A plea for the pathologically accurate sentinel node.
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Axilla↗
Biomedical subjects
E M Copeland
Publications and source records attributed to E M Copeland.
A cost-effectiveness analysis of axillary node dissection in postmenopausal woman with estrogen receptor-positive breast cancer and clinically negative axillary nodes.
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Axilla↗
Recent advances in the treatment and outcome of locally advanced rectal cancer.
OBJECTIVE: To compare the outcomes of treatment of locally advanced rectal cancer of the early era (1975-1990) with those of the late era (1991-1997). BACKGROUND: Preoperative therapy has been used in locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. At the University of Florida, preoperative radiation has been used since 1975, and it was combined with chemotherapy beginning in 1991. METHODS: The records of 328 patients who underwent preoperative radiation or chemoradiation followed by complete resection for locally advanced rectal cancer defined as tethered, annular, or fixed tumors were reviewed. The clinicopathologic characteristics, adjuvant treatment administered, surgical procedures performed, and local recurrence-free and overall survival rates were analyzed. RESULTS: There were 219 patients in the early era and 109 in the late era. No significant differences were seen in patients (age, gender, race) or tumor characteristics (mean distance from the anal verge, annularity, fixation). Preoperative radiation regimens were radiobiologically comparable. No patient in the early era received preoperative chemotherapy, compared with 64 in the late era. Of those receiving any pre- or postoperative chemotherapy, three patients received chemotherapy in the early era, compared with 76 in the late era. Sphincter-preserving procedures increased from 13% in the early era to 52% in the late era. Pathologic downstaging for depth of invasion increased from 42% to 58%, but lymph node negativity remained similar. The 1-, 3-, and 5-year local recurrence-free survival rates were comparable. However, in the late era, 1-, 3-, and 5-year overall survival rates improved significantly compared with those of the early era, and also compared with each of the preceding 5-year intervals. CONCLUSION: The addition of a chemotherapy regimen to preoperative radiation therapy improves survival over radiation therapy alone. Likewise, an improvement in downstaging is associated with an increase in sphincter-preserving procedures.
Combined Modality Therapy↗
Caspase-3-dependent organ apoptosis early after burn injury.
OBJECTIVE: To examine the role played by endotoxin, tumor necrosis factor-alpha (TNF-alpha), and caspase-3 in the increased apoptosis seen in solid organs in the early period after a burn injury. SUMMARY BACKGROUND DATA: Burn injury is often associated with immune suppression. Bacterial translocation and systemic endotoxemia have been reported after a burn injury, and caspase-3 activation due to TNF-alpha and Fas ligand (FasL) are presumed to initiate apoptosis. We hypothesized that endotoxin-induced TNF-alpha expression and caspase-3 activation could be the stimulus for the apoptosis after burn injury. METHODS: A 20% full-thickness scald burn was used in C57BL/6 mice. Three hours after burn injury, tissue samples were obtained from the thymus, lung, liver, and spleen. Lipopolysaccharide-nonresponsive (C3H/HeJ) and TNFalpha null B6x129tnf-/- mice were also used. To detect apoptosis, hematoxylin and eosin stain, in situ TUNEL, DNA extraction, and gel electrophoresis were all performed. Caspase-3 activity and TNF-alpha and FasL mRNA were also measured. RESULTS: Increased apoptosis and caspase-3 activity were observed in the thymus and spleen 3 hours after burn injury but were not seen in liver or lung. In the thymus and spleen, increased expression of FasL mRNA was also observed, whereas increased TNF-alpha mRNA was not. Increased apoptosis in thymus and spleen were also observed in C3H/HeJ and B6x129tnf-/- mice after burn injury. An inhibitor of the caspase-3 (Z-VAD-fmk) reduced apoptosis in both thymus and spleen. CONCLUSIONS: In the early period after a burn injury, increased apoptosis is observed primarily in the lymphoid organs and is independent of endotoxin or TNF-alpha. The increased caspase-3 activity in thymus and spleen contributes to apoptosis in these organs.
Animals↗
Application of gene therapy to acute inflammatory diseases.
