RESUMEN
While endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) are the most accurate techniques for locoregional staging of esophageal cancer, little evidence exists that these innovations impact on clinical care. The objective on this study was to determine the frequency with which EUS and EUS-FNA alter the management of patients with localized esophageal cancer, and assess practice variation among specialists at a tertiary care center. Three gastroenterologists, three medical oncologists, three radiation oncologists and four thoracic surgeons were asked to independently report their management recommendations as the anonymized staging information of 50 prospectively enrolled patients from another study were sequentially disclosed on-line. Compared to initial management recommendations, that were based upon history, physical examination, upper endoscopy and CT scan results, EUS prompted a change in management 24% (95% CI: 12-36%) of the time; usually to a more resource-intensive approach (71%), for example from recommending palliation to recommending neoadjuvant chemoradiation therapy. EUS-FNA plus cytology results altered management an additional 8% (95% CI: 6-15%) of the time. Agreement between specialists ranged from fair (intraclass correlation [ICC=0.32) to substantial (ICC=0.65); improving with additional information. Among specialists, agreement was greatest for patients with stage I disease. EUS and EUS-FNA changed patient management the most for patients with stages IIA, IIB or III disease. EUS, with or without FNA, significantly impacts the management of patients with localized esophageal cancer. With respect to the optimal treatment for each patient, agreement among physicians incrementally increases with endoscopic ultrasound results. Specialty training appears to influence therapeutic decision-making behavior.
Asunto(s)
Biopsia con Aguja Fina/métodos , Endosonografía , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/terapia , Esofagoscopía , Pautas de la Práctica en Medicina , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Gastroenterología , Humanos , Masculino , Oncología Médica , Persona de Mediana Edad , Estudios Prospectivos , Radiología , Cirugía TorácicaRESUMEN
Bartonella species are emerging pathogens that have been isolated worldwide from humans and other mammals. Our objective was to estimate the prevalence of Bartonella infection in free-ranging African lions (Panthera leo) and cheetahs (Acinonyx jubatus). Blood and/or serum samples were collected from a convenience sample of 113 lions and 74 cheetahs captured in Africa between 1982 and 2002. Whole blood samples available from 58 of the lions and 17 of the cheetahs were cultured for evidence of Bartonella spp., and whole blood from 54 of the 58 lions and 73 of the 74 cheetahs tested for the presence of Bartonella DNA by TaqMan PCR. Serum samples from the 113 lions and 74 cheetahs were tested for the presence of antibodies against Bartonella henselae using an immunofluorescence assay. Three (5.2%) of the 58 lions and one (5.9%) of the 17 cheetahs were bacteremic. Two lions were infected with B. henselae, based on PCR/RFLP of the citrate synthase gene. The third lion and the cheetah were infected with previously unidentified Bartonella strains. Twenty-three percent of the 73 cheetahs and 3.7% of the 54 lions tested by TaqMan PCR were positive for Bartonella spp. B. henselae antibody prevalence was 17% (19/113) for the lions and 31% (23/74) for the cheetahs. The prevalence of seropositivity, bacteremia, and positive TaqMan PCR was not significantly different between sexes and age categories (juvenile versus adult) for both lions and cheetahs. Domestic cats are thus no longer the only known carriers of Bartonella spp. in Africa. Translocation of B. henselae seronegative and TaqMan PCR negative wild felids might be effective in limiting the spread of Bartonella infection.
Asunto(s)
Acinonyx/microbiología , Infecciones por Bartonella/veterinaria , Bartonella henselae/aislamiento & purificación , Leones/microbiología , África Oriental/epidemiología , Animales , Anticuerpos Antibacterianos/sangre , Infecciones por Bartonella/microbiología , Bartonella henselae/genética , ADN Bacteriano/química , ADN Bacteriano/genética , Femenino , Técnica del Anticuerpo Fluorescente , Masculino , Reacción en Cadena de la Polimerasa/veterinaria , Polimorfismo de Longitud del Fragmento de Restricción , Estudios Seroepidemiológicos , Sudáfrica/epidemiologíaRESUMEN
PURPOSE: The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure. PATIENTS AND METHODS: All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy. Chemotherapy regimens were bolus fluorouracil (5-FU), 5-FU and leucovorin, 5-FU and levamisole, and 5-FU, leucovorin, and levamisole. Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy. RESULTS: One thousand six hundred ninety-five patients were entered and fully assessable, with a median follow-up of 7.4 years. There was no difference in overall survival (OS) or disease-free survival (DFS) by drug regimen. DFS and OS decreased between years 5 and 7 (from 54% to 50% and 64% to 56%, respectively), although recurrence-free rates had only a small decrease. The local recurrence rate was 14% (9% in low-risk [T1 to N2+] and 18% in high-risk patients [T3N+, T4N]). Overall, 7-year survival rates were 70% and 45% for the low-risk and high-risk groups, respectively. Males had a poorer overall survival rate than females. CONCLUSION: There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation. Local and distant recurrence rates are still high, especially in T3N+ and T4 patients, even with full adjuvant chemoradiation therapy.
