CA125 reference values change in male and postmenopausal female subjects.

BACKGROUND: In cancer patients, including women with a diagnosis of ovarian cancer, cancer antigen 125 (CA125) is used to evaluate the presence of peritoneal involvement. The aims of the present study were to assess CA125 reference intervals and reference change values (RCV) in postmenopausal reference women, postmenopausal women breast cancer free, reference men and cancer free men. METHODS: The series consisted of 433 subjects: 105 postmenopausal breast cancer free women and 56 cancer free men in addition to a total of 272 reference subjects (145 postmenopausal women and 127 men). Repeated CA125 measurements were made in a subset of 149 women and 54 men to calculate RCV and index of individuality. Serum CA125 levels were evaluated by a chemiluminescent assay. RESULTS: In postmenopausal reference women, the mean CA125 value and 2.5th-97.5th percentiles were 6.70, 2.60-11.00 kU/L, respectively, with a unidirectional RCV of 38.4%. In postmenopausal breast cancer free women, the mean CA125 value and 2.5th-97.5th percentile were 7.45, 4.09-10.92 kU/L, respectively, with a RCV of 34.5%. The difference between the means was statistically significant (t=-3.02, p=0.003). In the two male subgroups, the difference between the means for CA125 was not statistically significant (t=0.43, p=0.665). On considering the entire male population, the mean CA125 value and 2.5th-97.5th percentiles were 7.50 and 2.40-13.2 kU/L, respectively, while the unidirectional RCV was 34.3%. In all the studied groups, the indices of individuality were equal to or below 0.6. CONCLUSIONS: The extremely low index of individuality found underlines the importance of using the RCV instead of absolute values as a parameter when interpreting the CA125 data in the monitoring and follow-up of patients with ovarian cancer.

Differential diagnosis of lung nodules: breast cancer metastases and lung tuberculosis.

In a follow-up a 74-year-old woman with breast cancer (clinical stage T4N1M0 at onset, treatment by surgical resection and tamoxifen) presented a combination of two distinct diseases in the lung: breast cancer metastasis and tuberculosis. A CT scan showed multiple pulmonary nodular lesions and in only one lesion fine needle aspiration cytology (FNAC) diagnosed tuberculosis. After specific antibiotic therapy, isoniazide and rifampin, a CT scan highlighted disappearance of tubercular lesion. Because occurrence of tuberculosis during chemo or hormone therapy for metastatic breast cancer is rare, the present case is noteworthy. Indeed, it is worth pointing out the differential diagnosis of pulmonary nodular lesions in patients with cancer and the possible reactivation of tuberculosis even in patients without specific symptoms, without typical tubercular radiological features.

Thymidylate synthetase allelic imbalance in clear cell renal carcinoma.

PURPOSE: To investigate the allelic status of the thymidylate synthetase (TYMS) gene, located at chromosome band 18p11.32, in renal cell carcinoma (RCC). TYMS is a key target of the 5-fluorouracil (5-FU)-based class of drugs, frequently considered in combination therapies in advanced RCC. TYMS variants, such as the TYMS polymorphic 5'-untranslated region variable number tandem repeat sequence (VNTR), are under investigation to guide 5-FU treatment. Yet, no information is available with regard to changes in TYMS allele frequencies in RCC malignances. METHODS: Blood and matched tumor samples were collected from 41 histological proven clear cell RCC affected patients (30 males, 11 females.). TYMS VNTR genotype was first determined in blood to identify heterozygotes employing PCR techniques. To evaluate for allelic imbalance, fragment analysis was performed both in blood and matched tumor DNA of the heterozygote patients. Microsatellite analysis, employing the markers D18S59 and D18S476 mapping, respectively, at the TYMS locus (18p11.32) and 1.5 Mb downstream of the TYMS gene sequence (18p11.31), was performed to confirm TYMS allelic imbalance in tumors. RESULTS: Germ-line TYMS VNTR distribution was: 2R/2R (19.5%), TYMS 2R/3R (36.6%) and TYMS 3R/3R (43.9%). Allelic imbalance for the TYMS tandem repeat region was detected in 26.6% of the heterozygote patients. Microsatellite analysis confirmed the allelic imbalance detected by TYMS VNTR analysis and revealed that the overall frequence of allelic imbalance of chromosome band 18p11.32 was 35%, while the overall allelic imbalance of chromosome band 18p11.31 was 28%. CONCLUSIONS: By focusing on the TYMS polymorphic variants in renal cancer, we here provide evidence, to our knowledge, for the first time showing loss of 18p11.32 and 18p11.31 in renal cell carcinomas. As allelic imbalances involving TYMS locus may be an important variable affecting 5-FU responsiveness, this study may contribute to explain different responses of advanced RCC in combined chemotherapeutic regimens incorporating fluoropyridines.

Cardiac metastasis from renal cell carcinoma without inferior vena involvement: a review of the literature based on a case report. Two different patterns of spread?

