Clinical evaluation of urine laminin-γ2 monomer as a potent biomarker for non-muscle invasive bladder cancer.

BACKGROUND: To evaluate whether urine laminin-γ2 monomer (Ln-γ2m) offers a useful biomarker for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: Participants comprised 297 patients, including 111 patients with NMIBC, 136 patients with benign genitourinary disease (BD) and 50 healthy donors (HD). Urine Ln-γ2m was prospectively measured and accuracy was analyzed. Receiver operating characteristic (ROC) curves were determined and area under the ROC curve (AUC) was calculated for urine Ln-γ2m, and compared to those of traditional urine tumor markers such as nuclear matrix protein 22 (NMP22), bladder tumor antigen (BTA) and cytology. The net benefits of combining urine markers were analyzed by decision curve analysis. RESULTS: Mean urine Ln-γ2m was significantly higher in NMIBC than in BD or HD. The AUC for urine Ln-γ2m was significantly higher than those for urine NMP22, BTA or cytology when comparing NMIBC with HD. In patients with low-grade NMIBC, the AUC for urine Ln-γ2m was higher than the AUCs for NMP22, BTA or cytology. A net benefit of combined examination using urine Ln-γ2m/uCRN with NMP22 was demonstrated. CONCLUSION: These results suggest urine Ln-γ2m as a potentially useful biomarker for NMIBC, particularly in cases of low-grade cancer.

Re-Challenging with Nivolumab in Metastatic Renal Cell Carcinoma After Immune-Related Interstitial Pneumonia: A Case Report.

BACKGROUND The efficacy and safety of re-challenge with immune checkpoint inhibitors after immune-related adverse events have not been established. We report a case of successful re-administration of nivolumab in metastatic renal cell carcinoma after discontinuation due to immune-related adverse events. CASE REPORT Laparoscopic nephrectomy was performed on a 52-year-old man diagnosed with renal cell carcinoma pT1bN0M0. After surgery, left adrenal and lung metastases appeared. Nivolumab was administered as a sixth-line therapy, and he achieved a partial response, but interstitial pneumonia occurred. He was diagnosed with grade 2 immune-related adverse events, and nivolumab treatment was discontinued. Interstitial pneumonia was well controlled by steroids. He maintained a partial response for a long time, and the lung metastases disappeared 7 months after discontinuation. However, bilateral lung metastases reappeared 10 months after the discontinuation. We decided to re-administer nivolumab, while carefully monitoring the patient and fully explaining the risk of recurrence of immune-related adverse events. After 5 cycles of re-administration, computed tomography revealed a reduction in metastases without re-activation of interstitial pneumonia. He experienced a grade 1 fever the day after re-administration, but continued nivolumab therapy without other adverse events. After 7 cycles of re-administration, the lung metastases increased, and nivolumab treatment was terminated. Two months later, a grade 2 interstitial pneumonia recurred, but improved rapidly with oral steroids. CONCLUSIONS For patients who have discontinued immune checkpoint inhibitors due to immune-related adverse events, re-challenge of immune checkpoint inhibitors may be an option after explaining the risk of relapse of immune-related adverse events.

Comparative effectiveness of surgery and radiotherapy for survival of patients with clinically localized prostate cancer: A population-based coarsened exact matching retrospective cohort study.

Radical prostatectomy and radiotherapy are currently the main treatment options for localized prostate cancer. However, no large cohort study comparing surgery and radiation has been performed in Japan or Asia. The objective of the current study was to compare the survival outcomes of patients with clinically localized prostate cancer and in elderly and young patients receiving surgery and radiotherapy. The survival outcomes of patients with localized prostate cancer (age at diagnosis ≤79 years, clinical T1-3) initially treated with surgery or radiotherapy were retrospectively analyzed. Data were collected from the population-based cancer registry of the Kanagawa Prefecture, Japan. A 1:1 coarsened exact matching of age at diagnosis, clinical T stage and cancer differentiation was performed between the two treatment groups. Patients were also categorized into two subgroups by age using a cutoff of 70 years for analysis. The cohort comprised 4,810 patients aged 50-79 years. No significant difference in cancer-specific survival (CSS) was observed between the two groups (P=0.612). However, the surgery group had significantly better overall survival (OS; P=0.004). When stratified for age, similar tendencies were observed in the elderly group (aged 70-79 years; CSS, P=0.961 and OS, P=0.007). No significant difference in either CSS or OS was identified in the younger group (P=0.550 and P=0.408, respectively). Intrinsic deaths were more likely to occur in elderly patients treated with radiotherapy than those undergoing surgery (69.3 vs. 78.2%; P=0.128). The results indicated that surgery provided significantly better OS than radiotherapy, particularly among the elderly. However, no significant difference was observed in CSS. These results should be interpreted with caution, given that some important factors were unavailable in the present study, such as prostate-specific antigen values and Gleason scores. Prospective trials evaluating these therapies are warranted.

