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Biomedical subjects

B Webber

Publications and source records attributed to B Webber.

At least 19 recordsLinked to original sources

Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease.

PURPOSE: The study goal was to improve outcome in children with rhabdomyosarcoma by comparing risk-based regimens of surgery, radiotherapy (RT) and chemotherapy. PATIENTS AND METHODS: Eight hundred eighty-three previously untreated eligible patients with nonmetastatic rhabdomyosarcoma entered the Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) (1991 to 1997) after surgery and were randomized treatment by primary tumor site, group (1 to 3), and stage (I to III). Failure-free survival (FFS) rates and survival were the end points used in comparisons between randomized groups and between patient subgroups treated on IRS-III and IRS-IV. Most patients were randomized to receive vincristine and dactinomycin (VA) and cyclophosphamide (VAC, n = 235), or VA and ifosfamide (VAI, n = 222), or vincristine, ifosfamide, and etoposide (VIE, n = 236). Patients with group 3 tumors were randomized to receive conventional RT (C-RT) versus hyperfractionated RT (HF-RT). RESULTS: Overall 3-year FFS and survival were 77% and 86%, respectively. Three-year FFS rates with VAC, VAI, and VIE were 75%, 77%, and 77%, respectively (P =.42). No significant difference in outcome was noted with HF-RT versus C-RT (P =.85 and P =.90, respectively). Overall, patients with embryonal tumors benefited from intensive three-drug chemotherapy in IRS-IV (3-year FFS, 83%). The improvement was seen for patients with stage I or stage II/III, group 1/2 disease, many of whom received VA chemotherapy on IRS-III. Patients with stage 2/3, group 3 disease had similar outcomes on IRS-III and IRS-IV. Three-year FFS for the nonrandomized patient subsets was 75% with renal abnormalities; 81% for paratesticular, group 1 cases; and 91% for group 1/2 orbit or eyelid tumors. Patients with paratesticular primaries had poorer outcomes if they were more than 10 years old (3-year FFS, 63% v 90%). Myelosuppression occurred in most patients, but toxic deaths occurred in less than 1%. CONCLUSION: VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.

Adolescent↗

Development, characterization and therapy of a disseminated model of childhood neuroblastoma in SCID mice.

PURPOSE: To develop a highly reproducible model of disseminated childhood neuroblastoma in mice to allow secondary evaluation of therapeutics against microscopic disseminated disease. METHODS: CB17/Icr SCID were injected i.v. with 10(3) to 5 x 10(6) human NB-1691 neuroblastoma cells. NB-1691 cells were detected by PCR for synaptophysin and tyrosine hydroxylase in peripheral blood, and bone marrow. Therapeutic studies evaluated topotecan and vincristine as single agents or in combination. Topotecan was administered i.v. daily for 5 days on two consecutive weeks. Courses were repeated every 21 days for three cycles. Vincristine (1 mg/kg) was administered i.v. every 7 days for nine consecutive weeks. Treatment started 11-21 days after tumor cell inoculation. RESULTS: Following injection of > or = 1 x 10(5) cells 100% of mice developed disease. Mice inoculated with 10(7) cells survived a median of 42 days. Survival time was a linear function of the cell inoculum. At autopsy, gross tumor was routinely detected in many organs in particular liver, ovaries, kidneys and adrenals. NB-1691 cells were detected by PCR in peripheral blood, and bone marrow. Immunohistochemical staining showed that lesions were strongly positive for synaptophysin, chromogranin A and negative for leukocyte common antigen. Topotecan (0.6 mg/kg) alone extended median survival from 44 days (controls) to 95 days. When treatment was started 21 days after inoculation of NB-1691 cells, topotecan extended median survival from 39 days (controls) to 91 and 99 days at dose levels of 0.3 and 0.6 mg/kg, respectively. Vincristine (1 mg/kg) extended survival by a median of 9.5 days. In combination with vincristine (1 mg/kg), median survival was increased to 141 days (topotecan 0.6 mg/kg) and 159 days (topotecan 1.0 mg/kg). CONCLUSION: This model of disseminated neuroblastoma is highly reproducible. As this model may more closely simulate childhood disease it may be a valuable adjunct in developing new approaches to advanced stage, poor prognosis neuroblastoma.

Animals↗

Complications of an intra-arterial injection from an inferior alveolar nerve block.

