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J Astudillo

Publications and source records attributed to J Astudillo.

17 recordsLinked to original sources
PubMed2001

The role of chemotherapy in early non-small-cell lung cancer management.

Great advances have been made in chemotherapy in advanced and metastatic non-small-cell lung cancer (NSCLC), and a major milestone was reached with the administration of neoadjuvant chemotherapy in stage IIIA N2 disease. The systemic nature of lung cancer has been confirmed by many genetic analyses documenting micrometastases in negative lymph nodes and bone marrow, and mRNA gene overexpression as a surrogate of cancer cells has been identified in peripheral blood. Furthermore, serum or plasma cell-free tumor DNA has been observed even in tumors with a diameter of less than 2 cm. Pharmacogenetic screening can lead to tailored chemotherapy even in patients with early disease through the use of a genetic tool kit that will allow us to optimize the use of chemotherapy by using serial measurements of serum DNA that can help to detect residual disease and re-assess the chemosensitivity of sub-clinical micrometastatic disease. The ongoing (neo)adjuvant taxol/carboplatin hope (NATCH) trial is testing the value of three cycles of chemotherapy given pre- or post-operatively compared with surgery alone and will analyze genetic abnormalities in serum DNA at three different points during patient follow-up. Our major concern in this review is to analyze the pros and cons of chemotherapy in NSCLC. Although this review is not a formal meta-analysis, we have discussed the most relevant published studies in this field. We conclude that not only is there no evidence of detrimental effects of chemotherapy, in fact, there are many indications that chemotherapy induces response in up to 80% of patients and downgrades N2 disease in up to 50% of patients. This translates into significantly better survival when accompanied by complete resection. Since at least 50% of patients with stage IB disease develop distant metastases, it seems logical to explore the role of chemotherapy in early disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Preoperative high-dose cisplatin versus moderate-dose cisplatin combined with ifosfamide and mitomycin in stage IIIA (N2) non small-cell lung cancer: results of a randomized multicenter trial.

Preoperative chemotherapy has become an accepted treatment for stage IIIA (N2) non small-cell lung cancer (NSCLC). The majority of induction regimens employ cisplatin, although the importance of cis-platin dose in combination is unclear. A randomized trial was conducted to address whether higher pre-operative cisplatin doses result in improved survival and increased pathologic complete response in NSCLC. Patients with stage IIIA clinically enlarged and biopsy-proven N2 lesions were randomly assigned to receive either high-dose cisplatin (HDCP) (100 mg/m2) or moderate-dose cisplatin (MDCP) (50 mg/ m2) in combination with ifosfamide (3 g/m2) and mitomycin (6 mg/m2). Disease was restaged after 3 cycles, and those patients with response or stable disease underwent thoracotomy. From March 1993 to February 1997, 83 patients were randomized: 46 received HDCP, and 37 received MDCP. Clinical characteristics were well matched. Radiographic response rate was 59% for HDCP patients and 30% for MDCP patients (P = 0.01). Thoracotomy was performed in 71 patients (86%), 58 of whom had resectable disease. Complete resection rate was 61% in the HDCP group, and 51% in the MDCP group (P = 0.5). Postoperative mortality was 11%. Pathologic complete response was observed in one patient who received MDCP. Median survival in the HDCP and MDCP groups was 13 and 11 months, respectively (P = 0.3). In conclusion, higher radiographic response rate is observed in patients who receive HDCP, but this study fails to show any significant improvement in either overall survival or pathologic complete response in this group of patients.

Clinical Trial↗
PubMed1999

A novel anti-apoptosis gene: Re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers.

