The early response of renal cell carcinoma to tyrosine kinase inhibitors evaluated by FDG PET/CT was not influenced by metastatic organ.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for advanced renal cell carcinoma (RCC), but it has been unclear whether the antitumor effect of TKIs depends on the organ where the RCC metastasis is located. We previously reported that the FDG accumulation assessed by FDG PET/CT, was a powerful index for evaluating the biological response to TKI. In this study we investigated the differences in FDG accumulation and the response to TKI as assessed by FDG PET/CT among various organs where RCC were located. METHODS: A total of 48 patients with advanced RCC treated with a TKI (25 with sunitinib and 23 with sorafenib) were evaluated by FDG PET/CT before and at 1 month after a TKI treatment initiation. The maximum standardized uptake value (SUVmax) of all RCC lesions were measured and analyzed. RESULTS: We evaluated 190 RCC lesions. The pretreatment SUVmax values (mean ± SD) were as follows: in the 49 lung metastases, 4.1 ± 3.3; in the 40 bone metastases, 5.4 ± 1.6; in the 37 lymph node metastases, 6.7 ± 2.7; in the 29 abdominal parenchymal organ metastases, 6.6 ± 2.7; in the 26 muscle or soft tissue metastases, 4.4 ± 2.6; and in the nine primary lesions, 8.9 ± 3.9. Significant differences in the SUVmax were revealed between metastases and primary lesions (p = 0.006) and between lung metastases and non-lung metastases (p < 0.001). The SUVmax change ratios at 1 month after TKI treatment started were -14.2 ± 48.4% in the lung metastases, -10.4 ± 23.3% in the bone metastases, -9.3 ± 47.4% in the lymph node metastases, -24.5 ± 41.7% in the abdominal parenchymal organ metastases, -10.6 ± 47.4% in the muscle or soft tissue metastases, and -24.2 ± 18.3% in the primary lesions. There was no significant difference among the organs (p = 0.531). CONCLUSIONS: The decrease ratio of FDG accumulation of RCC lesions evaluated by PET/CT at 1 month after TKI treatment initiation was not influenced by the organs where the RCC metastasis was located. This result suggests that TKIs can be used to treat patients with advanced RCC regardless of the metastatic site.

Early assessment by FDG-PET/CT of patients with advanced renal cell carcinoma treated with tyrosine kinase inhibitors is predictive of disease course.

BACKGROUND: We reported previously that (18)F-2-fluoro-2-deoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) had potential for evaluating early response to treatment by tyrosine kinase inhibitors (TKIs) in advanced renal cell carcinoma (RCC). This time we investigated the relation of the early assessment by FDG PET/CT to long-term prognosis with an expanded number of patients and period of observation. METHODS: Patients for whom TKI treatment for advanced RCC was planned were enrolled. FDG PET/CT was performed before TKI treatment and after one month of TKI treatment. The relations of the FDGPET/CT assessment to progression free survival (PFS) and overall survival (OS) were investigated. RESULTS: Thirty-five patients were enrolled (sunitinib 19 cases, sorafenib 16 cases). The patients with RCC showing high SUVmax in pretreatment FDG PET/CT demonstrated short PFS (P =0.024, hazard ratio 1.137, 95% CI 1.017-1.271) and short OS (P =0.004, hazard ratio 1.210 95% CI 1.062-1.379). Thirty patients (sunitinib 16 cases, sorafenib 14 cases) were evaluated again after 1 month. The PFS of the patients whose SUVmax decreased<20% was shorter than that of the patients whose SUVmax decreased<20% (P = 0.027, hazard ratio 3.043, 95% CI 1.134-8.167). The PFS of patients whose tumor diameter sum increased was shorter than that of the patient with tumors whose diameter sum did not (P =0.006, hazard ratio 4.555, 95% CI 1.543-13.448). The patients were classified into three response groups: good responder (diameter sum did not increase, and SUVmax decreased ≥ 20%), intermediate responder (diameter sum did not increase, and SUVmax decreased<20%), and poor responder (diameter sum increased, or one or more new lesions appeared). The median PFS of good, intermediate, and poor responders were 458 ± 146 days, 131 ± 9 days, and 88 ± 26 days (good vs. intermediate P = 0.0366, intermediate vs. poor P = 0.0097, log-rank test). Additionally the mean OSs were 999 ± 70 days, 469 ± 34 days, and 374 ± 125 days, respectively (good vs. intermediate P = 0.0385, intermediate vs. poor P = 0.0305, log-rank test). CONCLUSIONS: The evaluation of RCC response to TKI by tumor size and FDG uptake using FDG PET/CT after 1 month can predict PFS and OS.

[Low-dose docetaxel, estramustine and dexamethasone combination chemotherapy for hormone-refractory prostate cancer].