Asunto(s)
Adenocarcinoma/patología , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Adyuvantes Inmunológicos/administración & dosificación , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Quimioterapia Adyuvante , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Inyecciones Intravenosas , Leucovorina/administración & dosificación , Levamisol/administración & dosificación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Dosificación Radioterapéutica , Radioterapia Adyuvante , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía , Factores Sexuales , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To retrospectively review ophthalmologic findings in German Pinschers in Finland. ANIMALS STUDIED: One hundred and twenty-two German Pinschers that had ophthalmologic examination performed according to the Finnish Kennel Club's Eye Scheme before June 15, 1999. PROCEDURES: A total of 154 eye examination reports of 122 dogs were analysed and all described findings were reported. RESULTS: Persistent hyperplastic tunica vasculosa lentis (PHTVL) was diagnosed in 8.4% of all cases, and hereditary cataract (HC) in 6.5%. Even higher numbers of similar changes were reported by ophthalmologists; some of the dogs, however, were officially diagnosed as "free of symptoms" of inherited ocular diseases. A relatively high number (4.5%) of dogs had reported changes in Y sutures. A pedigree analysis suggests recessive inheritance for both diseases. Because of missing information about many dogs in the pedigree, an autosomal incomplete inheritance pattern cannot be ruled out in either case. CONCLUSIONS: Both HC and PHTVL are inherited diseases in German Pinschers. Further studies are needed to determine the importance of the changes found in Y sutures. Discrepancies between the official diagnosis and described changes are probably partially due to the lack of familiarity with the published literature concerning this breed. Further studies are needed to ascertain the inheritance pattern for both diseases. So far breeding with affected animals should be avoided.
Asunto(s)
Catarata/veterinaria , Enfermedades de los Perros/genética , Enfermedades Hereditarias del Ojo/veterinaria , Enfermedades del Cristalino/veterinaria , Animales , Cruzamiento , Catarata/genética , Catarata/patología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/patología , Perros , Enfermedades Hereditarias del Ojo/epidemiología , Enfermedades Hereditarias del Ojo/genética , Enfermedades Hereditarias del Ojo/patología , Femenino , Finlandia/epidemiología , Hiperplasia , Incidencia , Enfermedades del Cristalino/epidemiología , Enfermedades del Cristalino/genética , Enfermedades del Cristalino/patología , Masculino , Tamizaje Masivo/veterinaria , Linaje , Estudios RetrospectivosRESUMEN
BACKGROUND: Surgical resection of adenocarcinoma of the stomach is curative in less than 40 percent of cases. We investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction. METHODS: A total of 556 patients with resected adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to surgery plus postoperative chemoradiotherapy or surgery alone. The adjuvant treatment consisted of 425 mg of fluorouracil per square meter of body-surface area per day, plus 20 mg of leucovorin per square meter per day, for five days, followed by 4500 cGy of radiation at 180 cGy per day, given five days per week for five weeks, with modified doses of fluorouracil and leucovorin on the first four and the last three days of radiotherapy. One month after the completion of radiotherapy, two five-day cycles of fluorouracil (425 mg per square meter per day) plus leucovorin (20 mg per square meter per day) were given one month apart. RESULTS: The median overall survival in the surgery-only group was 27 months, as compared with 36 months in the chemoradiotherapy group; the hazard ratio for death was 1.35 (95 percent confidence interval, 1.09 to 1.66; P=0.005). The hazard ratio for relapse was 1.52 (95 percent confidence interval, 1.23 to 1.86; P<0.001). Three patients (1 percent) died from toxic effects of the chemoradiotherapy; grade 3 toxic effects occurred in 41 percent of the patients in the chemoradiotherapy group, and grade 4 toxic effects occurred in 32 percent. CONCLUSIONS: Postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach or gastroesophageal junction who have undergone curative resection.
