Serological Biopsy Research Articles

Clinical value of serum pepsinogen in the diagnosis and treatment of gastric diseases.

Pepsinogen, secreted from the gastric mucosa, is the precursor of pepsin. It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity. The pepsinogen content that can enter the blood circulation through the capillaries of the gastric mucosa is approximately 1% and remains stable all the time. The pepsinogen content in serum will change with the pathological changes of gastric mucosa. Therefore, the level of pepsinogen in serum can play a role in serologic biopsy to reflect the function and morphology of different regions of gastric mucosa and serve as an indicator of gastric disease. This study conducts relevant research on serum pepsinogen 1, pepsinogen 2, and the ratio of pepsinogen 1 to pepsinogen 2, and reviews their important value in clinical diagnosis of Helicobacter pylori infection, gastric ulcer, and even gastric carcinoma, providing ideas for other researchers.

Significance of Serological Gastric Biopsy in Different Gastric Mucosal Lesions: an Observational Study.

Screening and timely treatment of precancerous gastric cancer diseases or of gastric cancer in the early stages has important significance in reducing the incidence and mortality of gastric cancer. Gastroscopy and histopathological biopsy are still the gold standards for the diagnosis of gastric diseases. But the application of astroscopy for the screening and diagnosis of gastric diseases is limited. In recent years, serum pepsinogen (PG), gastrin, and Helicobacter pylori (H. pylori) IgG antibodies have become indicators for "serological biopsy" of the gastric mucosa. From January 2016 to January 2018, a total of 2,394 patients with digestive tract symptoms underwent gastroscopy. According to the endoscopic examination and pathological diagnosis, there were four case groups: 1,376 cases of chronic non-atrophic gastritis, 708 cases of chronic atrophic gastritis, 265 cases of gastric ulcer, and 45 cases of gastric cancer. Serological gastric biopsies were performed and analyzed. The serum levels of PGI in the chronic atrophic gastritis group was significantly lower than that in the chronic non-atrophic gastritis group, gastric ulcer group, and gastric cancer group (p < 0.05). The serum levels of PGII and G-17 in the gastric cancer group were significantly higher than those in the chronic non-atrophic Gastritis group, chronic atrophic gastritis group, and gastric ulcer group (p < 0.05). The PGR in the gastric cancer group was significantly lower than that in the chronic non-atrophic gastritis group, chronic atrophic Gastritis group, and gastric ulcer group (p < 0.05). The H. pylori positive rates in the chronic atrophic gastritis group and gastric cancer group were higher than those in the chronic non-atrophic gastritis group and gastric ulcer Group (p < 0.05). Serological gastric biopsy is closely correlated to gastric mucosal disease and can be used as a Screening tool in gastric disease.

Caso clínico: Enfermedad Veno-Oclusiva Hepática secundaria a Quimioterapia en un paciente con Sarcoma de Ewing.

Introducción: A pesar del difícil acceso anatómico para los tumores de mediastino, la resección quirúrgica sigue siendo el mejor enfoque diagnóstico y terapéutico. El objetivo de la presente serie de casos presentamos la experiencia de un centro oncológico en el abordaje de tumores del mediastino y sus resultados. Métodos: En el departamento de Jefatura de Cirugía Oncológica del Instituto Oncológico nacional de Solca-Guayaquil, durante los meses de Enero del 2013 a Enero 2017 se realizó un estudio descriptivo, retrospectivo. Se analizaron todos los casos de pacientes derivados del área de pre admisión con diagnóstico inicial de tumor de mediastino, a los cuales previo a realizarles marcadores tumorales, Tomografía de Tórax, y a quienes se les realizó como método diagnóstico y en algunos casos terapéutico con abordaje quirúrgico. Se excluyeron pacientes con neoplasias de origen secundario, con historias clínicas incompletas que imposibilitaron el análisis. Se estudiaron las variables sexo, edad, Tipo de Técnica quirúrgica, localización del tumor, diagnostico histopatológico y mortalidad perioperatoria. El análisis estadístico realizado fue descriptivo. Resultados: Se evaluaron 22 pacientes con diagnóstico tumor de mediastino, con una edad media de 60 años. Fueron 13 hombres (59 %). Catorce pacientes con lesión maligna, 8 fueron operados con resección tumoral y 6 se sometieron a biopsia. Se reportaron fallecimientos post-operatorios hasta los 30 días postquirúrgicos en 5 casos (22.7%). Las intervenciones quirúrgicas realizadas con más frecuencia fueron toracotomías derechas con toma de biopsia o resección tumoral 7 casos (31.8 %). En relación al resultado anatomopatológico de los tumores de mediastino reportados más de la mitad constituyeron Adenocarcinomas 14 casos (63.6 %). Conclusión: Los pacientes portadores de neoplasia benigna en esta serie tuvieron una evolución posquirúrgica satisfactoria. El adenocarcinoma fue el tumor maligno más frecuente en esta serie.

