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Purpose: Eligibility for clinical trials is very strict and only patients who satisfy various criteria can enter trials. The individual use of pazopanib has not been adequately investigated. An optimal administration regimen for pazopanib in “real-world” patients with metastatic renal cell carcinoma (mRCC) is required. Our purpose was to determine the tolerability and efficacy of first-line pazopanib with a low starting dose in patients with mRCC who were ineligible for clinical trials. Materials and Methods: This study included patients with mRCC who underwent treatment with first-line pazopanib and were previously excluded from clinical trials because they did not meet the inclusion criteria. A 400 mg pazopanib starting dose is used routinely in patients with mRCC; if tolerated, dose escalation up to 800 mg may occur. Results: We identified 18 patients with mRCC who received first-line pazopanib and were previously determined ineligible for clinical trials. Pazopanib dose was escalated in 12 patients (66.6%), to 600 mg/day in 8 patients (44.4%) and to 800 mg/day in 4 patients (22.2%), and was not escalated in 6 patients (33.3%). In 3 patients (16.7%), pazopanib was discontinued owing to intolerability. The most common frequent adverse event was elevated alanine aminotransferase levels in 6 patients (33.3%), followed by a decreased platelet count in 5 patients (27.8%) and anorexia in 5 patients (27.8%). Partial response was seen in 5 patients (27.8%) and stable disease in 10 patients (55.6%); median progression-free survival was 11.9 months (95% confidence interval: 6.3–28.7 months). Conclusion: Our data indicated that a low starting dose of 400 mg pazopanib did not negatively affect treatment tolerability and efficacy in patients with mRCC ineligible for clinical trials. We found that lower starting doses may lead to better results. Additional studies are needed in a larger cohort and longer follow-up to attain authentic outcomes.

Objectives Dividing the intersegmental planes with a stapler during pulmonary segmentectomy leads to volume loss in the remnant segment. The aim of this study was to assess the influence of segment division methods on preserved lung volume and pulmonary function after segmentectomy. Methods Using image analysis software on computed tomography (CT) images of 41 patients, the ratio of remnant segment and ipsilateral lung volume to their preoperative values (R-seg and R-ips) was calculated. The ratio of postoperative actual forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) per those predicted values based on three-dimensional volumetry (R-FEV1 and R-FVC) was also calculated. Differences in actual/predicted ratios of lung volume and pulmonary function for each of the division methods were analysed. We also investigated the correlations of the actual/predicted ratio of remnant lung volume with that of postoperative pulmonary function. Results The intersegmental planes were divided by either electrocautery or with a stapler in 22 patients and with a stapler alone in 19 patients. Mean values of R-seg and R-ips were 82.7 (37.9-140.2) and 104.9 (77.5-129.2)%, respectively. The mean values of R-FEV1 and R-FVC were 103.9 (83.7-135.1) and 103.4 (82.2-125.1)%, respectively. There were no correlations between the actual/predicted ratio of remnant lung volume and pulmonary function based on the division method. Both R-FEV1 and R-FVC were correlated not with R-seg, but with R-ips. Conclusions Stapling does not lead to less preserved volume or function than electrocautery in the division of the intersegmental planes.

Studies reported that the mandibular cortical width (MCW) measured on dental panoramic radiographs (DPRs) was significantly correlated with bone mineral density. However, MCW is not a perfect index by itself, and studies suggest the added utility of mandibular cortical index (MCI). In this study, we propose a method for computerized estimation of mandibular cortical degree (MCD), a new continuous measure of MCI, for osteoporotic risk assessment. The mandibular contour was automatically segmented using an active contour model. The regions of interest near mental foramen were extracted for MCW and MCD determination. The MCW was measured on the basis of residue-line detection results and pixel profiles. Image features including texture features based on gray-level co-occurrence matrices were determined. The MCD were estimated using support vector regression (SVR). The SVR was trained using previously collected 99 DPRs, including 26 osteoporotic cases, by a computed radiography system. The proposed scheme was tested using 99 DPRs obtained by a photon-counting system with data of bone mineral density at distal forearm. The number of osteoporotic, osteopenic, and control cases were 12, 18, and 69 cases, respectively. The subjective MCD by a dental radiologist was employed for training and evaluation. The correlation coefficients with the subjective MCD were −0.549 for MCW alone, 0.609 for the MCD by the features without MCW, and 0.617 for the MCD by the features and MCW. The correlation coefficients with the BMD were 0.619, −0.608, and −0.670, respectively. The areas under the receiver operating characteristic curves for detecting osteoporotic cases were 0.830, 0.884, and 0.901, respectively, whereas those for detecting high-risk cases were 0.835, 0.833, and 0.880, respectively. In conclusion, our scheme may have a potential to identify asymptomatic osteoporotic and osteopenic patients through dental examinations.

557 Background: Current guidelines do not yet provide recommendations for any serum tumor markers in patients with upper tract urothelial carcinoma (UTUC) who received nephroureterectomy (NU). The criteria for adjuvant chemotherapy is also controversial. Previous studies have shown that serum cytokeratin levels (sCK) were correlated with depth of tumor invasion and metastases in patients with bladder cancer. We found that preoperative sCK was correlated with cancer specific survival(CSS) after NU. In this study we evaluated whether postoperative sCK (poCK) could predict early progression in patients who received NU. Methods: 160 patients with UTUC underwent NU from December 2003 to 2014 at our institution. The median age at diagnosis was 73 years (41-89). poCK19 had been measured in 112 patients within 8 weeks after NU. Patients were divided into two groups, a high-group and a low-group based on poCK19 levels (a cut-off value of 3.5 ng/mL). CSS and progression-free survival (PFS) were measured by Kaplan–Meier curves and log–rank test. Multivariate analysis was carried out using the Cox hazards model. Results: Of 112 patients ≤pT1 was 39 (34%), pT2 in 26 (23%), pT3 in 40 (35%), and pT4 in 7 (8%). The 5-year (5y) CSS rate was 86% and the 5yPFS rate was 60%. There were 24 (21%) patients in the high-group and 88 (79%) in the low-group. During the median follow-up period of 34.0 (1-152) months, 39 patients (35%) died. The 5yCSS rate of the high-group was 51%, which is significantly lower than the low-group (86%) (p

We developed a DentalSCOPE computer program to measure the bone mineral density (BMD) of the alveolar bone. Mineral density measurement of alveolar bone may be useful to predict possible patients who will occur medication-related osteonecrosis of the jaw (MRONJ). Because these osteoporosis medicines affect the mineral density of alveolar bone significantly. The BMD of alveolar bone was compared between dual-energy X-ray absorptiometry (DEXA) and the DentalSCOPE program. A high correlation coefficient was revealed between the DentalSCOPE measurement and the DEXA measurement.