Asunto(s)
Adenocarcinoma/cirugía , Antimetabolitos Antineoplásicos/uso terapéutico , Unión Esofagogástrica/cirugía , Fluorouracilo/uso terapéutico , Neoplasias Gástricas/cirugía , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/efectos adversos , Gastrectomía , Humanos , Leucovorina/uso terapéutico , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Dosis de Radiación , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/radioterapia , Tasa de SupervivenciaRESUMEN
BACKGROUND AND PURPOSE: Orbital non-Hodgkin's lymphomas (NHL) have traditionally been treated with radiation. Forty-eight patients presenting with orbital NHL were treated with radiation and were evaluated for local control, overall survival, cause-specific survival, and complications. MATERIALS AND METHODS: Forty-five patients had low-grade and 3 patients had intermediate-grade histologic findings. Orbit-only disease occurred in 22 patients, the conjunctiva in 16, both in five, and lacrimal gland only in five. Patient age ranged from 35 to 94 years (median, 68). Ann Arbor stages were cIEA (34), cIIEA (six), cIIIEA (two), and cIVEA (six). Radiation doses ranged between 15 and 53.8 Gy (median, 27.5 Gy). RESULTS: Follow-up ranged from 0.14 to 18.23 years (median, 5.35). Median overall survival and cause-specific survival were 6.5 and 15.5 years, respectively. Patients with clinical stage I or II disease had significantly better overall and cause-specific survival than patients with stage III or IV disease. Ten-year relapse-free survival in 41 patients with stage I or II disease was 66%. However, there was continued downward pressure on relapse-free survival out to 18 years. One local failure occurred. Twenty-five patients sustained acute complications. There were 17 minor and four major late complications. All major late complications occurred with doses more than 35 Gy. CONCLUSIONS: Excellent local control with radiation doses ranging from 15 to 30 Gy is achieved. Patients with stage I or II disease have better overall and cause-specific survival than patients with stage III or IV disease. Late relapse occurs in sites other than the treated orbit, even in patients with early-stage disease. Doses 35 Gy or higher result in significant late complications and are therefore not indicated for patients with low-grade tumors.
Asunto(s)
Linfoma no Hodgkin/radioterapia , Neoplasias Orbitales/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Masculino , Estadificación de Neoplasias , Neoplasias Orbitales/mortalidad , Neoplasias Orbitales/patología , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: Randomized studies have suggested that sucralfate is effective in mitigating diarrhea during pelvic radiation therapy (RT). This North Central Cancer Treatment Group study was undertaken to confirm the antidiarrheal effect of sucralfate. Several other measures of bowel function were also assessed. PATIENTS AND METHODS: Patients receiving pelvic RT to a minimum of 45 Gy at 1.7 to 2.1 Gy/d were eligible for the study. Patients were assigned randomly, in double-blind fashion, to receive sucralfate (1.5 g orally every 6 hours) or an identical looking placebo during pelvic RT. RESULTS: One hundred twenty-three patients were randomly assigned and found assessable. Overall, there was no significant difference in patient characteristics between those receiving sucralfate and those receiving placebo. Moderate or worse diarrhea was observed in 53% of patients receiving sucralfate versus 41% of those receiving placebo. Compared with patients receiving placebo, more sucralfate-treated patients reported fecal incontinence (16% v 34%, respectively; P =. 04) and need for protective clothing (8% v 23%, respectively; P =. 04). The incidence and severity of nausea were worse among those taking sucralfate (P =.03). Analysis of patient-reported symptoms 10 to 12 months after RT showed a nonsignificant trend toward more problems in patients taking sucralfate than in those taking placebo (average, 2.3 v 1.9 problems, respectively; P =.34). CONCLUSION: Sucralfate did not decrease pelvic RT-related bowel toxicity by any of the end points measured and seems to have aggravated some gastrointestinal symptoms.
