[A Case of Proliferative Cystitis Discovered as Protruding Lesion during Inspection of Secondary Infertility].

A 42-year-old man visited our hospital complaining of secondary infertility. An abdominal ultrasonography screening incidentally revealed a protruding lesion in the bladder. As the lesion extended from the prostatic urethra and bladder neck, there was a possibility of ejaculation dysfunction after resection of the lesion. Therefore, with the patient's informed consent, sperm cryopreservation was conducted for fertility preservation, and subsequently histological examination was performed by partial transurethral resection of bladder tumor. The pathological findings were proliferative cystitis including all three subtypes (glandularis, cystica, and papillary). Cyclooxygenase-2 immunostaining was positive in cytoplasm; weakly positive in cystic and papillary lesions, and strongly positive in glandular lesions. According to a literature review of massive proliferative cystitis, the patient was the 77th case in Japan. Novel postoperative immunological pharmacotherapies with cyclooxygenase-2 inhibitors have been introduced in recent years.

Short-term prognosis of low-risk prostate cancer patients is favorable despite the presence of pathological prognostic factors: a retrospective study.

BACKGROUND: Prostate cancer patients with pathological prognostic factors have a poor prognosis, but it is unclear whether pathological prognostic factors are associated with prognosis limited to low-risk patients with good prognosis according to NCCN guidelines. The present study examined whether prognosis is influenced by pathological prognostic factors using radical prostatectomy (RP) specimens from low-risk patients. METHODS: We evaluated diagnostic accuracy by examining biochemical recurrence (BCR)-free survival with respect to clinical and pathological prognostic factors in 419 all-risk patients who underwent RP. Clinical prognostic factors included age, prostate-specific antigen (PSA) levels, PSA density, and risk stratification, while pathological prognostic factors included grade group, lymphovascular space invasion, extraprostatic extension, surgical margins, seminal vesicle invasion, intraductal carcinoma of the prostate (IDCP), and pT. In a subsequent analysis restricted to 104 low-risk patients, survival curves were estimated for pathological prognostic factors using the Kaplan-Meier method and compared using log-rank and generalized Wilcoxon tests. RESULTS: In the overall risk analysis, the presence of pathological prognostic factors significantly shortened BCR-free survival (p < 0.05). Univariable analysis revealed that PSA density, risk categories, and pathological prognostic factors were significantly associated with BCR-free survival, although age and PSA were not. In multivariable analysis, age, risk categories, grade group, IDCP, and pT significantly predicted BCR-free survival (p < 0.05). Conversely, no statistically significant differences were found for any pathological prognostic factors in low-risk patients. CONCLUSIONS: In low-risk patients, pathological prognostic factors did not affect BCR-free survival, which suggests that additional treatment may be unnecessary even if pathological prognostic factors are observed in low-risk patients with RP.

[Idiopathic Thrombocytopenia Purpura After Pembrolizumab Treatment Against Locally Recurrent Bladder Cancer : A Case Report].

A man in his 70s visited our hospital for gross hematuria. He was diagnosed with invasive urothelial carcinoma (cT3N2M0) and underwent total cystectomy and ileum conduit construction after three courses of neoadjuvant chemotherapy. Eight months after the operation, the disease reoccurred in the pelvic lesion. He received pembrolizumab therapy but developed idiopathic thrombocytopenic purpura (ITP) immediately before the ninth course of administration; and, treatment was discontinued. Recovery of symptoms and normalization of blood test data were achieved 3.5months after starting steroid treatment. Reduction of recurrent disease has been maintained for 2 years.

Clinical significance and predictors of complete or near-complete histological response to preoperative chemoradiotherapy in patients with localized pancreatic ductal adenocarcinoma.

BACKGROUND: The clinical value and predictors of a favorable histological response to preoperative chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC) remains undefined. OBJECTIVE: To assess the significance and predictors of a favorable histological response to preoperative CRT in patients with localized PDAC. METHODS: The study included 203 patients with localized PDAC undergoing curative-intent resection after CRT. The rate of R0 resection and overall survival (OS) and recurrence-free survival (RFS) were correlated with the grading of histological response to determine optimal stratification. Clinical factors associated with a significant histological response were evaluated using multivariate regression analysis. RESULTS: Among all patients, eight patients (3.9%) had a grade 4 (pCR); 40 (19.4%) had a grade 3 estimated rate of residual neoplastic cells <10% (near-pCR); and 155 (76.7%) had a grade 1/2 limited response. The 48 patients with pCR/near-pCR achieved significantly higher R0 resection rate (100%) than those with grade 1/2 (80.0%). The 5-year OS and RFS rates were significantly higher in the patients with pCR/near-pCR (45.3% and 36.5%) than in those with grade 1/2 (27.1% and 18.5%). Gemcitabine plus S-1 based CRT, serum CA19-9 level after CRT <83 U/mL, and interval from initial treatment to surgery ≥4.4 months were independent predictive factors for pCR/near-pCR. CONCLUSIONS: pCR or near-pCR to preoperative CRT contributed to achieving a high rate of R0 resection and improving survival for localized PDAC. The use of gemcitabine plus S-1 as a radiosensitizer, lower serum CA19-9 level after CRT, and longer preoperative treatment duration were significantly associated with pCR or near-pCR.