C-reactive protein at 1 month after treatment of nivolumab as a predictive marker of efficacy in advanced renal cell carcinoma.

PURPOSE: Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Here, we investigate C-reactive protein (CRP) at 1 month after treatment of nivolumab as a target to predict the response of patients with metastatic renal cell carcinoma (mRCC) to nivolumab. METHODS: After approval of the study by our institutional review board, 64 patients with mRCC who underwent nivolumab treatment at Kanagawa Cancer Center and Yokohama City University Hospital were enrolled. The patient characteristics, blood examination data at start of nivolumab treatment and 1 month after treatment, response to treatment and progression-free survival (PFS) were evaluated. Tumour responses were assessed according to both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the immune RECIST (iRECIST) criteria. Moreover, in 12 patients who agreed to an additional blood examination, several serum inflammatory factors were investigated and their correlation with CRP level was examined. RESULTS: The median follow-up was 8.3 months (range 0.2-29.8 months). The median PFS period was 4.5 months and the median immune-PFS (iPFS) period was 5.3 months. RECIST 1.1 criteria underestimated the benefits of nivolumab in four (6.4%) cases. Multivariate analyses showed that an Eastern Cooperative Oncology Group performance status (≥ 2) at start of treatment and CRP level at 1 month after treatment (≥ 1.5 mg/dL) were independent risk factors for a poor iPFS of nivolumab. The CRP level at baseline was not an independent prognostic factor for iPFS. When compared with the responder group (iCR + iPR + iSD), the non-responder group (iPD) had a significantly higher CRP levels at 1 month after treatment (p < 0.001). In the responder group, there was significant decrease in the CRP level after nivolumab treatment when compared with the baseline (p = 0.002), whereas there was a significant increase in the non-responder group (p = 0.019). Even patients with high baseline CRP (≥ 1.5 mg/dL) obtained good iPFS if CRP was decreased (< 1.5 mg/dL) 1 month after treatment. In addition, the classification of Glasgow prognostic score (GPS), which is a cumulative prognostic score based on CRP and albumin, was a significant predictor for iPFS. A strong correlation (|r| > 0.7) with CRP level at 1 month after treatment was seen for sCD163, IL-34, MMP-1, MMP-2, osteopontin, sTNF-R1 and sTNF-R2. Of these, MMP-1 and MMP-2 were not correlated at baseline. CONCLUSION: Our results indicated that the CRP level at 1 month after treatment with nivolumab appears to be a promising predictive biomarker for response to nivolumab treatment in patients with mRCC. It is clinically useful to be able to predict the effect within a short period. Further prospective trials are needed to prove these preliminary findings.

Galectin-9 expression as a poor prognostic factor in patients with renal cell carcinoma.

