Sporadic and MEN1-related gastrinoma and Zollinger-Ellison syndrome: differences in clinical characteristics and survival outcomes.

PURPOSE: Gastrinoma with Zollinger-Ellison syndrome (ZES) may occur sporadically (Sp) or as part of the inherited syndrome of multiple endocrine neoplasia 1 (MEN-1). Data comparing Sp and MEN-1/ZES are scanty. We aimed to identify and compare their clinical features. METHODS: Consecutive patients with ZES were evaluated between 1992 and 2020 among a monocentric Italian patient cohort. RESULTS: Of 76 MEN-1 patients, 41 had gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), 18 of whom had ZES; of 320 Sp-GEP-NEN, 19 had Sp-ZES. MEN-1/ZES patients were younger (p = 0.035) and the primary MEN-1/ZES gastrinoma was smaller than Sp-ZES (p = 0.030). Liver metastases occurred in both groups, but only Sp-ZES developed extrahepatic metastases. 13 Sp-ZES and 8 MEN-1/ZES underwent surgery. 8 Sp-ZES and 7 MEN-1/ZES received somatostatin analogs (SSAs). Median overall survival (OS) was higher in MEN-1/ZES than in Sp-ZES (310 vs 168 months, p = 0.034). At univariate-logistic regression, age at diagnosis (p = 0.01, OR = 1.1), G3 grading (p = 0.003, OR = 21.3), Sp-ZES (p = 0.02, OR = 0.3) and presence of extrahepatic metastases (p = 0.001, OR = 7.2) showed a significant association with OS. At multivariate-COX-analysis, none of the variables resulted significantly related to OS. At univariate-logistic regression, age (p = 0.04, OR = 1.0), size (p = 0.039, OR = 1.0), G3 grade (p = 0.008, OR = 14.6) and extrahepatic metastases (p = 0.005, OR = 4.6) were independently associated with progression-free survival (PFS). In multivariate-COX-analysis, only extrahepatic metastases (p = 0.05, OR = 3.4) showed a significant association with PFS. Among SSAs-treated patients, MEN-1/ZES showed better PFS (p = 0.0227). After surgery, the median PFS was 126 and 96 months in MEN-1 and Sp, respectively. CONCLUSION: MEN-1/ZES patients generally show better OS and PFS than Sp-ZES as well as better SSAs response.

Second primary neoplasms in patients with lung and gastroenteropancreatic neuroendocrine neoplasms: Data from a retrospective multi-centric study.

BACKGROUND: Patients with sporadic neuroendocrine neoplasms may exhibit a higher risk of a second primary tumor than the general population. AIM: This study aimed to analyze the occurrence of second primary malignancies. METHODS: A retrospective cohort of 2757 patients with sporadic lung and gastro-entero-pancreatic neuroendocrine neoplasms, managed at eight Italian tertiary referral Centers, was included. RESULTS: Between 2000 and 2019, a second primary malignancy was observed in 271 (9.8%) neuroendocrine neoplasms patients with 32 developing a third tumor. There were 135 (49.8%) females and the median age was 64 years. The most frequent locations of the second tumors were breast (18.8%), prostate (12.5%), colon (9.6%), blood tumors (8.5%), and lung (7.7%). The second primary tumor was synchronous in 19.2% of cases, metachronous in 43.2%, and previous in 37.6%. As concerned the neuroendocrine neoplasms, the 5- and 10-year survival rates were 87.8% and 74.4%, respectively. PFS for patients with a second primary malignancy was shorter than for patients without a second primary malignancy. Death was mainly related to neuroendocrine neoplasms. CONCLUSION: In NEN patients the prevalence of second primary malignancies was not negligible, suggesting a possible neoplastic susceptibility. Overall survival was not affected by the occurrence of a second primary malignancy.

Risk of preoperative understaging of duodenal neuroendocrine neoplasms: a plea for caution in the treatment strategy.

