Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

[Port Site Recurrence After Laparoscopic Nephrectomy for Renal Cell Carcinoma --Report of Two Cases and Literature review-].

CASE 1: A male in his 60s underwent a right transperitoneal laparoscopic partial nephrectomy procedure for a right renal tumor. Rupture of a renal cyst located close to the tumor occurred intraoperatively. The histopathological diagnosis was clear cell renal cell carcinoma (CCRCC), pT1aN0M0, G2, v0, with negative resection margins. At 84 months after surgery, computed tomography (CT) revealed a 10 mm mass in the rectus abdominis muscle at the camera port site used for the partial nephrectomy. An open lumpectomy was then performed and the histopathological diagnosis was CCRCC. One year later, a 40 mm sized mass was detected in the mesentery of the small intestine by CT, which was removed laparoscopically with part of the mesentery and diagnosed as CCRCC. Since that surgery, the patient has been free from recurrence for 8 years. CASE 2: A male in his 60s underwent a left retroperitoneal laparoscopic nephrectomy procedure for a left renal tumor. The histopathological diagnosis was CCRCC, pT1aN0M0, G1, v0, with negative resection margins. At 31 months after surgery, CT revealed a 32 mm mass in the retroperitoneal cavity at the right hand port site used for the laparoscopic nephrectomy. The mass was removed with part of the twelfth rib and erector spinae muscles in a lump, and the histopathological diagnosis was CCRCC. Since that surgery, the patient has been free from recurrence for 19 months. For the treatment of solitary port site recurrence of renal cell carcinoma after a laparoscopic radical/partial nephrectomy, we recommend surgical resection for a good prognosis.

DNA maintenance methylation enzyme Dnmt1 in satellite cells is essential for muscle regeneration.

Epigenetic transcriptional regulation is essential for the differentiation of various types of cells, including skeletal muscle cells. DNA methyltransferase 1 (Dnmt1) is responsible for maintenance of DNA methylation patterns via cell division. Here, we investigated the relationship between Dnmt1 and skeletal muscle regeneration. We found that Dnmt1 is upregulated in muscles during regeneration. To assess the role of Dnmt1 in satellite cells during regeneration, we performed conditional knockout (cKO) of Dnmt1 specifically in skeletal muscle satellite cells using Pax7CreERT2 mice and Dnmt1 flox mice. Muscle weight and the cross-sectional area after injury were significantly lower in Dnmt1 cKO mice than in control mice. RNA sequencing analysis revealed upregulation of genes involved in cell adhesion and apoptosis in satellite cells from cKO mice. Moreover, satellite cells cultured from cKO mice exhibited a reduced number of cells. These results suggest that Dnmt1 is an essential factor for muscle regeneration and is involved in positive regulation of satellite cell number.

GPRC5A facilitates cell proliferation through cell cycle regulation and correlates with bone metastasis in prostate cancer.

The prognosis of patients with progressive prostate cancers that are hormone refractory and/or have bone metastasis is poor. Multiple therapeutic targets to improve prostate cancer patient survival have been investigated, including orphan GPCRs. In our study, we identified G Protein-Coupled Receptor Class C Group 5 Member A (GPRC5A) as a candidate therapeutic molecule using integrative gene expression analyses of registered data sets for prostate cancer cell lines. Kaplan-Meier analysis of TCGA data sets revealed that patients who have high GPRC5A expression had significantly shorter overall survival. PC3 prostate cancer cells with CRISPR/Cas9-mediated GPRC5A knockout exhibited significantly reduced cell proliferation both in vitro and in vivo. RNA-seq revealed that GPRC5A KO PC3 cells had dysregulated expression of cell cycle-related genes, leading to cell cycle arrest at the G2/M phase. Furthermore, the registered gene expression profile data set showed that the expression level of GPRC5A in original lesions of prostate cancer patients with bone metastasis was higher than that without bone metastasis. In fact, GPRC5A KO PC3 cells failed to establish bone metastasis in xenograft mice models. In addition, our clinical study revealed that GPRC5A expression levels in prostate cancer patient samples were significantly correlated with bone metastasis as well as the patient's Gleason score (GS). Combined assessment with the immunoreactivity of GPRC5A and GS displayed higher specificity for predicting the occurrence of bone metastasis. Together, our findings indicate that GPRC5A can be a possible therapeutic target and prognostic marker molecule for progressive prostate cancer.

[FACTORS AFFECTING SHORT-TERM RENAL FUNCTION AFTER PARTIAL NEPHRECTOMY].

(Objectives) Recently, partial nephrectomy has been recommended for patients with T1 renal cell carcinoma to preserve renal function. In this study, we retrospectively investigated the factors that affect renal function after laparoscopic or robotic partial nephrectomy using cold or warm ischemia. (Patients and methods) We reviewed 105 patients who underwent laparoscopic or robotic partial nephrectomy between March 2006 and July 2016. Patients who had a single kidney were excluded. Thirty-nine patients were managed with cold ischemia, and 66 were managed with warm ischemia. Renal function was assessed using the estimated glomerular filtration rate (eGFR) and glomerular filtration rate (GFR) categories of the stage of chronic kidney disease (CKD). (Results) In the cold and warm ischemia groups, the duration of ischemia was significantly correlated with deterioration of the eGFR at 12 months postoperatively, but the duration of ischemia was not significantly correlated with exacerbation of the GFR categories for the stage of CKD in multivariate analyses. (Conclusions) These results suggest that the ischemia time may not have an impact on prognosis. However, due to the lack of deaths from renal carcinoma or cardiovascular events postoperatively in this study, the influence of each factor on overall survival or cardiovascular events could not be evaluated. More investigations are necessary to discern the acceptable level of deterioration and the corresponding clinical implications for postoperative eGFR.

