Biomedical subjects

G Lyman

Publications and source records attributed to G Lyman.

At least 19 recordsLinked to original sources

PubMed2003

Colony stimulating factors for chemotherapy induced febrile neutropenia.

BACKGROUND: Febrile neutropenia is a frequent event for cancer patients undergoing chemotherapy and it is potentially a life threatening situation. The current treatment is supportive care plus antibiotics. Colony stimulating factors (CSF) are cytokines that stimulate and accelerate the production of one or more cellular lines in bone marrow. Some clinical trials addressed the question of whether the addition of CSF to antibiotics (ATB) could improve the outcomes of patients with febrile neutropenia. The results of these trials are conflicting and no definitive conclusion could be reached. OBJECTIVES: To evaluate the safety and effectiveness of adding colony stimulating factors to ATB when treating febrile neutropenia caused by cancer chemotherapy. SEARCH STRATEGY: The search covered the major electronic databases: CANCERLIT, EMBASE, LILACS, MEDLINE, SCI and The Cochrane Controlled Trials Register. Experts were consulted and references from the relevant articles scanned. SELECTION CRITERIA: We looked for all randomized controlled trials (RCTs) that compare CSF plus antibiotics versus antibiotics alone for the treatment of established febrile neutropenia in adults and children. DATA COLLECTION AND ANALYSIS: Two of the reviewers independently selected, critically appraised and extracted data from the studies. A meta-analysis of the select studies was performed, using Review Manager. MAIN RESULTS: More than 8000 references were screened. Thirteen studies were included. The overall mortality was not influenced by the use of CSF [Odds Ratio (OR) = 0.68; 95% Confidence Interval (CI) = 0.43 to 1.08; p=0.1]. A marginally significant result was obtained for the use of CSF in reducing infection related mortality [OR= 0.51; 95% CI = 0.26 to 1.00; p=0.05], but this result was highly influenced by one study. When this study is excluded from our analysis, this possible benefit disappears [OR= 0.85; 95% CI = 0.33 to 2.20; p= 0.7]. The group of patients treated with CSF had a shorter length of hospitalization [Hazard Ratio (HR) = 0.63; 95% CI = 0.49 to 0.82; p=0.0006] and a shorter time to neutrophil recovery [HR= 0.32; 95% CI = 0.23 to 0.46; p < 0.00001]. REVIEWER'S CONCLUSIONS: The use of CSF in patients with febrile neutropenia due to cancer chemotherapy does not affect overall mortality, but reduces the amount of time spent in hospital and the neutrophil recovery period. It was not clear whether CSF has an effect on infection-related mortality.

Adult↗

PubMed2000

Impact of hot flashes on quality of life among postmenopausal women being treated for breast cancer.

Hot flashes are among the most commonly reported symptoms among women who have completed treatment for breast cancer. Relatively little is known, however, about hot flashes among women while they are undergoing breast cancer treatment. The present study investigated the prevalence and severity of hot flashes of women during chemotherapy and radiotherapy for breast cancer. We also sought to identify the medical, demographic, and treatment correlates of hot flashes during treatment and to document the impact of hot flashes on quality of life. Seventy postmenopausal women with breast cancer completed a self-report questionnaire packet during chemotherapy and radiotherapy. Forty percent (n = 28) reported hot flashes during the week prior to assessment. Of the 28 women endorsing hot flashes, 25% (n = 7) rated them as severe, 39% (n = 11) rated them as moderate, and 36% (n = 10) rated them as mild. Women with hot flashes were significantly (p < 0.05) younger and reported significantly (p < 0.001) more fatigue, poorer sleep quality, and poorer physical health compared to women without hot flashes. Multivariate analyses revealed that, even after controlling for relevant medical, demographic, and treatment variables, the prevalence of hot flashes significantly (p < 0.05) predicted poorer sleep quality, more fatigue, and worse physical health. The results indicate that hot flashes are experienced by a sizable percentage of postmenopausal breast cancer patients as they undergo treatment. Hot flashes during cancer treatment appear to have a negative impact upon patient quality of life that may be due, in part, to fatigue and interference with sleep. Future research should seek to evaluate interventions to relieve hot flashes during breast cancer treatment as a means of improving patient quality of life.

