Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer.

PURPOSE: The goal of this study was to determine the efficacy of intensive-course fluorouracil (5FU) plus low-dose leucovorin given for 6 months following potentially curative resection of colon cancer. PATIENTS AND METHODS: Three hundred seventeen patients with high-risk stage II or stage III colon cancer were randomly assigned 3 to 4 weeks following surgery to receive either (1) chemotherapy with six cycles of 5FU (425 mg/m2) plus leucovorin (20 mg/m2) by rapid intravenous injection daily for 5 consecutive days every 4 to 5 weeks, or (2) observation. RESULTS: The median follow-up duration is 72 months for patients still alive. Patients who received postoperative 5FU plus leucovorin experienced significant improvement in time to relapse (P < .01) and survival (P = .02) compared with control patients treated with surgery alone. Stomatitis, diarrhea, and leukopenia were the predominant chemotherapy toxicities. There were no treatment-related deaths. CONCLUSION: These results indicate that intensive-course 5FU plus low-dose leucovorin is effective in preventing tumor relapse and improving survival in patients with high-risk colon cancer. These benefits were seen with only six cycles of treatment, using low-dose leucovorin in combination with 5FU on a schedule convenient for outpatient administration.

Acute treatment-related diarrhea during postoperative adjuvant therapy for high-risk rectal carcinoma.

PURPOSE: The combination of pelvic radiotherapy and 5-fluorouracil-based chemotherapy is associated with an increase in acute gastrointestinal toxicity during rectal adjuvant therapy, most notably an increased incidence of diarrhea. Previous randomized, prospective studies have limited their analysis to presenting rates of severe and life-threatening diarrhea (Grade 3 or greater), and few data are available detailing the extent of mild to moderate diarrhea. To provide baseline data for future studies, we conducted a detailed analysis of diarrhea from a prior clinical trial of adjuvant therapy for rectal cancer. METHODS AND MATERIALS: In a multiinstitutional clinical trial, 204 eligible patients with rectal carcinoma that either was deeply invasive (T3-T4) or involved regional lymph nodes were randomized to receive either postoperative pelvic radiotherapy alone (45 to 50.4 Gy) or pelvic radiotherapy and bolus 5-fluorouracil-based chemotherapy. Toxicity was assessed prospectively. RESULTS: For the 99 eligible patients who received pelvic radiotherapy alone, rates of Grades 0, 1, 2, 3, and 4 diarrhea during treatment were 59, 20, 17, 4, and 0%, respectively. For the 96 eligible patients who received radiotherapy and 5-fluorouracil, the overall rates of grades 0, 1, 2, 3, and 4 diarrhea were 21, 34, 23, 20, and 2%, respectively. The increased rates of diarrhea during adjuvant rectal therapy were manifested across all toxicity levels for patients receiving chemotherapy and pelvic radiotherapy. Of primary clinical importance is the substantial increase in severe or life-threatening diarrhea (Grade 3 or more) (22 vs. 4%,p = 0.001) Additionally, increased rates of any diarrhea and also severe or life-threatening diarrhea were observed in patients who had a low anterior resection compared with those who had an abdominoperineal resection (p < 0.001 and p = 0.006, respectively). CONCLUSION: These results will be of value as a baseline for investigators who want to use treatment toxicity as an end point in cancer control or cancer therapy trials utilizing similar treatment techniques. Patients receiving 5-fluorouracil and pelvic radiotherapy compared with patients receiving pelvic radiotherapy alone and patients with a prior history of a low anterior resection compared with patients who had a prior history of an abdominoperineal resection experienced increased rates of Grades 1 through 4 acute treatment-related diarrhea, and the most important increase occurred as Grade 3 toxicity.

Carcinoid tumors and sarcoidosis--does a link exist?

