Early decrease of serum biomarkers of type II collagen degradation (Coll2-1) and joint inflammation (Coll2-1 NO2 ) by hyaluronic acid intra-articular injections in patients with knee osteoarthritis: a research study part of the Biovisco study.

To measure the evolution of the serum levels of specific Osteoarthritis (OA) biomarker, Coll2-1 and Coll2-1 NO2 in knee osteoarthritic patients after viscosupplementation (VS). Fifty-one patients with unilateral symptomatic knee were recruited for this prospective open label study. They received three intra-articular injections of 2 ml of hyaluronic acid (Hylan GF-20) and were followed for 3 months. Walking pain was evaluated and serum samples were taken at each visit. Coll2-1 and Coll2-1 NO2 were measured in the serum using specific immunoassays. Variations over time of each parameter and predictive factor of response were studied. Forty-five patients were analyzed. The serum concentrations of Coll2-1 and Coll2-1 NO2 were significantly higher in KL III/IV patients compared to KL I/II patients at baseline and decreased systematically over time after VS. Its effect was ever more pronounced in patients with KL III/IV. The serum concentration of Coll2-1 was significantly lower at baseline in responders than in non-responders. This study suggests a rapid slowdown of type II collagen degradation and joint inflammation after VS with Hylan G-20 and gives additional information for the validation of accurate biomarkers for OA. The serum level of Coll2-1 appeared to be a predictive factor for response to treatment.

Continuing medical education in Europe: towards a harmonised system.

One of the first reports on the state of medical education was published in 1910 in North America, with the support of the Carnegie Foundation, showing that the interest for this issue dates back at least a century. Doctors (and nurses) are among the few professionals who managed to avoid for a long time any sort of evaluation of their knowledge and competence after the achievement of their diploma. But concern has been rising in society about the fast obsolescence of medical knowledge, particularly in the last 50 years when the development of research and technology in the field has been so fast. The concept of Continuing Medical Education gained growing interest after the Second World War as a necessity for health professionals, but also as a form of protection of patients, who have the right to be treated by competent and knowledgeable doctors and nurses. The United States (US)-based Josiah Macy Foundation recently sponsored a conference exploring the state of continuing education and the result is 'a picture of a disorganised system of education with obvious foci of excellence (most in universities) but with most commercially supported events shading more towards product promotion and the welfare of doctors than prioritised dedication to enhancing the care of patients'. Despite the fact that there is a lot to be learned from the US experience, Europe has to find its own way. Considerable progress was made since 1995 when UEMS (Union Européenne des Médecins Spécialistes) started to structure CME activities in Europe at translational level. A workshop on the issue was jointly organised by the European School of Oncology (ESO) and the Accreditation Council of Oncology in Europe (ACOE) in Berlin in September 2009.

Non-alcoholic duct destructive chronic pancreatitis.

BACKGROUND: The pathology of non-alcoholic chronic pancreatitis has not yet been sufficiently studied. AIMS: To identify the major changes of pancreatic tissue in patients surgically treated for non-alcoholic chronic pancreatitis. PATIENTS: Pancreatectomy specimens from 12 patients with non-alcoholic chronic pancreatitis, including four patients with autoimmune or related diseases (Sjögren's syndrome, primary sclerosing cholangitis, ulcerative colitis, and Crohn's disease), were reviewed. METHODS: Morphological changes were studied histologically and immunohistochemically (to type inflammatory cells) and compared with the pancreatic alterations found in 12 patients with alcoholic chronic pancreatitis. RESULTS: In patients with non-alcoholic chronic pancreatitis, with or without associated autoimmune or related diseases, pancreatic inflammation particularly involved the ducts, commonly resulting in duct obstruction and occasionally duct destruction. None of these features was seen in alcoholic chronic pancreatitis which, however, showed pseudocysts and calcifications. CONCLUSION: The pancreatic changes in patients with non-alcoholic chronic pancreatitis clearly differ from those with alcoholic chronic pancreatitis. The term chronic duct destructive pancreatitis is suggested for this type of pancreatic disease.

Numerical aberrations of chromosomes 1 and 17 in tumor cell lines of the exocrine pancreas as determined by fluorescence in situ hybridization.

The relationship between the copy numbers of chromosomes 1 and 17 and characteristics related to aggressiveness, histological grade, and doubling time was studied in 10 cell lines from pancreatic carcinomas (7 from primary tumors, 2 from ascites, and 1 from a liver metastasis). Fluorescence in situ hybridization with, respectively, the (peri-)centromeric pUC 1.77 (chromosome 1), and D17Z1 (chromosome 17) probes was applied to interphase nuclei. The results showed that most of these cell lines were hyperploid for both chromosomes studied in accordance with their chromosome counts in metaphase; moreover, there existed a statistically significant positive correlation between the results for both probes. Two of these cell lines had a higher mean copy number for chromosome 17 than for chromosome 1 (PaCa 44 and PaTu 2); two of them had a higher mean copy number for chromosome 1 than for chromosome 17 (Panc 1 and PSN 1). Although only a weak correlation was observed between the number of signals for either chromosomes 1 or 17 and the doubling time, lines of grade 1 and 2 showed a lower average number of spots per nucleus than grade 3 cell lines for both chromosomes studied.

Differentiation of pancreatic carcinoma induced by retinoic acid or sodium butyrate: a morphological and molecular analysis of four cell lines.

