Difference between genomic actions of estrogen versus raloxifene in human ovarian cancer cell lines.

Although there is growing evidence that estrogens promote tumor progression in epithelial ovarian cancer, the molecular mechanisms accounting for this are still unclear. Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain tissues while opposing it in others. The molecular mechanisms of the effects of SERMs such as raloxifene on the tumor progression of epithelial ovarian cancer are also still unclear. Here, we show that various genomic actions of estrogen differ from those of raloxifene in human ovarian cancer cell lines expressing estrogen receptor alpha (ERalpha). 17beta-Estradiol (E2) induced the gene expression of c-Myc and IGF-1 and increased the binding of ERalpha to the AP1 site of the promoters of c-Myc and IGF-1. ERalpha silencing abolished the E2-stimulated c-Myc expression. E2 induced the recruitment of co-activators such as SRC-1, SRC-3 and CBP to the promoters of c-Myc and IGF-1, and SRC-1 silencing abolished both the E2-stimulated c-Myc expression and cell-cycle progression. In contrast, although raloxifene increased the binding of ERalpha to the AP1 site of the promoters of c-Myc and IGF-1, raloxifene had no effect on the gene expression of c-Myc or IGF-1. Raloxifene induced the recruitment of co-repressors such as HDAC2, N-CoR and SMRT to the promoter of IGF-1. Thus, the difference between the genomic actions exerted by estrogen and raloxifene in human ovarian cancer cell lines expressing ERalpha appear to be dependent on the recruitment of co-regulators.

Clinical efficacy of conservative laser therapy for early-stage cervical cancer.

The objective of this study was to evaluate the clinical efficacy of conservative laser therapy for early-stage cervical cancer. Seven hundred fifty-two and 271 patients with carcinoma in situ (CIS) and microinvasive squamous cell carcinoma (MIC), respectively, were treated by laser conization with vaporization. One hundred eighty-four patients with preclinical invasive diseases underwent radical surgery without conization. Their postoperative histologic findings and clinical outcomes were evaluated retrospectively. The cone specimens of 1023 cases were reported as showing that 54 had dysplasia, 663 had CIS, 239 had stage Ia1 without lymph vascular space invasion (LVSI), 14 had stage Ia1 with LVSI, 14 had stage Ia2, and 39 had stage Ib1 diseases. Incomplete excision occurred in 4 (7.4%) of 54 dysplasia, 48 (7.2%) of 663 CIS, and 16 (6.7%) of 239 stage Ia1 cases, but failure rates were only 1 (1.9%), 8 (1.2%), and 4 (1.7%), respectively. The other 67 of 1023 cases underwent abdominal operation. Final pathology results were analyzed for 67 and 184 cases with stages Ia1 to Ib1 receiving radical surgery with or without initial laser therapy. Lymph node metastasis was not observed in 154 Ia1 and 30 Ia2 with stromal invasion of under 4 mm in depth regardless of LVSI, but was detected in 2 of 16 Ia2 with stromal invasion of over 4 mm in depth and in 9 of 51 Ib1 cases. CIS and Ia1 disease without LVSI can be treated only by laser therapy. The limit of stromal invasion for conservative laser therapy in stage Ia cancer may be 4 mm in depth regardless of LVSI.

Fas gene promoter -670 polymorphism in gynecological cancer.

Single-nucleotide polymorphism at -670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P= 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas -670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08-6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05-2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter -670 may be associated with the risk of cervical cancer in a Japanese population.

[A case of Bellini duct carcinoma producing granulocyte colony-stimulating factor (G-CSF)].

