Multidisciplinary treatment with immune checkpoint inhibitors for advanced stage hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a cytotoxic chemotherapy-resistant tumor and most HCCs arise in a background of liver cirrhosis of various causes. Although the IMBrave150 trial showed remarkable advancements in the treatment of unresectable HCC with atezolizumab plus bevacizumab (AteBeva), therapeutic outcomes were unsatisfactory in more than half of the patients. Accordingly, many ongoing trials combine conventional modalities with new drugs such as immune checkpoint inhibitors for better treatment outcomes, and they are expected to benefit patients with limited responses to conventional treatment. Here, two patients with advanced stage HCC with preserved liver function and good performance status showed partial response after treatment with combination or sequential therapy of AteBeva, hepatic arterial infusion chemotherapy, radiation therapy, and transarterial chemoembolization. These findings indicate the efficacy of multidisciplinary treatment against advanced HCC. Additional studies are required to establish optimal treatment strategies.

Prevalence trends of non-alcoholic fatty liver disease among young men in Korea: A Korean military population-based cross-sectional study

Background/Aims@#Non-alcoholic fatty liver disease (NAFLD) has become a major concern in Korea since its emergence as a dominant cause of chronic liver disease. However, no study has explored its prevalence in adults under 30 years of age. Therefore, we performed a cross-sectional study to investigate the prevalence of NAFLD in Korean men in their early 20s. @*Methods@#We collected data of 596,359 Korean soldiers who participated in a health examination between January 2015 and July 2021. A total of 571,872 individuals were analyzed after excluding those with missing data and hepatitis B antigen positivity. Hepatic steatosis was determined using the hepatic steatosis index (HSI). Participants with HSI >36 were considered to have NAFLD. @*Results@#All participants were men, and the mean age was 20.9±1.3 years. Of the 571,872 participants screened, 77,020 (13.47%) were classified as having NAFLD. The prevalence of NAFLD consistently increased from 2015 to 2021 (10.66% vs. 16.44%, P<0.001). Increases from 2015 to 2021 were also noted in the prevalence of hypercholesterolemia, hyperglycemia, and hypertension (P<0.001 for all). The mean body mass index also increased from 23.3±3.0 kg/m2 to 23.9±3.1 kg/m2 between 2015 and 2021 (P<0.001). @*Conclusions@#The prevalence of NAFLD and of other metabolic dysfunctions in Korean men in their early 20s increased from 2015 to 2021.

Infiltration of T Cells and Programmed Cell Death Ligand 1-expressing Macrophages as a Potential Predictor of Lenvatinib Response in Hepatocellular Carcinoma

Background/Aims@#Lenvatinib was recently proven to be non-inferior to sorafenib in treating unresectable hepatocellular carcinoma (HCC) in a phase-3 randomized controlled trial. In this study, we investigated whether the response to lenvatinib was affected by tumor immunogenicity. @*Methods@#Between May 2019 and April 2020, nine patients with intermediate-to-advanced HCC, who were treated with lenvatinib after liver biopsy, were enrolled. Immunohistochemical staining and multi-color flow cytometry were performed on specimens obtained from liver biopsy. @*Results@#Among the nine patients enrolled, four showed objective responses (complete responses+partial responses). Immunohistochemical staining for CD3, CD68, and programmed cell death ligand 1 (PD-L1) demonstrated that patients with objective responses showed marked infiltration of T cells and PD-L1-expressing macrophages in intra-tumoral and peri-tumoral tissues compared to those without objective responses. A significant difference in the numbers of infiltrated T cells, both in the intra-tumoral (P<0.01) and peri-tumoral regions (P<0.05), were identified between responders and non-responders. Regarding the number of infiltrated macrophages, no significant difference was found between the responders and non-responders, although the number of PD-L1-expressing tumor-associated macrophages was significantly higher in responders than that in non-responders (P<0.05). @*Conclusions@#Tumor immunogenicity, as indicated by T cell and PD-L1-positive macrophage infiltration, affects lenvatinib response in unresectable HCC.

Early Onset Polymorphic Post-transplant Lymphoproliferative Disease Mimicking a Solitary Necrotizing Abscess in a Graft Liver

Although post-transplantation lymphoproliferative disease (PTLD) after liver transplantation is very rare, its prognosis is worse than that of PTLD following other types of solid organ transplantation. Here, we report a rare case of early onset polymorphic PTLD in a graft liver occurring five months after deceased-donor liver transplantation due to hepatocellular carcinoma and hepatitis C virus infection. Initially, findings from contrast-enhanced magnetic resonance imaging mistakenly suspected the lesion was a necrotizing abscess with central necrosis. However, ¹⁸F-fluorodeoxyglucose positron emission tomography and biopsy findings confirmed an Epstein-Barr virus (EBV)-associated, B cell type polymorphic PTLD with central necrosis. Our case suggests regular monitoring of EBV serologic status for liver transplant recipients who were initially in an EBV seronegative state. Although early-onset PTLD is very rare after liver transplantation, PTLD should be suspected when recipients show the seroconversion for EBV proteins and the development of new tumors with various clinical presentations.

