Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications

To clarify the role of CD8+ effector T cells for infectious complications, 92 recipients were classified according to the hierarchical clustering of preoperative CD8+CD45 isoforms: Group I was naive, Group II was effector memory, and Group III was effector (E) T cell-dominant. The posttransplant infection rates progressively increased from 29% in Group I to 64.3% in Group III recipients. The posttransplant immune status was compared with the pretransplant status, based on the measure (% difference) and its graphical form (scatter plot). In Groups I and II, both approaches showed a strong upward deviation from pretransplant status upon posttransplant infection, indicating an enhanced clearance of pathogens. In Group III, in contrast, both approaches showed a clear downward deviation from preoperative status, indicating deficient cytotoxicity. The % E difference and scatter plot can be used as a useful indicator of a posttransplant infectious complication

Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation

Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports

Liver Transplantation for Hepatocellular Carcinoma : How Should We Improve the Thresholds?

Simple Summary The ideal treatment for hepatocellular carcinoma (HCC) is liver transplantation (LT), which both eliminates the HCC and cures the diseased liver. Once considered an experimental treatment with dismal survival rates, LT for HCC entered a new era with the establishment of the Milan criteria over 20 years ago. However, over the last two decades, the Milan criteria, which are based on tumor morphology, have come under intense scrutiny and are now largely regarded as too restrictive, and limit the access of transplantation for many patients who would otherwise achieve good clinical outcomes. The liver transplant community has been making every effort to reach a goal of establishing more reliable selection criteria. This article addresses how the criteria have been extended, as well as the concept of pre-transplant down-staging to maximize the eligibility. Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related mortality, and liver transplantation is the ideal treatment for this disease. The Milan criteria provided the opportunity for HCC patients to undergo LT with favorable outcomes and have been the international gold standard and benchmark. With the accumulation of data, however, the Milan criteria are not regarded as too restrictive. After the implementation of the Milan criteria, many extended criteria have been proposed, which increases the limitations regarding the morphological tumor burden, and incorporates the tumor's biological behavior using surrogate markers. The paradigm for the patient selection for LT appears to be shifting from morphologic criteria to a combination of biologic, histologic, and morphologic criteria, and to the establishment of a model for predicting post-transplant recurrence and outcomes. This review article aims to characterize the various patient selection criteria for LT, with reference to several surrogate markers for the biological behavior of HCC (e.g., AFP, PIVKA-II, NLR, 18F-FDG PET/CT, liquid biopsy), and the response to locoregional therapy. Furthermore, the allocation rules in each country and the present evidence on the role of down-staging large tumors are addressed

Prognostic Role of the Intrahepatic Lymphatic System in Liver Cancer

Although several prognosticators, such as lymph node metastasis (LNM), were reported for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the prognostic impact of intrahepatic lymphatic vessel invasion (LVI) in liver cancer has rarely been reported. We sought to clarify the prognostic impact of intrahepatic lymphatic system involvement in liver cancer. We systematically reviewed retrospective studies that described LVI and clinical outcomes of liver cancer and also included studies that investigated tumor-associated lymphangiogenesis. We conducted a meta-analysis using RevMan software (version 5.4.1; Cochrane Collaboration, Oxford, UK). The prognostic impact of intrahepatic LVI in HCC was not reported previously. However, tumor-associated lymphangiogenesis reportedly correlates with prognosis after HCC resection. The prognostic impact of intrahepatic LVI was reported severally for ICC and a meta-analysis showed that overall survival was poorer in patients with positive LVI than with negative LVI after resection of ICC. Lymphangiogenesis was also reported to predict unfavorable prognosis in ICC. Regarding colorectal liver metastases, LVI was identified as a poor prognosticator in a meta-analysis. A few reports showed correlations between LVI/lymphangiogenesis and LNM in liver cancer. LVI and lymphangiogenesis showed worse prognostic impacts for liver cancer than their absence, but further study is needed

microRNAs Associated with Gemcitabine Resistance via EMT, TME, and Drug Metabolism in Pancreatic Cancer

Despite extensive research, pancreatic cancer remains a lethal disease with an extremely poor prognosis. The difficulty in early detection and chemoresistance to therapeutic agents are major clinical concerns. To improve prognosis, novel biomarkers, and therapeutic strategies for chemoresistance are urgently needed. microRNAs (miRNAs) play important roles in the development, progression, and metastasis of several cancers. During the last few decades, the association between pancreatic cancer and miRNAs has been extensively elucidated, with several miRNAs found to be correlated with patient prognosis. Moreover, recent evidence has revealed that miRNAs are intimately involved in gemcitabine sensitivity and resistance through epithelial-to-mesenchymal transition, the tumor microenvironment, and drug metabolism. Gemcitabine is the gold standard drug for pancreatic cancer treatment, but gemcitabine resistance develops easily after chemotherapy initiation. Therefore, in this review, we summarize the gemcitabine resistance mechanisms associated with aberrantly expressed miRNAs in pancreatic cancer, especially focusing on the mechanisms associated with epithelial-to-mesenchymal transition, the tumor microenvironment, and metabolism. This novel evidence of gemcitabine resistance will drive further research to elucidate the mechanisms of chemoresistance and improve patient outcomes

Preoperative assessment of para-aortic lymph node metastasis in patients with pancreatic cancer

BACKGROUND: Para-aortic lymph node (PALN) metastasis is an important prognostic factor in patients with pancreatic cancer, but accurate preoperative diagnosis is difficult. The objective of this study was to assess the accuracy of diagnosis of PALN by computed tomography (CT), magnetic resonance imaging (MRI), and (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET). METHODS: From August 2005 to July 2008, 119 patients with invasive ductal adenocarcinoma of the pancreas were included in this study. PALNs with a longer diameter >10 mm on CT or MRI were suspected of being involved by metastasis, whereas FDG uptake exceeding that of the adjacent normal tissue was considered to be positive for metastasis on FDG-PET studies. The imaging findings were compared with the pathological diagnosis of PALN metastasis. RESULTS: PALN dissection was performed in 71 patients (60.0%). Although histopathological examination revealed metastasis in 6 patients (8.5%), none of these patients was positive in any of the preoperative imaging studies. The longer diameter, the shorter diameter, the ratio of the two diameters, and the calculated lymph node volume showed no significant differences between patients with and without PALN metastasis. CONCLUSIONS: Preoperative detection of PALN metastasis in patients with pancreatic cancer is very difficult. Intraoperative histopathological examination of frozen sections is necessary if radical resection is contemplated