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Biomedical subjects

G W Wirtanen

Publications and source records attributed to G W Wirtanen.

At least 19 recordsLinked to original sources

Diffuse testicular microlithiasis associated with intratubular germ cell neoplasia and seminoma.

Testicular microlithiasis is an uncommon condition in which multiple calcifications develop in the seminiferous tubules. Sonography demonstrates a typical pattern of diffuse, hyperechoic specks. This condition has been associated with premalignant and malignant changes of the testicle. We present a case of intratubular germ cell neoplasia and a microscopic focus of seminoma found in a patient with isolated testicular microlithiasis and no focal mass. Physicians should be more aware of testicular microlithiasis, and heightened surveillance is recommended to identify progression to tumor formation.

Adult↗

Intraarterial iododeoxyuridine infusion combined with irradiation. A pilot study.

The halogenated pyrimidine, iododeoxyuridine (IUdR), enhances cytotoxicity of ionizing irradiation experimentally. Continuous intraarterial infusion of IUdR was combined with irradiation to maximize drug concentration in tumor and reduce potential systemic toxicity. Percutaneous tumor-specific artery catheterization was utilized in five patients, with delivery of IUdR (20 mg/kg/day) by continuous infusion 5 days prior to irradiation treatments and continued for 10-14 days. Infusion vessels included the internal mammary, the internal iliac, the renal, the common femoral, and the bronchial arteries. Conventional radiotherapy fields, fractionation, and total doses were utilized, and therapy was well tolerated. Low-grade leukopenia and thrombocytopenia was observed several weeks following infusion. A clinically nonsignificant skin reaction was observed within the irradiation fields 2-3 weeks after initiation of irradiation in several patients. No alopecia or stomatitis was observed. This study minimizes initial hepatic dehalogenation of IUdR when given by intraarterial administration. Two patients have been free of disease for over 20 years, with no long-term toxicity from IUdR therapy.

Adolescent↗

Phase I trial of hepatic artery infusion of 5-iodo-2'-deoxyuridine and 5-fluorouracil in patients with advanced hepatic malignancy: biochemically based combination chemotherapy.

Eighteen patients with hepatic metastases primarily from colorectal carcinoma were treated on a phase I protocol employing hepatic artery infusion (HAI) of 5-fluorouracil (FUra) and 5-iodo-2'-deoxyuridine (IdUrd) via implantable infusion pump. Patients received a 14-day continuous HAI of 300 mg/day FUra. During days 8-14 of therapy, patients received IdUrd as a separate 3-h HAI daily x 7. Treatment cycles were repeated every 28 days. IdUrd was escalated from 0.1 to 2.86 mg/kg/day x 7. Myelosuppression and stomatitis were mild and not dose limiting. Hepatotoxicity was dose limiting and similar to that reported for 5-fluoro-2'deoxyuridine alone administered as a 14-day infusion every month. One patient developed a clinical picture consistent with sclerosing cholangitis and another had biopsy-proven cholestasis and triaditis. Catheter complications occurred in 7 of 18 patients. Plasma concentrations of FUra during the 7-day continuous HAI of FUra alone were consistently either undetectable or very low (less than or equal to 0.1 microM). At level 3 (1.0 mg/kg/day IdUrd) and beyond, measurable plasma concentrations of FUra, iodouracil, and IdUrd were found at the end of the daily 3-h infusion of IdUrd. The maximum tolerated dose of IdUrd as administered in this trial is 2.2 mg/kg/day x 7 and the recommended starting dose for further clinical investigation is 1.7 mg/kg/day x 7.

Animals↗

Combined hepatic artery 5-fluorouracil and irradiation of liver metastases. A randomized study.

The effect of hepatic irradiation (RT) after intraarterial 5-fluorouracil (5-FU) was evaluated in 37 randomized patients with colorectal adenocarcinoma hepatic metastases. Patients underwent percutaneous transbrachial artery catheterization of the hepatic artery followed by 21-day continuous 5-FU infusion (CT). Hepatic irradiation of 25.5 Gy was delivered to 19 patients 14 days after completion of infusion (CT + RT). All patients received subsequent weekly maintenance 5-FU. A 37% (seven of 19) response rate was observed in CT + RT, and a 50% response rate (nine of 18) in CT: median survival was 6 months for CT + RT, and 8 months for CT, (P = 0.106). Improved survival was observed in two subsets of patients. Tumor vascularity was graded angiographically from 0 to 4+; those patients with highest vascularity (4+) had a 20-month median survival (P = 0.0009). Patients with Grade 1, well-differentiated, histologic type had a median survival of 20 months (P = 0.0001). Four patients with both 4+ vascularity and Grade 1 histologic type had 27.5 months' median survival (P = 0.0019). Age, performance status, elevated liver function tests, previous systemic therapy, and time interval between diagnosis and entry on this study did not impact on survival (P greater than 0.05), nor did these variables eliminate the significance of vascularity and grade (P less than 0.05). Survival after intraarterial 5-FU infusion was not improved by this regimen of sequential external irradiation. Regional therapy may benefit those patients with 4+ vascular tumors and/or well-differentiated tumor grade. Future trials are needed to explore the interaction of halogenated pyrimidines with irradiation and determine whether these prognostic factors can aid in patient selection for regional therapy of hepatic metastases.

Adenocarcinoma↗

Primary anterior mediastinal malignant teratoma. A case report with long-term survival.

Primary anterior mediastinal malignant teratoma is an uncommon tumor. A 17-year-old girl presented with an advanced tumor extending parasternally. Therapy consisted of intraarterial iododeoxyuridine and irradiation followed by surgical resection after failing multidrug therapy. The patient is without evidence of disease 23 years after therapy.

Adolescent↗

Treatment of probable subclinical liver metastases and gross pancreatic carcinoma with hepatic artery 5-fluorouracil infusion and radiation therapy.

Since subclinical hepatic metastases are frequently present at time of diagnosis of pancreatic carcinoma, any meaningful effort to improve survival must include 'prophylactic' liver therapy in addition to treatment of the pancreatic primary. We report the results of a prospective, unrandomized clinical trial of a 2-week liver and pancreas infusion (by hepatic artery) of 5-fluorouracil (5-FU) and pancreatic irradiation to 50-60 Gy, combined with prophylactic irradiation of the liver with approximately 20 Gy. Of 21 evaluable patients, 17 completed therapy without excessive toxicity and had a median survival of 50 weeks. Contrary to historical controls, the liver in our series was rarely the first site of failure (6%), suggesting that the combination of hepatic artery 5-fluorouracil and 20 Gy liver radiation may suppress subclinical (microscopic) liver metastases without significant hepato-toxicity. When radiation doses to the pancreas were increased above 50 Gy there was improvement in primary tumor control, although failure in the pancreatic bed remained the most common site of failure. Future clinical investigation of this form of combined therapy for eradication of micro-metastasis in the liver, combined with more aggressive local pancreatic therapy, would seem appropriate.

Adenocarcinoma↗

Percutaneous lymph node aspiration in patients with gynecologic tumors.

Sixty-one patients with gynecologic malignancies had percutaneous transperitoneal lymph node aspiration performed by a flexible 8-inch needle guided to the nodes under monoplanar fluoroscopy. Of the patients who had malignant cells aspirated from pelvic and periaortic lymph nodes, 64% died or are alive with disease. Only 30% who had negative cytologic testing died or are alive with disease. Of the patients who had malignant cells aspirated from periaortic nodes, 69% died or are alive with disease whereas only 8% with negative cytologic testing died or are alive with disease. We believe that therapy such as extended field irradiation can be given on the basis of these results.

Aorta↗

High Z elements in human sarcomata: assessment by multienergy CT and neutron activation analysis.

"Tumor equivalent" phantoms containing inorganic salts (KH2PO4, CH3COOK, NaCl and Kl) were scanned on an EMI 5005 body scanner at 140 kVp, 28 mA; 120 kVp, 33 mA; and 81 kVp, 42 mA. Significant signal gain for the detection of higher atomic number elements by multiple energy scanning was noted. Certain sarcomas are known to accumulate high Z elements. Accordingly, excised specimens of various histologies of human sarcomata (chondrosarcoma, liposarcoma, and malignant fibrous histiocytoma) were scanned at 140 kVp and 81 kVp. Using selected areas of interest in the computed tomographic (CT) image to direct the in vitro biopsy of various regions of excised tumors, interesting correlations between the CT number variation and the respective, high Z elemental composition variation, as determined by thermal neutron activation analysis were observed. Further investigation with phantoms and excised sarcomata at 62 kVp and 42 mA suggested that dual energy CT scanning (at 140 kVp and 62 kVp) may be a method of monitoring "effective Z" and heavy element compositional changes. The authors are also attempting to develop these same low kilovoltage techniques as a method for the noninvasive clinical monitoring of an antisarcoma chemotherapeutic agent, cis-diammineaichloroplatinum (11).

Activation Analysis↗

Septic endarteritis due to intra-arterial catheters for cancer chemotherapy. I. Evaluation of an outbreak. II. Risk factors, clinical features and management, III. Guidelines for prevention.

