Metastatic embryonal carcinoma mimicking locally advanced non-small cell lung cancer.

A 50-year-old man with a history of smoking of 45 pack-years underwent right lower lobectomy after neoadjuvant chemoradiotherapy for locally advanced non-small cell lung cancer diagnosed on a bronchial biopsy and standard imaging examinations, including chest-abdominal contrast-enhanced computed tomography (CT) and whole-body F-18 fluorodeoxyglucose positron emission tomography/CT. Left orchiectomy was performed simultaneously to treat the slightly swollen left testis, which had remained unchanged for over five years. The thoracic tumor was proven to be in pathological complete remission and the testicular lesion was pathologically diagnosed as an embryonal carcinoma. Furthermore, a pathological reevaluation of the preoperative bronchial biopsy specimen revealed the lung tumor to be a metastatic embryonal carcinoma.

Potential of molecular targeted therapy of HER-2 and Cox-2 for invasive transitional cell carcinoma of the urinary bladder.

Expression of HER-2 and COX-2 was determined to assess the potential of molecular-targeted therapy against human epidermal growth factor receptor-2 (HER-2) and cyclooxygenase-2 (COX-2) for the treatment of invasive bladder cancer. The subjects were 46 patients who attended Aichi Medical University Hospital between January 2001 and August 2008, underwent total cystectomy with a diagnosis of M0 bladder cancer, and received a pathological diagnosis of invasive transitional cell carcinoma of the urinary bladder (pT2-pT4). Expression of HER-2 and COX-2 was determined by immunohistochemical staining, and the results were interpreted by two pathologists by classifying HER-2 expression into four grades, and considering COX-2 positive when 10% or more of the tumor cells were stained. In HER-2 immunostaining, 10 subjects (21.7%) were positive, all of whom had a Grade 3 tumor. Staging classification identified 2 subjects (2/22, 9.1%) with pT2 stage, 3 (3/16, 18.8%) pT3 stage, and 5 (5/8, 62.5%) pT4 stage. There was a correlation between HER-2 positivity and tumor stage (P=0.007). Lymph node metastasis was detected in 13 subjects, 3 of them (3/8, 37.5%) with pN2 metastasis were HER-2 positive. The 5-year cause-specific survival rate was 51.4% for HER-2-positive subjects and 83.4% for HER-2-negative subjects. The outcome was poorer in HER-2-positive subjects, but the difference in survival rate was not statistically significant (P=0.218). In COX-2 immunostaining, 27 subjects (58.7%) were found to be positive. Three (3/4, 75.0%) showed a Grade 2 tumor and 24 (24/42, 57.1%) a Grade 3 tumor. Staging classification identified 13 subjects (13/22, 59.1%) with pT2 stage, 9 (9/16, 56.3%) pT3 stage, and 5 (5/8, 62.5%) pT4 stage. There was no correlation between COX-2 positivity and tumor grade or stage (P=0.488 and 0.089, respectively). Classification by the extent of lymph node metastasis revealed that 6 subjects (6/8, 75.0%) with pN2 were COX-2 positive. There was a correlation between COX-2 positivity and the extent (pN1 or pN2) of lymph node metastasis (P=0.008). The 5-year cause-specific survival rate was 84.0% for COX-2-positive subjects and 71.7% for COX-2-negative subjects. However, the difference in survival rate was not significant (P=0.407). Seven subjects (7/46, 15.2%) were positive for both HER-2 and COX-2, and there was no statistically significant correlation between the status of HER-2 expression and that of COX-2 expression (P=0.2195). The present study failed to show any association between HER-2 or COX-2 positivity and outcome in subjects with invasive bladder cancer. However, HER-2-positive subjects tended to have a poorer outcome. This finding suggests that molecular-targeted therapy against HER-2 could be an effective therapy. Further studies involving a larger number of subjects are required.

The use of zoledronic acid in Japanese men with stage D2 prostate cancer.