The application of gene therapy to acute inflammation has not received as much research attention as has the treatment of genetically-based diseases, cancer, and viral infections. However, gene therapy as a drug delivery system offers several theoretical and practical advantages over current protein delivery systems. These include the ability to target therapies to individual tissues or cell types, to locally produce proteins that can act intracellularly or in an autocrine, juxtacrine, or paracrine fashion, and to sustain new protein synthesis for periods up to several weeks after a single administration. Although retrovirus, herpes simplex, and adeno-associated virus have been proposed for gene therapy in cancer and in genetic diseases, nonviral and adenovirus approaches appear most applicable as drug delivery systems due to their rapid onset and short duration of transgene expression. The relative modest transduction efficiencies obtained at present with nonviral approaches, and the inherent inflammatory properties of first-generation adenovirus constructs, however, have limited their usefulness to date. The present review discusses the theoretical and practical benefits of specific gene therapy approaches for the treatment of acute inflammatory diseases, as well as our experiences with liposome:plasmid DNA and adenovirus-based approaches. Although a number of technical and theoretical hurdles remain before it can be evaluated in humans with acute inflammation, gene therapy offers a novel approach for the treatment of acute inflammation, and will likely enter the armamentarium of critical care physicians in the near future.
Acute Disease↗
Discordant tumor necrosis factor-alpha superfamily gene expression in bacterial peritonitis and endotoxemic shock.
BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a member of a large family of predominantly homotrimeric type II membrane-associated proteins with both proinflammatory and apoptosis-inducing properties. Although TNF-alpha expression has been studied extensively, little is known about the expression of other members of the TNF-alpha superfamily during acute inflammatory processes. METHODS: TNF-alpha, Fas ligand (FasL), and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) messenger RNA (mRNA) expression were examined in liver, lung, spleen, and kidney after either a cecal ligation and puncture or endotoxemic shock with use of semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: Cecal ligation and puncture increased TNF-alpha mRNA in lung and liver (both P < .05) within 3 hours, which was paralleled by increased FasL mRNA. In the spleen TNF-alpha and FasL mRNA significantly declined (both P < .05). In contrast to TNF-alpha and FasL, TRAIL mRNA levels were unchanged in all organs except lung, where it was reduced at 24 hours (P < .05). Endotoxemic shock also increased lung TNF-alpha and FasL mRNA levels (both P < .05). CONCLUSIONS: In acute inflammatory processes TNF-alpha and FasL mRNA increase concordantly in several solid organs. In contrast, TRAIL mRNA levels do not consistently change during these acute inflammatory processes, suggesting that its expression is under independent and discordant regulatory control.
Animals↗
Stereotactic core biopsy reduces the reexcision rate and the cost of mammographically detected cancer.
The management of patients with mammographic abnormalities is rapidly shifting from needle-localized surgical biopsy (NLB) to stereotactic core biopsy (SCB). The precise role of SCB in the management of nonpalpable breast cancer remains to be defined. The purpose of this study was to compare SCB to NLB in the diagnosis of mammographically detected breast cancer in women who underwent breast-conserving surgery. The records of all patients with nonpalpable breast cancer who underwent breast-conserving surgery from 1/1/95 to 6/1/97 were analyzed with respect to method of diagnosis, time interval from detection to diagnosis and breast-conserving surgery, volume of breast tissue excised, margin status and reexcision rate, number of surgical procedures, and total charges and costs per patient. During a 30-month period, 117 patients with nonpalpable breast cancer underwent breast-conserving surgery. The diagnosis was made by NLB in 69 patients and SCB in 48 patients. The time from detection to diagnosis and breast-conserving surgery was 1.7 +/- 0.5 and 8.1 +/- 1.2 days for SCB patients and 6. 8 +/- 1.3 and 16.9 +/- 2.3 days for NLB patients (P < 0.01). The volume of breast tissue removed was 117.9 +/- 5.6 cm3 for SCB patients versus 75.2 +/- 2.9 cm3 for NLB patients (P < 0.01). Three SCB patients (6%) had positive margins, while 38 NLB patients (55%) had positive margins (P < 0.01). Only 1 SCB patient (2%) was reexcised, while 34 NLB patients (50%) were reexcised (P < 0.01). Eighty-nine percent of SCB patients had a single surgical procedure compared to 39% of NLB patients (P < 0.001). Patients who underwent SCB had reduced total charges and total costs per patient compared to NLB patients ($11,700 +/- $554 and $3537 +/- $167 per SCB patient versus $15,654 +/- $706 and $4853 +/- $198 per NLB patient, P < 0. 0001). Stereotactic core biopsy shortens the time from detection at mammography to diagnosis and breast-conserving therapy, permits appropriate discussion of treatment alternatives, reduces the positive margin rate and reexcision rate, and may represent a significant cost savings in the management of nonpalpable breast cancer.
