Improvement of Symptoms in Patients Affected by Chronic Atrophic Gastritis Using L-Cysteine (Acetium®).

BACKGROUND: Chronic atrophic gastritis (CAG) alone is a precancerous condition for gastric cancer. Achlorhydria plays an important role in the formation of a class I carcinogen, acetaldehyde. L-cysteine has been claimed to bind acetaldehyde covalently. Symptoms are present in 55% of CAG patients, of whom 70% have upper gastrointestinal complaints. The aim of this study was to investigate the properties of L-cysteine in the modification of symptom patterns in CAG patients. METHODS: Consecutive patients with histological diagnosis of CAG (OLGA ≥1 with gastric corpus involvement) were evaluated with serological determination of gastric function, clinical assessment of symptoms using the visual analog score (VAS) and the global symptomatic score (GSS), and considered for therapy with L-cysteine, 300 mg daily. Data regarding symptoms were collected at enrollment and after 3, 6, 12, 18, and 24 months, with an ultimate follow-up of 2 years. RESULTS: A total of 330 patients with CAG were divided in group 1 (77 patients treated with L-cysteine) and group 2 (50 patients who received no specific treatment - control group). A statistically significant improvement in the VAS score (7.8 at baseline vs. 4.5 after 24 months; p < 0.01) was observed in patients treated with L-cysteine, while no significant changes in symptom pattern/intensity were recorded in the 2-year follow-up of untreated patients with CAG. CONCLUSIONS: Long-term treatment with L-cysteine provides symptom improvement in CAG patients and might be proposed as maintenance therapy in such patients.

Appropriateness of Proton Pump Inhibitor Prescription Evaluated by Using Serological Markers.

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy.

Pepsinogen II in gastritis and Helicobacter pylori infection.

BACKGROUND AND AIM: In the gastric mucosa, pepsinogen II (PgII) is produced/secreted by glands in the mucus-secreting antral and cardia compartments, but also by the chief cells and the oxyntic glands. Increasing PgII serum levels are associated with the whole spectrum of gastric inflammatory diseases, including gastritis induced by Helicobacter pylori (H. pylori). This review critically addresses the clinical value of PgII serology for assessing gastric mucosal inflammation, and as a marker of H. pylori status, in both H. pylori-positive patients and after eradication therapy. RESULTS: A search in PubMed/Scopus records yielded 39 out of 1190 published scientific studies meeting the selection criteria for this study. In the studies considered, PgII levels were significantly associated with non-atrophic gastric inflammatory lesions (p-values: 0.025-0.0001). H. pylori-positive patients had significantly higher PgII levels than H. pylori-negative individuals (p-values: 0.o5-0.0001). While a significant drop in serum PgII levels is consistently reported in H. pylori-eradicated patients (p-values: from 0.05 to 0.0001), inconsistencies in the related negative and positive predictive values significantly lower the clinical reliability of PgII testing by comparison with other available non-invasive tests. CONCLUSIONS: PgII serology may provide clinically useful information on gastric inflammatory diseases, particularly if they are non-atrophic. PgII serology is inconsistent, however, for the purposes of distinguishing patients whose H. pylori eradication therapy is successful from those who remain infected.

Local excision of T1 colorectal cancer: good differentiation, absence of lymphovascular invasion, and limited tumor radial infiltration (≤4.25 mm) may allow avoiding radical surgery.

BACKGROUND: Early colorectal cancer (ECC) is defined as T1NXM0 colorectal cancer (CRC). Although a non-negligible number of T1-CRCs presents metastatic lymph-nodes, local excision is increasingly proposed as alternative to radical resection. Several criteria have been suggested to identify low-risk T1-CRC, but recommendations on this topic are still heterogeneous. This study aims to identify criteria associated with N+ T1-CRC, to select patients to undergo (or not) local excision. METHODS: A retrospective analysis of demographic, clinical, and histology criteria of 122 consecutive T1-CRC patients undergoing radical resection at Parma University Hospital between 2000 and 2018 has been performed. RESULTS: Lymph-node metastasis (LNM) was observed in 15/122 patients (12.3%). No LNM was observed among well-differentiated (G1) tumors (0/37), while 10/65 (15.4%) G2 cases as well as 5/20 (25%) G3 patients presented LNM. G1 was associated with absence of LNM (p = 0.013). After excluding G1 patients, the rate of N + T1-CRC was 17.6% (15/85). LNM was observed in 4/8 (50%) patients with lymphovascular invasion (LVI) and in 11/77 (14.2%) without LVI. LVI resulted being associated with LNM (p < 0.042). LNM was reported in 28.3% of cases with a tumor infiltration >4.25 mm (13/46), compared to 5.1% in cases with an infiltration ≤4.25 mm (2/39) (p = 0.012). In Cox regression analysis, the higher hazard ratio (HR) was reported for the LVI + and infiltration >4.25 mm (HR 24.849). CONCLUSIONS: In patients with ECC (pT1NXM0), good differentiation (G1), absence of lymphovascular invasion (LVI-), and tumor radial infiltration ≤4.25 mm may allow performing local resection and avoiding radical surgery.

