Sclerobanding in the treatment of second and third degree hemorrhoidal disease in high risk patients on antiplatelet/anticoagulant therapy without suspension: a pilot study.

Introduction: Around 20% of population in western countries is under anticoagulant treatment. However, there is paucity of evidence about the treatment of HD in patients under anticoagulant/antiplatelet therapy, although both suspension and continuation in the perioperative period may increase the risk of severe complications. The aim of this pilot study was to confirm the feasibility and safety of sclerobanding (Combined Rubber Band Ligation with 3% Polidocanol Foam Sclerotherapy), an office-based procedure, for the treatment of second-and third-degree HD in patients under anticoagulant/antiplatelet therapy without suspension. Materials and methods: Patients affected by second-third-degree haemorrhoids unresponsive to conservative treatment and under anticoagulant/antiplatelet were enrolled between November 2019 and October 2021. Postoperative complications, readmission, mortality and reintervention during the follow-up were evaluated. Results: Fifty-one patients were recruited, 23 female (45.1%) and 28 male (54.9%), with an average age of 65 years ± 11.4 SD (range 42-90). Twenty-seven patients (52.9%) had II-degree haemorrhoidal disease, and 24 (47.1%) had grade III-degree. The most frequently taken medications were dual antiplatelet therapy (51%) and new oral anticoagulants (NOACs) (21.6%). The mean follow-up was 23 months. No intraoperative complications were recorded. The rate of complications in the first postoperative month was 13.7%, represented by mild complications: 6 cases of moderate to severe pain and 1 case (2%) of thrombosis of a residual haemorrhoidal nodule, all regressing after conservative therapy. No severe complications were reported. Postoperative complications were not statistically significantly associated with the number of nodules treated (1, 2, or 3), the disease grade (2nd vs. 3rd) or the specific anticoagulant/antiplatelet regimen. During follow-up, 2 patients (4%) required a new procedure for recurrent bleeding: one an infrared photocoagulation as outpatient, and another a haemorrhoidectomy after 3 months. No cases of intraoperative or postoperative mortality occurred. Conclusions: Sclerobanding is a safe and effective technique in treating intermediate-grade haemorrhoidal disease in patients at high risk on anticoagulant/antiplatelet therapy. Sclerobanding is repeatable, usually does not require anaesthesia, and is cost-effective. Observational multicentre studies with a larger number of patients and controlled clinical trials will be needed to confirm these results.

Endoscopic retrograde appendicitis therapy versus appendectomy or antibiotics in the modern approach to uncomplicated acute appendicitis: A systematic review and meta-analysis.

INTRODUCTION: Endoscopic retrograde appendicitis therapy has been proposed as an alternative strategy for treating appendicitis, but debate exists on its role compared with conventional treatment. METHODS: This systematic review was performed on MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. The last search was in April of 2023. The risk ratio with a 95% confidence interval was calculated for dichotomous variables, and the mean difference with a 95% confidence interval for continuous variables. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool (randomized controlled trials) and the Risk of Bias in Non-Randomized Studies of Intervention tool (non-randomized controlled trials). RESULTS: Six studies met the eligibility criteria. Four studies compared endoscopic retrograde appendicitis therapy (n = 236 patients) and appendectomy (n = 339) and found no differences in technical success during index admission (risk ratio 0.97, 95% confidence interval [0.92,1.02]). Appendectomy showed superior outcomes for recurrence at 1-year follow-up (risk ratio 11.28, 95% confidence interval [2.61,48.73]). Endoscopic retrograde appendicitis therapy required shorter procedural time (mean difference -14.38, 95% confidence interval [-20.17, -8.59]) and length of hospital stay (mean difference -1.19, 95% confidence interval [-2.37, -0.01]), with lower post-intervention abdominal pain (risk ratio 0.21, 95% confidence interval [0.14,0.32]). Two studies compared endoscopic retrograde appendicitis therapy (n = 269) and antibiotic treatment (n = 280). Technical success during admission (risk ratio 1.11, 95% confidence interval [0.91,1.35]) and appendicitis recurrence (risk ratio 1.07, 95% confidence interval [0.08,14.87]) did not differ, but endoscopic retrograde appendicitis therapy decreased the length of hospitalization (mean difference -1.91, 95% confidence interval [-3.18, -0.64]). CONCLUSION: This meta-analysis did not identify significant differences between endoscopic retrograde appendicitis therapy and appendectomy or antibiotics regarding technical success during index admission and treatment efficacy at 1-year follow-up. However, a high risk of imprecision limits these results. The advantages of endoscopic retrograde appendicitis therapy in terms of reduced procedural times and shorter lengths of stay must be balanced against the increased risk of having an appendicitis recurrence at one year.

