The Diagnostic and Prognostic Potentials of Non-Coding RNA in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare biliary tract tumor with high malignancy. CCA is the second most common primary hepatobiliary cancer after hepatocarcinoma. Despite its rarity, the incidence of CCA is steadily increasing globally. Most patients with CCA are asymptomatic in the early stages, resulting in a late-stage diagnosis and poor prognosis. Finding reliable biomarkers is essential to improve CCA's early diagnosis and survival rate. Non-coding RNAs (ncRNAs) are non-protein coding RNAs produced by genomic transcription. This includes microRNAs, long non-coding RNAs, and circular RNAs. ncRNAs have multiple functions in regulating gene expression and are crucial for maintaining normal cell function and developing diseases. Many studies have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA. ncRNAs can be easily extracted and detected through tumor tissue and liquid biopsies, representing a potential tool for diagnosing and prognosis CCA. This review will provide a detailed update on the diagnostic and prognostic potentials of lncRNAs and cirRNAs as biomarkers in CCA.

Bariatric Surgery Induces Alterations in the Immune Profile of Peripheral Blood T Cells.

Low-grade inflammation is closely linked to obesity and obesity-related comorbidities; therefore, immune cells have become an important topic in obesity research. Here, we performed a deep phenotypic characterization of circulating T cells in people with obesity, using flow cytometry. Forty-one individuals with obesity (OB) and clinical criteria for bariatric surgery were enrolled in this study. We identified and quantified 44 different circulating T cell subsets and assessed their activation status and the expression of immune-checkpoint molecules, immediately before (T1) and 7-18 months after (T2) the bariatric surgery. Twelve age- and sex-matched healthy individuals (nOB) were also recruited. The OB participants showed higher leukocyte counts and a higher percentage of neutrophils. The percentage of circulating Th1 cells were negatively correlated to HbA1c and insulin levels. OB Th1 cells displayed a higher activation status and lower PD-1 expression. The percentage of Th17 and Th1/17 cells were increased in OB, whereas the CD4+ Tregs' percentage was decreased. Interestingly, a higher proportion of OB CD4+ Tregs were polarized toward Th1- and Th1/17-like cells and expressed higher levels of CCR5. Bariatric surgery induced the recovery of CD4+ Treg cell levels and the expansion and activation of Tfh and B cells. Our results show alterations in the distribution and phenotype of circulating T cells from OB people, including activation markers and immune-checkpoint proteins, demonstrating that different metabolic profiles are associated to distinct immune profiles, and both are modulated by bariatric surgery.

CD8+ Treg cells play a role in the obesity-associated insulin resistance.

Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4+ Treg cells. However, little is known about the CD8+ Treg cells. Therefore, we aim to characterize the CD8+ Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre- and post-bariatric surgery. A group of age- and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8+ Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8+ Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1- and Tc1/17-like CD8+ Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8+ Tregs infiltrated, compared to PB or VAT, while CD8+ Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3+CD8+ Tregs in circulation, and PD-1+CD8+ Tregs infiltrated in the VAT. An increase in the percentage of circulating Tc1-like CD8+ Treg cells expressing PD-1 was observed post-surgery. In conclusion, obesity induces significant alterations in CD8+ Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules.

Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy.

Colorectal cancer (CRC) is the third most prevalent type of cancer, and liver metastasis is the most common site of metastatic development. In the tumor microenvironment (TME), various innate immune cells are known to influence cancer progression and metastasis occurrence. CD274 (PD-L1) and CD206 (MRC1) are proteins that have been associated with poor prognosis and disease progression. We conducted a study on tumoral and non-tumoral biopsies from 47 patients with CRC liver metastasis, using flow cytometry to phenotypically characterize innate immune cells. Our findings showed an increase in the expression of CD274 on classical, intermediate, and non-classical monocytes when comparing tumor with non-tumor samples. Furthermore, tumor samples with a desmoplastic growth pattern exhibited a significantly decreased percentage of CD274- and CD206-positive cells in all monocyte populations compared to non-desmoplastic samples. We found a correlation between a lower expression of CD206 or CD274 on classical, intermediate, and non-classical monocytes and increased disease-free survival, which points to a better prognosis for these patients. In conclusion, our study has identified potential new targets and biomarkers that could be incorporated into a personalized medicine approach to enhance the outcome for colorectal cancer patients.

