Blood homocysteine levels are increased in hepatocellular carcinoma patients with portal vein thrombosis. A single centre retrospective cohort study

Abstract Background Portal vein thrombosis (PVT) is reported in 10–40% of hepatocellular carcinoma (HCC) patients. The development of PVT is a multifactorial process, resulting from a reduction in portal blood flow and hypercoagulability. Methods We evaluated 44 HCC patients with PVT, 50 HCC patients without PVT and 50 healthy subjects. Homocysteine (Hcy), Vitamin B6, Vitamin B12 and folate were measured. Results Hcy in HCC patients with PVT is significant higher than the patients without PVT and controls subjects. Conclusion Total Hcy is a sensitive marker of PVT in patients with HCC

Aging and Parkinson's Disease: Inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis

In order to better understand the pathogenesis of Parkinson's Disease (PD) it is important to consider possible contributory factors inherent to the aging process, as age-related changes in a number of physiological systems (perhaps incurred within particular environments) appear to influence the onset and progression of neurodegenerative disorders. Accordingly, we posit that a principal mechanism underlying PD is inflammaging, i.e. the chronic inflammatory process characterized by an imbalance of pro- and anti-inflammatory mechanisms which has been recognized as operative in several age-related, and notably neurodegenerative diseases. Recent conceptualization suggests that inflammaging is part of the complex adaptive mechanisms (\ue2\u80\u9cre-modeling\ue2\u80\u9d) that are ongoing through the lifespan, and which function to prevent or mitigate endogenous processes of tissue disruption and degenerative change(s). The absence of an adequate anti-inflammatory response can fuel inflammaging, which propagates on both local (i.e.- from cell to cell) and systemic levels (e.g.- via exosomes and other molecules present in the blood). In general, this scenario is compatible with the hypothesis that inflammaging represents a hormetic or hormetic-like effect, in which low levels of inflammatory stress may prompt induction of anti-inflammatory mediators and mechanisms, while sustained pro-inflammatory stress incurs higher and more durable levels of inflammatory substances, which, in turn prompt a local-to-systemic effect and more diverse inflammatory response(s). Given this perspective, new treatments of PD may be envisioned that strategically are aimed at exerting hormetic effects to sustain anti-inflammatory responses, inclusive perhaps, of modulating the inflammatory influence of the gut microbiota

Le complicanze chirurgiche de trapianto renale. La laparoscopia può essere d'aiuto?

L incidenza delle complicanze chirurgiche del trapianto renale è notevolmente diminuita nel corso degli ultimi anni; e questo non solo grazie all evoluzione dei mezzi diagnostici e ad una migliore conoscenza dei farmaci immunosoppressori ma anche grazie all evoluzione delle tecniche chirurgiche. Le complicanze più comuni si verificano nella maggior parte dei casi nel precoce periodo postoperatorio, mentre altre si manifestano diversi anni dopo. L'inizio della moderna urologia è segnata da due tappe fondamentali, la prima nefrectomia laparoscopica per via transperitoneale che risal agli inizi degli anni Novanta, descritta da Clayman e la prima nefrectomia eseguita per via retroperitoneale eseguita nel 1993 da Gaur con accesso diretto senza passare attraverso la cavità peritoneale. Oggi la nefrectomia laparoscopica è un intervento largamente diffuso in quasi tutti i Centri che praticano routinariamente la chirurgia laparoscopica. Dopo una prima fase di incertezze, legata ad una ancora non ben nota conoscenza dei risultati a distanza, oggi questa procedura è indicata anche per patologie oncologiche. La tecnica della nefrectomia laparoscopica su donatore vivente ha rivoluzionato il trapianto renale, infatti permette, riducendo la morbilità chirurgica pur mantenendo le possibilità di un buon risultato nel ricevente, di aumentare il numero dei donatori. Questa tecnica divenuta il metodo di prelievo di riferimento nei centri di trapianti in tutto il mondo, non presenta controindicazioni assolute. Scopo della tesi sarà attraverso una revisione della letteratura, individuare l'evidenza clinica delle complicanze chirurgiche dopo prelievo renale rispetto alle precedenti tecniche con particolare attenzione ai diversi aspetti relativi sia al donatore che al ricevente in termini di morbilità e di mortalità. Sulla base di una attenta analisi dell'esperienza clinica si è focalizzata l'attenzione sui problemi tecnici legati al prelievo del rene, sulla comparsa di linfoceli, sulle complicanze vascolari, urinarie e su quelle di ordine generale. La casistica osservata include pazienti (maschi e femmine) di età media tra i 20-70 anni sottoposti ad intervento chirurgico eseguito per complicanze dopo prelievo renale laparoscopico e non, nel periodo che va dal 2003 al 2013. Sono stati raccolti e analizzati vari fattori, quali la tecnica operatoria precedentemente utilizzata, il tipo di complicanze, l'anno del prelievo, il tipo di trattamento effettuato per complicanze e il periodo post operatori

