ABSTRACT
BACKGROUND: The aim of this study was to evaluate the safety and efficacy of radiofrequency ablation (RFA) for treating third degree haemorrhoids, with a follow-up over 2 years. METHODS: We conducted a prospective, two-centre study to assess RFA of third-degree haemorrhoids in an outpatient setting. Treatment was performed under local anaesthesia, optionally in combination with sedation. The primary endpoint was analysis of a proctological symptom score ([PSS] bleeding, itching, pain, soiling) and proctological examination to detect recurrence at 1, 6, 12 and 24 months after surgery. The secondary endpoints were postoperative complications, incidence of postoperative pain, including administration of analgesics and time to return to daily routine. RESULTS: Ninety-eight patients were included in the study. The mean age of the patients was 49.1 ± 10.9 (mean ± SD). 83 patients (84.7%) were male and 15 patients (15.3%) were female. The follow-up involved 100% (1 month), 95% (6 months), 86% (12 months) and 74% after 24 months. The individual symptom scores and overall PSS score decreased significantly in comparison to the initial score at each time point assessed. Prolapsed haemorrhoids decreased in comparison to the initial situation (100%) to 7.2% (1 month), 3.5% (6 months), 13.1% (12 months) and 13.7% (after 24 months). Thirteen patients (12.7%) required repeat haemorrhoid therapy during the 2-year follow-up period. The mean maximum pain score after the procedure was 2.5 ± 2.7 (determined with the visual analogue scale), while 33 (33.7%) patients reported having no pain. 59 (60.2%) patients did not take analgesics after the procedure. Eleven patients (11.2%) experienced minor complications (bleeding, fever, cramps, diarrhoea, anal venous thrombosis) but did not require additional treatment. Eight cases (8.2%) of major complications (infection, bleeding, severe pain) required treatment with antibiotics, a second intervention, analgesics or hospitalization. CONCLUSIONS: RFA is safe and effective for treatment of third-degree haemorrhoids. The main advantages of this new method are its use on an outpatient basis under local anaesthesia, a very low level of postoperative pain and significant control of haemorrhoid symptoms over 2 years.
Subject(s)
Catheter Ablation , Hemorrhoids , Catheter Ablation/adverse effects , Catheter Ablation/methods , Female , Hemorrhoids/complications , Hemorrhoids/surgery , Humans , Male , Pain, Postoperative/epidemiology , Pain, Postoperative/etiology , Prospective Studies , Recurrence , Treatment OutcomeABSTRACT
Adoptive transfer experiments were performed to define the immunological role of thymus and bone marrow cells in the induction of delayed hypersensitivity (DH). The results indicated the following, (a) Bone marrow from immune donors contained cells capable of being stimulated by antigen to initiate the expression of DH. (b) Bone marrow from nonimmune or tolerant donors contained cells that were needed to complete the expression of DH after the infusion of immune lymph node cells. (c) Normal bone marrow and thymus cells cooperated in the irradiated recipient to induce the most vigorous skin reactions to specific antigen; these reactions were seen only when the recipients were stimulated by antigen. Either cell type alone was ineffective. (d) In the presence of tolerant bone marrow cells, thymus cells from immune donors gave a more vigorous response than did thymus cells from normal or tolerant donors. (e) There was suggestive evidence that thymus cells were the source of trigger elements that initiated DH. (f) Antigen in the irradiated recipient was necessary to induce DH after infusion of bone marrow cells alone, or bone marrow and thymus cells together.
Subject(s)
Bone Marrow Cells , Bone Marrow/immunology , Hypersensitivity, Delayed/etiology , Thymus Gland/immunology , Animals , Immune Tolerance , Immunity, Cellular , Immunoglobulin G , Iodine Isotopes , Radiation Injuries, Experimental/immunology , RatsABSTRACT
Macrophage migration inhibitory factor (MIF) was found in media of human and mouse lymphocyte and fibroblast cell lines that were continuously growing. Its release was dependent on activation of the cells to enter the mitotic cycle, particularly on cells in S phase. The greatest quantity of MIF was detected in supernatants of lymphocytes collected during S phase after the cells were synchronized in G(1) and in supernatants of growing fibroblasts. When the latter were contact inhibited little or no MIF was found in media. MIF was also released into media of cells proliferating in homologous serum in the absence of fetal calf serum and into media lacking any protein. The MIF produced by lymphocyte lines eluted from Sephadex G-100 in the same fashion as MIF produced by the interaction of sensitized guinea pig cells and antigen. The results indicated that MIF is not a specific mediator of delayed hypersensitivity and cellular immunity and that MIF released by sensitized lymphocytes incubated with antigen merely reflects that fraction of cells activated by antigen to enter the mitotic cycle.
