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• Circadian rhythm was previously shown to correlate with treatment toxicity. • Such findings could not be reproduced in this institutional cohort. • This is the first study investigating the impact of seasons on treatment toxicity. • Radiotherapy delivery in the darker half of the year yielded higher acute toxicity. The potential impact of the daytime and season of radiotherapy application on acute and late toxicity burden was analyzed on a cohort of curatively treated head and neck squamous cell carcinoma patients. Through a retrospective chart review, patient and tumor characteristics, treatment parameters and outcome were obtained. Patients treated with definitive or adjuvant radiotherapy with and without chemotherapy receiving ≥60 Gy between 2002 and 2015 were included (n = 617). Daily fraction times and dates were extracted. Median radiotherapy delivery time of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by the median day of the treatment course. Each year was divided into DARK and LIGHT by the March and September equinoxes. Acute (T) and late (A) toxicity were defined by TAME methodology. Median follow-up was 51 months. Mean T and A scores during and after radiotherapy in DARK vs. LIGHT were 1.98 vs. 1.61 (p = 0.0127) and 0.41 vs. 0.30 (p = 0.1699), respectively. Mean T and A scores during and after AM vs. PM radiotherapy were 1.71 vs. 1.88 (p = 0.0387) and 0.31 vs. 0.41 (p = 0.2638), respectively. Multivariate analyses indicated DARK vs. LIGHT as the only independent treatment time-related factor among other factors such as tumor subsite, UICC stage, radiotherapy technique, and chemotherapy for T. This is the first study investigating the impact of seasonality on toxicity burden, showing higher acute toxicity with radiotherapy in DARK. The daytime did not predict the toxicity. The hypothesis-generating findings of this retrospective study should be further investigated. [ABSTRACT FROM AUTHOR]

• Circadian rhythm was previously shown to correlate with treatment toxicity. • This is the first study investigating the impact of seasons on oncologic outcome. • Radiotherapy delivery in the darker half of the year yields better tumor control. The potential impact of daytime and season of radiotherapy application on prognosis is unclear. This was analyzed in a retrospective cohort of patients who were diagnosed with non-metastatic head and neck squamous cell carcinoma (HNSCC) and treated with definitive radiotherapy with or without chemotherapy. Patient and tumor characteristics, treatment parameters and outcome until last follow-up or death were obtained. Median radiotherapy delivery daytime of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by median date of treatment course. Each year was divided into DARK and LIGHT according to equinoxes. Time-to-event endpoints were defined by first biopsy confirming the HNSCC. Six hundred fifty-five cases were identified who were treated with (chemo)radiotherapy between 2002 and 2015. Median follow-up was 47 months. No significant heterogeneity in patient, tumor and treatment characteristics were observed between DARK and LIGHT or regarding median daily fraction time (X2 p > 0.05). Five-year loco-regional control (73% vs. 61%; p = 0.0108) and progression-free survival (51% vs. 43%; p = 0.0374) were superior when radiotherapy was administered in DARK. Neither the daytime nor any other treatment time-related parameter affected prognosis. This is the first study investigating and presenting the prognostic impact of seasonality regarding the treatment course on loco-regional control and progression-free survival (DARK > LIGHT). The biological mechanism of action is unclear. These results should be interpreted with caution and our findings have to be validated externally. [ABSTRACT FROM AUTHOR]

Objective Signaling molecules derived from osteocytes have been proposed as a mechanism by which autografts contribute to bone regeneration. However, there have been no studies that determined the role of osteocytes in bone grafts. Material and method Herein, it was examined whether bone chips and demineralized bone matrix release sclerostin and FGF-23, both of which are highly expressed by osteocytes. Results Bone grafts from seven donors were placed in culture medium. Immunoassay showed that bone chips released sclerostin (median 1.0 ng/ml) and FGF-23 (median 9.8 relative units/ml) within the first day, with declining levels overtime. Demineralized bone matrix also released detectable amounts of sclerostin into culture medium, while FGF-23 remained close to the detection limit. In vitro expanded isolated bone cells failed to release detectable amounts of sclerostin and FGF-23. Conclusion These results suggest that autografts but also demineralized bone matrix can release signaling molecules that are characteristically produced by osteocytes. [ABSTRACT FROM AUTHOR]

The developing brain is vulnerable to the effects of ethanol. Glutamate is the main mediator of excitatory signals in the brain and is probably involved in most aspects of normal brain function during development. The aim of this study was to investigate vulnerability to and the impact of ethanol toxicity on glutamate uptake signaling in adolescent rats after moderate pre and postnatal ethanol exposure. Pregnant female rats were divided into three groups and treated only with water (control), non-alcoholic beer (vehicle) or 10% (v/v) beer solution (moderate prenatal alcohol exposure—MPAE). Thirty days after birth, adolescent male offspring were submitted to hippocampal acute slice procedure. We assayed glutamate uptake and measured glutathione content and also quantified glial glutamate transporters (EAAT 1 and EAAT 2). The glutamate system vulnerability was tested with different acute ethanol doses in naïve rats and compared with the MPAE group. We also performed a (lipopolysaccharide-challenge (LPS-challenge) with all groups to test the glutamate uptake response after an insult. The MPAE group presented a decrease in glutamate uptake corroborating a decrease in glutathione (GSH) content. The reduction in GSH content suggests oxidative damage after acute ethanol exposure. The glial glutamate transporters were also altered after prenatal ethanol treatment, suggesting a disturbance in glutamate signaling. This study indicates that impairment of glutamate uptake can be dose-dependent and the glutamate system has a higher vulnerability to ethanol toxicity after moderate ethanol exposure In utero. The effects of pre- and postnatal ethanol exposure can have long-lasting impacts on the glutamate system in adolescence and potentially into adulthood. [ABSTRACT FROM AUTHOR]

Highlights: [•] Prenatal alcohol exposure affects behavior (anxiety and cognition) in offspring. [•] The beer model was used to investigate moderate prenatal alcohol exposure. [•] Neuronal and glial targets were evaluated in hippocampus (NMDAR, NeuN, GFAP, S100B). [•] Results showed anxiolytic-like behavior and changes in memory/learning process. [•] NMDAR and S100B increments were observed in hippocampus. [ABSTRACT FROM AUTHOR]

Abstract: Hyperammonemia is a major element in the pathogenesis of hepatic encephalopathy (HE) and ammonia neurotoxicity involves an effect on the glutamatergic neurotransmitter system. Astrocytes are intimately related to glutamatergic neurotransmission and, in fact, many specific glial alterations have been reported as a result of ammonia exposure. S100B protein, particularly extracellular S100B, is used as a parameter of glial activation or commitment in several situations of brain injury. However, there is little information about this protein in ammonia toxicity and none about its secretion in astrocytes under ammonia exposure. In this study, we investigated S100B secretion in rat cortical astrocytes acutely exposed to ammonia, as well astrocyte morphology, glial fibrillary acidic protein (GFAP) content and glutamine synthetase (GS) activity. Moreover, we studied a possible effect of creatine on these glial parameters, since this compound has a putative role against ammonia toxicity in cell cultures. We found an increase in S100B secretion by astrocytes exposed to ammonia for 24h, accompanied by a decrease in GFAP content and GS activity. Since elevated and persistent extracellular S100B plays a toxic effect on neural cells, altered extracellular content of S100B induced by ammonia could contribute to the brain impairment observed in HE. Creatine addition did not prevent this increment in S100B secretion, but was able to prevent the decrease in GFAP content and GS activity induced by ammonia exposure. [Copyright &y& Elsevier]

