Neoadjuvant chemotherapy in women with invasive breast carcinoma: conceptual basis and fundamental surgical issues.
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Biopsy↗
Biomedical subjects
L A Newman
Publications and source records attributed to L A Newman.
Optimal care patterns in pediatric patients with dysphagia.
The pediatric population with dysphagia is diverse, ranging from premature infants to fully grown adolescents. A variety of medical conditions cause swallowing disorders in pediatric patients. Complications of swallowing disorders can have severe and even fatal consequences. Swallowing disorders have a direct impact on nutrition, and adequate nutrition is required for growth and development of all body systems in infants and children. Infants and children may not have the same symptoms and signs as adults with dysphagia do and learning to identify pediatric patients at risk for dysphagia is critical. The diagnosis must be thorough and accurate. Furthermore, management of swallowing disorders and nutrition must be aggressive and immediate because of the reduced nutritional reserve and high needs of the infant and child. This article discusses the following three areas for optimal care: identification of infants and children at risk for dysphagia, diagnostic procedures, and management.
Child↗
Special considerations in breast cancer risk and survival.
Experimental and clinical evidence suggests that breast neoplasia appears to be a hormone-dependent process that may also be influenced by dietary factors in many women. Conflicting reports on the relationship between exogenous hormones and the development, progression, and recurrence of breast cancer are critically examined in this report. The absolute breast cancer risk associated with either hormone replacement therapy or oral contraceptive use has not been clearly defined. Data from some large prospective studies have actually documented lower mortality rates for women taking hormone replacement compared with those for women who did not have hormone replacement therapy. In this regard, age, duration of use, and preexisting breast cancer risk factors must be taken into account. Although the results of two major prospective clinical trials addressing the role of timing of surgery within the menstrual cycle are forthcoming, the majority of studies have found no consistent association between timing of surgery and breast cancer survival. Recently reported prospective randomized data showing that selective-estrogen-receptor-modulators can act as effective chemoprevention agents in women at increased risk for breast cancer development are presented. Finally, information regarding the effect of dietary manipulation on breast cancer risk and survival is reviewed.
Breast Neoplasms↗
Survival among chronic renal failure patients requiring major abdominal surgery.
BACKGROUND: There is limited literature on survival of patients with chronic renal failure (CRF) who require major abdominal surgery. The goal of the present study was to evaluate indications for surgery and survival among dialysis patients undergoing major abdominal operations. STUDY DESIGN: Medical records for 26 CRF patients at our institution undergoing major nonvascular abdominal operations from 1990 to 1996 were reviewed. Results were evaluated by chi-square analysis. RESULTS: Surgery was performed emergently in 21 patients (81%) and electively in 5 patients (19%). The most common finding among the emergency surgery patients was ischemic colitis, occurring in 9 of 21 patients (43%). Postoperative (30-day) mortality among the emergency surgery patients was 38%. Longterm (1 year) survival was 28%. All 5 patients undergoing elective surgery are alive on followup of 1 to 5 years. The disparity in longterm survival between the emergency surgery versus the elective surgery patients was statistically significant (p = 0.004). CONCLUSIONS: Emergency surgery in patients with CRF is associated with poor survival rates. Colonic ischemia is a significant problem among these patients.
Adult↗
Aspiration: cause and implications.
The purpose of this investigation was to determine the overall prevalence of aspiration in dysphagic individuals referred for a modified barium swallow and the underlying anatomic and/or physiologic causes. A total of 166 patients were seen during a 1-month period at 5 participating institutions. Aspiration was detected in 51.2% of the patients. The most common causes were decreased laryngeal elevation and delayed triggering of the pharyngeal motor response. A history of aspiration pneumonia was significantly associated with the presence of aspiration on modified barium swallow study. The presence of a protective cough was present in only 53% of patients who aspirated, reinforcing the need for appropriate radiologic assessment in patients with suspected dysphagia.
Adult↗
Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy.