Asunto(s)
Antidiarreicos/uso terapéutico , Diarrea/prevención & control , Neoplasias Pélvicas/radioterapia , Sucralfato/uso terapéutico , Adulto , Diarrea/etiología , Método Doble Ciego , Femenino , Humanos , Masculino , Radioterapia/efectos adversos , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Testicular lymphoma is a rare extranodal presentation of non-Hodgkin lymphoma. The authors report long term follow-up information regarding a group of patients with testicular lymphoma evaluated at the Mayo Clinic and describe the outcome with special attention to patterns of recurrence. METHODS: The medical records of patients with testicular lymphoma seen at the Mayo Clinic between January 1970 and March 1993 were reviewed. Patients were included if they had evidence of testicular involvement at the time of diagnosis of lymphoma. Pathology specimens were reviewed for confirmation of diagnosis. RESULTS: Sixty-two patients with a diagnosis of testicular lymphoma were identified. Their median age was 68 years, and 60 patients underwent orchiectomy as the initial therapeutic and diagnostic procedure. Most of patients (79%) had localized or regional disease at the time of presentation. Other treatment modalities after diagnosis included radiotherapy (37%), combination chemotherapy (37%), and combination chemotherapy and radiotherapy (16%). Although 88% of patients had no residual disease after primary treatment, 80% subsequently experienced disease recurrence. There was no significant difference in the rate of recurrence, including Ann Arbor Stage I disease. Treatment did not appear to affect the recurrence rate. At a median follow-up of 2.7 years, 60% of patients had died of disease. Late recurrences were observed, and there appeared to be no plateau in the disease free survival curve. In half (51%) of the patients with disease recurrence, only extranodal locations were involved. Thirteen patients experienced recurrence in the central nervous system, 11 of whom had parenchymal lesions. In 8 of these 13 patients, the central nervous system was an isolated site of disease recurrence. CONCLUSIONS: Testicular lymphoma is a unique and aggressive extranodal non-Hodgkin lymphoma. Better treatment strategies are needed to prevent recurrences. The risk of extranodal recurrence is high, especially in the central nervous system.
Asunto(s)
Linfoma no Hodgkin/patología , Linfoma no Hodgkin/terapia , Neoplasias Testiculares/patología , Neoplasias Testiculares/terapia , Adulto , Anciano , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Incidencia , Linfoma no Hodgkin/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Orquiectomía , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias Testiculares/cirugía , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: This study was designed to assess the toxicity of pelvic radiation therapy, 5-fluorouracil (5-FU) administered by protracted venous infusion, and leucovorin. METHODS: Pelvic radiation therapy consisted of 50.4-54 gray (Gy) administered in 28-30 fractions. Systemic treatment consisted of leucovorin (10 mg daily) administered orally and protracted venous infusion of 5-FU. The initial daily 5-FU dose was 150 mg/m(2). Dose escalations were planned in increments of 25 mg/m(2). RESULTS: Forty eligible patients were registered, of whom 37 were evaluable for chemoradiotherapy-related toxicity. Grade 3 or 4 toxicity secondary to radiation therapy, protracted venous infusion of 5-FU, and leucovorin occurred in 2 of 17 patients at a daily 5-FU dose of 150 mg/m(2), in 5 of 10 patients at a daily 5-FU dose of 175 mg/m(2), and in 5 of 10 patients at a daily 5-FU dose of 200 mg/m(2). Diarrhea was dose-limiting in 7 of 8 patients with Grade 4 toxicity. Venous thrombosis, a treatment-related complication not directly related to chemotherapy or radiation therapy, occurred in 5 of the 40 patients entered into this study. Four thromboses occurred at the site of a central catheter. No thrombotic complications occurred in the last 7 patients, who were given warfarin orally (1 mg daily) during treatment. CONCLUSIONS: Toxicity due to radiation therapy, protracted venous infusion of 5-FU, and leucovorin when 5-FU is given daily at a dose of 150 mg/m(2) is similar to that observed in current chemoradiotherapy regimens for patients with rectal carcinoma. This regimen will be considered as a possible investigational treatment arm of a future trial of adjuvant therapy for rectal carcinoma patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Quimioterapia Adyuvante , Terapia Combinada , Relación Dosis-Respuesta a Droga , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intravenosas , Leucovorina/administración & dosificación , Pelvis/efectos de la radiación , Trombosis de la Vena/etiologíaRESUMEN