[FEMALE PARAURETHRAL LEIOMYOSARCOMA: A CASE REPORT].

A 54-year-old woman visited another hospital with complaining of a palpable mass in vagina and dysuria. The mass had gradually enlarged since the past 2 years. Ultrasonography and CT revealed the tumor located between the urethra and vaginal mucosa. Histopathological examination was well-differentiated leiomyosarcoma from transvaginal needle biopsy. She was referred to our hospital. On MRI, the 4-cm tumor showed no infiltration into the vaginal mucosa or urethra. PET/CT showed a high uptake of FDG. No metastatic disease was evident. We performed excision of the tumor transvaginally. The tumor cells demonstrated immunoreactivity for estrogen receptors and partially progesterone receptors in histopathological examination. We speculated that the developmental mechanism of female paraurethral leiomyosarcoma was associated with female leiomyosarcoma in other surrounding pelvic organs.

[Port-Site Metastasis of Urothelial Carcinoma after Laparoscopic Nephroureterectomy: A Case Report].

The patient was a 70-year-old woman with a chief complaint of right hydronephrosis and hydroureter detected by ultrasound by a local doctor. She came to our hospital in January, 2014 for further examination. Because a tumor was discovered in her right upper ureter by computed tomography (CT) and retrograde pyelography, a right laparoscopic nephroureterectomy was perfomed on the suspicion of a right ureter carcinoma (clinical stage T2 N0M0). The pathological examination showed urothelial carcinoma, grade 3, pT3. She was followed up carefully without adjuvant chemotherapy. At 10 months postoperatively, a subcutaneous tumor was found at the port-site by CT, and she underwent surgical resection of the subcutaneous tumor. Pathological diagnosis was urothelial carcinoma, and was confimed to be portsite metastasis of urothelial carcinoma. She received three courses of gemcitabine and carboplatin chemotherapy therapy from November, 2014. She has been followed up without signs of recurrence.

[Seroma formation associated with expanded polytetrafluoroethylene graft used for dialysis access: a case report].

The patient was a 67-year-old man with end stage renal failure. Hemodialysis had been started in 1998. An expanded polytetrafluoroethylene (PTFE) graft was inserted into his left forearm and used for vascular access. He received a partial replacement of the expanded PTFE graft in September 2013. A seroma formed after this intervention and subsequently grew larger. He thus underwent seroma removal and bypass graft surgery. Four months after the surgery, to date, he remains free of seroma recurrence.

Health-related quality of life in the first year after laparoscopic radical prostatectomy compared with open radical prostatectomy.

OBJECTIVE: To assess health-related quality of life in the first year after laparoscopic radical prostatectomy compared with that after open radical prostatectomy. METHODS: The subjects were 105 consecutive patients with localized prostate cancer treated with laparoscopic radical prostatectomy between January 2011 and June 2012. Health-related quality of life was evaluated using the International Prostate Symptom Score, Medical Outcome Study 8-Items Short Form Health Survey (SF-8) and Expanded Prostate Cancer Index Composite at baseline and 1, 3, 6 and 12 months after surgery. Comparisons were made with data for 107 consecutive patients treated with open radical prostatectomy between October 2005 and July 2007. RESULTS: The International Prostate Symptom Score change was similar in each group. The laparoscopic radical prostatectomy group had a better baseline Medical Outcome Study 8-Items Short Form Health Survey mental component summary score and a better Medical Outcome Study 8-Items Short Form Health Survey physical component summary score at 1 month after surgery. In Expanded Prostate Cancer Index Composite, obstructive/irritative symptoms did not differ between the groups, but urinary incontinence was worse until 12 months after surgery and particularly severe after 1 month in the laparoscopic radical prostatectomy group. The rate of severe urinary incontinence was much higher in the laparoscopic radical prostatectomy group in the early period. Urinary bother was worse in the laparoscopic radical prostatectomy group at 1 and 3 months, but did not differ between the groups thereafter. Urinary function and bother were good after nerve sparing procedures and did not differ between the groups. Bowel and sexual function and bother were similar in the two groups. CONCLUSION: Urinary function in the first year after laparoscopic radical prostatectomy is worse than that after open radical prostatectomy.

Surveillance biopsy and active treatment during active surveillance for low-risk prostate cancer.

BACKGROUND: The goals of the study were to examine surveillance biopsy and active treatment in patients under active surveillance (AS) for low-risk prostate cancer and to determine the active treatment-free survival rate. METHODS: The subjects were 87 patients with low-risk prostate cancer who were under AS between 2000 and 2010. The eligibility criteria for AS were T1c, Gleason score ≤ 6, prostate-specific antigen level ≤ 10 ng/ml, one or two positive biopsies, maximum cancer involvement ≤ 50 %, and age ≤ 80 years old. RESULTS: Of the 87 patients, 48 underwent the first surveillance biopsy (55.2 %). In this biopsy, no cancer was found in 33.3 % of cases, 27.1 % remained eligible for AS, and 39.6 % did not meet the AS criteria (up-grade 22.9 %, up-volume 16.7 %). A second surveillance-biopsy was performed at 1.9 years after the first biopsy. No cancer was found in 20.0 % of cases, 40.0 % remained eligible for AS, and 40.0 % did not meet the AS criteria (up-grade 26.7 %, up-volume 13.3 %). A total of 50 patients received treatment by 1.7 years after starting AS, mainly due to an up-grade or up-volume. However, some patients underwent radiotherapy despite biopsy results indicating no cancer or eligibility for AS. The active treatment-free survival rate was 64.1 % after 2 years. CONCLUSIONS: Surveillance biopsy is important for identifying patients who require active treatment. The results in this study allowed determination of the active treatment-free survival rate and are informative for making treatment decisions.