Emergency laparotomy for spontaneous intestinal and colonic perforations in cancer patients receiving corticosteroids and chemotherapy.

Thirty patients with lymphoma (12), leukemia (two), myeloma (one), or metastatic solid tumors (15) were explored for 31 episodes of spontaneous intestinal perforation during an 11-year period at Memorial Sloan-Kettering Cancer Center. Twenty-three patients (76.6%) were receiving corticosteroids alone or in combination with chemotherapy and seven patients (23.4%) were receiving chemotherapy alone at the time of perforation. Fourteen perforations (45%) occurred in the small intestine and 17 perforations (55%) occurred in the colon. Malignancy was histologically demonstrated at the site of perforation in 16 patients (52%). Twenty major postoperative complications occurred in 15 patients (50%) and the operative mortality rate was 53%. Factors such as age, sex, duration or type of symptoms, site of perforation, malignancy at the site of perforation, peripheral leukocyte count, and serum albumin and total protein levels were not significantly related to patient survival. Early diagnosis and aggressive surgical intervention is essential to improve survival following intestinal perforation in this high-risk population.

Cell therapy of a highly invasive human breast carcinoma implanted in immunodeficient (SCID) mice.

Although enormous progress has been made in the detection and treatment of localized (nonmetastatic) breast cancer, there has been relatively moderate progress toward the effective treatment of advanced disease. This study investigates the antitumor efficacy of a potent MHC nonrestricted cytotoxic human T cell line (TALL-104) upon transfer into a clinically relevant mouse model of metastatic breast cancer. Fragments from a surgical specimen of a patient with infiltrating ductal carcinoma were implanted s.c. in the flank region of severe combined immunodeficient (SCID) mice. One hundred % of the animals developed a local tumor mass that metastasized to subaxillary and inguinal lymph nodes, bones, lungs, liver, kidneys, ovaries, and brain, very closely mimicking the human disease. Multiple i.p. transfers of gamma-irradiated (nonproliferating) TALL-104 cells into mice bearing low tumor burden (the primary tumor mass weighed only 150 mg) completely arrested local tumor growth and prevented systemic spread into local lymph nodes and distant organs. Remarkably, cell therapy administered in an advanced disease stage (when the tumor weighed 2 g) induced a significant or total regression of established metastasis with no obvious effects on the primary tumor mass. Profound antitumor effects against both local and systemic disease were instead seen in mice that received cell therapy after surgical excision of the primary tumor. The implications of these data in adjuvant breast cancer therapy are discussed.

Phase I trial of TALL-104 cells in patients with refractory metastatic breast cancer.

The human cytotoxic T-cell line TALL-104 displays antitumor effects in animals with implanted and spontaneous malignancies. A Phase I trial was conducted to determine toxicity of TALL-104 cell therapy in women with metastatic refractory breast cancer. Fifteen patients with metastatic infiltrating ductal (n = 12), lobular (n = 2), or medullary (n = 1) carcinoma received escalating doses of lethally irradiated TALL-104 cells (three patients/group received 10(6), 3 x 10(6), 10(7), 3 x 10(7), and 10(8) cells/kg) for 5 consecutive days (induction course). Patients without progressive disease received monthly maintenance 2-day infusions at the same dose level. Mild grade I/II toxicity developed in 11 patients regardless of cell dose. One grade IV toxicity consequent to hepatic tumor necrosis occurred in a patient given 10(8) cells/kg, 3 weeks after the induction course. Nine patients progressed within 1 month from induction, and five patients had stable disease for 2-6 months. One patient (at 3 x 10(7)/kg) had improvement of liver metastases and ascites, and a second patient (at 10(6)/kg) experienced a dramatic relief in bone pain. Increases in blood natural killer cell activity and levels of IFN-gamma, interleukin-10, and activation markers (soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1) were often seen. Only one patient developed anti-HLA class I antibody responses against TALL-104 cells; specific CTL activity developed in three patients during induction and in four patients during the maintenance boosts. In conclusion, TALL-104 cells were well tolerated by patients with metastatic breast cancer at the doses and regimen tested. The clinical responses observed in this preliminary trial demonstrate that further investigation of TALL-104 cell therapy is warranted.