The Ephrin tyrosine kinase a3 (EphA3) is a novel mediator of RAGE-prompted motility of breast cancer cells.

BACKGROUND: The receptor for advanced glycation-end products (RAGE) and its ligands have been implicated in obesity and associated inflammatory processes as well as in metabolic alterations like diabetes. In addition, RAGE-mediated signaling has been reported to contribute to the metastatic progression of breast cancer (BC), although mechanistic insights are still required. Here, we provide novel findings regarding the transcriptomic landscape and the molecular events through which RAGE may prompt aggressive features in estrogen receptor (ER)-positive BC. METHODS: MCF7 and T47D BC cells stably overexpressing human RAGE were used as a model system to evaluate important changes like cell protrusions, migration, invasion and colony formation both in vitro through scanning electron microscopy, clonogenic, migration and invasion assays and in vivo through zebrafish xenografts experiments. The whole transcriptome of RAGE-overexpressing BC cells was screened by high-throughput RNA sequencing. Thereafter, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses allowed the prediction of potential functions of differentially expressed genes (DEGs). Flow cytometry, real time-PCR, chromatin immunoprecipitation, immunofluorescence and western blot assays were performed to investigate the molecular network involved in the regulation of a novel RAGE target gene namely EphA3. The clinical significance of EphA3 was explored in the TCGA cohort of patients through the survivALL package, whereas the pro-migratory role of EphA3 signaling was ascertained in both BC cells and cancer-associated fibroblasts (CAFs). Statistical analysis was performed by t-tests. RESULTS: RNA-seq findings and GSEA analysis revealed that RAGE overexpression leads to a motility-related gene signature in ER-positive BC cells. Accordingly, we found that RAGE-overexpressing BC cells exhibit long filopodia-like membrane protrusions as well as an enhanced dissemination potential, as determined by the diverse experimental assays. Mechanistically, we established for the first time that EphA3 signaling may act as a physical mediator of BC cells and CAFs motility through both homotypic and heterotypic interactions. CONCLUSIONS: Our data demonstrate that RAGE up-regulation leads to migratory ability in ER-positive BC cells. Noteworthy, our findings suggest that EphA3 may be considered as a novel RAGE target gene facilitating BC invasion and scattering from the primary tumor mass. Overall, the current results may provide useful insights for more comprehensive therapeutic approaches in BC, particularly in obese and diabetic patients that are characterized by high RAGE levels.

Abdominal Pain and Hypotension in a 70-Year-Old Woman.

A 70-year-old woman with hypertension, atrial fibrillation, congestive heart failure, and gallstones had 3 days of nausea, vomiting, and abdominal pain. Abdominal computed tomography showed a thickened gallbladder wall with intraluminal air adherent to the duodenum and a gallstone in the middle ileum with proximal bowel distension. What is the diagnosis and what would you do next?