BACKGROUND: Unintended intravascular injections from inferior alveolar nerve blocks result in frustrating complications, both systemically and locally. It is imperative that the dentist diagnose the complication and treat it appropriately. Sometimes, several reactions occur simultaneously. CASE DESCRIPTION: The authors present a case report that illustrates some of the many complications resulting from inferior alveolar nerve block injections. In this case, complications developed from intra-arterial injection of local anesthetic. The facial skin, intraoral structures and eye were affected. Within 60 minutes of the injection, all structures returned to their normal state. Prompt diagnosis and reassurance usually calm the patient. CLINICAL IMPLICATIONS: Even when clinicians use the utmost care, by aspirating before the injection and noting anatomical landmarks, intra-arterial injections can occur during inferior alveolar nerve blocks. Fortunately, permanent damage to nerves, facial and oral tissues, and eyes is rare. The practitioner should diagnose and treat the problems appropriately to avoid any irreversible complications.

Adult↗

TraumaSCAN: assessing penetrating trauma with geometric and probabilistic reasoning.

This paper presents TraumaSCAN, a prototype computer system for assessing the effects of penetrating trauma to the chest and abdomen. TraumaSCAN combines geometric reasoning about potentially injured anatomic structures with (probabilistic) diagnostic reasoning about the consequences of these injuries. We also present results obtained from testing TraumaSCAN retrospectively on 26 actual gunshot wound cases.

Bayes Theorem↗

Preoperative paclitaxel, carboplatin, and radiation therapy in advanced head and neck cancer (stage III and IV).

Preoperative chemotherapy and chemoradiation protocols are generally associated with high clinical response rates but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel and carboplatin plus concurrent, fractionated external-beam radiation, followed by organ-preserving or function-restorative surgery (when applicable to maximize locoregional tumor control). Operable patients staged by triple endoscopy received a percutaneous gastrostomy and vigorous dental and nutritional support during therapy. Paclitaxel 60 mg/m2 and carboplatin at an area under the concentration-time curve of 1 were administered weekly with radiation therapy 45 Gy, with repeat biopsy of the primary site at 5 weeks. Patients with a positive biopsy had definitive surgery within 4 to 5 weeks. Patients with a negative biopsy received 3 additional weeks of radiation therapy, to a total dose of 72 Gy plus paclitaxel and carboplatin. Forty-three patients were enrolled, including 33 men and 10 women ranging in age from 37 to 81 years. Fourteen patients had stage III disease, 19 patients had stage IVA disease, and 10 patients had stage IVB disease. Sites of disease included the floor of the mouth (n = 8), tongue (n = 8), oropharynx (n = 5), hypopharynx (n = 4), larynx (n = 12), palate-tonsil (n = 2), unknown primary (n = 3), and nasal cavity (n = 1). Of 38 patients evaluable for primary response (two patients had unknown primary tumor, two patients failed to complete the chemoradiation protocol, and one patient was evaluable for toxicity only), 18 patients had a complete clinical response and 20 patients had a partial response; the overall clinical response rate was 100%. A pathologic clinical response at the primary site occurred in 25 of these 38 patients (66%), who subsequently received completion radiation (67 to 72 Gy). After induction chemoradiation, 36 patients with N1-N3 nodes had neck dissection; seven had positive nodes (19%). Fourteen patients had residual cancer at the primary site at the time of the repeat biopsy. Sites of the lesions were the floor of the mouth/mandible (n = 4), nasal cavity/maxilla (n = 2), base of tongue (n = 2), and larynx (n = 6). All were resected with function-preserving reconstruction (two patients required total laryngectomy and one patient refused surgery). At a median follow-up of more than 16 months, progression-free and overall survival rates were 64% and 68%, respectively. Preoperative paclitaxel, carboplatin, and radiation was associated with a high clinical response rate at the primary site and a high level of organ preservation or functional restoration, if ablation was performed.

Adult↗

Preoperative chemoradiation coupled with aggressive resection as needed ensures near total control in advanced head and neck cancer.

