Fecal Chymotrypsin and Trypsin Determinations

Trypsin and chymotrypsin concentrations were determined in 180 spot stool specimens from 110 control patients in hospital. The lower limit of normality for each enzyme was placed at the 5% level: 95% of this population excreted feces containing more than 100 μg. of chymotrypsin and 30 μg. of trypsin per g. of feces. Chymotrypsin concentrations appeared to be a more reliable guide to pancreatic function than trypsin concentrations.Fecal chymotrypsin concentrations were subnormal in five patients with chronic pancreatitis, borderline in one patient with relapsing pancreatitis, subnormal in one patient after pancreatectomy, and subnormal in five of nine with carcinoma of the pancreas. Subnormal concentrations of fecal chymotrypsin were found in seven of 21 patients with chronic liver disease related to alcoholism, eight of 32 with a partial gastrectomy, three of 10 with adult celiac disease and five of 16 with psoriasis.It appears that the determination of fecal chymotrypsin concentrations provides a valuable screening test for pancreatic exocrine deficiency. However, normal results may be found in some patients with pancreatic disease and subnormal values may occur in some patients with other conditions.     

Prospective comparison of three non-invasive tests for pancreatic disease.

Ultrasonography, computed tomography (CT), and an oral pancreatic function test were evaluated prospectively in 107 consecutive patients suspected of having pancreatic disease, the final diagnosis being made independently of these tests. Seventeen patients proved to have either chronic pancreatitis or a pancreatic neoplasm. Five had an unfused ventral pancreas and 10 had "minimal change" pancreatograms. Seventy five patients did not have pancreatic disease. Among the 17 patients with pancreatic disease the sensitivities of ultrasound, CT, and the pancreatic function test were 70%, 71%, and 76% respectively; among those without disease values of specificity of the three tests were 75%, 87%, and 72%. All three tests failed to detect most of the patients with unfused ventral pancreases or minimal change pancreatograms. The predictive values of a positive result for the three tests were 43%, 67%, and 34%. The predictive value of a negative result was greater than 90% for all the tests. Results improved when CT was combined with either of the two other tests. These findings show that CT is the most accurate of the three tests in diagnosing pancreatic disease but that a combination of ultrasound and the oral pancreatic function test offers a more widely applicable and almost as accurate alternative.     

Influence of extrapancreatic digestive disorders on the indirect pancreatic function test with fluorescein dilaurate

The detection rate of pancreatic disease using the indirect pancreatic function test with orally administered substrate fluorescein dilaurate (FDL) was evaluated in 290 patients. The sensitivity of the test was 84% in chronic pancreatitis (99 patients). Results were abnormal in all 5 patients with advanced pancreatic cancer and in 3 of 19 patients tested after a single episode of acute pancreatitis. The specificity of the FDL test was 89% when healthy subjects or patients with functional gastrointestinal disorders served as controls. However, it dropped to 62% when all patients with different organic gastrointestinal disorders were considered. This decrease could be attributed to patients with subtotal gastric resection and extensive small bowel disease, who were found to have the highest of pathological FDL test results, i.e., 70 and 35%, respectively. Not restricting the oral FDL test to the detection of primary pancreatic disease, in subtotal gastrectomy and extensive small bowel disease this test provides the opportunity to detect secondary pancreatic dysfunction.     

Comparison of five detection methods for Helicobacter pylori

OBJECTIVE: To evaluate which diagnostic test is preferable for the diagnosis of Helicobacter pylori in patients with gastroduodenal disease. STUDY DESIGN: H pylori infection was diagnosed prospectively in 101 patients. Diagnosis of H pylori was made by tests based on five different principles: (1) culture, (2) direct histologic demonstration, (3) imprint cytology, (4) brushing cytology, and (5) gram staining of H pylori. Efficacy of each test was compared. RESULTS: All the tests were reliable for diagnosing H pylori infection; 73.3% of patients showed concordance in at least two tests. All the tests were positive in > 50% of patients. Significant concordance between brushing and imprint cytology was also determined. These two tests have almost similar specificity when compared to other tests. CONCLUSION: When patients undergo upper endoscopy, we recommend taking biopsy specimens for culture and histology. H pylori can be assessed equally well with all the tests, but imprint and brushing cytology have the advantage of rapid response, specificity, much lower cost and reproducibility.     

Preliminary evaluation of a single-day tubeless test of pancreatic function.

