Cell proliferation kinetics of normal and tumour tissue in vitro: quiescent reproductive cells and the cycling reproductive fraction.

Current methods for measuring the cell kinetics of human tumours are made and interpreted within the context of a simplistic two compartment model for cell proliferation, consisting of cells that are cycling and those that are not. It is now recognized that the non-cycling compartment of many tumours is heterogeneous, composed of non-reproductive end-stage cells and reproductive cells that are dormant/quiescent. We have developed an in vitro analysis that distinguishes for the first time quiescent reproductive cells from non-reproductive end-stage cells and have integrated this analysis with monolayer clonogenic and suicide assays to simultaneously quantitate the duration of the cell cycle and reproductive cells that are: cycling, quiescent, clonogenic, and non-reproductive end-stage cells. We have defined a new parameter, the Cycling Reproductive Fraction (CRF), which is the cycling cell population referenced specifically to the reproductive cell population. Measurements of CRF from 72 tumour biopsies and from 5 normal foreskins showed that CRF approached 100% in some tumours; however, CRF showed near normal values (< 1%) in others suggesting that cell cycle control may be maintained in some tumours. Because of CRF's improved specificity, we believe that CRF may enhance classification, prognostication, and the optimization and prediction of response to chemotherapy.

Neurofibromatosis and primary hyperparathyroidism.

Patients who have cutaneous and osseous neurofibromatosis, especially those with pathologic fractures, bone pain, roentgenographic evidence of cystic lesions, or hypercalcemia, should be evaluated carefully for the presence of a hormonally active parathyroid adenoma. They may have a reversible cause of osteitis fibrosa cystica. Palpation of the neck, serum and urine collections for measuring calcium and phosphorus levels, PTH determinations, bone roentgenograms, and bone biopsy help to establish the diagnosis.

Importance of initial mediastinal adenopathy in Hodgkin disease.

The importance of initial mediastinal disease was studied retrospectively in 189 patients with stages I, II, and III Hodgkin disease treated at the M. D. Anderson Hospital and Tumor Institute between 1969 and 1976. Stages I and II patients with mediastinal disease at presentation had an 88% 5 year survival rate compared with a 98% survival rate for those without mediastinal disease. Disease-free survival was 66% versus 78%. Stage III patients with and without initial mediastinal disease showed essentially the same 5 year survival rate (75% versus 78%), but showed a lower disease-free survival of 60% in those with mediastinal disease as compared with 74% in those without mediastinal disease. Because of the prognostic importance of mediastinal disease and its extent at initial presentation, computed tomography is recommended to evaluate patients with low neck or supraclavicular adenopathy in whom there is no obvious mediastinal adenopathy and in all Hodgkin disease patients in whom there is questionable mediastinal disease or suggestion of lung extension on routine radiographs. Treatment plans have been altered to include chemotherapy and low-dose irradiation to the lungs in those patients with mediastinal mass diameters of 7.5 cm or greater, regardless of stage.

Reassessment of prognostic factors in stage IIIA and IIIB Hodgkin's disease treated with MOPP and radiotherapy.

Prognostic factors have been re-evaluated for 88 patients with Stage III Hodgkin's disease to see if they have remained significant on a long-term basis. Treatment had consisted of two cycles of MOPP followed by radiotherapy to the mantle, abdomen, and pelvis; all patients had achieved complete remission. Case material was grouped according to the presence of absence of mediastinal disease. Five-year survivals for Stage IIIA and IIIB patients were 85 and 80%; corresponding disease-free survivals were 76 and 73%. Significant prognostic factors include age, histopathology, and extent of abdominal disease, but the relative importance of these factors differs for the mediastinal and nonmediastinal patients. Modifications of current treatment policy for both mediastinal and nonmediastinal patients are discussed in relation to the prognostic factors.

Adriamycin, bleomycin, DIC, CCNU, and prednisone (ABDIC) chemotherapy in MOPP-resistant Hodgkin's disease.

ABDIC was administered to 32 patients with MOPP-resistant Hodgkin's disease. Three were considered nonevaluable because of early death. All patients had received MOPP (medium of eight cycles), and five had also received other chemotherapy. Major radiotherapy had been used in 18 of the 29. Complete remission (CR) occurred in 10 of 29 (34.5%), partial remissions (PR) in 14 (48.2%), and no remissions (NR) in five (17.2%). Median survival and relapse-free survival for CR patients exceeded 28 months. Two relapsed at 8 and 18 months; one died at 9 1/2 months, and the other is disease-free with other treatment at 35 months. Seven of the remaining eight patients are alive without disease (10-35 months); 4 are on maintenance therapy, and the other died from an infection and eosinophilic granuloma of lung without evidence of recurrent Hodgkin's disease. Median survival of PR patients was eight months. One patient with Hodgkin's disease involving the liver is alive at 36 months with further therapy. Median survival of NR patients is 2.5 months, and all died within seven months. Survival of CR patients is greater than PR and NR patients (P = 0.002), and that of PR is greater than NR (P = 0.01). Four of the 29 patients had nodal relapse, and 25 had parenchymal relapse, with no difference in response rates (P = 0.47). ABDIC is useful in Hodgkin's disease patients who have had extensive prior chemotherapy and radiotherapy.

Laparotomy findings in lymphangiogram-staged I and non-Hodgkin's lymphomas.

Ninety patients with Stage I or II, including extranodal (E), presentations of non-Hodkin's lymphoma were investigated by laparotomy, either for the definitive staging of patients with peripheral presentations or for diagnosis of abdominal disease. Sixty-eight patients had staging laparotomies after extensive work-up, which included lymphangiography and bone marrow biopsy. The remaining 22 patients had laparotomies for diagnosis of abdominal symptoms or for management of unrelated surgical problems, with lyphoma being found incidentally. The incidence of positive abdominal findings in the 68 patients who had staging laparotomies depended on histologic subtype. In nodular lymphoma patients, abdominal disease was found in 17 of 28 (61%) and in diffuse lymphoma patients, in 9 of 40 (22.5%). For patients with nodular lymphomas upstaged by laparotomy, the positive findings tended to cluster around an axis consisting of the celiac, porta-hepatic, para-aortic, and root of the mesentery lymph nodes. In addition, 64% of these patients had splenic involvement. For the diffuse lymphoma upstaged by laparotomy, the distribution of positive findings was similar to that of the nodular lymphoma group; however, only 1 patient had splenic involvement. By contrast, in approximately half of the diffuse lymphoma patients who had laparotomies for diagnosis, the gastrointestinal tract was found to be involved in addition to the previously cited lymph nodes.

Evaluation of the significance of prognostic factors in stage III Hodgkin's disease treated with MOPP and radiotherapy.

One hundred consecutive Stage IIIA and IIIB Hodgkin's disease patients were treated between July 1969 and September 1976, on a combined chemotherapy-radiotherapy program consisting of two courses of MOPP followed by radiotherapy to the mantle, abdomen, and pelvis. Eighty-eight patients completed radiotherapy to all disease sites. At the time of this analysis, the mean follow-up period for the 100 patients was 45 months; 70 patients had been followed three to seven years. Projected five-year survival and disease-free survival figures for the 100 patients were 80% and 68% respectively; corresponding results for the 88 patients were 90% and 78%. To determine whether any of the following prognostic factors influenced results for either the 100 or the 88 patients, survival curves were calculated for age, sex, constitutional symptoms, histopathology, method of staging, and status of the mediastinum. Other than age, none of these factors influenced survival significantly. However, disease-free survival figures were influenced adversely by mediastinal disease as well as age.