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Biomedical subjects

M Pera

Publications and source records attributed to M Pera.

At least 37 records · Page 2Linked to original sources

Epidemiology of esophageal cancer, especially adenocarcinoma of the esophagus and esophagogastric junction.

The incidence of adenocarcinoma of the esophagus and esophagogastric junction (EGJ) has been increasing over the past 15 years in western countries. Surgical series and population-based studies show that, by 1994, adenocarcinomas of the esophagus accounted for half of all esophageal cancer among white men. The causes of this increase in incidence remain to be elucidated. Esophageal adenocarcinomas and a portion of EGJ adenocarcinomas arise from long and short segments of specialized intestinal metaplasia (Barrett's esophagus). The prevalence of long segments of Barrett's esophagus (> 3 cm) in patients having endoscopy for reflux symptoms is 3%, and 1% in those undergoing endoscopy for any clinical indication. However, a silent majority of patients with Barrett's esophagus remain unrecognized in the general population and may not be diagnosed unless adenocarcinoma develops. Recent studies document a rise in the diagnosis of specialized intestinal metaplasia of the cardia. Nearly all these patients have associated carditis, and Helicobacter pylori infection has been linked to this condition. The possible origin of EGJ adenocarcinomas in the sequence carditis--specialized intestinal metaplasia needs to be clarified. Smoking and obesity are additional risk factors for adenocarcinoma of the esophagus and EGJ. Current data does not confirm H. pylori as a risk factor for cancer of the EGJ.

Adenocarcinoma↗

Could age be an indication for laparoscopic colectomy in colorectal cancer?

BACKGROUND: The incidence of colorectal carcinoma increases in the elderly. Regardless of age as an isolated factor, postoperative complications represent the main factor in increasing hospital mortality. METHODS: The aim of this study was to compare the short-term results (first 30 postoperative days) after laparoscopically assisted colectomy (LAC) and open segmental colectomy (OC) in colorectal carcinoma between two groups of patients, older than 70 and younger than 70 years of age. In the study from November 1993 to June 1998, 255 patients were evaluated to participate. RESULTS: Peristalsis, oral intake, and discharge from the hospital occurred earlier in LAC than in OC treated patients, in the two age groups. The mean operative time was significantly longer in the LAC than in the OC patients in the two age groups. No differences were observed in morbidity between LAC and OC in the group younger than 70 years of age. However, the overall morbidity was significantly lower in the LAC group in patients older than 70 years. One patient in the LAC group older than 70 years died. CONCLUSION: These results suggest that laparoscopically assisted colectomy may be particularly indicated in elderly patients.

Age Factors↗

Duodenal-content reflux esophagitis induces the development of glandular metaplasia and adenosquamous carcinoma in rats.

Recent studies have demonstrated that refluxed duodenal contents cause esophageal carcinoma in rats without exposure to carcinogens. The histopathological spectrum of these carcinomas includes squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma. Pure adenocarcinomas are thought to arise in areas of columnar metaplasia adjacent to the anastomosis, similar to Barrett's esophagus in humans. In contrast, the histogenesis of adenosquamous carcinomas is unclear. The purpose here was to investigate the pathogenesis of esophageal adenosquamous carcinomas in a time-course experiment of chronic duodenal-content reflux without carcinogen. Forty-two 8-week-old male Sprague-Dawley rats were divided into seven groups and exposed to duodenal-content esophageal reflux during 10, 15, 20, 25, 30, 35 and 40 weeks, respectively. All animals underwent an esophagojejunostomy with gastric preservation in order to produce chronic esophagitis. The rats received a standard diet without addition of carcinogens. An increasing incidence of glandular metaplasia and carcinoma was observed over the time course, starting at 20 weeks. After 40 weeks of reflux, multiple foci of glandular metaplasia and adenosquamous carcinoma were found in 83 and 50% of the animals, respectively. Most of the carcinomas occurred in the middle and proximal esophagus and had a dual pattern of differentiation, glandular and squamous. These findings confirm that duodenal content reflux alone has a carcinogenic effect. We propose that chronic duodenal reflux induces the development of metaplastic cells with glandular differentiation from the stem cells of squamous epithelium, and that glandular metaplastic foci are the morphological element from which tumors with a dual pattern of differentiation arise.

