Masakazu Tsutsumi

The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: clinicopathological analysis

BackgroundWe evaluated the accuracy and feasibility of real-time elastography for detecting prostate cancer, using prostatectomy specimens.MethodsThis study was based on clinicopathological findings in 51 patients with prostate cancer who were referred for elastography at the time of prostate biopsy. We compared transverse pathology sections with elastographic moving images (EMIs) to determine the detection rate of cancer, the relationship between tumor location and the elastographic findings, and the relationship between the Gleason score and the elastographic findings.ResultsIn 15 patients (29%), all EMIs were in complete agreement with tumor location (category I), in 28 patients (55%), the EMIs agreed with tumor location, but showed some disagreement (category II), and in 8 patients (16%) there was disagreement of the elastographic findings with tumor location or the tumors were undetectable by elastography (category III). However, in category III, all tumors were detected as low-echoic by B-mode ultrasonography. We divided the prostate into three different regions (anterior, middle, and posterior), and found that 30/32 (94%) anterior tumors, 13/17 (76%) middle tumors, and 16/28 (57%) posterior tumors were detected by elastography. The proportions of cancers detected by elastography (categories I+II/total) was 100% in the patients with a Gleason score of 6, 85% in those with a score of 7 or 8, and 63% in those with a score of 9 or 10.ConclusionReal-time elastography in conjunction with B-mode ultrasonography significantly improves the detection of prostate cancer. One of the characteristic findings of elastography is its excellent detection of anterior tumors. The low detection rate of high-grade tumors in this analysis was likely due to the predominance of high-grade tumors in a peripheral location compared to the anterior location of the low-grade tumors.

Real-time Elastography for the Diagnosis of Prostate Cancer: Evaluation of Elastographic Moving Images

OBJECTIVE Elastography is a technique for detecting the stiffness of tissues. We applied elastography for the diagnosis of prostate cancer and evaluated the usefulness of elastography for prostate biopsy. METHODS The subjects of this study were 311 patients who underwent elastography during prostate needle biopsy at Hitachi General Hospital. Strain images obtained during compression of the prostate tissue were displayed on a monitor and recorded on the computer. The elastographic moving images (EMI) were evaluated retrospectively. The evaluable images and biopsy results were compared in terms of the feasibility and accuracy. RESULTS The median patient age was 67 years (range 50-85 years), the median serum level of prostate-specific antigen was 8.4 ng/ml (range 0.3-82.5 ng/ml) and the median prostate volume was 42.6 ml (range 12-150 ml). Among the 311 patients, prostate cancer was detected in 95 patients (30%) by biopsy. The diagnostic sensitivity was 37.9% for digital rectal examination (DRE) and 59.0% for transrectal ultrasonography (TRUS), whereas it was 72.6% for elastography and 89.5% for the combination of TRUS and elastography. Elastography-positive EMIs with negative biopsies were eventually determined to be due to benign prostatic hyperplasia. CONCLUSION Elastography has a significantly higher sensitivity for the detection of prostate cancer than the conventionally used examinations including DRE and TRUS. It is a useful real-time diagnostic method because it is not invasive, and simultaneous evaluation is possible while performing TRUS.

Real-Time Balloon Inflation Elastography for Prostate Cancer Detection and Initial Evaluation of Clinicopathologic Analysis

OBJECTIVE The use of elastography is limited for prostate cancer detection because of the difficulty in obtaining stable and reproducible images. To overcome these limitations, we developed a new technique called real-time balloon inflation elastography (RBIE); with RBIE, balloon inflation and deflation are used in place of manual compression. We present the accuracy and feasibility of the RBIE technique for detecting prostate cancer. MATERIALS AND METHODS The results of a pathologic analysis of 55 prostatectomy specimens were compared with elastographic moving images obtained at the time of biopsy of the prostate. RESULTS The RBIE technique generated stable and repeatable elastographic moving images. The percentage of images affected by artifact due to slippage in the compression plane was reduced to 1% using the RBIE method compared with 32% using the manual compression method. With regard to tumor location, elastographic moving images obtained using the RBIE technique were in complete agreement with clinicopathologic evaluation of tumor location in eight cases (15%), showed partial agreement in 43 cases (78%), and disagreed in four cases (7%). In three different regions of the prostate, 84% of anterior tumors, 85% of middle tumors, and 60% of posterior tumors were detected. The tumor detection rates by Gleason score were 60% in tumors with a Gleason score of 5 or 6, 73% in tumors with a Gleason score of 7, 72% in tumors with a Gleason score of 8, and 74% in tumors with a Gleason score of 9 or 10. CONCLUSION The RBIE method improved the quality of elastographic moving images compared with the manual compression method. High-grade tumors and tumors of impalpable regions of the prostate were more frequently detected using RBIE. We conclude that RBIE is a promising method with which to detect prostate cancer.

Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer

Purpose Opioid-induced constipation (OIC) is a frequent and debilitating adverse effect (AE) of opioids-common analgesics for cancer pain. We investigated the efficacy and safety of a peripherally acting μ-opioid receptor antagonist, naldemedine (S-297995), for OIC, specifically in patients with cancer. Patients and Methods This phase III trial consisted of a 2-week, randomized, double-blind, placebo-controlled study (COMPOSE-4) and an open-label, 12-week extension study (COMPOSE-5). In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned on a 1:1 basis to receive once-daily oral naldemedine 0.2 mg or placebo. The primary end point was the proportion of spontaneous bowel movement (SBM) responders (≥ 3 SBMs/week and an increase of ≥ 1 SBM/week from baseline). The primary end point of COMPOSE-5 was safety. Results In COMPOSE-4, 193 eligible patients were randomly assigned to naldemedine (n = 97) or placebo (n = 96). The proportion of SBM responders in COMPOSE-4 was significantly greater with naldemedine than with placebo (71.1% [69 of 97 patients] v 34.4% [33 of 96 patients]; P < .0001). A greater change from baseline was observed with naldemedine than with placebo in the frequency of SBMs/week (5.16 v 1.54; P < .0001), SBMs with complete bowel evacuation/week (2.76 v 0.71; P < .0001), and SBMs without straining/week (3.85 v 1.17; P = .0005). In COMPOSE-4, more patients treated with naldemedine than with placebo reported treatment-emergent AEs (TEAEs) (44.3% [43 of 97 patients] v 26.0% [25 of 96 patients]; P = .01); in COMPOSE-5, 105 (80.2%) of 131 of patients reported TEAEs. Diarrhea was the most frequently reported TEAE in COMPOSE-4 (19.6% [19 of 97 patients] v 7.3% [seven of 96 patients] with naldemedine v placebo) and COMPOSE-5 (18.3% [24 of 131 patients] with naldemedine). Naldemedine was not associated with signs or symptoms of opioid withdrawal and had no notable impact on opioid-mediated analgesia. Conclusion Once-daily oral naldemedine 0.2 mg effectively treated OIC and was generally well tolerated in patients with OIC and cancer.

An Organ-sparing Treatment Using Combined Intra-arterial Chemotherapy and Radiotherapy for Muscle-invading Bladder Carcinoma

Objective: We describe the results of an organ-sparing approach for the treatment of non-metastatic, invasive bladder carcinoma. Material and Methods: Twenty-three patients (mean age 71 years; age range 47-87 years) with bladder carcinoma of clinical stage T2-T3N0M0 and histologically proven muscle invasion were examined between 1992 and 1998. The median duration of follow-up was 30 months. The treatment protocol for intra-arterial chemotherapy consisted of methotrexate 30 mg/m 2 and cisplatin 50 mg/m 2 in 7 patients and cisplatin 50 mg/m 2 in 16 patients, administered in three cycles via catheters inserted in the internal iliac arteries. Concomitantly, 41.4 Gy of radiotherapy was given to the lesser pelvis. Transurethral biopsy and urine cytology were performed after the completion of treatment; patients were followed observationally if residual tumor was absent, and underwent radical cystectomy if it was present. Results: At the end of treatment, 18 patients (78%) showed a complete response (CR) and the bladder was spared in all cases. Radical cystectomy was performed for 4 non-CR cases, with the result that 2 cases had residual superficial cancer and the other 2 had muscle-invading cancer histologically. Among the patients with a CR, 2 experienced intravesical recurrence. Overall, 2 patients died of cancer, 5 died of other causes and 2 died during treatment. The 5-year disease-specific survival rate was 70.3% and the overall survival rate 46.4%. Conclusions: A bladder-sparing approach for the treatment of muscle-invading bladder carcinoma which utilizes combined intra-arterial chemotherapy and radiotherapy may arrest the decline in quality of life induced by urinary diversion and yield equivalent therapeutic benefit to that of radical cystectomy.