Clinical Impact of Preoperative Biliary Drainage in Patients with Ductal Adenocarcinoma of the Pancreatic Head.

Our aim was to study the association between preoperative biliary drainage (PBD) and morbidity following cephalic pancreaticoduodenectomy (CPD) for pancreatic ductal adenocarcinoma (PDAC) and its prognostic impact, which is still controversial in the literature. A retrospective study was conducted, which included 128 patients who underwent CPD for PDAC, divided into two groups: those who underwent PBD (group 1) and those who did not undergo this procedure (group 2). Group 1 was subdivided according to the drainage route: endoscopic retrograde cholangiopancreatography (ERCP), group 1.1, and percutaneous transhepatic cholangiography (PTC), group 1.2. 34.4% of patients underwent PBD, and 47.7% developed PBD-related complications, with 37% in group 1.1 and 64.7% in group 1.2 (p = 0.074). There was a significant difference between group 1 and 2 regarding bacterial colonization of the bile (45.5% vs. 3.6%, p < 0.001), but no difference was found in the colonization by multidrug-resistant bacteria, the development of Clavien-Dindo ≥ III complications, clinically relevant pancreatic fistula and delayed gastric emptying (DGE), intra-abdominal abscess, hemorrhage, superficial surgical site infection (SSI), and readmission. Between groups 1.1 and 1.2, there was a significant difference in clinically relevant DGE (44.4% vs. 5.9%, p = 0.014) and Clavien-Dindo ≥ III complications (59.3% vs. 88.2%, p = 0.040). There were no significant differences in median overall survival and disease-free survival (DFS) between groups 1 and 2. Groups 1.1 and 1.2 had a significant difference in DFS (10 vs. 5 months, p = 0.017). In this group of patients, PBD was associated with increased bacterial colonization of the bile, without a significant increase in postoperative complications or influence in survival. ERCP seems to contribute to the development of clinically significant DGE. Patients undergoing PTC appear to have an early recurrence.

Pancreatic Cancer Biomarkers: Oncogenic Mutations, Tissue and Liquid Biopsies, and Radiomics-A Review.

Pancreatic cancer is one of the most fatal malignancies, as approximately 80% of patients are at advanced stages by the time of diagnosis. The main reason for the poor overall survival is late diagnosis that is partially due to the lack of tools for early-stage detection. In addition, there are several challenges in evaluating response to treatment and predicting prognosis. In this article, we do a review of the most common pancreatic cancer biomarkers with emphasis in new and promising approaches. Liquid biopsies seem to have important clinical applications in early detection, screening, prognosis, and longitudinal monitoring of on-treatment patients. Together with biomarkers in imaging, can represent valuable alternative non-invasive tools in order to achieve a more effective management of pancreatic cancer patients.

Tumor Stroma Area and Other Prognostic Factors in Pancreatic Ductal Adenocarcinoma Patients Submitted to Surgery.

Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, responsible for up to 80% of its volume. The amount of stroma can be associated with prognosis, although there are discrepancies regarding its concrete impact. The aim of this work was to study prognostic factors for PDAC patients submitted to surgery, including the prognostic impact of the tumor stroma area (TSA). A retrospective study with PDAC patients submitted for surgical resection was conducted. The TSA was calculated using QuPath-0.2.3 software. Arterial hypertension, diabetes mellitus, and surgical complications Clavien-Dindo>IIIa are independent risk factors for mortality in PDAC patients submitted to surgery. Regarding TSA, using >1.9 × 1011 µ2 as cut-off value for all stages, patients seem to have longer overall survival (OS) (31 vs. 21 months, p = 0.495). For stage II, a TSA > 2 × 1011 µ2 was significantly associated with an R0 resection (p = 0.037). For stage III patients, a TSA > 1.9 × 1011 µ2 was significantly associated with a lower histological grade (p = 0.031), and a TSA > 2E + 11 µ2 was significantly associated with a preoperative AP ≥ 120 U/L (p = 0.009) and a lower preoperative AST (≤35 U/L) (p = 0.004). Patients with PDAC undergoing surgical resection with preoperative CA19.9 > 500 U/L and AST ≥ 100 U/L have an independent higher risk of recurrence. Tumor stroma could have a protective effect in these patients. A larger TSA is associated with an R0 resection in stage II patients and a lower histological grade in stage III patients, which may contribute to a longer OS.

