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F H Straus

Publications and source records attributed to F H Straus.

At least 19 recordsLinked to original sources
PubMed2002

Effective gene therapy for medullary thyroid carcinoma using recombinant adenovirus inducing tumor-specific expression of interleukin-12.

No satisfactory treatment of metastatic medullary thyroid carcinoma (MTC) is available. Cell-specific gene therapy offers a new approach. We have constructed a recombinant replication-defective adenoviral vector expressing murine interleukin-12 (mIL-12), driven by a modified CALC-I promoter (TCP). This vector (AdTCPmIL-12) includes two separate cassettes encoding mIL-12 p35 or p40 subunit controlled by TCP inserted in the E1 region of adenovirus type 5. In vitro and in vivo reporter gene expression using TCP revealed its cell-specific activity. AdTCPmIL-12-infected rat MTC (rMTC) cells produced high amounts of functional mIL-12 cells in vitro, while other cell lines infected with AdTCPmIL-12 did not. AdTCPmIL-12-transduced rMTC cells completely lost their tumorigenicity in syngenic WAG/Rij rats. Direct injection of 1 x 10(9) plaque forming units of AdTCPmIL-12 into subcutaneous rMTC tumors in WAG/Rij rats caused tumor regression in over 60% of animals within 20 days. Rats cured of tumors did not develop tumors after re-injection of naive rMTC cells, demonstrating lasting immunity. Treatment with AdTCPmIL-12 of one tumor resulted in regression of an established tumor at a distant site. Moreover, intratumoral or intravenous injection of AdTCPmIL-12 did not induce evident toxicity. These results indicate AdTCPmIL-12 can contribute to effective and less toxic gene therapy of MTC.

Adenoviridae↗
PubMed2001

Adenoviral-mediated gene therapy for thyroid carcinoma using thymidine kinase controlled by thyroglobulin promoter demonstrates high specificity and low toxicity.

A replication defective adenovirus transducing thymidine kinase (TK) gene under the control of the rat thyroglobulin (rTg) promoter (AdrTgtk) was developed to evaluate its cell-specific killing activity in gene therapy. We also developed adenoviruses containing the TK gene driven by the cytomegalovirus (CMV) promoter (AdCMVtk), and luciferase (Luc) gene driven by the rTg or CMV promoter (AdrTgLuc or AdCMVLuc). Luc activity in FRTL-5, HepG2, COS1, rMTC, hMTC, Hela, GH3, T98G, and CA77 cells was measured after infection with AdrTgLuc or AdCMVLuc. FRTL-5 cells produce thyroglobulin (Tg), whereas all other cells are non-Tg-producing cell lines. Transduction by AdCMVLuc caused high Luc activity in all cell lines. However, infection with AdrTgLuc induced Luc activity only in FRTL-5 cells. AdCMVtk or AdrTgtk was used to transduce various cell lines to evaluate the different killing effect. After infection with AdCMVtk vector followed by ganciclovir (GCV) treatment, cell growth was strongly suppressed in all cell lines compared both to noninfected cells and to cells infected by AdCMVLuc in the presence of GCV. When FRTL-5 cells were infected with AdrTgtk followed by GCV treatment, more than 90% were killed, but only a minimal effect was observed in other cell lines, indicating that the Tg promoter transduced TK expression only in Tg-producing cells. When adenovirus is given intravenously, liver and spleen are the major organs infected. A high Luc activity was found in liver and spleen of AdCMVLuc treated animals. No Luc activity was found in liver and spleen of AdrTgLuc-treated animals, indicating that rTg does not transduce Luc expression in non-Tg-producing tissues in vivo. No significant changes of the serum transaminase levels and histologic abnormalities were found in animals treated with AdrTgtk/GCV compared with control animals. High levels of serum transaminases, lymphocyte infiltration, some Kupffer's cell prominence, and extensive single cell hypatocyte death were found in AdCMVtk/GCV-treated animals, indicating severe liver damage induced, as expected, by a noncell-specific promoter. These results indicate that transfer of TK gene driven by the rTg promoter has thyroid cell-specific killing ability in the presence of GCV, little in vivo toxicity, and should be useful in the future for treating thyroid Tg-producing cancers.

