Successful treatment of metastatic adenocarcinoma of the urachus: report of 2 cases with more than 10-year survival.

Metastatic urachal cancer is often considered lethal. We report 2 cases of metastatic urachal carcinoma successfully treated with surgical excision followed by combinations of surgery, radiation, and chemotherapy against local recurrence and/or distant metastases, with a recurrence-free survival period of more than 10 years. These cases provide support for multimodal treatments of metastatic urachal cancer.

Combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin for metastatic urothelial cancer.

PURPOSE: To investigate the activity of combination chemotherapy with ifosfamide, 5-fluorouracil, etoposide and cisplatin in patients with metastatic urothelial cancer. METHODS: A group of 29 patients were treated with 2000 mg/m2 ifosfamide, 750 mg/m2 5-fluorouracil, 100 mg/m2 etoposide and 20 mg/m2 cisplatin. All four drugs were given intravenously on days 1 through 3 and the treatment was repeated every 3 weeks. Of the 29 patients, 14 had lymph node metastasis alone, and 15 had visceral lesions. RESULTS: An objective response was achieved in 17 patients (59%). There was no difference in response rates according to metastatic site including osseous lesions, which responded well in four of six patients. The 3-year survival rate for all patients was 16% with four patients who had undergone salvage surgery being alive with no evidence of disease 15 to 61 months after initiation of the treatment. A good performance status, lymph node metastasis alone and administration of chemotherapy at the full dosage had a significantly favorable impact on patient survival. Bone marrow toxicity was significant and one patient died of treatment-related sepsis. CONCLUSIONS: Ifosfamide, 5-fluorouracil, etoposide and cisplatin combination chemotherapy appeared to be active in the treatment of metastatic urothelial cancer. Although bone marrow toxicity was significant, the treatment was well tolerated by the majority of the patients. Further study may be warranted.

[Low dose CVD chemotherapy as a tumor dormancy therapy for extra-adrenal malignant pheochromocytoma: a case report].

A 38 year-old man presented with upper abdominal mass and hypertension pointed out at a medical examination. Blood pressure was 170/90 under medication of an alpha-blocker. Abdominal CT scan showed an 8 x 8 cm inter-aortocaval mass displacing pancreas head ventrally, and further a 4 x 4 cm mass at the aortic bifurcation, but there was no tumorous lesion in bilateral adrenal glands. Plasma nor-epinephrine level and urinary VMA excretion were excessive but plasma adrenaline level was within normal limits. MIBG scintigram showed hot spots in the 4th and 9th thoracic vertebrae. The destructive change of the 9th vertebra on magnetic resonance imaging strongly suggested metastasis of the tumor. Histologic and immunohistochemical findings of the biopsy specimen taken from the lower abdominal tumor in addition to the above clinical data led to the diagnosis of extra-adrenal malignant pheochromocytoma with spinal metastases. Since 2 cycles of full dose CYVADIC chemotherapy had no effects on lowering the high blood pressure and reducing the tumor size, low dose (60% of the full dose) CVD (cyclophosphamide, vincristine and dacarbazine) was given as a palliative chemotherapy on an out-patient clinic approximately every 4 weeks. After 4 cycles of the chemotherapy, his backache due to spinal metastasis markedly improved, hypertension as well as the plasma dopamine level was normalized and nor-epinephrine level was markedly decreased, though the tumor size was not reduced. Thereafter, no medication for hypertension was necessary. During 3 years and 6 months until now, 36 cycles of the chemotherapy has been repeated with no significant side effects. He has been at full-time work with quality of life being well preserved. Low dose CVD regimen appears to be an effective tumor dormancy therapy for advanced extra-adrenal pheochromocytoma.

The serum level of the amino-terminal propeptide of type I procollagen is a sensitive marker for prostate cancer metastasis to bone.

OBJECTIVE: To assess the level of a bone-formation marker, the amino-terminal propeptide of type I procollagen (PINP), for its utility in indicating bone metastasis in patients with prostate cancer. PATIENTS AND METHODS: Several bone formation markers, i.e. PINP, the carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BALP), and bone Gla protein (BGP), a bone resorption marker (pyridinoline cross-linked carboxy-terminal telopeptide, ICTP), and prostate specific antigen (PSA) were measured in 40 patients without and 25 patients with bone metastasis. No patient had undergone previous treatment, except for six who developed bone metastasis while undergoing hormone therapy. RESULTS: All markers except BGP were significantly higher in patients with bone metastasis than in those without. The levels of PINP correlated best with the extent of disease, although the levels of PSA, BALP and ICTP also correlated well. While PINP had the largest area under the receiver-operator characteristic curve, PSA, BALP and ICTP also produced useful curves. CONCLUSION: The bone formation marker PINP seems to be useful for discriminating patients with and without bone metastasis. PINP may help in the early and accurate diagnosis of bone metastasis in such patients.

