Prognostication in Lymph Node-Positive Prostate Cancer with No PSA Persistence After Radical Prostatectomy.

BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.

Prognosis based on postoperative PSA levels and treatment in prostate cancer with lymph node involvement.

BACKGROUND: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. METHODS: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). RESULTS: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. CONCLUSIONS: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.

Efficacy of fracture stem in reverse shoulder arthroplasty for 3- or 4-part proximal humerus fractures.

BACKGROUND: This study compared the clinical results of fracture stems and conventional stems using the same glenoid component in reverse shoulder arthroplasty for proximal humerus fractures in the elderly. METHODS: This retrospective study included 35 patients who underwent Grammont-type reverse shoulder arthroplasty for proximal humerus fractures from 2014 to 2020. The average age at surgery was 79.2 (range, 65-92) years, with 33 female shoulders. Fracture types per Neer classification were 3-part fracture, 4-part fracture, in 13 and 22 shoulders, respectively. The final follow-up period was 35 (range, 24-81) months. The Constant score, American Shoulder and Elbow Surgeons score, shoulder range of motion, and healing of greater tuberosities at the final follow-up of AEQUALIS™ REVERSED (Conventional stem group: n = 15) and AEQUALIS™ REVERSED FX (Fractured stem group: n = 20) were retrospectively investigated. RESULTS: There were no statistically significant differences in age at surgery, sex, body mass index, fracture type, waiting time from injury to surgery, or preoperative general condition between the groups. The Constant and American Shoulder and Elbow Surgeons scores of the fractured stem group were significantly higher than those of the conventional stem group (P = 0.038 and P = 0.023, respectively). The anterior elevation and external rotation at the side of the fractured stem group also showed significantly higher values than those of the conventional stem group (fractured stem group vs. conventional stem group: anterior elevation 127° ± 25° vs. 105° ± 35°, P = 0.041; external rotation 28° ± 13° vs. 13° ± 12°, P = 0.015). The greater tuberosity healing rate was 46.7% (7/15) in the conventional stem group and 85.0% (17/20) in the fractured stem group (P＝0.027). CONCLUSIONS: The findings suggest that use of a fracture-specific stem rather than a conventional stem in Grammont-type reverse shoulder arthroplasty for proximal humerus fractures improves tuberosity healing, postoperative range of motion, and clinical scores.

Radiotherapy plus androgen deprivation therapy for prostate-specific antigen persistence in lymph node-positive prostate cancer.

The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis-free survival (MFS) was the primary outcome. Patients were stratified by prostate-specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan-Meier method and log-rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15-0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.

Impact of adherence to criteria on oncological outcomes of radical prostatectomy in patients opting for active surveillance: data from the PRIAS-JAPAN study.

OBJECTIVES: This study aimed to evaluate whether oncological outcomes of radical prostatectomy differ depending on adherence to the criteria in patients who opt for active surveillance. MATERIALS AND METHODS: We retrospectively reviewed the data of 1035 patients enrolled in a prospective cohort of the PRIAS-JAPAN study. After applying the exclusion criteria, 136 of 162 patients were analyzed. Triggers for radical prostatectomy due to pathological reclassification on repeat biopsy were defined as on-criteria. Off-criteria triggers were defined as those other than on-criteria triggers. Unfavorable pathology on radical prostatectomy was defined as pathological ≥T3, ≥GS 4 + 3 and pathological N positivity. We compared the pathological findings on radical prostatectomy and prostate-specific antigen recurrence-free survival between the two groups. The off-criteria group included 35 patients (25.7%), half of whom received radical prostatectomy within 35 months. RESULTS: There were significant differences in median prostate-specific antigen before radical prostatectomy between the on-criteria and off-criteria groups (6.1 vs. 8.3 ng/ml, P = 0.007). The percentage of unfavorable pathologies on radical prostatectomy was lower in the off-criteria group than that in the on-criteria group (40.6 vs. 31.4%); however, the differences were not statistically significant (P = 0.421). No significant difference in prostate-specific antigen recurrence-free survival was observed between the groups during the postoperative follow-up period (median: 36 months) (log-rank P = 0.828). CONCLUSIONS: Half of the off-criteria patients underwent radical prostatectomy within 3 years of beginning active surveillance, and their pathological findings were not worse than those of the on-criteria patients.

