Brain metastases from transitional cell carcinoma of the bladder

We present our experience with 4 patients with transitional cell carcinoma of the bladder and brain metastases. In all 4 cases a solitary intracranial metastasis occurred. In 3 patients this represented the first site of recurrent disease following systemic chemotherapy. Aggressive therapy of the brain metastases was instituted in 3 patients, including external beam radiation and in 2 cases surgical resection. Although all patients died only 3 died as a result of metastatic transitional cell carcinoma, including 2 who died as a direct result of intracranial disease. A review of the literature suggests an increasing incidence of brain metastases from transitional cell carcinoma of the bladder with the advent of more aggressive therapy for bladder cancer, which includes radical surgery for high stage disease and combination chemotherapy. Aggressive intervention for solitary brain metastases from transitional cell carcinoma can relieve neurological dysfunction and may prolong survival.     

Histopathologic changes of transitional cell carcinoma of bladder after M-VAC chemotherapy

Over the past several years, we have utilized methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) as definitive, neoadjuvant, and adjuvant therapy for various stages of transitional cell carcinoma with reduced toxicities. Currently, there is little information concerning the histopathologic changes after M-VAC therapy. We report on the histopathologic changes of bladder transitional cell carcinoma following M-VAC chemotherapy in our protocol for treatment of bladder cancer. The main histopathologic findings after M-VAC therapy are squamous metaplasia, necrosis, fibrosis, and persistent transitional cell carcinoma. In 2 cases, there were persistent adenocarcinoma and squamous cell carcinoma. The importance of these observations in terms of diagnostic and therapeutic implications is reviewed.     

Experience with combination chemotherapy consisting of methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) in advanced urothelial cancer

The M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) regimen was used to treat 6 patients with metastatic transitional cell carcinoma of the urothelial tract. Three patients showed a partial response, all of them were made surgically disease free. Two of them are still alive 1 year and for 6 months after surgery with no evidence of disease and one other died of disease 11 months after surgery. The response in one case was no change and that in two others was a progressive disease. From our experience, we suggest that treatment with M-VAC is effective but that surgery after M-VAC appears essential for the successful management of the patients with metastatic transitional cell carcinoma of the urothelial tract.     

Carcinomatous meningitis from transitional cell carcinoma of bladder

The following case report presents a patient with transitional cell carcinoma of the bladder referred to this medical center after carcinomatous meningitis developed. Previously he had undergone surgical resection of the primary lesion and had received cis-platinum chemotherapy for lung metastasis. This unusual presentation of metastatic disease (carcinomatous meningitis) seems to alert the surgical and medical communities to new complications.     

Polychemotherapy using the M-VEC protocol (methotrexate, vinblastine, epirubicin, cisplatin) in advanced urinary bladder cancer--effectiveness and toxicity

We report on preliminary experience with a modified M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) regimen in which adriamycin was replaced by the less toxic 4-epirubicin at equal doses (M-VEC). This study includes 58 patients suffering from advanced bladder cancer, with a minimum observation time of 12 months; each patient received at least two courses of M-VEC (mean follow-up 22 months, average 3.9 cycles). Most (22; 37.9%) of the tumors were T3-4 NO MO; 20 (34.4%) were T3-4 N1-2 MO; and 16 (27.7%) were T3-4 NO-2 M1. Microscopically, 52 (89.6%) were pure transitional cell carcinoma, 5 were (8.6%) squamous cell/carcinomatous transformation; 1 (1.8%) sarcoma was found. Chemotherapy was given as palliative treatment in 34 (58.6%) patients, as neo-adjuvant therapy in 19 (32.8%) cases and as adjuvant therapy in 5 (8.6%) patients. The overall response rate was 72.3% (CR = 51.7%), with a mean duration of response of 18+ months. The disease-free survival so far amounts to 24/58 (41.4%). Squamous cell carcinoma does not respond to M-VEC. Locally advanced bladder cancer (T3-4 NO-2 MO) responds significantly better than metastatic (M1) disease (78.5% vs 56.2%), resulting in an increased survival rate (57% versus 12.5%) after 22 months. The toxicity of M-VEC is considerably lower than has been reported for other regimens (M-VAC, CMV, CM). The toxic effects included mucositis (3%), nadir sepsis (2.4%) and drug-related death (2.4%).     