Surgical Resection of a Recurrent Hepatocellular Carcinoma with Portal Vein Thrombosis: Is It a Good Treatment Option? A Case Report and Systematic Review of the Literature.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most frequent diagnosed tumor worldwide and the third leading cause of cancer related death. According to the EASL Guidelines, HCC with portal vein tumor thrombosis (PVTT) is classified as an advanced stage (BCLC stage C) and the only curative option is represented by systemic therapy. Therefore, treatment of HCC patients with PVTT remains controversial and debated. In this paper, we describe the case of a 66-year-old man with a recurrent HCC with PVTT who underwent surgical resection. A systematic review of the literature, comparing surgical resection with other choices of treatment in HCC patients with PVTT, is reported. METHODS: A systematic review of the literature regarding all prospective and retrospective studies comparing the survival outcomes of HCC patients with PVTT treated with surgical resections (SRs) or other non-surgical treatments (n-SRs) has been conducted. CASE PRESENTATION: A 66-year-old Caucasian man with a history of Hepatitis C Virus (HCV) related liver cirrhosis and previous hepatocellular carcinoma of the VI segment treated with percutaneous ethanol infusion (PEI) seven years before presented to our clinics. A new nodular hypoechoic lesion in the VI hepatic segment was demonstrated on follow-up ultrasound examination. A hepatospecific magnetic resonance imaging (MRI) scan confirmed also the presence of a 18 × 13 mm nodular lesion in the V hepatic segment with satellite micronodules associated with V-VIII sectoral portal branch thrombosis. The case was then discussed at the multidisciplinary team meeting, and it was decided to perform a right hepatectomy. The postoperative course was regular and uneventful, and the discharge occurred seven days after the surgery. At eight-month follow-up, there was no clinical nor radiological evidence of neoplastic recurrence, with well-preserved liver function (Child-Pugh A5). RESULTS: Nine studies were included in the review. Median Overall Survaival (OS) ranged from 8.2 to 30 months for SRs patients and from 7 to 13.3 for n-SRs patients. In SR patients, one-year survival ranged from 22.7% to 100%, two-year survival from 9.8% to 100%, and three-year survival from 0% to 71%. In n-SRs patients, one-year survival ranged from 11.8% to 77.6%, two-year survival from 0% to 47.8%, and three-year survival from 0% to 20.9%. CONCLUSION: The present systematic literature review and the case presented demonstrated the efficacy of surgery as a first-line treatment in well-selected HCC patients with PVTT limited or more distal to the right and left portal branches. However, further studies, particularly randomized trials, need to be conducted in future to better define the surgical indications.

The AGEs/RAGE Transduction Signaling Prompts IL-8/CXCR1/2-Mediated Interaction between Cancer-Associated Fibroblasts (CAFs) and Breast Cancer Cells.

Advanced glycation end products (AGEs) and the cognate receptor, named RAGE, are involved in metabolic disorders characterized by hyperglycemia, type 2 diabetes mellitus (T2DM) and obesity. Moreover, the AGEs/RAGE transduction pathway prompts a dysfunctional interaction between breast cancer cells and tumor stroma toward the acquisition of malignant features. However, the action of the AGEs/RAGE axis in the main players of the tumor microenvironment, named breast cancer-associated fibroblasts (CAFs), remains to be fully explored. In the present study, by chemokine array, we first assessed that interleukin-8 (IL-8) is the most up-regulated pro-inflammatory chemokine upon AGEs/RAGE activation in primary CAFs, obtained from breast tumors. Thereafter, we ascertained that the AGEs/RAGE signaling promotes a network cascade in CAFs, leading to the c-Fos-dependent regulation of IL-8. Next, using a conditioned medium from AGEs-exposed CAFs, we determined that IL-8/CXCR1/2 paracrine activation induces the acquisition of migratory and invasive features in MDA-MB-231 breast cancer cells. Altogether, our data provide new insights on the involvement of IL-8 in the AGEs/RAGE transduction pathway among the intricate connections linking breast cancer cells to the surrounding stroma. Hence, our findings may pave the way for further investigations to define the role of IL-8 as useful target for the better management of breast cancer patients exhibiting metabolic disorders.

WhatsApp video call communication between oncological patients and their families during COVID-19 outbreak.

BACKGROUND: On March 8th, 2020 the Italian Government implemented extraordinary measures to limit COVID-19 viral transmission. The aim of the study was to verify if the use of WhatsApp facilitates communication, improves health information, perception of safe and security, reduce emotional stress during the COVID-19 emergency. METHODS: In this study we identified two period, in the pre-COVID 1-month period (February 9th - March 8th, 2020) 34 patients underwent elective surgery for malignancies (21) and benign (13) diseases, respectively. We provided patients' families on a daily basis with clinical information face-to-face in the ward regarding their postoperative course. In the post-COVID 1-month period (March 9th - April 5th, 2020), 15 patients with malignancies were treated. In this period, patients and their families given a consent form to let the surgical team to communicate clinical data using WhatsApp. At the end of the study period we collected a satisfaction anonymous questionnaire of both patients and families. RESULTS: Statistically significant differences were observed in the pre- vs. post- COVID period regarding the number of surgical procedures (P=0.004). In the post-COVID period, the satisfaction questionnaire showed a good reliability (Cronbach's α 0.912) and a high percentage of satisfaction of patients and their families for the adopted communication tool, reassurance, privacy protection and reduction of emotional stress. CONCLUSIONS: WhatsApp is a safe and fast technology, it offers the opportunity to facilitate clinical communications, reduce stress, improve patient security, obtain clinical and psychological positive implications in patient's care preserving their privacy in the COVID-19 emergency period.

