Axillary Surgery for Early-Stage, Node-Positive Mastectomy Patients and the Use of Postmastectomy Chest Wall Radiation Therapy.

BACKGROUND: We examined axillary surgery in mastectomy patients with tumor-positive nodes and how the type of axillary surgery impacted use of postmastectomy chest wall radiation therapy (PMRT). METHODS: Using the National Cancer Data Base, we selected patients with AJCC cT1/T2c N0 breast cancer with one to three tumor-positive lymph nodes treated between 2013 and 2014. Type of axillary surgery was analyzed using the FORDS scope of regional lymph node surgery variable. Multivariable logistic regression modeling was used to identify independent predictors associated with SNB alone and the use of PMRT. RESULTS: Of 8089 patients, 2482 (30.7%) underwent SNB alone, 1339 (16.6%) underwent axillary dissection (ALND) alone, and 4268 (52.7%) underwent SNB followed by ALND. Fifty-seven percent of patients with micrometastases underwent SNB alone compared with 22.6% of patients with macrometastases. Independent predictors of SNB alone for patients with micrometastases were African American race, number of nodes positive, and PMRT. For patients with macrometastases, age, facility type and location, and PMRT were independent predictors for SNB alone. Of 2449 patients who underwent SNB alone, 1538 (62.8%) had no PMRT, 261 (10.7%) had PMRT alone, and 650 (26.5%) had PMRT with regional nodal irradiation. Patients undergoing SNB alone were 1.70 times [96% confidence interval (CI) 1.45-2.00] more likely to undergo PMRT than upfront ALND and 1.51 times (96% CI 1.34-1.71) more likely than SNB followed by ALND. CONCLUSIONS: Surgeons are omitting completion ALND in a third of early-stage, node-positive mastectomy patients. SNB alone patients are more likely to undergo PMRT than patients undergoing ALND.

A method for the quantitative analysis of human heat shock gene expression using a multiplex RT-PCR assay.

A quantitative multiplex RT-PCR assay is described to measure the levels of messenger RNAs for eight human genes encoding the heat shock proteins (HSP) and molecular chaperones hsp90alpha, hsp90beta, hsp70, hsc70, mtHsp75, Grp78 (BiP), hsp60 and hsp27. The basis of this assay is reverse transcription of total RNA isolated from human cells followed by amplification with PCR. By the careful selection of pairs of oligonucleotide primers corresponding to unique regions of each heat shock gene, selectivity can be attained such that messenger RNAs of multiple heat shock genes can be analyzed simultaneously in a single reaction. This method provides both the absolute and relative levels of each heat shock message by including in the reaction, reference control RNAs corresponding to in vitro transcripts of heat shock gene plasmids carrying small internal deletions.

Male breast cancer.

Breast cancer in men is a rare condition affecting only 1,000 men each year in the United States. Hormonal, genetic, and perhaps environmental factors appear to be important in development of the disease. Clinically, breast cancer in men resembles that seen in woman. Histologically the diseases are indistinguishable, although lobular cancer is rare in men. Tumors from men are more likely to be estrogen-receptor positive. Treatment strategies draw from experience in women and usually begin with surgical removal of the tumor. Additional modalities often include hormonal, radiation, and cytotoxic therapies. The prognosis corrected for age and stage is similar to that of women. The study of breast cancer in men may provide new insights into epidemiologic and pathogenic factors that affect both sexes.

Indeterminate fine-needle aspiration biopsy of the thyroid: identification of subgroups at high risk for invasive carcinoma.

