Esthesioneuroblastoma metastatic to the trachea.

Esthesioneuroblastoma is a rare tumour, for which a multimodal approach, including a combination of surgery and radiation, appears to provide the best disease-free and overall survival. Well-known for its tendency for local recurrence and distant spreading by both lymphatic and haematogenous routes, the most common sites of metastases are lungs and bones, followed by liver, spleen, scalp, breast, adrenals and ovary. One single case of metastasis to the trachea has been reported in the literature. The case is reported here of a patient who developed metastatic esthesioneuroblastoma to the trachea 18 months after primary surgery and radiation therapy. The patient was treated by two subsequent N-YAG laser endoscopic resections and chemotherapy.

D-aspartate and reproductive activity in sheep.

D-aspartic acid (D-Asp) has been isolated from neuroendocrine tissues of many invertebrates and vertebrates. Recently, it has been demonstrated that this D-amino acid may be converted to N-methyl-D-aspartic acid (NMDA), a neuromodulator associated with sexual activity. In this study, we determined D-Asp and NMDA concentrations in endocrine glands and other tissues in ewes after D-Asp administration and in controls. We also evaluated the effects of d-Asp administration on the reproductive activity of ewes by determining either progesterone concentrations or LH pulses in the presence or absence of estradiol benzoate. The pineal gland showed the highest natural content of D-Asp (1.47+/-0.22 micromol/g tissue), whereas the pituitary gland had the highest capability to store d-Asp, with a peak value (9.7+/-0.81 micromol/g tissue) 6 h after its administration. NMDA increased sharply 12 h following D-Asp administration, reaching values three times higher than the baseline in both the pituitary and brain. D-Asp was quickly adsorbed after subcutaneous administration, with a peak in plasma levels 2 h after administration and a return to baseline values after 6 h. D-Asp administration achieved a significant (P < 0.001) increase in LH values with respect to estradiol or estradiol + D-Asp treatments. d-Asp treatment once or twice a week did not successfully drive acyclic ewes into reproductive activity. In conclusion, the results obtained in this study demonstrated that D-Asp is endogenously present in sheep tissues and electively stored in endocrine glands and brain after its administration. NMDA and LH increase following D-Asp administration suggesting a role of this D-amino acid in the reproductive activity of sheep.

Testicular endocrine activity is upregulated by D-aspartic acid in the green frog, Rana esculenta.

This study investigated the involvement of D-aspartic acid (D-Asp) in testicular steroidogenesis of the green frog Rana esculenta and its effect on stimulation of thumb pad morphology and glandular activity, a typical testosterone-dependent secondary sexual characteristic in this amphibian species. In the testis, D-Asp concentrations vary significantly during the reproductive cycle: they are low in pre- and post-reproductive periods, but reach peak levels in the reproductive period (140-236 nmol/g wet tissue). Moreover, the concentrations of D-Asp in the testis through the sexual cycle positively match the testosterone levels in the gonad and the plasma. The racemase activity evaluated during the cycle expresses its peak when D-Asp and testosterone levels are highest, that is, during the reproductive period, confirming the synthesis of D-Asp from L-Asp by an aspartate racemase. Short-term in vivo experiments consisting of a single injection of D-Asp (2.0 micro mol/g body weight) demonstrated that this amino acid accumulates significantly in the testis, and after 3 h its uptake is coupled with a testosterone increase in both testis and plasma. Moreover, within 18 h of amino acid administration, the D-Asp concentration in the testis decreased along with the testosterone titer to prestimulation levels. Other amino acids (L-Asp, D-Glu and L-Glu) used instead of D-Asp were ineffective, confirming that the significant increase in testicular testosterone was a specific feature of this amino acid. In long-term experiments, D-Asp had been administered chronically to frogs caught during the three phases of the reproductive cycle, inducing testosterone increase and 17beta-estradiol decrease in the gonad during the pre- and post-reproductive period, and vice versa during the reproductive period. The stimulatory effect of D-Asp on testosterone production by the testis is consistent with the stimulation of spermatogenesis and the maturation of thumb pads occurring in D-Asp-treated frogs. In these last animals, there was an increase of seminiferous ampoule area and a higher number of spermatids and sperm. Moreover, in spermatogonia I and II and in spermatocytes, a proliferating cell nuclear antigen (PCNA) intense immunopositivity was observed. In addition, the thumb pads of D-Asp-treated frogs compared with controls showed a significantly thicker epithelial lining, a wider area of their glands with taller secretion cells, and more numerous, PAS-positive-rich secretions. Finally, these results provide functional evidence for a biologic role of D-Asp in amphibian male steroidogenesis; therefore, this unusual amino acid could be considered a modulatory agent for reproductive processes.

