Interstitial laser therapy of breast fibroadenomas with 6 and 8 year follow-up.

Fibroadenomas are non-cancerous breast tumors commonly seen in teenagers but also found in women at the time of first mammogram. They have distinct physical findings and imaging features but the definitive diagnosis is made by ultrasound or stereotactic guided needle biopsy. Treatment options are observation or surgical removal. Recently, removal by ultrasound-guided technique has been reported. Alternatively, the tumor may be ablated within the breast by cold (cryotherapy) or by heat (laser, radiofrequency, focused ultrasound and microwave). In this paper the laser treatment in two patients, one with bilateral fibroadenomas, with 6 and 8 year follow-up is presented.

Thermal ablation of the goat mammary gland as a model for post-lumpectomy treatment of breast cancer: preliminary observations.

BACKGROUND: Partial breast irradiation post-lumpectomy, with a balloon bearing a radioactive source in its center, is practiced as an alternative to whole breast irradiation in the treatment of breast cancer. The goal is to ablate residual malignant cells within 1 cm radius of the resected lumpectomy margin. We hypothesize that this goal may be achieved with a fluid-filled heated balloon. METHODS: Nubian-cross goats were treated under general anesthesia. The two mammary glands were sequentially bisected and a non-inflated balloon with a heating element was placed in the center of the gland which was re-sutured. Two series of experiments were conducted. In the first 22 goats (44 glands), the balloon was inflated with 5% dextrose to a pressure of 150 mmHg and heated at 87 degrees C over selected time intervals of 1-24 minutes. In the second series (16 glands), the re-programmed device operated at 50-80 mmHg over selected time intervals of 5-20 minutes. The depth of necrosis was histologically determined after sacrificing the goats and excising the glands. RESULTS: In the first series, glandular necrosis was noted to extend to a depth of 3.2-9.6 mm for the above heating cycles. Corresponding figures for the second series ranged from 4.7-8.6 mm for treatment times of one minute 'warm up' to 20 minutes of heating at 90 degrees C. The animals exhibited no systemic side effects post-treatment. CONCLUSION: An experimental model describing a thermal technique causing necrosis of the goat mammary gland is described.

Phase I/II trial of tamoxifen with or without fenretinide, an analog of vitamin A, in women with metastatic breast cancer.

PURPOSE: Considerable attention has been focused on the chemopreventive properties of fenretinide against carcinogen-induced rodent mammary cancer. Less is known about its direct antitumor effects. The combination of tamoxifen and fenretinide is more effective than tamoxifen or fenretinide alone in prevention of rat mammary cancer. However, the combined toxicity of tamoxifen plus fenretinide in humans is unknown. Therefore, we performed a phase I/II trial in women with estrogen receptor (ER)-positive or progesterone receptor (PR)-positive, previously untreated metastatic breast cancer. PATIENTS AND METHODS: Groups of three patients received tamoxifen 20 mg/d, or tamoxifen plus fenretinide 100, 200, 300, or 400 mg/d. Patients who received fenretinide enjoyed a 3-day "drug holiday" every 4 weeks. Serum levels of fenretinide and its major metabolites were monitored. Patients were monitored for known toxicities of tamoxifen and vitamin A analogs, as well as for response. RESULTS: There were no significant adverse effects on renal, hepatic, hematologic, or lipid values. Nyctalopia, photophobia, cheilitis, and pruritus were not observed. Improvement or stabilization of disease occurred in 12 of 15 patients. CONCLUSION: We conclude that tamoxifen administered with fenretinide is nontoxic. Phase III trials of tamoxifen versus tamoxifen plus fenretinide are warranted.

Therapeutic effect of N-(4-hydroxyphenyl)retinamide on N-methyl-N-nitrosourea-induced rat mammary cancer.

Virgin Sprague--Dawley rats received a single i.v. injection of 40 mg N-methyl-N-nitrosourea (MNU)/kg body wt. at 50 days of age. After the first palpable mammary tumor reached 10 mm in size, the animals were sequentially allocated to one of 4 groups: (I) placebo diet, (II) 10 micrograms tamoxifen s.c. 3 times per week, (III) 3 mmol N-(4-hydroxyphenyl)retinamide (4-HPR)/kg diet, or (IV) both (II) and (III). Weekly measurements of initial tumors and subsequent tumors were made throughout the study. 4-HPR administration resulted in a complete regression (non-palpable state) of the first mammary tumor in 6 animals (22%) and partial regression or nonprogression in 5 others (19%). Tamoxifen alone induced only partial response in 9 animals (33%). 4-HPR and tamoxifen resulted in 19% total and 26% partial response. The data suggests therapeutic value of 4-HPR in MNU-induced rat mammary carcinoma.

Evaluation of brush cytology as an independent technique for detection of esophageal carcinoma.