Subject(s)
Cell Migration Inhibition , Macrophages , Animals , Antigens , Cell Division , Cell Line , Chromatography , Contact Inhibition , Fibroblasts/metabolism , Humans , Hypersensitivity, Delayed/metabolism , Immunity, Cellular , In Vitro Techniques , Lymphocytes/metabolism , Lymphocytes/physiology , Mice , Mice, Inbred StrainsABSTRACT
Eight otherwise healthy male chronic marijuana smokers were hospitalized for a period of 30 days. Initially they received placebo, then a sustained dose of 210 milligrams of delta9-tetrahydrocannabinol (delta9-THC) per day for 18 days, followed by placebo. Lymphocyte responses to phytohemagglutinin were examined during each of these periods. Neither the daily ingestion of marijuana extract containing 210 milligrams of delta9-THC for 18 days nor the history of chronic marijuana smoking had a depressive effect on the lymphocyte responses of these subjects to phytohemagglutinin.
Subject(s)
Cannabis/pharmacology , Dronabinol/pharmacology , Lymphocyte Activation/drug effects , Adult , Female , Heart Rate/drug effects , Humans , Lectins , Male , Middle Aged , Plant LectinsABSTRACT
PURPOSE: This study was designed to evaluate the effect on CNS relapse (CNSR) and overall relapse rates of blast cells in the CSF containing < or = 5 cells/microL at the time of diagnosis of intermediate-risk acute lymphoblastic leukemia (ALL) in children entered onto a large randomized multicenter prospective therapeutic trial (Childrens Cancer Group [CCG]-105). PATIENTS AND METHODS: We studied outcome in terms of CNSR and event-free survival (EFS) in 1,544 patients who successfully completed remission-induction therapy and had been randomized to one of four systemic chemotherapy regimens and to one of two CNS prophylaxis regimens. We compared outcome between 1,450 patients who had varying degrees of pleocytosis but no blasts in the CSF at diagnosis (blast-negative group) with 94 who had blasts detected in the CSF after cytocentrifugation but had a total CSF WBC count of < or = 5/microL (blast-positive group). RESULTS: No statistically significant differences in overall CNSR or EFS rates were observed between the two groups and no differences were found when analyzed according to age or WBC count at diagnosis, sex, or type of CNS prophylaxis (intrathecal [IT] methotrexate [MTX] alone v IT MTX plus 18 Gy cranial irradiation [CXRT]). CONCLUSION: In intermediate-risk ALL, there was no significant difference in CNSR and systemic relapse rates after standard presymptomatic CNS therapy between patients with a CSF WBC count < or = 5/microL and those without identifiable blasts in the CSF. These findings suggest that certain approaches to therapy, such as that used in this study, may eliminate the need for any additional special treatment directed at this subset of patients with CSF blasts.
