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.     

Changes of cancer diagnosis disclosure to children in Japan in the last 20 years

International Journal of Clinical Oncology - The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change...     

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.     

Easier node dissection after chemoradiotherapy for lung cancer with collagen insertion at mediastinoscopy

Objective: Induction chemoradiotherapy followed by anatomical resection is a current therapeutic strategy for non-small-cell lung cancer with mediastinal node involvement. Dense peritracheal fibrosis and sclerosis after chemoradiotherapy cause difficult mediastinal node dissection. We evaluated a novel technique to make the mediastinal node dissection easier after induction therapy. Methods: At the end of mediastinoscopic node biopsy for staging of lung cancer, cotton-type collagen was inserted anterior and lateral to the trachea in patients with pathologically confirmed mediastinal node involve-ment (n=45). The induction therapy consisted of concurrent use of platinum-based chemotherapy and hyperfractionated radiotherapy. After the chemoradiotherapy all patients underwent a pulmonary resection with complete mediastinal node dissection 7–12 weeks after the collagen insertion. Surgical findings of the mediastinum and the time for node dissection were compared with those without collagen insertion at mediastinoscopy after chemoradiotherapy (n=5). Results: All five patients without collagen insertion showed sclerotic and fibrotic change of mediastinal nodes with severe adhesion to the trachea. In 42 of 45 patients with collagen insertion (93.3%) the collagen remained unabsorbed and separated the mediastinal nodes from the trachea. Mediastinal node dissection was easily accomplished by removing mediastinal tissues lateral and anterior to the collagen. The rate of mediastinal node separation was significantly higher with collagen insertion than without (p< 0.0001). The times for node dissection in patients with and without collagen insertion showed no significant difference. Conclusion: Cotton-type collagen insertion at staging mediastinoscopy for lung cancer separates the mediastinal nodes from the trachea and makes the node dissection easier after induction chemoradiotherapy.