Conference lecture: Electrophysiological diagnosis of inflammatory demyelinating neuropathies

Electrophysiology plays a crucial role in the characterization and diagnosis of peripheral neuropathies. It provides insight in the type and mechanism of peripheral neuropathy by giving information on the spatial pattern, the fibre type involved, pathology (axonal, demyelinating), and the severity and time course. Inflammatory demyelinating neuropathies constitute a significant proportion of the acquired peripheral neuropathies. They include Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), multifocal demyelinating neuropathy with persistent conduction block (Lewis-Sumner syndrome), and paraproteinemic neuropathies. A proper diagnosis as early as possible is very important because timely immune treatment can largely reduce morbidity and disability. The diagnosis is based on a constellation of clinical and laboratory features, including electrophysiological studies, spinal fluid examination, and in selected cases serological studies and peripheral nerve biopsy. Electrophysiological studies are key in the early detection and characterization of inflammatory demyelinating neuropathies and in differentiating these from primary axonal neuropathies. In CIDP, electrophysiological criteria for demyelination are designed to exclude abnormalities that can be explained by axonal degeneration (Eur J Neurol 2010). Therefore, lesser degrees of demyelination cannot be defined with certainty. Optimised electrophysiological criteria are capable, however, to support the diagnosis with different levels of probability (possible, probable, definite) in the very large majority of cases. In GBS, much effort has gone into developing criteria which can distinguish axonal and demyelinating subtypes. The discovery of reversible conduction failure (RCF) has led to the concept of nodopathy/paranodopathy, where conduction slowing and conduction block are due to the immune attack mainly at the nodal axolemma level. There is no actual demyelinisation as defined pathologically and if the immune attack continues, conduction failure may not reverse and axonal degeneration will ensue. Recent electrophysiological studies support this pathophysiological mechanism and show that the dichotomous distinction between axonal and demyelinating in GBS is not tenable (Muscle nerve, 2018).

Diffuse Alveolar Haemorrhage as Initial Presentation of Systemic Lupus Erythematosus

Diffuse alveolar hemorrhage results from accumulation of red blood cells in the alveolar space originating from alveolar capillaries. Alveolar hemorrhage in Systemic Lupus Erythematosus is rare but catastrophic and can rapidly progress to respiratory failure. We report a 22-year old lady who presented with dyspnoea on exertion, hemoptysis, bilateral leg swelling and oliguria. Diffuse alveolar hemorrhage was confirmed by bronchoalveolar lavage fluid analysis. Serologic tests and renal biopsy confirmed lupus nephritis. She was treated with systemic immunosuppressive therapy and plasma exchange, to which she had a favourable response. Lupus presenting as alveolar hemorrhage is rare which warrants prompt diagnosis and treatment to prevent complications. Keywords: Bronchoalveolar lavage; Case report; Diffuse alveolar hemorrhage; Systemic lupus erythematosus.

Premalignant Gastric Lesions in Patients Included in National Colorectal Cancer Screening.