OBJECTIVE: To determine the incidence and prognostic significance of documented eradication of breast cancer axillary lymph node (ALN) metastases after neoadjuvant chemotherapy. SUMMARY BACKGROUND DATA: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer and is being evaluated in patients with earlier-stage operable disease. METHODS: One hundred ninety-one patients with locally advanced breast cancer and cytologically documented ALN metastases were treated in two prospective trials of doxorubicin-based neoadjuvant chemotherapy. Patients had breast surgery with level I and II axillary dissection followed by additional chemotherapy and radiation treatment. Nodal sections from 43 patients who were originally identified as having negative ALNs at surgery were reevaluated and histologically confirmed to be without metastases. An additional 1112 sections from these lymph node blocks were obtained; half were stained with an anticytokeratin antibody cocktail and analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: Of 191 patients with positive ALNs at diagnosis, 23% (43 patients) were converted to a negative axillary nodal status on histologic examination (median number of nodes removed = 16). Of the 43 patients with complete axillary conversion, 26% (n = 11) had N1 disease and 74% (n = 32) had N2 disease. On univariate analysis, patients with complete versus incomplete histologic axillary conversion were more likely to have initial estrogen-receptor-negative tumors, smaller primary tumors, and a complete pathologic response in the primary tumor. The 5-year disease-free survival rates were 87% in patients with preoperative eradication of axillary metastases and 51% for patients with residual nodal disease after neoadjuvant chemotherapy. Of the 39 patients with complete histologic conversion for whom nodal blocks were available, occult nodal metastases were found in additional nodal sections in 4 patients (10%). At a median follow-up of 61 months, the 5-year disease-free survival rates were 87% in patients without occult nodal metastases and 75% in patients with occult nodal metastases. CONCLUSIONS: Neoadjuvant chemotherapy can completely clear the axilla of microscopic disease before surgery, and occult metastases are found in only 10% of patients with a histologically negative axilla. The results of this study have implications for the potential use of sentinel lymph node biopsy as an alternative to axillary dissection in patients treated with neoadjuvant chemotherapy.
Antimetabolites, Antineoplastic↗
Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy.
PURPOSE: To assess patient and tumor characteristics associated with a complete pathologic response (pCR) in both the breast and axillary lymph node specimens and the outcome of patients found to have a pCR after neoadjuvant chemotherapy for locally advanced breast cancer (LABC). PATIENTS AND METHODS: Three hundred seventy-two LABC patients received treatment in two prospective neoadjuvant trials using four cycles of doxorubicin-containing chemotherapy. Patients had a total mastectomy with axillary dissection or segmental mastectomy and axillary dissection followed by four or more cycles of additional chemotherapy. Patients then received irradiation treatment of the chest-wall or breast and regional lymphatics. Median follow-up was 58 months (range, 8 to 99 months). RESULTS: The initial nodal status, age, and stage distribution of patients with a pCR were not significantly different from those of patients with less than a pCR (P>.05). Patients with a pCR had initial tumors that were more likely to be estrogen receptor (ER)-negative (P<.01), and anaplastic (P = .01) but of smaller size (P<.01) than those of patients with less than a pCR. Upon multivariate analysis, the effects of ER status and nuclear grade were independent of initial tumor size. Sixteen percent of the patients in this study (n = 60) had a pathologic complete primary tumor response. Twelve percent of patients (n = 43) had no microscopic evidence of invasive cancer in their breast and axillary specimens. A pathologic complete primary tumor response was predictive of a complete axillary lymph node response (P<.01 ). The 5-year overall and disease-free survival rates were significantly higher in the group who had a pCR (89% and 87%, respectively) than in the group who had less than a pCR (64% and 58%, respectively; P<.01). CONCLUSION: Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery. Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate. However, a pCR does not entirely eliminate recurrence. Further efforts should focus on elucidating the molecular mechanisms associated with this response.
Antineoplastic Combined Chemotherapy Protocols↗
Policies and procedures reduce hospitals' liability in releasing patient information.
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Confidentiality↗
PACS saves money, staff time, but alienates radiologists in N.Y. system.
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Academic Medical Centers↗
Hospital system discovers people, not technology, first priority in merger.