Subject(s)
Central Nervous System Diseases/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/cerebrospinal fluid , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Diseases/prevention & control , Cerebrospinal Fluid/cytology , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Infant , Leukocyte Count , Life Tables , Male , Multivariate Analysis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Predictive Value of Tests , Prognosis , Prospective Studies , Recurrence , Risk Factors , Treatment OutcomeABSTRACT
PURPOSE: The Childrens Cancer Group (CCG) requires both a CSF WBC count of more than five cells per microliter and demonstration of blast cells in the cytocentrifuge specimen to support a diagnosis of CNS relapse. We reviewed the CSF examinations of patients with intermediate-risk acute lymphoblastic leukemia (ALL) to determine the clinical significance of blast cells reported in the cytocentrifuge when the total CSF cell count was normal. PATIENTS AND METHODS: Children treated on CCG-105 for ALL had CSF examinations every 12 weeks during maintenance therapy. The outcome of children who had a positive CSF cytocentrifuge examination without an elevated CSF WBC count was compared with that of children who did not have any CSF blast cells observed. RESULTS: Sixty-four patients had 81 CSF examinations with blast cells and a normal cell count. By Cox life-table regression analysis, patients with blasts had a different disease-free survival (DFS) distribution, with relapses tending to occur earlier (P = .008). However, the DFS for these patients was 63% +/- 9.6% at 5 years from the time of the abnormal cytocentrifuge result as compared with 69% +/- 1.5% for 1,490 children who did not have blasts in their CSF. This difference is not significant. CONCLUSION: Blast cells were infrequently identified in cytocentrifuge preparations of CSF when the cell count was normal. The majority of patients in whom such an event was observed have not experienced a subsequent relapse as measured by life-table analysis at 5 years. The data do not justify changing or augmenting therapy based on cytocentrifuge results alone.
Subject(s)
Lymphocytes , Precursor Cell Lymphoblastic Leukemia-Lymphoma/cerebrospinal fluid , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Centrifugation/instrumentation , Child , Child, Preschool , Cytological Techniques/instrumentation , Female , Humans , Leukocyte Count , Life Tables , Male , Treatment OutcomeABSTRACT
PURPOSE: Patients with lymphoblastic non-Hodgkin's lymphoma (LB NHL) were randomized to treatment with either modified LSA2L2 or ADCOMP, which added daunorubicin (DAUN) and asparaginase (L-ASP) to the methotrexate (MTX), cyclophosphamide (CYT), vincristine (VCR), and prednisone (PRED) (COMP) regimen, in a clinical trial to determine the relative effectiveness and toxicity of the two regimens. PATIENTS AND METHODS: Patients with LB NHL were eligible for this randomized study if they were less than 22 years of age at diagnosis and had < or = 25% blasts in the bone marrow. Of 307 patients registered, 281 were fully eligible and assessable. Patients were stratified by extent of disease at diagnosis. RESULTS: The 5-year event-free survival (EFS) rate for patients with localized disease was 84%, and for patients with disseminated disease, 67%. There were four relapses in 28 patients with localized disease. Two hundred six patients had mediastinal primary tumors and despite local radiation, 34 of 63 failures in these patients involved the primary tumor site with or without other involvement. After adjusting for extent of disease at diagnosis, the regimens did not differ significantly with respect to risk for adverse events. The acute toxicity was primarily neutropenia and thrombocytopenia, with greater initial toxicity in patients on the LSA2L2 regimen. Three patients developed acute myelogenous leukemia. CONCLUSION: Long-term EFS in children with LB NHL can be achieved in the majority of patients. Disease progression, which includes recurrence at the primary tumor site, is a major cause of treatment failure in patients with mediastinal presentations. Addition of DAUN and L-ASP to the COMP regimen does not produce a more effective treatment than LSA2L2.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Asparaginase/administration & dosage , Asparaginase/adverse effects , Cause of Death , Child , Child, Preschool , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Cytarabine/administration & dosage , Cytarabine/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Humans , Infant , Lymphoma, Non-Hodgkin/mortality , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prednisone/administration & dosage , Prednisone/adverse effects , Recurrence , Thioguanine/administration & dosage , Thioguanine/adverse effects , Treatment Failure , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
