Bilateral Cortical-sparing Adrenalectomy for the Treatment of Bilateral Aldosterone-producing Adenomas.

Aldosterone-producing adenoma (APA) is 1 of the major subtypes of primary aldosteronism (PA). Although most APA occurs unilaterally, bilateral APAs have rarely been documented. Because of its rarity, optimal management of patients with bilateral APAs has not been established. Here, we report a case of bilateral APAs that was successfully treated with simultaneous bilateral cortical-sparing surgery. A 44-year-old Japanese woman was referred to us for the evaluation of PA. She had typical clinical characteristics of PA, including hypertension, hypokalemia, and high plasma aldosterone concentration with suppressed renin. She was diagnosed as having PA based on the results of confirmatory testing. Computed tomography revealed bilateral adrenal nodules with diameters of 17 and 10 mm on the right and left adrenal gland, respectively. Adrenal venous sampling indicated excess aldosterone production from bilateral adrenal lesions. She underwent simultaneous bilateral laparoscopic partial adrenalectomy that normalized her blood pressure and serum potassium levels. Aldosterone synthase immunohistochemistry on the resected adrenal tumor tissue confirmed the diagnosis of bilateral APAs. Long-term postsurgical follow-up data suggest cure of the disease without the need for glucocorticoid replacement therapy. Bilateral cortical-sparing adrenalectomy appears to be a viable treatment option at least for selected patients with bilateral APAs.

Effectiveness and Safety of a Mixture of Nobiletin and Tangeretin in Nocturia Patients: A Randomized, Placebo-Controlled, Double-Blind, Crossover Study.

Nobiletin and tangeretin (NoT) are flavonoids derived from the peel of Citrus depressa, and they have been found to modulate circadian rhythms. Because nocturia can be considered a circadian rhythm disorder, we investigated the efficacy of NoT for treating nocturia. A randomized, placebo-controlled, double-blind, crossover study was conducted. The trial was registered with the Japan Registry of Clinical Trials (jRCTs051180071). Nocturia patients aged ≥50 years who presented nocturia more than 2 times on a frequency-volume chart were recruited. Participants received NoT or a placebo (50 mg once daily for 6 weeks), followed by a washout period of ≥2 weeks. The placebo and NoT conditions were then switched. Changes in nocturnal bladder capacity (NBC) were the primary endpoint, and changes in nighttime frequency and nocturnal polyuria index (NPi) were secondary endpoints. Forty patients (13 women) with an average age of 73.5 years were recruited for the study. Thirty-six completed the study, while four withdrew. No adverse events directly related to NoT were observed. NoT had little effect on NBC compared with the placebo. In contrast, NoT significantly changed nighttime frequency by -0.5 voids compared with the placebo (p = 0.040). The change in NPi from baseline to the end of NoT was significant (-2.8%, p = 0.048). In conclusion, NoT showed little change in NBC but resulted in decreased nighttime frequency with a tendency toward reduced NPi.

[Evaluation of Patients with Localized Prostate Cancer in whom Long-Term Successful Androgen Deprivation Therapy was Ceased].

We evaluated the clinical course of patients with localized prostate cancer in whom long-term successful androgen deprivation therapy (ADT) was ceased. Study subjects were 24 patients with stage B prostate cancer who were initially treated with ADT for a median duration of 93 months. The median age at the cessation of ADT was 84 years. The median nadir serum prostate specific antigen (PSA) level was 0.022 ng/ml. The median duration of follow-up from the cessation of ADT was 31 months. During follow-up, five patients showed PSA elevation of ≥2 ng/ml from the nadir. Serum testosterone level was tested in 20 patients, and five showed testosterone recovery ≥0.5 ng/ml. Seven patients died from diseases other than prostate cancer, but there were no deaths caused by prostate cancer. This study demonstrated that long-term successful ADT for localized prostate cancer could be ceased with adequate follow-up evaluation.

ACTH-independent production of 11-oxygenated androgens and glucocorticoids in an adrenocortical adenoma.