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Chicago↗
Monitoring women at risk for preterm labor.
BACKGROUND: Preterm birth is a major cause of perinatal morbidity and mortality. Whether the rate of preterm birth can be reduced by frequent contact between nurses and pregnant women or home monitoring of uterine activity is not known. METHODS: We randomly assigned 2422 pregnant women with known risk factors for preterm labor (including 844 women who were pregnant with twins) to receive education and to have one of the following: weekly contact with a nurse, daily contact with a nurse, or daily contact with a nurse and home monitoring of uterine activity. The nurses elicited the women's own assessments of their symptoms and signs of preterm labor. The primary end point was the incidence of birth at less than 35 weeks' gestation. Secondary end points included cervical status at the time preterm labor was diagnosed and birth weight. RESULTS: There were no significant differences among the groups in the incidence of birth at less than 35 weeks (14 percent in the weekly-contact group, 13 percent in the daily-contact group, and 14 percent in the home-monitoring group), in the mean amount of cervical dilatation at the time preterm labor was diagnosed (1.8 cm, 1.5 cm, and 1.4 cm, respectively), or in such neonatal outcomes as birth weights of less than 1500 g or less than 2500 g. However, daily contact with a nurse increased the mean number of unscheduled visits to obstetricians (1.2 in the weekly-contact group, 1.8 in the daily-contact group, and 2.3 in the home-monitoring group) and the proportion of women who received prophylactic tocolytic drugs (12 percent, 14 percent, and 19 percent, respectively). CONCLUSIONS: Women who have daily contact with a nurse, with or without home monitoring of uterine activity, have no better pregnancy outcomes than women who have weekly contact with a nurse.
Adult↗
Eating and weight changes following chemoradiation therapy for advanced head and neck cancer.
OBJECTIVE: To describe the functional outcomes of weight loss and eating following a targeted chemoradiation protocol consisting of a selective supradose of intra-arterial cisplatin (150 mg/m2 per week for 4 weeks) with parenteral sodium thiosulfate and external-beam irradiation (1.8-2.0 Gy per fraction per day for 35 days). SUBJECTS AND DESIGN: Forty-seven patients with advanced head and neck cancer treated with a targeted chemoradiation protocol were monitored for weight and eating status before treatment and as long as 18 months after treatment. RESULTS: A statistically significant weight loss (P<.001) occurred during the targeted chemoradiation protocol, with a mean weight ratio of 90% of the starting weight. The ability to eat also declined, with an increase in reported swallowing difficulties and a need for percutaneous endoscopic gastrostomy tubes from 4 (9%) to 12 (26%). There were no significant changes in weight after the initial weight loss. Tumor stage and nodal involvement had no effect on weight loss. At the start of treatment, 18 patients (38%) reported normal eating and 4 (8%) required a feeding tube. By 18 months after treatment, 41 (87%) were eating normally, 34 (72%) reported normal eating, and 6 (13%) required a percutaneous endoscopic gastrostomy tube. CONCLUSIONS: Patients undergoing a targeted chemoradiation protocol for head and neck cancer lost about 10% of their pretreatment weight and had a decline in eating ability. Difficulty swallowing during the treatment may be due to adverse effects such as mucositis and nausea. By 18 months after therapy, most were able to eat normally and maintain their weight.
Adult↗
Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer.
