Is a completion axillary dissection indicated for micrometastases in the sentinel lymph node?

OBJECTIVE: The purpose of this study is to determine if a completion axillary dissection (CAD) is necessary when microscopic metastasis (<2 mm) is detected in the sentinel lymph node (SLN) of patients diagnosed with breast cancer. METHODS: A retrospective chart review was performed on 227 consecutive breast cancer patients who underwent SLN mapping (SLNM) between June 1998 and March 2001. These patients underwent intraoperative lymphatic mapping with peritumoral injections of blue dye alone or in combination with technetium-labeled sulfur colloid. The SLN was assessed by touch preparation or frozen section at the time of surgery, and later, by hematoxylin and eosin stain. Patients in whom the SLN showed evidence of metastatic disease on frozen section underwent immediate CAD. RESULTS: One patient was excluded because of inability to identify the SLN. Of the 226 patients in whom SLNM was successful, 67 (27%) had macrometastasis in the SLN, and a completion CAD was performed. Thirty-four of these 67 patients (51%) had additional disease in the axilla. A total of 15 patients (6.7%) was determined to have micrometastasis. In 11 patients, micrometastasis was identified and CAD was performed with no further evidence of disease. The 4 patients diagnosed with micrometastatic disease on permanent staining did not have further surgical intervention. The 15 patients identified with micrometastasis show no evidence of local recurrence to date, with a mean follow-up of 13.5 months (range 1 to 27). CONCLUSIONS: This study suggests that CAD may not be necessary for the subset of breast cancer patients with micrometastasis detected upon SLNM. A larger randomized prospective study with long-term follow up is necessary to confirm these data.

Is DNA ploidy an independent prognostic indicator in infiltrative node-negative breast adenocarcinoma?

To evaluate DNA content as an independent, long-term prognostic indicator in infiltrative, node-negative adenocarcinoma of the breast, flow cytometric DNA analyses were performed retrospectively in 165 patients. The exclusive use of paraffin-embedded tissue permitted the study of patients for whom 3 to 15 years' follow-up was available. Other investigators have shown a relationship between DNA nuclear content and well-known prognostic indicators of breast carcinoma, such as estrogen receptors, age, menopausal status, and stage of tumor. However, very few of these studies were based on patients with long-term clinical follow-up and investigated the independent prognostic value of DNA nuclear content. The frequency of aneuploidy in the patients in this study was 57%, with DNA indices ranging from 0.73 to 2.59. Survival in patients with localized breast carcinoma with DNA aneuploid tumors was 84.1% at 5 years and 75.5% at 10 years. Those with diploid tumors showed survival of 87.8% at 5 years and 73.4% at 10 years. These data show no independent prognostic value for DNA nuclear content. The relationship between DNA content, tumor histologic type, and age was also investigated. High-grade tumors were more often aneuploid. There was no association between DNA content and age. Of 165 patients, information regarding estrogen receptor status was available in only 77; 45% of those with aneuploid tumors and 35% with diploid tumors were estrogen receptor-negative. This difference was not significant. The authors conclude that simple determination of DNA ploidy fails to indicate prognosis for infiltrative, node-negative breast carcinoma.

Follow-up on flow cytometric DNA analysis of squamous cell carcinoma of the tongue.

Preliminary data from this institution suggested that flow cytometric DNA analysis was an objective prognostic indicator in archival localized squamous cell carcinoma of the tongue. Technical improvements were made, including analysis of tumor, normal tissue, and a combination of the two; standardized cursor placement; mathematic determination of tetraploid populations; and development of a statistical analysis. A larger number of patients (60) with this disease were reviewed. DNA content was related to disease-free survival, local recurrence, regional metastasis, and incidence of second primary tumors. There was no significant difference between aneuploid and diploid tumors with respect to the variables analyzed. We believe these technical improvements will enhance flow cytometric DNA analysis of paraffin-embedded tissues. However, in this retrospective review of localized squamous cell carcinoma of the tongue, DNA analysis was not a valuable prognostic indicator. Only prospective studies will address this issue.

Results of surgical excision of one to 13 hepatic metastases in 98 consecutive patients.

Metastatic carcinoma to the liver is generally considered to be associated with a poor prognosis, with five-year survival of only 20% to 30% after resection of solitary lesions. Ninety-eight consecutive patients underwent the surgical removal of one to 13 metastatic lesions from the liver. A rising carcinoembryonic antigen level was considered an indication for reexploration. All gross tumor was removed in every patient; 66 had more than one metastasis. Survival was unexpectedly high: 91 of 98 were alive at 12 months, 50 (70%) of 71 at 13 to 24 months, 23 (66%) of 36 at 25 to 36 months, 14 (74%) of 19 at 37 to 48 months, six (60%) of ten at 49 to 60 months, four (80%) of five at 61 to 72 months, and two (50%) of four 73 to 84 months after resection of multiple liver metastases. The procedure appears to be a safe and, in some patients, beneficial surgical technique for the removal of multiple hepatic metastases.

