A case of renal cell carcinoma with antiphospholipid syndrome treated by robot-assisted partial nephrectomy.

Introduction: Antiphospholipid syndrome is an autoimmune disease that presents with thrombus hyperplasia. Although very rare, this disease is reported to become severe after the surgical invasion and other interventions. To our knowledge, there are no reports of partial nephrectomy in patients with antiphospholipid. Case presentation: A 45-year-old man visited our hospital for treatment of left renal cell carcinoma. He had a history of antiphospholipid syndrome and took two antithrombotic agents. We performed a robot-assisted partial nephrectomy. We selectively ligated only the feeding branch during the procedure. Postoperatively, there were no complications, and the patient was discharged on postoperative day 10. One year after surgery, there was no worsening of antiphospholipid syndrome. Conclusion: We reported the first case of robot-assisted partial nephrectomy for an antiphospholipid syndrome patient. Selective ligation of the renal artery might not have contributed to the severe antiphospholipid syndrome.

Limited predictive impact of tumor size dynamics on further tumor shrinkage after 4 cycles of first-line chemotherapy in patients with advanced urothelial carcinoma.

PURPOSE: To investigate the correlation between tumor size changes during the initial 4 cycles of first-line chemotherapy and tumor shrinkage following 2 additional cycles of chemotherapy in patients with advanced urothelial carcinoma (aUC) who experienced disease control after initial chemotherapy. METHODS: We retrospectively reviewed 128 patients with aUC who received first-line chemotherapy. We analyzed 51 patients with disease control (stable disease or better) at the end of the fourth cycle. Of these, 47 patients received 1 to 2 additional cycles of chemotherapy, whereas the remaining patients underwent observation. For patients who received additional chemotherapy, the change in tumor size after additional chemotherapy (cycles 5-6) was defined as "no shrinkage" (tumor growth), "minor shrinkage" (no tumor growth or ≤10% reduction in tumor size), or "shrinkage" (>10% reduction in tumor size). Then, we investigated the relationship between the rate of tumor size change during the initial 4 cycles and that after additional chemotherapy. RESULTS: Of the patients who received additional chemotherapy, the change in tumor size was categorized as no shrinkage in 21 patients (44.7%), minor shrinkage in 18 patients (38.3%), and shrinkage in 8 patients (17%). Regarding predictors of tumor shrinkage after additional chemotherapy, the rate of tumor size change between the cycles 3 and 4 (area under the receiver operating characteristics curve = 0.642) was correlated with the trend of the tumor shrinkage (P = 0.009) and the likelihood of beneficial tumor shrinkage after additional chemotherapy (minor shrinkage + shrinkage; P = 0.02). However, the change in tumor size between cycles 1 and 2, cycles 1 and 4, or cycles 3 and 4 was not satisfactorily predictive of further tumor shrinkage because of substantial overlaps of the tumor size changes. CONCLUSIONS: Only a small subset of patients would have substantial tumor shrinkage by additional cycles after successful induction of 4 cycle chemotherapy. Tumor size dynamics during the initial 4 cycles of chemotherapy displayed limited ability to predict the subset of patients with further tumor shrinkage after additional chemotherapy. Therefore, it might be better to consider switch maintenance immunotherapy for patients who experience disease control after the fourth cycle of first-line chemotherapy.

Clinical and molecular correlates of response to immune checkpoint blockade in urothelial carcinoma with liver metastasis.

Despite recent advancements in immunotherapy, urothelial carcinoma patients with liver metastasis have a poor response to immune checkpoint inhibitors (ICIs) and short survival durations. Here, we investigated the clinical activity and molecular correlates of resistance to ICI in patients with metastatic urothelial carcinoma (mUC), focusing on liver metastasis. In this study, 755 patients with mUC who received pembrolizumab (JUOG cohort), 144 mUC patients who were treated with atezolizumab (IMvigor210 cohort), and 59 mUC patients who had metastatic samples available were enrolled. The presence of liver metastasis was associated with increased peripheral monocytes and a reduction in lymphocytes when compared with other metastatic sites, and a poor prognosis for ICI therapy. The peripheral monocyte-to-lymphocyte ratio was significantly correlated with the CD163+M2-like tumor-associated macrophage (TAM)/CD8+ tumor-infiltrative lymphocyte (TIL) ratio in the primary and metastatic UC lesions. Exploratory molecular analyses indicated that ICI-resistant status, such as decreased tumor mutation burden, low CD8+ TILs and immune checkpoint signatures, and increased M2-like TAM markers, in primary tumors was correlated with the presence of liver metastasis. In metastatic lesions, the CD163+M2-like TAM/CD8+TIL ratio and expression of cancer-associated fibroblasts induced by the TGFß signaling pathway were higher in the liver versus the lung metastatic tumors. This study indicated that tumor-infiltrating lymphocyte and macrophage status in primary and metastatic lesions, which correlate with peripheral monocyte and lymphocyte status, may predict immunotherapy outcomes in UC patients with liver metastasis.