Recurrent breast cancer: presentation, diagnosis, and treatment.

Patients must be followed up closely after primary therapy for invasive breast cancer so that locoregional recurrences can be detected early. Once a recurrence has been detected, a thorough evaluation is indicated to exclude distant metastatic disease. If none is found, the patient may be a candidate for aggressive surgical intervention to render the patient disease-free. If distant disease is found, certain sites, such as the CNS or long bones, may warrant aggressive therapy because failure to treat these sites may lead to excessive morbidity. In most situations, patients with distant disease are treated with palliative measures. In selected instances, however, patients with metastatic breast cancer are candidates for aggressive intervention, including pulmonary or liver resection or high-dose chemotherapy in combination with autologous bone marrow transplantation, to rid the patient of the disease.

Accuracy of the extent of axillary nodal positivity related to primary tumor size, number of involved nodes, and number of nodes examined.

PURPOSE: While a number of studies have evaluated the minimum number of axillary nodes that need to be examined to accurately determine nodal positivity or negativity, there is little information on the number of nodes which must be examined to determine the extent of nodal positivity. This study attempts to determine for patients with 1-3 positive nodes the probability that the number of positive nodes reported is the true number of positive nodes as well as the probability that 4 or more nodes could be positive based on primary tumor size and number of nodes examined. MATERIALS AND METHODS: From 1979 to 1998, 1652 women with Stages I-II invasive breast cancer underwent an axillary dissection as part of their breast conservation therapy and had more than 10 lymph nodes examined. The mean and median number of nodes identified in the dissection was 19 and 17 (range, 11-75). The median age was 55 years. A total of 1155 women had T1 tumors and 497 had T2 tumors. Of the 459 node-positive women, 72% had 1-3 positive nodes, 18% had 4-9 positive nodes, and 10% had 10 or more positive nodes. A mathematical model based on tumor size and number of nodes examined was created using the hypergeometric distribution and Bayes Theorem. The resulting model was used to estimate the accuracy of the reported number of positive nodes and the probability of 4 or more positive nodes based on various observed sampling combinations. RESULTS: For patients with T1 tumors and 1, 2, or 3 positive nodes, the minimum number of nodes examined needed for a 90% probability of accuracy is 19, 20, and 20. For T2 tumors and 1, 2, or 3 positive nodes, a minimum of 20 nodes is required. The probability of 4 or more positive nodes increases as tumor size and the number of reported positive nodes increase and as the number of examined nodes decreases. For a 10% or less probability of 4 or more positive nodes, a patient with a T1 tumor and 1, 2, or 3 observed positive nodes would require a minimum of 8, 15, and 20 nodes removed. For a T2 tumor and 1, 2, or 3 observed positive nodes, the corresponding numbers are 10, 16, and 20. CONCLUSION: The accuracy of the extent of axillary nodal positivity is influenced by the number of observed positive nodes, tumor size, and the number of nodes examined. Underestimation of the number of positive nodes will result in errors in the assessment of an individual's risk for locoregional recurrence, distant disease, and breast cancer death and will adversely impact on treatment recommendations. This model provides the clinician with a means for assessing the accuracy of the number of positive nodes reported in patients with 1-3 positive nodes.

Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer.