The Impact of the Enhanced Recovery After Surgery (ERAS) Protocol on Colorectal Surgery in a Portuguese Tertiary Hospital.

INTRODUCTION: The benefits of the multimodal Enhanced Recovery After Surgery® (ERAS) program have been described all over the world. The adoption of several perioperative strategies translates into an improvement in the quality of the healthcare provided. The aim of this study was to report the results of the implementation of the ERAS® program for colorectal surgery in a tertiary hospital. MATERIAL AND METHODS: In this single-center observational study, 534 patients who underwent colorectal surgery between December 2018 and May 2021 were included. Two groups were considered: before and after the implementation of the ERAS® program. The primary outcome measure was 30-day morbidity. The length of hospital stay, readmission rate, reintervention and mortality among the two groups were also evaluated. RESULTS: The pre-ERAS group included 102 patients and the ERAS group included 432 patients. There was a statistically significant reduction in morbidity at 30 days (37.3% vs 26.5%, p < 0.05), length of stay (7 days vs 5 days, p < 0.001) and readmission rate (12.9% vs 6%, p < 0.05) after the implementation of the ERAS program. CONCLUSION: The ERAS® protocol for colorectal surgery was successfully and safely implemented in our hospital, contributing to an improvement in perioperative care provided to patients.

Extensive Phenotypic Characterization of T Cells Infiltrating Liver Metastasis from Colorectal Cancer: A Potential Role in Precision Medicine.

Colorectal cancer (CRC) is one of the most common cancers worldwide, with liver metastasis being its main cause of death. This study harvested fresh biological material from non-tumor and tumor tissue from 47 patients with CRC liver metastasis after surgery, followed by mechanical cellular extraction and stain-lyse-wash direct immunofluorescence technique. Here, 60 different T-cell populations were characterized by flow cytometry. Tumor samples were also subdivided according to their growth pattern into desmoplastic and non-desmoplastic. When we compared tumor versus non-tumor samples, we observed a significantly lower percentage of T-lymphocyte infiltration in the tumor in which the CD4+ T-cell density increased compared to the CD8+ T cells. T regulatory cells also increased within the tumor, even with an activated phenotype (HLA-DR+). A higher percentage of IL-17-producing cells was present in tumor samples and correlated with the metastasis size. In contrast, we also observed a significant increase in CD8+ follicular-like T cells (CD185+), suggesting a cytotoxic response to cancer cells. Additionally, most infiltrated T cells exhibit an intermediate activation phenotype (CD25+). In conclusion, our results revealed potential new targets and prognostic biomarkers that could take part in an algorithm for personalized medicine approaches improving CRC patients' outcomes.

Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis.

Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.

Clinicopathological prognostic factors for gallbladder carcinoma: a retrospective study.