Adenoviridae↗
PubMed1999

The use of collagen-GAG membranes in reconstructive surgery.

Porous collagen-glycosaminoglycan (PCG) membranes with a porous silicone elastomer coating have been useful as a scaffold for dermal replacement in burn victims. Critical physicochemical parameters of these membranes include pore size, cross-link density, the percentage of glycosaminoglycan, and the degree of banding of the collagen. These factors govern the immunobiological response. Optimizing these parameters can reduce inflammation, scarring, and contraction of wounds grafted with PCG membranes. PCG membranes are currently commercially manufactured (Integra, Integra Life Sciences, New Jersey) and available for clinical use. Because clinical outcomes have improved using these membranes for burn wound coverage, other skin reconstruction problems including scar resurfacing, keloids, treatment of donor sites, and treatment of chronic wounds can be considered as potential applications. This manuscript illustrates our early experience using Integra as a CG membrane for dermal replacement in reconstructive surgery. Our results indicate that CG membranes can lead to improved compliance and appearance compared to a meshed graft and may be sequentially placed in multiple layers to correct contour deformities. Also, in one case, we observed that, if placed on a wound bed with embedded skin epithelial cells, the PCG promotes epithelialization through the PCG matrix. The use of this material results in a supple integument with many similarities to normal skin.

Adult↗
PubMed1999

Benign adenomatous multicystic kidney tumor (Perlmann's tumor) and renal cortical carcinoma with adenomatous multicystic features: 12 cases.

OBJECTIVES: To re-examine clear cell cystic lesions of the kidney and to assess their potential clinicopathologic significance, as the long-forgotten diagnosis of benign adenomatous multicystic kidney tumor (Perlmann's tumor) has not been cited in the literature in more than 35 years. METHODS: We identified 12 patients between 1959 and 1996 who underwent a radical nephrectomy at our institution and were diagnosed with either adenomatous multicystic clear cell kidney tumor (n = 4) or with renal cell carcinoma (RCC) associated with features of adenomatous clear cell multicystic kidney tumors (n = 8). All diagnoses were reviewed histologically by a single pathologist. RESULTS: Nine of 1 2 patients had Stage T2NOMO disease, and 3 patients had Stage T1 NOMO disease. There were 8 men and 4 women. The average age at the time of surgery was 60.5 years (range 25 to 74). Six patients are still alive with a mean follow-up of 4.7 years (range 1.5 to 16.3) and have no evidence of recurrent disease. Of the 6 patients who died, mean survival time was 8.8 years (range 0 to 15.7). One patient died in the perioperative period, and the other 5 patients died of other causes, unrelated to their kidney tumor. CONCLUSIONS: Adenomatous clear cell multicystic kidney disease may represent a histologically distinct benign neoplasm, and its presence in association with RCC may confer a more favorable prognosis. Its distinction from usual solid hemorrhagic or focally necrotic RCC is important.

Adult↗
PubMed1999

Effective genetic therapy of established medullary thyroid carcinomas with murine interleukin-2: dissemination and cytotoxicity studies in a rat tumor model.

Replication-defective adenovirus (AdCMVmIL2) expressing murine interleukin-2 was directly injected into rat medullary thyroid carcinomas to examine antitumor activity. AdCMVmIL2 cured 42.9% of all treated tumor bearing animals. Most cured rats were protected against tumor growth after subsequent rechallenge with wild-type tumor cells, reflecting the immunity obtained from the original treatment. Studies of viral dissemination showed that the intratumoral inoculated viruses can enter the circulation, infect peripheral tissues, and express genes driven by the CMV promoter. Liver is the main target organ. In a toxicity study, AdCMVmIL2 was administered i.v. at a dose five times higher than that given directly into tumor. No detectable side effect was found. Histological studies showed variable degrees of lymphocyte infiltration in the livers of studied animals, and no functional change indicated by the normal serum level of glutamic oxalacetic transaminase and glutamic pyruvic transaminase was found in all animals studied. These data demonstrate that AdCMVmIL2 is an effective antitumor agent in this animal model, and that virus treatment can be given without significant toxicity to other organs.