Metástasis cutáneas de un carcinoma transicional vesical productor de β-HCG

In spite of the high incidence of transitional cell carcinoma, cutaneous metastases are infrequent, especially when they are the first sign of metastatic spread, with a low survival rate.Thirty five per cent of transitional cell carcinoma of the bladder have ectopic beta- human chorionic gonadotropin (β-HCG) production. It has been related with high grade tumors, advanced stage, metastatic disease, radioresistent tumors and low survival rate because of its effect as a growth modulator with a probably antagonist action in the apoptotic cascade. We present a thirty six years old woman affected by a transitional cell carcinoma of the bladder producing β-HCG that showed two cutaneous metastases as first sign of metastatic disease. The exceptional coincidence of these two circumstances announced a very aggressive tumor behaviour and bad prognostic, with a quickly multiple metastatic dissemination including a pericardic metastases.     

A case of primary transitional cell carcinoma of the prostate]

We report a rare case of primary transitional cell carcinoma of the prostate. A 66-year-old man was referred to our hospital with the chief complaints of pollakisuria and residual urine sensation on January 21, 1998. Under a preoperative diagnosis of benign prostatic hyperplasia, transurethral resection of the prostate was performed. Histopathological examination revealed grade 3 transitional cell carcinoma. Then the transrectal needle biopsy of the prostate and random biopsy of the urinary bladder were performed. Since no metastatic tumors or tumor cells were detected in either the prostate or urinary bladder or any other organs, this patient was diagnosed with primary transitional cell carcinoma of the prostate. Three courses of adjuvant chemotherapy (M-VAC) were performed, and tumor recurrence was not recognized 9 months after the operation. This is the 35th case of primary transitional cell carcinoma of the prostate in the Japanese literature.     

Carcinomatous meningitis from urothelial carcinoma of bladder and ureter: case report

Carcinomatous meningitis from urothelial carcinoma of the bladder and ureter is rare. A 77-year-old man with invasive bladder cancer and right ureter cancer had been treated with 3 courses M-VAC (methotrexate, vinblastine, epirubicin, cisplatin) chemotherapy. After chemotherapy we performed radical cystectomy and right nephroureterectomy (ileal-neobladder) (TCC, G3, pT3, N0, M0). Sixteen months after operation, patient complained of anorexia, muscular weakness, stiff neck. CT of chest and abdomen, and bone scintigraphy showed no metastasis. Brain CT and MRI showed hydrocephalus but no evidence of parenchymal metastasis. Because we suspected carcinomatous meningitis, we performed lumbar puncture. Cerebrospinal fluid cytology revealed class V (urothelial carcinoma). Patient died 6 days after diagnosis of carcinomatous meningitis.     

Clinical efficacy of modified M-VAC chemotherapy for advanced urothelial carcinoma and influence of squamous cell carcinoma-associated antigen on efficacy of the chemotherapy

The efficacy of modified M-VAC chemotherapy was evaluated in twenty-two patients with advanced urothelial carcinoma (18 cases of transitional cell carcinoma, 3 of transitional cell associated with squamous cell carcinoma and 1 of squamous cell carcinoma). Among the 22 patients, 14 underwent two or more courses of modified M-VAC chemotherapy and had lesions suitable for the evaluation. Three of the 14 patients achieved complete response and 6 partial response, resulting in a 64.3% response rate. With regard to the direct effect according to the site of the lesion, the response rate was 75% for the urinary bladder, 100% for lung, 100% for subcutaneous tissues, and 75% for lymph nodes metastasis, whereas the chemotherapy was ineffective for metastasis in the bone and muscle. With this neoadjuvant chemotherapy the primary tumor of the urinary bladder was downstaged from T2 to T0 in one patient who showed complete response. In 4 of 5 patients achieving partial response, the primary tumors were downstaged from T2 to T1. Of 9 patients given this chemotherapy for metastatic lesions, 2 achieved complete response and are alive, whereas all 3 without response died of cancer within the 1 year following the chemotherapy. Since most of the cases associated with the squamous cells carcinoma component showed no response to the therapy, it seems that the level of serum squamous cell carcinoma-associated antigen may be helpful for predicting the efficacy of modified M-VAC chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bladder carcinoma metastases presenting as intraperitoneal dissemination without local recurrence: a case report