Zoledronic acid (ZOL) is a new generation bisphosphonate with improved efficacy benefits over pamidronate in preclinical testing. In addition, ZOL is superior to pamidronate in the treatment of hypercalcemia of malignancy. ZOL is also the first bisphosphonate to demonstrate efficacy in patients with bone metastases from solid tumors other than breast cancer, such as prostate cancer. In this study, we investigated ZOL treatment in 17 Japanese men with advanced prostate cancer, treated at the Aichi Medical University Hospital between August 2006 and November 2007. The 17 patients had biopsy-confirmed prostate cancer and were found to harbor bone metastasis upon bone scintigraphy. ZOL was administered intravenously at a dose of 4 mg over 15 min every 4 weeks. ZOL was well tolerated with mild renal dysfunction in 2 patients (11.8%), while 1 patient (5.8%) developed skin rash. No significant side effects were observed. Subjective improvement in bone pain was reported in 14 patients (32.4%). ZOL, therefore, is a safe and effective drug that remains an important component of the urologist's armamentarium against advanced prostate cancer.

Investigation of risk factors for prostate cancer patients with bone metastasis based on clinical data.

It has not yet been determined whether certain types of prostate cancer with bone metastasis (M1b PC) are associated with a poor outcome. The present study retrospectively assessed the potential significance of various clinical data in predicting the outcome of M1b PC. The subjects were 104 patients who attended our hospital and received a diagnosis of M1b PC between January 1998 and December 2006. The age of the subjects ranged from 51 to 91 years (median 74). The observation period ranged from 4 to 122 months (median 43). The parameters investigated were T classification, N classification, Gleason score (GS), pre-treatment prostate-specific antigen (PSA) level, extent of disease (EOD) grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium and hemoglobin (Hb) levels and platelet count. The 5-year cause-specific survival rate was 56.6% and the 10-year cause-specific survival rate was 34.9%. Log-rank test and Cox univariate analysis identified the following factors with statistically significant differences: pre-treatment PSA level ≥192, N1, GS ≥8, EOD grade 3+4, high LDH, high ALP and low Hb. Multivariate Cox proportional hazard analysis identified the factors GS ≥8 and high LDH with significant differences. The hazard ratio was 4.967 and 2.728, respectively, and the probability value (P) was 0.029 and 0.004, respectively. When the subjects with GS ≥8 and high LDH were classified as the high-risk group, the 5-year cause-specific survival rate was 24.6%. The outcome was significantly poorer in this group (P<0.0001) than in the other group, which had a 5-year cause-specific survival rate of 67.7%. The present study showed that patients with M1b PC with GS ≥8 and high LDH have a very poor outcome and thus should be treated as a high-risk group requiring close follow-up.

Preliminary results of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced or metastatic transitional cell carcinoma of the urothelium.

OBJECTIVE: We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. SUBJECTS AND METHODS: The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of the urothelium. For mild hyperthermia, the patients' oral temperature was elevated to about 38 degrees C by heating for 20 min and retaining the heat for 20 min with a far-infrared heater. The antitumor effect was evaluated according to the RECIST, while adverse drug reactions were assessed based on the NCI-CTC. RESULTS: The antitumor effect was rated as partial remission (PR) in 10 of the 12 patients and stable disease in 2 patients, with an efficacy rate of 83% (10/12). All 10 patients who had achieved PR received three courses of treatment. Of the 12 patients, 5 died during the observation period, with survival for 9-23 months (mean: 15.6 months). Adverse drug reactions included myelosuppression in all patients (Grade 3 in 4 patients, Grade 4 in 8), and gastrointestinal toxicity, such as nausea or vomiting, which was mild (Grade 0 in 2 patients, Grade 1 in 8, Grade 2 in 1, Grade 3 in 1). CONCLUSIONS: The results of the present study suggest that M-VAC chemotherapy combined with mild hyperthermia, which potentiates the anticancer effect and reduces adverse drug reactions such as gastrointestinal symptoms, is a useful and safe method for the treatment of advanced transitional cell carcinoma of the urothelium.

