Leigh S. Hamby

Parathyroid adenoma and gatric carcinoma as manifestations of cowden's disease

Cowdens disease is a well-described clinical syndrome, the primary symptoms of which are orocutaneous hamartomas and disseminated gastrointestinal polyposis. In general, the gastrointestinal polyps are benign, and the incidence of malignant transformation is believed to be low. Other associated manifestations of Cowdens disease include breast cancer and thyroid disease (benign and malignant). A patient with previously unrecognized Cowdens disease underwent upper gastrointestinal endoscopy for surveillance of hyperplastic gastric polyps, and a gastric carcinoma in situ was detected. During the course of follow-up the patient was found to have primary hyperparathyroidism resulting from a parathyroid adenoma. Although several benign proliferative and malignant conditions are associated with Cowdens disease, neither parathyroid adenoma nor gastric carcinoma has been reported previously.

Management of local recurrence in well-differentiated thyroid carcinoma

Local recurrence of well-differentiated thyroid carcinoma has a reported mortality approaching 50%. The University of Kentucky experience was reviewed to determine whether aggressive surveillance and treatment with reoperation and/or I-131 ablation increased survival following recurrence. Records of 66 consecutive patients with well-differentiated thyroid carcinoma treated at the University of Kentucky Medical Center (1980-1989) were reviewed. Forty-nine cases of papillary carcinoma and 17 cases of follicular carcinoma were studied; median follow-up was 68 months. At presentation, patients with follicular carcinoma were older (48 versus 35 years; P less than 0.05) and more frequently had metastatic disease (17% versus 2%, P less than 0.05). Fifty-eight (88%) patients were alive and disease-free at last follow-up. Fifteen patients (24%) had developed recurrent disease; median time to recurrence was 24 months. Multivariate regression examined the variables of age, sex, histology, tumor size, cervical adenopathy, capsular and vascular invasion, multicentricity, and surgical procedure. While distant metastases affected actuarial survival, no factor independently predicted local recurrence. In six patients with local recurrence, nonpalpable disease was detected by I-131 scan. All were treated with ablation and remain disease-free (mean follow-up 42 months). Eight patients with local recurrence presented with palpable lesions; seven underwent surgery. While two patients developed repeated local recurrences, the other five remain disease-free (mean follow-up 52 months). Early detection and aggressive treatment of local recurrence improve survival in patients with well-differentiated thyroid carcinoma. To facilitate use of I-131, we advise total thyroidectomy for patients with well-differentiated thyroid carcinoma.

Prospective study correlating P120 antigen expression with established prognostic factors in breast cancer

P120 is a nucleolar proliferation antigen found in rapidly dividing cells and a variety of malignancies. Previous retrospective studies have demonstrated that, when detected in human breast cancer, P120 is associated with a poorer prognosis. To determine whether P120 expression correlates with other prognostic factors in breast cancer, we prospectively analysed pathologic and clinical data from 61 patients. P120 was detected in 40 of the 61 specimens (66%). No significant correlation existed between P120 expression and either tumour size or hormone receptors. A significant correlation was found between P120 expression and histological grade, degree of aneuploidy, S-phase fraction, degree of nodal involvement, and stage of disease. P120 is a biological marker indicative of tumour aggressiveness and may play an important role in determining which patients would most benefit from adjuvant therapy.

Phorbol dibutyrate plus ionomycin improves the generation of cytotoxic T cells from draining lymph nodes of patients with advanced head and neck cancer

Fifty-one cervical nodes from 19 patients with advanced head and neck cancer were stimulated with phorbol dibutyrate and ionomycin (PDBu + Io) to determine the effect of such stimulation on the generation of cytotoxic T cells and whether this stimulation could bypass the need for autologous tumor stimulation. Lymphocytes stimulated with PDBu + Io demonstrated a sixfold greater in vitro expansion and significantly increased DNA synthesis. Whereas fresh lymphocytes displayed no cytotoxicity, stimulation with PDBu + Io and culture in interleukin-2 (IL-2) led to significant cytotoxicity equivalent to that of lymphocytes stimulated with autologous tumor and IL-2. T cells with the greatest cytotoxicity were generated from patients with nodal metastases. In patients with stage IV tumors, effector cells demonstrating greater lysis of natural killer-resistant targets (Daudi cells) were associated with higher rates of recurrence (50% versus 12%, respectively, p < 0.001). Stimulation with PDBu + Io augments growth and proliferation of lymphocytes from draining lymph nodes and preserves cytotoxicity without the need for autologous tumor. Excluding the need for antigenic stimulation by autologous tumor may prove useful in adoptive immunotherapy procedures.

Optimizing Primary Treatment for Advanced Laryngeal and Pyriform Sinus Carcinoma

Advocates of chemotherapy plus radiation as the definitive treatment for patients with advanced laryngeal cancer often cite older studies that attribute cure rates of less than 50% to laryngectomy plus radiation. The outcomes of patients with stage III and IV laryngeal and pyriform sinus carcinoma from 1980 to 1989 (96 patients) were compared with those of patients treated from 1962 to 1977 (84 patients). Demographics, the extent of disease, and nodal involvement were similar between the groups. There were more operative complications (45% versus 22%; p < 0.01) and deaths (10% versus 2%; p < 0.01) in the patients who underwent irradiation preoperatively. Overall survival was improved in the recent group compared with the early group (73% versus 54% at 5 years; p < 0.03), as was disease-free survival (64% versus 38% at 5 years; p < 0.02). Results of treatment for advanced laryngeal and pyriform sinus carcinoma have improved significantly. These modern results should be used to evaluate newer treatment modalities.

Improved survival with adjuvant immunotherapy after surgical resection in a murine model

Background: Adoptive immunotherapy has met with limited success in the treatment of bulky metastatic disease. The purpose of this study was to determine whether lymphocytes stimulated in vitro could improve survival when given as an adjuvant to surgical resection in animals harboring microscopic metastatic disease.Methods: Lymphocytes from nodes draining the primary tumor (DLN lymphocytes) were stimulated in vitro with phorbol 12,13-dibutyrate and ionomycin and used as adjuvant immunotherapy after surgical resection of the primary tumor. Mice with advanced P-815 footpad tumors and disseminated microscopic metastases underwent amputation of the tumor-bearing extremity and were randomized to various adjuvant treatments.Results: Mice treated with adjuvant immunotherapy using stimulated DLN lymphocytes demonstrated significantly improved survival, showing that DLN lymphocytes stimulated in vitro can abrogate metastases that are invading multiple organs simultaneously. Mice successfully treated with adjuvant immunotherapy demonstrated long-term (80 days) in vivo antitumor activity by rejecting subsequent tumor challenge. In addition, stimulated DLN lymphocytes provided in vivo antitumor activity to naive mice.Conclusions: Adjuvant immunotherapy after resection in the face of residual microscopic tumor burden may prove to be a useful application of adoptive immunotherapy.