The urinary tract reconstruction in a robot-assisted surgery for rectal malignancy with combined prostate and seminal vesicle resection.

INTRODUCTION: In certain cases of rectal malignancy in which invasion is confined to the prostate and/or seminal vesicles, bladder-sparing surgery may be chosen instead of total pelvic exenteration. However, even if the bladder is preserved, postoperative urinary dysfunction and vesicourethral anastomotic leakage are concern. MATERIALS AND SURGICAL TECHNIQUE: We employ various techniques based on robot-assisted radical prostatectomy for reconstructing the urinary tract. These techniques include advanced reconstruction of vesicourethral support, total anatomical reconstruction, and a method called anterior reconstruction. In addition, suture fixation of bladder to the anterior abdominal wall, and re-approximation of bladder by peritoneal suture were done. DISCUSSION: Reliable robot-assisted vesicourethral anastomosis and reinforcement of the anastomotic wall could potentially enhance the self-voiding rate and decrease the risk of anastomotic failure.

TAS0313 plus Pembrolizumab for Post-Chemotherapy Immune Checkpoint Inhibitor-Naïve Locally Advanced or Metastatic Urothelial Carcinoma.

We evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint inhibitor-naïve patients with locally advanced/metastatic urothelial carcinoma (la/mUC). TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month progression-free rates were 46.4% and 36.5%, respectively. Median OS was not reached; 6-, 12-, and 24-month OS rates were 83.3%, 72.2%, and 55.1%, respectively. In post hoc analysis, patients with a tumor infiltrating CD8+ lymphocyte (CD8+ TIL) count ≥99 and/or programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥50 and lymphocyte count >1,380 cells/µL had higher ORRs and prolonged PFS versus patients with a CD8+ TIL count <99, PD-L1 CPS <50, and lymphocyte count ≤1,380 cells/µL. Thirty-four (94.4%) patients receiving combination therapy experienced treatment-related adverse events (AE), with pyrexia (n = 15, 41.7%), injection-site reactions (n = 15, 41.7%), injection-site induration (n = 6, 16.7%), and malaise (n = 6, 16.7%) the most common. No grade ≥3 treatment-related AEs occurred in ≥10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in la/mUC. Clinical Trial Registration: JapicCTI-183824.

[Testicular Preservation in a Patient with a Testicular Epidermoid Cyst Achieved by Preoperative Diagnosis : A Case Report].

Testicular epidermoid cysts are relatively rare, accounting for about 1% of all testicular tumors, and are often treated by high orchiectomy. We describe here the case of a testicular epidermoid cyst treated by testicle-sparing surgery due to a preoperative diagnosis. A 23-year-old man complained of a painless mass in the right scrotum. Physical examination revealed a firm little fingertip-sized smooth-surfaced mass in the right testis. Ultrasonography showed a hypoechoic lesion with an echogenic rim in the right testis. A T2-weighted magnetic resonance image showed a well-demarcated mass with a low signal outline. On the basis of a preoperative diagnosis of epidermoid cyst, intraoperative testicular frozen section was performed, and the mass was resected surgically while preserving the testis.

[A Case of Small Cell Carcinoma of the Bladder].

A 74-year-old man presented with further treatment for muscle invasive small cell carcinoma of the bladder. After three courses of neoadjuvant chemotherapy with cisplatine + etoposide (EP), total cystectomy was performed. The pathological findings revealed small cell carcinoma of the bladder (ypT2N0M0). Eleven months after the operation, thoracoabdominal computed tomography (CT) showed right pelvic lymph node metastasis. He underwent 9 courses of EP chemotherapy, and everolimus, finally, Amrubicin was administered. Amrubicin might be useful for small cell carcinoma of the bladder.

[Anatomical Variation of the Origin of the Right Renal Artery : Assessment with an Angle of the Origin and Ventral Protrusion].

The right renal artery has been considered to originate laterally from the anterior aspect of aorta. In some cases, it turns more ventrally than the aorta, which can lead to intraoperative right renal artery injury. For this reason, we evaluated how the right renal artery turns ventrally and analyzed the factors for ventral protrusion of the right renal artery. We examined contrast-enhanced computed tomography images of 195 individuals and measured their angles of the right renal artery and ventral protrusion from the aorta. Age and sex had no significant correlation with these variations. A weaknegative correlation was found between body mass index and these variations. Almost all the right renal artery originated from the ventral side of the aorta, and almost half the right renal artery arose ventrally more than the aorta. Careful attention should be paid to ventral protrusion of the right renal artery to prevent vascular injury during surgery using the anterior approach to the upper retroperitoneum.