Abstract: Background:: The use of orthotopic liver transplantation (OLT) for the treatment of patients with hepatocellular carcinoma (HCC) remains controversial because of the risk of both exclusion from the waiting list due to tumor progression and post OLT HCC recurrence. The aim of the present study was to evaluate the effect of an aggressive HCC treatment during the waiting list time on overall and recurrence-free survival of HCC transplanted patients in a single institutional study. Methods:: Since 1991, 40 HCC patients joined the OLT-waiting list. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. In all, 90% of the study group had HCC treatment while on the waiting list (transarterial chemoembolization, percutaneous therapies, chemotherapy). Results:: Only one patient (2.5%) was removed from the waiting list after developing neoplastic portal thrombosis 3 months after listing, while 33 (82.5%) underwent to OLT after a median waiting list time of 11 months (range 3–16 months). On histological examination, 42% of the group did not meet the “Milan criteria” and 42% were pTNM stages III and IV. The median follow-up was 42 months. The 5-year actuarial survival rate was 64% and recurrence-free survival was 91%. HCC recurred in only two patients (6%). Conclusions:: The use of routine pre-OLT tumor grading and of an aggressive HCC treatment during the waiting list, in our experience, resulted in a very low risk of pre OLT tumor progression leading to exclusion and of post OLT HCC recurrence. [Copyright &y& Elsevier]

Abstract: Objective: The objective of this study was to analyze experience on pediatric liver transplantation (LT) between June 1993 and September 2006, including split liver transplantation (SLT), living donor liver transplantation (LDLT), and auxiliary partial orthotopic liver transplantation (APOLT). Furthermore, hepatocyte transplantation (HT) had a role in one patient with metabolic disease. Methods: From November 1990 to September 2006, 657 LTs were performed including 63 pediatric LTs (9.6%) in 57 patients (32 boys and 25 girls). Six were retransplantations (9.5%). Thirty-two patients (57%) were younger than 5 years. The types of graft included the following: 26 whole organs (41%), 32 in situ split organs (51%), 4 reduced-size organs (6%), and 1 graft from a living donor (2%). Two patients received an APOLT, 4 patients received a combined kidney-liver transplantation (CKLT), and 1 patient received HT. Of the 63 pediatric LTs, 16 were behaved to be highly urgent (25%). Results: Overall 1-, 3-, 5-, and 10-year patient survival rates were 82%, 82%, 78%, and 78%, respectively. Overall 1-, 3-, 5-, and 10-year graft survival rates were 76%, 76%, 72%, and 72%, respectively. In patients younger than 1 year, the 5-year survival rate was 100%. Perioperative mortality was 8.8%. Vascular complications occurred in 4 patients (6.3%). Six children required retransplantation due to primary nonfunction (PNF) in 4 cases (7%) and vascular thrombosis in 2 cases (3.5%). Conclusions: Cholestatic liver disease and age younger than 1 year were the best prognostic factors for excellent survival. [Copyright &y& Elsevier]

The progressive increase in patients with end stage liver disease has lengthend the waiting- list for liver transplantation. Unfortunately this has not been followed by a suitable increase in the number of donors. The expanding “donor pool” has required use of “marginal” donors (ICU stay > 10 days, sepsi; steatosis > 30–40%, hypernatremia > 155 mmol/L, inotropic drugs). We report the case of a skier who remained for more than 1 hour in cardio-respiratory arrest under the snow; the 49-year-old women was extracted from the snow after 1 hour and 12 minutes and found to be asystolic, fixed pupils and deep hypothermia (27.2°C). After cardiopulmonary resuscitation, partial cardio-respiratory activity was re-established. In the ICU severe hypothermia (26.7°C) was treated with extracorporeal circulation until a re-establishment of satisfactory cardio-circulatory conditions was obtained. Unfortunately cerebral anoxic cerebral death was established and multiorgan procurement performed 3 days later. After liver transplantation into a 59 year-old patient with PNC–C was performed. The course was uneventful and the patient was discharged on the 19th postoperative day.: ConclusionsOrgan procurement from donors involved in accidental traumatic events with cardio-respiratory arrest and hypothermia, is similar to the non-heart-beating donor (NHBD) condition. Correct cardiopulmonary resuscitation and the use of extracorporeal circulation for gradual restoration of body temperature are necessary for optimal organ perfusion. In the present case the anoxic insult induced by the cessation of the cardio-respiratory function, was probably mitigated (if not even annulled) by the hypothermia. [Copyright &y& Elsevier]

Background: Therapeutic approach used for pancreatic ductal adenocarcinoma is usually translated also for the rarer acinar counterpart, which shows a different mutational landscape nevertheless. While dMMR/MSI-H status is rare in the ductal histotype, it appears to be more prevalent in pancreatic acinar cell carcinoma (PACC). Case presentation: We report the case of a patient with locally advanced MSI-H PACC in whom the treatment with the anti-PD-1 pembrolizumab, administered as third line, made possible surgical resection, achieving even an exceptional pathological complete response. Conclusions: Treatment of PACC should be tailored based on the peculiar molecular features that distinguish PACC from ductal adenocarcinoma. Evaluation of potentially therapeutically targetable alterations should be mandatory in case of PACC diagnosis. [ABSTRACT FROM AUTHOR]

Background: The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta‐analysis to estimate their predictive significance. Methods: A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included. Results: Seventeen studies reporting sufficient data met the inclusion criteria for meta‐analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD‐L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD‐L1 and CTLA‐4 were not correlated to the treatment response. Conclusion: This meta‐analysis indicated that high‐density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Textbook outcome (TO) is a novel composite measure that provides a comprehensive evaluation of a specific treatment which can be useful for procedures' standardization and reliable comparisons between different centers. This tool is gaining growing interest and widespread importance in many different fields. Considering liver surgery, however, an agreement was reached, and TO assessment was evaluated on a large scale only concerning liver resection. This study aimed to investigate the first TO for laparoscopic microwave ablation for hepatocellular carcinoma. Furthermore, the current study investigated the expendability of this tool for prognostic purposes. In the context of spreading interest in textbook outcome (TO) evaluation in different fields, we aimed to investigate an uncharted procedure, that is, laparoscopic microwave ablation (MWA) for hepatocellular carcinoma (HCC). Absence of post-MWA complications, a hospital stay of three days, no mortality nor readmission within 30 days, and complete response of the target lesion at post-MWA CT scan defined TO achievement. Patients treated between January 2014 and March 2021 were retrospectively reviewed, and of the 521 patients eligible for the study, 337 (64.7%) fulfilled all the quality indicators to achieve the TO. The absence of complications was the main limiting factor for accomplishing TO. At multivariable analysis, Child–Pugh B cirrhosis, age of more than 70 years old, three nodules, and MELD score ≥ 15 were associated with decreased probabilities of TO achievement. A score based on these factors was derived from multivariable analysis, and patients were divided into three risk groups for TO achievement. At survival analysis, overall survival (OS) was significantly (p = 0.001) higher in patients who achieved TO than those who did not. Moreover, OS evaluation in the three risk groups showed a trend coherent with TO achievement probability. The present study, having assessed the first TO for laparoscopic MWA for HCC, encourages further broader consensus on its definition and, on its basis, on the development of clinically relevant tools for managing treatment allocation. [ABSTRACT FROM AUTHOR]

