Impact of Histological Variants on Clinical Responses to Pembrolizumab in Patients With Metastatic Urothelial Cancer.

BACKGROUND: The efficacy of anti-programmed celldeath protein 1 treatment in patients with urothelial carcinoma (UC) with molecular subtypes of histological variants has not been investigated. This study aimed to examine the impact of histological variants classified according to molecular subtypes on clinical outcomes in patients with platinum-resistant metastatic UC treated with pembrolizumab. PATIENTS AND METHODS: Data of 168 patients with metastatic UC who received intravenous pembrolizumab after platinum-based chemotherapy between December 2017 and November 2020 were retrospectively reviewed. Relationships between histological variant type (basal or luminal molecular subtypes) and survival outcome and response to immunotherapy were examined. Clinicopathological factors were analyzed using the Cox proportional hazards model. RESULTS: UC with histological variants was identified in 19 (11.3%) cases (basal subtype in 12; luminal subtype in 7). The median age of the patients was 72.5 years (range=40-89 years). The performance status was 0-1 in 151 (89.9%) patients. Liver metastasis was detected in 44 (26.2%) patients. The median progression-free survival was 3.5 months (range=0.5-34.3 months). Treatment with immune checkpoint inhibitors resulted in an overall mean survival (from the start of treatment) of 8.1 months (range=1.2-34.3 months). Patients with basal-type UC had significantly shorter progression-free survival and cancer-specific survival than those with pure UC (p=0.010 and p=0.035, respectively). A complete response was observed in eight patients (seven with pure UC, one with basal type). CONCLUSION: The basal histological variant might be a potential prognostic indicator in patients with platinum-resistant metastatic UC treated with pembrolizumab.

Two cases of pelvic schwannomas simultaneously resected with the prostate by robot-assisted surgery.

INTRODUCTION: Schwannoma is a rare benign tumor of peripheral nerves arising from Schwann cells of the ubiquitous nerve sheath. The operative steps and technical aspects of robotic resection of pelvic schwannoma are described herein. CASE PRESENTATION: We describe two patients with pelvic tumors simultaneously resected with the prostate by robot-assisted surgery: a 69-year-old man with schwannoma of the right side of the pelvic floor and a 68-year-old man with schwannoma in the left pelvis. As metastasis of prostate cancer could not be ruled out, tumorectomy was performed using robotic-associated prostatectomy. Malignancy was absent in the two pelvic tumors, and the patients were diagnosed with schwannoma. CONCLUSION: For surgery in a narrow deep pelvis, robot-assisted surgery is minimally invasive, offers excellent mobility of robotic instruments and visibility of three-dimensional view, and is a useful approach.

[A PRIMARY BLADDER ALVEOLAR SOFT PART SARCOMA: A CASE REPORT].

A 32-year-old woman was admitted to our department for hematuria and dysuria.Computed tomography (CT) and cystoscopy revealed a 2-cm pedunculated tumor with rich blood supply and a smooth surface in the bladder trigone. We performed a transurethral resection of bladder tumor. The pathologic diagnosis was alveolar soft part sarcoma (ASPS). CT, bone scintigraphy, positron emission tomography, and pelvic magnetic resonance imaging revealed no other lesions; thus, she was diagnosed as having a primary bladder ASPS. Postoperative follow-up with regular cystoscopies and CTs over 10 years have shown no local recurrence or metastasis.Primary ASPS of the bladder is exceedingly rare, and this case is the 8th case (the 2nd case in Japan) reported in literature.

Presence of constipation predicts the therapeutic efficacy of pembrolizumab in metastatic urothelial cancer patients.

OBJECTIVES: To study bowel function in urothelial cancer patients treated with pembrolizumab and to assess its association with treatment efficacy. METHODS: This retrospective study was analyzed for patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment between December 2017 and June 2019 at Nagoya University and affiliated hospitals in Japan. The association between bowel dysfunction (defined as constipation or need for laxatives) and treatment efficacy was investigated. RESULTS: We retrospectively enrolled 73 patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment. All patients received pembrolizumab at 200 mg per bodyweight administered intravenously every 3 weeks. Performance status was 0-1 in 58 patients (79.5%), and liver metastasis was detected in 22 patients (30.1%). The median age was 72 years (range 40-89 years). A total of 45 patients had constipation. The median progression-free survival and overall survival from the start of immune checkpoint inhibitor treatment was 4.0 months (95% confidence interval 1.0-17.3) and 6.6 months (95% confidence interval 1.0-18.0), respectively. Patients with constipation had a significantly higher risk of disease progression (P = 0.005). There was no significant association between constipation and overall survival (P = 0.131). However, complete response was observed among two patients treated with immune checkpoint inhibitor, both of whom did not present constipation. CONCLUSION: The presence of constipation might be a prognostic factor for urothelial cancer patients undergoing immune checkpoint inhibitor treatment.