Background: Gallbladder carcinoma (GBC) is an uncommon neoplasm with poor long-term survival. Worldwide the incidence rates vary according to geographic area. The multifactorial aetiology and the rarity of the disease limits the studies to improve outcomes in patients, since the treatment remains mostly surgical. The aim of this study was to identify clinicopathological prognostic factors for survival in patients with GBC submitted to surgery in our institution-a tertiary centre in Portugal. Also, to assess the expression of possible biomarkers (HER2, CD44 and ALDH1) in GBC, as well as the frequency of microsatellite instability (MSI) tumours. Methods: Clinicopathological characteristics of 41 consecutive patients that underwent surgical resection for GBC (2008-2019) at our hospital were retrospectively reviewed. Clinicopathological factors were assessed and an immunohistochemical (IHC) analysis was done. Microsatellite stability (MSS) was considered if there was maintenance of nuclear expression of MLH1, MSH2, MSH6 and PMS2. Human epidermal growth factor receptor 2 (HER2) expression was evaluated according to the rules applied for gastric cancer and expression of CD44 and ALH1 was evaluated in order to detect cancer stem cells (CSC). Survival analysis was conducted using Kaplan-Meier and Cox regression was used to find prognostic factors. Results: Incidence of GBC in our cohort of patients was 0.45%, most commonly affecting females. Median overall survival (OS) was 23 months with a 39.6% 5-year survival rate. Stage > II [hazard ratios (HR) =8.58; P=0.007], lymphovascular invasion (LVI) (HR =4.06; P=0.045) and hepatic resection (HR =0.288; P=0.034) independently influenced survival. HER2 positivity and high expression of CD44 or ADLH1 did not show significant influence in survival (P=0.649, P=0.868 and P=0.914, respectively), although HER2 and ALDH1 positive patients showed a tendency to a shorter OS, compared to negative patients. We found no relation between these biomarkers expression and disease stage. All analysed samples had MSS. Conclusions: GBC patients with a worse prognosis can be identified. The overexpression of HER2 could select patients for targeted therapy and prompt tissue sampling in unresectable patients.

Investigating VEGF. miR-145-3p, and miR-101-3p Expression in Patients with Cholangiocarcinoma.

INTRODUCTION: Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer. Several factors, such as epigenetic changes in promoter genes, gene expression, and microRNAs (miR), can contribute to genomic instability in cancer. This study aimed at evaluating the expression of VEGF, miRs 145-3p, and 101-3p in patients with CCA and their potential as biomarkers for diagnosis and prognosis of CCA. MATERIAL AND METHODS: Sixty two patients were studied. Out of these 62 patients, 41 cases had confirm CCA and 21 cases had hepatopathies complications. The RNA was extracted from a paraffined tissue block, and then the synthesis of cDNA was performed. The analysis of the expression of VEGF, miR-145-3p, and miR-101-3p was carried out by polymerase chain reaction in real time.  Results: The findings revealed that miRs 145-3p and 101-3p were under expressed in the case group compared to the control group (0.46; 0.17; P = 0.0001, respectively). VEGF was overexpressed in the case group compared to the control group (11.8; P = 0.0001). An increase in miR-145-3p expression level was observed in patients with perihilar CCA compared to those with distal CCA (0.51 ± 0.41; 0.17 ± 0.13; P = 0.0698). Survival rate analysis showed that 41.9% of patients with intrahepatic CCA and 31.5% of patients with extrahepatic CCA were free from death within 11 months, leading to a significant difference (P> 0.05). CONCLUSION: The underexpression of miRNAs, tumor suppressors, the overexpression of VEGF, smoking, and aging were associated with CCA based on our findings. It seems that the reduced expression of the studies miRNAs and increased expression of VEGF can contribute to a decrease in survival rate of patients with tumor in their intrahepatic bile ducts.

Extracellular vesicles enriched with an endothelial cell pro-survival microRNA affects skin tissue regeneration.

Endothelial cell (EC) activity is essential for tissue regeneration in several (patho)physiological contexts. However, our capacity to deliver in vivo biomolecules capable of controlling EC fate is relatively limited. Here, we screened a library of microRNA (miR) mimics and identified 25 miRs capable of enhancing the survival of ECs exposed to ischemia-mimicking conditions. In vitro, we showed that miR-425-5p, one of the hits, was able to enhance EC survival and migration. In vivo, using a mouse Matrigel plug assay, we showed that ECs transfected with miR-425-5p displayed enhanced survival compared with scramble-transfected ECs. Mechanistically, we showed that miR-425-5p modulated the PTEN/PI3K/AKT pathway and inhibition of miR-425-5p target genes (DACH1, PTEN, RGS5, and VASH1) phenocopied the pro-survival. For the in vivo delivery of miR-425-5p, we modulated small extracellular vesicles (sEVs) with miR-425-5p and showed, in vitro, that miR-425-5p-modulated sEVs were (1) capable of enhancing the survival of ECs exposed to ischemia-mimic conditions, and (2) efficiently internalized by skin cells. Finally, using a streptozotocin-induced diabetic wound healing mouse model, we showed that, compared with miR-scrambled-modulated sEVs, topical administration of miR-425-5p-modulated sEVs significantly enhanced wound healing, a process mediated by enhanced vascularization and skin re-epithelialization.

