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Biomedical subjects

L Norton

Publications and source records attributed to L Norton.

At least 163 records · Page 9Linked to original sources

Decision for surgical management of perforation following endoscopic sphincterotomy.

Duodenal perforation resulting from endoscopic sphincterotomy (ES) is a serious complication with a high mortality. Diagnosis is often problematic and the optimum treatment is controversial. Eight proven perforations occurred following 441 ES at University of Colorado Hospital, a rate of 1.8 per cent. Physical and laboratory findings were of little diagnostic value, whereas plain abdominal radiographs showed evidence of perforation in 86 per cent. All patients were operated on promptly after diagnosis of perforation. Delay in diagnosis of perforation beyond 24 hours in six patients was associated with a high morbidity and two deaths. Analysis of published series confirmed that delay in diagnosis and delay in operation after perforation were associated with a higher mortality rate than early diagnosis with or without operation. We recommend operative intervention in all patients with clinical evidence of perforation following ES.

Adult↗

A randomized comparison of methotrexate dose and the addition of bleomycin to CHOP therapy for diffuse large cell lymphoma and other non-Hodgkin's lymphomas. Cancer and Leukemia Group B study 7851.

In 1978, Cancer and Leukemia Group B initiated a randomized study to determine the usefulness of the addition of bleomycin and/or high-dose methotrexate to standard therapy for the treatment of certain adult non-Hodgkin's lymphomas. Between 1978 and 1985, 177 patients with diffuse large cell lymphoma (DLCL) and 97 patients with other intermediate-grade non-Hodgkin's lymphoma were randomized to receive therapy with three courses of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) every 3 weeks with or without low-dose bleomycin by continuous IV infusion. Responders after three courses were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 gm/m2/week intravenously with leucovorin rescue) or standard-dose methotrexate (30 mg/m2/week orally without rescue). Therapy was concluded with three additional courses of CHOP. Neither the addition of low-dose infusion bleomycin nor the use of high-dose rather than low-dose methotrexate had significant effects on response for patients with DLCL; complete response rates for the four treatment programs ranged from 47% to 51%. Median failure-free survival (FFS) for the entire group of DLCL patients was 12 months; 5-year FFS was 27%. There was no significant effect on FFS from the addition of either low-dose bleomycin to CHOP (5-year FFS: CHOP, 28%; CHOP-B, 26%, P = 0.81), or from the use of different doses of methotrexate (5-year FFS: high-dose, 34%; standard-dose, 33%, P = 0.51). Patients with follicular large cell lymphoma, with or without diffuse areas, had a better FFS (5-year FFS, 47%) than patients with DLCL (5-year FFS, 27%), while the patients with the other histopathologic subtypes of diffuse lymphomas had the poorest FFS (5-year FFS, 16%).

Aged↗

Phase II study of MOPLACE chemotherapy for patients with previously treated Hodgkin's disease: a CALGB study.

To further evaluate possible non-cross-resistant regimens in Hodgkin's disease, a phase II trial utilizing antimetabolites and etoposide was initiated by the Cancer and Leukemia Group B (CALGB). Etoposide was included because of its known efficacy in relapsed Hodgkin's disease and to evaluate for synergy with an alkylating agent and vincristine. Cytosine arabinoside and methotrexate were included to evaluate their effectiveness in rapidly growing resistant disease. Forty-two patients with previously treated Hodgkin's disease were entered, of which 37 are evaluable for response and toxicity. All patients had at least 2 prior regimens of chemotherapy and 59% had additional radiation therapy. Complete and partial response was observed in 61%; there were 32% complete responders. Duration of complete response was a median of 8 months (range 2-28+ months). Duration of partial response was 7 months (range 1-17 months). Three patients remain in complete remission at 19, 19, and 28 months. Major toxicity was hematologic with severe or life-threatening toxicity in 54%. There was one patient with a fatal infection. Non-hematologic toxicity, save for nausea and vomiting, was mild and uncommon. There were two fatal and one severe pulmonary toxicities reported in patients who had previous exposure to bleomycin and mediastinal radiation. Three had interstitial pneumonitis and one pulmonary emboli. The interstitial pneumonitis was thought to be drug related. Survival of the entire group is estimated at 61% at 12 months. We conclude that MOPLACE is an effective regimen with an appreciable complete response rate in this heavily pretreated group of patients. Hematologic and pulmonary toxicities are severe and may necessitate dose modifications. The use of etoposide containing combinations requires further study as primary therapy in untreated patients.

Adolescent↗

Clinical cardiotoxicity of esorubicin (4'-deoxydoxorubicin,DxDx): prospective studies with serial gated heart scans and reports of selected cases. A Cancer and Leukemia Group B report.