SIGNIFICANCE STATEMENT: Due to its rarity, biochemical and histologic characteristics of androgen and glucocorticoid co-secreting adrenocortical adenomas are largely unknown. Herein, we report a case of adrenocortical adenoma that caused marked hyperandrogenemia and mild autonomous cortisol secretion. In this study, we investigated serum steroid profiles using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and histologic characteristics of the resected tumor. LC-MS/MS revealed highly elevated levels of 11-oxygenated androgens which have not been well studied in adrenal tumors. The expression patterns of steroidogenic enzymes determined by immunohistochemistry supported the results of steroid profiling and suggested the capacity of the tumor cells to produce 11-oxygenated androgens. Measurement of 11-oxygenated steroids should facilitate a better understanding of androgen-producing adrenocortical neoplasms.

[A Case of Emphysematous Pyelonephritis Complicated by Bacterial Endophthalmitis in which Multidisciplinary Therapy Led to Preservation of the Kidney].

A 49-year-old male with untreated diabetes mellitus type 2 experienced eyesight deterioration and general malaise, and was treated for uveitis and orbital cellulitis. Later, he was taken to a local hospital via ambulance for a consciousness disorder and was diagnosed with bilateral infectious endophthalmitis, a right ureteral stone, and emphysematous pyelonephritis. He was then referred to our hospital for further examination and treatment. We immediately initiated intravenous antibiotic therapy with meropenem and glycemic control with continuous subcutaneous insulin infusion, and placed a ureteral and percutaneous drain tube into the right ureter and the emphysema, respectively. We performed a diagnostic and therapeutic vitrectomy on the patient's left eye. Urinary, blood, and vitreous cultures were positive for Klebsiella aerogenes. Abdominal contrast-enhanced computed tomography showed bilaterally comparable renal contrast enhancement. On the 60th hospital day, we performed endoscopic combined intrarenal surgery (ECIRS) and completely removed the urinary stone. Although he lost light sensitivity in his right eye, his left eyesight improved, and his blood glucose level was adequately managed by oral medication. Three months after the surgery, he was discharged from our hospital and he showed no sign of recurrence of the infection at ten months after surgery.

Predictive factors and radiological findings of adrenohepatic adhesion during laparoscopic adrenalectomy.

Purpose: This retrospective study aimed to identify predictive factors and imaging features of adrenohepatic adhesion found during laparoscopic right adrenalectomy. Materials and Methods: Altogether, 77 patients underwent laparoscopic right adrenalectomy between January 2005 and December 2018. Adrenohepatic adhesion was defined as strict adhesion that required either partial adrenalectomy with coagulation of residual tissue or partial hepatectomy to accomplish complete resection. We assessed their surgical video records to determine if adrenohepatic adhesion was present. Age, sex, body mass index, tumor size, tumor diagnosis and radiological findings (attachment between the liver and the adrenal gland, diameters of the right and left adrenal veins and its ratio) were evaluated as preoperative variables. Results: Adrenohepatic adhesion was present in 11 of the 77 patients (14.3%). Age, sex, and body mass index were not statistically significant factors. Tumor size was significantly small in adhesion group (14.2 mm vs. 25.9 mm, p=0.02). Attachment to the liver and adrenal gland was frequently seen regardless of the adhesion. The mean right/left adrenal veins diameters ratio was significantly lower in the adhesion group (0.8 vs. 1.1, p=0.01). Multivariate logistic regression analysis demonstrated the right/left adrenal veins diameters ratio was the only significant predictor of adhesion. The sensitivity, specificity, negative predictive value and positive predictive value were 0.82, 0.76, 0.43, and 0.95 respectively when the optimal cutoff value for the ratio was 0.9 (area under the curve, 0.75; 95% confidence interval, 0.60-0.90). Conclusions: The right/left adrenal veins diameters ratio was possible predictor of adrenohepatic adhesion.

