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Biomedical subjects

W Wells

Publications and source records attributed to W Wells.

At least 19 recordsLinked to original sources

Stage I and II MALT lymphoma: results of treatment with radiotherapy.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following involved field radiation therapy (RT). PATIENTS AND METHODS: Seventy patients with Stage IE (62) and IIE (8) disease were treated between 1989 and 1998. Patients with transformed MALT were excluded. The median age was 62 years (range, 24--83 years), M:F ratio 1:2.2. Presenting sites included stomach, 15; orbital adnexa, 19; salivary glands, 15; thyroid, 8; lung, 5; upper airways, 3 (nasopharynx, 2; larynx, 1); urinary bladder, 3; breast, 1; and rectum, 1. Staging included site-specific imaging, CT abdomen in 66 patients (94%) and bone marrow biopsy in 54 (77%). Sixty-two patients received radiation therapy: 52 received RT alone, 7 received chemotherapy and RT, and 3 received antibiotics followed by RT. Median RT dose was 30 Gy (range, 17.5--35 Gy). Most frequently used RT prescriptions were 25 Gy (26 patients-18 orbit, 6 stomach, and 2 salivary glands), 30 Gy (23 patients), and 35 Gy (8 patients). Five patients had complete surgical excision of lymphoma and no other treatment (stomach 1, salivary 2, lung 2), whereas 2 patients with gastric lymphoma received antibiotics only. One patient refused treatment and was excluded from the analysis of treatment outcome, leaving 69 patients with a median follow-up of 4.2 years (range, 0.3-11.4 years). RESULTS: A complete response was achieved in 66/69 patients, and 3 patients had partial response (2 lung, 1 orbit). The 5-year disease-free survival (DFS) was 76%, and the overall survival was 96%. No relapses were observed in patients with stomach and thyroid lymphoma. The 5-year DFS for these patients was 93%, in contrast to 69% for patients presenting in other sites (p = 0.006). Among the 5 patients treated with surgery only, 2 relapsed locally (lung, and minor salivary gland). Among 62 patients who received RT, 8 relapsed (2 salivary, 3 orbit, 1 nasopharynx, 1 larynx, 1 breast). Three patients relapsed in the nonirradiated contralateral paired organ, 4 in distant sites, and 1 in both local and distant sites. The overall local control rate with radiation was 97% (60/62 patients). CONCLUSION: Localized MALT lymphomas have excellent prognosis following moderate-dose RT. Gastric and thyroid MALT lymphomas have better early outcome, as compared to the other sites where distant failure is more common. Relapses were observed in nonirradiated paired organs or distant sites. Further follow-up is required to assess the impact of failure on survival.

Adult↗

Solitary plasmacytoma treated with radiotherapy: impact of tumor size on outcome.

PURPOSE: Solitary plasmacytoma (SP) is a rare presentation of plasma cell neoplasms. In contrast to multiple myeloma, long-term disease-free survival and cure is possible following local radiotherapy (RT), particularly for soft tissue presentations. In this study, we attempt to identify factors that predict for local failure, progression to multiple myeloma, and disease-free survival (DFS) in patients mainly managed with local RT. METHODS AND MATERIALS: We identified 46 patients referred to the Princess Margaret Hospital between 1982 and 1993. The median age was 63 years (range 35-95), with a male:female ratio of 1.9:1. All patients had biopsy-proven SP (osseous: 32, soft tissue: 14). M-protein was abnormal in 19 patients (41%). All patients were treated with local RT (median dose 35 Gy), with 5 patients (11%) also receiving chemotherapy. Maximum tumor size pre-RT ranged from 0 to 18 cm (median 2.5). RESULTS: The 8-year overall survival, DFS, and myeloma-free rates were 65%, 44%, and 50%, respectively. The local control rate was 83%. Factors predictive of progression to myeloma (and poorer DFS) included bone presentation and older age. However, these two factors did not influence local control, which was affected by tumor size. All tumors < 5 cm in bulk (34 patients) were controlled by RT. Anatomic location did not predict outcome; however, 3 of the 5 tumors arising in paranasal sinuses did not achieve local control. Lower RT dose (< or =35 Gy) was not associated with a higher risk of local failure. CONCLUSION: Solitary plasmacytomas are effectively treated with moderate-dose RT, although osseous tumors have a high rate of recurrence as systemic myeloma. Large tumor bulk locally (> or =5 cm) predicts for local failure. Combined chemotherapy and RT should be investigated in these high-risk patients to increase the local control rate and the cure rate.