Three distinct outcomes in patients with colorectal adenocarcinoma and lymphovascular invasion: the good, the bad, and the ugly.

PURPOSE: In colorectal cancer (CRC), lymphovascular invasion (LVI) is a predictor of poor outcome and its analysis is nowadays recommended. Literature is still extremely heterogeneous, and we hypothesize that, within such a group of patients, there are any further predictors of survival. METHODS: A total of 2652 patients with I-III-stage CRC undergoing resection between 2002 and 2018 were included in a retrospective analysis of demographic, clinical, and histology with the aim of defining the impact of LVI on overall survival (OS) and its relationship with other prognostic factors. RESULTS: Overall, 5-year-OS was 62.6% (77-month-median survival). LVI was found in 558 (21%) specimens and resulted associated with 44.9%-5-year-OS (44 months) vs. 64.1% (104 months) of LVI cases. At multivariate analysis, LVI (p = 0.009), T3-4 (p < 0.001), and N ≠ 0 (p < 0.001) resulted independent predictors of outcome. LVI resulted as being associated with older age (p < 0.013), T3-4 (p < 0.001), lower grading (p < 0.001), N ≠ 0 (p < 0.001), mucinous histology (p < 0.001), budding (p < 0.001), and PNI (p < 0.001). Within the LVI + patients, T3-4 (p = 0.009) and N ≠ 0 (p < 0.001) resulted as independent predictors of shortened OS. In particular, N-status impacted the prognosis of patients with T3-4 tumors (p = 0.020), whereas it did not impact the prognosis of patients with T1-2 tumors (p = 0.393). Three groups (T1-2anyN, T3-4N0, T3-4 N ≠ 0), with distinct outcome (approximately 70%-, 52%-, and 35%-5-year-OS, respectively), were identified. CONCLUSIONS: LVI is associated with more aggressive/more advanced CRC and is confirmed as predictor of poor outcome. By using T- and N-stage, a simple algorithm may easily allow re-assessing the expected survival of patients with LVI + tumors.

Spontaneous Subarachnoid Haemorrhage in Spinal Hemangioblastoma: Illustrative Case and Discussion of a Pathophysiological Hypothesis.

Spontaneous non-aneurysmal subarachnoid haemorrhage (naSAH) is an unusual finding that could be burdened by significant mortality and morbidity rates. Rare pathologies and delayed diagnosis could be advocated as responsible of unfavourable outcomes. Herein, we describe an exceedingly rare giant lumbar spinal hemangioblastoma (80 × 23 mm) presenting as an intracranial naSAH. Based on our radiological and clinical findings a pathophysiological hypothesis linking intracranial naSAH to venous hypertension was discussed for the first time even among lumbar spinal tumors. Although rare, unusual causes should be investigated in presence of radiological atypical finding as a prompt evaluation and treatment could be needed.

2-Hydroxyglutarate Detection by Short Echo Time Magnetic Resonance Spectroscopy in Routine Imaging Study of Brain Glioma at 3.0 T.

OBJECTIVE: The objective of this study was to assess the effective performance of short echo time magnetic resonance spectroscopy (short TE MRS) for 2HG detection as biomarker of isocitrate dehydrogenase (IDH) status in all grade glioma (GL). METHODS: A total of 82 GL patients were prospectively investigated by short TE MRS at 3.0 T as part of a multimodal magnetic resonance imaging study protocol. Spectral analysis was performed using linear combination model. Tumor specimens were diagnosed as IDH mutant or wild type according to the 2016 World Health Organization (WHO) classification of brain tumors. Spectra were analyzed for the presence of 2HG. The performance of short TE MRS was evaluated in terms of sensitivity, specificity, and positive and negative likelihood ratio on the overall sample and on GL WHO grades II and III and glioblastoma separately. RESULTS: The specificity and sensitivity estimated on the overall sample were 88% and 77%, respectively. In GL WHO grades II and III, 100% specificity and 75% sensitivity were estimated. CONCLUSIONS: We reiterate the feasibility to identify IDH status of brain GL using short TE MRS at 3.0 T. The method can correctly detect 2HG as expression of IDH mutation in WHO grades II and III GL with a 100% specificity but a 75% sensitivity. In the evaluation of glioblastoma, short TE MRS performs poorly having a 17% false positive rate.

