Human skeletal muscle feed arteries: evidence of regulatory potential.

AIM: Recently, it has been recognized that human skeletal muscle feed arteries can be harvested during exploratory surgery for melanoma. This approach provides vessels for in vitro study from a wide spectrum of relatively healthy humans. Although, the regulatory role of skeletal muscle feed arteries in rodent models has been documented, whether such vessels in humans possess this functionality is unknown. METHODS: Therefore, skeletal muscle feed arteries (~950 µm OD) from 10 humans (48 ± 4, 27-64 years) were studied using pressure myography. Vessel function was assessed using potassium chloride (KCl), phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) concentration-response curves (CRCs) to characterize non-receptor and receptor-mediated vasoconstriction as well as endothelium-dependent and independent vasodilation respectively. To understand the physiological relevance of the diameter changes as a result of pharmacological stimulation, the estimated conductance ratio (CR) was calculated. RESULTS: Vessel function protocols revealed significant vasoconstriction in response to PE and KCl (35 ± 6; 43 ± 9%vasoconstriction, respectively) and significant vasodilation with ACh and SNP (85 ± 7; 121 ± 17% vasodilation, respectively). Both PE and KCl significantly reduced the CR (0.26 ± 0.05 and 0.23 ± 0.07, respectively), whereas ACh and SNP increased the CR (2.56 ± 0.10 and 5.32 ± 1.3, respectively). CONCLUSION: These novel findings provide evidence that human skeletal muscle feed arteries are capable of generating significant diameter changes that would translate into significant changes in vascular conductance. Thus, human skeletal muscle feed arteries likely play a significant role in regulating vascular conductance and subsequently blood flow in vivo.

Mendelian segregation for two-factor apomixis in Erigeron annuus (Asteraceae).

The inheritance of asexual seed development (apomixis) in Erigeron annuus (Asteraceae) was evaluated in a triploid (2n=3x=27) population resulting from a cross between an apomictic tetraploid (2n=4x=36) pollen parent and a sexual diploid (2n=2x=18) seed parent. Diplospory (unreduced female gametophyte formation) and autonomous development (embryo and endosperm together) segregated independently in the population yielding four distinct phenotype classes: (1) apomictic plants combining diplospory and autonomous development, (2) diplosporous plants lacking autonomous development, (3) meiotic plants with autonomous (though abortive) development and (4) meiotic plants lacking autonomous development. Each class was represented by approximately one-quarter of the population (n=117), thus corresponding to a two-factor genetic model with no linkage (chi(2)=2.59, P=0.11). Observations demonstrate that autonomous embryo and endosperm development (jointly) may occur in either reduced or unreduced egg cells. The cosegregation of the traits is attributed to tight linkage or pleiotropy. The data are consistent with the hypothesis that autonomous development in E. annuus is regulated by a single fertilization factor, F, which initiates development of both the embryo and the endosperm in the absence of fertilization.

Inheritance of apomeiosis (diplospory) in fleabanes (Erigeron, Asteraceae).

Unreduced egg formation (apomeiosis) in flowering plants is rare except when it is coupled with parthenogenesis to yield gametophytic apomixis via apospory or diplospory. Results from genetic mapping studies in diverse apomictic taxa suggest that apomeiosis and parthenogenesis are genetically linked, a finding that is compatible with the conventional rationale that apomeiosis is unlikely to evolve independently because of deleterious fitness consequences. An Erigeron annuus (apomictic) x E. strigosus (sexual) genetic mapping population, however, included a high proportion of plants that were highly apomeiotic (diplosporous) but nonapomictic; that is, they lacked autonomous seed production. To evaluate the function and inheritance of diplospory in Erigeron, a diplosporous triploid (2n=3x=27) seed parent was crossed with a sexual diploid (2n=2x=18) E. strigosus pollen parent to produce an F1 of 31 plants. Chromosome numbers and molecular markers (AFLPs) document the inheritance of the maternal genome through unreduced eggs resulting in recombinant but predominantly (77%) tetraploid F1s (2n=4x=36; 2n+n, B(III)). Quantitative evaluation shows continuous variation in the proportion of diplosporous (vs meiotic) ovules (41-89%) in tetraploid F1s despite the presumed equal genetic contribution from the diplosporous mother. These findings demonstrate the functional independence of diplospory and suggest that variation in the trait in F1s is likely due to segregating paternal modifiers. In addition, of six aneuploid (4x-1, 4x-2) F1s, three lack a subset of maternal AFLP markers. These plants likely arose from aberrant megagametogenesis resulting in the loss of maternal chromatin prior to fertilization.