Anastomosis, Surgical↗

[Association between human papillomavirus infection, premalignant lesions of anal cancer, and the human immunodeficiency virus: prospective study on subjects with condylomata acuminata].

BACKGROUND: Human immunodeficiency virus (HIV) increases the risk for anal premalignant lesions associated to human papillomavirus infection (HPV). The aim of this study was to compare the prevalence of HPV and squamous intraepithelial lesions (SIL) in patients with anal warts, with and without anti-HIV antibodies. PATIENTS AND METHODS: HPV was identified using in situ hybridization and SIL was classified in high and low grade. RESULTS: HPV infection was more frequent in anti-HIV positive patients although the difference was not statistically significant. All patients with a high grade SIL were anti-HIV positive (p < 0.05). CONCLUSION: HIV infection was associated with a high rate of high-grade SIL.

Adult↗

Deterioration of esophageal motility with age: a manometric study of 79 healthy subjects.

OBJECTIVE: Data are limited on the effect of age on esophageal function. We evaluated whether aging influences the motor activity of the esophagus. METHODS: Standard esophageal manometry was performed in 79 healthy, nonpaid volunteers of both sexes, 18-73 yr of age. Lower (LES) and upper esophageal sphincter (UES) characteristics and the properties of esophageal peristaltic waves were assessed by age groups: < or = 25 yr, 26-35 yr, 36-45 yr, 46-55 yr, 56-65 yr, and > 65 yr. RESULTS: Age correlated inversely with LES pressure and length, UES pressure and length, and peristaltic wave amplitude and velocity, and correlated directly with the proportion of simultaneous contractions. Age was inversely correlated with the upper limits of normality (95th percentiles) of LES pressure (r = -0.943, p = 0.005), UES pressure (r = -0.943, p = 0.005), middle and lower peristaltic wave amplitude (r = -0.947, p = 0.004, and r = -0.844, p = 0.035, respectively), upper/middle peristaltic progression speed (r = -0.943, p = 0.005), and the proportion of simultaneous contractions (r = 0.926, p = 0.008), but not with the lower normal limits (5th percentiles) of these variables. Gender did not affect esophageal motility variables. The 95th percentiles of LES pressure differed by 20 mm Hg, those of lower peristaltic amplitude by 82 mm Hg, and those of percent simultaneous contractions by a factor of 2, between the younger and the older age groups. CONCLUSIONS: The results suggest that normal esophageal motility deteriorates with advancing age. Thus, age-related normality limits of esophageal pressures should be considered before establishing the manometric diagnosis of hypercontractile esophageal motility disorders.

Adolescent↗

Hemoperitoneum due to a ruptured gastric stromal tumor.

BACKGROUND/AIMS: Gastrointestinal stromal tumors form a group of uncommon neoplasms originated from pluripotential mesenchymal cells. Many patients are asymptomatic and the tumor is discovered during an abdominal operation. Massive intraperitoneal bleeding is an exceptional complication associated with high mortality rates. Our aim is to report a case of a gastric stromal tumor in an 83-year-old patient presenting with intraperitoneal hemorrhage and hypovolemic shock, successfully operated. METHODS: Emergency laparotomy showed a hemoperitoneum caused by rupture of a large exogastric tumor attached to the greater curvature. Total gastrectomy and esophagojejunostomy was performed. RESULTS: Histological examination revealed proliferation of spindle-shaped cells but immunocytochemistry failed to identify specific markers of smooth muscle and neural cells. Diagnosis of a gastric stromal tumor was made. Postoperative evolution was uncomplicated. CONCLUSION: Gastric stromal tumor is a relatively rare neoplasm of mesenchymal origin whose nature and prognosis is unclear.

Aged↗

Triple-color FISH analysis of 12p amplification in testicular germ-cell tumors using 12p band-specific painting probes.

