Fewer systematic prostate core biopsies in clinical stage T1c prostate cancer leads to biochemical recurrence after brachytherapy as monotherapy.

BACKGROUND: After brachytherapy, fewer prostate biopsy cores at diagnosis can underestimate the pathological characteristics of prostate cancer (PCa) with lower concordance, resulting in improper treatment, particularly in patients with low-risk nonpalpable cT1c PCa. The aim of this study was to assess the relationship between the number of biopsy cores at diagnosis and long-term clinical outcomes after brachytherapy for cT1c PCa. METHODS: We reviewed 516 patients with localized cT1c PCa with Gleason scores of 3 + 3 = 6 or 3 + 4 = 7 who underwent brachytherapy as monotherapy without hormonal therapy between January 2005 and September 2014 at our institution. Clinical staging was based on the American Joint Committee on Cancer manual for staging. Thus, the cT1c category is based solely on digital rectal examination. The primary outcome was biochemical recurrence (BCR). Based on the optimized cutoff value for biopsy core number obtained from receiver operating characteristic analysis, patients were divided into the biopsy cores ≤8 (N = 123) and ≥9 (N = 393) groups. The BCR-free survival rate was compared between the groups. Prognostic factors for BCR were evaluated, including age, initial prostate-specific antigen (PSA) level, Gleason score, positive core rate, PSA density, prostate magnetic resonance imaging findings, and biopsy core number. RESULTS: The median patient age was 66.0 years (interquartile range [IQR]: 61.0-71.0 years), and the median follow-up time was 11.1 years (IQR: 9.5-13.3 years). The median number of core biopsies was 12 (IQR: 9-12). The area under the curve was 0.637 (95% confidence interval [CI]: 0.53-0.75), and the optimal biopsy core cutoff value for BCR prediction was 8.5 (sensitivity = 43.5%, specificity = 77.1%). Although fewer patients had Gleason scores of 3 + 4 = 7 (19/123 [15%] vs. 125/393 [32%], p < 0.02) in the biopsy cores ≤8 group, the 10-year BCR-free survival rate was significantly lower in the biopsy cores ≤8 group than in the biopsy cores ≥9 group (93.8% vs. 96.3%, p < 0.05). Multivariate analysis revealed that a lower biopsy core number (hazard ratio: 0.828, 95% CI: 0.71-0.97, p < 0.03) and a Gleason score of 3 + 4 = 7 (hazard ratio: 3.26, 95% CI: 1.37-7.73, p < 0.01) significantly predicted BCR. CONCLUSIONS: A low number of prostate core biopsies results in worse BCR-free survival after brachytherapy as monotherapy in patients with cT1c PCa.

Does grip strength on the unaffected side of patients with hemiparetic stroke reflect the strength of other ipsilateral muscles?

[Purpose] Grip strength is used as an indicator of overall body muscular strength. However, most studies on grip strength have been performed in healthy people, and no study has evaluated it in the unaffected side of patients with hemiparetic stroke. The purpose of this study was to determine if grip strength on the unaffected side of patients with hemiparetic stroke correlates with the strength of other ipsilateral musculature. [Subjects and Methods] The maximal strengths of the muscles on the unaffected side of 31 patients with hemiparetic stroke were measured, and correlation coefficients were calculated. [Results] The results revealed significant positive correlations between grip strength on the unaffected side and the strength of the other ipsilateral muscle groups, with relatively high correlations being observed for the upper extremity muscle groups. [Conclusion] This suggests that grip strength on the unaffected side of patients with hemiparetic stroke can be used as a simple way to estimate overall strength on that side.

Comparison of ankle plantar flexor activity between double-leg heel raise and walking.

[Purpose] We aimed to evaluate the difference in the muscle activity between the double-leg heel raise (DHR) and treadmill walking. [Subjects] Thirty healthy males aged 21.5 ± 1.6 years (body mass 63.6 ± 9.3 kg, height 171.0 ± 4.5 cm) participated in the study. [Methods] Electromyograms were simultaneously recorded from both heads of the gastrocnemius and the soleus of the right side during the DHR and treadmill walking. The DHR conditions were maximum plantar flexion (MPF), 3/4 MPF, 2/4 MPF, and 1/4 MPF, and the walking speeds were 20, 40, 60, 80, and 100 m/min. [Results] The muscle activity during the DHR and walking significantly increased with increments in the height of the heel raise and walking speed, respectively. Comparison of the muscle activity at MPF with that at each walking speed revealed that the muscle activity in the soleus and gastrocnemius medial head during walking exceeded that during the DHR in less than 3.3% of cases. [Conclusion] The DHR test is useful for evaluating the ankle plantar flexor activity necessary for walking.