Adenoviridae↗
PubMed1997

The presence of K-12 ras mutations in duodenal adenocarcinomas and the absence of ras mutations in other small bowel adenocarcinomas and carcinoid tumors.

BACKGROUND: Adenocarcinomas and carcinoid tumors are the most common malignant tumors of the small intestine. K-ras oncogene mutations at codon 12 are common in gastric, pancreatic, and colon carcinomas, with an incidence of 35-88%. K-ras mutations have not been extensively studied in either adenocarcinomas or carcinoid tumors of the small bowel. The purpose of this study was to determine whether ras mutations play an important role in the formation of these tumors. METHODS: Archival tissues from 28 adenocarcinomas and 22 carcinoid tumors of the small bowel were studied, along with archival tissues from 32 adenocarcinomas of the large bowel, which were used as controls. DNA from the small intestine tumors was analyzed for K-ras, H-ras, and N-ras oncogene mutations at codons 12, 13, and 61, using polymerase chain reaction and sequence specific oligonucleotide hybridization techniques. Large bowel adenocarcinomas were analyzed for K-ras mutations at codons 12 and 13. RESULTS: A point mutation of K-ras at codon 12 was detected in 4 of 28 (14.3%) of the small bowel adenocarcinomas, in 12 of 32 (37.5%) of the large bowel adenocarcinomas, and in 0 of 22 small intestine carcinoid tumors. No other K-ras, H-ras, or N-ras mutations were detected in any of the small bowel tumors. Each small intestine K-ras mutation was found in a duodenal adenocarcinoma (4 of 12 cases, 33%), whereas none occurred in 16 other jejunal or ileal adenocarcinomas. CONCLUSIONS: K-ras mutations appear to play a significant role in the pathogenesis of duodenal adenocarcinomas, but they do not appear to be important in the development of jejunal or ileal adenocarcinomas or of carcinoid tumors of the small intestine.

Adenocarcinoma↗
PubMed1997

Evaluating the role of Th0 and Th1 clones in autoimmune thyroid disease by use of Hu-SCID chimeras.

To study the role of Th0 and Th1 cells in autoimmune thyroid disease, thyroid tissues from patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and colloid nodular disease were xenografted into SCID mice, followed by ip injection of peripheral blood mononuclear cells (PBMC), T cell lines, and T cell clones (TCC). The antigen-specific TCC reactive to TSH receptor (TSH-R), thyroid peroxidase (TPO), or thyroglobulin (Tg), and their respective peptides, were classified into Th0 (secreting IL-4 and/or IL-5 and IFN-gamma) and Th1 (secreting IFN-gamma) according to their cytokine profile. Engraftment of autologous or HLA-matched allogeneic CD4+ thyroid-specific clones with Th0 or Th1 phenotypes induced the production of total IgG and thyroid-specific autoantibodies by B cells present in xenografted thyroid tissues. TSH-R-specific clones mainly enhanced thyroid-stimulating antibodies (TSAb) production, while clones reactive to TPO and Tg increased the synthesis of TPO and Tg autoantibodies. Total IgG production, but not TSAb, was also stimulated by PBMC and TSH-R lines. TSAb correlated with the viability and hyperplasia of thyroid follicles, but not with the serum T3 levels, which were normal. Thyroid tissue viability was maintained or increased by antigen-specific Th0 clones, and decreased by Th1 clones reactive to TSH-R or TPO. Thyroid lymphocytic infiltration was variable; however, Th0 and Th1 clones from HT patients caused high degree of lymphocytic infiltration compared to the control groups. These results demonstrate for the first time that T cells clones reactive to specific epitopes of TSH-R, TPO, or Tg can generate antibody-mediated and/or cell-mediated responses in the xenografted thyroid tissue microenvironment. Such effects depend on clonal specificity, HLA class II restriction, and cytokine profile of the clone. Th0 clones reactive to TSH-R stimulate both total IgG production and TSAb in SCID mice engrafted with thyroid tissue from GD patients. Th0 and Th1 clones specific for TPO and Tg also function as helper T cells, stimulating total IgG synthesis and autoantibodies against TPO and Tg. Th1 clones may also cause tissue destruction in GD and HT.

Adolescent↗
PubMed1996

Immunosuppression of thyroiditis.

Immunization of mice with 50 micrograms human thyroglobulin (TG) in complete Freund's adjuvant leads to histological thyroiditis; production of IgG, IgA, and IgM anti-TG antibodies; and in vitro proliferative responses after incubation of lymphocytes with TG. Oral administration of 500 micrograms TG at four intervals before Tg immunization and once afterward causes up to 80% suppression of these responses. The effect is antigen specific and dose dependent. Feeding TG after immunization produces a 40% reduction in responses. We wished to define the mechanism of this antigen-specific oral tolerization. Popliteal lymph nodes (PLN) of orally tolerized animals (T) are reduced in size compared to those in immunized (I) animals not fed TG. PLN and mesenteric lymph nodes (MLN) of I animals produce interleukin-2 (IL-2) and interferon-gamma (IFN gamma) after in vitro incubation with TG, typical of an inflammatory immune response. PLN and MLN of tolerized animals do not proliferate in response to antigen, do not produce IL-2 or IFN gamma, but do not produce the cytokines IL-4 and transforming growth factor-beta (TGF beta). Mixing in vitro of spleen cells from T and I animals causes a reduction in the immune response when incubated with TG, but no reduction in response to purified protein derivative (PPD) (the antigen in complete Freund's adjuvant). When T splenocytes are incubated with TG and PPD together, the response to TG and PPD is suppressed. Partially purified CD8+ cells from tolerized animals produce IL-4 and TGF beta after exposure to human TG and induce suppression, whereas partially purified CD4+ cells produce IL-2 and IFN gamma and do not cause suppression. MLN cells do not proliferate in response to antigen, but do produce inhibitory cytokines. T animals appear to shift the immune response from a Th-1 helper cell subset response to a Th-2 helper cell immunosuppressive response. In this model, oral tolerization produces a dramatic reduction in the immune response. Exposure of MLN to oral TG appears to cause the production of regulatory cells that migrate to spleen and PLN. In vitro studies demonstrate that on exposure to antigen, these regulatory cells produce IL-4 and TGF beta, which suppress all aspects of specific immune responsiveness and nonspecifically suppress other ongoing immune responses (bystander effect). Oral tolerization may include some element of T cell deletion or anergy. This model defines an experimental system with possible relevance to immunosuppression of human autoimmune thyroid disease.

Administration, Oral↗
PubMed1995

Feminizing Sertoli cell tumors in boys with Peutz-Jeghers syndrome.

