[Robot-Assisted Laparoscopic Radical Prostatectomy in a Short-Statured Man : A Case Report].

A 72-year-old man, who was extremely short-statured, underwent robot-assisted laparoscopic prostatectomy (RARP) for treatment of localized prostate cancer (cT1cNOMO). We report a case of congenital vertebral tip dysplasia with type II collagen dysplasia in a patient who underwent robot-assisted radical prostatectomy. Congenital vertebral tip dysplasia is characterized by short stature, and in this case, the height was 130 cm, which was equivalent to that of an 8-year-old child. The pelvic floor is narrow in short-statured individuals; therefore, the operative time tends to be longer than that required for routine surgery. However, using modifications in port positions and other adjustments, we performed RARP, and our perioperative results were similar to those obtained with routine RARPs.

[Case of Robot-Assisted Low Anterior Resection with Total Cystectomy for Rectal Cancer Invading the Urinary Bladder/Prostate in Collaboration with Urologists].

We present a case of a 72-year-old man diagnosed with rectal cancer invading the urinary bladder/prostate. Preoperative chemoradiotherapy substantially reduced the tumor size. In collaboration with urologists, robot-assisted low anterior resection with total cystectomy was performed using the da Vinci Xi system. Depending on the surgical situation, the colorectal surgeon and urologist could smoothly and rapidly play the role of a console surgeon. Although the first robot-assisted multi-organ resection of our institution, the surgery was completed safely without any complications. Although the patient developed urinary tract infection postoperatively, he recovered and was discharged after postoperative 23 days. In conclusion, robot-assisted surgery would be useful in pelvic surgery involving multiple departments such as colorectal surgery, urology, and gynecology.

FAN score comprising fibrosis-4 index, albumin-bilirubin score and neutrophil-lymphocyte ratio is a prognostic marker of urothelial carcinoma patients treated with pembrolizumab.

It is important to identify prognostic and predictive markers of metastatic urothelial carcinoma (mUC) treated with immunocheckpoint inhibitors. We sought to establish a prognostic marker for patients with mUC treated with pembrolizumab based on only blood test results. We included 165 patients with mUC in the discovery cohort and 103 with mUC who were treated with pembrolizumab in the validation cohort. Multivariate and Cox regression analyses were used to analyse the data. In the discovery cohort, the fibrosis-4 index (hazard ratio [HR]: 2.13, 95% confidence interval [CI] 1.20-3.76, p = 0.010), albumin-bilirubin score (HR 1.91, 95% CI 1.27-2.88, p = 0.002), and neutrophil-lymphocyte ratio (HR: 1.84, 95% CI 1.22-2.79, p = 0.004) were independent significant prognostic factors. We established a 'FAN score' that included these three aforementioned items, which were assigned one point each. We divided patients into the 0-1 point (n = 116) and 2-3 points (n = 49) groups. The FAN score was a significant prognostic marker for cancer-specific survival (CSS) (HR 1.48, 95% CI 1.19-1.83, p < 0.001) along with the Eastern Cooperative Oncology Group Performance Status. The FAN score was also a prognostic factor of progression-free survival (PFS) (HR: 1.25, 95% CI 1.01-1.54, p = 0.036) along with the presence of liver metastasis. In the validation cohort, the FAN score was a significant prognostic factor for CSS (HR: 1.48, 95% CI 1.19-1.85, p = 0.001) and PFS (HR: 1.29, 95% CI 1.02-1.62, p = 0.034). We established the FAN score as a prognostic marker for patients with mUC treated with pembrolizumab.

Case Report of Atypical Juxtaglomerular Cell Tumor.