Five-year potency preservation after iodine-125 prostate brachytherapy.

BACKGROUND: We aimed to evaluate long-term erectile function following prostate brachytherapy, based on patient characteristics and treatment factors. METHODS: Between 2003 and 2006, 665 men with localized prostate cancer were treated with (125)I permanent seed implantation. None was given adjuvant hormone therapy. Erectile function was assessed before treatment, and at 6 months, 1, 2, 3, 4 and 5 years after implantation using the Mount Sinai Erectile Function Score (MSEFS) of 0-3 (0 = no erections, 1 = erections insufficient for intercourse, 2 = suboptimal erections but sufficient for intercourse, 3 = normal erectile function). Potency was defined as score 2 or 3, and 382 men were potent before treatment. Univariate and multivariate analyses were performed on the data from these 382 patients to identify variables associated with potency preservation. RESULTS: In patients who were potent before treatment, the actuarial potency preservation rate fell to 46.2 % at 6 months after brachytherapy, and then slowly recovered reaching 52.0 % at 5 years after brachytherapy. In multivariate logistic regression analysis, patient age (p = 0.04) and pre-treatment MSEFS (p < 0.001) were predictors of 5-year potency preservation. Neoadjuvant hormone therapy affected potency preservation only at 6 months after brachytherapy. CONCLUSIONS: Patient age at implantation and pre-treatment erectile function are predictive factors for the development of erectile dysfunction following prostate brachytherapy.

Comparison of preplanning and intraoperative planning for I-125 prostate brachytherapy.

OBJECTIVE: To compare two widely used permanent prostate brachytherapy techniques, preplanning and intraoperative planning, based on postimplant dosimetry, toxicity and biochemical outcomes. METHODS: Between 2003 and 2006, 665 men with localized prostate cancer were treated with permanent interstitial implantation. The first 227 consecutive men were treated with the preplanning technique, followed by 438 men treated with the intraoperative technique. Late toxicity was scored by the Common Terminology Criteria for Adverse Events v.4.0. Biochemical failure was defined as a prostate-specific antigen increase of more than 2 ng/ml above the nadir value excluding a benign bounce. Univariate and multivariate analyses were performed to identify the variables associated with biochemical failure-free survival. RESULTS: Postimplant target coverage was similar in the two groups, with a small difference in risk organ doses. Mean V100 was 96.3 vs. 96.7% (P = 0.205), D90 was 119.6 vs. 119.4% (P = 0.884), urethral D10 was 157.5 vs. 146.1% (P = 0.010), rectal V100 was 0.57 vs. 0.43 cc (P = 0.002) in the preplanning and intraoperative planning groups, respectively. Acute and late Grade 3 genitourinary and gastrointestinal toxicities were <1% for both methods. The 5-year biochemical failure-free survival rate was 95.4% for the preplanning and 94.0% for the intraoperative planning group (P = 0.776). Multivariate analysis revealed Gleason score, biopsy positive rate and V100 to be predictors of biochemical failure-free survival, while the planning technique was not significant. CONCLUSION: This large-scale analysis of high-quality implants revealed similar postimplant dosimetry, toxicity profiles and biochemical failure-free survival for the preplanning and intraoperative planning methods.

[Two cases of bowel perforation in patients with metastatic renal cancer treated with a molecularly targeted drug].