The objective of this study was to evaluate the efficacy and safety of low-dose docetaxel, estramustine and dexamethasone combination chemotherapy in patients with hormone-refractory prostate cancer (HRPC). Sixty-nine patients with HRPC were enrolled. Docetaxel was given at a dose of 25 mg/m(2) on days 1 and 8 every 3 weeks, oral estramustine 280 mg twice daily on days 1 to 3 and 8 to 10, and oral dexamethasone 1 mg daily throughout the course. Cycles were repeated every 21 days. Treatment was continued until disease progression or excessive toxicity. Patients were evaluated for response and toxicity. Patients received a median of eleven cycles (range : 1-25). Prostatic-specific antigen (PSA) was decreased greater than 50% in 53 (77%) out of 69 patients and median duration of PSA response was 10.2 months. Median time to progression and overall survival 10.2 and 24 months, respectively. Grade 1-2 fatigue was the most common toxicity observed in 10 (15%) patients. Grade 3-4 toxicities were observed in five (7%) patients (2 thrombosis, 2 bilirubin elevation, and 1 aspartate transaminase/alanine transaminase elevation). Low-dose docetaxel, estramustine and dexamethasone combination chemotherapy is an effective and well tolerated treatment for Japanese HRPC patients.

[Metanephric adenoma: report of two cases].

We report 2 cases of metanephric adenoma a rare form of adenoma. One case occurred in a 54-year-old male preoperatively diagnosed with renal cell carcinoma who underwent left partial nephrectomy for a tumor 2 cm in size. Histology revealed a tumor with papillotubular structures consisting of small, uniform tumor cells. In immunohistochemical staining, tumor cells were positive for CD57 and WT-1. Thus, the patient was diagnosed with metanephric adenoma. The other case occurred in a 40-year-old male who underwent left nephroureterectomy for carcinoma of the renal pelvis. Carcinoma of the left renal pelvis was diagnosed as pT3N0M0. Incidental micronodules 2 mm in size and consisting of immature tubular structures were noted in the renal cortex. In immunohistochemical staining, tumor cells were positive for CD57 and WT-1, and the patient was diagnosed with metanephric adenoma. The aforementioned tumors frequently occur in middle-aged women and are often well-defined tumors that project from the renal surface outwards. On angiography, they have a hypovascular pattern and resemble papillary renal carcinoma. Preoperative differentiation of renal cell carcinoma and nephroblastoma is difficult. Mistaking such tumors for malignant tumors and subjecting patients to unnecessary adjuvant therapy must be avoided.

[Squamous cell carcinoma of the ureter arising seventeen years after total cystectomy for squamous cell carcinoma of the bladder: a case report].

We report a case of squamous cell carcinoma of the ureter. A 62-year-old woman had undergone total cystectomy and ileal conduit because of squamous cell carcinoma of the bladder when she was 44 years old. Seventeen years later, she complained of edema and oliguria. Antegrade pyelography and loopography revealed a left ureteral tumor. She underwent left ureterectomy and extirpation of the conduit. Pathological diagnosis was moderately differentiated squamous cell carcinoma of the ureter, pT2. The patient is alive without recurrence or metastasis in the first year after surgery.

[Two cases of retroperitoneal liposarcoma arisen from perirenal fat tissue, which could not be diagnosed preoperatively].

We report two cases of retroperitoneal liposarcoma arisen from the perirenal fat tissue, which could not be diagnosed preoperatively. Case 1 is a 58-year-old male. He complained of left flank tumor. Computed tomography and magnetic resonance image showed a mass over 10 cm that contained fat components in the retroperitoneal space. The tumor was resected with left nephrectomy and histological examination revealed well differentiated liposarcoma. As adjuvant therapy, he received chemotherapy and 30 months has passed uneventfully. Case 2 is a 70-year-old male. Screening ultrasonography revealed incidental retroperitoneal tumor. With clinical diagnosis as non-functioning adrenal tumor, he received left nephrectomy. The pathological diagnosis was well differentiated liposarcoma, sclerosing type. No adjuvant therapy was performed. He has stopped visiting our clinic due to aggravation of heart disease. The characteristics of the images of the two cases were different despite the histological resemblance. This difference was considered to be due to the difference in the distribution of lipomatous tissue in each patient.

Renal oncocytosis.

Renal oncocytosis is a rare disorder in which numerous oncocytic nodules develop in the kidney. An additional case is reported here. The patient was a 51-year-old woman who had received hemodialysis for 27 years. Nineteen years previously she had developed a tumorous lesion in the right kidney, which had been diagnosed as oncocytoma with laparotomic biopsy. Recently the kidney was removed because of enlargement of the tumor. The renal parenchyma was entirely replaced with numerous brownish nodules. Histologically, the nodules were composed of nests of uniform oncocytic cells. Ultrastructurally, the oncocytic cells contained numerous mitochondria. Immunohistochemical features of the nodules were identical to those of sporadic oncocytomas, that is, immunophenotypes similar to the distal nephron and reactivity with antimitochondrial antigen. Based on these findings, the lesion was diagnosed as renal oncocytosis. It was not possible to determine whether the larger nodules should be diagnosed as oncocytoma or a part of oncocytosis. Additionally, the germ line mutation of the Birt-Hogg-Dubé (BHD) syndrome gene was examined using the genomic DNA obtained from the peripheral lymphocytes, which failed to show any gene alteration. Despite the rare occurrence pathologists and urologists should be aware of renal oncocytosis, as a precursor lesion of renal oncocytoma and chromophobe renal cell carcinoma.