Kojiro Ohba

Nagasaki University Hospital, Nagasaki, Nagasaki, Japan

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Publications (29)70.27 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinicopathological features and prognosis of metastatic renal cell carcinoma (mRCC) vary by histopathological type. In this study, we analyzed these relationships with regard to non-clear cell RCC (nccRCC). We also analyzed the therapeutic trends for patients with mRCC. We initially identified 367 patients who were diagnosed with RCC and treated in our hospital between 2001 and 2013 ; 55 patients of whom were diagnosed with nccRCC. We reviewed their backgrounds, histopathological types and outcomes. Median age at diagnosis for patients with nccRCC was significantly younger (58.5 years) than for those with clear-cell RCC (66.3 years ; P=0.008) ; however, these histological types did not significantly differ by sex, affected side or rate of mRCC. Of the 55 nccRCC cases, 19 were mRCC, including 5 of the 8 cases of papillary type-2 RCC, and all patients who had either collecting duct carcinoma, sarcomatoid RCC or Xp11 translocation RCC. The most common metastatic site was lymph nodes. Although patients with papillary type-1 and Xp11 translocation RCC had relatively good prognoses, those with papillary type-2, collecting duct carcinoma and sarcomatoid RCC had poor prognoses. Among the 9 patients with nccRCC who received molecular targeted therapy, median survival was 13.3 months. Although existing therapeutic agents may be effective for some patients with nccRCC, identification of new target molecules and innovative drug development are needed in the future.
    Hinyokika kiyo. Acta urologica Japonica 02/2015; 61(2):43-47.
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    ABSTRACT: Met is a tyrosine kinase receptor that is considered to be a proto-oncogene. The hepatocyte growth factor (HGF)-Met signaling system plays an important role in tumor growth, invasion, and metastasis in many types of malignancies. Furthermore, Met expression has been reported to be a useful predictive biomarker for disease progression and patient survival in these malignancies. Many studies have focused on the clinical significance and prognostic role of Met in urological cancers, including prostate cancer (PCa), renal cell carcinoma (RCC), and urothelial cancer. Several preclinical studies and clinical trials are in progress. In this review, the current understanding of the pathological role of Met in cancer cell lines, its clinical significance in cancer tissues, and its predictive value in patients with urological cancers are summarized. In particular, Met-related malignant behavior in castration-resistant PCa and the different pathological roles Met plays in papillary RCC and other histological types of RCC are the subjects of focus. In addition, the pathological significance of phosphorylated Met in these cancers is shown. In recent years, Met has been recognized as a potential therapeutic target in various types of cancer; therapeutic strategies used by Met-targeted agents in urological cancers are summarized in this review.
    12/2014; 6(4):2387-403. DOI:10.3390/cancers6042387
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    ABSTRACT: Introduction Patients with muscle-invasive bladder cancer (MIBC) often undergo various preoperative treatments to improve survival; however, their efficacy and safety remain unclear. Materials and methods The anti-tumour effects and adverse events were evaluated in 163 MIBC patients who received systemic chemotherapy (SC, n = 34), intra-arterial chemotherapy (IAC, n = 50), or combined IAC and radiotherapy (IAC+R, n = 79). Results Pathological complete responses were observed in 17.6%, 22.0%, and 43.0% of patients in the SC, IAC, and IAC+R groups, respectively, with respective 5-year overall survival rates of 42.0%, 46.7%, and 50.3%. Multivariate analysis showed that successful IAC+R protocol administration was a significant predictor for survival (hazard ratio = 0.16, p = 0.028). The incidence of severe adverse events was higher in the IAC+R group (36.7%) than in the SC (9.8%) and IAC groups (16.0%). Conclusions IAC+R was useful for patients with MIBC. Successful completion and optimal patient selection were important for this treatment strategy.