PURPOSE: The survivin gene is a novel apoptosis inhibitor, related to the baculovirus gene, which is believed to play a pivotal role in fetal development and in cancer. We hypothesised that survivin would be expressed in tumors of patients with non-small-cell lung cancer (NSCLC), and we attempted to determine the influence of survivin re-expression on clinical outcome in patients with up to stage IIIA NSCLC who had undergone radical surgery. METHODS: We designed a reverse transcriptase polymerase chain reaction (RT-PCR) assay to study the expression of the survivin gene in 83 NSCLC tumor samples and compared the results with relevant clinical and pathologic data. RESULTS: The RT-PCR identified survivin gene transcript in 71 (85. 5%) of the tumor samples and in only 10 (12%) of the paired, histopathologically normal lung samples. There was no relationship between histologic subtype (squamous v nonsquamous) and survivin gene expression. The 12 patients without survivin expression had significantly better overall survival than the 71 patients with survivin expression (P =.01 by univariate analysis; relative risk, 2. 1). There was no significant correlation between survivin expression and age, sex, cigarette smoking, histologic subtype, tumor differentiation, tumor size, or the presence of mediastinal lymph node metastases in surgical specimens. CONCLUSION: The survivin gene was expressed in a vast majority of NSCLC tumors. We conclude that survivin transcript is a defining diagnostic marker for NSCLC that may also yield prognostic information and, as an apoptosis inhibitor, be an important target in cancer therapy.

Adult↗
PubMed1998

Detection of chromosome 3p alterations in serum DNA of non-small-cell lung cancer patients.

BACKGROUND: The generally dismal outcome of non-small-cell lung cancer (NSCLC) is believed to be associated with the systemic nature of this disease. In current practice, the decision to begin adjuvant chemotherapy in completely resected early stages is based on empirical criteria and has not yet been influenced by the presence of individual risk factors. Nonetheless, recent studies indicate that soluble tumor DNA is found in the serum and plasma of cancer patients, and microsatellite alterations have been identified in small-cell lung cancer and in head and neck neoplasms. PATIENTS AND METHODS: We have investigated serum DNA from 22 completely resected stage I-IIIA NSCLC patients using a polymerase chain reaction microsatellite analysis with four microsatellite markers at chromosome 3p (D3S1038, D3S1611, D3S1067 and D3S1284). RESULTS: Our analyses showed serum tumor DNA in 6 of 22 (28%) cases, with microsatellite alterations, either as a shift (changes in the size of the microsatellite sequence in the autoradiograph) or as a loss of heterozygosity (LOH). LOH in both tumor and serum DNA at one or more microsatellite markers was found in four patients. Although it is still premature to look for prognostic implications, one patient with stage I serum DNA was identified prior to the development of distant metastases. CONCLUSIONS: The findings suggest that detection of free circulating DNA in sera of NSCLC patients is incidentally linked to the systemic nature of lung cancer even at the earliest stage. These observations provide the first hint that serum tumor DNA is present in NSCLC patients. The detection of DNA from cancer cells in the sera of NSCLC patients could be useful for monitoring relapse in a relatively non-invasive way, and the potential sensitivity of this test may help in selecting candidates for adjuvant chemotherapy.

Adult↗
PubMed1997

Reduced survival in patients with stage-I non-small-cell lung cancer associated with DNA-replication errors.

To better understand whether replication-error-type instability (RER+) is a frequent genetic alteration event in surgical-pathologic stage-I non-small-cell lung cancer (NSCLC) and identify whether it constitutes an independent prognostic parameter, we examined 35 surgical-pathologic stage-I-NSCLC patients with complete follow-up in all cases for at least 49 months. The tumor samples and the paired histopathologically normal lung samples for each patient were analyzed for 8 microsatellite markers located at chromosomes 3p and 2p to investigate microsatellite alterations such as RER+ and loss of heterozygosity (LOH). Single-strand-conformation-polymorphism analysis for detection of p53 and k-ras gene mutations was also carried out. Genetic data were correlated with clinical outcome and histopathologically established prognostic factors. RER+ at one or both chromosomes was identified in 24 of the 35 patients; 9 patients showed LOH. A statistically significant correlation was found between RER+ and poor prognosis (p = 0.001). Furthermore, RER+ proved to be an independent factor that predicted decreased survival, ranking first, followed by visceral pleural invasion. A trend towards worse survival was strongest in the group of patients with tumor size greater than 3 cm (T2). Patients with other genetic abnormalities, such as K-ras mutations, p53 mutations or LOH, had prognoses similar to those of patients without such aberrations. The data suggest that RER+ is common in NSCLC, that it may provide important prognostic information in stage-I NSCLC and serve as a useful marker for relapse-risk assessment in operable NSCLC patients.

Adenocarcinoma↗
PubMed1997

Preoperative chemotherapy for stage IIIA non-small cell lung cancer.