Retroperitoneal cystic metastasis from a small clear cell renal carcinoma.

A 39-year-old housewife was referred to our hospital for the treatment of a small renal tumor. A 25 x 35 mm cystic mass that had been detected by computerized tomography scan just caudal to the renal hilus proved to be a metastasis from the renal carcinoma of clear cell type. The pathogenesis may have been due to tumor cells obstructing a lymphatic vessel draining the kidney. Cystic metastasis from renal cell carcinoma is very rare and this appears to be the second published case in the world.

Sympathetic efferent pathways projecting to the prostate in the dog.

BACKGROUND: The laterality of the signals passing through the splanchnic nerves to each lobe of the prostate has not been studied. METHODS: Bilateral distribution of sympathetic signal to both lobes of the canine prostate was determined by measuring contraction of the prostate by stimulation of thoracolumbar splanchnic nerves with or without transection of unilateral hypogastric nerve (HGN). RESULTS: The 2nd-5th lumbar splanchnic nerve (LSN) stimulation elicited prostatic contraction. Twenty-five of 27 right LSN stimulations elicited contraction of the lobe, 21 bilaterally and 4 unilaterally. Twenty-three of 25 left LSN stimulations elicited contraction of the lobe, 22 bilaterally and one unilaterally. The above stimulations did not elicit a dominant response in the lobe of the stimulated side. After transection of the right HGN, right and left LSN stimulation elicited contraction of the lobe bilaterally and did not induce dominant response in the lobe of the non-lesioned side. After transection of the left HGN, similar results were obtained. CONCLUSIONS: The results indicate that each of the LSNs sends signals to bilateral lobes via multiple routes with two crossing sites at the level of the caudal mesenteric plexus and prostate, and that the signals elicit contraction of the lobe without a dominant side.

[Treatment results of VIP (etoposide, ifosfamide and cisplatin) chemotherapy as a first-line therapy in metastatic germ cell tumors].

PURPOSE: We investigated the effectiveness and toxicity of VIP therapy as a first-line chemotherapy for patients with metastatic germ cell tumor. PATIENTS AND METHODS: From March 1994 to October 1997, we treated 16 patients with VIP therapy consisting of etoposide (100 mg/m2), ifosfamide, (1.2 g/m2) and cisplatin (20 mg/m2), all of which were generally given daily for 5 consecutive days every 3 weeks. Of the 16 patients, 6 were classified into a good, 5 into an intermediate, and 5 into a poor prognostic group according to the International Germ Cell Consensus Classification. RESULTS: Thirteen patients (81%) achieved complete response with VIP alone or VIP plus surgery. Three-year survival rate was 100% in good and intermediate prognostic group, while 40% in poor prognostic group. Although all patients had Grade 3 or higher myelosuppression, the treatment was well tolerated and no patient died of treatment-related complications. CONCLUSIONS: VIP appears to be an effective and safe regimen as an induction chemotherapy for good and intermediate risk patients with germ cell tumor. However, more intensive regimen may be necessary for poor-risk patients.

[Metastatic testicular tumor requiring inferior vena cava resection with polytetrafluoroethylene graft replacement: a case report].

A 31 year-old man with a biopsy-proved retroperiotoneal yolk sac tumor was referred to our clinic. Physical examination revealed a thum- tip sized left supra-clavicular mass, a huge right abdominal mass and a tiny hard mass of the right testis. On CT scan, the abdominal tumor, 13 cm in diameter, encircled the inferior vena cava. Serum levels of LDH, AFP and hCG-beta were 2,585 U/l, 19,922 ng/ml and 6.6 ng/ml, respectively. No visceral metastasis was found. Following the right high orchiectomy, 4 cycles of VIP chemotherapy consisting of ifosfamide, etoposide and cisplatin were given, which resulted in partial response of the retroperitoneal mass and complete regression of the supraculavicular node with normalization of all tumor markers. Thus, retroperitoneal lymph node dissection was carried out. Because of the marked adhesion to the tumor, the inferior vena cava was segmentally resected together with the tumor, which was followed by reconstruction of the vena cava using a 16 cm long polytetrafluoroethylene graft, since no collateral venous route was found on the pretreatment venacavography. Histologically, the tumor was nearly necrotic with mature teratoma in small part. Postoperative clinical course was uneventful except feeling of numbness at the right tip toe, and the inferior vena cava has been patent 18 months after the operation with no evidence of recurrence.

[Two cases of giant testicular tumor with widespread extension to the spermatic cord: usefulness of upfront chemotherapy].