[A Case of Castration-Resistant Prostate Cancer after Prostatectomy Treated with Resection of A Solitary Metastatic Site].

A 72-year-old man underwent a bilateral nerve-sparing radical retropubic prostatectomy (RRP) with pelvic lymph node dissection 11 years earlier. His prostate specific antigen (PSA) value at diagnosis was 61.024 ng/ml. Bone scans and computed tomographic (CT) scans showed no metastasis. Pathological findings and stage were adenocarcinoma, Gleason score 4+3, positive surgical margin, pT3b, and no lymph node metastasis. The postoperative PSA nadir was 0.218 ng/ml, and salvage radiotherapy (SRT, total 66 Gy) was performed six months after RRP. However, the PSA value continued to rise after SRT. Therefore, androgen deprivation therapy (ADT) was started 11 months after SRT. Nine years postoperatively, the PSA value showed a continuous rise despite ADT, and prostate cancer was considered to be castration-resistant. Although he was taking enzalutamide, his PSA value rose to 18. 271 ng/ml. Repeated bone scans and CT scans were negative. Eleven years after RRP, the fluoro-2-deoxy-D-glucosepositronemissiontomography (FDG-PET) revealed a nodule lesiondorsal to the left pubic bone. The patient underwent a resection of the lesion. Three months after the resection, his PSA level declined to 0.038 ng/ml, thus ADT was discontinued. Thirteen months after the resection, PSA re-elevation was absent, and follow-up without ADT is ongoing.

[A Case of Nivolumab-Induced Isolated Adrenocorticotropic Hormone Deficiency Presenting Dyspnea].

A 66-year-old man had undergone multiple treatments for metastatic renal cell carcinoma, including 11 cycles of nivolumab, which was discontinued because of disease progression. About three weeks after discontinuing nivolumab, he reported suffering from worsening of dyspnea. Pulse oximetry showed no desaturation. His cardiovascular and pulmonary functions were normal. His dyspnea slowly worsened with no underlying diagnosis. Two months after symptoms developed, he was diagnosed with isolated adrenocorticotropic hormone deficiency. His dyspnea disappeared soon after receiving hydrocortisone. Nivolumab-induced isolated adrenocorticotropic hormone deficiency may not present with typical symptoms, and can occur even after discontinuing nivolumab. Cortisol levels should be routinely monitored in patients who receive nivolumab.

Peritoneal Tuberculosis After Robot-Assisted Laparoscopic Prostatectomy with Extended Lymph Node Dissection.

Background: Peritoneal tuberculosis (TB) is a relatively uncommon presentation of extrapulmonary TB. Early diagnosis of peritoneal TB is difficult because of its nonspecific clinical manifestation such as abdominal pain, fever, or ascites. Especially early after surgery of abdomen or pelvis, these symptoms can be misdiagnosed as septic peritonitis. There are few reports of peritoneal TB as a postoperative complication of laparoscopic surgery. Here, we describe a first case of peritoneal TB after robot-assisted laparoscopic prostatectomy (RALP) with extended lymph node dissection. Case Presentation: A 78-year-old man presented 25 days after this surgery with fever and abdominal distension. Ultrasonography and computed tomography (CT) revealed massive abdominal ascites. Ascites sample was cloudy, with increased white blood cells and normal creatinine level. No anastomotic leak was found. Bacterial infection of a lymphocele was considered, and cefmetazole 2 g/day for 3 days was prescribed. Despite antibacterial therapy, fever persisted. Polymerase chain reaction testing of ascitic fluid was positive for Mycobacterium tuberculosis. The patient was effectively treated with anti-TB therapy. Conclusion: This is the first report of peritoneal TB as a postoperative complication of RALP with extended lymph node dissection. His preoperative chest CT showed granular shadows in left upper lung, indicating his old asymptomatic TB infection. Flare-up of TB can happen even after robot-assisted laparoscopic surgery, which is minimally invasive. Peritoneal TB must be considered especially when there is unexplained ascites unresponsive to antibiotics.

