IJU this issue

Abstract

Mototsugu Oya M.D., Associate Editor In this issue, I would like to focus on “degenerative” and “regenerative” medicine. The degenerative issue is renal cell carcimoma (RCC) arising in end-stage kidneys. Whether RCC arising in patients under hemodialysis (HD) is the same as or different from non-HD RCC in terms of oncogenesis is an important issue to be resolved. The most important molecule related to RCC oncogenesis is von Hippel-Lindau disease tumor suppressor gene. The mutation of the gene is observed both in sporadic non-HD patients and HD patients. In contrast, in pathological aspects, RCC arising in HD patients occasionally have different types of cancer tissues (described by Tickoo SK et al. cited #25 in Takagi's paper). This suggests a distinctly different oncogenic pathway. The most different feature, I believe, is that HD-related RCC are multifocal in contrast to the non-HD, which is single (unifocal). Multifocal tumors can arise in susceptible, pre-oncogenic tissues. For example, liver cancer arises from hepatitis virus-infected tissues that are susceptible to cancer. Takagi et al. described the clinical characteristics of RCC in HD patients in a single institution. They showed that bilateral occurrence did not influence the likelihood of death from cancer, suggesting de novo primary events rather than the metastases of the contralateral primary. Interestingly, a longer duration before surgery was an unfavorable prognosis. This suggests that the accumulation of molecular alteration in end-stage kidneys is related to progression of the cancer as well as the initiation. Molecular pathogenesis needs to be elucidated in this malignant phenotype of long HD-associated RCC. Venous extension or tumor thrombus is a feature of RCC that is rarely observed in other cancers. The 7th edition of UICC changed the T3 classification. The cephalad extent of the tumor was divided into three parts, namely, renal vein, inferior vena cava (IVC) below the diaphragm and IVC above the diaphragm, and assigned T3a, T3b and T3c. Nagata et al. assessed the revision of UICC using the clinical data in their institution retrospectively. Their Kaplan–Meier curves were clearly separated accordingly. They concluded that the new classification could be valid in Japan. T category in RCC is complex, as compared with other cancers. For example, T factor in bladder cancer is simply the extent of the invasion. In determining the T of RCC, tumor size, perinephric invasion, adrenal invasion and venous involvement should be evaluated. The 7th edition of UICC is not perfect. Based on accumulating publications, T factor might be changed in the future. Regenerative medicine is one of the main topics at present. Obinata et al. used a unique cell transplantation system named adipocyte-derived dedifferentiated fat (DFAT) cells to treat stress urinary incontinence (SUI) in a rat model. DFAT cells are easily isolated from a small amount (approximately 1 g) of subcutaneous adipose tissue and differentiated to smooth muscle-like cells by adding transforming growth factor-β1. A cross-section of the urethra showed a marked difference in terms of the thickness of the muscle layers in the DFAT-injected rats. As mentioned in the Editorial Comment by Pastor-Navarro, this injured model is not a permanent model. SUI is a permanent injury as a result of labor during childbirth. She mentioned a need for a permanent injury model to validate the results. I believe DFAT is easy and can be applicable to clinical use. However, several issues should be clarified. How and how long are the dedifferentiated muscle-like cells maintained in the tissues? How is the injected DFAT distributed and how about the injured muscle cells? An easy method that is replicable by other researchers can survive in regenerative medicine. To explore an easy way is a short cut to clinical use. None declared.