IFN-Gamma Expression in the Tumor Microenvironment and CD8-Positive Tumor-Infiltrating Lymphocytes as Prognostic Markers in Urothelial Cancer Patients Receiving Pembrolizumab.

Although immune checkpoint inhibitors have shown benefit for advanced urothelial carcinoma (aUC) patients, prognostication of treatment efficacy and response duration remains a clinical challenge. We evaluated the expression of immune markers in the tumor microenvironment and assessed their associations with response to and survival after pembrolizumab treatment in 26 aUC patients. High levels of CD8+ tumor-infiltrating lymphocytes (TILs) were associated with favorable objective responses (23.0% vs. 15.3%, p = 0.0425), progression-free survival (median, 8.8 vs 2.1 months; hazard ratio (HR), 0.24; 95% confidence interval (CI), 0.07-0.66, p = 0.0060), and overall survival (median, >24.0 vs. 5.3 months; HR, 0.17; 95% CI, 0.04-0.56, p = 0.0034) compared with low levels. High interferon-gamma (IFNγ) expression levels were associated with longer post-progression survival (median, 4.9 vs. 1.0 months; HR, 0.18; 95% CI, 0.04-0.59, p = 0.0027) compared with low expression. Multivariate analysis incorporating clinical prognosticators demonstrated that the coincidence of low CD8+ T cells/IFNγ was an independent factor for unfavorable overall survival after pembrolizumab treatment (HR, 4.07; 95% CI, 1.36-12.73; p = 0.0125). The combination of low CD8+ TILs and IFNγ expression was an independent prognostic factor with predictive ability equivalent to previously reported clinical prognosticators.

[A Case of Penile Pyoderma Gangrenosum Treated by Urethrocutaneostomy without Penectomy].

We herein report a case of penile pyoderma gangrenosum that was successfully treated with prednisolone and by urethrocutaneostomy without penectomy. A man in his 50s visite dour department because of painful urination. Pyuria and redness of the external urethral meatus were present. Treatment for urethritis with antibiotics did not improve his symptoms, and a painful ulcer and fistula formation between the glans and urethra subsequently developed. Microbiological cultures revealed no growth, and punch biopsy showed only nonspecific inflammation, leading to a diagnosis of penile pyoderma gangrenosum. We initiated prednisolone (PSL) at 40 mg once daily following placement of an indwelling suprapubic cystostomy tube for dysuria. However, the treatment was ineffective. Therefore, the dosage of PSL was increased to 65 mg once daily. The ulcer disappeared， but urethral stricture remained. Six hundred days after PSL treatment, we performed urethrocutaneostomy. The patient became free of the cystostomy and was able to urinate spontaneously. In recent years, there has been an increasing number of reports of penile preservation in the treatment of penile pyoderma gangrenosum, but knowledge regarding which patients require urethral surgery is lacking. Urologists should keep in mind increased susceptibility to infection, pathergy and possible recurrence, when considering urethral surgery for penile pyoderma gangrenosum.

Antitumor effect of WEE1 blockade as monotherapy or in combination with cisplatin in urothelial cancer.