We report the pathology findings in two cases of multicentric Sertoli cell testicular tumors in two young boys with probable Peutz-Jeghers syndrome. Four cases of such tumors occurring in boys with Peutz-Jeghers syndrome were previously reported. Each of the two boys reported in this paper had prominent gynecomastia, rapid growth, and advanced bone age. Serum levels of estradiol were markedly elevated. Anti-müllerian hormone was measured in the serum of one of the boys and was in the normal range for age. Bilateral orchiectomy was performed in each case because the neoplastic growth would most likely result in sterility, and curtailment of height potential was threatened from continued elevation of estradiol levels. Microscopically, greatly enlarged seminiferous tubules packed with ovoid Sertoli-like cells were present. Prominent eosinophilic basement membrane surrounded the tubules and intersected between the cells, forming hyalinized ovoid globules and microcalcifications. Ultrastructure revealed lamination of basement membranes surrounding adjacent cells, ovoid cells with abundant cytoplasm, and limited smooth endoplasmic reticulum. Studies of testicular tumor tissue from both cases revealed increased transcription of the aromatase cytochrome P450 gene using promoter II, the promoter directing aromatase expression in the normal ovary and testis. The levels of transcripts were comparable to corpus luteum, thus resulting in increased estrogen synthesis. Transcripts specific for placental-type aromatase promoters (I.1 and I.2) were not detected in significant levels in these tumors.

Anti-Mullerian Hormone↗
PubMed1995

Suppression of development of experimental autoimmune thyroiditis by oral administration of thyroglobulin.

Experimental autoimmune thyroiditis (EAT), which to some extent represents an experimental model of human chronic lymphocytic thyroiditis, is an organ-specific autoimmune disease characterized by autoantibody production to thyroid antigens (Ag) and mononuclear infiltration of the thyroid gland. EAT induced by immunization with human thyroglobulin (hTG) with Freund's adjuvant in CBA/J (H-2K) mice is associated with prominent B and T cell responses. We report that oral administration of hTG effectively reduces the immune responses in EAT in mice in an Ag-specific manner. Both cellular and humoral immune responses are reduced in a dose-dependent manner. Histological evidence of disease is dramatically reduced. Suppression of the immune responses is seen 2 weeks after Ag challenge, with partial inhibition of proliferative and antibody responses. Six weeks after immunization, further inhibition is observed of both T and B cell responses. Hyporesponsiveness of T and B cell reactivity is seen only to hTG; T and B cell responses to other immunogens are not affected, including purified protein derivative and the nonrelated Ag BSA. This model may provide the basis for immunotherapy of autoimmune thyroid diseases in man.

Administration, Oral↗
PubMed1995

Morbidity and mortality in follicular thyroid cancer.

The natural history and results of treatment have been analyzed in a group of 49 patients with follicular thyroid carcinoma who were followed for an average of 10.7 yr. Striking differences between the course of follicular thyroid carcinoma and the course of papillary carcinoma are evident. Deaths from cancer were double (16% for follicular), age at diagnosis was older, and age at death was younger. All deaths and recurrences happened within 13 yr, in contrast to the continued experience of deaths and recurrences in papillary cancer, even through 40 yr of observation. Adverse outcome correlated with extent of disease at diagnosis and with size of primary tumor, but did not correlate with vessel invasion, extent of capsule invasion, degree of dedifferentiation, extent of primary surgery, or radioactive iodide ablation. These observations are again in striking contrast to experience with papillary cancer. No patient with intrathyroidal disease who was under age 45 at diagnosis and with a primary tumor of less than 2.5 cm died. Our observations suggest that follicular cancer, even if apparently intrathyroidal, carries a high mortality rate in patients over age 45 or in those with tumors larger than 2.5 cm at the time of diagnosis and suggest that we must consider additional therapeutic measures in this group of patients, including larger radioiodine doses for initial therapy, external radiotherapy, and even possibly prophylactic chemotherapy.

Adenocarcinoma, Follicular↗
PubMed1994

Laparoscopic pelvic lymph node dissection: a review of 103 consecutive cases.

