Chronic carotid glomitis in heroin addiction.

The aim of the present work was to investigate the occurrence and immunological characteristics of chronic carotid glomitis in opiate addicts. Carotid bodies were sampled at autopsy from 50 subjects who died of heroin intoxication (mean age 28 years), and from 16 young (24 years) and 10 older subjects (66 years) who died of trauma. Sections were stained with haematoxylin-eosin and azan-Mallory, and immunohistochemistry was carried out with anti-CD45, -CD3, -CD8, -CD4, -CD20, -CD68, -CD56. Inflammatory aggregates were not observed in young cases, but were found in 21/50 (42%) opiate cases and in 4/10 (40%) older cases. Infiltrates were mainly located in subcapsular and interlobular positions, and were also found around nerve fibres. Inflammatory aggregates were mainly composed of T suppressor/cytotoxic lymphocytes (50-80%). Monocytic/macrophagic cells and B lymphocytes comprised about 10% and 5-20% of inflammatory cells, respectively. T helper lymphocytes were fewer and only rare Natural Killer cells were found. Chronic carotid glomitis must be included among the autopsy findings of opiate addiction, and may be ascribed to inflammatory reactions to exogenous immunogens or to responses to drug-induced degenerative changes of carotid body components.

Surgical anatomy of the radial nerve at the elbow.

An anatomical study of the brachial portion of the radial nerve with surgical implications is proposed. Thirty specimens of arm from 20 fresh cadavers (11 male, 9 female) were used to examine the topographical relations of the radial nerve with reference to the following anatomical landmarks: acromion angle, medial and lateral epicondyles, point of division between the lateral and long heads of the triceps brachii, lateral intermuscular septum, site of division of the radial nerve into its superficial and posterior interosseous branches and entry and exit point of the posterior interosseous branch into the supinator muscle. The mean distances between the acromion angle and the medial and lateral levels of crossing the posterior aspect of the humerus were 109 (+/-11) and 157 (+/-11) mm, respectively. The mean length and calibre of the nerve in the groove were 59 (+/-4) and 6 (+/-1) mm, respectively. The division of the lateral and long heads of the triceps was found at a mean distance of 126 (+/-13) mm from the acromion angle. The mean distances between the lateral point of crossing the posterior aspect of the humerus and the medial and lateral epicondyles were 125 (+/-13) and 121 (+/-13) mm, respectively. The mean distance between the lateral point of crossing the posterior aspect of the humerus and the entry point in the lateral intermuscular septum (LIS) was 29 (+/-6) mm. The mean distances between the entry point of the nerve in the LIS and the medial and lateral epicondyles were 133 (+/-14) and 110 (+/-23) mm, respectively. Our study provides reliable and objective data of surgical anatomy of the radial nerve which should be always kept in mind by surgeons approaching to the surgery of the arm, in order to avoid iatrogenic injuries.

The gracilis muscle and its use in clinical reconstruction: an anatomical, embryological, and radiological study.

The gracilis muscle is used widely in reconstructive surgery, as a pedicled or as a free microsurgical flap, for soft tissue coverage or as a functioning muscle transfer. Many studies, based on cadaver dissections, have focused on the vascular anatomy of the gracilis muscle and provided different data about the number, origin, and caliber of its vascular pedicles. Computed tomographic (CT) angiography of both thighs of 40 patients (35 males and 5 females, mean age: 63 years) have been analyzed to provide a detailed anatomical description of the arterial supply of the gracilis muscle. The gracilis muscle had a mean length of 41 +/- 2.1 cm. The principal pedicle enters the gracilis muscle at a mean distance (+/-SD) of 10 +/- 1 cm from the ischiopubic attachment of the muscle. Its caliber shows a mean value of 2.5 +/- 0.5 mm, and it is statistically larger when originating directly from the deep femoral artery (45%) than from its muscular branch supplying the adductors, i.e., the "artery to the adductors" (46%) (P < 0.01). A significant correlation between the caliber of the artery of the main pedicle and the volume of the gracilis muscle was found (P < 0.01). The mean number of distal accessory pedicles is 1.8 (range, 1-4,) and the artery of the first of these pedicles shows a mean caliber of 2.0 mm. There is no correlation between either the number or the caliber of the artery of the accessory pedicles and the volume of the gracilis muscle. CT angiography, providing detailed images of the muscular and vascular structures of the thigh of each patient, could be a useful preoperative study for the reconstructive surgeon. It would allow a personalized planning of a gracilis flap, reducing the risk of iatrogenic damage.

