Clinical significance of elevated serum chromogranin A levels

BACKGROUND: Chromogranin A (CgA) has been shown to be a useful marker in the diagnosis of neuroendocrine (NE) tumours. The clinical significance of CgA has been studied mostly in patients with known NE tumours. The diagnosis was evaluated in 153 consecutive patients in whom CgA was measured in a given time interval. METHODS: CgA in serum was measured by radioimmunoassay. Immunohistochemistry with an antibody against CgA was performed in tumours from patients with adenocarcinoma and elevated CgA levels using a conventional method and the more sensitive tyramide signal amplification (TSA) technique. RESULTS: Elevated serum CgA levels were found in 44 patients; 19 had NE tumours and 6 had tumours classified as adenocarcinomas. With the TSA technique, a high proportion of CgA-positive cells were disclosed in five of the adenocarcinoma patients. Patients with atrophic gastritis (no. 2) and patients treated with inhibitors of gastric acid secretion (no. 6) also had elevated levels of CgA. A modest increase in CgA levels was observed in 2 patients with renal impairment, and in 9 patients without any obvious cause. CONCLUSION: The current study confirms that serum CgA is a sensitive marker for the detection of NE neoplasia. Elevated levels found in patients with adenocarcinoma may indicate NE differentiation in the tumour. CgA is a useful tool in the monitoring of enterochromaffin-like (ECL) hyperplasia secondary to treatment with acid secretion inhibitors or atrophic gastritis.     

慢性心力衰竭患者血中CgA、BNP与NE水平变化的临床观察

目的:探讨不同程度心力衰竭患者血浆嗜铬粒蛋白A(CgA)、脑钠尿肽(BNP)及去甲肾上腺素(NE)水平的变化及其临床意义。方法: 慢性心力衰竭（CHF）患者50（男35,女15）例,年龄在37～79（60±12）岁;其中扩张性心肌病27例,缺血性心肌病23例;健康对照组30（男22,女8）例,年龄在45～68（56±10）岁。采用ELISA法检测CgA、NE。采用放免法测定BNP。所有入选者行超声心动图检查, 测量左室射血分数(LVEF)及左室舒张末期内径(LVEDD) 。比较CHF患者血浆CgA、BNP、NE水平与对照组之间的差异;血浆CgA、 BNP、NE水平与心功能及LVEF以及3种激素之间的相关性;CHF组治疗前及治疗后CgA、BNP、NE水平的变化。结果: CHF患者血浆CgA、BNP、NE水平与对照组相比明显升高［CgA(124±79) μg/L vs.(24±10)μg/L;BNP (262±111)n/L vs.(78±29)ng/L;NE (504±356)ng/L vs.(102±68)ng/L,均P<0.05)。血浆CgA、BNP、NE水平分别随心功能NYHA分级程度的加重而显著增高,并与LVEF呈负相关。患者血浆CgA分别与BNP、LVEDD正相关。CHF组治疗前、后比较,血浆BNP、NE水平明显下降,而CgA水平无变化。结论: CHF患者血浆CgA、BNP及NE水平的变化与心衰的发生和发展有关。     

血浆嗜铬粒蛋白A对多种神经内分泌肿瘤的诊断价值

目的 探讨血浆嗜铬粒蛋白A(CgA)对神经内分泌肿瘤的诊断价值,同时评价血浆CgA对胃肠胰腺内分泌肿瘤的诊断效力,初步探讨血浆CgA对胃肠胰腺内分泌肿瘤预后的监测作用.方法 应用酶联免疫试剂盒检测56例胃肠胰腺内分泌肿瘤、52例嗜铬细胞瘤和7例小细胞肺癌的血浆CgA浓度,同时以52例健康体检者作为对照,计算血浆CgA诊...     