Deferred radical prostatectomy in patients who initially elected for active surveillance: a multi-institutional, prospective, observational cohort of the PRIAS-JAPAN study.

BACKGROUND: This study aimed to evaluate the pathological findings and oncological outcomes of deferred radical prostatectomy in patients who initially elected for active surveillance in a Japanese cohort. METHODS: We retrospectively analyzed data collected from a multi-institutional prospective observational cohort of the Prostate Cancer Research International: Active Surveillance-JAPAN study between January 2010 and September 2020. Triggers for radical prostatectomy were disease progression based on pathological findings of repeat biopsy and patients' request. The primary end point was evaluation of prostate-specific antigen recurrence-free survival. Secondary end points were overall survival and comparison of pathological and oncological outcomes between patients stratified into immediate or late radical prostatectomy group by time to radical prostatectomy. RESULTS: Overall, 162 patients (15.7%) with prostate cancer underwent initial active surveillance followed by radical prostatectomy. The median time to radical prostatectomy was 18 months (interquartile range 14-43.3), and the median postoperative follow-up was 32 months (interquartile range 14-57.5). Prostate-specific antigen recurrence was observed in eight patients (4.9%). The 3-year prostate-specific antigen recurrence-free survival rate was 96.9%. The 5-year overall survival rate was 100%; however, one patient died of another cause. There were no significant differences in pathological findings between immediate and late radical prostatectomy groups. No significant difference in prostate-specific antigen recurrence-free survival was found between the two groups (log-rank p = 0.34). CONCLUSIONS: Radical prostatectomy after active surveillance, as an initial treatment option, does not lead to loss of curative chances in Japanese patients with early-stage prostate cancer in the short follow-up period.

Efficacy of combined androgen blockade therapy in patients with metastatic hormone-sensitive prostate cancer stratified by tumor burden.

OBJECTIVE: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. METHODS: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. RESULTS: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98. CONCLUSION: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.

Novel metastatic burden-stratified risk model in de novo metastatic hormone-sensitive prostate cancer.

The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.

Differential prognostic factors in low- and high-burden de novo metastatic hormone-sensitive prostate cancer patients.

Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens.

Genome-wide association study of individual sugar content in fruit of Japanese pear (Pyrus spp.).

BACKGROUND: Understanding mechanisms of sugar accumulation and composition is essential to determining fruit quality and maintaining a desirable balance of sugars in plant storage organs. The major sugars in mature Rosaceae fruits are sucrose, fructose, glucose, and sorbitol. Among these, sucrose and fructose have high sweetness, whereas glucose and sorbitol have low sweetness. Japanese pear has extensive variation in individual sugar contents in mature fruit. Increasing total sugar content and that of individual high-sweetness sugars is a major target of breeding programs. The objective of this study was to identify quantitative trait loci (QTLs) associated with fruit traits including individual sugar accumulation, to infer the candidate genes underlying the QTLs, and to assess the potential of genomic selection for breeding pear fruit traits. RESULTS: We evaluated 10 fruit traits and conducted genome-wide association studies (GWAS) for 106 cultivars and 17 breeding populations (1112 F1 individuals) using 3484 tag single-nucleotide polymorphisms (SNPs). By implementing a mixed linear model and a Bayesian multiple-QTL model in GWAS, 56 SNPs associated with fruit traits were identified. In particular, a SNP located close to acid invertase gene PPAIV3 on chromosome 7 and a newly identified SNP on chromosome 11 had quite large effects on accumulation of sucrose and glucose, respectively. We used 'Golden Delicious' doubled haploid 13 (GDDH13), an apple reference genome, to infer the candidate genes for the identified SNPs. In the region flanking the SNP on chromosome 11, there is a tandem repeat of early responsive to dehydration (ERD6)-like sugar transporter genes that might play a role in the phenotypes observed. CONCLUSIONS: SNPs associated with individual sugar accumulation were newly identified at several loci, and candidate genes underlying QTLs were inferred using advanced apple genome information. The candidate genes for the QTLs are conserved across Pyrinae genomes, which will be useful for further fruit quality studies in Rosaceae. The accuracies of genomic selection for sucrose, fructose, and glucose with genomic best linear unbiased prediction (GBLUP) were relatively high (0.67-0.75), suggesting that it would be possible to select individuals having high-sweetness fruit with high sucrose and fructose contents and low glucose content.