Aged↗

PubMed2000

Clinical relevance of molecular staging for melanoma: comparison of RT-PCR and immunohistochemistry staining in sentinel lymph nodes of patients with melanoma.

OBJECTIVE: To determine the clinical significance of a molecular assay based on the reverse transcriptase polymerase chain reaction (RT-PCR) for the presence of micrometastatic melanoma cells in sentinel lymph nodes (SLNs). SUMMARY BACKGROUND DATA: Routine histologic examination of lymph nodes often underestimates the presence of micrometastatic disease. The authors have previously shown that an RT-PCR assay designed to detect melanocyte-specific expression of the tyrosinase gene could be used to define a population of patients at higher risk for both recurrence and death compared with routine hematoxylin and eosin (H&E) histology. In this study, the authors used the tyrosinase RT-PCR assay in a patient population examined by a more detailed histologic analysis, including S-100 immunohistochemistry. METHODS: Patients underwent lymphatic mapping and SLN biopsy. SLN specimens were bivalved, and half of each specimen was serially sectioned and examined by routine H&E histology and S-100 immunohistochemistry. The other half of each specimen was analyzed by a nested RT-PCR assay. RESULTS: Hematoxylin and eosin histology detected metastatic disease in 36 (16%) of the 233 patients tested. S-100 immunohistochemistry detected micrometastatic disease in another 16 patients, and 114 (63%) of 181 patients with histology-negative nodes had positive findings on RT-PCR. There were significant differences between PCR-positive and PCR-negative patient groups in Breslow thickness, Clark level, and the presence of ulceration of the primary tumor, factors that have been shown to correlate with recurrence and survival. CONCLUSIONS: These results suggest that RT-PCR can increase the sensitivity of detection of metastatic melanoma cells in SLNs over the current standard methods, including H&E histology and S-100 immunohistochemistry. Further long-term follow-up is needed to detect actual differences in recurrence and overall survival.

Adult↗

PubMed1999

Cutaneous lymphatic drainage in patients with grossly involved nodal basins.

BACKGROUND: The development of lymphatic mapping techniques has facilitated the identification of the sentinel lymph node (SLN), the first node in the regional basin into which cutaneous lymphatics flow from a particular skin area. Previous studies have shown that SLN histology reflects the histology of the entire basin, because melanoma metastases progress in an orderly fashion, involving the SLN before higher nodes in the basin become involved with metastatic disease. It is uncertain whether these orderly cutaneous lymphatic flow patterns are maintained in grossly involved basins. Lymphatic mapping was performed in a population of melanoma patients with clinically palpable lymphadenopathy to address this question. We aimed to determine whether the presence of gross nodal disease in the basin alters lymphatic flow into that basin so that lymphatic mapping techniques are not applicable, and, in patients referred with a grossly involved basin, whether preoperative lymphoscintigraphy should be performed to identify other regional basins at risk for metastases. METHODS: Eight patients presented with grossly palpable disease in the regional basin and underwent preoperative lymphoscintigraphy. All patients with palpable disease and all basins indicated by lymphoscintigraphy to be at risk were dissected. Three patients presented with clinically palpable nodes at the time of diagnosis, and five developed nodal disease on clinical follow-up after undergoing initial wide local excision only. A total of 10 basins in the eight patients were dissected. Of these, eight of the basins had grossly palpable regional nodal disease, and the other two basins were identified by preoperative lymphoscintigraphy as being at risk for metastases. The SLN was identified with intraoperative mapping, harvested, and submitted to pathology. Complete therapeutic lymph node dissections were performed following the SLN harvest in the basins with grossly palpable disease. SLN biopsy alone was performed in the two basins that did not have clinically palpable adenopathy but showed cutaneous lymphatic flow from the scintigram. RESULTS: Sixteen SLNs were harvested from these eight basins with grossly palpable disease, and 14 (87.5%) contained tumor. In each case, one of the SLNs was the grossly palpable node, and in six of the basins (75%) it was the only site of melanoma metastases. An additional 190 higher level, non-SLNs were removed, 32 (16.8%) of which contained microscopic foci of metastatic melanoma (P = .015). The null hypothesis that melanoma nodal metastasis is a random event is rejected. Two patients with trunk melanoma primary sites were identified to have other basins at risk for metastatic disease on lymphoscintigraphy. SLN biopsies were performed in these two patients, and one had microscopic nodal disease in the SLN. CONCLUSIONS: These data support the fact that cutaneous lymphatic drainage patterns are maintained in patients with grossly involved basins, thus buttressing the idea that the SLN is the node most likely to develop metastatic disease. Gross disease in the basin does not significantly alter cutaneous lymphatic flow into the regional basin, as the sentinel lymph node identified under these circumstances is the same as with the grossly involved node. Preoperative lymphoscintigraphy in patients who present with grossly involved nodes in one basin may identify other regional basins with micrometastatic disease and deserves further study in this setting.