The outcome of treatment of Japanese patients with urachal cancer is not well known. The purpose of this study is to clarify the characteristics and outcomes of Japanese patients with urachal cancer. The medical records of patients with urachal cancer who were treated in our hospital between 1994 and 2014 were retrospectively reviewed and statistically analyzed. We found 28 patients who had been diagnosed with urachal cancer and treated in our hospital during the study period. The median age of these patients was 52.3 years [interquartile range (IQR), 46.0–56.8 years]. Seventeen patients underwent surgery in our department. The median observation period of these patients was 42.6 months (IQR, 21.1–49.7 months). Among patients who had undergone surgery, cancer recurred in 7 (41 %). The estimated median time from surgery to recurrence and overall survival (OS) period were 35.8 months [95 % confidence interval (CI), 7.7 months–not determined] and not reached, respectively. Seventeen patients received chemotherapy for metastatic disease. The estimated median OS time from initial metastasis was 23.5 months (95 % CI, 11.8–33.3 months). Urachal cancer is usually locally advanced at presentation and it has a high risk of distant metastases. However, long-term survival following surgical treatment occurs in a significant fraction of patients. This study indicates the current treatment results for patients with urachal cancer in Japanese clinical practice. To establish a standard operation method and chemotherapy, a multicenter, prospective study is needed in a larger population in the future.

To determine the indications for post-chemotherapy consolidative surgery in patients with clinical lymph node (LN) metastatic (cN+) urothelial carcinoma (UC). Sixty UC patients with measurable cN+ but without detectable systemic visceral/bone dissemination received induction platinum-based chemotherapy. Consolidative surgery was offered to all patients except for those with progressive disease. We retrospectively analyzed the clinicopathological response to induction chemotherapy and identified prognostic factors for overall survival (OS). The primary cancer site was the urinary bladder in 31 patients (52 %) and upper urinary tract in 29 (48 %). The median number of chemotherapy courses was 4. Forty-five patients (75 %) showed a clinically objective response to the induction chemotherapy. Fifty-one patients (85 %) underwent subsequent consolidative surgery. Histopathological analysis indicated pT0 status in 10 (20 %) and pN0 in 17 (33 %). When all 60 patients were considered, clinical tumor response was found to be significantly correlated with achievement of pathological complete response. At the median follow-up of 22 months, the median progression-free survival and OS periods were excellent: 18.6 and 31.6 months, respectively. In the multivariate analysis, clinical tumor response was found to be an independent pre-surgical prognostic factor for OS, and pathologically negative lymph node, negative resection margin, more LNs removed, and negative lymphovascular invasion were found to be independent post-surgical prognostic parameters for OS. The median OS in induction chemotherapy followed by consolidative surgery was very encouraging. Our results suggest that achieving a good clinical response to pre-surgical induction chemotherapy is a good indication for subsequent consolidative surgery in UC patients with cN+ to improve OS through a good pathological response.

In large disasters, dental record plays an important role in forensic identification. However, filing dental charts for corpses is not an easy task for general dentists. Moreover, it is laborious and time-consuming work in cases of large scale disasters. We have been investigating a tooth labeling method on dental cone-beam CT images for the purpose of automatic filing of dental charts. In our method, individual tooth in CT images are detected and classified into seven tooth types using deep convolutional neural network. We employed the fully convolutional network using AlexNet architecture for detecting each tooth and applied our previous method using regular AlexNet for classifying the detected teeth into 7 tooth types. From 52 CT volumes obtained by two imaging systems, five images each were randomly selected as test data, and the remaining 42 cases were used as training data. The result showed the tooth detection accuracy of 77.4% with the average false detection of 5.8 per image. The result indicates the potential utility of the proposed method for automatic recording of dental information.

45 Background: Does tumor location affect prostate cancer prognosis? To clarify this question we conducted a retrospective study to characterize the incidence and prognostic significance of tumor location of prostate cancer. Methods: From 2000 to 2017, radical prostatectomy with no neoadjuvant therapy was performed in 916 cases in our hospital. Serial whole mount sections were reviewed to determine the incidence, clinicopathological features and prognostic significance of tumor location in the prostate gland. For the tumor location, we defined the subzones, which were made from subdivision of the McNeal’s zonal anatomy, are shown in Table 1 in detail. The peripheral zone (PZ) is composed of 8 subzones including A1, A2, A3 , M1, M2, M3, M4, M5. The transition zone (TZ) is composed of 5 subzones including T1, T2, T3, T4 and B1. The central zone (CZ) is composed of 3 subzones including M6, B2 and B3. Results: The median age was 67 and PSA was 8.6 ng/ml. The subzonal tumor incidence divided by all cases was the highest in A2, followed by M4, A1, M3, T2 in that order, while the lowest in B3, followed by M6, T4, T3, B1 in that order. The median follow-up time was 67 months. A 5-year PSA failure rate (5Y-PSAFR) was 23%. Among the subzones, the highest 5Y-PSAFR was seen in B3, followed by M6, B2, T4, A3, and the lowest was seen in M4, A2, T2, A1 in that order. A multivariate analysis for PSAF risk among subzones showed that B3 (HR 8.6, p