(Case 1) An 82-year-old man started immunotherapy with interferon because of lung metastasis 5 years after he had undergone radical nephrectomy. Three years later, he developed multiple metastases, and was started on sorafenib (400 mg/day) and nonsteroidal anti-inflammatory drug (NSAID) orally. As his cancer-related pain worsened with time, he was administered 30 Gy radiation therapy for bone metastasis of L4. He was then admitted to our hospital for pain control because of ineffective radiation therapy. One day, he suddenly had abdominal pain and vomiting, and was diagnosed as bowel perforation based on computed tomography. He was managed conservatively by nasogastric suction and antibiotic course. (Case 2) A 62-year-old man diagnosed as metastatic renal cell cancer began immunotherapy soon after undergoing radical nephrectomy in Dec., 2006. Although he was started on oral sorafenib (800 mg/day) in July, 2008, metastatic foci enlarged after 18 months. He was then changed to sunitinib (50 mg/day). Sunitinib had immediate and long-lasting effect on the cancer for about 10 months, but he was then admitted to our hospital for pleural effusion. While under treatment for thoracic cavity drainage, he experienced upper abdominal pain and was diagnosis as bowel perforation based on computed tomography. He underwent emergency laparotomy. Molecular target drugs such as sorafenib and sunitinib have serious adverse effects. Bowel perforation is rare, but among those adverse effects. It should be remembered that caution is required for long-term use or combined radiation therapy and NSAIDs with molecular target drug.

[Sexual function after permanent seed implant prostate brachytherapy].

PURPOSE: The aim of this study was to evaluate the long-term effects of permanent seed implant prostate brachytherapy (BT) on sexual function (SF). MATERIALS AND METHODS: From September 2003 to July 2005, 56 patients underwent radical retropubic prostatectomy (RRP) without any hormone therapy, while 353 patients had undergone BT without any adjuvant hormone therapy in a single institute. Out of these 353 patients in the BT group, 305 patients received neoadjuvant hormone therapy (BT NHT + group), while 48 did not (BT NHT - group). SF was prospectively evaluated using the UCLA Prostate Cancer Index (UCLA-PCI). Potency was defined as the UCLA-PCI Q26 point of > or = 3. RESULT: The preimplant UCLA-PCI scores of SF for BT NHT - and BT NHT + groups were 50.9 and 13.4, respectively. The SF score of the NHT - group post operatively decreased to 38.9 within 6 months, but was maintained at the same level after that. With the recovery of the androgen, SF score of the NHT + group improved after BT: however, it did not reach up to that of the NHT - group. In the univariate analysis, patient's age was the only predictive factor for SF after BT. Thirty-four out of 48 patients in the BT NHT - group and 23 out of 56 patients in the RRP group showed adequate potency before surgery. Their 5-year potency preservation rate was 73.6% in the BT NHT - group and 4.3% in the RRP group. CONCLUSION: SF slightly decreased immediately after BT but was usually maintained during the course observation for 5 years. The 5-year SF preservation rate after BT was 73.6%.

Secondary bladder cancer during long-term follow-up after iodine-125 permanent seed implantation for localized prostate cancer.

INTRODUCTION: Brachytherapy for prostate cancer treatment may induce secondary bladder cancer during long-term follow-ups. This study reviews the risk and tumor characteristics of secondary bladder cancer after brachytherapy. METHODS: This single-institution retrospective study included 1162 patients treated with low-dose-rate permanent seed implantation brachytherapy with iodine-125, with or without external beam radiation therapy, for localized prostate cancer. We calculated and compared the rates of secondary bladder cancer among patients treated with brachytherapy and radical prostatectomy (n = 218) before and after a propensity score-matching analysis. Possible risk factors for secondary bladder cancer, such as patient age and external beam radiation therapy administration, were analyzed. RESULTS: Of 1162 patients with a median follow-up period of 11.4 (range: 0.7-15.5) years, 26 presented with urothelial carcinomas and 1 with adenocarcinoma at a median of 8.9 (range: 2.9-14.0) years after brachytherapy, although the incidence rates of secondary bladder cancer after brachytherapy were not significantly different from those after radical prostatectomy. No significant risk factors for secondary bladder cancer were identified. The initial symptoms of secondary bladder cancer were gross hematuria (74%) and microscopic hematuria with positive urine cytology (15%). Among 26 cases of secondary urothelial carcinoma, 54% were high-grade and 46% were invasive. After brachytherapy, invasive urothelial carcinoma occurred later than noninvasive urothelial carcinoma (p = 0.01). CONCLUSIONS: Considering the aggressive malignancy of secondary bladder cancer, cystoscopy and urine cytology should be performed for further investigation of the causes of gross or microscopic hematuria and rule out secondary bladder cancer in cases followed longer than 3 years after brachytherapy.

