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S D Williams

Publications and source records attributed to S D Williams.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ovarian germ cell tumors: an update.

Ovarian germ cell tumors, while very rare, are important beyond their incidence because they occur in young people and they are highly responsive to appropriate treatment. Since 1991, when this topic was last discussed in Seminars in Oncology, there have been a few important publications specifically devoted to ovarian germ cell tumors. In addition, a number of important studies have added to the knowledge base of chemotherapy in testis cancer. This article reviews and updates progress made in this field.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Activation of myocardial cAMP-dependent protein kinase by lysoplasmenylcholine.

Plasmalogen-specific, calcium-independent phospholipase A2 (iPLA2) is activated during myocardial ischemia. Accordingly, we have assessed the activation of myocardial protein kinases by the iPLA2 product, lysoplasmenylcholine. Lysoplasmenylcholine-activated protein kinase activity from heart cytosol fractionated on a DE-52 column was identified as cAMP-dependent protein kinase (PKA) based on the following: (1) protein kinase activity stimulated by cAMP and lysoplasmenylcholine co-eluted on sequential chromatographic steps; (2) lysoplasmenylcholine-activated protein kinase activity was inhibited by the PKA inhibitor, PKI; and (3) the unprimed PKA form generated from the primed form of PKA was activated by cAMP and lysoplasmenylcholine. These results demonstrate a novel mechanism for PKA activation by lysoplasmenylcholine.

Animals↗
PubMed1996

Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.

BACKGROUND: Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer. METHODS: The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals. RESULTS: Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group. CONCLUSIONS: As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.

Adult↗
PubMed1995

Practicing with the urban underserved. A qualitative analysis of motivations, incentives, and disincentives.

OBJECTIVE: To investigate the personal characteristics and professional experiences of medical providers working with medically underserved urban populations. DESIGN: Focus groups of primary care providers. SETTING: Public and private clinics in Salt Lake City, Utah, in which the providers had ongoing relationships with medically underserved patients. PARTICIPANTS: Twenty-four providers (11 men and 13 women), including 12 physicians (three family physicians, seven pediatricians, and two psychiatrists), one dentist, three physician assistants, and eight nurse practitioners participated in three focus groups. MAIN OUTCOME MEASURE: Interpretative analysis of verbatim quotations regarding personal beliefs, feelings, and practice experiences. RESULTS: Participants revealed a strong sense of service to humanity and pride in making a difference. They thrive on the challenge of creatively dealing with their patients' complex human needs with limited health care resources. Factors critical to survival in an urban underserved setting include a hardy personality style, flexible but controllable work schedule, and multidisciplinary practice team. The camaraderie and synergy of teams generate personal support and opportunities for continuing professional development. CONCLUSIONS: Increasing the numbers of health care professionals wanting to work with the medically underserved may be facilitated through refining admissions criteria to schools for health care professionals to include values and personality characteristics, emphasizing within curricula the important skills and practice styles necessary to work with underserved patients, and ensuring that underserved practice environments provide support through multidisciplinary teams and structured work hours. These potentially effective approaches could increase success in recruiting and retaining health care professionals to work with medically underserved patients.

Adult↗
PubMed1994

Early salvage therapy for germ cell cancer using high dose chemotherapy with autologous bone marrow support.

BACKGROUND: Patients with relapsed germ cell cancer (GCT) have a poor prognosis when treated solely with conventional chemotherapy; high dose chemotherapy with autologous bone marrow rescue (ABMR) has shown curative potential in patients with relapsed and refractory GCT. This protocol was designed to incorporate high dose therapy with initial salvage therapy. METHODS: Twenty-three patients in the first relapse of GCT received two cycles of conventional dose cisplatin-based therapy (either vinblastine, ifosfamide and cisplatin [VeIP] or cisplatin, vinblastine, and bleomycin) followed by carboplatin (1500-2100 mg/m2) and etoposide (1200-2250 mg/m2) given in divided doses with ABMR. RESULTS: Eighteen of 23 patients completed protocol therapy including high dose therapy. Five of 23 did not undergo high dose therapy due to: insurance refusal (1); patient refusal (1); active infection (1); central nervous system metastasis (1); death on induction therapy (1). Response to two courses of conventional dose induction therapy (N = 23) was complete response (CR), 8; partial response (PR), 12; stable disease (SD), 2; and toxic death, 1. Two of five individuals who did not continue with high dose therapy are alive and progression free after conventional salvage therapy and surgery with at least 24 months of follow-up. Outcome after high dose therapy (N = 18) was CR, 9, PR, 6, SD, 1, and PD, 2. Two patients who were in PR after receiving two cycles of conventional dose therapy were converted to CR using high dose therapy. There was only one treatment-related death in this cohort, a septic death during VeIP induction therapy. There were no transplant related deaths. Of those patients completing high dose therapy, 7 of 18 (39%) survived, progression free with a median follow-up of 26 months, 2 of 18 are alive with active disease, and 9 of 18 died of recurrent disease. CONCLUSIONS: Conventional dose induction therapy followed by consolidation with high dose therapy and ABMR is well tolerated and provides prolonged disease-free survival in some patients with chemosensitive relapsed germ cell cancer.