[ENDOSCOPIC REMOVAL OF INTRAVESICAL RARE FOREIGN BODY USING FLEXIBLE CYSTOSCOPY: A CASE REPORT].

A 50-year-old man was admitted to our hospital for urinary retention. Computed tomography revealed a spherical intravesical foreign body, measuring 1.7cm in diameter, and cystoscopy revealed glass ball in the bladder. Considering the shape of the object and the possibility of self-insertion, we used a flexible cystoscope, foreign body forceps, and a transvaginal echo probe cover to remove the intravesical foreign body. The end of the echo probe cover was grasped with the foreign body forceps, and a glass ball was inserted into the probe cover and extracted manually with a scooping action similar to using a landing net. No intraoperative hemorrhage was observed, and the glass ball was safely removed with good visual field.The patient's postoperative courses was uneventful, and he has shown no recurrence one year postoperatively.

[A CASE OF MALIGNANT PARAGANGLIOMA OF THE URINARY BLADDER TREATED WITH CYCLOPHOSPHAMIDE, VINCRISTINE, AND DACARBAZINE CHEMOTHERAPY AND METAIODOBENZYLGUANIDINE THERAPY].

A 34-year-old man, diagnosed with paraganglioma of the urinary bladder, was referred to our hospital. Computed tomography showed a bladder tumor measuring 64 mm along with right obturator lymphadenopathy. Abnormal uptake was observed on 123I-MIBG scintigraphy. The tumor was, therefore, diagnosed as malignant paraganglioma. We performed cystectomy, pelvic lymph node dissection, and neobladder reconstruction. Pathological examination revealed a malignant paraganglioma of the urinary bladder with right obturator lymph node metastasis. Postoperatively, both the uptake on 123I-MIBG scintigraphy and catecholamine levels in blood and urine normalized. However, 22 months later, positoron emission tomography-computed tomography showed the presence of 2 recurrent tumors in the pelvis. The patient underwent 9 courses of cyclophosphamide, vincristine, and dacarbazine chemotherapy and MIBG radiotherapy twice, following which the tumor size decreased by 35% and catecholamine levels normalized once again. At about 2 years of follow-up, the patient was found to be free of recurrence.

[RENAL ARTERIOVENOUS FISTULA (ANEURYSMAL TYPE) TREATED BY NEPHRECTOMY UNDER BALLOON CATHETER OCCLUSION OF RENAL ARTERY: A CASE REPORT].

A 60-year-old man presented with leg edema and shortness of breath. He was being treated with medication for chronic heart failure for the past 3 years and had been in a traffic accident when he was 13 years old. Computed tomography showed a huge right renal arteriovenous fistula (AVF). The right renal artery measured 16 mm in diameter, the renal aneurysm was observed to be 60 mm, renal vein 87 mm, and the inferior vena cava 60 mm in diameter. His high-output heart failure was attributed to his right renal AVF, for which treatment was deemed necessary. Due to the risk of pulmonary embolism associated with transcatheter arterial embolization, we performed a nephrectomy with temporary interruption of renal blood flow using a balloon catheter. He was observed to be asymptomatic immediately after surgery.

USEFULNESS OF FECAL INCONTINENCE CATHETER (Flexi-Seal®) FOR POSTOPERATIVE MANAGEMENT OF EVACUATION IN FOURNIER'S GANGRENE: TWO CASE REPORTS.

In patients with Fournier's gangrene, massive debridement is necessary. The debrided region is usually near the anus, which means that management of evacuation becomes difficult and a colostomy is often created for diversion of stool. Our two patients were a 72-year-old man with scrotal swelling and disturbance of consciousness and a 65-year-old man with scrotal swelling and fever. In both patients, CT scanning revealed air in the scrotal sac. We diagnosed Fournier's gangrene and operated on both patients immediately. After debridement, we used a fecal incontinence catheter, a Flexi-Seal® to keep the wound clean of stools without creating a colostomy. Both patients recovered without developing wound infection. These cases demonstrate the usefulness of the Flexi-Seal® for management of evacuation in Fournier's gangrene patients after debridement.

COMPARISON LOCALIZATION RESULTS BASED ON PROSTATE BIOPSY SPECIMENS WITH RESULTS BASED ON RADICAL PROSTATECTOMY SPECIMENS IN PROSTATE CANCER.