A case of angiomyolipoma presenting as a huge retroperitoneal mass.

Abstract A 60‐year‐old man was admitted to Hitachi General Hospital, Hitachi, Japan, with general fatigue and epigastric fullness. A large mass was palpated on whole abdomen and abdominal computed tomography scan showed a large lobulated fatty mass surrounding the right kidney, which indicated the existence of angiomyolipoma arising from the right kidney. The tumor was success‐fully resected through a thoracoabdominal incision. The total weight of the resected specimen was 3500 g, apparently the largest angiomyolipoma resected by operation in Japan.

Randomized phase III and extension studies: efficacy and impacts on quality of life of naldemedine in subjects with opioid-induced constipation and cancer

Abstract Background The efficacy and safety of naldemedine (a peripherally acting µ-opioid receptor antagonist) for opioid-induced constipation (OIC) in subjects with cancer was demonstrated in the primary report of a phase III, double-blind study (COMPOSE-4) and its open-label extension (COMPOSE-5). The primary end point, the proportion of spontaneous bowel movement (SBM) responders, was met. Here, we report results from secondary end points, including quality of life (QOL) assessments from these studies. Patients and methods In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 97) or placebo (n = 96) for 2 weeks, and those who continued on to COMPOSE-5 received naldemedine for 12 weeks (n = 131). Secondary assessments in COMPOSE-4 included the proportion of complete SBM (CSBM) responders, SBM or CSBM responders by week, and subjects with ≥1 SBM or CSBM within 24 h postinitial dose. Changes from baseline in the frequency of SBMs or CSBMs per week were assessed at weeks 1 and 2. Time to the first SBM or CSBM postinitial dose was also evaluated. In both studies, QOL impact was evaluated by Patient Assessment of Constipation-Symptoms (PAC-SYM) and PAC-QOL questionnaires. Results Naldemedine improved bowel function for all secondary efficacy assessments versus placebo (all P ≤ 0.0002). The timely onset of naldemedine activity versus placebo was evidenced by median time to the first SBM (4.7 h versus 26.6 h) and CSBM (24.0 h versus 218.5 h) postinitial dose (all P < 0.0001). In COMPOSE-4, significant differences between groups were observed with the PAC-SYM stool domain (P = 0.045) and PAC-QOL dissatisfaction domain (P = 0.015). In COMPOSE-5, significant improvements from baseline were observed for overall and individual domain scores of PAC-SYM and PAC-QOL. Conclusions Naldemedine provided effective and timely symptomatic relief from OIC and improved the QOL of subjects with OIC and cancer. Trial registration ID www.ClinicalTrials.jp: JAPIC-CTI-132340 (COMPOSE-4) and JAPIC-CTI-132342 (COMPOSE-5).Background The efficacy and safety of naldemedine (a peripherally-acting µ-opioid receptor antagonist) for opioid-induced constipation (OIC) in subjects with cancer was demonstrated in the primary report of a phase 3, double-blind study (COMPOSE-4) and its open-label extension (COMPOSE-5). The primary endpoint, the proportion of spontaneous bowel movement (SBM) responders, was met. Here, we report results from secondary endpoints including quality of life (QOL) assessments from these studies. Patients and methods In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned 1:1 to receive once-daily oral naldemedine 0.2 mg (n=97) or placebo (n=96) for 2 weeks, and those who continued on to COMPOSE-5 received naldemedine for 12 weeks (n=131). Secondary assessments in COMPOSE-4 included the proportion of complete SBM (CSBM) responders, SBM or CSBM responders by week, and subjects with ≥1 SBM or CSBM within 24 hours post-initial dose. Changes from baseline in the frequency of SBMs or CSBMs per week were assessed at Week 1 and Week 2. Time to the first SBM or CSBM post-initial dose was also evaluated. In both studies, QOL impact was evaluated by Patient Assessment of Constipation-Symptoms (PAC-SYM) and PAC-QOL questionnaires. Results Naldemedine improved bowel function for all secondary efficacy assessments vs placebo (all P≤0.0002). The timely onset of naldemedine activity vs placebo was evidenced by median time to the first SBM (4.7 vs 26.6 hours) and CSBM (24.0 vs 218.5 hours) post-initial dose (all P<0.0001). In COMPOSE-4, significant differences between groups were observed with the PAC-SYM stool domain (P=0.045) and PAC-QOL dissatisfaction domain (P=0.015). In COMPOSE-5, naldemedine significantly improved overall and individual domain scores of PAC-SYM and PAC-QOL from baseline (all P≤0.03). Conclusions Naldemedine provided effective and timely symptomatic relief from OIC and improved the QOL of subjects with OIC and cancer. Trial registration ID www.ClinicalTrials.jp: JAPIC-CTI-132340 (COMPOSE-4) and JAPIC-CTI-132342 (COMPOSE-5).