Adult↗

Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type arising in the urinary bladder: report of 4 cases with molecular genetic analysis.

CONTEXT: Primary lymphoma of the urinary bladder is rare. Only 84 cases have been reported in the English literature to date, and none of these cases has had molecular confirmation of clonal immunoglobulin gene rearrangement. OBJECTIVES: To review all cases with primary urinary bladder lymphoma in our records, to classify them using the REAL classification, to confirm their immunophenotype and genotype, and to determine their outcome. DESIGN: We identified 4 cases of primary urinary bladder lymphoma in our medical records from a 30-year period. Immunohistochemical detection of immunoglobulin light chains and molecular analysis of immunoglobulin heavy-chain genes using the polymerase chain reaction were performed on paraffin-embedded material. RESULTS: All patients were older than 60 years. The male-female ratio was 1:3. All patients had a history of chronic cystitis. Histologic features of mucosa-associated lymphoid tissue lymphoma with centrocyte-like cells, plasmacytoid B cells, or both were observed in all cases. Monoclonality of B cells was demonstrated by immunohistochemistry, polymerase chain reaction, or both methods in every case. All patients presented with stage IAE disease, were treated with radiotherapy alone, and have been in continuous complete remission for 2 to 13 years. CONCLUSIONS: Primary bladder lymphomas are usually of low-grade mucosa-associated lymphoid tissue type. They are more common in females and are associated with a history of chronic cystitis. Lymphoepithelial lesions are seen only in association with areas of cystitis glandularis. B-cell clonality is readily demonstrable by immunohistochemistry and/or polymerase chain reaction analysis. Local radiotherapy appears to confer long-term control.

Aged↗

Results of radiotherapy for epithelial skin cancer of the pinna: the Princess Margaret Hospital experience, 1982-1993.

PURPOSE: To assess the treatment outcome, late toxicity, and prognostic factors for radiotherapy (RT) of carcinoma of the pinna. METHODS AND MATERIALS: The charts of 313 patients treated between 01/82 and 12/93 were retrospectively reviewed. There were 334 lesions treated: 201 basal cell carcinoma (BCC), 122 squamous cell carcinoma (SCC), and 11 basosquamous carcinoma. RT was most commonly given by orthovoltage X-rays (278 lesions) or electrons (39 lesions). The most frequently used dose prescriptions were 35 Gy in 5 fractions (123 treatments with median field size = 4.9 cm(2)), 42. 5-45 Gy in 10 fractions (67 treatments with median field size = 10.5 cm(2)), and 50-65 Gy in 20-30 fractions (42 treatments with median field size = 81 cm(2)).2 cm. RESUL TS: The actuarial 2- and 5-year local control rates were 86.6% and 79.2 %. Multivariate analysis revealed two factors to be statistically signi ficant for increased local failure: tumor size > 2 cm (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.16-6.08), and a low biological effective dose (BED) (for each decrease of 5 BED units, HR = 1.76, 95% CI = 1.07-2.88). The 5-year actuarial rate of significant Grade 4 late toxicity was 7.3%. Factors statistically significant for this endpoint on univariate analysis were tumor size (p = 0.035), T-stage (p = 0.02), field size (p = 0.05), fraction size (p = 0.003), and BED (p = 0.05). CONCLUSIONS: RT is an eff ctive treatment option for epithelial skin cancer of the pinna. Large t umor size and low BED were independently statistically significantly ass ociated with increased local failure. Dose-fractionation schedules usin g fraction sizes < 4 Gy may reduce the risk of necrosis and ulceration, particularly for field sizes > 5 cm2.

Adult↗

Primary gastric lymphoma: brief overview of the recent Princess Margaret Hospital experience.