BackgroundGastric cancer is the fifth most common malignancy in the world with almost one million new cases annually. Helicobacter pylori infection causes 89% of all gastric cancers. Premalignant lesions (atrophy and intestinal metaplasia) develop after several decades of inflammation. Secondary prevention with gastroscopy is possible, but it is costly and has a low compliance rate. Alternative procedures like serology testing for pepsinogen I and II and pepsinogen I/II ratio are available to select patients for surveillance gastroscopies.Patients and methodsIn seven outpatient endoscopic units, 288 patients (154 men; 53.5%), average age 60.68 years, tested positive in National colorectal cancer screening programme SVIT, were included in the study. Gastropanel (BioHit, Finland) was used as a serologic biopsy method.ResultsWe found 24 patients (12 men, mean age 63.7 years) with pepsinogen (pepsinogen I/II < 3 and/or pepsinogen I < 30 μg/L). Premalignant changes were found on gastric biopsies in 21 patients (7.3% incidence). Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) ≥ 1 was found in 20 patients; Operative Link for Gastritis Assessment (OLGA) ≥ 1 was found in 19 patients. Combined accuracy for preneoplastic lesions in Gastropanel positive patients was 87.5%. H. pylori seropositivity was found in 219 patients (76%). Only 24% of our population had normal results.ConclusionsGastropanel test has proven to be a reliable non-invasive test for advanced gastric preneoplastic lesions that can select patients for further gastroscopy. We found high H. pylori seropositivity in older age groups in Slovenia.

Helicobacter pylori, gastric cancer and other gastrointestinal malignancies.

In a retrospective study performed in California, U.S.A., ca. 3% of patients with gastric intestinal metaplasia (GIM) developed gastric cancer (GC) within a median time period of 4.6years after diagnosis of GIM. This observation stresses the importance of targeted surveillance even in regions with a low GC prevalence. Patients with alcoholic liver disease as well as survivors of colorectal and lobular breast cancer were found to be at increased risk of secondary GC. A population-based Chinese study confirmed "serologic biopsy" as a useful screening tool for stratifying the individual risk of developing GC. Concerning GC therapy, a post hoc analysis of the MAGIC trial reported that regression of lymph node metastases, but not the tumor regression itself, predicts overall survival. Furthermore, in patients with high microsatellite instable tumors, perioperative chemotherapy leads to an increased risk of mortality. Two studies confirmed that eradication therapy is worthwhile as an initial treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma irrespective of the H.pylori infection status and stage. An increased risk of a second primary malignancy including GC was observed in these patients treated with immuno/chemotherapy but not in patients treated solely with an H.pylori eradication treatment. With respect to gastrointestinal malignancies other than GC, discrepant data have been published regarding the association of H.pylori with pancreatic cancer whereas no association has been reported with esophageal squamous cell carcinoma. The majority of published studies still support an association of H.pylori with colon neoplasms.

Abstract 5304: A serological biopsy using five stomach-specific circulating biomarkers for gastric cancer risk assessment: a multi-phase study

Abstract Objective: We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers—pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)—for identifying high-risk individuals and predicting risk of developing gastric cancer (GC). Methods: Among 12112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis. Results: In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low (&amp;lt;0.5 pmol/L) and high (2.0-4.7 or &amp;gt;4.7 pmol/L) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.801 (95% CI=0.787-0.815) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P&amp;lt;0.001) for identifying precancerous lesions at enrollment, and higher serological biopsy score based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend &amp;lt;0.001). Conclusions: A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals’ risk of developing GC and thus to guide targeted screening/precision prevention. Citation Format: Huakang Tu, Liping Sun, Xiao Dong, Yuehua Gong, Qian Xu, Jingjing Jing, Roberd M. Bostick, Xifeng Wu, Yuan Yuan. A serological biopsy using five stomach-specific circulating biomarkers for gastric cancer risk assessment: a multi-phase study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5304. doi:10.1158/1538-7445.AM2017-5304

A Serological Biopsy Using Five Stomach-Specific Circulating Biomarkers for Gastric Cancer Risk Assessment: A Multi-Phase Study.

We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers-pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)-for identifying high-risk individuals and predicting risk of developing gastric cancer (GC). Among 12,112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis. In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low (<0.5 pmol/l) and high (>4.7 pmol/l) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.803 (95% confidence interval (CI)=0.789-0.816) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P<0.001) for identifying precancerous lesions at enrollment, and higher serological biopsy scores based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend <0.001). A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals' risk of developing GC and thus to guide targeted screening and precision prevention.

Is renal biopsy always necessary to start immunosuppressive therapy in lupus nephritis?

