Exocrine pancreatic function in Sj?gren's syndrome

Pancreatic function testing was carried out in 19 patients with Sj?gren's syndrome (SS) (nine primary type, ten secondary) by the N-benzoyl-tyrosil-p-aminobenzoic acid (PABA) test, serum immunoreactive trypsin (IRT) levels, and stool fat measurements to evaluate the incidence and type of exocrine pancreatic alterations in this disease. Exocrine pancreatic impairment was found to be present in 63% of the patients. Three types of secretory patterns were observed: (1) normal PABA test results and normal IRT levels (37% [7/19] of the patients); (2) normal PABA test results and elevated IRT levels (42% [8/19]; and (3) low PABA test results and elevated IRT levels (21% [4/19]), including two patients with steatorrhea. Functional pancreatic impairment tended to be more severe in patients with longer disease duration and it was related to the degree of alteration of salivary flow but not to labial salivary gland histologic changes or the type of SS. Inasmuch as hypertrypsinemia was the common marker of pancreatic dysfunction in all patients, we suggest a periodic measurement of serum IRT levels in the follow-up of patients with SS to detect early stages of pancreatic involvement.     

Exocrine and endocrine pancreatic insufficiency after pancreatic surgery

The pancreas is the central organ for digestion and for control of glucose homeostasis. Indications for major pancreatic surgery are complications of chronic and acute pancreatitis and pancreatic malignancies. The postoperative pancreatic function is determined by type of resection, resection of adjacent organs, the underlying disease and preoperative pancreatic function. Standard treatment following major pancreatic surgery includes the administration of pancreatic enzyme preparations and inhibition of acid secretion by proton pump inhibitors. Postoperatively most patients also develop diabetes mellitus, which requires insulin substitution. Hypoglycemia is the most difficult clinical problem to handle following total pancreatectomy.     

Intrafamilial variable phenotypic expression of a CIAS1 mutation: from Muckle-Wells to chronic infantile neurological cutaneous and articular syndrome

Among hereditary inflammatory disorders, Muckle-Wells syndrome, chronic infantile neurological cutaneous and articular syndrome (CINCA), and familial cold urticaria have recently been shown to be caused by dominantly inherited mutations in the CIAS1 gene. Reports suggest that these 3 diseases result from distinct missense mutations, with very few overlapping symptoms. We describe a French family presenting an intrafamilial overlapping clinical phenotype of CINCA and Muckle-Wells syndrome, caused by a mutation in CIAS1 gene. Clinical and genetic observations suggest that Muckle-Wells syndrome, CINCA, and familial cold urticaria are various phenotypic expressions of the same disease.     

Exocrine pancreatic insufficiency in distal pancreatectomy: incidence and risk factors

BackgroundExocrine pancreatic insufficiency (EPI) is a known consequence of pancreatic resection; however, its incidence following distal pancreatectomy is not well defined. The aim of this study was to describe the prevalence of EPI in patients undergoing distal pancreatectomy and moreover identify risk factors for developing de-novo EPI after distal pancreatectomy.MethodsA prospectively maintained institutional pancreatic resection database was interrogated to identify patients who underwent distal pancreatectomy from 2005 to 2015. Pre- and post-operative exocrine function, histopathology, demographics and volume of pancreas resected were analyzed.ResultsThe cohort consisted of 324 patients, 22 (6.8%) presented with EPI pre-operatively. 38 (12.6%) patients developed new onset EPI requiring pancreatic enzyme replacement therapy. There was no relationship between patient demographics or diabetes status and requirement for pancreatic enzyme replacement therapy, and no significant effect of resection volume on the need for pancreatic enzyme replacement therapy post-operatively (p ≥ 0.05). Having an underlying obstructive pancreatic pathology (p = 0.002) or a presenting history of acute pancreatitis (p < 0.001) significantly predicted development of de-novo EPI.ConclusionThese results indicate that pre-existing EPI at time of surgery is not uncommon. Patients presenting for distal pancreatectomy should be assessed pre-operatively for the need for pancreatic enzyme replacement therapy.     

Non-Diamond Blackfan anemia disorders of ribosome function: Shwachman Diamond syndrome and 5q- syndrome

A number of human disorders, dubbed ribosomopathies, are linked to impaired ribosome biogenesis or function. These include but are not limited to Diamond Blackfan anemia (DBA), Shwachman Diamond syndrome (SDS), and the 5q- myelodysplastic syndrome (MDS). This review focuses on the latter two non-DBA disorders of ribosome function. Both SDS and 5q- syndrome lead to impaired hematopoiesis and a predisposition to leukemia. SDS, due to bi-allelic mutations of the SBDS gene, is a multi-system disorder that also includes bony abnormalities, and pancreatic and neurocognitive dysfunction. SBDS associates with the 60S subunit in human cells and has a role in subunit joining and translational activation in yeast models. In contrast, 5q- syndrome is associated with acquired haplo-insufficiency of RPS14, a component of the small 40S subunit. RPS14 is critical for 40S assembly in yeast models, and depletion of RPS14 in human CD34(+) cells is sufficient to recapitulate the 5q- erythroid defect. Both SDS and the 5q- syndrome represent important models of ribosome function and may inform future treatment strategies for the ribosomopathies.     

Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship

Shwachman-Diamond syndrome (SDS) is an autosomal-recessive disorder characterized by short stature, exocrine pancreatic insufficiency, and hematologic defects. The causative SBDS gene was sequenced in 20 of 23 unrelated patients with clinical SDS. Mutations in the SBDS gene were found in 75%, being identical in 11 patients. Hematologic parameters for all 3 lineages were determined over time such as absolute neutrophil counts (ANCs), granulocyte functions, and erythroid and myeloid colony formation (erythroid burst-forming unit [BFU-E] and granulocyte-monocyte colony-forming unit [CFU-GM]) from hematopoietic progenitor cells, percentage of fetal hemoglobin (HbF), and platelet counts. Persistent neutropenia was present in 43% in the absence of apoptosis and unrelated to chemotaxis defects (in 65%) or infection rate. Irrespective of the ANC in vivo, abnormal CFU-GM was observed in all patients with SDS tested (14 of 14), whereas BFU-E was less often affected (9 of 14). Cytogenetic aberrations occurred in 5 of 19 patients in the absence of myelodysplasia. One child died during allogeneic bone marrow transplantation. In conclusion, neutropenia and defective chemotaxis did not result in severe clinical infection in SDS. CFU-GMs were impaired in all patients tested. From the SBDS sequence data, we conclude that in patients with genetically proven SDS a genotype-phenotype relationship in SDS does not exist in clinical and hematologic terms.     

Exocrine pancreatic function: evaluation with MR imaging before and after secretin stimulation

Secretin-stimulated magnetic resonance cholangiopancreatography (SS-MRCP) enhances standard pancreatic imaging in chronic pancreatitis. Diffusion-weighted MRI added to SS-MRCP allows a qualitative and potentially quantitative estimate of pancreatic exocrine secretion, providing an alternative to standard "tube" tests.     

Exocrine pancreatic function in intestinal malabsorption and small bowel disease

Exocrine pancreatic function was studied by means of secretin/pancreozymin stimulation in 50 patients with small bowel disease. Forty-five patients had clinical and biochemical evidence of malabsorption. In none of the patients was there evidence of primary pancreatic disease. Impaired amylase or bicarbonate concentration was found in 62% of the patients; however, in only 6 was there gross pancreatic insufficiency and in only 2 of these was the volume output also decreased. Insufficient dietary protein intake, malabsorption and protein loss in the bowel, with subsequent amino acid and albumin deficiency, are suggested as major causes of pancreatic dysfunction in small bowel disease. In some cases a combination of factors, including folic acid deficiency and chronic malnutrition secondary to intestinal disease with weight loss, are likely causes. In this series, pancreatic function was abnormal in 78% of patients with low serum albumin and 52% of patients with normal serum albumin. The pancreatic insufficiency in intestinal disease is rarely as pronounced as that found in pancreatic steatorrhea; there is usually little difficulty in distinguishing the two, although the secretin/pancreozymin test is not completely discriminatory.Supported by the Medical Research Council of South Africa.     

Exocrine pancreatic enzyme and calcium secretion in health and pancreatitis.

Calcium, enzyme, and total protein secretion were measured in secretin stimulated pancreatic juice in health, "early" chronic pancreatitis, and in chronic calcific pancreatitis. Increased concentrations of trypsin, total protein, and calcium, and increased outputs of calcium and protein were shown to be present in the "early" stages of the disease, indicating that an environment conducive to the formation of protein plugs and possibly later calcification already exists.     

Exocrine pancreatic insufficiency and pancreatic fibrosis due to duodenal somatostatinoma in a patient with neurofibromatosis.

A case of duodenal somatostatinoma is described in a patient with Von Recklinghausen neurofibromatosis. The patient presented with exocrine pancreatic insufficiency, probably due to distal obstruction of the pancreatic duct by the tumor. Preoperative evaluation with calcium-pentagastrin and tolbutamide stimulation tests were nondiagnostic. At laparotomy, local excision of the tumor was performed. Pathological findings were compatible with duodenal somatostatinoma, causing pancreatic fibrosis. Somatostatin extracted from the tumor coeluted with the somatostatin-14 standard on high performance liquid chromatography (HPLC).     

Exocrine pancreatic function in the early period after pancreatoduodenectomy and effects of preoperative pancreatic duct obstruction

Exocrine pancreatic function in the early period after pancreatoduodenectomy was investigated. The effects of preoperative pancreatic duct obstruction on exocrine pancreatic function were also investigated. The volume of pancreatic juice and its amylase activity were investigated in 39 patients who underwent pancreatoduodenectomy (including pylorus-preserving pancreatoduodenectomy). TheN-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA) test was performed on 23 of 39 patients about 40 days after pancreatoduodenectomy. The exocrine pancreatic function was inhibited three to eight days after pancreatoduodenectomy (amylase activity: 23,700±4300 IU/day), and recovered on days 9–15 (48,000±8400 IU/day) in patients with a normal main pancreatic duct. In patients with pancreatic duct obstruction, the exocrine pancreatic function was almost eliminated (amylase activity: 440±260 IU/day) and BT-PABA test results were low (45±17%). In patients with narrowed pancreatic duct, amylase secretion was significantly inhibited even in patients with a normal number of acinar cells. There was a good positive correlation (Spearman's rank correlation coefficient,rs=0.715,P<0.01) between amylase secretion and BT-PABA test. Amylase secretion more than 10,000 IU/day is essential for a normal BT-PABA test and normal digestive function. The inhibited digestive function in patients with pancreatic duct obstruction may be due to the decreased number of acinar cells and the inhibition of exocrine pancreatic function.