Rationale and design of a multicenter, double-blinded, randomized, placebo-controlled trial to investigate the effects of naldemedine on opioid-induced constipation for patients with cancer pain: A study protocol.

Background: It is unclear which laxatives are appropriate to prevent opioid-induced constipation (OIC). This study will evaluate whether prophylactic use of naldemedine prevents OIC in patients with cancer who start opioid administration. Methods: This study is a multicenter, double-blinded, randomized, placebo-controlled trial. Patients who meet the eligibility criteria and give consent will be randomly assigned to the naldemedine or placebo group. Both groups will take each drug once a day after breakfast for 14 days. Results: The primary endpoint is the proportion of patients with a Bowel Function Index of less than 28.8 on Day 14. The secondary endpoints include assessment scales of the impact of constipation on comprehensive quality of life. Conclusions: This is the first study proposed to assess the superiority of naldemedine over placebo in the prevention of OIC. If naldemedine is found to be effective in reducing OIC compared with the placebo, it will be regarded as a new standard for OIC prophylaxis at opioid initiation. Trial registration: jRCT identifier: jRCTs031200397. Registered March 5, 2021, https://rctportal.niph.go.jp/en/detail?trial_id=jRCTs031200397.

Domino Cross-Scholl Reaction of Tetracene with Molecular Benzene: Synthesis, Structure, and Mechanism.

A domino-type multiple C-H functionalization of tetracene with molecular benzene is reported. Under the typical conditions of the Scholl reaction, a domino reaction occurs between tetracene and six molecules of benzene in one pot to furnish an aromatic compound with a curved π-system. This reaction sequence involves oxidative cross-dehydrogenative coupling/annulation and Friedel-Crafts-type reactions. Eight C-C bonds are formed via this intermolecular domino reaction without mediation by a metal or the assistance of a specific substituent.

[A Case of Metachronous Bilateral Epididymal Tuberculosis after BCG Instillation Therapy].

Beginning in May 2016, an 83-year-old male underwent three transurethral resections for recurrent bladder cancer. In June 2017, following a positive urine cytology exam, a random biopsy of the bladder was performed. The histopathological findings revealed urothelial carcinoma, high grade, pTis. Treatment consisted of bacillus Calmette-Guerin (BCG) instillation. In February 2018, he complained of left scrotal swelling and pain ; and, was diagnosed with left epididymitis. However, based on resistance to the antibiotic agent, epididymal tuberculosis after BCG therapy was suspected and resection of the left testis and epididymis was performed. Histopathological findings revealed epididymal tuberculosis. Three months after the left orchiectomy, the patient complained of right scrotal swelling and pain. Based on antibiotic resistance and the positive findings of a urinary mycobacterium tuberculosis polymerase chain reaction assay, metachronous right epididymal tuberculosis was suspected and the patient underwent resection of the right epididymis. While the histopathological findings did not indicate tuberculosis, the urinary mycobacterium culture was positive. The patient was diagnosed with right epididymal tuberculosis and after surgery was administered an antituberculosis drug.

[TWO CASES OF FALSE POSITIVE 123I-MIBG SCINTIGRAPHY FINDINGS OF UPTAKE IN ADRENAL TUMORS].

Case 1 was a 71-year-old female who had been examined by her primary care physician for palpitation and hypertension. Urinary hormone test results revealed elevated urine metanephrine at 0.20 mg/day, urine normetanephrine at 0.45 mg/day and urine noradrenalin at 234.9 µg/day. 123I-MIBG scintigraphy showed uptake in the right suprarenal area, thus she was referred to our department because of pheochromocytoma. She underwent a laparoscopic right adrenalectomy and pathological results led to a diagnosis of adrenocortical adenoma. Case 2 was a 70-year-old female who had been examined at our hospital for hypertension. Blood hormone test results revealed elevated noradrenalin at 0.70 ng/ml. 123I-MIBG scintigraphy showed uptake in the left suprarenal area and she was referred to our department because of pheochromocytoma. She underwent a laparoscopic left adrenalectomy, thus pathological results showed no tumor lesion.

[A Case of Bilateral Renal Tumors, Renal Cell Carcinoma and IgG4- Related Retroperitoneal Fibrosis].

