Intra-operative autotransfusion in radical cystectomy.

OBJECTIVE: To assess the feasibility of intra-operative autotransfusion (IAT) as a method of decreasing or avoiding homologous blood transfusion during radical cystectomy. PATIENTS AND METHODS: IAT was performed in 10 patients with bladder cancer who underwent radical cystectomy. The patients were divided into two groups: group 1 consisted of six patients without and group 2 of four patients with pre-deposited blood. Blood shed in the operative field was collected and processed with an IAT device. RESULTS: In group 1, the intra-operative blood loss ranged from 1.08 to 2.67 L (mean 1.82) and homologous blood transfusion ranged from 0 to 1 L (mean 0.47). The amount of autologous blood processed and transfused by the IAT device ranged from 0.38 to 0.98 L (mean 0.64). Two patients did not require homologous blood transfusion. In group 2, the volume of pre-deposited blood ranged from 0.8 to 1.2 L (mean 0.9). The intra-operative blood loss ranged from 1.03 to 3.24 L (mean 1.8). The amount of processed autologous blood transfused ranged from 0.4 to 0.6 L (mean 0.45). None of the patients in group 2 required homologous blood transfusion. CONCLUSION: Although there are theoretical risks with IAT, they were not substantiated by the clinical data. IAT seems to be a feasible method of reducing or avoiding homologous blood transfusion in radical cystectomy. These results suggest that IAT in combination with pre-deposited blood will abolish the need for homologous blood transfusion during radical cystectomy.

Assessment of the availability of intraoperative autotransfusion in urological operations.

PURPOSE: Intraoperative autotransfusion in urological operations has the risks of reinfusing urine constituents, bacteria and cancer cells. We assessed the efficacy of intraoperative autotransfusion and leukocyte removal filters to separate red blood cells from these constituents. MATERIALS AND METHODS: Concentrated red blood cells were mixed with urine, bacteria (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae) and tumor cells (KK47 and ACHN), and processed with the intraoperative autotransfusion device. Biochemical analyses of erythrocytes collected in reinfusion bags (collected erythrocyte solution) from the mixtures of concentrated red blood cells and urine (mixture 1), and cultures of collected erythrocyte solution from the mixtures of concentrated red blood cells and bacteria (mixture 2) were performed. Cytology was done on collected erythrocyte solution from the mixtures of concentrated red blood cells and tumor cells (mixture 3) and filtrates were passed through leukocyte removal filters. RESULTS: Biochemical analyses of collected erythrocyte solution from mixture 1 indicated complete removal of urine constituents, while cultures from mixture 2 yielded bacterial growth. Tumor cells from both cell lines were found in the collected erythrocyte solution from mixture 3 although tumor cells were not found in filtrates through leukocyte removal filters. CONCLUSIONS: Our results suggest that intraoperative autotransfusion is safe for urological operations in which bacteria and tumor cells are not present in the operative field. Our data also indicate that intraoperative autotransfusion may be safe for urological cancer operations if it is combined with leukocyte removal filters to prevent unexpected reinfusion of tumor cells.

Local treatment of rabbit VX2 rectal carcinoma with combined hyperthermia and intratumoral CDDP injection.

The efficacy of combined use of hyperthermia and intratumoral cisplatin (CDDP) injection was investigated in rabbit rectal carcinoma models produced by VX2 carcinoma injection. Local hyperthermia was administered with a 13.56 MHz radiofrequency generator at 42-43 degrees C for 30 min. CDDP (3 mg) was injected into two sites within tumours. Temperatures in the VX2 rectal carcinomas reached 42-43 degrees C within 3 min following initiation of heating and remained stable. Tumour growth was inhibited markedly in rabbit undergoing combined treatment with intratumoral CDDP and hyperthermia, when compared with rabbit treated with hyperthermia or intratumoral CDDP alone. Histological examination further revealed that combined treatment resulted in more extensive tumour necrosis, when compared with hyperthermia or CDDP alone. Therefore, combined hyperthermia and CDDP intratumoral injection may be useful for neoadjuvant preoperative treatment of advanced rectal carcinomas as well as patients with recurrent rectal carcinoma.

[Local injection of peplomycin adsorbed on activated carbon particles combined with 60Co radiation against inoperable advanced esophageal cancer--two long-term survivors].

We have developed a new dosage form, PEP-CH, consisting of peplomycin adsorbed onto small activated carbon particles. Ten patients with inoperable advanced esophageal cancer were treated with endoscopic local injection of PEP-CH combined with radiation using 60Co. Two of 5 patients who completed the treatment have survived over one year (19 and 23 months) now.