412 Background: Current guidelines do not yet provide any recommendations for any serum tumor markers in patients with upper tract urothelial carcinoma (UTUC). Even today radiological images cannot diagnose muscle invasion correctly. Previous studies have shown that serum cytokeratin levels were correlated with depth of tumor invasion and metastases in patients with bladder cancer. In this study we evaluated whether preoperative serum cytokeratin 19 fragment levels (sCK19) could be a prognostic marker for survival in patients who received nephroureterectomy (NU). Methods: 160 cases with UTUC underwent NU from December 2003 to 2014 at our institution. The median age was 73 years. Preoperative sCK19 was measured in 138 cases. The patients were divided into two groups, high sCK19 group (HG) and low group (LG) based on sCK19 (a cut-off value: 3.5 ng/mL). Cancer-specific survival (CSS) and progression-free survival (PFS) were measured by Kaplan–Meier curves and statistical analysis was performed by the log–rank test. Multivariate analysis was carried out using the Cox proportional hazards model. Results: Of 138 cases ≤pT1 was 54 (39%), pT2 in 31 (22%), pT3 in 45 (32%) and pT4 in 8 (5%). 37 cases (23%) were the HG and 101 (78%) were the LG. sCK19 were significantly correlated with pT (rs 0.213, p=0.013, Spearman rank correlation). The median follow-up time was 34.0 months. In all cases the 5-year CSS was 78% and PFS was 60%. The 5-year CSS of the HG (57%) was significantly lower than the LG (86%) (p=0.001). The 5-year PFS of the HG (36%) was significantly lower than that of the LG (67%) (p

Dental records play an important role in forensic identification. To this end, postmortem dental findings and teeth conditions are recorded in a dental chart and compared with those of antemortem records. However, most dentists are inexperienced at recording the dental chart for corpses, and it is a physically and mentally laborious task, especially in large scale disasters. Our goal is to automate the dental filing process by using dental x-ray images. In this study, we investigated the application of a deep convolutional neural network (DCNN) for classifying tooth types on dental cone-beam computed tomography (CT) images. Regions of interest (ROIs) including single teeth were extracted from CT slices. Fifty two CT volumes were randomly divided into 42 training and 10 test cases, and the ROIs obtained from the training cases were used for training the DCNN. For examining the sampling effect, random sampling was performed 3 times, and training and testing were repeated. We used the AlexNet network architecture provided in the Caffe framework, which consists of 5 convolution layers, 3 pooling layers, and 2 full connection layers. For reducing the overtraining effect, we augmented the data by image rotation and intensity transformation. The test ROIs were classified into 7 tooth types by the trained network. The average classification accuracy using the augmented training data by image rotation and intensity transformation was 88.8%. Compared with the result without data augmentation, data augmentation resulted in an approximately 5% improvement in classification accuracy. This indicates that the further improvement can be expected by expanding the CT dataset. Unlike the conventional methods, the proposed method is advantageous in obtaining high classification accuracy without the need for precise tooth segmentation. The proposed tooth classification method can be useful in automatic filing of dental charts for forensic identification. A new application of deep convolutional neural network to dental images was explored.Good classification performance was obtained even with a small number of data.Data augmentation, especially the intensity transformation was effective in improving the classification performance.Performance was not strongly dependent on resizing methods except for the crop method.DCNN was effective in tooth classification without the need for precise tooth segmentation

Alveolar bone resorption, which can be observed on dental panoramic radiographs (DPRs), is one of the most important signs of the progression of periodontal disease. However, quantitative and consistent evaluation of alveolar bone resorption is labor intense, because of a large number of DPR examinations performed each year. In our previous study, we developed an automated scheme for detection of three lines, corresponding to an occlusion line, an alveolar line and a root apex line, to measure the alveolar bone ratio (ABR), which may be useful to dentists in early detection of periodontal disease. In this study, we propose a new image transformation that maps the tooth region to a standardized dentition image for improved visualization and detection of alveolar crest points by probability estimation. The proposed method was applied to 92 DPRs with 4 degrees of alveolar bone resorption. The ABR measurement obtained by the proposed method was compared with the manual measurement of alveolar bone loss (ABL). In this preliminary investigation, the computer-estimated ABR was moderately correlated with the manual ABL. The result indicates the potential usefulness of the method for early detection and consistent diagnosis of periodontal disease.

Enzalutamide is a novel, non-steroidal anti-androgen that was approved for the treatment of patients with castration-resistant prostate cancer (CRPC) in 2014 in Japan. To assess the potency of enzalutamide treatment in Japan, we performed a pilot retrospective study. Among 91 patients who received treatment in our Institution between May 2014 and July 2015, 51 patients with docetaxel-naïve CRPC (56.0%) underwent enzalutamide therapy. The median progression-free survival (PFS) and overall survival (OS) were 10.2 months and 27.9 months, respectively. The remaining 40 patients with CRPC (44.0%) underwent enzalutamide therapy after docetaxel. The median PFS and OS were 4.4 months and not reached, respectively. Among patients with docetaxel-naïve CRPC, 12 (24%) experienced adverse events, whereas 16 (40%) experienced adverse events after docetaxel. Fatigue (15%) and appetite loss (13%) were the most common. We partially clarified the characteristics of enzalutamide therapy in Japan. The PFS associated with enzalutamide might be shorter in Japanese patients.

Purpose The REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/Dkk-3 type-a in a broad range of human malignancies. Methods We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed. Results The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2′-deoxycytidine treatment. We found that estrogen receptor–positive breast cancers were significantly more common among the methylated group than among the non-methylated group. Conclusions REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies.

The biological responses to mesh in vivo have been evaluated in some papers, but the in vivo condition of mesh and plugs have not been sufficiently evaluated. This study evaluated the endoscopic observations and histological assessments of mesh plugs using swine models.An artificial abdominal hernia was established in the porcine abdomen, and repaired using three different sizes of two types of plug, Proloop (ATRIUM Medical Corporation, Hudson, NH, USA) or Perfix (BARD Medical Division, Covington, GA, USA). The in vivo conditions of each plug were periodically observed using a laparoscope. Moreover, a histological evaluation of the plugs was performed 3 months after implantation.The laparoscopic observation revealed that inversion of the plugs occurred in 10 out of 18 cases repaired with Perfix, while no case repaired with Proloop inverted. The large and medium sizes of Perfix plugs were inclined by an average of more than 30°. In addition, the triangular shape of Perfix plugs was broken and the vertical/horizontal ratio was enlarged during the observation period, while Proloop plugs shrank both vertically and horizontally. The inflammatory cell count was significantly lower within the Proloop plugs than within Perfix plugs.Proloop plugs are apparently superior because they are stable even 3 months after implantation.

