Combining nutritional status with TNM stage: a physiological update on gastric cancer staging for improving prognostic accuracy in elderly patients

International Journal of Clinical Oncology - The tumor-node-metastasis (TNM) staging system does not take the patient’s physiological status into consideration, reportedly making it...     

Outcomes of Patients with Hepatocellular Carcinoma Treated with Conventional Transarterial Chemoembolization Using Guidance Software

Purpose

To evaluate the outcomes of conventional transarterial chemoembolization using guidance software for hepatocellular carcinoma (HCC) patients.

The role of endothelin-B receptors in hypoxic pulmonary hypertension]

Endothelin-1 (ET-1) is a potent vasoactive peptide, and is thought to play an important role in the regulation of pulmonary vascular tone. Previous studies suggested that ET-1 can act as a vasoconstrictor via the endothelin-A and -B 2 receptors located on smooth muscle cells, and also act as a vasodilator through the endothelin-B 1 receptor situated on endothelial cells in the pulmonary circulation. To determine the role of endothelin-B receptors in hypoxic pulmonary hypertension, we examined the hemodynamic effects of a selective endothelin-B receptor agonist (IRL 1620) in chronic hypoxic pulmonary hypertensive rats. In rat lungs perfused with a half-blood solution, vasoconstriction by KCl administration was gradually reversed by IRL 1620 in normoxic rats, but not in chronic hypoxic rats. In in vivo studies, small doses of IRL 1620 induced transient vasodilation in normoxic rats, but had no obvious effects in chronic hypoxic rats. A high dose of IRL 1620 mediated vasoconstriction only in chronic hypoxic rats. Endothelin-B receptor messenger-RNA expression was lower in the lungs of chronic hypoxic rats than in normoxic rats. These results suggested that although the vasodilatory response mediated by endothelin-B receptor can be expected to play a protective role in the development of pulmonary hypertension, that response is diminished in hypoxic pulmonary hypertension.     

Triphasic differentiations of Merkel cell carcinoma in primary and metastatic lesions

We present a rare case of Merkel cell carcinoma (MCC) with heterologous differentiation. The patient was an 86‐year‐old female patient with MCC who presented with a forearm skin tumor and left axillary lymph node swelling. Histopathologically, the malignant components of the primary and metastatic lesions showed the intermingled features of triphasic phenotype differentiation, which had distinct cell populations; MCC, sweat gland carcinoma (SGC) and malignant poorly differentiated spindle cells with myogenic differentiation were immunohistochemically showed. Moreover, an electron microscopic observation of the tumor cells revealed intracytoplasmic canaliculi and junctional structures that indicated ductal differentiation. To our knowledge, this is the first case of MCC admixed with SGC and sarcomatous components in both the primary and metastatic lesions. An immunohistochemical study, using several stem cell markers, indicated that the MCC arose from pluripotent epidermal stem cells.     

Cases with a spontaneous regression of an infiltrating non‐crateriform keratoacanthoma and squamous cell carcinoma with a keratoacanthoma‐like component

We herein report the natural course of an early/proliferative stage keratoacanthoma (KA) with infiltrating islands of cytological malignancy (case 1) and a squamous cell carcinoma (SCC) with a KA‐like component (case 2), which were observed until their complete regression. The presented case 1 suggests that one of the histopathological forms of KA includes this unusual, infiltrating, non‐crateriform architecture, and also indicates the possibility of complete remission in the KA associated with infiltrating islands of cytological malignancy. In the presented case 2, the peripherally‐associated KA‐like focus was histopathologically considered to be either a remnant of KA focus or verrucous keratosis (hyperplasia). Therefore, the complete spontaneous regression of case 2 suggests that SCC arising in KA still has the potential of spontaneous regression, or that an extremely rare event, namely, the spontaneous regression of (traditional) SCC occurred in the present case.     

Telomerase activity in cell lines and lymphoma originating from Bloom syndrome.

Bloom syndrome (BS) is characterized by premature aging and high predisposition to various types of cancer. BLM is the causative gene for BS. BLM functions as a DNA helicase in the direction of 3' to 5' and small subsets of telomeres colocalize with BLM protein. We investigated telomerase activity and telomere repeat length in the cells from BS patients. In Epstein-Barr-virus (EBV) transformed lymphoblastoid cell lines and lymphoma cells from BS patients, telomerase activity was detected as in the control and compared. The metastatic tumor from BS patient, which had a 9-bp deletion of p53 DNA showed the strongest telomerase activity. Telomere repeat length in BS cells showed that there is no large difference compared with normal cells. Collectively, the results show that the BLM gene is not a major structural and regulatory factor in maintaining telomere repeat length and telomerase activity.     

Locoregional therapy with α‐emitting trastuzumab against peritoneal metastasis of human epidermal growth factor receptor 2‐positive gastric cancer in mice

Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine‐211 (²¹¹At‐trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)‐positive PMGC in a xenograft mouse model. We first observed that ²¹¹At‐trastuzumab can specifically bind and effectively kill NCI‐N87 (N87) cells, which are HER2‐positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test α‐particle radioimmunotherapy with ²¹¹At‐trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of ²¹¹At‐trastuzumab (1 MBq) was a more efficient means of delivery of ²¹¹At into metastatic tumors than i.v. injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of ²¹¹At‐trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2‐positive GC xenografts in two of six treated mice by inducing DNA double‐strand breaks, and to drastically reduce the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or significant biochemical changes in liver or kidney function were observed in the treatment group. Accordingly, locoregionally administered ²¹¹At‐trastuzumab significantly prolonged the survival time of HER2‐positive PMGC mice compared with control treatments. Our results provide a proof‐of‐concept demonstration that locoregional therapy with ²¹¹At‐trastuzumab may offer a new treatment option for HER2‐positive PMGC.