[Laparoscopic adrenalectomy. Lateral transabdominal tecnique "step by step" and analysis of 41 consecutive patients]. / Adrenalectomía laparoscópica. Técnica transabdominal lateral "paso a paso" y análisis de 41 pacientes consecutivos.

Since the initial report in 1992, laparoscopic adrenalectomy has proved substantial advantages over the conventional procedure in terms of decreased postoperative pain and hospital stay, allowing earlier return to normal activity. The technical details are in permanent evolution and the most widely accepted laparoscopic surgery for the adrenal gland is the transabdominal lateral approach. We hereby describe step by step the way we perform the lateral approach after 41 consecutive cases.

Adrenalectomía laparoscópica. Técnica transabdominal lateral “paso a paso” y análisis de 41 pacientes consecutivos / No disponible

Desde su descripción en 1992, la adrenalectomía laparoscópica ha demostrado ventajas sustanciales sobre la cirugía convencional en términos de dolor postoperatorio, estancia hospitalaria y retorno del paciente a su actividad sociolaboral cotidiana. Los detalles técnicos están en permanente evolución y el abordaje más aceptado en la actualidad es el transabdominal con el paciente en decúbito lateral. En esta revisión se describe paso a paso nuestro modo de realizar la técnica para hacerla más reproducible, a la luz de 41 casos intervenidos(AU)

Since the initial report in 1992, lapa-roscopic adrenalectomy has proved substantial advan-tages over the conventional procedure in terms of de-creased postoperative pain and hospital stay, allowing earlier return to normal activity. The technical details are in permanent evolution and the most widely accepted laparoscopic surgery for the adrenal gland is the transabdominal lateral approach. We hereby describe step by step the way we perform the lateral approach after 41 consecutive cases(AU)

Intrinsic defects explain altered proliferative responses of T lymphocytes and HVS-derived T-cell lines in gastric adenocarcinoma.

We have taken advantage of a recently described technique of transformation and immortalization of T lymphocytes using the lymphotropic Herpesvirus saimiri, to achieve long-lasting T-cell lines from gastric cancer patients and healthy volunteers. Blood samples were drawn and T lymphocytes were transformed. Once sustained growth was observed, lines were subjected to phenotypic and functional analyses, and the results compared with freshly isolated peripheral blood mononuclear cells. Cytofluorometric analysis revealed that CD3 and CD45 were found at lower proportion in primary cells from patients than from control individuals (54% vs 75%, p<0.001, 90% vs 96%, p<0.05, respectively), and in HVS-derived T-cell lines (90% vs 98%, p<0.05, 97% vs 100%, p<0.05, respectively). Proliferative analyses showed that primary isolated cells were unable to respond adequately to CD3-, CD2-, and PHA-mediated stimulation, as compared to controls. Similarly, T-cell lines from patients proliferated to a lesser extent when CD3- and CD2-mediated stimuli were considered, especially when simultaneous stimulation via CD3 and CD2 molecules was carried out (47,824 counts per minute [cpm] vs 121,478 cpm, p<0.05). Altogether these results show that the defects reported in T cells from patients with cancer are not exclusively due to tumour-derived factors, since the alterations persist in long-lasting, HVS-transformed, T-cell lines, suggesting that this model seems a suitable one to disclose them.

Preoperatively irradiated rectal carcinoma: analysis of the histopathologic response and predictive value of proliferating cell nuclear antigen immunostaining.

OBJECTIVES: To investigate the relationship between the histopathologic effects of preoperative chemoradiotherapy in rectal cancer and the proteins, proliferating cell nuclear antigen (PCNA) and p53. METHODS: Samples from 73 tumors were examined. The histopathologic effects observed in the resected specimens induced by preoperative chemoradiotherapy were correlated with the inmunohistochemical expression of PCNA and p53 in biopsies obtained by rectoscopy before chemoradiotherapy. RESULTS: Thirty-five tumors showed a high PCNA index (48%). Nuclear accumulation of p53 protein was detected in 53 tumors (72%). Specimens were assigned one of four grades based on the amount of residual viable tumor. Three neoplasms (4%) showed complete regression; 8 other carcinomas (11%) showed only small numbers of tumor cells scattered within the field of stromal reaction. In these cases, it was considered that the tumor had responded significantly to radiotherapy. Tumors with a high PCNA index responded to chemoradiotherapy more frequently (8/35; 72%) than tumors with a low index (3/38; 43%) (p = 0.07). p53-negative tumors responded more frequently (4/20; 20%) than positive tumors (7/53; 13.2%) (p = 0.50). When pathologic and immunohistochemical characteristics of the tumors were included in a logistic regression model, only high PCNA index (odds ratio 5.35, 95% confidence interval 1.07-26.7) (p = 0.04) was significantly associated with the histologic response to preoperative chemoradiotherapy. CONCLUSION: High proliferative activity of rectal cancer, as determined by PCNA immunostaining, is predictive of the response to preoperative chemoradiotherapy.

