Abnormal expression of MDM2 in prostate carcinoma.

Mutation of p53 is rare in localized prostate carcinoma. The oncoprotein MDM2, whose gene has a response element for p53, promotes the degradation of p53 protein and inhibits its transcriptional activation of genes related to cell cycle arrest and apoptosis, constituting a negative feedback control. We studied p53 and MDM2 expression by immunohistochemistry and looked for mutations in p53 exons 5 to 8 by polymerase chain reaction-single strand conformational polymorphism in 118 patients submitted to radical prostatectomy for localized prostate cancer. In 28 cases, we studied cell proliferation by immunohistochemistry, using antibody for Ki-67, and apoptosis by the deoxynucleotidyl transferase mediated dUTP biotin nick end labeling technique. Although no p53 mutations were found, p53 protein was detected in 31.4% of the cases, and these cases had higher Gleason scores (P = .03) and more advanced tumor stages (P = .02). MDM2 was overexpressed in 40.7% of the cases, and these cases had greater tumor volumes (P = .001). Tumors that were positive for both p53 and MDM2 were larger (P = .003) and of more advanced stage (P = .03). Within the 28-case subset, the proliferative index was higher among MDM2-positive tumors (P = .046), and the apoptotic index was lower among p53-positive tumors (P = .01). We conclude that, although p53 mutation is a rare event in prostate carcinogenesis, the detection of p53 protein by immunohistochemistry is common and is associated with decreased apoptosis and increased histologic grade and tumor stage. We also conclude that the overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume. Finally, we propose that the MDM2-positive/p53-positive phenotype identifies prostate cancers with aggressive behavior.

Presence of apolipoprotein E epsilon4 allele in cerebral palsy.

The apolipoprotein E gene, which is located on chromosome 19, has three alleles (epsilon2, epsilon3, and epsilon4). Several recent publications associate the presence of the apolipoprotein E epsilon4 allele with the occurrence of neurologic diseases, and consider it a risk factor for the development of central nervous system affections. A group of 40 patients with cerebral palsy was studied and compared to a control group of 40 subjects, and higher occurrence of the allele epsilon4 in the group of subjects with cerebral palsy was observed. A significantly higher risk of developing cerebral palsy was demonstrated among those subjects with the apolipoprotein E epsilon4 allele.

Prevention of neoplastic port site implants in laparoscopy: an experimental study.

Enthusiasm about the application of videolaparoscopy to oncologic diseases has been limited by the growing number of port site implants. Adult Wistar rats were submitted to 6-7 mm Hg carbonic gas pneumoperitoneum. Rats were randomly divided into two groups: group I rats with tumor (200,000 viable cells of Walker tumor) and group 11 rats with no tumor. The pneumoperitoneum was deflated after 30 min. Group I was further randomized into five groups: no treatment; or abdominal irrigation with saline, heparin, chemotherapy (doxorubicin), or chemotherapy associated with heparin. After a period lasting no more than 18 days, the abdominal wall and intraperitoneal organs macroscopically affected were studied histologically. Chemotherapy groups had no port site implants and were significantly different (p < 0.05) than the no treatment, saline, and heparin solution groups, which had incisional implants at frequencies of 100%, 85.7%, and 82.5%, respectively. Intraperitoneal irrigation with chemotherapy solution was effective in preventing incisional implants in this animal model.

Genetic damage in exfoliated cells of the uterine cervix. Association and interaction between cigarette smoking and progression to malignant transformation?

OBJECTIVE: To determine, through the micronucleus (MN) test, the cytogenetic effects of cigarette smoking on exfoliated cells from the uterine cervix in women with normal smears and women with inflammatory atypia, squamous intraepithelial lesion (SIL) (cervical intraepithelial neoplasia [CIN] 1-3) and cervical cancer. STUDY DESIGN: The study group consisted of 200 women divided into three subgroups: group 1 (n = 116), women periodically undergoing cervical cytology and residents of Salvador-Bahia; group II (n = 57), women residing in São Paulo and previously selected because of a possible cytopathologic test positive for such conditions as human papillomavirus infections or malignant or premalignant cervical lesions (CIN 1-3); group III (n = 27), inmates of the Tatuapé Penal Institution, São Paulo. All the women underwent cytologic and colposcopic examination, and biopsies were performed on 68 of them. RESULTS: Considering the samples as a whole and using the chi(2) test for rare events, the number of MNs in smokers was significantly greater than in nonsmokers. It was also greater in women with larger exposure to smoking. The occurrence of MN was significantly lower in women with normal smears (smokers and nonsmokers) than in those showing any kind of pathologic alteration. In nonsmokers the occurrence of MN was similar between those with inflammatory atypia (IA) or low grade (L) SIL (CIN 1) and significantly higher in women with more severe lesions or high grade (H) SIL (CIN 2 and 3). Smokers with LSIL (CIN 1) showed a higher number of MNs than nonsmokers with a comparable diagnosis and smokers with IA. No differences were observed when compared with smokers with HSIL (CIN 2 and 3). MN occurrence was not associated with other risk factors for SIL or cancer development, such as age at first coitus, number of sexual partners, multiparity and use of hormonal contraceptives. CONCLUSION: These results suggest that the mutagenic effect of cigarette smoking occurs in cervical cells and that the progression of SIL is associated with increased frequency of chromosomal damage. Moreover, the data suggest that cigarette smoking introduces an additional risk to the progression of low grade LSIL (CIN 1). MN testing would be helpful in monitoring smokers with this kind of lesion.