BACKGROUND: Preoperative chemotherapy or chemoradiation protocols are generally associated with high clinical response rates, but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel 60 mg/M2, and carboplatin (AUC of 1) plus concurrent fractionated external beam radiation (45 Gy) followed by organ-preserving (or function restorative) surgery when applicable to maximize local-regional tumor control. PATIENTS AND METHODS: Operable patients staged by triple endoscopy received a percutaneous endoscopic gastrostomy and vigorous dental and nutritional support during therapy. Weekly paclitaxel 60 mg/M2, carboplatin (AUC of 1), and radiation 45 Gy were given with rebiopsy of the primary site at 5 weeks. Patients with positive biopsy had definitive surgery in 4 to 5 weeks. Patients with negative biopsy-results received 3 additional weeks of radiation, to a total dose of 72 Gy plus carboplatin and paclitaxel. RESULTS: The 35 patients were 29 men and 6 women, aged 40 to 71 years, with stage III (12) or stage IV (23) cancer. The site of the cancer was oral cavity, 10; base of tongue, 3; oropharynx, 3; hypopharynx, 4; larynx, 12 (glottic, 6; supraglottic, 6), unknown primary, 2; other, nasal cavity, 1. Of 34 evaluable patients, 16 (47%) had a complete clinical response (CR) and 18 (53%) had a partial response (PR); total clinical response rate was 100%. A pathologic CR at the primary site occurred in 23 of 34 patients (68%; 2 had an unknown primary) who went on to completion radiation at 67 to 72 Gy. After induction chemoradiation 21 patients with N1-3 nodes had neck dissection; 6 (31%) had positive nodes. Twelve patients had residual cancer at the primary site at time of rebiopsy: mandible, 4; maxilla, 1; base of tongue, 2; larynx, 4; floor of mouth, 1; and nasal cavity, 1. All were resected with function-preserving reconstruction. At median follow-up of >12 months, progression-free and overall survivals were 71% and 83%, respectively. CONCLUSION: Preoperative treatment with paclitaxel, carboplatin, and radiation is associated with high CR at the primary site and a high level of organ preservation or functional restoration if ablation is done.

Adult↗

Ewing's sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991.

PURPOSE: One hundred thirty of 2,792 patients (5%) registered on three Intergroup Rhabdomyosarcoma Study clinical trials (IRS-I, -II, and -III) from 1972 to 1991 had an extraosseous Ewing's sarcoma (EOE). We report here the results of multimodality therapy for this tumor. PATIENTS AND METHODS: The 130 patients were less than 21 years of age; 70 (54%) were males. Primary tumor sites were on the trunk in 41 patients, an extremity in 34, the head/neck in 23, the retroperitoneum/pelvis in 21, and other sites in 11. One hundred fourteen patients had no metastases at diagnosis. In 21 patients, the tumor was completely resected; in 30, the localized or regional tumor was grossly resected, and in 63 patients, grossly visible sarcoma was left behind. Sixteen patients (12%) had distant metastases at diagnosis. All patients were given multiagent chemotherapy and most received irradiation (XRT); none were treated with bone marrow transplantation. RESULTS: One hundred seven patients (82%) achieved a complete response. At 10 years, 62%, 61%, and 77% of the patients were alive after treatment on IRS-I, IRS-II, or IRS-III therapeutic protocols, respectively, similar to figures obtained in all IRS patients. At last follow-up evaluation, 42 patients had died of progressive tumor and one of infection. Survival at 10 years was most likely for patients with tumor that arose in the head and neck, extremities, and trunk, and for those who underwent grossly complete tumor removal before initiation of chemotherapy. For patients with localized, gross residual tumor, adding doxorubicin (DOX) to the combination of vincristine, dactinomycin, cyclophosphamide (VAC), and XRT did not significantly improve survival in 39 patients (62% alive at 10 years) compared with that of 24 patients treated with VAC and XRT without DOX (65% alive at 10 years, P = .93). CONCLUSION: This series indicated that EOE in children is similar to rhabdomyosarcoma (RMS) in its response to multimodal treatment. No benefit was apparent from the addition of DOX to VAC chemotherapy in patients with gross residual EOE.

Adolescent↗

Probabilistic predictions of penetrating injury to anatomic structures.

This paper presents an interactive 3D graphical system which allows the user to visualize different bullet path hypotheses and stab wound paths and computes the probability that an anatomical structure associated with a given penetration path is injured. Probabilities can help to identify those anatomical structures which have potentially critical damage from penetrating trauma and differentiate these from structures that are not seriously injured.

Anatomy, Cross-Sectional↗

The argument for conservative, delayed surgery in the management of prostatic rhabdomyosarcoma.