Adrenalectomía laparoscópica / Laparoscopic adrenalectomy

Los avances de la cirugía mínimamente invasiva han hecho posible extirpar órganos como la glándula suprarrenal por vía endoscópica. Desde su descripción en 1992 han sido publicados más de 1.000 casos demostrando la eficacia, seguridad y reproducibilidad de la técnica. La adrenalectomía laparoscópica ha demostrado ventajas sustanciales sobre la cirugía convencional en términos de dolor postoperatorio, estancia hospitalaria y retorno del paciente a su actividad sociolaboral cotidiana. Las indicaciones son esencialmente las mismas que las de la cirugía abierta, exceptuando grandes tumores mayores de 10 cm y la patología neoplásica maligna, cuyo abordaje laparoscópico todavía es controvertido. En esta revisión se describe la técnica quirúrgica más extendida, el abordaje transabdominal lateral. Aunque la cirugía abierta siga teniendo vigencia en casos concretos todo cirujano con interés por la patología suprarrenal debe dominar el abordaje laparoscópico. (AU)

Time-dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma.

BACKGROUND: This study examined the prognostic information regarding the risk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemical expression of p53 protein in tumor tissue from patients with colorectal carcinoma. METHODS: A retrospective study of 174 patients (AJCC/UICC Stages I, II and III) was conducted. Serum CEA levels were determined by an enzyme-linked immunoadsorbent assay. Immunohistochemical expression of nuclear p53 protein was assessed in formalin fixed, paraffin embedded archival tumor tissue. The results of both factors were categorized by clinical and histopathologic variables. The relative prognostic significance of all factors with regard to disease free survival was assessed by Cox proportional hazards regression analysis. The stability of the predictive value of both markers was assessed: 1) by splitting the follow-up into three intervals and performing separate analyses for each period and 2) graphically by plotting the corresponding cumulative hazards ratio along the follow-up. RESULTS: Eighty-two (47%) tumors manifested overexpression of p53 protein and 60 tumors (34.4%) exhibited elevated serum CEA levels (cutoff value of 5 ng/mL). p53 positive immunostaining and elevated CEA levels were associated with low cumulative disease free survival at 60 months' of follow-up, and proved to have independent prognostic significance. Analysis performed in different time periods of follow-up showed that the prognostic effect of both markers was not stable over time. The predictive significance of CEA and p53 changed along the study periods. An elevated preoperative CEA level was an indicator of a high risk of recurrence only during the first 2 years after surgery (hazards ratio, 3.26; 95% confidence interval 95% CI, 1.65-6.42). The presence of p53 immunoreactivity in the primary tumor was an indicator of a high risk of recurrence only after the first year of follow-up (hazards ratio, 4.02; 95% CI, 1.68-9.6). CONCLUSIONS: The serum CEA level and expression of p53 protein provide complementary prognostic information. Time-dependency of the prognostic influence of both parameters should be taken into consideration when establishing postoperative predictive estimations.

Influence of tumor localization on the prognostic value of P53 protein in colorectal adenocarcinomas.

BACKGROUND: The prevalence of genetic alterations is different in primary carcinomas from the proximal colon when compared with carcinomas from the distal colorectum. The objective of this work was to explore the existence of possible differences in the informative weight of the risk of tumor recurrence provided by p53 immunostaining depending on the localization of the neoplasm. PATIENTS AND METHODS: Nuclear immunohistochemical expression of p53 protein was determined in formalin-fixed paraffin-embedded archival tumor tissue samples from 190 primary colorectal adenocarcinomas. The relative prognostic importance on the risk of recurrence of each variable was assessed in a Cox's proportional hazard regression analysis. Multiplicative interaction terms between p53 and tumor site were included in the multivariate models in order to test their joint effect on survival. RESULTS: One hundred and one patients (53.1%) manifested nuclear accumulation of the protein. P53 overexpression was more frequent in distal than in proximal tumors (58.5% ve s 41.7%) (p = 0.03). Disease-free survival was lower in p53-positive cases (75% versus 38%) (p = 0.006), but significance of the association varied according to the localization of the tumor (p = 0.004 in proximal carcinomas and p = 0.049 in distal carcinomas). Multivariate analysis identified p53 positivity and distal tumor localization as the factors significantly associated with a high risk of recurrence Interaction between p53 expression and localization was present. P53 exhibited different prognostic value in distal and proximal colon. While adjusted hazard ratio for positive p53 was 1.99 in distal cancers, it was 8.04 for proximal tumors. CONCLUSION: The prognostic with value of tumor recurrence associated overexpression of p53 protein is influenced by the location of the tumor. The negative predictive weight is significantly higher in proximal than in distal cancers.

