Akiyoshi Kinoshita

Rationale: Antineutrophil cytoplasmic antibody–associated vasculitis (AAV) is a systemic necrotizing vasculitis that predominantly affects small vessels. Glucocorticoids are the standard therapeutic agents for AAV; however, their long-term use can cause damage. Avacopan is a small-molecule complement component 5a receptor antagonist that reduces vasculitis and can potentially be used as an alternative to glucocorticoids. However, its therapeutic efficacy remains unknown, and drug-induced liver injury (DILI) is a concern associated with its use. Patient concerns: A 74-year-old woman with a history of granulomatosis with polyangiitis was admitted to our hospital with a 1-week history of fatigue and anorexia. Diagnoses: She had started avacopan 3 months before hospitalization. Blood tests showed severe liver injury, and since other diseases were ruled out, she was diagnosed with DILI secondary to avacopan. Interventions: Avacopan was discontinued, and glucocorticoid doses were increased and ursodeoxycholic acid was administered; however, the liver injury did not resolve. Therefore, mycophenolate mofetil (MMF) was started. Outcomes: The liver injury was resolved after starting MMF. Lessons: MMF is effective in treating DILI caused by avacopan.

Patients with cirrhosis are at high risk for sarcopenia and malnutrition, which are associated with reduced quality of life and increased mortality. We investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) and sarcopenia/gait speed and assessed the usefulness of the GNRI for predicting sarcopenia in patients with cirrhosis. We evaluated 202 patients with cirrhosis and divided them into three groups based on baseline GNRI values: low (L)-GNRI (< 94.0, n = 49), intermediate (I)-GNRI (between 94.0 and 109.5, n = 103), and high (H)-GNRI groups (> 109.5, n = 50). Sarcopenia was diagnosed according to the criteria of the Japan Society of Hepatology. The prevalence of sarcopenia and slow gait speed was the lowest in the H-GNRI group (8.0% and 26.0%, respectively) and the highest in the L-GNRI group (49.0% and 44.9%, respectively). They increased stepwise with a decline in the GNRI group (p < 0.001 and p = 0.05, respectively). The GNRI values were significantly and positively correlated with handgrip strength, skeletal muscle mass index, and gait speed. Multivariate analysis identified lower GNRI as an independent risk factor for sarcopenia. The optimal cutoff value of the GNRI for predicting sarcopenia was 102.1 (sensitivity/specificity, 0.768/0.630). The GNRI was significantly associated with sarcopenia and physical performance and could be a helpful screening tool for predicting sarcopenia in patients with cirrhosis.

Neuroendocrine neoplasms are rare epithelial neoplasms with neuroendocrine differentiation. Few cases of primary testicular poorly differentiated neuroendocrine carcinomas (PD-NECs) have been reported, and secondary testicular neoplasms are rare. A 61-year-old man with a chief complaint of left testicular swelling was referred to our hospital. An orchiectomy was performed in order to determine the pathological diagnosis. Pathological examination showed diffuse sheets of highly atypical cells that were positive for neuroendocrine markers and a Ki-67 proliferation index of 80%. The patient was diagnosed with poorly differentiated small-cell NEC. Contrast-enhanced computed tomography revealed multiple metastases to the pancreas, adrenal glands, and lymph nodes. Esophagogastroduodenoscopy showed multiple gastric metastases, and biopsy revealed the same histological findings as observed for the testicular tumor. Contrast-enhanced magnetic resonance imaging of the head also revealed multiple brain metastases. The confirmed diagnosis was PD-NEC of unknown primary with metastases to the testis, stomach, pancreas, adrenal glands, brain, and lymph nodes. We started the first-line chemotherapy with etoposide and cisplatin. Stereotactic radiotherapy for the brain metastases was administered between the first and second cycles. After five cycles, a partial response was observed; however, disease progression was observed after seven cycles with recurrence of the brain metastases and enlargement of all tumors. To our knowledge, this is the first report of an unknown primary PD-NEC with metastasis to the testis.

Background/Aim: We aimed to investigate the association between The Geriatric Nutritional Risk Index (GNRI) and the tolerability of lenvatinib in patients with hepatocellular carcinoma (HCC). Patients and Methods: We retrospectively evaluated 61 HCC patients treated with lenvatinib and compared those with low GNRI (≤98, n=26) to those with high GNRI (>98, n=35). Results: The discontinuation of lenvatinib due to adverse events was more frequent in the low GNRI group (46.2%) than in the high GNRI group (17.1%) (p=0.014). Multivariate analysis revealed that low GNRI (p=0.014), hypothyroidism (model 1 p=0.021, model 2 p=0.013), and advanced age (p=0.026) were independently associated with the discontinuation of lenvatinib. The progression-free survival in the low GNRI group was significantly shorter than that in the high GNRI group (p=0.047). Conclusion: The GNRI might be independently associated with the tolerability of lenvatinib in patients with HCC.