Objective: Most of the patients with proliferative lupus nephritis (LN) have high titer of anti-dsDNA antibody and low complement levels. In this study, we tried to predict proliferative LN with serological profile. Methods: This prospective study was conducted in fifty pateints with known systemic lupus erythematosus (SLE) with laboratory evidence of LN (proteinuria, microscopic hematuria, or increased serum creatinine). Serological profile (anti-dsDNA, C3, and C4) and renal biopsy were done in all patients. Results: Of 50 patients, 35 had Class IV (70%), 7 Class II (14%), 4 Class V (8%), and 4 had Class IV and V (8%) on renal biopsy. Totally, 39 (78%) patients had proliferative LN (Class IV and Class IV and V). The prevalence of anti-dsDNA, low C3, and low C4 was 97.1%, 68%, and 74% with LN and 97.4%, 84.6%, and 87.2% with proliferative LN (P < 0.001), respectively. About 72% (28 of 39 patients) with proliferative LN had the combination of anti-dsDNA positivity, low C3, and low C4 levels. However, whoever had the combination of anti-dsDNA positivity, low C3, and low C4 showed only proliferative LN on biopsy. Positive predictive value was 100% (P < 0.05). None of the patients with Class II or Class V (nonproliferative LN) had this combination of serology. Conclusion: In this study, it was found that proliferative LN can be predicted by serological profile alone. Thus it might be argued that immunosuppressive therapy (steroids and mycophenolate mofetil) may be started without renal biopsy in a known SLE patient with laboratory evidence of LN and positive serology; however, robust studies are required.

The clinical analysis of autoimmune pancreatitis: a report of 21 cases

To investigate the clinical feature, diagnostic and therapeutic experience of autoimmune pancreatitis (AIP). Twenty-one patients with AIP treated in the First Affiliated Hospital, Harbin Medical University from January 2006 to July 2014 were analyzed retrospectively. There were 15 men and 6 women among the 21 cases and the age ranged from 36 to 64 years. The characters of diagnosis and treatment of AIP were explored through clinical symptoms, imaging features, serologic test results, diagnostic treatment, and histopathologic characteristics. All the patients showed obstructive jaundice and upper abdominal pain to different extents as major manifestations and the levels of serum IgG4, CA19-9, CEA were elevated in 16 cases (76.2%), 6 cases (28.5%) and 3 cases (14.2%), respectively. CT showed diffuse enlargement of the pancreas in 9 cases, localized pancreatic head enlargement in 3 cases and focally pancreatic mass in 9 cases. AIP was confirmed by extrapancreatic involvement, radiological and serological results plus biopsy in 11 cases (52.4%), interpretation of response to steroid in 3 cases (14.3%) and open laparotomy in 7 cases (33.3%). Surgery included choledochojejunostomy in 3 cases, cholecystojejunostomy in 1 case, pancreaticoduodenectomy in 2 cases and distal pancreatectomy combined with splenectomy in 1 case. The pathologic results displayed massive lymphocytes and plasma cells infiltration in the pancreatic tissues as well as parenchymal fibrosis. Except for 1 patient who had no symptom, the regular steroid therapy was performed (oral prednisone) and all the patients were cured. The follow-up time range was from 3 to 93 months, 4 cases (19.0%) were recurrent followed by the symptoms alleviated after the steroid was applied again. AIP is rare and characterized by non-specific clinical manifestations so that the early diagnosis is difficult with a high misdiagnosis rate. The clinicians should strengthen the recognition of AIP and the definite diagnosis depends on the combination of clinical manifestations, radiological, serological and histopathological results so as to avoid the unnecessary operation.

“Serological biopsy” and screening of gastric cancer

High morbidity and mortality of gastric cancer in Russia determine relevance of developing of a national strategy for gastric cancer and preneoplastic diseases of the stomach screening, especially atrophic gastritis. Review of the literature shows that the best non-invasive method to identify individuals at high risk of gastric cancer are H. pylori serological tests and markers of pepsinogens atrophy. H. pylori eradication is the most promising strategy to reduce the incidence of gastric cancer.