    European Journal of Surgical Oncology 09/2014; 41(3). DOI:10.1016/j.ejso.2014.07.043 · 2.89 Impact Factor
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    ABSTRACT: Background Cardiac metastasis of renal cell carcinoma is an exceptional event, particularly when there is lack of inferior vena cava involvement. Indeed, only a few cases have been reported worldwide thus far. Moreover, discussion of treatment and follow-up strategies for cardiac metastasis of renal cell carcinoma is important because of the high risk of sudden death. Case presentation We report the case of a 75-year-old Japanese man with metastatic tumor in the left atrium from renal cell carcinoma. He had a history of right renal cell carcinoma, for which he had undergone hand-assisted laparoscopic nephrectomy. Lung and bone metastases were detected after nephrectomy, and treatment with interferon-alpha was initiated. After disease progression, he was treated concurrently with targeted molecular therapy and radiotherapy for bone metastasis. After these therapies, a 42 × 24 mm mass was found on transthoracic echocardiography in left atrium without involvement of the right atrium or inferior vena cava. The provisional diagnosis was metastatic mass or myxoma, and surgical resection was performed. Histopathological examination led to a final diagnosis of metastatic tumor from clear cell renal cell carcinoma. Conclusion Cardiac metastasis, metastasis to the left atrium in particular, is rare in patients with renal cell carcinoma. In our study, surgery of the cardiac mass was effective to avoid sudden death and quality of life decline resulting from heart failure. We describe this case and review cardiac metastasis of renal cell carcinoma.
    BMC Research Notes 08/2014; 7(1):520. DOI:10.1186/1756-0500-7-520
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    ABSTRACT: Key Clinical MessagePelvic organ prolapse (POP) is common among multiparous elderly women. POP related to obstructive anuria is very uncommon, but can be life-threatening if untreated. In this report, the patient survived from a septic shock with multidisciplinary treatment and was completely cured of POP after tension-free vaginal mesh repair.
    08/2014; 2(4). DOI:10.1002/ccr3.74
  • The Journal of Urology 04/2014; 191(4):e426-e427. DOI:10.1016/j.juro.2014.02.1318 · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e916-e917. DOI:10.1016/j.juro.2014.02.2476 · 3.75 Impact Factor
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    ABSTRACT: Twist has been reported to play crucial roles for malignant aggressiveness; however, detailed pathological significance of Twist in renal cell carcinoma (RCC) is not fully understood. The present study was to clarify clinical significance and molecular functions of Twist in patients with RCC.
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    ABSTRACT: Angiogenesis plays an important role in cancer progression in many types of cancer. Evaluation of angiogenesis is often performed, but the optimal methodology for human cancer has not been agreed upon. As adequate evaluation of angiogenesis in cancer tissues might be important for prediction of prognosis and treatment decisions, we evaluated angiogenesis semiquantitatively by assessing microvessel density (MVD) in urothelial cancer of the upper urinary tract (UC-UUT). We compared the performance of three endothelial cell markers (CD31, CD34, and CD105) on formalin-fixed tissues from 122 patients diagnosed with UC-UUT without metastasis. Vascular endothelial growth factor (VEGF)-A expression was also evaluated immunohistochemically. Correlations between MVD with each marker and pT stage, grade, survival, and VEGF-A expression were investigated. Mean (standard deviation) MVD as estimated by immunohistochemical staining with anti-CD31, anti-CD34, and anti-CD105 were 47.1 (17.9)/high-power field (HPF), 70.9 (19.5)/HPF, and 31.2 (16.7)/HPF, respectively. Although all MVDs were significantly associated with pT stage and grade, CD105-MVD showed the strongest association. Similarly, CD105-MVD showed the strongest correlation with VEGF-A expression (r = 0.530, p < 0.001). Although all MVDs were associated with metastasis-free survival and cause-specific survival on univariate analysis, only CD105-MVD was retained as an independent predictor in multivariate analysis including pT stage and grade. CD105-MVD may be the preferred marker for semiquantitative assessment of angiogenesis in patients with UC-UUT.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2013; 463(5). DOI:10.1007/s00428-013-1463-8 · 2.56 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e245. DOI:10.1016/j.juro.2013.02.1996 · 3.75 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e463-e464. DOI:10.1016/j.juro.2013.02.750 · 3.75 Impact Factor