A 69-year-old man was referred to our hospital for a right renal pelvic tumor noted on a computed tomography (CT) scan at another hospital. Urine cytology was negative. Dynamic CT revealed a right renal pelvic tumor and, accidentally, a small left renal tumor enhanced in the arterial phase and washed out in the venous phase. No defect in the urinary tract was found on retrograde urography, and upper urinary cytology was negative. The patient's level of IgG4 was high, but other tumor markers were negative. We judged the right renal pelvic tumor to be an extrapelvic lesion, probably IgG4-related disease. We temporarily followed up the right renal pelvic tumor but performed retroperitoneal left partial nephrectomy for the small left renal tumor. Histopathology led to a diagnosis of clear cell renal cell carcinoma. Follow-up CT showed no change in the right renal pelvic tumor. We diagnosed the right renal tumor as IgG4-related disease and began steroid administration. After one monthof administration, the IgG4 value and the size of the tumor were reduced.

[Urothelial Carcinoma within a Calyceal Diverticulum Difficult to Distinguish from Cystic Renal Cell Carcinoma].

A 64-year-old man visited our hospital because of right renal cyst and microscopic hematuria which was found in a medical checkup. Contrast computed tomography (CT) and contrast magnetic resonance imaging (MRI) suggested cystic renal cell carcinoma. A laparoscopic nephrectomy was performed, and the surgical specimens showed urothelial carcinoma within the calyceal diverticulum. At a later date, ureterectomy was performed. The surgical specimens had no malignant findings. There has been no recurrence. To our knowledge only 10 cases of urothelial carcinoma within the calyceal diverticulum have beenreported inJapan. A few cases have beenreported overseas.

[Urethrocutaneous Fistula Caused by a Vesical Foreign Body in an Adolescent Boy : A Case Report].

In daily medical practice, we occasionally encounter patients with a foreign body in the urinary bladder. However, the identification of such a foreign body in an adolescent and the occurrence of an urethrocutaneous fistula caused by the foreign body are extremely rare. Only two cases have been reported previously. Herein we present a case of a foreign body in the urinary bladder and an urethrocutaneous fistula in a young patient. A 14-year-old boy with fever, left scrotal pain and urinary incontinence was referred to our department. Intravenous pyelography and micturition cystourethrography findings revealed a vesical foreign body and an urethrocutaneous fistula. He mentioned that he had inserted two dozen magnets into the urethra for masturbation one year previously. As the foreign bodies were spherical small magnets, we performed transurethral surgery and successfully removed the magnets. His postoperative course was uneventful and he was discharged from our department on the seventh day after surgery. Three months following surgery, the fistula had closed spontaneously.

Results of weekday-on and weekend-off administration schedule of sunitinib therapy for advanced renal cell carcinoma.

BACKGROUND: Sunitinib is widely prescribed as first-line therapy for metastatic renal cell carcinoma. To reduce the ratio of severe adverse events and improve the relative dose intensity, we prospectively tried our own alternative medication schedule, which we called the "weekday-on and weekend-off regimen". Here we report the results of this regimen compared to the conventional medication schedule. METHODS: In total, 58 patients were enrolled in this study. Twenty patients were treated under the alternative schedule (group I: weekday-on and weekend-off regimen) and 38 patients were treated using the conventional schedule (group II: 4 weeks on and 2 weeks off regimen). The relative dose intensity (6W-RDI) and prognoses were compared between the two groups. RESULTS: Median 6W-RDI of all the patients was 75.0%. Group I patients demonstrated significantly higher 6W-RDI compared to group II (77.2 vs. 70.4%) (p = 0.019). Multivariate analysis showed that the alternative sunitinib administration schedule was significantly associated with maintaining 6W-RDI above 75% for RCC patients treated with sunitinib (OR 3.592, 95% CI 1.042-12.383, p = 0.043). On the other hand, there were no significant differences between 2 groups regarding occurrence rate of severe adverse events and prognosis by multivariate analysis. CONCLUSIONS: We report the results of an alternative medication schedule, the "weekday-on and weekend-off regimen", as a means of increasing 6W-RDI for metastatic RCC patients.