Pediatric endocrinologists' practices in screening for celiac disease in patients with type 1 diabetes

Background: Undiagnosed CD may lead to unstable blood glucose levels, weight loss, growth failure, osteopenia. The primary objective of the study was to review CD screening practices in one center, describe symptoms at the time of diagnosis, and implement screening guidelines. The secondary objective was to carry out an educational intervention, to review practices after screening guidelines were established. Methods: A total of 532 charts of patients with T1D treated in our center from 2007-2009 were reviewed. Data collected included times of screenings for CD, results of serologic tests, symptoms, and intestinal biopsy results. Two hundred and fifty charts from 2010-2012 were reviewed after an educational intervention with the same group of physicians. Results: After the educational intervention to encourage implementation of screening guidelines, there was a statistically significant reduction in the interval between the diagnosis of T1D and first screening for CD. The majority were diagnosed in the first year after T1D diagnosis, only 30% were symptomatic. Conclusion: Our results suggest that patients with T1D should be screened within the first several months after diagnosis, on an annual basis thereafter, even in the absence of gastroenterologic symptoms of CD. This will allow early dietary intervention and reduce morbidities in this high-risk population.

Pepsinogen I and II expressions in situ and their correlations with serum pesignogen levels in gastric cancer and its precancerous disease

BackgroundSerum pepsinogen (PG) I/II ratio has been widely used as “serological biopsy” for the screening of gastric cancer (GC) and atrophic gastritis (GA). However, study concerning in situ expression of PGs is currently insufficient, particularly for their relationship with serum PGs levels. This study was designed to investigate in situ expression of PGI and PGII in subjects with normal mucosa (NOR), superficial gastritis (GS), GA and GC, and to evaluate the correlations between PGs expressions in situ and in serum.Methods185 subjects were enrolled for the study, including 30 NOR, 70 GS, 54 GA and 31 GC. PGI and PGII expressions in situ and in serum were detected by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) respectively. H. pylori immunoglobulin (Ig) G was also determined by ELISA.ResultsIn situ expressions of PGI, PGII and PGI/II ratio consistently decreased in sequence of NOR/GS- > GA- > GC. The expressions of PGI, PGII and PGI/II ratio in situ were statistically higher in youngers than in olders (P < 0.05). In the NOR subjects, PGI staining was statistically higher in males than that in females (p = 0.02). For the correlations between in situ and serum expressions of PGI, PGII and PGI/II ratio, a borderline correlation in the total study sample (r = 0.131, P = 0.076) and a statistical correlation in GA cases (r = 0.307, P = 0.027) were observed for the PGI/II ratio. The PGI expression correlated well with that of PGII in situ and in serum.ConclusionsThe in situ levels of PGI, PGII and PGI/II ratio sharply decreased in the GA and GC cases. The youngers exhibited higher levels of PGI, PGII and PGI/II ratios than the olders. The in situ PGI/II ratio rather than PGI and PGII alone showed certain correlation with that in serum, and the PGI expression correlated well with PGII expression. Further studies with large-scale samples are still required to validate our findings.

Celiac disease and gluten-free diet

Celiac disease is an autoimmunity inflammatory disorder of the small intestine caused by the ingestion of gluten in genetically predisposed individuals. The prevalence of the disorder is around 1 % of the Western population and is still increasing. The symptoms of celiac disease include chronic abdominal pain, diarrhoea, and growth retardation in children, and chronic fatigue and headache, bowel complaints, reduced fertility, dermatitis herpetiformis, osteoporosis, nerve and brain disorders, increasing risk of intestinal cancer. The clinical diagnosis of the disease is based on the serological tests and bowel biopsy. The treatment is a long-life gluten-free diet. It is necessary exclude from the diet wheat, rye, barley and probably oats and buckwheat and their products. The novel approaches for celiac disease are focused on the genetic manipulation of nontoxic gluten proteins, enzyme therapy, immune modulation, and induction of oral tolerance to gluten.