Adolescent↗
PubMed1994

Second-look laparotomy in ovarian germ cell tumors: the gynecologic oncology group experience.

The Gynecologic Oncology Group (GOG) experience with second-look laparotomy in malignant ovarian germ cell tumors is reviewed. All patients in this study were enrolled prospectively on one of three protocols that employed relatively brief cisplatin-based chemotherapy after initial surgical staging and cyto-reduction. Forty-five surgical procedures were done in patients who received three courses of cisplatin-based adjuvant therapy after complete tumor resection. Findings were no tumor or mature teratoma in 43; 2 patients had immature teratomas. One of the latter patients received further chemotherapy and one did not. Both of these patients and 44 of the total are disease free. Seventy-two patients were treated with similar chemotherapy for advanced incompletely resected tumor. Forty-eight of these patients did not have teratoma elements in their primary tumor. At surgery, 45 patients had no tumor and 3 had persistent endodermal sinus tumor or embryonal carcinoma. All three of the latter patients are dead despite further treatment. Twenty-four patients had teratoma elements in their primary tumor. Of these patients, 16 had mature teratoma at second-look, which in 7 was bulky or progressive. Fourteen of the total 16 and 6 of the 7 with bulky residual tumor remain disease free after surgical resection. Second-look laparotomy is not necessary in patients completely resected initially or in those patients with advanced tumor that does not contain teratoma. However, enough patients with incompletely resected tumor which initially contains elements of teratoma benefit from the procedure to warrant its general use.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Persistent cancer in postchemotherapy retroperitoneal lymph-node dissection: outcome analysis.

Surgery following chemotherapy for treatment of metastatic testis cancer is reserved for partial remissions with localized tumors considered resectable. After primary chemotherapy, about 90% will have teratoma or necrosis and only 10% will have cancer. The concept of two cycles of post operative chemotherapy in this small group with cancer is supported by a 70% long term cure rate. A more difficult group of patients are those who have had not only primary but also salvage chemotherapy for refractory tumor. About 55% of these patients undergoing post (salvage) chemotherapy RPLND surgery have persistent cancer in the resected specimen. There is no data to support the routine use of repeat salvage chemotherapy post operatively. Of 91 patients presenting for surgery post salvage chemotherapy, 53 were considered completely resected and 36 incompletely resected. Of the 53 realistic candidates for cure with complete resections, 25 were given post operative repeat salvage chemotherapy and 28 received none. 9 (36%) receiving more chemotherapy remained NED and 12 (43%) receiving none remained NED. 12 in each group died of disease. Therefore, there is no data to support routine repeat salvage chemotherapy in patients considered completely resected who had already received salvage chemotherapy pre-operatively. Rather the outcome in this cohort depends more on the completeness of its resectability.

Antineoplastic Agents↗
PubMed1994

Clinical and radiological features in three cases of pulmonary involvement from recurrent respiratory papillomatosis.

Clinical case reports of 3 children with recurrent respiratory papillomatosis who developed lung dissemination of the disease are presented. The radiological features of the primary pulmonary disease included papillomata in the distal airway and multiple, nodular lung lesions, both solid and cavitated. Changes secondary to pulmonary papillomatosis included atelectasis, infection and bronchiectasis. Respiratory papillomatosis involving pulmonary parenchyma is associated with a poor prognostic outcome. Early detection of such involvement and aggressive treatment of secondary infection are required to limit parenchymal damage.

