[Adult hepatoblastoma. A case report]. / Hepatoblastoma del adulto. Presentación de un caso.

Adult hepatoblastoma is a rare pathology. Its pathogeny is not well understood and prognosis is very bad. We pre-sent a case of adult hepatoblastoma treated in our centre. A 65 year-old male, without previous hepatopathy, who consulted due to right hypochondrial pain with a subacute evolution. The pathological diagnosis was adult epithelial hepatoblastoma, with free surgical margins. The patient recei-ved a second surgical intervention 5 months later due to early recurrence and died 10 months after the diagnosis due to a new massive recurrence. His definitive diagnosis is histological. Radical surgery is the only treatment that increases survival, but recurrence is frequent. There are no well-defined patterns of adjuvant chemotherapy nor is there any trans-plant experience.

Hepatoblastoma del adulto. Presentación de un caso / Adult hepatoblastoma. A case report

El hepatoblastoma del adulto es una patología inusual, de patogenia no bien conocida y de muy mal pronóstico. Presentamos un caso de hepatoblastoma del adulto tratado en nuestro centro. Varón de 65 años, sin hepatopatía previa, que consulta por dolor en hipocondrio derecho de evolución subaguda. El diagnóstico anatomopatológico fue hepatoblastoma epitelial del adulto, con bordes quirúrgicos libres. Fue reintervenido 5 meses después por recidiva precoz y falleció 10 meses después del diagnóstico por nueva recidiva masiva. Su diagnóstico definitivo es histológico. La cirugía radical ofrece el único tratamiento que aumente la supervivencia, pero frecuentemente recidiva. No existen pautas bien definidas de quimioterapia adyuvante, ni experiencia en trasplante (AU)

Adult hepatoblastoma is a rare pathology. Its pathogeny is not well understood and prognosis is very bad. We present a case of adult hepatoblastoma treated in our centre. A 65 year-old male, without previous hepatopathy, who consulted due to right hypochondrial pain with a subacute evolution. The pathological diagnosis was adult epithelial hepatoblastoma, with free surgical margins. The patient received a second surgical intervention 5 months later due to early recurrence and died 10 months after the diagnosis due to a new massive recurrence. His definitive diagnosis is histological. Radical surgery is the only treatment that increases survival, but recurrence is frequent. There are no well-defined patterns of adjuvant chemotherapy nor is there any transplant experience (AU)

[Epithelioid angiosarcoma of the gallbladder. Case report and review of the literature]. / Angiosarcoma epitelioide de vesícula.

Angiosarcoma of the gallbladder is an infrequent pathology but has a high morbidity and mortality. There are only 10 references in the international literature. We present a case treated in our center and we review the cases published since 1956. An 81 year-old male patient with abdominal pain, asthenia and dyspnea. Analytically anemia and leukocytosis. Exploration found a distended abdomen, right hypochondrium pain, with defense. Abdominal echography and a CT were requested with a diagnosis of acute cholecystitis and he was admitted for antibiotic treatment. The patient did not evolve favorably and was subjected to emergency surgery, which found a haemoperitoneum and a gallbladder with a tumoral appearance that could not be totally extirpated. He died 20 days after the operation. The report from pathological anatomy was compatible with epithelioid angiosarcoma of the biliary gallbladder. Gallbladder angiosarcoma is a neoplasia with a bad prognosis, whose clinical presentation can be mistaken for acute cholecystitis. Improving the prognosis of this disease involves carrying out early diagnosis and surgical treatment.

Angiosarcoma epitelioide de vesícula. Presentación de un caso y revisión bibliográfica / Epithelioid angiosarcoma of the gallbladder. Case report and review of the literature

El angiosarcoma de vesícula es una patología poco frecuente pero con una alta morbi-mortalidad del que sólo hay 10 referencias en la literatura internacional. Presentamos un caso tratado en nuestro centro y realizamos una revisión de los casos publicados desde 1956. Paciente varón de 81 años con dolor abdominal, astenia y disnea. Analíticamente anemia y leucocitosis. En la exploración destacaba un abdomen distendido, doloroso en hipocondrio derecho, con defensa. Se solicitó ecografía abdominal y un TC con diagnóstico de colecistitis aguda y se ingresó para tratamiento antibiótico. El paciente no evolucionó favorablemente y se intervino de urgencia hallando un hemoperitoneo y una vesícula de aspecto tumoral que no se pudo extirpar en su totalidad. Falleció a los 20 días de la intervención. El informe de anatomía patológica fue compatible con angiosarcoma epiteloide de vesícula biliar. El angiosarcoma de vesícula es una neoplasia de mal pronóstico, cuya presentación clínica puede confundirse con la colecistitis aguda. Conseguir mejorar el pronóstico de esta enfermedad pasa por realizar un diagnóstico y tratamiento quirúrgico precoces (AU)

