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.

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.

Synoviorthesis with radioactive gold in haemophilia.

According to the experiences of the Malmö Haemophilia Centre, the best way to avoid recurrent joint bleedings and synovitis in haemophilic patients and to prevent progressive joint disease is prophylactic factor treatment. If prophylaxis is impracticable and also in patients with factor inhibitors, radioactive synoviorthesis seems to be a good treatment option if started early.

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.

[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%).

Synoviorthesis with 198Au colloid gold in haemophilia patients. A preliminary report.

In 1988-1989 fifteen patients with severe haemophilia A and recurrent bleedings into the knee joint, aged from 19 to 44 years were treated by an intraarticular injection of 198Au colloid gold. So far 10 of them were assessed after 6 months follow-up. In 6 cases cesseation and in 2 cases reduction in number and volume of bleedings were observed. Only in 2 patients the frequency of haemarthroses remained unchanged. No significant difference in tracer uptake was observed between pretreatment 99mTc-pertechnate gamma scans of the knee joints and controls completed 6 months after the radiogold injections. It is worthy to stress the lower costs of the 198Au synoviorthesis as compared with surgical synovectomy of the knee joint. The radioisotope method is also much less traumatic to the patient than the surgical one.

[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.

[Adjuvant radioactive gold therapy of primary stage I c ovarian cancer]. / Adjuvante Radiogoldtherapie des primären Ovarialkarzinoms im Stadium I c.

47 patients with primary ovarian cancer stage I c have been treated following radical operation additionally with an intraperitoneal instillation of 5.5 GBq radioactive gold colloid. 5-year survival rate was 87 per cent. Severe complications have not been observed.

[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.

[Combination therapy of rectal cancer using 198Au]. / Kombinirovannoe lechenie raka priamoi kishki s ispol'zovaniem 198Au.

The authors analyzed the results of therapy of 2 groups of patients with stage I-III rectal cancer. Combined therapy of 92 patients included preoperative large fractional radiotherapy at a total focal dose of 20-25 Gy, radical operation and i.v. injection of 1.48-1.85 GBq of 198Au shortly after the operation. The control group of 131 patients underwent surgery only. The groups did not differ significantly in the main prognostic characteristics. The combined therapeutic method was shown to be more effective than surgery alone, and the 5-year survival rates were 70.6 +/- 5.2 and 55.4 +/- 4.91% respectively (P X2 less than 0.05). The frequency of postoperative complications and lethality were not increased. Leukopenia was of temporary nature and disappeared either by itself or as a result of leukostimulating and substitution therapy.

[Comparative evaluation of the long-term results of treatment of cervical cancer using radiocolloids]. / Sravnitel'naia otsenka otdalennykh rezul'tatov lecheniia raka sheiki matki s primeneniem radiokolloidov.

The author provided a comparative analysis of the results of therapy of 127 cervical cancer patients. 198Au-(75 patients) and 90Y-colloids (52 patients) were administered intraparametrially for adjuvant radiotherapy. The summary absorbed dose in combined modality radiation therapy was 90-100 Gy at the point A and 40-50 Gy at the point B. The author presented 5- and 10-year survival rates which were higher with 90Y-colloid as compared to those with 198Au-colloid. Early radiation reactions and late radiation injuries developed somewhat more frequently with 90Y. However statistical differences were insignificant. Thus, combined modality radiation therapy of cervical cancer using 90Y-colloid for adjuvant radiotherapy considerably enhances therapeutic efficacy without increasing the number of radiation complications.

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.