Natriuretic peptides and heart failure in the patient with chronic kidney disease: a review of current evidence.

Natriuretic peptides such as brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are commonly used in the diagnosis and evaluation of heart failure. However, their utility in patients with chronic kidney disease (CKD) is less clear as renal dysfunction itself can be associated with elevated concentrations of these biomarkers. Given the high prevalence of left ventricular hypertrophy and left ventricular systolic dysfunction in patients with CKD, diagnosis or exclusion of heart failure becomes important in this population. Most studies to date indicate that upward adjustment of diagnostic cut points preserves the usefulness of both BNP and NT-proBNP in the CKD patient, with similar clinical performance of each biomarker. We review the role of natriuretic peptide in heart failure in the setting of chronic renal disease.

N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age.

BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support. RESULTS: Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.

Successful treatment of metastatic retinoblastoma.

BACKGROUND: In the past, patients with metastatic retinoblastoma have had a poor prognosis when treated with conventional modalities. In the current study, the authors evaluated the use of combined intensive conventional chemotherapy, high dose chemotherapy with autologous stem cell rescue (ASCR), and radiation therapy. METHODS: Four patients with metastatic retinoblastoma were treated. All had orbital and bone marrow metastases. In addition, three patients had bone metastases and two patients had liver metastases. None had central nervous system disease. Patients received intensive conventional chemotherapy that included vincristine, cyclophosphamide, etoposide, and either cisplatin or carboplatin. Stem cells were harvested after bone marrow disease was no longer detectable. High dose chemotherapy with carboplatin (500 mg/m(2)/day x 3 days or area under the curve = 7 via the Calvert formula) and thiotepa (300 mg/m(2)/day x 3 days) with (n = 3 patients) or without (n = 1 patient) etoposide (250 mg/m(2)/day x 3 days) was administered with ASCR. Sites that originally harbored bulky disease were irradiated after recovery from the high dose chemotherapy. RESULTS: The therapy was associated with substantial acute hematopoietic and mucosal toxicities. At last follow-up, all four patients had survived event free from 46-80 months after the diagnosis of metastatic disease. CONCLUSIONS: The treatment strategy described in the current study is effective for patients with metastatic retinoblastoma that does not involve the central nervous system. However, a multicenter trial should be considered to evaluate it in a larger group of patients.

Corrective osteotomy of malunited fractures of phalanges and metacarpals.

We have retrospectively reviewed our experience of corrective osteotomies for phalangeal and metacarpal malunions in eleven patients over a 5-year period. Rotational metacarpal malunion treated by metacarpal osteotomy and AO plate fixation can be performed with confidence of achieving a good or excellent result. Phalangeal osteotomy remains a daunting undertaking for most hand surgeons. Our indifferent results are probably due to the inclusion of three intraarticular malunions treated by extraarticular osteotomy. An alternative approach to these malunions may be appropriate.

Prone breast radiotherapy in early-stage breast cancer: a preliminary analysis.

PURPOSE: Women with large breasts have marked dose inhomogeneity and often an inferior cosmetic outcome when treated with breast conservation compared to smaller-sized patients. We designed a prone breast board, which both minimizes breast separation and irradiated lung or heart volume. We report feasibility, cosmesis, and preliminary local control and survival for selected women with Stage 0-II breast cancer. MATERIALS AND METHODS: Fifty-six patients with clinical Stage 0-II breast cancer were treated with lumpectomy and breast irradiation utilizing a prototype prone breast board. A total of 59 breasts were treated. Indications for treatment in the prone position were large or pendulous breast size (n = 57), or a history of cardiopulmonary disease (n = 2). The median bra size was 41D (range, 34D-44EE). Cosmesis was evaluated on a 1-10 (worst-to-best) scale. RESULTS: Acute toxicity included skin erythema (80% of patients experienced Grade I or Grade II erythema), breast edema (72% of patients experienced mild edema), pruritus (20% of patients), and fatigue (20% of patients reported mild fatigue). One patient required a treatment break. The only late toxicity was related to long-term cosmesis. The mean overall cosmesis score for 53 patients was 9.37 (range, 8-10). Actuarial 3- and 5-year local control rates are 98%. Actuarial overall survival at 3 and 5 years are 98% and 94%. CONCLUSION: Our data indicate that treating selected women with prone breast radiotherapy is feasible and tolerated. The approach results in excellent cosmesis, and short-term outcome is comparable to traditional treatment techniques. This technique offers an innovative alternative to women who might not otherwise be considered candidates for breast conservation.

Pediatric chest wall Ewing's sarcoma.

BACKGROUND: Chest wall tumors of primitive neuroectodermal origin (PNET, Ewing's sarcoma [ES]) are rare and have a poor prognosis. Multimodality therapy has improved survival results, and long-term survival is possible. Whether adjuvant radiation therapy is uniformly beneficial remains unclear. METHODS: A retrospective analysis of the authors' institutional experience between 1979 and 1998 was performed. RESULTS: Twenty consecutive patients with PNET-ES of the chest wall were identified. The median age was 12 years (range, 2.5 to 21 years). Median follow-up was 3 years (range, 7 months to 19.4 years). Seven patients presented with a mass, 12 with pain, 1 with respiratory distress, and 1 with a neuropathy. Initial therapy consisted of biopsy and neoadjuvant chemotherapy followed by chest wall resection in 12 patients. Of the remaining 8 patients, 6 underwent biopsy, followed by chest wall resection and adjuvant chemotherapy, 1 underwent biopsy, chemotherapy, and resection of a lung nodule, and 1 underwent biopsy, chemotherapy, and a laminectomy and decompression procedure. All 20 patients were included in institutional-based trials using multiagent chemotherapy. Fifteen patients received radiation therapy with a median dose of 3,000 cGy. At last follow-up, 11 patients are alive and disease free, with a median survival of 7.5 years (range, 7 months to 19.4 years). Seven of 11 (64%) survivors had neoadjuvant therapy followed by chest wall resection. Seven of 11 (64%) survivors had radiation therapy. There was no surgical mortality. Twelve patients had treatment-related complications, 3 of which were related to surgical resection. There were no survivors among patients with recurrent disease. Three of the patients who died of disease had both local and distant recurrences, 4 patients had distant recurrence only, and one patient had local recurrence only. Only 4 of 9 (44%) patients who died were treated initially with chemotherapy followed by chest wall resection. All but 1 of those that died (89%) received initial radiation therapy. All 9 patients who did not survive received additional salvage radiotherapy as well. CONCLUSIONS: Long-term survival is possible with ES-PNET after complete chest wall resection. This may be facilitated by neoadjuvant chemotherapy. Long-term survival without radiation therapy is possible, and consideration of radiation therapy should be made on a case-by-case basis.

Local control with multimodality therapy for stage 4 neuroblastoma.

PURPOSE: To evaluate the efficacy of 21 Gy hyperfractionated radiotherapy for local control in conjunction with surgery and intensive systemic therapy for patients with Stage 4 neuroblastoma. METHODS AND MATERIALS: After achieving a partial or complete remission, 47 children, ages 1-10 years, with Stage 4 neuroblastoma were treated on four consecutive institutional protocols (N4-N7) with dose-intensive multi-agent chemotherapy, maximal surgical debulking, and hyperfractionated radiotherapy (1.5 Gy twice a day to 21 Gy). Radiotherapy fields encompassed the initial tumor volume and regional lymph nodes plus a 3-cm margin. This was followed by consolidation with either autologous bone marrow transplantation (N4 and N5) or immunotherapy (N6 and N7). RESULTS: Forty-five of 47 patients had a complete response to surgery and chemotherapy prior to radiotherapy. Five-year actuarial rates of local control, progression-free survival, and overall survival were 84%, 40%, and 45%, respectively. Among 26 patients who relapsed, 1 failed only at the primary site, 22 developed distant metastases exclusively, and 3 had both local and distant failures. There were no acute complications of radiotherapy. CONCLUSION: Hyperfractionated radiotherapy to 21 Gy, in conjunction with dose-intensive systemic therapy and aggressive surgical resection, is well tolerated and is associated with durable local control for most patients with Stage 4 neuroblastoma.

Treatment-related toxicity from a randomized trial of the sequencing of doxorubicin and radiation therapy in patients treated for early stage breast cancer.

