Hajime Tanaka

Role of diffusion-weighted magnetic resonance imaging in predicting sensitivity to chemoradiotherapy in muscle-invasive bladder cancer.

PURPOSEnIn chemoradiation (CRT)-based bladder-sparing approaches for muscle invasive bladder cancer (MIBC), patients who respond favorably to induction CRT enjoy the benefits of bladder preservation, whereas nonresponders do not. Thus, accurate prediction of CRT sensitivity would optimize patient selection for bladder-sparing protocols. Diffusion-weighted MRI (DW-MRI) is a functional imaging technique that quantifies the diffusion of water molecules in a noninvasive manner. We investigated whether DW-MRI predicts CRT sensitivity of MIBC.nnnMETHODS AND MATERIALSnThe study cohort consisted of 23 MIBC patients (cT2/T3xa0= 7/16) who underwent induction CRT consisting of radiotherapy to the small pelvis (40 Gy) with two cycles of cisplatin (20 mg/day for 5 days), followed by partial or radical cystectomy. All patients underwent DW-MRI before the initiation of treatment. Associations of apparent diffusion coefficient (ADC) values with CRT sensitivity were analyzed. The proliferative potential of MIBC was also assessed by analyzing the Ki-67 labeling index (LI) in pretherapeutic biopsy specimens.nnnRESULTSnThirteen patients (57%) achieved pathologic complete response (pCR) to CRT. These CRT-sensitive MIBCs showed significantly lower ADC values (median, 0.63 × 10(-3) mm(2)/s; range, 0.43-0.77) than CRT-resistant (no pCR) MIBCs (median, 0.84 × 10(-3) mm(2)/s; range, 0.69-1.09; pxa0= 0.0003). Multivariate analysis identified ADC value as the only significant and independent predictor of CRT sensitivity (p < 0.0001; odds ratio per 0.001 ×10(-3) mm(2)/s increase, 1.03; 95% confidence interval, 1.01-1.08). With a cutoff ADC value at 0.74 × 10(-3) mm(2)/s, sensitivity/specificity/accuracy in predicting CRT sensitivity was 92/90/91%. Ki-67 LI was significantly higher in CRT-sensitive MIBCs (pxa0= 0.0005) and significantly and inversely correlated with ADC values (ρxa0= -0.67, pxa0= 0.0007).nnnCONCLUSIONSnDW-MRI is a potential biomarker for predicting CRT sensitivity in MIBC. DW-MRI may be useful to optimize patient selection for CRT-based bladder-sparing approaches.

Diffusion‐weighted magnetic resonance imaging in the differentiation of angiomyolipoma with minimal fat from clear cell renal cell carcinoma

The aim of the present study was to evaluate diffusion‐weighted (DW) magnetic resonance imaging (MRI) in differentiating between minimal fat angiomyolipoma (MFAML) and clear cell renal cell carcinoma (CCRCC). Forty‐one solid renal tumors without visible macroscopic fat on unenhanced computed tomography images were evaluated by MRI, including DW‐MRI, and were diagnosed pathologically as CCRCC (nu2003=u200336) or MFAML (nu2003=u20035). To evaluate the heterogeneity of diffusion in each tumor, the signals of the tumors on DW‐MRI were analyzed subjectively and the apparent diffusion coefficient (ADC) values and histograms assessed objectively. Thirty‐three of 36 CCRCC (92%) exhibited a heterogeneous signal on DW‐MRI and several peaks in the ADC value histogram, whereas four of five MFAML exhibited a homogeneous signal on DW‐MRI and a single prominent peak in the histogram. The standard deviations of the ADC values were significantly smaller for MFAML than for CCRCC (Pu2003=u20030.0015). In conclusion, DW‐MRI can be considered a useful and noninvasive addition to the preoperative differentiation of CCRCC and MFAML.

