腎・尿路・膀胱

泌尿器癌患者に対する定量的なフレイル評価は予後予測に有効性である

演　　者：: 畠山真吾¹，相馬理¹, 山本勇人¹, 米山高弘¹, 古家琢也¹, 中路重之², 大山力¹
所属機関：: ¹弘前大学・泌尿器科, ²弘前大学・社会医学

Objectives: As optimal tools for evaluating frailty among urological cancer patients remain unclear, we aimed to investigate the clinical implication of quantitative frailty on prognosis in urological cancer patients.
Materials and Methods: Total 605 urological cancer patients presenting to our hospital underwent a prospective frailty assessment. Controls were selected from 2280 community-dwelling subjects. Frailty was assessed via physical status, blood biochemical tests, and mental status. We compared frailty variables between pair-matched controls and urological cancer patients. Then, we developed Frailty discriminant score (FDS) using frailty variables, and compared with the Fried criteria. The influence of FDS on overall survivals was investigated by Kaplan-Meier analysis and Cox regression analysis.
Results: Gait speed, hemoglobin, serum albumin, exhaustion, and depression were significantly worse in patients with all types of cancers than in pair-matched controls. FDS showed clear separation between controls and urological cancer patients, and significant association with the Fried criteria. Overall survivals were significantly shorter in patients with a higher score (>2.30) than in those with a lower score among nonprostate cancer (bladder, upper tract urothelial carcinoma, and renal cell carcinoma) patients. In prostate cancer patients, overall survivals were significantly shorter in patients with a higher score (>3.30) than in those with a lower score.
Conclusions: FDS was significantly associated with frailty and prognosis in urological cancer patients. This tool for frailty assessment can help patients and physicians make more informed decisions. Further validation study is required.

腎盂尿管癌患者の腹腔鏡下腎尿管全摘除術における気腹時間と術後膀胱内再発率との関連

演　　者：: 茂田啓介¹，菊地栄次¹, 萩原正幸², 武田利和¹, 松本和宏¹, 篠島利明¹, 宮嶋哲³, 大家基嗣¹
所属機関：: ¹慶應義塾大学・泌尿器科, ²東京歯科大学市川総合病院・泌尿器科, ³東海大学・泌尿器科

Some investigators have reported that upper tract urothelial carcinoma (UTUC) patients treated with laparoscopic radical nephroureterectomy (LRNU) had an increased risk of intravesical recurrence (IVR) as compared to those treated with open RNU. Herein,we speculated that continuous high pressure during a laparoscopic procedure could lead to increased flow of cancer cells into the lower urinary tract resulting in a higher incidence of IVR.
We identified 129 patients who underwent LRNU in our institution. We reviewed all recorded videotapes and divided the surgical procedure into three categories; extirpation of the kidney, bladder cuff excision, and total operation.We assessed the association of the IVR rate and the patient's clinico-pathological characteristics and surgery related factors.
Sixty patients(46.5%) were diagnosed with IVR within a median follow-up of 19.4 months. The mean pneumoperitoneum, bladder cuff excision, and total operation times were 151.0±58.1, 157.0±130.0, and 300.6±98.5 minutes, respectively. Multivariate analysis revealed that prolonged pneumoperitoneum time and presence of lymphovascular invasion were independent risk factors for IVR after LRNU. The 3year and 5year IVR free survival rates were 41.1% and 21.8% in patients with a prolonged pneumoperitoneum time of ≧150 minutes, respectively, which were significantly lower than those in their counterparts (55.7% and 48.3%, respectively, p=0.024). Furthermore, by dividing pneumoperitoneum time with 60 minutes interval, the subsequent IVR rates were 27.3% for a pneumoperitoneum time of less than 90 minutes, 35.8% for that of 90-150 minutes, 55.0% for that of 150-210 minutes, 61.1% for that of 210-270 minutes, and 85.7% for that of more than 270 minutes.
From these findings, continued presence of a high-pressured environment during a laparoscopic procedure due to a longer operative time may promote tumor cancer cell seeding implantation to bladder epithelium.