Adult↗

PubMed1998

Measurement of fatigue in cancer patients: development and validation of the Fatigue Symptom Inventory.

Although fatigue is one of the most common and debilitating symptoms experienced by cancer patients, it has received little systematic attention. This situation is due in large part to the lack of adequate instruments to measure fatigue. The primary aim of this study was to validate a newly developed measure of fatigue for use with cancer patients: the Fatigue Symptom Inventory (FSI). This 13 item self-report measure was designed to measure the intensity and duration of fatigue and its impact on quality of life. The psychometric properties of the FSI were assessed in women undergoing treatment for breast cancer, women who had completed treatment for breast cancer and women with no history of cancer. A seven-item interference subscale was found to have good internal consistency, with alpha coefficients above 0.90 in all three groups. The complete FSI was found to have rather weak to moderate test-retest reliability among patients in active treatment and healthy comparison subjects assessed on three separate occasions. Convergent validity was demonstrated using comparisons with existing measures of fatigue. Construct validity was demonstrated using comparisons between and within groups as well as comparisons with measures of anxiety and depression. Overall, the FSI was established as a valid and reliable measure of fatigue in cancer patients and healthy individuals. Suggestions are made for the potential application of the measure in clinical research.

Adult↗

PubMed1997

Cytologic evaluation of lumpectomy margins in patients with ductal carcinoma in situ: clinical outcome.

BACKGROUND: Breast conservation therapy is controversial for ductal carcinoma in situ (DCIS) due to recently reported high recurrence rates. We believe that cytologic evaluation of lumpectomy margins improves efficiency and leads to a lower recurrence rate following lumpectomy for DCIS. METHODS: A prospectively accrued database of 1255 breast cancer patients at the H. Lee Moffitt Cancer Center and Research Institute was found to have 218 patients with DCIS (17.4%). Of those 218 cases, 114 were treated with lumpectomy, axillary dissection, and radiation therapy; the remaining 104 patients were treated with mastectomy with or without reconstruction. Imprint cytology was used to evaluate all lumpectomy margins. Permanent sections and imprint cytology were reviewed by the same pathologist. RESULTS: All lumpectomy specimens (116 tumors in 114 patients) were evaluated. The median follow up was 57.5 months (range 2-110 months). One hundred and three patients with 104 tumors were selected on the basis of pure DCIS (with or without microinvasion), and treated with lumpectomy, axillary dissection and radiation therapy. Of the 104 tumors utilizing attempted breast conservation therapy, 7 (6.6%) required mastectomy. There were 6 recurrences (6.1%) with a median time for recurrence of 47.5 months (range 27-85 months); four recurrences were comedo and two were noncomedo at original diagnosis. CONCLUSIONS: The determination of lumpectomy margins in DCIS patients using imprint cytology leads to an overall recurrence rate of 6.1% with reduction in operative time, and re-excision rate. Significant recurrence rates were associated with microinvasion and multifocal tumors (28%) versus simple DCIS at 5 years. Breast conservation therapy and surgical margin determination with imprint cytology for DCIS is a cost-effective and reliable method of treatment for simple DCIS.

