Rubin H. Flocks and colloidal gold treatments for prostate cancer.

In the early 1950s, Rubin H. Flocks of the University of Iowa began to treat prostate cancer patients with colloidal gold (Au(198)) therapy, evolving his technique over nearly 25 years in 1515 patients. We reviewed the long-term outcomes of Flocks' prostate cancer patients as compared to those patients treated by other methods at the University of Iowa before Flocks' chairmanship. We reviewed archived patient records, Flocks' published data, and long-term survival data from the Iowa Tumor Registry to determine short- and long-term outcomes of Flocks' work with colloidal gold. We also reviewed the literature of Flocks' time to compare his outcomes against those of his contemporaries. The use of colloidal gold, either as primary or adjunctive therapy, provided short- and long-term survival benefit for the majority of Flocks' patients as compared to historical treatment options (p < 0.001). Flocks' use of colloidal gold for the treatment of locally advanced prostate cancer offered short- and long-term survival benefits compared to other contemporary treatments.

Metallic colloid nanotechnology, applications in diagnosis and therapeutics.

In recent years the fields of medicine and biology assist to an ever-growing innovation related to the development of nanotechnologies. In the pharmaceutical domain, for example, liposomes, polymer based micro and nanoparticles have been subjects of intense research and development during the last three decades. In this scenario metallic particles, which use was already suggested in the first half of the '80, are now experiencing a real renaissance. In the field of diagnosis, magnetic resonance imaging is one of the first and up to now the most developed application of metallic particles. But beside this application, a very new generation of biosensors based on the optical properties of colloidal gold and fluorescent nanocrystals, called quantum dots seems to be ready to be implemented in diagnosis and medical imaging. Concerning therapeutic applications, the potentialities of metal nanoparticles to help fulfilling the need of time and space controlled release of drugs has been intuited for a long time. Nowadays, magnetically guided carriers or thermal responsive matrices, in which drug release is triggered by the heating of metal nanoparticles, are effective examples of their application in drug delivery, while more recently efforts to develop metallic nanoobjects to be used as vectors of nucleic acids for vaccination and transfection have been multiplied. In the future, one of the most interesting challenges is certainly the use of metallic nanoparticles for an innovating, effective and selective physical treatment of solid tumors via targeted intracellular hyperthermia.

Transpalatal insertion of radioactive gold grain for the treatment of persistent and recurrent nasopharyngeal carcinoma.

PURPOSE: To evaluate the efficacy of radioactive gold grain implant via the split palate approach in the control of locally recurrent or persistent nasopharyngeal carcinoma. METHODS AND MATERIAL: Forty-three patients, 10 for persistent NPC, 28 for first relapse in the nasopharynx, and five for second relapse in the nasopharynx, were treated. The diameter of the tumors at the time of gold grain implant ranged from 0.5 to 5 cm, the number of gold grains inserted varied from 4 to 14, the median number was seven. RESULTS: There was no significant difference in the control of the primary tumor for persistent disease (80% at 5 years), first relapse (61% at 5 years) and second relapse (80% at 3 years), p = 0.8845. The difference in survival between the three subgroups of patients, however, was highly significant (p = 0.0040). Thirty patients had CT evaluation before gold grain implant and the tumor was found confined to the nasopharynx in 21, in the remaining nine patients erosion of the sphenoid sinus or other parts of the base of skull was noted. The difference in the control between those patients with tumors confined to the nasopharynx and those patients with extranasopharyngeal extension of tumor almost reached statistical significance (81% and 44% respectively at 5 years, p = 0.0554). For the six patients who developed local recurrence after gold grain implant and were evaluable for the pattern of failure, the recurrent tumors were considered originating from another region of the nasopharynx in four, and in-field failure in the other two cases. CONCLUSION: Radioactive gold grain implant as salvage treatment provides satisfactory control of persistent and recurrent nasopharyngeal carcinoma. The local control was better when the tumor was localized to the nasopharynx, thus underlines the importance of close follow-up for early recognition of relapse and persistent tumor. However, such patients still suffered from high incidence of regional and distant failure, the pathophysiology and management of which require further investigation.

Suppression of hepatic hematopoiesis with radioactive gold (198Au).

A patient with idiopathic myelofibrosis of some 20 yr duration developed esophageal varices and ascites. No explanation for increased portal pressure other than hepatic hematopoiesis was found. Consequently, a trial of cobalt irradiation to the liver was undertaken with definite but transient decrease in ascites. Subsequently, two courses of radioactive colloidal gold were given, again with definite but transient beneficial effects on the degree of ascites. This latter benefit occurred without suppression of marrow function.

Use of radioactive gold in the treatment of pleural effusions caused by metastatic cancer.

This paper presents a series of 12 patients suffering from advanced gynecological cancer with the occurrence of pleural effusions. All patients received at least one intrapleural dose of radioactive gold (100 m Ci Au198) when the necessity for thoracentesis became more than once every three weeks. Three showed no recurrence of fluid, five a significant slowing down of effusion, and four did not show any response. Severe complications were minimal, and were comparable to those resulting from thoracentesis in general.

Complications following parametrial radiogold treatment for cervical carcinoma.

Between January 1950 and March 1965, 382 patients with carcinoma of the uterine cervix were treated with parametrial radiogold injections. One hundred and ninety-two patients are known to have survived 5 or more years after the treatment without evidence of recurrence. Major complications with significant morbidity requiring hospitalization or additional surgery was observed in 9.4% of the patients. Parametrial radiogold injection is associated with a high incidence of major lower urinary tract complications, including an increased incidence of ureteral obstruction as a result of radiation fibrosis, Heterogenous distribution of radioactive material with localized areas of heavy irradiation is probably responsible for the development of late major complications.