[PSA bounce after brachytherapy with permanent seed implantation for prostate cancer].

PURPOSE: To evaluate prostate specific antigen (PSA) bounce that may occur as a time PSA rise phenomenon during follow up period after brachytherapy (BT) with permanent seed implantation for prostate cancer. (Materials and methods) Seven hundred and forty-six patients had undergone BT from November 2003 to April 2007 in a single institute, and of 130 patients who did not receive hormone therapy and had minimal 3-year follow up are analyzed. PSA bounce was defined as a rise of at least 0.4 ng/ml with spontaneous return to pre-bounce level or lower. RESULT: Among the 130 patients, 40 patients (30.8%) developed PSA bounce, and median time to PSA bounce was 18 months after the BT. With univariate analysis, younger patients (P = 0.027) and larger prostate (P = 0.030) had statistically significant correlation with PSA bounce. With multivariate analysis, younger patients were identified as only independent factor for predicting PSA bounce. Eight patients out of 130 patients (6.2%) triggered the Phoenix definition (nadir + 2 ng/ml) of PSA failure, however, clinical failure was seen only in 3 patients, and other 5 patients were considered as PSA bounce. CONCLUSION: PSA bounce is likely to occur in younger patients within 3 years after BT. It is clinically important to distinguish PSA bounce from PSA failure during following period after BT.

Effect of adding androgen deprivation therapy to permanent iodine-125 implantation with or without external beam radiation therapy on the outcomes in patients with intermediate-risk prostate cancer: A propensity score-matched analysis.

PURPOSE: The purpose of the study was to evaluate the effect of adding androgen deprivation therapy (ADT) to brachytherapy with or without external beam radiation therapy on oncological outcomes in prostate cancer. METHODS AND MATERIALS: Overall, 1,171 patients with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy with or without ADT between 2003 and 2013 were identified. Propensity score matching was used to counter biases between the ADT and non-ADT groups. The biochemical failure-free rate (bFFR), local recurrence-free rate, and overall survival rate were evaluated using Kaplan-Meier curves, and predictors were identified using Cox proportional hazards regression models. RESULTS: After propensity score matching, 405 patients were included in each group. The median followup duration was 9.1 years; the median ADT duration was 6 months. In the ADT versus non-ADT groups, the 9-year bFFR, local recurrence-free rate, and overall survival rate were 93.4% versus 87.8% (p = 0.016), 96.9% versus 98.1% (p = 0.481), and 88.1% versus 90.4% (p = 0.969), respectively. On multivariate analyses, Gleason score (hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 1.58-4.03) and ADT use (HR: 0.55, 95% CI: 0.34-0.89) were associated with biochemical failure. Supplemental external beam radiation therapy use (HR: 0.38, 95% CI: 0.16-0.91) was associated with lower local recurrence rates. Age (HR: 1.12, 95% CI: 1.08-1.16) and comorbidities (HR: 1.56, 95% CI: 1.04-2.34) were associated with all-cause mortality. CONCLUSIONS: A risk-benefit assessment between bFFR improvement and the potential side effects of adding ADT to brachytherapy-based radiotherapy is warranted before incorporating ADT as routine practice.

[A case of chronic expanding hematoma in retroperitoneal space].

A 34-year-old female patient visited a nearby hospital with a chief complaint of right flank pain and decreased weight. Computed tomography showed a right retroperitoneal mass 10 cm in diameter on the right kidney, displacing the liver and the right kidney. The patient was referred to Kawasaki Municipal Hospital for further evaluation. The mass was suspected to be chronic expanding hematoma or neurogenic tumor of renal capsule origin. A retroperitoneal tumorectomy was performed with a right subcostal incision. A mass was noted in the smooth capsule. The mass was easily removed from the right renal capsule. However, there was significant adhesion between the mass and the peritoneum as well as the liver capsule. Therefore, a partial hepatectomy was needed for complete resection of the mass including the capsule. A fibrous capsule was noted and most of the mass was blood clot-like tissue. The histopathological diagnosis was chronic expanding hematoma with no malignancy. A retroperitoneal chronic expanding hematoma has very rarely been reported.

[Testicular tumor presenting as acute scrotum with infection caused by gas-producing bacteria].