Child, Preschool↗
PubMed1994

Incidence of neutropenic fever in patients treated with standard-dose combination chemotherapy for small-cell lung cancer and the cost impact of treatment with granulocyte colony-stimulating factor.

PURPOSE: We sought to determine the incidence of neutropenic fever associated with the use of standard-dose combination chemotherapy for small-cell lung cancer (SCLC) and to use these data as a template to analyze the costs and benefits of the routine use of granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: We retrospectively reviewed records of 137 consecutive, unselected patients with SCLC treated with combination chemotherapy from January 1987 to March 1992. Admission criteria for neutropenic fever were temperature > or = 38.5 degrees C and an absolute neutrophil count < or = 500/microL. Neutropenic fevers were managed with a 25% dose reduction of the myelosuppressive drugs in subsequent cycles. Charge estimates for hospitalization ($1,244 per day) and G-CSF use ($2,027 per course) were estimated by reviewing charges to patients at Indiana University hospitalized for neutropenic fever or treated with outpatient G-CSF. We imposed assumptions from the Neupogen (filgrastim; Amgen Inc, Thousand Oaks, CA) licensing trial regarding the effectiveness of G-CSF and the Indiana University charge estimates on three models of G-CSF use: (1) preemptive--with all courses of chemotherapy, (2) reactive--with all cycles of chemotherapy following a neutropenic fever, and (3) dose reduction only (no G-CSF)--to derive charge estimates for G-CSF use. RESULTS: Records of 137 patients with SCLC were identified and reviewed. The incidence of neutropenic fever was 12% in the first cycle of chemotherapy, and 18% overall, compared with the placebo- and G-CSF-treated arms of the Neupogen licensing trial, in which the incidence of neutropenic fever was 77% and 40%, respectively. Other therapeutic outcomes, such as neutropenic septic deaths, response rates, and survival, were comparable. We derived the following charge estimates for the three models of G-CSF: (1) preemptive--total charges = $1,287,481; (2) reactive--total charges = $276,154; and (3) dose reduction only--total charges = $192,820. CONCLUSION: The incidence of neutropenic fever with standard-dose chemotherapy for SCLC was 18%. Routine use of G-CSF in SCLC patients treated with standard-dose chemotherapy appears to be expensive and is not associated with an obvious therapeutic benefit or cost savings. We suggest that careful analysis of the incidence of infectious complications, rather than granulocyte nadir and duration, be performed, and that clinical guidelines for the use of these effective, but expensive, products be developed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Understanding physicians' decisions to practice in rural areas as a basis for developing recruitment and retention strategies.

The shortage of providers in rural areas is threatening the quality and availability of health care in many communities. The causes of the provider shortage are many and varied-from economic to social to personal. Government programs have addressed the issue of provider supply by offering scholarships and loan repayment programs for medical students who then must fulfil service obligations in underserved settings, among which are rural areas. Experience has shown that once providers complete their obligations under these grant programs, retention of providers in rural areas becomes an even more critical issue. Using focus group research, this study explores the practice setting choices of a group of physicians currently practicing in rural areas. The discussion reveals that personal values are one of the primary motivators for choosing to practice in rural settings while lack of availability of career opportunities for spouses and educational opportunities for children are major obstacles. The health care system poses barriers to success for providers in rural settings. The key rewards from rural practice are the ability to become integrated into the local community and the provider/patient relationships that develop in such settings. These findings are used as the basis for proposing recruitment and retention strategies for providers to improve access to medical care by patients in rural areas.

Career Choice↗
PubMed1994

Salvage chemotherapy for recurrent germ cell cancer.

Clinical trials of chemotherapy in germ cell cancer have explored the full range of the relationship of chemotherapy dose and intensity. In good-risk patients, successful efforts have diminished the duration of treatment or number of drugs required to reliably cure the illness. In patients with a poor prognosis, efforts to intensify therapy have been undertaken. In the setting of disease recurrence after primary chemotherapy, the outlook is considerably less hopeful, as only 20% to 30% of patients survive recurrent illness. Current standard treatment in this setting is combination therapy with ifosfamide and cisplatin, given with either etoposide or vinblastine. High-dose chemotherapy with bone marrow or peripheral blood stem cell support can cure a small portion of selected patients with multiple recurrences of germ cell cancer. The impact of earlier treatment with high-dose chemotherapy (either as initial salvage therapy or primary treatment) is less certain. Clinical trials in these settings have not yet demonstrated a definite advantage over less toxic conventional-dose therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Current management of ovarian germ cell tumors.