A 76-year-old woman presented with gross hematuria and was referred to our OPD. Cystoscopy showed broad-based papillary tumors on the left bladder wall. TUR-BT was performed and pathological diagnosis was grade 3 transitional cell carcinoma of pT1a. Although no intravesical tumor recurrence had been observed, a solid palpable mass was noted in the lower abdomen nine months after TUR-BT, and computed tomography suggested a large ovarian tumor. Subsequently performed was the operation at Gynecology, which revealed a large tumor involving the whole major omentum. Frozen sections of the tumor were diagnosed as transitional cell carcinoma metastases of the bladder cancer, and the final pathological report was the same. Although receiving 4 courses of M-VAC systemic chemotherapy after the operation, she died 14 months later. Autopsy disclosed intraperitoneal cancer dissemination and metastases without any intravesical nor left perivesical tumor recurrence, and it was suggested that the bladder tumor metastases occurred not by direct invasion but by either lymphatic or vascular mechanism in this case.     

Primary transitional cell carcinoma of prostate: case with lymph node metastasis eradicated by neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) therapy

A case of transitional cell carcinoma of the periurethral prostatic ducts received neoadjuvant chemotherapy consisting of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), which eradicated pelvic lymph node metastasis, followed by cystoprostatectomy. M-VAC therapy may be indicated for metastatic transitional cell carcinoma of the periurethral prostatic ducts.     

Outcome of treatment with surgical resection of the remaining tumor after modified M-VAC treatment for advanced urothelial carcinoma

We retrospectively evaluated the effect of the surgical resection of the remaining tumor after modified M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) (m-M-VAC) treatment for locally advanced or metastatic urothelial carcinoma. In m-M-VAC therapy, methotrexate and vinblastine on 15 and 22 days were omitted from the classical M-VAC to avoid the discontinuation and the dose reduction, and duration of 1 course was shortened to 21 days from 28 days of the classical M-VAC. Seven patients with locally invasive or metastatic carcinoma of the renal pelvis, ureter, and bladder, 6 males and 1 female, with a median age 64.1 years, ranging from 49 to 77 years received m-M-VAC chemotherapy without severe side effects. In all patients, the residual viable carcinoma was completely resected and they achieved complete remission. The median survival time was 20 months (range, 7 to 61). Five of these 7 patients were still alive. Two patients had no recurrence and achieved long-term survival (survival duration; 61 and 39 months). Although further studies and long-term follow up are required, these results suggest that patients who present with locally advanced or metastatic urothelial carcinoma may benefit from surgical resection after m-M-VAC.     

Squamous cell carcinoma of bladder

Examination of the histology of all bladder tumors presented to the London Hospital over a ten-year period revealed a surprisingly low incidence of squamous bladder carcinoma. We would support the view of other workers that this tumor usually presents at an advanced stage and carries with it a poor prognosis. However, when no evidence of metastatic disease is evident, treatment with standard protocol of radiation therapy and cystectomy should achieve the same results as for the transitional cell tumor. Squamous cell carcinoma of the bladder would appear to be as radiosensitive as its transitional cell counterpart.     