Development of an SSR marker set for efficient selection for resistance to black spot disease in pear breeding.

Black spot disease, which is caused by Alternaria alternata (Fries) Keissler Japanese pear pathotype, is one of the most harmful diseases in Japanese pear cultivation. Because of the potential harm of fungicides to consumers and the environment, resistant cultivars are desired. In this study, to enable efficient marker-assisted selection in pear breeding, we conducted comprehensive inoculation tests and genotyping with 207 pear cultivars. We identified a marker set (Mdo.chr11.27 and Mdo.chr11.34) suitable for selection for black spot resistance. In most susceptible cultivars, Mdo.chr11.27 amplified a 220-bp band and Mdo.chr11.34 amplified a 259-bp band. The genotype of Mdo.chr11.34 corresponds perfectly to the estimated genotype of Japanese pears susceptible to black spot disease. Using linkage analysis, we identified the positions of the gene for susceptibility to black spot disease in Chinese pear. Mdo.chr11.27 and Mdo.chr11.34 were tightly linked to susceptibility in Chinese pear, and the susceptibility gene was mapped at the top of linkage group 11, similar to that in Japanese pear. This marker set and the accumulation of phenotypic data will enable efficient marker-assisted breeding for black spot resistance in pear breeding.

Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

BACKGROUND: The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs. METHODS: We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center's Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD. RESULTS: The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030-2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18, P < 0.001), and will comprise notably high proportions of patients with prostatic, breast, and uterine cancers (1.80, 1.57, and 1.66, P < 0.001, respectively). CONCLUSION: Future cancer patients will be older and more likely to have CVD. Although men will continue to dominate this population, the increase in the number of women will be pronounced. Cancer care providers should be trained to recognize CVD and provide any necessary interventions concurrently with cancer therapy.

Correction to: Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

n the original publication, in a title of Table 2.

Characteristics of dynamic magnetic resonance imaging of idiopathic severe frozen shoulder.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of current techniques for dynamic 3-dimensional magnetic resonance imaging (MRI) in the diagnosis of idiopathic severe frozen shoulder (FS). MATERIALS AND METHODS: Subjects consisted of 5 healthy volunteers and 16 patients with idiopathic severe FS. We defined severe idiopathic FS as follows: range of motion ≤100° in forward flexion, ≤10° in external rotation, and ≤L5 in internal rotation. All patients suffered from continued global range of motion loss for at least 6 months. We evaluated the diagnostic characteristics of 3-dimensional dynamic MRI in FS patients compared with those in healthy volunteers. RESULTS: MRI of all FS patients displayed an abnormal intake of blood flow from the acromial arterial network and the branches of circumflex humeral arteries into the axillary pouch and the rotator interval. We named this finding "burning sign." The burning sign was present at all phases of the condition. In the FS group, the patients with enhanced deposition of contrast medium in the axillary pouch in the delayed phase (n = 11) had a statistically significant score for pain during exercise, higher than that of patients with reduced deposition of contrast medium at the same site (n = 5; P = .027). CONCLUSION: Burning sign is an abnormal finding that appears in dynamic MRI of severe FS. Hence, the burning sign may be associated with pain and inflammation in idiopathic FS.

Short-term clinical results of frozen shoulder treated with shoulder manipulation under ultrasound-guided cervical nerve root block at outpatient setting: A case series.

BACKGROUND: We evaluated the short-term clinical outcomes of frozen shoulder treatment via shoulder manipulation under ultrasound-guided cervical nerve root block (MUC). METHODS: This study included frozen shoulder patients who were unresponsive to conservative therapy for at least 6 months and were then treated with MUC. Patients with a rotator cuff tear, calcifying tendinitis, osteoarthritis, or any other shoulder disorder were excluded following X-ray, ultrasound, and magnetic resonance imaging evaluation. Although 25 patients were initially included, three patients were not followed-up for at least 1 year. We investigated a final total of 22 patients; the average age was 58 years and 59% were female. We measured shoulder pain, shoulder range of motion, and American Shoulder and Elbow Surgeons shoulder scores immediately prior to MUC, 1 week after MUC, and 1 year after MUC. A Short-Form 36-Item Health Survey was administered before MUC and 1 year after MUC. We used the Friedman and Wilcoxon signed-rank tests to identify statistical differences. Significance was defined as p < 0.05. RESULTS: MUC significantly improved shoulder pain during motion, range of motion, and American Shoulder and Elbow Surgeons scores 1 week after MUC. This improvement persisted at the 1-year follow-up. Seven of the eight Short-Form 36-Item Health Survey measures were significantly improved 1 year after MUC. One patient (4.5%) developed Horner's syndrome, although symptoms resolved within several hours without treatment. CONCLUSION: MUC for frozen shoulder was safe and resulted in a significant improvement in shoulder pain and range of motion 1 week after the procedure. This improvement persisted at the 1-year follow-up.