Expression pattern of squamous cell carcinoma antigen in oesophageal dysplasia and squamous cell carcinoma.

The aim of the present study was to evaluate the tissue expression of squamous cell carcinoma antigen (SCCA) in oesophageal dysplasia and squamous cell carcinoma (SCC) with reference to its clinico-pathologic and prognostic significance. Immunohistochemistry using SCCA polyclonal antibody was performed on SCCs from 61 surgical oesophagectomies. Fifteen cases of low-grade dysplasia (LGD) and 37 non-coexistent high-grade dysplasia (HGD) were also sampled from these materials, together with sixteen chronic cases of oesophagitis. SCCA immunoreactivity was present in the maturative compartments of all normal epithelia and oesophagitis. LGDs showed no SCCA immunoreactivity in the dysplastic proliferative component but only in the superficial normal layers. In 94.6% of HGDs, no SCCA immunoreactivity was detected throughout the thickness of the epithelium. In SCCs, SCCA expression higher than 25% was found in 54% of cases. SCCA positivity showed an inverse correlation with histological grade, whereas no statistically significant correlation was found with TNM classifications, stage, or survival. SCCA is not expressed in early oesophageal carcinogenesis but, in SCC, it represents an indicator of histologic differentiation. In differentiated SCC, SCCA may represent a negative factor for cancer invasiveness, through inhibition of proteases.

Endoscopic treatment of pseudosarcomatous squamous carcinoma of the esophagus: case report and personal experience.

Spindle cell (or pseudosarcomatous) squamous carcinoma (PSC) is a rare malignant neoplasm of the esophagus, potentially capable of causing lymph node and distant metastases. Indications for surgery are the same as for squamous cell carcinoma (SCC) of the esophagus. The aims of this paper were to report a case of endoscopically treated PSC and to review our experience of surgically-treated patients with PSC in order to identify patients potentially suitable for endoscopic treatment. In our series of 4,460 patients with carcinoma of the esophagus observed between 1980 and 2003, 28 (0.6%) had the histological features of PSC. One had a PSC histologically confirmed (8cm-long polyp with a 3cm-large base) and endoscopically treated for high surgical risk. The patient had a close follow-up with endoscopic biopsies and ultrasonography with no local recurrence at 3 years. The overall survival rate was 22% for PSC and 17% for SCC (P = n.s.); after 5 years, the survival rates were 22% and 13%, respectively (P = n.s.). In our opinion the limited tendency to parietal infiltration and the good chance of disclosure in an early stage with endoscopic ultrasonography, justify non-surgical solutions in patients with a high surgical risk, possibly associated with adjuvant chemo- and radiotherapy since lymph node involvement is reported in 50% of cases. The limited number of patients with PSC involved in the present series prevent any significant statistical comparisons between the different groups, but the survival rates were roughly the same in the nonsurgical curative therapy as in the curative resection group, while the chances of survival were significantly lower in patients given palliative surgery and or non-curative treatments (P < 0.05).

Sertoli cell tumor: a rare case in an elderly patient.

Sertoli-Leydig cell tumors constitute < 1% of ovarian tumors, mostly in young women with virilization; however, not all present endocrine manifestations. A 72-year-old female presented with an abdominal mass and no signs of virilization. Total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy and selective pelvic lymphadenectomy was performed. The pathologic diagnosis was poorly-differentiated sex cord-stromal tumor with Sertoli cells. No adjuvant chemotherapy or radiation was administered. At 12-month follow-up the patient showed no evidence of disease.

Histopathology of carotid body in heroin addiction. Possible chemosensitive impairment.

AIMS: To perform a morphometric analysis of carotid bodies in opiate addicts. METHODS AND RESULTS: Carotid bodies were sampled at autopsy from 35 subjects who died of heroin intoxication (mean age 26 years), and from eight young (22 years) and eight older subjects (66.5 years) who died of trauma. Sections were stained with haematoxylin-eosin, azan-Mallory, and double-labelling immunohistochemistry with antineuronal specific enolase and anti-S100, to count type I and type II cells. Interlobular and intralobular connective tissue was increased both in the opiate cases (43.45 +/- 6.79%, P < 0.001, and 13.34 +/- 5.72%, P < 0.001, respectively) and older cases (46.67 +/- 1.65%, P < 0.001, and 9.62 +/- 2.11%, P < 0.05, respectively) compared with young cases (33.17 +/- 6.41% and 4.33 +/- 1.84%, respectively). The percentage of type II cells in the opiate cases (51.6 +/- 7.3%, P < 0.001) and in the older controls (49.0 +/- 7.2%, P < 0.01) was higher than in the young cases (37.9 +/- 3.0%). Among type I cells, the light cell percentage in the opiate cases (65.85 +/- 11%, P < 0.001) was reduced with respect to the two control groups (82.8 +/- 5.34%, young; 81.62 +/- 8.58%, older). CONCLUSIONS: The increases in connective tissue and type II cells are similar to findings in ageing and chronic pulmonary disease, and may be ascribed to glomic hypoxia. A direct action of opiates should be taken into account for the decrease in light cells in heroin addiction. The histopathological changes in the carotid body, by impairing chemosensivity, may play a role in the fatal cardiorespiratory derangement of heroin addicts.