Angiosarcoma of the gallbladder is an infrequent pathology but has a high morbidity and mortality. There are only 10 references in the international literature. We present a case treated in our center and we review the cases published since 1956. An 81 year-old male patient with abdominal pain, asthenia and dyspnea. Analytically anemia and leukocytosis. Exploration found a distended abdomen, right hypochondrium pain, with defense. Abdominal echography and a CT were requested with a diagnosis of acute cholecystitis and he was admitted for antibiotic treatment. The patient did not evolve favorably and was subjected to emergency surgery, which found a haemoperitoneum and a gallbladder with a tumoral appearance that could not be totally extirpated. He died 20 days after the operation. The report from pathological anatomy was compatible with epithelioid angiosarcoma of the biliary gallbladder. Gallbladder angiosarcoma is a neoplasia with a bad prognosis, whose clinical presentation can be mistaken for acute cholecystitis. Improving the prognosis of this disease involves carrying out early diagnosis and surgical treatment (AU)

Prognostic factors in elderly patients with malignant pleural mesothelioma: results of a multicenter survey.

BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. There are no specific guidelines for their management. METHODS: The clinical records of elderly patients (⩾70 years old) with MPM referred from January 2005 to November 2011 to six Italian Centres were reviewed. Age, gender, histology, International Mesothelioma Interest Group (IMIG) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and treatment modalities were analysed and correlated to overall survival (OS). RESULTS: In total, 241 patients were identified. Charlson Comorbidity Index was ⩾1 in 92 patients (38%). Treatment was multimodality therapy including surgery in 18, chemotherapy alone in 180 (75%) and best supportive care in 43 cases (18%). Chemotherapy was mainly pemetrexed based. Median OS was 11.4 months. Non-epithelioid histology (HR 2.32; 95% CI 1.66-3.23, P<0.001), age ⩾75 years (HR 1.44; 95% CI 1.08-1.93, P=0.014), advanced (III-IV) stage (HR 1.47; 95% CI 1.09-1.98, P=0.011) and CCI⩾1 (HR 1.38; 95% CI 1.02-1.85, P=0.034) were associated to a shorter OS. Treatment with pemetrexed was associated with improved OS (HR 0.40; 95% CI 0.28-0.56, P<0.001). CONCLUSIONS: Non-epithelioid histology, age ⩾75 years, advanced IMIG stage and presence of comorbidities according to CCI were significant prognostic factors in elderly patients with MPM. Treatment with pemetrexed-based chemotherapy was feasible in this setting. Prospective dedicated trials in MPM elderly patients selected according to prognostic factors including comorbidity scales are warranted.

Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma.

BACKGROUND: The aim of this open label phase II study (NCT00407459) was to assess the activity of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab combined with pemetrexed and carboplatin in patients with previously untreated, unresectable malignant pleural mesothelioma (MPM). METHODS: Eligible patients received pemetrexed 500 mg m(-2), carboplatin area under the plasma concentration-time curve (AUC) 5 mg ml(-1) per minute and bevacizumab 15 mg kg(-1), administered intravenously every 21 days for six cycles, followed by maintenance bevacizumab. The primary end point of the study was progression-free survival (PFS). A 50% improvement in median PFS in comparison with standard pemetrexed/platinum combinations (from 6 to 9 months) was postulated. RESULTS: Seventy-six patients were evaluable for analysis. A partial response was achieved in 26 cases (34.2%, 95% CI 23.7-46.0%). Forty-four (57.9%, 95% CI 46.0-69.1%) had stable disease. Median PFS and overall survival were 6.9 and 15.3 months, respectively. Haematological and non-haematological toxicities were generally mild; however, some severe adverse events were reported, including grade 3-4 fatigue in 8% and bowel perforation in 4% of patients. Three toxic deaths occurred. CONCLUSION: The primary end point of the trial was not reached. However, due to the limitation of a non-randomised phase II design, further data are needed before drawing any definite conclusion on the role of bevacizumab in MPM.

Long-Term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency.