The number of participants in thoracic or abdominal examinations using multi-detector-row CT (MDCT) has been increasing recently. If the degree of progress of osteoporosis can be estimated using these images, it may be useful as it will allow predictions of vertebral fractures without an additional radiation exposure. The aims of this study were to investigate segmental variations in bone mineral density (BMD) distributions of thoracic and lumbar vertebral bodies and to show specific differences according to age and gender. A large database including 1,031 Japanese subjects for whom MDCT was used to examine various organs and tissues was utilized in this study for trabecular BMD at thoracic and lumbar vertebrae. In relationship to vertebral level, L3 had the lowest trabecular BMD. BMD tended to gradually increase from L3 to T1 in all age categories. Also, there was a moderate correlation between vertebrae whose distance from each other was great whereas there was a high correlation between adjacent vertebrae. It may be appropriate to use an arbitrary vertebra as a first approximation for assessing vertebrae that are in the area of predilection for the fracture; however, to better understand their behavior, it may be necessary to measure BMD directly in this region. This study showed trabecular BMD distribution at healthy thoracic and lumbar vertebrae in Japanese subjects and specific differences in age and gender. Improved knowledge about vertebral BMD may help with the diagnosis of primary osteoporosis using MDCT.

This report presents a very rare case of a primary diaphragmatic hemangioma, which was successfully treated by laparoscopic surgery. A 64-year-old man with a left diaphragmatic mass without any significant symptoms was treated by laparoscopic surgery and thus was diagnosed to have a diaphragmatic hemangioma following a pathological examination. Laparoscopic treatment in the deep and narrow abdominal spaces such as the diaphragmatic region is very useful as a less invasive treatment, as well as providing an excellent observation from which to make an accurate diagnosis.

142 Background: Low-dose-rate brachytherapy (BT) is the internal radiation therapy for non-metastatic prostate cancer by implanting radioactive isotope Iodine 125 into the prostate. The carcinogenetic effect of radiation for the treatment of cancer has been proven during the last decades. However, few studies have been reported about brachytherapy-induced secondary malignancies. In this study, we assessed the BT-induced secondary malignancies in our institution. Methods: We reviewed 487 patients treated with low-dose-rate BT from 2006 to 2016 in our hospital. We checked the occurrence of metachronous malignancies (MM) in all the patients and examined the features of MM including the number, organ sites, histology, period from BT to the occurrence, and analyzed whether the features meet the criteria of radiation-induced malignancies. We also examined the relationship between the BT-related radiation doses and the occurrence of MM. We adopted the criteria of radiation-induced cancer proposed by Sakai et al in 1981; different pathological feature from the organ of origin, the follow-up duration after radiation therapy (over 5 years), and whether the lesion is located in the irradiated field. Results: After a median follow-up period of 57 months (range 10-125 months), 23 MM occurred, which were bladder cancer in 4 cases (0.8%), esophageal in 2 (0.4%), gastric in 5 (1.0%), colon in 4 (0.8%), rectal in 3 (0.6%), pancreatic in 1 (0.2%), lung in 3 (0.6%), and brain in 1 (0.2%). Time from initial treatment to MM was 36 months (range 1-85 months). None of the cases had experienced biochemical recurrence. Average radiation dose to the urethra and the rectum including UD90, UD5, U200, R100, R150 showed no significant difference compared to the patients without occurrence of MM. According to the Sakai’s criteria, one bladder and one rectal cancer were judged as radiation-induced secondary malignancies (0.2%). Conclusions: The risk of secondary malignancies in patients undergoing BT was very low. Further studies with longer follow-up are required because it has been only about 10 years since low-dose-rate brachytherapy started in Japan.

487 Background: Lipid cell variant (LCV) of urothelial carcinoma (UC) which was first described by Mostofi et al in 1999 is a very rare variant of UC. Because it has only been documented in occasional case reports and a small series about this variant since then, clinicopathological characteristics of LCV are not yet clarified. In this study, we assessed the clinicopathological characteristics of LCV experienced in our hospital. Methods: The medical records of patients with LCV, who were treated in our hospital between September 2015 and September 2017, were retrospectively reviewed and analyzed. Results: In this period, of 301 patients undergoing TURBT and 42 patients undergoing nephroureterectomy, 13 patients including 10 patients with bladder cancer and 3 with pelvic ureter cancer, were found to be diagnosed as LCV of UC at our hospital. The median observation period of these patients was 6 months (IQR, 4-9 months). Among 10 bladder cancer patients who had confirmed this variant in transurethral resection of bladder tumor (TURBT) specimens, all cases had concurrent high-grade UC and the most cases had tumor features including pT2 or more local stages and lympho-vascular invasion (LVI) positive. Co-existence of micropapillary and/or plasmacytoid variant were seen in 5 patients. Lymph node metastases were observed in 3 patients, and this variant was histologically confirmed within the lymph node metastatic tissue in one case. No patient had distant metastasis. Among 3 pelvic ureter cancer patients who had undergone nephroureterectomy, all cases had concurrent high-grade UC and the most cases had tumor features including pT3 local stage and LVI positive. Micropapillary variant was coexisted in one patient. No patient had distant metastasis. 7 patients were no evidence of disease and 6 were alive with disease. The estimated median time from surgery to recurrence was not reached. The 6-months disease-free survival rate was 59%. Conclusions: LCV is seen in the patients who have high-grade UC, and tends to be accompanied with other aggressive variants including micropapillary and plasmacytoid. All patients with this variant had advanced stage cancer at presentation with high recurrence rates.