[Deep and Durable Response After Discontinuation of Nivolumab/Ipilimumab Combination Therapy for Metastatic Renal Cell Carcinoma : A Case Report].

A 47-year-old man was referred to our hospital for epigastric pain and cough, and was given a diagnosis of left clear cell renal carcnoma with multiple pulmonary metastases based on the results of renal tumor biopsy (cT3aN0M1). He received nivolumab/ipilimumab combination therapy, but developed diarrhea (grade 3) on day71, and treatment was discontinued. However, a deep and durable response after discontinuation of treatment was shown, and we were able to perform nephrectomy on day336. He is undergoing nivolumab therapy for pulmonary metastases.

[Low-Dose Estramustine Phosphate Monotherapy in Castration-Resistant Prostate Cancer Patients].

We retrospectively evaluated the efficacy and toxicity of low-dose estramustine phosphate (EMP) monotherapy in patients with castration-resistant prostate cancer (CRPC). We administered EMP at 140 or 280 mg/day to 89 patients between January 2003 and December 2012. None of the patients were receiving concomitant dexamethasone and none had ever been treated with docetaxel. Fifty-three patients (59.6%) experienced a decline in prostate-specific antigen (PSA) levels, including 20 (22.5%) with a decline of more than 50%. The median time to PSA progression was 90 days. PSA-progression-free survival was significantly longer in patients treated with EMP 140 mg compared with patients treated with EMP 280 mg, and there was no significant difference in the incidence of adverse events between the two groups. The most frequent toxicities were nausea and anorexia. Two patients had grade 3 adverse events of pulmonary embolism and liver dysfunction. EMP treatment was discontinued in nine patients (10.1%) because of side effects (nausea and anorexia in 7, liver dysfunction and lacunar infarction in 1). Low-dose EMP monotherapy is well tolerated and can effectively reduce PSA levels.

[A Case of Bisphosphonate-Related Osteonecrosis of the Jaw with Difficulty in Treatment].

A 65-year-old man with urination difficulty visited our hospital. Because his prostate-specific antigen level was 1,619 ng/ml, we performed a prostate biopsy. The biopsy specimen yielded a diagnosis of adenocarcinoma with a Gleason score of 4＋4. Computed tomography and bone scintigraphy showed lymph node, lung, and bone metastasis (cT3bN1M1). After 13 months of combined androgen blockade, he underwent treatment with a bisphosphonate. At 22 months of treatment, he developed bisphosphonate-related osteonecrosis of the jaw, and all necrotic bone and teeth were removed. He subsequently underwent repeated cleaning and fixation (splinting) for an oral fistula and mandibular fracture. Emergency transcatheter arterial embolization was then performed to treat a bleeding of the facial artery aneurysm. An oral infection and aspiration pneumonia repeatedly developed secondary to the oral fistula. The patient underwent a gastrostomy, after which his nutritional status improved and he was discharged.

[LAPAROSCOPIC ADRENALECTOMY: COMPARISON OF TRANSPERITONEAL AND RETROPERITONEAL APPROACHES].

OBJECTIVE: Laparoscopic adrenalectomy is generally performed by either a transperitoneal approach (TA) or a retroperitoneal approach (RA). However, the optimal selection criteria for each approach are unclear. We investigated the factors affecting the safety of laparoscopic adrenalectomy to evaluate the optimal criteria for each approach. PATIENTS AND METHODS: In total, 149 patients who underwent laparoscopic adrenalectomy from February 1994 to July 2013 were retrospectively analyzed. We performed TA for 75 tumors in 73 patients and RA for 78 tumors in 76 patients. Patient characteristics and operative outcomes were compared between the two groups. Furthermore, operative outcomes in patients with some surgical risks were specifically compared between the two approaches. RESULTS: Patient characteristics were similar between the two groups, although the patients in the RA group were significantly older than those in the TA group. Four patients with a large pheochromocytoma in the TA group had excessive blood loss and one of them was given blood transfusion. However, there was no difference in intraoperative blood loss (p = 0.091). The other serious adverse events were not observed. CONCLUSIONS: The present findings suggest that both RA and TA can be effective surgical strategies, with close attention to large pheochromocytoma to avoid excessive hemorrhage.

A phase 2 study of abiraterone acetate in Japanese men with metastatic castration-resistant prostate cancer who had received docetaxel-based chemotherapy.