Biopsy, Needle↗
Transfection of the type II TGF-beta receptor into colon cancer cells increases receptor expression, inhibits cell growth, and reduces the malignant phenotype.
OBJECTIVE: To determine if transfection of SW48 colon cancer cells with the type II transforming growth factor-beta (TGF-beta) receptor restores growth inhibition and reverses the in vitro and in vivo malignant phenotype. SUMMARY BACKGROUND DATA: The authors have previously shown that SW48 colon cancer cells that are replication error positive in both alleles lack functional cell surface TGF-beta type I (RI) and type II (RII) receptors and are insensitive to TGF-beta1-induced growth inhibition. METHODS: SW48 cells were stably transfected with the cDNA for the normal type II TGF-beta receptor (RII). Once transfected, the cells were evaluated for in vitro phenotypic changes and in vivo changes in tumor growth. RESULTS: Denaturing sequencing gel electrophoresis of the reverse transcriptase-polymerase chain reaction product from SW48 cells revealed that the RII coding sequence contained a single base deletion mutation. When these cells were transfected with normal RII cDNA, Northern and Western blot analyses revealed increased levels of RII mRNA and protein. Affinity labeling techniques revealed that RII-transfected SW48 cells produced functional RI and RII protein. Transfection of SW48 cells also led to changes in cell phenotype, as shown by inhibition of both in vitro growth rate and incorporation of [3H]-thymidine. SW48 cells expressing normal RII also exhibited reduced cloning efficiency in semisolid medium and reduced growth as a xenograft in NOD/LtSz-scid/J mice. CONCLUSIONS: The results confirm that RII is a tumor-suppressor protein that is required for TGF-beta-induced growth inhibition in SW48 colon cancer cells.
Animals↗
Increased leptin expression in mice with bacterial peritonitis is partially regulated by tumor necrosis factor alpha.
Plasma leptin and ob gene mRNA levels were increased in mice following bacterial peritonitis, and blocking an endogenous tumor necrosis factor alpha (TNF-alpha) response blunted the increase. However, plasma leptin concentrations did not correlate with the associated anorexia. We conclude that leptin expression is under partial regulatory control of TNF-alpha in peritonitis, but the anorexia is not dependent on increased leptin production.
Animals↗
Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting.
The ob gene product leptin is known to produce anorexia and loss of body fat when chronically administered to both lean and genetically obese mice. The current study was undertaken to examine whether administration of recombinant leptin in quantities sufficient to produce decreases in food intake and body weight and alterations in body composition would elicit either an hepatic acute phase protein response or preferential loss of carcass lean tissue. Mice were administered increasing quantities of recombinant human leptin or human tumor necrosis factor-alpha as a positive control. Although leptin (at 10 mg/kg body wt) produced significant anorexia and weight loss (both P < 0.05), human leptin administration did not appear to induce an hepatic acute phase protein response in either lean or genetically obese mice, as determined by protein synthetic rates in the liver or changes in the plasma concentration of the murine acute phase protein reactants, amyloid A, amyloid P, or seromucoid (alpha1-acid glycoprotein). In addition, human leptin administration did not induce a loss of fat-free dry mass (protein) in lean or obese animals. The findings suggest that at doses adequate to alter food intake and body weight leptin is not a significant inducer of the hepatic acute phase response nor does leptin promote the preferential loss of somatic protein characteristic of a chronic inflammatory process.
Acute-Phase Reaction↗
Proinflammatory cytokines, nutritional support, and the cachexia syndrome: interactions and therapeutic options.
BACKGROUND: Protein calorie malnutrition remains endemic in hospitalized patients with both acute and chronic inflammation secondary to either cancer, chronic infectious processes, surgical injury, trauma, or burns. For the patients who cannot support themselves by enteral feeding, total parenteral nutrition remains an essential tool to minimize nitrogen losses and replete the depleted patient. However, in patients with active inflammation, nitrogen retention and lean tissue accretion are often impaired during total parenteral nutrition. Production of humoral factors, including proinflammatory cytokines, regulates many of the anabolic and catabolic processes that accompany inflammation. METHODS: The investigators' experience with total parenteral nutrition and proinflammatory cytokines is reviewed. RESULTS: Cytokines such as interleukin-1, tumor necrosis factor-alpha, and, in particular, interleukin-6 appear to play central roles in both the loss of skeletal muscle protein and the initiation of the acute phase response to inflammation, as well as in modulating the utilization of exogenously administered nutrients. CONCLUSIONS: Although innovative second- and third-generation nutritional formulations for the acutely ill patient may represent one approach for improving the effectiveness of total parenteral nutrition, understanding the humoral response to inflammation and modifying cytokine actions pharmacologically may prove equally effective in improving the utility of exogenously administered nutrients. Future studies need to determine whether the effectiveness of exogenously administered nutrients in the patient with inflammation can be improved by efforts to modulate the proinflammatory cytokine response through cytokine inhibitors or antagonists.