628 Background: LDA in solid RCC on CT is often interpreted as ‘central necrosis’ in routine clinical practice. However, the details of clinicopathological (CP) features of LDA of RCC on CT and their prognostic significance have not been shown. We retrospectively investigated LDA of RCC to clarify the CP features and prognostic significance. Methods: Of 428 surgically treated patients for RCC between January 2007 and March 2017 at Nippon Medical School hospital, we found 267 cases who had dynamic CT performed before operation. Among them, we selected and analyzed 199 consecutive cases whose tumor had low density area and whose cancer status resulted in no evidence of disease after surgery. We first examined pathological features of LDA. Then, we examined the correlation between pathological features of LDA and CP parameters and prognosis. The differences of values between the three groups were examined with the Kruskal-Wallis test. Recurrence free survival (RFS) was examined with the Kaplan-Meyer curves and the log-rank test. Results: The histology of LDA was divided into two groups: central necrosis (+) or (-: NN). Central necrosis (+) group was further divided into two subgroups: with neutrophilic infiltration (NI+) and without NI (NI-). This means that, in the end, there were three groups according to microscopic findings: group A (NI+, n = 20, 10%), B (NI-, n = 55, 28%), C (NN, n = 124, 62%). The pathological features of the NN group were composed of hyaline degeneration, hydropic degeneration, fibrosis, scars, and so on. The results of the comparison between CP parameters among the three groups were as follows: C-reactive protein, WBC, platelet, and alkaline phosphatase are statistically higher, and hemoglobin, triglyceride, and albumin were statistically lower in group A. CT value was statistically lower in group A and B. Median follow-up was 35months, and 3-year RFS (group A, B, C, p value) was (49.8%, 77.9%, 94.3%, p < 0.0001). Conclusions: In RCC patients only about one-third of LDA on CT was shown to be central necrosis. Necrosis with NI was clinically most closely associated with poor prognosis. Central necrosis may be predictive from lower CT values compared to non-necrotic tissues.

We examined the methylation status in 100 specimens of lung adenocarcinomas measuring 2cm or less and with bronchioloalveolar carcinoma (BAC) components (Noguchi types A-C) and then compared the methylation status between noninvasive tumors (Noguchi type A or B) and invasive tumors (Noguchi type C). Methylation-specific PCR was used to determine the methylation statuses of p16(INK4a), RASSF1A, CDH13, RARbeta, and Cyclin D2. The methylation index that was regarded as representing the degree of methylation was calculated. We also determined the mutational statuses of EGFR exons 19 and 21 using a PCR-based method. A multivariate analysis showed that the aberrant methylation of p16(INK4a), RASSF1A, and CDH13 was significantly more frequent in invasive tumors than in noninvasive tumors [p16(INK4a), 36.5% versus (vs.) 8.3%, P=0.0023; RASSF1A, 46.2% vs. 14.6%, P=0.0012; CDH13, 42.3% vs. 10.4%, P=0.0006]. The methylation index was significantly higher in invasive tumors than in noninvasive tumors (P=0.004). The methylation of p16(INK4a) was significantly more frequent in EGFR wild-type tumors than in EGFR mutant tumors (P=0.021). Our results indicate the involvement of epigenetic alterations in the progression of adenocarcinoma with BAC components.

Computed tomography (CT) guided lung biopsy is a useful examination in diagnosing pulmonary diseases, but the complications such as pneumothorax or pulmonary hemorrhage can not be ignored. Among them, air embolization is a severe complication, although it is infrequently encountered. Forty two-year-old man admitted to our department for the examination of left lung tumor. CT guided lung biopsy was performed. After examination, the patient showed disturbance in cardiac function, which recovered in several minutes. Chest CT revealed air bubble in the left ventricle. After 2-hours head down position followed by bed rest, air bubble is confirmed to be dissappeared by CT.

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with an extremely poor prognosis. The incidence of MPM is increasing as a result of widespread exposure to asbestos. The molecular pathogenesis of MPM remains unclear. The present study analyzed the frequency of various genomic copy number gains (CNGs) in MPM using reverse transcription-quantitative polymerase chain reaction. A total of 83 primary MPMs and 53 primary lung adenocarcinomas were analyzed to compare the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2. In MPM, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 12 (14.5%), 8 (9.6%), 5 (6.0%), 4 (4.8%) and 1 (1.2%) of the samples, respectively. In lung adenocarcinomas, the CNGs of EGFR, KRAS, MET, FGFR1 and SOX2 were detected in 21 (39.6%), 12 (22.6%), 5 (9.4%), 10 (18.9%) and 0 (0.0%) of the samples, respectively. The CNGs of EGFR, KRAS and FGFR1 were significantly less frequent in the MPMs compared with the lung adenocarcinomas (P=0.0018, 0.048 and 0.018, respectively). Overall, the MPMs exhibited these CNGs less frequently compared with the lung adenocarcinomas (P=0.0002). The differences in CNGs between the two tumor types suggested that they are genetically different.

Findings on dental panoramic radiographs (DPRs) have shown that mandibular cortical index (MCI) based on the morphology of mandibular inferior cortex was significantly correlated with osteoporosis. MCI on DPRs can be categorized into one of three groups and has the high potential for identifying patients with osteoporosis. However, most DPRs are used only for diagnosing dental conditions by dentists in their routine clinical work. Moreover, MCI is not generally quantified but assessed subjectively. In this study, we investigated a computer-aided diagnosis (CAD) system that automatically classifies mandibular cortical bone for detection of osteoporotic patients at early stage. First, an inferior border of mandibular bone was detected by use of an active contour method. Second, regions of interest including the cortical bone are extracted and analyzed for its thickness and roughness. Finally, support vector machine (SVM) differentiate cases into three MCI categories by features including the thickness and roughness. Ninety eight DPRs were used to evaluate our proposed scheme. The number of cases classified to Class I, II, and III by a dental radiologist are 56, 25 and 17 cases, respectively. Experimental result based on the leave-one-out cross-validation evaluation showed that the sensitivities for the classes I, II, and III were 94.6%, 57.7% and 94.1%, respectively. Distribution of the groups in the feature space indicates a possibility of MCI quantification by the proposed method. Therefore, our scheme has a potential in identifying osteoporotic patients at an early stage.