OBJECTIVE: In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxel-based chemotherapy. METHODS: Men (aged ≥20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: ≥5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with ≥1 regimen being docetaxel) for prostate cancer, were enrolled in this open-label, single-arm study. Primary efficacy endpoint was proportion of patients achieving a ≥50% prostate-specific antigen decline from baseline (prostate-specific antigen response rate) after 12-week treatment. Safety and pharmacokinetics were also assessed. RESULTS: Confirmed prostate-specific antigen response rate by Week 12 was 28.3% (90% confidence interval: 17.6%; 41.1%) or 13 out of 46 (full analysis set) treated patients. However, total prostate-specific antigen response rate including confirmed and unconfirmed responses was 34.8% (90% confidence interval: 23.2%; 47.9%). Secondary efficacy endpoints and outcomes were: improvement in Eastern Cooperative Oncology Group performance status score by ≥1 unit: 7/16 patients (43.8%); objective radiographic response: complete response, partial response and stable disease in 0, 1/22 (4.5%) and 9/22 (40.9%) patients, respectively; pain palliation response: 9/16 (56.3%) patients. The most common adverse events (>20% patients) were upper respiratory tract infection (13/47, 27.7% patients) and hepatic function abnormal (10/47, 21.3% patients, Grade 3: 8.5%). All mineralocorticoid-related toxicities were Grade 1/2. CONCLUSIONS: Abiraterone acetate plus prednisolone showed favorable efficacy in metastatic castration-resistant prostate cancer Japanese patients who had received chemotherapy. Abiraterone acetate plus prednisolone had an acceptable safety profile. CLINICAL TRIAL REGISTRATION NO: NCT01795703.

[Effect of change to flutamide for prostate cancer patient who developed breast pain during bicalutamide treatment (BIP-F study)].

In Japan, prostate cancer is treated with non-steroidal anti-androgen (flutamide and bicalutamide). Development of breast pain during bicalutamide treatment, in prostate cancer patients reduces their quality of life (QOL) and treatment compliance. We studied the safety and effectiveness of switching from bicalutamide to flutamide in 13 prostate cancer patients who developed breast pain during bicalutamide treatment. We estimated the change in breast pain using a face scale and the Expanded Prostate Cancer Index Composite (EPIC) and EPIC-hormone domain (HD) score. The switch to flutamide relieved breast pain in nine patients, had no effect in one patient, and increased breast pain in two patients. One patient dropped out. Furthermore, summary score and hormone function were improved with a significant difference in the EPIC-HD score. Switching to flutamide in prostate cancer patients who develop breast pain during bicalutamide is safe and effective.

[A case of primary mucosa-associated lymphoid tissue-type lymphoma of the urinary bladder that progressed after antibiotic therapy].

We report a case of primary mucosa-associated lymphoid tissue (MALT)-type lymphoma of the urinary bladder, which temporarily regressed after antibiotic therapy and progressed 1 year after the treatment. The patient was a 72-year-old female with a history of recurrent cystitis. She was referred to our hospital for microscopic hematuria. Urinalysis also showed microscopic pyuria and cystoscopy revealed an erythematous and edematous submucosal lesion in the right side wall of the bladder. She was diagnosed with acute cystitis and treated with antibiotics. Cystoscopy after 2 months was normal. However, she presented with macroscopic hematuria and fever 1 year after the treatment. Computed tomography (CT) scan showed a solitary mass measuring 25×40 mm above the right ureteric orifice and right hydronephrosis. Transurethral resection was performed, and the histopathological findings were consistent with MALT-type lymphoma. No evidence of lymphoma was found on positron emission tomography-CT scan and bone marrow biopsy, and she was diagnosed with primary MALT-type lymphoma of the bladder. She was successfully treated with a combination of rituximab and radiotherapy. Since MALT-type lymphoma of the bladder sometimes regresses temporarily after antibiotic therapy, it should be followed carefully.

Urinary retention in a female patient caused by a urethral venous thrombus with massive edema.

Female urinary retention is rarely caused by an unknown condition. In such a case, common causes including neurogenic, anatomical, traumatic and iatrogenic voiding dysfunction are excluded. Both the radiological and histological findings specific to the condition remain unclear. We herein report a 75-year-old woman in whom a large venous mass and massive edema at the proximal urethra caused urinary outlet obstruction based on magnetic resonance images and histological findings. Ultrasonography and cystoscopy showed a urethral mass lesion protruding into the bladder neck. Fat-suppressed T2-weighted and gadolinium-enhanced T1-weighted magnetic resonance images suggested thrombosed veins with massive edema under the urethral mucosa. Transurethral resection of the mass lesion was carried out, and histopathological analysis proved the presence of thrombosed large veins. The patient regained normal urination, and the mass lesion did not recur. Thrombosed venous mass with edema at the proximal urethra might be an important cause of atypical urinary retention in women.