Multiple approach to the exploration of genotype-phenotype correlations in familial adenomatous polyposis.

PURPOSE: Familial adenomatous polyposis (FAP), caused by a mutation in the APC gene, is a colorectal cancer predisposition syndrome associated with several other clinical conditions. The severity of the FAP is related to the position of the inherited mutation in the APC gene. We analyzed a large series of FAP patients to identify associations among major clinical manifestations and to correlate the mutation site with specific disease manifestations. MATERIALS AND METHODS: APC mutations were identified in 953 FAP patients from 187 families. We used unconditional logistic regression models and a method involving generalized estimating equations to investigate the association between genotype and phenotype. We used multiple correspondence analysis to represent the interrelationships of a multiway contingency table of the considered variables. RESULTS: APC germline mutations were located between codons 156 and 2011 of the APC gene. Mutations spanning the region between codons 543 and 1309 were variable, but strongly associated with congenital hypertrophy of retinal pigment epithelium. Mutations between codons 1310 and 2011 were associated with a six-fold risk of desmoid tumors relative to the low-risk reference region (159 to 495). Mutations at codon 1309 were associated with early development of colorectal cancer. Mutations between codons 976 and 1067 were associated with a three- to four-fold increased risk of duodenal adenomas. The cumulative frequency of extracolonic manifestations was highest for mutations between codons 976 and 1067, followed by mutations between 1310 and 2011. CONCLUSION: Analysis of the relation between APC mutation site and phenotype identifies subgroups of FAP patients at high risk for major extracolonic disease, which is useful for surveillance and prevention.

Botulinum toxin type A (Dysport) for the treatment of Zenker's diverticulum.

The standard treatment for Zenker's diverticulum (ZD) is surgical, but transendoscopic section of the diverticular spur has also been performed with good results. We treated two patients with the injection of 300-350 IU of botulinum toxin type A (Dysport) into the diverticular spur. Both patients were dysphagic because of a large ZD. A few hours after the treatment, the patients were able to return to a normal, nonrestricted diet. They remain symptom-free 12 and 3 months later, respectively. No complications have been observed. As a result of its ease of application and efficacy, this treatment can be recommended for patients who are unable to undergo the surgical operations; it can be considered a valid alternative to the other endoscopic procedures.

Blood lead reference values: the results of an Italian polycentric study.

This paper presents the results of a polycentric study carried out in seven different areas, organized by the Italian Society of Reference Values (SIVR) for assessing reference values of lead in blood (B-Pb) at the current doses of the metal to general population. The estimated arithmetic mean for B-Pb in males was of 45.1 microg/l and 30.6 microg/l in females; the 95th centile was 100 and 60 for males and females, respectively. The main variables influencing B-Pb levels were gender, age, BMI, outside sport practice, alcohol consumption and smoking habits, while the geographic area and the urban residence did not affect the metal concentration in blood.

Effect of lifestyle, smoking, and diet on development of intestinal metaplasia in H. pylori-positive subjects.