Background. Our knowledge on long-term outcome in CAH remains incomplete. Methods. In a prospective study (33 CAH patients, 33 age-matched controls), reproductive outcomes, self-rating of genital appearance and function, and sexuality were correlated to degree of initial virilisation, genotype, and surgery. Results. Patients had larger median clitoral lengths (10.0 mm [range 2-30] versus 3.5 [2-8], P < .001), shorter vaginal length (121 mm [100-155] versus 128 [112-153], P = .12), lower uterine volumes (29.1 ml [7.5-56.7] versus 47.4 [15.9-177.5], P = .009), and higher ovarian volumes (4.4 ml [1.3-10.8] versus 2.8 [0.6-10.8], P = .09) than controls. Satisfaction with genital appearance was lower and negatively correlated to degree of initial virilisation (r(s) = ≤-0.39, P ≤ .05). More patients had never had intercourse (P = .001), and age at 1st intercourse was higher (18 yrs versus 16 yrs, P = .02). Conclusion. Despite overall acceptable cosmetic results, reproductive outcomes were suboptimal, supporting that multidisciplinary teams should be involved in adult follow up of CAH patients.

Pulmonary embolism with minimal D-dimer increase - disagreement between clinic and laboratory: case report.

Pulmonary embolism is still currently considered a very insidious disease and if not diagnosed and treated rapidly is lethal in almost 10 percent of all cases. Clinical and patient history data are essential for the diagnosis and evaluation of the clinical risk of pulmonary embolism. Pulmonary embolism, particularly during minor episodes, was primarily identified by abnormalities in D-dimer concentration during laboratory testing. Indeed, an increase in D-dimer plasma levels was consequently identified as a valid diagnostic element for pulmonary embolism and therefore, in the absence of D-dimer abnormalities, a tendency to exclude such diagnosis exists. This case report describes the importance of carrying out level II diagnostic investigations which may be particularly valid in patients with a minimal rise in D-dimer levels and a clinical suspicion of a pulmonary embolism. This method allows for a quick diagnosis with early therapeutic measures which improve survival rates during the acute and critical phase.

Ivabradine use in refractory unstable angina: a case report.

In this report, we describe the clinical results of ivabradine use in a patient with a serious form of unstable angina. For this patient, it was proposed that no other therapeutic, pharmacologic or surgical, option was available. The patient is a 75-year-old woman who presented with repeated episodes of retrosternal chest pain. She notably had a history of type II diabetes mellitus treated by insulin for several years and complicated by diabetic macro-angiopathy. ECG tracings recorded during these episodes showed abnormalities of the lateral repolarization phase of ischaemic nature. There was no measured increase in cardiac enzymes. She was transferred to our CCU with a diagnosis of unstable angina. In our CCU, the patient was treated with nitrates, metoprolol, aspirin, clopidogrel and atorvastatin at maximal sustainable doses. Following persistent clinical-instrumental instability, she was subjected to coronary angiography. This study revealed severe multi-vessel coronary artery disease not amenable to surgery or angioplasty revascularization. In addition to the therapy already provided, a beta-blocker (metoprolol 50 mgx2/die) and diltiazem (30 mgx2/die) were added despite their potentially dangerous and adverse chronotropic effects. Despite this treatment, the patients heart rate remained high (between 80 and 100 beats/min). This heart rate appeared to be the main driving cause of her anginal symptoms. At this point, the use of ivabradine seemed the only option, even though use would be off-label compared to current indications for the drugs use. We started with a low dose of 2.5 mg/b.i.d. and titrated up to 5 mg b.i.d. As we titrated, we witnessed a gradual reduction in heart rate. A consequent stabilization of her clinical pattern progressed into an almost unexpected asymptomatic state. After about a week of clinical observation, the patient recovered. After three months, she remains asymptomatic.

Lenograstim in the treatment of severe neutropenia in patients treated with Peg-IFN and ribavirin: the experience of a single hepatology unit.

Lenograstim is a G-CSF that allows therapy with Peg-IFN-alpha to be continued in cases of haematotoxicity. This study evaluates the efficacy of lenograstim administration in a group of eight patients with chronic HCV-related hepatitis who developed neutropenia during antiviral treatment. Patients with absolute neutrophil counts less than 900 cells/mmc and early viral response received lenograstim at the dosage of 263 mcg 24 hours prior to administration of Peg-IFN alpha 2b. All patients receiving lenograstim completed the antiviral treatment (48 weeks) with standard doses of PEG-IFN alpha, with six of the eight patients (75%) showing a sustained virological response.

Ablation of large HCCs using a new saline-enhanced expandable radiofrequency device().

