Supplementary Material for: Hemorrhagic Macular Cysts in Patients with Terson’s Syndrome Observed through an Ophthalmic Surgical Microscope

The characteristics of hemorrhagic macular cysts (HMCs) in patients with Terson’s syndrome, focusing on the vitreoretinal interface observed through an ophthalmic surgical microscope, are described. Between May 2015 and February 2022, 19 eyes (17 patients) with vitreous hemorrhage (VH) occurring after subarachnoid hemorrhage underwent pars plana vitrectomy. After removing dense VH, 2 of 19 eyes had HMCs. In both cases with HMCs, they formed a dome-like shape and were located beneath the internal limiting membrane (ILM), lying beyond the clean posterior precortical vitreous pocket (PPVP) without hemorrhage despite the severe VH. Based on the microsurgical findings, it appears that two types of HMCs consisting of subhyaloid and sub-ILM hemorrhages in Terson’s syndrome may be involved in the impairment of adhesion of the posterior border of the PPVP and the ILM surface of the macula due to micro bleeding, and that the PPVP may prevent the sub-ILM type of HMC from breaking into the subhyaloid space and transforming into the subhyaloid type. In conclusion, the PPVP may play an important role in the formation of HMCs in Terson’s syndrome

Supplementary Material for: Adequacy of Using Consensus Guidelines for Diagnosis of Dementia with Lewy Bodies in Clinical Trials for Drug Development

<b><i>Background/Aims:</i></b> To evaluate the adequacy of using the consensus diagnostic criteria for dementia with Lewy bodies (DLB) to recruit patients with homogeneous characteristics in future clinical trials, where multiple departments of multinational centres are expected to participate with a long enrolment period, and additionally, to contribute to the possible future criteria revision. <b><i>Methods:</i></b> Using data from 2 trials of donepezil for DLB, conducted 3 years apart, characteristics in patients with probable DLB were analysed and compared between studies and between psychiatric and neurological centres. <b><i>Results:</i></b> In 273 patients (phase II: 135, phase III: 138; psychiatric: 73, neurological: 184), clinical characteristics overall were very similar between studies, and between specialty centres, excluding distinctive parkinsonism in the neurological versus psychiatric centres: incidence of parkinsonism (91.8 vs. 71.2%, p < 0.001), Hoehn and Yahr stage (III: 55.0 vs. 21.2%, p < 0.001), and concomitant anti-Parkinson medication (24.5 vs. 11.0%, p = 0.017). Rapid eye movement sleep behaviour disorder, depression, and delusion, suggestive or supportive features, were observed in 35-40%. Additionally, a high prevalence (55.3%) of anxiety was observed. <b><i>Conclusion:</i></b> Employing the consensus criteria is adequate to enrol homogeneous DLB patients into future clinical trials regardless of the specialty of centres and time. Further discussion could involve adding anxiety to future criteria

Supplementary Material for: Host MICA Polymorphism as a Potential Predictive Marker in Response to Chemotherapy for Colorectal Liver Metastases

<b><i>Background:</i></b> Understanding the genetic background of a tumor is important to better stratify patient prognosis and select optimal treatment. For colorectal liver metastases (CLM), however, clinically available biomarkers remain limited. <b><i>Methods:</i></b> After a comprehensive sequencing of 578 cancer-related genes in 10 patients exhibiting very good/poor responses to chemotherapy, the A5.1 variant of the <i>MICA</i> gene was selected as a potential biomarker for CLM. The clinical relevance of <i>MICA</i> A5.1 was then investigated in 58 patients who underwent CLM resection after chemotherapy. <b><i>Results:</i></b> The A5.1 variant was observed in 16 (27.6%) patients examined using direct DNA sequencing, and a very high concordance rate (56/58, 96.6%) for the <i>MICA</i> variant was confirmed between tumor tissues and normal liver parenchyma. A multivariate analysis of 38 patients with no history of treatment with anti-EGFR antibodies confirmed that <i>MICA</i> A5.1 was significantly correlated with an optimal CT morphologic response (OR 11.67; 95% CI 2.08–65.60; <i>p</i> = 0.005) and tended to be correlated with a tumor viability of < 20% after chemotherapy (OR 5.91; 95% CI 0.97–36.02; <i>p</i> = 0.054). <i>MICA</i> A5.1 was also associated with a decreased risk of progression after CLM resection. <b><i>Conclusion:</i></b> The <i>MICA</i> A5.1 polymorphism was associated with a better CT morphologic response to chemotherapy and a reduced risk of relapse after CLM resection. Given the high concordance rate in <i>MICA</i> variants between normal liver tissue and CLM, the genetic background of the host could be a new biomarker for CLM

Supplementary Material for: A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial)

Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 minutes as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC

Supplementary Material for: A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial)

Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 minutes as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC