Budget impact analysis of a breast rapid diagnostic unit.

BACKGROUND: The Odette Cancer Centre's recent implementation of a rapid diagnostic unit (rdu) for breast lesions has significantly decreased wait times to diagnosis. However, the economic impact of the unit remains unknown. This project defined the development and implementation costs and the operational costs of a breast rdu in a tertiary care facility. METHODS: From an institutional perspective, a budget impact analysis identified the direct costs associated with the breast rdu. A base-case model was also used to calculate the cost per patient to achieve a diagnosis. Sensitivity analyses computed costs based on variations in key components. Costs are adjusted to 2015 valuations using health care-specific consumer price indices and are reported in Canadian dollars. RESULTS: Initiation cost for the rdu was $366,243. The annual operational cost for support staff was $111,803. The average per-patient clinical cost for achieving a diagnosis was $770. Sensitivity analyses revealed that, if running at maximal institutional capacity, the total annual clinical cost for achieving a diagnosis could range between $136,080 and $702,675. CONCLUSIONS: Establishment and maintenance of a breast rdu requires significant investment to achieve reductions in time to diagnosis. Expenditures ought to be interpreted in the context of institutional patient volumes and trade-offs in patient-centred outcomes, including lessened patient anxiety and possibly shorter times to definitive treatment. Our study can be used as a resource-planning tool for future rdus in health care systems wishing to improve diagnostic efficiency.

A novel germline p53 splicing mutation in a pediatric patient with a second malignant neoplasm.

A novel germline p53 splicing mutation was identified in a pediatric patient with two metachronous primary cancers that are constituent tumors of the Li-Fraumeni syndrome. Genomic DNA from the second tumor showed the same mutation and loss of heterozygosity at the p53 locus. The mutant mRNA and protein were present in the tumor tissue. In contrast, in the normal tissues bearing the germline mutation in the heterozygous state, predominantly normal mRNA was expressed and the mutant p53 protein was not detectable. The functional silence and relative lack of mutant p53 mRNA expression in the normal tissues of this patient may be caused by decreased stability or decreased production. If this proves a more general pattern of expression of mutant p53 in individuals with germline mutations, these findings may explain the paucity of tumors in individuals affected with the Li-Fraumeni syndrome.

Unrelated donor bone marrow transplantation for children with severe aplastic anemia: minimal GVHD and durable engraftment with partial T cell depletion.

Both increased graft rejection and increased graft vs host disease (GVHD) remain obstacles to success for unrelated donor (URD) BMT for patients with SAA. Partial T cell depletion (PTCD) may decrease the risk of severe GVHD, while still maintaining sufficient donor T lymphocytes to ensure engraftment. We report on 12 patients with SAA who underwent PTCD URD BMT. All patients had failed medical therapy or relapsed following initial responses, and were transfusion dependent. The median age was 6 years, and there were five males. Donors were matched for four patients, and mismatched for eight. All patients received total body irradiation with either Ara-C or thiotepa and cyclophosphamide. PTCD was accomplished using monoclonal antibody T10B9 or OKT3 and complement. All patients engrafted, with a median time of 18 days to ANC >500. Only one patient had greater than grade II acute GVHD; two patients had limited and one patient extensive chronic GVHD. Nine patients are alive and transfusion independent at a median months post BMT. Three patients died from infection or renal failure. This series suggests that an aggressive immunosuppressive conditioning regimen with PTCD results in successful engraftment and minimal GVHD in pediatric patients with SAA, even with HLA mismatched donors.

Outcomes of transplantation with partial T-cell depletion of matched or mismatched unrelated or partially matched related donor bone marrow in children and adolescents with leukemias.

Graft-versus-host disease (GVHD) remains a major barrier to successful hematopoietic stem cell transplant for patients who lack a matched related donor. Partial T-cell depletion (TCD) of the graft may decrease the risk of severe GVHD with unrelated donors (URD) and partially matched related donors (PMRD) while retaining an antileukemic effect. We analyzed our experience using URD and PMRD for pediatric patients with leukemias from 1990 to 2001. A subgroup of 'matched' URD donor pairs was retrospectively analyzed for high-resolution class I. Partial TCD was accomplished with monoclonal antibody T10B9 or OKT3 and complement. There were 76 URD (45% matched) and 28 PMRD recipients. Event-free survival (EFS) was 38.3%, and overall survival (OS) 45.1% at 3 years. On multivariate analysis, there was no difference in survival based upon marrow source, but nonrelapse mortality was higher with the use of PMRD. Relapse occurred in 6% of ALL patients, and 22.8% of AML/MDS patients. Grades III-IV GVHD was observed in only 6.7% of patients. Partial TCD allows use of matched or mismatched URD, or PMRD with little mortality from GVHD, durable engraftment, and no increase in relapse risk.