BACKGROUND: We examined the various cytologic features of indeterminate thyroid fine-needle aspirates along with known clinical and radiologic risk factors to determine whether any parameters were predictive of malignancy. METHODS: Indeterminate fine-needle aspirates were prospectively categorized into four subgroups: (1) suspicious for papillary carcinoma, (2) follicular neoplasm, (3) Hürthle cell neoplasm, and (4) hypercellular follicular aspirates with colloid. Several clinical risk factors were examined, and subgroup comparisons were performed with Fisher's exact test. RESULTS: Of 571 fine-needle aspirate cytologic findings 104 were interpreted as indeterminate for malignancy, and 81 patients underwent thyroidectomy. Invasive cancer was diagnosed in 9 of 10 lesions cytologically suspicious for papillary carcinoma, 8 of 43 follicular neoplasms, 5 of 18 Hürthle cell neoplasms, and 0 of 10 hypercellular aspirates. Cytologic subgroup (p < 0.0001) and age of 50 years or older (p = 0.008) were the only significant predictors of malignancy. When used together, age of 50 years or older and a cytologic diagnosis of follicular or Hürthle cell neoplasm also identified a subgroup of patients at high risk (9 of 20) of invasive malignancy (p = 0.01). CONCLUSIONS: The majority of invasive cancers (18 of 22, 82%) were found in patients whose lesions were suspicious for papillary carcinoma or in patients 50 years or older with follicular or Hürthle cell neoplasms. The risk of carcinoma in these combined subgroups (18 of 30, 60%) warrants early surgical intervention.

An analysis of male and female breast cancer treatment and survival among demographically identical pairs of patients.

BACKGROUND: Male breast cancer is rare, and there are no large comparative studies to guide treatment. We used National Cancer Data Base data on 4755 men and 624,174 women who had breast cancer (1985-1994) to identify equivalent groups of male and female breast cancer patients. METHODS: For each man with breast cancer, the next woman treated at the same hospital was sought who matched the man's age (within 5 years), ethnicity, income category, and stage. We identified 3627 closely matched pairs of male and female patients with breast cancer. RESULTS: Men were more likely to be treated with mastectomy (modified radical, 65% of men versus 55.1% of women; radical, 2.5% of men versus 0.9% of women; simple, 7.6% of men versus 3.4% of women; P <.001), and more likely to receive radiation therapy after mastectomy (men, 29%; women, 11%; P <.001). Men treated with lumpectomy were less likely to receive radiation therapy (men, 54%; women, 68%; P <. 001). Men were also less likely to receive chemotherapy (26.7% of men versus 40.6% of women; P <. 001) after any surgical treatment. CONCLUSIONS: This large comparative study is the first to detail stage-specific differences in contemporary treatment strategies for highly comparable groups of men and women treated for breast cancer. Further studies of male breast cancer should focus on identifying prognostic factors and defining optimal therapy.

Total lobectomy and total thyroidectomy in the management of thyroid lesions.

OBJECTIVE: To study an unselected consecutive series of patients undergoing thyroidectomy for tumors to establish the complication rates of total lobectomy with isthmectomy and total thyroidectomy. DESIGN: Retrospective study. PATIENTS: Two hundred eight consecutive, unselected patients were operated on by one surgeon from 1980 to 1990. One hundred nineteen patients (57%) had a total lobectomy and isthmectomy and 85 patients (41%) had total thyroidectomy. Four patients (2%) had partial excision for technical reasons, two with anaplastic cancers and two with advanced thyroiditis. RESULTS: Forty-two malignant lesions (20%) were diagnosed with a mean follow-up of 5 years. Malignant lesions were diagnosed in 15 (31%) of 48 males and 27 (17%) of 160 women. Ten patients (5%) had parathyroid adenomas. Long-term follow-up revealed that there were no deaths, permanent hypocalcemia, or recurrent laryngeal nerve damage. One patient was returned to the operating room to control bleeding. CONCLUSION: This study suggests that total thyroid lobectomy with isthmectomy and total thyroidectomy are both safe procedures in the management of thyroid tumors.

National treatment trends for ductal carcinoma in situ of the breast.