Internal irradiation for cystic craniopharyngioma.

The authors report the results of internal irradiation with labeled chromic phosphate (32P) and gold-198 (198Au) colloid in eight cases of cystic craniopharyngiomas. They used a newly developed dosimetric formula, by which the radiation dose at the cyst wall and at any point far from the radioactive source can be calculated. Ten courses of irradiation in eight patients were carried out by injection of either 32P or 198Au colloid into the cyst through an Ommaya drainage system that had been placed at craniotomy. Follow-up studies ranging from 13 to 156 months revealed that all cysts were effectively treated, with elimination of fluid or collapse of the cyst. This was confirmed by Conray cystography and/or computerized tomography. Not only the dose delivered to the wall but also the thickness of the cyst wall and the location of the cyst are important factors in planning internal irradiation. A safe and adequate dose to the cyst wall could range between 9000 to 30,000 rads for craniopharyngioma. This treatment is suitable for large cysts that are thought to be difficult to remove radically, recurrent cysts resistant to previous treatment, or multiple cysts. Internal irradiation may also be applicable in other cystic intracranial tumors if dosimetry is calculated accurately.

[Cytogenetic investigations in patients receiving an intraarticular injection of gold-198 (author's transl)]. / Chromosomenuntersuchungen nach intraartikulärer Injektion von Gold-198

The chromosomes of lymphocyte cultures from the peripheral blood were investigated in 10 patients (rheumatoid arthritis, ankylosing spondylitis, osteoarthrosis of the knee) before and at short-term intervals (1 day, 3 to 4 days, 14 to 18 days) after the injection of gold-198 (5 to 20 mC; usually 8 mC; average particle size 300 A) into the knee-joint. The number of structural chromosomal abberrations increased markedly in 4 of the 10 patients. On the first day after the gold injection the mean aberration rate was significantly higher than the control value (Chi2-5.18; df=1; P less than 0.05). Most of the observed aberrations were chromatid aberrations and this finding is discussed.

Radioactive gold-198 seeds for the treatment of squamous cell carcinoma in the eyelid of a cat.

A 19-year-old, speyed, domestic short-hair cat was presented with an eyelid tumour of 3 months duration. Ophthalmic examination revealed a large, raised, ulcerated and bleeding mass affecting the left lower eyelid. The mass was 12 mm x 10 mm in size, extended to the medial canthus and had eroded 10 mm of eyelid margin. Mandibular lymph nodes were not palpably enlarged. A diagnosis of squamous cell carcinoma was confirmed by histologic examination. Due to involvement of more than half the lower eyelid, it was decided that treatment with radioactive gold-198 seeds was appropriate. Nine radioactive gold-198 seeds were implanted, delivering a minimum tumour dose of 65 Gy. Three weeks postoperatively the mass had resolved, with only a small scab remaining. After a further 3 weeks, there was no evidence of the eyelid tumour. Although approximately 7 mm of eyelid margin was absent, this did not cause any clinical signs other than mild conjunctivitis. There was no evidence of the tumour 10 months postoperatively, when the cat was euthanased for unrelated disease.

[Contact radiotherapy of rheumatoid arthritis]. / Kontaktnaia luchevaia terapiia revmatoidnogo artrita.

The authors have devised a method of contact radiotherapy with open radionuclides (198Au) to be used in the treatment of patients suffering from rheumatoid arthritis. Indications for therapy have been defined. In 360 patients suffering from rheumatoid arthritis, radioactive colloid gold was administered to the affected joints. The therapeutic effect was slow in development. The best clinical results were recorded at month 12. Considerable improvement was noticed in 70% of the patients, improvement in 20%, and in 10% of the patients, no therapeutic effect could be recorded. Good effect was ascertained in patients with X-ray Stage I and II disease (70%).

[Evaluation of the effectiveness of the radiation component in the combined treatment of cervical cancer]. / Otsenka éffektivnosti luchevogo komponenta pri kombinirovannom lechenii raka sheiki matki.

The author presents an analysis of the issues of different variants of the combination treatment for cervical cancer in 551 patients. In 246 of them the therapeutic schedule included the preoperative irradiation, in 305--the postoperative one. The preoperative irradiation was conducted following the fractional-protracted and large fractional techniques. Use of the irradiation preoperatively made it feasible to increase a 5-year survival in the patients; the fractional-protracted technique, however, yielded a greater number of the postoperative complications. Irradiation conducted in the regimen of large fractionation dose allowed obviating many of these complications and retaining the advantages of the combination treatment with preoperative radiotherapy.

[Characteristics of the postoperative period in stomach cancer patients undergoing combined treatment]. / Osobennosti posleoperatsionnogo perioda u bol'nykh rakom zheludka pri kombinirovannom lechenii.

Postoperative course was studied in 423 radically treated patients: 175--surgery only, 96--preoperative 5-fluorouracil chemotherapy, 79--intravenous radioactive colloid gold postoperatively, and 73--both 5-fluorouracil preoperatively and colloid gold postoperatively. The two latter procedures did not affect postoperative course adversely; nor did they influence the spectrum of postoperative complications or increase lethality rate.

[Treatment of patients with cancer of the colon]. / Lechenie bol'nykh rakom obodochnoi kishki.

Experience in the treatment of 317 patients with cancer of the colon is discussed. Surgery was conducted in 226 patients, 91 patients received combined treatment (operation and intravenous injection of radioactive colloidal gold). Postoperative mortality was 5.99%. The main cause of death was peritonitis (4.1%) due to incompetence of the anastomosis. Combined treatment of patients with stage III cancer of the colon improves somewhat the late-term results of management.