The first case was a 55-year-old man with biopsy-proven seminoma of the left inguinal undescended testis. The tumor, 10 x 9 x 9 cm in size, with a calculated weight of 520 g invaded the left spermatic cord up to the level of the renal hilum and metastasized to the retroperitoneal lymph nodes (13 x 10 cm). The serum level of lactate dehydrogenase (LDH) and beta human chorionic gonadotropin (beta-hCG) was 3,669 U/l and 1.3 ng/ml, respectively. The second case was a 38-year-old man with non-seminoma of the left testis. The testicular tumor, 32 x 28 x 28 cm in size, with a calculated weight of 7,000 g invaded the left spermatic cord up to the level of the aortic-bifurcation and metastasized to the retroperitoneal and the left supraclavicular lymph nodes. The serum level of LDH, alphafetoprotein (AFP) and beta-hCG was 2,040 U/l, 240 ng/ml and 5.6 ng/ml, respectively. Both patients were initially treated with VIP chemotherapy (etoposide, ifomide and cis-platinum), 4 cycles for the 1st case and 3 for the 2nd, and followed by high orchiectomy and retroperitoneal lymph node dissection. Histologic section of all resected specimens revealed only necrosis and fibrosis. The patients have been free of recurrence for 15 and 13 months, respectively, after the operation. In the Japanese literature, 42 cases of giant testicular tumor (> 400 g) including these two cases have been reported. To our knowledge, our second case is the largest among the non-seminomatous tumors. For giant testicular tumor with extensive invasion to the spermatic cord, initial chemotherapy followed by surgical resection appears to be a better management.

[Successful multidisciplinary treatment for bladder cancer with priapism. A case report].

A 44-year-old man suspected of having transitional cell carcinoma (TCC) of the prostate was referred to our hospital. He had a painful semi-erect penis at his first visit. Then needle biopsy of the corpus cavernosum histologically revealed metastatic TCC. CT of the pelvis showed bilateral ureteral obstruction caused by the advanced tumor but no lymph node swelling was found. Under the diagnosis of prostatic TCC with penile metastasis, bilateral percutaneous nephrostomy followed by two courses of combination chemotherapy (IFEP regimen) was carried out, which resulted in the disappearance of priapism. Radical cystectomy with total penectomy was performed. The final pathological diagnosis was corrected to TCC of the urinary bladder with invasion to the prostate and metastasis of the corpus cavernosum and the right obturator lymph node. Enlargement of the prostate proved to be caused by glandular hyperplasia with atypical hyperplasia of the prostate gland. Three courses of adjvent IFEP chemotherapy was given post-operatively and he has been alive with no evidence of the disease for 10 months.

[Successful management for chemorefractory testicular cancer with brain and lung metastases. A case report].

This is a report of successful management for a far advanced, chemorefractory testicular cancer patient. A 29-year-old male was referred to our hospital for the treatment of progressive lung metastases with elevated hCG level, which had recurred after complete remission following 3 courses of BEP chemotherapy and progressed after transient partial regression following 2 courses of intensified EP chemotherapy. In addition, a 3 cm in diameter, solitary brain metastasis was detected on CT. First, we performed wedge resection of bilateral pulmonary lower lobe for chemorefractory pulmonary metastases. Histological examination revealed viable embryonal carcinoma identical to the primary one. Thereafter, whole brain irradiation in combination with VIP chemotherapy (etoposide 100 mg/m2, cisplatin 20 mg/m2 and ifosfamide 1200 mg/m2 daily for 5 consecutive days) was carried out to treat brain metastasis. By 2 cycles of VIP therapy and irradiation (36 Gy), partial tumor regression and normalization of hCG level were achieved, leading to salvage surgery of the brain metastasis which histologically proved to be necrosis. Following an additional cycle of VIP therapy, the patient has been free of recurrence 24 months after completion of the treatment.

Telomere length and telomerase activity in bladder and prostate cancer cell lines.

BACKGROUND: Specific repeats of oligonucleotides at the ends of chromosomes (telomeres) are shortened by cell division in somatic cells and are thought to be related to aging. Immortal cells such as germ-line cells or cancer cells have demonstrated increased activity of the telomere-elongating enzyme (telomerase). The length of the telomeres of these cells is stable regardless of cell division. We examined the telomere length and telomerase activity in 3 bladder (JTC30, JTC32, and T24) and 2 prostate cancer (LNCaP and DU145) cell lines. METHODS: Telomere lengths were evaluated by Southern blot analysis with a oligonucleotide probe, (TTAGGG)5, and telomerase activities were detected with a polymerase chain reaction-based assay method. RESULTS: Telomerase activity was detected in all of the cell lines. Each cell line had a specific telomere length. In 2 bladder cancer cell lines (JTC30 and JTC32), the telomere length decreased with increased passage of the cells. CONCLUSION: The presence of telomerase may be a biological character of bladder and prostate cancers as well as other malignancies, although it does not always compensate telomere shortening.

Prognostic significance of prostate-specific antigen levels two months after hormonal manipulation of metastatic prostate cancer.