OBJECTIVE: To evaluate the national treatment trends for the management of ductal carcinoma in situ as related to the individual characteristics of patients and to the reporting of demographics. DESIGN: National Cancer Data Base review. PATIENTS: Patients (N = 39010) who were diagnosed as having ductal carcinoma in situ between 1985 and 1993. MAIN OUTCOME MEASURES: Treatment principles, including the use of breast-preserving surgery, axillary lymph node dissection, and radiotherapy, as related to the following variables: age, income level, and ethnicity of the patient; the tumor size, grade, and anatomical subsite; year of diagnosis; geographic location of treatment; and hospital type and caseload. RESULTS: During the 8 years of analysis, the use of breast preservation therapy increased from 31% to 54%. Treatment selection varied to some degree with each of the variables examined. Tumors with favorable sizes and grades were associated with increased rates of breast preservation and lower rates of axillary lymph node dissection and radiotherapy utilization. Overall, only 45% of the patients who were treated with breast preservation received adjuvant radiotherapy. However, during this study, radiotherapy utilization increased from 38% to 54%. Axillary lymph node dissection was performed in 49% of the patients with a 12% reduction in use over time. CONCLUSIONS: Breast-preserving surgery now accounts for more than half of all cases of ductal carcinoma in situ followed by the National Cancer Data Base. However, there still remains an inappropriately high rate of axillary lymph node dissection and a low rate of radiotherapy utilization. Clinical trial results and professional education should continue to optimize the management of patients with ductal carcinoma in situ.

Prospective, randomized trial of Doppler-assisted subclavian vein catheterization.

OBJECTIVE: To examine the rate of success and complications of Doppler-guided subclavian vein catheter insertion compared with standard insertion in patients considered at high risk for failure. DESIGN: Prospective, randomized, crossover trial. SETTING: University-affiliated tertiary care medical center. PATIENTS: Two hundred forty patients were enrolled in the study. Patients were stratified for 3 known risk factors: (1) prior surgery in the subclavian vein region, (2) prior radiotherapy at the attempted catheterization site, and (3) an abnormal weight-height ratio. INTERVENTIONS: Subclavian vein catheterization was performed either in standard or Doppler-guided fashion using the Smart Needle (Peripheral Systems Group, Mountain View, Calif), which is a Doppler probe at the tip of a cannulating needle. If subclavian vein catheterization was unsuccessful after 2 attempts, patients were crossed over to the other technique. MAIN OUTCOME MEASURE: Successful cannulation of the subclavian vein. RESULTS: The success rate, either as an initial technique or as a salvage technique, and complication rate were not significantly different with use of the Smart Needle. A subgroup of physicians had a significantly lower success rate using the Smart Needle. CONCLUSIONS: Doppler guidance did not increase the success rate or decrease the complication rate of subclavian vein catheterization when compared with the standard technique in high-risk patients. Doppler guidance was not more useful than the standard technique as a salvage technique following a previous failure of catheterization. Furthermore, real-time Doppler guidance of subclavian vein catheterization is a technique that is highly operator dependent.

The importance of DNA flow cytometry in node-negative breast cancer.

DNA flow cytometric analysis and conventional clinical factors were compared with disease outcome in 257 patients with node-negative infiltrating ductal carcinoma who had been treated between 1976 and 1983. Median follow-up was 80 months; none of the patients received adjuvant therapy. The relative prognostic importance of clinical variables, ploidy, and S-phase fraction was analyzed by Cox multivariate analysis. Ploidy was analyzable for 198 tumors and did not predict survival. Nuclear grade predicted disease-free survival for all patients. For 71 patients with diploid tumors, only high S-phase had a statistically significant association with relapse. For 127 patients with aneuploid tumors, tumor diameter predicted both disease-free survival and cancer death; histologic grade was also significant for predicting disease-free survival. In conclusion, flow cytometric determination of ploidy and S-phase fraction can provide valuable predictive information in node-negative breast cancer in addition to conventional variables.

Laparoscopic inguinal hernia repair. A preliminary experience.