The test for pancreatic exocrine function using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BTP test) does not require duodenal intubation, but misleadingly abnormal results often occur in patients with liver or bowel disease because the p-aminobenzoic acid (PABA) released by chymotrypsin hydrolysis of the peptide either is not conjugated or is malabsorbed. This study evaluated a modified BTP test, using a tracer dose of 14C-PABA to eliminate misleading results, to assess exocrine function from a single six-hour collection of urine. The test clearly distinguished all patients with pancreatic steatorrhoea from normal subjects and identified patients with less severe pancreatitis as often as did the Lundh test. Furthermore, in patients with bowel or liver disease the misleadingly abnormal results of the unmodified BTP test were eliminated by the modified test in all but one case. These findings suggest that the modified BTP test provides a practical alternative to conventional tests of pancreatic function that entail duodenal intubation.     

Meal-stimulated and atropine-inhibited secretion of pancreatic polypeptide in healthy subjects, members of MEA I families and patients with malignant endocrine tumours of the gastrointestinal tract

Pancreatic polypeptide has been suggested as a marker for endocrine malignancies of the gastrointestinal tract. However, the secretion of PP shows great intra- and inter-individual variation, causing both false negative and positive results. In order to reduce these risks, we have evaluated a new combined stimulatory and inhibitory test of PP secretion. Six healthy subjects, 23 members of three MEA I families, seven patients with malignant pancreatic endocrine tumours and four patients with carcinoid tumours of the gastrointestinal tract were subjected to a standardized test meal, followed by intravenous atropine 60 min after the start of the meal. Serum PP was monitored during 2 h. In healthy subjects the meal caused a rapid increase in serum PP within 20 min and intravenous atropine caused a significant (P less than 0.05) decrease of serum PP within 15 min. Patients with malignant endocrine pancreatic tumours or carcinoids had a delayed response after the test meal, with maximum levels at 45 min, but still with a significant inhibition by atropine. Even tumour patients with initially normal or slightly increased basal PP levels showed this secretion pattern. Healthy members of MEA I families displayed identical PP curves to healthy subjects, whereas members with elevated basal PP levels who had been previously affected by hyperparathyroidism and/or prolactinomas showed similar secretion patterns to pancreatic tumour patients. We think that a meal stimulatory test is of great value in the diagnosis of gastrointestinal endocrine tumours and also in the identification of subjects with the MEA I trait, who are at high risk of having pancreatic endocrine tumours.     

Use of Glucagon in the Treatment of Pancreatitis

Four patients with pancreatic disease received glucagon intravenously. In two a definite decrease in the volume of pancreatic exocrine secretion was shown, and in one of these pancreatic juice protein and bicarbonate levels also fell. Two patients with acute pancreatitis had pronounced relief of epigastric pain associated with falls in plasma amylase after intravenous glucagon.Several mechanisms could account for the possible beneficial effect of glucagon in pancreatitis, and further studies of its use in this disease are justified.     

CA19-9及CA72-4联合检测在胰腺癌诊断中的应用价值

目的:探究联合检测血清糖类抗原(CA)19-9和CA72-4水平在胰腺癌诊断中的应用价值。方法:回顾性选取我院2016年1月～2017年12月收治的72例胰腺癌患者作为胰腺癌组,以同期住院的68例良性胰腺病患者作为良性胰腺疾病组,同时纳入67例健康体检者作为对照组。检测三组人群血清CA19-9和CA72-4水平,采用受试者工作特征曲线(ROC曲线)及曲线下面积(AUC)分析评估各单项检测指标及联合检测指标对胰腺癌特异性诊断的价值。结果:胰腺癌组患者血清CA19-9和CA72-4水平分别为(137.69±25.32)U/mL和(6.96±1.25)U/mL,显著高于良性胰腺疾病组和对照组(P0.05)。血清CA19-9和CA72-4联合检测诊断胰腺癌的ROC曲线AUC高于其单独检测(P0.05),CA19-9和CA72-4的最佳临界值分别为86.94 U/m L和4.23 U/m L,此时联合检测诊断胰腺癌的敏感性为94.7%,特异性为95.2%。结论:联合检测血清CA19-9和CA72-4诊断胰腺癌的临床价值明显优于其单独检测。     

Clinical value of serum immunoreactive trypsin concentration.