Adult↗

PubMed1997

Investment in new technology research can save future health care dollars.

OBJECTIVE: To perform a cost analysis of the emerging technology of lymphatic mapping for patients with malignant melanoma. DESIGN: A retrospective, computer-aided chart and financial cost and charge review of consecutive patients with the diagnosis of melanoma registered at a cancer center from December, 1995 to March, 1996. PARTICIPANTS: 73 consecutive patients with the diagnosis of Stage 1 and 2 melanoma (cutaneous disease only) had nodal staging of their disease with either a sentinel node (SLN) biopsy or an elective complete node dissection (ELND). This was determined largely by patient choice and the protocol in operation at the time of the presentation of the patient to the clinic. OUTCOMES MEASURED: There were no deaths in the series. Patient morbidity endpoints included rates of infection, incidence of extremity lymphedema, development of a seroma in the regional nodal basin wound and wound healing. Clinical outcome was measured by the ability to obtain complete nodal staging information with the new lymphatic mapping technology, and recurrence rates in the nodal basin after a negative SLN biopsy. Total charges, direct costs and total costs were calculated from all hospital, OR, pathology and lab charges. Professional fees were included in the analysis. RESULTS: Group 1 patients (50) had melanomas greater than 0.76 mm in thickness treated with a wide local excision (WLE), lymphatic mapping and SLN biopsy under general anesthesia. Five patients (Group 2) had their procedure performed under a straight local anesthesia. Group 3 patients (18) had nodal staging performed with an elective node dissection. In Groups 1 and 2, if the SLN was positive for micrometastases, the patients were taken back to the OR for a complete node dissection. The total charges per patient were $13,835, $6,853 and $19,285, respectively. Significant dollar savings were achieved if the nodal staging could be accomplished with the lymphatic mapping technology (p = 0.001). Morbidity was significantly less in Groups 1 and 2 compared to Group 3. After a mean follow-up of three years, only one patient has recurred in a SLN negative basin. CONCLUSIONS: With 38,300 new cases of melanoma diagnosed each year in the United States, a projected savings of $172 million per year (general anesthesia) and $350 million per year (local anesthesia) could be realized if this new mapping technology could be incorporated into the care of the melanoma patient. Patient morbidity is minimized, nodal staging is complete and patients return to work sooner. Recently approved adjuvant therapy can be applied in a selective fashion, treating only those patients in which a documented benefit has been obtained, saving the health care system more dollars. Initial investment in defining the technology was minimal.

Anesthesia, General↗

PubMed1996

Intraoperative radio-lympho-scintigraphy improves sentinel lymph node identification for patients with melanoma.