Related donor liver transplant for veno-occlusive disease following T-depleted unrelated donor bone marrow transplantation.

Veno-occlusive disease (VOD) is the third leading cause of mortality after bone marrow transplant. Management consists of supportive care, with restricted fluids and diuretics. Most patients will recover, but approximately 25% may develop severe life threatening VOD with subsequent respiratory compromise and multiorgan failure. Orthotopic liver transplant has been attempted for a few patients with intractable VOD, but this approach is limited by availability of a cadaveric organ. We report a child who underwent a T-depleted unrelated donor bone marrow transplant for severe aplastic anemia as a manifestation of Schwachman-Diamond syndrome who developed severe VOD. She had evidence of engraftment when liver transplant was considered, and had no evidence of major organ dysfunction. The left lateral segment of her mother's liver was transplanted at day +33 following bone marrow transplantation. The child remains well ten months post-BMT and nine months after liver transplant. A related donor liver transplant may be a justifiable approach in a patient with severe VOD post-BMT.

Recombinant human tissue plasminogen activator for the treatment of severe hepatic veno-occlusive disease in pediatric bone marrow transplant patients.

Nine pediatric patients were treated with recombinant human tissue plasminogen activator (tPA) for severe hepatic veno-occlusive disease (VOD) which developed after bone marrow transplantation. Recombinant human tPA (5-10 mg/day x 2-4 days) and heparin were begun a median of 15 days (range, 11-32 days) post-transplant. A second course was given if the patient did not respond. The median total serum bilirubin and percent weight gain above baseline were 5.5 mg/dl (range, 1.3-26.1 mg/dl) and 22% (range, 7-44%) respectively at the start of tPA administration. Three patients had their heparin infusion interrupted or discontinued for bleeding symptoms, none of which were life-threatening. Five of the nine patients had complete resolution of their VOD. Another patient was salvaged with a partial maternal liver transplant. We conclude that the incidence and severity of bleeding complications with these doses of tPA and heparin do not preclude their use in pediatric patients. Further study in a larger group setting will be necessary to determine the optimal dosing regimen as well as treatment efficacy.

Bone marrow transplantation in pediatric patients with therapy-related myelodysplasia and leukemia.

Eleven children underwent BMT for therapy-related MDS or leukemia, four from HLA-identical siblings and seven from unrelated donors. Ten of the 11 were conditioned with busulfan and cyclophosphamide as the majority had received prior irradiation to the chest and/or abdomen. All patients engrafted. Regimen-related toxicity was more common when compared to historical controls. Eight patients developed acute GVHD and four of eight who survived 100 days post transplant developed extensive chronic GVHD. Non-relapse related mortality occurred in three patients. Five patients developed recurrent malignancy: one died from recurrence of osteosarcoma, three died of recurrent leukemia or MDS and another developed two subsequent malignancies (duodenal carcinoma and anaplastic astrocytoma). Three survive disease-free at 14+, 22+ and 43+ months for a 2 year actuarial cancer-free survival of 24% (95% confidence interval = 5-53%). Although allogeneic BMT can be curative, regimen-related toxicity is frequent and recurrent malignancy remains the major obstacle.

A study of thiotepa, etoposide and fractionated total body irradiation as a preparative regimen prior to bone marrow transplantation for poor prognosis patients with neuroblastoma.