Recently, the effectiveness of anti-programmed death 1 (PD-1) antibody therapy in the treatment of renal cell carcinoma (RCC) has been established. Nevertheless, efficacy has been reported to be limited to only 10-30% of patients. To develop more effective immunotherapy for RCC, we analyzed the immunological characteristics in RCC tissues by immunohistochemistry (IHC). We prepared a tissue microarray that consisted of tumor tissue sections (1 mm in diameter) from 83 RCC patients in Kanagawa Cancer Center between 2006 and 2015. IHC analysis was performed with antibodies specific to immune-related (CD8 and Foxp3) and immune checkpoint (programmed death ligand 1 (PD-L1) and 2 (PD-L2), B7-H4 and galectin-9) molecules. The numbers and proportions of positively stained tumor cells or immune cells were determined in each section. From multivariate analysis of all 83 patients, higher galectin-9 expression was detected as a factor associated with worse overall survival (OS) (P = 0.029) and that higher stage and higher B7-H4 expression were associated with worse progression-free survival (PFS) (P < 0.001 and P = 0.021, respectively). Similarly, in multivariate analysis of 69 patients with clear cell RCC, though not statistically significant, there was a trend for association between higher galectin-9 expression and worse OS (P = 0.067), while higher stage was associated with worse PFS (P < 0.001). This study suggests that higher galectin-9 expression is an independent adverse prognostic factor of OS in RCC patients. Therefore, to develop more effective personalized immunotherapy to treat RCC, it may be important to target not only PD-1/PD-L1, but also other immune checkpoint molecules such as galectin-9.

A lower psoas muscle volume was associated with a higher rate of recurrence in male clear cell renal cell carcinoma.

BACKGROUND: Sarcopenia is defined as a low skeletal muscle volume. Recent studies have reported that sarcopenia is associated with a poor prognosis in various cancers. The purpose of this study is to evaluate the correlation between the psoas muscle volume and recurrence-free survival in patients with localized clear cell renal cell carcinoma (ccRCC). METHODS: A total of 316 male patients with localized ccRCC who underwent radical nephrectomy at Yokohama City University Hospital (Yokohama, JAPAN) and Kanagawa Cancer Center (Yokohama, JAPAN) between 2002 and 2018 were enrolled in this study. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area on the contralateral side of the tumor on axial CT, which was calculated at the level of L4 (mm2) divided by the square of the body height (m2). We divided patients into two groups based on the median PMI (409.64mm2/m2). RESULTS: The lower PMI group showed poorer recurrence-free survival (RFS) than the higher PMI group (p = 0.030). Regarding 5-year RFS, a lower PMI was a significant predictor of recurrence (p = 0.022, hazard ratio (HR): 2.306) and a multivariate analysis revealed that a lower PMI (4 cm (p = 0.044, HR: 2.341), and pathological stage >2 (p<0.001, HR: 3.660) were independent risk factors for poor RFS. CONCLUSIONS: The presence of sarcopenia (lower PMI) was found to be associated with poor RFS in male ccRCC patients. The PMI might serve as a measure of patient frailty and might be useful for prognostic risk stratification in ccRCC.

[A CASE OF EXTRASKELETAL EWING'S SARCOMA IN THE RETROPERITONEUM].

A 23-year-old man was admitted to our hospital with a huge pelvic tumor. MRI showed a tumor mixed with a solid component and polycystic cyst with maximum diameter of about 20 cm. Percutaneous tumor needle biopsy was performed and diagnosis was Ewing sarcoma. At that time, operation is extremely difficult, so the neoadjuvant chemotherapy with ifosfamide, etoposide, Adriamycin, and vincristine were administered. After 6 courses, MRI showed tumor reduction to maximum diameter of 10 cm. We planned tumor resection with total cystectomy for radical resection, but we also tried to preserve bladder considering the young age and quality of life. Although the bladder was partially resected, tumor resection was succeeded without removing surrounding organs. Histopathological examination revealed viable cells remained, but more than 95% was disappeared and the surgical margins were negative. Here we report a case of extra skeletal Ewing sarcoma in the retroperitoneum that was treated with chemotherapy and surgery without scarifying surrounding organs.

Outcome of Palliative Urinary Diversion and Observation for Malignant Extrinsic Ureteral Obstruction.