PURPOSE: There is concern that breast cancer patients treated with left-sided radiation therapy (XRT) and doxorubicin (DOX) may have an increased risk of cardiac toxicity. In addition, the effect of different sequencing of XRT and chemotherapy (CT) on the likelihood of cardiotoxicity, as well as cellulitis, arm edema, or brachial plexopathy, is not well understood. We reviewed the records of patients treated on a randomized trial testing the sequencing of CT and XRT to determine if there was an increase in cardiac events or other complications in patients treated with a total dose of DOX of 180 mg/m2 and XRT, comparing patients with treatment to the left breast and the right breast, and comparing patients treated with initial CT and initial RT. MATERIALS AND METHODS: From June 1984 to December 1992, 244 patients with clinical stage I or II breast cancer were randomized following conservative surgery to receive CT (4 cycles of CAMFP at 3 week intervals) either before or after XRT (45 Gy to the entire breast, followed by a boost of 16 Gy; nodal radiation therapy was optional). Two hundred thirty-one patients were evaluable for the development of cardiac toxicity. The median age at diagnosis was 45 years (range, 20-68). CT doses were: doxorubicin, 45 mg/m2 IV bolus, d 3; methotrexate, 200 mg/m2 IV, d 1 and 15; 5-fluorouracil, 500 mg/m2 IV, d 1; cyclophosphamide, 500 mg/m2 IV, d 1; prednisone 40 mg p.o., d 1-5. A cardiac event was defined as a myocardial infarction or clinical evidence of congestive heart failure. Median follow-up time was 53 months. RESULTS: No cardiac events were observed for patients with either left- or right-sided breast cancer. The sequencing of CT and XRT had no significant effect on the risk of cardiac toxicity, cellulitis, arm edema or brachial plexopathy. CONCLUSIONS: We observed no evidence of an increased risk of cardiac toxicity from the addition of left breast tangential irradiation to DOX at a total dose of 180 mg/m2. Additional follow-up is needed to exclude possible late events. In addition, the sequencing of CT and XRT does not appear to affect the risk of cellulitis, arm edema, or brachial plexopathy.

Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors.

PURPOSE: This study evaluates the outcome of myeloablative chemotherapy and autologous bone marrow rescue (ABMR) with or without radiotherapy in children younger than 6 years of age with recurrent malignant brain tumors who had not previously been exposed to conventional fractionated external-beam irradiation. PATIENTS AND METHODS: Patients underwent surgery and/or conventional chemotherapy at the time of recurrence to achieve minimal residual disease (two of these patients also underwent local single-fraction gamma-knife radiosurgery). Myeloablative chemotherapy was then administered with carboplatin, thiotepa, and etoposide (16 patients), thiotepa and etoposide (three patients), or thiotepa, etoposide, and carmustine (BCNU; one patient). Autologous bone marrow was re-infused 72 hours after chemotherapy. Twelve patients received external-beam irradiation after recovery from ABMR. RESULTS: Twenty patients with recurrent brain tumors aged 0.7 to 5.9 years (median, 2.9 years) at ABMR were evaluated. Two patients died of toxicity related to myeloablative therapy. Eight patients died of progressive disease. Ten of 20 (50%) patients (primitive neuroectodermal tumor (PNET)/medulloblastoma, three patients; cerebral PNET, three patients; glioblastoma multiforme, two patients; anaplastic astrocytoma, one patient; pineal PNET, one patient) are alive and disease free at a median of 37.9 months (range, 9.7 to 98.2 months) from ABMR (3-year overall survival [OS] rate of 43% +/- 13% and event-free survival [EFS] rate of 47% +/- 14%]. Seven of these 10 patients also received irradiation post-ABMR. CONCLUSION: Myeloablative chemotherapy with ABMR followed by additional external-beam irradiation appears to be an effective retrieval therapy for some young children with recurrent malignant brain tumors.

Pediatric rhabdomyosarcoma of the head and neck.