PURPOSE: To compare outcome for ipsilateral breast tumor recurrence (IBTR), or regional node recurrence, initial and subsequent distant metastases, and overall and cause-specific survival in women treated with conservative surgery and radiation based on whether or not radiation was targeted to the internal mammary nodes (IMN). METHODS AND MATERIALS: From 1979-1994, 1383 women with Stage I-II breast cancer underwent wide excision, axillary node dissection with >/=10 nodes removed, and radiation. Median follow-up was 6 years; median age was 55 years. A total of 114 women had radiation targeted to the IMN with deep tangents and 1269 did not. Women who received IMN treatment were more often axillary node-positive (40% vs. 25%, p = 0. 002), had central or inner quadrant tumors (61% vs. 40%, p = 0.001), and had T2 tumors (47% vs. 31%, p = 0.001). All axillary node-positive women received adjuvant chemotherapy and/or tamoxifen. For axillary node-negative women, 13% of the IMN treatment group received adjuvant systemic therapy compared to 37% of the no treatment group (p = 0.001). Radiation was directed to the breast only in 97% of the axillary node-negative women who had IMN treatment and 99% of the no IMN treatment group. For axillary node-positive women, 98% of the IMN-treated group had radiation to the breast and supraclavicular nodes +/- a posterior axillary field compared to 77% of the no IMN treatment group (p = 0.001). There were no significant differences between the two groups for median age, menopausal status, histology, final surgical margin, estrogen and progesterone receptor status, or the number of positive nodes. RESULTS: There were no significant differences in the 5- and 10-year cumulative incidence of an IBTR, regional node recurrence, initial or total distant metastases for the two groups. Similarly 5- and 10-year actuarial overall and cause-specific survival were not significantly different. However, subset analysis revealed a statistically significant increase in initial (29% vs. 15% at 10 yr, p = 0.002) and total (30% vs. 17% at 10 yr, p = 0.01) distant metastases and a significant decrease in cause-specific survival (76% vs. 89% at 10 yr, p = 0.02) for postmenopausal women who received IMN treatment. These findings could not be attributed to differences in the use of systemic therapy or the number of positive nodes. Axillary node-positive patients did not experience a significant decrease in initial (36% vs. 22% at 10 yr, p = 0.21) or total distant metastases (37% vs. 28% at 10 yr, p = 0.62) or a significant improvement in cause-specific survival (72% vs. 76% at 10 yr, p = 0.76) with IMN treatment regardless of whether the tumor was lateral or medial/central in location. IMN treatment was not associated with an increase in non-breast cancer deaths during this period of observation. CONCLUSIONS: This retrospective series was unable to identify a significant benefit for IMN irradiation in terms of distant metastases or cause-specific survival for the entire patient population, and in particular, for patients with positive axillary nodes and medially located lesions. The results of the proposed or ongoing prospective randomized trials will further address this controversial issue.

Should internal mammary lymph nodes in breast cancer be a target for the radiation oncologist?

PURPOSE: The elective treatment of internal mammary lymph nodes (++IMNs) in breast cancer is controversial. Previous randomized trials have not shown a benefit to the extended radical mastectomy or elective IMN irradiation overall, but a survival benefit has been suggested by some for subgroups of patients with medial tumors and positive axillary lymph nodes. The advent of effective systemic chemotherapy and potential for serious cardiac morbidity have also been factors leading to the decreased use of IMN irradiation during the past decade. The recent publishing of positive trials testing postmastectomy radiation that had included regional IMN irradiation has renewed interest in their elective treatment. The purpose of this study is to critically review historical and new data regarding IMNs in breast cancer. METHODS AND MATERIALS: The historical incidence of occult IMN positivity in operable breast cancer is reviewed, and the new information provided by sentinel lymph node studies also discussed. The results of published randomized prospective trials testing the value of elective IMN dissection and/or radiation are analyzed. The data regarding patterns of failure following elective IMN treatment is studied to determine its impact on local-regional control, distant metastases, and survival. A conclusion is drawn regarding the merits of elective IMN treatment based on this review of the literature. RESULTS: Although controversial, the existing data from prospective, randomized trials of IMN treatment do not seem to support their elective dissection or irradiation. While it has not been shown to contribute to a survival benefit, the IMN irradiation increases the risk of cardiac toxicity that has effaced the value of radiation of the chest wall in reducing breast cancer deaths in previous randomized studies and meta-analyses. Sentinel lymph node mapping provides an opportunity to further evaluate the IMN chain in early stage breast cancer. Biopsy of "hot" nodes may be considered in the future to select patients who are most likely to benefit from additional regional therapy to these nodes. CONCLUSIONS: Irradiation of the IMN chain in conjunction with the chest wall and supraclavicular region should be considered only for those with pathologically proven IMNs with the goal of improving tumor regional control.

Effect of protein-intake on tumor-growth and host survival in tumor-bearing animals.