PURPOSE: This study (Childrens Cancer Group [CCG]-105) was designed in part to determine in a prospective randomized trial whether intrathecal methotrexate (IT MTX) administered during induction, consolidation, and maintenance could provide protection from CNS relapse equivalent to that provided by cranial radiation (CXRT) in children with acute lymphoblastic leukemia (ALL) and intermediate-risk features. PATIENTS AND METHODS: We randomized 1,388 children with intermediate-risk ALL to the two CNS regimens. They received either IT MTX at intervals throughout their course of therapy or CXRT (18 Gy) during consolidation with IT MTX during induction, consolidation, and delayed intensification. Systemic therapy was randomized to one of four treatment regimens derived from a regimen used by CCG in recent studies for this patient population and three more intensive regimens based on the Berlin-Frankfurt-Munster trials. RESULTS: Life-table estimates at 7 years show a 93% and 91% CNS relapse-free survival rate for the CXRT and IT MTX groups, respectively. The corresponding event-free survival (EFS) rates are 68% and 64%. The differences are not significant. Patients who received more intensive systemic therapy had a 94% CNS relapse-free survival rate on either CXRT or IT MTX, while patients who received standard systemic therapy had 90% and 80% rates for CXRT and IT MTX, respectively (P < .0001). Patients less than 10 years of age who received CXRT or IT MTX had 72% and 71% EFS rates if they received more intensive systemic therapy. Patients 10 years or older who received CXRT had an improved EFS (61% v 53%) with a more intensive systemic program. This was primarily due to fewer bone marrow relapses (P = .04). CONCLUSIONS: IT MTX during induction, consolidation, and maintenance provides protection from CNS relapse in patients with intermediate-risk ALL equivalent to that provided by CXRT if more intensive systemic therapy is given. The CNS relapse rate with either CXRT or IT MTX is in part dependent on the associated systemic therapy. For intermediate-risk patients less than 10 years of age, IT MTX with an intensified systemic regimen provided CNS prophylaxis comparable to that provided by CXRT, whereas older patients had fewer systemic relapses if they received CXRT.
Subject(s)
Central Nervous System Neoplasms/prevention & control , Cranial Irradiation , Methotrexate/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Central Nervous System Neoplasms/secondary , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Infant , Injections, Spinal , Life Tables , Male , Prospective Studies , Survival AnalysisABSTRACT
PURPOSE: The Berlin-Frankfurt-Munster (BFM) 76/79 trial of acute lymphoblastic leukemia (ALL) in children produced impressive disease-free survival (DFS) rates with a protocol that began with 8 weeks of intensive therapy, followed by 8 weeks of maintenance therapy, and then another 6 weeks of intensive treatment. The current study was conducted to determine the relative contributions of each of these periods of intense therapy on the DFS rates of ALL patients with intermediate presenting features. In addition, due to concerns regarding the toxicity of CNS irradiation, we compared cranial irradiation (CXRT) with intrathecal methotrexate (IT MTX) administered during induction and consolidation to IT MTX during all phases of the treatment program. PATIENTS AND METHODS: Between May 1983 and April 1989, more than 1,600 children with ALL and intermediate presenting features, as defined by the Childrens Cancer Group (CCG), were entered into a randomized trial that tested four systemic therapy regimens and two CNS programs. RESULTS: The results with a median follow-up of 57 months show that systemic regimens with a delayed intensification (Delint) phase of therapy had a 5-year event-free survival (EFS) rate of 73% compared with the control regimen EFS rate of 61% (p = .006). For children less than 10 years of age, standard three-drug induction and Delint produced a 77% 5-year EFS. IT MTX during all phases of therapy provided CNS protection comparable to the CXRT regimen in children less than 10 years of age. Children 10 years of age or older appear to have a better EFS rate with intensive induction, Delint, and CXRT. CONCLUSION: Delint improves the EFS rate of children with ALL and intermediate presenting features. Maintenance IT MTX can be safely substituted for CXRT for presymptomatic CNS therapy in children with intermediate-risk characteristics less than 10 years of age.