BACKGROUND: Induction chemotherapy has become the standard of care for patients with locally advanced breast cancer (LABC) and currently is being evaluated in prospective clinical trials in patients with earlier-stage disease. To better gauge the role of axillary lymph node dissection in patients with LABC this study was performed to assess initial axillary status on physical and ultrasound examination, axillary tumor downstaging following induction chemotherapy, and the accuracy of physical examination compared with axillary sonography in predicting which patients will have axillary lymph node metastases found on pathologic examination. METHODS: Between 1992 and 1996, 147 consecutive patients with LABC were registered in a prospective trial of induction chemotherapy using 5-fluorouracil, doxorubicin, and cyclophosphamide. Physical and ultrasound examinations of the axilla were performed at diagnosis and after induction chemotherapy. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed, followed by postoperative chemotherapy and irradiation of the breast or chest wall and regional lymphatics. RESULTS: Following induction chemotherapy, 43 (32%) of the 133 patients with clinically positive lymph nodes on initial examination had axillary tumor downstaging as assessed by physical and ultrasound examination. The sensitivity of axillary sonography in identifying axillary metastases was significantly higher than that of physical examination (62% vs. 45%, P=.012). The specificity of physical examination (84%) was higher than that of sonography (70%), but the difference did not reach statistical significance. Among the 55 patients in whom the findings of both physical and ultrasound examination of the axilla were negative following induction chemotherapy, 29 patients (53%) were found to have axillary lymph node metastases on pathologic examination of the axillary contents. However, 28 (97%) of these patients had either 1 to 3 positive lymph nodes or only micrometastases 2 to 5 mm in diameter. CONCLUSIONS: Preoperative clinical assessment of the axilla by physical examination combined with ultrasound examination is not completely accurate in predicting metastases in patients with LABC following tumor downstaging. However, patients with negative findings on both physical and ultrasound examinations of the axilla may be potential candidates for omission of axillary dissection if the axilla will be irradiated because minimal axillary disease remains. Patients who have positive findings on preoperative physical or ultrasound examinations should receive axillary dissection to ensure local control. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following induction chemotherapy is currently underway.
Antineoplastic Combined Chemotherapy Protocols↗
Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer.
BACKGROUND: This study was performed to validate the prognostic significance of residual axillary lymph node metastases in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other clinicopathologic factors that might be independent predictors of disease-free survival (DFS) in an attempt to identify patients in whom axillary dissection might be omitted. METHODS: One hundred sixty-five assessable patients with LABC were treated in a prospective trial of neoadjuvant chemotherapy utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients were treated with segmental mastectomy and axillary dissection or modified radical mastectomy. Patients subsequently received additional chemotherapy followed by irradiation of the breast or chest wall and draining lymphatics. The median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph nodes found at axillary dissection (P = 0.05) were the only independent predictors of DFS. Patients with a complete clinical response had a predictably excellent DFS and those with no change or progressive disease had a poor DFS. In patients with a partial response, the number of residual metastatic lymph nodes further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS: Clinical response and residual metastatic axillary lymph nodes following neoadjuvant chemotherapy are important predictors of DFS. Patients with a clinically positive axilla following neoadjuvant chemotherapy should undergo axillary dissection to ensure local control. However, the benefit of axillary dissection in patients with a clinically negative axilla may be minimal if the axilla will be irradiated, and histologic staging does not affect subsequent systemic treatment. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.
Antineoplastic Combined Chemotherapy Protocols↗
Phytoremediation of trichloroethylene with hybrid poplars.
Axenic tumor cultures of poplar cells, clone H11-11, were grown in the presence of [14C]-trichloroethylene (TCE) (uniformly labeled). The cells were capable of metabolizing TCE to produce trichloroethanol, di- and trichloroacetic acid. Some of the carbon from TCE was found in insoluble, nonextractable cell residue, and small amounts were mineralized to [14C]CO2. Poplar cuttings grown in soil and exposed to TCE produced the same metabolites. In field trials, trees were planted in soil in test cells and exposed to TCE via underground water injection during the growing season. During the growing season, at least 95% of the TCE was removed from the influent water stream in cells containing trees. Mass balance studies conducted in the laboratory indicated that 70 to 90% of the TCE was transpired; however, greenhouse and field study results showed that less than 5% of the total TCE taken up by the plants is transpired. These results show that significant TCE uptake and degradation occur in poplars. Poplars appear to be useful for in situ remediation of TCE-contaminated sites under proper conditions.
Biodegradation, Environmental↗
Age-related differences in breast cancer stage at diagnosis between black and white patients in an urban community hospital.