Esorubicin (4'-deoxydoxorubicin, DxDx) has undergone extensive Phase II investigation for the treatment of cancer. Based on in vitro and animal data, esorubicin may possess less myocardial toxicity when compared to doxorubicin. One hundred thirty-six patients with histologically or cytologically documented non-small cell lung cancer or advanced breast cancer were enrolled in two concurrent CALGB clinical trials using esorubicin at a dose of 30 mg/m2 administered intravenously every 21 days. No patient had previously received an anthracycline agent or had evidence of severe cardiovascular disease. Cardiotoxicity was observed in eleven patients. Four patients developed symptoms of congestive heart failure and three asymptomatic patients had a significant fall in left ventricular ejection fraction (LVEF) as measured by gated pool heart scan. Four patients had cardiac signs or symptoms of indeterminate relationship to esorubicin therapy. Of 44 patients receiving more than four cycles of therapy, 36 patients (82%) had serial gated pool heart scans permitting assessment of subclinical myocardial toxicity. A 5% drop in LVEF was observed following approximately 240 mg/m2 esorubicin; a 10% drop was observed after approximately 480 mg/m2. If further clinical studies are undertaken with esorubicin, investigators are advised to monitor cardiac function frequently once the cumulative esorubicin dose exceeds 240 mg/m2. If congestive failure appears during therapy, prompt cessation of esorubicin and institution of inotropic agents may provide effective palliation. Normal myocardial function may be restored within several months.

Adult↗

The surgical management of atypical mycobacterial soft-tissue infections.

Group IV atypical mycobacterial infections, especially Mycobacterium fortuitum and M. chelonei, are being reported with increased frequency. We report our experience with five cases of soft-tissue infection with these acid-fast bacilli. Often these infections are chronic, with formation of abscesses and multiple fistulas. Optimal surgical treatment often requires wide excision of all diseased tissue followed by delayed closure. Presentation, optimal surgical management, and antibiotic therapy are discussed.

Abscess↗

Arterial thrombosis associated with adjuvant chemotherapy for breast carcinoma: a Cancer and Leukemia Group B Study.

PURPOSE: Multiagent chemotherapy and chemohormonal therapy for breast cancer are associated with an increased risk for venous thromboembolic complications. We observed instances of arterial thrombosis in two studies of breast cancer involving multiagent chemotherapy for stages II and III disease. Our purpose in this study was to determine the incidence of this complication and whether it appeared to be related to the chemotherapy or was a random event. PATIENTS AND METHODS: Episodes of arterial thrombotic events were identified from record reviews of 1,014 assessable patients with breast cancer entered on two Cancer and Leukemia Group B protocols. Details of the kind of arterial event, when it occurred, the outcome, and the occurrence of metastases were analyzed. RESULTS: Thirteen (1.3%) patients had an arterial thrombosis: six (5.3%) of 113 patients with stage III disease and seven (0.8%) of 901 patients with stage II disease. Four of these patients had a peripheral arterial thrombosis and nine had strokes (four were fatal). All these events occurred while the patients were receiving adjuvant chemotherapy. Only one additional arterial event (a stroke approximately four years later) has occurred in this patient group after chemotherapy was completed. CONCLUSION: Arterial thrombosis is also associated with multiagent chemotherapy in patients with breast cancer. The mechanism is unknown.

Aged↗

A Gompertzian model of human breast cancer growth.

The pattern of growth of human breast cancer is important theoretically and clinically. Speer et al. (Cancer Res., 44: 4124-4130, 1984) have recently proposed that all individual tumors initially grow with identical Gompertzian parameters, but subsequently develop kinetic heterogeneity by a random time-dependent process. This concept has elicited interest because it fits clinical data for the survival of untreated patients, for the progression of shadows on serial paired mammograms, and for time-to-relapse following mastectomy. The success of these curve-fits is compelling, and the model has been applied to clinical trials. However, the assumption of uniform nascent growth is not supported by theory or data, and individual cancers have not been shown to follow the complex growth curves predicted by the Speer model. As an alternative, if kinetic heterogeneity is understood to be an intrinsic property of neoplasia, the same three historical data sets are fit well by an unadorned Gompertzian model which is parsimonious and has many other intuitive and empirical advantages. The two models differ significantly in such clinical projections as the estimated duration of silent growth prior to diagnosis and the anticipated optimal chemotherapy schedule postsurgery.

Breast Neoplasms↗

Operative versus endoscopic gastrostomy. Preliminary results of a prospective randomized trial.

