Segmental Distribution of Hepatocellular Carcinoma Correlates with Microvascular Invasion in Liver Explants Undergoing Transplantation

Introduction: Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor after liver transplantation and/or resection. Any correlation between MVI and segmental location of HCC has yet to be studied. Our aim is to evaluate the segmental location of HCC and any correlation with the presence of MVI, portal vein thrombosis (PVT) in explanted livers, and the recurrence of HCC after transplantation. Another objective of the study is to assess the treatment history (ablation or transarterial chemoembolization (TACE)) and size of the tumor with respect to the risk of MVI. Methods: A single center, retrospective chart review, including 98 HCC patients, aged 18 years and older who had liver transplantation in our institute between 2012 and 2017. We reviewed the radiological images of the HCC tumors, the pathological findings of the explanted livers, and the follow-up imaging after transplantation. Results: 98 patients with the diagnosis of HCC underwent liver transplantation between 2012 and 2017. The mean age of the cohort was 63 +/- 8.2. Males represented 75% and Caucasian race represented 75% of the cohort. The most common etiology of cirrhosis was chronic hepatitis C virus infection followed by alcohol abuse and nonalcoholic steatohepatitis (NASH) with percentages of 50%, 23%, and 10%, respectively. Microvascular invasion was found in 16% of the patients while PVT and the recurrence of HCC were found in 17% and 6 % of the cohort, respectively. MVI was found in 10 single HCC and 6 multifocal HCC. Right lobe HCC had more MVI when compared to the left and multilobar HCC, with percentages of 11%, 2%, and 3%, respectively. Localization of HCC in segment 8 was associated with the highest percentage of MVI when compared to all other segments. The risk of MVI in segment 8 HCC was 3.5 times higher than the risk from the other segments (p=0.002) while no vascular invasion was found in segments 1, 3, and 5. The risk of vascular invasion in untreated HCC is 3 times the risk in treated HCC (P=0.03). Conclusion: Our data indicate that the risk of microvascular invasion is highest in tumors localized to segment 8. The size and number of HCC tumors were not associated with an increased risk of microvascular invasion

Video Capsule Endoscopy in the Assessment of Portal Hypertensive Enteropathy

Background. The features of the portal hypertension enteropathy (PHE) vary from mild mucosal changes to varices with or without bleeding. The prevalence and the development are not fully understood. Aim. Our aim is to examine the prevalence and the different manifestations of PHE using video capsule endoscopy (VCE). Methods. It is a single center retrospective study of patients with cirrhosis, who had VCE. Based on the published literature, we divided the PHE lesions into vascular lesions and mucosal lesions. Results. Of the 100 patients with cirrhosis that had a VCE study, the mean age was 62.82 years. Male gender was predominant (64%), while Caucasians represented 82% of the cohort. The most common etiology of cirrhosis was chronic alcohol abuse followed by chronic hepatitis C virus and nonalcoholic steatohepatitis. VCE detected small bowel lesions in 71% of the patients while the features of PHE were found in 65% from the total cohort. AVMs and inflammatory changes were the most common findings, followed by bleeding. More than 50% of the lesions were vascular in nature. The risk of finding PHE in decompensated cirrhosis is twice that in compensated cirrhosis. Forty-five patients had negative EGD exam for any active bleeding, esophageal varices, portal hypertensive gastropathy, or gastric varices. Of these, 69% had features of PHE in their VCE. Conclusions. VCE detected small bowel lesions in 71% of our cohort. There is a high prevalence of PHE in decompensated cirrhosis. Vascular lesions are the most common finding in the small bowel of this population

Nano-Encapsulation of Arsenic Trioxide Enhances Efficacy against Murine Lymphoma Model while Minimizing Its Impact on Ovarian Reserve <em>In Vitro</em> and <em>In Vivo</em>

<div><p>Advances in cancer therapy have increased the rate of survival of young cancer patients; however, female lymphoma patients frequently face a temporary or permanent loss of fertility when treated with traditional cytotoxic agents. The potential loss of fertility is an important concern that can influence treatment decisions for many premenopausal cancer patients. The negative effect of chemotherapeutic agents and treatment protocols to patients’ fertility–referred to as fertotoxicity–are thus an increasingly important cancer survivorship issue. We have developed a novel nanoscale formulation of arsenic trioxide, a potent drug for treatment of hematological malignancies, and demonstrate that it has significantly better activity in a murine lymphoma model than the free drug. In parallel, we have developed a novel <i>in vitro</i> assay of ovarian follicle function that predicts <i>in vivo</i> ovarian toxicity of therapeutic agents. Our results reveal that the nanotherapeutic agent is not only more active against lymphoma, but is fertoprotective, i.e., it is much less deleterious to ovarian function than the parent drug. Thus, our <i>in vitro</i> assay allows rapid evaluation of both established and experimental anticancer drugs on ovarian reserve and can inform the selection of efficacious and fertility-sparing treatment regimens for reproductive-age women diagnosed with cancer.</p> </div

NB(Ni,As) inhibits mantle cell lymphoma growth.