Clinical response to induction chemotherapy predicts improved survival outcome in urothelial carcinoma with clinical lymph nodal metastasis treated by consolidative surgery

BackgroundTo determine the indications for post-chemotherapy consolidative surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial carcinoma (UC).MethodsSixty UC patients with measurable cN+ but without detectable systemic visceral/bone dissemination received induction platinum-based chemotherapy. Consolidative surgery was offered to all patients except for those with progressive disease. We retrospectively analyzed the clinicopathological response to induction chemotherapy and identified prognostic factors for overall survival (OS).ResultsThe primary cancer site was the urinary bladder in 31 patients (52xa0%) and upper urinary tract in 29 (48xa0%). The median number of chemotherapy courses was 4. Forty-five patients (75xa0%) showed a clinically objective response to the induction chemotherapy. Fifty-one patients (85xa0%) underwent subsequent consolidative surgery. Histopathological analysis indicated pT0 status in 10 (20xa0%) and pN0 in 17 (33xa0%). When all 60 patients were considered, clinical tumor response was found to be significantly correlated with achievement of pathological complete response. At the median follow-up of 22xa0months, the median progression-free survival and OS periods were excellent: 18.6 and 31.6xa0months, respectively. In the multivariate analysis, clinical tumor response was found to be an independent pre-surgical prognostic factor for OS, and pathologically negative lymph node, negative resection margin, more LNs removed, and negative lymphovascular invasion were found to be independent post-surgical prognostic parameters for OS.ConclusionsThe median OS in induction chemotherapy followed by consolidative surgery was very encouraging. Our results suggest that achieving a good clinical response to pre-surgical induction chemotherapy is a good indication for subsequent consolidative surgery in UC patients with cN+ to improve OS through a good pathological response.

Stepwise algorithm using computed tomography and magnetic resonance imaging for diagnosis of fat-poor angiomyolipoma in small renal masses: Development and external validation

To develop a stepwise diagnostic algorithm for fat‐poor angiomyolipoma in small renal masses.

Supramolecular flower micelle formation of polyrotaxane-containing triblock copolymers prepared from macro-chain transfer agents bearing molecular hooks

Polyrotaxane (PRX)-containing triblock copolymers are a unique class of supramolecular polymers. In combination with the intrinsic properties of polymer chains, the supramolecular properties of PRXs, such as the freely mobile character of threading α-cyclodextrins (α-CDs) and the intermolecular hydrogen bonding, can be utilized as biomaterials. However, it is difficult to synthesize well-defined PRX-containing triblock copolymers with regulated polymeric chain length and the number of threading α-CDs. Herein, we described the precise synthetic method of PRX-containing triblock copolymers via reversible addition–fragmentation chain transfer (RAFT) polymerization using a novel PRX macro-chain transfer agent (CTA) with terminal hooks of phenylalanyl groups. The terminal phenylalanyl groups of PRX macro-CTA act as a hook to inhibit the dethreading of α-CDs during polymerization to achieve the regulation of molecular weight of the polymer chains while maintaining the number of threading α-CDs in the PRX segments. Additionally, we first prepared self-assembled polymeric micelles with an outermost PRX layer using the PRX-containing triblock copolymers. The hydroxyethyl group-modified triblock copolymers composed of PRX and hydrophobic poly(benzyl methacrylate) (PBzMA) were found to form polymeric micelles 47 nm in diameter and with a narrow size distribution. The supramolecular polymeric micelles show a core–shell-type structure comprising a core of hydrophobic PBzMA surrounded by the PRX flower loops. This micelle formation allows the incorporation of water-insoluble anticancer drugs within the PBzMA core as well as biological ligands into the α-CDs of the PRX flowers toward receptor proteins of target cell membranes. Finally, it is expected that the obtained polymeric micelles with the outermost PRX layer could be applied as a supramolecular drug carrier.

Acute kidney injury and intermediate-term renal function after clampless partial nephrectomy

To evaluate the incidence and predictors of acute kidney injury after clampless partial nephrectomy, and its impact on intermediate‐term renal function.

