Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209.

BACKGROUND: This study aimed to determine the clinical benefit of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy. PATIENTS AND METHODS: Patients with MIBC (T2-4aN0M0) were randomised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy (NAC arm) or radical cystectomy alone (RC arm). The primary end point was overall survival (OS). Secondary end points were progression-free survival, surgery-related complications, adverse events during chemotherapy, proportion with no residual tumour in the cystectomy specimens, and quality of life. To detect an improvement in 5-year OS from 45% in the RC arm to 57% in the NAC arm with 80% power, 176 events were required per arm. RESULTS: Patients (N = 130) were randomly assigned to the RC arm (N = 66) and the NAC arm (N = 64). The patient registration was terminated before reaching the initially planned number of patients because of slow accrual. At the second interim analysis just after the early stoppage of patient accrual, the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion. OS of the NAC arm was better than that of the RC arm, although the difference was not statistically significant [hazard ratio 0.65, multiplicity adjusted 99.99% confidence interval 0.19-2.18, one-sided P = 0.07]. In the NAC arm and the RC arm, 34% and 9% of the patients had pT0, respectively (P < 0.01). In subgroup analyses, OS in almost all subgroups was in favour of NAC. CONCLUSIONS: This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC. NAC with MVAC can still be considered promising as a standard treatment. UMIN CLINICAL TRIALS REGISTRY IDENTIFIER: C000000093.

Relationship between papillary and nodular transitional cell carcinoma in the human urinary bladder.

A total of 186 cystectomized specimens were examined by step-sectioning to determine the relation between papillary and nodular transitional cell carcinomas of the urinary bladder. Tumors were classified as papillary (PC), nodular (NC), and carcinoma in situ (CIS) according to their gross and microscopic configurations. These cases, grouped as simple combinations of PC, NC, and CIS, namely, PC, PC + CIS, PC + NC, PC + NC + CIS, NC, NC + CIS, and CIS, were analyzed with respect to (a) the time from the initial symptom to cystectomy, (b) the treatment before cystectomy, (c) the grade, (d) the stage of tumors, (e) the multiplicity of tumors, (f) the presence of papillary structures inside or on the surface of nodular carcinoma, and (g) data on survival after cystectomy. Of the tumors, 17 were classified as CIS and 80 as PC and PC + CIS. Studies on 57 cases suggested an early change from PC to a mixture of PC and NC through papillonodular carcinoma during development, whereas 6 showed late development of NC during repeated recurrence of PC. These courses indicate that some cases of NC developed from PC. On the other hand, 26 cases exhibited direct progression from CIS to NC. Thus nodular invasive carcinomas may develop in two ways: by emergence of a more anaplastic cell population within a preexisting low grade papillary carcinoma; and by de novo development of an invasive nodular carcinoma directly from CIS.

Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis.

The presence of mRNAs for vascular endothelial growth factor (VEGF) and a VEGF-related protein, placenta growth factor (PIGF) was examined in 29 cases of renal cell carcinoma tissues and adjacent normal kidney tissues and in 4 human renal cell carcinoma cell lines. Northern blot analysis showed that 26 of 27 hypervascular renal cell carcinoma tissues (96%) exhibited a markedly elevated level (3-13 fold) of VEGF mRNA compared to the adjacent normal kidney tissues. Even tumors of small size, whenever they were hypervascular, overexpressed VEGF mRNA. We also demonstrated that mRNA for PIGF was expressed in 21 of 23 hypervascular renal cell carcinoma tissues (91%) but was not detected in the adjacent normal kidney tissues. Two hypovascular carcinoma tissues neither overexpressed VEGF mRNA nor had PIGF mRNA. VEGF mRNA was detected in four human renal cell carcinoma cell lines, while PIGF mRNA was not. There was no difference in the level of basic fibroblast growth factor mRNA between tumor tissues and normal kidney tissue, although our previous study demonstrated elevated basic fibroblast growth factor protein in the serum of renal cell carcinoma patients (K. Fujimoto et al., Biochem. Biophys. Res. Commun., 180: 386-392, 1991). Taken together, these results suggest that VEGF, PIGF, and basic fibroblast growth factor are cooperatively working to increase the angiogenesis in renal cell carcinoma in vivo.