Long-term results and management of ureteral transitional cell carcinoma using the holmium: YAG laser via rigid-ureteroscopy.

The standard operative procedure for ureteral transitional cell carcinoma is nephrouterectomy with partial cystectomy at the affected ureteral orifice. However, nephron-sparing surgery and endoscopic surgery and management have become common practice for low-grade and low-stage cases. We investigated the follow-up results of patients who underwent endoscopic surgery using the holmium:YAG laser, and evaluated its treatment effect. The patients were 4 men and 3 women aged from 68 to 87 years (mean: 74.7 years). Two were imperative cases and 5 were elective cases. The tumor size ranged from 8 to 25 mm (mean: 15.4 mm). Hydronephrosis was not found in any case, and urinary cytology was negative in all cases. Biopsy revealed 5 cases of grade 1, and 2 of grade 2. A Versa Pulse Select 80 laser generator, a 365-microm slim line laser fiber, and a rigid ureteroscope with 8F-point diameter were used. A 6F double J catheter was placed postoperatively for 3 weeks. Pulse energy was set at 0.5-1.0 J (mean: 0.8 J) with a frequency of 10 Hz. The total amount of energy was 0.9-11.22 KJ (mean: 2.89 KJ) and the operation time including ureteral stent placement was 20-97 min (mean: 66 min). Neither urinary tract perforation nor ureteral stricture associated with laser irradiation was observed. The postoperative follow-up period ranged from 23-88 months (mean: 67.8 months). Patients underwent urinary cytological examination once a month, and cystoscopy, retrograde pyelography and urethroscopy once every 3 months for 2 years, then once every 6 months thereafter. One patient developed tumor recurrence 23 months after surgery and received another laser treatment, but no recurrence has been observed in the other 6 patients (85.7%). Transurethral endoscopic surgery and management using the holmium:YAG laser is safe and effective nephron-sparing surgery for ureteral transitional cell carcinoma, and good long-term treatment results can be expected even in elective cases if the indications are carefully selected.

Potential for HER-2/neu molecular targeted therapy for invasive bladder carcinoma: comparative study of immunohistochemistry and fluorescent in situ hybridization.

Analysis of HER-2/neu expression in invasive bladder carcinoma was performed in order to evaluate the potential for molecular targeted therapy targeting HER-2. The subjects were 40 patients who were pathologically diagnosed with invasive transitional cell carcinoma of the bladder (pT2 to pT4). A Hercep test kit was used to detect HER-2 expression, and a Path Vysion kit was used for gene amplification. On immunohistochemical (IHC) staining, the primary tumors were HER-2 positive in 17 patients (17/40, 42.5%). According to the classification of grade, one Grade 2 patient (1/3) and 16 Grade 3 patients (16/37) were positive (P=0.99). According to the classification of stage, 12 pT2 patients (12/22, 54.5%), 2 pT3 patients (2/13, 15.3%), and 3 pT4 patients (3/5, 60%) were positive (P=0.55). Lymph node metastasis was found in 10 patients, and 3 pN2 patients were HER-2 positive (3/6, 50%) (P=0.32). A statistically significant difference was observed between HER-2-positive primary tumors and metastatic lymph nodes (P=0.02). In fluorescent in situ hybridization (FISH), HER-2/neu gene amplification was detected in the primary tumors in 5 patients (5/40, 12.5%). In all these patients, IHC staining was determined as 3+. Lymph node metastasis was found in 3 pN2 patients (3/6) (P=0.32), and in these patients with HER-2/neu gene-amplified metastatic lymph nodes, the primary tumors were also positive for gene amplification (P=0.02). In these cases, IHC staining was 3+ as well. The concordance rate of IHC-positive cases with cases positive for HER-2/neu gene amplification in FISH was 12.5% (5/40), and the concordance rate of IHC 3+ and gene amplification was 71%. This result suggests that, at present, patients who may potentially benefit from molecular targeted therapy targeting HER-2/neu for invasive bladder carcinoma should be identified by gene amplification analysis using FISH in IHC 3+ patients. In addition, it suggested that efficacy of molecular targeted therapy can be expected even for patients with metastatic lymph nodes as long as the primary tumors are positive for HER-2 expression.