Intraepithelial G3 adenocarcinoma of the endometrium after tamoxifen treatment.

CASE REPORT: In this paper we describe a case of endometrial carcinoma observed in a post-menopausal patient who was treated with tamoxifen for 5 years after a mastectomy for cancer. She came to our department because of vaginal bleeding 2 years after the end of tamoxifen treatment. TREATMENT: She underwent hysteroscopy and a D and C. A polypoid endometrium completely filled the uterine cavity and was carefully removed by curettage; histology showed a highly undifferentiated neoplasia with a component of serous adenocarcinoma, which was likely to originate from endometrial polyps. OUTCOME: The patient underwent radical hysterectomy, but no residual tumor was found in the uterus or in the tubes, ovary, or pelvic nodes, in spite of its low differentiation grade and high potential aggressiveness, and even though the patient was already symptomatic. Two years after surgery the patient is disease free, which is consistent with the evaluation of the surgical specimen, but unusual in poorly differentiated neoplasms.

Role of acid and bile reflux in development of specialised intestinal metaplasia in distal oesophagus.

BACKGROUND: Barrett's oesophagus is defined as specialised intestinal metaplasia in the distal oesophagus, regardless of extension. AIM: To study distal oesophagus function, and acid and bile exposure in patients with Long Segment (>3 cm), Short Segment (1 to 2 cm) and Ultra-short Segment (<1 cm) Barrett's Oesophagus, and in patients with gastro-oesophageal reflux disease without intestinal metaplasia. PATIENTS: Study population comprised 17 patients with Long, 8 with Short, 9 with Ultra-Short Segment Barrett's oesophagus, 32 with reflux disease and 12 healthy volunteers. METHODS: Patients were evaluated by manometry and by 24-hour pH and bile monitoring. RESULTS: Patients with intestinal metaplasia had greater acid exposure of the distal oesophagus than healthy volunteers. Patients with Long Segment Barrett's oesophagus had a longer history of symptoms, worse lower oesophageal sphincter pressures and longer bile and acid exposure than the other patients. Long Segment Barrett's oesophagus was predicted by low oesophageal pressure and increased bile exposure, age and male sex. CONCLUSION: Acid exposure in the distal oesophagus is probably the aetiological factor behind intestinal metaplasia, but a severely damaged antireflux barrier and bile in the refluxate are necessary for Long Segment Barrett's Oesophagus to develop.

Prevalence of intestinal metaplasia in the distal oesophagus, oesophagogastric junction and gastric cardia in symptomatic patients in north-east Italy: a prospective, descriptive survey. The Italian Ulcer Study Group "GISU".

BACKGROUND: Incidence of adenocarcinoma of distal oesophagus and gastric cardia, probably arising from areas of intestinal metaplasia, has been increasing rapidly. AIMS: To define prevalence of intestinal metaplasia of distal oesophagus, oesophagogastric junction and gastric cardia and to evaluate potential associated factors, by means of a prospective multicentre study including University and teaching hospitals, and primary and tertiary care centres. PATIENTS: Each of 24 institutions involved in study enrolled 10 consecutive patients undergoing first-time routine endoscopy for dyspeptic symptoms. METHODS: Patients answered symptom questionnaires and underwent gastroscopy Three biopsies were taken from distal oesophagus, oesophago-gastric junction and gastric cardia, and were stained with haematoxylin and eosin. Specimens were also evaluated for Helicobacter pylori infection. RESULTS: A total of 240 patients (124 male, 116 female; median age 56 years, range 20-90) were enrolled in study. Intestinal metaplasia affected distal oesophagus in 5, oesophago-gastric junction in 19 and gastric cardia in 10 patients. Low-grade dysplasia was found at distal oesophagus and/or oesophago-gastric junction of 3/24 patients with intestinal metaplasia vs 2/216 without intestinal metaplasia (p<0.05). A significant association was found between symptoms and presence of intestinal metaplasia, regardless of location, and between Helicobacter pylori infection and intestinal metaplasia at oesophago-gastric junction. CONCLUSIONS: Intestinal metaplasia of distal oesophagus, oesophagogastric-junction and gastric cardia is found in a significant proportion of symptomatic patients undergoing gastroscopy and is associated with dysplasia in many cases. Although prevalence of dysplasia seems to decrease when specialized columnar epithelium is found in short segment, or even focally in oesophago-gastric junction, these small foci of intestinal metaplastic cells may represent source of most adenocarcinomas of cardia.