Recent studies have shown that preoperative chemotherapy is feasible and advisable for patients with stage IIIA mediastinoscopically confirmed N2 involvement in non-small cell lung cancer. Such studies confirm the crucial pillar of attaining complete resection, and the importance of downstaging N2 disease as a useful surrogate for long-term survival. Resectability rate is about 70% in almost all studies examined. Better means of predicting resectability and relapse are addressed, such as the potential role of positron emission tomography and some hints for the management of replication error-positive non-small cell lung cancer patients. A major issue for the role of preoperative chemotherapy is how not to confuse apples and oranges. Although the role of surgery alone or radiotherapy is considered suboptimal for treatment of stage IIIA N2, whether surgery is required remains to be clarified. Furthermore, large randomized studies of chemoradiation followed by surgery versus chemoradiation alone are needed as well as modification of the current tumor, node, metastasis classification in order to better select those patients for whom preoperative chemotherapy would be beneficial. The surgeon's judgment and skill are essential in the identification of eligible patients and multimodality treatment research is also spreading toward early disease and some subsets of T4 non-small cell lung cancers.

Biomarkers↗
PubMed1994

[Hysteroscopic study in patients with abnormal uterine bleeding].

The experience of hysteroscopy performed in our Service in Abnormal Uterine Bleeding (AUB) is presented in order to show the utility of this procedure as a diagnostic method and compare these results with Dilatation and Curettage (DC). Eighty five patients underwent diagnostic hysteroscopy procedure, followed by DC; 54 were postmenopausal (63.6%) and 31 were premenopausal (36.4%). The distention media used was liquid. In 47 patients (55.2%) the hysteroscopic diagnostic was normal or atrophic endometrium, in 16 patients (18.8%) was hyperplasia, in 17 patients (20%) was endometrial polyp, 4 cases (4.7%) were described as cancer and in 1 case (1.3%) the diagnostic was bone metaplasia. We compared the results with the histology of DC obtaining a correlation of 93%. These results confirm the high accuracy of this procedure as a diagnostic method in uterine bleeding regarding its specificity and sensibility.

Adult↗
PubMed1993

Prognostic significance of metastases to mediastinal lymph node levels in resected non-small cell lung carcinoma.

BACKGROUND: The prognosis of patients who have non-small cell lung carcinoma (NSCLC) with mediastinal lymph node metastases remains a controversial issue. This study was performed to evaluate survival by level of mediastinal lymph node metastasis and the number of mediastinal levels involved. METHODS: The authors retrospectively reviewed the cases of 113 patients with NSCLC and pathologic mediastinal lymph node involvement who underwent a complete tumor resection and ipsilateral mediastinal lymphadenectomy. RESULTS: Most patients presented with involvement of only one mediastinal lymph node level (68.2%). The overall survival rate was 17% at 3 years. No differences in survival were observed in relation to which lymph node level was involved (P = 0.667). Differences in survival based on the number of lymph node levels involved were statistically significant (P = 0.001). CONCLUSIONS: Although there were no differences in survival when only one of any of the three defined levels was involved, metastasis to more than one level was associated with significantly poorer survival.

Adenocarcinoma↗
PubMed1993

[Unilateral lung transplantation: the first 2 cases. Group of Lung Transplantation of the University General Hospital of the Vall d'Hebron].

Since 1983 unilateral lung transplantation has become a clinical reality. The initial experience of the Hospital General Universitario de la Vall d'Hebron is presented with the description of the two first unipulmonary transplants. The first was a 20 year-old woman with idiopathic pulmonary fibrosis in whom a left unipulmonary transplant was carried out and who, at present is at home following the 23rd postoperative month. The second case was a 27 year-old man with pneumoconiosis who, at 12 months following the left lung transplantation, carries on a normal life. Among the complications observed, the presence of pneumonitis by cytomegalovirus in both patients is of note. Stenosis and partial dehiscence of the bronchial suture in the first patient and isolation of syncitial respiratory virus in the second patient were also observed. The effort and integration into a normal life style of the second patient is excellent. In contrast, the first patient presents an important postoperative functional deterioration secondary to her complications. The present study demonstrates that unipulmonary transplantations is a reality in Spain which must be considered by all respiratory disease specialists in their daily clinical practise.

Adult↗
PubMed1992

Effect of zinc on human sperm motility and the acrosome reaction.