Subject(s)
Methotrexate/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Child , Child, Preschool , Combined Modality Therapy , Cranial Irradiation , Drug Administration Schedule , Female , Humans , Infant , Injections, Spinal , Life Tables , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Remission Induction , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
PURPOSE: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. RESULTS: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/classification , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Age Factors , Central Nervous System Diseases/etiology , Child , Child, Preschool , Cytogenetics/methods , DNA, Neoplasm/analysis , Disease-Free Survival , Humans , Immunophenotyping , Infant , Karyotyping , Leukocyte Count , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prognosis , Risk Factors , Treatment OutcomeABSTRACT
Pharmacodynamic measures of neutropenia, such as absolute neutrophil count at nadir and neutrophil survival fraction, may not reflect the overall time course of neutropenia. We developed a pharmacokinetic-pharmacodynamic model to describe and quantify the time course of neutropenia after administration of topotecan to children and to compare this with nonhuman primates (NHPs) as a potential preclinical model of neutropenia. Topotecan was administered as a 30-min infusion daily for 5 days, repeated every 21 days. As part of a Phase I Pediatric Oncology Group study, topotecan was administered at 1.4 and 1.7 mg/m(2)/day without filgrastim (POG), and at 1.7, 2, and 2.4 mg/m(2)/day with filgrastim (POG+G). In NHPs, topotecan was administered at 5, 10, and 20 mg/m(2)/day without filgrastim. A pharmacokinetic-pharmacodynamic model was fit to profiles of topotecan lactone plasma concentrations and neutrophil survival fraction from cycle 1 and used to calculate topotecan lactone area under the plasma concentration-versus-time curve from 0 to 120 h (AUC(LAC)) and the area between the baseline and treatment-related neutrophil survival fraction (ABC) from 0 to 700 h. The mean +/- SD neutrophil survival fraction at nadir for the POG, POG+G, and NHP groups was 0.12 +/- 0.09, 0.11 +/- 0.17, and 0.09 +/- 0.08, respectively (P > 0.05). The mean +/- SD for the ratio of ABC to AUC(LAC) for the POG and NHP groups was 1.02 +/- 0.38 and 0.16 +/- 0.09, respectively (P < 0.05). The model estimate of ABC and the ratio of ABC to AUC(LAC) in children and NHPs may better reflect sensitivity to chemotherapy-induced neutropenia.
Subject(s)
Neutropenia/pathology , Topotecan/pharmacokinetics , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Area Under Curve , Child , Child, Preschool , Clinical Trials, Phase I as Topic , Disease Models, Animal , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Male , Metabolic Clearance Rate , Neoplasms/drug therapy , Neoplasms/metabolism , Neutropenia/chemically induced , Neutropenia/metabolism , Neutrophils/drug effects , Recombinant Proteins , Time Factors , Topoisomerase I Inhibitors , Topotecan/administration & dosage , Topotecan/adverse effectsABSTRACT
Fourteen children (aged 3 to 14 years) with average-risk acute lymphoblastic leukemia were studied after an oral dose of 6-mercaptopurine (6-MP) (75 mg/m2) administered alone and, on the next day, concurrently with oral methotrexate (20 mg/m2). When 6-MP was administered alone, both the peak plasma concentration (15 to 150 ng X ml-1) and the AUC (36 to 340 ng X ml-1 X hr) were highly variable. Concurrent methotrexate resulted in a 31% increase in the AUC (P less than 0.01) and a 26% increase in peak plasma levels (P less than 0.05) of 6-MP. The AUC of methotrexate correlated with the degree of increase in 6-MP plasma concentrations. These findings are consistent with previous in vitro studies demonstrating that methotrexate is an inhibitor of xanthine oxidase, the enzyme that catabolizes 6-MP to the inactive metabolite thiouric acid. Although the increases in 6-MP AUC and peak plasma concentrations resulting from concurrent methotrexate administration were statistically significant, this interaction is probably not clinically significant at standard low oral doses of methotrexate in light of the wide interpatient variability in these pharmacokinetic parameters of 6-MP.