PIP: Previous studies have shown that cigarette smoking increases the risk of developing squamous intraepithelial lesion (SIL) and cervical cancer. The present study used the micronucleus test to assess the cytogenic effects of smoking on exfoliated cells from 3 subgroups of Brazilian women: group 1 (n = 116), women periodically undergoing cervical cytology; group 2 (n = 57), women with a possibly positive cytologic test for human papillomavirus or malignant or premalignant cervical intraepithelial neoplasia (CIN 1-3); and group 3 (n = 27), inmates of the Tatuape Penal Institute. Overall, micronucleus frequency was significantly greater in smokers than in nonsmokers. The occurrence of micronuclei was significantly lower in women with normal smears (regardless of smoking status) than in women with any evidence of pathologic alterations. In nonsmokers, micronucleus frequency was similar in women with inflammatory atypia or low-grade CIN and significantly higher in women with more severe lesions and CIN 2-3. Smokers with CIN 1 had more micronuclei than nonsmokers with a comparable diagnosis and smokers with inflammatory atypia. No differences were observed in comparisons with smokers with CIN 2-3. Micronucleus occurrence was not associated with age at first coitus, number of sexual partners, multiparity, or use of hormonal contraception. These findings suggest that the mutagenic effect of smoking occurs in cervical cells and that SIL progression is associated with an increased frequency of chromosomal damage. The data further suggest that smoking adds to the risk of progression of low-grade SIL (CIN 1). Micronucleus testing, along with the cervical cytologic smear, is recommended to monitor smokers with this type of lesion.

Hemodynamic and metabolic effects of CO2 pneumoperitoneum in an experimental model of hemorrhagic shock due to retroperitoneal hematoma.

BACKGROUND: Diagnostic laparoscopy has been used in abdominal trauma patients, although its role is not well defined. The safety of laparoscopic evaluation in trauma patients with severe intraabdominal hemorrhage has not yet been analyzed. The purpose of this study is to evaluate the hemodynamic and metabolic effects of CO2 pneumoperitoneum (COI) in hemorrhaged animals through a retroperitoneal hematoma (RH). METHODS: Twenty-two 15-20-kg mongrel dogs were monitored for systemic and pulmonary hemodynamics, inferior vena cava pressure, and arterial blood gases. After 1 h of baseline, all animals were submitted to a RH. After 45 min the dogs were randomized into two groups. Control (CTR): dogs were submitted only to a RH; pneumoperitoneum (PN): dogs were submitted to a RH and 45 min later they were insufflated to an intraabdominal pressure of 10 mmHg with medical-grade CO2 gas for 30 min. Echocardiography was performed, only in PN animals, at baseline, 45 and 60 min after RH. RESULTS: RH induced a shock condition with low, sustained levels of arterial pressure, cardiac index, left ventricular stroke index, base excess, and oxygen delivery which were further depressed following COI. Three deaths occurred in the PN group, all of them toward the end of COI. During COI, hypercapnia was observed in one animal. COI did not impair systolic function or ejection fraction. CONCLUSIONS: COI with an IAP of 10 mmHg may be deleterious in animals with hemorrhagic shock due to an intraabdominal lesion. These findings could be clinically significant in abdominal trauma patients.

Hyperthermia increases the metastatic potential of murine melanoma.