Technical and statistical improvements for flow cytometric DNA analysis of paraffin-embedded tissue.

Flow cytometric DNA analysis of paraffin-embedded solid tumors has permitted review of large series of archival tissue in attempts to relate abnormal DNA content to prognosis. Limitations of the technique include: 1) a laborious, time-consuming procedure; 2) variation in technique between laboratories; and 3) lack of an objective method of computing DNA indices. Critical evaluation of our technique has shortened the time involved in dewaxing and rehydration, selectively utilized patient's own normal tissue as the internal standard, proved reproducibility of stored specimens, standardized DNA index computation, and developed a statistical analysis to confirm aneuploidy. These technical improvements and the development of a statistical analysis provide a way to shorten the procedure time and standardize the data generated from flow cytometric DNA analysis so as to improve the quality of retrospective reviews of paraffin-embedded tumors and accelerate the definition of flow cytometry's role as a prognostic indicator.

Radioimmunoguided surgery using monoclonal antibody.

The potential proficiency of radioimmunoguided surgery in the intraoperative detection of tumors was assessed using labeled monoclonal antibody B72.3 in 66 patients with tissue-proved tumor. Monoclonal antibody B72.3 was injected 5 to 42 days preoperatively, and the hand-held gamma-detecting probe was used intraoperatively to detect the presence of tumor. Intraoperative probe counts of less than 20 every 2 seconds, or tumor-to-adjacent normal tissue ratios less than 2:1 were considered negative (system failure). Positive probe counts were detected in 5 of 6 patients with primary colon cancer (83 percent), in 31 of 39 patients with recurrent colon cancer (79 percent), in 4 of 5 patients with gastric cancer (80 percent), in 3 of 8 patients with breast cancer (37.5 percent), and in 4 of 8 patients with ovarian cancer (50 percent) undergoing second-look procedures. Additional patients in each group were scored as borderline positive. Overall, radioimmunoguided surgery using B72.3 identified tumors in 47 patients (71.2 percent), bordered on positive in 6 patients (9.1 percent), and failed to identify tumor in 13 patients (19.7 percent). Improved selection of patients for antigen-positive tumors, the use of higher affinity second-generation antibodies, alternate routes of antibody administration, alternate radionuclides, and more sophisticatedly bioengineered antibodies and antibody combinations should all lead to improvements in radioimmunoguided surgery.

Use of polar solvents in chemoprevention of 1,2-dimethylhydrazine-induced colon cancer.

To examine the effect of the polar solvents on 1,2-dimethylhydrazine (DMH)-induced colon cancer, 100 male Sprague-Dawley rats were randomly allocated to a control and three treatment groups. Treated animals received N-methylformamide (NMF), dimethylsulfoxide (DMSO), or methylsulfonylmethane (MSM) added to drinking water 1 week before carcinogen injections commenced and for the duration of the experiment. Primary tumors were detected by serial laparotomy under ether anesthesia performed at 2-month intervals and commencing after carcinogen injections had been completed. The average time to tumor onset was significantly delayed in rats receiving NMF and MSM (P = 0.0141 and 0.0398 respectively, Mantel-Haenszel test). In addition, fewer poorly differentiated tumors were noted in treatment groups. No weight loss or toxicity was observed. These findings demonstrate that the polar solvents significantly reduce the latent period to tumor onset in DMH-induced colon cancer and indicate the need to further investigate such compounds as chemopreventive agents.

Multiple reoperations in recurrent colorectal carcinoma. An analysis of morbidity, mortality, and survival.

Fifty-eight patients in an existing prospective study were evaluated to determine if multiple reoperations for recurrent colorectal carcinoma extended survival. All patients had at least three major operative procedures. The median survival from first, second, third, fourth, and fifth recurrence was 29.9, 17.3, 16, 12.3, and 7.2 months, respectively. The median postoperative hospital stay was 11 days, with a range of 1 to 96 days. The major complication rate was 17%. Twenty-one patients are still alive 19 to 140 months from diagnosis (mean, 50.3 months), 9 to 125 months from the first recurrence (mean, 31.1 months), and 5 to 109 months (mean, 22 months) from the second recurrence. Eleven patients have no evidence of disease. Reoperation for recurrent colorectal carcinoma can be done with acceptable morbidity and mortality and an increase in survival.

Radioimmunoguided surgery using the monoclonal antibody B72.3 in colorectal tumors.

