Immune microenvironment of hepatocellular carcinoma,intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma: Relationship with histopathological and molecular classifications

Tumor tissue is composed of tumor cells and tumor stroma. Tumor stroma contains various immune cells and non-immune stromal cells, forming a complex tumor microenvironment which plays pivotal roles in regulating tumor growth. Recent successes in immunotherapies against tumors, including immune checkpoint inhibitors, have further raised interests in the immune microenvironment of liver carcinoma. The immune microenvironment of tumors is formed because of interactions among tumor cells, immune cells and non-immune stromal cells, including fibroblasts and endothelial cells. Different patterns of immune microenvironment are observed among different tumor subtypes, and their clinicopathological significance and intertumor/intratumor heterogeneity are being intensively studied. Here, we review the immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma, focusing on its histopathological appearance, clinicopathological significance, and relationship with histological and molecular classifications. Understanding the comprehensive histopathological picture of a tumor immune microenvironment, in addition to molecular and genetic approaches, will further potentiate the effort for precision medicine in the era of tumor-targeting immunotherapy.     

Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m²), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m²), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m²), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m²). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe.     

Five‐year efficacy of finasteride in 801 Japanese men with androgenetic alopecia

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.     

Lenalidomide in the management of eosinophilic dermatosis of hematological malignancy

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.