Intraoperative sonographic localization of breast masses: success with specimen sonography and surgical bed sonography to confirm excision.

OBJECTIVE: To assess the use of intraoperative sonography for localization of breast masses at excisional biopsy, with specimen and surgical bed sonography to confirm excision. METHODS: A computer search of the 5-year period from January 1993 through January 1998 revealed 138 consecutive women referred for sonographically guided excisional biopsy of 148 masses; 35 masses were excluded because they had no postoperative mammograms. One hundred thirteen masses constituted the study group. Specimen sonography (n = 60) or surgical bed sonography (n = 53) was performed as the initial evaluation to confirm excision, but ultimately, surgical bed sonography may have been necessary after specimen sonography, and specimen sonography may have been necessary after surgical bed sonography. The miss rates determined by postoperative imaging were calculated for each group and compared with those of mammographically guided needle localization series from the literature. RESULTS: Follow-up physical examination and mammography showed no residual mass in the region of surgery in any patient. However, follow-up sonography had 1 miss in the initial specimen sonogram group (1 [1.7%] of 60) and 1 miss in the initial surgical bed group (1 [1.9%] of 53). As shown by the Fisher exact test, there was no significant difference between the miss rates of the 2 initial methods of confirming lesion excision or between the miss rates of these initial methods, both groups combined, and 6 mammographic localization series from the literature. CONCLUSION: Intraoperative breast sonography, using specimen sonography and scanning the surgical bed, has miss rates comparable with those of mammographic needle localization. Follow-up sonography must be performed if there is any doubt of complete excision.

Who bounces back? Physiologic and other predictors of intensive care unit readmission.

OBJECTIVE: To determine the influence of changes in acute physiology scores (APS) and other patient characteristics on predicting intensive care unit (ICU) readmission. DESIGN: Secondary analysis of a prospective cohort study. SETTING: Single large university medical intensive care unit. PATIENTS: A total of 4,684 consecutive admissions from January 1, 1994, to April 1, 1998, to the medical ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The independent influence of patient characteristics, including daily APS, admission diagnosis, treatment status, and admission location, on ICU readmission was evaluated using logistic regression. After accounting for first ICU admission deaths, 3,310 patients were "at-risk" for ICU readmission and 317 were readmitted (9.6%). Hospital mortality was five times higher (43% vs. 8%; p < .0001), and length of stay was two times longer (16 +/- 16 vs. 32 +/- 28 days; p < .001) in readmitted patients. Mean discharge APS was significantly higher in the readmitted group compared with the not readmitted group (43 +/- 19 vs. 34 +/- 18; p > .01). Significant independent predictors of ICU readmission included discharge APS >40 (odds ratio [OR] 2.1; 95% confidence interval [CI] 1.6-2.7; p < .0001), admission to the ICU from a general medicine ward (Floor) (OR 1.9; 95% CI 1.4-2.6; p < .0001), and transfer to the ICU from other hospital (Transfer) (OR 1.7; 95% CI 1.3-2.3; p < .01). The overall model calibration and discrimination were (H-L chi2 = 3.8, df = 8; p = .85) and (receiver operating characteristic 0.67), respectively. CONCLUSIONS: Patients readmitted to medical ICUs have significantly higher hospital lengths of stay and mortality. ICU readmissions may be more common among patients who respond poorly to treatment as measured by increased severity of illness at first ICU discharge and failure of prior therapy at another hospital or on a general medicine unit. Tertiary care ICUs may have higher than expected readmission rates and mortalities, even when accounting for severity of illness, if they care for significant numbers of transferred patients.

The importance of bacterial sepsis in intensive care unit patients with acquired immunodeficiency syndrome: implications for future care in the age of increasing antiretroviral resistance.