Clinical trial: inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects

Background and Aim: Revaprazan is a novel acid pump antagonist. The aim of this study was to investigate the inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects. Methods: In a double‐blind, three‐way cross‐over study, 30 healthy male volunteers were randomized to 100, 150 or 200 mg of oral revaprazan daily for 7 days. Serum gastrin concentration was measured, and 24‐h intragastric pH was recorded at baseline and on days 1 and 7 of each administration period. Serial blood samples were processed for pharmacokinetics. Results: Median intragastric pH over 24 h and mean percentage time that pH was > 4 increased in a dose‐dependent manner and were significantly higher on days 1 and 7 compared with baseline in all groups (P < 0.05). The antisecretory effect of revaprazan was rapid and nearly maximal on day 1 in all groups. Serum gastrin levels were rapidly normalized by 100 and 150 mg/day of revaprazan on days 1 and 7, but were significantly higher in the 200 mg/day revaprazan group. The pharmacokinetic effect was rapidly absorbed and eliminated on days 1 and 7 in all groups. Conclusions: Revaprazan rapidly and effectively inhibits gastric acid secretion in healthy male subjects. Therefore, revaprazan can be used as an effective drug for acid‐related disease.     

Clinical significant of serum chromogranin A levels for diagnosing pheochromocytoma in hypertensive patients

OBJECTIVE: CMA is a widespread glycoprotein located in the secretory vesicles of neuroendocrine cells and is co-released with peptides and biogenic amines into the circulation. The present study set out to investigate the clinical utility of assessing serum CGA levels in comparison with the urinary KTCO and their urinary metabolites concentrations, which are to date the gold standard validated diagnostic test. METHODS: From January 2000 to June 2001, 202 consecutive patients, aged 53 +/- 12.7, 102 males, were admitted to our department for a hypertension evaluation. Blood samples for measurements of plasma concentrations of chromogranin A were collected and serum CGA levels were quantified by RIA technique (RIACT). This radioimmunometric technique consisted in using 2 monoclonal antibodies directed to 2 specific antigenic domains of the middle portion of the CGA. The fixed threshold value for identifying positive results was, set at 100 ng/ml according to previous studies. RESULTS: No pheochomocytoma was diagnosed by conventional urinary KTCO essay. Of the 202 CGA blood samples, 32 turned out to be positive, due to commonly encountered false positive causes (inhibitor of the pump with protons, corticotherapy, hypergastrinemia, chronic renal insufficiency, respectively, in 11, 2, 1, 18 cases). The CGA plasma concentration averaged 77 +/- 77 mg/ml and 203 +/- 125 ng/ml in the CGA subgroup over the threshold value. CONCLUSION: The reliability of immunoradiometric serum CGA concentrations appeared according to this work to be comparable to that of the urinary KTCO levels and their urinary metabolites in hypertensives. Moreover, it solely requires a simple, easily done blood taking, less expensive than urinary KTCO collection. Besides, no antihypertensive drugs interfered with the analysis of CGA levels. However, some false positive results have to be mentioned in the presence of renal impairment, hypergastrinemia, corticotherapy, inhibitor of the pump with protons.     

MDM2在消化管癌表达的临床意义

目的探讨MDM2在消化管癌表达的意义.方法利用免疫组织化学SP法检测MDM2在164例消化管癌和32例慢性萎缩性胃炎伴不典型增生中的表达.结果慢性萎缩性胃炎伴不典型增生组总阳性率(±～+)为46.87%,消化管癌阳性(+)者23.17%,弱阳性者(+)为39.02%.高分化组阳性率高于低分化组;有转移组阳性率高于无转移组;黏液腺癌组阳性率低于鳞状细胞癌和管状腺癌组(均P＜0.05).结论MDM2与肿瘤发生发展、病理类型和临床治疗有关.     

Clinical significance of elevated serum interferon- inducible protein-10 levels in hepatitis C virus carriers with persistently normal serum transaminase levels