Development of a genomic predictive model for cholangiocarcinoma using copy number alteration data.

AIMS: Cholangiocarcinoma (CC) is a rare tumour arising from the biliary tract epithelium. The aim of this study was to perform a genomic characterisation of CC tumours and to implement a model to differentiate extrahepatic (ECC) and intrahepatic (ICC) cholangiocarcinoma. METHODS: DNA extracted from tumour samples of 23 patients with CC, namely 10 patients with ECC and 13 patients with ICC, was analysed by array comparative genomic hybridisation. A support vector machine algorithm for classification was applied to the genomic data to distinguish between ICC and ECC. A survival analysis comparing both groups of patients was also performed. RESULTS: With these whole genome results, we observed several common alterations between tumour samples of the same CC anatomical type, namely gain of Xp and loss of 3p, 11q11, 14q, 16q, Yp and Yq in ICC tumours, and gain of 16p25.3 and loss of 3q26.1, 6p25.3-22.3, 12p13.31, 17p, 18q and Yp in ECC tumours. Gain of 2q37.3 was observed in the samples of both tumour subtypes, ICC and ECC. The developed genomic model comprised four chromosomal regions that seem to enable the distinction between ICC and ECC, with an accuracy of 71.43% (95% CI 43% to 100%). Survival analysis revealed that in our cohort, patients with ECC survived on average 8 months less than patients with ICC. CONCLUSIONS: This genomic characterisation and the introduction of genomic models to clinical practice could be important for patient management and for the development of targeted therapies. The power of this genomic model should be evaluated in other CC populations.

Plasmatic Oxidative and Metabonomic Profile of Patients with Different Degrees of Biliary Acute Pancreatitis Severity.

Acute pancreatitis (AP) is an inflammatory process of the pancreas with variable involvement of the pancreatic and peripancreatic tissues and remote organ systems. The main goal of this study was to evaluate the inflammatory biomarkers, oxidative stress (OS), and plasma metabolome of patients with different degrees of biliary AP severity to improve its prognosis. Twenty-nine patients with biliary AP and 11 healthy controls were enrolled in this study. We analyzed several inflammatory biomarkers, multifactorial scores, reactive oxygen species (ROS), antioxidants defenses, and the plasma metabolome of biliary AP and healthy controls. Hepcidin (1.00), CRP (0.94), and SIRI (0.87) were the most accurate serological biomarkers of AP severity. OS played a pivotal role in the initial phase of AP, with significant changes in ROS and antioxidant defenses relating to AP severity. Phenylalanine (p < 0.05), threonine (p < 0.05), and lipids (p < 0.01) showed significant changes in AP severity. The role of hepcidin and SIRI were confirmed as new prognostic biomarkers of biliary AP. OS appears to have a role in the onset and progression of the AP process. Overall, this study identified several metabolites that may predict the onset and progression of biliary AP severity, constituting the first metabonomic study in the field of biliary AP.

Necrotising fasciitis of the thoracic wall: a rare case with favourable outcome.

Necrotising fasciitis (NF) is a severe infection of the subcutaneous tissue and fascia that can rapidly lead to sepsis and shock with high mortality rates. Its initial signs are often non-specific making it difficult for an early diagnosis to be reached. Nevertheless it is of the utmost importance to begin proper treatment including wide surgical debridement as soon as possible in order to avoid death. We present the case of a patient with NF of the thoracic wall which is a rare location for this disease but often associated with worse prognosis. Even though he progressed to septic shock within less than 24 hours of its presentation, due to early surgical management, aggressive resuscitation and intensive care support, he reached a favourable outcome. After three surgical revisions and 2 weeks in an intensive care unit, the patient was discharged from hospital 35 days after admission.