OBJECTIVE: To attempt to determine whether a relationship exists between carcinoid tumors and sarcoidosis. MATERIAL AND METHODS: We present a series of seven case reports and discuss hypotheses about possible disease associations. RESULTS: Certain malignant lesions have tended to occur in patients with sarcoidosis. Seven patients who were encountered at Mayo Clinic Rochester between 1950 and 1994 had both sarcoidosis and carcinoid tumors. These patients ranged in age from 31 to 66 years, and three of the patients had a history of benign thyroid disorders. Malignant tumors have been thought to be related to sarcoidosis in one of two ways: (1) immunologic abnormalities in sarcoidosis may promote the development of neoplasms or (2) malignant disease may promote the onset of sarcoidosis either by causing local sarcoid reactions that progress or by directly initiating the manifestations of systemic sarcoidosis. Because the chronology of events differed in our seven cases, various mechanisms of action may have a role in the manifestations of these two disease entities. Our cases emphasize the importance of avoiding the diagnosis of disseminated malignant disease in patients with cancer and associated hilar and mediastinal lymphadenopathy without biopsy confirmation of metastatic disease. CONCLUSION: Application of the knowledge gained about the mechanisms of disease in sarcoidosis will perhaps facilitate identification of the pathogenesis of carcinoid tumors and other neuroendocrine tumors.

Hepatosplenic gammadelta T-cell lymphoma: ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation.

Hepatosplenic gammadelta T cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopenias. Detailed clinicopathological, ultrastructural, and cytogenetic analyses of these lymphomas are limited; functional characteristics of these lymphomas are unknown. We have undertaken a clinicopathological, immunophenotypic, ultrastructural, cytogenetic, and functional analysis of three hepatosplenic gammadelta TCLs. All patients presented with massive hepatosplenomegaly and anemia, thrombocytopenia, or severe neutropenia; terminal blastlike transformation occurred in one patient. Combination chemotherapy had no response in two patients, but induced complete remission in one. gammadelta T cell receptor (TCR) expression and clonal TCRdelta gene rearrangements were documented in each case. Two different subsets of gammadelta TCL were identified based on delta chain variable region usage; two lymphomas were Vdelta1+, whereas the third was negative for both Vdelta1 and Vdelta2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q and probable trisomy 8 was shown in one of the Vdelta1+ lymphomas, whereas the Vdelta1 negative lymphoma had 14p+ with t(1;14)(q21;p13). NK cell-associated antigens (CD11c, CD16, or CD56) and cytotoxic T lymphocyte (CTL) effector proteins (perforin, granzyme B, TIA-1, and Fas ligand) were expressed by each lymphoma; dense core cytolytic granules were observed by electron microscopy in both lymphomas studied. Functional studies performed in two cases showed TCR-mediated cytolysis of P815 x 2 FcR+ cells induced by anti-CD3 in a redirected cytolysis assay in one of the CD56+, Vdelta1+ lymphomas, whereas IFNgamma secretion was induced by anti-CD3 in the CD56-, Vdelta1 negative lymphoma. These studies show that hepatosplenic gammadelta TCLs have CTL differentiation, retain functional activity in vitro, and are derived from at least two gammadelta T cell subsets.

Chemoprevention for colorectal carcinoma.

The literature on chemoprevention for colorectal carcinoma can be summarized as follows: (1) Aspirin and NSAIDs usage can decrease polyp formation and promote polyp regression and have a strong epidemiologic link to colorectal cancer prevention. (2) Fiber intake is strongly associated with a decreased incidence of colorectal carcinoma. Whether supplemental fiber can prevent colorectal neoplasia is not yet clear. (3) Calcium and vitamin D intake is inversely proportional to the risk of developing colorectal carcinoma. Prospective trials make the role of supplemental calcium as a chemoprotective agent unclear: (4) Chemoprevention is an exciting area of research. More work needs to be done to establish the precise steps necessary for neoplastic transformation of cells so that pharmaceuticals can be developed to target carcinogenesis at several levels.

The contribution of alpha1-antitrypsin to the total antitrypsin activity of human serum. A study of two phenotype PI OO individuals.

Comparison of the levels of alpha1-AT, alpha2-M, inter alpha-AT, C1 inactivator and antiplasmin and global antitrypsin activity in a group of normal phenotype PI MM individuals, a group of normal individuals with phenotypes with intermediate alpha1 AT activities and alpha2-AT-deficient persons show that alpha1-AT contributes more than 90 percent of the total antitrypsin activity of normal plasma. AT III and fast reacting antiplasmin are shown to contribute to the remaining activity. It can be assumed that due to test conditions the antitrypsin activity of alpha2-M is not assessed. C1 inactivator and inter alpha1-AT do not contribute to a perceptible extent to the overall antitrypsin activity estimated according to the method of Eriksson (Eriksson, S. (1965) Acta Med. Scand. 177, 1).

Postpartum acquired hemophilia (factor VIII inhibitors): a case report and review of the literature.