Simple Summary: Anastomosis leakage is a serious postoperative complication after colorectal resection for ovarian cancer that can lead the delay of first line chemotherapy. Known risk factors for anastomosis leakage are age, Charlson Comorbidity Index, serum albumin level, prior chemotherapy or radiotherapy, number and length of bowel resection, level of anastomosis close to anal verge, absence of protective stoma. Intrabdominal drains and protective stoma may be used only in selected cancer ovarian patients undergoing debunking surgery with rectosigmoid resection. Objective: to evaluate the incidence of anastomotic leakage (AL), risk factors and utility of drainage and stoma in patients undergoing intestinal surgery for ovarian cancer in a single institution and in a review of the literature. Methods: retrospective study that includes consecutive patients undergoing debulking surgery with en bloc pelvic resection with rectosigmoid colectomy for ovarian cancer between 1 November 2011 and 31 December 2021. Data regarding patient and tumour characteristics, surgical procedure, hospitalisation, complications and follow-up were recorded and analysed. The PubMed database was explored for recent publications on this topic. Results: Seventy-five patients were enrolled in the study. All anastomoses were performed at a distance of >6 cm from the anal margin, with negative leak tests and tension-free anastomosis. Diverting stoma were performed in just three patients (4%). At least one perianastomotic pelvic drain was positioned in 71 patients (94.7%) and was removed on average on postoperative day 7. Four patients (5.3%) experienced AL. In all cases, the drain content was not the only sign of complication, as the clinical signs were also highly suggestive. Just one patient received conservative treatment. Average postoperative hospitalisation was 14.6 days (SD: ±9.7). There were no deaths at 30 and 60 days after surgery. Between the AL and non-AL groups, statistically significant differences were observed for age, Charlson Comorbidity Index, length of the intestinal resection and fitness for chemotherapy at 30 days. In ovarian cancer, rectosigmoid resection is a standardised procedure with comparable results for AL, and risk factors for AL are discretely homogeneous. What is neither homogeneous nor standardised according to the literature is the use of stomas and/or drains. Conclusion: use in the future of protective stoma and/or intra-abdominal drains is to be explored in selected and standardised situations to verify their preventive role. [ABSTRACT FROM AUTHOR]

Intraneuronal aggregates of neurofibrillary tangles (NFTs), together with beta-amyloid plaques and astrogliosis, are histological markers of Alzheimer’s disease (AD). The underlying mechanism of sporadic AD remains poorly understood, but abnormal hyperphosphorylation of tau protein is suggested to have a role in NFTs genesis, which leads to neuronal dysfunction and death. Okadaic acid (OKA), a strong inhibitor of protein phosphatase 2A, has been used to induce dementia similar to AD in rats. We herein investigated the effect of intracerebroventricular (ICV) infusion of OKA (100 and 200 ng) on hippocampal tau phosphorylation at Ser396, which is considered an important fibrillogenic tau protein site, and on glucose uptake, which is reduced early in AD. ICV infusion of OKA (at 200 ng) induced a spatial cognitive deficit, hippocampal astrogliosis (based on GFAP increment) and increase in tau phosphorylation at site 396 in this model. Moreover, we observed a decreased glucose uptake in the hippocampal slices of OKA-treated rats. In vitro exposure of hippocampal slices to OKA altered tau phosphorylation at site 396, without any associated change in glucose uptake activity. Taken together, these findings further our understanding of OKA neurotoxicity, in vivo and vitro , particularly with regard to the role of tau phosphorylation, and reinforce the importance of the OKA dementia model for studying the neurochemical alterations that may occur in AD, such as NFTs and glucose hypometabolism. [ABSTRACT FROM AUTHOR]

Background and Purpose Autografts are used for bone reconstruction in regenerative medicine including oral and maxillofacial surgery. Bone grafts release paracrine signals that can reach mesenchymal cells at defect sites. The impact of the paracrine signals on osteogenic, adipogenic, and chondrogenic differentiation of mesenchymal cells has remained unclear. Material and Methods Osteogenesis, adipogenesis, and chondrogenesis were studied with murine ST2 osteoblast progenitors, 3 T3- L1 preadipocytes, and ATDC5 prechondrogenic cells, respectively. Primary periodontal fibroblasts from the gingiva, from the periodontal ligament, and from bone were also included in the analysis. Cells were exposed to bone-conditioned medium ( BCM) that was prepared from porcine cortical bone chips. Results BCM inhibited osteogenic and adipogenic differentiation of ST2 and 3 T3- L1 cells, respectively, as shown by histological staining and gene expression. No substantial changes in the expression of chondrogenic genes were observed in ATDC5 cells. Primary periodontal fibroblasts also showed a robust decrease in alkaline phosphatase and peroxisome proliferator-activated receptor gamma ( PPARγ) expression when exposed to BCM. BCM also increased collagen type 10 expression. Pharmacologic blocking of transforming growth factor ( TGF)-β receptor type I kinase with SB431542 and the smad-3 inhibitor SIS3 at least partially reversed the effect of BCM on PPARγ and collagen type 10 expression. In support of BCM having TGF-β activity, the respective target genes were increasingly expressed in periodontal fibroblasts. Conclusions The present work is a pioneer study on the paracrine activity of bone grafts. The findings suggest that cortical bone chips release soluble signals that can modulate differentiation of mesenchymal cells in vitro at least partially involving TGF-β signaling. [ABSTRACT FROM AUTHOR]

Cigarette smoking is associated with a wide variety of adverse reproductive outcomes, including increased infant mortality and decreased birth weight. Prenatal exposure to tobacco smoke, of which nicotine is a major teratogenic component, has also been linked to the acceleration of the risk for different psychiatric disorders, including conduct disorder and attention deficit hyperactivity disorder (ADHD). Whether this increased risk is influenced by the direct effects of gestational nicotine exposure on the developing fetus remains uncertain. In this study we provide experimental evidence for the effects of prenatal nicotine exposure on measures of attention and impulsivity in adult male rats. Offspring of females exposed during pregnancy to 0.06 mg/ml nicotine solution as the only source of water (daily consumption: 69.6±1.4 ml/kg; nicotine blood level: 96.0±31.9 ng/ml) had lower birth weight and delayed sensorimotor development measured by negative geotaxis, righting reflex, and grip strength. In the 5-choice serial reaction time test, adult rats showed increased numbers of anticipatory responses and omissions errors, more variable response times, and lower accuracy with evidence of delayed learning of the task demands when the 1 s stimulus duration was introduced. In contrast, prenatal nicotine exposure had no effect on exploratory locomotion or delay-discounting test. Prenatal nicotine exposure increased expression of the D5 dopamine receptor gene in the striatum, but did not change expression of other dopamine-related genes (DRD4, DAT1, NR4A2, and TH) in either the striatum or the prefrontal cortex. These data suggest a direct effect of prenatal nicotine exposure on important aspects of attention, inhibitory control, or learning later in life. [ABSTRACT FROM AUTHOR]

Abstract: Background: Tumor progression before liver transplantation (OLT) is the main cause of dropout from the waiting list (WL) of patients with hepatocellular carcinoma (HCC). The aim of this study was to show a correlation between adopted dropout criteria and dropout/intention-to-treat survival rates of WL HCC patients. Methods: The study period was 2000 to 2007. The dropout criteria were macroscopic vascular invasion, metastases, or a poorly differentiated tumor. Adult patients with benign chronic liver disease enlisted for primary OLT in the same period represented the control group. Results: Dropout probability of study (n = 128) versus control group (n = 377) subjects was similar: namely, 12% at 1 year in both groups (P = NS). Intention-to-treat survival curve of the HCC group overlapped that of the benign group (5-year survival rates were 73% and 71%, respectively; P = NS). At the time of listing, 103 study group patients were within the Milan criteria (MC): among these patients, 29 (28%) showed tumor progression beyond MC before OLT. Simulating the dropout of these 29 patients at the time of diagnosis of tumor progression, we compared the dropout probability of the 103 patients within MC with that of the control group. As a result, the 1- and 2-year dropout rates became 37% and 53%, respectively, in the study group, which were significantly higher than those in the controls (P < .01). Conclusion: HCC patients on the WL showed a significantly greater dropout rate than subjects with benign cirrhosis when too restrictive radiologic dropout criteria were used. The adoption of criteria more related to biological aggressiveness of a tumor decreased the dropout risk for HCC patients without impairing their intention-to-treat survival rates. [Copyright &y& Elsevier]