PURPOSE: Pretreatment staging is the milestone for planning either surgical or endoscopic treatment in duodenal neuroendocrine neoplasms (dNENs). Herein, a series of surgically treated dNEN patients was evaluated to assess the concordance between the pre- and postsurgical staging. METHODS: Retrospective analysis of patients with a histologically confirmed diagnosis of dNENs, who underwent surgical resection observed at eight Italian tertiary referral centers. The presurgical TNM stage, based on the radiological and functional imaging, was compared with the pathological TNM stage, after surgery. RESULTS: From 2000 to 2019, 109 patients were included. Sixty-six patients had G1, 26 a G2, 7 a G3 dNEN (Ki-67 not available in 10 patients). In 46/109 patients (42%) there was disagreement between the pre- and postsurgical staging, being it understaged in 42 patients (38%), overstaged in 4 (3%). As regards understaging, in 25 patients (22.9%), metastatic loco-regional nodes (N) resulted undetected at both radiological and functional imaging. Understaging due to the presence of distal micrometastases (M) was observed in 2 cases (1.8%). Underestimation of tumor extent (T) was observed in 12 patients (11%); in three cases the tumor was understaged both in T and N extent. CONCLUSIONS: Conventional imaging has a poor detection rate for loco-regional nodes and micrometastases in the presurgical setting of the dNENs. These results represent important advice when local conservative approaches, such as endoscopy or local surgical excision are considered and it represents a strong recommendation to include endoscopic ultrasound in the preoperative tools for a more accurate local staging.

Impact of the SARS-CoV2 pandemic dissemination on the management of neuroendocrine neoplasia in Italy: a report from the Italian Association for Neuroendocrine Tumors (Itanet).

INTRODUCTION: The organization of the healthcare system has significantly changed after the recent COVID-19 outbreak, with a negative impact on the management of oncological patients. The present survey reports data collected by the Italian Association for Neuroendocrine Tumors on the management of patients with neuroendocrine neoplasia (NEN) during the pandemic dissemination. METHODS: A survey with 57 questions was sent to NEN-dedicated Italian centers regarding the management of patients in the period March 9, 2020, to May 9, 2020 RESULTS: The main modification in the centers' activity consisted of decreases in newly diagnosed NEN patients (- 76.8%), decreases in performed surgical procedures (- 58%), delays to starting peptide receptor radionuclide therapy (45.5%), postponed/canceled follow-up examinations (26%), and canceled multidisciplinary teams' activity (20.8%). A low proportion of centers (< 10%) reported having to withdraw systemic anti-tumor medical treatment due to concerns about the pandemic situation, whereas PRRT was withdrawn from no patients. CONCLUSION: Although the COVID-19 outbreak induced the centers to reduce some important activities in the management of NEN patients, the Italian network was able to provide continuity in care without withdrawing anti-tumor treatment for the majority of patients.

Mutation in NADPH oxidase 3 (NOX3) impairs SHH signaling and increases cerebellar neural stem/progenitor cell proliferation.

Abnormalities in cerebellar structure and function may cause ataxia, a neurological dysfunction of motor coordination. In the course of the present study, we characterized a mutant mouse lineage with an ataxia-like phenotype. We localized the mutation on chromosome 17 and mapped it to position 1534 of the Nox3 gene, resulting in p.Asn64Tyr change. The primary defect observed in Nox3eqlb mice was increased proliferation of cerebellar granule cell precursors (GCPs). cDNA microarray comparing Nox3eqlb and BALB/c neonatal cerebellum revealed changes in the expression of genes involved in the control of cell proliferation. Nox3eqlb GCPs and NSC produce higher amounts of reactive oxygen species (ROS) and upregulate the expression of SHH target genes, such as Gli1-3 and Ccnd1 (CyclinD1). We hypothesize that this new mutation is responsible for an increase in proliferation via stimulation of the SHH pathway. We suggest this mutant mouse lineage as a new model to investigate the role of ROS in neuronal precursor cell proliferation.

Liver stiffness measurement reliability and main determinants of point shear-wave elastography in patients with chronic liver disease.