Cyclooxygenase-2 expression in invasive transitional cell carcinoma of the urinary bladder.

Cyclooxygenase-2 (COX-2) activity is reported to increase apoptosis, inhibit angiogenesis and reduce metastasis. We analyzed COX-2 expression in patients with invasive bladder cancer to evaluate the feasibility of selective COX-2 inhibitor treatment targeting COX-2. Forty patients with pathologically diagnosed invasive transitional cell carcinoma of the urinary bladder (pT2-pT4) were evaluated. Immunohistochemical staining was used to evaluate COX-2 expression, and cases with staining of ≥10% of tumor cells were defined as positive. In 2 patients, 0% of the primary tumors stained for COX-2, while 1-5% was stained in 16 patients, 5-10% in 3 patients and ≥10% in 19 patients (19/40, 47.5%). In terms of grade, 2 patients with grade 2 (2/3, 66.6%) and 17 patients with grade 3 (17/37, 45.4%) were COX-2 positive. When categorized by stage, 11 patients with pT2 (11/22, 50.0%), 6 with pT3 (6/13, 46.1%) and 2 with pT4 (2/5, 40.0%) were positive. Lymph node metastasis was observed in 10 patients; 2 of them, with pN2, were COX-2 positive. Those with COX-2-positive metastatic lymph nodes had grade 3 primary tumors, which were also COX-2 positive. In addition, COX-2-negative metastatic lymph node patients also had negative primary tumors. The results of this study suggest that 47.5% of patients with invasive bladder cancer may benefit from treatment with selective COX-2 inhibitors targeting COX-2, and that treatment efficacy can be expected in patients with lymph node metastasis when their primary tumors are COX-2 positive.

Potential for molecular targeted therapy of HER-2/neu for invasive bladder cancer: examination of gene amplification by fluorescence in situ hybridization.

Analysis of HER-2/neu gene amplification by fluorescence in situ hybridization was performed in 40 patients with invasive bladder cancer in order to evaluate the potential for molecular targeted therapy of HER-2 as a tailor-made treatment for patients with invasive bladder cancer. This study included 40 patients seen at the Aichi Medical University Hospital from January 2001 to December 2004 and were pathologically diagnosed with invasive transitional cell carcinoma of the bladder (pT2-pT4). The PathVysion kit was used to evaluate the status of HER-2/neu gene amplification, and a signal ratio > or =2.0 was considered positive for HER-2/neu gene amplification. In primary foci 5 patients (12.5%) were positive for HER-2/neu gene amplification. According to the classification of grade and stage, no statistically significant difference was observed. Lymph node metastasis was found in 10 patients, and 3 patients (30%) were positive for HER-2/neu gene amplification. In the patients with HER-2/neu gene-amplified metastatic lymph nodes, primary foci were also positive for gene amplification, showing a statistically significant difference. This study indicates that 12.5% of patients with invasive bladder cancer may benefit from molecular targeted therapy of HER-2, and that molecular targeted therapy can be expected to be effective even for patients with lymph node metastases as long as their primary foci are positive for HER-2/neu gene amplification.

Lactate dehydrogenase is a prognostic indicator for prostate cancer patients with bone metastasis.