Subject(s)
Leukemia, Lymphoid/metabolism , Mercaptopurine/metabolism , Methotrexate/pharmacology , Administration, Oral , Adolescent , Biological Availability , Child , Child, Preschool , Chromatography, High Pressure Liquid , Drug Interactions , Female , Humans , Kinetics , Male , Mercaptopurine/bloodABSTRACT
PURPOSE: This study attempted to determine if central nervous system (CNS) disease at diagnosis is a poor prognostic factor in children with acute lymphoblastic leukemia (ALL) and whether 6 Gy of spinal irradiation is an adequate dose for these patients. METHODS AND MATERIALS: Previously the Children's Cancer Group (CCG) treated patients with ALL and CNS disease at diagnosis with cranio (24 Gy)-spinal (12 Gy) irradiation, as well as systemic and intrathecal chemotherapy. In a series of CCG trials completed in 1989 the spinal dose was empirically reduced to 6 Gy for patients receiving systemic chemotherapy with an intensive consolidation phase to limit hematopoietic toxicity. The spinal dose was left at 12 Gy for patients treated with a less intensive consolidation phase. RESULTS: With a median follow-up for surviving patients of 74 months, the 5-year event-free survival for 53 patients with CNS disease at diagnosis was 69 +/- 13% (+/- 2 standard deviations), similar to the value obtained for 3364 patients without CNS disease, 67 +/- 2%. Corresponding values for 5-year survival were 77 +/- 12% and 80 +/- 1%, and for freedom from isolated first CNS relapse, were 90 +/- 9% and 94 +/- 1%. Event-free survival, survival, and freedom from isolated first CNS relapse in the 6-Gy group were as good as in the 12-Gy group. CONCLUSION: CNS disease at diagnosis is not a poor prognostic factor for children with ALL who are treated with intensive systemic chemotherapy, craniospinal irradiation, and intrathecal chemotherapy. Six Gy is an adequate dose of spinal irradiation for these patients.
Subject(s)
Central Nervous System Neoplasms/radiotherapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Infant , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prognosis , Spinal Cord Neoplasms/radiotherapy , Survival AnalysisABSTRACT
A newborn with graft-vs-host (GVH) disease following an exchange transfusion was treated by attempting to eradicate the incompatible graft and to reconstitute the child hematologically and immunologically with a bone marrow transplant. The patient was a female term infant (blood group B, Rh+ Coombs test positive) who received a one-unit group O, Rh- exchange transfusion from an unrelated female donor for hyperbilirubinemia due to ABO incompatibility on day 2. Signs of acute GVH disease began on day 8 and the clinical diagnosis was supported by skin biopsy. With antithymocyte globulin and high dose dexamethasone, the GVH reaction improved somewhat. Cyclophosphamide, 200 mg/kg total dose, was given over four days followed by a marrow graft from a brother who was HLA-A, B identical, and probably also D locus compatible in mixed lymphocyte culture. All signs of GVH resolved with cyclophosphamide treatment and hematologic reconstitution was evident by 14 days after transplant. Two weeks later the GVH reaction and aplastic anemia recurred and Y chromatin was detected in only 6% of marrow cells. The infant died on day 80. Autopsy showed disseminated candidiasis, disseminated cytomegalovirus infection, thymic dysplasia, hypoplastic marrow, and other histopathologic changes consistent with GVH disease. The persistence of female cells in blood and bone marrow and the destruction of the reconstituted marrow suggest that the original incompatible transfusion-derived graft was not eliminated and that it ultimately rejected the histocompatible marrow graft.