Minimally Invasive Stage 1 to Protect Against the Risk of Liver Failure: Results from the Hepatocellular Carcinoma Series of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Italian Registry.

Introduction: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been described to treat hepatocellular carcinoma (HCC) but burdened, in its pioneering phase, by high morbidity and mortality. With the advent of minimally invasive (MI) techniques in liver surgery, surgical complications, including posthepatectomy liver failure (PHLF), have been dramatically reduced. The primary endpoint of this study was to compare the short-term outcomes of MI- versus open-ALPPS for HCC, with specific focus on PHLF. Methods: Data of patients submitted to ALPPS for HCC between 2012 and 2020 were identified from the ALPPS Italian Registry. Patients receiving an MI Stage 1 (MI-ALPPS) constituted the study group, whereas the patients who received an open Stage 1 (open-ALPPS) constituted the control group. Results: Sixty-six patients were enrolled from 12 Italian centers. Stage 1 of ALPPS was performed in 14 patients using an MI approach (21.2%). MI-ALPPS patients were discharged after Stage 1 at a significantly higher rate compared with open-ALPPS (78.6% versus 9.6%, P < .001). After Stage 2, major morbidity after MI-ALPPS was 8.3% compared with 28.6% reported after open-ALPPS. Mortality was nil after MI-ALPPS. Length of hospital stay was significantly shorter in MI-ALPPS (12 days versus 22 days, P < .001). Univariate logistic regression analysis (Firth method) found that both MI-ALPPS (odds ratio [OR] = 0.05, P = .040) and partial parenchymal transection (OR = 0.04, P = .027) were protective against PHLF. Conclusion: This national multicenter study showed that a less invasive approach to ALPPS first stage was associated with a lower overall risk of PHLF.

Acute Kidney Ischemic Injury in a Rat Model Treated by Human Omental Mesenchymal Stem Cells.

BACKGROUND: Mesenchymal stem cells (MSCs) may provide a novel clinical approach for acute kidney injury (AKI), which represents a severe health care condition. The human omentum is an important source of MSCs. We investigated the effects of human omental mesenchymal stem cells (HO-MSCs) after induction of ischemic AKI in a rat model. METHODS: The ischemic-reperfusion injury (IRI) was induced at reperfusion following a 45-minute clamping of renal vessels. Twenty animals were used in this study. Each rat was randomly assigned to 1 of 2 groups: G1 (control, n = 10; IRI infusion of phosphate buffer solution) or G2 (HO-MSCs, n = 10; IRI infusion of HO-MSCs). The infusions were performed in the parenchyma at reperfusion. Renal function at 1, 3, 5, and 7 days was assessed. At sacrifice, histologic samples were analyzed by light, and renal injury was graded. RESULTS: HO-MSCs induced an accelerated renal exocrine functional recovery, demonstrated by biochemical parameters and confirmed by histology showing that histopathological alterations associated with ischemic injury were less severe in cell-treated kidneys as compared with control groups (P < .05). The renal damage degree was significantly less in the animals of the HO-MSC group (P < .0001). CONCLUSIONS: These results suggest that HO-MSCs could be useful in the treatment of AKI in a rat model with possible potential implication in clinical setting.

The Italian National Registry for minimally invasive pancreatic surgery: an initiative of the Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS).