Abstract 3606: Dynamic expression of pepsinogen I in gastric diseases sequence and relationship with Helicobacter pylori infection

Abstract Serum PG I and PG I /PGII levels seemed to be related to the functional changes in the stomach, and their use as ‘serological biopsy’ in gastric cancer and precancerous diseases has been reported over 20 years. But the dynamic expression of pepsinogen I in situ of gastric mucosa and the value to detect gastric cancer and precancerous diseases, relative to the serum pepsinogen I is still unclear. Helicobacter pylori is a gram-negative bacterium that colonizes the stomach. More than 50% of the adult population are infected with H. pylori worldwide. Numerous studies have reported that healthy volunteers and gastric ulcer patients with H pylori infection have increased serum pepsinogen I levels which decrease after H pylori eradication. The evidence whether expression of pepesinogen I in situ affected by H pylori infection is not available. We thus conducted this study to investigate the dynamic expression of pepsinogen I in superficial gastritis, atrophic gastritis, gastric cancer and also H.pylori-associated gastric lesions and evaluate the application value of pepsinogen I in classifying gastric cancer and its precancerous diseases, and also the influence of H pylori on pepsinogen I expression. The expression of pepsinogen I was determined by immunohistochemistry method in 185 cases with mucosa taken from gastric corpus as well as from antrum. H.pylori infection was determined by histological examination and ELISA. Serum pepsinogen I and II were determined by ELISA. We found that Pepsinogen I was only expressed in the gastric corpus. There were 185 cases from gastric corpus and the positive rate of pepsinogen I expression in superficial gastritis, atrophic gastritis and gastric cancer decreased significantly in sequence (P&amp;lt;0.05;100% vs. 83.3%vs0.0%), and the over-expression rate also decreased along with the sequence: normal, superficial gastritis, atrophic gastritis and gastric cancer (p&amp;lt;0.05; 93.3%vs72.9% vs22.2vs0.0%). The over-expression rate of pepsinogen I in superficial gastritis with H pylori infection was higher than that without H pylori infection (P=0.035; β2 = 4.46).The serum expression of Pepsinogen I had no statistical difference (P&amp;gt;0.05) and the ratio of sPGA to sPGC decreased along with the above groups. (P&amp;lt;0.05). In conclusion, expression of PGI in situ has positive correlation with the degree of malignancy of gastric mucosa. and it is good biomarker for the diagnosis of gastric cancer and precancerous diseases. Also, The expression of PGI has positive correlation with H.pylori infection, and maybe is an important part in the H pylori- related damage or a good marker for screening H.pylori infection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3606. doi:1538-7445.AM2012-3606

Clinical Usefulness of the Serological Gastric Biopsy for the Diagnosis of Chronic Autoimmune Gastritis

Aim. To assess the predictive value for chronic autoimmune gastritis (AIG) of the combined assay of anti-parietal-cell antibodies (PCA), anti-intrinsic-factor antibodies (IFA), anti-Helicobacter pylori (Hp) antibodies, and measurement of blood gastrin. Methods. We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency. Results. 83 patients (45.8%) tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1) 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2) 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3) 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4) 21 patients with multifocal atrophic gastritis with “borderline” PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases. Conclusions. The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic “serological biopsy.”

S1928 Reprimo: A Novel Non-Invasive Biomarker for Gastric Cancer Detection

Although gastric cancer is one of the highest mortality cancers in the world, no methods for non-invasive diagnosis have been described. Aberrant hypermethylation, an epigenetic mechanism of inactivation of tumor suppressor genes, is an emerging approach to noninvasive diagnosis of gastric cancer. We have previously shown high prevalence of aberrant hypermethylation of Reprimo (RPRM) a novel tumor suppressor gene, in plasma from gastric cancer but not in plasma from healthy donors (Clin Cancer Res. 2008;14:6264-9). This finding suggested that RPRM promoter methylation could be a sensitive and specific biomarker for the non-invasive detection of gastric cancer. Here we explore in a prospective and blind fashion specificity and sensitivity of RPRM for non-invasive diagnoses of gastric cancer. Methods. We prospectively collect 83 gastric cancer patients from two hospitals and 223 healthy donors from corresponding blood banks. Detection of RPRM was perform by methylation specific PCR (MSP). We perform endoscopy in healthy donors that were RPRM(+) in plasma. Results. Aberrant hypermethylation of RPRM was identified in 67/74 (90.5%) and 75/79 (94.9%) of tumor and plasma from gastric cancer patients, respectively. Among healthy donors, methylation of RPRM was identified in 29.1% (65 of 223) of tested cases. These differences were statistically significant (p< 0.001 by Fisher's exact test). The sensibility and specificity of RPRM detection in plasma were 89% (95% CI: 81%-98%) and 67% (95% CI: 58%-75%) respectively. We perform endoscopy in 5 RPRM positive healthy donors, and no cancer was found. Only one healthy donor was diagnosed with chronic gastritis. Discussion. Our data indicate that detection of RPRM promoter methylation in cell free plasma DNA is a promissory method for non-invasive detection of gastric cancer. RPRM could be included in the serologic biopsy along with pepsinogen and gastrin 17 not only for the identification of gastric atrophy, the precursor lesion of gastric cancer but also for direct identification of gastric cancer. Supported by FONDECYT grant 1080563 from Government of Chile