Forty-nine surgical specimens and nine germ cell tumor lines were analyzed by triple-color FISH using microdissected probes for the cytogenetic bands of chromosome arm 12p (12p11.2, p12, and p13). FISH analysis demonstrated amplification of material from all three bands in all tumors. This amplification was in the form of increased copy number of 12p or i(12p) and/or 12p amplified regions (AMP12p). The number of copies of 12p was variable (4-11 copies) from case to case but tended to remain relatively constant in all clones of the same tumor, even when the amplification took the form of an amplified region composed of 12p material. In tumors with multiple clones, i(12p) and AMP12p were never found in the same cell. No correlation was found between 12p copy number and tumor type. We describe, for the first time, a relative overrepresentation of 12p13 or 12p12-p13 regions in six tumors (two surgical samples and four cell lines), either as "partial 12p" (five cases) or within a 12p amplified region (one case). The ubiquitous amplification of all three 12p bands in germ-cell tumors supports the hypothesis that 12p harbors more than one gene important for oncogenesis of adult male germ-cell tumors, and that these genes may be located in different areas of 12p.

Adult↗

Port site metastases and recurrence after laparoscopic colectomy. A randomized trial.

BACKGROUND: This study was performed to prospectively assess the impact of the laparoscopic approach to the patterns of port site metastases (PSM) and recurrence rate (RR) of resected colon carcinomas as compared with conventional colectomies. METHODS: All patients were included in a prospective randomized trial comparing laparoscopic-assisted colectomy (LAC) versus open colectomy (OC) for colon cancer. The randomization was stratified for localization of the lesion. Patients with metastasic disease at time of the surgery were excluded. Follow-up in the outpatient clinic was done every 3 months for a minimum of 12 months. Endpoints for the study were metastasis at port site and laparotomy incision as well as recurrence rate. RESULTS: Of 91 segmental colectomies performed from November 1993 to January 1996, there were 44 LAC and 47 OC. Patient data were similar in both groups (age, sex, Dukes stage, type of operation). Mean follow-up was 21.4 months, with a range of 13 to 41 months. There were no wounds or PSM in those series. RR was similar for both groups. For LAC, it was five of 31 (16.1%); for OC, it was six of 40 (15%). CONCLUSIONS: The laparoscopic approach has a recurrence rate similar to that for open procedures for colon cancer. However, additional follow-up of these patients is needed before we can determine whether or not the laparoscopic approach influences overall survival.

Aged↗

Epithelial cell hyperproliferation after biliopancreatic reflux into the esophagus of rats.

BACKGROUND: Chronic reflux of duodenal contents into the esophagus of rats produces severe esophagitis and exerts a co-carcinogenic effect on the proliferating cells by enhancing the formation of nitrosamine-induced esophageal carcinomas. We investigated the effect of the different components of the duodenal reflux on the epithelial cell proliferation of the lower esophagus. METHODS: Sprague-Dawley rats underwent three surgical reflux models (biliopancreatic, pancreatic, and biliary) and a sham operation. Animals were sacrificed at 72 hours, 6 weeks, and 9 weeks after the operation. Histology and cell proliferation, determined by ornithine decarboxylase activity, polyamine (putrescine, spermidine, spermine) levels, and proliferating cell nuclear antigen labeling index of the basal and suprabasal layers, were studied in the distal esophagus. RESULTS: Both biliopancreatic and pancreatic reflux induced severe esophagitis starting on week 6. Suprabasal proliferating cell nuclear antigen labeling index significantly increased throughout the 9 weeks of the study in the biliopancreatic and pancreatic reflux groups, although this increase was earlier in the former group. Ornithine decarboxylase activity and polyamine levels were significantly increased in the biliopancreatic and pancreatic groups on week 6, decreasing on week 9. CONCLUSIONS: Increased esophageal cell proliferation after both biliopancreatic and pancreatic reflux into the lower esophagus may therefore be one mechanism by which duodenal-content reflux stimulates esophageal carcinogenesis in experimental animals.

Animals↗

Potential benefits of cell cloning for human medicine.