Small cell carcinoma of the urinary bladder with synchronous esophageal cancer and incidental lung cancer: a case report]

We present a case of triple primary cancers occurring synchronously in the urinary bladder, esophagus, and incidentally in the lung. A 65-year-old man with a chief complaint of gross hematuria was admitted to our hospital. Cystoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) revealed a non-papillary broad-based bladder tumor. Histological diagnosis was transitional cell carcinoma of the urinary bladder and he underwent one course of neoadjuvant chemotherapy (M-VAC) with the preoperative diagnosis of T3bN0M0. After one course of chemotherapy, chest CT, lymph node biopsy and esophagoscopy revealed squamous cell carcinoma of the esophagus. He first underwent radiochemotherapy (total 70 Gy, CDDP 5 mg x 41, 5-FU 250 mg x 24) for esophageal cancer and achieved complete remission. Then, he underwent radiotherapy for a total of 60 Gy for bladder cancer. However, his general condition gradually became worse and he died from metastatic cancer. The autopsy proved that he died from multiple metastases of small cell carcinoma of the urinary bladder and incidentally squamous cell carcinoma of the lung was identified.     

Diabetes insipidus due to pituitary metastasis from bladder cancer

We report a 41-year-old man with bladder cancer who developed polyuria following successful treatment of hypercalcemia and who was found to have a transitional cell carcinoma within the pituitary gland at autopsy. He also had widespread bone metastases. Although primary urogenital cancers rarely metastasize to the pituitary, the patient's clinical course led us to suspect metastatic disease from the bladder cancer. Metastasis to the pituitary gland is more common than generally thought and should be considered in patients with advanced cancer who develop polyuria and polydipsia.     

Contribution of 11C-choline positron emission tomography/computerized tomography to preoperative staging of advanced transitional cell carcinoma

PURPOSE: Current imaging modalities for preoperative staging of advanced transitional cell carcinoma of the bladder or upper urinary tract are not sensitive for detection of metastases. This study examines the contribution of 11C-choline positron emission tomography/computerized tomography to preoperative staging of transitional cell carcinoma. MATERIALS AND METHODS: We prospectively evaluated 18 patients with 19 advanced transitional cell carcinomas (17 bladder tumors and 2 upper tract transitional cell carcinomas). All patients had computerized tomography of the chest, abdomen and pelvis negative for metastases. 11C-choline positron emission tomography/computerized tomography was performed on a Discovery ST(R) positron emission tomography/computerized tomography system. Finally 16 patients underwent radical surgery and positron emission tomography/computerized tomography images were compared to histopathological findings. Two patients were not operated on due to the findings on 11C-choline positron emission tomography/computerized tomography. RESULTS: 11C-choline uptake was found in all primary transitional cell carcinomas, with a maximum standardized uptake value of 7.3 +/- 3.2 (mean +/- SD). The series included 3 patients with refractory bladder carcinoma in situ, which was visualized in all 3, with a standardized uptake value of 6.9 +/- 5.6. In 6 patients uptake of 11C-choline in lymph nodes as small as 5 mm was visualized (standardized uptake value 3.8 +/- 1.4). Of these patients 4 underwent surgery and histopathology confirmed malignancy in 3 of 4. No additional patients with positive lymph nodes were found on histopathology. Metastases were visualized in bones with normal architecture on computerized tomography in 4 patients (standardized uptake value 5.2 +/- 1.1) and were confirmed by followup computerized tomography. CONCLUSIONS: In this small series 11C-choline positron emission tomography/computerized tomography was highly sensitive for primary and metastatic transitional cell carcinoma. Carcinoma in situ, lymph node metastases and early bony metastases were visualized. 11C-choline positron emission tomography/computerized tomography is a promising tool for preoperative staging of advanced transitional cell carcinoma.     

Solitary cerebellar metastasis from transitional cell carcinoma of bladder.

Brain metastasis from transitional cell carcinoma of the bladder is unusual, occurring most often in the presence of widespread systemic metastases. We report on a patient who presented with an isolated cerebellar metastasis and recurrent carcinoma of the bladder, after treatment with local excision and intravesical thiotepa. Further evaluation failed to demonstrate other distant metastases. Excision of the cerebellar lesion revealed transitional cell carcinoma identical to the original bladder tumor. In a review of the literature, we found reports of two similar patients in whom a solitary cerebellar lesion was the first sign of metastasis from carcinoma of the bladder; neither patient had evidence of other distant metastases, and neither previously had received systemic chemotherapy. These observations indicate that central nervous system metastasis from carcinoma of the bladder, while rare, should be considered in the differential diagnosis of solitary intracerebellar lesions in such patients.     

