Yukio Yamada

Assessment of Mitotic Activity in Pituitary Adenomas and Carcinomas.

Assessment of mitotic activity represents one of the oldest and most routinely used histopathologic methods of evaluating the biological aggressiveness of human tumors. In the case of pituitary tumors, however, the relevance of this approach as a means of gaging tumor behavior remains ill-defined. In this article, the relationship between the mitotic index and biological aggressiveness of pituitary tumors was evaluated in a series of 54 pituitary adenomas and 6 primary pituitary carcinomas. All tumors were fully classified by immunohistochemistry and electron microscopy; adenomas were further stratified on the basis of their invasion status, the latter being defined as gross, operatively, or radiologically apparent infiltration of dura or bone. Mitotic figures were present in 11 tumors, 10 being either invasive adenomas or pituitary carcinomas. A significant association between the presence of mitotic figures and tumor behavior was noted, as evidenced by progressive increments in the proportion of cases expressing mitotic figures in the categories of noninvasive adenoma, invasive adenoma, and pituitary carcinoma (3.9, 21.4, and 66.7%, respectively; Fisher’s exact test, two-tailed,p<0.001). The mitotic index, however, appeared to be a less informative parameter, being extremely low in all cases (mean=0.016%±0.005 [±SEM]). Although the mean mitotic index in pituitary carcinomas (0.09%±0.035) was significantly higher than the mean mitotic index of either noninvasive adenomas (0.002%±0.002) or invasive adenomas (0.013%±0.005), no practical threshold value capable of distinguishing these three groups was evident. Comparison of the mitotic index with Ki-67 derived growth fractions in these tumors revealed a significant but weak linear correlation (r=0.41,p<0.01). These data suggest that when, mitotic figures are present, they do provide some indication of the behavior and invasive potential of pituitary tumors. For routine diagnostic purposes, however, the discriminating power of this parameter is somewhat limited, being superseded by alternative and more informative methods of growth fraction determination such as that provided by the Ki-67 immunolabeling.

Prognostic Factors for Renal Cell Carcinoma With Bone Metastasis: Who Are the Long-Term Survivors?

PURPOSEnRenal cell carcinoma is sometimes associated with bone metastasis. Several risk factors have been reported but some are still controversial. Also, the significance of laboratory tests has not been fully examined for such cases.nnnMATERIALS AND METHODSnWe collected data on 94 renal cell carcinoma cases with bone metastasis treated at 3 tertiary referral centers. Clinicopathological parameters and outcome data were analyzed to search for predictors of overall survival retrospectively. The log rank test and the Cox proportional hazard model were used for univariate and multivariate analyses, respectively.nnnRESULTSnThere were 64 males with a median age of 63.9 years. Histological diagnosis showed clear cell renal cell carcinoma in 63 patients, nonclear cell renal cell carcinoma in 7 and unclassified cancer in 6. Sarcomatoid differentiation was found in 17 cases. Metastasis was detected synchronously in 37 patients or metachronously at a median interval of 33.1 months. Multivariate analysis identified sarcomatoid differentiation (p = 0.001), vertebral bone involvement (p = 0.003), extraosseous metastasis (p = 0.021), alkaline phosphatase increased to 1.5 times the upper limit of normal (p = 0.0003) and C-reactive protein increased to greater than 0.3 mg/dl (p = 0.018) as significant risk factors. Cases were classified into 3 groups based on the number of risk factors, including low risk-28 with 0 or 1 risk factor, intermediate risk-26 with 2 risk factors and high risk-40 with 3 to 5 risk factors. This grouping clearly separated survival among these groups (each p <0.001). It also confirmed the usefulness of the Memorial-Sloan Kettering Cancer Center classification system.nnnCONCLUSIONSnOur risk classification incorporating 5 risk factors enables accurate prediction of survival, which can be helpful to make clinical decisions in cases of renal cell carcinoma with bone metastasis.