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    ABSTRACT: Human antigen R (HuR) regulates the stability of mRNA and is associated with cell proliferation, angiogenesis, and lymphangiogenesis. However, the clinical significance and pathological role of HuR in bladder cancer remains unclear. The main objective of this investigation was to clarify the relationships between HuR expression and clinical significance and cancer cell proliferation, angiogenesis, lymphangiogenesis, and expressions of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-A, -C, and -D. All expressions were examined by immunohistochemical techniques in 122 formalin-fixed specimens of bladder cancer patients. HuR expression was evaluated separately with cytoplasmic and nuclear staining. Cell proliferation, angiogenesis and lymphangiogenesis were measured as the percentage of Ki-67-positive cell (proliferation index, PI), CD34-stained vessels (microvessel density, MVD), and D2-40-stained vessels (lymph vessel density, LVD). Relationships between each HuR expression and clinicopathological features, prognosis, and expressions of COX-2 and VEGFs were analyzed by multi-variate analyses. HuR expression was also investigated in 10 mice of N-Butyl-N-[4-hydroxybutil] nitrosamine (BBN) induced bladder cancer model. In human tissues, high cytoplasmic expression was seen in 5% and 25.4% of normal and cancer cells, respectively. Nuclear HuR expression bore no significant relationship to any pathological features. However, cytoplasmic HuR expression appeared positively associated with pT stage and grade (P<0.001). In mouse tissues, similar trends were confirmed. Cytoplasmic expression correlated with PI, MVD, and LVD, as well as expression of VEGF-A and -C, but not VEGF-D. High cytoplasmic expression of HuR was a significant predictor of metastasis and cause-specific survival, and was identified as a prognostic correlative factor for metastasis (hazard ratio, 4.75; P = 0.028) in a multivariate analysis model that included pathological features. Cytoplasmic HuR appears to play important roles in cell proliferation, progression, and survival of bladder cancer patients. Its expression was associated with angiogenesis, lymphangiogenesis, and expressions of VEGF-A and -C.
    PLoS ONE 03/2013; 8(3):e59095. DOI:10.1371/journal.pone.0059095 · 3.53 Impact Factor
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    ABSTRACT: The biological activities of prostaglandin E2 are mediated through their specific receptors, E prostanoid receptors (EPRs). This family comprises 4 subtypes (EP1R-4R), and has been associated with cancer development and progression. In urological cancers, expression of EP2R and EP4R can be significant predictors of survival for renal cell carcinoma (RCC). On the other hand, EP1R, EP2R, and EP4R are known to be associated with carcinogenesis and malignant aggressiveness in prostate cancer. In addition, EP4R has been associated with tumor progression and prognosis in urothelial cancer of the upper urinary tract. There is a general agreement that non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of several malignancies including colorectal cancer. However, NSAIDs often cause gastrointestinal injury and nephropathy. On the other hand, cyclooxygenase (COX)-2-selective inhibitors can reduce the progression of cancer via the suppression of cell proliferation angiogenesis without decreasing adverse reactions. However, COX-2-selective inhibitors might increase the risk of cardiovascular disease, including myocardial infarction. More selective and detailed control of COX-2-mediated signals is thus needed to improve anti-tumor effects and to decrease adverse reactions. EPRs are expected to serve as new therapeutic targets in urological cancer, because they are more selective in malignant phenotypes. Finally, we speculate that some EPRs inhibitors may reduce adverse events and exert more intense effects on urological cancer.
    Hinyokika kiyo. Acta urologica Japonica 02/2013; 59(2):83-9.
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    ABSTRACT: OBJECTIVE: To clarify the detailed pathologic roles of prostaglandin E(2) in prostate cancer tissues, the present study investigated the clinical significance and prognostic roles of the density of tumor-associated stromal cells expressing specific receptors for prostaglandin E(2), termed "E-prostanoid (EP)1-4 receptors (EP1R-4Rs)." METHODS: The expression of each receptor was immunohistochemically examined in 114 formalin-fixed biopsy specimens. Correlations with clinicopathologic features were investigated in these specimens. Angiogenesis and lymphangiogenesis were measured by the percentage of CD34-stained vessels (microvessel density) and D2-40-stained vessels (lymph vessel density). The relationships between the density of each EPR-stained cells and the microvessel density or lymph vessel density were evaluated in 62 prostate cancer tissues obtained by radical surgery for more detailed analysis in a wider area of prostate cancer tissue. RESULTS: The density of tumor-associated cells with EP2R expression was positively associated with the N (P < .001) and M (P = .002) stages. Similarly, EP3R-positive stromal cell density was significantly associated with the N (P = .033) and M (P = .026) stages. The density of EP2R- and EP3R-stained cells correlated with the microvessel density (r = 0.42, P < .001) and lymph vessel density (r = 0.36, P = .012), respectively. A greater density of EP2R-stained cells was recognized as an independent predictor of progression (hazard ratio 7.26, P = .002) on multivariate analysis. CONCLUSION: EP2R- and EP3R-stained cells might play important roles in tumor progression, angiogenesis, and lymphangiogenesis in prostate cancer. The density of EP2R-stained stromal cells could offer a useful predictor of biochemical recurrence after radical surgery.