The successful cloning of a mammal from an adult somatic cell nucleus opens new avenues for major advances in reproductive medicine, biotechnology and cellular-based transplantation therapies for degenerative diseases. At the same time, this breakthrough has generated much heated discussion concerning the ethics of cloning. Twinning is a form of cloning, and there are instances in clinical assisted reproduction in which the deliberate formation of twins by embryo dissection would seem ethically acceptable. Nuclear transfer technology might facilitate the derivation of human embryonic stem cells, capable of differentiation into a wide variety of somatic cell lineages. Directed differentiation of human embryonic stem cells into specific cell types in vitro could provide a universal source of cells for transplantation therapy. The potential benefits of therapeutics based on cloning technologies are considerable, and hasty legislation to ban all such procedures could block progress in critical arenas of biomedical research.

Animals↗

[Endoscopic ultrasonography in the staging of esophageal cancer. Therapeutic implications].

Endoscopic ultrasonography (EUS) provides accurate visualization of the different layers of the gastrointestinal wall and surrounding structures, allowing TN staging of tumors prior surgery. The aim of this study was to evaluate the sensitivity, specificity and accuracy of EUS in the staging of esophageal carcinoma as well as its applicability and usefulness in tumors with nontraversable stenoses. EUS was performed in 43 patients with esophageal carcinoma. The technique was carried out with a radial echoendoscope under sedation with i.v. midazolam. Both, the infiltration of the tumor through the layers of the esophageal wall (T staging) and the presence of lymph nodes in different areas (N and M staging) were determined. In cases with nontraversable stenoses, only the proximal tumor margin was assessed by means of EUS. EUS showed T1 stage in only one case and more advanced stages in the remaining patients: T2 (n = 12), T3 (n = 22) and T4 (n = 4). We know the outcome of 28 patients, 14 of whom underwent surgery. In these patients, the sensitivity for T and N staging was 86% and 92% respectively, and the accuracy 86% in both. Both, T and N, were overstaged in one case (7%) and understaged in another (7%). The tumor caused nontraversable stenoses in 59% of patients (n = 26). In 4 patients the staging could not be assessed with sufficient reliability. In the subgroup of patients with nontraversable stenoses who underwent surgery, the accuracy of EUS when comparing with histopathology was 80%. Endoscopic ultrasonography has a high sensitivity and accuracy in the staging of esophageal tumors even in cases with nontraversable stenoses.

Aged↗

Liver transplantation for alcoholic cirrhosis with anti-HCV antibodies.

The results of orthotopic liver transplantation (OLT) in patients with alcoholic liver cirrhosis (ALC) are currently similar to those obtained in patients with other indications. However, the frequent association of ALC with hepatitis C virus (HCV) infection may impair these results. We retrospectively studied the consequences of HCV infection on survival and graft function in 59 patients with ALC undergoing OLT. Patients were classified into two groups depending on their HCV serology before transplantation: group 1 comprised 24 anti-HCV-positive patients, and group 2, 35 anti-HCV-negative patients. Patient and graft survival were similar in both groups. Liver function tests 1 and 4 years after OLT showed AST and ALT values that were significantly higher in group 1 patients and post-transplant histologically proven chronic hepatitis was found in 45% and 61% of these patients at 1 and 4 years, respectively. We conclude that pretransplant HCV infection in patients with ALC does not affect survival after OLT. However, one must bear in mind the high incidence of post-transplant chronic hepatitis secondary to recurrence of HCV infection and be cautious when drawing this conclusion.

Adult↗

Sleeve recording of upper esophageal sphincter resting pressures during cricopharyngeal myotomy.

OBJECTIVE: The manometric effects of a 6-cm cricopharyngeal myotomy are recorded while the operation is being performed from cervical esophagus to the cricopharyngeus and then to the hypopharynx. SUMMARY BACKGROUND DATA: Cricopharyngeal myotomy is used in the treatment of oropharyngeal dysphagia of different causes. The operation decreases the resting pressure in the upper esophageal sphincter (UES). The components responsible for this decrease have not been clarified. METHODS: Fourteen patients with oropharyngeal dysphagia underwent a sleeve recording of the UES resting pressures under general anesthesia before and after sequential myotomy of the pharyngoesophageal junction. Patients were assessed in the awake state before and after the whole myotomy. RESULTS: Upper esophageal pressures remain unchanged after division of 2 cm of the cervical esophageal muscle. Section of 2 cm of the cricopharyngeal area results in a significant decrease of the sphincter resting pressure (p < 0.01). The division of 2 cm of hypopharyngeal muscle results in a further significant reduction of the resting pressure (p < 0.005). CONCLUSIONS: Extension of the cricopharyngeal myotomy over hypopharyngeal musculature produces a more significant decrease of UES resting pressure.