Overcoming cisplatin (CDDP) resistance is a major issue in urothelial cancer (UC), in which CDDP-based chemotherapy is the first-line treatment. WEE1, a G2 /M checkpoint kinase, confers chemoresistance in response to genotoxic agents. However, the efficacy of WEE1 blockade in UC has not been reported. MK-1775, a WEE1 inhibitor also known as AZD-1775, blocked proliferation of UC cell lines in a dose-dependent manner irrespective of TP53 status. MK-1775 synergized with CDDP to block proliferation, inducing apoptosis and mitotic catastrophe in TP53-mutant UC cells but not in TP53-WT cells. Knocking down TP53 in TP53-WT cells induced synergism of MK-1775 and CDDP. In UMUC3 cell xenografts and two patient-derived xenograft lines with MDM2 overexpression, in which the p53/cell cycle pathway was inactivated, AZD-1775 combined with CDDP suppressed tumor growth inducing both M-phase entry and apoptosis, whereas AZD-1775 alone was as effective as the combination in RT4 cell xenografts. Drug susceptibility assay using an ex vivo cancer tissue-originated spheroid system showed correlations with the in vivo efficacy of AZD-1775 alone or combined with CDDP. We determined the feasibility of the drug susceptibility assay using spheroids established from UC surgical specimens obtained by transurethral resection. In conclusion, WEE1 is a promising therapeutic target in the treatment of UC, and a highly specific small molecule inhibitor is currently in early phase clinical trials for cancer. Differential antitumor efficacy of WEE1 blockade alone or combined with CDDP could exist according to p53/cell cycle pathway activity, which might be predictable using an ex vivo 3D primary culture system.

[Kidney Auto-Transplantation for Intraoperative Right Renal Artery Injury in a Single Kidney Patient : A Case Report].

A man in his 70's who had undergone left radical nephrectomy for kidney cancer had the right renal artery ablated unexpectedly during pancreatoduodenectomy for a huge duodenal tumor. For this intraoperative emergency, an autologous kidney transplantation was performed with the right kidney being removed, perfused, and transplanted into the right iliac fossa. Warm ischemic time was over 2 hours. The patient developed postoperative hemorrhagic infarction of a renal artery branch, which was successfully treated with intravascular intervention. The patient was weaned off hemodialysis and was discharged in 16 weeks postoperatively.

[A Case of Rectum-Infiltrating Prostate Cancer Mimicking Prostate-Infiltrating Rectal Cancer].

A 71-year-old man was admitted to the department of general surgery at our hospital due to constipation. A large bowel endoscopic examination revealed a stenosis of the rectum near the anus. The pathological diagnosis of the biopsy was poorly differentiated adenocarcinoma. After a computed tomography/magnetic resonance imaging examination, rectal cancer infiltrating the prostate was the diagnosis. External beam radiation therapy and chemotherapy were performed. After those neoadjuvant therapies, an abdominoperineal resection of the rectum (Miles) and a retropubic radical prostatectomy were performed. The final pathological diagnosis was prostate cancer infiltrating the rectum. Prostate cancer infiltrating the rectum is rare because of the Denonvillier's fascia barrier. However, it is difficult to distinguish prostate cancer infiltrating the rectum from rectal cancer infiltrating the prostate. Thus, when we see rectal cancer infiltrating the prostate, prostate cancer infiltrating the rectum should be suspected, serum prostate specific antigen (PSA) level should be determined, and PSA immunostaining should be performed.

[Two Cases of Metastatic and Recurrent Non-Clear Cell Renal Cell Carcinoma Re-Diagnosed as Renal Mucinous Tubular and Spindle Cell Carcinoma during Long-Term Follow-Up].

Renal mucinous tubular and spindle cell carcinoma (MTSCC) is a rare, low-grade renal epithelial neoplasm. MTSCC has a lower malignant potential and shows relatively good prognosis, but can be difficult to distinguish from other renal cell carcinoma (RCC) subtypes. Here, we report two cases of metastatic and recurrent renal MTSCC diagnosed after long-term follow-up. Case 1 was a 79-year-old man with a history of macroscopic hematuria in whom a right kidney mass was detected and diagnosed as RCC (cT3bN0M0). After a radical nephrectomy, microscopic findings showed that the tumor consisted of spindle cells arranged in tubular patterns embedded in sarcomatoid tissues ; we diagnosed it as unclassified RCC with sarcomatoid differentiations (pT3aN0M0). Thereafter, metastases were twice detected and resected completely. The patient had no evidence of disease at his most recent follow-up, 10 years 1 month after the initial surgery. Case 2 was in a 72-year-old man in whom a right kidney mass, swollen lymph nodes, and a lung node were incidentally detected. This tumor was diagnosed as RCC (cT4N2M1), and radical nephrectomy and lymph node dissections were carried out. From the microscopic findings, we diagnosed papillary RCC type-2 (pT3aN2M1). After the surgery, pleural and bone metastases was detected. Despite sequential treatments with IFN-α and sunitinib, the patient suffered indolent-growing metastases and died at 5 years 6 months after operation. As these patients had relatively good prognoses despite assumed aggressive RCC subtypes, we reviewed their pathological findings. In both cases, tumor samples showed tubules lined by short cuboidal cells that were set within myxoid stromata and spindle cells ; we finally diagnosed these cases as renal MTSCC.