The external radiotherapy with three-dimensional conformal boost after the neoadjuvant androgen suppression for patients with locally advanced prostatic carcinoma.

PURPOSE: To analyze the results in patients with locally advanced prostatic carcinoma treated by hormonal therapy followed by external radiotherapy using three-dimensional conformal radiation therapy (3D-CRT) boost. METHODS AND MATERIALS: From 1987 to 1995, 46 patients with histologically proven locally advanced adenocarcinoma of the prostate were treated with 3D-CRT at the National Cancer Center Hospital, Tokyo. The neoadjuvant androgen suppression started immediately after the diagnosis followed by radical radiation therapy, according to the prospective protocol. They were treated with photons of 6-14 MV for wide fields and the boost, of which a multiple-leaf collimator of 2-cm width was available. The boosted dose was delivered with the rotational 3D-CRT, after the delivery of whole pelvis 4-field box from a dose of 40-46 Gy up to 66 Gy. The planning target volume encompassed 1 cm outside throughout the clinical target volume, and the prostate and the seminal vesicles were included in the boost field. RESULTS: The 3D-CRT boost treatment completed as planned in all 46 patients. The median follow-up for all the patients was 60 months (range, 5-120 months). Nineteen of 46 patients died. Of these, 11 patients died of the intercurrent diseases. For all 46 patients, the 5- and 8-year overall survival rates were 61.3% and 42.4%, and the 5- and 8-year cause-specific survival rates were 82.4% and 64.4%, respectively. The prostate-specific antigen (PSA) relapse-free rates for 5- and 8-year were 64.6% and 52.5%, and the clinical local control rates for 5 and 8 years were 75.3% and 69.9%, respectively. The preradiation therapy PSA and the Gleason score were the factors that significantly associated with PSA relapse-free survival. Sixteen of 46 patients (35%) showed at least one form of late toxicities. Of these, 3 patients experienced late complications of Grade 3 (urinary, 2, proctitis, 1). CONCLUSION: The treatment results were fairly good and were consistent with those in Western countries, indicating that this study shows the preliminary status of 3D-CRT for the locally advanced prostate cancer in Japan. Preradiation therapy PSA seems to be a significant predictor of PSA relapse-free survival (p = 0.004) after neoadjuvant androgen suppression.

Urinary incontinence after non-nerve-sparing radical prostatectomy with neoadjuvant androgen deprivation.

OBJECTIVES: The impact of non-nerve-sparing retropubic radical prostatectomy (RRP) for prostate cancer combined with neoadjuvant androgen deprivation on urinary control is not well documented. We examined the incidence and severity of urinary incontinence after such therapy and determined the etiologic factors causing this complication. METHODS: We examined the postoperative continence status of 104 consecutive patients admitted to the National Cancer Center Hospital who underwent RRP with wide resection of the pelvic nerves after neoadjuvant androgen deprivation. Incontinence was scored according to the number of pads used daily by the patient for urinary leakage. The severity of incontinence was analyzed according to patient age, weight of resected specimen, status of cancer stage, duration of neoadjuvant androgen blockade therapy, preoperative length of membranous urethra, and duration of urethral catheterization after surgery. We also measured the configuration and diameter of the reconstructed bladder neck by retrograde cystourethrography. RESULTS: In 104 patients examined, the percentage of patients who became dry postoperatively was 22% at 1 month, 47% at 3 months, 69% at 6 months, and 78% at 1 year. Of 81 patients who became dry postoperatively at any interval, 22 (27%) became continent within 1 month of RRP, 49 (61 %) were continent within 3 months, 71 (88%) became continent by 6 months, and another 10 (12%) became continent between 6 and 12 months postoperatively. Of 48 patients who were followed up for more than 1 year and for whom continence status at 1 month after surgery was available, all patients who used 1 to 2 pads per day (13 of 13) at 1 month after surgery regained continence by 1 year after surgery. However, only 62% of patients (16 of 26) who required more than 3 pads per day at 1 month after surgery became dry by 1 year after surgery. Only age (older than 70 years) and large prostate size (weight of surgical specimen more than 40 g) temporarily influenced the recovery of urinary continence after surgery. Dilation of the bladder neck evaluated by retrograde cystourethrography was prominent in severely incontinent patients in the immediate postoperative period. CONCLUSIONS: Our experience in patients who undergo non-nerve-sparing RRP after neoadjuvant androgen deprivation closely matches published surveys of patient-reported complications. Postoperative incontinence is not a major contraindication for non-nerve-sparing RRP after neoadjuvant endocrine therapy. Dilation of the bladder neck affected the recovery from incontinence, highlighting the importance of adequate reconstruction of the bladder neck.