A Case of Hereditary Persistence of α-Fetoprotein: Diagnostic Usefulness of the Subfraction Profile

α-Fetoprotein is a well-established tumor marker for non-seminomatous germ cell tumors. Elevated α-fetoprotein levels, however, result from a variety of clinical conditions. Hereditary persistence of α-fetoprotein is a rare benign disorder in which serum α-fetoprotein levels are persistently elevated, but there are no disabilities and symptoms. A 35-year-old man was diagnosed with pT1 testicular embryonal carcinoma. Post-orchiectomy α-fetoprotein levels remained persistently elevated without clinical or radiographic abnormalities. His mothers elevated α-fetoprotein levels confirmed the diagnosis of hereditary persistence of α-fetoprotein. Lens culinaris agglutinin-reactive α-fetoprotein fractions have been reported as a useful diagnostic marker for non-seminomatous germ cell tumors; in this patient, its measurement showed high non-reactive α-fetoprotein levels, which indicated the low probability of residual tumors. The present case represents the third case of hereditary persistence of α-fetoprotein in Japan, and the first in which the α-fetoprotein subfraction was evaluated.

Intensity ratio curve analysis of small renal masses on T2-weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell carcinoma

To assess the diagnostic ability of a pixel intensity‐based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat‐poor angiomyolipoma from renal cell carcinoma.

Impact of Immunohistochemistry-Based Subtypes in Muscle-Invasive Bladder Cancer on Response to Chemoradiation Therapy

PURPOSEnA bladder-sparing strategy is a useful option for patients with muscle-invasive bladder cancer (MIBC), in which the response to chemoradiation therapy (CRT) is primarily important in achieving favorable oncologic outcomes. Our objective is to evaluate the impact of immunohistochemistry (IHC)-based subtyping in MIBC on prediction of CRT response.nnnMETHODS AND MATERIALSnTreatment protocol consisted of induction CRT followed by partial or radical cystectomy as consolidative surgery; 118 eligible patients with nonmetastatic MIBC were retrospectively analyzed. Of these patients, 92 eventually underwent partial or radical cystectomy after CRT. We applied the IHC-based subtyping model developed by Lund University, which classifies patients into urobasal (Uro), genomically unstable (GU), and squamous cell cancer-like (SCCL) subtypes. GU and SCCL cancers are supposed to be highly aggressive and to have worse prognoses than Uro. Correlations of subtypes with CRT response were analyzed clinically in all patients and pathologically in 92 cystectomized patients. The impact of each subtype on cancer-specific mortality (CSM) was also analyzed.nnnRESULTSnOf all patients, 26 (22%), 61 (52%), and 31 (26%) were classified into Uro, GU, and SCCL subtypes, respectively. Clinical complete response (CR) was achieved in 42% of patients overall after CRT, with a significantly higher proportion in GU patients (52%) and SCCL patients (45%) than in Uro patients (15%; Pxa0<xa0.001 and Pxa0=xa0.01, respectively). On multivariate analysis, the GU/SCCL subtype was a significant predictor of clinical CR, as was absence of hydronephrosis or concomitant carcinoma in situ. Analyses for pathologic CR in the cystectomized patients revealed analogous findings. Five-year CSM of Uro, GU, and SCCL patients was 16%, 23%, and 28% overall, respectively, and 19%, 22%, and 23% in cystectomized patients, respectively, with no significant difference among the subtypes. CR status after CRT was significantly and independently correlated with low CSM in both clinical and pathologic evaluations.nnnCONCLUSIONSnGU and SCCL cancers showed significantly more favorable CRT response than did Uro cancers. IHC-based subtyping may improve clinical decisions about the indication of CRT for MIBC patients.