We report the toxicity and efficacy of a new conditioning regimen for bone marrow transplantation (BMT) in children with poor prognosis neuroblastoma (NBL). Twenty-seven patients with poor prognosis NBL were treated with teniposide (360 mg/m2) or etoposide (500 mg/m2), thiotepa (600-900 mg/m2), and 1200 cGy fractionated total body irradiation (fTBI) followed by autologous marrow rescue (n = 19) or allogeneic BMT from HLA-identical siblings (n = 8). The two patients who received teniposide, 600 mg/m2 thiotepa and fTBI had minimal toxicity but relapsed 4 and 12 months post-auto BMT. The next two patients received 750 mg/m2 thiotepa, 500 mg/m2 etoposide and TBI. They tolerated the conditioning regimen well and are alive and in remission 77 and 75 months post-BMT. At the next thiotepa dose level (900 mg/m2), the first two allograft recipients both experienced fatal regimen-related toxicity. All subsequent allograft recipients received 750 mg/m2 thiotepa and autograft recipients received 900 mg/m2 thiotepa. As of 1 April 1995, eight of the 19 patients who received autologous marrow are surviving disease-free 21 to 77 months post-BMT. Nine autograft recipients relapsed at 2 to 37 months following transplantation. One patient died of hepatic veno-occlusive disease 2 months after auto BMT, and one of pneumonia 6 months post-transplantation. Three allograft recipients have relapsed at 6, 10 and 39 months post-transplant and three are alive and in remission 75, 53 and 27 months post-BMT. Overall, 11/27 patients (41%) are alive and in remission 21-77 months (median 47 months) following BMT. A conditioning regimen consisting of 500 mg/m2 etoposide, thiotepa (750 mg/m2 for allograft recipients and 900 mg/m2 for autograft recipients) and 1200 cGy fTBI has acceptable toxicity and is at least as effective as melphalan-containing regimens in the treatment of high-risk NBL.

Successful use of extracorporeal membrane oxygenation (ECMO) during BMT for SCID.

An 8-month-old girl with SCID presented with severe bronchiolitis. She received an HLA-identical sibling BMT without conditioning or GVHD prophylaxis. She deteriorated despite mechanical ventilation but had normal cardiac, hepatic and renal function. ECMO was instituted on day +3 and subsequent improvement was seen concurrently with emergence of CD4+ cells on day +11. She was taken off ECMO on day +18 and suffered a left-sided stroke evidenced by a dense left hemiplegia. She was extubated on day +25 and weaned from supplemental oxygen on day +36 and at day +100 has recovered strength in her extremities. This is the first successful use of ECMO as a bridge to engraftment in a BMT patient.

Chorioretinal folds. A comparison of unilateral and bilateral cases.

We retrospectively reviewed the records, photographs, and fluorescein angiograms of patients with chorioretinal folds to compare features of unilateral and bilateral involvement. We studied 78 eyes of 54 patients and found that 30 (56%) of these patients had unilateral folds and 24 (44%) had bilateral folds. No significant difference was found in comparing visual acuity, refractive error, age, or race in the unilateral vs the bilateral cases. There were significantly more women in the bilateral group (P = .043). The frequency of causes of unilateral cases differed from bilateral cases, but this could not be statistically proven owing to our small sample size. This analysis contains the largest number of chorioretinal folds reported in the literature, and is the first attempt to compare unilateral and bilateral cases.

Molluscum contagiosum eyelid lesions as the initial manifestation of acquired immunodeficiency syndrome.

PURPOSE: To report molluscum contagiosum as the initial manifestation in acquired immunodeficiency syndrome (AIDS). METHOD: Case report. A 34-year-old man was examined with atypical, extensive molluscum contagiosum of the eyelids. RESULTS: Biopsy of the lesions confirmed molluscum contagiosum, and a previously normal fundus now disclosed bilateral cotton wool spots and classic signs of cytomegalovirus retinitis in the left eye. Human immunodeficiency virus (HIV) antibody testing was positive. CONCLUSIONS: Manifestation of atypical and extensive eyelid molluscum contagiosum may warrant additional history taking, comprehensive ophthalmic examination, including dilated ophthalmoscopic examination, and HIV testing.

Suture abscesses after penetrating keratoplasty.

Eighteen suture abscesses that developed after penetrating keratoplasty in 15 patients were reviewed. The time from keratoplasty to the diagnosis of an abscess ranged from 1 to 53 months with a mean of 21.5 months. In 13 of the 18 cases, the patient was taking topical steroids at the time of diagnosis. All were culture-proven bacterial ulcers, except for one case that had a positive Gram's stain, but no growth on culture. The organisms cultured were Staphylococcus epidemidis (six eyes), Streptococcus pneumoniae (five eyes), Sta. aureus (four eyes), Str. viridans (two eyes), Klebsiella oxytoca (one eye), Serratia marcescens (one eye), Moraxella sp (one eye), and Escherichia coli (one eye). The offending suture was removed in all cases, and the eyes were treated with topical fortified antibiotics (cefazolin and tobramycin). After treatment, 67% (12 of 18 eyes) had clear grafts, 17% (three of 18 eyes) were scarred, and 16% (three of 19 eyes) had failed grafts. Intensive topical steroid therapy was used when a subsequent graft rejection developed. Retained sutures following corneal transplants can result in sight-threatening infections and should be considered for removal as soon as the wound is well healed.