Primary gastric lymphoma is the commonest form of presentation for gastrointestinal lymphomas and the stomach is one of the most frequent sites of extranodal lymphoma. We present a review of the Princess Margaret Hospital (PMH) experience to illustrate the favorable prognosis and examine the long-term outcomes in this disease. Between 1967 and 1996, 149 consecutive patients with gastric lymphoma were treated at the PMH. The majority (122 patients) presented with diffuse large-cell lymphoma and 78 had stage I disease. In the past, the standard treatment was surgery (partial gastrectomy) followed by post-operative radiation therapy (RT; 78 patients). The overall 10-year survival was 62%. For patients who were treated with surgery and post-operative RT (operable disease) between 1967 and 1985, the 10-year rates of overall survival and cause-specific survival were 66.2% and 88%, respectively. In the past decade, combined-modality therapy with chemotherapy followed by RT was introduced for large-cell lymphoma, while RT alone was used for mucosa-associated lymphoid tissue (MALT) lymphoma. In 45 patients treated in the past decade, the overall 5-year survival was 86%, the cause-specific survival was 95.5%, and the relapse-free rate was 87.3%. These results support the view that primary gastric lymphoma is a highly curable disease. Future efforts should focus on reducing treatment morbidity, while preserving excellent results.

Adult↗

Spaceflight hardware allowing unilateral irradiation and chemical fixation in petri dishes.

To accommodate a spaceflight experiment with moss (SPM), experiment-unique equipment (EUE) was developed by engineers at Kennedy Space Center. The hardware allows sterile culture for an extended period of time in commercial petri dishes, lateral illumination of each culture with light of a specific wavelength (660 nm; other wavelengths are possible) and a range of intensities (0.05-5 micromoles photons m-2 s-1), incubation in complete darkness, and chemical fixation to terminate the experiment under conditions of microgravity. The use of a fixative required triple containment to protect the astronaut crew. An external panel on the experiment container allowed the timing of illumination and fixation to be controlled by the crew. Light quality is provided by light emitting diodes (LEDs) that are located in the lid of the outer container, the BRIC (Biological Research In Canisters)-LED. Each canister accommodates 6 Petri Dish Fixation Units (PDFUs), and each PDFU holds one 6 cm petri dish. All components are autoclavable. LED illumination is piped through a transparent glass rod. Each PDFU contains fixative in a reservoir that is released by the depression of an actuator. This hardware performed well during its first flight, the 16-day STS-87 mission in Nov./Dec., 1997 as part of the Collaborative USA and Ukrainian Experiment (CUE). It supported vigorous and sterile moss growth, cells were maintained in position and were well-fixed, and there was a vigorous and consistent response to light. Although here used for moss, in future flight experiments this unique new hardware can be used for many types of organisms normally grown in petri dishes, with or without a requirement for illumination.

Bryopsida↗

Aneurysm of the ductus arteriosus: a congenital lesion.

The objective of this study was to evaluate the clinical, radiological, and echocardiographic findings in 11 neonates with aneurysm of ductus arteriosus presented in our institutions between 1993 and 1996, and to postulate a new theory for the pathogenesis of this lesion. Medical records, radiographic studies, and echocardiograms were reviewed. All infants underwent follow-up echocardiograms every 2 to 3 days until the aneurysm spontaneously resolved or surgery was performed. The infants were predominantly term males; six had evidence of fetal distress, two were diagnosed prenatally by fetal echocardiogram, chest X ray evidenced mediastinal mass in six patients. The first echocardiogram showed structurally normal heart with an aneurysmal patent ductus arteriosus. In eight patients the aneurysm completely resolved by 5 to 10 days. One infant underwent surgical resection of the aneurysm after observation for 11 days with no change in size. Thrombosis of the aneurysm was noted in two patients; both underwent surgery. Increasing reports of ductal aneurysms in infants may reflect the availability of high-resolution echocardiography and more frequent use of echocardiography in the neonatal intensive care unit. Spontaneous resolution occurred in the majority of cases as in previous reports. We postulate that, at least in some cases, aneurysm of the ductus arteriosus is a congenital lesion that may represent poststenotic dilation of the ductus due to turbulent flow through a stenotic segment at its pulmonary artery end during fetal life. The presence of aneurysm of the ductus arteriosus should be excluded in selected cases of fetal distress, by fetal echocardiography.

Aortic Aneurysm, Thoracic↗

[Maternal brain death during pregnancy].