Abstract: S100B expression, particularly extracellular S100B, is used as a parameter of glial activation and/or death in several situations of brain injury. Several immunoassays for S100B measurement are available, which differ with regard to specificity, sensitivity, sample application, and, of course, economic costs. We standardized two protocols for S100B measurement (range between 1.9pg and 10ng/mL) in human and rat samples from brain and adipose tissues, blood serum, cerebrospinal fluid, urine and cell culture. Abundance and secretion of this protein in adipose tissue reinforces the caution about its origin in blood serum. Interestingly, S100B recognition was affected by the redox status of the protein. This aspect should be considered in S100B measurement, assuming that oxidized and reduced forms possibly coexist in vivo and the equilibrium can be modified by oxidative stress of physiological or pathological conditions or even by obtaining sample conditions. [Copyright &y& Elsevier]

Introduction: Abdominal wall complications are common after kidney transplantation, and although they have a minor impact on patient and graft survival, they increase the patient's morbidity and may have an impact on quality of life. Abdominal wall complications have an overall incidence of 7.7–21%. Methods: This review will explore the natural history of abdominal wall complications in the kidney transplant setting, with a special focus on wound dehiscence and incisional herni, with a particular emphasis on risk factors, clinical characteristics, and treatment. Results: Many patient‐related risk factors have been suggested, including older age, obesity, and smoking, but kidney transplant recipients have an additional risk related to the use of immunosuppression. Wound dehiscence usually does not require surgical intervention. However, for deep dehiscence involving the fascial layer with concomitant infection, surgical treatment and/or negative pressure wound therapy may be required. Conclusions: Incisional hernia (IH) may affect 1.1–18% of kidney transplant recipients. Most patients require surgical treatment, either open or laparoscopic. Mesh repair is considered the gold standard for the treatment of IH, since it is associated with a low rate of postoperative complications and an acceptable rate of recurrence. Biologic mesh could be an attractive alternative in patients with graft exposition or infection. [ABSTRACT FROM AUTHOR]

Therapeutic options for blunt hepatic trauma include both non-operative and operative management. We have reviewed our experience of the management of blunt hepatic trauma, from non-operative to liver transplantation. A total of 72 patients with blunt hepatic injury observed at the first surgical unit of Padua in a 3-year period (1998–2000) were analysed; we also included a patient who had a liver transplant in 1993 for severe liver trauma. Twenty-nine patients (39.7%) were treated conservatively, with a 93% success rate; 60.3% were treated surgically. Suture hepatorraphy was the most common procedure performed (52.3%). Advantages of non-operative management in our experience were the reduced need for transfusion (1.1 U versus 4.3 U) with 92% of patients not needing transfusion, and a reduced stay in the intensive care unit; there was no liver-related mortality. The overall morbidity in surgical patients was 30%, with 16% liver-related complications. Twelve surgical patients (27.2%) died, with a liver-related mortality of 18.2%. A large number of patients may present with an associated endo-abdominal injury, even in low-grade liver trauma, requiring rapid laparotomy. In high-grade hepatic trauma, the evolution toward liver failure is an indication for liver transplantation. [Copyright &y& Elsevier]

Background: The aim of this retrospective comparative study was to assess the impact of COVID-19 and delayed emergency department access on emergency surgery outcomes, by comparing the main clinical outcomes in the period March–May 2019 (group 1) with the same period during the national COVID-19 lockdown in Italy (March–May 2020, group 2). Methods: A comparison (groups 1 versus 2) and subgroup analysis were performed between patients' demographic, medical history, surgical, clinical and management characteristics. Results: Two-hundred forty-six patients were included, 137 in group 1 and 109 in group 2 (p = 0.03). No significant differences were observed in the peri-operative characteristics of the two groups. A declared delay in access to hospital and preoperative SARS-CoV-2 infection rates were 15.5% and 5.8%, respectively in group 2. The overall morbidity (OR = 2.22, 95% CI 1.08–4.55, p = 0.03) and 30-day mortality (OR = 1.34, 95% CI 0.33–5.50, =0.68) were significantly higher in group 2. The delayed access cohort showed a close correlation with increased morbidity (OR = 3.19, 95% CI 0.89–11.44, p = 0.07), blood transfusion (OR = 5.13, 95% CI 1.05–25.15, p = 0.04) and 30-day mortality risk (OR = 8.00, 95% CI 1.01–63.23, p = 0.05). SARS-CoV-2-positive patients had higher risk of blood transfusion (20% vs 7.8%, p = 0.37) and ICU admissions (20% vs 2.6%, p = 0.17) and a longer median LOS (9 days vs 4 days, p = 0.11). Conclusions: This article provides enhanced understanding of the effects of the COVID-19 pandemic on patient access to emergency surgical care. Our findings suggest that COVID-19 changed the quality of surgical care with poorer prognosis and higher morbidity rates. Delayed emergency department access and a "filter effect" induced by a fear of COVID-19 infection in the population resulted in only the most severe cases reaching the emergency department in time. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To assess the indications and results of endoscopic retrograde cholangio-pancreatography (ERCP) in patients who have undergone ortotopic liver transplantation (OLT). Methods: We reviewed data from 42 consecutive patients who underwent ERCP for biliary complications after OLT over an 8-year period, in particular recording indications and success of the treatment after a mean of 17 months follow-up. Results: Cholangiograms performed in 33/42 patients (79%) displayed anastomotic strictures in 17 patients (52%), bile duct stones in 8 (24%), both bile duct stones and an anastomotic stricture in 2 (6%), papillary stenosis in 1 (3%), and anastomotic biliary leakage in 1 (3%). In contrast, the contrastogram was normal in four patients (12%). Stone extraction was completed in 9/10 patients (90%) with a mean of 1.2 sessions, while stricture dilation was achieved in 12/19 patients (63%) after a mean of 1.7 sessions, by stent positioning (n = 7), balloon dilation (n = 4), or Soehendra dilator (n = 1). Both biliary leakage and papillary stenosis were cured by ERCP. Only one procedure-related complication—severe pancreatitis (2.4%)—was observed and no mortality. Conclusion: ERCP is a safe and effective mode of management of bile duct complications after OLT. It should be attempted before a surgical approach. Better results are obtained for treatment of biliary stones than of anastomotic strictures. [Copyright &y& Elsevier]

Abstract: Background/aims: The aim of this retrospective study is to analyze the prognostic impact of Model for End-Stage Liver Disease (MELD) score in patients undergoing liver transplantation (OLT) with suboptimal livers. Methods: Between January 2002 and January 2006, 160 adult patients with liver cirrhosis received a whole liver for primary OLT at our institution including 81 with a suboptimal liver (SOL group) versus 79 with an optimal liver (group OL). The definition of suboptimal liver was: one major criterion (age >60 years, steatosis >20%) or at least two minor criteria: sodium >155 mEq/L, Intensive Care Unit stay >7 days, dopamine >10 μg/kg/min, abnormal liver tests, and relevant hemodynamic instability. Results: Baseline recipients characteristics were comparable in the two study groups. The SOL group had a significantly greater number of early graft deaths (<30 days) than the OL group, while the 3-year Kaplan-Meier patient survivals were similar. Using logistic regression, MELD score was significantly related to patient death only in the SOL group (P = .01), and the receiver operator characteristics curve method identified 17 as the best MELD cutoff with the 3-year survival of 93% versus 85% for MELD ≤7 versus >17, respectively (P > 05). In comparison, it was 94% and 72% in the SOL group (P < .05). Similarly, MELD >17 was significantly associated with early graft death rates only in the SOL group. Conclusion: This study advised surgeons to not use suboptimal livers for patients with advanced MELD scores, thus supporting a donor-recipient matching policy. [Copyright &y& Elsevier]