The aim of this study was to assess the immuno- logical profile in hepatitis C virus carriers with persistently normal serum transaminase levels. Forty-two serum HCV RNA positive patients with persistently normal serum transaminase levels (22 natural 'asymptomatic HCV carriers' and 20 biochemical responders to IFN therapy) and 23 complete responders to IFN therapy were enrolled. The HCV genotypes and serum HCV RNA levels were determined before IFN therapy in treatment responders, and at entry in the others. The serum levels of IFN-inducible protein-10 (IP-10) (a protein mainly induced by IFN-γ), interleukin (IL)-10, and IL-4 were measured in all patients while the serum transaminase levels were normal. The serum transaminase levels and platelet counts were then monitored for the next 4 years and the changes in liver fibrosis were assessed. The serum levels of IP-10 in infected and biochemically normal patients were significantly higher than the levels in complete responders to therapy, whereas the serum levels of IL-10 and IL-4 did not vary significantly among the different groups. During the 4-year follow-up period, 10/20 (50%) biochemical responders and 12/22 (55%) asymptomatic carriers had an elevation of the serum transaminase levels. A significant ( P =0.0370) increase in platelet count after 4 years and improvement in liver fibrosis were noted in treatment responders but not in infected patients. The weak but significant residual immune response as reflected by the increased serum IP-10 level may underlie the outcome of HCV carriers with persistently normal serum transaminase levels.     

Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy

Objectives: Faecal Calprotectin (FC) is a sensitive marker for gut inflammation. However, slightly elevated FC levels are also common in subjects without inflammation. We investigated the association between FC and clinical factors including concomitant use of medical therapy in patients with a normal colonoscopy.

Material and methods: Out-patients (n?=?1263) referred for colonoscopy, performed FC test (CALPRO) the day before the start of bowel preparation. All subjects answered questionnaires that included questions on the present and past health history, concomitant medical treatment and gastrointestinal symptoms (GSRS). A medical record chart review was performed to check for concomitant disease, cause of referral and the result of the colonoscopy including biopsies. Inclusion criteria were a normal colonoscopy. Exclusion criteria were inflammatory bowel disease, colon cancer and high-grade dysplasia.

Results: Five hundred ninety subjects fulfilled the inclusion criteria and completed the study. Thirty-six per cent of the subjects had a FC >50 µg/g. In a logistic regression analysis, age (adjusted OR: 1.051; CI: 1.032–1.071), and the use of proton pump inhibitors (adjusted OR: 3.843; CI: 2.338–6.316), non-steroid anti-inflammatory drugs (adjusted OR: 2.411; CI: 1.162–5.002) and acetylsalicylic acid (adjusted OR: 2.934; CI: 1.085–3.448) were significantly associated with an elevated FC (>50 µg/g).

Conclusions: More than one-third of the patients with a normal colonoscopy performed in clinical routine had a slightly elevated FC level. Our results emphasise the need for attention to age, the use of proton pump inhibitors, non-steroid anti-inflammatory drugs and acetylsalicylic acid in the interpretation of FC tests in clinical practice.     

Clinical usefulness of serum antibodies as biomarkers of gastrointestinal and liver diseases

The progressively growing knowledge of the pathophysiology of a number of immune-mediated gastrointestinal and liver disorders, including autoimmune atrophic gastritis, coeliac disease, autoimmune enteropathy, inflammatory bowel disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and autoimmune pancreatitis, together with the improvement of their detection methods have increased the diagnostic power of serum antibodies. In some cases – coeliac disease and autoimmune atrophic gastritis – they have radically changed gastroenterologists’ diagnostic ability, while in others – autoimmune hepatitis, inflammatory bowel disease and autoimmune pancreatitis – their diagnostic performance is still inadequate. Of note, serum antibody misuse in clinical practice has raised a number of controversies, which may generate confusion in the diagnostic management of the aforementioned disorders. In this review, we critically re-evaluate the usefulness of serum antibodies as biomarkers of immune-mediated gastrointestinal and liver disorders, and discuss their pitfalls and merits.     

Clinical outcomes of esophagogastroduodenoscopy in critically ill patients using high-dose proton pump inhibitor for suspected bleeding: A retrospective cohort study