Background: Urologists are often referred to manage the extrinsic malignant ureteral obstruction (MUO) caused by nonurological malignancies. Usually palliative urinary diversion (ureteral stent or nephrostomy) will be performed; however, in the cases of no symptom or poor prognosis, observation (OBS) without any intervention will be selected. There are few reports about outcome of the OBS policy for MUO. Objective: To evaluate the outcome of palliative urinary diversion or OBS for MUO. Design: We retrospectively reviewed the selection of treatment and the prognosis. Setting/Subjects: A total of 151 cases were introduced to our department as MUO between April 2011 and December 2016. Measurements: The patients were divided to immediate palliative urinary diversion (immediate-DIV) or OBS. The latter patients were subdivided to OBS followed by deferred palliative urinary diversion (deferred-DIV), and observation only (OBS-only). Results: There was no significant difference between immediate-DIV and OBS about overall survival (OS) from the consultation. In OBS group, deferred-DIV did not prolong prognosis from the consultation more than OBS-only. In the same way, there was no significant difference between immediate-DIV and deferred-DIV in OS from the intervention. Unfavorable prognostic factors for OS were lack of anticancer treatment after consultation, symptoms of MUO, and gastrointestinal cancer. When we classified the patients by these factors, the group with three factors showed significantly poorer prognosis than the others. Conclusion: Immediate-DIV or OBS did not influence the prognosis in the whole patients. Three prognostic factors that will be judged by urologists easily might be useful for the indication and timing of palliative urinary diversion.

[PREDICTIVE AND PROGNOSTIC SIGNIFICANCE OF PRE-TREATMENT LYMPHOCYTE COUNT IN PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA TREATED WITH PLATINUM-BASED FIRST-LINE CHEMOTHERAPY].

(Purpose) Pre-treatment low lymphocyte count may result from cytokine secretion by the tumor microenvironment, in association with aggressive tumor biology. We sought to establish the prognostic impact of the absolute lymphocyte count (ALC) in advanced urothelial carcinoma. (Patients and method) We retrospectively reviewed 63 patients with unresectable or metastatic urothelial carcinoma who were treated with platinum-based first-line systemic chemotherapy between January 2011 and April 2018. We evaluated the importance of the ALC in patients who underwent systematic chemotherapy. (Results) Thirty-eight patients (60%) died from urothelial carcinoma, with a median follow-up interval of 12.2 months. The median overall survival (OS) duration was 15.3 months. The mean ALC in the stable and progressive disease group was lower than that in the complete and partial response group (1,312 /µL and 1,666 /µL, respectively, p=0.004). The ALC of 1,460 /µL was determined as the cut-off on Receiver operating characteristic curve analysis. The log-rank test revealed that the lymphocytopenia group (ALC <1,460 /µL) showed significantly poorer prognoses than the non-lymphocytopenia group (p=0.001). Multivariate analyses showed that lymphocytopenia was an independent poor prognostic factor (hazard ratios of 3.46, p=0.002). (Conclusions) Pre-treatment low lymphocyte count is an independent poor prognostic factor in patients with urothelial carcinoma who underwent platinum-based first-line systemic chemotherapy.

Case of acute respiratory distress syndrome in a patient with an extragonadal germ cell tumor without lung metastasis in which choriocarcinoma syndrome was suspected.

INTRODUCTION: Choriocarcinoma syndrome is caused by bleeding from metastatic germ cell tumors with choriocarcinoma components. Here, we report a case of acute respiratory distress syndrome, which arose after first-line chemotherapy for an extragonadal germ cell tumor without lung metastasis. CASE PRESENTATION: A 41-year-old male visited our institution with chief complaints of back pain and weight loss. Computed tomography showed multiple lymph node metastases in the retroperitoneal cavity. There were no lung metastases. A lymph node biopsy resulted in a diagnosis of choriocarcinoma. Bleomycin etoposide cisplatin therapy was started as induction chemotherapy. On the first day, he was diagnosed with acute respiratory distress syndrome due to choriocarcinoma syndrome. We administered high-dose hydrocortisone therapy for 3 days. The patient's respiratory status improved. CONCLUSION: In patients who are at high risk of developing choriocarcinoma syndrome, induction chemotherapy might lead to the development of acute respiratory distress syndrome due to the release of cytokines despite the absence of lung metastasis.

[A CASE OF METASTATIC KIDNEY CANCER FOR WHICH THE EFFICACY OF NIVOLUMAB THERAPY WAS MAINTAINED EVEN AFTER THE DEVELOPMENT OF INTERSTITIAL PNEUMONIA].