    Urology 11/2012; 81(1). DOI:10.1016/j.urology.2012.08.014 · 2.13 Impact Factor
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    ABSTRACT: The prognosis of patients with advanced and recurrent urothelial cancer (UC) is poor. Although cisplatin (CDDP)-containing chemotherapy is the most effective regimen in these patients, there is no other established chemotherapeutic regimen. We administered combination therapy with low-dose gemcitabine (GEM) and paclitaxel (PTX), named low-dose gemcitabine-paclitaxel (LD-GP) therapy, as salvage therapy for these patients. The aim was to evaluate the anti-tumoral effects, relief of pain, and toxicity of LD-GP therapy in patients with resistance to CDDP-containing therapy. Thirty-five patients with advanced UC, previously treated with CDDP-containing regimens, were treated with LD-GP therapy (GEM, 700 mg/m(2) + PTX, 70 mg/m(2) on day 1 and 8, repeated every 28 days). Pain was measured on a visual analog scale before and after treatment. Pain relief and survival were compared between this and other treatment regimens. None of the patients had complete response to LD-GP therapy. Partial response and stable disease were seen in 25.7 and 62.9 % of patients, respectively. Kaplan-Meier curves showed better survival in patients with LD-GP therapy than with others (p = 0.034). Twenty-eight patients (80.0 %) had adequate pain relief, and only two patients needed to increase their analgesics. Other regimens demonstrated pain relief in 30.4 % of patients. Common toxicities included leukopenia, with five patients requiring granular colony-stimulating factor therapy (14.3 %). The most common non-hematologic toxicity was fatigue (n = 7, 17.1 %). LD-GP therapy is feasible and well tolerated as salvage therapy in patients with advanced UC with resistance to CDDP-containing therapy.
    Cancer Chemotherapy and Pharmacology 08/2012; 70(3):451-9. DOI:10.1007/s00280-012-1938-3 · 2.57 Impact Factor
  • The Journal of Urology 04/2012; 187(4):e257. DOI:10.1016/j.juro.2012.02.710 · 3.75 Impact Factor
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    ABSTRACT: Squamous cell carcinoma (SCC) of the bladder is a relatively rare malignancy and the standard treatment is surgical resection. Prognosis of unresectable and recurrent SCC of the bladder is poor because no effective treatment is available at present. Here, we describe the response of one patient with this cancer to combination chemotherapy of gemcitabine and paclitaxel. A 47-year-old man with recurrent bladder SCC underwent radical cystectomy, but initially refused any adjuvant therapy. The pathological diagnosis was pT3. The patient was treated with three cycles of methotrexate, vinblastin, epirubicin, and cisplatin but with no response (no decrease in tumor volume). Subsequently, he received the combination chemotherapy of gemcitabine (GEM, 700 mg/m(2) on days 1 and 8) and paclitaxel (PTX, 700 mg/m(2) on days 1 and 8) per each 28-day cycle. After five cycles, the tumor volume had decreased from 562 to 101 cm(3) (18.0%). The combination therapy was reduced to GEM monotherapy, but the tumor volume increased to 573 cm(3). GEM+PTX administration was re-instituted; however, the patient died 21 months after recurrence. The combination GEM+PTX chemotherapy was applied at the outpatient treatment and caused no severe side-effects. Although the maintenance chemotherapy of GEM+PTX did not induce complete remission, it improved quality of life and had no serious side-effects, making it a promising combination chemotherapy for recurrent SCC of the bladder. Although further studies are necessary to determine its therapeutic efficacy, we suggest that this combined therapy is a useful option in the treatment of this disease including recurrent cases.