Nutritional repletion of the tumor-bearing host remains controversial. The present study was performed to determine the effect of protein intake on tumor growth and host survival in tumor-bearing animals. Forty-three female C2H mice with subcutaneous mammary tumor implants (MA 16/C) were randomized to receive standard protein diet or an isocaloric, protein-depleted diet ad libitum per os. Body weight and tumor volume were measured throughout the study and ail animals were maintained on these diets until death. Body weight was significantly greater in animals receiving standard protein intake compared to those given the protein-depleted diet. However, tumor growth was significantly stimulated and host survival reduced in animals given standard protein diet compared to animals maintained on protein-depleted diet. Thus, exogenous protein intake preferentially benefitted tumor versus host anabolism in this animal model with significant reduction in host survival.

Effect of protein-intake on dihydrofolate-reductase activity of host and tumor-tissues.

Although previous laboratory research has found that methotrexate toxicity is significantly increased by protein depletion, the cause of this phenomenon is unclear. Protein depletion can potentially increase methotrexate toxicity by altering methotrexate pharmacokinetics, changing levels of its target enzyme, dihydrofolate reductase, or by other mechanisms. To determine the specific effect of protein malnutrition on dihydrofolate reductase activity of tumor and host tissues, 30 Lewis/Wistar rats with subcutaneous mammary tumor implants (AC-33) were randomized to receive a standard protein diet (22.0% protein; 4.20 kcal/g) or protein-depleted diet (0.03% protein; 4.27 kcal/g) ad libitum per os. At sacrifice, specific activity of dihydrofolate reductase was determined in critical host target tissues (bone marrow, liver, gastrointestinal mucosa) and tumors. Our results indicate a differential effect of protein depletion on dihydrofolate reductase activity of tumor and various host tissues. Protein depletion reduced enzyme activity in bone marrow and tumors to 50% and 85%, respectively, of levels found in animals receiving standard protein intake (p<0.05). In contrast, dihydrofolate reductase activity in liver was unchanged and in gastrointestinal mucosa was increased to 136% with protein depletion compared to standard protein intake. Thus, increased myelosuppression from methotrexate in depleted animals may result, in part, from reduced dihydrofolate reductase activity in bone marrow. Other mechanisms must be implicated to account for increased hepatic or gastrointestinal toxicity observed in the protein-depleted, tumor-bearing host.

Differential-effects of omega-3 and omega-6 Fatty-acids on primary tumor-growth and metastasis.

The amount and type of dietary lipid can significantly influence spontaneous tumor development and tumor progression. To determine the effect of fish oil (rich in omega-3 polyunsaturated fatty acids) and corn oil (rich in omega-6 polyunsaturated fatty acids) on primary tumor growth, metastasis and carcass weight, 45 female Lewis/Wistar rats with subcutaneous mammary tumor implants (MAC-33) were randomized to 1 of 3 diets with 30% lipid consisting of: (i) corn oil alone, (ii) combined 50%:50% corn oil:fish oil, or (iii) fish oil alone. Primary tumor weight was significantly reduced in animals which were fed fish oil or corn oil alone compared to animals given combined corn oil:fish oil diet. Biochemical analysis (protein, DNA, RNA) of the primary revealed no difference between dietary groups. Cell cycle analysis of the primary tumor showed no difference in percent G(0)-G(1), S, G(2)-M or growth fraction (% S + G(2)-M) between dietary groups. In contrast, lung metastasis, was reduced in animals fed the combined corn oil:fish oil diet. Thus, dietary, lipid intake can significantly influence primary tumor growth and tumor metastasis. Differential effects of omega-3 and omega-6 polyunsaturated fatty acids occur on primary tumor growth and development of distant pulmonary metastases in this animal model.

Relation of preoperative use of aspirin to increased mediastinal blood loss after coronary artery bypass graft surgery.

To evaluate the potential effect of aspirin, a platelet inhibitory agent, on postoperative bleeding complications after coronary artery bypass graft surgery, we compared each of nine patients who had taken aspirin within 7 days prior to operation to one or two control subjects (total 16 patients) matched for age, sex, extent of coronary disease, number of grafts placed total operative time, bypass time, and preoperative use of propranolol. Preoperative prothrombin time, partial thromboplastin time, and platelet counts were normal for all patients. Mean mediastinal blood loss was significantly greater in the aspirin group (919 +/- 164 ml., S.E.) than in the control group (437 +/- 61 ml., p less than 0.001). The degree of mediastinal blood loss did not correlate with patient age, total operative time, bypass time, number of vessels diseased, or grafts placed. In addition, compared to controls the aspirin group required prolonged chest tube drainage (33 +/- 5 hours versus 19 +/- 1 hour, p less than 0.001).