Juxtaglomerular cell tumor (JGCT) is a rare renal tumor, producing renin and behaving almost in a benign fashion. So far, only three cases have been reported as malignant. We report a rare case with atypical JGCT. A 74-year-old male was referred to our hospital due to hypertension, proteinuria, and hematuria. Abdominal CT revealed a mass measured in 9.7×7.0 cm in the lower portion of the right kidney. Right kidney was removed laparoscopically. Grossly, white to tan tumor with massive hemorrhage and necrosis occupied the lower portion of the right kidney. Microscopically, tumor grew in a solid fashion. Tumor cells were polygonal to ovoid cells with round nuclei and clear to eosinophilic cytoplasm. Mitosis was found in 5 per 10 HPF. Immunohistochemically, tumor cells were stained by vimentin and CD34. Some tumor cells were also positive for renin. Electron micrograph showed near rhomboid crystalline structure in the tumor cells. Because of massive necrosis and mitotic figures, diagnosis of atypical (potentially malignant) JGCT was rendered. Gene mutations for IDH1, PIK3CA, K-ras, N-ras, Braf, and EGFR were not found by MBP-QP system.

[Urachal Actinomycosis : A Case Report].

The patient was a 66-year-old woman who was examined by a local physician for the chief complaint of a mass palpable in the left lower abdomen. Abdominal plain computed tomography (CT) indicated a subcutaneous mass extending continuously from the apex of the bladder to the retropubic space, and she was referred to our medical department. Tumor markers were normal, and cystoscopic examination indicated no clear findings. Abdominal contrast-enhanced CT and plain abdominal magnetic resonance imaging results led to suspicion of actinomycosis. An open biopsy was performed on the subcutaneous mass, and subsequent histopathological testing led to a definitive diagnosis of actinomycosis. After 2 weeks of antibiotic therapy, the mass had diminished on CT. There has been no relapse approximately 24 weeks after discontinuation of the antibiotic therapy.

[A Case of Epithelioid Angiomyolipoma of the Kidney with Tumor Thrombus Extending into the Renal Vein : Case Report].

A 31-year-old man was referred to our hospital for macroscopic hematuria. An abdominal computed tomography (CT) scan showed a 36×30 mm enhancing left renal tumor with tumor thrombus extending into the left renal vein. Therefore,we diagnosed the tumor as a clinically classified cT3aN0M0 left renal cell carcinoma. Retroperitoneal laparoscopic radical left nephrectomy with renal vein thrombectomy was performed,with removal of the left kidney with the mass and tumor thrombus en bloc. The pathological diagnosis was epithelioid angiomyolipoma (EAML) of the left kidney. EAML is a rare tumor with malignant potential. In this case,although no signs of recurrence or metastasis have been observed for 9 months post-operation,we recommended a careful follow-up regimen.

[Metastasis to the Tongue from Renal Cell Carcinoma 10 Years after Nephrectomy : A Case Report].

A 71-year-old woman underwent left radical nephrectomy for renal cell carcinoma (clear cell carcinoma, pT1bN0M0) ten years previously. She noticed a tumor on the tip of her tongue and was admitted for dental and oral surgery. The tumor was about 10 mm in size, and tumor resection was done. It was pathologically diagnosed as clear cell carcinoma, which was metastasis of renal cell carcinoma. Computer tomography scan during the same period revealed left hilar lymph node and bilateral lung metastases. We chose to use sunitinib as the treatment for the metastases. Computer tomography revealed a complete response (CR) after sunitinib treatment was given for 10 months, and we are still continuing the treatment to maintain the CR status.

[A Case of Arteriovenous Malformation Located in Retroperitoneum].

A 67-year-old woman was referred to our hospital for precise examination and treatment as an abdominal computed tomographic (CT) scan showed a retroperitoneal tumor located below the hilus of the right kidney. The enhanced CT and magnetic resonance imaging (MRI) revealed contrast enhancement in both early and late phase, which confirmed that the tumor showed abundant blood perfusion and adhered to the duodenum. We performed open surgery in order to remove the tumor and make a precise diagnosis. The tumor was excised en bloc with a part of the gonadal vein because the right gonadal vein was adjacent to the tumor in the craniocaudal direction. The pathological diagnosis was arteriovenous malformation. Arteriovenous malformation located in the retroperitoneum is very rare.