A feasible method for expansion of peripheral blood lymphocytes by culture with immobilized anti-CD3 monoclonal antibody and interleukin-2 for use in adoptive immunotherapy of cancer patients.

Cultivation of T lymphocytes with immobilized anti-CD3 monoclonal antibody and human recombinant interleukin-2 induced a rapid proliferative response. This procedure was applied to expansion culture of peripheral blood lymphocytes obtained from cancer patients for use in adoptive immunotherapy. Peripheral blood mononuclear cells were separated from 20 ml of blood and cultured in anti-CD3 coated flasks with rIL-2 for 6 days, then transferred to a gas-permeable culture bag and culture continued for an additional 8 days with an increasing volume of medium. Cell numbers increased about 2000-fold during this 2-week culture. The final population contained about 30% CD4+ and 60% CD8+ cells, and all were CD3+ & HLA-DR+. NK cells comprised less than 5%. In clinical trials involving 12 cases receiving 35 infusions, the mean number of harvested T cells after 14 days culture was 3.5 x 10(10) (R = 1.6-6.8 x 10(10)), and the mean expansion index was 1560-fold (R = 409-4091). This method could be of benefit not only in immunotherapy but also for obtaining somatic cells from a small volume of blood for use in molecular or genetic analysis instead of having to perform EB virus transformation of B cells.

Hepatectomy for metastatic renal cell carcinoma.

The experience with hepatectomy for metastatic renal cell carcinoma (RCC) has been very rarely reported, because multiple organ metastases ordinarily coexist when hepatic metastases are found out. Three patients who underwent hepatectomy for metastatic RCC are presented here. Radical nephrectomy was performed for the primary renal lesions in all the patients, and their hepatic metastases were resected simultaneously in one of them with a solitary tumor, and about one month later in two of them with multiple (3 and 6) tumors. These operations produced no distinct complications. The patients with 1 and 3 hepatic metastatic lesions survived without tumor recurrence for 12 and 21 months, respectively, while the patient with 6 hepatic metastatic lesions had tumor-free interval of only 2 months and died 10 months after hepatectomy due to lung metastasis. Hepatectomy may be the only promising treatment for hepatic metastases from RCC, but the indication for surgery should be evaluated according to the number of hepatic metastases.

[Long-term survival of stage D2 prostatic carcinoma patient treated with total cysto-prostatectomy: a case report].

A 52-year-old male was admitted to this hospital as stage D2 prostatic carcinoma. He had been previously treated with transurethral resection of prostate and hormonal therapy. Rectal examination revealed the prostate bigger than a hen-egg with stony-hard nodules. Both whole body bone X-ray and bone scintigram showed multiple bone metastasis. Total cysto-prostatectomy and pelvic lymph node dissection were performed because the patient was relatively young, was in good general status and the tumor was not sensitive to hormonal therapy. In addition, he was expected to have obstructive uropathy soon and the reported results of radiotherapy for local control of advanced prostate cancer were unsatisfactory. He was followed by bone X-ray and bone scintigram every six months. Osteoplastic area diminished in size and hot lesions in bone scintigram disappeared gradually. The patient is very active in his daily life without evidence of local recurrence or new metastasis more than seven years after operation. The validity of mass reduction surgery for hormone-resistant stage D2 prostatic carcinoma is discussed.

[Ultrasound-guided renal cyst puncture and 95% ethanol instillation. Part 2: Morphological and functional alterations].