PURPOSE: Survival for pediatric rhabdomyosarcoma has improved with the use of multidrug chemotherapy and external beam radiotherapy. This study was performed to determine survival in a cohort of patients treated on one of three multidrug treatment protocols for head and neck rhabdomyosarcoma and to identify factors that place patients at risk for treatment failure. METHODS: Pertinent prognostic variables including age, sex, subsite of origin, resectability, and TNM stage were analyzed by the Kaplan-Meier methods with comparisons between variables performed using the Prentice-Wilcoxon test statistic. RESULTS: Overall 5-year survival was 74% (95% confidence interval 64% to 84%). Local failure accounted for the cause of death in 10 patients, and 8 died of disseminated disease. On univariate analysis, each variable contributing to the TNM staging system was significant in determining survival; invasiveness (P = 0.01), size (P = 0.02), nodal metastases (P <0.01), and distant disease (P <0.01). CONCLUSION: Survival has improved for head and neck rhabdomyosarcoma treated with multimodality therapy. Patients with advanced-stage disease are at greatest risk for treatment failure and require the most aggressive therapy.

Chest wall rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in the pediatric age group. The primary tumor site is an important prognostic determinant. Axial lesions are associated with decreased survival and provide a clinical challenge. METHODS: A retrospective analysis of the authors' institutional experience between 1972 and 1996 was performed. Patients were from a data base of 302 consecutive cases. RESULTS: Fifteen consecutive patients with chest wall rhabdomyosarcoma were identified. The median age was 16 years (range, 6 months-25 years). Median follow-up was 6.6 years (range, 10 months-18.5 years). Nine patients presented with a mass, six with pain, two with respiratory distress, and one with ulnar neuropathy. The median lesion size was 7 cm (range, 3-16 cm). A surgical procedure was the initial therapy for 13 of 15 patients. Fourteen patients received radiation therapy with a median dose of 4400 cGy. All but one were included in institutional-based trials using multiagent chemotherapy. At last follow-up, 10 patients were alive and disease free, with a median survival of 123 months (range, 51-221 months). Seven of ten survivors underwent a complete resection as their initial therapy. There was no surgical mortality, and only two patients had treatment-related complications. Of the five patients who died, two underwent complete resection as their initial therapy. All five patients had invasive tumors. Four were > 10 cm, 3 were of alveolar subtype, and 2 were embryonal. CONCLUSIONS: Complete resection of chest wall rhabdomyosarcoma is recommended. However, survival is possible for patients with microscopically positive surgical margins with the addition of chemotherapy and radiation.

Breast-conserving therapy for stage I-II synchronous bilateral breast carcinoma.

BACKGROUND: Synchronous bilateral breast carcinoma (SBBC) is an uncommon presentation, and the management of patients with this disease is not well established. METHODS: In order to evaluate whether patients with early-stage SBBC could be safely and effectively treated with bilateral breast-conserving therapy (BCT), the authors retrospectively reviewed the records of 24 patients with clinical Stage I-II SBBC treated during the period 1977-1989 with bilateral BCT. SBBC was defined as bilateral invasive carcinomas diagnosed no more than 1 month apart. The median age at diagnosis was 56 years (range, 32-85 years), and the median follow-up for surviving patients was 95 months (range, 68-157 months). Pathology slides were available for review in 19 cases. Cosmetic results and complications after BCT were scored. Outcome was compared with that of 1314 patients with unilateral Stage I or II breast carcinoma, within the same age range, treated during the same time period. RESULTS: There were no significant differences between the SBBC and unilateral groups in actuarial disease free survival (70% and 74%, respectively, at 5 years), overall survival (88% and 87%, respectively, at 5 years), or crude distribution of sites of first failure. Multivariate analysis of overall survival and disease free survival also did not show bilaterality to be a significant factor. The cosmetic results for the SBBC group were not significantly different from those for the unilateral group. Physician assessment of cosmetic outcome was excellent in 57% and good in 43% of SBBC patients evaluated 25-48 months after BCT. Long term complications were rare in both groups. CONCLUSIONS: Patients with early-stage SBBC can be safely treated with carefully planned, bilateral BCT, with outcome that appears to be comparable to that of patients with early-stage unilateral breast carcinoma.

Visual outcome after surgery for Peters' anomaly.