Multi-institutional retrospective analysis of learning curves on dosimetry and operation time before and after introduction of intraoperatively built custom-linked seeds in prostate brachytherapy.

This multi-institutional retrospective analysis examined learning curves for dosimetric parameters and operation time after introduction of intraoperatively built custom-linked (IBCL) seeds. Data from consecutive patients treated with seed implantation before and after introduction of IBCL seeds (loose seed, n = 428; IBCL seed, n = 426) were collected from 13 centers. Dose-volume histogram parameters, operation times, and seed migration rates were compared before and after introduction of IBCL seeds. At the 1-month CT analysis, no significant differences were seen in dose to 90% of prostate volume between before and after IBCL seed introduction. No learning curve for dosimetry was seen. Prostate and rectal volume receiving at least 150% of prescription dose (V150 and RV150) were higher in the loose-seed group than in the IBCL-seed group. Operation time was extended by up to 10 min when IBCL seeds were used, although there was a short learning curve of about five patients. The percentage of patients with seed migration in the IBCL-seed group was one-tenth that in the loose-seed group. Our study revealed no dosimetric demerits, no learning curve for dosimetry, and a slightly extended operation time for IBCL seeds. A significant reduction in the rate of seed migration was identified in the IBCL-seed group.

Microvessel area of immature vessels is a prognostic factor in renal cell carcinoma.

OBJECTIVES: To analyze the presence of immature vessels as a predictive factor of prognosis in patients with renal cell carcinoma. METHODS: Tissue samples were obtained from 50 renal cell carcinoma patients who underwent radical nephrectomy, and the blood vessels were stained using antibodies to cluster of differentiation 34 and α-smooth muscle actin. Immature vessels were defined as those positive for cluster of differentiation 34, and mature vessels as those positive for both cluster of differentiation 34 and α-smooth muscle actin. The extent of vascularization was quantified by calculating the microvessel area and microvessel density. RESULTS: The microvessel area of immature vessels was positively associated with tumor grade (P < 0.0001), T stage (P < 0.0001) and American Joint Committee on Cancer stage (P < 0.0001), and was significantly higher in tumors with metastasis than in those without metastasis (P < 0.0001). The microvessel density did not associate with tumor grade or T stage. The disease-free survival and overall survival were significantly shorter in patients with high microvessel area. CONCLUSIONS: The microvessel area of immature vessels seems to be associated with renal cell carcinoma aggressiveness, suggesting this might be considered as a novel prognostic factor in patients with these tumors.

White blood cell count is positively associated with benign prostatic hyperplasia.

OBJECTIVES: To determine whether low-grade systemic inflammation is associated with prostatic enlargement/benign prostatic hyperplasia. METHODS: Prostate volume was measured by transrectal ultrasonography in 576 Japanese men. The association between prostate volume and routine clinical inflammatory markers (C-reactive protein level, white blood cell count, or the differential white cell count [neutrophils, lymphocytes, basophils, eosinophils, and monocytes]) were analyzed. Contributors to prostate volume were identified in univariate and multivariable linear regression models. RESULTS: Prostate volume was found to have a positive association with serum prostate-specific antigen level (P < 0.001), white blood cell count (P = 0.027) and absolute neutrophil count (P = 0.010). In univariate linear regression models, a large prostate volume was associated with older age, higher prostate-specific antigen, and higher white blood cell and neutrophil counts. A multivariable model adjusted for age, prostate-specific antigen, and C-reactive protein showed that the white blood cell count and the neutrophil count were independently associated with prostate volume. An increased white blood cell count was also associated with higher total International Prostatic Symptom Scores (P < 0.001). CONCLUSIONS: White blood cell count seems to be associated with the degree of prostate enlargement and lower urinary tract symptoms. Chronic low-grade systemic inflammation might be involved in the etiology of benign prostatic hyperplasia.