Ultrasound-guided renal cyst puncture was performed on 22 cysts which were then 95% ethanol instilled to prevent recurrence of cystic fluid. Cystic lesions disappeared on the ultrasonogram in the follow-up period of 3 to 28 months. On CT, cystic lesions became smaller size but did not disappear. Average CT numbers of the cyst were 8.75 +/- 3.83 before and 12.96 +/- 3.27 after ethanol instillation. The cystic wall became thicker. Caliceal distortion and/or pelvis compression by cystic lesions improved on IVP 2 to 3 days after ethanol instillation. The renal image on Tc-99m-DMSA scintigram showed morphological improvement and DMSA renal uptake rate increased slightly but significantly 2 to 4 weeks after ethanol instillation. There were no major complications with this procedure except for one case in which the tip of the catheter became stuck in the cyst and broke off when the catheter was removed. A slight local irritable pain was noticed in all cases. Half of the patients had hot flushes and/or somewhat drunken sense but these symptoms were only temporary. Antabuse phenomenon appeared in one case with concomitant use of a cephem antibiotics after ethanol instillation. This method of therapy is a safe non-surgical approach to treat renal cysts. 95% ethanol instillation in the cyst seems to prevent recurrence of cystic fluid.

[Hyperparathyroidism after radioactive iodine therapy for Graves' disease: a case report].

Herein we report a 36-year-old man with hyperparathyroidism and a past history of internal irradiation to the thyroid. Twelve years previously at age 24 years he had received 8 mCi of radioactive iodine for Graves' disease. An additional dose of 4 mCi was required 3 years later. A right lower parathyroid adenoma (28 X 23 X 20 mm, 5.7 g) was found at neck exploration. Although the association of external ionizing radiation to the head and neck and the subsequent development of hyperfunctioning parathyroid glands has been described in recent years, there are only 4 cases in the literature of parathyroid surgery for hyperparathyroidism secondary to earlier treatment with radioactive iodine for Graves' disease. In a long-term follow-up of 180 patients treated with radioactive iodine for Graves' disease, neither hypercalcemia nor hypophosphatemia was found. Whether internal radiation therapy can be a causative factor in the development of hyperparathyroidism should be elucidated in future. However, it seems reasonable to suggest that patients whose hyperthyroidism has been treated with radioactive iodine should have their serum calcium levels examined at 5-year intervals.

[Analysis of renal cell carcinoma with tumorous legion in the liver].

We presented 3 cases of renal cell carcinoma with hepatic lesion, for which it was difficult to make a diagnosis preoperatively. The hepatic lesion was cavernous hemangioma of the liver, liver metastasis of renal cell carcinoma or hepatocellular carcinoma. To discuss the strategy of treatment for liver metastasis of renal cell carcinoma at the time of nephrectomy, or in the follow-up period after nephrectomy, we reviewed the 188 cases of renal cell carcinoma which were nephrectomized from December, 1962 to June, 1988. At the time of nephrectomy, there was only 1 case that had concurrent liver metastasis. In 4 cases, liver metastasis was found at autopsy, and in 15 cases, in the follow-up period after nephrectomy. We analysed these 15 cases and classified them into 2 groups. One was "early metastasis group", i.e., liver metastasis was found within 18 months after nephrectomy, and the other was "late metastasis group", i.e., liver metastasis detected more than 6 years after nephrectomy. In the "early metastasis group", 2 lived 10 months or 57 months, but 5 died within 1 month after the appearance of liver metastasis. In the "late metastasis group", 4 of 7 lived more than 2 years after the appearance of liver metastasis and the median survival was 21 months. In both groups, when liver metastasis was found, there were metastases in multiple organs and the hepatic lesions were multiple.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bladder replacement by enterocystoplasty after total cystectomy].

