Endocrine organ metastases in subjects with lobular carcinoma of the breast.

OBJECTIVE: To define the frequency and pattern of endocrine organ metastases in patients dying of invasive lobular carcinoma. DESIGN: Postmortem microscopic evaluation of the ovaries and adrenal, pituitary, thyroid, and parathyroid glands for breast cancer metastases. SETTING: Roswell Park Cancer Institute, Buffalo, NY, between 1971 and 1990. SUBJECTS: One hundred eighteen subjects who died of their cancer: 86 had infiltrating ductal carcinoma; 32, invasive lobular carcinoma. MEAN OUTCOME MEASURE: Quantitative measurements to allow frequency determinations and statistical comparisons. RESULTS: Endocrine organ metastases were found in 91% of the subjects with invasive lobular carcinoma vs 58% of subjects with infiltrating ductal carcinoma. The adrenal gland was most frequently involved. Multiple endocrine metastases were most common in the group with invasive lobular carcinoma. CONCLUSIONS: A relationship exists between invasive lobular carcinoma and endocrine metastases. This indicates that antemortem endocrine evaluation may subsequently improve quality-of-life treatment.

Results of salvage mastectomy for local recurrence after breast-conserving surgery without radiation therapy.

BACKGROUND: Between 1975 and 1987, 128 patients with infiltrating breast cancer, categorized as clinical Stage I and II disease, were treated by breast conservation surgery without radiation therapy. MATERIALS: After a median disease-free interval of 20 months (range, 8-64 months), 25 of 128 patients had local recurrence, for which salvage mastectomy was performed. The results of modified radial mastectomy as a salvage procedure were analyzed in these 25 patients. RESULTS: After a median disease-free interval of 52 months (range, 8-75 years) after the salvage procedure, 12 patients had chest wall and distant recurrences, whereas 13 patients remained free of disease. The 5-year actuarial disease-free and overall survival rates after the salvage mastectomy were 51% and 65%, respectively. CONCLUSIONS: Univariate analyses of factors affecting disease-free survival and overall survival showed that the size of the local recurrence (< or = 2 cm) (P = 0.009) and the number of pathologically positive axillary nodes at the time of the salvage procedure (fewer than four nodes) (P = 0.002) were associated with a better prognosis.

Survival of patients with stage B2 colon carcinoma. The Gastrointestinal Tumor Study Group experience.

The Gastrointestinal Tumor Study Group, a multispecialty collaborative clinical research program, executed two studies of surgically resected colon carcinoma, including patients with serosal penetration but no positive regional lymph nodes (stage B2). In the first study, 232 patients with stage B2 disease were operated on and survival was unaffected by therapy. In the stage B2 group, survival was 78% at five years, and is estimated to be 64% ten years after surgery. A second study, begun in 1979, compared survival and recurrence data on patients who underwent surgical resection and were treated postoperatively with fluorouracil and hepatic irradiation vs those who were observed. Hematologic toxicity of the regimen and accumulation of data from the first study caused the termination of randomization of patients with stage B2 disease with continued registration to observation only. One hundred twenty-four untreated patients with stage B2 carcinoma had a five-year survival rate of 77%, confirming the relatively high survival of this group of patients who are treated with surgery alone. Our patients' five-year survival of 78% corresponds favorably to the 87% survival rate anticipated in an age-, sex-, and race-matched cohort of Americans not specifically diagnosed as having cancer. Adjuvant trials, in seeking improved survival, should recognize that our review of 356 patients implies a considerably higher-than-anticipated five-year survival for the patient with stage B2 disease who undergoes surgical resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraoperative photodynamic therapy for retroperitoneal sarcomas.

A pilot study was done to determine the feasibility of adjuvant photodynamic therapy (PDT) in recurrent retroperitoneal sarcomas. Ten patients, who had recurrences after conventional methods of treatment, had repeated resections of the tumor and intraoperative photodynamic treatment to the tumor bed. The methods and equipment used are detailed. In eight of ten patients, a complete resection was possible, and two patients are alive without recurrence at 28 and 24 months. There were no complications from the therapy. Tumors elicited red fluorescence, which helped in identifying residual tumor areas. Adjuvant PDT is a feasible alternative although its effectiveness should be evaluated further.

Description of a murine model of experimental hepatic metastases.

A murine model of experimental hepatic metastases has been developed. The cecum is exteriorized through a midline incision, and 1.5 X 10(5) MCA-38 liver-derived (LD) tumor cells in 0.1 ml was injected into the ileocolic vein (ICV). Ninety-eight percent of injected mice developed hepatic foci. The operative mortality was 6.1%. Micrometastases could first be detected on day 11. Laparotomy of 21 days revealed the presence of a mean of 18 hepatic foci. Experimental hepatic metastases could be palpated 35 days following ICV injection. Mice bearing MCA-38 LD foci survived an average of 53.3 days. This model will be of use in the development of novel approaches for the treatment of hepatic metastasis.

Abdominal exploration for suspected recurrent carcinoma of the colon and rectum based upon elevated carcinoembryonic antigen alone or in combination with other diagnostic methods.