The case of a pregnant patient who had a massive intracraneal haemorrhage at 18 weeks of gestation is presented. Patient's neurological damage evolved to brain death, but the fetus continued in good condition. The decision of withdrawing life support or to continue supporting the mother's life to allow fetal development aroused difficult ethical questions, both to relatives and professionals. This is an exceptional situation of a heart beating cadaver and a non viable fetus whose life depends on the continuation of treatments that are considered as experimental. A good decision should be based on the respect to a body in brain death, the fetal right to life, family's wishes and values, the use of experimental treatments, and the rational use of a public hospital's resources. The conclusion was that the continuation of life support treatments was not an ethical obligation. Withdrawing life support to allow fetal death in this case means foregoing an experimental treatment and to respect family's autonomy and the right of the patient's death with dignity. Similar cases need to be discussed with a multidisciplinary analysis in their own particularity.

Adult↗

The corticotropin-releasing hormone challenge in depressed abused, depressed nonabused, and normal control children.

Hypothalamic-pituitary-adrenal (HPA) axis disturbances in depressed children with a history of abuse were examined. Thirteen depressed abused, 13 depressed nonabused, and 13 normal control children were given 1.0 microgram/kg of human corticotropin-releasing hormone (CRH) intravenously. Blood samples for corticotropin (ACTH) and cortisol were obtained at nine intervals. When compared to depressed nonabused and normal control children, depressed abused children had significantly greater peak, total, and net ACTH secretion post-CRH. Increased ACTH secretion was only observed in depressed abused children experiencing ongoing chronic adversity (marital violence, emotional abuse, poverty, lack of supports). The pattern of findings of the depressed abused children experiencing ongoing adversity parallels the pattern of HPA axis dysregulation reported in animal studies of chronic stress. They add to a growing body of literature suggesting measures of past trauma and current adversity are important sources of variability in psychobiological correlates of major depression.

Adolescent↗

The combination of in situ hybridization and immunohistochemical analysis: an evaluation of Her2/neu expression in paraffin-embedded breast carcinomas and adjacent normal-appearing breast epithelium.

The combination of in situ hybridization and immunohistochemical techniques can successfully identify viral DNA/RNA in specific subsets of cellular populations. We recently modified this method to evaluate amplification of the oncogene Her2/neu and overexpression of its protein c-erbB-2 in a series of 15 breast carcinomas. This combination allows the simultaneous evaluation of the oncogene and its corresponding protein expression in single cells and specific cellular populations in histologic tissue sections. Double staining demonstrated heterogeneity within breast carcinomas. In addition, both nuclear and cytoplasmic signals were often detected in morphologically normal-appearing adjacent breast epithelium. The ability to view both the oncogene and its corresponding protein in single cells offers a unique look at the biology of c-erbB-2.

Breast↗

Cervical thymic cyst: case reports and review of the literature.

Due to its rarity, cervical thymic cyst is seldom included in the differential diagnosis of a neck mass. Approximately 80 cases have been reported thus far, and most of these cases have occurred asymptomatically in children and adults. Only 5 cases have involved patients younger than 1 year of age. The authors report four new patients with thymic cyst in the neck. Two of the patients were newborns in whom the cyst caused airway obstruction and dysphagia. All four patients underwent successful resection of the lesions, with complete resolution of symptoms. The embryology, histopathology, and differential diagnosis of cervical thymic cysts are also reviewed. The authors recommend that despite its infrequent occurrence cervical thymic cyst should be considered in the evaluation of neck masses in children.

Child, Preschool↗

Clinical trials of bispecific antibody MDX-210 in women with advanced breast or ovarian cancer that overexpresses HER-2/neu.

MDX-210 is a bispecific antibody (BsAb) that recognizes Fc gamma R1 on monocytes and macrophages and the cell surface product of the HER-2/neu oncogene, which is overexpressed on some breast and ovarian cancers. Clinical trials have demonstrated that treatment with MDX-210 is well tolerated and that MDX-210 is both immunologically and clinically active. Optimization of the dose and schedule of MDX-210 and development of combination treatments with cytokines that modulate immune effector cells will greatly enhance the efficacy of this novel BsAb construct for treatment of tumours that overexpress HER-2/neu. We envision that MDX-210 will be effective for treating patients with tumors that overexpress HER-2/neu, especially in the minimal disease setting.

Antibodies, Anti-Idiotypic↗