The role of endoscopic ultrasound in children with Pancreatobiliary and gastrointestinal disorders: a single center series and review of the literature.

BACKGROUND: The role of endoscopic ultrasound (EUS) in the management of pancreatobiliary and digestive diseases is well established in adults, but it remains limited in children. The aim of this study was to evaluate the feasibility, safety, and clinical impact of EUS use in children. METHODS: This is a retrospective analysis of a prospectively acquired database of consecutive pediatric (< 18 years) patients presenting an indication for EUS for pancreatobiliary and gastrointestinal disorders. RESULTS: Between January 2010 and January 2016, 47 procedures were performed in 40 children (mean age of 15.1 ± 4.7 years; range 3-18). The majority of EUS (n = 32; 68.1%) were performed for pancreatobiliary and upper gastrointestinal pathologies, including suspected common bile duct stones (CBDs), acute biliary pancreatitis, recurrent/chronic pancreatitis, cystic pancreatic mass, recurrent hypoglycemia, duodenal polyp, gastric submucosal lesion, and perigastric abscess. In only 2 out of 18 children with suspected CBDs or acute biliary pancreatitis, EUS confirmed CBDs. EUS-guided fine needle aspiration was performed in 3 (6.4%) patients. Fifteen (31.9%) procedures were performed for lower gastrointestinal tract disorders, including suspected anal Crohn's disease, fecal incontinence, and encopresis. Overall, EUS had a significant impact on the subsequent clinical management in 87.2% of patients. CONCLUSION: The present findings were consistent with results observed in the current relevant literature and support EUS as a safe and feasible diagnostic and therapeutic tool, which yields a significant clinical impact in children with pancreatobiliary and gastrointestinal disorders.

Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer.

AIM: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC). MATERIALS & METHODS: Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone. RESULTS: Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone. CONCLUSION: A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.

PPIs and gastric cancer: any causal relationship?

Hydrochloric acid is crucial in gastric physiology. In 1978 cimetidine, the first H2 antagonist of histamine receptors on the gastric parietal cell was introduced into therapy, inducing acid. Lasting the years, several studies focused on the potential relationship between inducing hypo-achlorhydria and risk of developing gastric cancer. In 1988 omeprazole, the first proton pump inhibitor, entered therapy. In 1996, Kuipers underlined the danger of progression of chronic atrophic gastritis in subjects taking PPIs. In 2018, one paper from Korea and an another on from Sweden suggested a possible relationship between long-term PPI therapy and the development of gastric cancer. Over the years, several articles, meta-analyzes and population based  focused on relationship between long-term of PPI use and the onset of gastric cancer, with conflicting results. As reported, the presence of bias in the collection of cases, in particular concerning the evaluation of the H.p. status and presence of atrophic gastritis and intestinal metaplasia in subjects treated with PPI, can lead to noticeable errors in the results and conclusions, as demonstrated in the literature by exhaustive methodological studies of pharmacoepidemiology. A possible bias in the collection of case histories is due to the fact that PPIs are often administered to dyspeptic patients, among which there are patients already carriers of gastric neoplasia: the so-called inverse causality.  Literature data, amended by methodological bias (sampling errors, lack of comparative assessment of Hp status and atrophic gastritis) NOT support a causal relationship between long-term PPIs therapy and the onset of gastric cancer.

A comparison of different symptomatic reflux esophagitis treatments: A real-world study.