From May 1987 to April 1988, 7 male patients, 43-69 years old in age, underwent enterocystoplasty after total cystectomy. In 5 of them, a selected intestinal segment, consisted of the terminal portion of the ileum, the cecum and the proximal part of the ascending colon, was freed and detubularized for construction of "bladder" substitution. In the remaining two patients with a previous history of cholecystectomy, having severe intestinal adhesions, the ileum or the sigmoid-colon were used. At 3 months after operation, 6 patients had a vesical capacity of 300 ml or more and the maximum volume of urine excreted at one voiding was 200 ml or more. Daytime continence had been achieved in 6 patients at 3 months after operation, whereas nighttime continence had been achieved in 5 patients at 6 months after operation. Serum electrolytes, pH value of arterial blood and renal function, were all normal during the follow-up period (5-13 months). Potency was preserved in 2 patients. All the patients, except one whose "bladder" was constructed with ileum and who was performing daily intermittent selfcatheterization, were able to enjoy almost the same activity of daily life as before operation. The final shape of the "bladder" and its position in the pelvic space seemed to be an important factor for the "bladder" function after operation. By our hand, however, postoperative cystogram revealed a sigmoid shape in all cases, though the reservoirs had an oval shape at the time when they had been constructed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Tumor recurrence and grade and/or stage progression in low grade tumor. Analysis of 154 patients with superficial transitional cell carcinoma of the bladder].

The clinicopathological findings of 154 patients with initially superficial (stage pTa or pT1) transitional cell carcinoma in the bladder were analyzed to study risk factors for tumor recurrence or progression in grade and/or stage of the low grade tumor. The number, size, grade and stage of tumor at the first presentation were the significant predictors for the first tumor recurrence. However, only the tumor grade and size at the first recurrence were the predictors for the second recurrence. In 19 (33%) of 57 patients with recurrence, low grade superficial tumor progressed in tumor grade and/or muscle invasion. The progression of low grade tumor correlated with short tumor free intervals and tumor size. Grade and/or stage progression was observed in 14% of the tumor of 1 cm or less in diameter, whereas in 42% of the tumor more than 1 cm in diameter (Chi-square test: p < 0.25). These results indicate that tumor grade and size are important predictors for recurrences. Short tumor free intervals and sizes of tumors in the second recurrence are significant predictors for grade and/or stage progression in low grade superficial cancer.

[A case of proliferative chronic cystitis, progressing to obstructive nephropathy, treated by total cystectomy and enterocystoplasty].

A 52 year-old man, being pointed out as with microscopic hematuria and suspected of carcinoma of the urinary bladder at another institution, visited this hospital for further examination. DIP demonstrated an irregular right lateral wall of the urinary bladder. CT of the pelvic cavity revealed a protrusive mass lesion inside the urinary bladder. Cystoscopy proved a circular, edematous and irregular mass lesion around the urinary bladder neck. The pathological examination of TUR specimens showed a proliferative chronic cystitis. However, after about half a year, there was a recurrence of mass lesions in the urinary bladder. Moreover, right non-functional kidney and left hydronephrosis were observed. For preserving renal function, total cystoprostatectomy was performed. Nerve sparing technique for sexual function, and total bladder replacement using a detubularized sigmoid colon to obviate the need for a stoma were adopted. Postoperative course was uneventful and the function of both kidneys was recovered. Normal urination from the urethra and sexual function are both preserved. Pathological examination of the cystectomized specimen confirmed only proliferative cystitis with extensive deep ulceration and thick connective tissues. A rare case in which obstructive nephropathy was caused by proliferative cystitis is reported and discussed.

[Significance of transrectal ultrasound and sextant systematic core biopsy for performing radical prostatectomy].