A cluster of three cases of staphylococcal septic endarteritis originating from percutaneously inserted brachial artery catheters for regional cancer chemotherapy prompted an epidemiologic and clinical study of bacteremic infections associated with this therapeutic modality. Nine cases were identified over a 3 1/2-year period (1.6% of all catheterizations), all caused by Staphylococcus aureus. The cluster followed discontinuation of hexachlorophene for scrub of the extremity prior to cannulation; phage-typing suggested the three cases were caused by the patients' own strains of Staphylococcus. These infections produced a distinctive clinical syndrome which facilitates implicating the catheter in the genesis of fever occurring in a patient receiving intra-arterial chemotherapy: early localized pain (89%) and hemorrhage (78%), and Osler's nodes distally (44%), later followed by local inflammation (78%), purulence (56%) and signs of systemic sepsis (100%) (each factor, p less than or equal to .005). Duration of cannulation did not influence susceptibility to infection. However, difficult cannulations or need for repositioning the catheter (p = .0096), prior radiation therapy (p = .033), leukopenia (p less than .05) and hypoalbuminemia (p less than .05) were all associated with septicemia. In the 25 months since implementation of specific control measures, there have been no further catheter-related septicemia in 310 catheterization (p less than .001). Guide-lines for prevention and management of these infections are provided.

Adult↗

Bipedal lymphangiography in malignancies of the uterine corpus.

Bipedal lymphangiography was performed in 116 selected patients with primary endometrial malignancy since 1970. A total of 32 were interpreted as positive and 84 as negative. Although histologic confirmation of nodal interpretation was seldom obtained, short term follow-up indicates that a positive interpretation is associated with an extremely poor prognosis. Lymphangiograms are recommended in all stage I patients except those with well differentiated histology, a small corpus, and no deep myometrial invasion. This study is also recommended for all stage II and III patients and for selected patients with stage IV disease.

Adenocarcinoma↗

Accuracy of bipedal lymphography in Hodgkin's disease.

Bipedal lymphography was used as part of the initial staging evaluation of 145 patients with Hodgkin's disease. Histologic correlation was available in 131 patients. The accuracy of interpretation was 95%. A review of other large series confirms that at least 85%-90% accuracy can be expected. Reasons for false positive and false negative interpretations are discussed.

Biopsy↗

Clinical and theoretical aspects of the treatment of surgically unresectable retroperitoneal malignancy with combined intra-arterial actinomycin-D and radiotherapy.

A small pilot series (eight patients) of surgically unresectable retroperitoneal tumors treated with radiotherapy and a selective, prolonged, continuous intra-arterial infusion of actinomycin-D is discussed, in addition to the possible theoretical advantages for this therapy. For such tumors, there is a very low probability of obtaining local control with conventional radiotherapy alone. However, on the basis of recent knowledge from radiobiology and molecular biology, the technique is a rational attempt to improve the local control probability. Geographic miss with radiotherapy portals is another major cause for local failure with such tumors. We also emphasize the importance of detailed tumor localization procedures. The local responses, some of the local controls, the palliation achieved, and the lack of significant morbidity with this technique have been encouraging. We therefore consider it worthy of further clinical investigation.

Adolescent↗

Further clinical studies with intrahepatic arterial infusion with 5-fluorouracil.

A total of 419 patients with progressive liver disease, in nearly all cases metastatic from gastrointestinal primaries, were treated by intrahepatic arterial infusion with 5-FU. Three-fourths of these patients had had prior trials with intravenous 5-FU for 1 or 2 months to several years and had been switched to the infusion upon the development of progression. Catheters were placed percutaneously and the patients infused with 5-FU at a dose of 20 to 30 mg/kg/day X 4, then 15 mg/kg/day X 17, at which point the catheter was removed and the patient sent home on weekly i.v. doses at 15 mg/kg. Toxicity, morbidity, and mortality were minimal with the intrahepatic arterial infusion treatment and the rigid criteria of improvement were met by 55% of the study cases. The survival rate of those patients who responded to the treatment was greater than the survival rate of those who failed to respond.

Fluorouracil↗

Combined intra-arterial actinomycin D and radiation therapy for surgically unresectable hypernephroma.

One primary goal of preoperative radiotherapy for hypernephroma is to reduce the volume of tumor and, therefore, improve the possibility of resection. It is important that this goal be accomplished promptly so that 4 to 6 weeks after radiation therapy nephrectomy can be attempted. A longer waiting period may allow fibrosis of the normal surrounding tissues and make surgery more difficult. In addition, longer waiting periods could theoretically increase the probability of metastasis. Therefore, we plan to continue clinical investigation on the use of combined intra-arterial actinomycin D and radiotherapy as a possible useful means of improving the possibility of prompt surgical resection, since theoretically this regimen may be a method of increasing the effective radiation dose to the hypernephroma without increasing the effective radiation dose to surrounding normal tissue, such as bowel. The method may also have merit as an improved means of palliating selected patients with metastases who are symptomatic from a bulky primary hypernephroma.

Adenocarcinoma↗