OBJECTIVES: This study aimed to evaluate the influence of environmental and sociodemographic factors and the effect of smoking, alcohol, and dietary habits on the risk of gastric intestinal metaplasia (IM) in Helicobacter pylori-infected subjects. METHODS: The investigation was based on 2598 consecutive volunteer blood donors tested for the presence of antibodies against H. pylori from March 1995 to March 1997. Endoscopy with multiple biopsies was offered to all H. pylori-positive, symptomatic subjects. The presence or absence of IM was diagnosed by gastric biopsies. A serologically H. pylori-positive subject with gastric IM was defined as a case, whereas serologically H. pylori-positive subjects without IM were used as controls. All patients answered a detailed questionnaire collecting sociodemographic characteristics and smoking, alcohol drinking, and dietary habits. Odds ratios (ORs) and their 95% CIs were estimated by unconditional logistic regression, including terms for age and sex, to assess the association between the data collected and IM. RESULTS: Three hundred forty-four subjects with serological H. pylori infection and upper-GI symptoms underwent GI endoscopy, during which biopsies were taken for histological diagnosis. Histology revealed metaplasia in 74 subjects (21.5%). Incomplete IM was found in 37.8% of these cases. No significant associations were found between IM and anthropometric or sociodemographic factors. There was a significant association between age and IM (chi2 for trend, 6.67; p value, 0.009). Current smokers of over 20 cigarettes per day had a 4-fold risk of IM (OR, 4.75, 95% CI, 1.33-16.99). A 2-fold increased risk was found for high butter consumers (OR, 2.17; 95% CI, 1.14-4.11). No significant specific associations were found between the variables studied and complete or incomplete IM. CONCLUSIONS: This study found that smoking and high butter consumption may increase the risk of having gastric IM in H. pylori-positive subjects.

Use of self-expanding metal stents for palliation of rectosigmoid cancer.

BACKGROUND: Patients with large bowel obstruction can be palliated by colostomy or by endoscopic modalities that restore luminal patency. The clinical results of a series of patients with rectosigmoid cancer in whom self-expanding metal stents were inserted at endoscopy are presented. METHODS: Thirty-seven patients with symptoms related to obstructive rectosigmoid adenocarcinoma were treated by endoscopic insertion of self-expanding metal stents. RESULTS: Metal stents were correctly placed in 36 of 37 patients (97%) with no immediate complications. Early dislodgment of the stent (within 1 week) was observed in 3 cases. The remaining 33 patients (92%) were followed for a median of 7 months (3 weeks-33 months). In 28 patients (78%) there was long-term restoration of luminal patency and disappearance of obstructive symptoms without further treatments. They experienced no pain, tenesmus, or incontinence during the follow-up period. The incidence of complications (early and late) and the mortality rate related to the procedure were 22% and 3%, respectively. CONCLUSIONS: Endoscopic metal stents can be considered a simple and effective solution for long-term palliation of rectosigmoid cancer.

Preoperative endoscopic ultrasonography in patients with gastric cancer.

AIMS AND BACKGROUND: There is a need to assess the accuracy of endoscopic ultrasonography (EUS) in the diagnosis and staging of gastric cancer, especially in the early and very advanced stages of the disease when the therapeutic approach is still controversial. METHODS: A retrospective study was performed on 79 patients with gastric cancer in order to compare the stage defined by preoperative EUS with that assessed histopathologically. All patients underwent laparotomy for final diagnosis, staging, and eventually treatment. The results of EUS were correlated with the histologic findings of the resected specimens. RESULTS: In the uT1 group, which corresponds to early gastric cancer, the diagnosis was histologically confirmed in 85.7% of the cases. In patients with advanced tumors defined as uT3-uT4, i.e., tumors infiltrating the serosa or neighboring structures, the diagnostic concordance was 91.1%. In contrast, concordance for less advanced lesions confined to the muscular layer was only 31.2%. As regards the lymph nodes, they were defined metastatic in 31 patients and confirmed to be histologically involved in 77.4%. In contrast, when the lymph nodes were assessed as negative at EUS, they proved to be metastatic in more than half the cases. CONCLUSIONS: From the data it appears that EUS has proven to be valuable in correctly staging most of the patients. EUS shows not only tumor depth and local spread but also the passage from a pathologic to a normal wall and lymph node metastasis. EUS appears to represent an important advance in the staging and follow-up of patients with gastric cancer. Instruments and techniques will continue to evolve, but the next level of research should be designed to show that the improved staging provided by EUS has clinical utility and can affect patient outcome. It is noteworthy that the highest accuracy of EUS has been shown in those conditions (uT1 and uT3-4) which currently are under consideration for a therapeutic approach that differs from the standard one.

Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adenomatous polyposis. Hereditary Colorectal Tumors Registry.

OBJECTIVE: To identify factors influencing the occurrence of cancer in the rectal remnant in patients with familial adenomatous polyposis (FAP) after colectomy and ileorectal anastomosis (IRA). SUMMARY BACKGROUND DATA: The risk for rectal cancer in patients with FAP after colectomy and IRA remains a major concern. METHODS: Between 1955 and 1997, 371 patients (206 men, 165 women) from the Registry of Hereditary Colorectal Tumors underwent colectomy and IRA as a primary surgical procedure. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard models were fitted to assess the relative excess risk of rectal cancer and to control for confounding factors. A multivariate analysis was performed to assess the relation between cancer risk in the rectum and sex, age, number of rectal polyps, colon cancer, and APC germline mutation. RESULTS: Median follow-up was 81 months. Eighty-nine patients (24%) had colon cancer at the time of surgery. The APC mutation was found in 200 patients. In 27 patients, cancer developed in the retained rectum 1 to 26 years after surgery. The incidence of rectal carcinoma appears to increase with time: at 10, 15, and 20 years after surgery, the cumulative risk was 7.7%, 13.1%, and 23.0%, respectively. Multivariate analysis identified as independent predictors the presence of colon cancer at IRA and a mutation occurring between codons 1250 and 1464; both factors increased the risk nine times. CONCLUSIONS: The presence of cancer at IRA and APC mutation type are the most important risk factors for the future development of cancer in the rectal remnant in patients with FAP.

Molecular characterization of P-29, a metacestode-specific component of Echinococcus granulosus which is immunologically related to, but distinct from, antigen 5.

In this work the characterization of P-29, a novel 29 kDa antigen from Echinococcus granulosus is reported. E. granulosus was identified while looking for parasite antigens distinct from those present in hydatid cyst fluid. A monoclonal antibody (mAb 47H.PS) prepared against protoscolex components revealed that P-29 is localized to the tegument and rostellum of protoscoleces, and to the germinal layer of the cyst, but it is absent in hydatid cyst fluid or adult worm extracts. Several internal fragments of P-29 showed sequence identity to the amino acid sequence encoded by Eg6, a partial gene sequence reported to code for an epitope of antigen 5 (Ag5), one of the major diagnostic antigens of the parasite. We confirmed that Eg6 encodes a sub-fragment of P-29 by mapping the epitope of mAb 47H.PS, and isolating the full length P-29 cDNA. Since Eg6 had been, postulated to encode a fragment of Ag5, we specifically studied the relationship of P-29 and Ag5 by: (i) examining the cross-reactivity displayed by different mAbs; (ii) comparison of their peptide finger prints; and (iii) a comparative study of their diagnostic value. Our results prove unequivocally that P-29 and Ag5 are immunologically related, but different proteins, raising several questions on the current knowledge of Ag5.

Management of malignant mucinous adenomas.