Weekly, low-dose docetaxel combined with estramustine for Japanese castration-resistant prostate cancer: its efficacy and safety profile compared with tri-weekly standard-dose treatment.

BACKGROUND: We retrospectively investigated the efficacy and safety profile of weekly low-dose docetaxel (DTX) with estramustine in comparison with triweekly standard-dose DTX treatment for Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: Between April 2002 and January 2011, 75 CRPC patients were treated with triweekly DTX (60-75 mg/m(2) every 3 weeks) (standard-dose group), and 76 CRPC patients were treated with weekly low-dose DTX (20-30 mg/m(2) on days 2 and 9 with estramustine 560 mg on days 1-3 and 8-10) every 3 weeks (low-dose group). Prostate-specific antigen (PSA) response and progression-free and overall survival were analyzed in each group. RESULTS: Median serum PSA level of the standard-dose group and low-dose group was 25.0 and 35.5 ng/ml, respectively. In the standard-dose and low-dose groups, 57.8 and 65.2 % of patients, respectively, achieved a PSA decline ≥ 50 %. There was no significant difference in either median time to progression between the standard-dose group (10.0 months) and low-dose group (7.1 months) or in median duration of survival between the standard-dose group (24.2 months) and low-dose group (30.6 months). Multivariate analysis with a Cox proportional hazards regression model showed that DTX treatment protocol did not influence the risk of death. Incidences of grade 3-4 neutropenia, febrile neutropenia, and thrombocytopenia were significantly higher in the standard-dose versus low-dose group (58.7 vs. 7.9 %, 16.0 vs. 3.9 %, and 8.0 vs. 0 %, respectively). CONCLUSION: For Japanese CRPC patients, weekly low-dose DTX combined with estramustine has similar efficacy to standard-dose DTX but with fewer adverse events.

[Subclinical Cushing's syndrome with primary aldosteronism with the developing symptom of complications : a case report].

A 42-year-old female patient had been receiving medication for hypertension. Her symptoms worsened in 2007. A computed tomography image revealed a 2.5 cm round mass in the right adrenal gland. According to a careful examination, the patient was diagnosed with primary aldosteronism and subclinical Cushing's syndrome. There were no remarkable physical features related to Cushing's syndrome. The patient chose a medical therapy instead of surgery. In 2012, regardless of strict diet therapy, however, the patient gained 10 kg weight in a year. The diagnosis was the same as that determined in 2007, except for exceeding value of cortisol over the criterion for Cushing's syndrome. A laparoscopic right adrenalectomy was performed to attenuate Cushing's syndrome. The histopathological examination revealed an adrenocortical adenoma. The patient lost 4.5 kg of weight 2 months after the surgery.

[Renal neuroendocrine tumor (carcinoid) : a case report].

A 32-year-old man was referred to our hospital for treatment of left renal cystic tumor, which was detected by computed tomographic (CT) scan 3 years ago. CT scan showed a multilocular cyst (5 cm in diameter) with a solid tumor in the left kidney which was enhanced with contrast. There was no evidence of extrarenal invasion or distant metastasis. We performed retroperitoneal laparoscopic radical nephrectomy. Pathological examinations revealed a cellular arrangement specific to carcinoid tumor and positive for CD56 (NCAM) and neuron-specific enolase. The cell proliferation rate was estimated to be under 2% with Ki67 staining. The pathological diagnosis was renal neuroendocrine tumor (carcinoid). At the 9-month follow up, he had no evidence of local recurrence or metastasis.

EMMPRIN promotes angiogenesis, proliferation, invasion and resistance to sunitinib in renal cell carcinoma, and its level predicts patient outcome.