OBJECTIVE: To evaluate the safety and efficacy of laparoscopic inguinal hernia repair. DESIGN: Nonrandomized trial. SETTING: Veterans Affairs hospital and a large university hospital. PATIENTS: The study included 38 patients (36 male and two female) who had an acceptable risk for general anesthesia, presented electively, and gave informed consent; patients were excluded for whom general anesthesia had a high risk or who had incarcerated or strangulated hernias. INTERVENTION: Laparoscopic inguinal hernia repair was performed with general anesthesia through bilateral, lower-abdominal, 12-mm lateral rectus sheath ports with an umbilical 30 degrees viewing laparoscope. After the peritoneum was incised and flaps were raised, an onlay patch of polypropylene mesh, secured with staples, covered both indirect and direct hernia regions in each patient. Small hernia sacs were usually reduced or excised. RESULTS: From December 1991 through October 1992, 40 inguinal hernias were repaired; two patients had bilateral hernias. There were 22 indirect and 17 direct inguinal hernias and one femoral hernia. Nine of the hernias repaired were recurrent, and five were sliding hernias. Complications occurred in nine patients, but there were no recurrences during a median follow-up of 26 weeks. All but one patient resumed preoperative activities by 7 days after the operation. CONCLUSIONS: Laparoscopic inguinal hernia repair is an effective operation with low morbidity. Long-term follow-up is needed to determine the durability of the repair.

Intercostal hemangioma presenting as a chest wall tumor.

Skeletal muscle hemangiomas are uncommonly described in a variety of locations. This report details the diagnosis and management of a 39-year-old woman with a right chest wall mass detected on physical examination. After a negative diagnostic evaluation, exploratory thoracotomy revealed an intercostal hemangioma, undescribed in recent literature. The lesion was excised.

Intraoperative radioisotope sentinel lymph node mapping in non-small cell lung cancer.

BACKGROUND: Lymph node metastases are the most significant prognostic factor in localized non-small cell lung cancer (NSCLC). Nodal micrometastases may not be detected. Identification of the first nodal drainage site (sentinel node) may improve detection of metastatic nodes. We performed intraoperative Technetium 99m sentinel lymph node (SN) mapping in patients with resectable NSCLC. METHODS: Fifty-two patients (31 men, 21 women) with resectable suspected NSCLC were enrolled. At thoracotomy, the primary tumor was injected with 2 mCi Tc-99. After dissection, scintographic readings of both the primary tumor and lymph nodes were obtained with a handheld gamma counter. Resection with mediastinal node dissection was performed and findings were correlated with histologic examination. RESULTS: Seven of the 52 patients did not have NSCLC (5 benign lesions, and 2 metastatic tumors) and were excluded. Forty-five patients had NSCLC completely resected. Mean time from injection of the radionucleide to identification of sentinel nodes was 63 minutes (range 23 to 170). Thirty-seven patients (82%) had a SN identified; 12 (32%) had metastatic disease. 35 of the 37 SNs (94%) were classified as true positive with no metastases found in other intrathoracic lymph nodes without concurrent SN involvement. Two inaccurately identified SNs were encountered (5%). SNs were mediastinal (N2) in 8 patients (22%). CONCLUSIONS: Intraoperative SN mapping with Tc-99 is an accurate way to identify the first site of potential nodal metastases of NSCLC. This method may improve the precision of pathologic staging and limit the need for mediastinal node dissection in selected patients.

A comparative analysis of lobular and ductal carcinoma of the breast: presentation, treatment, and outcomes.

BACKGROUND: Compared with invasive ductal carcinoma, invasive lobular carcinoma of the breast is considered by many to be a more indistinct and multicentric form of cancer that is detected later and is treated less optimally by breast-preservation techniques. This study analyzed the presentation, treatment trends, and survival rates of women who had invasive lobular and ductal breast carcinoma. The objective was to determine the utility of breast-preservation therapy for invasive lobular carcinoma by analysis of historic data on tumor features and survival. STUDY DESIGN: Data on 291,273 women diagnosed with invasive carcinoma between 1985 and 1993 were obtained from the National Cancer Data Base. Analysis included the patient's age at diagnosis; tumor histology, anatomic site, diameter, grade, and stage; treatment; and disease status 5 years after diagnosis. RESULTS: The mean patient age at diagnosis was 61.0 years for invasive ductal carcinoma, 63.0 years for invasive lobular carcinoma, and 60.6 years for tumors with combined histology. The anatomic location, tumor diameter, and tumor grade were similar for each histotype. Breast-preservation therapy was less frequent for invasive lobular carcinoma. The 5-year overall survival and local disease-free survival rates for women treated with breast preservation were similar for invasive ductal carcinoma (84% overall survival; 97% disease-free survival) and invasive lobular carcinoma (87% overall survival; 98% disease-free survival). CONCLUSIONS: Invasive lobular carcinoma presents with a similar age distribution, anatomic subsite, diameter, and grade as invasive ductal carcinoma. Breast preservation is selected less commonly for women who have invasive lobular carcinoma, but this choice of therapy does not compromise the disease-free or overall survival status of this group of patients.