OBJECTIVE: To describe the clinical characteristics and outcomes of patients with acquired immunodeficiency syndrome (AIDS) admitted to the intensive care unit (ICU). DESIGN: An observational cohort study with retrospective chart review. SETTING: ICU of an urban university medical center. PATIENTS: Consecutive ICU admissions of patients with AIDS at an urban university medical center between December 1993 and June 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each patient, we recorded ICU admission diagnosis, clinical characteristics, and outcome. Among 129 ICU admissions of patients with AIDS, 102 (79%) were admitted for infections, of which (45%) had infections caused by bacteria. Pseudomonas aeruginosa, Staphylococcus aureus, and other enteric pathogens were the most frequent isolates. Pneumonia accounted for 65% of 102 admissions for infections. Overall hospital mortality was 54%, but mortality was higher (68%) for patients with bacterial sepsis. Neutropenia was associated with differences in unadjusted survival rates, whereas CD4 counts were not. Independent predictors of hospital mortality included increasing acute physiology scores and severity of sepsis. CONCLUSIONS: In our ICU, among patients with AIDS, sepsis resulting from bacterial infection is now a more frequent cause of admission than Pneumocystis carinii pneumonia. Severity of illness and the presence of severe sepsis were the clinical predictors most associated with increased mortality. Patients who are not receiving or responding to highly active antiretroviral therapy may become as likely to be admitted to an ICU with a treatable bacterial infection as with classic opportunistic infections. Therefore, broad-spectrum empirical antibacterial therapy is particularly important when the etiology of infection is uncertain.

Intensive care unit length of stay: recent changes and future challenges.

OBJECTIVE: To compare case-mix adjusted intensive care unit (ICU) length of stay for critically ill patients with a variety of medical and surgical diagnoses during a 5-yr interval. DESIGN: Nonrandomized cohort study. SETTING: A total of 42 ICUs at 40 US hospitals during 1988-1990 and 285 ICUs at 161 US hospitals during 1993-1996. PATIENTS: A total of 17,105 consecutive ICU admissions during 1988-1990 and 38,888 consecutive ICU admissions during 1993-1996. MEASUREMENTS AND MAIN RESULTS: We used patient demographic and clinical characteristics to compare observed and predicted ICU length of stay and hospital mortality. Outcomes for patients studied during 1993-1996 were predicted using multivariable models that were developed and cross-validated using the 1988-1990 database. The mean observed hospital length of stay decreased by 3 days (from 14.8 days during 1988-1990 to 11.8 days during 1993-1996), but the mean observed ICU length of stay remained similar (4.70 vs. 4.53 days). After adjusting for patient and institutional differences, the mean predicted 1993-1996 ICU stay was 4.64 days. Thus, the mean-adjusted ICU stay decreased by 0.11 days during this 5-yr interval (T-statistic, 4.35; p < .001). The adjusted mean ICU length of stay was not changed for patients with 49 (75%) of the 65 ICU admission diagnoses. In contrast, the mean observed hospital length of stay was significantly shorter for 47 (72%) of the 65 admission diagnoses, and no ICU admission diagnosis was associated with a longer hospital stay. Aggregate risk-adjusted hospital mortality during 1993-1996 (12.35%) was not significantly different during 1988-1990 (12.27%, p = .54). CONCLUSIONS: For patients admitted to ICUs, the pressures associated with a decrease in hospital length of stay do not seem to have influenced the duration of ICU stay. Because of the high cost of intensive care, reduction in ICU stay may become a target for future cost-cutting efforts.

Patients readmitted to ICUs* : a systematic review of risk factors and outcomes.

STUDY OBJECTIVE: To evaluate the causes, risk factors, and mortality rates associated with unexpected readmission to medical and surgical ICUs. DATA SOURCES: MEDLINE citation review of primary articles focusing on ICU readmission or ICU outcomes from January 1966 to June 1999, and contact with authors of primary studies. STUDY SELECTION: Eight primary studies of ICU readmission and eight multi-institutional ICU outcome studies that reported ICU readmission rates were included. DATA EXTRACTION: We abstracted data on the methodology and design of the primary studies, overall rates, causes, predictors, outcomes, and measures of quality of care associated with ICU readmission. DATA SYNTHESIS: The average ICU readmission rate of 7% (range, 4 to 14%) has remained relatively unchanged in both North America and Europe. Respiratory and cardiac conditions were the most common (30 to 70%) precipitating cause of ICU readmission. Patients readmitted to ICUs had average hospital stays at least twice as long as nonreadmitted patients. Hospital death rates were 2- to 10-times higher for readmitted patients than for those who survived an ICU admission and were never readmitted. Predictors of ICU readmission have been neither well studied nor reproducible. Unstable vital signs, especially respiratory and heart rate abnormalities, and the presence of poor pulmonary function at time of ICU discharge appear to be the most consistent predictors of ICU readmission. There were no consistent data supporting the use of readmission rates as a measure of quality of care. CONCLUSIONS: ICU readmission is associated with dramatically higher hospital mortality. Unstable vital signs at the time of ICU discharge are the most consistent predictor of ICU readmission. Further studies focusing on processes of ICU and hospital care are needed to determine if ICU readmission rates are a measure of quality of care.