BACKGROUND: Malignant polyps are defined as adenoma with cancerous tissue penetrating into or through the muscolaris mucosae in the submucosa, and endoscopic removal is the most common treatment for such polyps. In the presence of malignant mucinous adenoma, defined as a malignant adenoma in which a significant amount of mucus is present in the stroma, the therapeutic approach is controversial and authors have performed surgical resection in all cases. The purpose of the study was to demonstrate that malignant mucinous adenoma is not a condition suggesting by itself a bowel resection. METHODS: Ten patients with malignant mucinous adenoma were enrolled in the study: endoscopic treatment alone was performed in 4 cases, and polypectomy was followed by surgical resection in 6 cases. RESULTS: At a median follow-up of 74.2 months no distant metastases had occurred in any of the patients treated with endoscopic polypectomy alone; during the follow-up, 1 patient had a local recurrence and surgical resection was performed. Only one case of residual disease was found at histology among the patients in which endoscopic polypectomy was followed by surgical resection. No complications occurred after endoscopic treatment in any case. CONCLUSIONS: In the absence of unfavorable histologic parameters, malignant mucinous adenomas should be managed with the same criteria of other malignant adenomas, and endoscopic polypectomy is considered as a safe and effective treatment when radicality criteria are fulfilled.

Endoscopic treatment of carpet-like adenomas of the rectum.

BACKGROUND: Transanal microsurgery, endoscopic laser photocoagulation and snare resection have all been used to treat large sessile adenomas of the rectum alternatively to a surgical approach. However, such modalities are often defective due to the carpet-like shape and the frequently large extension of the lesions. METHODS: Ten patients with carpet-like adenoma were submitted to transanal endoscopic resection by urological resectoscope. RESULTS: Complete eradication was obtained in all lesions. The mean number of treatment sessions was 3 (range, 1-5). The mean time between the first treatment and the complete eradication was 6 months (range, 1-18). The only complications were an intraoperative and an early postoperative bleeding. There was no early or late mortality related to the procedure. CONCLUSIONS: Transanal endoscopic resection by urological resectoscope appears to be a suitable therapeutic approach for sessile and carpet-like adenomas of the rectum or for pTI cancer in patients who refuse major surgery.

Determinants of Helicobacter pylori seroprevalence among Italian blood donors.

BACKGROUND/AIM: Helicobacter pylori is a worldwide infection. It is estimated that approximately 50% of the general population is affected, but this percentage varies considerably between countries. To investigate the prevalence of H. pylori infection, a cross-sectional epidemiological study, based on the serological determination of the IgG antibodies against H. pylori, was carried out in healthy Italian blood donors by using a commercially available kit. METHODS: From March 1995 to March 1997, a total of 2598 consecutive volunteer blood donors were tested for the presence of antibodies against H. pylori. All patients answered a detailed questionnaire which collected sociodemographic characteristics, and smoking, alcohol drinking and dietary habits. Test-positive subjects with gastrointestinal symptoms underwent endoscopy, with biopsies taken for histological diagnosis. RESULTS: The global prevalence of H. pylori infection in our study was 1161/2598 (45%). It was directly correlated with age (67% in subjects aged > or = 50 years). The prevalence of H. pylori infection was higher in men (46.4%) than women (38.4%), and more frequent in patients with a low educational level, in the lower quintile of height and in the upper quintile of body mass index (BMI). No significant association with smoking and alcohol drinking was found. Inverse associations were found with elevated consumption of milk (chi-square for trend 5.49, P < 0.05), but not other examined food groups. Multivariate analysis selected sex, age, BMI and educational level as the variables independently related to H. pylori infection. CONCLUSION: This study confirms relatively high prevalence of H. pylori seropositivity among Italian healthy adults and points to sex, age, BMI and sociocultural class as persisting determinant features of H. pylori infection.

Reducing colorectal cancer mortality by repeated faecal occult blood test: a nested case-control study.

