Validation of the risk stratification newly defined in the Japanese Urological Association guidelines 2019 for non-muscle invasive bladder cancer: A multi-institutional collaborative study.

OBJECTIVES: To validate the risk stratification newly defined in the Japanese Urological Association guidelines 2019 for non-muscle invasive bladder cancer and provide a more accurate stratification model for a heterogeneous intermediate-risk group. METHODS: A total of 1610 patients, who underwent transurethral resection, diagnosed with non-muscle invasive bladder cancer in nine collaborating hospitals were retrospectively reviewed. They were classified into low-risk, intermediate-risk, high-risk, and highest-risk groups, and recurrence-free survival, progression-free survival, cancer-specific survival, and overall survival were compared among the groups. The intermediate-risk group was subdivided into two groups based on the multivariable Cox regression model of recurrence and progression risk factors, and a revised risk model was created. RESULTS: The progression-free survival, cancer-specific survival, and overall survival were well stratified, while the recurrence-free survival of the intermediate-risk group was the shortest among the four groups (p < 0.001). The independent risk factors for recurrence and progression-free survival in the intermediate-risk group were as follows: age ≥ 70 years, sex, multiple tumors, tumor size ≥3 cm, and recurrent cases. The intermediate-risk group was subdivided into two groups: favorable intermediate-risk group and unfavorable intermediate-risk group. The revised risk model showed significant differences. CONCLUSION: We validated the Japanese Urological Association guidelines 2019 stratification model. The revised risk model provided a more accurate treatment selection for this disease subset.

A new risk stratification model for intravesical recurrence, disease progression, and cancer-specific death in patients with non-muscle invasive bladder cancer: the J-NICE risk tables.

BACKGROUND: The aim of this study is to establish new risk tables for the current clinical setting, enabling short- and long-term risk stratification for recurrence, progression, and cancer-specific death after transurethral resection in non-muscle invasive bladder cancer (NMIBC). Currently available risk tables lack input from the 2004 World Health Organization grading system and risk prediction for cancer-specific death. METHODS: This was a multi-institutional database study of 1490 patients diagnosed with NMIBC (the development cohort). A multivariate Fine and Gray subdistribution hazard model was used to assess the prognostic impact of various factors. Patients were classified into low-, intermediate-, and high-risk groups according to a sum of the weight of selected factors, and predicted cumulative rates were calculated. Internal validation was conducted using 200 bootstrap resamples to assess the optimism for the c-index and estimate a bias-corrected c-index. External validation of the developed risk table was performed on an independent dataset of 91 patients. RESULTS: The Japanese NIshinihon uro-onCology Extensive collaboration group (J-NICE) risk stratification table was derived from six, five, and two factors for recurrence, progression, and cancer-specific death, respectively. The internal validation bias-corrected c-index values were 0.619, 0.621, and 0.705, respectively. The application of the J-NICE table to an external dataset resulted in c-indices for recurrence, progression, and cancer-specific death of 0.527, 0.691, and 0.603, respectively. CONCLUSIONS: We propose a novel risk stratification model that predicts outcomes of treated NMIBC and may overcome the shortcomings of existing risk models. Further external validation is required to strengthen its clinical impact.

Repeat hepatectomies for hepatic malignant lymphoma and hepatocellular carcinoma associated with chronic hepatitis C: report of a case.

We report a case of repeat hepatectomies for hepatic malignant lymphoma and hepatocellular carcinoma (HCC). A 75-year-old man with chronic hepatitis C underwent partial hepatectomy for a 25 mm hepatic tumor in S5. The histological diagnosis was diffuse large B-cell malignant lymphoma and as postoperative (18)F-fluorodeoxyglucose-positron emission tomography showed no hot spots, the mass was presumed to be primary hepatic lymphoma. Thus, adjuvant systemic chemotherapy was given following the hepatectomy. Abdominal ultrasonography, done 12 months after the hepatectomy, showed a hepatic tumor in S6 and repeat partial hepatectomy was performed. This tumor was histologically diagnosed as HCC.