Exenteration is no longer required for most patients who have rhabdomyosarcoma (RMS) of the prostate. This site comprised only about 5% of newly diagnosed cases in the IRS-III (1984-1991). The mean age at the time of diagnosis was 5.3 yrs (range, 0 to 19 years). Most tumors were relatively large, had embryonal histology, and were clinically localized but unresectable without major loss of organ function. The 44 patients with group III tumors (gross residual disease) were treated according to the IRS-III protocol. Forty-three of them underwent biopsy only, and one patient had subtotal resection as the initial procedure. The average number of surgical procedures per patient was two (range, one to five). Six of the 44 patients had no additional surgery. The second-look procedures performed in the other 38 patients included exenteration (14), prostatectomy (7), cystoscopic/perineal needle biopsy (8), laparotomy with biopsy (6), and subtotal excision with bladder salvage (3). Additional surgery was required for four patients, for evaluation of a residual mass, postoperative fistula, ureteral stricture, or small bowel obstruction. Six patients with relapse or residual disease underwent additional chemotherapy and late exenteration (3), prostatectomy (1), or biopsy (2). Four of the six have been cured, one is in treatment for a second malignancy, and the other has residual disease after exenteration. Thirty-six of the 44 patients with group III tumors have been cured (minimum follow-up period, 6 years; range, 6 to 11 years), compared with 23 of the 47 in IRS-II (1978-1984) (P = .001). Two of the six deaths in this group were caused by infection. The bladder salvage rate for those cured of their disease also was better (64% v 57% for IRS-II). The two patients with group IIA tumors were cured by gross primary excision, local radiotherapy, and vincristine and actinomycin therapy. By contrast, all patients with metastatic disease (group IV) died of the tumor. Conservative, delayed surgery, performed after intensive chemotherapy with or without radiotherapy, yields a better cure rate while maintaining a high rate of bladder salvage in children with group III prostatic RMS.

Adolescent↗

Linking anatomy and physiology in modeling respiratory mechanics.

We present an integrated 3D virtual environment for the quantitative modeling of the anatomy and the physiology of the pulmonary system. Our approach formally integrates 3D deformable object modeling with conventional models of respiratory mechanics. We demonstrate quantitatively, aspects of the behavior of the respiratory system qualitatively known to clinicians, such as normal quiet breathing and an open sucking chest wound. Our methodology is general and can be used to model both the anatomy and the physiology at many levels of detail. Another important aspect of our approach is that based on our previously developed computer vision techniques we can make such a simulation patient specific. The usefulness of such a system is manifold. Medical education, surgical planning, disease diagnosis are some of the many areas such a system can be applied.

Computer Simulation↗

Children with vesical rhabdomyosarcoma (RMS) treated by partial cystectomy with neoadjuvant or adjuvant chemotherapy, with or without radiotherapy. A report from the Intergroup Rhabdomyosarcoma Study (IRS) Committee.

PURPOSE: Children with bladder rhabdomyosarcoma (RMS) are currently treated with primary chemotherapy and usually with local irradiation. More than 30% of this group ultimately require total cystectomy. The purpose of this study was to review the results of the use of partial as opposed to total cystectomy in 40 patients with bladder RMS during Intergroup Rhabdomyosarcoma Study (IRS)-I, -II, and -III (1972-1989). PATIENTS AND METHODS: A total of 171 children with primary RMS of the bladder were enrolled in the IRS during this interval. Partial cystectomy was performed in 40, in 33 before any other therapy and in seven after 10-57 weeks of chemotherapy (primarily vincristine, actinomycin-D, and cyclophosphamide, i.e., VAC) +/- radiotherapy. Surviving patients have been observed for 4-22 years. RESULTS: Thirty-one of 40 patients (78.5%) have been disease free for 2-16 years. Survival among all other IRS cases with bladder RMS during the same interval was 79.5%. Of the 31 surviving patients, one required secondary total cystectomy and two required bladder augmentation procedures for benign bladder contracture. Three quarters of the total group of living patients who have undergone partial cystectomy are without bladder-related symptoms or demonstrable lower urinary tract disease. The remaining patients have a history of functional bladder problems related to contracture or incontinence. CONCLUSIONS: Partial cystectomy is an alternative to total cystectomy for bladder RMS when the tumor site makes it anatomically feasible. In such patients, it should be considered before total cystectomy and in patients with persistent areas of questionable residual tumor after otherwise apparently successful regimens of primary chemotherapy +/- radiotherapy.

Adolescent↗

Generating penetration path hypotheses for decision support in multiple trauma.

We present a 3D graphical system that allows users to visualize different penetration path hypotheses for (multiple) gunshot or stab wounds, using a 3D graphical model of a human body with appropriate anatomical structures. The system also identifies the anatomical structures associated with each hypothesis. The various penetration path hypotheses follow from a combinatorial analysis of the set of surface wounds. The affected structures are determined by performing a detailed interpenetration analysis between 3D models of a penetration path and each anatomical structure within the body.