BACKGROUND: Breast cancer mortality is significantly higher among black patients compared to white patients. Black women are reportedly at increased risk for early-onset breast cancer. Our goal was to evaluate stage distribution relative to age among black and white breast cancer patients in an institution with a relatively high minority patient population. METHODS: We evaluated 425 patients diagnosed with breast cancer between 1990 and 1994: 56% white, 34% black, the remainder were other ethnicities. Patients were stratified by age: under 50 years versus 50 and older. Socioeconomic status was estimated by utilization of medical care in the private-practice setting versus the public clinic. RESULTS: Significantly more black patients were younger at diagnosis compared to white patients (32% vs. 20%; p = 0.008). There was a significantly more advanced stage distribution among the younger black patients, but not among the older black patients. Most of the black and white patients received private-practice care. CONCLUSIONS: These age-related differences in breast cancer stage distribution between black and white patients (which appeared independent of socioeconomic status) indicate that more aggressive screening and public education programs directed toward younger black women is warranted, and they lend support to the possibility of ethnicity-related variation in primary tumor biology.
Adult↗
The predictive value of tumor regression rates during chemoradiation therapy in patients with advanced head and neck squamous cell carcinoma.
OBJECTIVE: The value of tumor regression rates in predicting survival outcome during chemoradiation therapy was prospectively evaluated. METHODS AND MATERIALS: Sixty-two patients diagnosed with locally advanced stage III/IV unresectable head and neck squamous cell carcinoma underwent weekly clinical and endoscopic serial assessment of primary and nodal tumor sizes during chemoradiation therapy between July 1993 and September 1995. Chemoradiation therapy consisted of protocol treatment using supradose intra-arterial targeted cisplatin (SIT-P) at 150 mg/m2 four times at weekly intervals along with intravenous sodium thiosulfate at 9 g/m2 and concurrent conventionally fractionated radiotherapy at 1.8 to 2.0 Gy/fraction (fx) to a total dose of 68 to 74 Gy. Tumor reduction was serially measured as a percentage of the original pretreatment size at weekly intervals by the same team of surgical and radiation oncologists. Correlations were then made between tumor regression rates and survival. RESULTS: Complete or near complete regression of disease during chemoradiation therapy as compared with nonresponsive/partially responsive disease was associated with better survival outcome (P = 0.001 and P = 0.013, respectively). Among patients exhibiting complete or near complete regression of disease, rapid tumor reduction (median = 4.2 weeks) was associated with inferior survival outcome when compared with slower disease regression (median = 6.4 weeks, P = 0.007). CONCLUSIONS: Our findings fail to support the "traditional" hypothesis that rapid tumor regression during treatment is predictive of an improved survival outcome. Treatment strategies that alter ongoing therapy based upon initial tumor regression rates should be avoided.
Antidotes↗
Exercise during pregnancy and pregnancy outcome.
To investigate the effects of participation in aerobic exercise on pregnancy outcome, 388 women (mean age = 31.7, range = 18-42) were followed from a mean 16.5-wk gestation through delivery. Frequency, duration, and mode of aerobic exercise prior to conception and during the first trimester were determined by in-person interviews. Activity patterns during the second and third trimesters were assessed by telephone interviews. For each time period, women were categorized into one of the following exercise groups: Level I = aerobic exercise, excluding vigorous walking, at least three times a week for at least 20 min a time; Level II = aerobic exercise at least three times a week and 20 min at a time, if and only if vigorous walking is included; Level III = aerobic exercise less than three times a week, 20 min a time; and Level IV = aerobic exercise less than once a week. Mean birthweight was statistically unrelated to level of exercise preconceptionally or in any trimester. Gestational age, weight gain, and other pregnancy outcomes were also unassociated with exercise level. However, pregnancy symptoms were inversely associated with level of exercise; women who exercised more earlier in pregnancy reported fewer discomforts later in pregnancy (P = 0.01). These data suggest that participation in aerobic exercise during pregnancy at a level great enough to produce or maintain a training effect does not adversely affect birthweight or other maternal and infant outcomes but may be associated temporally with fewer perceived pregnancy-associated discomforts.
Adult↗