Purpose: To compare the level of agreement between the Goldmann applanation tonometer (GAT), iCare IC200 rebound tonometer (IRT), and noncontact tonometer (NCT) in patients who underwent Descemet membrane stripping endothelial keratoplasty (DSEK), and to identify factors contributing to variations in intraocular pressure (IOP) measurements among the three tonometers. Methods: We retrospectively analyzed the medical records of 41 patients who underwent DSEK. IOP was measured using NCT, IRT, and GAT, in this order. We evaluated the level of agreement among IOP measurements using the three tonometers, and analyzed whether clinical factors affected the results. Results: We analyzed 49 eyes of 41 patients (average age: 62.0 years). The IOP values measured by IRT and NCT were lower than those measured by GAT, although the difference was not significant (p = 0.098 and p = 0.320, respectively). A Bland-Altman plot showed greater agreement between IOP measurements obtained by IRT and GAT than those obtained by NCT and GAT. In multivariate regression analysis, the IOP measured by GAT (β = 0.215, p = 0.022), corneal curvature (β = -1.692, p = 0.037), and postoperative duration (β = 0.042, p = 0.018) affected the difference in IOPs measured by GAT and IRT. The IOP measured by GAT (β = 0.301, p = 0.013) and corneal curvature (β = -2.670, p = 0.010) affected the difference in IOP measurements obtained by GAT and NCT. Conclusions In DSEK eyes, IRT showed good agreement and high correlation with GAT, suggesting that it is useful for IOP measurement. However, the IOP measured by GAT, corneal curvature, and postoperative duration should be considered when measuring IOP with an IRT.

Purpose: To report a case of orbital infarction syndrome in a patient with hemophagocytic lymphohistiocytosis (HLH).Case summary: A 70-year-old woman with diabetes mellitus and hypertension was referred to the Department of Ophthalmology for sudden-onset left upper eyelid ptosis after being diagnosed with HLH. After 3 days, the best corrected visual acuity in the right eye was 0.8, while there was no light perception in the left eye. In the left eye, the ocular motility examination showed limitations in all fields of gaze. On fundus examination, optic disc pallor, retinal hemorrhage, and narrowed retinal arteries were observed in the left eye. Fluorescein angiography showed no blood flow in the retinal arteries and veins in the left eye. On neck computed tomography angiography, the left distal internal carotid artery was narrowed. Orbit computed tomography showed exophthalmos and extraocular muscle hypertrophy in the left eye. Orbit magnetic resonance imaging confirmed optic nerve edema, enhancement of the optic nerve sheath, and high signal intensity of the intraocular fat in the left eye. Slit-lamp examination revealed ischemia of the anterior segment and ischemic necrosis of the eyelid in the left eye. The patient was diagnosed with orbital infarction syndrome. Conclusions Several factors may lead to ischemia of the orbital tissues in patients with HLH, including coagulopathy, an increased incidence of blood clots, and inflammation in the orbit. It is necessary to consider the possibility of orbital infarction syndrome when HLH patients present with visual loss, ocular movement limitations, and anterior segment ischemia.

Background/aims: Circulating tumor cells (CTCs) with cancer stemness have been demonstrated to be a direct cause of tumor recurrence, and only few studies have reported the role of CTCs in liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods: Epithelial cell adhesion molecule+ (EpCAM+), cluster of differentiation 90+ (CD90+) and EpCAM+/CD90+ CTCs were sorted via fluorescence-activated cell sorting, and transcripts level of EpCAM, K19 and CD90 in the peripheral blood were analyzed via real-time polymerase chain reaction preoperatively and on postoperative days 1 and 7 in 25 patients who underwent living donor liver transplantation (LDLT) for HCC. EpCAM protein was assessed in HCC tissue using immunohistochemical staining. The median follow-up duration was 40 months. Results: HCC after LDLT recurred in four out of 25 patients. Detection of EpCAM+ or CD90+ CTCs correlated well with their messenger RNA levels (p<0.05). EpCAM+ CTCs were readily detected in HCC tissue expressing EpCAM protein. The detection of EpCAM+ CTCs or EpCAM+/CD90+ CTCs before surgery and on postoperative day 1 was significantly associated with HCC recurrence after LT (all p<0.05). Pretransplant serum PIVKA-II >100 mAU/mL and postoperative day 1 EpCAM+/CD90+ CTCs were independent risk factors for HCC recurrence (hazard ratio, 14.64; 95% confidence interval, 1.08 to 198.20; p=0.043 and hazard ratio, 26.88; 95% confidence interval, 1.86 to 387.51; p=0.016, respectively). Conclusions EpCAM+/CD90+ CTCs can be used preoperatively and 1 day after LDLT as key biological markers in LT candidate selection and post-LDLT management.

Background/Aims: This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Methods: The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated. Results: The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001). Conclusions Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.

Hepatocellular carcinoma (HCC) with distant metastasis is an absolute contraindication for liver transplantation (LT). However, it is still unclear whether LT is feasible or acceptable in such patients, albeit after being treated with a multidisciplinary approach and after any metastatic lesion is ruled out. We report one such successful treatment with living donor LT (LDLT) after completely controlling far-advanced HCC with inferior vena cava tumor thrombosis and multiple lung metastases. The patient has been doing well without HCC recurrence for eight years since LDLT. The current patient could be an anecdotal case, but provides a case for expanding LDLT indications in the context of advanced HCC and suchlike.