Estimation of loss of genetic diversity in modern Japanese cultivars by comparison of diverse genetic resources in Asian pear (Pyrus spp.).

BACKGROUND: Pears (Pyrus spp.) are one of the most important fruit crops in temperate regions. Japanese pear breeding has been carried out for over 100 years, working to release new cultivars that have good fruit quality and other desirable traits. Local cultivar 'Nijisseiki' and its relatives, which have excellent fruit texture, have been repeatedly used as parents in the breeding program. This strategy has led to inbreeding within recent cultivars and selections. To avoid inbreeding depression, we need to clarify the degree of inbreeding among crossbred cultivars and to introgress genetic resources that are genetically different from modern cultivars and selections. The objective of the present study was to clarify the genetic relatedness between modern Japanese pear cultivars and diverse Asian pear genetic resources. RESULTS: We genotyped 207 diverse accessions by using 19 simple sequence repeat (SSR) markers. The heterozygosity and allelic richness of modern cultivars was obviously decreased compared with that of wild individuals, Chinese pear cultivars, and local cultivars. In analyses using Structure software, the 207 accessions were classified into four clusters (K = 4): one consisting primarily of wild individuals, one of Chinese pear cultivars, one of local cultivars from outside the Kanto region, and one containing both local cultivars from the Kanto region and crossbred cultivars. The results of principal coordinate analysis (PCoA) were similar to those from the Structure analysis. Wild individuals and Chinese pears appeared to be distinct from other groups, and crossbred cultivars became closer to 'Nijisseiki' as the year of release became more recent. CONCLUSIONS: Both Structure and PCoA results suggest that the modern Japanese pear cultivars are genetically close to local cultivars that originated in the Kanto region, and that the genotypes of the modern cultivars were markedly biased toward 'Nijisseiki'. Introgression of germplasm from Chinese pear and wild individuals that are genetically different from modern cultivars seems to be key to broadening the genetic diversity of Japanese pear. The information obtained in this study will be useful for pear breeders and other fruit breeders who have observed inbreeding depression.

Advances in Japanese pear breeding in Japan.

The Japanese pear (Pyrus pyrifolia Nakai) is one of the most widely grown fruit trees in Japan, and it has been used throughout Japan's history. The commercial production of pears increased rapidly with the successive discoveries of the chance seedling cultivars 'Chojuro' and 'Nijisseiki' around 1890, and the development of new cultivars has continued since 1915. The late-maturing, leading cultivars 'Niitaka' and 'Shinko' were released during the initial breeding stage. Furthermore, systematic breeding by the Horticultural Research Station (currently, NARO Institute of Fruit Tree Science, National Agriculture and Food Research Organization (NIFTS)) began in 1935, which mainly aimed to improve fruit quality by focusing on flesh texture and black spot disease resistance. To date, 22 cultivars have been released, including 'Kosui', 'Hosui', and 'Akizuki', which are current leading cultivars from the breeding program. Four induced mutant cultivars induced by gamma irradiation, which exhibit some resistance to black spot disease, were released from the Institute of Radiation Breeding. Among these cultivars, 'Gold Nijisseiki' has become a leading cultivar. Moreover, 'Nansui' from the Nagano prefectural institute breeding program was released, and it has also become a leading cultivar. Current breeding objectives at NIFTS mainly combine superior fruit quality with traits related to labor and cost reduction, multiple disease resistance, or self-compatibility. Regarding future breeding, marker-assisted selection for each trait, QTL analyses, genome-wide association studies, and genomic selection analyses are currently in progress.