[Presurgical Treatment with Axitinib and Pembrolizumab Reduced Operation Risk by Downsizing the Vena Cava Tumor Thrombus in Clear Cell Renal Cell Carcinoma : A Case Report].

A woman in her seventies complained of chest pain during exertion and visited a local hospital. Computed tomographic scan showed right renal cell carcinoma with inferior vena cava (IVC) tumor thrombus extending above the diaphragm, and the patient was referred to our hospital. She was diagnosed with right renal cell carcinoma cT3cN0M0, with level IV IVC thrombus by Mayo classification. Axitinib and pembrolizumab were administered against intractable advanced renal cell carcinoma. The dose of axitinib was reduced due to grade 3 liver dysfunction. Right nephrectomy together with IVC thrombectomy was performed because the primary lesion had shrunk, and the level of IVC thrombus had become level III. The pathological results were clear cell carcinoma, pT3c, G3, Fuhrman grade3, INFA, v1, and ly0. Axitinib and pembrolizumab might be a presurgical option against an intractable renal cell carcinoma with an IVC thrombus.

First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors.

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (µg/µg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4-5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.

SOX11-induced decrease in vimentin and an increase in prostate cancer cell migration attributed to cofilin activity.

SOX11 is a transcription factor in the SOX family of genes that regulate multiple cellular events by influencing the expression of key genes in developmental, physiological, and tumorigenic cells. To elucidate the role of SOX11 in prostate cancer cells, PC-3 prostate cancer cells were cloned (S6 and S9 cells) to highly express SOX11. We demonstrated that both S6 and S9 lose vimentin expression, acquiring epithelial marker proteins, which indicates the Epithelial state phenotype. S6 and S9 cells have cancer-promoting characteristics that include higher migratory properties compared with control cells. The mechanisms that are responsible for the enhanced migration are cofilin activity and keratin 18 expression. TCGA (The Cancer Genome Atlas) dataset analysis revealed that metastatic prostate cancer tumors tend to have more SOX11 gene amplification compared with primary tumors. These results suggest the tumor promotive role and epithelial protein induction of SOX11 in prostate cancer cell.

[Neoajuvant Chemotherapy with Gemcitabine and Cisplatin Plus S-1 for Primary Female Urethral Adenocarcinoma].

A 67-year-old female presented for evaluation of a left inguinal mass. Contrast-enhanced computed tomography revealed a tumor surrounding the urethra. Magnetic resonance imaging showed that the tumor had invaded the bladder neck on the anterior aspect of the urethra. The serum carbohydrate antigen 19-9 level was elevated. The clinical diagnosis was a primary adenocarcinoma of the female urethra (cT4N2M0). The initial treatment consisted of gemcitabine plus cisplatin (GC) and oral fluoropyrimidine (S-1). A total cysto-urethrectomy with anterior vaginal wall resection, pelvic and inguinal lymphadenectomy, and urinary diversion with ileal conduit formation were performed. The final diagnosis was urethral adenocarcinoma (ypT4ypN2, stage IV). Twelve months post-operatively, there was no evidence of recurrence or distant metastases.

Antifibrotic Agent Pirfenidone Suppresses Proliferation of Human Pancreatic Cancer Cells by Inducing G0/G1 Cell Cycle Arrest.