A specialized home care intervention improves survival among older post-surgical cancer patients.

CONTEXT: Changes in the healthcare system have resulted in shortened hospital stays, moving the focus of care from the hospital to the home. Patients are discharged post-operatively with ongoing needs, and whether they receive nursing care post-hospitalization can influence their recovery and survival. Little information is available about the factors that influence outcomes, including the survival of older cancer patients after cancer surgery. OBJECTIVE: To compare the length of survival of older post-surgical cancer patients who received a specialized home care intervention provided by advanced practice nurses (APNs) with that of patients who received usual follow-up care in an ambulatory setting. We also assessed potential predictors of survival in terms of depressive symptoms, symptom distress, functional status, comorbidities, length of hospital stay, age of patient, and stage of disease. DESIGN: A randomized controlled intervention study. SETTING: Discharged older cancer patients after surgery at a Comprehensive Cancer Center in southeastern Pennsylvania. PATIENTS: Three hundred seventy-five patients aged 60 to 92, newly diagnosed with solid cancers, were treated surgically between February 1993 and December 1995. One hundred ninety patients were randomized to the intervention groups and 185 to the usual care group. INTERVENTION: The intervention was a standardized protocol that consisted of standard assessment and management post-surgical guidelines, doses of instructional content, and schedules of contacts. The intervention lasted 4 weeks and consisted of three home visits and five telephone contacts provided by APNs. Both the patients and their family caregivers received comprehensive clinical assessments, monitoring, and teaching, including skills training. MAIN OUTCOME MEASURE: Time from enrollment of patients into the study until death or last date known alive at the end of November 1996. RESULTS: During the 44-month follow-up period, 93 (24.8%) of 375 patients died. Forty-one (22%) of those who died were patients in the specialized home care intervention group, compared with 52 (28%) in the usual care group. Stage of disease at diagnosis differed between the two groups at baseline (38% late stage patients in the intervention group compared with 26% in the control group, P = .01), so stratified analysis was performed. Overall, the specialized home care intervention group was found to have increased survival (P = .002 using stratified log-rank test). Among early stage patients only, there was no difference in survival between the intervention and control groups. Among late stage patients, there was improved survival in the intervention group. For example, 2-year survival among late stage intervention group cases was 67% compared with 40% among control cases. When Cox's proportional hazard model was used to adjust for significant baseline covariates, the relative hazard of death in the usual care group was 2.04 (CI: 1.33 to 3.12; P = .001) after adjusting for stage of disease and surgical hospitalization length of stay. CONCLUSIONS: This is the first empirical study of post-surgical cancer patients to link a specialized home care intervention by advanced practice nurses with improved survival. Additional research is needed to test home care interventions aimed at maintaining quality of life outcomes and their effects on survival of post-surgical cancer patients.

Total parenteral nutrition and tumor metastasis.

A major clinical concern with providing total parenteral nutrition to the tumor-bearing host is the potential to stimulate tumor growth. This study was performed to determine the effect of total parenteral nutrition on primary tumor growth and spontaneous pulmonary metastasis in Lobund rats with subcutaneous prostate adenocarcinoma (PA-III) implants. Significant acceleration of primary tumor growth and tumor metastasis occurred in animals receiving parenteral nutrition consisting of amino acids, dextrose, and lipid or standard enteral nutrition compared to control animals. This study represents the first report of stimulating tumor metastasis with specific parenteral nutrients and clearly indicates that both primary tumor growth and tumor metastasis can be altered by exogenous substrate administration.

Effect of growth hormone and protein intake on tumor growth and host cachexia.