A case of Bellini duct carcinoma producing granulocyte colony-stimulating factor (G-CSF) is reported. The patient was a 75-year-old female with the chief complaint of appetite loss. Abdominal ultrasonography and abdominal computed tomography revealed left renal pelvic tumor. Left radical nephrouretrectomy was performed. The histopathological report showed Bellini duct carcinoma. Immunohistochemical staining using the anti-G-CSF antibody showed positive staining in the cancer cells. Preoperatively, the white blood cell count and serum G-CSF concentration were elevated to 34,100/microliter and 334 pg/ml respectively. After operation these values became normal. However, these values were elevated again and CT scan revealed a left pulmonary metastasis 3 months after the operation. In spite of chemotherapy, she died of brain metastases 7 months after the operation.

Left internal mammary-to-left circumflex coronary artery collateral pathway in a patient with occluded left circumflex artery.

A unique case of left internal mammary artery-to-circumflex coronary artery collateral pathway, which was conceivably encouraged to develop by coronary occlusion. The pathway provided sufficient collateral perfusion to preserve the local myocardial performance.

Correlation between thymidine phosphorylase expression and invasion phenotype in cervical carcinoma cells.

The correlation between thymidine phosphorylase (dThdPase) expression and invasion phenotype in human uterine cervical carcinoma cells was investigated using 10 cervical carcinoma cell lines. Semi-quantitative reverse transcription-polymerase chain reaction analysis was performed to investigate the mRNA levels of dThdPase and matrix metalloproteinase (MMP)-2 with beta-actin coamplified as an internal standard. dThdPase protein expression levels were detected by highly sensitive enzyme-linked immunosorbent assay. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were evaluated by haptotactic migration and invasion assay. Although dThdPase mRNA and protein expression levels differed remarkably among the cell lines, there was a statistical correlation between them (r = 0.743, p = 0.0139). dThdPase gene and protein expression levels were well correlated with the number of cells that migrated and invaded (p < 0.05). Moreover, there was a close correlation between MMP-2 gene and dThdPase gene and protein expression levels (p < 0.05). Tumor cells that produce dThdPase may have a higher invasive and metastatic potential because of their capacity to pass through tissue barriers.

[A case of primary localized amyloidosis of the urinary bladder].

A case of primary amyloidosis of the bladder is reported. A 59-year-old man visited our hospital with a complaint of gross hematuria. Cystoscopy revealed several elevated lesions with yellowish surface accompanied by proliferated vessels at the posterior wall. Transurethral mucosal biopsy was performed. Histopathological diagnosis was a primary localized amyloidosis of AL type in the bladder. Systemic amyloidosis was clinically excluded. He is followed for 38 months without symptoms but mucosal lesions persisted.

[Treatment outcome on 52 patients with 53 testicular germ cell tumors].

Between August 1983 and April 1996, 53 testicular germ cell tumors in 52 patients were treated at Toranomon Hospital. The average age of the patients was 36.1 years (range 21-89). The affected side was the right side in 24, left in 27 and bilateral in 1 case. Of the 53 tumors 34 (64.2%) were seminoma and 19 (35.8%) were non-seminomatous germ cell tumor (NSGCT). High ligation orchiectomy was performed in all cases. Of 29 stage I seminomas, post-operative adjuvant radiotherapy was performed in 6 cases prior to 1991. None of these tumors recurred. Two cases of relapses (8.7%) were found among the 23 stage I seminomas followed by surveillance. Of 8 stage I NSGCTs followed by surveillance, 4 (50.0%) tumors which contained embryonal carcinoma element and vascular invasion relapsed within 12 months after orchiectomy. A case of stage IIA seminoma was treated successfully by irradiation. Seven cases of stage II (3 seminomas and 4 NSGCTs) and 8 cases of stage III (1 seminoma and 7 NSGCTs) as well as cases of 6 stage I patients who developed relapse during surveillance were treated by VAB-6 chemotherapy. Of these 21 cases, 11 (52.4%) achieved complete response (CR) and 10 (47.6%) partial response (PR). Salvage surgery and/or additional chemotherapy was successful to bring the 10 PR cases into CR condition. One NSGCT patient, however, died of electrolyte imbalance during the maintenance chemotherapy for disease progression after achieving CR. All 34 patients with seminomas and 18 of the 19 with NSGCTs were alive without evidence of disease after a mean follow up period of 61.1 months (range 4-150 months).