PURPOSE: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to play crucial roles, including in angiogenesis, in several carcinomas. However, the correlation between EMMPRIN levels and angiogenesis expression profile has not been reported, and the role of EMMPRIN in renal cell carcinoma (RCC) is unclear. In the present study, we evaluated the association of EMMPRIN with angiogenesis, its value in prognosis, and its roles in RCC. EXPERIMENTAL DESIGN: EMMPRIN expression was examined in 50 RCC patients treated with radical nephrectomy. Angiogenesis, proliferation, and invasion activity were evaluated using EMMPRIN knockdown RCC cell lines. The size of EMMPRIN-overexpressing xenografts was measured and the degree of angiogenesis was quantified. EMMPRIN expression was evaluated in RCC patients who received sunitinib therapy and in sunitinib-resistant cells. Further, the relation between EMMPRIN expression and sensitivity to sunitinib was examined. RESULTS: EMMPRIN score was significantly associated with clinicopathological parameters in RCC patients, as well as being significantly correlated with microvessel area (MVA) in immature vessels and with prognosis. Down-regulation of EMMPRIN by siRNA led to decreased VEGF and bFGF expression, cell proliferation, and invasive potential. EMMPRIN over-expressing xenografts showed accelerated growth and MVA of immature vessels. EMMPRIN expression was significantly increased in patients who received sunitinib therapy as well as in sunitinib-resistant 786-O cells (786-suni). EMMPRIN-overexpressing RCC cells were resistant to sunitinib. CONCLUSION: Our findings indicate that high expression of EMMPRIN in RCC plays important roles in tumor progression and sunitinib resistance. Therefore, EMMPRIN could be a novel target for the treatment of RCC.

Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer.

BACKGROUND: A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). METHODS: Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. RESULTS: The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. CONCLUSIONS: The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.

Impact of hyponatremia on survival of patients with metastatic renal cell carcinoma treated with molecular targeted therapy.

OBJECTIVES: Hyponatremia is reported to be associated with poor survival in localized renal cell carcinoma and metastatic renal cell carcinoma treated with immunotherapy. However, there are no reports on the relationship between hyponatremia and prognosis of metastatic renal cell carcinoma treated with molecular targeted therapy. We evaluated the prognostic significance of hyponatremia in metastatic renal cell carcinoma treated with molecular targeted therapy as first-line therapy. METHODS: We retrospectively analyzed a database comprising 87 patients treated from April 2008 to July 2011 with sorafenib or sunitinib as first-line therapy for metastatic renal cell carcinoma. Patients were divided into three groups according to serum sodium level: severe hyponatremia (≤134 mEq/L), mild hyponatremia (135-137 mEq/L) and normal natremia (≥138 mEq/L). RESULTS: Median cancer-specific survival time was 8.8 months in the patients with severe and mild hyponatremia, and 32.6 months in the patients with normal natremia (P < 0.001). Multivariate analysis showed severe and mild hyponatremia to be significantly associated with cancer-specific survival (hazard ratio 6.228; 95% confidence interval 2.161-17.947, P = 0.001; hazard ratio 3.374; 95% confidence interval 1.294-8.798, P = 0.013), respectively. Neutrophilia and high C-reactive protein level (C-reactive protein ≥1.0 mg/dL) were significant prognostic factors to predict inferior cancer-specific survival. In Harrell's concordance index calculation, hyponatremia could significantly improve the predictive accuracy for estimation of survival probability (P = 0.028). CONCLUSIONS: Hyponatremia (<138 mEq/L), neutrophilia and high C-reactive protein levels seem to represent significant predictive factors for cancer-specific survival in metastatic renal cell carcinoma patients treated with molecular targeted therapy as first line therapy. Furthermore, hyponatremia might be significantly associated with chronic inflammation and tumor aggressiveness.

Co-expression of ERCC1 and Snail is a prognostic but not predictive factor of cisplatin-based neoadjuvant chemotherapy for bladder cancer.