Hyperthermia, either alone or combined with radio-, immuno- or chemotherapy, can control tumor growth, but its effect on metastasis is still controversial. In the present study, we investigated the influence of hyperthermia on the metastatic potential of B16-F10 murine melanoma cells. Incubation of melanoma cells at 43 degrees C for 30 min led to a significant decrease in cell viability. About half of the cells survived the acute exposure to heat. These thermoresistant cells displayed a longer lag phase as compared to control unheated B16-F10 melanoma cells. Other parameters of cell growth such as doubling time and saturation density were equivalent in both control and thermoresistant cells. Both control and treated cells were adherent, but thermoresistant cells failed to spread during the first 48 h after heat exposure. B16-F10 cells colonize the lungs of C57BL/6J mice when injected intravenously; the number of lung colonies is a measure of the metastatic potential of injected cells. Median values of 22, 10.5 and 31 colonies per injected mouse were observed for control cells, cells heated to 43 degrees C for 30 min and thermoresistant cells, respectively, with statistically significant differences between groups (Mann-Whitney test, P < 0.02). Thus, despite its cytotoxic action, heat exposure induced the acquisition of a more metastatic phenotype in a subpopulation of B16-F10 cells.

Hyperthermia increases the metastatic potential of murine melanoma

Hyperthemia, either alone or combined with radio-, immuno- or chemotherapy, can control tumor growth, but its effect on metastasis is still controversial. In the present study, we investigated the influence of hyperthermia on the metastatic potential of B16-F10 murine melanoma cells. Incubation of melanoma cells at 43 degrees Celsius for 30 min led to a significant decrease in cell viability. About half of the cells survived the acute exposure to heat. These thermoresistant cells displayed a longer lag phase as compared to control unheated B16-F10 melanoma cells. Other parameters of cell growth such as doubling time and saturation density were equivalent in both control and thermoresistant cells. Both control and treated cells were adherent, but thermoresistant cells failed to spread during the first 48 h after heat exposure. B16-F10 cells colonize the lungs of C57BL/6J mice when injected intravenously; the number of lung colonies is a measure of the metastatic potential of injected cells. Median values of 22, 10.5 and 31 colonies per injected mouse were observed for control cells, cells heated to 43 degrees Celsius for 30 min and thermoresistant cells, respectively, with statistically significant differences between groups (Mann-Whitney test, P<0.02). Thus, despite its cytotoxic action, heat exposure induced the acquisition of a more metastatic phenotype in a subpopulation of B16-F10 cells.

Gastro-esophageal isoperistaltic bypass in the palliation of irresectable thoracic esophageal cancer.

METHODS: The authors retrospectively review 22 patients with irresectable esophageal cancer in whom an isoperistaltic substernal gastric esophagogastric bypass was performed. RESULTS: After the operation eighteen patients (82%) regained normal swallowing. Seven patients developed anastomotic stenosis that was successfully treated in six by surgery or endoscopic dilatation. Two patients evolved with cervical fistulae until their death. As a whole, there was a statistically significant improvement in swallowing capability (p = 0.0352). Seventeen patients (77%) had postoperative complications, the most common being cervical fistulae (in 13.59%), pneumonia (in 10.45%) and anastomotic stenosis (in 7.32%). Postoperative morbidity was significantly associated with preoperative diseases and ASA class III (p < 0.05). There were three postoperative deaths (14%). Postoperative mortality was significantly related to severe malnutrition and preoperative associated disease (p < 0.05). CONCLUSIONS: The conclusion is that the procedure has acceptable morbidity and mortality for the population under consideration, permitting palliation of dysphagia in the majority of cases.

[Multicentric myxoid, metachronous and synchronous and multifocal liposarcoma: report of a case]. / Lipossarcomas mixoides multicêntricos e multifocais sincrônicos e metacrônicos: relato de caso.

A case of a male patient, 66 years old, who exhibited in a period of six years many multicentric and multifocal synchronic and metachronic myxoid liposarcomas is reported. The authors made a revision of cytogenetics and DNA alterations recently identified in this type of tumor. The chromosomic alterations are represented by the translocation t(12;16) (q13;p11) and trisomy of the chromosome 8. The genic analysis revealed the presence of altered restriction fragments due to highly specific and reproducible methylation differences. In conclusion the authors suggest that the presence of the multiple tumors of this type in the same patient could be due to a common etiologic factor, not yet known, as being the initiator of this systemic illness of the fat tissue.

[Gastric epithelioid leiomyosarcoma simulating pancreatic pseudocyst. Report of a case and review of the literature]. / Leiomiossarcoma epitelióide gástrico simulando pseudocisto de pâncreas. Relato de um caso e revisão da literatura.