[Long-term results of surgical treatment for renal pelvic and ureteral tumors].

Fifty eight cases of primary tumors in the renal pelvis and ureter were treated at Toranomon Hospital between 1983 and 1992. They consisted of 32 renal pelvic tumors, 21 ureteral tumors and 5 tumors at both sites. The age of the patients ranged from 30 to 84 years (mean 63.1). Surgery was performed in 56 cases. Radical nephroureterectomy with concomitant ipsilateral retroperitoneal lymph node dissection was performed in 38 cases. The other surgeries were radical nephroureterectomy without lymph node dissection in 9, nephrectomy in 4, resection of ureter and reanastomosis in 3, radical nephroureterectomy and cystectomy in 1 and partial nephrectomy in 1. Pathologically, 53 were transitional cell carcinoma (TCC), 2 were TCC plus squamous cell carcinoma and 1 was TCC plus adenocarcinoma. Over-all survival rates (Kaplan-Meier) of 56 surgical cases at 1, 3, 5 years were 92.2, 83.7 and 72.8%, respectively. Combination chemotherapy (M-VAC or CAP) was performed in 9 cases of metastatic disease and 1 case of bilateral disease. Of these 10 cases, one achieved complete remission, 2 no change and 7 had progressive disease. Adjuvant chemotherapy was performed in 21 cases after surgery. These 21 patients were of high risk in recurrence either Grade 3 or pT3. However, the 5-year survival rate was 77.3% in these patients. Thus we conclude that the adjuvant chemotherapy in high risk patients was effective in our cases.

[Torsion of a seminoma in an intrascrotal testis. A case report].

We report a case of torsion of an intrascrotal testicular tumor. The patient was a 54-year-old man with a chief complaint of swelling and pain in the left scrotum. A testicular scan using 99mtechnetium RBC demonstrated a large cold area of isotope uptake showing loss of blood flow in his left scrotal content. Pre operative diagnosis was acute testicular torsion. A torsed testicle was delivered through an inguinal incision. The testicle appeared to be twisted 720 degrees clock wise. It was swollen and bluish in color. The blood flow did not recover after the relief of twisting. Radical orchiectomy was performed. The histology demonstrated a seminoma. He was free of disease 4 years after surgery. A torsion of testicular tumor in an undescended testis has been reported sporadically. However, the torsion of the intrascrotal testicular tumor is very rare. There have been 5 reported cases in the world literature and this case seems to be the first one in Japan.

[Endourologic treatment of the upper urinary tract obstruction in the advanced cancer patients].

88 cancer patients with an upper urinary tract obstruction were endourologically treated. The obstructions were caused by metastasis or invasion of cancer in all patients. First we tried to insert a ureteral stent catheter (STENT). When it failed percutaneous nephrostomy (PCN) was performed. Initially 69 and 19 patients were treated by STENT and PCN, respectively. Of 69 patients with STENT, 13 received PCN later. The average survival of all patients after treatment was 5.7 months. About 60% of the patients were discharged from hospital. The patients treated by STENT and PCN survived for 5.4 months and 6.7 months in average. The STENT was changed 1.8 times on the average in all patients. 79% of the patients who had been treated by STENT experienced only one or two times of STENT changes before dying. Patency period of inserted STENT was studied. On the average the STENT occluded after 72.4 days. The patent period of STENT was longer in the patients group of prophylactic STENT insertion for hydronephrosis. The period was shorter in the patients who showed gross hematuria at the time of surgery. Patent period of STENT was not related to STENT size. Although survival was not so long, over 60% of the patients were able to return to their homes. Endourologic treatment of urinary obstruction was performed in only 6 patients in 1985. The number of such cases has been increasing gradually and currently 20 patients are treated annually. It is supposed that there are many more cancer patients with urinary tract obstruction in their end-stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure changes following extracorporeal shock wave lithotripsy for urolithiasis.