We analyzed clinical data to identify prognostic indicators in prostate cancer patients with bone metastasis. The subjects were 60 patients with bone metastasis out of 165 patients diagnosed with prostate cancer at our clinic over 6 years from January 1998 to December 2003. The age at the initial diagnosis was 61 to 91 (mean: 73.7 +/- 7.5) years old. The following items were considered to be possible prognostic indicators: T (type) classification, N (node) classification, Gleason score, prostate specific antigen (PSA) value before therapy, disease grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), serum calcium (Ca), hemoglobin (Hgb), and platelet count (Plt). The 5-year overall survival rate was 45.7% in the 60 patients. Univariate analysis showed statistically significant differences in N (1), Gleason score 7 + 8/Gleason score 9 + 10, and LDH level (p = 0.0053, 0.0261, and 0.0049, respectively). Multivariate Cox proportional hazard analysis of these three items showed a statistically significant difference in LDH level and Gleason score 9 +/- 10 (p = 0.0167 and 0.0371). LDH was suggested to be an excellent prognostic indicator, because of its objectivity and convenience of measurement, in prostate cancer patients with bone metastasis.

Potential for molecular-targeted therapy targeting human epidermal growth factor receptor-2 for invasive bladder cancer.

Expression of human epidermal growth factor receptor-2 (HER-2/neu or HER-2) oncoprotein in invasive bladder cancer was examined by immunohistochemical staining in order to evaluate the potential for molecular-targeted therapy targeting HER-2 as a tailor-made treatment for patients with invasive bladder cancer. This study included 40 patients who were examined at Aichi Medical University Hospital and were pathologically diagnosed with invasive transitional cell carcinoma of the bladder (pT2 to pT4). Immunohistochemical staining using a Hercep test kit was performed to detect HER-2 expression, which was classified into four levels from 0 to 3+ by two experienced pathologists, with 2+ and 3+ determined as positive. HER-2 staining in the primary tumor was determined as 0 in 9 (22.5%) patients, 1+ in 14 (35%), 2+ in 10 (25%), and 3+ in 7 (17.5%), resulting in 17 (17/40, 42.5%) HER-2-positive patients. According to the classification of grade, one (1/3, 33.3%) grade 2 patient and 16 (16/37, 43.2%) grade 3 patients were HER-2 positive (p=0.99). According to the classification of stage, 12 (12/22, 54.5%) pT2 patients, 2 (2/13, 15.3%) pT3 patients, and 3 (3/5, 60%) pT4 patients were HER-2 positive (p=0.05). Lymph node metastasis was found in 10 patients, and 3 (3/6, 50%) pN2 patients were HER-2 positive (p=0.32). There was a statistically significant difference between patients with HER-2-positive primary tumors and those with HER-2-positive metastatic lymph nodes (p=0.02). This study suggested that 42.5% of patients with invasive bladder cancer may benefit from molecular-targeted therapy targeting HER-2, and that the efficacy of molecular-targeted therapy can be expected even for patients with lymph node metastases as long as their primary tumors are HER-2 positive.

A case of primary leiomyoma of the ureter.

This report describes a case of primary leiomyoma of the ureter in which only partial ureterectomy was performed based on the diagnosis of benign tumor by rapid diagnosis using a frozen section during the operation. Surgical treatment was opted for upon diagnosis of a submucosal tumor of the right ureter, with no abnormal findings in the ureteral mucosa by ureteroscopy. To our knowledge, nine cases have been reported worldwide since 1955, suggesting this case to be the 10th.

An immunohistochemical study of chromogranin A and human epidermal growth factor-2 expression using initial prostate biopsy specimens from patients with bone metastatic prostate cancer.

