Yukiko Nishijima

S Phase Fraction of Human Bladder Tumor Measured in Situ with Bromodeoxyuridine Labeling

A total of 18 patients with transitional cell bladder cancer was given a 0.5-hour intravenous infusion of bromodeoxyuridine at the time of endoscopic biopsy or transurethral resection to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method with anti-bromodeoxyuridine monoclonal antibody as the first antibody. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. All grade 1 tumors had an S phase fraction of lower than 10 per cent. The average S phase fractions for noninvasive (11 cases) and invasive (7) tumors were 9.8 and 20.0 per cent, respectively. Two distant metastatic bladder tumors showed an average S phase fraction of 25.3 and 30.0 per cent. Thus, transitional cell bladder cancers with an S phase fraction of greater than 10 per cent appears to grow faster and be more invasive more often than those with an S phase fraction of less than 10 per cent. The higher S phase fraction may indicate greater biological malignancy. Our preliminary results suggest that measurement of the bromodeoxyuridine labeling index in bladder tumors may be a new objective and quantitative assay of biological potential of individual tumors.

Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection

BackgroundIn a prospective study we compared the usefulness of urinary nuclear matrix protein 22 (NMP22) with that of urine cytology and other urinary markers in the monitoring of superficial bladder cancer after transurethral resection (TURBT).MethodsThe subjects were 156 patients, comprising 99 patients with superficial bladder cancer in whom TURBT was planned (untreated group) and 57 patients without tumors in the bladder who had been followed up after TURBT (follow-up group).ResultsAmong the 156 patients, who were monitored for 11–26 months (median, 21 months), recurrence was observed in 51 patients (33.0%). At the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%, and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor size and urinary WBC. The size of recurrent tumors was significantly smaller (P ≪ 0.05) than that of the initial tumors. Based on receiver operating characteristic (ROC) curves calculated from the data of patients with recurrence, the ideal cutoff values at recurrence were recommended to be 5.0 U/ml for NMP22 and 6.0 ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and BFP were 48.8% and 44.2%, respectively.ConclusionsBecause the size of recurrent bladder tumors is usually smaller than that of the initial tumors, the cutoff values of urinary markers should be reduced to detect these tumors. We recommend 5.0 U/ml as a cutoff value of NMP22 for detection of recurrence of bladder tumor.

Effects of a new bisphosphonate (AHBuBP) on osteolysis induced by human prostate cancer cells in nude mice.

A new bisphosphonate, 4-amino-1-hydroxybutylidene-1, 1-bisphosphonate (AHBuBP), was compared with 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) assessing their effects on tumor induced osteolysis using human prostate adenocarcinoma cells in nude mice. The method consisted of inoculating transplantable human prostate cancer cells subcutaneously over the calvaria in nude mice resulting in a local tumor causing fragmentation of the bone. The parameters included assessing the extent of decreased osteolysis in bone as judged by X-ray and histological examination. The results showed the following sequence of potency: AHBuBP greater than AHPrBP greater than HEBP. The compounds were active not only when administered preventively before establishment of bone resorption, but also in an inhibitory fashion once the variables were already under the influence of the tumor. This inhibition was obtained with no apparent effect on the growth of the tumor. AHBuBP appears to be an interesting new bisphosphonate for future clinical use.

Clinical significance of the vertebral vein in prostate cancer metastasis.

A total of 75 prostate cancer and 67 lung cancer patients with positive bone scintigrams were studied. The patterns of spread in the axial skeleton and pelvis were different between the groups. The differences in the distribution of bony metastases between prostate and lung are explained by the role of Batsons vertebral venous plexus. We developed an animal model of spinal bone metastasis to prove this route. As suspension of tumor cells was injected into the tail vein of mice with vena caval occlusion. This procedure reproducibly resulted in metastatic tumor growth in the lumbar region of the vertebral column. The prevalence of spinal bone metastasis is attributed to passage of tumor cells via the vertebral venous plexus.