BACKGROUND: Liver stiffness (LS) measured by transient elastography (TE) accurately predicts the severity of chronic liver diseases (CLD). Point quantification shear-wave elastography (pSWE) is a new technique incorporated into a conventional ultrasound system for measuring LS. We evaluated pSWE feasibility, reproducibility and diagnostic accuracy in consecutively recruited CLD patients who concomitantly underwent TE and liver biopsy. AIM: To evaluate pSWE feasibility, reproducibility and diagnostic accuracy in consecutively recruited CLD patients who concomitantly underwent TE and liver biopsy. METHODS: Over 2 years 186 CLD patients (116 males, 132 viral hepatitis) consecutively underwent pSWE (10 valid measurements by ElastPQ) blindly performed by two raters. A further operator performed TE. Inter-observer agreement for pSWE was analysed by intraclass correlation coefficient (ICC) and correlated with histological liver fibrosis (METAVIR). Main determinants of pSWE were investigated by linear regression model. RESULTS: Three hundred and seventy-two (100%) reliable measurements were obtained by pSWE and 184 by TE (99%). LS was 8.1 ± 4.5 kPa for pSWE with the first rater and 8.0 ± 4.2 kPa with the second one vs. 8.8 ± 3.6 kPa for TE. pSWE ICC was 0.89 (95% CI 0.85-0.91), not influenced by age, sex, BMI, liver enzymes, liver aetiology. ICC increased over time with year 1 at 0.86 and 95% CI 0.81-0.90 vs. year 2 at 0.92 and 95% CI 0.87-0.95. Liver fibrosis was the only independent determinant of LS on pSWE. The AUROCs for diagnosing F ≥ 2, F ≥ 3 and F = 4 were 0.77, 0.85 and 0.88 for pSWE vs. 0.81, 0.88 and 0.94 for TE. After 1-year training they were 0.86, 0.94 and 0.91. CONCLUSION: Point quantification shear-wave elastography reliably and reproducibly evaluates liver stiffness, matching transient elastography for accuracy after a 1-year learning curve or 130 examinations.

Gastro-esophageal reflux and antisecretory drugs use among patients with chronic autoimmune atrophic gastritis: a study with pH-impedance monitoring.

BACKGROUND: Patients with chronic autoimmune atrophic gastritis (CAAG) often refer digestive symptoms and are prescribed antisecretory medications. Aims were to investigate: (i) gastro-esophageal reflux (GER), (ii) psychopathological profile, (iii) frequency of use and clinical benefit of antisecretory drugs. METHODS: Prospective observational study on 41 CAAG patients who underwent: 24 h multichannel intra-luminal impedance-pH (MII-pH) monitoring off-therapy, standardized medical interview and psychological questionnaire (i.e., SCL-90R). The medical interview was repeated at least 1 month after MII-pH in patients who were using antisecretory drugs. Statistical analysis was performed calculating median (10th-90th percentiles) and risk ratios (RR) with 95% confidence interval. KEY RESULTS: Median intra-gastric pH was 6.2 (4.6-7.0). One patient had acid reflux (AC) associated with symptoms, five had increased total reflux number and four had symptoms associated to non-acid reflux (NA) (patients referred as 'GER positive'). Using patients 'GER negative' with normal SCL-90R as reference, the RR of being symptomatic in patients GER positive was 2.1 (1.1-4.1) if SCL-90R was normal and 0.9 (0.5-1.7) if it was altered (difference in RR significant being p = 0.04). Seventeen/28 (61%) symptomatic patients were on antisecretory drugs, which were stopped in 16 of them according to results of MII-pH and clinical evaluation after 574 days (48-796) showed that symptoms were unchanged. CONCLUSIONS & INFERENCES: In patients with CAAG (i) AC reflux rarely occurred whereas increased NA reflux was not infrequent both being related to symptoms in some patients, (ii) psychopathological profile has a role in symptoms' occurrence, (iii) antisecretory drugs were generally inappropriately used and clinically ineffective.

Feasibility and reproducibility of spleen transient elastography and its role in combination with liver transient elastography for predicting the severity of chronic viral hepatitis.