BACKGROUND: The sentinel lymph node (SLN), the first node draining the primary tumor site, has been shown to reflect the histologic features of the remainder of the lymphatic basin in patients with melanoma. Intraoperative localization of the SLN, first proposed by Morton and colleagues, has been accomplished with the use of a vital blue dye mapping technique. Technical difficulties resulting in unsuccessful explorations have occurred in up to 20% of the dissections. OBJECTIVES: The authors aimed to define the SLN using gamma detection probe mapping and to determine whether intraoperative radiolymphoscintigraphy using technetium sulfur colloid and a hand-held gamma-detecting probe could be used to improve detection of all SLNs for patients with melanoma. METHODS: To ensure that all initial nodes draining the primary site were removed at the time of selective lymphadenectomy, the authors used intraoperative radiolymphoscintigraphy to confirm the location of the SLN, which was determined initially with the preoperative lymphoscintigram and the intraoperative vital blue dye injection. PATIENT POPULATION: The patient population consisted of 106 consecutive patients who presented with cutaneous melanomas larger than 0.75 mm in all primary site locations. RESULTS: The preoperative lymphoscintigram revealed that 22 patients had more than one lymphatic basin sampled. Two hundred SLNs and 142 neighboring non-SLNs were harvested from 129 basins in 106 patients. After the skin incision was made, the mean ratio of hot spot to background activity was 8.5:1. The mean ratio of ex vivo SLN-to-non-SLN activity for 72 patients who had SLNs harvested was 135.6:1. When correlated with the vital blue dye mapping, 139 of 200 (69.5%) SLNs demonstrated blue dye staining, whereas 167 of 200 (83.5%) SLNs were hot according to radioisotope localization. With the use of both intraoperative mapping techniques, identification of the SLN was possible for 124 of the 129 (96%) basins sampled. Micrometastases were identified in SLNs of 16 of the 106 (15%) patients by routine histologic analysis. CONCLUSION: The use of intraoperative radiolymphoscintigraphy can improve the identification of all SLNs during selective lymphadenectomy.

Adolescent↗

PubMed1996

The tumor biology of melanoma nodal metastases.

Approximately 20 per cent of melanomas greater than 0.76 mm in thickness will metastasize to the regional lymph nodes if treated with wide local excision alone (WLE). Elective lymph node dissection (ELND) is associated with significant morbidity, which includes lymphedema, wound complications, and paresthesias of the extremity. An alternative operative approach uses selective lymphadenectomy with the identification of the sentinel node, defined as the first node in the lymphatic basin that drains the primary cutaneous site. This study consisted of 132 patients with melanomas greater than 0.76 mm. One hundred nine patients (83%) had histologic negative sentinel nodes, and 23 patients (17%) had one or more sentinel nodes positive for disease. In patients with metastatic disease, 30/35 (86%) sentinel nodes were positive, and 25/357 (7%) nonsentinel nodes were positive (P < 0.001). In 18 patients (78%) of the 23 patients with metastatic disease, the sentinel node was the only node positive, strongly suggesting that there is an orderly progression of metastases. Two patients developed metastatic nodal disease after removal of a negative sentinel node (false negative rate = 1.5). The mean follow-up was 1 year. Sentinel node histology reflects the histology of the remainder of the nodes in the lymphatic basin and "skip" metastases, defined as a negative sentinel node but positive nodes higher in the regional chain positive for metastases or an axillary recurrence after a negative sentinel node biopsy, are rare for malignant melanoma. Harvesting the sentinel node in patients with intermediate or greater thickness melanoma will, therefore, identify a subset of patients with metastatic disease who have the most to benefit from a complete node dissection. This surgical approach allows for complete pathological staging and therapeutic management of patients while significantly reducing expense and overall morbidity.

Adolescent↗

PubMed1995

The identification and mapping of melanoma regional nodal metastases: minimally invasive surgery for the diagnosis of nodal metastases.

The most controversial part of melanoma surgical care involves the role of elective lymph node dissection (ELND). Whereas proponents cite retrospective studies demonstrating the ability to control regional metastases and more accurate staging, opponents cite the unnecessary morbidity of a complete node dissection for the majority of patients. The technology of sentinel node mapping and selective lymphadenectomy, defined as the identification and removal of the first node into which the primary melanoma drains, may revolutionize melanoma care. If the sentinel node is negative, then theoretically the remainder of the nodes should also be negative (no "skip" metastases), and a complete lymphadenectomy would not be required to control occult nodal disease. The location of the sentinel node may be variable in the lymphatic basin. Ideally, the surgeon needs a map of the position of the sentinel node in reference to the other nodes in the basin in order to do the procedure under local anesthesia with small incisions. In this way, patients are subjected to minimal morbidity and the procedure can be performed as an out-patient. Twenty-nine patients with clinically negative nodes and melanomas greater than 0.76 mm in thickness were judged to be candidates for ELND. Preoperative lymphoscintigraphy in two planes was used to mark the sentinel node, and the patients were taken to the operating room for intraoperative lymphatic mapping and sentinel node biopsy followed by complete dissection.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1994

Age as a prognostic factor in the malignant melanoma population.