Targeted biopsy based on ADC map in the detection and localization of prostate cancer: a feasibility study.

PURPOSE: To investigate the feasibility of targeted biopsy based on an apparent diffusion coefficient (ADC) map in the detection and localization of prostate cancer. MATERIALS AND METHODS: This study included 288 consecutive patients with high or increasing serum prostate-specific antigen (PSA) levels who underwent prostatic magnetic resonance imaging (MRI) examination with an ADC map. Four core-targeted biopsies of low ADC lesions were performed under transrectal-ultrasound guidance with reference to ADC map. The positive predictive values (PPVs) of low ADC lesions were calculated and compared for the peripheral zone (PZ), transition zone (TZ), and anterior portion, respectively. Comparisons of ADC values and sizes between malignant and nonmalignant lesions were also performed. RESULTS: A total of 313 low ADC lesions were detected in 195 patients and sampled by targeted biopsies. The PPVs were 55.3% (95% confidence interval [CI]: 50-61) in total, 61.0% (95% CI: 53-69) for PZ, 50.6% (95% CI: 43-58) for TZ, and 90.9% (95% CI: 81-100) for the anterior portion. The most common nonmalignant pathology of low ADC lesions was hyperplasia, followed by chronic prostatitis. There were significant differences in ADC values and sizes between malignant and nonmalignant low ADC lesions. CONCLUSION: Targeted biopsies could be capable of detecting cancers well wherever they may be in the prostate, although the PPVs varied depending on the location of low ADC lesions.

[Heparin as bridging anticoagulant and antiplatelet therapy during the perioperative period].

Anticoagulant and antiplatelet medications are commonly used for the treatment and prevention of cardiovascular diseases. We studied 84 patients who received heparin as a bridging anticoagulant and antiplatelet therapy during the perioperative period. Hospitalization was extended for adjusting anticoagulant and antiplatelet drugs and also bleeding complications in the perioperative period. There were 25 instances of bleeding complications (29.7%) in this study. These complications mainly occurred when anticoagulant and antiplatelet medications were restarted in the postoperative period. In transurethral surgery, patients taking warfarin and antiplatelet drugs (aspirin or ticlopidine) had a statistically significant increase in bleeding complications compared to patients taking warfarin alone. We compared 51 cases of transurethral resection of bladder tumor, transurethral resection of the prostate holium laser enucleation of the prostate, nephroureterectomy and percutaneous nephrolithotomy with heparinization were compared to 692 cases with no heparinization. The heparinization group had a statistically significant longer hospitalization period and an increase in bleeding complications. There was one instance of thromboembolism (1.2%) in our series. This involved stent thrombosis of a patient who had drug-eluting stent in the left anterior descending coronary artery. She died three days postoperatively. The number of patients taking anticoagulant and/or antiplatelet drugs is predicted to increase in the future due to aging of the population. Guidelines for the management of anticoagulant and antiplatelet therapy in the urological period are considered necessary.

Detection and localization of prostate cancer with the targeted biopsy strategy based on ADC map: a prospective large-scale cohort study.

PURPOSE: To investigate the usefulness of targeted biopsy strategy based on apparent diffusion coefficient (ADC) maps in the detection and localization of prostate cancer. MATERIALS AND METHODS: Institutional review board approval and informed consent from all participants were obtained. This study included 1448 consecutive patients suspected of having prostate cancer based on PSA level, who were divided into two groups: Group A included 890 patients with low-ADC lesions who underwent targeted and systematic biopsies; Group B included 558 patients with no low-ADC lesions who underwent only systematic biopsies. The cancer detection rates (CDR) of each group, positive predictive value (PPV), and negative predictive value (NPV) of ADC maps were calculated. RESULTS: The CDR was 70.1% for Group A, higher than those for overall patients (48.1%) and for Group B (13.1%) with significant difference (P < 0.001). In the serum, PSA range from 4 to 20 ng/mL, the CDR was higher for the Group A than for the Group B and overall patients with significant differences. PPV and NPV of MR findings were 70.1% and 86.9%, respectively. Especially, the PPV of the MR findings for the anterior portion was as high as 90.1%. Among the false negatives of MR findings, Gleason score proved 6 or smaller in 79.5%, and positive core number was merely one or two in 80.8%. CONCLUSION: The targeted biopsy strategy based on ADC maps can be useful in the detection and localization of prostate cancer with high PPV.