Liver transient elastography (L-TE) is a reliable, noninvasive predictor of disease severity in chronic liver disease of viral aetiology (CLD). Owing to the relationships among severity of CLD, portal hypertension and spleen involvement, the assessment of splenic stiffness (S-TE) may have an added value in staging CLD. Of 132 CLD patients of viral aetiology, 48 with myeloproliferative disorders (MD) and 64 healthy volunteers (HV), were concurrently investigated by both L-TE and S-TE. Liver disease severity was staged by liver biopsy (LB; Metavir) taken concurrently with TE examination and upper gastrointestinal tract endoscopy for gastro-oesophageal varices. The S-TE inter-observer agreement was analysed by an intra-class correlation coefficient (ICC); L-TE and S-TE accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis assessed the independent effect of L-TE and S-TE as predictors of hepatic fibrosis stage. S-TE failed in 22 CLD (16.6%), 12 (25%) MD and 12 (18%) HV. In the three groups, the ICC was 0.89 (0.84-0.92), 0.90 (0.85-0.94) and 0.86(0.80-0.91), respectively. In the CLD group, L-TE and S-TE independently predicted significant fibrosis (OR 5.2 and 4.6) and cirrhosis (OR 7.8 and 9.1), but at variance from L-TE, S-TE was independent from liver necroinflammation and steatosis. The NPV of S-TE for gastro-oesophageal varices was 100% using a 48 kPa cut-off. In CLD, spleen stiffness alone or in combination with hepatic stiffness can be reliably and reproducibly assessed by TE with the added value of improving the noninvasive diagnosis of severe liver disease and excluding the presence of oesophageal varices.

Dual cut-off transient elastography to assess liver fibrosis in chronic hepatitis B: a cohort study with internal validation.

BACKGROUND: Transient elastography has gained popularity to stage liver fibrosis in chronic viral hepatitis, however, diagnostic cut-offs for severe fibrosis in chronic hepatitis B are poorly defined. AIM: To evaluate an algorithm with two distinct cut-offs for positive and negative prediction of significant fibrosis and cirrhosis in chronic hepatitis B patients. METHODS: Two cohorts of treatment-naïve patients with chronic hepatitis B (125 training and 92 validations) were consecutively and concurrently examined by percutaneous liver biopsy and transient elastography. Fibrosis was staged by Metavir (significant fibrosis = F ≥ 2; cirrhosis = F4) in ≥ 2 cm long liver tissue cores. RESULTS: A >13.1 kPa positive and a ≤ 9.4 kPa negative cut-off for cirrhosis had a >90% sensitivity and specificity, with an accuracy of 94%. The corresponding cut-offs for F ≥ 2 were >9.4 and ≤ 6.2 kPa, thus classifying 56% of patients with an overall accuracy of 90%. In the validation cohort, F4 and F ≥ 2 were predicted by the above transient elastography cut-offs with an overall accuracy >90%. In 165 patients with higher than upper limit of normal transaminase activity the dual cut-off algorithm of transient elastography was as accurate as in the 52 patients with normal alanine aminotransferase values in the prediction and exclusion of cirrhosis, only. CONCLUSIONS: A dual cut-off algorithm allowed for correctly classifying both significant fibrosis and cirrhosis in the majority of the patients with chronic hepatitis B, independent of alanine aminotransferase values, thus reducing the need for liver biopsy investigations.

Chromogranin A levels in chronic liver disease and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the relevant cause of death in patients with compensated cirrhosis. Alpha-fetoprotein (AFP) is used for screening HCC, with limited success. AIM: We evaluated plasma chromogranin A (CgA) as a marker of HCC. PATIENTS: CgA plasma levels and AFP serum levels were prospectively measured in 30 patients with HCC, 14 with cirrhosis, 79 with chronic hepatitis and 65 controls. METHODS: CgA was measured with an enzyme-linked immunosorbent assay (DAKO A/S Glostrup, Denmark). AFP was measured by electrochemiluminoimmunoassay (Elecsys, Roche S.p.A., Italy). RESULTS: CgA levels were significantly higher in the three groups of patients than in controls and in patients with HCC they were significantly higher than in chronic hepatitis patients [median 44.5 (interquartile range 21-145.9)U/L vs. 15.3 (10.9-29.25)U/L, p<0.001]. AFP values were above the upper reference limit in 75% of patients with HCC, 50% of cirrhotic patients and 11% of chronic hepatitis patients (p<0.005). CgA values significantly correlated with AFP levels (r(s)=0.42, p<0.0001). The overall diagnostic accuracy of CgA was 75% (CI 66-82), with a sensitivity of 70% (CI 50.6-85.2) and a specificity of 67% (CI 55.9-76.3). CONCLUSIONS: Despite the evidence of higher CgA levels in patients with HCC, this test has low-diagnostic accuracy. Its pathophysiological meaning remains unknown, even if it could suggest an endocrine phenotype of HCC.