Pathologic inhibitors of blood coagulation as a cause of postpartum acquired hemostatic failure are rare. Since 1937, 96 cases of postpartum factor VIII (FVIII) inhibitors, including the current case, have been reported. Suspicion for the diagnosis of this condition is often low. We report a case of postpartum FVIII inhibitor formation in a 24-year-old woman who developed intermittent postpartum bleeding that resulted from the inhibitors she formed to FVIII. A unique form of therapy was used in treatment of her disorder. She did not respond to conventional surgical or medical management of her bleeding until Autoplex T (Baxter Healthcare, Glendale, CA), an activated prothrombin complex concentrate (aPCC) was used. The literature concerning acquired hemophilia is reviewed, and new therapeutic medical advances are emphasized.

Neuroacanthocytosis masquerading as Huntington's disease: CT/MRI findings.

Neuroacanthocytosis (NA) is a rare, degenerative, presumably autosomal-recessive disorder of the nervous system presenting in adulthood and is associated with acanthocytosis of the peripheral blood. The clinical spectrum of NA shares similarities with Huntington's disease (HD), including dyskinetic choreiform movements and degeneration of the caudate nucleus. A woman presented with choreiform movements and was given a presumed diagnosis of HD. Neuroimaging studies were consistent with HD. She lacked the genetic marker for HD, and further evaluation revealed acanthocytosis of the peripheral blood. The case illustrates the similarities and differences in the clinical presentations and neuroimaging studies of these two disease entities, emphasizing the need for a careful clinical evaluation.

[Comparison of certain commercial immune plates used for the assay of alpha 1 antitrypsin]. / Comparaison de quelques immunoplaques commerciales servant au dosage de l'alpha-1-antitrypsine

Commercial immune plates for determination of alpha-1-antitrypsin levels were compared. The coefficient of variation of determinations of alpha-1-antitrypsin varied from one lot to another, even for immune plates of the same origin. The consequences of this observation are discussed.

Lupus aortitis: a case report and review of the literature.

Systemic lupus erythematosus is a complex immunological and rheumatological disease that has numerous complications. Central to the pathogenesis of systemic lupus erythematosus is immune complex formation and deposition in blood vessels and end organs. This is a case report of an autopsy of a patient with systemic lupus erythematosus, end stage renal disease, peripheral vascular occlusive disease, pancreatitis, and aortitis. The aortitis was found to be immune complex mediated with deposition of IgG, C3, as well as fibrinogen in the wall of the aorta as shown by immunofluorescence. The hypercoagulable state of the patient is discussed with particular emphasis on the role of anticardiolipin antibodies, antiphospholipid antibodies, and anti-beta-2-glycoprotein I in the pathogenesis. This case is unique in that the immune complex mediated aortitis has not been described in the literature over the past 25 years. We recommend that the diagnosis of immune complex mediated aortitis be considered in the differential diagnosis of aortitis, particularly in the background of a patient with systemic lupus erythematosus.

Chronic thrombotic thrombocytopenic purpura masquerading as other disease entities.

A 37-year-old woman with a chief complaint of nausea, headache and, prolonged menses was diagnosed with thrombotic thrombocytopenic purpura based on a peripheral smear with active microangiopathic hemolytic anemia and a platelet count of 4,000/mm3. Her past medical history was significant for several conditions including multiple sclerosis, Bell's palsy, Raynaud's syndrome and HELLP syndrome. In retrospect, it appears that this patient's clinical history was most consistent with one unifying diagnosis, chronic thrombotic thrombocytopenic purpura. Physicians should search for the elusive clinical and laboratory clues for chronic thrombotic thrombocytopenic purpura that can masquerade as other disease entities.

Factors affecting the coming out process for lesbians.

Cass' model (1979) of identity development and her Stage Allocation Measure (1984a) were assessed to determine their utility in describing the subjective experience of coming out as a lesbian and whether proposed stages could be tied to behavioral correlates of the Openness Questionnaire (Graham, Rawlings, & Girten, 1985). The process was considered in terms of a woman's differentiation from her family, sex-role attitudes, and levels of internalized homophobia. Eighty-one lesbians anonymously completed questionnaires. The results suggest that subjective labeling and behavior are congruent, but that rate of progression through stages does not imply integration of behavior. Four patterns of identity development were identified which suggest that relevant stages, speed of development, and stage attainment are characteristic of certain women. Intergenerational intimidation was significantly related to stage development, sex-role attitudes, openness behavior, and levels of internalized homophobia.