Esophagogastroduodenoscopy (EGD) is a useful procedure performed for gastrointestinal (GI) bleeding. No definite clinical guidelines recommend EGD implementation in intensive care unit (ICU) patients with suspected GI bleeding. The objective of this study was to compare the clinical effectiveness of EGD in critically ill patients who are using high-dose proton pump inhibitor (PPI) for suspected GI bleeding.We retrospectively analyzed ICU patients using high-dose PPI for suspected GI bleeding from January 2012 to September 2020. Major cases of GI bleeding, such as those with hematemesis and hematochezia, were excluded, and 1:1 propensity score matching was performed. The change in hemoglobin level, requirement of red blood cell transfusion, re-suspected bleeding event, length of ICU stay, and ICU mortality were compared between the EGD and non-EGD groups.Of the 174 subjects included, 52 patients underwent EGD within 24 hours of PPI administration. In the EGD group, 22 (42.3%) patients showed normal findings, while esophagitis and gastritis were most common abnormal finding (n = 11, 21.2%), and 14 patients (26.9%) underwent a hemostatic procedure. While comparing the 2 groups, the EGD group required a higher amount of red blood cell transfusion (packs) than the non-EGD group for a week (3.04 ± 0.44 vs 2.07 ± 0.25, P = .01). There was no significant difference in the change in hemoglobin level after 1 week (P = .15). After propensity score matching, the EGD group showed similar the requirement of red blood cell transfusion and change in hemoglobin level for a week (P = .52, P = .97, respectively). In analyses for all patients and propensity score matched patients, there was no statistically significant difference in term of re-suspected bleeding event rate, duration of ICU stay, and ICU mortality. However, re-suspected bleeding event rate and ICU mortality were lower trend in the EGD group than the non-EGD group.This study showed that EGD had no definite clinical benefit in ICU patients using high-dose PPI for suspected GI bleeding and aggressive EGD is not necessarily recommended. However, it is necessary to consider EGD in patients who are tolerant.     

Clinical significance of serum levels of secretory leukocyte protease inhibitor in patients with systemic sclerosis

Abstract

We aimed to investigate the clinical significance of serum levels of secretory leukocyte protease inhibitor (SLPI), which is widely expressed in lung tissues and serves as a useful marker reflecting the activity of various lung diseases, in patients with systemic sclerosis (SSc). Serum SLPI levels were measured by a specific enzyme-linked immunosorbent assay (ELISA) in 58 SSc patients and 16 healthy controls. Serum SLPI levels in diffuse cutaneous SSc and in limited cutaneous SSc with interstitial lung disease (ILD) were significantly higher than those in healthy controls (43.1 ± 18.4 vs. 30.9 ± 3.76 ng/ml, p < 0.05 and 39.8 ± 10.3 vs. 30.9 ± 3.76 ng/ml, p < 0.01, respectively). The incidences of decreased percent diffusing capacity for carbon monoxide (%DLco) and decreased percent vital capacity (%VC) were significantly greater in SSc patients with elevated SLPI levels than in those with normal levels (73 vs. 31%, p < 0.01 and 24 vs. 4%, p < 0.05, respectively). Furthermore, serum SLPI levels were inversely correlated with %DLco (r = ?0.40, p < 0.01), while they were positively correlated with surfactant protein D (r = 0.28, p < 0.05). Longitudinal study revealed the association of serum SLPI levels with the disease activity of SSc-ILD. SLPI serves as a useful serum marker for evaluating SSc-ILD.     

Classification of gastric neuroendocrine tumors and its clinicopathologic significance

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肺癌转移与术后复发患者血清CEA、CA211水平的临床意义

目的探讨CEA、CYFRA21-1两种肿瘤标志物的血清水平对肺癌转移和术后复发的诊断价值。方法应用化学发光免疫检测正常组、复发组、转移组CEA、CYFRA21-1的血清水平和阳性率,并进行统计学分析。结果复发组和转移组血清CEA、CYFRA21-1水平都显著高于正常对照组(P0.05),CEA、CYFRA21-1在复发组中阳性率分别为53.46%、56.67%,在转移组中阳性率分别57.78%、62.22%,两种标志物联检复发组和转移组的阳性率分别为83.33%、88.89%。结论CEA、CYFRA21-1具有诊断肺癌复发和转移的临床价值,两者联检可以提高诊断的准确性。     

Clinical, virologic, and pathologic significance of elevated serum alpha-fetoprotein levels in patients with chronic hepatitis C

Elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C is not uncommonly seen, but the pathogenesis of this phenomenon remains unclear. The aims of this study were to assess the prevalence of elevated serum AFP in patients with chronic hepatitis C and to evaluate the clinical, virologic, and histopathologic significance of this phenomenon. One hundred and fifteen Chinese patients with a histologic diagnosis of chronic hepatitis C were enrolled. None had evidence of hepatocellular carcinoma by image study at enrollment and for at least 2 years' follow-up. Of the 115 patients, 33 (29%) had elevated serum AFP (more than 12 ng/mL). There was a significantly lower mean serum albumin (4.0 +/- 0.1 vs. 4.3 +/- 0.1 gm/dL, p <0.001) and higher mean scores for periportal necroinflammation (3.3 +/- 0.3 vs. 2.3 +/- 0.2, p = 0.007) and fibrosis (2.3 +/- 0.2 vs. 1.1 +/- 0.1, p < 0.001) in patients with elevated serum AFP when compared with patients without elevated serum AFP. Patients with elevated serum AFP had significantly more incidences of genotype 1b infection when compared with patients without elevated serum AFP (77% vs. 51%, p = 0.021). Mean serum hepatitis C virus (HCV) RNA titer showed no significant difference between the two groups. Multivariate logistic regression analysis showed that as serum albumin of less than 4.2 gm/dL, a histology fibrotic score of more than 3, and HCV genotype 1b infection were significantly independent predictors associated with elevated serum AFP. In conclusion, elevated serum AFP levels were significantly correlated with lower serum albumin levels, advanced fibrosis/cirrhosis, and genotype 1b infection in patients with chronic hepatitis C.     

In vivo effect of proton-pump inhibitors on gastric plasmin-dependent fibrinolysis: A study in a porcine model

Introduction

Alkalization of gastric fluids could inhibit plasmin-mediated and/or pepsin-mediated fibrinolysis. We evaluated the gastric antifibrinolytic effect of proton pump inhibitors in a live porcine model.

Material and methods

Six pigs were randomly assigned to treatment with proton pump inhibitors vs no treatment. After endoscopic mucosal resection, 8 μm sections were incubated on fibrin films. Fibrinolytic activity was assessed through focal lysis time. One-hundred-and-forty-two mucosal sections and 129 submucosal sections were analysed. Twenty-four additional sections were analysed on plates containing tranexamic acid to explore pepsin-mediated fibrinolysis.

Results

Focal lysis times in treated vs control groups were 21.0 min vs 21.2 min (p = 0.39) in the mucosa, and 22.2 min vs 20.2 min (p = 0.56) in the submucosa. No lysis could be seen on the plasmin-inhibited fibrin plates.

Conclusion

Only plasmin-mediated fibrinolysis was observed. Proton pump inhibitors had no significant plasmin-dependant antifibrinolytic effect. They may enhance haemostasis through different pathways.     

Intra-abdominal sequestration of the lung and elevated serum levels of CA 19-9: a diagnostic pitfall

Background

Extralobar pulmonary sequestration is an uncommon congenital abnormality that is rarely diagnosed after the age of 40 years. We describe a 64-year-old woman with an intra-abdominal sequestration of the lung and elevated carbohydrate antigen (CA) 19-9 serum levels.

Case outline

On abdominal ultrasound a semi-solid cystic tumour was demonstrated that showed tight connection to the tail of the pancreas according to computed tomography. Cytological examination of the percutaneous biopsy did not lead to a definitive diagnosis. CA 19-9 serum levels were repeatedly elevated >250 IU/ml. With a tentative diagnosis of a tumour of the tail of pancreas the semi-solid cystic mass was resected. Frozen section histology suggested the diagnosis of pulmonary sequestration, which was confirmed by definitive histological examination. Immunohistochemical staining of the specimen with a specific monoclonal antibody against CA 19-9 showed strong immunoreactivity. Three months later the elevated CA 19-9 serum levels returned to normal.

Discussion

Elevated CA 19-9 serum levels have been described in benign pulmonary and mediastinal cystic lesions and in one case of extralobar intrathoracic lung sequestration. Although there is evidence that malignancies may arise in congenital lung cysts, CA 19-9 serum levels have not been investigated in such cases. Based on our results elevated serum values of CA 19-9 in combination with a cystic semi-solid mass in the left subphrenic space should include the differential diagnosis of extralobar pulmonary sequestration.