MAGE, BAGE, and GAGE gene expression in patients with esophageal squamous cell carcinoma and adenocarcinoma of the gastric cardia.

BACKGROUND: The MAGE, BAGE, and GAGE gene families code for distinct, tumor specific antigens that are recognized by cytotoxic T lymphocytes in the context of HLA molecules. The purpose of this study was to analyze MAGE, BAGE, and GAGE gene expression in the two major histologic types of esophageal carcinoma, squamous carcinoma (ESCc) and adenocarcinoma (CAc), and to correlate their expression patterns with the principal prognostic parameters and long term survival. METHODS: Gene expression was analyzed in surgical samples from 24 patients with ESCc and 24 patients with CAc by reverse transcriptase-polymerase chain reaction amplification (RT-PCR). None of the patients had received preoperative chemotherapy or radiotherapy, and all were followed until death or for a minimum of 4 years. RESULTS: Sixteen ESCc samples (67%) and 9 CAc samples (37.5%) expressed at least one of the genes under study. The expression of each MAGE gene in the two histologic types was not significantly different, with the exception of MAGE-4, which was expressed more in ESCc samples than in CAc samples. BAGE and GAGE expression was rather low and, in every case, was associated with the expression of at least one MAGE gene. CONCLUSIONS: In the group as a whole, and in both ESCc and CAc subgroups, no significant correlation emerged between the expression of any gene and prognostic parameters, such as pathologic tumor, lymph node, or disease stage. Nevertheless, BAGE or GAGE expression was related significantly to a poor prognosis, whereas the expression of MAGE genes (in the absence of BAGE and GAGE expression) was related significantly to a good prognosis.

The p53 gene in patients under the age of 40 with gastric cancer: mutation rates are low but are associated with a cardiac location.

BACKGROUND: Determining both the frequency and the spectrum of p53 gene mutation in young patients with gastric cancer might provide clues to the host related genetic mechanism(s) in gastric carcinogenesis. PATIENTS AND METHODS: p53 mutations were assessed (by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), followed by DNA sequencing) in a cohort of 105 consecutive Italian patients in whom gastric cancer was ascertained before the age of 41. RESULTS: A low prevalence of p53 mutations (eight of 105) was observed, with no significant difference between intestinal (three of 31; 10%) and diffuse (five of 74; 7%) phenotypes. A significantly higher prevalence of p53 mutations was associated with the cardiac location (odds ratio, 7.09; confidence interval, 1.56 to 32.11). In all but one case, p53 mutations were associated with a stage higher than I. All eight mutations were located at CpG sites, where G : C to A : T transitions have been associated with frequent methylation at the C5 position of cytosine. CONCLUSIONS: These findings show that, unlike what has been consistently demonstrated in the general population, p53 mutations are uncommon in gastric cancer occurring in young patients, and in such patients, p53 alterations are significantly associated with the cardiac location.

Oesophageal resection for high-grade dysplasia in Barrett's oesophagus.

BACKGROUND: The aims of this study were to evaluate the prevalence of invasive cancer in patients with high-grade dysplasia in Barrett's oesophagus and to verify whether a second endoscopy with multiple biopsies could improve the accuracy of preoperative diagnosis. In addition, the mortality, morbidity and survival rates in patients with high-grade dysplasia having oesophageal resection were recorded. METHODS: Fifteen patients were observed from 1982 to 1998; the first seven patients were offered primary oesophageal resection after diagnosis. The other eight patients underwent a second endoscopy with a median of 12 biopsies examined. All later underwent oesophageal resection. RESULTS: Invasive adenocarcinoma was found in five patients, with a minimal difference between the first and second periods (two of seven versus three of eight). There were no perioperative deaths. Early morbidity was observed in eight patients and late morbidity in four. The actuarial survival rate was 79 per cent at 5 years. The Karnofsky status was unchanged from preoperative values in 13 of 15 patients after a median follow-up of 46 months. CONCLUSION: These patients with high-grade dysplasia had a 33 per cent probability of harbouring invasive oesophageal carcinoma but even a second endoscopy failed to identify patients with invasive tumour. Oesophagectomy was performed with no deaths and remains a rational treatment in patients fit for surgery.