CONTEXT: Carcinoma of the esophagus traditionally has been treated by surgery or radiation therapy (RT), but 5-year overall survival rates have been only 5% to 10%. We previously reported results of a study conducted from January 1986 to April 1990 of combined chemotherapy and RT vs RT alone when an interim analysis revealed significant benefit for combined therapy. OBJECTIVE: To report the long-term outcomes of a previously reported trial designed to determine if adding chemotherapy during RT improves the survival rate of patients with esophageal carcinoma. DESIGN: Randomized controlled trial conducted 1985 to 1990 with follow-up of at least 5 years, followed by a prospective cohort study conducted between May 1990 and April 1991. SETTING: Multi-institution participation, ranging from tertiary academic referral centers to general community practices. PATIENTS: Patients had squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, adequate renal and bone marrow reserve, and a Karnofsky score of at least 50. Interventions Combined modality therapy (n = 134): 50 Gy in 25 fractions over 5 weeks, plus cisplatin intravenously on the first day of weeks 1, 5, 8, and 11, and fluorouracil, 1 g/m2 per day by continuous infusion on the first 4 days of weeks 1, 5, 8, and 11. In the randomized study, combined therapy was compared with RT only (n = 62): 64 Gy in 32 fractions over 6.4 weeks. MAIN OUTCOME MEASURES: Overall survival, patterns of failure, and toxic effects. RESULTS: Combined therapy significantly increased overall survival compared with RT alone. In the randomized part of the trial, at 5 years of follow-up the overall survival for combined therapy was 26% (95% confidence interval [CI], 15%-37%) compared with 0% following RT. In the succeeding nonrandomized part, combined therapy produced a 5-year overall survival of 14% (95% CI, 6%-23%). Persistence of disease (despite therapy) was the most common mode of treatment failure; however, it was less common in the groups receiving combined therapy (34/130 [26%]) than in the group treated with RT only (23/62 [37%]). Severe acute toxic effects also were greater in the combined therapy groups. There were no significant differences in severe late toxic effects between the groups. However, chemotherapy could be administered as planned in only 89 (68%) of 130 patients (10% had life-threatening toxic effects with combined therapy vs 2% in the RT only group). CONCLUSION: Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Estudios de Seguimiento , Humanos , Estudios Prospectivos , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To assess the frequency and clinical features of treatment-induced bowel injury in rectal carcinoma patients receiving perioperative external beam radiotherapy (EBRT). The frequency of and factors associated with treatment-induced intestinal injury have previously not been well quantified for rectal cancer patients. Postoperative adjuvant chemoirradiation is recommended for Stage II and III rectal cancers, making such data of significant interest. METHODS AND MATERIALS: The records of 386 consecutive patients undergoing radiotherapy with or without chemotherapy (CT) for rectal carcinoma between 1981-90 were reviewed. Eight-two patients were excluded for receiving nontherapeutic EBRT or modalities other than EBRT. RESULTS: Symptomatic acute treatment-related enteritis (within 30 days of EBRT +/- CT) was diagnosed in 13 patients, 3 of whom developed chronic bowel injury. Chronic treatment-related enteritis was identified in 18 patients and reoperation was required in 17 (5% of the 304 patients with complete follow-up). Chronic proctitis was documented in 38 patients, including 3 patients with small bowel injury. The probability of developing treatment-induced bowel injury at 5 years following treatment was 19%. Variables associated with an increased risk of bowel injury using multivariate analysis were transanal excision (p = 0.002), escalating radiation dose (p = 0.005), and increasing age (p = 0.01). Twenty of the affected patients required operative treatment, and 2 deaths resulted from treatment-induced enteritis. CONCLUSION: Patients with rectal carcinoma treated with EBRT +/- CT have the risk of developing treatment-induced bowel injury. The pelvic radiation dose should be limited to < or = 5040 cGy unless small bowel can be displaced. Reperitonealization of the pelvis, or other surgical methods of excluding the small intestine should be used whenever possible.