Ovarian germ cell tumors, although rare, are important because they occur in young individuals and frequently are fulminant if initial treatment is inadequate. These tumors can be broadly divided into dysgerminomas and nondysgerminomatous tumors, although in reality many tumors are of mixed pathology. Surgical staging is important, and when performed by inexperienced surgeons is often inadequate. However, except for localized purely dysgerminomatous tumors, prompt institution of chemotherapy is more appropriate than repeat exploration to establish more precise staging. Tumors other than dysgerminoma are most often treated with etoposide-containing regimens, and recent studies suggest that patients with dysgerminomas also should be treated primarily with chemotherapy.

Antineoplastic Agents↗
PubMed1993

Thymic carcinoma. A distinct clinical entity responsive to chemotherapy.

BACKGROUND: Thymic carcinomas are rare tumors of the anterior mediastinum. These tumors are distinct thymic neoplasms that differ from their more common counterpart, thymoma. As opposed to thymomas, thymic carcinomas are histologically malignant neoplasms with a clinical course that tends to be much more aggressive than that of patients with thymoma. METHODS: Between 1984 and 1990, five patients with thymic carcinoma treated with cisplatin-based combination chemotherapy were seen at Indiana University Hospital. These patients' diagnoses, courses, and treatments were reviewed. RESULTS: Three patients responded (two completely) to cisplatin-based chemotherapy. CONCLUSIONS: This form of chemotherapy merits additional study in such patients, and our experience indicates that at least some will have clinically meaningful responses. The optimum regimen is unclear, but would contain cisplatin and probably should be similar to that used in germ cell tumors.

Adult↗
PubMed1993

Secondary leukemia associated with a conventional dose of etoposide: review of serial germ cell tumor protocols.

BACKGROUND: Case reports have suggested that treatment with high-dose etoposide can result in development of a unique secondary leukemia. PURPOSE: This study was designed to estimate the risk of developing leukemia for patients receiving conventional doses of etoposide along with cisplatin and bleomycin. METHODS: We reviewed the records at Indiana University of all untreated patients entering clinical trials using etoposide at conventional doses (cumulative dose, 2000 mg/m2 or less) for germ cell cancer between 1982 and 1991. The records of all patients who received a chemotherapy regimen containing etoposide, ifosfamide, or cisplatin after failing to respond to primary chemotherapy were also reviewed. RESULTS: Between 1982 and 1991, 538 patients entered serial clinical trials with planned cumulative etoposide doses of 1500-2000 mg/m2 in combination with cisplatin plus either ifosfamide or bleomycin. Of these 538 patients, 348 received an etoposide combination as initial chemotherapy and 190 received etoposide as part of salvage treatment. To date, 315 patients are alive, with median follow-up of 4.9 years, and 337 patients have had follow-up beyond 2 years. Two patients (0.37%) developed leukemia. One developed acute undifferentiated leukemia with a t(4;11) (q21;q23) cytogenetic abnormality 2.0 years after starting etoposide-based therapy, and one developed acute myelomonoblastic leukemia with no chromosome abnormalities 2.3 years after beginning chemotherapy. During this period, several hundred patients were treated with etoposide-based chemotherapy and did not enter clinical trials. Three of these patients are known to have developed hematologic abnormalities, including one patient with acute monoblastic leukemia with a t(11;19)(q13;p13) abnormality. CONCLUSIONS: Secondary leukemia after treatment with a conventional dose of etoposide does occur, but the low incidence does not alter the risk-to-benefit ratio of etoposide-based chemotherapy in germ cell cancer. IMPLICATIONS: The reports of leukemia associated with high doses of etoposide emphasize the need for diligent follow-up of patients and make careful risk-to-benefit analysis imperative.

Adolescent↗
PubMed1993

Dose intensity in germ cell cancer: continued lessons from a model neoplasm.