BACKGROUND: The incidence of malignant melanoma is increasing faster than any other cancer, and the state of Florida has one of the highest incidence of melanoma in the United States. This increased incidence is thought to be due to the intense sunlight exposure and ultraviolet radiation exposure in the elderly population. With the increased emphasis on issues of aging, it is appropriate to study the role of age as a prognostic factor for malignant melanoma in the Florida population. METHODS: A retrospective, computer-aided search identified 442 consecutively registered patients with malignant melanoma at the Cutaneous Oncology Program. All patients had stage 1 or 2 disease (cutaneous disease only) at diagnosis. Prognostic variables analyzed included the most powerful factors for stage 1 and 2 melanoma, tumor thickness, ulceration, and Clark level of invasion. Other prognostic variables included in the analysis were the clinical variables of sex and primary site (axial vs. extremity). The population was divided into patients < or = 65 and > 65 years of age. RESULTS: Significant disease-free survival differences were encountered in the older population, with only 55% of the elderly population being disease free at 5 years compared with 65% for the younger population (p = 0.0073). However, a greater percentage of patients with melanoma who were > 65 years of age had ulcerated lesions (17.5% vs. 12.9%) and a greater percentage of thick lesions at diagnosis (67.2% vs. 62.7%). Both of these prognostic factors would bias the older population with a poorer survival. A stepwise regression analysis of the entire population was performed, treating age as a continuous variable. Surprisingly, increasing age along with tumor thickness were the only significant predictors for disease-free survival. After inclusion of these two prognostic variables, none of the other prognostic factors, including Clark level, ulceration, sex, and primary site, added to the prognostic model. CONCLUSIONS: From this analysis, it is apparent that geriatric patients with melanoma have a worse prognosis than a younger control population, even after the correction for the more commonly cited prognostic factors. This information should be used in mathematical modeling to identify high-risk populations who are candidates for perhaps more aggressive primary or adjuvant therapies.

Adult↗

PubMed1994

The orderly progression of melanoma nodal metastases.

OBJECTIVE: The aim of this study was to determine the order of melanoma nodal metastases. SUMMARY BACKGROUND DATA: Most solid tumors are thought to demonstrate a random nodal metastatic pattern. The incidence of skip nodal metastases precluded the use of sampling procedures of first station nodal basins to achieve adequate pathological staging. Malignant melanoma may be different from other malignancies in that the cutaneous lymphatic flow is better defined and can be mapped accurately. The concept of an orderly progression of nodal metastases is radically different than what is thought to occur in the natural history of metastases from most other solid malignancies. METHODS: The investigators performed preoperative and intraoperative mapping of the cutaneous lymphatics from the primary melanoma in an attempt to identify the "sentinel" lymph node in the regional basin. All patients had primary melanomas with tumor thicknesses > 0.76 mm and were considered candidates for elective lymph node dissection. The sentinel lymph node was harvested and submitted separately to pathology, followed by a complete node dissection. The null hypothesis tested was whether nodal metastases from malignant melanoma occurred in equal proportions among sentinel and nonsentinel nodes. RESULTS: Forty-two patients met the criteria of the protocol based on prognostic factors of their primary melanoma. Thirty-four patients had histologically negative sentinel nodes, with the rest of the nodes in the basin also being negative. Thus, there were no skip metastases documented. Eight patients had positive sentinel nodes, with seven of the eight having the sentinel node as the only site of disease. In these seven patients, the frequency of sentinel nodal metastases was 92%, whereas none of the higher nodes had documented metastatic disease. Nodal involvement was compared between the sentinel and nonsentinel nodal groups, based on the binomial distribution. Under the null hypothesis of equality in distribution of nodal metastases, the probability that all seven unpaired observations would demonstrate that involvement of the sentinel node is 0.008. CONCLUSIONS: The data presented demonstrate that nodal metastases from cutaneous melanoma are not random events. The sentinel lymph nodes in the lymphatic basins can be mapped and identified individually, and they have been shown to contain the first evidence of melanoma metastases. This information can be used to revolutionize melanoma care so that only those patients with evidence of nodal metastatic disease are subjected to the morbidity and expense of a complete node dissection. Because sentinel node histology accurately reflects the histology of the remainder of the lymphatic basin, information gained from the sentinel node biopsy can be used as a prognostic factor for melanoma. These findings demonstrate effective pathologic staging, no decrease in standards of care, and a reduction of morbidity with a less aggressive, rational surgical approach.