The clinical value of estimation of serum concentrations of immunoreactive trypsin was evaluated by studying 46 healthy controls, 23 controls in hospital, 44 patients with chronic pancreatic disease, and 184 patients with non-pancreatic conditions in which pancreatic disease commonly enters into the differential diagnosis. Serum trypsin concentration had a log normal distribution in the controls, and the calculated normal range was considerably wider than that previously reported. The concentration was abnormal in only 13 out of 27 patients with chronic pancreatitis and was extremely variable in patients with pancreatic cancer. Abnormal results occurred in 11% of the patients with non-pancreatic disease. Eighteen patients had a subnormal trypsin concentration, of whom six did not have pancreatic disease and 12 had either chronic pancreatitis or pancreatic cancer. There was no correlation between serum trypsin concentration and mean tryptic activity as measured by the Lundh test. Of 11 patients with pancreatic steatorrhoea, only seven had subnormal trypsin concentrations. There results suggest that the serum concentrations of immunoreactive trypsin has a low specificity and sensitivity for pancreatic disease and does no reflect the degree exocrine insufficiency in patients with proved chronic pancreatitis.     

Cold pressor test in diagnosis of coronary artery disease: echophonocardiographic method.

The cold pressor test was used to induce myocardial ischaemia in patients with coronary artery disease and the rise in left ventricular filling pressure used as the index of myocardial ischaemia. Left ventricular filling pressure was derived from a non-invasive echophonocardiographic method. A study group of 19 consecutive patients with chest pain underwent the cold pressor test before coronary angiography. Eighteen responded with a rise in filling pressure exceeding 30% and, of these, 17 had serious coronary artery disease (three single vessel, one two vessel, and 13 triple vessel disease; one had coronary artery spasm only). The remaining patient, who showed no rise in filling pressure, did not have coronary artery disease. None of 15 normal controls showed a rise greater than 5% (patients with coronary artery disease versus normal controls p less than 0.001). The cold pressor test would be suitable for patients who cannot or should not exercise and may be combined with exercise electrocardiograms to improve the information content, as it uses a different marker of myocardial ischaemia.     

Serum proteomics signature of cystic fibrosis patients: a complementary 2-DE and LC-MS/MS approach

Complementary 2D-PAGE and 'shotgun' LC-MS/MS approaches were combined to identify medium and low-abundant proteins in sera of Cystic Fibrosis (CF) patients (mild or severe pulmonary disease) in comparison with healthy CF-carrier and non-CF carrier individuals aiming to gain deeper insights into the pathogenesis of this multifactorial genetic disease. 78 differentially expressed spots were identified from 2D-PAGE proteome profiling yielding 28 identifications and postulating the existence of post-translation modifications (PTM). The 'shotgun' approach highlighted altered levels of proteins actively involved in CF: abnormal tissue/airway remodeling, protease/antiprotease imbalance, innate immune dysfunction, chronic inflammation, nutritional imbalance and Pseudomonas aeruginosa colonization. Members of the apolipoproteins family (VDBP, ApoA-I, and ApoB) presented gradually lower expression from non-CF to CF-carrier individuals and from those to CF patients, results validated by an independent assay. The multifunctional enzyme NDKB was identified only in the CF group and independently validated by WB. Its functions account for ion sensor in epithelial cells, pancreatic secretion, neutrophil-mediated inflammation and energy production, highlighting its physiological significance in the context of CF. Complementary proteomics-based approaches are reliable tools to reveal pathways and circulating proteins actively involved in a heterogeneous disease such as CF.     

Combined use of brushing cytology and endoscopic retrograde pancreatography for the early detection of pancreatic cancer

Seventy-two cases of pancreatic cancer were examined by brushing cytology combined with endoscopic retrograde pancreatography. The results of this combined method were better than those reported for the exfoliative cytologic study of pancreatic fluid. The method detected a minute cancer of the main pancreatic duct that was not detected with any other method. The cells obtained by this technique had very well-preserved cytoplasm and nuclear chromatin, which facilitated making a correct diagnosis. Though this method can be applied only to the main pancreatic duct, it is effective for the diagnosis of ductal cell carcinoma, especially those located at the head of the pancreas, which is the most common site for pancreatic cancer. It is a safe procedure, with no complications seen in this series. The differentiation of carcinoma cells from the benign atypical cells of chronic pancreatitis is illustrated and emphasized.     

Rational sequence of tests for pancreatic function.

Of 144 patients with suspected pancreatic disease in whom a 75Se-selenomethionine scan was performed, endoscopic retrograde pancreatography (ERP) was successful in 108 (75%). The final diagnosis is known in 100 patients and has been compared with scan and ERP findings. A normal scan reliably indicated a normal pancreas, but the scan was falsely abnormal in 30%. ERP distinguished between carcinoma and chronic pancreatitis in 84% of cases but was falsely normal in five patients with pancreatic disease. In extrahepatic biliary disease both tests tended to give falsely abnormal results. A sequence of tests to provide a rapid and reliable assessment of pancreatic function should be a radio-isotope scan, followed by ERP if the results of the scan are abnormal, and a Lundh test if the scan is abnormal but the findings on ERP are normal.     