Asunto(s)
Enteritis/epidemiología , Proctitis/epidemiología , Traumatismos por Radiación/epidemiología , Neoplasias del Recto/radioterapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad Crónica , Enteritis/etiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Proctitis/etiología , Traumatismos por Radiación/etiología , Dosificación Radioterapéutica , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Análisis de SupervivenciaRESUMEN
BACKGROUND: A retrospective study was performed to examine the outcome of patients with colorectal cancer who had metastatic spinal cord compression (MSCC) and received radiation therapy (RT). METHODS: Forty episodes of MSCC were treated with external beam RT in 34 patients with metastatic colorectal cancer. The median total dose was 3000 cGy (1800-4750 cGy), and the daily fraction size was 300 cGy (151-400 cGy). All patients were followed until death. RESULTS: Median overall survival for the entire cohort was 4.1 months. Of 21 patients ambulatory before RT, 20 remained ambulatory after treatment, whereas only 2 of 9 patients who were nonambulatory regained full ambulatory status. Patients with rectal primary tumors had improved survival (median 7.9 months) compared with those who had colon primary tumors (2.7 months) (P = 0.002). Patients who received a total dose of more than 3000 cGy had a better survival (7 months) than those who received 3000 cGy or less (3.1 months) (P = 0.024). There was a trend for improved survival in patients fully ambulatory at diagnosis (P = 0.056) and after RT (P = 0.07). Unlike other primary sites in which approximately 70% of lesions are located in the thoracic spine, the location of epidural metastasis in colorectal primary tumors was most frequently in the lumbar spine (55% of lesions). CONCLUSIONS: Prognostic features and outcomes for MSCC with primary colorectal cancer are similar to those for other primary sites. There is a suggestion that rectal primary tumors may be associated with an improved outcome compared with colon primary tumors. Patients who received more than 3000 cGy total dose had a longer survival than those who received lower total doses.
Asunto(s)
Neoplasias Colorrectales/patología , Compresión de la Médula Espinal/etiología , Neoplasias de la Médula Espinal/complicaciones , Neoplasias de la Médula Espinal/secundario , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Región Lumbosacra , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Terapia Recuperativa , Compresión de la Médula Espinal/fisiopatología , Neoplasias de la Médula Espinal/radioterapia , Neoplasias de la Médula Espinal/cirugía , Análisis de Supervivencia , CaminataRESUMEN
PURPOSE: The combination of pelvic radiotherapy and 5-fluorouracil-based chemotherapy is associated with an increase in acute gastrointestinal toxicity during rectal adjuvant therapy, most notably an increased incidence of diarrhea. Previous randomized, prospective studies have limited their analysis to presenting rates of severe and life-threatening diarrhea (Grade 3 or greater), and few data are available detailing the extent of mild to moderate diarrhea. To provide baseline data for future studies, we conducted a detailed analysis of diarrhea from a prior clinical trial of adjuvant therapy for rectal cancer. METHODS AND MATERIALS: In a multiinstitutional clinical trial, 204 eligible patients with rectal carcinoma that either was deeply invasive (T3-T4) or involved regional lymph nodes were randomized to receive either postoperative pelvic radiotherapy alone (45 to 50.4 Gy) or pelvic radiotherapy and bolus 5-fluorouracil-based chemotherapy. Toxicity was assessed prospectively. RESULTS: For the 99 eligible patients who received pelvic radiotherapy alone, rates of Grades 0, 1, 2, 3, and 4 diarrhea during treatment were 59, 20, 17, 4, and 0%, respectively. For the 96 eligible patients who received radiotherapy and 5-fluorouracil, the overall rates of grades 0, 1, 2, 3, and 4 diarrhea were 21, 34, 23, 20, and 2%, respectively. The increased rates of diarrhea during adjuvant rectal therapy were manifested across all toxicity levels for patients receiving chemotherapy and pelvic radiotherapy. Of primary clinical importance is the substantial increase in severe or life-threatening diarrhea (Grade 3 or more) (22 vs. 4%,p = 0.001) Additionally, increased rates of any diarrhea and also severe or life-threatening diarrhea were observed in patients who had a low anterior resection compared with those who had an abdominoperineal resection (p < 0.001 and p = 0.006, respectively). CONCLUSION: These results will be of value as a baseline for investigators who want to use treatment toxicity as an end point in cancer control or cancer therapy trials utilizing similar treatment techniques. Patients receiving 5-fluorouracil and pelvic radiotherapy compared with patients receiving pelvic radiotherapy alone and patients with a prior history of a low anterior resection compared with patients who had a prior history of an abdominoperineal resection experienced increased rates of Grades 1 through 4 acute treatment-related diarrhea, and the most important increase occurred as Grade 3 toxicity.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Diarrea/etiología , Fluorouracilo/efectos adversos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Enfermedad Aguda , Antimetabolitos Antineoplásicos/administración & dosificación , Quimioterapia Adyuvante/efectos adversos , Diarrea/epidemiología , Fluorouracilo/administración & dosificación , Humanos , Estudios Prospectivos , Radioterapia/efectos adversos , Dosificación Radioterapéutica , Neoplasias del Recto/patologíaRESUMEN
Sphincter-preserving treatment with combined radiation and chemotherapy has replaced abdominoperineal resection as the standard of care for patients with carcinoma of the anal canal. Randomized studies have shown that the combination of radiation therapy, fluorouracil (5-FU), and mitomycin (Mutamycin) is superior to radiation alone or to radiation combined with 5-FU in these patients and that the colostomy-free survival rate is 71%. Research is underway to determine whether other combinations, such as higher doses of radiation with 5-FU and cisplatin (Platinol), will result in lower or equivalent toxicity or better locoregional control and potentially improved survival. Currently, radiation combined with 5-FU and mitomycin remains the treatment of choice in most patients with carcinoma of the anal canal.