Metachronous Epstein-Barr virus-related smooth muscle tumors in a child after heart transplantation: case report and review of the literature.

Soft tissue tumors are uncommon manifestations of Epstein-Barr virus (EBV) infection in patients who have had transplants. The authors report 2 metachronous EBV-containing smooth muscle tumors in a child who had a heart transplant, and review the literature on posttransplant soft tissue tumors.

Haemophilus influenzae central corneal ulcer associated with cosmetic lens wear.

PURPOSE: We report a case of keratitis caused by Haemophilus influenzae involving daily wear contact lens use. METHODS: After positive cultures from corneal scrapings and contact lenses, the patient was diagnosed with Haemophilus influenzae keratitis. RESULTS: After 16 days of treatment with topical ciprofloxacin and trimethoprim sulfate-polymyxin B sulfate, the keratitis resolved. CONCLUSIONS: Cultures will help identify rare corneal pathogens such as Haemophilus influenzae and help in directing appropriate treatment.

Clinical experience with N-butyl cyanoacrylate (Nexacryl) tissue adhesive.

BACKGROUND: To investigate the indications, outcomes, and complications of N-butyl cyanoacrylate tissue adhesive for ocular clinical use. This tissue adhesive is under investigation by the Food and Drug Administration. METHODS: N-butyl cyanoacrylate was used as an investigational device on 44 patients at the authors' institution over a 2-year period. The charts of these patients were reviewed. RESULTS: The indications for glue application included corneal perforation (19 eyes), descemetoceles (9 eyes), leaking filtering blebs (6 eyes), stromal thinning (5 eyes), wound leaks (4 eyes), and exposure keratopathy (1 eye). A bandage contact lens was used over the dried tissue adhesive in 38 of the 44 eyes. Length of glue adherence ranged from 1 to 660 days (mean, 72 days). Outcome was penetrating keratoplasty (19 eyes), no further intervention (14 eyes), enucleation (4 eyes), surgical revision of a filter (2 eyes), scleral patch graft (1 eye), conjunctival transplant (1 eye), failed tarsorrhaphy (1 eye), suturing of wound (1 eye), and a lamellar graft (1 eye). Vision improved in 52% (23/44) of eyes. CONCLUSION: This tissue adhesive may soon be available to all ophthalmologists, and the authors' experience demonstrates that it is an effective method of temporary or permanent closure of an impending or frank perforation.

Bone marrow transplantation in pediatric patients with severe aplastic anemia: cyclophosphamide and anti-thymocyte globulin conditioning followed by recombinant human granulocyte-macrophage colony stimulating factor.

PURPOSE: Graft rejection remains a serious problem in patients transplanted for severe aplastic anemia. Although additional immunosuppression with irradiation may decrease graft failure, significant sequelae may ensue. We evaluated a nonirradiation containing conditioning regimen for children with severe aplastic anemia with matched sibling donors utilizing cyclophosphamide and anti-thymocyte globulin (ATG). To accelerate myeloid recovery, GM-CSF was used posttransplant. PATIENTS AND METHODS: Twelve patients, with a median age of 3 years underwent BMT from HLA identical sibling (n = 11) or syngeneic (n = 1) donors. Conditioning was cyclophosphamide 50 mg/kg x 4 days and anti-thymocyte globulin 30 mg/kg x 3 days. GM-CSF was administered at 10 micrograms/kg until a neutrophil count of 1,000 was achieved. Cyclosporine alone was used for graft-versus-host disease prophylaxis. RESULTS: All patients achieved durable engraftment at follow-up of 5-51 + months, with the exception of the identical twin. Median time to neutrophil counts > 200/microliters, 500/microliters, and 1,000/microliters were 12, 13, and 15 days, respectively. Acute GVHD of less than or equal to grade II occurred in four patients; one patient had grade III. This has resolved in all but one. CONCLUSION: The nonradiation conditioning regimen of cyclophosphamide/ATG appears to achieve durable engraftment in transfused children with matched sibling donors. GM-CSF may accelerate myeloid recovery without exacerbating GVHD, but its contribution to allogeneic transplant required further study.