A 48-year-old woman with a 3-month history of back pain was admitted for further examination of multiple left pleural nodules. She had undergone bilateral breast augmentation with silicone implants 10 years previously. Nine years after the operation, both ruptured implants were removed, and autologous fat was injected. Computed tomography revealed multiple pleural nodules suggestive of malignant pleural mesothelioma. Thoracoscopic exploration revealed multiple pleural nodules with massive pleural adhesions. The nodules were filled with viscous liquid and were histologically determined to be siliconomas. Disseminated pleural siliconoma should be recognized as a late adverse event of silicone breast implantation.

We are developing a computer-aided diagnosis (CAD) system for extracting and recognizing thoracic organ regions from chest CT images. In a previous study, we have shown that this system can automatically recognize nine kinds of human organ and tissue regions from multi-slice CT images and provide some useful applications for visualizing CT images three-dimensionally (3-D) or two-dimensionally (2-D) based on preliminary recognition results. In this paper, we propose some further studies for this system that focus on lung structure recognition. These studies include: (1) identification of thoracic cage region, (2) extraction of major and minor fissures and classification of lung regions, (3) classification of lung surface and identification of hilus pulmonis. The proposed methods have been applied to three chest CT images for recognizing lung structure and have demonstrated promising results.

The purpose of this study was to improve an automated scheme for detecting carotid artery calcification (CAC) in dental panoramic radiographs (DPRs). Using 100 DPRs, the sensitivity of CAC detection employing our previous method was 90.0% with 5.0 false positives (FPs) per image. This study describes two enhancements. One is the adoption of a new feature for the position of CACs in addition to previous features. The other is feature selection employing the support vector machine using all combinations. Five of 12 features were selected. Using our proposed method, the average sensitivity for the same database proved to be 90.0%, with only 2.5 FPs per image. These results indicate the potential effectiveness of the new positional feature and feature selection.

Hemorrhagic radiation cystitis is an example of a typical radiotherapy-induced adverse event. However, the optimal treatment for hemorrhagic radiation cystitis is not known. There are limited data regarding the use of argon plasma coagulation for hemorrhagic radiation cystitis. Here, we present the use of argon plasma coagulation using a gastrointestinal endoscope to treat hemorrhagic radiation cystitis. The patient was a 75-year-old male patient with hemorrhagic radiation cystitis due to external beam irradiation for prostate adenocarcinoma. Six years after radiotherapy, the patient presented with macroscopic hematuria over the preceding 4 months, and laboratory investigations revealed a low hemoglobin level. The hematuria was not controlled with 2 days of bladder irrigation using normal saline. Thus, argon plasma coagulation using an upper gastrointestinal endoscope was considered for treatment of the hemorrhagic radiation cystitis. The cystoscopic examination revealed diffuse radiation cystitis with oozing telangiectasia and coagula. All of the bleeding sites and telangiectasia were coagulated using argon plasma coagulation. Following treatment, the patient's clinical symptoms improved and did not recur. The hemoglobin level also recovered. No complications associated with the treatment were observed during the 6-month follow-up period. Thus, argon plasma coagulation using a gastrointestinal endoscope is a safe and effective treatment for hemorrhagic radiation cystitis.

INTRODUCTION AND OBJECTIVES: F-FDG PET/CT is widely used to diagnose metastases in many kinds of cancer, including bladder cancer. It may also be useful in patients with upper tract urothelial carcinoma (UTUC); however, the utility of PET/CT in the management of UTUC has not been reported. In the current study, the clinical course of patients with UTUCwho underwent PET/CTwas retrospectively analyzed to investigate its clinical value and impact on patient management. METHODS: Between October 2012 and September 2013, 59 consecutive patients with UTUC underwent F-FDG PET/CT for initial staging (n 1⁄4 48) or restaging (n 1⁄4 11) following conventional CT or MRI. The imaging findings were validated using histopathology or serial imaging, and the diagnostic accuracy of PET/CT and CT/MRI for detecting metastases were assessed and compared statistically using McNemar0s test in both patient-based and lesion-based analyses. In addition, the clinical impact of PET/CT on patient management was analyzed by comparing questionnaires that were completed by the attending physicians before and after PET/CT. RESULTS: In the patient-based analysis, 26 (44%) of the 59 patients were diagnosed as having metastases. The sensitivity/specificity/accuracy were 96%/94%/95% in PET/CT and 81%/88%/85% in CT/MRI. The accuracy of PET/CT was significantly superior to CT/MRI (P 1⁄4 0.031). There were 212 lesions analyzed in 59 patients. In the lesion-based analysis, 179 (84%) of the 212 lesions were diagnosed as metastases. PET/CT had a significantly better sensitivity (77%) than CT/MRI (57%, P

Several studies have reported the presence of carotid artery calcifications (CACs) on dental panoramic radiographs (DPRs) as a possible sign of arteriosclerotic diseases. However, CACs are not easily visible at the common window level for dental examinations, and dentists, in general, are not looking for CACs. Computerized detection of CACs may help dentists in referring patients with a risk of arteriosclerotic diseases to have a detailed examination at a medical clinic. Downside of our previous method was a relatively large number of false positives (FPs). In this study, we attempted to reduce FPs by including an additional feature and selecting effective features for the classifier. A hundred DPRs including 34 cases with calcifications were included. Initial candidates were detected by thresholding the output of top-hat operation. For each candidate, 10 features and a new feature characterizing the relative position of a CAC with reference to the lower mandible edge were determined. After the rule-based FP reduction, candidates were classified into CACs and FPs by a support vector machine. Based on the leave-one-out cross-validation evaluations, an average number of FPs was 3.1 per image at 90.4% sensitivity using seven features selected. Compared to our previous method, the number of FPs was reduced by 38% at the same sensitivity level. The proposed method has a potential in identifying patients with a risk of arteriosclerosis early via general dental examinations.