酸性尿による経尿道的膀胱腫瘍切除後の上部尿路上皮癌発生リスクの上昇

演　　者：: 井手広樹^1,2，菊地栄次², 荻原広一郎², 枡田司², 大家基嗣²
所属機関：: ¹東京都済生会中央病院・泌尿器科, ²慶應義塾大学・泌尿器科

Objective: Several risk factors contribute to carcinogenesis of upper tract urothelial carcinoma (UTUC). Recently, a lower urinary pH was found to be significantly associated with bladder carcinogenesis in patients with smoking history (SH) because acidic urine activates aromatic amines derived from cigarettes. However, no study has evaluated the association between pH and UTUC.
Methods: Our study population was comprised of 647 non-muscle invasive bladder cancer (NMIBC) patients with no history of UTUC. Mean follow-up duration was 75 months. Urinary pH was defined as the median of 3 consecutive data after surgery and 6.0 was defined as a cut-off point. We evaluated the association between clinico-pathological factors including pH and UTUC in NMIBC.
Results: Urinary pH was less than 6.00 and 6.00 or more in 379 and 268, respectively. UTUC developed in 21 (3.2%). There were no significant differences of clinico-pathological factors between two groups. UTUC rates were 4.5 and 1.5% in low and high pH, respectively (p=0.034). Multivariate analysis revealed low pH to be an independent factor for UTUC in overall (p=0.024, HR=4.115) and patients with SH (N=374, p=0.049, HR=7.692). Focusing on patients with SH, UTUC rates in low and high pH were 5.2 and 0.7%, respectively (p=0.024). Meanwhile, in patients without SH, there was no significant difference between them. In patients with longer smoking duration (≧20 years) and higher smoking intensity (≧20 per day), low pH had significantly higher UTUC rates (5.5 and 5.4%) than high pH (0.9 and 0.0%, p=0.039 and 0.021), respectively. Meanwhile, in patients with shorter duration (<20 years) and lower intensity (<20 per day), there was no significant difference between them.
Conclusions: Low urinary pH increases UTUC rate in NMIBC, especially with SH. Urine alkalization have a potential for preventing UTUC.

転移性腎癌に対する一次スニチニブ治療において、治療中の筋肉量低下は予後に相関する

演　　者：: 石原弘喜¹，高木敏男¹, 近藤恒徳², 吉田一彦¹, 飯塚淳平¹, 田邉一成¹
所属機関：: ¹東京女子医科大学・泌尿器科, ²東京女子医科大学東医療センター・泌尿器科

Background: Cancer cachexia, namely sarcopenia, is associated with patient outcomes. Sarcopenia is a state of degenerative skeletal muscle wasting and can be diagnosed using the imaging evaluation. Based on this definition, we previously reported that pre-treatment sarcopenia was associated with patient survival after first-line sunitinib therapy for metastatic renal cell carcinoma (mRCC).

Objective: The aim of this study was to evaluate the impact of changing of skeletal muscle mass during first-line sunitinib therapy on oncological outcome in patients with mRCC.

Patients and methods: Sixty-nine patients who did not receive any therapies to sunitinib were retrospectively evaluated. Skeletal muscle index (SMI) was calculated on the computed tomography images conducted before the initiation of and after two cycles of sunitinib. ΔSMI was calculated as [(post-treatment SMI - pre-treatment SMI)/pre-treatment SMI]×100. We divided the patients into the two groups as follows; ΔSMI ≧ 0 (not decreasing of SMI) vs. < 0 (decreasing of SMI). Factors for progression-free survival (PFS) and overall survival (OS) were analyzed.

Results: Median ΔSMI was -0.81. Skeletal muscle mass was decreased in 39 patients (56.5%). Decreasing SMI was associated with the histological type of non-clear cell carcinoma (p = 0.0381). PFS and OS were significantly shorter in patients with ΔSMI < 0 compared to those with ΔSMI ≧ 0 (median PFS: 9.86 vs. 28.4 months, p = 0.0007; OS: 20.0 vs. 52.6 months, p = 0.0007). Multivariate analyses for PFS and OS showed that ΔSMI was an independent predictor for PFS (HR: 0.36, 95% CI: 0.19 - 0.66, p = 0.0009) and OS (HR: 0.27, 95% CI: 0.12 - 0.55, p = 0.0003). Also, objective response rate was significantly lower in patients with ΔSMI < 0 (23.1% vs. 50.0%, p = 0.0199).

Conclusions: Decreasing of skeletal muscle mass during first-line sunitinib therapy was significantly associated with poor oncological outcomes in patients with mRCC.

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