Reliable lymphatic drainage to axillary sentinel lymph nodes regardless of tumor location within the breast.

BACKGROUND: This analysis was performed in order to determine whether primary tumor location in breast cancer affects the axillary sentinel lymph node (SLN) identification (ID) rate, the false negative (FN) rate, incidence of axillary nodal metastases, or the number of SLN identified. METHODS: In this prospective multi-institutional study, SLN biopsy was performed on clinical stage T1-2, N0 breast cancer patients using blue dye alone or in combination with radioactive colloid, followed by completion axillary LN dissection. RESULTS: Central tumor location was associated with an improved FN rate, which may be related to reliable drainage from the subareolar lymphatic plexus. Tumor location did not significantly affect the SLN ID rate or the mean number of SLN identified. Medial tumor location was associated with a decreased rate of axillary nodal metastasis. CONCLUSIONS: Breast cancers drain reliably to the axillary lymph nodes regardless of tumor location within the breast.

Defining the optimal surgeon experience for breast cancer sentinel lymph node biopsy: a model for implementation of new surgical techniques.

OBJECTIVE: To determine the optimal experience required to minimize the false-negative rate of sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Before abandoning routine axillary dissection in favor of SLN biopsy for breast cancer, each surgeon and institution must document acceptable SLN identification and false-negative rates. Although some studies have examined the impact of individual surgeon experience on the SLN identification rate, minimal data exist to determine the optimal experience required to minimize the more crucial false-negative rate. METHODS: Analysis was performed of a large prospective multiinstitutional study involving 226 surgeons. SLN biopsy was performed using blue dye, radioactive colloid, or both. SLN biopsy was performed with completion axillary LN dissection in all patients. The impact of surgeon experience on the SLN identification and false-negative rates was examined. Logistic regression analysis was performed to evaluate independent factors in addition to surgeon experience associated with these outcomes. RESULTS: A total of 2,148 patients were enrolled in the study. Improvement in the SLN identification and false-negative rates was found after 20 cases had been performed. Multivariate analysis revealed that patient age, nonpalpable tumors, and injection of blue dye alone for SLN biopsy were independently associated with decreased SLN identification rates, whereas upper outer quadrant tumor location was the only factor associated with an increased false-negative rate. CONCLUSIONS: Surgeons should perform at least 20 SLN cases with acceptable results before abandoning routine axillary dissection. This study provides a model for surgeon training and experience that may be applicable to the implementation of other new surgical technologies.

Factors that predict the presence of sentinel lymph node metastasis in patients with melanoma.

BACKGROUND: This analysis was performed to identify prognostic factors that are predictive of sentinel lymph node (SLN) metastasis in melanoma. METHODS: Analysis was performed of a multi-institutional, prospective, randomized trial of SLN biopsy for melanoma. Eligibility criteria included age 18 to 70 years, Breslow thickness of 1.0 mm or more, and clinically negative regional lymph nodes. SLNs were evaluated by serial sectioning and immunohistochemistry for S100. Univariate chi-square and multivariate logistic regression analyses were performed to assess factors predictive of the presence of a positive SLN. Probability values of less than.05 were considered significant. RESULTS: SLNs were identified in 99.7% of patients. A total of 1058 patients were evaluated; 961 patients had complete data and were included in the statistical analysis. SLNs were positive for tumor in 208 of 961 patients (22%). Breslow thickness, Clark level, ulceration, and patient age were factors that were found to be independently predictive of the presence of SLN metastasis. CONCLUSIONS: Increasing Breslow thickness, Clark level of more than III, the presence of ulceration, and patient age of 60 years or less are the most important independent prognostic factors associated with the finding of positive SLN in patients with melanoma.

Accuracy of sentinel lymph node biopsy for patients with T2 and T3 breast cancers.