Multiple primary malignancies. A rare case of five metachronous tumours

The Authors report on a patient admitted several times for the occurrence of five multiple metachronous primary malignancies (laryngeal carcinoma, endometrial adenocarcinoma, rectal cancerous polyp, Vater papilla carcinoma and transverse colon cancer). All five carcinomas were independent primary cancers and the lenghty time intervals between the onsets of each individual tumours confirm their independent non-metastatic origin. Classification, pathogenesis, genetic and environmental interactions of these tumours are discussed; in the case reported a family history of colon cancer was present, while no genetic markers abnormalities or chronic exposure to carcinogens were found. The case report suggests that an aggressive, appropriate surgical approach together with a through follow-up monitoring offers a chance of long-term survival for patients with metachronous malignant primary tumours

Iatrogenic nerve lesion following laparoscopic surgery. A case report

Background: Peripheral neuropathy after surgical treatment is an under recognized potential untoward event. Pelvic surgery may be associated with nerve lesions by essentially three main mechanisms: transection, entrapment and pressure-stretching; the latter is the modality most frequently linked to patient's positioning on the operating room table. Presentation of the case: A 25 years old woman, after undergoing a laparoscopic gynaecologic procedure lasted >3 hours, on postoperative day one presented with numbness over her lateral right leg and dorsum of the foot, right foot drop and gait instability due to compression-stretching of the right superficial peroneal nerve. Discussion: Patient's diagnostic work up, treatment and outcome are reported and measures on how to prevent the occurrence of such type of lesion are outlined together with the importance of an early postoperative diagnosis in order to avoid permanent nerve damage. Conclusion: Such lesions are sometimes so unexpected that delayed diagnosis leads to damages which are difficult or impossible to repair. Primary prevention plays a key role and it is realized by adhering to specific protocols. In the occurrence of the lesion a prompt diagnosis is highly recommendable and a comprehensive therapeutic plan is necessary to correctly address the specific pathology

Gut–Liver Axis and Non-Alcoholic Fatty Liver Disease: A Vicious Circle of Dysfunctions Orchestrated by the Gut Microbiome

Non-alcoholic fatty liver disease (NAFLD) is a prevalent, multifactorial, and poorly understood liver disease with an increasing incidence worldwide. NAFLD is typically asymptomatic and coupled with other symptoms of metabolic syndrome. The prevalence of NAFLD is rising in tandem with the prevalence of obesity. In the Western hemisphere, NAFLD is one of the most prevalent causes of liver disease and liver transplantation. Recent research suggests that gut microbiome dysbiosis may play a significant role in the pathogenesis of NAFLD by dysregulating the gut–liver axis. The so-called “gut–liver axis” refers to the communication and feedback loop between the digestive system and the liver. Several pathological mechanisms characterized the alteration of the gut–liver axis, such as the impairment of the gut barrier and the increase of the intestinal permeability which result in endotoxemia and inflammation, and changes in bile acid profiles and metabolite levels produced by the gut microbiome. This review will explore the role of gut–liver axis disruption, mediated by gut microbiome dysbiosis, on NAFLD development

Predictive Value of the Number of Harvested Lymph Nodes and Cut-Off for Lymph Node Ratio in the Prognosis of Stage II and III Colorectal Cancer Patients

Purpose/aim: The appropriate staging of colorectal cancer requires at least 12 lymph nodes to be sampled. We evaluated whether lymph node sampling (LNS) and lymph node ratio (LNR) can predict the prognosis of stage II-III patients. Materials and methods: This is a retrospective study on 432 patients classified in LNS ≥12 and LNS <12. Disease-free survival (DFS) was computed using the Kaplan–Meier method. We stratified stage III patients into 4 quartiles base on LNR values. To determine the optimal LNR cut-off, receiver operating characteristic (ROC) curve analysis was performed. Results: There was a positive association between the number of lymph node sampled and the number of metastatic lymph nodes (p < 0.01). Among stage II patients, the DFS was 81% for LNS ≥ 12 and 72% for LNS < 12 (p = 0.158). Among stage III patients, the DFS was 58% (p < 0.001). We found a significant association between LNR quartiles and relapse in stage III patients but only in the LNS ≥ 12 group. ROC curve analysis indicated an ideal LNR cut-off value at 0.194 (sensitivity 65% and specificity 61%). The DFS of patients with LNR below 0.194 was 71%, and that of patients with LNR above 0.194 was 45% (log-rank test, p < 0.001). In the patients with LNS ≥ 12, the cut-off of 0.257 could predict recurrence (specificity 86%). Conclusions: Stage II patients with LNS < 12 tend to have shorter DFS than stage II patients with LNS ≥ 12. In stage III patients, an appropriate LNR cut-off is a better prognostic predictor than LNR quartile, especially in patients with LNS ≥ 12