[Gastric metastasis from renal cell carcinoma: two case reports].

Gastric metastasis from renal cell carcinoma (RCC) is a very rare event and treatment for such patients has not been established. We report two cases of gastric metastasis from RCC. The first case was in a 67- year-old man with a past history of right radical nephrectomy for RCC (ypT3aN0M0) six years ago. The whole-body computed tomography (CT) revealed multiple lung nodules. We performed gastrointestinal endoscopy to find the primary lesion, and detected multiple submucosal tumors in the gastric body. Needle biopsy of these tumors revealed gastric metastasis from RCC. Oral sorafenib tosylate therapy was started. Twenty months later, gastrointestinal endoscopy showed only gastric erosion without malignant evidence. The second case was in a 70-year-old man complaining of epigastralgia. He had undergone right partial nephrectomy for RCC (pT1aN0M0) six years ago, and thoracoscopic wedge resection of a solitary lung nodule one year ago. Gastrointestinal endoscopy detected a solitary hyperplastic polyp in the anterior wall of the gastric body. Needle biopsy of this polyp revealed gastric metastasis from RCC. We performed laparoscopic partial gastrectomy. Gastrointestinal endoscopy and CT showed no evidence of metastasis or recurrence for 14 months after gastrectomy.

[Efficacy of prophylactic intravesical mitomycin C in patients with non-muscle-invasive bladder cancer].

Intravesical chemotherapy is beneficial for patients with non-muscle-invasive bladder cancer (NMIBC), but optimal drug and regimen selection can be controversial. Mitomycin C (MMC) is commonly used as adjuvant treatment for NMIBC. We retrospectively evaluated the outcomes of 73 patients with NMIBC who were treated with weekly doses of low-dose MMC (20 mg ; n=28 ; 38.4%) or high-dose MMC (40 mg ; n=45 ; 61.6%) for 6 weeks each, at our hospital between 2001 and 2010. Treatment outcomes were examined by Kaplan‒Meier analysis with log-rank tests. Patients in the high-dose group showed greater recurrent-free survival (61.3%) at 2 years than did patients in the low-dose group (32.6%) (P<0.05). We also found that a single early dose of pirarubicin following transurethral resection of bladder tumor improved MMC efficacy in the high-dose group. The high-dose group had a somewhat higher incidence of dysuria, urinary frequency and drug eruption, but the difference was not significant.

[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.

Antimicrobial prophylaxis to prevent perioperative infection in urological surgery: a multicenter study.

We prospectively investigated the rates of incidence of surgical site infection (SSI), urinary tract infection (UTI), and remote infection (RI) in 4,677 patients who underwent urological surgery from January to December 2010, including 2,507 endourological cases, 1,276 clean cases, 807 clean-contaminated cases, and 87 contaminated cases involving bowel segments. A single dose of antimicrobial prophylaxis (AMP) was administered in the endourological, clean, and clean-contaminated surgery cases, except for patients who underwent transurethral resection of the prostate (TURP) or percutaneous nephrolithotripsy (PNL). AMP was administered within 72 h in TURP and PNL, and AMP was administered within 48 h in contaminated surgery cases. In cases of endourological surgery, UTI was observed in 4% and RI in 0%, and SSI, UTI, and RI were seen in 1%, 1%, and 1%, respectively, of clean surgery cases, in 3%, 3%, and 2%, respectively, of clean-contaminated surgery cases, and in 17%, 30%, and 10%, respectively, of contaminated surgery cases. In multivariate analysis of the risk factors for infection, operative time was a significant risk factor for UTI in endourological surgery, and American Society of Anesthesiologists score and operative time were significant risk factors for RI in clean surgery. No significant risk factor was found in analyses of clean-contaminated and contaminated surgery cases. A single-dose AMP regimen was shown to be effective and feasible for prevention of perioperative infection in urological surgery.

[The role of dynamic contrast-enhanced magnetic resonance imaging in diagnosis of torsion of the testicular appendix : a case report].