Absence of renal artery pseudoaneurysm on computed tomography after minimally-invasive partial nephrectomy using clampless and sutureless techniques

DOI: 10.1111/iju.13340 PN is widely carried out as standard care for SRMs, and can contribute to favorable oncological outcomes with better-preserved renal function than RN. PN, however, involves greater risks of perioperative complications. One of the most serious complications after PN is RAP, which can be life threatening. The incidence of RAP after PN was previously reported at 1– 5%, and patients were usually diagnosed with symptoms such as gross hematuria, flank pain or anemia. Recently, Takagi et al. showed that asymptomatic RAP, which can be diagnosed radiologically, occurred more frequently, in 15% of patients early after surgery, although it resolved in some patients without any treatment. The same group also reported that early unclamping during PN resulted in fewer patients with RAP, suggesting the importance of better identifying bleeding and hemostasis within the resection bed. Previous studies have also suggested that suturing the renal bed after tumor removal might lacerate arterioles, which subsequently become pseudoaneurysms after closure of renal defects. Since 2010, we have carried out minimally-invasive PN without renal vascular clamping or renorrhaphy for patients with SRMs. Our surgery is carried out retroperitoneally through a single minimum incision of approximately 4–5 cm, using an endoscope without gas insufflation (gasless single-port retroperitoneoscopic PN). For tumor resection without vascular clamping, bleeding is concurrently identified and controlled under endoscopic magnified view, which makes it possible to complete the operation without renorrhaphy. This clampless and sutureless technique aims to better preserve renal function compared with the conventional method, by preventing renal ischemia and reperfusion injury. Our technique might also contribute to the prevention of RAP, as we did not observe symptomatic RAP in any patient in our series who underwent this surgery. To examine for the presence of asymptomatic RAP, we carried out DCE-CT early after surgery in the recent cohort of patients undergoing gasless single-port retroperitoneoscopic PN. The present study was approved by the ethics committee at Tokyo Medical and Dental University (approval number 1937). Between August 2014 and July 2016, 103 consecutive patients with SRMs underwent gasless single-port retroperitoneoscopic PN. Surgery was carried out using the RoboSurgeon system, which uses a 3-D endoscope and 3-D head-mounted displays (HMM-3000MT; Sony, Tokyo, Japan) to provide magnified stereovision. For hemostasis during tumor resection, an I/O electrode with the soft-coagulation system of VIO 300D (ERBE Elektromedizin GmbH, Tübingen, Germany) was used with the effect level set at 7, and at a maximum output of 90 W. Absorbable hemostats (Integran; Koken, Tokyo, Japan and/or TachoSil; Nycomed, Z€urich, Switzerland) were placed in the resection bed as required. PN was completed without renal vascular clamping or renorrhaphy in all patients. The calyx was only sutured closed in cases in which the collecting system was open. None of the patients developed symptomatic RAP after PN. Patients were offered DCE-CT early after surgery; of the 103 patients, 74 patients with 76 tumors who had no contraindication for contrast agent and who agreed to undergo DCE-CT were included in the present study. Two patients had two ipsilateral renal tumors each, which were concurrently removed for each patient. CT images were interpreted by experienced radiologists, and the presence of RAP was recorded. Patient and tumor characteristics are summarized in the Table 1. Median blood loss and surgical time were 267 mL and 223 min, respectively. No patient received perioperative blood transfusion. DCE-CT was carried out on postoperative day 4–14 (median day 7). CT showed that there was no RAP development in the 74 patients. No patient experienced postoperative hemorrhage. Seven patients (9%) developed postoperative complications classified as Clavien–Dindo grade 3a; all seven were urinary leakages, which were treated with a ureteral stent insertion. No grade 3b or greater complications were observed. As confirmed by enhanced CT early after surgery, none of our patients who underwent minimally-invasive PN without renal vascular clamping or renorrhaphy developed RAP, which suggests that the PN using clampless and sutureless techniques could eliminate the potential risk of RAP. Under the endoscopic magnified view, soft-coagulation devices greatly