PURPOSE: Evaluation of a new device designed to achieve large volumes of necrosis in hepatocellular carcinoma (HCC) nodules by application of radiofrequency ablation (RFA). MATERIALS AND METHODS: 29 consecutive patients with 31 HCC nodules ≥3 cm in diameter (range 3-7.5 cm; mean diameter 5.5 cm) underwent ultrasound (US) guided percutaneous RFA using an expandable electrode with 7 active arrays and saline injection designed to create tissue ablation in areas of up to 7 cm (Starburst XLi-enhanced RFA device). Treatment was performed in general anesthesia (6 patients) or deep sedation (23 patients). Treatment efficacy was assessed by three-phase contrast-enhanced computed tomography (CT) and bimonthly US follow-up. RESULTS: One to three electrode insertions (mean number 1.6) were performed in each patient. CT showed complete necrosis in 23/31 HCC nodules (74%) in 22 patients. Follow-up of these 22 patients ranged from 2 to 15 months (mean time 8.3 months). In 6/22 patients (28%) intrahepatic recurrence occurred within 5-10 months (mean time 8.3 months). Major complications were post-ablation syndrome in 7/29 (24%), peritoneal effusion in 4/29 (14%), pleural effusion in 2/29 (7%) and transient obstructive jaundice in 1/29 (3.4%) patients. One patient died 6 months after treatment because of tumor progression. CONCLUSIONS: In the treatment of large HCC nodules, Starburst XLi-enhanced is an effective and safe device.

Characterization of a Staphylococcus aureus strain showing high levels of biofilm formation isolated from a vascular graft: case report.

A methicillin-susceptible Staphylococcus aureus strain, SA-DZ1, was isolated from an infected bypass crossover graft. Its general microbiological features were reminiscent of those previously described for the wound Wiley strain. Removal of the prosthetic device was necessary to resolve the infection. SA-DZ1 grown under different conditions showed a very strong and distinctive biofilm-producing phenotype, which was also visualized by confocal laser scanning microscopy. The biofilm extracellular matrix was essentially polysaccharidic, as determined by differential growth and physicochemical tests. By Multi Locus Sequence Typing (MLST), SA-DZ1 was classified as st94, a single locus variant of st8. Several other genetic traits assayed by PCR, such as agr-type and the presence of gene encoding proteins involved in adhesion and virulence (e.g. ica operon), confirmed the identifying features of this clinical isolate.

No evidence of involvement of Chlamydia pneumoniae in lung cancer by means of quantitative real-time polymerase chain reaction.

Chlamydia pneumoniae, an obligate intracellular pathogen, is well-known as etiological agent of acute respiratory infections; the repeated or prolonged exposure to chlamydial antigens may promote the persistence of C. pneumoniae in the respiratory tract leading to chronic diseases, such as chronic obstructive pulmonary disease and asthma. The predilection of C. pneumoniae to cause respiratory tract infections combined with its persistent nature suggest that it might play a role in lung cancer. The aim of our study is to evaluate the involvement of C. pneumoniae in pathogenesis of lung cancer. We therefore investigated the presence of C. pneumoniae DNA in tumor lung tissues by using real-time PCR assay. Simultaneously, tumor and healthy tissues from the same patient with primary carcinoma lung were analyzed. C. pneumoniae DNA was not detected in a single lung tumor tissue by means of an highly sensitive, and specific real-time PCR assay based on FRET hybridization probes. In conclusion, this study does not support the involvement of C. pneumoniae in the pathogenesis of lung cancer, suggesting that further investigations are needed to clarify other potential causative factors for the development of this malignancy.

Antibacterial activity and anti-biofilm effect of chitosan against strains of Streptococcus mutans isolated in dental plaque.

Streptococcus mutans is the major cause of dental plaque and is often associated with biofilm formation. The aim of this study is to evaluate the activity of a hydrosoluble derivative of chitosan against S. mutans biofilms in vitro and in vivo. Strains of S. mutans were isolated from the dental plaque of 84 patients enrolled in the study. The antibacterial activity of chitosan was determined by broth microdilutions. The effect of chitosan at different concentrations and exposure times on S. mutans biofilms at different phases of development was assessed by a clinical study using the classical "4-day plaque regrowth" experiment in adult volunteers. The MIC values of chitosan were between 0.5 and 2 g/L. Compared to distilled water, the chitosan solution significantly decreased the vitality of plaque microflora (p