Evaluation of IGF-I levels during long-term somatostatin analogs treatment in patients with gastroenteropancreatic endocrine tumors.

Previous experiments reported desensitization to SS action in rat anterior pituitary cells and cell lines. The aim of the study was to verify whether the lack of desensitization to SS analogs (SSa) observed in acromegalic patients was also present in subjects with normal hypothalamic-pituitary function. The effect of chronic treatment with octreotide long-acting release (o-LAR, 10-30 mg/28 days) on IGF-I levels was then evaluated in 23 patients with gastroenteropancreatic (GEP) endocrine tumors (8 gastrinomas, 6 carcinoids, and 9 functioning pancreatic tumors). Serum IGF-I, clinical symptoms, plasma chromogranin-A (CgA) and markers of hepatic synthesis were evaluated before and after a short-term period in all the patients (median 4.5 months), after a medium-term period in 12 (median 18 months) and after a long-term follow-up period in 9 of them (median 48 months). Mean IGF-I levels decreased from 17.3+/-7.0 to 12.8+/-6.2 nmol/l in the short-term (p<0.005) being reduced from baseline concentrations in 87% and under the normal range for age in 35% of patients. Afterwards, they always remained stable both in the medium- and long-term periods, still being low in 3/12 and 2/9 patients, respectively. No alterations in biochemical markers of liver function were found either before or during therapy. No correlation between IGF-I levels, CgA concentrations and/or clinical definitive outcome was observed. In conclusion, the study demonstrated that: a) similarly to that observed in acromegalic patients, chronic o-LAR treatment did not induce desensitization of pituitary SS receptors (SSR) in humans with intact hypothalamic-pituitary axis, and b) in patients with GEP endocrine tumors, GH/IGF-I inhibition did not contribute to SSa efficacy.

Elective surgery for benign liver tumours.

BACKGROUND: Benign liver tumours (haemangioma, focal nodular hyperplasia, and hepatic adenoma) have different prevalence and prognosis. Spontaneous rupture and malignant transformation can complicate hepatic adenoma. Elective surgery is controversial, and indications are represented by uncertain diagnosis, presence of symptoms, and prevention of major complications. OBJECTIVES: To assess the beneficial and harmful effects of elective surgery of benign liver tumours. We identified 31 cases series. These were small (with less than 60 participants) and the types of tumours mixed. These studies reported no significant mortality, but in the six studies with mortality it ranged from 1% to 17%. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (searches in Issue 1, 2006), MEDLINE, EMBASE, CancerLit, and Science Citation Index Expanded (SCI-EXPANDED) (searched December 2005). A further search included the proceedings of major hepatological and surgical congresses (Annual Meetings of the American Association for the Study of the Liver (AASLD) and European Association for the Study of the Liver (EASL)), and examination of the references of relevant papers and reference lists of the identified studies. SELECTION CRITERIA: Randomised clinical trials in adult patients with benign liver tumours without indications for emergency surgery in which elective surgery (resection) versus no intervention or sham operation are compared. DATA COLLECTION AND ANALYSIS: All trials identified through searches were evaluated for eligibility for inclusion. We intended to extract relevant data in order to analyse the outcomes as per our published protocol using intention-to-treat analysis. MAIN RESULTS: We could not identify any randomised clinical trials. AUTHORS' CONCLUSIONS: We were unable to find evidence supporting or refuting elective surgery for patients with benign liver tumours. We need large, long-term randomised clinical trials with adequate methodology to assess the benefits and harms of elective surgery.

Inducing mutations in the mouse genome with the chemical mutagen ethylnitrosourea.

When compared to other model organisms whose genome is sequenced, the number of mutations identified in the mouse appears extremely reduced and this situation seriously hampers our understanding of mammalian gene function(s). Another important consequence of this shortage is that a majority of human genetic diseases still await an animal model. To improve the situation, two strategies are currently used: the first makes use of embryonic stem cells, in which one can induce knockout mutations almost at will; the second consists of a genome-wide random chemical mutagenesis, followed by screening for mutant phenotypes and subsequent identification of the genetic alteration(s). Several projects are now in progress making use of one or the other of these strategies. Here, we report an original effort where we mutagenized BALB/c males, with the mutagen ethylnitrosourea. Offspring of these males were screened for dominant mutations and a three-generation breeding protocol was set to recover recessive mutations. Eleven mutations were identified (one dominant and ten recessives). Three of these mutations are new alleles (Otop1mlh, Foxn1sepe and probably rodador) at loci where mutations have already been reported, while 4 are new and original alleles (carc, eqlb, frqz, and Sacc). This result indicates that the mouse genome, as expected, is far from being saturated with mutations. More mutations would certainly be discovered using more sophisticated phenotyping protocols. Seven of the 11 new mutant alleles induced in our experiment have been localized on the genetic map as a first step towards positional cloning.