    Anticancer research 12/2011; 31(12):4465-8. · 1.87 Impact Factor
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    ABSTRACT: To clarify the clinical and prognostic significance of cortactin and phosphorylated cortactin in patients with sarcomatoid renal cell carcinoma (SRCC). We retrospectively reviewed the data from 31 patients with SRCC and 33 with conventional renal cell carcinoma matched for clinicopathologic features. The immunoreactive score for cortactin, pY421 cortactin, and pY466 cortactin were measured using immunohistochemistry. The relationships between each immunoreactive score and the clinicopathologic features and survival were investigated. The immunoreactive score of p421 cortactin, but not that of cortactin and pY466 cortactin, was significantly greater in SRCC than in conventional renal cell carcinoma (P < .001). The expression of pY421 cortactin in SRCC correlated with the pT stage and metastasis (P < .001). The expression of pY466 cortactin showed a similar trend with pT stage (P = .043) but not with metastasis. Although both of pY421 cortactin and pY466 cortactin were identified as useful predictors for survival in univariate analyses, only pY421 cortactin expression was considered an independent predictor in patients with SRCC (odds ratio 4.53, 95% confidence interval 1.07-19.12, P = .040) in the multivariate analysis model, including pT stage and metastasis. Our results have demonstrated that phosphorylation of cortactin is a key process in malignant aggressiveness, and its expression is a useful predictor of cause-specific survival and could be a useful potential therapeutic target in patients with SRCC.
    Urology 06/2011; 78(2):476.e9-15. DOI:10.1016/j.urology.2011.03.019 · 2.13 Impact Factor
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    ABSTRACT: Urachal cancer is a rare malignancy and the standard treatment is surgical resection. The prognosis of recurrent and metastatic urachal cancer is extremely poor because there is no established chemotherapy regimen. Here, the response of one patient with recurrent urachal cancer to combination chemotherapy of gemcitabine (GEM) and cisplatin (CDDP) (GC) is described. And the chemo- and radiotherapeutic regimens available for such patients are reviewed. A 67-year-old man diagnosed with stage IIIA urachal cancer underwent complete surgical resection. However, pelvic recurrence was detected on computed tomography (CT) 5 months after surgery. GC therapy was started immediately and resulted in a pronounced reduction in pelvic mass after three cycles. However, a follow-up CT scan taken 5 months later showed growth of the pelvic mass and new liver metastasis. He received GC therapy again, which resulted in reduction of the pelvic and liver metastatic masses after two cycles. However, the patient refused another course of GC therapy due to severe side-effects. Subsequent progression of the disease included spread in both regions, followed by death 16 months after recurrence. Various treatment strategies offer relatively long survival of patients with urachal cancer including those with recurrence and metastasis. Although further studies are necessary to determine its therapeutic efficacy, GC therapy may be a useful option in the treatment of urachal tumors, including recurrent tumours.
    Anticancer research 06/2011; 31(6):2335-8. · 1.87 Impact Factor
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    ABSTRACT: The clinical significance of prostaglandin E2 receptor (EPR) expression in renal cell carcinoma (RCC) tissues remains unclear. Patients and Μethods: Four subtypes of EPRs were examined in 112 human RCC tissues by immunohistochemical and Western blot analysis. The relationships between EPR immunoreactivity score (IS) and various pathological features and survival were then analyzed. The IS of EP4R was significantly higher (p < 0.001) in cancer cells (mean = 2.7 and SD = 2.1) than in normal kidney tissues (1.8 and 1.2). EP4R expression correlated with pT stage, metastasis, and grade. EP2R expression was also associated with metastasis. Expressions of both EP2R and EP4R were found to be significant predictors for cause-specific survival on Kaplan-Meier survival analysis (p = 0.006 and 0.023, respectively). EP2R and EP4R may play important roles in malignant behavior. EP4R in particular was closely associated with pathological features, implicating this receptor as a potential therapeutic target in patients with RCC.
    Anticancer research 02/2011; 31(2):597-605. · 1.87 Impact Factor