BACKGROUND: To estimate the usefulness of sextant systematic core biopsy or transrectal ultrasonography (TURS) for performing radical prostatectomy. METHODS: The findings of sextant biopsy and TRUS were compared with 52 step-sectioned specimens obtained from radical prostatectomy. RESULTS: In 34 cases with no influence of hormonal therapy at the time of TRUS and biopsy, sextant systematic core biopsy provided tumor distribution rather precisely. In 33% of the cases who had received hormonal therapy, tumor cells were not detected by this sextant biopsy series. In these cases, majority of residual cancer existed in transition zone, paraurethral or fibromuscular stroma. Six cases showed small adenocarcinoma in only one biopsy tip obtained from sextant biopsy, while 4 cases were revealed well differentiated adenocarcinoma (Gleason score less than 4) by these core biopsies. Comparing with tumor mapping, Gleason score, PSA level and pT stage of the radical prostatectomy specimens, these tumors presented as, not clinically insignificant, but clinically significant prostate cancer. Playing special attention to distraction of normal ultrasound zonal configuration, TRUS detected neurovascular invasion with 94.7% sensitivity, 78.3% positive predictive value and 90. 9% negative predictive value, while seminal vesicle invasion with 75% sensitivity, 50% positive predictive value, 90.9% negative value. CONCLUSION: Sextant biopsy tended to underestimate the tumors located in the transition zone, paraurethral and fibromuscular lesion. Additional or direct biopsies in transition zone are indispensable for accurate diagnosis. Findings of TRUS and distribution of positive core biopsy from sextant biopsy enable to extract stage C prostate cancer providing negative surgical margin.

[Prognosis after radical surgery in prostatic cancer patients with lymph nodes metastases].

We investigated prognosis of clinically localized prostatic adenocarcinoma patients who revealed to have had lymph nodes metastases by undergoing radical surgery. Eighty six patients were operated during the last 15 years under the clinical diagnosis of A2, 9 patients, B1, 15 B2, 13 and C, 49, respectively. Total prostatectomy was done to 51, total cystoprostatectomy to 33 and total pelvic excentration to 2 patients. Of these patients, 22.2% with stage A2, 20.2% with B1, 7.7% with B2 and 43.8% with C had positive nodes and the rate of positive nodes in stage C was significantly higher than that in other stages (p < 0.01). Regarding histological differentiation, 15.4% of well, 23.7% of moderate and 51.6% of poor by differentiated had positive nodes and the rate of positive nodes in poor by differentiated was significantly higher (p < 0.01). In 2 of 21 cases whose lymph nodes were dissected to the level of the aortic bifurcation, positive nodes were detected only in the external and common iliac areas. These two cases were missed, i.e., "false negative" if limited nodes dissection was performed. All patients with positive nodes were treated with hormonal therapy. The 5-year cancer specific survival rate of patients with positive (n = 27) and negative (n = 59) nodes were 66.4% and 92.4%, respectively. The prognosis of patients with positive nodes were significantly worse than that of patients with negative nodes (p < 0.001). Among 27 patients with positive nodes, significant prognostic factor was not number or extent of positive nodes, but histological differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

[The efficacy of neoadjuvant chemotherapy and morphological classification of invasive bladder cancer according to chemoresponse].

BACKGROUND: We investigated the propriety of neoadjuvant chemotherapy and the possibility of bladder preservation based on clinical and pathological responses in invasive bladder cancer. METHOD: Nineteen cases of invasive bladder cancer which had been subjected to two courses of neoadjuvant chemotherapy followed by radical cystectomy were analyzed. RESULTS: The overall response rate was 79% (5/19), and 7 cases (37%) had a pathological complete response (pCR). Many cases showed degeneration or necrosis of cancer cells and infiltration of lymphocytes around the original cancer sites. Foamy macrophage or fibrous change was observed in high response cases. Thickening of the bladder wall were found after chemotherapy in such cases, which led to over-staging of the CT scan. We divided invasive bladder cancers into four different types based on gross tumor appearance and histology from TUR biopsy specimen: Type 1 which has an nodularly elevating pedunculated structure: Type 2A which has an elevating nonpedunculated structure with partly papillary component and no lymph vessel invasion: Type 2B which has an elevating nonpedunculated structure with partly papillary component and marked lymph vessel invasion: and Type 3 which has a nonelevating diffuse invasive structure with CIS lesion. The therapeutic effect was greater than grade 2 in 7 cases out of 8 (88%) Type 1, 2 cases out of 3 (67%) Type 2A, no case out of 6 (0%) type 2B, and 1 case out of 2 (50%) type 3. CONCLUSION: This classification will indicate the appropriate preoperative treatment for invasive bladder cancer, and will be useful when formulating criteria for bladder preservation. In particular, Type 1 or Type 2A is chemosensitive and may be considered for bladder preservation.

[Stage IV renal cell carcinoma producing alpha-fetoprotein treated with multimodal treatment. A case report].