Asunto(s)
Neoplasias del Ano/terapia , Neoplasias del Ano/tratamiento farmacológico , Neoplasias del Ano/radioterapia , Neoplasias del Ano/cirugía , Braquiterapia , Terapia Combinada , Estudios de Seguimiento , Humanos , Terapia RecuperativaAsunto(s)
Neoplasias del Ano/epidemiología , Neoplasias del Ano/etiología , Neoplasias del Ano/patología , Neoplasias del Ano/terapia , Terapia Combinada , Predicción , Humanos , Estadificación de Neoplasias , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
The genetic map of the domestic cat has been developed as a model for studying both feline analogues of human genetic disease and comparative genome organization of mammals. We present here the results of syntenic mapping of 35 genes based upon concordant occurrence of feline gene homologues with feline chromosomes and previously mapped loci in a panel of 41 rodent x cat somatic cell hybrids. These somatic cell hybrids retain rodent chromosomes and segregate feline chromosomes, but in different combinations in each hybrid cell line. Thirty-three of the 35 new locus assignments extend and reaffirm conserved chromosome segment homologies between the human and cat genomes previously recognized by comparative mapping and zoo-FISH. These results demonstrate the extensive syntenic conservation between the human and feline genomes and extend the feline gene map to include 105 assigned loci.
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Enfermedades de los Gatos/genética , Gatos/genética , Mapeo Cromosómico , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Congénitas/veterinaria , Animales , Cromosomas Humanos , Clonación Molecular , Marcadores Genéticos , HumanosRESUMEN
PURPOSE: The combination of radiation therapy with fluorouracil (5-FU)-based chemotherapy is generally accepted as appropriate postoperative therapy for patients with adenocarcinomas of the rectum that extend through the bowel wall or with lymph nodes positive for tumor. We attempted to determine whether the efficacy of this postoperative therapy could be improved by the addition of leucovorin and/or levamisole. METHODS: A total of 1,696 patients were randomized and eligible for treatment with one of four treatment schemes. All patients received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic radiation therapy with chemotherapy and two more cycles of the same systemic chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with levamisole, or 5-FU with leucovorin and levamisole. RESULTS: With a median follow-up duration of 48 months, there is no statistically significant advantage to any of the treatment regimens compared with bolus 5-FU alone. There is evidence of increased gastrointestinal toxicity with the three-drug combination compared with bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either levamisole-containing combination will be shown to be of value with further follow-up evaluation. CONCLUSION: There is no evidence at present for a beneficial effect of levamisole in the adjuvant treatment of rectal cancer. Definitive evaluation of the effect of the addition of leucovorin to 5-FU and pelvic radiation will require further follow-up evaluation.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Antimetabolitos Antineoplásicos/uso terapéutico , Fluorouracilo/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Adulto , Anciano , Agranulocitosis/etiología , Antídotos/administración & dosificación , Antídotos/efectos adversos , Antimetabolitos Antineoplásicos/efectos adversos , Causas de Muerte , Quimioterapia Adyuvante , Terapia Combinada , Diarrea/etiología , Esquema de Medicación , Femenino , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Leucopenia/etiología , Levamisol/administración & dosificación , Levamisol/efectos adversos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: For locally advanced primary colorectal cancer, our institution has combined intraoperative electron irradiation (IOERT) with external beam irradiation (EBRT) +/- 5-fluorouracil (5-FU) and surgical resection. Disease control and survival were compared with the current IOERT and prior non-IOERT regimens. METHODS AND MATERIALS: From April 1981 through August 1995, 61 patients received an IOERT dose of 10-20 Gy, usually combined with 45-55 Gy of fractionated EBRT; 56 had minimum