Power Doppler ultrasonography-directed prostate biopsy in men with elevated serum PSA levels: An evaluation of the clinical utility and limitations

OBJECTIVESnTo determine the utility and limitations of power Doppler ultrasonography (PDU)-directed prostate biopsy in patients with elevated serum prostate-specific antigen (PSA) levels.nnnMETHODSnA total of 108 men (mean age 67.7 years, range 50 to 86) with serum PSA levels of greater than 4.0 ng/mL were assessed using digital rectal examination (DRE), gray-scale transrectal ultrasonography (TRUS), and PDU. Prostate vasculature identified on PDU was judged using a grading system. Subsequently, these patients underwent systematic six-core transperineal biopsy and additional biopsies for positive sites on DRE, gray-scale TRUS, and PDU.nnnRESULTSnA hypervascular site and prostate cancer on PDU was identified in 43 (40%) and 40 (37%) cases, respectively. PDU-directed and systematic six-core biopsies could independently detect 36 and 30 cancer cases, respectively. The sensitivity of PDU for cancer detection was 90%, specificity 90%, positive predictive value 84%, negative predictive value 94%, and accuracy 90%. High test performance was also observed in 53 cases with serum PSA levels of 4.1 to 10 ng/mL (sensitivity 77%, specificity 88%, positive predictive value 67%, negative predictive value 92%, and accuracy 85%). These values were superior or comparable to those of DRE and gray-scale TRUS. Inflammatory reactions and prostatic calculi were probable major causes of false-positive and false-negative results on PDU, respectively.nnnCONCLUSIONSnPDU can identify appropriate sites for biopsy and improve the cancer detection rate. However, PDU-directed biopsy does not appear to identify prostate cancer with sufficient accuracy to omit the systematic biopsy, and combined use of these methods should be preferable.

Hydrodistension with or without fulguration of hunner lesions for interstitial cystitis: Long‐term outcomes and prognostic predictors

Hydrodistension of the bladder, with optional fulguration of Hunner lesions, is one of the recommended therapies for interstitial cystitis (IC). The aims of this study are to evaluate long‐term outcomes of hydrodistension and identify outcome predictors.

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response

To determine whether botulinum toxin type A can represent an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies.

Fabrication of dynamic optical head phantoms from an MRI head model

Optical tomography is a new modality of noninvasive diagnosis for imaging the distribution of optical properties in human bodies. In the process of developing optical tomography systems which can be applicable to human heads for diagnosis of disease and study of brain functions, we need realistic optical phantoms which anatomically and optically simulate human heads with complicated and multi- layered structures. Previously we have reported design and fabrication methods of optical head phantoms based on an MRI human head image. The phantoms have simulated the multi- layered structure with different optical properties specified to each layer. They had five layers; i.e., skin, skull, cerebrospinal fluid layer, gray matter and white matter. Also some inclusions simulating hematoma were embedded in some part of the head phantoms. However, the phantoms were made all of solid plastic resin and the temporal variation of physiological functions in brain could not be simulated by the static phantoms. We have improved the fabrication method and succeeded in making dynamic optical phantoms which are able to include some parts simulating the temporal variation of blood flow rate and oxygenation status.

Adjuvant Chemotherapy Is Possibly Beneficial for Locally Advanced or Node-Positive Bladder Cancer

BACKGROUNDnThis study aimed to evaluate the outcomes of cisplatin-based adjuvant chemotherapy (AC) after radical cystectomy (RC) in non-organ-confined bladder cancer.nnnMETHODSnSixty-one patients who did not receive neoadjuvant chemotherapy (NAC) underwent RC for locally advanced (pT3-4) or node-positive (pN1-3) bladder cancer, or both, between 1990 and 2012. Of these patients, 39 (64%) received cisplatin-based AC after RC (AC group) and the remaining 22 patients (36%) did not (non-AC group). Cancer-specific survival (CSS) and recurrence-free survival (RFS) were compared between the groups.nnnRESULTSnThe AC group was significantly younger (P = .004), but no significant differences were noted between the groups for pT stage, pN stage, nuclear grade, renal function, and salvage chemotherapy rates after recurrence. During a follow-up of 29 months (median), 40 patients (67%) experienced recurrence/metastasis and 34 (56%) died of recurrent bladder cancer. The AC group showed better RFS than the non-AC group, but the difference was not statistically significant (median survival time [MST], 23.7 vs. 11.4 months, respectively; P = .154). CSS was significantly better for the AC group than for the non-AC group (MST, 57.4 vs. 17.9 months, respectively; P = .008). On multivariate analysis, AC was an independent predictive factor for both RFS (hazard ratio [HR], 0.325; P = .005) and CSS (HR, 0.186; P < .001), along with surgical margin status and lymphovascular invasion (LVI). In a subgroup analysis of 31 node-positive cases, the AC group had a significantly better CSS compared with the non-AC group (P = .029). Analysis of node-negative cases (n = 30) yielded no significant benefit for AC.nnnCONCLUSIONnOur observations suggest that postoperative cisplatin-based AC improves survival in locally advanced or node-positive bladder cancer, especially in node-positive cases.