BACKGROUND: Proton pump inhibitors (PPIs) are currently the reference drugs for gastroesophageal reflux disease (GERD), but symptoms often recur after their withdrawal. Moreover, whether prokinetics or barrier drugs used alongside PPIs are more effective remains under debate. OBJECTIVES: The aim of the study was to assess the efficacy of different therapeutic approaches to GERD treatment. MATERIAL AND METHODS: We enrolled 211 grade A reflux esophagitis patients who consented to participate in this non-randomized, open-label trial. The study consisted of 6 sequentially administered medical treatments for GERD, lasting 2 months, with a 3-week washout period between each drug schedule: Group A: PPI (esomeprazole 40 mg/day before breakfast); Group B: mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, 3 times daily after a meal); Group C: prokinetics (levosulpiride 25 mg or domperidone 10 mg, 3 times daily before a meal); Group D: barrier drug (alginate 3 times daily after a meal); Group E: PPI (esomeprazole 40 mg/day before breakfast) and mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, before sleep); Group F: PPI (esomeprazole 40 mg/day before breakfast) and prokinetics (levosulpiride 25 mg or domperidone 10 mg before lunch and dinner). Symptoms were evaluated using the visual analogue scale (VAS) and global symptomatic score (GSS), as follows: heartburn: 0-3; retrosternal chest pain: 0-3; regurgitation: 0-3. RESULTS: All but 2 treatments (groups C and D) significantly improved VAS and GSS, with group E showing the most significant GSS improvement. Group C had the highest number of dropouts due to treatment failure and reported more side effects. CONCLUSION: Using PPIs and mucosal protective drugs resulted in significant symptom alleviation. However, the administration of prokinetics caused higher dropouts due to treatment failure.

Burning Mouth Syndrome Etiology: A Narrative Review.

Burning mouth syndrome (BMS) is defined as "idiopathic orofacial pain with intraoral burning or dysesthesia recurring daily for more than 2 hours per day and more than 3 months, without any identifiable causative lesions, with or without somatosensory changes" in International Classification of Orofacial Pain, 2020. Worldwide prevalence of BMS was estimated to be 1.73% in population-based studies, while female and elderly are at higher risk of BMS. The aim of this narrative review is to clarify the main etiopathogenetic factors of BMS investigated so far in the scientific literature. There is growing evidence of an important role of peripheral neuropathology in BMS, supported by immunohistochemical studies which have demonstrated a significant loss of epithelial and subepithelial nerve fibers. Other possible etiopathogenetic factors emerging from literature are laryngopharyngeal reflux and hormonal and salivary changes related to aging and menopause. Finally, the role of the oral microbiota in BMS has not yet been thoroughly investigated. Further studies are necessary to investigate the probably multifactorial etiopathogenesis of primary BMS, a pathology which has a serious impact on the quality of life of our patients, a disease we find ourselves treating without the adequate therapy and the necessary knowledge.

Recovery of gastric function in patients affected by chronic atrophic gastritis using l-cysteine (Acetium®): one year survey in comparison with a control group.

BACKGROUND AND AIM: Chronic Atrophic Gastritis (CAG) is a precancerous condition for gastric cancer (GC) as single risk factor, being a consequence of a previous Helicobacter pylori (Hp) infection or based on autoimmune mechanisms. Achlorhydria plays an important role towards the formation of a class I carcinogen, acetaldehyde, after food intake. L-cysteine has been claimed to be able to bind in a covalent way acetaldehyde when administered at means. METHODS: In this study we enrolled two CAG groups of patients, one treated whit 300 mg/daily of L-cysteine for one year, the other one untreated. We assessed gastric function lasting the one year follow-up by using non invasive surrogates, i.e. Pepsinogen I (PGI) and gastrin 17 (G17). RESULTS: In the group of 77 CAG on therapy we found a statistically significative increase in PGI values and a decrease in G17 levels, in comparison with unchanged values in control group. CONCLUSIONS: L-cysteine seems able to provide a recovery in gastric function when administered in CAG patients and could be proposed as a possible therapy in such patients.

Burning mouth syndrome and Reflux Disease: relationship and clinical implications.

BACKGROUND AND AIM: An association between reflux and burning mouth syndrome (BMS) has been proposed. Aims of this study were: 1) to investigate the frequency of BMS in a sample of GERD patients; 2) to measure G17, in a sample of BMS patients; 3) to assess the efficacy of different therapeutical schedules for GERD in BMS patients. METHODS: We divided the study in 3 main steps. In step one, we analyzed 500 consecutive GERD patients' type and frequency of extraesophageal manifestations including BMS. In step two, we collected 124 consecutive BMS patients' symptoms and  G17.  In step three, we evaluate the efficacy of 3 different drugs on BMS. RESULTS: In step one, 204 patients complained heartburn; 31 globus pharyngeus; 52 chronic cough; 54 pharyngitis; 31 postnasal drip; 56 burning mouth symptoms; 34 noncardiac chest pain; 17 asthma and 21 sleep apnea. In step two, 29 patients had G17 ≤ 1 pg/L; 64 patients between 1 and 3; and 31 patients ≥ 3. In step three, 49 patients reported slight benefit with PPI, 75 no benefit. 61 patients reported slight benefit with sodium alginate and sodium bicarbonate, 63 no benefit. 23 reported an almost complete remission with HYCHSA, 26 slight benefit, 33 no benefit. CONCLUSIONS: Prevalence of BMS in GERD patients was similar to that reported for chronic chough and pharyngitis. Low levels of G17 were found in the majority of BMS patients. Finally, we observed a greater benefit from barrier drugs therapy than from PPI therapy in BMS patients. (www.actabiomedica.it).