Adolescent↗

PubMed1993

The medical legal implications of following mammographic breast masses.

Delay in breast cancer diagnosis continues to account for the highest percentage of medical malpractice cases in the United States. A retrospective, computer-aided study was undertaken to investigate a number of parameters used in making medical-legal decisions in missed breast cancer cases. Over a 5-year period, 435 women with invasive breast cancers were registered at the Comprehensive University Breast Cancer Center. A close correlation between mammographic and final histologic size was verified (R = 0.74). In 5-mm increments, starting with a 1.0-mm tumor, there was an increasing percentage of positive nodes identified with increasing size of the tumor. Major percentage increases in frequency of positive nodes were noted at tumor sizes of 11 and 21 mm. This corresponded to an increasing number of recurrences and a decreasing 5-year disease-free survival (DFS) between consecutive 5-mm increments, although the differences were not significant. A multivariate regression analysis confirmed that the most important predictor of DFS was lymph node status (p = 0.0046) and not tumor size. After adjusting for lymph node status, tumor size was not significant. It is concluded that a period of observation, in which a breast cancer may increase in size is not substandard care since tumor size, after accounting for lymph node status is not significant at predicting DFS.

Breast↗

PubMed1992

A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck.

PURPOSE: To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer, we compared the efficacy and toxicity of cisplatin (CP) and fluorouracil (5-FU), alone and in combination in a phase III trial. PATIENTS AND METHODS: Two hundred forty-nine patients with recurrent head and neck cancer were randomized to one of three treatments: CP (100 mg/m2) and 5-FU (1 g/m2 x 4), CP, or 5-FU every 3 weeks. RESULTS: The overall response rate to the combination (32%) was superior to that of CP (17%) or 5-FU (13%) (P = .035). Response was associated with good performance status (PS) but not with primary site, site of recurrence, histology, prior irradiation, or relative dose intensity. Median time to progression was less than 2.5 months, and there was no significant difference in median survival (5.7 months) among the groups. By multivariate analysis, patients with better PS and poorly differentiated tumors had superior survival. Hematologic toxicity and alopecia were worse in the combination arm. CONCLUSION: Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents, survival did not improve.

Analysis of Variance↗

PubMed1991

Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer.