[Case of primary retroperitoneal GIST (gastrointestinal stromal tumor) with rapid progression].

A 69-year-old man complaining of left abdominal pain was referred from a private clinic for retroperitoneal masses that were discovered on abdominal ultrasound in November 2010. CT scan showed retroperitoneal masses, located above the left kidney, measuring 10 cm. Para-aortic lymph nodes were swelling. We performed open biopsy to make the diagnosis in December 2010. The diagnosis was primary retroperitoneal GIST (gastrointestinal stromal tumor). We started imatinib 400 mg/day according to the Japan GIST guideline in January 2011. However the tumor pogressed rapidly, after 1 month the patient died.

Preoperative diagnostic value of single-balloon enteroscopy for successful surgical treatment of three independent-origin gastrointestinal malignant tumors: report of a case.

A 67-year-old woman with bloody stools underwent esophagogastroduodenoscopy and colonoscopy, which revealed the presence of a submucosal tumor in the stomach and an adenocarcinoma in the ascending colon. Preoperative screening disclosed an additional 10-cm tumor in the abdomen between the gastric and colonic lesions. Single-balloon enteroscopy was therefore performed. A nonstenotic, circumferential, bleeding ulcerative lesion was found in the jejunum, and the biopsy revealed malignant lymphoma (ML). A partial resection of the small intestine, ascending colectomy, and wedge resection of the stomach were performed, then systemic chemotherapy for ML was started 2 weeks after surgery. Triple gastrointestinal malignant tumors with different histologies are extremely rare, and have not been previously reported. Single-balloon enteroscopy in this case led to a definite diagnosis by biopsy, thus allowing the patient to receive chemotherapy as soon as possible after surgery.

[A case of primary pleural angiosarcoma metastasing to the bladder].

The patient was a 79-year-old man who underwent right extrapleural lucite ball plombage for pulmonary tuberculosis at aged 19. He was followed BPH with medication from May 2008 at our hospital. He presented with macrohematuria in January 2010, but cystoscopy and CT scan showed no significant abnormalities. He was admitted to complaining of general fatigue and anemia in February 2010. TURBT was performed 10 days after admission, and showed the bleeding sites with oozing in mucosa at the bilateral and posterior wall of the bladder. Neither CT nor cytological examinations were helpful in diagnosing this disease, although histological observation implied a possibility of malignant vasoformative tumor. He died one month after admission. Autopsy revealed a huge bloody mass at the right upper thoracic wall and same metastatic tumors of both adrenals, the bone, the stomach and the urinary bladder. Microscopic examination revealed that atypical cells had proliferated and formed vascular structures, which were stained positively with CD31, and vimentin. Finally, the diagnosis was made of pleural angiosarcoma and multiple metastasis. Metastatic angiosarcoma of the bladder is very rare and difficult to make definite diagnosis, however we have to keep in mind the presence of this disease.

A new 7-point method facilitates accurate diagnosis of high-grade urothelial carcinoma in routine urinary cytology practice.

INTRODUCTION: This study was designed to identify the minimal and necessary cell morphologies to be considered for high-precision diagnosis of high-grade urothelial carcinoma (HGUC) in a routine urinary cytology practice. MATERIALS AND METHODS: We included 338 urine cytology specimens from 11 medical facilities in Japan. Six experts evaluated these Papanicolaou-stained specimens using their own diagnostic criteria to categorize them within an initial 4-tiered classification system. Of the 338 cases, 70 HGUC and 32 benign cases (with a complete consensus diagnosis of 6 experts) were included for the analysis. Two of the cytologists evaluated the specimens for 20 specific cellular features. The results were analyzed using a contingency table and by discriminant analysis. RESULTS: Of the original 338 cases, 165 were originally diagnosed as HGUC, but only 70 (42.4%) were scored as malignant by all participating cytologists; of the 101 benign cases, only 32 (31.7%) were classified as such in all examinations. These specimens were re-evaluated by 6 experts using a panel of 20 specific cellular features used to distinguish between HGUC and benign diseases; tests of significance and discriminant analyses identified 7 critical features that were most useful for cytological diagnosis. Statistical analysis revealed that a focus on these 7 features led to a diagnosis of HGUC with a probability of over 95%. CONCLUSIONS: The accuracy of our presently used method to evaluate urinary cytology is not consistently high. This novel classification system, which focuses on 7 critical features, facilitates the high accurate diagnosis of HGUC in routine cytology practice.