BACKGROUND: Growth hormone supplementation has been shown to stimulate muscle protein synthesis and to improve nitrogen balance in a variety of catabolic states. The role of growth hormone to support the tumor-bearing host is complicated by the risk that growth hormone or its intermediaries may stimulate tumor growth. The purpose of this study is to examine the effect of growth hormone supplementation in tumor-bearing rats. This is studied in the protein-fed and protein-starved state in an attempt to isolate a selective benefit for the host over the tumor. METHODS: Forty Lewis rats bearing a metastatic mammary adenocarcinoma (MAC-33) were divided into four groups: one receiving a regular diet plus saline solution, one receiving a regular diet plus growth hormone (1 IU/kg/day), one receiving protein-depleted diet plus saline solution, and one receiving a protein-depleted diet plus growth hormone. After 25 days of growth hormone treatment, animals were killed to determine primary tumor size, tumor/carcass ratio, host organ composition, pulmonary metastasis, and serum amino acid levels. RESULTS: The tumor/carcass ratio was decreased as a result of growth hormone treatment in both the protein-fed and protein-starved groups. Growth hormone supplementation resulted in increased carcass weight, muscle weight, and muscle protein content in the protein-fed, tumor-bearing animals (p < 0.05). In the protein-starved, tumor-bearing rats growth hormone supplementation resulted in a significant decrease in tumor volume and tumor protein content. Amino acid analysis suggests that the amino acid tyrosine is a rate-limiting substrate for tumor cell proliferation in this model. CONCLUSIONS: Growth hormone has a differential effect on tumor and host growth in the protein-fed and protein-starved state. Growth hormone supplementation inhibited tumor growth in protein-deprived animals. This is most likely accomplished indirectly by limiting amino acid substrate availability to the tumor.

Reversal of tumor-associated hyperglucagonemia as treatment for cancer cachexia.

BACKGROUND: The tumor-bearing state is associated with increased circulating glucagon levels that may play an etiologic role in cancer cachexia. The secretion of glucagon can be inhibited with long-term somatostatin analogs, and, in combination with insulin, should maximally reverse the low insulin/glucagon ratio seen in cancer cachexia. The goal of this study is to examine the effect of somatostatin (octreotide) and insulin in a model of cancer cachexia and to determine whether inhibition of glucagon secretion will reverse some of the abnormalities in carbohydrate metabolism to selectively benefit host versus tumor metabolism. METHODS: Sixty-seven female Lewis rats were subcutaneously inoculated with 1 x 10(6) metastasizing mammary adenocarcinoma tumor cells. On day 30 the animals were randomized into four groups to receive (1) tumor-bearing control (saline injections); (2) octreotide, 150 microgram/kg intraperitoneally twice a day; (3) neutral protamine Hagedorn insulin, 5 units/kg subcutaneously twice a day; or (4) both insulin and octreotide injections. A fifth group of non-tumor-bearing controls was included. The animals received treatment for 5 days and were then killed. RESULTS: The tumor-bearing state was found to be associated with an increase in glucagon levels and a significant decrease in the insulin/glucagon ratio. The combination of somatostatin+insulin resulted in a 23-fold increase in the insulin/glucagon ratio without causing significant host morbidity from hypoglycemia. This increased insulin/glucagon ratio was associated with increased carcass weight, increased muscle weight, increased muscle protein, increased liver cellular protein, increased liver microsomal P-450 content, and decreased tumor protein content compared with the tumor-bearing controls. These results were not seen with insulin or somatostatin alone. Hepatic lactate dehydrogenase, glucose-6-phosphatase, and fructose-1, 6-diphosphatase activities were increased as a result of combination hormone treatment. CONCLUSIONS: Combination hormone treatment with somatostatin and insulin results in a marked increase in the insulin/glucagon ratio and a selective nutritional benefit to the host. The inhibition of tumor-associated hyperglucagonemia should be considered in the treatment of cancer cachexia.

Colon invasion by primary splenic lymphoma: a case report and review of the literature.

Primary splenic lymphoma accounts for 1% of lymphomas. The definition of primary splenic lymphoma is controversial and its clinical presentation is variable. This report describes a patient with primary non-Hodgkin's lymphoma of the spleen with transmural colonic invasion. This unique case represents the first reported instance of splenic lymphoma with histologically demonstrated invasion to the colonic mucosa. The clinical and pathologic features of this case and primary splenic lymphoma in general are reviewed.

Adjuvant, pulse total parenteral nutrition and tumor response to cycle-specific and cycle-nonspecific chemotherapy.