非典型局限性胰腺脂肪沉积的CT诊断

目的:研究探讨CT扫描检查对非典型局限性胰腺脂肪沉积的应用价值。方法:选择2013年1月~2016年12月期间我院消化内科收治的非典型局限性胰腺脂肪沉积患者42例为观察组,同时期在本院进行健康体检的50例正常人群为对照组。比较两组受试者的CT扫描检查结果。结果:观察组患者在普通CT结果显示胰腺形态和大小未改变,胆总管无扩张现象,增强CT扫描显示胰腺内有均匀的低密度影出现。观察组增强CT的动脉、静脉、延时期的扫描值分别为(68.19±2.01)、(44.34±3.52)、(36.28±4.96),对照组分别为(90.39±4.67)、(83.37±6.02)、(66.08±5.91),组间比较有显著差异性(P0.05)。结论:采用普通CT结合增强CT扫描检查可以准确诊断非典型局限性胰腺脂肪沉积的发病,能够较好的对该病作出诊断与鉴别诊断,但应注意与其他胰腺疾病进行鉴别区分。     

Different actions of secretin and Gly-extended secretin predict secretin receptor subtypes

Only one secretin receptor has been cloned and its properties characterized in native and transfected cells. To test the hypothesis that stimulatory and inhibitory effects of secretin are mediated by different secretin receptor subtypes, pancreatic and gastric secretory responses to secretin and secretin-Gly were determined in rats. Pancreatic fluid secretion was increased equipotently by secretin and secretin-Gly, but secretin was markedly more potent for inhibition of basal and gastrin-induced acid secretion. In Chinese hamster ovary cells stably transfected with the rat secretin receptor, secretin and secretin-Gly equipotently displaced (125)I-labeled secretin (IC(50) values 5.3 +/- 0.5 and 6.4 +/- 0.6 nM, respectively). Secretin, but not secretin-Gly, caused release of somatostatin from rat gastric mucosal D cells. Thus the equipotent actions of secretin and secretin-Gly on pancreatic secretion appear to result from equal binding and activation of the pancreatic secretin receptor. Conversely, secretin more potently inhibited gastric acid secretion in vivo, and only secretin released somatostatin from D cells in vitro. These results support the existence of a secretin receptor subtype mediating inhibition of gastric acid secretion that is distinct from the previously characterized pancreatic secretin receptor.     

Water and enzyme secretion are tightly coupled in pancreatic secretion stimulated by food or CCK-58 but not by CCK-8

Pancreatic secretion of protein, water, chloride, and bicarbonate under basal conditions and in response to intravenous and intraduodenal stimuli were studied in awake rats fully recovered from surgery. During the basal phase of pancreatic secretion, protein output and water output were weakly correlated or uncorrelated, consistent with separate regulation and distinct cellular origin of enzyme (acinar cells) and water (duct cells), referred to as the two-component paradigm of pancreatic secretion. When pancreatic secretion was stimulated physiologically, water and protein output abruptly became strongly and significantly correlated, suggesting that protein secretion and water secretion are tightly coupled or that protein secretion is dependent on water secretion. The apparent function of this coupling is to resist or prevent increases in protein concentration as protein output increases. This pattern of secretion was reproduced by intravenous infusion of the CCK-58 form of cholecystokinin, which strongly stimulates pancreatic water and chloride secretion, but not by CCK-8, which only weakly stimulates water and chloride secretion in a non-dose-dependent manner. The remarkably tight association of water and protein secretion in food-stimulated and CCK-58-stimulated pancreatic secretion is consistent with a single cell type as the origin of both water and enzyme secretion, i.e., the acinar cell, and is not consistent with the two-component paradigm of pancreatic secretion. Because CCK-58 is the only detectable endocrine form of cholecystokinin in the rat and its bioactivity pattern is markedly and qualitatively different from CCK-8, actions previously recorded for CCK-8 should be reexamined.     