Abstract: Introduction: Liver transplantation represents the gold standard for the treatment of chronic liver disease. The whole transplantation process was assessed using an intention-to-treat analysis and considering patients from the time of their inclusion on the list and throughout lengthy follow-up. Materials and methods: From January 1, 1999 to June 1, 2004, 373 adults joined the waiting list for liver transplantation at our institution. The main variables analyzed were: age, gender, etiology, Model for End-stage Liver Disease score, Child-Pugh class, United Network for Organ Sharing (UNOS) status. Global survival was evaluated using intention-to-treat analysis from the time of patient inclusion in the list to the end of their late follow-up. Results: The median waiting time was 20 months (range 0.1 to 70.2). By univariate analysis, the variables significantly influencing survival when patients joined the waiting list were: encephalopathy; ascites, poor nutritional status, Child-Pugh class C, UNOS 2, hepatitis C virus (HCV) and bilirubin > 2 mg/dL. By multivariate analysis, only HCV-related cirrhosis emerged as having an independent prognostic value. By intention-to-treat analysis, the 5-year survival rate was 67% and 79% for HCV-positive and HCV-negative patients, respectively (P = .0003). Conclusions: HCV-related cirrhosis is an independent prognostic factor for survival according to an intention-to-treat analysis. Different inclusion criteria or treatments while on the waiting list and after transplantation need to be considered in the future for HCV-positive patients. [Copyright &y& Elsevier]

Background: Fluorescence imaging by means of Indocyanine green (ICG) has been applied to intraoperatively determine the perfusion of the anastomosis. The purpose of this Individual Participant Database meta-analysis was to assess the effectiveness in decreasing the incidence of anastomotic leak (AL) after rectal cancer surgery.Methods: We searched PubMed, Embase, Cochrane Library and ClinicalTrial.gov, EU Clinical Trials and ISRCTN registries on September 1st, 2019. We considered eligible those studies comparing the assessment of anastomotic perfusion during rectal cancer surgery by intraoperative use of ICG fluorescence compared with standard practice. We defined as primary outcome the incidence of AL at 30 days after surgery. The studies were assessed for quality by means of the ROBINS-I and the Cochrane risk tools. We calculated odds ratios (ORs) using the Individual patient data analysis, restricted to rectal lesions, according to original treatment allocation.Results: The review of the literature and international registries produced 15 published studies and 5 ongoing trials, for 9 of which the authors accepted to share individual participant data. 314 patients from two randomized trials, 452 from three prospective series and 564 from 4 non-randomized studies were included. Fluorescence imaging significantly reduced the incidence of AL (OR 0.341; 95% CI 0.220-0.530; p < 0.001), independent of age, gender, BMI, tumour and anastomotic distance from the anal verge and neoadjuvant therapy. Also, overall morbidity and reintervention rate were positively influenced by the use of ICG.Conclusions: The incidence of AL may be reduced when ICG fluorescence imaging is used to assess the perfusion of a colorectal anastomosis. Limitations relate to the consistent number of non-randomized studies included and their heterogeneity in defining and assessing AL. Ongoing large randomized studies will help to determine the exact role of routine ICG fluorescence imaging may decrease the incidence of AL in surgery for rectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: The advantages of biological meshes for ventral hernia repair are still under debate. Given the high financial cost, the proper indications for biological meshes should be clarified to restrict their use to properly selected patients.Methods: A retrospective database was instituted to register all cases of abdominal wall defect treated with biological meshes from 1/2010 to 3/2016.Results: A total of 227 patients (mean age: 64 years) whose ventral abdominal defects were reconstructed with a biological mesh were included in the study. Patients were divided according to the 2010 four-level surgical-site complication risk grading system proposed by the Ventral Hernia Working Group (VHWG): Grade 1 (G1, 12 cases), Grade 2 (G2, 68 cases), Grade 3 (G3, 112 cases), and Grade 4 (G4, 35 cases). The surgical site complication rate was higher in patients with one or more risk factors (33.6% vs 19% in patients with no risk factors) (P = 0.68). Statistically significant risk factors associated with the onset of one or more postoperative surgical site complications included: diabetes, coronary artery disease, immunosuppression, and obesity. Recurrence was more common in patients with surgical site complications and mainly associated with infection (38.9%) and wound necrosis (44.4%), and in cases of inlay positioning of the mesh (36%).Conclusions: Due to their high costs, biological mesh should not be used in G1 patients. In infected fields (G4), they should only be used if no other surgical solution is feasible. There is a clear need to prospectively evaluate the performance of biological meshes. [ABSTRACT FROM AUTHOR]

Gestational exposure to environmental toxins such as nicotine may result in detectable gene expression changes in later life. To investigate the direct toxic effects of prenatal nicotine exposure on later brain development, we have used transcriptomic analysis of striatal samples to identify gene expression differences between adolescent Lister Hooded rats exposed to nicotine in utero and controls. Using an additional group of animals matched for the reduced food intake experienced in the nicotine group, we were also able to assess the impact of imposed food-restriction on gene expression profiles. We found little evidence for a role of gestational nicotine exposure on altered gene expression in the striatum of adolescent offspring at a significance level of p<0.01 and |log2 fold change >0.5|, although we cannot exclude the possibility of nicotine-induced changes in other brain regions, or at other time points. We did, however, find marked gene expression differences in response to imposed food-restriction. Food-restriction resulted in significant group differences for a number of immediate early genes (IEGs) including Fos, Fosb, Fosl2, Arc, Junb, Nr4a1 and Nr4a3. These genes are associated with stress response pathways and therefore may reflect long-term effects of nutritional deprivation on the development of the stress system. [ABSTRACT FROM AUTHOR]

Abstract: Autism spectrum disorders (ASD) are characterized by deficits in social interaction, language and communication impairments and repetitive and stereotyped behaviors, with involvement of several areas of the central nervous system (CNS), including hippocampus. Although neurons have been the target of most studies reported in the literature, recently, considerable attention has been centered upon the functionality and plasticity of glial cells, particularly astrocytes. These cells participate in normal brain development and also in neuropathological processes. The present work investigated hippocampi from 15 (P15) and 120 (P120) days old male rats prenatally exposed to valproic acid (VPA) as an animal model of autism. Herein, we analyzed astrocytic parameters such as glutamate transporters and glutamate uptake, glutamine synthetase (GS) activity and glutathione (GSH) content. In the VPA group glutamate uptake was unchanged at P15 and increased 160% at P120; the protein expression of GLAST did not change neither in P15 nor in P120, while GLT1 decreased 40% at P15 and increased 92% at P120; GS activity increased 43% at P15 and decreased 28% at P120; GSH content was unaltered at P15 and had a 27% increase at P120. These data highlight that the astrocytic clearance and destination of glutamate in the synaptic cleft might be altered in autism, pointing out important aspects to be considered from both pathophysiologic and pharmacological approaches in ASD. [Copyright &y& Elsevier]

Abstract: Background/Aim: Prognosis assessment in surgical patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Barcelona Clinic Liver Cancer (BCLC) classification, but its prognostic ability in surgical patients has not been yet validated. The aim of this study was to investigate the value of known prognostic systems in 400 Italian HCC patients treated with radical surgical therapies. Methods: We analyzed a prospective database collection (400 surgical, 315 nonsurgical patients) observed at a single institution from 2000 and 2007. By using survival times as the only outcome measure (Kaplan–Meier method and Cox regression), the performance of the BCLC classification was compared with that of Okuda, Cancer of the Liver Italian Program, United Network for Organ sharing TNM, and Japan Integrated Staging Score staging systems. Results: Two hundred twenty-five patients underwent laparotomy resection; 55, laparoscopic procedures (ablation and/or resection); and 120, liver transplantations. In the surgical group, BCLC proved the best HCC prognostic system. Three-year survival rates of patients in BCLC Stages A, B, and C were 81%, 56%, and 44% respectively, (P < .01); whereas all other tested staging systems did not show significant stratification ability. When all 715 HCC patients were considered, surgery proved to be a significant survival predictor in each BCLC stage (A, B, and C). Conclusions: BCLC staging showed the best interpretation of the survival distribution in a surgical HCC population. The BCLC treatment algorithm should consider the role of surgery also for intermediate-advanced stages of liver disease. [Copyright &y& Elsevier]