Animals↗
Involvement of 26-kDa cell-associated TNF-alpha in experimental hepatitis and exacerbation of liver injury with a matrix metalloproteinase inhibitor.
TNF-alpha is a pleiotropic cytokine that exists both as a 26-kDa cell-associated and a 17-kDa soluble form. Recently, a class of matrix metalloproteinase inhibitors has been identified that can prevent the processing by TNF convertase of 26-kDa TNF-alpha to its 17-kDa form and can reduce mortality from normally lethal doses of D-galactosamine plus LPS (D-GalN/LPS). Here we report that a matrix metalloproteinase inhibitor, GM-6001, improves survival but does not protect against liver injury from D-GalN/LPS-induced shock in the mouse. In Con A-induced hepatitis, GM-6001 actually exacerbates hepatocellular necrosis and apoptosis despite greater than 90% reduction in plasma TNF-alpha concentrations. Treatment with GM-6001 also has minimal effect on the concentration of membrane-associated TNF-alpha in the livers of animals with Con A induced hepatitis. In contrast, a TNF binding protein (TNF-bp), which neutralizes both membrane-associated and soluble TNF-alpha, prevents D-GalN/LPS- and Con A-induced hepatitis. Our studies suggest that cell-associated TNF-alpha plays a role in the hepatocellular necrosis and apoptosis that accompany D-GalN/LPS- or Con A-induced hepatitis, and that matrix metalloproteinase inhibitors are ineffective in preventing this hepatic injury.
Animals↗
Nitric oxide contributes to adriamycin's antitumor effect.
UNLABELLED: Recently, several antitumor drugs have been shown to stimulate nitric oxide (NO) production. PURPOSE: To determine if adriamycin induces NO production in breast cancer cells in vitro and whether NO contributes to adriamycin's antitumor effect in vivo. METHODS: Murine breast cancer cells (EMT-6) were incubated with adriamycin (ADRIA, 0, 10, 100, 1000 microM) in the presence or absence of the NO synthase inhibitor aminoguanidine (AG, 1 mM). Twenty-four hours later nitrite accumulation (Greiss reagent) and cell viability (MTT assay) were assessed. Supernatants from adriamycin-stimulated cells were also analyzed at 6, 8, and 24 hr for TNF, IL-1, and IFN gamma (ELISA). For in vivo experiments, 10(5) EMT-6 cells were injected into the flank of BALB/c mice (n = 20) and 1 hr later mice received one of four treatments: (1) saline, (2) ADRIA (10 mg/kg ip), (3) AG (100 mg/kg sc BID), or (4) ADRIA (10 mg/kg ip) and AG (100 mg/kg sc BID). Two weeks later tumor size was measured and in situ tumor cell apoptosis was determined by fluorescent microscopy and flow cytometry. RESULTS: Adriamycin was cytotoxic to EMT-6 cells with 100 microM resulting in nearly 100% killing (P < 0.01). Adriamycin also stimulated nitrite accumulation with 100 microM producing 6.5 +/- 0.26 microM nitrite (P < 0.001). AG blocked adriamycin-stimulated nitrite accumulation (P < 0.05), but did not inhibit cytotoxicity in vitro. In vivo, adriamycin inhibited tumor size by nearly 400% (P < 0.001), while AG attenuated adriamycin's effect on tumor growth (P < 0.05). There was no difference in the detection of apoptotic tumor cells between the adriamycin and adriamycin and AG groups as determined by immunohistochemistry and flow cytometry. CONCLUSIONS: These findings suggest that adriamycin stimulated NO production in EMT-6 cells, but adriamycin's cytotoxicity in vitro was NO-independent. In vivo, adriamycin inhibited tumorigenesis partially via an NO-dependent, nonapoptotic mechanism.
Animals↗
Inhibition of transforming growth factor alpha stimulation of human squamous cell carcinoma of the head and neck with anti-TGF-alpha antibodies and tyrphostin.