Subject(s)
Bone Marrow Transplantation , Exchange Transfusion, Whole Blood/adverse effects , Graft Rejection , Graft vs Host Reaction , Infant, Newborn, Diseases/etiology , ABO Blood-Group System , Blood Group Incompatibility/therapy , Female , Humans , Infant, Newborn , Jaundice, Neonatal/therapy , Rh-Hr Blood-Group System , Transplantation ImmunologyABSTRACT
The prognostic importance of T-lineage acute lymphoblastic leukemia (ALL) in contemporary programs of intensive chemotherapy has been controversial. We therefore assessed the impact of this biological feature in risk-adjusted frontline chemotherapy studies of the Children's Cancer Group (CCG), conducted from 1983 to 1994. A substantially greater proportion of T-lineage patients (N = 730) presented with poor-risk features as compared to B-lineage patients (N = 3668) treated in the same studies (71.1% vs. 39.7%, P < 0.0001). Consequently, in the CCG-100 series of clinical trials (1983-1989), which tested regimens that were largely of moderate intensity, T-lineage ALL patients had an excess of adverse early events compared to patients in the B-lineage group: 3-year event-free survival (EFS) estimate, 65.8% vs 78.2% (P < 0.0001). With the introduction of more intensive chemotherapy in studies from 1989 to 1994 (CCG-1800 series). We observed a progressive and significant improvement in the clinical outcome of patients with T-lineage immunophenotype. Three- and 5-year EFS probabilities increased from 65.8% to 78.1% and from 61.0% to 75.2%, respectively, becoming comparable to or slightly better than results for B-lineage ALL patients. When adjusted for the competing effects of leukocyte count, age, organomegaly and other poor-risk features, T-lineage immunophenotype showed no important impact on the overall EFS pattern. These findings demonstrate the loss of adverse prognostic by T-lineage ALL in a large program of intensive chemotherapy developed over the past decade.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Adolescent , Adult , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Immunophenotyping , Infant , Leukemia-Lymphoma, Adult T-Cell/mortality , Male , Prognosis , Treatment OutcomeABSTRACT
BACKGROUND: Internal drainage with transhepatically or endoscopically placed endoprostheses has been used for many years as a temporary or definitive treatment for biliary tract obstruction. As a late complication, stent migration may occur. METHODS: We reviewed our records to identify patients who were operated on for a migrated endoprosthesis that was causing complications. In all, five such patients were identified. RESULTS: One patient had a large bowel perforation. Bowel penetration led to an interenteric fistula in one patient and to a biliocolic fistula formation in another. Small bowel distension was found in two patients. Surgical treatment consisted of local excision in three patients, segmental resection in one patient, and a bypass operation in the patient with biliocolic fistula. Postoperatively, four patients recovered without problems, but one patient died during a complicated postoperative course. CONCLUSION: If a stent becomes stuck in the gastrointestinal tract and is not accessible for endoscopic removal, early operative revision is mandatory to prevent further complications.
Subject(s)
Colon , Foreign-Body Migration/surgery , Jejunum , Stents/adverse effects , Adult , Aged , Anastomosis, Surgical , Biliary Fistula/etiology , Biliary Fistula/surgery , Cholangiopancreatography, Endoscopic Retrograde , Cholestasis/surgery , Colon, Sigmoid , Colonoscopy , Fatal Outcome , Female , Foreign-Body Migration/etiology , Humans , Intestinal Fistula/etiology , Intestinal Fistula/surgery , Intestinal Perforation/etiology , Intestinal Perforation/surgery , Liver Transplantation , Male , Middle Aged , Neoplasms/complications , Neoplasms/surgery , Pancreatic Pseudocyst/surgery , Pancreatitis/surgery , Postoperative Complications/surgery , Retrospective StudiesABSTRACT
Splenomegaly is usually the result of systemic disease. The differential diagnosis can logically be subdivided into infectious, hematologic, metabolic, vascular, and neoplastic diseases which result in abnormalities of the lymphoid, reticuloendothelial, or vascular components of the spleen. Splenic enlargement increases the risk of traumatic rupture of the spleen. Splenectomy, although indicated in some conditions, does not always relieve the hypersplenic state, and its benefit must be weighed against the hazard of life-threatening episodes of sepsis.
Subject(s)
Splenomegaly/etiology , Cardiovascular Diseases/complications , Child , Child, Preschool , Female , Hematologic Diseases/complications , Humans , Infant, Newborn , Infant, Newborn, Diseases/etiology , Infections/complications , Metabolism, Inborn Errors/complications , Neoplasms/complications , Splenectomy , Splenomegaly/diagnosis , Splenomegaly/surgeryABSTRACT
Surgery is the definitive treatment in familial adenomatous polyposis coli (FAP). Proctocolectomy with ileal pouch anal anastomosis is recommended for the majority of FAP patients. Only in patients with attenuated FAP, is a colectomy with ileorectal anastomosis (IRA) accepted, although the risk for rectum carcinoma remains increased. Sulindac, a chemoprophylactic agent, regresses colorectal adenomas in patients with FAP. Under systemic Sulindac-therapy, three carcinomas in the rectum after colectomy with IRA have been described. We report the first known case of rectum carcinoma in a patient with FAP, 51 months after IRA and local Sulindac therapy.