A 46-year-old male patient visited our hospital with the chief complaint of a right scrotal swelling and pain. The enlarged scrotum was 8 cm in diameter with redness of the skin of the right scrotum. There was a firm mass in the scrotum with marked tenderness. The patient's body temperature was 38.0C, and blood tests showed increased inflammatory markers. The results of computed tomography and magnetic resonance imaging showed that the enlarged scrotum was filled with gas and there was a mass partially composed of fat inside it. The patient was treated with antibiotics, but the fever persisted and the inflammatory markers further increased. The size of the right scrotum gradually increased. A right high inguinal orchiectomy was performed to control the inflammation and makea diagnosis. Thehistopathological diagnosis was necrosis of seminoma, and culture of thene crotic tissuewas positivefor Clostridium. Thepre sent caseappe ars to bethefirst caseof a testicular tumor associated with acute scrotum due to tumor growth, necrosis and infection caused by gas-producing bacteria.

Whole-gland salvage treatment for recurrent prostate cancer after initial definitive radiotherapy: A case series of 125I brachytherapy and robot-assisted radical prostatectomy.

PURPOSE: To analyze outcomes following whole-gland salvage treatments applied to patients with pathology-proven, locally recurrent prostate cancer following primary definitive radiotherapy. MATERIAL AND METHODS: Eighteen consecutive patients who received whole-gland salvage treatments at our institution were retrospectively reviewed. All patients underwent transperineal template-guided mapping biopsy (TTMB) using the standard iodine-125 (125I) brachytherapy (BT) setup. Twelve patients received 125I BT, and six patients underwent robot-assisted laparoscopic prostatectomy (RARP). Prostate-specific antigen (PSA) failure was determined using the Phoenix definition (nadir + 2 ng/ml) following BT and a PSA level of > 0.2 ng/ml following RARP. Toxicities were graded according to CTCAE version 4.0. RESULTS: The median follow-up times were 71 and 11 months for the BT and RARP groups, respectively. In the BT group, the median dose to 90% of the prostate was 131 Gy. The median time to biochemical failure was 47 months, and the biochemical relapse-free survival (BRFS) rates were 56% (95% confidence interval [CI]: 33-94%) and 46% (95% CI: 25-88%) at 3 years and 5 years, respectively. Four patients (33%) developed grade 2 genitourinary (GU) toxicity, and two (17%) developed grade 3 GU toxicity. No patients developed grade ≥ 2 gastrointestinal (GI) toxicity. In the RARP group, three out of six patients (50%) had PSA failure, and four patients (67%) developed grade 2 GU toxicity. No patients developed grade 3 GU toxicity or grade ≥ 2 GI toxicity. On pre-salvage magnetic resonance imaging (MRI), no patients were suspected of having T3 or higher stage lesions. However, three patients (50%) had pT3a and two patients (33%) had pT3b (i.e., seminal vesicle invasion) stage lesions. CONCLUSIONS: Whole-gland salvage BT is an effective treatment with an acceptable toxicity profile. The pathology findings from RARP imply that there is a room for improvement in diagnoses made by MRI in the pre-salvage setting.

Establishment of orthotopic mouse superficial bladder tumor model for studies on intravesical treatments.

Various animal models of bladder tumor have been developed for the preclinical evaluation of therapeutic modalities for the treatment of bladder cancers. The ideal model for the investigation of therapeutic effects of proposed novel intravesical treatments requires the mass of the implanted tumor to be confined to the urothelium of the bladder at least for the initial phase. However, previously reported bladder tumor models are not suitable for the evaluation of intravesical therapies for the treatment of superficial bladder cancer, since the muscle invasive tumors have developed from the beginnings of the experiments. These models are too aggressive to study local treatment effects. In the current study, we demonstrated that careful instillation of MBT-2 mouse bladder cancer cells into the bladder of a syngenic C3H/HeJ mouse could establish a superficial bladder tumor with an incidence of 100%. The procedure and technique for handling animals are simple for standard animal investigators. Maintenance of the in vitro conditions of MBT-2 cells without contamination of Mycoplasma and careful selection of the substrain of C3H mouse seem to be essential for stable tumor establishment. This bladder tumor model appeared to be easy to reproduce among several investigators in different institutions. The orthotopic bladder tumor model, which was confined to urothelium, lets us evaluate various intravesical treatment strategies.