Efficacy and pattern of use of sputum cytology as a diagnostic test

Sputum cytology is regarded by many clinicians as a noninvasive, cheap and simple test for the diagnosis of bronchogenic carcinoma. Since the introduction of fibre-optic bronchoscopy and more easily obtained bronchial biopsies reliance on sputum cytology has diminished. However, in Edinburgh it was perceived that sputum samples were still being sent as well as, rather than instead of, bronchoscopic specimens. This retrospective study was undertaken to determine whether or not cytological examination of sputum is an efficient and sensitive test in the investigation of patients with suspected bronchogenic carcinoma. It demonstrated that the Lothian University Hospitals NHS Trust Pathology Directorate receives many sputa from departments not specializing in respiratory disease when there is no indication for the test. In addition, we have shown that the absolute sensitivity of the test is only 5% and that when there is a strong clinical suspicion of bronchogenic carcinoma the results of sputum cytology do not play a significant role in the management of the patient. We recommend that sputum cytology is restricted to those patients under the care of Respiratory Units in whom bronchoscopy is inappropriate or unsuccessful.     

Fine needle aspiration cytology of endocrine neoplasms of the pancreas. Morphologic and immunocytochemical findings in 20 cases

OBJECTIVE: To analyze the role of fine needle aspiration (FNA) cytology in the preoperative diagnosis of pancreatic endocrine neoplasms. METHODS: Cytologic and histologic diagnoses of pancreatic endocrine tumors were reviewed. A total of 20 FNA cytologic procedures from 20 patients were selected. A false positive case, a retroperitoneal paraganglioma, was also reviewed. Two groups of patients were established: (1) those in whom a surgical biopsy with an immunohistochemical study was available (n = 13), and (2) those with a pancreatic tumor in which the diagnosis was confirmed by immunocytochemical studies (n = 7). In 13 cases the pancreatic tumor was aspirated, while in 7, liver metastases were studied. The immunoexpression of chromogranin and synaptophysin was evaluated in alcohol-fixed smears from 12 and 11 cases, respectively. RESULTS: One false negative and 1 false positive diagnosis were present. In the remaining 19 cases a cytologic diagnosis of pancreatic endocrine tumor was given. Main cytologic features were: (1) a prominent cellular dissociation with many single cells and small, poorly cohesive groups; (2) intermediate to large size cells with ill-defined cytoplasm, naked or eccentric nuclei, and frequent binucleation; and (3) variable nuclear pleomorphism with the characteristic finely granular distribution of the chromatin. Immunocytochemical evidence of endocrine differentiation (chromogranin or synaptophysin) was present in the 12 cases analyzed. CONCLUSION: FNA cytology offers the possibility of a precise preoperative, noninvasive diagnosis of pancreatic endocrine tumors. Cytologic features differ considerably from those of pancreatic adenocarcinoma, allowing differentiation from nonfunctioning endocrine neoplasms. In difficult cases immunocytologic studies are very helpful.     

Value of EUS‐FNA cytological preparations compared with cell block sections in the diagnosis of pancreatic solid tumours

Y. Kopelman, S. Marmor, I. Ashkenazi and Z. Fireman
Value of EUS‐FNA cytological preparations compared with cell block sections in the diagnosis of pancreatic solid tumours Objective: Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is performed in order to achieve a definite tissue diagnosis of pancreatic lesions. This in turn is a guide to the appropriate treatment for the patient. Tissue samples collected by the same needle for cytological preparations and cell block histological sections (often referred to as FNA‐cytology and FNA–biopsy, respectively) are handled differently. The specific contribution of each of these tests was evaluated. Methods: One hundred and two consecutive patients underwent EUS‐FNA while being investigated for pancreatic solid lesions. Diagnosis was made by cytology, cell block sections or both. The diagnosis was confirmed by clinical outcome. Results: Male/female ratio was 61/41. Mean age was 65 ± 12 years (range, 22–94). Mean lesion size was 3.1 ± 1.8 cm (range, 0.6–10 cm); 68% were >2 cm and 75% were located in the pancreatic head. The average number of needle passes was two (range, 1–4 passes). Final tissue diagnosis was malignant in 66 (65%) patients. Sensitivity, specificity and accuracy were 73%, 94% and 81%, respectively, for cytology alone, and 63%, 100% and 78%, for cell blocks alone. Eighty‐two patients (80%) had cytology and cell blocks, which matched in 64 (78%) patients. EUS‐FNA results that relied on both techniques had 84% sensitivity, 94% specificity and 88% accuracy. Cytology revealed 13 malignancies not diagnosed on cell blocks, while cell blocks revealed five malignancies not diagnosed by cytology. Malignant lesions were more common in men; they were larger in size and located in the pancreatic head. Conclusion: EUS‐FNA cytology was more sensitive than cell blocks but less specific for the diagnosis of solid pancreatic lesions. The two methods are complementary and implementing both improves the diagnostic value of EUS‐FNA.