Endoscopic local injection of a new drug-delivery format of peplomycin for superficial esophageal cancer: a pilot study.

BACKGROUND: A new drug-delivery format comprising activated carbon particles adsorbing peplomycin (PEP-CH) was developed for the treatment of superficial esophageal cancer. METHODS: The drug distribution was measured in rats that received subcutaneous injections of PEP-CH or peplomycin aqueous solution. In 6 patients with superficial esophageal cancer, peplomycin as PEP-CH, 5-10 mg once a week for 4-10 weeks (total, 40-100 mg/patient) was injected endoscopically into primary lesions. RESULTS: Rats given PEP-CH had significantly higher peplomycin levels in the regional lymph nodes and the injection site than rats given aqueous solution. Five patients have survived to the present or died without cancer after 27-72 months. The remaining patient has survived without cancer for 8 months after a second course of PEP-CH against recurrence. CONCLUSIONS: PEP-CH therapy seems to have a good therapeutic effect on superficial esophageal cancer, although the present clinical study may have been biased by patient selection.

Pharmacologic effects of cisplatin microspheres on peritoneal carcinomatosis in rodents.

BACKGROUND: A new drug-delivery formulation of cisplatin, whereby cisplatin was incorporated in lactic acid oligomer microspheres (CDDP-MS), has been developed in dosage form for peritoneal carcinomatosis and has been designed to release 70% of the incorporated cisplatin slowly during a period of 3 weeks. In this study, its pharmacologic effects were examined in rodents. METHODS: CDDP-MS was tested to determine (1) tissue distribution of cisplatin after intraperitoneal administration of cisplatin at 3.0 mg/kg body weight to rats, (2) acute toxicity in mice when injected intraperitoneally, and (3) therapeutic effects on peritoneal carcinomatosis induced by transplantable M5076 tumors in mice. RESULTS: These experiments revealed the following: (1) CDDP-MS resulted in a higher cisplatin concentration in tissues adjacent to the peritoneum for a longer period, and the concentration of cisplatin measured in the rest of the body was lower than that delivered by the cisplatin aqueous solution; (2) the 50% lethal dose value, determined by the Litchfield-Wilcoxon method, was 23.8 mg/kg body weight in CDDP-MS in terms of cisplatin, whereas in the cisplatin aqueous solution it was 13.5 mg/kg body weight; (3) CDDP-MS enhanced therapeutic effects when compared with the same toxicity dosage of cisplatin aqueous solution. CONCLUSIONS: Intraperitoneal CDDP-MS releases cisplatin into the peritoneal cavity for a long time, and it results in less systemic toxicity and greater therapeutic effects on peritoneal carcinomatosis than does cisplatin aqueous solution.

Preoperative combined treatment with radiation, intraluminal hyperthermia, and 5-fluorouracil suppositories for patients with rectal cancer.

A clinical trial of a novel modality consisting of preoperative irradiation and intraluminal hyperthermia therapy, with or without 5-fluorouracil (5-FU) suppositories, was conducted on 30 patients with rectal cancer. To create hyperthermia in rectal cancer, an intraluminal electrode connected to a radiofrequency system was devised. Patients were treated preoperatively with a total irradiation dose of 30 Gy, being 3 Gy every 2 days, and 5 applications of hyperthermia given twice a week, with or without 5-FU suppositories, given as 100 mg a day to a total of 2,000 mg. Twenty patients received irradiation, intraluminal hyperthermia, and 5-FU suppositories, being the three-combination treatment, and the remaining 10 received irradiation and intraluminal hyperthermia, being the two-combination treatment. Shrinkage of the rectal cancer was observed macroscopically in 26 patients, resulting in a flattened cancerous crater or shallow ulcer. Microscopic examination revealed a marked decrease in the number of cancer cells. In fact, three resected specimens showed no evidence of cancer cells microscopically. These striking reductions in cancer size enabled us to successfully perform super-low anterior resections in four patients, with anastomoses being made just above the dentate line with a sufficiently safe margin. No serious complications were encountered in this series.

Significant clinical response of activated carbon adsorbed-peplomycin against esophageal cancer: a pilot study.

Activated carbon particle adsorbed-peplomycin (PEP-CH) was administered to three patients who had advanced esophageal cancer and its clinical usefulness was evaluated. The PEP-CH was injected endoscopically into the tumor or the adjacent normal esophageal tissue. Case 1 and case 3 were treated by topical injection of PEP-CH with or without surgery and case 2 was subjected to the PEP-CH treatment with radiation. The barium swallow and endoscopic examination exhibited a marked tumor reduction in all the patients at the end of the PEP-CH treatment. Although a marked clinical response was seen, case 1 died of postoperative complication. Two patients were capable of oral food intake after the treatment, which had been impossible before the treatment. There were no serious adverse side effects caused by the PEP-CH treatment in all the patients. PEP-CH should prove valuable as a new form of chemotherapy for the treatment of esophageal cancer patients.

