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.

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.

Resection of hepatocellular carcinoma in elderly patients and the role of energy balance.

INTRODUCTION: Progressive functional impairment with age has a significant impact on perioperative risk management. Chronic liver diseases induce a strong oxidative stress; in the elderly, in particular, impaired elimination of free radicals leads to insufficient DNA repair. The events associated with a weak response to growth factors after hepatectomy leads to a decline in liver regeneration. Hypercholesterolemia is highly prevalent in the elderly, which may alter the coenzyme Q10 (CoQ) levels and in turn the cellular energy balance. This condition is commonly treated with statins. The aim of this study is to investigate the role of preoperative cellular energy balance in predicting hepatocellular carcinoma (HCC) postresection outcomes. MATERIALS AND METHODS: In a 5-year period (2009-2013), elderly patients with hypercholesterolemia, cardiovascular disease, and diabetes mellitus, undergoing HCC resection, were recruited and grouped by age (<75 and ≥ 75 years old). All patients were previously treated with statins. The risk factors associated with hospital morbidity/mortality and prolonged length of stay (LOS) were evaluated. RESULTS: Forty-five elderly patients were recruited and grouped according to their treatment: Group 1 (n = 23) was treated with statins alone (control group), whereas Group 2 (n = 22) was treated with statins and a CoQ analogue, 3 weeks from the surgery and at least a month later (experimental group). The majority of our patients were treated with atorvastatin [n = 28 (53.84%)] and the minority with simvastatin [n = 17 (32.69%)], 20 mg/day, for at least 3 years before the surgery. Perioperative mortality was observed in one patient of Group 1 (4.3%). Morbidities were noted in 13 patients of Group 1 (56.5%) and four patients of Group 2 (18.2%). The control group showed delayed functional recovery, muscle weakness, increased infection rate, and pleural effusion due to prolonged bed rest (hospital stay 13 days (7-19) vs. 8.5 days (5-12)), compared with the experimental group. The overall survival at 5 years was similar for both groups (n = 10 patients (43%) in Group 1 vs. n = 10 patients (45%) in Group 2). CONCLUSION: In the elderly population, survival is closely linked to postoperative morbidity and mortality. In our study, prolonged LOS was found to be related to delayed bioenergetic recovery. When limited, risk factors such as infections, neutropenia, and red blood cell transfusions could lower LOS and mortality of elderly patients with HCC. Higher age was associated with greater postoperative morbidity and successful hospital stay.

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.

Optimizing Patient Surgical Management Using WhatsApp Application in the Italian Healthcare System.

INTRODUCTION: Smartphones changed the method by which doctors communicate with each other, offer modern functionalities sensitive to the context of use, and can represent a valuable ally in the healthcare system. Studies have shown that WhatsApp™ application can facilitate communication within the healthcare team and provide the attending physician a constant oversight of activities performed by junior team members. The aim of the study was to use WhatsApp between two distant surgical teams involved in a program of elective surgery to verify if it facilitates communication, enhances learning, and improves patient care preserving their privacy. METHODS: We conducted a focused group of surgeons over a 28-month period (from March 2013 to July 2015), and from September 2014 to July 2015, a group of selected specialists communicated healthcare matters through the newly founded "WhatsApp Surgery Group." Each patient enrolled in the study signed a consent form to let the team communicate his/her clinical data using WhatsApp. Communication between team members, response times, and types of messages were evaluated. RESULTS: Forty six (n = 46) patients were enrolled in the study. A total of 1,053 images were used with an average of 78 images for each patient (range 41-143). 125 h of communication were recorded, generating 354 communication events. The expert surgeon had received the highest number of questions (P, 0.001), while the residents asked clinical questions (P, 0.001) and were the fastest responders to communications (P, 0.001). CONCLUSION: Our study investigated how two distant clinical teams may exploit such a communication system and quantifies both the direction and type of communication between surgeons. WhatsApp is a low cost, secure, and fast technology and it offers the opportunity to facilitate clinical and nonclinical communications, enhance learning, and improve patient care preserving their privacy.