The authors report a case of malignant gastric leiomyoblastoma (epithelioid leiomyosarcoma) which was mistaken for a pseudocyst of the pancreas. The patient was operated several times in another hospital. At one of the operations a cystogastrostomy was performed. In november, 1989, when operated again by us, a large tumoral mass arising from the posterior gastric wall was found. The histopathological diagnosis was leiomyoblastoma of the stomach. It is concluded that the wall of a pancreatic cystic lesion should always be submitted to histologic examination in order to be excluded the possibility of a malignant neoplasm.

Identification of the external branch of the superior laryngeal nerve during thyroidectomy.

Seventy-six patients underwent preoperative vocal evaluation and were randomized into 3 groups: (1) those with the superior thyroid pole dissected by the first author, with the external branch of the superior laryngeal nerve (EBSLN) identified by means of a nerve stimulator; (2) those patients whose dissection was executed by a resident, with no nerve search; and (3) those whose dissection was undertaken by the first author, without any nerve search. Postoperative analysis consisted of voice evaluation and electromyography of the cricothyroid muscle. No lesion occurred in patients in group 1. Twenty-eight percent of patients in group 2 and 12% in group 3 experienced a complete lesion of the EBSLN (p = 0.0123). When the patients in group 1 were compared with the patients with 62 nerves corresponding to nonoperated thyroid lobes, patients in group 1 exhibited no increased risk, whereas a significantly increased hazard was evident in both groups 2 (p = 0.0002776) and 3 (p = 0.0346393). In this study, effective prevention of iatrogenic EBSLN lesions during thyroidectomies was achieved only by the intraoperative identification of the nerve with the nerve stimulator.

Situação de trabalho de médicos egressos de programas de residência médica no Estado de São Paulo / Work situation of physicians graduating from medical residency programs in the State of São Paulo, Brazil

The authors report on a study conducted to analyze the professional situation of physicians residing in the State of São Paulo, Brazil, five years after completion of a medical residency program. At least 50 of the professionals were interviewed in each specialty. A heavy work load was observed in physicians working both in the metropolitan area of the State capital and in other regions of the State. Male doctors had a higher income than female ones. The latter, however, had a higher proportion working in a single specialty, although 16.8 did not practice in the specialty in which they were trained. The most frequent working environment was a hospital, followed by an ambulatory facility and a private office. The metropolitan area physicians exceeded the remaining in teaching activities and public hospital appointments. They had also a higher tendency to work in a different specialty. This study offers significant information with respect to professional decisions as well as regarding the creation or expansion of residency programs.

[Work situation of physicians graduating from medical residency programs in the State of São Paulo, Brazil]. / Situação de trabalho de médicos egressos de programas de residência médica no Estado de São Paulo.

The authors report on a study conducted to analyze the professional situation of physicians residing in the State of São Paulo, Brazil, five years after completion of a medical residency program. At least 50% of the professionals were interviewed in each specialty. A heavy work load was observed in physicians working both in the metropolitan area of the State capital and in other regions of the State. Male doctors had a higher income than female ones. The latter, however, had a higher proportion working in a single specialty, although 16.8% did not practice in the specialty in which they were trained. The most frequent working environment was a hospital, followed by an ambulatory facility and a private office. The metropolitan area physicians exceeded the remaining in teaching activities and public hospital appointments. They had also a higher tendency to work in a different specialty. This study offers significant information with respect to professional decisions as well as regarding the creation or expansion of residency programs.

[Recurrence in post-splenectomy spherocytosis anemia due to presence of accessory spleens]. / Recidiva em anemia esferocítica pós-esplenectomia conseqüente à presença de baços acessórios.

A young female patient had a recurrence of severe spherocytic anemia there years after having been submitted to splenectomy. The presence of two accessory spleens with a size of 3.5 cm and 4.0 cm, was demonstrated by technetium scanning and ultrasound images. Surgical removal of these noduli resulted again in prompt recovery. The development of the spleen beings in the fifth week of intrauterine life at the dorsal mesogastrium. The lack of fusion of splenic lobuli is responsible for the occurrence of accessory spleens. A surgeon performing splenectomy for the treatment of hemolytic anemia should always search for possible existences of accessory spleens.

Prognostic factors in primary retroperitoneal soft-tissue sarcomas.