Inducing mutations in the mouse genome with the chemical mutagen ethylnitrosourea

When compared to other model organisms whose genome is sequenced, the number of mutations identified in the mouse appears extremely reduced and this situation seriously hampers our understanding of mammalian gene function(s). Another important consequence of this shortage is that a majority of human genetic diseases still await an animal model. To improve the situation, two strategies are currently used: the first makes use of embryonic stem cells, in which one can induce knockout mutations almost at will; the second consists of a genome-wide random chemical mutagenesis, followed by screening for mutant phenotypes and subsequent identification of the genetic alteration(s). Several projects are now in progress making use of one or the other of these strategies. Here, we report an original effort where we mutagenized BALB/c males, with the mutagen ethylnitrosourea. Offspring of these males were screened for dominant mutations and a three-generation breeding protocol was set to recover recessive mutations. Eleven mutations were identified (one dominant and ten recessives). Three of these mutations are new alleles (Otop1mlh, Foxn1sepe and probably rodador) at loci where mutations have already been reported, while 4 are new and original alleles (carc, eqlb, frqz, and Sacc). This result indicates that the mouse genome, as expected, is far from being saturated with mutations. More mutations would certainly be discovered using more sophisticated phenotyping protocols. Seven of the 11 new mutant alleles induced in our experiment have been localized on the genetic map as a first step towards positional cloning.

Human IgG but not IgM antibodies can protect mice from the challenge with live O6 Escherichia coli.

We evaluated the ability of human anti-lipopolysaccharide (LPS) O6 immunoglobulin G (IgG) and IgM antibodies to protect mice challenged with Escherichia coli serotype O6:K2ac. Purified whole IgG, commercial gammaglobulin, whole IgM-effluent, pool of normal human serum (NHS), agammaglobulinaemic serum (test groups) or phosphate-buffered saline (control group) was injected into adult male 18 h before a challenge with viable O6 E. coli. The mortality rate was assessed over a period of 72 h. To determine the opsonic and phagocytic activity of the antibody isotypes, we incubated peritoneal macrophages from the control and test groups collected at different times after challenge with the live bacteria with acridine orange for fluorescent analysis. Tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 were quantified in serum of both the test and control groups. All mice that received commercial gammaglobulin or NHS survived. Purified whole IgG (containing 1.1 mg/l of anti-LPS O6 IgG antibodies) protected 87.5% of the animals tested in this experiment, while whole IgM-enriched effluent with 1.5 mg/l of anti-LPS O6 IgM antibodies protected only 12.5%. The agamma serum showed no protective capacity compared with PBS (serving as control). The minimal concentration of anti-LPS O6 IgG antibodies able to protect 50% of animals was 0.137 mg/l of purified whole IgG. Whole IgM-enriched effluent showed no protective capacity independently of the concentration tested (0.048-17.0 mg/l of anti-LPS O6 IgM antibodies). Fluorescent analysis of peritoneal macrophages from animals pretreated with purified whole IgG showed no bacteria at 8 h after the challenge. By contrast, whole IgM effluent showed an increasing number of live bacteria at the same time. Mice that had received whole IgM effluent (1.5 mg/l of anti-LPS O6 IgM antibodies) before the challenge with LPS O6 presented 20.5 microg/l of IL-6 and 1.5 microg/l of TNF-alpha. Serum from animals pretreated with purified IgG did not present any detectable pro-inflammatory cytokine. Our findings suggest that IgG but not IgM antibodies protect animals from a challenge with E. coli O6 serotype.

Gastric involvement in a patient with secondary syphilis.