A 7-year-old male presented to our hospital with pain and swelling in the right scrotum for 9 days. On physical examination a swollen right scrotum was noted and right side cremasteric reflex disappeared. Ultrasound examination showed enlarged right testis and epididymis. Subsequent dynamic contrast enhanced magnetic resonance imaging (MRI) showed a 7 mm area of high signal intensity anterior to the right testis on coronal imaging of T2-weighted. Subtraction MRI revealed testicular perfusion and a nonenhanced mass was also identified anterior to the right testis. These findings indicated a diagnosis of torsion of the testicular appendix. We performed excision of the torsed appendage.

[A case report of Cowper's syringocele in an adult treated with transurethral unroofing].

We present an adult case of Cowper's syringocele. A 19-year-old male presented with the chief complaint of persistent post-voiding dribbling 5 months after onset. Urethroscopy demonstrated a thin membrane with a small orifice on the ventral aspect distal to the external sphincter. Magnetic resonance imaging showed a restiform shadow on the left side of the corpus spongiosum. Retrograde urethrogram showed filling of diverticulum-like structure in the region of urethral bulb terminating in the urogenital diaphragm. Considering the results mentioned above, we diagnosed the patient with Cowper's syringocele. Transurethral unroofing of the Cowper's syringocele was performed with a cold knife, and the excessive tissue on the edge of syringocele was electroresected to avoid recurrence. His post-voiding dribbling resolved completely after the procedure and has not recurred in 13 months postoperatively. Cowper's syringocele is typically diagnosed presenting with hematuria, urinary tract infection, and disuria in male infants and children. Adult cases of Cowper's syringocele are rare, and only 32 cases including the present case have been reported. Proper awareness of this entity and careful evaluation are important if patients present with persistent adult-onset voiding dysfunction.

[Usefulness of MRI prior to prostate needle biopsy in PSA gray zone].

To evaluate the diagnostic accuracy of prostate magnetic resonance imaging (MRI), we compared MRI findings with the results of biopsy as well as findings from specimens following total prostatectomy. The subjects consisted of 260 males who showed a prostate specific antigen (PSA) level in the gray zone (4 ng/ml ≤PSA <10 ng/ml) and also underwent digital rectal examination (DRE), transrectal ultrasound (TRUS), and MRI prior to prostate biopsy between April 2005 and December 2009. In Evaluation 1, the results of DRE/TRUS/MRI were compared with those of prostate biopsy. The biopsy-positive rate was higher in males positive in each examination. However, 24.8% of males negative in all examinations were biopsypositive. Thus, these examinations were considered to be inappropriate for secondary screening. In evaluation 2, the prostate was divided into 4 regions, and the findings from specimens following total prostatectomy were compared with MRI findings in each region. For the region containing prostate cancer, MRI showed a sensitivity of 26.0%, specificity of 98.3%, positive predictive value of 96.2%, and negative predictive value of 44. 4%. In patients with a Gleason score ≥7, cancer foci were more frequently detectable using MRI. MRI prior to prostate biopsy in patients in the PSA gray zone is inappropriate for secondary screening due to its low sensitivity. However, by virtue of its high positive predictive value, MRI is useful for determining patients indicated for biopsy, as well as DRE and TRUS. Accurate evaluation of the localization of all cancer lesions is difficult using MRI. However, when MRI findings are present, they frequently indicate the cancer lesion, which may be useful information for treatment.

[Risk factors for falls and fractures at night in relation to lower urinary tract symptoms: a survey of outpatients and inpatients at a general hospital].

We investigated potential risk factors, including factors related to lower urinary tract symptoms (LUTS), for falls and fractures at night among outpatients and inpatients in a general hospital, via a questionnaire. The questionnaire included items to record the age, sex, number of consulting doctors, history of 11 particular medical diseases, LUTS, sleep, and falls and fractures at night. We distributed the questionnaire to 1,334 patients 51 years old or older in our hospital. Of the questionnaires completed, 96.9% were valid for analysis. Multivariate analyses revealed that "drinking water before bedtime or while in bed" was the strongest risk factor (odds ratio＝7.499) for bone fractures while "postural syncope" was the strongest risk factor (odds ratio＝5.041, except past medical history) for falls. In terms of LUTS, urge incontinence was a significant risk factor for falls.