Sentinel lymphadenectomy for breast cancer: experience with 180 consecutive patients: efficacy of filtered technetium 99m sulphur colloid with overnight migration time.

BACKGROUND: Axillary node status remains the most important prognostic indicator of survival in breast cancer patients. Only 25% to 35% of patients having standard level I/II axillary dissection have involved nodes, yet all accept the potential for morbidity after the operation. This study was conducted to assess whether status of the sentinel node(s) was an accurate predictor of the presence of metastatic disease in axillary or internal mammary nodes. STUDY DESIGN: In 180 patients, technetium 99m sulphur colloid was injected in a 4-quadrant peritumoral distribution. During the first phase of the study, 72 patients had sentinel node excision followed by a level I/II axillary dissection. During the second phase of the study, 108 patients had sentinel node excision and only those with positive nodes had completion axillary dissection. Nodes were examined after formalin fixation by taking 10 sections at 20-microm intervals and staining with hematoxylin-eosin. RESULTS: Sentinel nodes were found in 162 (90%) of 180 patients. The mean number of sentinel nodes examined was 3.1. Of the 162 patients with successful lymphatic mapping, positive sentinel nodes were found in 44 (27%). In 23 (66%) of 35 patients with positive sentinel nodes who had a completion level I/II axillary dissection, the sentinel nodes were the only positive nodes. The concurrent negative predictive value was 4% in the first 72 patients who had completion axillary dissection after sentinel node excision, and 2% for the entire series. With evolution of technique, identification of sentinel nodes with radiolabeled colloid was successful in 97% of the last 100 patients. CONCLUSIONS: Because the concurrent negative predictive value was low, sentinel node excision appeared to accurately identify node status, potentially avoiding the need for standard level I/II axillary dissection in sentinel node-negative patients.

The spectrum of vascular lesions in the mammary skin, including angiosarcoma, after breast conservation treatment for breast cancer.

BACKGROUND: With the general acceptance of lumpectomy, axillary staging, and radiotherapy as local treatment for infiltrating breast cancer, an appreciation is evolving for the spectrum of vascular lesions that occur in the mammary skin after this treatment. Most of these lesions develop within the prior radiation field after breast conservation treatment. STUDY DESIGN: A retrospective chart and slide review was conducted, consisting of five patients with cutaneous vascular lesions after breast conservation treatment for infiltrating breast cancer. RESULTS: The latent time interval from definitive treatment of breast cancer to the clinical recognition of vascular lesions ranged from 5 to 11 years. Two patients did not have either arm or breast edema, two patients had breast edema, and the fifth patient had arm edema. Lesions arising in the irradiated mammary skin included extensive lymphangiectasia (one), atypical vascular lesions (two), and cutaneous angiosarcoma (four). CONCLUSIONS: Atypical vascular lesions at the skin margins of mastectomy may be predictive of recurrence after resection of angiosarcoma. Excision of skin from the entire radiation field may be necessary to secure local control of the chest wall in patients with cutaneous angiosarcoma after therapeutic breast radiotherapy.

The correlation of axillary ultrasonography with histologic breast cancer downstaging after induction chemotherapy.

BACKGROUND: The goal of this study was to examine the role of ultrasonography in detecting axillary lymph node metastases in stage II breast cancer patients after induction chemotherapy (IC). METHODS: Of 172 consecutive patients with T1-3, N0-1, M0 breast cancer registered in a prospective IC trial, a subset of 130 evaluable patients were chosen, with (1) both physical and ultrasonographic examinations of the axilla before and after IC; (2) exactly four cycles of IC; (3) no presurgical radiation therapy; and (4) an axillary lymph node dissection. RESULTS: Before IC, 32 patients (25%) were negative for axillary involvement by both physical and ultrasonographic examinations. After IC, this number increased to 64 (49%). Of these, 31 (48%) were positive by pathology examination. In most cases, however, the residual tumor was minimal. CONCLUSIONS: Stage II breast cancer patients who were or became node negative by both ultrasonographic and physical examinations after IC had a 48% incidence of nodal metastases. Because the residual tumor was minimal, irradiation may be sufficient for adequate local control of the axilla.