Osteoporosis has become an increasingly important public health problem because of the rapidly aging populations. To obtain the sophisticated knowledge on normal vertebral anatomy is essential to understand the vertebral fracture risk. Multi-detector row computed tomography (MDCT) method can be used for quantitative analysis of vertebral anatomy such as volumetric bone mineral density (vBMD), geometry, and alignment with high accuracy and precision from the same dataset. This chapter described our latest two findings on statistical analysis and image analysis for vertebral anatomy by use of the image processing technique on the MDCT scanning. One was the population-based statistical analysis on vBMD at vertebrae. It showed the trabecular vBMD distribution at healthy thoracic and lumbar vertebrae in Japanese subjects and specific differences in age and gender. The other presented a computerized scheme to quantify the vertebral geometry. The scheme provided appropriate values on the vertebral geometry with numerous CT cases. It is likely that such computer-based attempts will help us to achieve the sophisticated vertebral anatomy.

Background Both visceral pleural invasion (VPI) and lymphovascular invasion (LVI) have been shown to be adverse prognostic factors for early-stage non–small-cell lung cancer (NSCLC). Positive VPI upstages the T category of tumors ≤ 2 cm (T1a) to T2a, whereas LVI is not adapted as a descriptor for the Tumor, Node, Metastasis classification system. This study was conducted to evaluate the prognostic impacts of VPI and LVI in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. Methods We reviewed records of a total of 142 patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm, who underwent lobectomy with hilar and mediastinal lymph node dissection between January 2001 and December 2009. We conducted univariate and multivariate analyses to evaluate the impact of VPI, LVI, and other clinicopathologic factors on survival. Results Visceral pleural invasion and LVI were diagnosed as positive in 18 (12.7%) and 22 (15.5%) patients, respectively. Male sex, squamous cell carcinoma, positive VPI, and positive LVI were risk factors for overall survival. Squamous cell carcinoma, positive VPI, and positive LVI were risk factors for relapse-free survival. In multivariate analysis, squamous cell carcinoma and positive LVI were independent risk factors for overall survival, and positive LVI was an independent risk factor for relapse-free survival. Conclusions Positive LVI was more important than VPI as a prognostic factor in patients with pN0 NSCLC and a tumor diameter of ≤ 2 cm. Adjuvant chemotherapy should be considered for such patients, to improve the treatment outcomes.

Purpose Mandibular cortical width (MCW) measured on dental panoramic radiographs (DPRs) was significantly correlated with bone mineral density. We developed a computer-aided diagnosis scheme that automatically measures MCW to assist dentists in describing a possible osteoporotic risk and suggesting further examinations. Methods In our approach, potential mandible edges are detected by modified Canny edge detector. On the basis of the edge information, a contour model is selected from the reference data and is fitted to the test case by using the active contour model. The reference mental foramina positions of the model are employed as the MCW measurement locations. The MCW is measured on the basis of the grayscale profiles obtained along the lines perpendicular to the fitted mandible contour. One hundred DPRs, including 26 DPRs from osteoporotic cases, were used to evaluate our proposed scheme. Results Experimental results showed that the average MCWs for osteoporotic and control cases were 2.2 and 3.9 mm, respectively. When a threshold of 2.7 mm was applied, the sensitivity and specificity for identifying osteoporotic patients were 88.5 and 97.3 %, respectively. Conclusion An automated MCW measurement technique is feasible using DPRs, and this method has a potential to identify asymptomatic osteoporotic patients.

Osteoporosis is a common disease characterized by low bone mass and microstructural deterioration of bone tissue, with an increased fracture risk. With an aging population, osteoporosis and its related fractures have become an increasingly important health and socioeconomic issue. The aim of osteoporosis screening and treatment is to prevent bone fracture. A fracture occurs when the external force applied to a bone exceeds its strength. The ability of a bone to resist fracture depends on its amount, spatial distribution, and intrinsic properties. Sophisticated bone imaging techniques, as new modalities, improve the potential for non-invasive study of bone anatomy, physiology and pathophysiology. The objective of bone imaging in osteoporosis is to minimize fracture occurrence by identifying the osteoporotic process at an early stage, differentiate distinctive patterns of bone loss, predict fracture risk accurately and monitor treatment response precisely. Non-invasive imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), provide structural information, beyond bone mineral density (BMD). Non-invasive or non-destructive imaging techniques can provide important structural information about the local and systemic skeletal status and about the propensity to fracture. These advanced imaging techniques provide information about bone beyond standard bone mineral densitometry. In this chapter, we will discuss recent progress in bone imaging in a range from the macroto micro-structures in order to investigate the structural basis of the skeletal fragility underlying osteoporosis.

To identify asymptomatic patients is the challenging task and the essential first step in diagnosis. Findings of dental panoramic radiographs include not only dental conditions but also radiographic signs that are suggestive of possible systemic diseases such as osteoporosis, arteriosclerosis, and maxillary sinusitis. Detection of such signs on panoramic radiographs has a potential to provide supplemental benefits for patients. However, it is not easy for general dental practitioners to pay careful attention to such signs. We addressed the development of a computer-aided detection (CAD) system that detects radiographic signs of pathology on panoramic images, and the design of the framework of new screening pathway by cooperation of dentists and our CAD system. The performance evaluation of our CAD system showed the sensitivity and specificity in the identification of osteoporotic patients were 92.6 % and 100 %, respectively, and those of the maxillary sinus abnormality were 89.6 % and 73.6 %, respectively. The detection rate of carotid artery calcifications that suggests the need for further medical evaluation was approximately 93.6 % with 4.4 false-positives per image. To validate the utility of the new screen ing pathway, preliminary clinical trials by using our CAD system were conducted. To date, 223 panoramic images were processed and 4 asymptomatic patients with suspected osteoporosis, 7 asymptomatic patients with suspected calcifications, and 40 asymptomatic patients with suspected maxillary sinusitis were detected in our initial trial. It was suggested that our new screening pathway could be useful to identify asymptomatic patients with systemic diseases. Keywords: Dental panoramic radiography, Computer-aided detection system, Osteoporosis, Carotid artery calcifications, Maxillary sinusitis, New screening pathway