The Prevalence of Cervical Foraminal Stenosis on Computed Tomography of a Selected Community-Based Korean Population

BACKGROUND: Cervical foraminal stenosis (CFS) is one of the degenerative changes of the cervical spine; however, correlations between the severity of stenosis and that of symptoms are not consistent in the literature. Studies to date on the prevalence of stenosis are based on images obtained from the departments treating cervical lesions, and thus patient selection bias may have occurred. The purpose of this study was to investigate the prevalence of CFS according to the site, extent, and morphology of stenosis using cervical computed tomography (CT) images obtained from patients who were visiting not because of symptoms related to the cervical spine, cervical pain, or upper limb pain. METHODS: Among patients who underwent CT from January 2016 to March 2016 for reasons other than cervical spine symptoms, a total of 438 subjects were enrolled, and 2,628 cervical disc images (C4–5, C5–6, and C6–7; left and right sides) were examined. Three orthopedic surgeons performed two measurements each at 4-week intervals. Values were used for analysis if matched by more than two surgeons; if no match was found, the median values were used for analysis. The left and right sides on the same axial image were independently classified. RESULTS: Left C5–6 stenosis was most common (24.66%) among patients. At the left C6–7, there were 20 focal types and 33 diffuse types. At bilateral C4–5 and right C6–7, the focal type was more common, whereas at bilateral C5–6 and left C6–7, the diffuse type was more common. Age and the severity of stenosis showed statistically significant correlation at all cervical levels. CONCLUSIONS: The prevalence of CFS was highest at the C5–6 level (19.06%). Compared to other levels, focal stenosis was more frequent at C4–5 and diffuse stenosis was more common at C5–6. At C6–7, the incidence of focal stenosis was higher on the right side and that of diffuse stenosis was higher on the left side.

The Detection of Messenger RNA for Carcinoembryonic Antigen and Cytokeratin 20 in Peritoneal Washing Fluid in Patients with Advanced Gastric Cancer / 대한소화기학회지

BACKGROUND/AIMS: Peritoneal micrometastasis is known to play an important role in the recurrence of gastric cancer. However, its effects remain equivocal. Herein, we examine the messenger RNA (mRNA) as tumor markers, carcinoembryonic antigen (CEA), and cytokeratin 20 (CK20), in peritoneal washing fluid. Moreover, we evaluate whether these results could predict the recurrence of gastric cancer following curative resection. METHODS: We prospectively enrolled 132 patients with gastric cancers, who had received an operation, between January 2010 and January 2013. The peritoneal lavage fluid was collected at the operation field and semi-quantitative PCR was performed using the primers for CEA and CK20. We excluded patients with stage IA (n=28) early gastric cancer, positive cytologic examination of peritoneal washings (n=7), and those who were lost during follow up (n=18). RESULTS: A total of 79 patients with gastric cancers were enrolled, and the mean follow-up period was 39.95±19.25 months (range, 5-72 months). According to the multivariate analysis, T4 stage at the initial diagnosis was significantly associated with recurrence. All cases of recurrence were CEA positive and 6 cases were CK20 positive. The positive and negative predictive values of CEA were 32.0% and 100%, respectively, whereas those of CK20 were 37.5% and 71.4%, respectively. Disease free survival of CK20-negative cases was 36.17±20.28 months and that of CK20-positive cases was 32.06±22.95 months (p=0.39). CONCLUSIONS: It is unlikely that the real time polymerase chain reaction results of mRNA for CEA and CK20 in peritoneal washing fluid can predict recurrence. However, negative results can convince surgeons to perform curative R0 resection.

Timing of Surgical Management of Papillary Thyroid Cancer Diagnosed during Pregnancy

BACKGROUND AND OBJECTIVES: Although the thyroid cancer occurs in every one of 1000 pregnant women, the optimal timing of surgery is still uncertain. The aim of this study is to propose the timing of surgical management of papillary thyroid cancer in pregnant woman. MATERIALS AND METHODS: The authors reviewed the medical records of papillary thyroid cancer patients diagnosed during pregnancy in our hospital from May 1st, 2013 to April 30th, 2015. We analyzed the changes of radiologic and pathologic findings during prenatal and postpartum period. RESULTS: 17 of 4978 patients were diagnosed with papillary thyroid cancer. 10 of 17 patients enrolled in this study. Each size of thyroid cancer in 1st trimester, in 2nd trimester, in 3rd trimester, and after delivery was 11.30±6.01 mm, 12.74±7.79 mm, 13.82±9.93 mm, and 13.82±8.19 mm, respectively. No patient showed the recurrence or death after surgery. CONCLUSION: There was no statistical significance on the prognosis of papillary thyroid cancer during prenatal and postpartum period. The authors propose that the surgical treatment of papillary thyroid cancer diagnosed during pregnancy could be delayed after delivery.

Timing of Surgical Management of Papillary Thyroid Cancer Diagnosed during Pregnancy

BACKGROUND AND OBJECTIVES: Although the thyroid cancer occurs in every one of 1000 pregnant women, the optimal timing of surgery is still uncertain. The aim of this study is to propose the timing of surgical management of papillary thyroid cancer in pregnant woman. MATERIALS AND METHODS: The authors reviewed the medical records of papillary thyroid cancer patients diagnosed during pregnancy in our hospital from May 1st, 2013 to April 30th, 2015. We analyzed the changes of radiologic and pathologic findings during prenatal and postpartum period. RESULTS: 17 of 4978 patients were diagnosed with papillary thyroid cancer. 10 of 17 patients enrolled in this study. Each size of thyroid cancer in 1st trimester, in 2nd trimester, in 3rd trimester, and after delivery was 11.30±6.01 mm, 12.74±7.79 mm, 13.82±9.93 mm, and 13.82±8.19 mm, respectively. No patient showed the recurrence or death after surgery. CONCLUSION: There was no statistical significance on the prognosis of papillary thyroid cancer during prenatal and postpartum period. The authors propose that the surgical treatment of papillary thyroid cancer diagnosed during pregnancy could be delayed after delivery.