Underexpression of miR-126-3p in Patients with Cholangiocarcinoma.

OBJECTIVES: To evaluate the expression of miR-126-3p and its potential as a biomarker for cholangiocarcinoma (CCA) and to better understand the prognosis, comorbidities, and lifestyle habits associated with the disease. METHODS: Fifty-nine individuals were distributed into either the study group (38 CCA patients) or the control group (21 individuals without liver diseases). Total RNA was extracted, cDNA synthesis was performed, and miR-126-3p expression was assessed using real-time PCR. For statistical analysis, alpha error was set at 5%. RESULTS: MiR-126-3p was found to be underexpressed in the study group relative to the controls (0.42; P=0.001). Additionally, marked underexpression was found in the study group in when associated with smoking (0.28; P=0.0001), alcoholism (0.19; P=0.0001), hypertension (0.29; P=000.1), and diabetes (0.12; P=0.0003) relative to the controls. No association was found between miR-126-3p expression and tumor subtypes (iCCA=0.42; pCCA=0.45; dCCA=0.72; P=0.9155). A total of 67% of dCCA patients were event-free at 16 months of follow up, while both pCCA and iCCA exhibited event-free survival rates of 25%, though there was no significant difference between these subgroups (P=0.273). CONCLUSION: The underexpression of mir-126-3p is associated with cholangiocarcinoma and can be potentiated by alcoholism, hypertension, diabetes, and smoking, the latter of which is an independent risk factor for this cancer. Furthermore, dCCA patients exhibit higher survival rates relative to patients with pCCA and iCCA.
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Morphophenotypic Classification of Hepatocellular Carcinoma: the Biliary/Stem Cell Subgroup and Worst Outcome-Implications on Patient Selection.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Current clinical/pathological criteria contribute to risk stratification, but are far from the desired on individualized medicine. Recently, HCC classifications have been published based on immunohistochemical and morphological features. METHODS: A retrospective review of patients submitted to surgical treatment-partial hepatectomy (PH) or liver transplantation (LT), with pathological diagnosis of HCC, in a 9-year period (2007-2015) was performed. RESULTS: Applying the classification of Srivastava et al. (#1), based on the expression of CD31, p53, AFP and CD44, tumour size and presence of vascular invasion, HCC were categorized as low- and high-risk HCC. With the classification of Tsujikawa et al. (#2), HCC were classified into biliary/stem cell marker positive, Wnt signalling positive and the "all negative" HCC, according to the expression of CK19, SALL4, ß-catenin glutamine synthetase, EpCAM and p53. There were sixty-six patients (53 males; 13 females), with median age of 64.5 ± 9.46 years (range 38-86), with solitary HCC, comprehending 37 PH (56.1%) and 29 LT (43.9%). The mean overall survival (OS) was 75.4 ± 6.9 months. Biliary/stem cell type of HCC was a predictive factor of worse OS on the overall population (24.4 versus 78.3 months, p = 0.032) and in PH cohort (11.5 versus 64.01 months, p = 0.016), on uni- and multivariate analyses. CONCLUSION: These results support the relevance of a risk stratification classification of HCC. Classification #2 seems adequate to our reality demonstrating OS impact, allowing its application in future biopsies, prompting individualized medicine.

Predicting liver metastases growth patterns: Current status and future possibilities.

Colorectal cancer is highly incident worldwide and presents a health burden with elevated mortality rate despite prevention, detection, and treatment, mainly due to metastatic liver disease. Histological growth patterns of colorectal cancer liver metastases have emerged as a reproducible prognostic factor, with biological implications and therapeutic windows. Nonetheless, the histological growth patterns of colorectal cancer liver metastases are only known after pathological examination of a liver resection specimen, thus limiting the possibilities of pre-surgical decision. Predicting the histological growth pattern of colorectal cancer liver metastases would provide valuable information for patient-tailored medicine. In this article, we perform a review of the histological growth patterns and their implications, with a focus on the possibilities for their prediction.