Laparoscopic pelvic lymph node dissection is a recently introduced technique for the surgical evaluation of the regional pelvic lymph nodes in genitourinary malignancies. We report the results of a laparoscopic pelvic lymph node dissection performed on 103 consecutive patients for staging of clinically localized prostatic, bladder and penile carcinomas. In 20 patients (group 1) the adequacy of the laparoscopic pelvic lymph node dissection was evaluated with a subsequent open dissection. In this group 87 to 95% of the lymph nodes within a modified template could be reliably removed laparoscopically. In 73 patients (group 2) laparoscopic pelvic lymph node dissection was performed as a solitary operation. Mean hospitalization was 1.6 +/- 2.4 days, while postoperative narcotic requirements were minimal. Mean operative time for bilateral laparoscopic pelvic lymph node dissection was 156 +/- 41.2 minutes. The overall complication rate in these 2 groups was 13.5%. Group 3 includes 10 patients (9.7% of the total) in whom laparoscopic pelvic lymph node dissection was unsuccessful. The minimally invasive surgical techniques of laparoscopic pelvic lymph node dissection seem to provide adequate staging accuracy in patients with genitourinary neoplasms. The complication rate and recovery period appear to be decreased relative to those for open surgical lymphadenectomy.

Adenocarcinoma↗
PubMed1994

An immunohistochemical study of thyroid Hurthle cells and their neoplasms: the roles of S-100 and HMB-45 proteins.

The histological and cytological features of follicular thyroid neoplasms with oxyphilic change (Hurthle cell tumors) may lead to the differential diagnosis of metastatic malignant melanoma. S-100 and HMB-45 staining was studied in 18 Hurthle cell tumors, 6 Hurthle cell carcinomas, and 5 cases of Hashimoto's thyroiditis using a rabbit polyclonal antibody to S-100 protein, a mouse monoclonal antibody to HMB-45 protein, and the avidin alkaline phosphatase method. All 6 carcinomas and 17 of 18 Hurthle cell tumors exhibited strong cytoplasmic and nuclear staining for S-100. One Hurthle cell carcinoma also contained a spindle cell anaplastic area that was negative for S-100. All cases of Hashimoto's thyroiditis displayed intense staining in Hurthle cells for S-100, with weak to negative staining in nonoxyphilic follicular epithelium. In the three studied lesions, all cases were negative for HMB-45 protein. Three nonthyroid oncocytic tumors (renal oncocytoma, oncocytic carcinoma of the parotid, and parathyroid oxyphilic adenoma) were found to be negative for both S-100 and HMB-45 staining. Hurthle cell lesions should be included in the differential diagnosis of S-100-positive tumors. HMB-45 remains a marker more restricted to melanocytic lesions.

Adenocarcinoma↗
PubMed1994

Increased incidence of thyroid cancer in patients with primary hyperparathyroidism: a continuing dilemma.

A number of previous studies have reported a greater incidence of thyroid disease in patients with primary hyperparathyroidism (HPT) than in normal patients. However, few of these studies utilized controls, and most have dealt only with gross thyroid nodules and not with total histologic abnormalities. In order to clarify this problem, thyroid pathology was determined in each of 100 consecutive patients operated upon for HPT. Thyroid nodules were excised, but in addition, a random biopsy of the thyroid was performed in all cases. Patients in this group were matched by age, race, and sex with non-HPT autopsy controls. Histologic slides were reviewed by a single pathologist blinded to the patient's group. Data for the matched pairs were analyzed by the Sign test. There was no significant difference in the prevalence of colloid nodular disease between patients with HPT (45) and the autopsy control group (43, P = 0.2). There was also no significant difference in the prevalence of lymphocytic thyroiditis between HPT patients (24) and control (15, P = 0.07). There was likewise no significant difference in the prevalence of other benign thyroid gland diseases between the two groups. Only nonmedullary cancer of the thyroid was shown to be statistically more prevalent in HPT patients than in autopsy controls (7% vs 0%, respectively; P < 0.02). The major factor that accounts for the coexistence of benign thyroid lesions and HPT is that both are prevalent in middle-aged women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1993

Methotrexate, vinblastine, doxorubicin and cisplatin followed by radiotherapy or surgery for muscle invasive bladder cancer: the University of Chicago experience.