The authors have developed a hand-held gamma-detecting probe (GDP) for intraoperative use that improves the sensitivity of external radioimmunodetection. Radiolabeled monoclonal antibody (MAb) B72.3 was injected in six patients with primary colorectal cancer and 31 patients with recurrent colorectal cancer an average of 16 days preoperatively. The GDP localized the MAb B72.3 in 83 percent of sites. The technique, known as a radioimmunoguided surgery (RIGS) system did not alter the surgical procedure in patients with primary colorectal cancer but did alter the approach in 26 percent (8/31) of patients with recurrent colorectal cancer. Two patients avoided unnecessary liver resections and two underwent extraabdominal approaches to document their disease. The RIGS system may influence the short-term morbidity and mortality of surgery for colorectal cancer. Larger series and longer follow-up are needed to determine whether the RIGS system confers a survival advantage to the patient with colorectal cancer.

Needle localization of mammographically detected lesions in perspective.

Needle localization of mammographically detected lesions has been shown to detect early breast cancer. One hundred seven patients who underwent needle localized biopsy from June 1977 to September 1985 were reviewed. Eighty percent of the biopsies were benign and 20 percent were cancers (22 patients). In patients undergoing modified radical mastectomy, 80 percent of the axillary specimens were node-negative. During the same 8 year period, 570 breast cancers were diagnosed. Needle localization was responsible for only 4 percent of all cancers found. Though needle localization represents an advance in the detection of early breast cancer, the majority of cancers are found by physical examination. The importance of routine examination by a physician and self-breast examination remains paramount.

Variation in recognition of recurrent colonic cancer by different CEA assays.

Forty-six patients were followed with serial CEA determinations by two CEA assays after curative resection of a primary or recurrent colonic cancer. Thirteen have had a histologically proven recurrence, of which only six (46 percent) were predicted by both assays, while seven (54 percent) were predicted by one assay only. The assays appear complementary in indicating tumor recurrence, and preliminary findings suggest that it may be beneficial to follow patients with more than one CEA assay after resection of a primary or recurrent colonic cancer.

Polar solvents in the chemoprevention of dimethylbenzanthracene-induced rat mammary cancer.

Differentiating agents have been used experimentally and clinically as an adjuvant in the treatment of cancer, but their role in chemoprevention is limited. We used 5% dimethylsulfoxide (DMSO), 1% and 4% methylsulfonylmethane (MSM), 0.3% N-methylformamide (NMF), and retinol acetate (RA) in the chemoprevention of rat mammary breast cancer. One hundred fifty 42-day-old Sprague-Dawley rats were randomized into six groups (control, RA, DMSO, 1% MSM, NMF, and 4% MSM) and received chemopreventive agents along with standard rat chow ad libitum. Eight days later, 15 mg of 7,12-dimethylbenzanthracene was given by oral gastric intubation. The animals were examined weekly for tumor incidence and size (biplanar analysis). Animals were followed up for 240 to 300 days. Tumor incidence was not statistically affected. Time to appearance (latency period) of both tumors and cancers were prolonged by NMF, DMSO, and 4% MSM. Doubling times of all cancers produced were prolonged by DMSO and RA. No group exhibited toxic reactions or significant weight loss. Polar solvents and differentiating agents, specifically NMF, DMSO, and 4% MSM, were effective in the chemoprevention of dimethylbenzanthracene-induced mammary cancers.

Flow cytometric analysis of DNA content as a prognostic indicator in squamous cell carcinoma of the tongue.

The mortality of squamous cell carcinoma of the tongue has not significantly improved in decades. Much of the information that has been gathered to date has been based on retrospective analyses. There is little consensus on treatment of the disease. In an attempt to define an objective prognostic indicator of aggressiveness of these tumors, a retrospective analysis of 15 paraffin-embedded specimens using flow cytometry was performed. Ten patients (67 percent) had aneuploid tumors and had a 5 year disease-free survival rate of 33 percent, whereas patients with diploid tumors (33 percent) had a 5 year disease-free survival rate of 80 percent. Although the number of patients was small, it appears that flow cytometry may be an objective prognostic indicator in patients with squamous cell carcinoma of the tongue. Larger series of archival paraffin-embedded flow cytometry analyses are recommended, as well as examination of variables other than the disease-free survival rate.

Combined chemotherapy, radiation, and surgery for epithelial cancer of the anal canal.

Combined chemotherapy and radiation therapy have been reported to produce a high incidence of complete regression of epithelial cancer of the anal canal, resulting in prolonged disease-free survival. This modality has been advocated as an alternative to abdominoperineal resection as a primary treatment for this disease. Our group treated 19 patients between 1979 and 1985. Treatment included two infusions of 5-fluorouracil (1000 mg/m2/24 hours), one dose of mitomycin C (15 mg/m2), and simultaneous whole-pelvis radiation (3000 rad). The complete response rate was 88%. Three patients had anal cancer incompletely controlled by that therapy. They underwent abdominoperineal resections and are alive without disease at 10, 39, and 43 months, respectively. Actuarial disease-free survival at 40 months was 87.5 +/- 8.8 (% +/- standard error of the mean [SEM]). Complications included gastrointestinal, hematologic, and cutaneous toxicity. These results confirmed a high complete response rate to this therapy. Local treatment failures may occur, but these may be salvaged with abdominoperineal resection.