Valor pronóstico de la afectación del margen circunferencial en pacientes con cáncer de recto localmente avanzado / Prognostic value of circumferential resection margin involvement in patients with locally-advanced rectal cancer

Introducción. La afectación del margen circunferencial (MC) en los pacientes intervenidos por neoplasia de recto es un factor de mal pronóstico en cuanto a posibilidad de recidiva local, recidiva a distancia y supervivencia, y esta afectación se ha relacionado con la calidad de la cirugía. Analizamos la tasa de afectación del MC en pacientes con cáncer de recto localmente avanzado, sometidos a tratamiento neoadyuvante, y su relación con la supervivencia libre de enfermedad (SLE) y la supervivencia específica (SE). Material y métodos. Se incluye a 101 pacientes diagnosticados de adenocarcinoma de recto entre enero de 2001 y diciembre de 2005, e intervenidos tras recibir radioquimioterapia neoadyuvante. El MC se consideró positivo cuando la distancia del tumor al borde quirúrgico fue menor de un milímetro. La afectación del MC se relaciona con la SLE y la SE mediante el test log-rank. Resultados. La media de edad fue de 66,6 años. La tasa de afectación del MC fue del 10,8% (11 casos), en 7 casos por cercanía o contacto del MC con el tumor, en 2 por cercanía de adenopatías, en un caso por infiltración perineural en el MC y en otro por crecimiento discontinuo del tumor. Con un seguimiento medio de 25,4 meses, se diagnosticó recidiva de la enfermedad en 13 pacientes: en 3 (2,97%) como recidiva local y en 10 (9,9%) como metástasis a distancia. Once (10,8%) pacientes fallecieron por evolución de la enfermedad. La afectación del MC se relacionó significativamente con la SLE (p = 0,0167) y con la SE (p = 0,0176). Conclusión. En pacientes intervenidos por cáncer de recto después de tratamiento neoadyuvante con radioquimioterapia, la afectación del MC es un factor pronóstico negativo para SLE y SE (AU)

Introduction. Circumferential resection margin (CRM) involvement in patients undergoing surgery for rectal tumors is a factor predicting poor prognosis in terms of the possibility of local recurrence, distant recurrence, and survival. CRM involvement has been related to the quality of the surgery. We analyzed the rate of CRM involvement in patients with locally-advanced rectal cancer undergoing neoadjuvant therapy and its relation with disease-free survival (DFS) and disease-specific survival (DSS). Material and methods. A total of 101 patients diagnosed with rectal adenocarcinoma between January 2001 and December 2001 who underwent surgery after receiving neoadjuvant radiochemotherapy were included. The CRM was considered positive when the distance between the tumor and the surgical border was less than 1 mm. The relation between CRM involvement and DFS and DSS was evaluated using the log-rank test. Results. The mean age was 66.6 years. The rate of CRM involvement was 10.8% (11 patients); CRM involvement was due to proximity or contact of the CRM with the tumor in 7 patients, proximity of enlarged nodes in 2 patients, perineural invasion in the CRM in 1 patient and discontinuous tumoral growth in 1 patient. With a mean follow-up of 25.4 months, disease recurrence was diagnosed in 13 patients: local recurrence occurred in 3 (2.97%) patients and distant metastases in 10 (9.9%). Eleven (10.8%) patients died from disease progression. CRM involvement was significantly related to DFS (p = 0.0167) and DSS (p = 0.0176). Conclusion. In patients undergoing surgery for rectal cancer after neoadjuvant radiochemotherapy, CRM involvement is a negative prognostic factor for DFS and DSS (AU)

[Hormonal therapy in oncologic treatment: pathogenic hypotheses and interactions between thyroid and breast pathologies]. / La terapia ormonale nel trattamento oncologico: ipotesi patogenetiche e interazioni tra patologia tiroidea e mammaria.