The purpose of this study is to develop an automated carotid artery calcification (CAC) detection scheme on dental panoramic radiographs (DPRs). The CAC is one of the indices for predicting the risk of arteriosclerosis. First, regions of interest (ROIs) that include CACs were determined on the basis of inflection points of the mandibular contour. Initial CAC candidates were detected by using a grayscale top-hat filter and simple grayscale thresholding technique. Finally, a rule-based approach and support vector machine to reduce the number of false positive (FP) findings were applied using features such as area, location, and circularity. Thirty-four DPRs were used to evaluate the proposed scheme. The sensitivity for the detection of CACs was 93.6% with 4.4 FPs per image. Experimental results showed that our computer-aided detection scheme may be useful to detect CACs.

For gaining a better understanding of bone quality, a great deal of attention has been paid to vertebral geometry in anatomy. The aim of this study was to design a decision support scheme for vertebral geometries. The proposed scheme consists of four parts: (1) automated extraction of bone, (2) generation of median plane image of spine, (3) detection of vertebrae, (4) quantification of vertebral body width, depth, cross-sectional area (CSA), and trabecular bone mineral density (BMD). The proposed scheme was applied to 10 CT cases and compared with manual tracking performed by an anatomy expert. Mean differences in the width, depth, CSA, and trabecular BMD were 3.1 mm, 1.4 mm, 88.7 mm 2 , and 7.3 mg/cm 3 , respectively. We found moderate or high correlations in vertebral geometry between our scheme and manual tracking ( r > 0.72). In contrast, measurements obtained by using our scheme were slightly smaller than those acquired from manual tracking. However, the outputs of the proposed scheme in most CT cases were regarded to be appropriate on the basis of the subjective assessment of an anatomy expert. Therefore, if the appropriate outputs from the proposed scheme are selected in advance by an anatomy expert, the results can potentially be used for an analysis of vertebral body geometries.

The multidetector row computed tomography (MDCT) method has the potential to be used for quantitative analysis of osteoporosis with higher accuracy and precision than that provided by conventional two-dimensional methods. It is desirable to develop a computer-assisted scheme for analyzing vertebral geometry using body CT images. The aim of this study was to design a computerized scheme for the localization of vertebral bodies on body CT images. Our new scheme involves the following steps: (i) Re-formation of CT images on the basis of the center line of the spinal canal to visually remove the spinal curvature, (ii) use of information on the position of the ribs relative to the vertebral bodies, (iii) the construction of a simple model on the basis of the contour of the vertebral bodies on CT sections, and (iv) the localization of individual vertebral bodies by using a template matching technique. The proposed scheme was applied to 104 CT cases, and its performance was assessed using the Hausdorff distance. The average Hausdorff distance of T2-L5 was 4.3 mm when learning models with 100 samples were used. On the other hand, the average Hausdorff distance with 10 samples was 5.1 mm. The results of our assessments confirmed that the proposed scheme could provide the location of individual vertebral bodies. Therefore, the proposed scheme may be useful in designing a computer-based application that analyzes vertebral geometry on body CT images.

X-ray CT images have been widely used in clinical diagnosis in recent years. A modern CT scanner can generate about 1000 CT slices to show the details of all the human organs within 30 seconds. However, CT image interpretations (viewing 500-1000 slices of CT images manually in front of a screen or films for each patient) require a lot of time and energy. Therefore, computer-aided diagnosis (CAD) systems that can support CT image interpretations are strongly anticipated. Automated recognition of the anatomical structures in CT images is a basic pre-processing of the CAD system. The bone structure is a part of anatomical structures and very useful to act as the landmarks for predictions of the other different organ positions. However, the automated recognition of the bone structure is still a challenging issue. This research proposes an automated scheme for segmenting the bone regions and recognizing the bone structure in noncontrast torso CT images. The proposed scheme was applied to 48 torso CT cases and a subjective evaluation for the experimental results was carried out by an anatomical expert following the anatomical definition. The experimental results showed that the bone structure in 90% CT cases have been recognized correctly. For quantitative evaluation, automated recognition results were compared to manual inputs of bones of lower limb created by an anatomical expert on 10 randomly selected CT cases. The error (maximum distance in 3D) between the recognition results and manual inputs distributed from 3-8 mm in different parts of the bone regions.

This paper describes a fully automated segmentation and recognition scheme, which is designed to recognize lung anatomical structures in the human chest by segmenting the different chest internal organ and tissue regions sequentially from high-resolution chest CT images. A sequential region-splitting process is used to segment lungs, airway of bronchus, lung lobes and fissures based on the anatomical structures and statistical intensity distributions in CT images. The performance of our scheme is evaluated by segmenting lung structures from high-resolution multi-slice chest CT images from 44 patients; the validity of our method was proved by preliminary experimental results.

Computer-aided diagnosis (CAD) has been expected to help radiologists to improve the accuracy of abnormality detection and reduce the burden during CT image interpretations. In order to realize such functions, automated segmentations of the target organ regions are always required by CAD systems. This paper describes a fully automatic processing procedure, which is designed to identify inter-lobe fissures and divide lung into five lobe regions. The lung fissures are disappeared very fuzzy and indefinite in CT images, so that it is very difficult to extract fissures directly based on its CT values. We propose a method to solve this problem using the anatomy knowledge of human lung. We extract lung region firstly and then recognize the structures of lung vessels and bronchus. Based on anatomy knowledge, we classify the vessels and bronchus on a lobe-by-lobe basis and estimate the boundary of each lobe region as the initial fissure locations. Within those locations, we extract lung fissures precisely based on an edge detection method and divide lung regions into five lung lobes lastly. The performance of the proposed method was evaluated using 9 patient cases of high-resolution multi-slice chest CT images; the improvement has been confirmed with the reliable recognition results.