Thirty-six patients underwent abdominal exploration due to elevated carcinoembryonic antigen (CEA) levels after a curative resection for carcinoma of the colon and rectum. Three groups were evaluated. In group 1, CEA elevation alone was the indication for the exploration in 13 asymptomatic patients. In group 2, 13 other asymptomatic patients underwent exploration because of elevated CEA levels in combination with other findings. In group 3, ten patients were symptomatic with an elevated CEA level at the time of exploration. Five patients from groups 1 and 2 underwent a curative resection for recurrent tumor (14 per cent). Three of these patients are still alive more than five years after exploration. Nine patients had negative findings at exploration for tumor recurrence (25 per cent false-positive results). Six of these patients are alive while three have died of metastatic disease. Twenty-two of the 36 patients (61 per cent) had unresectable disease at the time of exploration. Four of these patients underwent some form of surgical palliative procedure. Considering the five patients who underwent a curative resection with the latter four patients, this results in 25 per cent of the patients benefitting from surgical exploration.

Skin pressure measurements on various mattress surfaces in cancer patients.

Twenty-eight patients with histologically proven carcinoma were studied on two dynamic and six static mattress surfaces to determine which mattress surface would provide the least skin surface pressure at the sacrum, dorsal spine, trochanter and heels. Measurements were taken with an especially designed inflatable bladder, and the mean of the maximum skin surface pressures was determined for the static and dynamic surfaces in the inflated and deflated state. Using less than or equal to 32 mm Hg as the skin surface pressure at which the arteriolarcapillary blood flow is interrupted, we concluded that the mud gel bed generally tended to record the lowest skin surface pressure for all of the sites. Although some of the static surfaces recorded pressures less than or equal to 32 mm Hg at the sacrum and dorsal spine, the deflated dynamic surfaces were superior to the remaining static surfaces in reducing the skin surface pressures.

Surgery in recurrent malignant melanoma.

Seventy-nine consecutive patients with resectable, recurrent malignant melanoma were treated with surgical excision, followed by adjuvant chemotherapy. Of 7 Stage IIIA patients, 6 remain alive; 5 are disease-free at 27 months. Of 33 patients with advanced stage IIIB disease with fixed tumor masses, including 16 cases that involved two nodal groups, 10 patients (30%) remain disease-free at 30 months. Of 12 Stage IIIAB patients, one remains disease-free at 26 months. Of 27 Stage IV patients, 7 (25%) remain disease-free at 36 months. Characteristic of those patients who remain disease-free is the initial presence of 3 or less discrete metastatic lesions, and a long prior disease-free interval. Surgical removal of metastatic lesions of malignant melanoma, in combination with chemotherapy, offers improved palliation in patients with a small number of metastatic lesions and a long previous disease-free interval.

CEA monitoring among patients in multi-institutional adjuvant G.I. therapy protocols.

The Gastrointestinal Tumor Study Group (GITSG) has since 1975 included protocols for monitoring carcinoembryonic antigen (CEA) levels in its colorectal cancer adjuvant trials. Among the 563 patients on the colon cancer study (GI 6175) and the 207 patients on the rectal cancer study (GI 7175), one third had preoperative CEA determinations and more than 90% had some postoperative CEA monitoring. Colon cancer patients whose preoperative CEA was greater than 5 ng/ml had a greater probability of recurring than those whose values were lower (33% versus 18% recurrence with 21 months minimum follow-up; p < 0.05). The prognostic value of preoperative CEA was apparent only in patients with Dukes' C1 colon tumors. Preoperative CEA values were not of prognostic significance among the rectal adenocarcinoma patients. Although elevated levels of CEA after resection of either colon or rectum cancers were strongly associated with subsequent tumor recurrence, no single CEA value, arbitrarily defined as "elevated", provided an adequate screening test with both high sensitivity and high specificity. Postoperative CEA elevations were more strongly predictive of recurrence when part of a steadily rising trend. In the colon cancer study, the median monthly increase in CEA for disease-free patients was estimated to be zero, and for the relapsed patients 5.8%. The corresponding estimates for patients on the rectal cancer protocol were zero and 7.8%. Only 36 of the 344 disease-free patients on the colon protocol and 14 of the 94 disease-free patients on the rectal protocol (15%) exhibited a rate of increase of CEA as high as 3% per month over the entire period of observation. Two thirds of the relapsed patients on both studies showed a rate of increase this high or higher. The patterns of CEA rise in individual patients were quite varied, however, and monthly rates of increase as established in our study are not to be used as guidelines in patient management.

Malignant melanoma with unknown primary site.

From 1955 to 1976, 129 patients were seen with metastatic malignant melanoma from an unknown primary site, comprising 8.1% of all the referred patients with malignant melanoma. Eighty-two percent of the patients presented with a history of mass or lump. Overall median survival and 5-year survival rates after onset of symptoms were 10 months and 13%, respectively. Patients with lesions of the head and neck area had 5-year disease-free survival of 25%, whereas those with lymph node disease had a survival of 18%. Twenty-nine patients with regional disease had wide excision (usually lymphadenectomy) and their 5-year disease-free survival was 58%. Regional disease in patients with malignant melanoma of unknown primary site should be treated with radical surgical excision, since the survival is comparable or better to that of patients with regional disease having known and excised primary site.