INTRODUCTION: The aim to individuate the eventual correlation between the two pathologies has justified deeper studies to achieve new prospective approaches for both disease. BACKGROUND: We have selected 4 groups of patients who presented an association between the two pathologies: a) malignant breast pathology associated to a malignant thyroid pathology, b) patients with breast carcinoma who presented association with some thyroid alterations, c) patients with thyroid carcinoma who presented association with some breast alterations, d) patients who presented some associations between benign breast pathology and benign thyroid pathology. MATERIALS AND METHODS: We have excluded all patients with a clear physiological or surgical menopausal status, and we've so considered only patients with a regular menstrual cycle. We've so selected a group of 120 patients and we've performed in all these patients during the early follicular phase the following exams: breast echographic evaluation and thyroid echographic-structure and volume determination and finally hormonal determinations we have so obtained two breast subgroups: 32 patients with hyperestrogenic integrative hormonal characteristics, 28 patients subjected to adjuvant hormonal therapy with hypoestregenic hormonal status and finally two thyroid subgroups, 22 patients showing clinical or subclinical hypothyroidism, 38 patients showing clinical or subclinical hyperthyroidism. We've compared these data to a random age-matched health control women group of 25 patients. RESULTS: The first group of patient showed a thyroid hormonal pattern of subclinical hypothyroidism or at least free T3 and free T4 mean value currently under and TSH and TPO Ab levels curve currently over the mean values of the control group. The second group showed the TSH suppressed with free T3 and free T4 curves currently over the mean value of the control group. The third group showed slight elevations in serum PRL levels curve. The fourth group showed increased estrogen levels-curve, often over the mean value of the control group. CONCLUSION: How much is it allowed to perform an hormonal therapy, specially for a benign pathology if we're not yet able to understand the deep and unknown interaction between breast and thyroid?

[Intraoperative cholangiography in videolaparoscopic cholecystectomy: indications, advantages, and limitations]. / Colangiografia intraoperatoria in corso di colecistectomia videolaparoscopica: indicazioni, vantaggi, limiti.

Consensus doesn't exist about the intraoperative cholangiography specially if is need in every one laparoscopic cholecystectomy either exclusively in case of anatomical doubts or suspect of injures or stones of the common duct. We have considered 450 patient subjected to laparoscopic cholecystectomy during 1992-2000. Patients suspicious to be affected by common duct lithiasis (28 cases) are subjected to ERCP with cleaning of the biliary tree. In 18 patients (4%) it has been necessary the laparotomic conversion; 176 patients (39%) have been subjected to intraoperative cholangiography, selected on anatomical regional disposition or anamnesis and biochemical and instrumental results (history of jaundice or gallstones pancreatitis, abnormal serum level of the biliary stasis biochemistry, common bile duct major of 8 mm, michrolitiasis of the gallbladder). In 7 cases (4%) we have discovered common bile duct stones. We don't attempt intraoperative cholangiography in every one laparoscopic cholecystectomy, but only in cases where we suspect presence of common bile duct stones either iatrogenic injuries or when we retain it necessary to clarify the regional anatomy. Unlikely just in patients where would be more useful, causes major risk of intra- and post-operative complications, it is very difficult, often impossible, to attempt the intraoperative cholangiography. Routinary employing of the intraoperative cholangiography could be useful just for a little number of patients, while selective employing reduce 60% the X-ray. Collaboration with the radiologist is able to reduce the mistaken on the interpretation of the radiograms.

Intensified CHOP regimen in aggressive lymphomas: maximal dose intensity and dose density of doxorubicin and cyclophosphamide.

BACKGROUND: Following our previous study of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) intensification in non-Hodgkin's lymphoma (NHL), in the present report we attempted to further increase dose intensity by shortening the between-course intervals with the support of growth factors. PATIENTS AND METHODS: A total of 67 patients were enrolled. With a fixed dose of doxorubicin 75 mg/m(2), cyclophosphamide (CTX) was started at a dose of 1750 mg/m(2) and increased by 250 mg/m(2) in consecutive cohorts of patients provided that no dose-limiting toxicity occurred. After the maximal tolerated dose (MTD) had been identified, this was used to treat more patients in order to confirm the feasibility of the regimen on a large scale, with the number of cycles being varied on the basis of disease extension. RESULTS: Twenty-three cases were enrolled in the CTX dose finding phase. Dose-limiting non-hematological toxicity occurred at 2250 mg/m(2). As the intermediate level of 2000 mg/m(2) had a borderline toxicity profile, a CTX dose of 1750 mg/m(2) was defined as the MTD. A total of 53 patients then received the MTD during the course of the study as a whole. At the MTD, toxicity was acceptable. Only 10 of 189 cycles (4%) required hospitalization due to infection or febrile neutropenia. Seventy-four percent of the patients achieved complete remission. Freedom from progression and overall survival at 12 months were 71% and 86% in the whole series, and 58% and 71% for high-risk cases, respectively. CONCLUSIONS: This intensified CHOP regimen is feasible on an outpatient basis. It can be safely considered a definitive treatment in patients at low and intermediate risk, and as induction before high-dose consolidation in high-risk cases.