OBJECTIVES: To investigate, using prostate needle-biopsy specimens at diagnosis from patients with bone metastatic prostate cancer, whether the relationship between neuroendocrine (NE) cell differentiation and human epidermal growth factor-2 (HER-2) expression is a prognostic factor for outcome. PATIENTS AND METHODS: The study included 50 patients diagnosed as having bone metastatic prostate cancer between January 1998 and December 2001. We tested for NE cell differentiation by using immunohistochemical (IHC) staining for chromogranin A (CgA), and for HER-2, using a commercial test for IHC staining. RESULTS: Eleven patients (22%) were positive for CgA; there was a significant difference in the time to recurrence (P = 0.025) but no significant differences in cause-specific survival rate or survival rate after recurrence. In all, 21 patients (42%) were positive for HER-2; the cause-specific survival rate, time to recurrence and survival rate after recurrence were all significantly more favourable in the HER-2-negative group (P = 0.008, 0.049 and 0.025, respectively). In the 49 patients for whom both factors could be determined, there was no significant correlation between CgA and HER-2 positivity. CONCLUSIONS: NE cell differentiation of the primary tumour in patients with bone metastatic prostate cancer does not reflect the prognosis, whereas HER-2 overexpression is a prognostic factor for an unfavourable outcome. These results suggest that NE cell differentiation is not induced by HER-2.

Is neuroendocrine cell differentiation detected using chromogranin A from patients with bone metastatic prostate cancer a prognostic factor for outcome?

We evaluated the usefulness of overexpression of neuroendrocrine (NE) cell differentiation determined by immunohistochemical staining for chromogranin A (Cg A) in diagnostic needle biopsy specimens of bone metastatic prostate cancers. A total of 50 patients diagnosed as having bone metastatic prostate cancer were studied. The period of observation was between 6.9 and 79.4 months (median 48.7 months). Cg A was detected by immunostaining using the labeled streptavidin biotin method. Cg A-positivity was defined as the presence of immunostained cells in 10% or more of the tumor. All statistical analyses were carried out using the Statistical Package for Social Sciences Software, version 10.0 for Windows. Eleven patients (22%) were classified into the Cg A-positive group. There were no significant differences in clinical data between the Cg A-positive and Cg A-negative groups. The 5-year cause-specific survival rate was 34.1% for the Cg A-positive group and 55.2% for the Cg A-negative group (p=0.3763). The 3-year non-recurrence rate was 9.1% for the Cg A-positive group and 35.9% for the Cg A-negative group, and this difference was significant (p=0.0253). The 3-year cause-specific survival rates after recurrence were 38.4% and 42.3% respectively (p=0.8125). We consider that NE cell differentiation of the primary tumor in cases of bone metastatic prostate cancer is not a prognostic factor for outcome.

Clinical features of renal cell carcinoma less than 25 millimeters in diameter.

BACKGROUND: We retrospectively investigated the clinicopathological features and prognosis of patients who underwent surgical treatment at our department for renal cell carcinoma (RCC) less than 25 mm in diameter. METHODS: Of the 158 patients who underwent surgical treatment between April 1975 and April 1998, 16 (17 kidney, 10.1%) were included in this study. The study included 11 men and 5 women (ratio: 2.2). The age range was 35-76 years (average: age 53). The right kidney was involved in 9, left kidney in 6 and bilateral kidneys in 1 patient. The follow-up period was 26-157 months (mean: 86 months). RESULTS: Thirteen tumors (81.2%) were incidental carcinomas. No patients had a tumor of rapid growing type. Radical nephrectomy was performed for 12 kidneys (70.6%), simple nephrectomy for 2 (11.8%) and partial nephrectomy for 3 (17.8%). Seven patients (43.7%) received interferon-alpha as postoperative adjuvant therapy. All tumors were pathologically classified as expansive type; 11 (64.8%) as clear cell carcinoma; 3 (17.6%) cyst-associated, and 3 (17.6%) papillary. Nine (52.9%) tumors were grade 1, and 8 (47.1%) were grade 2. Fourteen patients were pNo and V(-). The 5- and 10-year survival rates were excellent (100%). CONCLUSION: The features of small RCCs less than 25 mm were as follows: many tumors were incidental to clear cell carcinomas; all tumors were low grade, low stage and expansive type; no tumors showed acute phase reactants; and few tumors were of the solid type. Thus, the prognosis seemed to be excellent.