The value of minimally invasive pancreatic surgery (MIPS) is still uncertain, despite the growing number of publications, including reviews and meta-analyses, and the quick diffusion of these procedures worldwide. The Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS) was created under the auspices of three Scientific Societies: Associazione Italiana Studio Pancreas (AISP), Associazione Italiana Chirurgia Epato-Bilio-Pancreatica (AICEP, former IT-IHPBA), and Società Italiana di Chirurgia Endoscopica (SICE). The main aim of IGoMIPS is to develop and implement a national registry for MIPS. IGoMIPS was founded on February 22, 2019 in Pisa. The IGoMIPS registry became operational in September 2019, following approval by the Ethic Committees of founding Institutions, inscription into the Registry of Patient Registries (RoPR), and a wrap-up meeting held in Bologna during the Annual Congress of the Italian Surgical Society. During this meeting IGoMIPS members approved that the Italian Registry will provide data to the European Registry, while retaining the right to analyze and publish Italian data. An audience survey was also conducted to obtain information on perceived value and current implementation of MIPS in founding Institutions. MIPS is performed in 94.7% of IGoMIPS centers, including pancreaticoduodenectomy in 42.1%. Robotic assistance was employed in 52.6% of Institutions. The annual volume of MIPS was 6-10 cases in 38.9% of the centers, 11-20 cases in 16.7%, 21-30 cases in 22.2%, and > 30 cases in 22.2%. The registry was felt to be extremely important for both safety improvement and educational purposes by 94.5% of the centers.

Partial Portal Vein Arterialization to Treat Toxic Acute Liver Failure in Elderly Rats.

INTRODUCTION: Toxic acute liver failure can be fatal even after liver transplantation. Since there are data only in young rats, the aim of our study was to verify the effectiveness of the increase of oxygen to the liver by partial portal vein arterialization (PPVA) in elderly rats with acute liver failure induced by carbon tetrachloride (CCl4) intoxication. METHODS: Twenty elderly (30 months) Sprague-Dawley rats underwent a CCl4 intoxication (5 mL/kg). Animals were divided after 24 hours (n = 10 per group) to either undergo PPVA (G1, treated group) or be untreated (G2, control group). PPVA consisted of a shunt between the left renal artery and splenic vein after nephrectomy and spelnectomy. The G2 group animals underwent nephrectomy and splenectomy only. The 10-day survival was evaluated. Before euthanasia, blood samples from the portal vein were detected for blood gas analysis. Liver injury was evaluated by the serum alanine aminotransferase (ALT) and prothrombin time levels. Histology was done to evaluate the liver necrosis. Hepatocyte regeneration was assessed by the mitotic index at immunohistochemistry. RESULTS: The PPVA has resulted in a significant increase in the oxygen partial pressure and saturation in portal blood. A survival improvement at 10 days was registered in the PPVA-treated rats (90% vs 30%; P = .0065). After 24 hours from intoxication, ALT was high in both groups. A rapid decrease of ALT was observed in G1 as compared to G2. At the same time, livers showed a severe centrolobular necrosis. In the suviving G2 rats, a moderate necrosis was present, while only a mild necrosis was observed in the G1 rats. An higher mitotic index was detected in rats treated with PPVA. CONCLUSIONS: In our experimental study, the presence of oxygenated blood in the portal venous system following the PPVA procedure had positive effects on liver regeneration and rats' survival. The PPVA treatment had beneficial effects in elderly rats.

Siblings Diagnosed With Primary Neuroendocrine Tumor of the Left Hepatic Duct.

Primary left hepatic duct neuroendocrine tumors are extremely rare. We describe 2 cases of siblings, a 51-year-old brother and a 48-year-old sister, who were both diagnosed with primary left hepatic duct neuroendocrine tumor. Both patients underwent successful left hepatectomy and are both alive with no recurrence. For this rare malignancy, while definitive diagnosis is made only by histopathology, a margin-free surgical resection remains the only curative treatment modality to date.

Post-operative outcomes and predictors of mortality after colorectal cancer surgery in the very elderly patients.