The Serological Gastric Biopsy: A Non-endoscopical/Histopathologic Diagnostic Approach in Management of the Dyspeptic Patients

Objective: To asses the sensitivity, specificity and the predictive value of a 'gastropanel' blood test, including serum pepsinogen I (S-PGI) and amidated gastrin-17 (S-G-17) in the diagnosis of atrophic gastritis most probably due to helicobacter pylori (Hp) and to compare the results of serology with the endoscopic/histopathologic findings as a gold standard diagnostic tool. This study comprised 86 dyspeptic outpatients who underwent a diagnostic gastroscopy with multiple biopsies from the antrum and corpus for histopathologic examination. Histopathologically, the series of cases included 46 patients diagnosed as having atrophic gastritis. Twenty five had an antral atrophy, 6 had corpus atrophy and 15 patients had an atrophic gastritis in both the antrum and corpus (multifocal atrophic gastritis) MAG. The remaining 40 cases were considered as controls, 32 had a non-atrophic gastritis (NAG) and both the antrum and corpus were normal and healthy in 8 subjects. The fasting levels of S-PGI and antibodies to Hp IgG-antibodies (S-HpAb) and postprandial amidated S-G-17 (S-G-17prand) were measured 20 min after a protein-rich drink and were determined using enzyme immunoassay (EIA) methods. The serologic and morphologic results were compared with estimating the sensitivity, specificity, positive and negative predictive (PPV and NPV) and accuracy values of the tests (S-G-17 and S-PGI). Mean values of both S-G-17prand and S-PGI decreased with increasing grade of antral and corpus atrophy, respectively. A low S-PGI (<25 mg L-1) was found in 4 of 6 patients with corpus atrophy (66.70%) and in 5 of 32 (15.62%) patients with NAG in the biopsy specimens. A low S-G-17prand (<5 pmol L-1) was found in 13 patients with Hp-associated antral atrophy and in 5 of 32 (15.62%) patients with NAG. The diagnosis of gastritis obtained with the blood test panel is in good agreement with the endoscopic and biopsy findings: 92% of the patients went into same gastritis categories with both the panel and endoscopic/histopathologic findings. The sensitivity, specificity, PPV, NPV and accuracy values of the blood test panel (S-G-17prand and S-PGI) in delineation of patients with atrophic gastritis (either in the antrum or the corpus, or both) versus NAG and normal stomach were 87.5, 82.60, 81.40, 88.40 and 85% respectively. Low levels of S-G-17prand and S-PGI are conceivable biomarkers of atrophic gastritis. The serologic method gave a reasonable sensitivity, specificity, PPV, NPV and accuracy values in the diagnosis of atrophic gastritis. So, it may be offered as the screening tool for atrophic gastritis.

Haemophagocytic syndrome associated with hepatitis-B virus infection responding to etoposide

Haemophagocytic syndrome (HPS) secondary to viral infections usually has a variable course and can be life-threatening. We report a 53-year-old male patient who presented with fever, hepatosplenomegaly and pancytopenia. He had deranged liver function, abnormal clotting and markedly elevated serum ferritin. Bone marrow biopsy showed prominent haemophagocytosis. The patient was investigated thoroughly and found to have evidence of chronic hepatitis B-virus (HBV) infection by serological tests and liver biopsy. Other conditions associated with HPS such as lymphoma, malignancy and other viral or bacterial infections were not present. The patient did not respond to steroids, intravenous immunoglobulins or cyclosporin but responded to etoposide and became apyrexial. He also became HBV negative on lamivudine. The patient died of infection later on but there was no evidence of recurrence of HPS. To the best of our knowledge this is the first case report of HPS associated with isolated HBV infection.