Although numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine the axillary nodal status for early breast cancer some studies have suggested that SLN biopsy may be less reliable for tumors >2 cm in size. This analysis was performed to determine whether tumor size affects the accuracy of SLN biopsy. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study involving 226 surgeons. The study was approved by the Institutional Review Board of each institution, and informed consent was obtained from all patients. Patients with clinical stage T1-2 N0 breast cancer were eligible for the study. Some patients with T3 tumors were included because they were clinically staged as T2 but on final pathology were found to have tumors >5 cm. This analysis includes 2148 patients who were enrolled from August 1997 through October 2000. All patients underwent SLN biopsy using a combination of radioactive colloid and blue dye injection followed by completion Level I/II axillary dissection. Statistical comparison was performed by chi-square analysis. The SLN identification rate, false negative rate, and overall accuracy of SLN biopsy were not significantly different among tumor stages T1, T2, and T3. We conclude that SLN biopsy is no less accurate for T2-3 breast cancers compared with T1 tumors.

Sentinel lymph node biopsy for breast cancer: impact of the number of sentinel nodes removed on the false-negative rate.

BACKGROUND: Numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine axillary nodal status for breast cancer, but unacceptably high false negative rates have also been reported. Attention has been focused on factors associated with improved accuracy. We have previously shown that injection of blue dye in combination with radioactive colloid reduces the false negative rate compared with injection of blue dye alone. We hypothesized that this may be from the increased ability to identify multiple sentinel nodes. The purpose of this analysis was to determine whether removal of multiple SLNs results in a lower false negative rate. STUDY DESIGN: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multiinstitutional study. Patients with clinical stage T1-2, N0 breast cancer were eligible for enrollment. All patients underwent SLN biopsy using blue dye alone, radioactive colloid alone, or both agents in combination, followed by completion level I and II axillary dissection. RESULTS: A total of 1,436 patients were enrolled in the study from August 1997 to February 2000. SLNs were identified in 1,287 patients (90%), with an overall false negative rate of 8.3%. A single SLN was removed in 537 patients. Multiple SLNs were removed in 750 patients. The false negative rates were 14.3% and 4.3% for patients with a single sentinel node versus multiple sentinel nodes removed, respectively (p = 0.0004, chi-square). Logistic regression analysis revealed that use of blue dye injection alone was the only factor independently associated with identification of a single SLN (p<0.0001), and patient age, tumor size, tumor location, surgeon's previous experience, and type of operation were not significant. CONCLUSIONS: The ability to identify multiple sentinel nodes, when they exist, improves the diagnostic accuracy of SLN biopsy. Injection of radioactive colloid in combination with blue dye improves the ability to identify multiple sentinel nodes compared with the use of blue dye alone.

Predicting the status of the nonsentinel axillary nodes: a multicenter study.

BACKGROUND: Sentinel lymph node (SLN) biopsy is a minimally invasive procedure that provides accurate nodal staging information. The need for completion axillary dissection after finding a positive SLN for breast cancer has been questioned. HYPOTHESIS: The presence of nonsentinel node (NSN) metastases in the axillary dissection specimen correlates with tumor size, the number of SLNs removed, and the number of positive SLNs. DESIGN: Prospective, multi-institutional study. PARTICIPANTS AND METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a nationwide study involving 148 surgeons. All patients underwent SLN biopsy, followed by level I/II axillary dissection. All SLNs were evaluated histologically at a minimum of 2-mm intervals. Immunohistochemical analysis using antibodies for cytokeratin was performed at the discretion of each participating institution. All NSNs were evaluated by routine histologic examination. RESULTS: An SLN was identified in 1268 (90%) of 1415 patients. Increasing tumor size was significantly correlated with increasing likelihood of positive NSNs: T1a, 14%; T1b, 22%; T1c, 30%; T2, 45%; and T3, 57% (P =.002, chi(2) test). The presence of positive NSNs was not significantly associated with the number of SLNs removed. Patients with more than 1 positive SLN were more likely to have positive NSNs than those with only 1 positive SLN (50% vs 32%; P<.001, chi(2) test). Increasing tumor size and the presence of multiple positive SLNs were also associated with the presence 4 or more positive axillary nodes. Multivariate analysis confirmed that tumor size and the number of positive SLNs were independent factors predicting the presence of positive NSNs. CONCLUSIONS: The likelihood of positive NSNs correlates with increasing tumor size and the presence of multiple positive SLNs. However, even patients with small primary tumors have a substantial risk of residual axillary nodal disease after SLN biopsy. These data will be helpful in counseling patients regarding the need for completion axillary dissection after a positive SLN is identified.

Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: results of a multiinstitutional study.