[A case of bilateral renal calculi in a 1-year-old female with adenine phosphoribosyl transferase partial deficiency].

We report a case of bilateral renal calculi in a 1-year-old female with adenine phosphoribosyl transferase (APRT) partial deficiency. She initially visited another institution with high fever as the major complaint. Computed tomography revealed a bilateral renal stone and left hydro nephrosis. In the urine, there were 2, 8-dihydroxyadenine (DHA) crystals. An analysis of the APRT gene revealed the APRT deficiency and the genotype to be APRT*J/APRT*Q0. We performed extracorporeal shock wave lithotripsy (ESWL) under general anesthesia, and as dissolution therapy we administered Meylon through the nephrostomy and citric acid orally. The stone disappeared from her kidney. The analysis of the stone fragments revealed 2,8- dihydroxyadenine (DHA) urolithiasis.

Determination of the cutoff level of apparent diffusion coefficient values for detection of prostate cancer.

PURPOSE: The aim of this study was to determine the cutoff level of apparent diffusion coefficient (ADC) values for diagnosing prostate cancer. MATERIALS AND METHODS: A total of 45 consecutive patients with prostate cancer who underwent diffusion-weighted magnetic resonance imaging (MRI) with ADC maps before radical prostatectomy were included in this retrospective study. MRI findings were correlated retrospectively with histopathological results of surgical specimens. Comparisons of ADC values between cancer and noncancer areas were performed with the two-tailed unequal variance t-test. The cutoff ADC level was determined in a way to achieve the best accuracy for detecting prostate cancer. RESULTS: The mean ADC value of all the cancer lesions (n =60) was 1.04 ± 0.31 (×10(-3) mm(2)/s). In the peripheral zone, the mean ADC values of cancer lesions and noncancer areas were 1.07 ± 0.35 and 1.94 ± 0.31, respectively (P < 0.001). In the transition zone, the mean ADC values of cancer lesions and noncancer areas were 1.00 ± 0.22 and 1.56 ± 0.14, respectively (P<0.001). The cutoff level for the ADC value was determined to be 1.35×10(-3) mm(2)/s. It provided sensitivity, specificity, and accuracy of 88%, 96%, and 93%, respectively. CONCLUSION: The cutoff ADC level determined on the basis of the results obtained from radical prostatectomy specimens can help differentiate malignant from nonmalignant lesions.

[Long-term outcome of initial treatment with Bacillus Calmette-Guérin for carcinoma in situ of the upper urinary tract].

To assess appropriate treatment strategies for transitional cell carcinoma in situ (CIS) of the upper urinary tract (UUT), we evaluated the long-term outcome of Bacillus Calmette-Guérin (BCG) perfusion therapy for CIS of UUT. We retrospectively reviewed the medical records of 24 patients who underwent BCG perfusion therapy for CIS of UUT between August 1993 and August 2009. Patients received at least one course of BCG (once weekly for 6 weeks). The median follow-up period was 48.5 months (range 16-201 months). In 23 patients (96%), cytology became negative after one course of BCG perfusion and 12 patients (50%) remained disease-free for a median follow-up of 38. 5 months. In 11 patients positive cytology recurred, and in five of them nephroureterectomy was performed after radiologic studies showed the presence of a tumor in the UUT. Histopathology showed invasive tumor (pT3) in all cases, and three of them experienced distant metastases after surgery. In conclusion, BCG perfusion therapy is effective for the treatment of CIS of UUT with long-term follow-up. However, in cases with a poor response or recurrence of CIS, there is a high risk of developing invasive tumor. Surgical intervention should be immediately considered in such cases after the first course of BCG perfusion therapy.

[Intravesical migration of intrauterine contraceptive device (IUCD) with stone formation].

Migration of an intrauterine contraceptive device (IUCD) into the bladder and secondary stone formation are uncommon complications associated with the insertion of IUCD. To our knowledge, there have been no such reported cases in Japan. In the present report, we describe the case of a 59-year-old woman who underwent an operation for the removal of an IUCD from the bladder, which had been inserted 30 years ago. The patient was referred to our facility because of hematuria and recurrent urinary tract infections. A plain film revealed a calcified mass in the pelvis, and cystoscopy revealed a fully mobile calculus in the bladder. During a transurethral cystolithotripsy, the IUCD was found within the calculus and removed transurethrally. No fistulae or defects were found in the bladder wall.