The patient was a 52-year old man who underwent laparoscopic radical nephrectomy for kidney cancer. Left adrenal and lung metastases occurred 5 and 11 years after the surgery, respectively. Various molecular-targeted therapies were ineffective, so nivolumab treatment was started 12 years after the surgery. Treatment was discontinued when the patient developed interstitial pneumonia after three courses of nivolumab treatment. After steroid treatment for interstitial pneumonia, both the symptoms and findings of the imaging tests improved quickly. On the other hand, while the effect of Partial Response (PR) was evident in the lungs and adrenal glands, on the basis of the image assessments performed after three courses of treatment, the effect was maintained without regrowth even at the last follow-up, 10 months after discontinuing the treatment.

Enhanced expression of PD-L1 in non-muscle-invasive bladder cancer after treatment with Bacillus Calmette-Guerin.

Immune checkpoint molecules, such as PD-1/PD-L1, are reported to be closely associated with suppression of antitumor immunity, and their inhibitors have been used to treat various cancers including bladder cancer. However, there have been only a few studies investigating the effects of Bacillus Calmette-Guerin (BCG) administration on expression of the immune checkpoint molecules in bladder cancer. The current study examined the expression of PD-L1 and PD-L2 before and after BCG in non-muscle-invasive bladder cancer (NMIBC) patients. Tissue microarrays of 22 BCG-resistant NMIBC patients were stained by immunohistochemistry with antibodies against PD-L1, PD-L2, and CD8, and were compared between before and after BCG. The expression levels of PD-L1, but not of PD-L2, were significantly increased after BCG treatment on tumor cells (p < 0.001) and tumor-infiltrating inflammatory cells (p = 0.030) within tumor tissues, as well as on inflammatory cells within non-tumor normal tissues (p = 0.003). Although CD8+ T cells were significantly increased within tumor tissues (p = 0.005) and non-tumor normal tissues (p = 0.007) after BCG treatment, they might be not effective for anti-tumor immunity. This study demonstrated for the first time that expression of PD-L1, which might contribute to the immune escape mechanism, was enhanced on tumor tissue after BCG treatment in BCG-resistant NMIBC patients. Our finding thus propose that immunotherapy with anti-PD-1/PD-L1 antibodies could be feasible as combination treatment with BCG or as secondary treatment at relapse after BCG in NMIBC patients.

Urachal Carcinoma with Peritoneal Dissemination Treated with Chemotherapy and Surgical Resection Leading to Prolonged Survival with No Recurrence.

A 56-year-old man was admitted to our hospital for urachal carcinoma with peritoneal dissemination. He received first-line chemotherapy with gemcitabine and cisplatin. After the fifth cycle, a computed tomography (CT) scan revealed abdominal fluid, and his serum tumor marker levels were increased. The patient was started on second-line therapy with FOLFIRI. After 11 cycles, his tumor decreased in size and no new metastatic lesions were detected. The patient underwent complete tumor resection with partial cystectomy and pelvic lymph node dissection. The tumor was removed, along with adhering surrounding organs, including the omentum, peritoneum, abdominal rectus muscle, and vermiform appendix. Although pathological examination confirmed peritoneal dissemination, his tumor markers normalized soon after surgery. The patient has survived 62 months after surgery without any adjuvant therapy and with no evidence of recurrence. To our knowledge, this is the longest duration of survival without recurrence of a patient with urachal carcinoma with peritoneal dissemination who received multimodal therapy.

Significant response to nivolumab for metastatic chromophobe renal cell carcinoma with sarcomatoid differentiation: a case report.

BACKGROUND: The treatment of advanced or metastatic renal cell carcinoma (RCC) has drastically changed since the approval of immune checkpoint therapy. Nivolumab is a treatment option for patients with metastatic RCC, previously treated with targeted antiangiogenic therapy. The efficacy of nivolumab for patients with RCC was established by the Checkmate 025 clinical trial. Chromophobe RCC (CRCC) represents around 5% of RCC cases, but non-clear cell RCC (non-ccRCC) subtypes were excluded from the Checkmate 025 clinical trial. We report a case in which the use of nivolumab as the seventh-line therapy elicited a significant response in the treatment of metastatic CRCC with sarcomatoid differentiation. CASE PRESENTATION: We report a case of a 41-year-old woman with metastatic CRCC with sarcomatoid differentiation. She was treated with sunitinib, pazopanib, everolimus, sorafenib, axtinib, and temsirolimus, but treatment was discontinued because of disease progression or strong adverse events. Seventh-line treatment with nivolumab was initiated and significant clinical improvement was noted after 4 cycles. The treatment was well-tolerated with no significant side effects and the patient continues with nivolumab treatment at present. CONCLUSIONS: Nivolumab may be an attractive treatment option for non-ccRCC patients with sarcomatoid differentiation that exhibited aggressive characteristics and poor prognosis. Further investigation is warranted.