Abstract: Background: The system that controls the waiting list (WL) and organ allocation for liver transplantation (OLT) seeks to achieve 3 main goals: objectivity, low dropout risks and good post-OLT results. We sought to prospectively validate a priority allocation model that is believed to achieve objectivity without penalizing dropout risk and post-OLT results. Methods: We evaluated a study group of 272 patients enrolled in 2006–2007. WL candidates were divided into 2 categories: cirrhotic patients classified according to Model for End-Stage Liver Disease (MELD) score (MELD list and patients with hepatocellular carcinoma (HCC) organized according to a specific score (non-MELD list). The allocation algorithm for donor–recipient match assigned an optimal graft to the first MELD candidate with a MELD score of ≥20; a suboptimal graft, to the first non-MELD patient. A respective control group of 327 patients transplanted from 2003–2006 was characterized by a unique WL with a free allocation policy. We performed an interim analysis of this prospectively controlled study. Results: Although the study group showed a lower percentage of OLT (P < .05) than the control group (37% vs 45%), it selected patients for OLT based on a higher MELD score (P < .05), thus obtaining similar dropout, post-OLT survivals, and intention-to-treat (ITT) survival probabilities as the controls. Among MELD patients, we observed a significantly reduced dropout and better ITT survival profiles than those of the control group (P = .02), whereas the similar results were delivered among non-MELD patients (P > .05). Among patients with a MELD score of ≥20, the prevalences of suboptimal grafts (0% vs 48%) and of early graft losses (0% vs 21%) were lower in the study than in the control group (P < .05). Conclusions: We prospectively validated a priority allocation model based on objective criteria that achieved high ITT survival rates. [Copyright &y& Elsevier]

Abstract  It is well established that the brain is particularly susceptible to oxidative damage due to its high consumption of oxygen and that astrocytes are involved in a variety of important activities for the nervous system, including a protective role against damage induced by reactive oxygen species (ROS). The use of antioxidant compounds, such as polyphenol resveratrol found in red wine, to improve endogenous antioxidant defenses has been proposed for neural protection. The aim of this study is to evaluate the putative protective effect of resveratrol against acute H2O2-induced oxidative stress in astrocyte cultures, evaluating ROS production, glutamate uptake activity, glutathione content and S100B secretion. Our results confirm the ability of resveratrol to counteract oxidative damage caused by H2O2, not only by its antioxidant properties, but also through the modulation of important glial functions, particularly improving glutamate uptake activity, increasing glutathione content and stimulating S100B secretion, which all contribute to the functional recovery after brain injury. [ABSTRACT FROM AUTHOR]

Abstract  Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenol present in grapes and red wine, which has antioxidant properties and a wide range of other biological effects. In this study, we investigated the effect of resveratrol, in a concentration range of 10–250 μM, on primary cortical astrocytes; evaluating cell morphology, parameters of glutamate metabolism such as glutamate uptake, glutamine synthetase activity and glutathione total content, and S100B secretion. Astrocyte cultures were prepared of cerebral cortex from neonate Wistar rats. Morphology was evaluated by phase-contrast microscopy and immunocytochemistry for glial fibrillary acidic protein (GFAP). Glutamate uptake was measured using l-[2,3-3H]glutamate. Glutamine synthetase and content of glutathione were measured by enzymatic colorimetric assays. S100B content was determined by ELISA. Typical polygonal morphology becomes stellated when astrocyte cultures were exposed to 250 μM resveratrol for 24 h. At concentration of 25 μM, resveratrol was able to increase glutamate uptake and glutathione content. Conversely, at 250 μM, resveratrol decreased glutamate uptake. Unexpectedly, resveratrol at this high concentration increased glutamine synthetase activity. Extracellular S100B increased from 50 μM upwards. Our findings reinforce the protective role of this compound in some brain disorders, particularly those involving glutamate toxicity. However, the underlying mechanisms of these changes are not clear at the moment and it is necessary caution with its administration because elevated levels of this compound could contribute to aggravate these conditions. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hepatitis C virus (HCV) reinfection after liver transplantation is a virtually constant finding and leads to chronic hepatitis and cirrhosis in variable proportions. This study aimed to assess the safety and efficacy of α-interferon (IFN) plus ribavirin for recurrent HCV following liver transplantation. Patients and Methods: Thirty of 55 patients (54.5%) with histologically proven HCV recurrence after liver transplantation were given antiviral therapy (α-IFN at a dose of 6 MU × 3 × week IM associated with oral ribavirin 1 g/d for 12 months) and followed up for a further 12 months after the end of the treatment. Liver and renal function tests, hemocytometric values, and HCV-RNA were assessed every 3 months throughout the therapy and follow-up. Liver biopsy was performed before and after the treatment and after another 12 months of follow-up. Results: Eight patients (26.7%) were withdrawn from the treatment due to adverse events and another 8 (26.7%) needed a dosage reduction. Eleven patients (36.7%) had a biochemical and virological response, becoming aminotransferase and HCV-RNA negative at the end of the treatment; 6 patients (20%) still had a sustained response after 12 months of follow-up. All 6 patients are clinically stable at 6 years after completing the antiviral therapy. A low viral load before therapy was a positive predictor of sustained response. No histologically significant improvement was seen at the end of the therapy or after the follow-up. Conclusions: The combination of α-IFN plus ribavirin induced a sustained virologic response in 20% of liver transplant recipients with recurrent HCV, but intolerance of the therapy prompted its discontinuation or a dosage reduction in a large proportion of patients. However, we have observed a long-term efficacy of the antiviral therapy in the sustained responders. [Copyright &y& Elsevier]

Background/Aims: The Barcelona Clinic Liver Cancer (BCLC) classification offers a prognostic stratification of patients with hepatocellular carcinoma (HCC). We recently demonstrated the BCLC''s peculiar prognostic ability in a retrospective cohort of HCC patients. The aim of this study was to evaluate the BCLC system prospectively in a subsequent separate group of HCC patients enrolled at the same surgically oriented liver unit. Methods: One hundred and ninety-five consecutive HCC patients were prospectively enrolled and their liver disease was staged before therapy. Unlike the BCLC treatment protocol, nodule size and number were not used as absolute exclusion criteria for radical treatment. Predictors of survival were identified using the Cox model. Results: The median survival time was 23 months overall, and 53, 16, 7 and 3 months, respectively, for BCLC categories A, B, C, and D. In our cohort, BCLC had the best independent predictive power for survival when compared with the Okuda, CLIP, UNOS-TNM, and JIS prognostic systems (linear trend χ 2=43.01, likelihood χ 2=57.94, AIC 885.98). Moreover, the BCLC classification showed a better prognostic ability than the AJCC-TNM 2002 system in surgical patients. Conclusions: The discriminating power of BCLC staging was prospectively assessed in an Italian cohort of HCC patients treated mainly with radical therapies. [Copyright &y& Elsevier]

Background: This study aimed to evaluate the incidence of cystadenoma diagnosis in a series of laparoscopic treatments for nonparasitic liver cysts, as well as its management.Methods: From 1996 to 2004, 26 patients with a nonparasitic cyst of the liver were selected for laparoscopic liver surgery. Solitary nonparasitic liver cysts were, whenever feasible, completely enucleated.Results: In four patients, the histopathologic examination showed a cystadenoma. Three patients with 13, 9, and 12-cm cysts, respectively, had undergone complete enucleation of the lesion, with no evidence of recurrence in the follow-up visit. One patient with multicystic liver experienced a recurrence and required an open hepatic resection.Conclusions: When a complete laparoscopic enucleation of the cyst can be ensured, a strict follow-up assessment should be considered as the definitive treatment, with surgical intervention demanded only in the case of recurrence or high suspicion for malignancy. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is a high-fat, low-protein and low-carbohydrate diet included as medical practice against seizure disorders, particularly in children refractory to conventional anti-epileptic drug treatment. However, the molecular basis of its therapeutic effect remains unclear. Considering the growing evidence for the importance of glial cells for neuronal development, survival and plasticity, we investigated astrocyte protein markers from KD fed rats, in different regions of hippocampus, a brain structure commonly involved in seizure disorders. We found a transitory increment in GFAP in the CA3 hippocampal region, but not in the CA1 or dentate gyrus (DG). This change was not accompanied by changes in S100B content or glutamine synthetase activity. In order to evaluate possible hippocampal involvement we investigated spatial-cognitive behavior using the water-maze task. No changes were observed. This transitory gliosis in CA3 could be related to, or precede, other associated changes proposed to be involved in the attenuation of seizure disorders. These data reinforce the importance of hippocampal astrocytes as cell targets during KD feeding. [ABSTRACT FROM AUTHOR]