Percutaneous endoscopic gastrostomy in 23 patients was compared with operative gastrostomy in 25 patients in a prospective randomized fashion. Procedure-related morbidity occurred in five patients in each group. Tube feeding was initiated within 48 hours in 96 percent of the percutaneous endoscopic gastrostomy group and in 82 percent of the operative gastrostomy group (p less than 0.1). There were no deaths in the percutaneous endoscopic gastrostomy group, but two patients in the operative gastrostomy group died within 30 days of operation (p less than 0.1). Neither death appeared directly attributable to gastrostomy placement. The cost for a percutaneous endoscopic gastrostomy was less than that of an operative gastrostomy ($757 versus $1,446); however, if endoscopically placed tubes required replacement, as was seen in six patients, total percutaneous endoscopic gastrostomy cost increased to $1,198. Definitive conclusions regarding the superiority of one technique over the other cannot be drawn from this data. Trends favoring the use of percutaneous endoscopic gastrostomy merit continued study.

Adult↗

A phase I-II study of intensive-dose adriamycin for advanced breast cancer.

Twenty-six women with metastatic breast cancer were treated with intensive Adriamycin (Adria Laboratories, Columbus, OH) as a single agent administered for three successive days once a month. Dosing started at 25 or 30 mg/m2/d three times, and was escalated by 5 mg/m2/d monthly to maximal tolerance based on hematologic, mucosal, or cardiac toxicities. Four patients (15%) had complete remissions (CRs) pathologically proven, and six others (23%) sustained complete CRs, but were found to have microscopic residual tumor (three) or refused biopsy (three). Twelve patients (46%) attained partial remission (PR). The overall response (85%) and CR rates (38%) were approximately double those reported with conventional Adriamycin doses. Median unmaintained remission duration for the ten patients in CR was 11 months. Cardiotoxicity, determined by radionuclide physiologic studies, occurred in 16 patients at a mean dose of 459 mg/m2; three patients developed reversible congestive failure. There were no toxic deaths. The median overall survival was 18 months. These data suggest that there is steep dose responsiveness to Adriamycin in metastatic breast cancer, and that more effective techniques for using Adriamycin may exist than those conventionally used.

Adult↗

A randomized trial of high-dose methotrexate versus standard-dose methotrexate following cyclophosphamide, doxorubicin (adriamycin), vincristine, and prednisone with or without bleomycin in the therapy of diffuse large cell lymphoma: preliminary report of Cancer and Leukemia Group B Study 7851.

Between 1979 and 1985, 166 patients with diffuse large cell (histiocytic) lymphoma were randomized to receive therapy with 3 courses of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisone (CAVP), with or without low-dose bleomycin, by continuous iv infusion. Responders were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 g/m2 iv weekly with leukovorin rescue) or low-dose methotrexate (30 mg/m2 orally weekly without rescue). Therapy was concluded with 3 additional courses of CAVP. No significant differences among the 4 treatment programs were observed in complete response rates (ranging from 46% to 51%) or in failure-free survival. Of the 38 relapses that have occurred in patients treated with low-dose methotrexate, 5 included relapse in the central nervous system in conjunction with systemic relapse. However, none of 31 relapses observed in patients receiving high-dose methotrexate have occurred with involvement of the central nervous system. Patients entering this study with "B" symptoms had significantly poorer treatment results than those patients entering study without "B" symptoms.

Antineoplastic Combined Chemotherapy Protocols↗

Hyperglycemic complications associated with adjuvant chemotherapy of breast cancer. A cancer and leukemia group B (CALGB) study.

Many adjuvant chemotherapy regimens used for breast cancer include prednisone, which has the potential to cause hyperglycemia. We reviewed the results of three CALGB studies employing prednisone as part of adjuvant therapy to determine the incidence and severity of hyperglycemic complications. All treatment regimens included cyclophosphamide, methotrexate or doxorubicin, 5-fluorouracil, and vincristine in addition to prednisone. Among 1,237 evaluable patients receiving a five-drug regimen including prednisone, there were 98 patients (7.9%) who experienced any degree of hyperglycemia. Thirty patients (2.4% overall; 30.6% of those having any hyperglycemia) had severe or life-threatening degrees of hyperglycemia, including two patients whose hyperglycemia contributed directly to death. We conclude that prednisone administration as part of adjuvant chemotherapy regimens in breast cancer produces an appreciable incidence of hyperglycemia. Serum glucose levels should be monitored during therapy to help prevent the occasional severe or life-threatening episode of hyperglycemia in these patients.

Antineoplastic Combined Chemotherapy Protocols↗