Time-dependent change in relapse sites of renal cell carcinoma after curative surgery.

We investigated time-dependent changes in the relapse features of renal cell carcinoma (RCC) after curative surgery. Between 1985 and 2015, 1398 patients with RCC (1226 clear cell RCC, 89 papillary RCC, and 53 chromophobe RCC) underwent curative surgery at Yokohama City University Hospital and its affiliated hospitals. We retrospectively reviewed the clinicopathologic factors of patients with relapse after surgery. Median follow-up was 56.3 months. Recurrence occurred in 245 patients (217 clear cell RCC, 12 papillary RCC, and 3 chromophobe RCC). Papillary RCC and chromophobe RCC had no recurrence beyond 5 years after surgery, but 20 cases of clear cell carcinoma had recurrence beyond 10 years after surgery. The typical recurrence sites of clear cell RCC were lung (46.6%), bone (17.9%), liver (7.6%), and lymph nodes (6.5%). The proportion of recurrences at these typical sites was 83.9% for recurrences within 5 years, 76.3% between 5 and 10 years, and 40.0% beyond 10 years. In contrast, the proportion of retroperitoneal organ recurrence, including contralateral kidney, pancreas, and adrenal glands, increased with increasing time after surgery. Interestingly, the hazard ratio of typical site relapse decreased whereas that of retroperitoneal organ relapse increased in a time-dependent manner. In summary, clear cell RCC showed potential to relapse beyond 10 years after surgery. Recurrence at typical sites decreased whereas retroperitoneal organ recurrence increased in a time-dependent manner. Clinicians should check for recurrence at various sites beyond 10 years, especially in clear cell RCC.

[RETROPERITONEAL LIPOSARCOMA WITH MULTIPLE RECURRENCE OF LUNG METASTASES TREATED BY MULTIMODAL THERAPY CENTERING ON THE OPERATION: A CASE REPORT].

A 34-year-old man presented with scrotal pain and slight fever. The scrotal pain was improved by the treatment of antibiotics, but the slight fever remained and an abdominal protuberance appeared. Computed tomography showed a 22 cm abdominal tumor with lipid density. He was then referred to our hospital. He was diagnosed as retroperitoneal liposarcoma and a surgical resection was performed for retroperitoneal tumor and surrounding organs. Histopathological diagnosis was dedifferentiated liposarcoma. 3 months after surgery, a PET/CT scan showed multiple lung metastases. We treated the patient with AI therapy by doxorubicin and ifosfamide. After 6 courses were performed, a complete response was achieved. 30months after the initial surgery, a PET/CT scan showed there was just one metastasis which was in the left lung. Thoracoscopic lung tumor resection was performed. Histopathological diagnosis was metastatic dedifferentiated liposarcoma. As adjuvant therapy, we treated with IE therapy by ifosfamide and VP-16. 3 courses were performed. 3 years and 6 months after the first surgery, he has had no recurrence up to the present day.

[A Case of Long Survival in Aggressively Growing Small Cell Carcinoma of the Bladder Successfully Treated by Combined Chemotherapy of Methotrexate, Etoposide and Cisplatin].

A 74-year-old man underwent transurethral resection for a bladder tumor (TURBT). The pathological diagnosis was urothelial carcinoma, grade 3 pT2 at least. He desired preservation of the bladder. Thus, MEC (methotrexate 100-150 mg/body (day 1), etoposide 100 mg/m2 (day 2-4), cisplatin 20 mg/m2 (day 2-6)) chemotherapy was administered for 2 courses. The next year, he had a relapse in the bladder, and the pathological diagnosiswasurothelial carcinoma, grade 2 pTa and pTis. He underwent Calmette-Guerin Bacillus (BCG) immunotherapy for 6 courses that resulted in a complete response without recurrence for 6 years. Six months after the latest examination, he complained of difficulty in voiding. An 8 cm tumor in the bladder and enlargement of obturator lymph node were detected. The pathological diagnosis by TURBT was small cell carcinoma. He rejected cystectomy, so we applied MEC therapy again. After 2 courses of MEC therapy, the bladder tumor and lymphadenopathy markedly shrunk in image and almost disappeared subsequently. The patient refused further therapy, but he had been followed without recurrence for 48 monthsafter the chemotherapy.