OBJECTIVE: To determine the optimal radioactive colloid injection technique for sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: The optimal radioactive colloid injection technique for breast cancer SLN biopsy has not yet been defined. Peritumoral injection of radioactive colloid has been used in most studies. Although dermal injection of radioactive colloid has been proposed, no published data exist to establish the false-negative rate associated with this technique. METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multiinstitutional study involving 229 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed at the discretion of the operating surgeon. Peritumoral injection of isosulfan blue dye was performed concomitantly in most patients. The SLN identification rates and false-negative rates were compared. The ratios of the transcutaneous and ex vivo radioactive SLN count to the final background count were calculated as a measure of the relative degree of radioactivity of the nodes. One-way analysis of variance and chi-square tests were used for statistical analysis. RESULTS: A total of 2,206 patients were enrolled. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed in 1,074, 297, and 511 patients, respectively. Most of the patients (94%) who underwent radioactive colloid injection also received peritumoral blue dye injection. The SLN identification rate was improved by the use of dermal injection compared with subdermal or peritumoral injection of radioactive colloid. The false-negative rates were 9.5%, 7.8%, and 6.5% (not significant) for peritumoral, subdermal, and dermal injection techniques, respectively. The relative degree of radioactivity of the SLN was five- to sevenfold higher with the dermal injection technique compared with peritumoral injection. CONCLUSIONS: Dermal injection of radioactive colloid significantly improves the SLN identification rate compared with peritumoral or subdermal injection. The false-negative rate is also minimized by the use of dermal injection. Dermal injection also is associated with SLNs that are five- to sevenfold more radioactive than with peritumoral injection, which simplifies SLN localization and may shorten the learning curve.

Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed?

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases (50%), the less radioactive positive sentinel node contained 50% or less of the radioactive count of the hottest lymph node. The cervical lymph node basin was associated with an increased likelihood of finding a positive sentinel node other than the hottest node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group.

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.

Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used.

PURPOSE: Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS: A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS: There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P <.05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3. 9%; P <.05). CONCLUSION: In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.

Two independent loci control agamospermy (Apomixis) in the triploid flowering plant Erigeron annuus.

Asexual seed production (agamospermy) via gametophytic apomixis in flowering plants typically involves the formation of an unreduced megagametophyte (via apospory or diplospory) and the parthenogenetic development of the unreduced egg cell into an embryo. Agamospermy is almost exclusively restricted to polyploids. In this study, the genetic basis of agamospermy was investigated in a segregating population of 130 F(1)'s from a cross between triploid (2n = 27) agamospermous Erigeron annuus and sexual diploid (2n = 18) E. strigosus. Correlations between markers and phenotypes and linkage analysis were performed on 387 segregating amplified fragment length polymorphisms (AFLPs). Results show that four closely linked markers with polysomic inheritance are significantly associated with parthenogenesis and that 11 cosegregating markers with univalent inheritance are completely associated with diplospory. This indicates that diplospory and parthenogenesis are unlinked and inherited independently. Further, the absence of agamospermy in diploid F(1)'s appears to be best explained by a combination of recessive-lethal gametophytic selection against the parthenogenetic locus and univalent inheritance of the region bearing diplospory. These results may have major implications for attempts to manipulate agamospermy for agricultural purposes and for interpreting the evolution of the trait.

ITS sequence data support a single origin for North American Astereae (Asteraceae) and reflect deep geographic divisions in Aster s.l.

The Astereae is the largest tribe of Asteraceae in North America. Morphological diversity suggests that the North American assemblage is polyphyletic as 12 endemic genera, as well as lineages of the genus Erigeron and Conyza (Conyzinae), have been hypothesized to represent at least five separate invasions of North America from Africa, Australia, Eurasia, and South America. This hypothesis was tested with a phylogenetic analysis of nucleotide sequence data from the internal transcribed spacers (ITS) of nuclear ribosomal DNA. Sequences for 62 taxa represent seven outgroup taxa and all major Northern and Southern Hemisphere groups of Astereae, including broad taxonomic and geographic sampling of Conyzinae and Aster s.l. (sensu lato). Parsimony analyses indicate that all North American Astereae are members of a strongly supported clade, and that a diverse group of predominantly woody taxa from Africa, Australia, and South America, are basal Astereae. Furthermore, Aster s.l. is deeply polyphyletic as Eurasian taxa, including Aster s.s. (sensu stricto), appear more closely related to Southern Hemisphere taxa than to North American Aster segregates. There is only low to moderate agreement between proposed higher level Astereae relationships based on ITS and those based either on morphology or chloroplast restriction site data.