Introduction: Management of elderly patients with cancer has become a global issue. We investigated the safety and tolerability of lenvatinib in hepatocellular carcinoma (HCC) patients ≥80 years old. Methods: We retrospectively evaluated 61 HCC patients and divided them into 2 groups: an elderly group (n = 13, ≥80 years old) and a younger group (n = 48, <80 years old). We compared the adverse events (AEs), administration period, dose intensity, objective response, and progression-free survival (PFS) between the two groups. Results: The discontinuation of lenvatinib due to AEs was more frequent in the elderly group (8/13, 61.5%) than in the younger group (10/48, 20.8%) (P = 0.0043). Fatigue and appetite loss accounted for half of the cases discontinued due to AEs in the elderly group. The elderly group had a significantly lower 8-week-delivered dose intensity/body surface area ratio (147.2) and 8-week-relative dose intensity (50.0%) than those in the younger group (267.4, 67%) (P = 0.003, 0.029). The objective response rate was significantly lower in the elderly group (15.4%) than in the younger group (61.5%) (P = 0.021). The PFS in the elderly group tended to be shorter than that in the younger group (P = 0.058, hazard ratio [HR] 1.98). The modified albumin-bilirubin (mALBI) grade (hepatic function) (HR, 2.60; P = 0.01) and objective response (HR, 0.41; P = 0.011) were independently associated with the PFS in the multivariate analysis. Conclusion: The management of AEs is crucial for adherence and maintaining the dose intensity of lenvatinib in elderly HCC patients.

Objectives We aimed to investigate the association between the digit symbol test (DST) and clinical characteristics, including the nutritional status of LC patients. Methods Fifty-nine cirrhotic patients without a history of overt hepatic encephalopathy were retrospectively evaluated. We examined neuropsychological abnormalities (NPAs) using the DST. We also estimated the detailed nutritional status using the Food Frequency Questionnaire (FFQ). The patients were divided into two groups according to their DST status: patients with normal DST scores (DST-Nor group, n=45) and those with abnormal DST scores (DST-Abn group, n=14). The clinical and nutritional findings of the two groups were compared. Results Overall, 14 (23.7%) patients had a DST abnormality. There were significant differences between the two groups in serum albumin (Alb; p=0.0043), valine (Val; p=0.0016), leucine (Leu; p=0.0078), isoleucine (Ile; p=0.0022), the molar ratio of total branched-chain amino acids to tyrosine (BTR; p=0.00025), total-bilirubin (T-Bil; p=0.0071), prothrombin time (%) (PT; p=0.028), and serum sodium (Na; p=0.035). A multivariate analysis found the BTR to be the only independent predictor of a DST abnormality (hazard ratio, 9.24; p<0.031). An FFQ analysis, revealed that the nutritional findings of patients with and without a DST abnormality, were similar. Conclusion The BTR was useful for predicting the risk of NPAs, as defined by a DST abnormality. The risk of NPAs may be estimated by monitoring the BTR.

Aim: Opportunities to treat older patients with hepatitis C virus infection have increased. We investigated the efficacy and safety of glecaprevir/pibrentasvir in patients with HCV infection aged ≥75 years.Methods: We retrospectively evaluated 131 patients with hepatitis C virus infection treated with glecaprevir/pibrentasvir at nine institutions in Japan. The patients were divided into two groups according to their age: the elderly group (n = 43, aged ≥75 years) and younger group (n = 88, aged P = 0.30). In the modified intention‐to‐treat population, all patients achieved sustained virologic response 12. A total of 27.5% of patients experienced adverse events. The most frequently observed adverse events was pruritus, and was significantly associated with female sex, the presence of hemodialysis and serum albumin at baseline Geriatr Gerontol Int 2020; ••: ••–••.

To evaluate the efficacy and safety of nab paclitaxel (nab-P) plus gemcitabine (GEM) in elderly patients ≥ 75 years old with unresectable pancreatic cancer (PC) compared with younger patients.

Aim We investigated the clinical characteristics and short‐term outcomes in acute cholecystitis (AC) patients aged ≥80 years. We therefore sought to determine the ideal treatment for elderly patients with AC. Methods We retrospectively evaluated 253 patients with AC. The patients were divided into two groups according to their age: elderly group (n = 77, aged ≥80 years) and non‐elderly group (n = 176, aged P = 0.0055), higher severity grade of AC (P = 0.00071) and higher in‐hospital mortality (P = 0.029) than the non‐elderly group. The multivariate analysis showed that the serum creatinine level (hazard ratio 12.43; P = 0.002) was independently associated with the in‐hospital mortality. The elderly group (20.8%) underwent subsequent cholecystectomy less frequently than the non‐elderly group (63.2%; P < 0.0001). The recurrence rate of AC was comparable between the two groups (P = 0.89). The proportion of patients in the elderly group who received percutaneous drainage in the latter period (64.3%) was significantly higher than in the former period (33.3%; P = 0.015). Conclusions More attention should be paid to AC patients with chronic renal disease after treatment. Percutaneous drainage might serve as a definitive treatment without subsequent cholecystectomy in elderly AC patients with various comorbidities. Geriatr Gerontol Int 2018; ••: ••–••.