[A Case of Squamous Cell Carcinoma in Bladder Diverticulum Producing Granulocyte Colony Stimulating Factor].

We report a rare case of squamous cell carcinoma (SCC) in bladder diverticulum producing granulocyte colony stimulating factor (G-CSF). A 59-year-old man complaining of hematuria and right hip pain was admitted with a large cancer in the bladder diverticulum. His laboratory data showed leukocytosis of 20,100/ µ l (neutrophils : 92%) with an elevated G-CSF of 76. 6 pg/ml in the peripheral blood. After neoadjuvant chemotherapy (gemcitabine and cisplatin), radical cystectomy was performed to normalize serum leukocytosis and G-CSF. Histopathological diagnosis was G-CSF-producing SCC pT4N0. He appeared with left pelvic lymph node metastasis and right pulmonary metastasis 3 months after surgery. Therefore, he was treated with four courses of combination chemotherapy (paclitaxel, ifosfamide and nedaplatin) and radiation therapy at left pelvic lymph node metastasis. Computed tomography after these treatments showed complete response. The patient is alive with no evidence of tumor 16 months after surgery.

[Renal Cell Carcinoma with Retroperitoneal Metastases and Renal Invasion from Breast Cancer : A Case Report].

A 67-year-old female was hospitalized with back pain. Computed tomography (CT) incidentally revealed a tumor in her left kidney tumor (33 mm) and bilateral breast tumors. She underwent a breast biopsy and was diagnosed with breast cancer (invasive lobular cancer, cT2N0M0). The renal tumor was suspected to be clear cell carcinoma, cT1aN0M0, based on contrast-enhanced CT. Surgery was considered necessary for both the breast cancer and renal tumor. First, laparoscopic radical nephrectomy was performed for the renal tumor. However, the lateroconal fascia adhered strongly to the perirenal fat, and so simple nephrectomy was carried out after conversion to open surgery. The perirenal fat was also excised after the nephrectomy. A histopathological examination revealed clear cell carcinoma and renal invasion by invasive lobular cancer cells. Also, scattered metastases were detected in the perirenal fat and the lateroconal fascia. So, it was considered that retroperitoneal metastases from the breast cancer had directly invaded the kidney. After the operation, the patient received hormonal therapy for her breast cancer, and she was still alive and symptom-free 5 months after the operation.

Pretreatment Neutrophil-to-Lymphocyte Ratio Can Predict the Prognosis in Bladder Cancer Patients Who Receive Gemcitabine and Nedaplatin Therapy.

Introduction and Objectives. Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a simple marker of the systemic inflammatory response in critical care patients. We previously assessed the utility of NLR as a biomarker to predict tumor recurrence and cancer death in bladder cancer patients who underwent radical cystectomy. In this study, we evaluated the prognostic impact of NLR in bladder cancer patients who received gemcitabine and nedaplatin (GN) chemotherapy. Methods. A total of 23 patients who received GN chemotherapy for advanced bladder cancer were enrolled in this study. The cut-off point of NLR according to the sensitivity and specificity levels was derived from the area under receiver operator characteristics (AUROC) curve plotted for disease progression or overall mortality. Results. The NLR cut-off point was determined as 4.14 for both tumor progression and overall mortality. Median progression-free survival (PFS)/overall survival (OS) in the higher NLR group (NLR ≥ 4.14) and lower NLR group (NLR < 4.14) were 194/468 days versus 73/237 days, respectively. Kaplan-Meier analysis showed that higher NLR significantly correlated with poorer PFS (p = 0.011) and OS (p = 0.045). Conclusions. NLR may serve as a new biomarker to predict responses to GN-based chemotherapy in advanced bladder cancer patients and/or their prognosis.