Acute Thrombosis in a Contralateral Kidney after Radical Nephrectomy: Successful Treatment by Thrombolytic Therapy Using a Tissue-Type Plasminogen Activator

A 67‐year‐old male became anuric immediately after a right radical nephrectomy tor renal cell carcinoma. The patient was diagnosed with an acute arterial thrombosis of the remaining kidney within 4 hours after surgery by both CT scan and angiography. Thrombolytic therapy was started by a transcatheteral infusion of tissue‐type plasminogen activator (TPA) resulting in a complete recanalization. Hydration and systemic administration of heparin followed, and renal function recovered within 3 weeks. This is the first report of acute thrombosis in a contralateral renal artery immediately after a radical nephrectomy which was successfully treated with TPA. It is probable that compression of the contralateral renal artery by the retractor for an extended period of time during surgery led to this unfavorable condition.

Impact of Living at the Japanese Antarctic Research Expedition Base on Urinary Status

Urinary disorders are generally well understood, but there are few reports on the urinary status of people living in unusual climates such as the polar regions. We studied the impact of living conditions on the urinary status of members of the Japanese Antarctic Research Expedition.

Feasibility of classical secondary hormonal therapies prior to docetaxel therapy in Japanese patients with castration-resistant prostate cancer: Multicenter retrospective study

Background We retrospectively analyzed castration-resistant prostate cancer (CRPC) patients treated with secondary hormonal therapies (SHTs) prior to docetaxel therapy. Methods The cases of 73 CRPC patients who underwent docetaxel therapy in 2005–2011 at four hospitals in Ibaraki, Japan were analyzed. We determined the cause-specific survival (CSS) from the start of docetaxel therapy and the time point of CRPC diagnosis, and we compared the CSS achieved with/without prior classical SHTs, which were defined as low-dose steroid and estramustine phosphate. Results Of the 73 enrolled patients, 26 underwent docetaxel therapy (DOC group), and 47 underwent SHTs (SHTs-DOC group) as the initial treatment for CRPC. In the docetaxel therapy, the rate of prostate-specific antigen responses were higher in the DOC group compared with the SHTs-DOC group (76.9% vs. 44.7%, P = 0.0066). The median CSS from the docetaxel therapy initiation was not significant but longer in the DOC group than in the SHTs-DOC group (23.4 months vs. 16.6 months, P = 0.0969). However, the median CSS from the time of CRPC diagnosis did not significantly differ between the DOC and SHTs-DOC groups (23.4 months vs. 24.7 months, P = 0.9233). In a univariate analysis, pain and visceral metastasis appeared to be risk factors for the CSS in the SHTs-DOC group. The patients with pain and/or visceral metastasis had significantly poorer survival than those without these factors in the SHTs-DOC group (31.5 months vs. 16.8 months, P = 0.0053). Conclusion The induction of SHTs prior to docetaxel therapy is an acceptable treatment option with some survival benefits for CRPC patients without pain and visceral metastases.