A case report of sarcomatoid carcinoma of the bladder with metastasis to small intestine

A 67-year-old male presented to our clinic with gross hematuria. Cystoscopic examination revealed a broad-based tumor of 2.5 cm in diameter on the lateral side of the right ureteral orifice. Under the clinical diagnosis of TCC G2 > G3, T3bNOM0, radical cystectomy with orthotopic bladder substitution was performed. Pathological diagnosis was TCC G3 with sarcomatoid carcinoma, pT2pR0pL1 pVlpN0. Adjuvant chemotherapy was not performed because of his transient poor conditions. Lung metastasis was observed 6 months postoperatively. Despite of M-VAC therapy and radiation therapy, additional metastases to brain and liver were observed. One month later, partial ileectomy specimen for occlusive ileum revealed the same histologic findings, TCC G3 with sarcomatoid carcinoma. He died 9 months postoperatively. To our knowledge, this is the first case of sarcomatoid carcinoma of the bladder with metastasis to small intestine, although 6 cases of transitional cell carcinoma of the bladder with metastasis to small intestine has been reported in Japan.     

Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to 2003: a report from the National Cancer Data Base

PURPOSE: Studies of perioperative chemotherapy for muscle invasive bladder cancer have shown a survival benefit with combined modality therapy. We reviewed chemotherapy use in patients with stage III transitional cell carcinoma of the bladder from 1998 to 2003 to evaluate perioperative chemotherapy treatment patterns. MATERIALS AND METHODS: The National Cancer Data Base collected data on approximately 60% of all newly diagnosed bladder cancer cases in the United States from 1998 to 2003. We queried the National Cancer Data Base for all treatment of male and female patients 18 years old or older with bladder transitional cell carcinoma diagnosed between 1998 and 2003. A total of 224,060 bladder transitional cell carcinoma records were reviewed. Perioperative chemotherapy was defined as chemotherapy given within 4 months before and 4 months after surgery. Of 11,339 cases of stage III bladder cancer treatment, analysis was possible for 7,161. RESULTS: Treatment patterns were analyzed in 7,161 patients with stage III bladder transitional cell carcinoma. Perioperative chemotherapy was administered to 11.6% of patients with stage III bladder transitional cell carcinoma with 10.4% receiving adjuvant chemotherapy and 1.2% receiving neoadjuvant chemotherapy. When comparing perioperative chemotherapy use by diagnosis year in 1998 and 2003, a small statistically significant increase was observed using the Pearson's chi-square test with Bonferroni correction (p <0.05) at 11.3% of patients in 1998 vs 16.8% in 2003. CONCLUSIONS: Perioperative chemotherapy is underused in the management of surgically resectable stage III transitional cell carcinoma of the bladder. This finding may reflect a delay in implementing the results of recently reported randomized trials, a low incidence of referrals by urologists for chemotherapy and/or confidence in salvage chemotherapy as an equivalent alternative. Further followup will determine if this treatment pattern changes in the future.     

Lokal fortgeschrittenes oder metastasiertes Harnblasenkarzinom Aktuelle Aspekte in der Therapie

The prognostic factors for infiltrating tumors established by the TNM system in 1997 include: Depth of infiltration, degree of differentiation, status of lymph nodes distant metastases. Of the additional factors investigated, only tumor size and hydronephrosis appear to be of prognostic significance. In the scope of molecular markers, the loss of expression of the epithelial cell-cell adhesion molecule E-cadherin signals an unfavorable clinical course. In cases of carcinoma of the urinary bladder without metastases (T2-4,N0,M0), radical cystectomy is the therapy of choice. A preceding neoadjuvant systemic regimen of chemotherapy with three cycles of M-VAC (methotrexate, vinblastine, adriamycin, cisplatin) significantly improves the survival rate. In patients with locally advanced urinary bladder carcinoma, however, adjuvant systemic chemotherapy with M-VAC after cystectomy and lymphadenectomy offers no advantages for survival. Quality of life in patients with metastatic bladder cancer disease is improved by new cytotoxic drugs, i.e. gemcitabine or taxanes.