Computer Simulation↗

Neonatal rhabdomyosarcoma: the IRS experience.

Neonatal rhabdomyosarcoma is rare, and the characteristics and optimal therapy for patients with this condition have not been well described. Of 3,217 eligible patients entered in the Intergroup Rhabdomyosarcoma Study (IRS), 14 were less than 30 days old at the time of diagnosis. Among these patients, male gender, Caucasian race, caudal tumors, and embryonal/botryoid and undifferentiated histology predominate. Although half the neonates survived, neither histology, tumor size, nor type of surgery were predictive of outcome. The presence of necrosis and small round cell configuration coincides with a poor prognosis, regardless of histological diagnosis. Neonatal rhabdomyosarcoma of caudal origin has a favorable prognosis.

Age Factors↗

A prospective study of nonrhabdomyosarcoma soft tissue sarcomas in the pediatric age group.

Nonrhabdomyosarcoma soft tissue sarcomas in infants and children are rare malignancies with most of the clinical data gained by retrospective analysis. In 1986, a prospective multicentered study was initiated by the Pediatric Oncology Group (POG) with a total of 75 cases now entered for epidemiologic examination. Median age of presentation was 12 years (range, newborn to 20 years). The male to female ratio was 2.3 to 1. The most common soft tissue tumor was synovial cell sarcoma (32/75, 42%), followed by fibrosarcoma (10/75, 13%), malignant fibrous histiocytoma (9/75, 12%), and malignant neurogenic tumors (8/75, 10%). Sixty-five percent of all tumors presented on the extremities (44% lower extremity, 21% upper extremity). Tumors of the trunk accounted for 28% (abdomen 15%, thorax 13%), whereas head and neck tumors were 7%. By TNMG classification, 16% presented as stage I, 21% as stage II, 33% as stage III, and 30% as stage IV. Age at presentation did not affect clinical site or stage. All upper extremity tumors presented with localized disease, whereas lower extremity tumors presented with regional nodal disease in 7% and metastatic disease (pulmonary) in 23% of the cases. Seventy-eight percent of the abdominal tumors were metastatic at diagnosis; the other 22% had extensive regional disease. In the thorax 78% had localized lesions with 22% having extensive regional disease. Ninety percent of synovial cell sarcomas were on the extremities: 84% localized disease and 12% metastatic spread at presentation. Sixty percent of the fibrosarcomas presented on the extremities with 80% having localized disease and 20% metastatic spread. Only 25% of the neurogenic tumors presented with localized disease, whereas 50% had metastases at the time of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Late effects of therapy in patients with paratesticular rhabdomyosarcoma. Intergroup Rhabdomyosarcoma Study Committee.

PURPOSE: We report on long-term health-related problems determined from extended follow-up of 86 children and adolescents who were treated for paratesticular rhabdomyosarcoma on the Intergroup Rhabdomyosarcoma Studies I and II (IRS I-II). PATIENTS AND METHODS: Patients were treated between 1972 and 1984, and ages at diagnosis ranged from 10 months to 19 years. The majority of these patients had initial retroperitoneal lymph node dissection (RLND) or sampling performed. RESULTS: Problems related to surgical procedures included bowel obstruction in nine patients, loss of normal ejaculatory function in eight, development of a hydrocele in five, and lymphedema of the leg in five. Sequelae related to radiotherapy were difficult to assess with the exception of three patients whose remaining testes were in the field of radiotherapy. In general, kidney and bladder function were normal in patients who received radiotherapy to the paraaortic lymph nodes and/or bladder. Four patients who had abdominal radiotherapy had chronic diarrhea. Two patients had urethral strictures and urethritis. Four patients had bone or soft tissue hypoplasia in the field of radiotherapy. Chemotherapy-related late effects were primarily hemorrhagic cystitis or gonadal dysfunction after cyclophosphamide. A third of the patients who received cyclophosphamide developed hemorrhagic cystitis, and half of these had extended periods of gross hematuria after therapy was discontinued. The testicular size was small in children whose testes were irradiated and in some who received cyclophosphamide. Tanner staging was normal in 45 patients for whom it was recorded. Elevated follicle-stimulating hormone (FSH) values or known azoospermia occurred in more than half the patients for whom data were available. CONCLUSIONS: A variety of sequelae related to therapy were determined in this patient population. These findings suggest that some aspects of therapy warrant reevaluation and that improved plans for follow-up care need to be provided.

Adolescent↗