue Donors/supply & distribution , Tissue and Organ Procurement , Waiting Lists , Adolescent , Adult , Aged , Argentina , Chi-Square Distribution , Diagnostic Errors , Female , Humans , Liver Diseases/diagnosis , Liver Diseases/mortality , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Severity of Illness Index , Time Factors , Treatment Outcome , Young Adult
19.
Liver Int ; 30(1): 85-93, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19747191

ABSTRACT

BACKGROUND: The management of hydatid liver disease (HLD) includes various nonsurgical and surgical treatment options. METHODS: The purpose of the present longitudinal study was to report the changes in surgical management and the consequent outcome of HLD patients in 10 referral surgical centres in Argentina from 1975 to 2007. The study result analysis was divided into two study periods (1975-1990 and 1991-2007). RESULTS: A total of 1412 patients underwent radical (Group 1: 396 patients), conservative (Group 2: 748 patients) or combined (Group 3: 536 interventions in 268 patients) surgical procedures. The overall mortality and complication rate (Clavien I-IV) was 1.8 and 39% respectively. The complication rate was significantly lower in Group 1 (26%) compared with Group 2 (45%) and Group 3 (42%) There was a significant decrease in mortality (2.3 vs. 1%), complication (42 vs. 34%) and early reoperation (12 vs. 6%) rates between the first study part (918 patients) and the second study part (494 patients). During a median follow-up of 7 years, there was a significant decrease in the first part of this study in the late reoperation rate (8.4-3%) and in disease recurrence (9-1.6%). CONCLUSION: This large national observational multicentre series shows a significant improvement in surgical management of HLD in Argentina, with a decrease in mortality, morbidity, early and late reoperation and recurrence rates. A recent trend was observed in favour of an earlier diagnosis, less complicated clinical presentation and recent use of minimally invasive approaches.


Subject(s)
Echinococcosis, Hepatic/surgery , Adolescent , Adult , Aged , Argentina/epidemiology , Child , Echinococcosis, Hepatic/mortality , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Selection , Postoperative Complications/epidemiology , Recurrence , Survival Rate , Treatment Outcome , Young Adult
20.
Rev. argent. cir ; 92(1/2): 28-36, ene.-feb. 2007. tab, graf
Article in Spanish | LILACS | ID: lil-508471

ABSTRACT

Antecedentes: Algunos factores que generan una alta morbilidad de hapatectomías en pacientes con carcinoma hepatocelular sobre hepatopatías crónicas pueden modificarse para aumentar la aplicabilidad y reducir la morbilidad. Objetivo: Analizar las estrategias utilizadas en la selección de pacientes candidatos a la resección, su evaluación funcional y el manejo preoperatorio. Lugar: Unidad de cirugía hepatobiliar. Diseño: Coherte retrospectivo. Población: 42 pacientes con CHC sobre hepatopatía crónica (11 fibrosis, 31 cirrosis) que recibieron 44 hepatectomías entre 1995 y 2005. Método: Se analizaron los criterios de selección, tipos de resección, manejo anestésico, requerimientos transfusionales, morbilidad y supervivencia alejada. Análisis estadísticos con log-rank test y Kaplan Meier. Resultados: De las 44 resecciones, 33 (75%) fueron hepatectomías menores. de ellas, 20 (60%) resecciones segmento-orientadas. Sólo 25% de los casos recibió sangre de banco. La morbilidad fue de 23% y la mortalidad 2,3%. La supervivencia actuarial a 1 y 5 años fue de 85 y 50% respectivamente, 72 y 50% libre de enfermedad. Conclusiones: Una correcta selección y racional manejo anestésico y de táctica quirúrgica permite obtener resultados alentadores con morbimortalidad similar a las hepatectomías en pacientes con fusión hepática normal.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/therapy , Hepatectomy/adverse effects , Hepatectomy/standards , Embolization, Therapeutic , Fibrosis , Intraoperative Care , Liver Cirrhosis , Postoperative Care , Postoperative Complications , Preoperative Care , Retrospective Studies , Survival Analysis , Treatment Outcome
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