Hepatocellular carcinoma (HCC) with distant metastasis is an absolute contraindication for liver transplantation (LT). However, it is still unclear whether LT is feasible or acceptable in such patients, albeit after being treated with a multidisciplinary approach and after any metastatic lesion is ruled out. We report one such successful treatment with living donor LT (LDLT) after completely controlling far-advanced HCC with inferior vena cava tumor thrombosis and multiple lung metastases. The patient has been doing well without HCC recurrence for eight years since LDLT. The current patient could be an anecdotal case, but provides a case for expanding LDLT indications in the context of advanced HCC and suchlike.

Background/Aims: This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Methods: The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated. Results: The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001). Conclusions Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.

PURPOSE: The risk of posthepatectomy liver failure (PHLF) after right hepatectomy remains substantial. Additional parameters such as computed tomography volumetry, liver stiffness measurement by FibroScan, indocyanine green retention rate at 15 minutes, and platelet count used to properly assess future liver remnant volume quality and quantity are of the utmost importance. Thus, we compared the usefulness of these modalities for predicting PHLF among patients with hepatocellular carcinoma after right hepatectomy. METHODS: We retrospectively reviewed patients who underwent right hepatectomy for hepatocellular carcinoma between 2007 and 2013. PHLF was determined according to International Study Group of Liver Surgery consensus definition and severity grading. Grades B and C were defined as clinically relevant posthepatectomy liver failure (CRPHLF). The results were internally validated using a cohort of 97 patients. RESULTS: Among the 90 included patients, 15 (16.7%) had CRPHLF. Multivariate analysis confirmed that platelet count < 140 (109/L) (hazard ratio [HR], 24.231; 95% confidence interval [CI], 3.623–161.693; P = 0.001) and remnant liver volume-to-body weight (RVL/BW) ratio < 0.55 (HR, 25.600; 95% CI, 4.185–156.590; P < 0.001) were independent predictors of CRPHLF. Among the 12 patients with a platelet count < 140 (109/L) and RLV/BW ratio < 0.55, 9 (75%) had CRPHLF. Likewise, 5 of 38 (13.2%) with only one risk factor developed CRPHL versus 1 of 40 (2.5%) with no risk factors. These findings were confirmed by the validation cohort. CONCLUSION RLV/BW ratio and platelet count are more important than the conventional RLV/TFLV, indocyanine green retention rate at 15 minutes, and liver stiffness measurement in the preoperative risk assessment for CRPHLF.

Glial cell line-derived neurotrophic factor (GDNF) has been reported to be involved in negatively regulating the effects of addictive disorders. The objective of this study was to investigate alterations in the levels of GDNF in patients with Internet gaming disorder (IGD) and to assess the relationship between GDNF levels and the severity of IGD indices. Nineteen male patients with IGD and 19 sexmatched control subjects were evaluated for alteration of plasma GDNF levels and for relationship between GDNF levels and clinical characteristics of Internet gaming, including the Young's Internet Addiction Test (Y-IAT). The GDNF levels were found to be significantly low in patients with IGD (103.2±62.0 pg/mL) compared with the levels of controls (245.2±101.6 pg/mL, p<0.001). GDNF levels were negatively correlated with Y-IAT scores (Spearman's rho=-0.645, p=<0.001) and this negative correlation remained even after controlling for multiple variables (r=-0.370, p=0.048). These findings support the assumed role of GDNF in the regulation of IGD.
Case-Control Studies ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Immunoglobulin D ; Internet ; Male ; Neuroglia ; Pilot Projects ; Plasma

BACKGROUND/AIMS: Lysyl oxidase-like 2 (LOXL2), a collagen-modifying enzyme, has been implicated in cancer invasiveness and metastasis. METHODS: We evaluated the expression of LOXL2 protein, in addition to carbonic anhydrase IX (CAIX), keratin 19, epithelial cell adhesion molecule, and interleukin 6, in 105 resected hepatocellular carcinomas (HCCs) by immunohistochemistry. RESULTS: LOXL2 positivity was found in 14.3% (15/105) of HCCs, and it was significantly associated with high serum α-fetoprotein levels, poor differentiation, fibrous stroma, portal vein invasion, and advanced TNM stage (p < 0.05 for all). Additionally, LOXL2 positivity was significantly associated with CAIX (p=0.005) and stromal interleukin 6 expression (p=0.001). Survival analysis of 99 HCC patients revealed LOXL2 positivity to be a poor prognostic factor; its prognostic impact appeared in progressed HCCs. Furthermore, LOXL2 positivity was shown to be an independent predictor of overall survival and disease-specific survival (p < 0.05 for all). Interestingly, co-expression of LOXL2 and CAIX was also an independent predictor for overall survival, disease-specific survival, disease-free survival, and extrahepatic recurrence-free survival (p < 0.05 for all). CONCLUSIONS: LOXL2 expression represents a subgroup of HCCs with more aggressive behavior and is suggested to be a poor prognostic marker in HCC patients.
Carbonic Anhydrases ; Carcinoma, Hepatocellular* ; Disease-Free Survival ; Epithelial Cells ; Extracellular Matrix ; Humans ; Immunohistochemistry ; Interleukin-6 ; Keratin-19 ; Neoplasm Metastasis ; Portal Vein ; Prognosis*