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.

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.

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.

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.

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).

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.

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.

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.

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 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.

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.

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.

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.

Abnormal Levels of Pepsinogen I and Gastrin 17 in a case of Ménétrier Disease.

BACKGROUND AND AIM: We describe a case of Ménétrier disease, occurred in female patient. METHODS: We decide to assess by non-invasive way (serum pepsinogens and gastrin 17) the secretory status of gastric mucosa, to confirm previous data of the literature, claiming high levels of both acid secretion and hypergastrinemia in this rare pathological condition. RESULTS AND CONCLUSION: We find in the subject the highest values of pepsinogen 1 - a marker of acid secretion - never described in the literature to our knowledge: 1940 mcg/L, being normal values ranging from 30-160 mcg/L. Similarly, gastrin 17, produced 90% in the antrum and responsible for negative acid feedback, was very high: 139 pg/L, ranging normal values between 1-10 pg/L. (www.actabiomedica.it).

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.

Low Levels of Gastrin 17 are Related with Endoscopic Findings of Esophagitis and Typical Symptoms of GERD.

BACKGROUND AND AIMS: In clinical practice, most patients with symptoms suggestive of gastroesophageal reflux disease (GERD) undergo esophago-gastro-duodenoscopy (EGD), despite its low sensitivity in detecting reflux stigmata. Gastrin 17 (G-17) has been proposed to be related with GERD, due to the negative feedback between acid secretion and this hormone. We assessed the clinical usefulness of fasting G-17 serum determination for a non-invasive diagnosis of GERD in patients with typical symptoms. METHODS: We consecutively enrolled patients complaining of typical GERD symptoms in two different settings: a single referral center and a primary care setting. Control groups consisted of dyspeptic patients. All subjects underwent assessment of serum levels of G-17 and EGD. RESULTS: At the academic hospital, 100 GERD patients (n=89 with erosive esophagitis and 11 with Barrett's esophagus) had statistically significant low levels of G-17 as compared with 184 dyspeptic patients (1.7±1.2 pg/L vs 8.9±5.7 pg/L p<0.0001). Similarly, in the primary care setting, 163 GERD patients had statistically significant low levels of G-17 as compared with 132 dyspeptic patients (0.5±0.2 pg/L vs. 4.0±2.6 pg/L, p<0.0001). Moreover, in the primary care setting, no statistically significant differences were found for G-17 levels between patients with erosive and non-erosive reflux pattern (0.4±0.2 vs 0.7±0.3; p=0.08). In primary care, the accuracy of G-17 less than 1 pg/L to diagnose non-invasively GERD was 94.3%. CONCLUSIONS: Low levels of G-17 were detected in patients with erosive esophagitis and Barrett's esophagus in a referral center and in patients with typical GERD symptoms in a sample of patients from a primary care setting.

Retrospective survival analysis of stage II-III rectal cancer: tumour regression grade, grading and lymphovascular invasion are the only predictors.

BACKGROUND: Tumour regression grade is gaining interest as a prognostic factor of patients undergoing neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer. METHODS: A series of 68 consecutive patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy and surgery between 2010 and 2016 was retrospectively studied. The impact on disease-free survival (DFS) and overall survival (OS) of several criteria was analysed. Univariate analysis was performed through Kaplan-Meier statistics. Multivariate analysis was performed through Cox regression model. Using criteria found to be related to long-term outcomes, a predictive model of patient's OS was calculated. RESULTS: Poor tumour regression grade - TRG3 (P = 0.010), poor grading - G3 (P = 0.001) and lymphovascular invasion (LVI; P = 0.030) were associated with short OS at univariate analysis. OS was associated with TRG3 and G3 at multivariate analysis (P = 0.016 and P = 0.027, respectively). DFS was associated with LVI (P = 0.001), G3 tumours (P = 0.046) and TRG3 (P = 0.045) at univariate analysis. At multivariate analysis, only LVI was associated with DFS (P = 0.041). A score, pondering the impact of three parameters (2 points for TRG3, 2 for G3 and 1 for LVI), was created and resulted to predict patient OS (P = 0.008), ranging from 94.5 months (score = 0-1) to 32 months (score = 3-5). CONCLUSION: TRG3 and G3 were associated with poor OS, and LVI was the most significant predictor of DFS. An easy-to-use score may allow for a more accurate prediction of OS.

Stage III and Metastatic Lymph Node Ratio Are the only Independent Prognostic Factors in Colorectal Signet-ring Cell Carcinoma Patients.

BACKGROUND/AIM: Signet-ring cell carcinoma (SRCC) is an uncommon histological variant of colorectal cancer (CRC). Knowledge is scarce due to its rarity. Our aim was to better evaluate the clinicopathologic and prognostic features of this little-known malignancy. PATIENTS AND METHODS: Thirty-nine consecutive patients with non-metastatic colorectal SRCC undergoing curative resection at University Hospital of Parma between 2000 and 2018 were examined in this retrospective analysis. RESULTS: Mean overall (OS) and disease-free survival (DFS) were 33.6 and 31.5 months, respectively. At univariate analysis, the lymph-related parameters (nodal status, Stage III, metastatic lymph node ratio and lymphovascular invasion) were significantly associated with shorter OS and poorer DFS. At multivariate analysis, Stage III and a metastatic lymph node ratio ≥25% were found to be the only independent prognostic factors significantly correlated with worse OS and DFS. CONCLUSION: Nodal and lymphatic status should be carefully pondered when planning the most appropriate management of patients with colorectal SRCC.

Functional Dyspesia.

Dyspepsia is a functional GI disorder consisting in a wide range of symptoms. The main diagnostic challenge has been whether to perform an EGD or an abdominal US in order not to miss organic lesions, but to avoid unnecessary and sometimes invasive tests. Pepsinogen serology has been proposed as an useful non-invasive test to explore the status of the gastric mucosa, suggesting this strategy as an adequate approach in management of dyspepsia. In a primary care setting, 266 dyspeptic patients were investigated to establish the proper diagnosis. The workup included upper GI endoscopy with biopsies, a structured questionnaire including type and severity of symptoms, serological determination of serum pepsinogens, gastrin 17 and IgG against Hp. Inclusion criteria were dyspeptic symptoms (epigastric pain, nausea and/or vomiting, post prandial fullness, early satiation) lasting more than 1 year and the association between symptoms and food ingestion.. Helicobacter pylori infection was present in 114 subjects, characterized by high levels of pepsinogen II and IgG against Hp. Twenty subjects were classified according with the diagnosis of chronic body atrophic gastritis. Nausea and post prandial fullness were the most frequent symptoms (48% and 41%, respectively) in the studied population, followed by epigastric pain and early satiation (37% and 26% respectively). A diagnosis of normality by serological diagnosis was found in half of patients experiencing epigastric pain and in about 60% of subjects with the three other symptoms (nausea, post prandial fullness, and early satiation). In conclusion, this experience confirms the clinical usefulness of serology in dyspepsia, contributing to correctly diagnosing CAG and H.p. infection in such patients and providing a good correlation with the clinical picture.