BACKGROUND: The frailty of the very elderly patients who undergo surgery for colorectal cancer negatively influences postoperative mortality. This study aimed to identify risk factors for postoperative mortality in octogenarian and nonagenarian patients who underwent surgical treatment for colorectal cancer. METHODS: This is a single institution retrospective study. The primary outcomes were risk factors for postoperative mortality. The variables of the octogenarians and nonagenarians were compared by using t-test, chi-square test, and Fisher exact test. A multivariate logistic regression analysis was carried out on the combined cohorts. RESULTS: we identified 319 octogenarians and 43 nonagenarians (N = 362) who underwent surgery for colorectal cancer at the Sant'Orsola-Malpighi university hospital in Bologna between 2011 and 2015. The 30-day post-operative mortality was 6% (N = 18) among octogenarians and 21% (N = 9) for the nonagenarians.The groups significantly differed in the type of surgery (elective vs. urgent surgery, p < 0.0001), ASA score (p = 0.0003) and rates of 30-day postoperative mortality (6% vs. 21%, p = 0.0003).In the multivariate analysis ASA > III (OR 2.37, 95% CI [1.43-3.93], p < 0,001), and urgent surgery (OR 2.17, 95% CI [1.17-4.04], p = 0.014) were associated to post-operative mortality. On the contrary, pre-operative albumin≥3.4 g/dL (OR 0.14, 95% CI [0.05-0.52], p = 0.001) was associated with a protective effect on postoperative mortality. CONCLUSIONS: In the very elderly affected by colorectal cancer, preoperative nutritional status and pre-existing comorbidities, rather than age itself, should be considered as selection criteria for surgery. Preoperative improvement of nutritional status and ASA risk assessment may be beneficial for stratification of patients and ultimately for optimizing outcomes.

How Safe is Performing Cholecystectomy in the Oldest Old? A 15-year Retrospective Study from a Single Institution.

BACKGROUND: Globally, the number of people aged 80 years or over, the "oldest old," is the fastest growing population group. Because of the strong association between age and gallstone disease, both prevalence and incidence of this disease are increasing. The feasibility of the cholecystectomy in octogenarians has been evaluated in several studies that confirmed the safety of the operation. However, the safety of this procedure in nonagenarians is still controversial. The aim of this study was to evaluate the safety of cholecystectomies in nonagenarians and identify related predictors for postoperative hospital length of stay (LOS) and in-hospital mortality up to 30 days postoperatively. METHODS: More than 500 cholecystectomies, both open and laparoscopic, were performed between January 2000 and September 2015 at our institution in patients 80 years and older. These statistics include both elective and emergent admissions. A retrospective review of charts over the last 15 years was conducted to compare mortality and length of postoperative stay among two patient groups: 319 octogenarians and 36 nonagenarians. Parameters evaluated include demographics, surgical presentation, American Society of Anesthesiologists (ASA) score, main diagnosis, comorbidities, type of surgery performed, LOS and in-hospital mortality. All data were analyzed with STATA (v.13) software, using a multivariate logistic regression after determining the statistically significant variables through a stepwise regression. CONCLUSIONS: We found out that being nonagenarian, compared to octogenarian, is not a significant risk factor in terms of LOS and in-hospital mortality within 30 days postoperatively. Despite that, the mortality rate among nonagenarians is still remarkably high as almost every patient was admitted in an emergent setting. The most remarkable predictor for mortality among the two groups was an "afternoon/night emergency" surgical presentation (OR 25.5, CI 1.53-42.35, p = 0.02). Thus, the surgical emergency management for gallbladder disease at our institution should be critically reevaluated. Performing the procedure in laparoscopy predicted a significant reduction (-5 days, CI -8.5 to -1.4, p = 0.006) of LOS, while presenting with "gallbladder and bile duct stones" (+6.3 days, CI 1.5-11.1, p = 0.01) or "acalculous cholecystitis" (+4.7 days, CI 0.4-9.2, p = 0.03) had the opposite effect. Despite the remarkable mortality rate of our series, being nonagenarian should not be considered as a reason to avoid gallbladder surgery in case of need. Our study suggests that nonagenarians are more suitable surgical candidates than may have previously expected.

Mast cells positive to tryptase, endothelial cells positive to protease-activated receptor-2, and microvascular density correlate among themselves in hepatocellular carcinoma patients who have undergone surgery.