The authors reviewed the charts of 22 patients with Peters' anomaly. Various surgical procedures were performed on 30 eyes of 18 patients (mean number of procedures = 3.3 per eye). Follow-up averaged six years. Visual acuity varied widely, with six eyes having an acuity of 20/400 or better, and 11 eyes with no light perception. Concomitant or secondary glaucoma required a greater number of surgical procedures (4.1 vs 3.4) per eye and was associated with a poorer visual outcome. No eyes with glaucoma had visual acuity better than 20/400. In bilaterally operated patients, visual results in one eye were independent of the outcome of the fellow eye. The range of visual acuity in bilaterally operated patients was similar to the vision in those operated unilaterally. Visual outcome in patients with Peters' anomaly remains guarded. With modern surgical techniques and aggressive attempts at visual rehabilitation, many patients may benefit from surgery. Some patients may have moderately good visual acuity for months or years before vision is lost. In the interim they may learn tasks they may not have otherwise acquired.

Combined trabeculectomy, cataract extraction, and foldable lens implantation.

The efficacy of foldable silicone intraocular lenses in combined glaucoma/cataract surgery was retrospectively analyzed in 19 consecutive operations. Preoperatively all patients were receiving medical treatment for glaucoma; 21% had intraocular pressures above 21 mm Hg despite the medical therapy. Postoperatively, reduction of intraocular pressure to 21 mm Hg or less was achieved in 84% of eyes, with 58% requiring no antiglaucoma medications. Mean improvement of Snellen visual acuity was 4.9 lines; 84% of eyes achieved a final acuity of 20/40 or better. Median follow-up was 59 weeks (range 25 to 88 weeks). Thirteen eyes (68%) had a filtration bleb present when last examined. These preliminary results suggest that foldable silicone IOLs are an effective alternative to poly(methyl methacrylate) lenses in combined glaucoma/cataract surgery.

Modulation of corneal wound healing after excimer laser keratomileusis using topical mitomycin C and steroids.

A 193-nm excimer laser system was used to create deep stromal ablations in seven New Zealand white rabbits and shallow ablations in three. Eyes were randomized for treatment with topical mitomycin C, steroids, and erythromycin; topical steroids and erythromycin; or topical erythromycin only. All treatment regimens were instituted twice daily for 14 days. All eyes reepithelialized normally within 3 to 5 days. During 10 weeks of follow-up, all eyes developed moderate reticular subepithelial haze without significant differences among treatment groups. Results of light, fluorescence, and electron microscopic examination showed anterior stromal scarring and markedly reduced new subepithelial collagen formation in the group treated with mitomycin C, corticosteroids, and erythromycin. Focal abnormalities of Descemet's membrane and endothelial abnormalities were present in all treatment groups. Combination therapy with topical steroids, mitomycin C, and erythromycin to control the corneal wound healing response after refractive laser surgery appears promising and warrants further study.

Long-term survival rate after vitreous surgery for complications of diabetic retinopathy.

The survival rate after vitreous surgery for complications of diabetic retinopathy was studied in 552 consecutive patients who underwent operations between 1979 and 1984. The 5-year postoperative survival rate was 74.7%. Factors associated with a lower survival rate included older age, older age at diagnosis of diabetes, history of renal disease, and a longer duration of diabetes. Factors unrelated to survival rate included insulin treatment, sex, and anatomic and visual outcome. Improved management of systemic diabetic complications has improved survival rates, a finding reflected in the relatively high rate of long-term survival after diabetic vitrectomy.

Evaluation of corrected loss variance as a visual field index. I. CLV exceeds RMS in discriminating between glaucoma-suspect patients with no loss of visual sensitivity and normal observers.

Octopus visual fields were compared for three groups of patients: (1) diagnosed glaucoma patients; (2) glaucoma-suspect patients, and (3) control observers. Four visual field indices were analyzed for each visual field: mean sensitivity, short-term fluctuation (root mean square), mean defect, and corrected loss variance. Among the four indices, corrected loss variance was the only index that discriminated the glaucoma-suspect group from the control group, while, as expected, the glaucoma group differed from the other two study groups for all four indices. These data support the view that corrected loss variance may provide highly sensitive information on which to base an early clinical diagnosis of glaucoma in patients who do not demonstrate traditional field loss.