Skeletal-related events and prognosis in urothelial cancer patients with bone metastasis

BackgroundThe aim of the present study was to elucidate the details of bone metastasis (BM) and the resulting skeletal-related events (SREs), and survival and prognostic factors, in urothelial cancer (UC) patients with BM.MethodsA total of 48 UC patients with BM who were treated at our institution between 1994 and 2013 were enrolled. Details of BM and SREs were investigated. The Kaplan–Meier method was used to estimate survival duration. Relationships between several clinical features and survival were analyzed using the log-rank test and the Cox hazard model.ResultsOf the 48 patients, 39 (81.3%) were male, with a median age at diagnosis of BM of 68xa0years [interquartile range (IQR), 61–75xa0years]. Frequent metastatic sites included the pelvis (31 patients, 64.6%) and spine (28, 58.3%). SREs occurred in 31 patients (64.6%) at a median duration of 0.9xa0months (IQR, 0.3–5.4xa0months) after diagnosis of BM, including radiation therapy (nxa0=xa023; 74.2%), spinal cord compression (nxa0=xa04; 12.9%), pathological fracture (nxa0=xa03; 9.7%) and hypercalcemia (nxa0=xa01; 3.2%). Median overall survival periods after diagnosis of BM and SREs were 6.2 and 5.6xa0months, respectively. On multivariate analysis, factors significantly associated with survival after BM were performance status [hazard ratio (HR) for ≥2 vs. 0–1, 4.94; Pxa0=xa00.0003], liver metastasis (HR, 4.08; Pxa0=xa00.0018), chemotherapy after BM (HR, 0.31; Pxa0=xa00.0018), and use of bone-modifying agents (HR, 0.36; Pxa0=xa00.0147).ConclusionsWe revealed clinicopathological factors that are predictive of prognosis of UC patients with BM. Although the prognosis is poor, chemotherapy and bone-modifying agents may confer survival benefits.

A survey on clinical practice of interstitial cystitis in Japan

Background To explore the real-life practice of clinical management of interstitial cystitis (IC) in Japan. Methods A questionnaire on the number of IC patients, cystoscopic findings, diagnostic methods, and the treatment modalities was sent via e-mail to 114 medical institutions belonging to the Society of Interstitial Cystitis of Japan (SICJ). Results Completed questionnaires were returned from 62 institutions (20 university hospitals, 26 general hospitals and 16 clinics), with a response rate of 54%. The median of patient number per institution was 20 and the national number of IC patients was counted as 4,531 in Japan. The number of new patients in 2013 was 7 (median) per institution and calculated as 1,214 in total. The case volume per institution distributed broadly and skewed to a lower volume. The patients were categorized according to cystoscopic findings as either Hunner type IC with Hunner lesions (n=2,066, 45%), non-Hunner type IC with glomerulations on hydrodistension (n=1,720, 38%) or hypersensitive bladder without endoscopic abnormalities (n=304, 7%), excluding unknown (n=441, 10%). The proportion of Hunner type IC was highly variable among the institutions, ranging from 0% to 100% with a median of 29%. As for evaluation, symptom and quality of life (QOL) assessment by questionnaires, frequency volume chart, urinalysis, urine cytology, urine culture, post-void residual measurement, uroflowmetry, ultrasound and cystoscopy were widely adapted. Administration of oral medicines and intravesical instillation therapy were undertaken at 98% and 63% of institutions, respectively. Hydrodistension was commonly performed, totaling in 812 procedures at 53 institutions, while only five cystectomies were reported from four institutions. Conclusions The survey estimated about 4,500 IC patients and 2,000 Hunner type IC patients in Japan. It also revealed a wide range of case volume, acceptable adherence to clinical guidelines, and high variability in the proportion of Hunner type IC. The variable proportions of Hunner type IC despite a high performing rate of endoscopy suggest inconsistency in diagnostic criteria for the Hunner lesion.

Digital quantitative analysis of mast cell infiltration in interstitial cystitis

To evaluate the significance of mast cell infiltration in interstitial cystitis (IC) by comparison with equally inflamed controls using a digital quantification technique.