Treatment of adenocarcinoma of the stomach with resection, intraoperative radiotherapy, and adjuvant external beam radiation: a phase II study from Radiation Therapy Oncology Group 85-04.

BACKGROUND: Fewer than 10% of patients presenting with adenocarcinoma of the stomach in the United States can expect to be cured. These discouraging results have led to trials of various adjuvant therapies. Some studies suggest a role for radiation in improving regional control. Radiation doses, however, are limited by the tolerance of abdominal organs. METHODS: Between 1985 and 1989, the Radiation Therapy Oncology Group conducted a phase II study to determine the feasibility of using intraoperative radiotherapy (IORT) in the treatment of adenocarcinoma of the stomach. Forty-three patients were entered into the study. Patients underwent maximal surgical resection (subtotal or total gastrectomy and regional node dissection) and IORT doses of 12.5-16.5 Gy were delivered in 27 patients. Adjuvant external beam radiation was given to 23 of the 27 patients with total doses ranging from 24 to 50 Gy. RESULTS: Two-year actuarial survival in the 27 patients receiving IORT was 47% and median survival was 19.3 months. Disease-free survival was 27%. Fifteen percent failed locally only, 26% with distant metastases only and 22% with both. Acute postoperative complications occurred in 14% with one fatality. Severe late complications occurred in 7% with one fatality. CONCLUSIONS: Intraoperative radiotherapy combined with surgical resection and postoperative radiotherapy appears to be feasible without excessive morbidity in a multiinstitutional study. Its ultimate value requires further study.

Evaluation of preoperative radiation therapy in operable colorectal cancer.

MATERIALS AND METHODS: Patients with operable colorectal cancer in the ascending colon, descending colon, and rectum were randomized to 500 cGy before definitive surgery. Patients with stage A and B1 lesions received no further treatment. All patients with stage B2, B3, C1, C2, and C3 received a minimum of 4500 cGy postoperatively. RESULTS: Three hundred fifty-three patients were registered for the study. Three hundred one patients were available for analyses. Follow-up was a minimum of 5 years on all study patients. The majority of patients had rectal cancer. Complications of treatment were acceptable. Two hundred thirty-one patients had stage B2, B3, C1, C2, or C3 tumors. Estimated 5-year rates for no preoperative therapy versus preoperative therapy were as follows: local recurrence 29% versus 26%; metastasis 41% versus 43%; and survival 54% versus 54%. No statistical benefit was observed for preoperative treatment. CONCLUSIONS: In a prospective randomized trial designed to test the value of low-dose preoperative irradiation followed by surgery and postoperative irradiation, the authors were unable to observe any benefit to low-dose preoperative therapy in patients with unfavorable stages.

Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a Southwest Oncology Group study.

PURPOSE: A national cooperative group trial was conducted in patients with early-stage cutaneous malignant melanoma to determine if oral vitamin A can increase disease-free survival or survival. PATIENTS AND METHODS: Two hundred forty-eight patients with completely resected melanoma of Breslow's thickness greater than 0.75 mm and clinically negative lymph nodes were randomized to oral vitamin A (100,000 IU/d) for 18 months or to observation. Patients were stratified by Breslow's thickness of primary lesion (0.76 to 1.50 mm, 1.51 to 3.00 mm, or > 3.00 mm), sex, and type of therapy (excision, excision plus node dissection, excision plus perfusion, or excision plus both). The median duration of follow-up observation of living patients is greater than 8 years. The relative risk (RR) in disease-free survival and overall survival in the treatment compared with the observation group was calculated using Cox proportional hazards models. RESULTS: Overall, there was no difference in disease-free survival or overall survival between the two groups. Examination of treatment by stratification interactions and subset analysis did not show any treatment-effect differences based on sex or type of therapy. There was also no difference between groups in disease-free survival based on Breslow's thickness of the primary lesion. Overall, 12% of patients who received vitamin A experienced grade 3 or 4 toxicities. CONCLUSION: Based on the lack of overall survival benefit, further evaluation of vitamin A as adjuvant therapy for melanoma does not appear warranted.