A total of 29 patients with muscle invasive bladder cancer, clinical stage T2N0 (12), T3aN0 (9), T3bN0 (5), T3N2 (2) or T4N2 (1), underwent 2 to 4 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by either radiotherapy (15), radical cystectomy (11) or no local therapy (3). The overall response rate to M-VAC chemotherapy was 69%, with 31% clinical complete responses and 38% clinical partial responses. A functioning bladder was maintained in 55% of the responding patients, although bladder wall calcifications were observed in 4 of 15 irradiated patients. Overall survival was 71% and disease-free survival was 55% at a median followup of 57 months. For the 12 stage T2N0 cancer patients overall survival was 100% at a median followup of 52 months. For the stages T3a and T3bN0 cancer patients overall survival was 63%, while all 3 node positive patients died. Neoadjuvant chemotherapy with a modified M-VAC regimen is well tolerated and may result in bladder preservation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Response to orchiectomy following Zoladex therapy for metastatic prostate carcinoma.

Serum testosterone and prostate-specific antigen (PSA) levels were measured in 3 patients with Stage D2 prostate cancer before and after discontinuation of the long-acting LHRH agonist, goserelin acetate (Zoladex). The patients had received goserelin acetate for ten, sixteen, and thirty months prior to discontinuing the drug because of progressive metastatic disease. In all 3 patients, PSA and testosterone levels increased after goserelin acetate was discontinued. In 2 patients the testosterone level reached normal levels. A bilateral orchiectomy was performed one hundred sixty, one hundred, and seven days, respectively, after the drug was discontinued. In all 3 cases PSA and testosterone levels were reduced following castration, although PSA levels again began to increase within two weeks of orchiectomy in 2 of the 3 patients. These findings suggest that suppression of testosterone by LHRH agonists is not permanent and if tumor progression occurs, maintaining hormone suppression may still be beneficial.

Aged↗
PubMed1990

Natural history, treatment, and course of papillary thyroid carcinoma.

We have analyzed the course of papillary thyroid carcinoma in 269 patients managed at the University of Chicago, with an average follow-up period of 12 yr from the time of diagnosis. Patients were categorized by clinical class; I, with intrathyroidal disease; II, with cervical nodal metastases; III, with extrathyroidal invasion; and IV, with distant metastases. Half of the patients had a history of thyroid enlargement known, on the average, for over 3 yr. In 15% of patients given thyroid hormone, the mass decreased in size. The peak incidence of cancer was when subjects were between 20-40 yr of age. Tumors averaged 2.4 cm in size; 21.6% had tumor capsule invasion, and 46% of patients had multifocal tumors. Sixty-six percent of the patients had near-total or total thyroidectomy. The overall incidence of postoperative hypoparathyroidism was 8.4%, but the incidence was zero in 83 near-total or total thyroidectomies carried out by 1 surgeon. Twenty-five percent of the patients had continuing or recurrent disease, and 8.2% died from cancer. Deaths occurred largely in patients with class III or IV disease. Cervical lymph nodes were associated with increased recurrences, but not increased deaths. Extrathyroidal invasion carried an increased risk of 5.8-fold for death, and distant metastases increased this risk 47-fold. Age over 45 yr at diagnosis increased the risk of death 32-fold. Tumor size over 3 cm increased the risk of death 5.8-fold. Surgical treatment combining lobectomy plus at least contralateral subtotal thyroidectomy was associated, by Cox proportional hazard analysis, with decreased risk of death in patients with tumors larger than 1 cm and decreased risk of recurrence among all patients, including patients in classes I and II, compared to patients who underwent unilateral thyroid surgery or bilateral subtotal resections. By chi 2 analysis, 131I ablation of residual thyroid tissue after operation was associated with decreased risk of recurrence in tumors larger than 1 cm and decreased risk of death in patients in classes I and II with tumors more than 1 cm in size. The data strongly support the use of more extensive initial surgery in class I and II patients with tumors more than 1 cm in size as well as postoperative radioactive 131I ablation of thyroid remnant tissue.

Age Factors↗