Integrated MRI-Immune-Genomic Features Enclose a Risk Stratification Model in Patients Affected by Glioblastoma.

BACKGROUND: The aim of the present study was to dissect the clinical outcome of GB patients through the integration of molecular, immunophenotypic and MR imaging features. METHODS: We enrolled 57 histologically proven and molecularly tested GB patients (5.3% IDH-1 mutant). Two-Dimensional Free ROI on the Biggest Enhancing Tumoral Diameter (TDFRBETD) acquired by MRI sequences were used to perform a manual evaluation of multiple quantitative variables, among which we selected: SD Fluid Attenuated Inversion Recovery (FLAIR), SD and mean Apparent Diffusion Coefficient (ADC). Characterization of the Tumor Immune Microenvironment (TIME) involved the immunohistochemical analysis of PD-L1, and number and distribution of CD3+, CD4+, CD8+ Tumor Infiltrating Lymphocytes (TILs) and CD163+ Tumor Associated Macrophages (TAMs), focusing on immune-vascular localization. Genetic, MR imaging and TIME descriptors were correlated with overall survival (OS). RESULTS: MGMT methylation was associated with a significantly prolonged OS (median OS = 20 months), while no impact of p53 and EGFR status was apparent. GB cases with high mean ADC at MRI, indicative of low cellularity and soft consistency, exhibited increased OS (median OS = 24 months). PD-L1 and the overall number of TILs and CD163+TAMs had a marginal impact on patient outcome. Conversely, the density of vascular-associated (V) CD4+ lymphocytes emerged as the most significant prognostic factor (median OS = 23 months in V-CD4high vs. 13 months in V-CD4low, p = 0.015). High V-CD4+TILs also characterized TIME of MGMTmeth GB, while p53mut appeared to condition a desert immune background. When individual genetic (MGMTunmeth), MR imaging (mean ADClow) and TIME (V-CD4+TILslow) negative predictors were combined, median OS was 21 months (95% CI, 0-47.37) in patients displaying 0-1 risk factor and 13 months (95% CI 7.22-19.22) in the presence of 2-3 risk factors (p = 0.010, HR = 3.39, 95% CI 1.26-9.09). CONCLUSION: Interlacing MRI-immune-genetic features may provide highly significant risk-stratification models in GB patients.

Barrett's esophagus: results from an Italian cohort with tight endoscopic surveillance.

BACKGROUND AND AIM: Barrett's Esophagus represents a condition that predisposes to the development of esophageal adenocarcinoma. The aim of the present study was to analyze the demographic and clinical characteristics of patients with BE, to establish the presence of risk factors for this condition, and to determine the frequency of dysplastic lesions as well as the evolution towards adenocarcinoma under tight endoscopic control. METHODS: In this study, we retrospectively collected and analyzed data from a cohort of patients with Barrett's Esophagus identified through endoscopic records of ULSS7 in Northern Italy, who underwent upper esophagogastroduodenoscopy over a 10-year period from July 2008 to December 2020. RESULTS: A total of 264 patients were identified as having BE and included in the study. Mean follow-up was 6.7 years (range: 3 months-13 years). Demographic characteristics of the study population included mean age of 62.7 years (range 33-90 years), with 62.5% of the study population being aged 60 or older, and a male predominance. Females were significantly older than males (65.7 years, range 37-90 vs 61.9 years, range 33-87, p=0.043, respectively). CONCLUSIONS: The present study confirms the importance of tight endoscopic control in the management of BE, favoring early detection of BE degeneration towards high-grade dysplasia or adenocarcinoma. In a subset of patients with high-risk factors including male sex, cigarette smoking and heavy alcohol intake, it may be worthwhile to consider endoscopic control over time in order to detect the development of BE.

A non-invasive combined strategy to improve the appropriateness of upper gastrointestinal endoscopy.