Randomised trials have shown the efficacy of faecal occult blood testing (FOBT) in reducing colorectal cancer mortality, but observational studies are needed to monitor such efficacy in population programmes. We conducted a nested case-control study on a cohort of 21,879 subjects who participated in a colorectal screening programme from 1978 to 1995, undergoing at least one FOBT test. 95 fatal cases of colorectal cancer were eligible for the study. For each fatal case, 5 non-fatal matched controls were randomly selected from the cohort. FOBT screening history was less common among cases than controls. The odds ratio of colorectal cancer mortality among 'attenders' (defined as those who underwent a second FOBT within 2 years of study entry) with respect to 'non-attenders' was 0.64 (95% confidence interval 0.36-1.15). We also computed odds ratios defining exposure as one or more tests in the detectable preclinical period, hypothesising various lengths for the latter, which, however, yielded an efficacy estimate biased towards the null. A strong inverse relationship was observed between mortality and the number of tests, but this phenomenon is interpretable as 'healthy screenee bias'. The results suggest that the potential efficacy in preventing colorectal cancer mortality through annual FOBT screening may be of the order of one third.

Preoperative radiation therapy for patients with T2-T3 carcinoma of the middle-to-lower rectum.

BACKGROUND: The aim of this study was to determine the effects of preoperative radiation therapy (RT) on the objective responses of patients with rectal carcinoma to their treatment. These effects were assessed with endorectal ultrasound (EUS) evaluation, histopathologic grading of postirradiation tumor mass reduction in the surgical specimen, and analysis of local and distant recurrences. METHODS: Fifty-nine consecutive patients with palpable adenocarcinoma of the rectum, classified by EUS examination as uT2-uT3 (which meant involvement of the muscular layer and the perirectal adipose tissue, respectively), received 45 grays (Gy) over 3 weeks (2 fractions per day of 1.5 Gy each) given as photons supplied through a high-energy linear accelerator (18 MeV) through 3 fields: 1 posterior and 2 opposed lateral. Surgery was scheduled 2-3 weeks after the end of RT and included a sphincter-saving resection (39 patients) and an abdominoperineal resection (20 patients). RESULTS: Greatest tumor dimension, which was evaluated with rectal endoscopy before RT and measurement of the lesion in the fresh specimen, showed a decrease among two-thirds of the patients; the decrease amounted to approximately one-third of the initial measurement. An echoendoscopic downstaging of the T component was observed among 24.5% of the patients. Complete tumor regression occurred in 8.5% of patients, whereas in 69% only the presence of rare residual cancer cells and prominent fibrosis were found at the pathologic examination of the specimen. Finally, the tumor regressed to pT0 and pT1 in 13.6% of the patients. The overall and disease free 2-year survival rates were 94.0% and 73.7%, respectively, for pT2 and pT3 patients, and 100% for those whose tumors regressed to pT0-pT1 after a median follow-up of 2 years. CONCLUSIONS: Hyperfractionated preoperative RT appears to be efficient in achieving tumor shrinkage and destroying the tumor. In this study, the subset of patients with a good response to RT therapy had an excellent clinical outcome at the time of a 2-year follow-up.

Total parenteral nutrition and tumor growth in malnourished patients with gastric cancer.

AIMS AND BACKGROUND: Evidence that total parenteral nutrition (TPN) can stimulate tumor growth in humans is scanty and contradictory. The purpose of this study was to evaluate the impact of TPN on tumor cell proliferation in malnourished patients receiving preoperative TPN. METHODS: We evaluated variations in the S-phase cell fraction, defined as 3H-thymidine labeling index (TLI), before and after 10 days of TPN or non-administration of nutritional support in 19 malnourished patients (weight loss, > or = 10%) with gastric cancer. TLI was determined on endoscopic biopsies at the time of diagnosis, and subsequently on the operative specimen or through intraoperative sampling. RESULTS: At diagnosis, a higher median TLI value was observed in the control than in the TPN group. Administration of TPN enhanced tumor cell proliferation in 50% of patients; however, at surgery there was no difference in the median TLI value of the two groups. CONCLUSIONS: The TPN regimen seems to be associated with increased tumor cell proliferation, even though this stimulating effect was moderate and at surgery the TLIs of TPN patients and controls were not different. Although the potential stimulation probably has little consequence for patients receiving short-term preoperative nutrition, it may call for further investigation in cancer patients undergoing long-term home TPN.