Hypertension after extracorporeal shock wave lithotripsy (ESWL) has been a controversial subject. Changes in blood pressure were studied in 262 patients (mean age 47.8 years) 18.6 months after ESWL. According to World Health Organization criteria the number of patients who showed a decrease exceeded those who showed an increase in blood pressure. The patients who have been on antihypertensive therapy showed a significantly greater decrease in blood pressure than those without medication. Of 192 normotensive patients diastolic pressure increased 1.2 mm. Hg and 2 (1.0%) had hypertension 18.4 months after ESWL. Annualized increase in diastolic pressure and new onset of hypertension were calculated to be 0.78 mm. Hg and 0.65%, respectively. Significant elevation of diastolic pressure was noted in the patients who received a larger number of shock waves. Blood pressure should be carefully followed after ESWL especially in patients who have been treated by a greater number of shock waves.

[Treatment of renal cell carcinoma with human lymphoblastoid interferon alpha and UFT in combination. A prospective multicenter trial].

A cooperative study of combination of UFT (a compound of FT and Uracil) and human lymphoblastoid interferon (IFN-alpha) was conducted in the cases of metastatic renal cell cancer. IFN-alpha was administered over 3 times a week at a dose of 3 X 10(6) units in combination with UFT at a daily dose of 600 mg FT equivalent. Twenty-eight patients from 16 collaborating institutions were the subjects of the present study. The antitumor effects of the drugs were clinically evaluable in 25 cases according to the response criteria of Japan Society for Cancer Therapy. Complete responses and partial responses were observed in 3 and 2 cases, respectively, showing a response rate of 20 per cent. One complete responder had bone and liver metastases and has been alive for more than 2 years without any evidence of relapse. All of the other responders had lung metastasis. The survival durations of the other two complete responders were 716 days and 255 days. The two partial responders had been alive for more than 819 days and 471 days. The adverse effects of this combination therapy were minimal. Combination of a biological response modifier and a cancer chemotherapeutic agent seems to be a way to increase the treatment efficacy of renal cell cancer.

[Treatment in 50 cases of transitional cell carcinoma in renal pelvis and ureter].

A total of 50 cases of primary tumors in the renal pelvis and ureter were treated in Tokyo University Branch Hospital (20 cases in 1966-1982) and in Tranomon Hospital (30 cases in 1977-1987). They were composed of 42 men and 8 women (5.3:1) with a mean age of 61 years. 31 patients suffered from renal pelvic tumors, 15 ureteral tumors and 4 tumors in both sites. The tumors were located in the left side in 33 cases, right in 16, and both sides in 1.86% of patients showed gross hematuria. The findings on IVP were filling defect (42%) and nonvisualization (33%). Positive urine cytology was obtained in 12 of 25 cases (48%). Surgery was performed in 47 cases. The remaining 3 cases were with advanced diseases. The surgeries were total nephroureterectomy plus ipsilateral retroperitoneal lymph node dissection in 26 cases, total nephroureterectomy without node dissection in 7, total nephroureterectomy and total cystectomy in 3, nephrectomy in 9, partial nephrectomy in 1 and segmental excision of ureter with ureteroureterostomy in one. Histologically, all tumors were transitional cell carcinoma. Over-all survival rates (Kaplan-Meier's method) of the operated patients at 1, 3, 5 years were 84.2%, 73.1% and 69.4%, respectively. The stage and grade of the tumors affected the prognosis. N factor at lymph node dissection was the most determining factor of prognosis. 3 advanced cases who did not receive surgery for primary site were treated with 5FU in 2, and with CAP in 1.2 of them died of the disease within 1 year after diagnosis, one patient was lost in follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of inverted papilloma with subsequent heterotopical recurrence of transitional cell carcinoma].