360-degree screen-free floating 3D image in a crystal ball using a spatially imaged iris and rotational multiview DFD technologies.

A rotational multiview depth-fused 3D (DFD) display and 360-deg displaying optics using a spatially imaged iris method are proposed to realize a 360-deg 3D image. This method enables displaying clear floating images in a crystal ball. Its symmetric optics provide clear and natural 360-deg images with smooth motion parallax in horizontal and vertical directions using the directional selectivity of a spatially imaged iris method and natural 3D images of a rotational multiview DFD display.

[Simultaneous Hepatorenal Transplantation from a Brain-Dead Donor for Graft Dysfunction and Renal Insufficiency in a Liver Transplant Recipient : A Case Report].

We report a case of lethal hepatorenal insufficiency in a 52-year-old man who received successful simultaneous hepatorenal transplantation from a deceased donor. The patient had undergone live-donor liver transplantation for type-C hepatitis and liver cirrhosis 11 years before he developed graft liver dysfunction due to recurrent viral hepatitis and cirrhosis. At that instance, he also developed end-stage renal dysfunction due to calcineurin inhibitor nephropathy and hepatorenal syndrome. Although he needed three open hemostases and abundant blood transfusion, he was withdrawn from continuous hemodiafiltration on the 55th day and discharged from the hospital on the 272nd day postoperatively. Simultaneous hepatorenal transplantation was reported to be associated with more favorable outcomes of graft function, lower rejection rates, but higher perioperative complication rates compared with liver transplantation alone in patients on hemodialysis. Particularly, close attention should be paid for hemostasis since patients have a hemorrhagic tendency until the recovery of graft liver function.

A 45,X/46,XY Male with Orchidopexy Diagnosed with Mixed Germ Cell Tumor After 21-year Follow-up.

A case of a 45,X/46,XY boy with gonadal dysgenesis is presented. The patient showed hypospadias and right undescended testis. He underwent underwent repair surgery for hypospadias, right orchidopexy, and bilateral testicular biopsy. Testicular biopsy revealed no malignant finding. He was followed-up annually by scrotum palpation. When the patient grew up to 24 years old, he was diagnosed to have right testicular tumor. High orchiectomy revealed pT1 seminoma. The management of undescended testis in men with gonadal dysgenesis and disordered sexual development is discussed.

[A Case of Thyroid-Like Follicular Carcinoma of the Kidney].

A 51-year-oldwoman with a right renal mass was referredto our hospital. Computedtomographic (CT) scan demonstrated a 30 mm-diameter renal mass with delayed enhancement. She underwent a robotassistedlaparoscopic right partial nephrectomy. The pathological examination showedthat tumor cells with eosinophilic, clear cytoplasm formedtubules of various sizes containing colloid-like material, which resembled the findings of thyroidfollicular carcinoma. The tumor was immunoreactive for vimentin andcytokeratin (CK) 7, whereas it lackedreactivity for thyroidtranscription factor-1 (TTF-1) or thyroglobulin. No tumors were detectedin the thyroidglandor other organs of the patient. Subsequently, the diagnosis of thyroidlike follicular carcinoma of the kidney (TLFCK) was determined. At 4 months postoperatively, the patient is alive with no evidence of disease recurrence. TLFCK is an extremely rare subtype of renal cancer, and only 26 cases have been reportedpreviously. We provide a brief literature review on this cancer.

[A Case of Hemodialysis-Associated Pelvic Amyloidoma Mimicking Renal Cancer-Associated Etiology].

Patients with renal insufficiency receiving long-term hemodialysis often develop so-called hemodialysis amyloidosis characterized by systemic ß 2-microglobulin amyloid lesions, while patients with renal cell carcinoma may develop amyloid A(AA) amyloidosis. Herein, we present a 67-year-old man on thirty-yearlong hemodialysis who was diagnosed to have left renal cell carcinoma coincident with a large spaceoccupying lesion adjacent to the psoas muscle in the pelvic cavity. An ultrasound-guided percutaneous needle biopsy was performed at the time of laparoscopic radical nephrectomy. The pathological work-up on the needle biopsy specimen revealed that the lesion was not an AA amyloidoma but a ß2-microglobulin amyloidoma, which is a rare manifestation of hemodialysis amyloidosis.