Spectrum of mammographically detected breast cancers.

Mammographic screening of women at both ends of the age spectrum presents a number of challenges. The purpose of this study was to characterize experience with mammographic detection of breast cancer. The two goals were 1) to establish the cancer detection rate of screening mammography and 2) to compare the tumor size of cancers found by mammography, physical examination, or both modalities. From January 1994 through June 1997, data on 609 consecutive female primary breast cancer patients were collected concurrent with definitive surgical therapy. The method of detection was determined by the surgeon, after reviewing mammogram and physical examination. Screening ultrasound was not used. For the 184 patients under 50 years of age, 53 (29%) cancers were detected by mammography only and 48 (26%) by physical examination only. Women under 50 years of age had fewer cancers detected by mammography only (P < 0.001) and more cancers detected by physical examination only (P = 0.0014) than those over 50. With increasing age, the proportion of women with ductal carcinoma in situ decreased (P = 0.004), and the proportion with T1c or T2 tumors increased (P = 0.006). We conclude that 1) when examining women under 50 years of age, the surgeon must be clearly focused on the double-edged sword of screening mammography in this age group, and 2) community cancer programs should encourage annual screening of women over 40 years of age but focus on those over 70, without an arbitrary upper age limit.

Male breast cancer.

Male breast cancer is an uncommon malignancy, making it difficult to accurately define the features and optimal management of this disease. As more information is generated, it appears that the pathogenesis is related in large part to hormonal alterations but that the histologic features, biologic behavior, and prognosis are similar to tumors in female patients. As a result of larger studies based upon female patients, treatment algorithms have evolved to include multimodality therapy and less radical surgery. Continued research of this disease will continue to define improved methods of detection, prevention, and treatment, and, without the confounding variables of the menstrual cycle, menopause, and childbirth, may also provide a clearer understanding of breast cancer in women.

The National Cancer Data Base report on the results of a large nonrandomized comparison of breast preservation and modified radical mastectomy.

BACKGROUND: Although the conclusions reached in the National Surgical Adjuvant Bowel and Breast Protocol B-06 trial and other clinical trials appear to remain intact, questions persist regarding the equivalency of breast preservation compared with modified radical mastectomy for patients with invasive carcinoma. Documentation and assessment of comparative survival rates in a large cohort of nonrandomized breast carcinoma patients was undertaken to understand better these outcome patterns. METHODS: Information gathered from the medical records of 96,030 women diagnosed with early stage carcinoma of the breast between 1985 and 1988 was reviewed to determine the age at diagnosis; tumor stage, grade, dimension; treatment; and disease status. RESULTS: Of these 96,030 Stage I and II (based on the American Joint Committee on Cancer staging system) patients, 8583 (8.9%) were treated with segmental mastectomy, axillary lymph node dissection, and radiotherapy without systemic treatment. Three thousand seven hundred and ninety-seven patients (4.0%) were treated with segmental mastectomy, axillary lymph node dissection, radiotherapy, and systemic therapy. Forty-four thousand two hundred and forty-nine patients (46.0%) were treated with modified radical mastectomy without systemic therapy, and 18,322 patients (19.1%) were treated with modified radical mastectomy with systemic therapy. Within each stage, reported survival was equal to or more favorable for patients managed with breast preservation compared with those treated with modified radical mastectomy. This comparability was observed in all subsets analyzed including those defined by age at diagnosis, histologic grade, and tumor dimension. CONCLUSIONS: These findings are consistent with the hypothesis that AJCC Stage I and II patients treated with breast preservation appear to have survival rates equivalent to those treated with modified radical mastectomy.