Previous work has demonstrated that substrate-induced alterations of tumor metabolism can be exploited to enhance tumor response to a cycle-specific chemotherapeutic agent (methotrexate). This study was designed to further investigate the biologic mechanism of this phenomenon by determination of tumor response to additional cycle-specific (Adriamycin) and cycle-nonspecific (Cytoxan) chemotherapeutic agents. Significant potentiation of tumor response during adjuvant total parenteral nutrition (TPN) was observed with methotrexate and Adriamycin but not with Cytoxan. This may imply that tumor sensitization by adjuvant TPN occurs by acceleration of the growth rate of proliferating tumor cells and not by recruitment of dormant tumor cells into the cell cycle.

Factors associated with a positive reexcision after excisional biopsy for invasive breast cancer.

BACKGROUND: Breast-conserving therapy followed by adjuvant radiotherapy represents an alternative to mastectomy as a treatment for invasive breast cancer. When excisional biopsy has been performed outside the parent institution, reexcision is often performed, with tumor being identified in 32% to 62% of the subsequent specimens. We analyzed not only the factors associated with a positive reexcision but also those factors associated with final surgical margins that are positive for tumor. METHODS: Between 1978 and 1991, 956 female patients with American Joint Committee on Cancer clinical stage I or II breast cancer were treated with breast-conserving therapy where a total of 420 patients underwent reexcision after an initial excisional biopsy. Several factors were analyzed to determine their association with a positive reexcision, the status of the final surgical margin, and the nature of the disease present within the reexcision specimen. RESULTS: Factors that correlated with a positive reexcision in both univariate and multivariate analysis were clinical tumor size, method of detection, the pathologic status of the axillary lymph nodes, and the histologic appearance. Those factors associated with finding invasive disease at the time of reexcision were clinical tumor size, clinical presentation, and nodal status. The single factor associated with finding residual in situ disease at the time of reexcision was histologic appearance of the primary tumor. A final positive margin was associated with method of tumor detection, age of the patient, and the presence of axillary lymph node metastases. CONCLUSIONS: The most significant factors associated with a positive reexcision are clinical tumor size, method of tumor detection, pathologic nodal status, and histologic appearance. Patients with larger tumors or those that are detected by physical examination, as well as invasive lobular carcinomas, may require a more generous initial resection to achieve negative surgical margins and avoid the likelihood of reexcision.

Biochemical modulation of tumor-growth, metastasis and host metabolism.

Exogenous nutrients, hormones and metabolites can significantly alter tumor growth, metastasis, and host nutritional status. Arginine, serine and methionine are critical amino acids required for protein, DNA and RNA synthesis and, thus, for cellular proliferation. To determine the effect of these specific amino acids on host metabolism, primary tumor growth and metastasis, 48 Lewis rats bearing the mammary adenocarcinoma MAC-33 were randomized to receive similar diets with 3% supplements of serine, arginine, methionine or glycine (control). After 25 days on each diet, animals were sacrificed to determine primary tumor biochemical composition and growth kinetics, number of lung metastases and carcass weight. A significant reduction in lung metastases occurred with serine and methionine supplementation (p<0.01) with no significant change in primary tumor size. However, increased mortality (p<0.001) and low carcass weight (p<0.05) were found in the methionine group indicating significant host toxicity. Serine-supplemented animals had a mortality rate and carcass weight comparable to the control group. Arginine supplementation had no effect on primary tumor growth, metastasis or carcass weight; however, increased mortality was observed in this group compared to controls. These results suggest that serine supplementation selectively supports host growth and inhibits metastasis in tumor-bearing animals. This study demonstrates the potential to differentially effect host and tumor growth with exogenous amino acid supplements.

An improved operative technique for placement of brachytherapy catheters in treatment of soft tissue sarcomas.

Two patients with malignant soft tissue sarcomas were treated with local excision followed by a combination of brachytherapy and external beam radiation therapy. The involved areas were large resulting in extensive and irregular sites of resection. The individual placement of multiple brachytherapy catheters in such large, irregular contours can be a time-consuming and technically difficult task often resulting in an uneven distribution of the catheters within the sites of resection. We therefore describe a technique of catheter distribution.