P53 protein expression in gastric adenocarcinoma. Negative predictor of survival after postoperative adjuvant chemotherapy.

BACKGROUND: The aim of the present study was to evaluate the influence of p53 protein on the survival of patients undergoing radical gastrectomy and postoperative adjuvant chemotherapy for gastric cancer. PATIENTS AND METHODS: It was a retrospective study of 46 patients with gastric adenocarcinoma (Stage II and III of the Japanese staging system). Alypatients were treated by curative radical gastrectomy with regional lymphadenectomy plus adjuvant chemotherapy. This regime included Mitomycin (20 mg one hour before surgery, followed by 10 mg the day after) and Fluorinated Pyrimidine (UFT) (400 mg/m2/day orally) (started four weeks after operation, and continued for one year). Immunohistochemical expression of p53 protein was determined on tumor samples from the removed specimens. The influence of p53 on survival was assessed in a Cox's proportional hazard regression analysis. RESULTS: Sixteen tumors (34.7%) manifested nuclear overexpression of p53 protein. Patients with p53-negative tumors showed higher cumulative survival at 4 years follow-up than patients with p53-positive tumors (82% versus 45%) (p < 0.01). Multivariate analysis identified p53 overexpression as a negative independent predictive factor (hazard ratio: 11.15) (95% CI: 1.93-64.42). Multivariate analysis performed on patients with Stage III tumors, separately, confirmed the predictive effect of p53 overexpression. CONCLUSION: The results suggest that postoperative adjuvant chemotherapy acted differently in p53-positive than in p53-negative gastric tumors. Absence of p53 overexpression is associated to longer survival when adjuvant therapy is administered.

Clinical, histopathological, cytogenetic and prognostic differences between mucinous and nonmucinous colorectal adenocarcinomas.

OBJECTIVE: To assess the clinical and biological significance of histological typing of colorectal carcinomas. PATIENTS AND METHODS: The retrospective analysis of 142 consecutive patients who underwent surgical resection of a mucinous (MC; n = 27; 19%) or a nonmucinous (nMC; n = 115; 81%) colorectal adenocarcinoma was carried out. The two groups were compared in terms of the clinical features, p53 gene expression (antiserum CM1), proliferating cell nuclear antigen (PCNA) labeling index, DNA ploidy (by flow cytometry), histopathological features, prognosis and recurrence rate. RESULTS: The two types of tumors differed with respect to patient age, location, morphology, pattern of genetic lesions and type of tumor recurrences. Twenty-five percent of the patients with MC and 9% of those with nMC (p = 0.04) were under 50 years of age. The incidences of right MC and left MC were similar, while the majority of the nMC were located on the left side (p = 0.04). The MC were of higher grade and their margins more infiltrative than those of the nMC (p = 0.001 and p = 0.01, respectively), p53 nuclear staining was observed less frequently in the MC than in the nMC (30% vs 55%; p = 0.03). The PCNA labeling index was higher in the nMC (46% vs 21%; p = 0.05). We observed no significant differences with respect to tumor stage, incidence of vascular invasion or prevalence of lymphocytic infiltration. The prognosis was similar in both groups, although their recurrence patterns differed, with a tendency toward locoregional recurrence in the cases of MC. CONCLUSION: These findings suggest that, despite their similar prognoses, these two types of lesions are epidemiologically, phenotypically and genotypically different and, thus, result from distinct carcinogenic pathways.

Histopathologic prognostic score in colorectal adenocarcinomas.

OBJECTIVE: To analyze the prognostic value of a set of pathological variables after curative resection for large bowel adenocarcinoma and to test a prognostic score derived from factors with independent effect. PATIENTS AND METHODS: The study is based on data from 292 consecutive unselected patients (B-C Astler-Coller stages). Histopathological features were evaluated prospectively on the resected primary tumors. Relationship between these factors and risk of recurrence was assessed by a Cox's proportional regression analysis. RESULTS: Four variables retained independent prognostic significance: extent of bowel wall invasion, peritumoral lymphocytic infiltration, number of positive nodes and vascular invasion. A prognostic score based on the regression coefficients attained by such variables was developed. This system revealed four prognostic groups. Group I included 14% of patients, with 94% 5-year disease-free survival. These figures were: 35% and 60% in group II; 43% and 46% in group III; and 7% and 24.4% in group IV. Histopathologic score applied to bearers of Astler-Coller B2 tumors permitted the identification of two populations, one characterized by a low risk of relapse and another with high risk (p = 0.002). CONCLUSION: A prognostic score based in the evaluation of four histopathologic parameters concerning the tumor phenotype enables the identification of groups of patients at risk of relapse after curative resection for colorectal adenocarcinoma.