[Acquired hemophilia A developing at bilateral renal bleeding: a case report].

A 82-year-old woman with asymptomatic gross hematuria was referred to us for a consultation. Computed tomography and magnetic resonance imaging revealed hydronephrosis in the right kidney and retrograde pyelography showed a filling defect in the right renal pelvis. Cystoscopy revealed gross hematuria from right ureteral orifice concomitant with superficial papillary bladder tumor (catheterized urine cytology: positive) (transurethral resection of bladder tumor UC G1 pTa). She was diagnosed with right renal pelvic carcinoma, and we performed a total right nephroureterectomy. Histolopathological findings showed no evidence of malignancy, but extensive hemorrhaging was observed in the subepithelium. There was hematoma in the retoroperitoneum and she suffered from endotoxic shock after the operation. In the post-operative period, she showed complications involving left renal bleeding. She was diagnosed with acquired hemophilia A based on a decline in factor VIII activity, prolonged APTT and the presence of anticoagulant. Although we administered steroids to her, her general condition deteriated and she died of postrenal renal failure 37 days after the operation. To our knowledge, this is the fourth case worldwide and the third case in Japan of acquired hemophilia A discovered by renal bleeding.

Association of XRCC1 gene polymorphisms with the susceptibility and chromosomal aberration of testicular germ cell tumors.

It is known that many genomic and genetic alterations caused by aging or environmental factors are responsible for cancer development and progression. XRCC1 is involved in the repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. The objective of this study was to investigate the association of genomic alterations and the susceptibility of testicular germ cell tumors with XRCC1 polymorphisms. Two polymorphisms of XRCC1, Arg194Trp and Arg399Gln, were genotyped in 83 patients with testicular germ cell tumors (TGCT) and 87 male controls. Allelic imbalances (AI) were evaluated using 4 microsatellite markers in a subgroup of 50 patients. Patients with at least one Gln allele of the Arg399Gln polymorphism had an increased risk of TGCT than those with the Arg/Arg genotype (aOR=1.775, 95% CI=1.045-3.016, P=0.034). Furthermore, the increased risk associated with the Gln allele against the Arg homozygote was more strongly observed in patients with pure seminoma (aOR=2.242, 95% CI=1.149-4.374, P=0.018) or with metastasis (aOR=2.481, 95% CI=1.267-4.862, P=0.008). In the Arg194Trp polymorphism, there was no significant difference in the genotype distribution between TGCT patients and the controls. In AI analysis, the frequency of AI was significantly higher in tumors with at least one Gln allele than those with the Arg/Arg genotype in D13S317 (P=0.010) and in a combination of 4 markers (0.51+/-0.32 vs 0.32+/-28, P=0.028). Our results suggest that the Gln allele of the XRCC1 Arg399Gln polymorphism may genetically modify the development and progression of TGCT through genomic instability.

Association of BCL10 germ line polymorphisms on chromosome 1p with advanced stage testicular germ cell tumor patients.

The association between four BCL10 single nucleotide polymorphisms at codons 5, 8, 162, and intron 1 and the susceptibility or progression for germ cell tumors (GCTs) was investigated in 73 testicular GCT patients and 72 controls. GCT patients with metastatic disease were more likely to have a variant type allele of the polymorphisms at codon 5 (age-adjusted odds ratio (aOR)=6.25; 95% CI=1.09-35.83; P=0.040) and codon 8 (aOR=4.63; 95% CI=1.35-15.93; P=0.015) than those with the localized disease. Therefore, BCL10 polymorphisms at codons 5 and 8 may play a role in the progression to advanced stage GCTs.