Background and aim Increasing the appropriateness of upper gastrointestinal endoscopy (UGIE) improves the quality of care while containing costs. The aim of this study was to improve the appropriateness of UGIE through a process involving evaluation of prescriptions and the use of a non-invasive alternative. Materials and methods A senior endoscopist evaluated the appropriateness of all outpatient referrals for UGIE and established the proper timing. Referrals were either accepted and programmed, canceled, or substituted by a non-invasive evaluation of gastric function, determining serum levels of gastrin-17 (G17), Pepsinogen I (PGI) and II (PGII), and antibodies against Helicobacter pylori. Results A total of 5102 requests for UGIE examinations were evaluated; 540 (10.4%) were inappropriate and had been prescribed for: gastroesophageal reflux disease (n=307), surveillance with erroneous timing (n=113), dyspepsia (n=66), other indications (n=20), and absence of written indication (n=34). Gastric function was evaluated in 282/540 patients; findings included normal values in 94 patients without proton-pump inhibitor therapy (PPI) and in 48 on PPI, active H pylori infection in 56, previous H pylori infection in 30, GERD in n=50, and atrophic gastritis in n=4. UGIE was performed in the latter 4 cases.  Within 2 years (range 1-22 months) of the initial refusal, 105/504 patients underwent UGIE, with normal endoscopic findings in 71/105 (67.5%), and with no cases of cancer. Conclusions This strategy, based on a strict control of prescriptions, is effective to increase the appropriateness while containing public health costs. The use of gastric function testing improves patient selection for UGIE endoscopy.

Mechanism of acid hypersecretion post curative gastrinoma resection.

BACKGROUND: Some patients with Zollinger-Ellison syndrome post curative gastrinoma resection continue to show gastric acid hypersecretion; however, the mechanism is unknown. AIM: The aim of this study was to prospectively study acid secretion following curative gastrinoma resection and analyze factors contributing in patients with Zollinger-Ellison syndrome. METHODS: Fifty patients cured post gastrinoma resection were studied with serial assessments of acid secretory status, cure status and ECL-cell status/activity (with serial biopsies, CgA, urinary N-MIAA). Correlative analysis was performed to determine predictive factors. RESULTS: Hypersecretion occurred in 31 patients (62%) and 14 had extreme-hypersecretion. There was an initial decline (3-6 months) in BAO/MAO, which then remained stable for eight years. Preoperative BAO correlated with the postoperative secretion, but not other clinical, tumoral, laboratory variables, the degree of postoperative acid suppression or type of antisecretory drug needed. Hypersecretors had greater postoperative ECL changes (P=0.005), serum CGA (P=0.009) and 24-h urinary N-MIAA (P=0.0038). CONCLUSIONS: Post curative resection, gastric hypersecretion persists long term (mean 8 years) in 62% of patients and in 28% it is extreme, despite normogastrinemia. No preoperative variable except BAO correlates with postresection hypersecretion. The persistent increased ECL-cell extent post curative resection suggests prolonged hypergastrinemia can lead to changes in ECL-cells that are either irreversible in humans or sustained by unknown mechanisms not involving fasting hypergastrinemia and which can result in hypersecretion, in a proportion of which it can be extreme. Whether similar findings may occur in patients with idiopathic GERD treated for prolonged periods (>10 years) with PPIs, at present, is unknown.

Is CD10 a reliable marker of invasive colorectal cancer?

AIM: Previous studies reported that CD10 positive Colorectal Cancer Cells (CRC) characterized by deeply invasive neoplasia. MATERIALS AND METHODS: We have examined 50 pts surgically treated for colorectal cancer on at least 5 years follow up. TNM, grading score and survival have been compared to CD10 expression. RESULTS: Thirty-four out of fifty cases have been analyzed (18 males and 16 female) of whom nineteen were CD10 positive and fifteen were CD10 negative. The remaining 16 cases were droping out. No difference in survival rate between CD10 positive and negative in N0, N1, N2. No difference on survival rate and grading 1, 2, 3. We have then analyzed CD10 positive and CD10 negative cases, according to neoplasia grading, in patients with positive linphonodes N1 and N2. We showed a statistical difference between the CD10 positive/N2 (grading 1.66 +/- 0.5) and the CD10 negative/N2 (grading 3) (p < 0.005). CONCLUSIONS: We can hypothesize that CD10 positive neoplasia display a more invasive behaviour, independently from the N score and the G score, compared to CD10 negative neoplasia.