Balloon dilatation for anastomotic stricture after upper gastro-intestinal surgery.

We report our study on the correlation between the types of anastomosis and the incidence of anastomotic stricture formation in the upper gastro-intestinal tract. Our experience with balloon dilatation is also reported. We examined the incidence of stricture formation among patients who had an anastomosis between the esophagus and stomach following subtotal esophagectomy for esophageal cancer, and esophagojejunostomy following proximal or total gastrectomy for gastric cancer in the past 17 years. Among 283 patients undergoing esophagojejunostomy, 7 cases of stricture (excluding 3 cases of cancer recurrence) were observed (conventional anastomosis 1.8%; stapling anastomosis 4.6%). There were 17 cases of stricture among 56 patients who had anastomosis between the esophagus and stomach following subtotal esophagectomy (conventional anastomosis 28.6%; stapling anastomosis 50.0%). One month or more after the operation, the diameter of the esophagojejunostomy was estimated using a barium study. The mean diameter of the anastomosis using the stapling method was 11.9 +/- 2.9 mm, whereas the mean diameter of serosubmucosal single layer hand-sewn anastomosis (Jourdan's) was 19.8 +/- 2.2 mm, and that of vertical mattress hand-sewn anastomosis was 19.0 +/- 2.0 mm. Balloon dilatation was used in 29 patients with anastomotic stricture of the upper gastro-intestinal tract (esophageal cancer, 19 patients, gastric cancer, 10 patients). With repeated dilatation, we were able to obtain satisfactory efficacy for benign strictures and there were no severe complications. We believe that balloon dilatation is an easy, safe and effective therapy for anastomotic stricture of the upper gastro-intestinal tract.

Prophylaxis with carbon-adsorbed mitomycin against peritoneal recurrence of gastric cancer.

Attempts to prevent peritoneal carcinomatosis after surgery for gastric cancer by intraperitoneal administration of anticancer drugs have not been successful, largely because the drugs are not retained in the peritoneal cavity. We have assessed the prophylactic efficacy of a delayed-release preparation--mitomycin adsorbed onto activated charcoal (M-CH). 50 patients with gastric cancer and serosal infiltration were randomly assigned intraperitoneal treatment with M-CH (50 mg mitomycin intraoperatively) or no anticancer prophylaxis (control). Survival rates for the 3 years of follow-up were significantly higher among the 24 M-CH recipients (1 was lost to follow-up) than among the 25 controls (p less than 0.01). There were significant differences in survival between the groups at 1.5 years after randomisation (difference 34.6% [95% confidence interval 8.5-60.8%]; p less than 0.01) and at 2.0, 2.5, and 3.0 years (41.7% [14.2-69.1%]; p less than 0.005). The concentration of mitomycin was significantly higher in peritoneal exudate than in plasma for 24 h after drug administration. Side-effects were slight and well tolerated. Thus, peroperative intraperitoneal treatment with M-CH seems to improve survival after gastrectomy for gastric cancer, presumably by a prophylactic effect on peritoneal recurrence.

The prognosis of patients with gastric cancer possessing sex hormone receptors.

Estrogen receptors (ER) and progesterone receptors (PgR) were immunohistologically investigated in 107 patients with gastric cancer who underwent curative resection. Both ER and PgR were detected only in the cancer cell nucleus. The ER positive rate was 27.7% for males and 31.0% for females, while the PgR positive rate was 9.2% for males and 11.9% for females. Clinicopathologically, the ER positive rate was slightly higher in young females and in cases of poorly differentiated gastric cancer. When cumulative survival rates were analyzed in relation to the presence or absence of receptors, the 10-year cumulative survival rate after surgery was significantly lower in the ER positive cases, being 15.7% cent, than in the ER negative cases, being 62.7%, and also significantly lower in the PgR positive cases, being 18.2%, than in the PgR negative cases, being 48.3%. The coexistence of ER and PgR in gastric cancer tissues suggests that the ER is physiologically active, or that ER positive gastric cancer is hormone-dependent. The poor prognosis of patients with receptor positive gastric cancer suggests that gastric cancer with these receptors is highly malignant.

Characterization of estrogen receptor in human gastric cancer.

