RESUMEN
Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard.
Asunto(s)
Adenoma de Células Hepáticas , Carcinoma Hepatocelular , Diabetes Mellitus , Neoplasias Hepáticas , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Adenoma de Células Hepáticas/etiología , Adenoma de Células Hepáticas/metabolismo , Animales , Carcinoma Hepatocelular/metabolismo , Proteínas de Unión a Ácidos Grasos/metabolismo , Glutamato-Amoníaco Ligasa/genética , Glutamato-Amoníaco Ligasa/metabolismo , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/metabolismo , Masculino , Síndrome Metabólico/complicaciones , Ratones , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/etiología , Proteína Amiloide A Sérica/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
We here present a case report of a patient with Stage IV gastric cancer with peritoneal metastasis (P1, CY1) who underwent conversion surgery after a successful response to chemotherapy (S-1 + oxaliplatin + nivolumab). The patient was a woman in her 60 s. Her chief complaint was epigastric pain. Upper gastrointestinal endoscopy showed Type 4 advanced carcinoma on the lesser curvature of the gastric body. Biopsy showed Group 5 (poorly differentiated adenocarcinoma) and HER2 was negative. Staging laparoscopy revealed seeding in the round ligament of the liver (P1) and adenocarcinoma cells in ascites (CY1). Ten courses of chemotherapy (S-1 + oxaliplatin + nivolumab) were administered, after which contrast-enhanced computed tomography showed that the primary tumor had shrunk and seeding was no longer detectable. Upper gastrointestinal endoscopy revealed scar-like changes. A second staging laparoscopy revealed that ascites cytology was negative and a biopsy of the round ligament of the liver showed no malignant cells (P0, CY0). Conversion surgery comprising laparoscopic total gastrectomy with D2 lymph node dissection and resection of the round ligament of the liver was performed. The postoperative course was uneventful. Histopathological examination of the resected specimen revealed no tumor cells in the gastric mesentery or the round ligament of the liver. The pathological diagnosis was gastric cancer [M, U, L, Less, Ant, Post, type4, T3(SS), N0, M0 (H0, P0, CY0), ypStage IIA]. Adjuvant chemotherapy (S-1) was commenced. The patient is still alive 7 months later with no evidence of recurrence.