BACKGROUND: Pirfenidone (PFD), which is an antifibrotic agent used for treatment of idiopathic pulmonary fibrosis, induces G0/G1 cell cycle arrest in fibroblasts. We hypothesized that PFD-induced G0/G1 cell cycle arrest might be achieved in other types of cells, including cancer cells. Here we investigated the effects of PFD on the proliferation of pancreatic cancer cells (PCCs) in vitro. METHOD: Human skin fibroblasts ASF-4-1 cells and human prostate stromal cells (PrSC) were used as fibroblasts. PANC-1, MIA PaCa-2, and BxPC-3 cells were used as human PCCs. Cell cycle and apoptosis were analyzed using flow cytometer. RESULTS: First, we confirmed that PFD suppressed cell proliferation of ASF-4-1 cells and PrSC and induced G0/G1 cell cycle arrest. Under these experimental conditions, PFD also suppressed cell proliferation and induced G0/G1 cell cycle arrest in all PCCs. In PFD-treated PCCs, expression of p21 was increased but that of CDK2 was not clearly decreased. Of note, PFD did not induce significant apoptosis among PCCs. CONCLUSIONS: These results demonstrated that the antifibrotic agent PFD might have antiproliferative effects on PCCs by inducing G0/G1 cell cycle arrest. This suggests that PFD may target not only fibroblasts but also PCCs in the tumor microenvironment of pancreatic cancer.

Benign Fibrous Histiocytoma of the Talus: A Case Report.

Benign fibrous histiocytoma (BFH) is a rare benign primary bone lesion that occurs most frequently in the nonmetaphysis region of the long bones and the pelvic bones. The talus is a rare location for a BFH, which has not been reported previously in the literature. We report the case of a 19-year-old male patient with BFH of the talus, who was treated with curettage, followed by filling of the bone defect with calcium phosphate cement. The patient was free of pain and without local recurrence 5 years after the surgery. We describe the detailed radiographic findings of this rare lesion and discuss the differential diagnosis of such talar lesions.

Calcified amorphous tumor of the heart in a hemodialysis patient.

We report a case of calcified amorphous tumor (CAT) of the heart in a 60-year-old Japanese man on hemodialysis. Because the masses in the mitral annulus developed during two-year echocardiographic follow-up, he underwent surgical resection with mitral valve replacement. Histological examination showed that the tumor contained multiple calcified nodules, which confirmed the diagnosis of CAT. This case report reinforces the need to deeply and periodically investigate for cardiac involvement of CAT in all patients on hemodialysis.

Margin-negative limited resection of metastatic pancreatic tumors from rectal cancer preoperatively diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsies: report of two cases.

Pancreatic tumor metastasis from colorectal cancer is very rare. This study evaluated the significance of an endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) and surgical treatment. Case 1 was a 67-year-old male with a history of rectal cancer (6 years ago) and lung metastases (5 years ago) who had two masses in the pancreatic head and body. Case 2 was a 58-year-old male with the history of rectal cancer and simultaneous lung metastasis (7 years ago) who had a mass in the pancreatic body. Imaging studies showed stenosis of the pancreatic duct with distal dilatation in both cases, mimicking primary pancreatic cancer. An EUS-FNAB with immunohistochemical staining made a definitive diagnosis of pancreatic metastasis from rectal cancer. Both patients received margin-negative limited resection, middle-segment-preserving pancreatectomy and distal pancreatectomy, respectively, and were alive 16 and 6 months after pancreatectomy, respectively. An EUS-FNAB is helpful to make a definitive diagnosis of pancreatic metastasis and in determining the subsequent therapeutic approach.

[Urinary tract tumors].

The General Rule for Clinical and Pathological Studies on Bladder Cancer (3rd edition) and General Rule for Clinical and Pathological Studies on Renal Pelvic and Ureteral Cancer (2nd edition) were integrated, and the General Rule for Clinical and Pathological Studies on Renal Pelvic, Ureteral, and Bladder Cancer was published in April 2011. For histopathological diagnosis, a modification in line with the World Health Organization/International Urological Pathology 2004 classification is performed. Urothelial carcinoma is divided into non-invasive urothelial carcinoma and invasive urothelial carcinoma. With respect to the tumor grade classification for non-invasive papillary urothelial carcinoma, a two-grade classification, which is divided into low and high grade, is adopted instead of the three-grade classification adopted in the previous General Rule for Clinical and Pathological Studies. With respect to tumor subtyping for invasive urothelial carcinoma, twelve subtypes are adopted in the latest General Rule for Clinical and Pathological Studies. Subtyping also complies with the WHO/ISUP2004 classification. The handling of urothelial carcinoma with squamous, glandular, or trophoblastic differentiation is modified and they are classified in subtypes. Nine rare subtypes are also added. In the subtype classification, subtypes that are required to be differentiated from benign lesions or malignant tumors, involved in treatment selection, or related to the prognosis are included.

Prediction of prognosis using artificial intelligence-based histopathological image analysis in patients with soft tissue sarcomas.