Clinical trials of chemotherapy in germ cell cancer have explored the full range of dose intensity. In good risk patients, efforts have been successful in diminishing duration of treatment or number of drugs required to cure the illness reliably. In patients with poor prognosis, efforts to intensify therapy have been undertaken. It has been difficult to demonstrate improved outcome using higher doses of conventional agents in the setting of primary treatment of poor risk disease. It is more likely that improvement will come with the discovery of new active agents. High dose chemotherapy with bone marrow or peripheral blood stem cell support can cure a small portion of selected patients with multiple recurrences of germ cell cancer. The impact of earlier treatment with high dose chemotherapy as initial salvage therapy or even primary treatment is less certain. Clinical trials in these settings have not yet demonstrated a definite advantage over less toxic conventional dose therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Outcome analysis for patients with persistent nonteratomatous germ cell tumor in postchemotherapy retroperitoneal lymph node dissections.

PURPOSE: We review the long-term outcome of patients with viable nonteratomatous germ cell tumor (NTGCT) in retroperitoneal lymph node dissection (RPLND) specimens after primary or salvage chemotherapy, and the impact of postoperative therapy with two courses of standard-dose cisplatin-based induction chemotherapy. PATIENTS AND METHODS: All patients with viable NTGCT in postchemotherapy RPLND specimens from surgeries performed at Indiana University between July 1975 and March 1991 were retrospectively reviewed. RESULTS: Of 580 postchemotherapy RPLNDs performed, 133 had viable NTGCT in their pathology specimens. Of these 580 postchemotherapy RPLNDs, 417 were performed after primary chemotherapy, and 43 (10%) had viable NTGCT in their pathology specimens. There were 163 RPLNDs performed after salvage chemotherapy and 90 (55%) had viable NTGCT in their pathology specimens. After primary chemotherapy, 34 of 43 had complete resections, and 27 of the 34 received postoperative cisplatin-based chemotherapy. Nineteen of 27 (70%) are continuously disease-free (c-NED). All seven who received no postoperative chemotherapy have relapsed. After salvage chemotherapy, 53 of 90 had complete resections. Of those 53, 25 received postoperative chemotherapy, and nine (36%) are c-NED. Twenty-eight received no postoperative chemotherapy, and 12 (43%) are c-NED. Overall, 43 of 133 patients had incomplete resections, and only four are currently disease-free. There were four postoperative deaths (PODs). CONCLUSION: (1) Incomplete resection of viable NTGCT after primary or salvage chemotherapy portends a very poor prognosis. (2) For patients with complete resection of viable NTGCT following primary chemotherapy, two additional courses of cisplatin-based chemotherapy appear to be safe and effective therapy for reducing the risk of relapse. (3) Additional standard-dose chemotherapy appears to offer no benefit to patients with viable NTGCT in the resected specimen after salvage chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Effects of time-in-clinic, clinic setting, and faculty supervision on the continuity clinic experience.

STUDY OBJECTIVE: To evaluate the effects of setting, type of supervision, and time in clinic on the resident continuity clinic experience. DESIGN: Prospective cohort with preintervention and postintervention measures. SETTINGS: Pediatric residents selected one of three clinic settings for their continuity clinic experience. These included a traditional, university-based clinic, private practice offices, and publicly funded community-based clinics. SUBJECTS: All pediatric residents at the University of Utah Health Sciences Center, July 1985 through June 1991. INTERVENTIONS: Using varied clinic sites, matching residents one or two to one with preceptors for their continuity clinic, increasing continuity clinic from 1 to 2 half-days per week. MEASUREMENTS AND MAIN RESULTS: Residents in private offices had the most varied experience, seeing more patients, more acute care, and a broader age range of patients than residents at other sites. They were more likely both to be observed by their preceptors during patient visits and to observe their preceptors delivering care. Because the number of patients seen per session rose, increasing continuity clinic time from one to two half-days per week more than doubled the number of patients seen per week. Increased time away from hospital did not affect scores on the Pediatric In-Training Examination. While test scores were similar for incoming residents, those in private offices scored higher on the final Behavioral Pediatrics Examination (P < .05). CONCLUSIONS: Clinic setting, time in clinic, and faculty supervision affect the quality of the continuity clinic experience. Increased time in clinic resulted in a broader exposure to patients. Residents placed in private offices had a more varied patient mix, were more closely supervised, and seemed to gain primary care skills more rapidly than residents at other sites.

Clinical Competence↗