Morphological, immunohistochemical, and genomic analyses of papillary renal neoplasm with reverse polarity.

Papillary renal neoplasm with reverse polarity (PRNRP) is a recently proposed entity of renal tumor. It shows a far better prognosis than papillary renal cell carcinoma (PRCC) and frequently has KRAS missense mutation. In this study, we compared 14 cases of PRNRP and 10 cases of PRCC type 1 (PRCC1) and type 2 (PRCC2) from clinical, morphological, immunohistochemical, and molecular biological perspectives. We subjected all PRNRP and PRCC cases to immunohistochemical analysis. Whole-exome sequencing using next-generation sequencing (NGS) was performed for six cases of PRNRP, three cases of PRCC1, and four cases of PRCC2. A search for KRAS gene mutation in the remaining eight cases of PRNRP was performed by polymerase chain reaction (PCR) sequencing. The results showed that all cases of PRNRP were pT1N0M0, none of which followed a course of recurrence or tumor-related death. Immunohistochemical analysis revealed diffuse staining of CK7, EMA, PAX8, and GATA3 but weak or negative staining of CD10, CD15, and AMACR in PRNRP. By NGS and PCR, KRAS missense mutation was detected in 11 of 14 PRNRP cases, although pathogenic KRAS mutation was not observed in PRCC1 and PRCC2. NGS analysis revealed less tumor mutation burden in PRNRP than in PRCC. PRNRP also showed no specific chromosomal copy number abnormalities, including gains of 7 and 17. In conclusion, we propose that PRNRP is a distinct condition from PRCC.

Real-time balloon inflation elastography for prostate cancer detection and initial evaluation of clinicopathologic analysis.

OBJECTIVE: The use of elastography is limited for prostate cancer detection because of the difficulty in obtaining stable and reproducible images. To overcome these limitations, we developed a new technique called real-time balloon inflation elastography (RBIE); with RBIE, balloon inflation and deflation are used in place of manual compression. We present the accuracy and feasibility of the RBIE technique for detecting prostate cancer. MATERIALS AND METHODS: The results of a pathologic analysis of 55 prostatectomy specimens were compared with elastographic moving images obtained at the time of biopsy of the prostate. RESULTS: The RBIE technique generated stable and repeatable elastographic moving images. The percentage of images affected by artifact due to slippage in the compression plane was reduced to 1% using the RBIE method compared with 32% using the manual compression method. With regard to tumor location, elastographic moving images obtained using the RBIE technique were in complete agreement with clinicopathologic evaluation of tumor location in eight cases (15%), showed partial agreement in 43 cases (78%), and disagreed in four cases (7%). In three different regions of the prostate, 84% of anterior tumors, 85% of middle tumors, and 60% of posterior tumors were detected. The tumor detection rates by Gleason score were 60% in tumors with a Gleason score of 5 or 6, 73% in tumors with a Gleason score of 7, 72% in tumors with a Gleason score of 8, and 74% in tumors with a Gleason score of 9 or 10. CONCLUSION: The RBIE method improved the quality of elastographic moving images compared with the manual compression method. High-grade tumors and tumors of impalpable regions of the prostate were more frequently detected using RBIE. We conclude that RBIE is a promising method with which to detect prostate cancer.

