ObjectivesTo identify risk factors and develop a model for predicting recurrence of upper urinary tract urothelial carcinoma (UTUC) in the bladder in patients without a history of bladder cancer after radical nephroureterectomy (RNU). Patients and MethodsWe retrospectively reviewed 754 patients with UTUC without prior or concurrent bladder cancer or distant metastasis at 13 institutions in Japan. Univariate and multivariate Fine and Gray competing risks proportional hazards models were used to examine the cumulative incidence of bladder recurrence of UTUC. A risk stratification model and a nomogram were constructed. Two prediction models were compared using the concordance index (c-index) focusing on predictive accuracy and decision-curve analysis, which indicate whether a model is appropriate for decision-making and determining subsequent patient prognosis. ResultsThe cumulative incidence rates of bladder UTUC recurrence at 1 and 5 years were 15 and 29%, respectively; the median time to bladder UTUC recurrence was 10 months.Multivariate analysis showed that papillary tumour architecture, absence of lymphovascular invasion and higher pathological T stage were both predictive factors for bladder cancer recurrence. The predictive accuracy of the risk stratification model and the nomogram for bladder cancer recurrence were not different (c-index: 0.60 and 0.62). According to the decision-curve analysis, the risk stratification was an acceptable model because the net benefit of the risk stratification was equivalent to that of the nomogram. The overall cumulative incidence rates of bladder cancer 5 years after RNU were 10, 26 and 44% in the low-, intermediate-and high-risk groups, respectively. ConclusionsWe identified risk factors and developed a risk stratification model for UTUC recurrence in the bladder after RNU. This model could be used to provide both an individualised strategy to prevent recurrence and a risk-stratified surveillance protocol. Keywordsupper tract urothelial carcinoma, radical nephroureterectomy, bladder recurrence
Abbreviations & Acronyms CI = confidence interval CSS = cancer-specific survival DUx = distal ureterectomy EAU = European Association of Urology eGFR = estimated glomerular filtration rate HR = hazard ratio NCCN = National Comprehensive Cancer Network NUx = nephroureterectomy RFS = recurrence-free survival UC = urothelial carcinoma UUT-UC = upper urinary tract urothelial carcinoma Objectives: To investigate the oncological and functional outcome of distal ureterectomy compared with nephroureterectomy in the management of distal ureteral urothelial carcinoma. Methods: Using a database including upper urinary tract urothelial carcinoma patients (n = 1329), 282 patients were identified with urothelial carcinoma localized in the distal ureter on clinical evaluation. To adjust for potential baseline differences between groups, 43 patients undergoing distal ureterectomy were matched with 86 patients undergoing nephroureterectomy using propensity scoring. Cox regression models tested the effect of surgery type on recurrence-free survival and cancer-specific survival. Estimated glomerular filtration rate was measured before and after surgery. Results: The median follow-up period was 50 months. There were no significant differences in 5-year recurrence-free survival and cancer-specific survival rates between the distal ureterectomy and nephroureterectomy groups (P = 0.22 and P = 0.70, respectively). Multivariate analysis showed that surgery type was not associated with recurrence-free survival and cancer-specific survival (P = 0.90 and P = 0.28, respectively). In the subanalysis, recurrence-free survival and cancer-specific survival in the distal ureterectomy group were equivalent to those of the nephroureterectomy group in both pTa-1 and pT2-4 patients. Renal function was better preserved in the distal ureterectomy group than in the nephroureterectomy group (rate of change in estimated glomerular filtration rate 2% vs −20%; P < 0.001). Conclusions:The oncological outcome of distal ureterectomy is comparable with that of nephroureterectomy in distal ureteral urothelial carcinoma patients, and distal ureterectomy provides better preservation of renal function. Distal ureterectomy would be feasible for carefully selected patients with distal ureteral urothelial carcinoma.