BACKGROUND: Prompt histopathological diagnosis with accuracy is required for soft tissue sarcomas (STSs) which are still challenging. In addition, the advances in artificial intelligence (AI) along with the development of pathology slides digitization may empower the demand for the prediction of behavior of STSs. In this article, we explored the application of deep learning for prediction of prognosis from histopathological images in patients with STS. METHODS: Our retrospective study included a total of 35 histopathological slides from patients with STS. We trained Inception v3 which is proposed method of convolutional neural network based survivability estimation. F1 score which identify the accuracy and area under the receiver operating characteristic curve (AUC) served as main outcome measures from a 4-fold validation. RESULTS: The cohort included 35 patients with a mean age of 64 years, and the mean follow-up period was 34 months (2-66 months). Our deep learning method achieved AUC of 0.974 and an accuracy of 91.9% in predicting overall survival. Concerning with the prediction of metastasis-free survival, the accuracy was 84.2% with the AUC of 0.852. CONCLUSION: AI might be used to help pathologists with accurate prognosis prediction. This study could substantially improve the clinical management of patients with STS.

Choledochocele with hyperplastic epithelium in a patient who developed severe acute pancreatitis and underwent subtotal stomach-preserving pancreatoduodenectomy: a case report.

Choledochocele is defined as a congenital dilatation of the distal intramural part of the common bile duct protruding into the wall of the descending duodenum, typically without pancreaticobiliary maljunction. However, some cases present with a similar pathophysiology to pancreaticobiliary maljunction, including reciprocal reflux of pancreatic juices and bile, leading to protein plugs, pancreatitis, and biliary tract carcinogenesis. Choledochocele is relatively rare and its anatomy, physiology, pathology, and clinical features are thus not well known. We describe a patient with choledochocele who suffered from repeated severe acute pancreatitis and underwent subtotal stomach-preserving pancreatoduodenectomy, in whom the pathological findings of choledochocele showed hyperplasia.

Female pelvic organ-preserving robot-assisted simple cystectomy and intracorporeal ileal neobladder reconstruction on a young woman with Hunner-type interstitial cystitis.

Introduction: Cystectomy is the last treatment option for Hunner-type interstitial cystitis. However, consensus regarding optimal patient selection or treatment approaches is lacking. Case presentation: A 27-year-old woman presented to a regional hospital with bladder pain and frequent urination. Antimicrobial therapy was administered; however, her symptoms persisted and she was finally diagnosed with HIC. Multiple endoscopic fulgurations of Hunner's lesions with bladder hydrodistension or intravesical therapy were performed; however, the symptoms persisted. A urethral catheter was inserted 1 month before she visited our clinic because of a severely contracted bladder. We performed female pelvic organ-preserving robot-assisted simple cystectomy and intracorporeal ileal neobladder reconstruction. The patient's postoperative course was uneventful and her symptoms resolved. Conclusion: This is the first report of pelvic organ-preserving robot-assisted simple cystectomy and intracorporeal ileal neobladder reconstruction in a young woman with HIC.

A simple risk stratification model for prostate cancer using histopathologic findings of radical prostatectomy.

OBJECTIVES: To develop a simple postoperative risk stratification based on histopathologic findings from radical prostatectomy specimens. METHODS: This study included 3 cohorts of patients with a preoperative diagnosis of clinically localized prostate cancer: 1 derivation cohort (n = 432) and 2 validation cohorts (n = 506 and n = 720). First, a postoperative risk stratification model was developed in the derivation cohort using the factors extraprostatic extension, surgical margin status, seminal vesicle invasion, and lymph node involvement. Each of the first 3 factors was assigned 0 or 1 point for negative or positive results, respectively, and the sum of the points, ranging from 0 to 3, was scored. pN1 was not scored but was analyzed separately. Validation cohorts were then used to evaluate the predictive accuracy of the model. Additionally, we compared the model with the Cancer of the Prostate Risk Assessment (CAPRA) score. RESULTS: Because the log-rank test showed no statistically significant differences between scores 1 vs 2 or score 3 vs pN1 in the derivation cohort, the following 3-level risk stratification was created: low risk (score 0), intermediate risk (score 1-2), and high risk (score 3 or pN1). There were statistically significant differences in recurrence-free survival between any of 2 groups of 3-level risk stratification. This model similarly worked in both validation cohorts. The C indexes for the model were higher than those for the CAPRA score. CONCLUSIONS: This simple postoperative risk stratification model, based on radical prostatectomy findings, has a prognostic impact that has been validated in a multicenter population.