A 63 year old man, having right renal cell carcinoma which was found after initial symptoms of left supraclavicular tumor and gross hematuria, is presented. The points to note with this case are; (1) An unusual production of alpha-fetoprotein (AFP), (2) Being discovered at a very advanced stage and that the disease progressed rapidly (at initial presentation the patient had lymph nodes metastases from the paraaorta, mediastinum to the left supraclavicular region. Later the patient had a recurrent tumor in the left supraclavicular area and multiple cutaneous metastases), (3) Various modalities of treatment were given (right nephrectomy, abdominal lymph nodes dissection, resection of the supraclavicular and mediastinal lymph nodes metastases, hyperthermia combined with irradiation for the recurrent tumor in the supraclavicular region and systemically adoptive immunotherapy with tumor infiltrating lymphocytes). During this treatment course, the drift of serum AFP showed a good correlation. The possibility of AFP as a tumor marker of renal cell carcinoma in selected cases was presented and the suitability of the treatments performed to this patient was discussed.

[Promotive effects of intravesical instillation of dimethylsulfoxide on bladder carcinogenesis in mice].

The effect of intravesical instillation of dimethylsulfoxide (DMSO) on bladder carcinogenesis was examined in mice. Experiment 1: Fifty-five female C3H/He mice were administered 0.05% N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) in their drinking water for 8 weeks. In week 9 they were divided into two groups consisting of 25 mice each. Then, under nembutal anesthesia the first group was given weekly intravesical inatillations of 0.1 ml DMSO (minimum 99.0%) for 10 weeks. The second group received no treatment except anesthesia. All mice were killed 30 weeks after the begining of the experiment and their urinary bladder resected for histological examination. The incidence of bladder carcinoma was 93.7% (15.16) and 27.7% (6/22) in groups 1 and 2, respectively. These incidences differed significantly between the two groups. Experiment 2: One hundred and twenty female C3H/He mice were divided into two groups. The first group was given 0.05% BBN in their drinking water for 5 weeks and then tap water. The second group was not given BBN. In week 6, the first group was divided again into three groups (1, 2 and 3) consisting of 28, 26, and 27 mice, respectively. The second group was divided into groups 4 and 5 consisting of 21 and 18 mice, respectively. Under nembutar anaesthesia groups 1 and 4 received weekly intravesical instillation of 0.05 ml DMSO (minimum 99.0%) from weeks 6 to 13, Group 2 received weekly intravesical instillation of 0.05 ml distilled water from weeks 6 to 13. Groups 3 and 5 received no treatment except anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

[A randomized trial of PVB, VAB-6, BVP regimen versus PEB chemotherapy in patients with disseminated testicular tumors].

During 2 years and 7 months from June, 1985 to December, 1987, a randomized multi-center trial of PVB, VAB-6, BVP regimen (group A) without etoposide versus PEB chemotherapy (bleomycin, etoposide and cisplatinum) (group B) was given to patients with disseminated testicular tumors. Of 34 patients registered, 10 patients were with minimal disease in stages IIA, IIIO and IIIA and 24 with extensive disease in IIB, IIIB2 and IIIC. Seminomas were found in 10 patients, while non-seminomatous tumors in 24. Among groups A and B, there was no statistical difference in clinicopathological profiles. A group patients were given either PVB, VAB-6 or BVP according to the physician's discretion. In groups A and B, 35% and 43% of the patients achieved complete response, and 45% and 50% achieved partial response, respectively. The difference in CR rates among both groups was not statistically significant even when calculated according to the stage or histologic grouping. Salvage treatments mainly with surgical resection of residual tumors after the chemotherapy, however, were more successful in group B (88%) than group A (61%). It appears likely that the higher response of induction chemotherapy in patients with extensive disease made the salvage surgery more successful in group B than in group A. The 3 year survival rate was 100% in group B, whereas it was 76% in group A. Although the incidence of myelosuppression and alopecia was significantly higher in group B, neuropathy was significantly more frequent in group A. From the above results, PEB seems to be a better induction chemotherapy than the conventional one for advanced testicular tumors.