OBJECTIVE: To assess the prognostic significance of prostate-specific antigen (PSA) levels before and during therapy in patients with metastatic adenocarcinoma of the prostate receiving hormonal manipulation. METHODS: The PSA levels before and during treatment, together with various clinicopathological parameters, were measured retrospectively in 48 patients with newly diagnosed metastatic prostate cancer. The prognostic importance of these measurements was analyzed by both univariate and multivariate techniques. RESULTS: PSA levels 2 months after treatment were the most useful predictors of progression-free (p = 0.004) or cause-specific survival (p = 0.006) in a multivariate Cox proportional-hazard model including histologic grade, age, performance status and pretreatment hemoglobin. CONCLUSIONS: We have found that a low PSA level 2 months after treatment is prognostically superior to conventional clinicopathological parameters, such as histologic grade, in patients with metastatic prostate cancer undergoing treatment by hormonal manipulation.

Multiple primary malignant neoplasms associated with prostate cancer in 312 consecutive cases.

The relative risk for a second primary cancer after the diagnosis of prostate cancer and the prognostic impact of the association of multiple primary malignant neoplasms (MPMNs) in patients with prostate cancer were analyzed in a retrospective study. The development of MPMNs was examined in 312 consecutive patients who had been diagnosed with prostate cancer between 1966 and 1992. The population-based cancer incidence rates in Japan were utilized to calculate the expected number of MPMNs. Of the 312 patients, 60 fulfilled the diagnosis of MPMNs. In 13 men, prostate cancer and other malignancies were diagnosed simultaneously. In 35 of the 312 patients, prostate cancer was the second or third cancer diagnosis. In the remaining 287 patients, prostate cancer developed initially. Of the 287 patients, 12 developed a second primary malignancy compared with 17 expected (relative risk 0.71, 95% confidence interval 0.45-1.4). No single anatomic site showed a significantly increased risk above that expected either. The overall survival of patients with prostate cancer was not reduced by the association with MPMNs. This may be explained by the fact that the stage of the prostate cancer was lower in patients with MPMNs than in patients without MPMNs.

Significant telomere reduction in human superficial transitional cell carcinoma.

OBJECTIVE: To investigate telomere reduction and telomerase activity in human transitional cell carcinomas (TCCs) of the bladder, using primary tissue preparations, and their relationship to the clinicopathological properties of the TCC. MATERIALS AND METHODS: Tumour tissues were obtained from 21 patients together with apparently normal urothelia as controls. The mean telomere length of each sample was determined using southern blot analysis with an oligonucleotide probe (TTAGGG)4 and telomerase activity was semi-quantified using a polymerase chain reaction based assay. RESULTS: The mean (SE) telomere length was 6.6 (0.7) kb in tumour tissues and 11.5 (0.4) kb in apparently normal urothelia adjacent to the tumour (P < 0.001). Furthermore, it was 8.9 (1.4) kb and 3.4 (0.9) kb in superficial and invasive tumours (P = 0.002), respectively. Telomerase activity was detected in all 13 of the tumour tissues examined, with no relationship to telomere reduction, while it was undetectable in any of the control tissues. CONCLUSIONS: In human TCCs, telomere length was reduced in tumour tissue, more so in superficial than in invasive tumours. Telomerase was detectable only in tumour tissues and its activity was unrelated to telomere reduction.

[Mesonephric adenocarcinoma arising in the female urethral diverticulum].

A forty four-year-old house-wife presented with gross hematuria and difficulty on urination of a year and 3 months duration. Transvaginal examination showed a hen egg-sized soft mass on the anterior vaginal wall. Urine cytology revealed many clusters of malignant cells suggestive of adenocarcinoma. Cystourethrography revealed two urethral diverticula, whose orifices were cystoscopically located at the proximal and distal side of urethral sphincter, respectively. By vaginal digital pressing, a soy-bean sized papillary tumor came out of the proximal diverticulum. Histopathological examination of the biopsied tumor suggested poorly differentiated transitional cell carcinoma with inverted growth. Under the diagnosis of carcinoma arising in the urethral diverticulum, anterior pelvic exenteration with formation of Indiana pouch was carried out. The tumor in the proximal diverticulum was histologically composed of a variety of adenocarcinomatous pattern, such as tubular, papillary and cystic structure with a distinctive pattern of tubules lined by a superficial layer of hobnail cells, leading to the diagnosis of mesonephric adenocarcinoma of urethral diverticulum. Postoperative radiation therapy was given because the diverticulum was adherent to the pubic bone, though lymph node metastasis was negative. She has been well with no evidence of the disease for 1 year and 4 months after the operation. Although the histogenesis of female urethral mesonephric adenocarcinoma was still controversial, this case seems to be the forty fourth case in the world literature.