follow-up of 18 months. The amount of residual disease remaining at IOERT after exploration and maximal resection in the 56 patients was gross in 16, < or = microscopic in 39, and unresected in 1. RESULTS: Survival (SR) and disease control were analyzed as a function of potential prognostic factors. Factors that achieved statistical significance for improved overall survival included treatment sequence of preop EBRT + 5-FU (vs. postoperative EBRT + 5-FU, p = 0.003) and < or = microscopic residual disease after maximal resection (vs. gross residual, p = 0.005). Those that appeared to favorably impact disease-free survival included EBRT + 5-FU (vs. EBRT alone, p = 0.01), < or = microscopic residual (vs. gross, p = 0.0014), and colon site of primary (vs. rectum, p = 0.009). Failures within an irradiation field have occurred in 4 of 16 patients (25%) who presented with gross residual after partial resection vs. 2 of 39 (5%) with < or = microscopic residual after gross total resection (p = 0.01). The significant prognostic factors for a decrease in distant metastases were the same as for disease-free SR with respective p-values of 0.013 (EBRT + 5-FU), 0.008 (microscopic residual), and 0.03 (colon primary). The current data suggests a relationship between IOERT dose and incidence of Grade 2 or 3 neuropathy (< or = 12.5 Gy--1 of 29 or 3%, > or = 15 Gy--6 of 26 or 23%, p = 0.03). CONCLUSIONS: Both overall survival and disease control appear to be improved with the addition of IOERT to standard treatment. More routine use of systemic therapy is indicated as a component of IOERT containing treatment regimens because the incidence of distant metastases was 50% of patients at risk.
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Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/radioterapia , Electrones/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Terapia Combinada , Femenino , Fluorouracilo/uso terapéutico , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasia Residual , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/patología , Estudios Prospectivos , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Análisis de Supervivencia , Insuficiencia del TratamientoRESUMEN
PURPOSE: The purpose of this study was to develop a satisfactorily tolerated regimen of radiation therapy, continuous infusion 5-fluorouracil, and leucovorin in patients with locally advanced upper-abdominal gastrointestinal cancer. METHODS AND MATERIALS: Patients with locally advanced or locally recurrent gastric, pancreatic, or extrapelvic colon cancer were eligible for this study. Radiation therapy consisted of 45 Gy in 25 fractions to the tumor and regional lymph nodes, followed by 5.4-9 Gy in three to five fractions to the tumor. Treatment with leucovorin, 10 mg orally daily, and continuous infusion 5-fluorouracil was initiated on the first day of radiation therapy. 5-Fluorouracil was administered at an initial daily dose of 125 mg/m2, with dose escalation planned in 25-mg increments, depending on patient tolerance. RESULTS: Twenty-one evaluable patients participated in this study. Six were treated at the initial daily 5-fluorouracil dose of 125 mg/m2. One patient experienced Grade 4 anorexia and nausea. No other Grade > or = 3 toxicity was observed at this dose. Fifteen evaluable patients were entered at a planned 5-fluorouracil dose of 150 mg/m2 daily; 6 of them experienced Grade 3 toxicity, and none experienced Grade > or = 4 toxicity. Grade 3 toxicities and the number of patients who developed each were: vomiting (three patients); nausea (two patients); diarrhea (two patients); and skin toxicity, hand-foot syndrome, catheter-related infection, and stomatitis in one patient each. Four of the six patients who experienced Grade 3 toxicity developed more than one type of Grade 3 toxicity. CONCLUSIONS: In patients with upper-abdominal gastrointestinal cancer, continuous infusion 5-fluorouracil (150 mg/m2 daily), leucovorin (10 mg orally daily), and radiation therapy (50-54 Gy) resulted in a 40% rate of severe toxicity but no life-threatening toxicity. This clinical trial excludes, with 90% confidence, a 20% risk of Grade 4 toxicity with this combination. The 40% rate of severe toxicity suggests that this combination of agents is near the maximal tolerated dose.