Report of a rare case of significant hemobilia and review of this entity.

Hemobilia, regardless of the etiology, is a serious manifestation of disease and/or injury. It is an abnormal communication of intra- or extra-hepatic bile ducts with blood vessels, and often not considered in the differential diagnosis of upper gastrointestinal hemorrhage. If appropriate treatment is delayed or omitted, the end result may be devastating. Malignant melanoma, a ubiquitous tumor, metastasizes to practically every body part. It is almost never responsible for significant hemobilia. An example of a patient with hemobilia caused by melanoma is reported and discussed.

Biologic markers in cancer diagnosis and treatment.

We have reviewed several tumor markers that our advocates feel are now clinically useful, involve current assay technology, and are based on already available information. These include, in selected instances, estrogen receptors for breast cancer, thyrocalcitonin for medullary cancer of the thyroid, prostatic acid phosphatase for cancer of the prostate, alpha-fetoprotein for hepatocellular cancer, and carcinoembryonic antigen for monitoring colon cancer. We have considered the potential use of measurement of serum proteases and protein degradation products due to their activity as possible future areas of development, and we have explored measurement of tissue aryl hydrocarbon hydroxylase to identify populations at risk of cancer resulting from chemical carcinogenesis. It is clear that the study of tumor markers is already improving patient care in some specific areas and offers exciting potential for the future.

The surgical treatment and outcome of soft-tissue sarcoma.

Cases of 251 patients with soft-tissue sarcoma of the extremities, trunk, head and neck, and retroperitoneum were reviewed. The overall five-, ten-, and 15-year survival rates were 45%, 30%, and 24%, respectively. The five-year survival rates after wide soft-tissue resections, local excision, and amputation were 59%, 42%, and 39%, respectively. Factors that significantly affected prognosis were tumor size, histologic type, local extent of the tumor, and the adequacy of the surgical procedure. The local recurrence rate was 36% after wide resection, 8% after amputation, and 65% after local excision. Local recurrence alone was treatable and evidenced overall five- and ten-year survival rates of 43% and 33%, respectively. Amputation was the most effective method to treat local recurrences in the extremities. Some guidelines are suggested to select high-risk patients for adjuvant treatment.

New surgical approaches to pancreatic cancer.

Surgery as the best means to careful staging is stressed, in spite of many other methods of staging. Especially in those instances where resection is remotely possible it is proposed that, if possible, surgery should be done in centers specializing in this type of operation. A final opinion on the use of extended pancreatectomy awaits additional data. It is stressed that the surgeon should be fully aware of combined modality programs for treating pancreatic cancer and that new surgical techniques be considered as their proper employment demands. Finally, possible new techniques, such as intraoperative photoradiation using a laser and hematoporphyrin, intraoperative radiation therapy and heat, and the use of microwave-induced hyperthermia are discussed. The surgeon may well find that what is new in surgical treatment of cancer of the pancreas lies in a combined modality approach, primarily using intraoperative therapy.

Isolation, characterization and clinical evaluation of a pancreas cancer-associated antigen.

A pancreas cancer-associated antigen (PCAA) was identified and isolated from ascites fluid of human pancreatic cancer. Purified PCAA was homogeneous as determined by polyacrylamide gel electrophoresis. PCAA was a glycoprotein with a molecular weight of approximately 1,000,000 and consisted of 20% carbohydrates and 80% peptides, had an isoelectric point of 4.7, and migrated to alpha 2-beta region. It possessed a sedimentation coefficient of 14S and appeared to be a fibrous or fibroglobular protein. Immunoreactivity of PCAA was sensitive to proteolytic enzymes, perchloric acid, KSCN, glycine-HCl at pH 2.5, urea and lithium diiodosalicylate; and insensitive to neuraminidase or beta-glucosidase. Immunohistochemical technique revealed that PCAA was located in the cytoplasm of ductal epithelial cells of malignant pancreas. Using heteroantiserum raised against purified PCAA, horseradish peroxidase and CNBr-activated Sepharose 4B, an enzyme-immunoassay (EIA) for circulating PCAA has been developed. From a group of 40 healthy blood donors, an upper limit of 16.2 micrograms of PCAA/ml of serum has been tentatively determined. An elevated PCAA was shown in 67% (29/43) of patients with pancreas cancer, as well as in 30% (11/36) of lung cancer patients, 27% (10/37) of colonic cancer patients, and in 16% (6/36) of breast cancer patients. The reactive antigen in sera of these cancers was shown to be immunologically identical. PCAA also was detected in extracts of various human tissues, particularly pancreatic tumors, colonic tumors, and in a normal colon. Further, PCAA exhibited heterogeneity in molecular weight, isoelectric point, and electrophoretic mobility.