BACKGROUND: Neutropenia and infection are major dose-limiting side effects of chemotherapy. Previous studies have suggested that recombinant methionyl granulocyte colony-stimulating factor (G-CSF) can reduce chemotherapy-related neutropenia in patients with cancer. We conducted a randomized clinical trial to test this hypothesis and the clinical implications. METHODS: Patients with small-cell lung cancer were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of recombinant methionyl G-CSF to study the incidence of infection as manifested by fever with neutropenia (absolute neutrophil count, less than 1.0 x 10(9) per liter, with a temperature greater than or equal to 38.2 degrees C) resulting from up to six cycles of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. The patients were randomly assigned to receive either placebo or G-CSF, with treatment beginning on day 4 and continuing through day 17 of a 21-day cycle. RESULTS: The safety of the study treatment could be evaluated in 207 of the 211 patients assigned to either drug, and its efficacy in 199. At least one episode of fever with neutropenia occurred in 77 percent of the placebo group, as compared with 40 percent of the G-CSF group (P less than 0.001). Over all cycles of chemotherapy, the median duration of grade IV neutropenia (absolute neutrophil count, less than 0.5 x 10(9) per liter) was six days with placebo as compared with one day with G-CSF. During cycles of blinded treatment, the number of days of treatment with intravenous antibiotics, the number of days of hospitalization, and the incidence of confirmed infections were reduced by approximately 50 percent when G-CSF was given, as compared with placebo. Mild-to-moderate medullary bone pain occurred in 20 percent of the patients receiving G-CSF. CONCLUSIONS: The use of G-CSF as an adjunct to chemotherapy in patients with small-cell cancer of the lung was well tolerated and led to reductions in the incidence of fever with neutropenia and culture-confirmed infections; in the incidence, duration, and severity of grade IV neutropenia; and in the total number of days of treatment with intravenous antibiotics and days of hospitalization.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Concentrated albumin infusion as an aid to postoperative recovery after pelvic exenteration.

Twenty-eight patients underwent pelvic exenterations for gynecologic malignancies between June 1986 and June 1989. The postoperative fluid and electrolytes were managed by one of two regimens. One group of 10 patients was given concentrated 25% albumin infusion for the first 16 hr after surgery in addition to maintenance intravenous crystalloid solution according to ideal body weight. The second group of 18 patients received only a standard crystalloid solution. The albumin infusion group was found to have a more stable postoperative course as evidenced by less fluid boluses (P less than 0.01), fewer electrolyte bolus requirements (P less than 0.01), and easier management of blood pressure and urine output. There was a 50% decrease in total fluid requirement, a higher mean right atrial pressure (P less than 0.05), and a lower maintenance intravenous fluid rate (P less than 0.01). As a consequence, central hyperalimentation was started earlier (P less than 0.01) and the albumin infusion group left the Intensive Care Unit sooner than the non-albumin infusion group. There was not a single instance of clinical fluid overload with this slow infusion technique. Thus, concentrated albumin infusion was beneficial in the acute fluid management of these difficult patients.

Aged↗

PubMed1990

Human factor IXLincoln Park: a molecular characterization.

Using genomic DNA prepared from peripheral blood samples of a patient with factor IX deficiency, all eight exons as well as sequences around the splice junctions and putative promoter region of human factor IX DNA have been subjected to polymerase chain reaction (PCR) amplification and sequenced. Comparison of these sequences with normal factor IX gene sequences revealed an insertion in exon VIII that resulted in the alteration of 11 amino acids and the addition of 23 amino acids, all at the carboxy terminal of factor IX. This insertion destroys an Msp I restriction site; carrier detection and antenatal diagnosis in affected kindreds can be performed by testing for the absence of this site. This is the first characterization of a mutation in which insertion in the carboxy terminal region of factor IX causes factor IX deficiency. The genetic change in factor IX in this patient is called Factor IXLincoln Park.

Amino Acid Sequence↗

PubMed1989

Cloning and characterization of the 5' end (exon 1) of the gene encoding human factor X.

Human blood-coagulation factor X (hBCFX) is a serine protease zymogen which participates in the middle phase of blood coagulation. Recently, we and others have reported the cDNA sequences. At present, partial hBCFX gene structure is available. In this paper, we report the isolation of two genomic clones, the X-emb lambda phage clone encoding exons 1 and 2 of the hBCFX gene, and the X-cos cosmid clone encoding exons 2-8. The restriction map of the hBCFX region spans 55 kb. The gene itself was found to be 27 kb long. The sequence of the 5' region of the hBCFX gene has been determined and reveals an ATTTG pentanucleotide, which also occurs in a similar location in the genes encoding factors VII, IX, protein CC and C prothrombin, suggesting that this motif might be of importance in the regulation of these genes.

Base Sequence↗