BACKGROUND: Mast cells (MCs) can stimulate angiogenesis, releasing several proangiogenic cytokines stored in their cytoplasm. In particular MCs can release tryptase, a potent in vivo and in vitro proangiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase phosphorylation. Nevertheless, no data are available concerning the relationship between MC density positive to tryptase (MCDPT), endothelial cells positive to PAR-2 forming microvascular density (PAR-2-MVD), and classical MVD (C-MVD) in hepatocellular carcinoma (HCC) angiogenesis. This study analyzed the correlation between MCDPT, PAR-2-MVD, and C-MVD, each correlated to the others and to the main clinicopathological features, in early HCC patients who underwent surgery. METHODS: A series of 53 HCC patients with early stage (stage 0 according to the Barcelona Clinic Liver Cancer Staging Classification) were selected and then underwent surgery. Tumor tissue samples were evaluated by means of immunohistochemistry and image analysis methods in terms of number of MCDPT, PAR-2-MVD, and C-MVD. RESULTS: A significant correlation between MCDPT, PAR-2-MVD, and C-MVD groups, each correlated to the others, was found by Pearson t-test analysis (r ranged from 0.67 to 0.81; P-value ranged from 0.01 to 0.03). No other significant correlation was found. CONCLUSION: Our in vivo pilot data suggest that MCDPT and PAR-2-MVD may play a role in HCC angiogenesis and could be further evaluated as a target of antiangiogenic therapy.

Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers.

Hepatic ischemia reperfusion injury (IRI) is not only a pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. Hepatic IRI can seriously impair liver function, even producing irreversible damage, which causes a cascade of multiple organ dysfunction. Many factors, including anaerobic metabolism, mitochondrial damage, oxidative stress and secretion of ROS, intracellular Ca(2+) overload, cytokines and chemokines produced by KCs and neutrophils, and NO, are involved in the regulation of hepatic IRI processes. Matrix Metalloproteinases (MMPs) can be an important mediator of early leukocyte recruitment and target in acute and chronic liver injury associated to ischemia. MMPs and neutrophil gelatinase-associated lipocalin (NGAL) could be used as markers of I-R injury severity stages. This review explores the relationship between factors and inflammatory pathways that characterize hepatic IRI, MMPs and current pharmacological approaches to this disease.

Liver resection for metastases from colorectal cancer in very elderly patients: New surgical horizons.

INTRODUCTION AND AIM: Patients with colorectal cancer (CRC) may develop liver metastases. Surgical resection remains the best treatment of choice for colorectal liver metastases (CRLM) according to resectability criteria, with a long-term survival of 25% up to 41% after 5 years. Advanced age is associated with a higher incidence and co-morbidity, particularly cardiovascular disease, as well as deteriorating physiological reserves. The aim of this study was to analyse the overall and disease-free survival for patients with CRLM according to their chronological age. METHODS: Patients with CRLM were enrolled in the study. Data on gender, age, co-morbidity, metastasis characteristics (number, size and total metastatic volume (TMV)), use of perioperative chemotherapy and operative and post-operative complications were collected. Then, according to recent World Health Organization (WHO) guidelines, the patients were grouped by age. Statistical analysis was performed using the software R (ver. 2.14.1). RESULTS: Hepatic resection was performed in 149 patients (21 patients in the very elderly group, 79 in the elderly group and 49 in the younger group). The three groups were comparable in terms of operative duration, transfusion rate, length of high-dependency unit (HDU) stay and post-operative hospital stay. The very elderly group showed a non-significant increase in post-operative morbidity. The 30-day and 60-day/inpatient mortality rates increased with age without any significant statistically difference between the three groups (very elderly group 4.8% and 4.8%; elderly group: 2.5% and 3.8%; and younger group 0% and 2%). At 5 years, the overall survival was 28.6% for very elderly patients (≥75 years), 33.3% for elderly patients (≥65 to <75 years) and 43.5% for younger patients (≤65 years). The 1-, 3- and 5-year disease-free survival was similar across the groups. CONCLUSIONS: Liver resection for CRLM in carefully selected patients above the age of 75 can be performed with acceptable morbidity and mortality rates, similar to those in younger patients. Moreover, the severity of CRLM in elderly patients is proven to be lesser than in younger patients. Thus, we can conclude that advanced chronological age cannot be considered a contraindication to hepatic resection for CRLM.