Metastases of pancreatic adenocarcinoma: A systematic review of literature and a new functional concept.

INTRODUCTION: Pancreatic cancer, especially Pancreatic Adenocarcinoma, is still associated with a high mortality and morbidity for affected patients notwithstanding considerable progresses in diagnosis and both surgical pharmacological therapy. Despite metastases from colorectal, gastric and neuroendocrine primary tumor and their treatment are widely reported, the literature has been rarely investigated the impact of localization and numbers of pancreatic metastases. This study performed a systematic analysis of the most recent scientific literature on the natural history of Pancreatic Adenocarcinoma focusing attention on the role that the "M" parameter has on a possible prognostic stratification of these patients. MATERIAL AND METHODS: PubMed and Science Direct databases were searched for relevant articles on these issue. RESULTS: Initial database searches yielded 7231 studies from PubMed and 29101 from Science Direct. We evaluated 1031 eligible full text articles. CONCLUSIONS: An updated insight into the world of Pancreatic Tumors might help physicians in better evaluating mechanisms of metastases, patients selection and survival and in programming appropriate interventions to modify the worst outcomes of advanced disease.

Surgical resection of synchronous and metachronous metastases from pancreatic adenocarcinoma. Two case reports in the light of recent evidences.

UNLABELLED: Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related mortality in the western countries for both men and women. Until in 2015, it remains one of the most challenging malignancies with a dismal prognosis and limited therapeutic options. The 5-year survival rate for pancreatic cancer is around 5%, which is the lowest among all different cancer sites. The poor prognosis of PDAC is largely attributed to delayed diagnosis due to nonspecific symptoms in the early stages of the disease, biological aggressiveness leading to rapid metastases, lack of effective screening methods, and resistance to radiation and chemotherapies. In the event of metastases, patients were traditionally referred to palliative treatments. Thanks to continuous progresses in the surgical expertise, synchronous and metachronous metastases resections seem technically feasible nowadays. These reports describe 2 several clinical cases in which patients with Pancreatic Adenocarcinoma, and synchronous and metachronous liver metastases respectively, were treated with a surgical approach. Patients showed a better survival rate compared current data in the literature. Our results, often in conflict with the guidelines and recent evidences, confirm the need for a new vision of the metastases "problem" in patients with Pancreatic Adenocarcinoma. KEY WORDS: Metastases, Pancreatic Adenocarcinoma, Surgical resection.

Portal blood arterialization with an extracorporeal device to treat toxic acute hepatic failure in a swine model.

PURPOSE: This study aimed to determine whether a controlled portal blood arterialization by a liver extracorporeal device (L.E.O2 NARDO) is effective in treating acute hepatic failure (AHF) induced through CCl4 administration in a swine model. METHODS: 20 swine with AHF induced by intraperitoneal injection of carbon tetrachloride (CCl4) in oil solution, were randomly divided into two groups: animals receiving L.E.O2 NARDO treatment 48 h after the intoxication (study group); animals sham operated 48 h after the intoxication (control group). Blood was withdrawn from the iliac artery and reversed in the portal venous system by an interposed extracorporeal device. Each treatment lasted 6 h. The survival was assessed at 5 days after L.E.O2 NARDO treatment or sham operation. In both groups blood samples were collected for biochemical analysis at different time points and liver biopsies were collected 48 h after intoxication and at sacrifice. RESULTS: We observed decreased transaminases levels and a more rapid INR recovery in the study group, as compared to the control group. Eight animals of the study group vs. two animals of the control group survived at five days after surgery with a statistically significant difference (p<0.05). Liver biopsies performed at sacrifice showed a reduction of the damaged hepatic areas in the study group as compared to the control group. CONCLUSIONS: Arterial blood supply in the portal system through the L.E.O2 NARDO device is easily applicable, efficacious, and safe in a swine model of AHF induced by CCl4 intoxication.