Aged↗

Duodenal content reflux esophagitis in the rat: an animal model for the ulcer-associated cell lineage (UACL)?

We have studied the histological changes observed in the mucosa of 10 rats in the region of a esophagojejunostomy to evaluate it as a model for the ulcer-associated cell lineage (UACL). In man, the UACL has a distinctive morphology, proliferative organization, and pattern of trefoil peptide localization. We have therefore examined these aspects aided by immunohistochemistry and in situ hybridization to the trefoil peptides TFF1, TFF2, and TFF3. Only TFF2 was studied by immunohistochemistry, whereas the mRNAs for all three peptides were examined by in situ hybridization using 35S-labeled riboprobes. The marker MIB-1 to the Ki67 proliferation-related antigen was used to examine the proliferative organization of UACL-like changes. In all cases, columnar epithelialization of the distal esophagus was seen, and in all, glands with morphological and gene expression attributes of the UACL were identified. TFF3 mRNA localized patchily throughout the UACL, whereas TFF1 mRNA was found in the upper portions of the lineage and TFF2 mRNA and its product in the acini. These lineages showed virtually no intrinsic proliferative activity. These appearances are similar to those seen in early human UACL, and we therefore propose this that this represents the first published animal model of this lineage.

Animals↗

Comparative analysis of cell surface antigens expressed by cell lines derived from human germ cell tumours.

The pattern of cell surface antigen expression of a set of cell lines derived from human germ cell tumours and corresponding to various cell phenotypes found within these tumours was studied using immunofluorescence. Twenty-two different antibodies were used. Many of these antibodies have been noted to recognise epitopes that are either preferentially expressed by embryonal carcinoma (EC) cells, or by more differentiated cell types. Using scatter plots and rank correlations, 6 groups of antibodies were distinguished with respect to their staining patterns on the cell lines tested. Several antibodies showed a specific staining pattern in relation to the differentiation state of the cells. Two groups of antibodies included those recognising high m.w. glycoproteins (antibodies TRA-1-60, TRA-1-81, GCTM2, 3-177, K4 and K21) and the ganglioseries glycolipid antigens SSEA-3 and -4 (antibodies MC631 and MC813-70). These antibodies mostly stained EC cells but not other cell types, confirming previously published data. However, one of these groups, comprising antibodies K4 and MC631, was more exclusively associated with the EC cell phenotype than was the other group. Antibodies recognising the liver isozyme of alkaline phosphatase (TRA-2-49 and TRA-2-54) also reacted strongly with most EC cell lines, although they reacted significantly with a number of other cell lines as well, whereas antibodies to the placental isozyme tended to react only weakly with EC cells. The antibodies recognising the ganglioseries glycolipids GD2 and GD3 (VIN2PB22 and VINIS56) preferentially stained cells with neuroectodermal characteristics. Other antibodies showed a heterogeneous staining pattern for the cell lines with different phenotypes. The data obtained from the cell lines were, in general, similar to data obtained from immunohistochemical studies on tissue sections of primary germ cell tumours of the adult testis, including carcinoma in situ.

Adult↗

[Paraesophageal hernias in elderly patients. An indication for laparoscopic surgery].

Paraesophageal hernias are uncommon conditions which appear mainly in elderly people, frequently associated with sliding hernias or gastric volvulus. Considered a high risk pathology, surgical management is preferred to avoid serious complications. Due to advanced age and operative risks, a laparoscopic approach was performed in the three patients with paraesophageal hernia. In mixed hernias, a Nissen or Toupet fundoplication and closure of the hiatal defect was carried out. In a case with gastric rotation, reduction of the herniated stomach and posterior partial fundoplication with gastropexy was performed. No postoperative complications occurred and recovery was satisfactory. Laparoscopic management seems to be a good choice for elective treatment of paraesophageal hernias in elderly patients.

Aged↗