[Vesical Perforation Caused by a Foreign Body : A Case Report --A Clinical Review of 41 Cases in Japan-].

In daily medical practice, we occasionally encounter a foreign body present in the urinary bladder. However, the occurrence of vesical perforation caused by a foreign body is rare. A 53-year-old man with vesical pain and macrohematuria was referred to our department because of the presence of a foreign body in his urinary bladder. He seemed to have inserted the foreign body from the urethra during use of a stimulant drug according to his story. Cystoscopy revealed that the plastic foreign body had a few barbs and had penetrated the bladder through the left lateral wall. On performing computed tomography, we did not detect any injuries to other organs or hematoma formation. Therefore, we performed elective suprapubic cystostomy and removed the plastic foreign body. The patient's postoperative course was favorable, and he left our department on the sixth day after surgery.

[A Case of Clear Cell Adenocarcinoma Arising from a Female Urethral Diverticulum].

Adenocarcinoma arising from the female urethral diverticulum is very rare, as only about 100 cases have been reported worldwide. An 82-year-old woman presented with asymptomatic macrohematuria. A transvaginal examination revealed a firm circular mass on the anterior vaginal wall. Cystourethroscopy showed a urethral tumor, which was determined to be clear cell adenocarcinoma after transurethral resection of the urethral tumor. However, we could not resect all of the tumor, so anterior pelvic exenteration and ileal conduit urinary diversion were performed. The final pathological diagnosis was clear cell adenocarcinoma arising from the urethral diverticulum. However multiple lymph node metastases appeared 10 months after surgery. The patient refused additional therapy and died 23 months after surgery.

[LAPAROSCOPIC BILATERAL ADRENALECTOMY FOR REFRACTORY CUSHING DISEASE: A CASE REPORT].

A 64-year-old man was diagnosed as having Cushing's disease due to multiple lumbar compression fracture in 2009. Although various treatments including three times transsphenoidal surgery and twice radiotherapy were performed, his serum cortisol level rose again and intractable cutaneous ulcer occurred. Just after discontinuation of medication to treat the progression due of severe hepatic dysfunction, deep vein thrombosis and pulmonary artery embolism occurred. To control the Cushing's disease, laparoscopic bilateral adrenalectomy was performed.

[Primary Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma with Large Cell Transformation of the Prostate : A Case Report].

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate is rare. MALT lymphoma with large cell transformation like a diffuse large B-cell lymphoma (DLBCL) of the prostate is extremely rare. To the best of our knowledge, only one case has been previously reported. A 65-year-old man with difficulty on urination was referred to our department, in April 2014, because of abnormal findings of magnetic resonance imaging (MRI) and positron emission tomography-computed tomography imaging. Routine laboratory tests including prostate specific antigen and soluble interletkin-2 recepter were within normal limits, and the physical examination was unremarkable. In July 2007 and August 2009, he was submitted for a transrectal prostate biopsy, and then a histological examination for chronic prostatitis. In addition to the biopsy, transurethral resection of the prostate was performed. Histological examination revealed primary MALT lymphoma with large cell transformation of the prostate. Complete clinical investigation, including bone marrow biopsy, did not show any involvement of other sites by lymphoma, he received 3 cycles of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by radiation therapy with a total dose of 46 Gy. The patient has been in complete remission for 6 months after the chemoradiation therapy.

[Intrarenal Bacillus Calmette-Guerin perfusion therapy was effective for carcinoma in situ of the upper urinary tract after ileal conduit replacement : a case report].

A 63-year-old man who had undergone radical cystectomy and ileal conduit formation for invasive bladder cancer 3 years before presented with continuous positive urinary cytology in the ileal conduit. His diagnosis was carcinoma in situ (CIS) of the left upper urinary tract. He was treated with Bacillus Calmette-Guérin (BCG) perfusion therapy using a single-J ureteric stent. BCG (80 mg) in 100 ml saline was instilled in a one-hour period weekly for 6 weeks. Usage of another catheter was effective for continuing the therapy. Urinary cytology in the left upper urinary tract and the ileal conduit became negative after the therapy. There was no evidence of recurrence or metastasis of urothelial carcinoma 6 months after the therapy.