In this study the accuracy of indirect brush cytology for detection of esophageal carcinoma is evaluated against current standard methods of diagnosis and is compared with the known accuracy rate of endoscopically directed brush cytology. A standard endoscopic nylon brush placed inside a nasogastric tube was used in 203 patients with various esophageal problems. Correct diagnosis was made in 78% of cancers, 95% of potentially premalignant cases, and 100% of cases of normal esophageal mucosa with both indirect and directed brushing procedures. The technique meets most requirements of a new screening procedure as being simple, safe (no complications), relatively inexpensive, and acceptable to patients (98% compliance). Currently it is employed to monitor high-risk esophageal conditions and post-treatment courses of patients with pharyngoesophageal tumors for local recurrence or a new primary lesion in the esophagus.

Percutaneous interstitial laser therapy of a patient with recurrent hepatoma in a transplanted liver.

We report in situ treatment, by focal hyperthermia, of a recurrent hepatoma in the transplanted liver of a 53-year-old man. Hyperthermia was generated by neodymium-yttrium-aluminum-garnet laser, which was delivered through a fiber placed inside a 19-gauge needle and inserted percutaneously into the liver under ultrasound guidance. The effect was monitored in real time by ultrasound and subsequently confirmed by computerized tomography and needle core biopsy. Objectively the tumor growth was halted for 3 months, indicating partial response to this minimally invasive treatment.

Cytologic diagnosis of occult breast lesions using stereotaxic needle aspiration. A preliminary report.

In mammographically detected breast lesions, only 10% to 25% of biopsy specimens are malignant. Furthermore, the current method of needle localization of these lesions is cumbersome and inefficient. Stereotaxic needle aspiration was used to examine 84 patients. Successful localization with the needle tip within 1 to 2 mm of the suspected lesion was possible in 80 cases (95.2%). Following aspirate cytology, the lesion was localized with indigo carmine and Kopans' wire and every patient underwent a standard open excisional biopsy. Twelve cases of breast cancer were diagnosed histologically. Eleven of these cases were correctly diagnosed cytologically, while one case yielded a false-negative result. In the remaining 72 histologically benign cases, four lesions were reported cytologically to be atypical. There were no complications. Stereotaxic needle aspiration localizes occult breast lesions precisely and in conjunction with mammography, and it is an acceptable preoperative method of diagnosing nonpalpable breast tumors.

Stereotactically guided laser therapy of occult breast tumors: work-in-progress report.

HYPOTHESIS: Mammographically detected breast tumors can be completely ablated with laser energy. DESIGN: Nonrandomized control trial. SETTING: A university hospital ambulatory care center. PATIENTS: Thirty-six patients with mammographically detected well-defined breast tumors were selected. INTERVENTIONS: The diagnosis of malignant neoplasms and determination of prognostic factors were established by image-guided needle-core biopsy. Patients were treated on a stereotactic table, using a 16- to 18-gauge laser probe, with an optic fiber transmitting a predetermined amount of laser energy. A multisensor thermal probe was inserted into the breast adjacent to the laser probe to monitor treatment. In the last 10 patients, the tumor blood flow was evaluated before and after laser therapy with contrast-enhanced color Doppler ultrasound. One to 8 weeks after laser therapy, the tumors were surgically removed and serially sectioned. MAIN OUTCOME MEASURE: Complete necrosis in 66% of tumors. RESULTS: Total tumor ablation with negative margins was observed whenever 2500 J/mL of tumor was given or the thermal sensors recorded 60 degrees C. Microscopic examination at 1 week showed disintegration of malignant cells, with peripheral acute inflammatory response and at 4 to 8 weeks extensive fibrosis. Contrast-enhanced color Doppler ultrasound revealed loss of tumor circulation after therapy, and positron emission tomography scan correlated well with histologic findings. There were no systemic adverse effects. Two patients sustained 3 x 4-mm skin burns around the laser needle. CONCLUSION: A stereotactically guided minimally invasive technique may be effective for the treatment of mammographically detected breast cancer.

Cryosurgery of breast cancer.