Zebrafish embryo as avatar of patients with colorectal cancer and hepatic colorectal metastasis: preliminary experience toward a personalized medicine

Background: In the last years, a new concept of personalized medicine called ‘Mouse Avatars’ or ‘co-clinical trials’ has emerged, with the purpose to develop models to study the response of tumor to therapy on an individual basis. A big limitation of xenograft experiments in murine hosts is the requirement of immune-permissive strains and the long duration of time before the detection of human engrafted cells. We propose the use of rejection-free 0-5 days post fertilization (dpf) Zebrafish Avatars for patients affected by colorectal (CR) cancer or colorectal liver metastasis (CRLM), in alternative to the expensive, time consuming and high ethical impact models of nude mouse xenografts. The aim of the project is to evaluate the usability of Zebrafish embryos as avatar and to test the chemosensibility to the different chemotherapy schemes used for the treatment of patients affected by CR cancer or CRLM. Methods: Patients with CR cancer or CRLM were enrolled. For each enrolled patient, a fragment of the tumor was taken after the specimen removal. After its elaboration, the tissue, fluorescently labeled with Dil, is pushed inside the yolk of 2 dpf zebrafish. At 2 hours post-injection (hpi) transplanted embryos were distributed in 24-well plates and incubated in E3 media with the presence or absence of drugs. The transplanted embryos were exposed for 48 hours to the standard combinations of chemotherapy used for the treatment of colorectal cancer (5-FU, FOLFIRI, FOLFOX, FOLFOXIRI) added to E3 medium (treated grated zebrafish embryos subgroups – treated-ZE subgroups). The control grafted zebrafish embryos subgroup (control-ZE) was exposed only to E3 medium. Each subgroup (control-ZE vs treated-ZE) were composed by 10 zebrafish embryos. For each protocol, the human plasma equivalent concentration was used as reference and we used a conversion factor human-to-fish calculated with a toxicity/efficacy study on the zebrafish model. Every day the fluorescent cancer cells were imaged by microscopic observation to evaluate the effect of the drug of interest. We used mass progression/regression as primary measure and cell migration along the zebrafish embryos’ body and tail as secondary measure. A ratio between the tumor mass area at 2 hpi and 48 hpi was calculated for each ZE subgroup and compared to each other. The percentage of cell migration revealed in the grafted zebrafish of the control-ZE subgroup was compared with the percentage revealed in each treated-ZE subgroup. A p&lt;0.1 was considered statistically significant. Results: Ten patients with colon cancer (CR group) and two patients with colorectal liver metastasis (CRLM group) were enrolled between January 2018 and November 2018. In all cases of both CR and CRLM group the tumor cells successful grafted in the yolk sack of zebrafish embryos and in the control-ZE subgroup the tumor mass increased at 48 hpi respect 2 hpi in all cases. The mass progression/regression analysis revealed a statistically significant difference of tumor mass progression in the treated-ZE subgroups respect the control-ZE subgroup in 4/10 cases (40%) of CR group and 2/2 (100%) cases of CRLM group. In the CR group, one chemotherapy scheme was statistically more efficient in 2/10 cases, two chemotherapy schemes in 1/10 case and three chemotherapy schemes in 1/10 case. In the CRLM group, one chemotherapy scheme was statistically more efficient in 1 case while in the other case two chemotherapy schemes resulted more efficient. Cell migration was detected in a percentage of grafted zebrafish embryos of the control-ZE subgroup in 7/10 cases (70%) of CR group and in 2/2 cases (100%) of CRLM group. A significant reduction of the cell migration percentage in the treated-ZE subgroups compared to the control-ZE subgroup was revealed for almost one chemotherapy scheme in 7/7 cases of CR group and in 2/2 cases of CRLM group. In the CR group, the reduction of cell migration percentage was revealed for one chemotherapy scheme in 3/7 cases, for two and three chemotherapy schemes in 1/7 case and for all chemotherapy schemes in 2/4 cases. In the CRLM group, the reduction of cell migration percentage was revealed for three chemotherapy schemes in one case and for all in the other case. Conclusions: In our experience, zebrafish embryos could be a model as avatar for oncological patients because in all cases the tumor cells successful grafted in the yolk sack of zebrafish embryos. Probably the protocol used for the tests of chemosensibility should be improved and better defined the human-to-fish dose. Since we have noticed a tendency to inhibit the tumor cells proliferation by the chemotherapy treatments without reaching statistically significant, we have already tried to increase the chemotherapy doses with the intent to reach it. Moreover, a prospective co-clinical trial is under way to evaluate the concordance between the results of tests in zebrafish and the response to chemotherapy in oncological patients