BACKGROUND: Transforming growth factor alpha (TGF-alpha) and its receptor (EGF-R) may regulate normal and malignant epithelial cell growth by an autocrine mechanism. We investigated the role of TGF-alpha in regulating head and neck SCC tumor growth. METHODS: TGF-alpha and EGF-R levels were measured in 7 SCC cell lines and 14 SCC biopsies by RIA, Scatchard, and Western analysis. TGF-alpha autocrine stimulation of DNA synthesis in SCC cell lines was assessed by incubation with TGF-alpha neutralizing antibodies and tyrphostin AG 1478, a selective and potent inhibitor of EGF-R kinase. RESULTS: All SCC cell lines synthesized TGF-alpha and expressed elevated EGF-R levels compared to normal keratinocytes. Twelve of the 14 SCC biopsies contained TGF-alpha protein and 8 had specific EGF-R. Exogenous TGF-alpha or EGF significantly increased DNA synthesis in 4 of 5 SCC cell lines. TGF-alpha neutralizing antibodies or tyrphostin AG 1478 reduced DNA synthesis in the two SCC cell lines (FaDu and SCC9) tested. CONCLUSIONS: These results indicate that SCC cell lines and tumors usually synthesize TGF-alpha, have elevated levels of EGF-R, and are mitogenically stimulated by a TGF-alpha autocrine system. Selective inhibition of the TGF-alpha system by EGF-R kinase inhibitors or TGF-alpha neutralizing antibodies may be useful strategies for treating SCC that overexpress TGF-alpha and its receptor.
Autocrine Communication↗
Exogenously administered interleukin-10 decreases pulmonary neutrophil infiltration in a tumor necrosis factor-dependent murine model of acute visceral ischemia.
INTRODUCTION: Visceral ischemia and reperfusion associated with thoracoabdominal aortic aneurysm (TAAA) repair results in lung injury, which appears to be mediated in part by proinflammatory cytokines. The purpose of this study was to determine the effect of exogenous administration of the antiinflammatory cytokine, recombinant human IL-10 (rhIL-10), on proinflammatory cytokine production (IL-6 and TNF alpha) and pulmonary neutrophil infiltration after acute visceral ischemia-reperfusion. METHODS: Two hours before 25 minutes of supraceliac aortic occlusion, 80 C57BL/6 mice (20 to 22 g) received an intraperitoneal injection of rhIL-10 (0.2 microgram [n = 20], 2 micrograms [n = 20], 5 micrograms [n = 25], or 20 micrograms [n = 15]), and 16 mice received murine anti-IL-10 IgM 200 micrograms. Twenty-five additional mice underwent visceral ischemia-reperfusion without treatment (controls), and 16 mice underwent laparotomy without aortic occlusion (sham). RESULTS: Pretreatment with exogenous rhIL-10 resulted in significant reductions in lung neutrophil infiltration with 0.2 microgram, 2 micrograms, and 5 micrograms per mouse of rhIL-10 compared with lung neutrophil levels in control mice that underwent acute visceral ischemia-reperfusion alone (p < 0.05). In addition, serum TNF alpha was detected in 50% of control mice and in 75% of mice that received murine anti-IL-10, but in none of the mice that received rhIL-10 (2 micrograms per mouse) or the mice that underwent sham operative procedures (p < 0.05 by chi 2 analysis). CONCLUSION: Exogenous IL-10 limits pulmonary neutrophil recruitment and the appearance of TNF alpha in this model of visceral ischemia-reperfusion injury. Thus the use of exogenous IL-10 may offer a novel therapeutic approach to decrease the complications that are associated with TAAA repair.
Acute Disease↗
Fulfilling the social contract between medical schools and the public.