<p>18 days after inoculation with Z138C lymphoma cells, Rag2M mice were randomized and treated with weekly injections of NB(NaCl), As₂O₃ (4, 6, or 8 mg/kg), or NB(Ni,As) (4, 6, or 8 mg/kg). (A) Tumors treated with NB(Ni,As) were significantly smaller than those treated with NB(NaCl). **, <i>P</i>>0.01, ***, <i>P</i>>0.001. Arrows indicate treatment. (B) Weight was monitored daily during the treatment period. Injection of As₂O₃ was acutely toxic, whereas mice injected with NB(NaCl) showed normal weight gain. Mice injected with any dose of NB(Ni,As) lost weight, though mice treated with 4 mg/kg showed the least amount of weight loss during the treatment period.</p

Arsenic plasma concentrations and uptake in mouse tissues and cultured mouse ovaries.

<p>(A) NB(Ni,As)-treated (4 mg/kg) mice had reduced clearance of arsenic in plasma and increased peak plasma concentration compared with As₂O₃-treated (4 mg/kg) mice. (B) Arsenic levels in the uterus and ovaries peaked and cleared more rapidly in mice treated with As₂O₃ compared with mice treated with NB(Ni,As). (C) Arsenic levels in the liver and kidney paralleled those in the uterus. Error bars represent ± SEM.</p

Effect of As₂O₃ and NB(Ni,As) on ovarian histology.

<p>Hematoxylin and eosin staining of ovarian sections from mice following 3.5-weeks of treatment with (A) PBS (4× magnification); (B) 4 mg/kg NB(NaCl) 4×magnification); (C, E, F) 4 mg/kg As₂O₃ (4× and 10× magnification); or (D) 4 mg/kg NB(Ni,As) (4× magnification). (A, B, D) Ovaries from PBS-, NB(NaCl)-, and NB(Ni,As)-treated mice show normal ovarian histology and contain follicles of all stages as well as corpora lutea. (C, E, F) Ovaries isolated from As₂O₃-treated mice contained blood filled cysts and leaky vasculature. Measurement bars represent 100 µm (A–D) and 200 µm (E, F). Follicles are indicated with arrowheads and corpora lutea are labeled “CL.” Blood-filled cysts are indicated with arrows and areas of leaky vasculature are labeled “Bl” in panels C, E, and F.</p

Follicle survival after <i>in vitro</i> arsenic exposure.

<p>Isolated ovarian follicles were incubated in PBS or (A) 3, (B) 30, or (C) 90 µM As₂O₃, NB(NaCl), or NB(Ni,As) for 3 hours. Individual follicles were then encapsulated in alginate and cultured for 10 days to analyze survival rate. (A) At 3 µM As₂O₃, follicle survival was not statistically significantly different compared with PBS, NB(NaCl), or NB(Ni,As). (B) At 30 µM As₂O₃, follicle survival was significantly less starting at day 4. C, At 90 µM As₂O₃, follicle survival dropped to 30% by day 4. At all concentrations, NB(Ni,As)-treated follicle survival was not significantly different than that of PBS or NB(Ni,As). (D) Ovaries were incubated in PBS or 3, 30, or 90 µM As₂O₃, NB(NaCl), or NB(Ni,As) for 3 hours. Arsenic content in the cultured ovaries was examined by ICP-MS. Arsenic content was significantly higher in As₂O₃-treated ovaries than in PBS-, NB(NaCl)-, or NB(Ni,As)-treated ovaries at 30 and 90 µM. Arsenic content in NB(NaCl)-treated ovaries was only significantly less than in ovaries treated with the highest dose of NB(Ni,As) (90 µM). (a) is <i>P</i><0.01 compared with PBS, (b) is <i>P</i><0.01 compared with NB(Ni,As) at the same concentration, (c) is <i>P</i><0.01 compared with NB(NaCl) at the same concentration. Error bars represent ±SEM.</p