We report the case of a 59-year-old man with advanced renal cell carcinoma (RCC), without inferior vena cava (IVC) involvement, treated with radical nephrectomy, palliative radiotherapy for bone metastasis, and medical therapy for bone and lung metastases. The patient died of cardiac arrest after evidence of massive malignant pericardial effusion. At autopsy, massive myocardial and pericardial neoplastic invasion was found. Heart involvement via the IVC is a well-known phenomenon during RCC progression, while in the absence of IVC involvement, clinically evident cardiac involvement is exceptional, with few cases reported in the worldwide literature. Analysis of prior reports and of the present case provides evidence on how the cardiac metastasis may have two distinct origins and clinical features. The first is hematogenous, via the IVC, even in the absence of renal vein involvement; it is generally circumscribed and has a good prognosis after surgery. The second is through the intrathoracic lymphatic system, in the presence of disseminated disease, especially pulmonary metastasis, and this type has a very poor prognosis.

A phase I study of cisplatin, temozolomide and thalidomide in patients with malignant brain tumors.

BACKGROUND: There is pre-clinical evidence of synergism between cisplatin (P) and temozolomide (T) due to higher inhibition by T of O6-alkyl-guanine-alkyltransferase (AGAT), an enzyme involved in the mismatch repair system. T and P are active against malignant gliomas while thalidomide (TH) is emerging as an inhibitor of angiogenesis. PATIENTS AND METHODS: Triplets of patients with malignant brain tumors received escalating doses of P, T and TH up to the dose-limiting-toxicity (DLT) and the maximal tolerated dose (MTD). RESULTS: Seventeen patients were enrolled and a total of 74 cycles were delivered. The MTD was P 75 mg/m2 day 1 and T 150 mg/m2 days 1 to 5 every 21 days with a concomitant 200 mg total daily dose of TH. DLT events were G4 thrombocytopenia and febrile neutropenia. CONCLUSION: Concomitant administration of P 75 mg/m2 day 1, T 150 mg/m2 days 1 to 5 every 21 days and concomitant TH at a total daily dose of 150 mg is feasible and safe. Early efficacy data are encouraging and a phase II study is ongoing.

A phase II study of gemcitabine at fixed infusion rate of 10 mg/m2/min with or without immunotherapy in advanced renal cancer.

BACKGROUND: Advanced renal cancer remains a challenge for oncologists since no treatment other than surgery has demonstrated a clear survival advantage. PATIENTS AND METHODS: Gemcitabine was given to suitable patients at a fixed infusion rate of 10 mg/m2/min. Eighteen patients received concomitant immunotherapy, mostly low doses of interleukin 2 (IL2). RESULTS: Thirty patients were enrolled. The overall response rate was 14% (22% in the subset of patients treated with both chemotherapy and immunotherapy) with a median progression-free survival time of 4.1 + months. Toxicity was not mild, mostly fatigue, nausea and anaemia, even though not life threatening. CONCLUSION: Gemcitabine at the fixed infusion rate of 10 mg/m2/min with concomitant low doses of IL2 could be useful in the palliative treatment of symptomatic patients with renal carcinoma progressing after tyrosine kinases inhibitor.

Current opinion in diagnosis and treatment of laryngeal carcinoma.

Laryngeal carcinoma is the 11th commonest form of cancer in men world-wide, with 121,000 new cases in 1985. More than 95% of all laryngeal malignancies are squamous cell carcinomas. Treatment indications in cancer of the larynx are often controversial, since there are few comparative studies of different available therapeutic approaches. Surgery and radiotherapy are both widely used, and the choice between these two procedures is the most common therapeutic decision which has to be taken. Laryngeal function preservation has gained more and more weight in the last decades and chemotherapy is also a significant component of several curative approaches. In the last decades, several organ-preserving surgical techniques have become available and consequently total laryngectomy results less applied. Regardless of the treatment modality, Tis, T1, T2 laryngeal carcinomas have an 80-90% probability of cure, whereas for more advanced tumours this is approximately 60%. The most effective approach to laryngeal cancer remains prevention and early diagnosis when this cancer is curable with function preserving treatments.

Effect of hemodialysis on the metabolic clearance of 5-Fluorouracil in a patient with end-stage renal failure.

A 64-year-old man on chronic hemodialysis for end-stage renal disease developed peritoneal carcinomatosis, and palliative chemotherapy with fluorouracil was started. The drug was administered (325 mg/m as IV bolus, at 2 PM) on 2 separate occasions, ie, 1 hour after dialysis and 2 days later, 49 hours after dialysis. The time course of the fluorouracil plasma concentration was determined, and the main pharmacokinetic parameters were calculated. The slope of the monoexponential decay of plasma concentration was significantly greater 1 hour (0.161 minutes) than 49 hours after dialysis (0.127 minutes), and plasma clearance was correspondingly higher (1.78 L/min versus 1.46 L/min). The volume of distribution did not change (11.1 L versus 11.5 L). Because fluorouracil is minimally excreted by the renal route (about 10% of the dose) and is almost entirely metabolized by dihydropyrimidine dehydrogenase (DPD), it is suggested that plasma factors that accumulate during the interdialytic period and are removed by dialysis may inhibit DPD activity and, consequently, fluorouracil metabolic clearance.