A 30-year-old man was referred because of a short lasting history of severe epigastric pain and early satiety, with remarkable weight loss. Physical examination was fully consistent with secondary syphilis and upper GI tract endoscopy revealed multiple gastric mucopurulent erosions and several nodular lesions ranging from 2 to 3 cm in diameter, with central crater, abruptly ending at the pyloric level. Appropriate antibiotic treatment obtained a dramatic improvement and complete reversal of cutaneous and gastric lesions.

Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids.

OBJECTIVE: In atrophic body gastritis (ABG) chronic hypergastrinaemia stimulates enterochromaffin-like (ECL) cell proliferation with development of cell hyperplasia, dysplasia and possibly type-1 gastric carcinoids. As circulating chromogranin A (CgA) levels are a marker of neuroendocrine tumours, we evaluated the clinical usefulness of CgA assay in ABG patients to detect those with carcinoids. DESIGN AND METHODS: Plasma CgA levels were measured using a commercial ELISA in 45 healthy volunteers, nine patients with type-1 gastric carcinoids and 43 consecutive ABG patients (21 without and 22 with ECL cell hyperplasia/dysplasia). RESULTS: CgA levels were significantly higher in ABG patients with and without gastric carcinoids than in healthy subjects (P < 0.001). The highest values occurred in patients with carcinoids (median (interquartile range): 58.1 (44.5-65.3) U/l) and with ECL cell hyperplasia/dysplasia (35.5 (31.8-48.65) U/l) but there were no significant differences in CgA among the various subgroups of ABG patients classified according to ECL cell status. Nevertheless, in ABG patients without carcinoids CgA values correlated with the presence and severity of ECL cell lesions (r(s) = 0.428, P < 0.01). The sensitivity and specificity of the CgA assay in identifying patients with carcinoids were 100 and 23% respectively. CONCLUSIONS: CgA plasma levels reflect the histological degree of ECL cell lesions in patients with ABG but the assay specificity is too low to detect among these patients those with gastric carcinoids.

Skin morphology of the mutant hairless USP mouse.

The morphology of the skin of the mutant hairless USP mouse was studied by histological, histochemical and immunohistochemical methods and compared to the skin of BALB/c mice. Representative sections of the dorsal skin from mice of both strains aged 18 days, and 1, 3, 6, and 8 months were studied. Sections stained with hematoxylin and eosin showed cystic formations called utricles and dermal cysts in the dermis that increased in size and number during growth. Skin thickness increased significantly at 8 months. Sections stained with picrosirius and examined with polarized light, displayed different colors, suggesting different thicknesses of dermal collagen fibers (probably types I and III). Weigert, Verhoeff and resorcin-fuchsin stains revealed fibers of the elastic system. The PAS and Alcian blue methods revealed neutral and acid glycosaminoglycans in the skin ground substance of both mouse strains. Immunohistochemical staining for fibronectin and laminin did not show differences between the mutant and BALB/c mice. Mast cells stained by the Gomori method and macrophages positive for HAM 56 antibodies were observed in both mouse strains. Except for the presence of enlarged cysts in the hairless strain, no qualitative differences were found during development of the skin of BALB/c and the mutant hairless mice.

Skin morphology of the mutant hairless USP mouse

The morphology of the skin of the mutant hairless USP mouse was studied by histological, histochemical and immunohistochemical methods and compared to the skin of BALB/c mice. Representative sections of the dorsal skin from mice of both strains aged 18 days, and 1, 3, 6, and 8 months were studied. Sections stained with hematoxylin and eosin showed cystic formations called utricles and dermal cysts in the dermis that increased in size and number during growth. Skin thickness increased significantly at 8 months. Sections stained with picrosirius and examined with polarized light, displayed different colors, suggesting different thicknesses of dermal collagen fibers (probably types I and III). Weigert, Verhoeff and resorcin-fuchsin stains revealed fibers of the elastic system. The PAS and Alcian blue methods revealed neutral and acid glycosaminoglycans in the skin ground substance of both mouse strains. Immunohistochemical staining for fibronectin and laminin did not show differences between the mutant and BALB/c mice. Mast cells stained by the Gomori method and macrophages positive for HAM 56 antibodies were observed in both mouse strains. Except for the presence of enlarged cysts in the hairless strain, no qualitative differences were found during development of the skin of BALB/c and the mutant hairless mice.