Among 753 autopsy prostatic cancer cases with a metastasis, 476 (63%) had a lymph node metastasis, whereas 277 (37%) did not. Two different lymph node metastatic patterns were observed: Type 1, combined metastasis involving the pelvic and paraaortic lymph nodes; and Type 2, metastasis to the paraaortic lymph nodes, but not to the pelvic lymph nodes. Type 1 metastasis cases showed a significantly more frequent metastasis to the bladder and rectum, and a less frequent metastasis to the lungs and liver. Hydronephrosis occurred more frequently (P < 0.01) in the Type 1. Furthermore, in the Type 1 cases the lymph node metastasis appeared to be continuously invasive, but in the Type 2 cases, metastasis appeared to be the skip type or some metastases may have spread via the vertebral vein bypass route and may have been associated with a hematogenous metastasis. Cancer 65:1843-1846,1990. TTEMPTS TO RECONSTRUCT the pathway Of a me-A tastasis from the autopsy findings have been made, but the interpretation of the findings is difficult because of the complex interrelationships. The authors based their studies on the hypothesis that, even in autopsy cases, those with a smaller number of organs involved in metastasis can be suspected of clinically having been in the early stage of their disease.'-' Quite different results in the frequencies of a metastasis to various organs were seen between cases with a smaller number of metastatic organs involved and those with three or more metastatic organs. Furthermore, some metastasis may have been much more rapidly fatal, and so may have appeared more frequently in the autopsy series. However, cases without metastasis or with only metastasis to one organ may have died from causes other than cancer. Thus, this report mainly presents the results in cases with metastasis confined to one organ with regard to determining the possible mode of a lymph node metastasis of a prostatic cancer by using the same methods as in previous studies.'-' Materials and Methods The mode of metastasis have been studied in 753 autopsy cases of a prostatic cancer with metastasis collected from the Annuals of Pathological Autopsy Cases in Japan, from 1958 through 1980, published by the Japanese Pathological Society.6 Metastasis-free cases and double cancer cases with a prostatic cancer were excluded in the current study. The cases were classified into those with metastasis confined to one organ, those with metastasis to the pelvic and/or paraaortic lymph nodes, and those with metastases of multiple organs, and a comparison was made concerning the frequency of hydronephrosis and that of metastasis to other lymph nodes and to various other organs using the chi-square test. It is not known if the organs were involved in invasion or in metastasis. Therefore, metastasis has been used as a general term throughout this report. Results Among the 753 cases with metastasis, 206 (27%) had metastasis confined to only one organ and 547 (73%) had combined metastases to multiple organs. Among the 206 cases, bone metastasis was...
: The role of tubular structures that contribute to the passage of spermatozoa is not solely passive; these structures actively contribute to their own functions, although these tubules and ducts are contiguous and collaborate in the development of the male gamete along their lengths. The testis has the specific function to generate spermatozoa and spermatozoa undergo numerous changes as they pass through the epididymis. A member of the p53 family of genes, p63, is highly expressed in the basal layers of epithelial tissues and plays a key role in maintaining their cell populations, whereas Notch 1 and its ligand Jagged 2 have an important role in the differentiation of germ cells and Jagged 2 is up‐regulated by TAp63, one of the p63 isoforms, which transactivates p53 target genes and induces apoptosis. Although the presence of p63 in most epithelia is established, the role of p63 and its possible relationship with the Notch system in the seminiferous epithelium have not been examined. Therefore, we investigated the expression of p63, Jagged 2, and Notch 1 in the testis during postnatal development in comparison with their expression levels in the vaso‐epididymal epithelium. In the testis, the expression of TAp63 mRNA increased at day 14 after birth and the expressions of Jagged 2 and Notch 1 mRNA increased at day 16 after birth, suggesting that TAp63‐mediated Jagged 2 induction activates the Notch signaling system. On the other hand, the strong signal of ΔNp63 mRNA was already recognized in the vas deferens at day 0 after birth and advanced chronologically along the duct to the caput epididymis and p63 protein was expressed in basal cells in their epithelium, whereas the mRNAs of Jagged 2 and Notch 1 were maintained at a low level. Consequently, examination of our data raises the probability that TAp63 has an important role for maintenance of germ cell numbers, triggering or balancing the development, differentiation, and apoptosis of germ cells in the testis, which is completely different from the role of ΔNp63 in other epithelial tissues.
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