(Objective) The Clinical Practice Guidelines for Prostate Cancer (2012 Edition) recommend a 10- to 12-core biopsy comprising six standard cores from the apex, midgland, and base as well as cores from six peripheral zones (PZ) outside these sites. In this study, we compared localization results (mapping) based on 12-core prostate biopsy specimens from the six standard sites and six PZ outside these sites with results based on radical prostatectomy specimens. (Subjects and methods) Of the 208 patients with prostate cancer who underwent radical prostatectomy at our hospital between January 2011 and July 2014, the 139 who had a 12-core biopsy before surgery were included in this study. Prostate needle biopsies were performed transrectally and the same pathologist evaluated preoperative biopsy specimens and resected pathology specimens. Patient age ranged from 52 to 77 years (median: 68 years). Prostate-specific antigen levels at the time of biopsy ranged from 3.1 to 84.7 ng/ml (median: 7.3 ng/ml) and the weight of excised tissue ranged from 17 to 90 g (median: 37 g). The surgical method was laparotomy in 63 cases, laparoscopy in 12 cases, and robot-assisted in 64 cases. The preoperative T classification was cT1c in 84 cases, cT2a in 29 cases, cT2b in 15 cases, and cT2c in 11 cases. The preoperative Gleason score was 3+3=6 in 36 cases, 3+4=7 in 48 cases, 4+3=7 in 33 cases, 4+4=8 in 9 cases, 4+5=9 in 11 cases, and 5+4=9 in 2 cases. The postoperative T classification was pT2a in 38 cases, pT2b in 12 cases, pT2c in 17 cases, pT2+in 20 cases, pT3a in 47 cases, and pT3b in 5 cases. The postoperative Gleason score was 3+3=6 in 19 cases, 3+4=7 in 60 cases, 4+3=7 in 39 cases, 4+4=8 in 1 case, 4+5=9 in 14 cases, 5+4=9 in 5 cases, and 5+5=10 in 1 case. (Results) The concordance rate for detection of cancer (localization) in the 12 sites of the preoperative biopsy and the same sites of resected specimens was 59.2% (median: 7.11/12). Furthermore, the Gleason score of the resected specimen was higher than the preoperative score for 79 patients (56.8%) and 63 of the 88 patients (71.6%) whose cancer was classified as unilateral on the basis of the preoperative biopsy were found to have cancer on the other side as well when the resected specimen was examined. (Conclusion) The results suggest that localization is not always consistent between positive biopsy sites and sites in resected specimens. This indicates that when attempting to localize prostate cancer preoperatively, it is necessary to use other tests such as MRI as well.

[Case of multiple lung metastases of renal cell carcinoma failing to respond to Interferon-alpha (IFN-alpha) and sunitinib but markedly responding to everolimus].

The case pertains to a 47-year-old male. He consulted our institute regarding a tumor in his right kidney. Endoscopic retroperitoneal nephrectomy of the right kidney was conducted to remove the tumor. The postoperative pathology was Renal Cell Carcinoma (Clear cell carcinoma, pT1b, pNx, V (+), Fuhrman grade 4). Multiple lung metastases were observed upon CT scan the following year. Sunitinib was administered following Interferon alpha (IFN-alpha) therapy; however, the lung metastases became larger, so administration of everolimus at 10 mg/day was commenced. The lung metastatic lesion became smaller upon CT scan from 6 weeks following administration, and it was determined that the therapeutic effect was PR. The PR was still maintained upon CT scan 31 weeks following administration but the lung metastatic lesion still remained; therefore, right lower lobe resection and lymph node biopsy were conducted upon obtaining informed consent. The administration of everolimus at 10 mg/day is still subsequently being continued due to viable tumor cells being observed in the lung metastatic lesion and the lymph node. At present, 43 weeks have past since the start of everolimus administration, but no new metastatic lesions have been observed.

Alpha methylacyl-CoA racemase (AMACR) in prostate adenocarcinomas from Japanese patients: is AMACR a "race"-dependent marker?

BACKGROUND: Alpha methylacyl-CoA racemase (AMACR) is a useful diagnostic marker for prostate adenocarcinoma. However, its usefulness has not been fully validated in Japanese patients. The aim of this study was to evaluate the diagnostic utility of AMACR in prostate needle biopsy examination in Japanese patients. METHODS: A total of 119 prospective consecutive prostate needle biopsy specimens (680 cores) obtained from Japanese patients were examined. Sixty patients had adenocarcinoma (adenocarcinoma, 160 cores; benign, 204 cores), 14 patients had high-grade prostatic intraepithelial neoplasia (HGPIN; 19 cores), and 45 patients did not have any neoplastic lesions (297 cores). AMACR expression was scored semi-quantitatively as 0 (no expression), 1+ (partial and/or weak expression), or 2+ (strong, circumferential expression). The number of positively stained glands was counted. RESULTS: 2+ AMACR expression was observed in 70.1% of adenocarcinoma cases and in 52.6% of HGPIN cases. Of the adenocarcinoma cases showing 2+ AMACR expression, 34.8% demonstrated a heterogeneous expression pattern, with 1-75% of AMACR-positive glands. Three hundred eighty-five of the benign glands with an adenocarcinoma component showed 2+ AMACR expression (35 cases, 94 cores). 2+ AMACR expression was observed in 67 non-neoplastic benign glands (9 cases, 19 cores). CONCLUSIONS: The sensitivity and specificity of AMACR for the diagnosis of prostate adenocarcinoma and benign glands in Japanese patients are lower than those previously reported in Western countries. Pathologists should be cautious while interpreting AMACR expression pattern in Japanese patients.