Prognostic value of flow cytometric DNA analysis in non-small-cell lung cancer: rationale of sequential processing of frozen and paraffin-embedded tissue.

The objective of this study was to determine the prognostic information provided by flow cytometric DNA analysis in non-small-cell lung cancer. Lung samples of 132 consecutive patients submitted to surgery were prospectively processed. When no aneuploid populations were detected in fresh frozen samples, the process continued as a second step in paraffin-embedded tissue, consuming all the tumor available. The influence of ploidy on the postoperative outcome was studied by both a univariate and a multivariate analysis. Aneuploidy was found in 81 patients (61.4%). Fourteen patients showed no aneuploidy in fresh frozen samples; and only after further analysis in paraffin-embedded tissue was abnormal DNA detected. Overall, the 36-month survival was 69% for the diploid group and 24% for the aneuploid group (p = 0.0006). Including subjects submitted to complete tumor removal (stages I, II, and IIIA) in a multivariate analysis adjusted for TNM stage and histologic type, bearers of aneuploid tumors exhibited a higher risk of relapse (hazard ratio 2.65; CI 95% 1.5-4.66;p = 0.004) or death (hazard ratio 2.17; CI 95% 1.08-4.39;p = 0.032) than patients with diploid tumors. DNA ploidy resulted an independent prognostic factor of survival and tumor relapse in completely resected non-small-cell lung cancer. Sequential analysis of fresh and paraffin-embedded samples can help avoid the bias due to intratumoral DNA content heterogeneity. DNA ploidy could be an useful parameter in any future multifactorial analysis of outcome in such tumors.

[A comparative study on the prognostic value of the nuclear expression of protein p53 vis-à-vis histopathology in colorectal cancer]. / Estudio comparativo sobre el valor predictivo de la expresión nuclear de la proteína p53 frente a la histopatología en el cáncer colorrectal.

OBJECTIVE: To determine the predictive value of p53 nuclear overexpression in comparison with established prognostic pathological features in colorectal adenocarcinoma. PATIENTS AND METHODS: 61 patients operated on for cure between January 1989 an December 1991 were included. Expression of p53 protein was examined by immunohistochemistry in paraffin-embedded sections. Tumor localization, depth of bowel wall involvement, lymph nodes metastasis, vascular invasion and PCNA Labelling index were studied in all patients. RESULTS: Nuclear staining was detected in 27 (44.2%) cases. Positivity was more frequent in tumors with venous invasion and in rectal cancer. p53-positive tumours exhibited a higher likelihood of relapse and lower survival. After adjustment for the other covariates, p53 overexpression was the only factor showing independent prognostic significance on the risk of recurrence. None of the factors analysed evinced independent significant relationship with the risk of death. CONCLUSION: Nuclear p53 protein overexpression is closely related to the development of postoperative recurrences and has higher predictive value than standard pathological variables.

Prediction of recurrence in B-C stages of colorectal cancer by p53 nuclear overexpression in comparison with standard pathological features.

This study investigated the predictive value of p53 nuclear overexpression on recurrence of colorectal adenocarcinomas compared with established prognostic pathological features. Sixty-one paraffin-embedded sections from primary tumours were examined by immunohistochemistry. Specific nuclear staining was detected in 27 (44.2%) cases. Positivity was more frequent in tumours with venous invasion (76.9%) (P = 0.06) and in rectal cancer (68.4%) (P = 0.06). After a median observation time of 46 months, p53-positive tumours exhibited a higher percentage of recurrence (40.7% vs 11.7%) (P = 0.03), and a higher likelihood of relapse at 5-year follow-up (46% vs 13%) (P = 0.006). Among the pathological variables analysed, only the extent of bowel wall invasion showed a relationship with recurrence. After adjustment for the other covariates in a Cox's regression model, p53 overexpression was the only factor showing independent prognostic significance (hazard ratio: 4.96; 95% Confidence Interval (CI): 1.47-16.71) (P = 0.012). The results of this study show that nuclear p53 protein overexpression has higher predictive value than standard pathological variables.

Serum CEA, CA125, and SCC antigens and tumor recurrence in resectable non-small cell lung cancer.

Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CA125 were determined pre- and postoperatively in non-small cell lung cancer patients (NSCLC) to assess the relationship between serum levels and postoperative recurrent disease. Ninety-five patients who underwent curative surgical resection were included (TNM stages I, II, IIIa). CEA and CA125 were determined by solid-phase enzyme-immunoassay, SCC by radio-immunoassay. Tumor relapse was detected in 41 patients (43%): 16 (39%) with locoregional disease and 25 (61%) with disseminated disease. The overall 36-month disease-free survival rate was 42%. The sensitivity for recurrence was 58% for CEA, 53.6% for CA125, and 51.2% for SCC; 87.8% of patients showed at least one elevated marker. The sensitivity of CEA and CA125 increased significantly in patients with preoperative serum concentrations above the cut-off: 86.6% versus 42.3% (p < 0.01), and 93% versus 18% (p < 0.01), respectively. Preoperative CA125 above 15 U/ml identified a high-risk group of patients: a lower 36-month disease-free survival rate (0% versus 56%) (p < 0.001), a 3.02-fold higher risk of recurrence (p < 0.05), and a 6.22-fold higher risk of disseminated failure (p < 0.001). The identification of CEA and CA125 producer-tumors, based on preoperative serum values, enhances the clinical performance of a postoperative surveillance program in surgically treated NSCLC. Preoperative serum CA125 is a prognostic factor to identify patients at high risk of postoperative tumor recurrence.

[Epidermal growth factor receptor in non-small cell cancer of the lung]. / Receptor para el factor de crecimiento epidérmico en el cáncer de pulmón no microcítico.

In this study we determined the concentration of epidermic growth factor receptors (EGFr) in non-small cell carcinoma of the lung (NSCCL) and analyzed its relation to the anatomical, pathological and clinical factors of these neoplasms. The concentration of EGFr in 62 tumor tissue samples was 9.9 +/- 14 fmol/mg, higher than that found in 14 tissue samples from cases of spontaneous pneumothorax (3.9 +/- 3.6 fmol/mg) (p = 0.005). EGFr concentration in lung tissue with no signs of neoplasm was 6.5 +/- 10 fmol/mg. In 21 (33%) cases of NSCCL the concentration exceeded the normal threshold of 10 fmol/mg. EGFr concentration was higher in cases of epidermoid carcinoma than in other tissue samples (p = 0.042). No significant association was found between EGFr levels and status of tumor node metastasis, degree of differentiation and mitotic index. The probability of remaining free of tumor recurrence and of survival after 24 months among patients whose tumoral EGFr concentration was below 10 fmol/mg was 34 and 40%, respectively. The rates for patients with concentrations that exceeded the threshold were 20% (p = 0.32) and 25% (p = 0.26), respectively. The results seem to indicate that the study of EGFr concentration alone does not yield practically important information for the management of patients with NSCCL who have undergone surgery. The concentration of EGFr marks degree of differentiation in NSCCL and has prognostic implications derived from its association with other factors.

Quantitative analysis of carcinoembryonic antigen, squamous cell carcinoma antigen, CA 125, and CA 50 cytosolic content in non-small cell lung cancer.

BACKGROUND: The cytosolic content of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC), CA 125, and CA 50 antigens in non-small cell lung cancer (NSCLC) is analyzed in this study. The aim was to ascertain the relationship between tumor marker content and the clinicopathologic aspects of this neoplasm. METHODS: Lung tissue samples were obtained at the time of surgery from 75 patients with NSCLC patients (samples of tumor and unaffected tissue) and 29 subjects with idiopathic pneumothorax. All determinations were performed on cytosols obtained from lung specimens. CEA and CA 125 were determined by enzyme immunoassay, SCC antigen by radioimmunoassay, and CA 50 by fluoroimmunoassay. Tumor marker content was analyzed by TNM stage, histologic type, tumor grade, and number of atypias. RESULTS: The concentration of the four markers was significantly higher in cytosol obtained from neoplastic tissue. Frequency of elevated levels of CEA was higher in adenocarcinoma (87% cases expressing high levels of the marker), SCC antigen in epidermoid carcinoma (65% expressing high levels), and CA 125 in large cell carcinomas (100% expressing high levels). No association was found between TNM stage and cytosol concentration for any of the four markers. CEA exhibited significantly greater concentration in well differentiated tumors, whereas this was true of CA 125 in poorly differentiated tumors. CA 125 content was higher in tumors with more atypia. CONCLUSIONS: Cytosolic quantification of tumor markers may be an adjuvant mechanism to evaluate histologic subtypes of non-small cell lung cancer and identification of tumors with poorly differentiated features.