Definition and refinement of chromosome 11 regions of loss of heterozygosity in breast cancer: identification of a new region at 11q23.3.

Chromosome 11 is frequently altered in several types of human neoplasms. In breast cancer, loss of heterozygosity has been described in two regions of this chromosome, 11p15 and 11q22-23. In this report we have dissected the two regions using high-density polymorphic markers, and have found that there are at least two independent areas of loss of heterozygosity in each region, suggesting that multiple genes on chromosome 11 may be targets of genetic alteration during tumor establishment or progression. The regions defined are: at 11p15, between loci D11S576 and D11S1318 and between D11S988 and D11S1318; at 11q23, between D11S2000 and D11S897 and between D11S528 and D11S990. The narrowing of these regions of loss should facilitate the cloning of the regions in yeast artificial chromosomes to identify the critical tumor suppressor genes.

Ten-year results in 1070 patients with stages I and II breast cancer treated by conservative surgery and radiation therapy.

BACKGROUND: One thousand seventy patients treated conservatively for Stages I and II breast cancer between the years 1982 and 1994 were reviewed. The median follow-up was 40 months with a maximum follow-up of 152 months. METHODS: All patients had a wide local excision and lower lymph axillary node dissection followed by radiation therapy. The entire breast received an external beam dose of 4500 cGy at 180 cGy/5 days/week. An additional boost dose of 2000 cGy to the tumor bed was given at the time of lumpectomy (perioperative) with an Ir-192 implant or with electron beam therapy after the external beam therapy. RESULTS: The 5- and 10-year disease specific survival results were 97 and 90%, respectively for Stage I and 87 and 69% for patients with Stage II disease. The 5- and 10-year local control rates were 93 and 85% for Stage I and 92 and 87% for Stage II, respectively. The risk factors for local failure were premenopausal status and estrogen receptor-negative status at the univariate level but at the multivariate level the premenopausal and margins status were significant. CONCLUSION: These 10-year results were at least equivalent to reported series of similarly staged patients treated by mastectomy. This should encourage more surgeons to offer conservative treatment as an alternative to mastectomy to patients with Stage I and II breast cancer.

Detection and cloning of a common region of loss of heterozygosity at chromosome 1p in breast cancer.

The short arm of chromosome 1 is frequently affected by rearrangements in a variety of human malignancies. Genetic alterations, predominantly deletions, which are indicative of the presence of a putative tumor suppressor gene at chromosome 1p, are observed in breast cancer. In order to define the altered locus, eleven highly polymorphic microsatellite markers on chromosome 1p were used to detect loss of heterozygosity. We analyzed 52 cases of breast cancer and found 4 common deleted regions at chromosome 1p. Twenty-two of 52 (42%) informative patients showed at least 1 affected locus. The region most frequently exhibiting loss of heterozygosity was 1p31 (11/39; 28%); the other three common deleted regions were 1p36 (10/44; 23%), 1p35-36 (5/40; 13%), and 1p13 (8/39; 21%). These data suggest that one or more putative tumor suppressor genes may reside on chromosome 1p. We have cloned the entire region of interest at 1p31 in yeast artificial chromosomes. This yeast artificial chromosome contig can be used for fine mapping of the region and cloning of the candidate tumor suppressor gene.

Loss of heterozygosity at 11q22-q23 in breast cancer.