We report the first case of auxiliary partial orthotopic liver transplantation (APOLT) in a patient with isoniazid (INH)-related fulminant hepatic failure (FHF) with the aim to determine the ability of the native liver (NL) to recover after this particular toxic event. A 10-year-old boy with INH-related FHF underwent APOLT after left hepatectomy on the NL. Neurological status and liver function rapidly improved, but, on postoperative day 22, urgent re-transplantation was needed for graft–hepatic artery thrombosis (HAT) and the NL’s incapacity to sustain adequate liver function. Histological examination of the NL showed signs evident of its regeneration, however. In conclusion, though we faced the clinical failure of the NL functionally to sustain the patient in the presence of the graft HAT 3, weeks after APOLT, such a failure may be interpreted as time related. In fact, the histological picture in this particular case may suggest the potential for NL recovery after INH-related FHF. [ABSTRACT FROM AUTHOR]

Background: Alpha-fetoprotein (AFP) messenger RNA (mRNA) in the blood reflects the presence of circulating hepatocellular carcinoma (HCC) cells and is a sensitive marker of HCC extrahepatic metastases. The specificity of this molecular marker and its correlation with the main HCC clinical–pathological parameters remains controversial, however. Methods: AFPmRNA was determined in 50 HCC patients and in 50 patients with diagnosis of cirrhosis (6), or colon (24) or, pancreatic (20) carcinoma. HCC patients with clinically evident extrahepatic metastasis were excluded. HCC diagnosis was confirmed in all patients by histology on percutaneous biopsies or surgical specimens; pathological grading was assessed at the same time. Results: AFPmRNA was positive in 20 HCC patients (40%) and in 18 patients without HCC (36%). The presence of AFPmRNA in the blood correlated significantly with cholestatic indices (p<0.01), nodule size (p=0.03), vascular invasion (p=0.006) and moderately or poorly differentiated HCC (p<0.0001). Moreover, survival analysis showed a significant impact of AFPmRNA detection on overall (p=0.04) and recurrence-free survival (p=0.0007) after a median follow-up of 17 months. Conclusions: Although AFPmRNA is frequently detected in the blood, even in benign liver diseases or gastroenteric tumors, in HCC patients without clinical evidence of extrahepatic metastases it seemed to identify the biologically more aggressive tumors. [Copyright &y& Elsevier]

Background/Aims: Prognosis assessment in patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Okuda classification, but new staging systems (Cancer of the Liver Italian Program score, Chinese University Prognostic Index, French classification and Barcelona Clinic Liver Cancer, BCLC, staging) have been recently described. We investigated the value of known prognostic systems in the particular setting of a surgically oriented Liver Unit where 187 HCC Italian patients were mainly treated with radical therapies (resection and percutaneous ablation).Methods: A retrospective analysis of 187 HCCs observed at a single Institution from 1990 and 1999 was performed. By using survival time as the only outcome measure (Kaplan–Meier method and Cox regression), the performance of any prognostic system was assessed according the criteria of discriminatory and stratification abilities between different stages, homogeneity of survival within each stage and additional explanatory power respect to the other classifications.Results: In the particular cohort studied, BCLC proved the best HCC prognostic system. This was true for the whole study group and for the 2 subgroups of surgical and non-surgical patients.Conclusions: BCLC staging showed the best interpretation of the survival distribution in an HCC population comprising a large proportion of tumors treated with potentially radical therapies. [Copyright &y& Elsevier]

: IntroductionHepatocellular carcinoma (HCC) is one of the most common tumors worldwide. In the Western world the current epidemic of cirrhosis due to the hepatitis C virus (HCV) is increasing the number of new cases. Liver transplantation (OLTx) represents a radical treatment for HCC and the underlying cirrhosis. Whether adjuvant chemotherapy is indicated in the postoperative period to prevent recurrence is controversial.: Material and patientsForty-eight HCC patients underwent liver transplantation during 11 years, including 21 who were chemo-treated (CT) patients. Thirty-one patients (65%) had post-necrotic virus-C cirrhosis (PNC-C). Twenty-one cases (44%) were p-TNM stages III–IV, and 15 cases (31%) incidental HCC detected in the explanted liver. Seven HCV patients (15%) received chemotherapy (before 1998).: ResultsOne-, 3-, and 5-year overall survival rates were 100%, 85%, 79% (CT group), and 89%, 71%, 71% (no CT group), respectively. The HCV recurrence-free survival rates at 3, 6, and 12 months were 29%, 14%, 0% for the CT group, versus 76%, 38%, 25% for the no CT group (P = .005).: ConclusionsDiscontinuation of HCV-HCC patients by chemotherapeutic adjuvant protocols after transplantation appears rational due to the early hepatitis C recurrence confirmed in our series. Moreover, few studies have demonstrated that CT prolongs survival of HCC transplanted patients. New pharmacological approaches are necessary to solve these questions. [Copyright &y& Elsevier]

Background: The authors present their experience in the laparoscopic management of hepatic cysts and polycystic liver disease (PLD). Methods: Between January 1996 and January 2002, 16 patients underwent laparoscopic liver surgery. Indications were solitary giant cysts (n = 10) and PLD (n = 6). Data were collected retrospectively. Results: Laparoscopic fenestration was completed in 15 patients. Median operative time was 80 min. There was no deaths. Complications occurred in four patients: one patient with a solitary liver cyst experienced diarrhea, while a pleural effusion, a bleeding from the trocar-insertion site, and ascites occurred in three patients with PLD. Median follow-up was 34 months. There was one asymptomatic recurrence (11%) in one patient with a solitary cyst. Two patients with PLD had a symptomatic recurrence of a liver cyst. Conclusion: Laparoscopic fenestration could be the preferred treatment of solitary liver cysts and PLD. Adequate selection of patients and type of cystic liver together with a meticulous surgical technique are recommended. [ABSTRACT FROM AUTHOR]

Abstract: Background: Polycystic liver disease (PLD) is due to a genetic disorder and frequently coexists with polycystic kidney disease (PKD). If the cysts produce symptomatology owing to their number and size, many palliative treatments are available. When none of the liver parenchyma is spared, or kidney insufficiency is marked, the only potentially curable treatment is liver transplantation (LT). Case Report: A 49-year old woman, diagnosed with PLD and PKD, was listed in January 2008 for combined LT and kidney transplantation (KT). A compatible organ became available 8 months later. Despite preserved liver function, the patient''s clinical condition was poor; she experienced dyspnea, advanced anorexia, abdominal pain, and severe ascites. At LT, which took 9 hours and was performed using the classic technique, the liver was hard, massive in size (15.5 kg), and not dissociable from the vena cava. The postoperative course was complicated by many septic episodes, the last one being fatal for the patient at 4 months after transplantation. Discussion: LT for PLD in many series shows a high mortality rate. The Model for End-Stage Liver Disease (MELD) score does not stage patients properly, because liver function is usually preserved. The liver can achieve a massive size causing many symptoms, especially malnutrition and ascites; in this setting LT is the only possible treatment. Patients with a low MELD score undergo LT with severe malnutrition that predisposes them to greater susceptibility to sepsis. To identify predictor factors, beyond MELD criteria that relate to the increased liver volume before development of late symptoms is essential to expeditiously treat patients with the poorest prognosis to improve their outcomes. [Copyright &y& Elsevier]