Real-time elastography for the diagnosis of prostate cancer: evaluation of elastographic moving images.

OBJECTIVE: Elastography is a technique for detecting the stiffness of tissues. We applied elastography for the diagnosis of prostate cancer and evaluated the usefulness of elastography for prostate biopsy. METHODS: The subjects of this study were 311 patients who underwent elastography during prostate needle biopsy at Hitachi General Hospital. Strain images obtained during compression of the prostate tissue were displayed on a monitor and recorded on the computer. The elastographic moving images (EMI) were evaluated retrospectively. The evaluable images and biopsy results were compared in terms of the feasibility and accuracy. RESULTS: The median patient age was 67 years (range 50-85 years), the median serum level of prostate-specific antigen was 8.4 ng/ml (range 0.3-82.5 ng/ml) and the median prostate volume was 42.6 ml (range 12-150 ml). Among the 311 patients, prostate cancer was detected in 95 patients (30%) by biopsy. The diagnostic sensitivity was 37.9% for digital rectal examination (DRE) and 59.0% for transrectal ultrasonography (TRUS), whereas it was 72.6% for elastography and 89.5% for the combination of TRUS and elastography. Elastography-positive EMIs with negative biopsies were eventually determined to be due to benign prostatic hyperplasia. CONCLUSION: Elastography has a significantly higher sensitivity for the detection of prostate cancer than the conventionally used examinations including DRE and TRUS. It is a useful real-time diagnostic method because it is not invasive, and simultaneous evaluation is possible while performing TRUS.

[A case of gastrointestinal stromal tumor with liver and bone metastases effectively treated with radiofrequency ablation and imatinib mesylate].

A 58-year-old man was admitted because of perforation of the small intestine by a gastrointestinal stromal tumor (GIST). First, the small intestine including a GIST was resected; and then 2 month later, a part of the liver (S5) conforming to metastatic lesion was surgically removed. Twelve months later, another liver metastases was found, and surgical treatment was recommended; but the patient requested non-surgical therapy, so a radiofrequency ablation (RFA) was successfully performed. After that, recurrence of liver metastasis was not observed, but another metastasis was observed on the fifth lumbar vertebra; so administration of imatinib mesylate was started. 28 months after the initial administration the metastatic liver lesion was still invisible, and the bone metastatic lesion had not grown. The patient is alive with good performance status. This report shows that multi-modality therapy by surgery, RFA and imatinib mesylate was effective for liver and bone metastases of GIST.

Early gastric cancer with Krukenberg tumor and review of cases of intramucosal gastric cancers with Krukenberg tumor.

A 47-year-old woman was admitted because of hypermenorrhea. Transvaginal ultrasonography revealed an ovarian tumor and myoma uteri, and total hysterectomy with bilateral salpingo-oophorectomy was performed. Histology revealed signet-ring cell carcinoma in the right ovary. In order to find out the primary site of this tumor, gastroendoscopy was performed after the operation, and showed a IIc lesion in the lower body of the stomach; biopsy specimens showed signet-ring cell carcinoma similar to that in the right ovary. Total gastrectomy revealed that the lesion was an early gastric cancer confined to the mucosa, but there was lymphatic invasion slightly beneath the muscularis mucosa, with regional lymph node metastasis. In the light of a review of the seven cases of early gastric cancer with Krukenberg tumor previously reported, lymphatic metastasis seemed to be the most likely pathway of ovarian metastasis in early gastric cancers.

Cystic tumor of the atrioventricular nodal region.

We report a case of a 66-year-old female who presented exertional dyspnea and palpitation. Echocardiography, transesophageal echocardiography and computed tomography showed a right atrial cystic mass attached to the interatrial septum. The patient underwent successful excision of the mass. The histopathological findings confirmed the lesion as a cystic tumor of the atrioventricular nodal region. This is the third known case of this condition diagnosed antemortem and treated successfully with surgical excision.

An unusual enteropathy-associated T-cell lymphoma with MYC translocation arising in a Japanese patient: a case report.