Intratubular trophoblasts in the contralateral testis caused elevation of serum human chorionic gonadotropin following complete remission of stage II testicular tumor: a case report.

We report the case of a 22-year-old male who had a history of metastatic right testicular tumor successfully treated with chemotherapy and surgery. Twenty-one months after the initial treatment, the serum human chorionic gonadotropin started to increase gradually, but whole body imaging including the left testis revealed no abnormal finding except testicular microlithiasis. A biopsy of the left testis revealed intratubular germ cell neoplasia, unclassified type. After the human chorionic gonadotropin level reached 6.6 mIU/ml, he underwent left high orchiectomy. Histology demonstrated a small malignant germ cell tumor as well as intratubular germ cell neoplasia, unclassified type, both of which were negative for human chorionic gonadotropin staining. Besides these lesions, there were tiny foci of human chorionic gonadotropin-immunoreactive intratubular trophoblasts. Serum human chorionic gonadotropin normalized immediately after the orchiectomy, and he had no sign of recurrence at 6 months. The present case will provide new insight into the diagnosis of testicular tumor recurrence with isolated elevation of a serum tumor marker.

Oncological outcomes of metastatic testicular cancers under centralized management through regional medical network.

OBJECTIVE: To investigate the dose intensity of induction chemotherapy and oncological outcomes of metastatic testicular cancer under centralized management through a regional medical network. MATERIALS AND METHODS: We retrospectively analyzed the outcomes of 86 metastatic testicular cancer patients who were given induction chemotherapy at Tsukuba University Hospital and four branch hospitals between January 2000 and November 2010. Principally, management of patients with poor-prognosis disease and patients having risk factors for bleomycin, etoposide and cisplatin were referred to Tsukuba University Hospital before chemotherapy. For high-risk groups, etoposide and cisplatin or etoposide, ifosfamide and cisplatin was used as an alternative to bleomycin, etoposide and cisplatin. RESULTS: Overall, 56 and 30 patients were treated at Tsukuba University Hospital and branch hospitals, respectively. Forty-seven, 18 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Eighteen of the 21 patients (86%) with poor-prognosis disease were treated at Tsukuba University Hospital from the beginning of induction chemotherapy. Induction chemotherapy with a high relative dose intensity was possible in most patients. The average relative dose intensity of each drug was >0.96. Treatment procedures other than induction chemotherapy were efficiently centralized; 74% of post-chemotherapy surgery and all second-line or subsequent chemotherapies were performed at Tsukuba University Hospital. The 5-year overall survival rates of the good-, intermediate- and poor-prognosis groups were 97, 93 and 84%, respectively. CONCLUSIONS: Induction chemotherapy with high relative dose intensity, post-chemotherapy surgery and salvage chemotherapy was accomplished efficiently through centralization of management. Oncological outcomes were excellent, especially in patients with poor-prognosis disease, whose 5-year OS reached 84%.

Risk factors for chronic kidney disease after chemotherapy for testicular cancer.

OBJECTIVE: To elucidate the patterns of and risk factors for deterioration of renal function after chemotherapy in metastatic testicular cancer survivors using the estimated glomerular filtration rate. METHODS: A total of 96 patients who were treated with cisplatin-based chemotherapy for metastatic testicular cancer between January 1981 and December 2010 were enrolled in this study. The estimated glomerular filtration rate was based on the serum creatinine concentration using the formula of the Japanese Society of Nephrology. Risk factors for chronic kidney disease were examined by multivariate logistic-regression analysis. RESULTS: The median follow-up period was 70 months (range 15-342). The median pretreatment estimated glomerular filtration rate was 98 mL/min/1.73 m(2) (range 44-216), and it gradually decreased for 1 year after the end of chemotherapy, although there was no significant change in estimated glomerular filtration rate beyond 1 year. One year after chemotherapy, 22 of 96 patients (23%) showed chronic kidney disease (less than 60 mL/min/1.73 m(2) estimated glomerular filtration rate). The multivariate analysis showed that the patients with mild renal damage (estimated glomerular filtration rate 60-89 mL/min/1.73 m(2) ) and elevated blood pressure (higher than 130/80 mmHg) before treatment had a significant risk with odds ratios of 2.63 (95% confidence interval 1.09-6.73) and 4.22 (95% confidence interval 1.45-12.6), respectively. CONCLUSIONS: Close monitoring of renal function is important for at least 1 year after chemotherapy for testicular cancer, especially in patients having elevated blood pressure and/or mild renal damage before chemotherapy.