To gain a better understanding of the effects of medical schools related to transformations in medical practice, science, and public expectations, the Association of American Medical Colleges (AAMC) established the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) in 1994. Recognizing the privileges academic medicine enjoys as well as the power of and the strain on its special relationship with the American public, APMOMS formed the Working Group on Fulfilling the Social Contract. That group focused on the question: What are the roles and responsibilities involved in the social contract between medical schools and various interested communities and constituencies? This article reports the working group's findings. The group describes the historical and philosophical reasons supporting the concept of a social contract and asserts that medical schools have individual and collective social contracts with various subsets of the public, referred to as "stakeholders." Obligations derive implicitly from the generous public funding and other benefits medical school receive. Schools' primary obligation is to improve the nation's health. This obligation is carried out most directly by educating the next generation of physicians and biomedical scientists in a manner that instills appropriate professional attitudes, values, and skills. Group members identified 27 core stakeholders (e.g., government, patients, local residents, etc.) and outlined the expectations those stakeholders have of medical schools and the expectations medical schools have of those stakeholders. The group conducted a survey to test how leaders at medical schools responded to the notion of a social contract, to gather data on school leaders' perceptions of what groups they considered their schools' most important stakeholders, and to determine how likely it was that the schools' and the stakeholders expectations of each other were being met. Responses from 69 deans suggested that the survey provoked thinking about the broad issue of the social contract and stakeholders. Leaders on the same campuses disagreed about what groups were the most important stakeholders. Similarly, the responses revealed a lack of national consensus about the most important stakeholders, although certain groups were consistently included in the responses. The group concludes that medical school leaders should examine their assumptions and perspectives about their institutions' stakeholders and consider the interests of the stakeholders in activities such as strategic planning, policymaking, and program development.
Administrative Personnel↗
A matrix metalloproteinase inhibitor prevents processing of tumor necrosis factor alpha (TNF alpha) and abrogates endotoxin-induced lethality.
Excessive tumor necrosis factor alpha (TNF alpha) production in response to Gram-negative bacteremia or endotoxemia can often lead to hypotension, shock, and increased mortality. Current approaches used to block the deleterious effects of exaggerated TNF alpha production rely on monoclonal antibodies or immunoadhesins that bind TNF alpha and thus prevent the interaction with its cellular receptors. This report examines whether a previously described inhibitor of matrix metalloproteinases, GM-6001, can inhibit TNF alpha processing and release and attenuate endotoxin-induced mortality. In human peripheral blood mononuclear cells stimulated in vitro with 1 microgram/mL endotoxin, GM-6001 at concentrations > 5 micrograms/mL blocked release of TNF alpha, but did not affect the release of either IL-1 beta or IL-6. GM-6001 also inhibited the release of soluble TNF receptor (p75) from peripheral blood mononuclear cells stimulated with endotoxin and/or TNF alpha. To confirm the role of secreted TNF alpha in endotoxic shock-induced mortality, C57BL/6 mice were challenged with either endotoxin alone (500 micrograms/mouse) or endotoxin (100 ng/mouse) plus D-galactosamine (8 mg/mouse). GM-6001 pretreatment (100 mg/kg) significantly attenuated the 90-minute plasma TNF alpha response in both models and improved survival in mice treated with low-dose endotoxin plus D-galactosamine. However, plasma IL-1 beta and IL-6 concentrations at 90 min after endotoxin treatment were unaffected by GM-6001 following lethal endotoxin challenge, confirming the in vivo specificity of this matrix metalloproteinase inhibitor for TNF alpha processing. These findings demonstrate that a novel inhibitor of matrix metalloproteinases can prevent the release of TNF alpha both in vitro and in vivo, and can abrogate the harmful sequelae of endotoxemic shock.
Animals↗
Conservative treatment of rectal adenocarcinoma with endocavitary irradiation or wide local excision and postoperative irradiation.
PURPOSE: To evaluate the role of endocavitary irradiation and wide local excision followed by irradiation in the treatment of early-stage rectal adenocarcinoma. MATERIALS AND METHODS: Sixty-five patients with early-stage adenocarcinoma of the rectum were treated with endocavitary irradiation (n = 20) or wide local excision followed by external-beam irradiation (n = 45) between 1974 and 1994 at the University of Florida. All patients were monitored for a minimum of 2 years or until death. RESULTS: The rates of local-regional control at 5 years were 80% after endocavitary irradiation and 86% after wide local excision and radiotherapy. The ultimate 5-year local-regional control rates were 85% and 92%, respectively. Multivariate analysis of local-regional control with sphincter preservation showed that tumor configuration (exophytic v ulcerative) significantly influenced this end point; local-regional control was decreased in patients with ulcerated cancers. Five-year cause-specific survival rates were 84% after endocavitary irradiation and 88% after wide local excision and radiotherapy. Multivariate analysis revealed that tumor configuration significantly influenced cause-specific survival; patients with ulcerated tumors had a worse prognosis. CONCLUSION: Endocavitary irradiation is a highly effective treatment for properly selected patients with early-stage rectal adenocarcinoma. Patients with less favorable lesions that appear to be limited to the muscularis propria have a high chance of cure with sphincter preservation after wide local excision and external-beam irradiation.
Adenocarcinoma↗