Enteropathy-associated T-cell lymphoma (EATL) is a rare peripheral T-cell lymphoma classified into 2 types, with or without celiac disease, based on histology. Type 2 EATL is less commonly associated with celiac disease, in which cells are characterized by being monomorphic and small- to medium-sized. Cells are characterized by CD8 and CD56 expression and c-MYC oncogene locus gain. We present an atypical case of type 2 EATL in the jejunum, with human T-lymphotropic virus-1 that was CD4- CD8+ CD56- CD30- CD25- TIA-1+ and granzyme B+ on immunohistological staining. It also displayed translocation of chromosome 8p24 (c-MYC), as determined by fluorescent in situ hybridization. Mucosal spreading and intraepithelial invasion by lymphoma with villous atrophy were detected adjacent to the mucosal layer. The lymphoma may be derived from intraepithelial CD8+ T cells, similar to celiac disease.

Extraskeletal osteosarcoma of the pleura: a case report.

We herein present an exceedingly rare case of pleural osteosarcoma that was surgically resected in an elderly patient. A 74-year-old man, complaining of a dry cough and breathlessness on effort, was found to have massive pleural effusion on a chest X-ray. The chest CT and MRI scans indicated a massive effusion and a pleural tumor encasing the left lower lung. The resected tumor was histologically an osteosarcoma, measuring 11.3 x 9.0 x 6.0 cm. Because there was no evidence of any other primary tumor, the diagnosis of extraskeletal osteosarcoma was appropriate.

The impact of real-time tissue elasticity imaging (elastography) on the detection of prostate cancer: clinicopathological analysis.

BACKGROUND: We evaluated the accuracy and feasibility of real-time elastography for detecting prostate cancer, using prostatectomy specimens. METHODS: This study was based on clinicopathological findings in 51 patients with prostate cancer who were referred for elastography at the time of prostate biopsy. We compared transverse pathology sections with elastographic moving images (EMIs) to determine the detection rate of cancer, the relationship between tumor location and the elastographic findings, and the relationship between the Gleason score and the elastographic findings. RESULTS: In 15 patients (29%), all EMIs were in complete agreement with tumor location (category I), in 28 patients (55%), the EMIs agreed with tumor location, but showed some disagreement (category II), and in 8 patients (16%) there was disagreement of the elastographic findings with tumor location or the tumors were undetectable by elastography (category III). However, in category III, all tumors were detected as low-echoic by B-mode ultrasonography. We divided the prostate into three different regions (anterior, middle, and posterior), and found that 30/32 (94%) anterior tumors, 13/17 (76%) middle tumors, and 16/28 (57%) posterior tumors were detected by elastography. The proportions of cancers detected by elastography (categories I+II/total) was 100% in the patients with a Gleason score of 6, 85% in those with a score of 7 or 8, and 63% in those with a score of 9 or 10. CONCLUSION: Real-time elastography in conjunction with B-mode ultrasonography significantly improves the detection of prostate cancer. One of the characteristic findings of elastography is its excellent detection of anterior tumors. The low detection rate of high-grade tumors in this analysis was likely due to the predominance of high-grade tumors in a peripheral location compared to the anterior location of the low-grade tumors.

Chronic renal failure with severe mesangiolysis in a hematopoietic stem cell transplant recipient.

Chronic progressive renal failure is a well-recognized complication in hematopoietic stem cell transplantation (HSCT) recipients. Although thrombotic microangiopathy or chemotherapeutic agents are frequently associated, total body irradiation might also be one of the suspected etiologic factors. This study describes a 38-year-old female patient with acute lymphoblastic leukemia treated with HSCT who developed chronic renal dysfunction after transplantation. Renal biopsy revealed focal and diffuse glomerulosclerosis with extensive mesangiolytic lesions. Her clinical course implied that pretransplant irradiation might have the most impact on the expression of this glomerular lesion.