This study has assessed the effect of zinc on human sperm motility and the acrosome reaction in vitro. Progressively motile human sperm were selected by swim-up and by glass bead columns and then incubated in a medium in which capacitation happened in an asynchronous way. Different doses of zinc (1, 10, 100 and 1000 microM) were added for periods of 2, 4 or 6 h. Other samples were incubated with zinc (1000 microM), and after 1 h incubation, the zinc was removed. Aliquots of each culture were used to evaluate progressive motility and the acrosome reaction using a triple-stain technique. Sperm motility was reduced when the amount of zinc added was greater than or equal to 100 microM, and these doses also caused a significant reduction in the % of sperm undergoing the acrosome reaction. After removal of zinc and further incubation in zinc-free medium for 1 h, an increase in the percentage of motile and acrosome-reacted sperm was observed. However, the increase in acrosome reaction did not reach the values observed in controls. Results suggest that extracellular zinc acts as an inhibitor of human sperm motility and the acrosome reaction (and/or capacitation and the acrosome reaction). This inhibitory effect is reversible and occurs in a dose-dependent fashion. The probable mechanisms involved are discussed.

Acrosome↗
PubMed1991

[Vibration and acoustic stimulation during labor with external monitoring. Pathology of fetal heart rate].

Vibratory acoustic stimulation was done in patients with an abnormal fetal heart rate tracing in external continuous electronic monitoring during labor, correlating with Apgar score, meconium staining and umbilical cord pH, describing a 83.3% sensitivity, 81.3% specificity and 62.5% positive predictive value. The authors recommend the use of vibratory acoustic stimulation in those cases with an abnormal fetal heart rate tracing in external continuous electronic monitoring, when we can not install internal electronic monitoring or obtain a fetal blood pH on assessment of fetal well-being.

Acoustic Stimulation↗
PubMed1990

Role of postoperative radiation therapy in stage IIIa non-small cell lung cancer.

One hundred forty-six patients with pathological stage IIIa non-small cell lung cancer were retrospectively analyzed to determine whether postoperative radiation therapy improves survival and reduces locoregional recurrences. The survival rate of the overall group at 1, 3, and 5 years was 56%, 24%, and 17%, respectively. Regarding the type of resection and histology, we did not observe statistically significant differences. Patients with N0 and N1 disease were grouped and compared with the N2 group, and survival at 3 and 5 years was 41% and 27%, respectively, for the T3 N0-1 group and 17% and 15%, respectively, for the T3 N2 group (p less than 0.001 and p = 0.05, respectively). Eighty-six patients received postoperative irradiation (45 to 50 Gy) and 60 did not. We have not observed any improvement in survival with postoperative radiation therapy, except in those patients with N2 disease. Median survival time was 6 months for patients without irradiation and 15 months for those with irradiation (p = 0.071). According to locoregional recurrences, a slight benefit with postoperative radiation therapy was observed.

Carcinoma, Non-Small-Cell Lung↗
PubMed1989

Thyroid function in neonates from goitrous and nongoitrous iodine-sufficient areas.

We compared thyroid function between newborns from goitrous and nongoitrous localities in which iodine intake has been supplemented since 1955. Cord serum samples were analyzed in 185 infants born during a 9-month period (1986-1987) in 2 goitrous and 1 nongoitrous localities of western Colombia. Urinary iodine was determined in all mothers before delivery. No significant differences were found among neonates of the 3 localities (Kruskal-Wallis test) for the various thyroid hormone values, and all values were within the normal range, although there was a trend in distribution of TSH to higher values in both goiter areas. Thyroid autoantibodies (antithyroglobulin and antithyroid microsomal) were negative in all neonates, and iodine intake, as indicated by urinary iodine, was adequate and similar among the mothers of the 3 groups. Those newborn infants with serum TSH values higher than 20 mU/L were reexamined 5-7 months later. At this time, all infants had lower serum TSH values and their serum free T4 index and T3 values were normal. Gestational age, weight, and height at birth were normal and also equal among the neonates in the 3 localities. These results indicate that neonates from goitrous iodine-sufficient areas have thyroid function similar to that of infants born in nongoitrous areas equally supplemented with iodine, and therefore, they are not more at risk to develop congenital hypothyroidism.

Colombia↗