Abstract: Tumor progression before orthotopic liver transplantation (OLT) is the main cause of dropouts from waiting lists among patients with hepatocellular carcinoma (HCC). Performing a porto-caval shunt (PCS) before parenchymal liver transection has the potential to allow an extended hepatectomy in patients with decompensated liver cirrhosis, reducing portal hyperflow and therefore the sinusoidal shear-stress on the remnant liver. We report the case of a 59-year-old man affected by hepatitis C virus (HCV)-related decompensated liver cirrhosis (Child Pugh score presentation, C-10; Model for End Stage Liver Disease score, 18) and HCC (2 lesions of 2 and 2.8 cm). The patient began the evaluation to join the OLT waiting list, but, in the 3 months required to complete the evaluation, he developed tumor progression: 3 HCC lesions, the largest 1 with a diameter of about 4.4 cm. These findings excluded transplantation criteria and the patient was referred to our center. After appropriate preoperative studies, the patient underwent a major liver resection (trisegmentectomy) after side-to-side PCS by interposition of an iliac vein graft from a cadaveric donor. The patient overcame the worsened severity of cirrhosis. After 6 months of follow-up, he developed 2 other HCC nodules. He was then included on the waiting list at our center, undergoing OLT from a cadaveric donor at 8 months after salvage treatment. At 36 months after OLT, he is alive and free from HCC recurrence. Associating a partial side-to-side PCS with hepatic resection may represent a potential salvage therapy for patients with decompensated cirrhosis and HCC progression beyond listing criteria for OLT. [Copyright &y& Elsevier]

Abstract: Introduction: Organ transplant recipients show an increased incidence of cancer ranging from 4% to 16% owing to several causes: immunosuppression, viral infection, individual predisposition, and so on. Materials and Methods: We retrospectively reviewed the records of 43/683 (6.3%) recipients of 734 liver transplants performed from November 1991 to November 2008 who experienced a de novo neoplasm. Conclusion: Alcohol abuse significantly increased the rate of all de novo neoplasms and particularly pharyngogastroesophageal cancers among population of liver transplant recipients. Minimization of immunosuppressive therapy is necessary to reduce the risk of a de novo neoplasm. Strict posttransplant follow-up is required to identify early gastroenteric tumors. [Copyright &y& Elsevier]

Abstract: Liver transplantation still represents the only effective treatment for patients with liver failure, but many patients die while awaiting transplantation, even though many attempts have been made to increase the organ procurement rates and to partially support hepatic function in recent years. Our aim was to design an “open” ex vivo perfused liver model to simplify liver support using an isolated porcine liver perfused with arterial and portal blood from the recipient pig, while monitoring the metabolic capacity of the supporting graft. It was possible to perfuse the isolated liver for 6 hours as a bridging procedure with satisfactory hemodynamic homeostasis controlled by software biofeedbacks. [Copyright &y& Elsevier]

Abstract: Background/Aim: The main indications for combined liver and kidney transplantation (CLKT) are as follows: (1) cirrhosis with renal damage dependent or not upon liver disease, (2) renal failure with dialysis and concomitant liver end-stage disease, (3) congenital diseases, and (4) enzymatic liver deficiency with concomitant renal failure. The aim of this study was to evaluate our results with CLKT both in adult and pediatric patients. Methods: From September 1995 to September 2006, 15 CLKT (2.8%) among 541 liver transplantations included 4 pediatric patients (27%). The main indications for CLKT were hepatitis C virus (HCV) and polycystic diseases in adult patients, and primary hyperoxaluria in pediatric patients. Results: The double transplantation was performed from the same donor in all cases. All adult patients received whole liver grafts, whereas 3 split transplants and 1 whole liver graft were transplanted in the pediatric patients. Median liver and kidney cold ischemia times were 468 and 675 minutes, respectively. After a median follow-up of 36 months (range, 1–125), the overall survival rate was 80%. Five-year patient and graft survival rates were 100% for adult CLKT, whereas they were 50% for pediatric patients. We observed only 2 cases (18%) of delayed renal function, requiring temporary hemodialysis with progressive graft improvement. There was only 1 case of kidney retransplantation due to early graft nonfunction in a pediatric patient. Conclusion: Although CLKT is related to major surgical risks, results after transplantation are satisfactory with an evident immunological advantage. [Copyright &y& Elsevier]

: IntroductionHepatoblastoma (HEP) is the most frequent liver malignancy occurring in childhood. Surgical resection currently represents the gold standard for treatment. In patients with initially unresectable tumors, chemotherapy may induce remarkable reductions in size. In nonresponder patients, liver transplantation (OLTx) may offer a chance of cure.: Materials and methodsFrom 1990 to 2003, a total of 400 OLTx (31 pediatric transplants) have been performed at Padua University. Seven patients (4 males and 3 females) underwent OLTx for hepatoblastoma. All patients presented with bilobar liver involvement and had received chemotherapy according to the SIOPEL-1. In all patients preoperative staging was negative for extrahepatic involvement.: ResultsThe mean age of the pts was 8.2 years (range 6.4 months to 34 years). Mean follow-up after OLTx was 41.4 months (median 36, range 3 to 108 months). Actuarial patient survival rates after OLTx for hepatoblastoma are 83.3%, 83.3%, and 56% at 1, 3, and 5 years, respectively. Five of seven subjects with HEP are alive after transplant at 3, 12, 36, 65, and 108 months. Two patients died owing to recurrent disease after 6 and 60 months, respectively, from transplantation. Another subject, primarily treated with surgical resection, shows HEP recurrence at 40 months after OLTx. The remaining 4 patients are alive and well at a mean follow-up of 28 months (median 24, range 3 to 65 months).: ConclusionsLiver transplantation may represent a valid therapeutic option for patients with unresectable HEP, but it is contraindicated in cases of recurrence following previous resection surgery. Neo-adjuvant chemotherapy is of paramount importance to obtain good long-term results. [Copyright &y& Elsevier]

Abstract: Background and aim: Hepatitis C virus (HCV)-related cirrhosis is one of the leading indication for liver transplantation (LT) and a major risk factor for the development of hepatocellular carcinoma (HCC). HCV recurrence after LT is universal. This study evaluated HCV recurrence and survival in patients transplanted for HCV and HCC. Methods: We evaluated all adults transplanted for HCV cirrhosis between January 1999 and December 2006, HCC was diagnosed on the explant and HCV recurrence confirmed on protocol liver biopsies performed at 6 months and yearly after LT. The sustained viral response (SVR) was defined as HCV-RNA undetectable at 6 months after therapy discontinuation. The patient survival rates were assessed with Kaplan-Meier curves and the chi-square test was used when appropriate. Results: Two hundred sixteen patients underwent LT for HCV including 153 men and 63 women of mean age 54 years with a mean follow-up of 35 months. There were 71 (33%) HCC+ patients. At 1, 3, and 5 years from LT severe fibrosis (Scheuer 3–4) due to the HCV recurrence was reported in 18%, 14%, and 11% for HCC+ and 14%, 16%, and 28% for HCC− patients respectively (P = NS). HCC recurred only in 3 (4%) patients at a mean follow-up of 3 years. Patients who received antiviral treatment after LT were 10% HCC+ and 12% HCC− patients (P = NS). SVR was seen in 3/7 (43%) of HCC+ and in 10/18 (55%) of HCC− patients (P = NS). At 1, 3, and 5 years the patient survivals was 91%, 86%, and 86% for HCC+ and 94%, 86%, and 83% for HCC− patients, respectively (P = NS). Conclusions: Severe fibrosis due to HCV recurrence, which increases over time, involves one third of transplanted patients at 5 years after LT. The long-term survival was identical among HCC+ compared to HCC− recipients. The recurrence of HCC was negligible and did not affect patient survival. [Copyright &y& Elsevier]