Neoadjuvant chemotherapy (NC) for bladder cancer has been reported to significantly improve the 5-year survival rate. The aim of the present study was to examine the roles of ERCC1 and Snail in determining the response to chemotherapy in bladder cancer treated with NC and radical cystectomy (RC). The expression of the Snail and ERCC1 proteins was determined by immunohistochemical staining of specimens obtained from 58 patients with bladder tumors treated with NC and RC. The correlation between clinical response and the expression of Snail and ERCC1 was investigated. Snail and ERCC1 were co-expressed in 24 (41.4%) of the 58 patients. A marked correlation was found between the expression of Snail and ERCC1 (P=0.001). The co-expression of Snail and ERCC1 was not able to predict pathological complete response (P=0.202). Results of the univariate analysis revealed that the co-expression of Snail and ERCC1 predicted shorter disease-free survival (DFS) and overall survival (OS) than the negative expression of Snail and/or ERCC1. Moreover, the co-expression of ERCC1 and Snail was the only predictive factor for both DFS (P=0.029) and OS (P=0.040). The expression of Snail was correlated with that of ERCC1 and the co-expression of Snail and ERCC1 was the only significant predictive factor of shorter DFS and OS in patients with bladder cancer treated with NC and RC.

Importance of continuing therapy and maintaining one-month relative dose intensity in sunitinib therapy for metastatic renal cell carcinoma.

Sunitinib is a multikinase inhibitor used as first- and second-line treatment of metastatic renal cell carcinoma. However, there are few reports on the necessary doses of sunitinib to get better clinical outcome in general practice with Japanese patients. We examined the relationship between the efficacy and the necessary doses of sunitinib therapy in a multi-institutional retrospective study. A study population of 94 metastatic renal cell carcinoma patients was eligible for this investigation. The most frequent grade 3/4 laboratory adverse events were decreased platelet (31.9 %) and white blood cell (21.3 %) counts. Treatment was discontinued in 18 patients (31.0 %) initially receiving a 50-mg/day dose within only one course, and median 1-month relative dose intensity was 74.3 %. Median progression-free survival time was 2.3 months in patients treated for only one course and 10.8 months in patients treated for more than one course (P < 0.001). Multivariate analysis showed that only one course of treatment and 60 % and less of 1-month relative dose intensity were significantly associated with inferior progression-free survival (P < 0.001 and P = 0.027, respectively). Moreover, modified Memorial Sloan-Kettering Cancer Center poor risk was significantly associated with progression-free survival time. It is difficult for Japanese patients to continue an initial dose of sunitinib therapy without drug withdrawal. Continuing therapy for more than one course and maintaining more than 60 % of 1-month relative dose intensity were very important in the prolongation of progression-free survival time regardless of the initial treatment doses.

Solitary skin metastasis adjacent to ureterocutaneostomy 4 years after radical cystectomy for bladder cancer.

A 65-year-old Japanese woman underwent radical cystectomy and right nephroureterectomy for muscle-invasive bladder cancer. A left ureterocutaneostomy was constructed for urinary diversion. There was no evidence of recurrence for 4 years after the surgery. At 54 months after the surgery, however, she was referred with a chief complaint of painless skin erosion around the stoma. An incisional biopsy of the lesion showed no evidence of malignancy. Thereafter, the lesion was treated as a benign skin erosion. However, the erosion expanded over the next 4 months, and a second incisional biopsy revealed that the erosion was overlying malignant cells. Computed tomography showed a skin tumor of 4 cm in diameter. No other metastases were revealed on whole-body imaging examinations. Urine cytology was negative. A skin tumor extirpation was performed, and the specimen showed that the skin tumor consisted of malignant growth of papillary cells adjacent to the ureter, which were identical to those of the primary bladder cancer. A malignant component was not observed in the lumen of the resected ureter. No evidence of disease was observed in the first 3 months after extirpation. Reports of solitary skin metastasis from bladder cancer are rare, and only a few cases have been reported in the English literature. Because skin metastasis from bladder cancer can mimic a number of different benign conditions, a high index of suspicion may be necessary to make a definitive diagnosis.