OBJECTIVE: To determine the feasibility and efficacy of cryosurgery of breast cancer. DESIGN: In phase 1, carcinogen-induced mammary adenocarcinomas in 13 Sprague-Dawley rats were treated by cryosurgery and were then examined for histopathologic change. In phase 2, transplantable mammary adenocarcinomas in 50 DBA/IJ mice were treated by cryosurgery to determine the effect of varying tumor temperatures, and duration and number of freeze-thaw cycles on tumor viability. In phase 3, 2- to 3-cm ultrasound-monitored cryolesions were formed in the breasts of 4 dogs and 4 sheep. These animals were followed up for procedure-related complications; the histopathologic necrosis of the cryolesions were correlated with the ultrasound images. Based on the results of these experiments, ultrasound-guided cryosurgery of breast cancer was initiated in a human clinical trial. RESULTS: In phase 1, a single, short-term (< 7 minutes) freeze killed only tumors smaller than 1.5 cm in diameter, despite an apparent decrease to -40 degrees C at the periphery of each tumor. In phase 2, varying the peripheral tumor temperature to as low as -70 degrees C, using a single, short-term (< 7 minutes) freeze did not alter the results from phase 1. If the ice ball fully encompassed the tumor, however, maintaining it for at least 15 minutes achieved 100% tumor kill independent of tumor size. In phase 3, creation of a reproducible ultrasound-monitored cryolesion was facilitated when 2 freeze-thaw cycles were performed. No procedure-related complications were noted. In the human trial, 2 invasive lobular carcinomas from 1 patient were treated by cryosurgery and were negative for persistent tumor by core needle biopsy performed 4 and 12 weeks after a well-tolerated procedure. CONCLUSIONS: In situ breast cryosurgery has been proved to be feasible and efficacious in small and large animal studies and has been successfully performed in 1 patient with breast cancer. The results of this study suggest that ultrasound-guided cryosurgery of breast cancer warrants further investigation.

Sentinel node biopsy in the staging of breast cancer.

BACKGROUND: The role of axillary lymph node dissection (ALND) in breast cancer is currently being reevaluated. Sentinel node biopsy (SNB) holds promise for replacing full dissection in a large number of patients with breast cancer. MATERIALS: We evaluated SNB utilizing an intraoperative gamma probe localization technique following injection of technetium sulfur colloid in 80 patients with primary breast cancer and clinically negative axillae. Forty-eight patients were evaluated at Baptist Medical Center, Montgomery, Alabama, and 32 at Rush-Presbyterian-St. Luke's Medical Center in Chicago, Illinois. RESULTS: At least one sentinel node was found in 70 of the 80 patients (88%). One patient had a sentinel node in both the axilla and internal mammary chain. The remainder had axillary sentinel nodes only. The sentinel nodes accurately predicted the status of the axilla in 69 of the 70 patients (99%). One of 14 node-positive patients would have been missed with sentinel node biopsy alone, for a false negative rate of 7%. Four node-positive patients would have been missed with routine ALND without serial sectioning (SS) and immunohistochemical staining (IH) of the sentinel node. CONCLUSIONS: Sentinel node biopsy with SS and IH more precisely predicted the status of the axilla than routine ALND in this group of patients. SNB will likely replace full axillary dissection in the majority of patients with breast cancer.

Image-guided surgery of small breast cancers.

BACKGROUND: Widespread screening mammography has resulted in detection of many breast cancers smaller than one cm. Image-guided percutaneous needle sampling provides accurate diagnostic and prognostic information for adjuvant therapy. Less invasive methods based on imaging techniques are emerging as an alternative to wire localization and lumpectomy. DATA SOURCES: Information presented in this overview was provided by seven investigators from five medical centers in the United States. These researchers are currently developing various techniques of image-guided percutaneous therapy of small (Tis, 1) breast cancers. CONCLUSIONS: Several percutaneous treatment modalities for treatment of early breast cancer, either excisional or in-situ ablative, are described in this overview and their potential applications are discussed.

Brush cytology for the early detection of esophageal carcinoma among patients with upper aerodigestive malignancies.

The incidence of associated esophageal carcinoma (EC) among patients with upper aerodigestive tract malignancies is high. Esophageal brush cytology, as developed and evaluated as a screening device for early detection of EC among villagers of northeastern Iran, was employed to examine 56 clinic patients with known tumors of the upper aerodigestive tract on 106 occasions. Two asymptomatic EC were detected and are presented. The procedure was also used as an adjunct to endoscopy in order to monitor the response of tumors under treatment. Sensitivity of 40% and specificity of 90% were found and could be improved with more judicious application of the procedure. The use of this simple test for early detection of EC among this high risk subset of clinic patients is recommended.

Stereotaxic fine needle aspiration cytology of clinically occult malignant and premalignant breast lesions.