Selection of patients who would not require long-term prostate-specific antigen monitoring after low-dose-rate brachytherapy.

PURPOSE: To identify patients at extremely low risk of biochemical recurrence (BCR) of prostate cancer after low-dose-rate brachytherapy (LDR-BT) to determine when prostate-specific antigen (PSA) monitoring can be stopped. METHODS AND MATERIALS: We retrospectively reviewed clinicopathologic data of patients with prostate cancer who underwent LDR-BT between 2003 and 2011. Of 1569 patients reviewed, 689 (43.9%) received combination external beam radiotherapy, and 970 (61.8%) had neoadjuvant hormonal therapy. We stratified patients according to risk factors identified by multivariate analysis and assessed the factors for an association with BCR (defined as ≥2 ng/mL higher than the nadir). RESULTS: The median followup was 96 months. Of 1531 patients who were BCR-free at 3 years after treatment, 76 subsequently developed BCR; of 1500 who were BCR-free at 5 years, 45 eventually had BCR. On multivariate analysis, independent risk factors for BCR were the National Comprehensive Cancer Network risk group at diagnosis and PSA levels at 3 or 5 years after radiotherapy. In the low-risk group, no patient with a PSA level ≤0.2 ng/mL at 3 years after radiotherapy subsequently developed BCR. In the intermediate-risk group, no patients with a PSA level ≤0.2 ng/mL at 5 years subsequently developed BCR. CONCLUSIONS: The National Comprehensive Cancer Network risk group at diagnosis and PSA values at 3 and 5 years after LDR-BT are independently associated with a risk of later BCR. Using these two factors may help to select patients for whom PSA monitoring could be stopped because they have an extremely low risk of later BCR.

Predictive factors of long-term rectal toxicity following permanent iodine-125 prostate brachytherapy with or without supplemental external beam radiation therapy in 2216 patients.

PURPOSE: We analyzed factors associated with rectal toxicity after iodine-125 prostate brachytherapy (BT) with or without external beam radiation therapy (EBRT). METHODS AND MATERIALS: In total, 2216 prostate cancer patients underwent iodine-125 BT with or without EBRT between 2003 and 2013. The median followup was 6.9 years. Cox proportional hazards modeling was used for univariate and multivariate analyses to assess clinical and dosimetric factors associated with rectal toxicity. Dosimetric parameters from 1 day after implantation (Day 1) and 1 month after implantation (Day 30) were included in the analyses. RESULTS: The 7-year cumulative incidence of Grade 2 or higher rectal toxicity was 5.7% in all patients. The multivariate analysis revealed that antiplatelet or anticoagulant therapy, neoadjuvant androgen deprivation therapy, treatment modality, Day 1 rectal volume receiving 100% of the prescribed dose (RV100), and the Day 30 minimal percent of the prescribed dose delivered to 30% of the rectum (RD30) were associated with rectal toxicity. Day 1 RV100 was a common predictor in both BT-alone and the BT + EBRT groups. The 5-year cumulative incidence of Grade 2 or higher rectal toxicity was 12.6%, 5.9%, and 1.7% for BT + 3-dimensional conformal radiation therapy, BT + intensity-modulated radiation therapy, and the BT-alone groups, respectively (p < 0.001). CONCLUSIONS: Rectal dosimetric parameters in BT were associated with late rectal toxicity. Although the risk of rectal toxicity was higher when EBRT was combined with BT, with proper and achievable rectal dose constraints intensity-modulated radiation therapy yielded less toxicity than 3-dimensional conformal radiation therapy.

[Vesicovaginal fistula after sexual intercourse: a case report].

A 53-year old female visited our hospital with a complaint of continuous urinary incontinence after sexual intercourse. She had been diagnosed with carcinoma of uterine cervix stage I b2 and had undergone radical hysterectomy and radiation therapy (45 Gy). Cystoscopy revealed vesicovaginal fistula in the trigone which measured almost 3 cm. We repaired it by transabdominal and vaginal routes 5 days after the injury. She was discharged with a Foley catheter. Three months after the operation, cystography revealed improvement of vesicovaginal fistula.