We analyzed independent treatment variables (age, sex, signs and symptoms, site, size, histopathologic findings, grade, and clinical presentation) and treatment-dependent variables (resectability, type of operation, surgical margins, surgical boundaries, microscopic margins, adjuvant radiotherapy, and adjuvant chemotherapy) in 80 patients with primary retroperitoneal soft-tissue sarcomas admitted from 1982 through 1988. Both univariate and multivariate analysis of survival and disease-free survival were performed. The major factor in survival outcome was the ability to completely resect the lesion. When the 62 patients who underwent complete resection were examined, the only independent prognostic factor for both survival and disease-free survival was grade. We conclude that completeness of resection and grade of the lesion are primary determinants of survival. Once all tumor is macroscopically removed, no advantage could be demonstrated by more extensive surgical resection or current adjuvant therapy.

Axillary dissection in melanoma. Prognostic variables in node-positive patients.

We evaluated the importance of 14 clinical and pathologic variables as determinants of prognosis in patients with malignant melanoma and positive regional lymph nodes at axillary dissection. The records of 197 patients operated on between 1974 and 1984 were reviewed. Univariate analysis indicated as prognostically significant the number (p less than 0.001) and percentage (p less than 0.001) of positive nodes, highest nodal status (p less than 0.001), macroscopic or microscopic nodal metastases (p = 0.002), presence or absence of extranodal disease (p = 0.003), clinical stage (III versus less than III, p = 0.015), and site (considered as trunk versus other locations, p = 0.02). However, by multivariate analysis, only three variables were shown to be independent determinants of survival: percentage of positive nodes (p = 0.004), presence or absence of extranodal disease (p = 0.012), and site (trunk versus other locations, p = 0.019). Combining these three variables, subsets of patients with markedly different prognoses could be generated. It is possible to predict a favorable outcome for patients with less than 10% positive nodes, no extranodal disease, and a primary lesion at a site other than the trunk. It is also possible to recognize that the prognosis is very poor for patients with extranodal disease and truncal primary lesions, regardless of the percentage of positive lymph nodes. Finally it was verified that the prognosis is always unfavorable when the percentage of positive lymph nodes is very high.

[Traumatic rectal injuries]. / Ferimentos traumáticos de reto.

The authors review the cases of traumatic rectal injuries admitted to the Emergency Service of the "Hospital das Clínicas", University of São Paulo Medical School, during the period of July 1981 to July 1988. Forty-five patients (62.5%) had their injuries due to gunshot, 14 (19.4%) due to foreign bodies on the rectum, 10 (13.8%) due to blunt trauma and 3 (4.1%) due to stab wounds. The intraperitoneal rectum was injured in 32 patients (44.4%) and extraperitoneal portion of the rectum in 40 patients (55.5%). On the intraperitoneal injuries the management adopted were simple suture (14 patients), associated with a colostomy (17 patients) and in one patient the Hartmann procedure was adopted. On the extraperitoneal wounds the management adopted were rectal repair (when feasible), colostomy, distal washout and drainage. The complications rate was 27.8%, and from them, the majority (70%) were related to infectious nature. Seven patients died (9.7%), four of them as a consequence of sepsis. The morbidity and mortality of the rectal injuries were closed related to infectious complications as a consequence of late diagnosis. For this reason, the authors consider that all efforts should be employed to establish the prompt diagnosis.

[Body composition in various nutritional conditions. Experimental study]. / Composição corpórea em diferentes condições nutricionais. Estudo experimental.

Body composition parameters were studied in different nutritional conditions in Wistar rats with experimental cancer. Results were submitted to statistical analysis. Under a hyperlipidic diet, fat increased in control rats and decreased in animals with tumor; sodium increase and potassium decrease was verified in rats with tumor. The NA/K ratio increased in both groups and the N/K ratio increased in rats with tumor under standard diet, but decreased in rats with tumor under hyperlipidic diet. Fat decreased in the animals with tumor under an aproteic diet, but sodium increased. Potassium increased in undernourished animals of both groups. The Na/K ratio increased in rats with tumor. A comparison was made according to two different standards: "fresh body weight" and "fat-free body mass". The parameters analysed showed no significant differences in body composition.

An experimental study of the impact of cancer on nitrogen metabolism and wound healing.

In Wistar rats bearing a Walker-256 carcinoma flank tumor, a standard skin wound was inflicted on the backs of the animals. Nitrogen intake and nitrogen balance measures were obtained. The standard wound did not promote tumor growth. Wound contraction in tumor-bearing animals was not different from that in tumor-free animals. Tumor-bearing rats had anorexia, lower nitrogen intake and a tendency to lower their nitrogen balance. These findings suggest that both cancer and wound healing are privileged metabolic events, having as a consequence sacrifice of the host.