Studies of loss of heterozygosity (LOH) in breast tumor DNA suggest that several tumor suppressor genes participate in the pathogenesis of breast cancer. Although the short arm of chromosome 11 has been implicated in breast cancer development, no previous LOH studies have indicated the involvement of a suppressor gene on 11q in breast carcinoma. To this end, tumor samples and corresponding normal tissue were collected from 62 unselected patients with primary breast cancer, and the extracted DNA was analyzed by polymerase chain reaction using microsatellite markers on chromosome 11. We found that 39% of the tumors (22 of 57 informative cases) revealed allelic loss in the region 11q22-23, and this loss was independent of LOH found to occur on 11p15. Interestingly, more than 90% of the tumors showed concordant loss of alleles at both 11q and 17p. The marker D11S528, showing LOH in 39% of informative cases, had the highest frequency of LOH among the markers that were used. The data presented indicate that the common overlapping region of LOH is between the loci D11S35 and D11S29, suggesting that this area contains a tumor suppressor gene frequently lost in breast cancer.

Perioperative implantation of iridium-192 as the boost technique for stage I and II breast cancer: results of a 10-year study of 655 patients.

PURPOSE: To assess the efficacy of perioperative implantation of iridium-192 for stage I and II breast cancer. MATERIALS AND METHODS: The authors retrospectively reviewed findings from 655 patients with stage I and II cancer treated with conservative surgery and Ir-192 implantation between 1982 and 1992. Hollow plastic tubes were placed in the tumor bed as a single- or double-plane implant at lumpectomy. Ribbons with Ir-192 seeds were inserted into the tubes 4-6 hours later. The Ir-192 was left in place for approximately 50 hours. External-beam irradiation was given to the whole breast 10-14 days later. RESULTS: Follow-up ranged from 2 to 146 months. The local control at 10 years for stage I and II disease was 93% and 87%, respectively. The 10-year actuarial survival rate was 92% +/- 1 for stage I disease and 72% +/- 4 for stage II disease. The rate of survival with no evidence of disease for stage I and II disease combined was 82% +/- 1 at 5 years and 75% +/- 3 at 10 years. CONCLUSION: Perioperative implantation produced excellent local control equal to that with electron-beam therapy.

The role of radiotherapy in the treatment of breast cancer: results of perioperative implantation.

Between 1982 and 1993, 620 of 938 patients with pathologically staged I-II breast cancer were treated at the time of reexcision (perioperatively), with an iridium-192 (Ir-192) implant to the tumor bed to give 2000 cGy to the 30 to 40 cGy/ph isodose line. This was followed by 4500 cGy to the entire breast at 180 cGy/d for 25 fractions. The local control for the 620 patients at 5 and 10 years was 93 and 89%, respectively. The actuarial survival at 5 and 10 years was 92 and 81%. The cosmetic results were good to excellent for 87% of the patients. Chemotherapy had no impact on local control in this study. Ir-192 implant is especially useful for deep tumors, making possible more flexibility in the techniques used to boost the tumor volume. Perioperative implantation has increased the accuracy of placing the boost dose, shortened the overall treatment time, and, for some patients, eliminated the need for rehospitalization and anesthesia.

Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma.

From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance.

CT-pathologic correlation of axillary lymph nodes in breast carcinoma.

A prospective study was performed to determine whether thoracic CT yielded useful information regarding the status of axillary lymph nodes (LNs) in patients with breast cancer. Thirty-five consecutive patients with clinically suspected stage II or III breast carcinomas were scanned preoperatively from the supraclavicular regions to the lung bases. Axillary LNs measuring greater than or equal to 1 cm were considered abnormal. The lymph nodes were classified according to their relationship to the pectoralis muscle. Extracapsular lymph node extension was diagnosed when there was irregularity and spiculation of the lymph node margin with surrounding fatty infiltration. Correlation with axillary dissection was obtained in 20 patients, giving a positive predictive value for axillary metastases of 89% with 50% sensitivity, 75% specificity, and 20% negative predictive value. CT was also able to detect the level of axillary involvement accurately when the lymph nodes were enlarged and to evaluate extracapsular LN extension. Although superior to physical examination, CT was not an accurate predictor of axillary LN involvement, primarily because of its low negative predictive value.

The left spectrum, the Levitzki radical, and noncommutative schemes.

This note contains a brief exposition of the basics of a noncommutative version of affine, quasi-affine, and projective algebraic geometry. In this version, to any associative ring (with unity) a quasi-affine (resp. affine) left scheme is assigned. The notion of the left spectrum of a ring plays the key role.