Toe skin temperature as a guide to epidural anaesthesia dosing

To determine the time for additional epidural anaesthesia, skin temperature of the big toe was evaluated in 50 patients undergoing mastectomy. Epidural catheters were placed at or near the T5−6 intervertebral space and 12 ml, lidocaine 1.5% with 1:200,000 epinephrine were injected. When the skin temperature, which had increased following epidural anaesthesia, decreased by 0.3° C without an increase of systolic arterial blood pressure (ABP) of more than 20%, 8 ml lidocaine 1.5% were injected. If the skin temperature increased, the monitor was judged to have been useful. When ABP increased > 20% without a decrease of skin temperature, the monitor was judged not to have been useful. Monitoring of toe skin temperature was useful in 39 patients (78%) in estimating the time for the first additional dose of epidural anaesthetic. First, second and third intervals between injection were 96.5 ± 21.0 (n = 39), 69.7 ± 14.2 (n = 35) and 50.1 ± 12.2 min (n = 7), respectively. We conclude that, when epidural puncture is performed at upper thoracic levels, toe skin temperature can be a useful monitor to judge the time for additional anaesthetic.RésuméPour déterminer le moment de la dose de rappel pour l’anesthésie épidurale, la température cutanée du gros orteil est mesurée chez 50 patientes pendant une mastectomie. Un cathéter épidural est placé au niveau ou près de T5−6. De la lidocaïne 1,5% avec épinéphrine 1:200 000 est injectée. Quand la température déjà en hausse après l’épidurale baisse de 0,3° C sans diminution de la tension artérielle (TA) supérieure à 20%, on ajoute 8 ml de lidocaïne 1,5%. Si la température cutanée augmente, ce type de monitorage est jugé utile. Quand la TA augmente de 20% sans diminution de la température, le moniteur est jugé inutile. Ce monitorage de la température cutanée est jugé utile chez 39 patients (78%) pour déterminer le moment de la première dose de rappel. Le premier, le deuxième et le troisième intervalle entre les injections a été de 96,5 ± 21,0 (n = 39), 69,7 ± 14,2 (n = 35) et 50,1 ± 12,2 min (n = 7) respectivement. Nous concluons que lorsque la ponction épidurale est effectuée au niveau thoracique supérieur, la temperature cutanée du gros orteil peut s’avérer utile pour monitorer le moment d’injection d’une dose anesthésique additionnelle.

Minimum effective combination dose of epidural morphine and fentanyl for posthysterectomy analgesia: a randomized, prospective, double-blind study.

Recent studies have produced conflicting results regarding whether the addition of epidural fentanyl improves postoperative analgesia from epidural morphine. Therefore, we prospectively determined the dose-response relationship and the minimum effective combination dose of epidural morphine and fentanyl (fentanyl given after morphine) for posthysterectomy analgesia. We studied 120 patients undergoing radical abdominal hysterectomy. All patients had epidural lidocaine 1.5% with epinephrine (1:200,000) for surgical anesthesia followed by light general anesthesia with endotracheal intubation. They were assigned randomly into six groups according to the combination of each narcotic dose: morphine 2 mg, morphine 2 mg/fentanyl 50 micrograms, morphine 2 mg/fentanyl 100 micrograms, morphine 4 mg, morphine 4 mg/fentanyl 50 micrograms, and morphine 4 mg/fentanyl 100 micrograms. Morphine and fentanyl were given epidurally in a double-blind manner approximately 60 and 15 min, respectively, before the completion of surgery. For 2 mg of morphine, the addition of 50 or 100 micrograms of fentanyl improved pain relief during the first 6 h postoperatively (P < 0.05), provided longer duration of analgesia (P < 0.05), and required less analgesic supplement (P < 0.05), but did not alter the incidence of side effects. For 4 mg of morphine, the same conclusion was drawn, except that vomiting occurred more frequently with addition of 100 micrograms of fentanyl (P < 0.05). Among fentanyl groups, there was no significant difference in pain scores, duration of analgesia, and analgesic requirements. Therefore, we conclude that epidural fentanyl given after morphine improves early postoperative analgesia from epidural morphine, and the minimum effective combination dose is morphine 2 mg/fentanyl 50 micrograms for posthysterectomy surgery analgesia.

New method to evaluate the distribution of metastatic tumor cells in bone marrow with bromodeoxyuridine labeling

BackgroundThe development of tumor micrometastases as an early event in the distribution of tumor cells to target organs, especially bone marrow, has been difficult to analyze due to a lack of suitably sensitive markers. The inability to discriminate small numbers of tumor cells from normal tissue cell populations has interfered with marker development.MethodsTo overcome this problem, human prostate cancer cell lines (PC-3) were labeled with bromodeoxyuridine (BrdU) and subsequently injected into athymic nude mice using the tail veins with or without compression of vena cava.ResultsUsing a direct immunoperoxidase method with anti-BrdU monoclonal antibody, the BrdU-labeled tumor cells in the bone marrow stained intensely, while neighboring normal bone marrow cells were not stained. Staining of BrdU-labeled tumor cells is specific and extremely sensitive in detecting tumor cells in metastatic bone marrow.ConclusionsThese findings demonstrate the effectiveness and sensitivity of BrdU labeling as a maker in experimental studies for early metastatic events and that BrdU labeling provides a tool in virtually any tumor system for examining the distribution of tumor cells in target organs and their relationship to host organ microenvironments.

A case of nonseminomatous testicular tumor with liver metastases, treated by intrahepatic arterial cisplatinum-diaminedichloride infusion.

We report a case of nonseminomatous testicular tumor with lymph node involvement and multiple lung and liver metastases. The patient was considered to have a poor prognosis. He received systemic chemotherapy and cytoreductive surgery. Postoperatively a residual metastatic tumor in the liver was treated by intrahepatic arterial cisplatinum-diaminedichloride infusion. Follow-up observation has revealed no evidence of recurrence for 30 months since the last treatment.