Stereotaxic fine needle aspiration (FNA) cytology was used to study clinically occult (nonpalpable) breast lesions in 114 consecutive patients with mammographically suspicious findings prior to excisional biopsy. The aspirate contained insufficient material for cytologic evaluation in 15 cases (13.2%), which were histologically diagnosed as benign (7 cases), atypical hyperplasia (7 cases) or carcinoma in situ (1 case). The cytologic findings indicated a benign lesion in 77 cases (67.5%), which were histologically diagnosed as benign (71 cases) or atypical ductal hyperplasia (6 cases). The cytologic sample showed atypia in eight cases (7.0%), which were histologically diagnosed as severe atypical ductal hyperplasia (three cases), carcinoma in situ (one case) or proliferative fibrocystic disease (four cases). In the eight cases (7.0%) cytologically interpreted as probably malignant, histology confirmed six invasive carcinomas, one carcinoma in situ and one fibrocystic disease. Of six cases (4.4%) cytologically reported as malignant, five were histologically diagnosed as invasive carcinoma and one as carcinoma in situ. Overall, stereotaxic FNA cytology reported as malignant or probably malignant 14 of the 15 cases with a histologic confirmation of malignancy, for a sensitivity of 93.3%. Cytology correctly identified 78 of the 83 histologically negative cases, for a specificity of 94.0%. The 16 cases histologically diagnosed as ductal hyperplasia, which carries a high risk for subsequent malignancy, were studied in detail in an effort to define histologic and cytologic criteria for this entity. Using selected histologic criteria, 11 of these cases were graded as showing mild-to-moderate atypical hyperplasia and 5 as showing severe atypical hyperplasia. Three of the latter cases were similarly identified by an analogous cytologic grading; the other two cases had insufficient cytologic samples. The total results in this series of 114 cases support the use of stereotaxic FNA cytology in the diagnosis of these nonpalpable breast lesions, examples of which are illustrated. In particular, it may help to raise the low specificity yielded by mammography alone, which would represent a significant advance for the patient in terms of the accuracy, expediency and reduced cost of diagnosing these lesions.

Positron emission tomography with fluorine-18 fluorodeoxyglucose to evaluate response of early breast carcinoma treated with stereotaxic interstitial laser therapy.

Stereotaxic interstitial laser therapy is a promising new alternative to surgery to treat early-stage breast cancer. With this, laser energy coagulates the tumor with controlled heat, leading to fibrosis. Fluorodeoxyglucose positron emission tomography (FDG PET) scanning was performed in four patients treated by this technique to determine the degree of necrosis after interstitial laser therapy. The results showed that FDG PET scanning was in close agreement with histopathologic findings, confirming complete necrosis in one patient and variable response in the other three patients. Uptake of FDG appears to be a reliable means to monitor treatment response after interstitial laser therapy and may be useful in the management of breast cancer when used with this new procedure.

Early detection of cancer of oesophagus along Caspian Littoral. Report of a pilot project.

A simple mass-screening procedure for the early detection by brush cytology of oesophageal cancer in 280 adults in high-incidence villages of the Caspian Littoral is described. The presence of atypical cells in 7%, and the discovery of frank carcinoma in 3 symptom-free people encourages continuation of the project.

Colorectal carcinomas: diagnostic implications of their changing frequency and anatomic distribution.

This retrospective review included 1,694 consecutive cases of colorectal carcinoma diagnosed at the University of Chicago Medical Center during a 25-year period (1960 through 1984). The number and percentage of tumors occurring within 7 anatomic segments of the large bowel were determined. The statistical data for a recent 5-year interval were then compared with those of the 2 preceding decades. There was a 10.2% increase in the frequency of cancers originating in the cecum or ascending colon, while rectal and rectosigmoid carcinomas declined by 15.8% during the same study period. These data provide further evidence for a progressive left-to-right shift in cancer distribution within the colon during the past quarter century. Currently, the most proximal and distal 20-25 cm segments of the large bowel (cecum or ascending colon versus rectum and rectosigmoid) each harbor approximately 25% of the tumors. Therefore, the classic medical teaching that over 50% of colorectal cancers would be detectable by digital examination and/or proctosigmoidoscopy is no longer accurate. This documented increase in proximal colon cancers and redistribution of lesions within various large bowel segments indicate the growing importance of barium enema and colonoscopy as the optimal techniques for detection of colorectal neoplasms.

Histologic evaluation of rat mammary tumor necrosis by interstitial Nd:YAG laser hyperthermia.

The extent of coagulative necrosis caused by interstitial laser hyperthermia was measured for different quantities of laser energy in a rat mammary tumor model. Continuous wave Nd:YAG laser at a power level of 5 W was focused onto a 600 mu diameter bare tip quartz fiber and placed inside a 19-gauge needle, which allowed the para-axial flow of normal saline at 1 cc/min. A microthermocouple soldered to the outside of the probe continuously provided the interstitial temperature. After the probe was inserted into the tumor, it was withdrawn as laser energy was administered at a rate sufficient to maintain the temperature within 42-45 degrees C. Tumors were excised after 48 hours, fixed in formalin, cut in 3 mm slices, and the coagulated surfaces measured microscopically. Laser fiber transmission loss was 1% per 1,000 J of laser energy and the average time required to coagulate 1 cc of tumor was 2 minutes. There was a statistically significant correlation between the volume of tumor necrosis and the level of laser irradiation (r = 0.71, P less than 0.001). It is concluded that the described technique is an efficient method of tumor coagulation by interstitial laser hyperthermia and proportionally larger volumes of necrosis are created with greater amounts of laser energy.