Estrogen receptors (ER) were examined in cytosol, nuclear potassium chloride (KCl) extractable fraction, and nuclear KCl unextractable fraction by the dextran-coated charcoal adsorption method in various gastric cancer tissue. The overall ER-positive rate in the cytosol and nuclear fraction was 19.2%. The maximum binding site (Bmax) was 36.0 to 175.0 fmol/mg of protein, and the dissociation constant (Kd) was 0.6 to 1.6 X 10(-9) in cytosol fraction. In the nuclear fraction, Bmax was 7.5 fmol/mg of DNA and Kd was 2.3 X 10(-9). Estrogen receptors were characterized in cytosol protein. In cytosol, the estrogen (E2)-ER complex was sedimented at approximately the 5S and 8S regions by 5% to 20% linear sucrose gradient centrifugation. A steroid specificity study of ER showed the presence of an binder in gastric cancer tissue. In conclusion, these results that gastric cancer tissue has E2 binding sites with the same biochemical characteristics as in breast cancer and endometrial cancer strongly suggest the hormonal dependency of gastric cancer.

[Mass-screening for breast cancer using C-mode display ultrasonography].

In order to elevate the detection rate of breast cancer in mass-screening, we examined whether the C-mode display ultrasonography is useful for detection of breast cancer. 1) Diagnostic sensitivity of C-mode ultrasonography was 88.2%, specificity was 66.7% and predictive value was 58.8%, respectively. 2) The detection rate of C0mode ultrasonography was 100% for tumors more than 5.0cm, 87.5% for 2.0-5.0cm, 74.2% for less than 2.0cm. Especially, the diagnostic value of lesser than 1.0cm breast cancer was high, 66.7%. 3) In findings of C-mode ultrasonography, images characteristic of carcinoma can be obtained regarding their unclear margin (70.6%), heterogenous (88.2%) and hypoechoic (70.6%) internal echoes and malignant halo (61.8%). Our present data suggest that C-mode ultrasonography is very useful for the mass screening for breast cancer.

[Study on follow-up of patients with biopsy-proven breast disease].

Eight hundred forty-one patients with biopsy-proven benign breast disease were followed annually in prospective manner for 1-10 years to analyse breast cancer development at aspect of histologic features, age at entry and mammographic patterns by Wolfe. No association was found between patients who developed cancer and those who did not with respect to the initial histologic features. The rate of breast cancer development in patients in thirties was the highest. The breast cancer development was found most often in less than three years follow-up period. The breast parenchymal patterns at entry related to cancer development. In 10 cancer patients, 8 patients showed DY pattern and 2 showed P2 patterns. The present results demonstrate that the patients with biopsy-proven benign breast disease in thirties, in less than 3 years follow up period and have parenchymal patterns of P2 or DY should be followed carefully.

[Immunocytochemical staining of estrogen receptor in conventional formalin-fixed paraffin sections in human breast cancer].

Immunocytochemical staining for estrogen receptor (ER) was examined in conventional formalin-fixed paraffin sections in 63 patients with breast cancer. The ER staining was performed by avidin-biotin peroxidase complex method (ABC) using monoclonal antibody against ER (H222). The ER stainability in formalin-fixed paraffin sections was compared with the levels of ER measuring dextran-coated charcoal (DCC) method, and with the stainability of ER in frozen sections. ER positive rates of paraffin sections and frozen sections were 52%, and 65% respectively. ER positive level of DCC method was seen in 62 percent of the cases. Results of ER staining in paraffin sections correlated well to those of DCC method and to those of ER staining in frozen sections. In paraffin sections as well as in frozen sections, ER staining was located at the nuclei of cancer cells. Furthermore, the variety that this method for ER can be used for retrospective studies of ER on stored blocks of breast cancer.

Immunohistochemical demonstration of estrogen, progesterone, CEA and ferritin in breast cancer and their clinical value for the prediction of early postoperative recurrence.

The aim of this paper is to determine whether the incidence of estrogen-, progesterone-, CEA-, and ferritin- positive staining of primary tumors, by using the PAP method, is related to the prognosis of breast cancer status. A significantly higher incidence (71 per cent) of CEA-positive tumors was observed in patients who had a recurrence of breast cancer within 2 years after radical operation. Patients, whose tumors were positive in estrogen or negative in CEA, showed a relatively good prognosis, even after a recurrence of the disease. Distant metastases were seen in most of the patients positive in CEA (78 per cent). Before the recurrence of breast cancer, those patients positive in progesterone had a good prognosis. After the recurrence, however, there was no relationship between the prognosis of recurrent disease and the progesterone-staining of primary tumors. Our data suggest that the immunohistological staining of estrogen, progesterone and CEA might offer the effective prognostic indices in breast cancer patients.