Intestinal metaplasia is the probable common precursor of adenocarcinoma in barrett esophagus and adenocarcinoma of the gastric cardia.

BACKGROUND: Intestinal metaplasia in the tubular esophagus is the recognized precancerous lesion of adenocarcinoma in Barrett esophagus. However, it is not yet clear whether adenocarcinoma of the gastric cardia arises from the same premalignant lesion, i.e., intestinal metaplasia of the gastric cardia. The purpose of this study was to compare adenocarcinomas in Barrett esophagus and adenocarcinomas of the gastric cardia at an early stage, when it was more likely that intestinal metaplasia had not been completely overgrown by the tumor. METHODS: The authors compared the epidemiologic, clinical, and pathologic features of early stage adenocarcinoma in Barrett esophagus and adenocarcinoma of the gastric cardia from 42 patients who underwent resection surgery. The presence of intestinal metaplasia was assessed in the resected specimens by using Alcian blue (pH 2.5) staining. RESULTS: Intestinal metaplasia was detected in the mucosa adjacent to neoplasia in 25 of 26 patients with adenocarcinoma in Barrett esophagus and in 11 of 16 (69%) patients with adenocarcinoma of the gastric cardia. Patient and tumor characteristics and survival were comparable in both groups. CONCLUSIONS: Intestinal metaplasia is a very common finding in the mucosa adjacent to early stage adenocarcinoma of the gastric cardia. Adenocarcinoma in Barrett esophagus and adenocarcinoma of the gastric cardia may represent the same disease; the former arises from longer segments of intestinal metaplasia and the latter from intestinal metaplasia of the cardia.

Anomalous transcripts and allelic deletions of the FHIT gene in human esophageal cancer.

The fragile histidine triad (FHIT) gene is localized on chromosome 3p14 and spans the common fragile site FRA3B. Even though its role in carcinogenesis is still unclear, this gene is frequently inactivated by carcinogen-induced intragenic deletions in many types of cancers, and FHIT abnormal transcripts are found in many primary tumors and tumor-derived cell lines. We evaluated FHIT gene involvement in 39 esophageal carcinomas (18 adenocarcinomas [AC¿, 21 squamous cell carcinomas [SCC]) by both reverse transcriptase-polymerase chain reaction (RT-PCR) amplification and loss of heterozygosity analysis (LOH). Thirty cases (77%) displayed either aberrant FHIT transcripts (12 cases) and/or LOH (24 cases); among these, only 6 samples displayed both aberrant transcripts and LOH, thus suggesting that the two events are probably independent. Moreover, LOH was significantly higher in SCC (80%) than in AC (44%), and because most of our patients are heavy smokers and/or alcohol consumers, these results suggest that the FHIT gene might be a common target for carcinogens also in the esophagus.

Microsatellite instability and/or loss of heterozygosity in young gastric cancer patients in Italy.

Gastric cancers are rarely diagnosed before the age of 40 years and the incidence reaches a peak during the 7th decade in the general population. A molecular mechanism of early tumor onset may be determined by comparing microsatellite instability (MSI), indicative of error-prone mismatch repair, and loss of heterozygosity (LOH) between gastric cancers in patients < or = 40 years of age and those of older ages. Three to 5 chromosomal loci, where MSI and/or LOH are commonly found in gastric cancers in the general population, were examined in formalin-fixed, paraffin-embedded samples from 102 patients < or = 40 years of age using a polymerase chain reaction-based non-radioactive screening method. MSI and/or LOH at a minimum of 1 locus were detected in 11/102 patients. The frequency of MSI and/or LOH at the D11S904 locus was significantly higher than that at the D2S119, D2S123, D5S409 and IFNA regions. No preferential genetic changes at the D11S904 locus were observed in elderly patients. Among several clinicopathological variables, a statistically significant association with MSI and/or LOH was observed only for tumors located at the cardia, compared with tumors at the antrum and the corpus. Our findings suggest that a unique mechanism may be involved in increasing the susceptibility of the D11S904 locus for either MSI or LOH, especially for cardia tumors in young patients. Early onset of gastric cancers in patients < or = 40 years of age is associated with genetic changes at preferential chromosomal loci, including D11S904.