A case of inverted papilloma with subsequent heterotopical recurrence of inverted type transitional cell carcinoma is reported. A 24-year-old man had a medical examination of our hospital with chief complaint of asymptomatic macroscopic hematuria on October 23, 1982. Cystoscopy revealed a smooth surfaced and finger-tip sized tumor at the bladder neck. Because of the large bulk and the location of the tumor, the tumor was resected through cystotomy. After histological examination, the tumor was diagnosed as inverted papilloma. Cystoscopy was repeated every 3-6 months. The tumor recurred 4 times heterotopically, 19, 35, 43 and 53 months after the initial surgery. The pathological examinations of these tumor specimens showed transitional carcinoma mostly of inverted growth. Most of the urologists and pathologists believe inverted papilloma to be a benign neoplasm, but several reports and this case suggest the possibility of recurrence and malignant transformation of inverted papilloma.

[Urachal carcinoma accompanied with calcification: report of a case].

Carcinoma of urachus accompanied with calcification is rarely encountered. A 37-year-old man presented with the complaint of mucus discharge on voiding. A plain X-ray film of his abdomen showed the presence of calcification at the urinary bladder. A hemispheric tumor at the top of the urinary bladder was seen on cystoscopic examination. The results of urine cytology and cold-punch biopsy supported the diagnosis; carcinoma of urachus. En bloc segmental resection was performed. Histopathologically, the tumor was composed of moderately differentiated adenocarcinoma producing mucus. Now, he is alive and has no evidence of recurrence. This is the 9th report on carcinoma of urachus with calcification in the Japanese literature.

[Arteritis and fatty degeneration of the spermatic cord resembling periarteritis nodosa: a case report].

A 23-year old male was admitted to our hospital because of swelling of the left scrotum for one month without any particular past history. Blood count, chemistry, urinalysis, chest X-ray and electrocardiogram revealed normal findings. Scrotal exploration was performed. A soft, dumbbell-like tumor enveloped in a thin membrane was found above the left testis. Pathology revealed fibrinous exudation and fibrinoid necrosis in the whole vessel wall indicating resemblance to the panarteritis in periarteritis nodosa. Some granulomatous lesions with many histiocytes were also noted around these arteries. The findings suggested that a inflammation like periarteritis nodosa had occurred at the spermatic cord and subsequently developed into fatty degeneration in the surroundings. Since local periarteritis nodosa-like lesion may progress to systematic disease, further observation is mandatory for this case.

[Computed tomography for the diagnosis of a renal mass].

The accuracy of differential diagnosis of renal mass lesions by computed tomography (CT) was evaluated. A retrospective study was done on 23 patients with renal mass lesion suspected by conventional IVP. Cases studied included 6 renal cell carcinomas, 1 nephroblastoma, 2 transitional cell carcinomas of renal pelvis, 3 parapelvic cysts, 2 polycystic kidneys and 9 other benign renal lesions. CT, especially with enhancement, is advantageous for evaluation of the extent of the tumor and also for the differentiation between cystic and solid masses by their attenuation. However, angiography and venography could provide valuable information for surgery of malignancy; and, retrograde pyelography also would help in assessing the extent of tumor spread in the renal pelvis. Two of our cases of parapelvic cyst and a case of renal bleeding could not be distinguished accurately by CT. Sonography or other diagnostic procedures might be helpful in such cases.

[Squamous cell carcinoma of the bladder--report of two cases].

Two cases of squamous cell carcinoma of the urinary bladder are presented. Initial pathologic diagnosis was based on biopsy findings; it was confirmed by findings on resected specimens. Since aggressive surgical therapy has been reported to be successful, we attempted radical surgery in both of our patients. A 76-year-old woman underwent total cystectomy with resection of segments of rectal and vaginal walls with ureterocutaneostomy and colostomy. The other patient, a 66-year-old woman was inoperable due to wide tumor invasion. She died two months later of cerebrovascular accident apparently unrelated to original disease. The ultrastructural findings, which typically show numerous tonofilaments, ribosomes and desmosomes, are presented and discussed.