[Spontaneous Infection of an Atrophic Ureter with an Ectopic Ureteral Opening after Living-Donor Renal Transplantation in a Patient with Kabuki Syndrome].

A 24-year-old woman with a high fever presented at our hospital. She had been diagnosed with Kabuki syndrome at the age of 4 years because she had the typical facial features of the condition ; she had undergone living donor renal transplantation 12 years prior. She was prescribed a course of antibiotics to treat pyelonephritis of the transplanted kidney and the high fever disappeared, but the fever developed again 3 days after the discharge. Abdominal computed tomography revealed a tubular structure of recent onset running from the left dorsal side to the lower part of the bladder. This structure was filled with pus, which we drained. We also performed laparoscopic ureterectomy of the left ureter to achieve a complete cure. No complication was observed after the surgery and the graft renal function did not deteriorate further.

[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.

Catheter-related fungemia due to fluconazole-resistant Candida nivariensis.

We report on a case of fungemia due to fluconazole-resistant Candida nivariensis (MIC, > or =128 microg/ml). Internal transcribed spacer PCR followed by microchip gel electrophoresis with a blood culture that tested positive revealed a unique pattern different from those of other pathogenic yeasts.

Neuroprotection and enhanced recovery with edaravone after acute spinal cord injury in rats.

STUDY DESIGN: The effect of edaravone, a novel free radical scavenger, was assessed functionally and histologically using a rat spinal cord contusion model. OBJECTIVE: To investigate the effect of edaravone on neuroprotection after spinal cord injury in rats. SUMMARY OF BACKGROUND DATA: The spinal cord injury results in immediate physical damage (primary injury), followed by a prolonged neural tissue disorder (secondary injury). This secondary injury process has been suggested to be induced by lipid peroxidation. Edaravone has been reported to inhibit lipid peroxidation in cerebral ischemia models. METHODS: Spinal cord injury at the T10 level was induced with a weight drop device (10 g weight, 25 mm height). Edaravone was administered intravenously as a bolus dose of 5 mg/kg at 5 minutes, 24 hours, and 48 hours after injury (edaravone-treated rats). In control rats, nothing was administered. Functional assessment was conducted weekly using the Basso-Beattie-Bresnahan locomotor rating scores. Histologically, a percentage of spared white matter area was calculated. The effects of intravenous administration of edaravone on lipid peroxide formation in rat spinal cord homogenate were examined using the thiobarbituric acid test for malonyldialdehyde production. RESULTS: Six weeks after injury, edaravone-treated rats showed significantly higher motor score and larger spared white matter area than control rats. The administration of edaravone attenuated malonyldialdehyde production in spinal cord homogenate by >45%. CONCLUSION: Edaravone enhanced functional recovery and preserved more spinal cord tissue after spinal cord injury in rats. The attenuation of posttraumatic lipid peroxide formation by edaravone partially contributed to this enhancement.

Luminance addition of a stack of multidomain liquid-crystal displays and capability for depth-fused three-dimensional display application.

A stack of liquid-crystal displays is expected to reduce visual fatigue caused by a flat-panel three-dimensional (3D) display. We previously developed a compact depth-fused 3D (DFD) display by using a stack of two twisted-nematic (liquid-crystal) LC panels, but its viewing-angle characteristics and color reproducibility were not so good. Therefore recent wide-view LC panels should be used. We report calculated and measured luminance addition characteristics, which are essential for evaluating 3D display characteristics, of a stack of two multidomain LC panels. We found that LC panels with super in-plane switching, patterned vertical alignment, multiple vertical alignment, and continuous pinwheel alignment modes are suitable for DFD display application.

Apparent 3-D image perceived from luminance-modulated two 2-D images displayed at different depths.

An apparent 3-D image can be perceived from only two 2-D images displayed at different depths, when an observer views them from the direction in which they are overlapped. The two 2-D images are created from an original 2-D image by dividing its luminance according to independently obtained depth information. Subjective test results show that (1) an apparent 3-D image is perceived and (2) the perceived depth continuously varies according to the change in luminance ratio between the two 2-D images.