Fine mapping of the gene for susceptibility to black spot disease in Japanese pear (Pyrus pyrifolia Nakai).

Black spot disease, which is caused by the Japanese pear pathotype of the filamentous fungus Alternaria alternata (Fries) Keissler, is one of the most harmful diseases in Japanese pear cultivation. We mapped a gene for susceptibility to black spot disease in the Japanese pear (Pyrus pyrifolia Nakai) cultivar 'Kinchaku' (Aki gene) at the top of linkage group 11, similar to the positions of the susceptibility genes Ani in 'Osa Nijisseiki' and Ana in 'Nansui'. Using synteny-based marker enrichment, we developed novel apple SSR markers in the target region. We constructed a fine map of linkage group 11 of 'Kinchaku' and localized the Aki locus within a 1.5-cM genome region between SSR markers Mdo.chr11.28 and Mdo.chr11.34. Marker Mdo.chr11.30 co-segregated with Aki in all 621 F1 plantlets of a 'Housui' × 'Kinchaku' cross. The physical size of the Aki region, which includes three markers (Mdo.chr11.28, Mdo.chr11.30, and Mdo.chr11.34), was estimated to be 250 Kb in the 'Golden Delicious' apple genome and 107 Kb in the 'Dangshansuli' Chinese pear genome. Our results will help to identify the candidate gene for susceptibility to black spot disease in Japanese pear.

Clinicopathological features and outcomes in patients with late recurrence of renal cell carcinoma after radical surgery.

OBJECTIVES: To characterize patients experiencing late recurrence after primary radical surgery for renal cell carcinoma and to approach the mechanism of late recurrence. METHODS: We retrospectively analyzed 657 consecutive patients who underwent radical surgery for pathologically confirmed ≤stage III renal cell carcinoma in a single institution between January 1981 and December 2008. Early or late recurrence was defined as a recurrence occurring before or after 60 months after primary surgery. RESULTS: Of 657 patients, 96 (14.6%) experienced early recurrence, and 41 (6.2%) developed late recurrence. Patients with late recurrence had smaller diameter of primary tumor (median 5 cm vs 8 cm, P < 0.001), lower pathological stage (P < 0.001) and lower nuclear grade (P = 0.004) at primary surgery than those with early recurrence. On multivariate analysis, vascular invasion (including microscopic and gross invasion) was the predictor of late recurrence (P < 0.01, HR 3.79). Overall survival and disease-specific survival after recurrence were longer in patients with late recurrence (median 64 and 76 months, respectively) than in those with early recurrence (34.5 and 35 months, respectively; P = 0.008 and 0.002). CONCLUSIONS: These results suggest that micrometastasis at the time of surgery associated with vascular invasion at primary tumor site and their relatively lower malignant potential could lead to late recurrence. Further studies are warranted for better understanding and managing late recurrence of renal cell carcinoma.

Effect of preoperative chemotherapy on survival of patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.

OBJECTIVES: To determine the effect of preoperative chemotherapy on survival in patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes. METHODS: We retrospectively analyzed 55 consecutive patients who received radical nephroureterectomy with or without preoperative chemotherapy for upper urinary tract urothelial carcinoma clinically involving regional lymph nodes at a single institution between January 1991 and December 2013. RESULTS: Median follow up was 18 months (range 2-193). Of 55 patients, 24 (43.6%) received preoperative chemotherapy (study group) and 31 (56.4%) underwent primary surgery (control group). Preoperative chemotherapy consisted of two to four cycles (median 3) of cisplatin-containing regimens. The fraction of patients with lower pathological T stage and N stage than clinical T stage and N stage was higher in the study group (29.2% and 54.2%) compared with the control group (3.2% and 16.1%; P = 0.013 and 0.010, respectively). The 5-year overall survival rate was significantly higher in the study group than in the control group (44.0% vs 12.9%, log-rank, P = 0.003). In multivariate analysis incorporating age at diagnosis, Eastern Cooperative Oncology Group Performance Status, clinical N stage and the number of removed lymph nodes, preoperative chemotherapy was a predictor of better overall survival (P = 0.047, HR 0.47, 95% CI 0.22-0.99). CONCLUSIONS: Preoperative chemotherapy might provide better survival outcomes in patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.