The antiproliferative and differentiation-inducing effects of all-trans retinoic acid (RA) and sodium butyrate (SB) were investigated in four pancreatic ductal adenocarcinoma cell lines, two poorly differentiated ones (PT45 and PaTu-II), one moderately to poorly differentiated one (Panc-1) and one highly differentiated one (A818-1). Treatment with 20 microM RA resulted in moderate inhibition of cell growth in all cell lines, but clear evidence of cytodifferentiation (including elongated cell processes, increased rough endoplasmic reticulum, intensified immunostaining for the mucin marker (M1) was found only in PT45 and Panc-1. These phenotypic changes were paralleled by upregulation of RAR (retinoic acid receptor)-alpha and -gamma mRNA. SB (1 and 2 mM) treatment inhibited the cell growth of all cell lines much more prominently than RA. Cytodifferentiation was also largely restricted to PT45 and Panc-1. A noticeable phenomenon was enhancement of the expression of the neuroendocrine markers synaptophysin and Lcu7 in Panc-1 cells. In conclusion, it is evident that the original differentiation status of cells and their responsiveness to the agents are not clearly associated, and that RA responsiveness correlates with upregulation of RAR-alpha and -gamma mRNA.

Three cases of bronchial stump aspergillosis: unusual clinical presentations and beneficial effect of oral itraconazole.

Bronchial stump aspergillosis (BSA), i.e. Aspergillus infection of bronchial granulation tissue surrounding endobronchial suture threads, is a very rare variant of localized suppurative bronchial Aspergillus infection. The majority of reported cases have occurred within one year after lung surgery. We present three more patients, in whom BSA occurred very late (4.5, 6 and 7 yrs) after pulmonary resection. Other unusual features were: complete absence of symptoms in one patient, and simultaneous occurrence of aspergilloma in another. Removal of the endobronchial suture probably constitutes the key therapy for BSA. In all three of our patients oral itraconazole resulted in clinical, histological and microbiological improvement. In conclusion, BSA should be considered in the differential diagnosis of haemoptysis occurring up to 7 yrs after lung surgery, although an asymptomatic presentation is possible. Furthermore, BSA can be associated with other clinical presentations of Aspergillus infection, e.g. aspergilloma. Finally, long-term oral itraconazole therapy may represent a valid alternative when removal of the suture is not feasible.

[Development of chronic pancreatitis from acute pancreatitis: a pathogenetic concept]. / Die Entwicklung der chronischen Pankreatitis aus der akuten Pankreatitis: Ein pathogenetisches Konzept.

Clinically, alcohol-induced chronic pancreatitis is commonly indistinguishable from acute pancreatitis. A relationship between these two forms of pancreatitis has therefore been suggested. This article presents a pathogenetic model which views the development and course of chronic pancreatitis as a consequence of severe acute pancreatitis.

Serous oligocystic and ill-demarcated adenoma of the pancreas: a variant of serous cystic adenoma.

Serous cystic tumours of the pancreas are uncommon and are usually classified as microcystic adenomas (MCA). As new types of serous cystic tumours of this organ have been reported we reviewed a series of 14 lesions and from macroscopic findings two groups were distinguished: ten tumours revealed the features of MCA, while four were clearly distinct from MCA. Grossly, the latter tumours showed only few cysts which were irregularly assembled in fibrous stroma. On the cut surface, there was neither a central stellate scar nor a circumscribed tumour border, features characterizing MCA. Microscopically, the cysts were lined by cuboidal, non-mucin-producing cells. Immunocytochemical staining for cytokeratins 7, 8, 18 and 19 revealed a ductal phenotype. All non-MCA were found in the head of the pancreas and three of them occurred in men. There were no tumour recurrences or signs or malignant transformation after resection (mean follow-up, 2.9 years). These results suggest that there are serous cystic tumours distinct from MCA which may represent another variant of the category of serous cystic adenomas of the pancreas. We propose the term serous oligocystic and ill-demarcated adenoma (SOIA) for these tumours. It is possible that the recently described macrocystic sybtype of serous cystadenoma and SOIA and variants of the same tumour.

Human ductal adenocarcinomas of the pancreas express extracellular matrix proteins.

Pancreatic ductal adenocarcinomas are characterised by a dense connective tissue reaction. To test the hypothesis that stroma components are synthesised and produced by the tumour cells themselves, eight cell lines as well as six xenografted tumours from human ductal adenocarcinomas of the pancreas were examined for the expression of extracellular matrix proteins (ECM), using cDNA probes and antibodies to collagen types I, III and IV, vitronectin, fibronectin, undulin and laminin. All tumour cell lines (CAPAN-1, CAPAN-2, AsPC-1, BxPC-3, PANC-1, PaCa-2, PaCa-3, PaCa-44) and xenografted human pancreatic tumours expressed at least one of the examined ECM at the RNA (collagen type IV > laminin = fibronectin = vitronectin > collagen type III > undulin > collagen type I) or protein level (collagen type IV = collagen type III > vitronectin > laminin > collagen type I = fibronectin > undulin). In nude mouse tumours expression of laminin and collagen I was most pronounced in well-differentiated carcinomas. In a few tumours, collagen type III, vitronectin and undulin were expressed on the luminal side of the neoplastic glands, suggesting loss of normal polar differentiation. Incubation with fetal calf serum modulated ECM RNA levels to a varying extent in all but one cell line (AsPC-1). The results suggest that human pancreatic ductal adenocarcinomas cells are capable of synthesising and producing extracellular matrix proteins in vitro and in vivo, but that the extent and pattern of ECM expression differs between the various tumours and conditions tested.

Ki-ras oncogene activation in preinvasive pancreatic cancer.

Activation of the Ki-ras oncogene by specific point mutations at codon 12 occurs at a remarkably high frequency in pancreatic ductal adenocarcinoma and is likely to be an important event in the pathogenesis of this cancer. To determine whether ras activation also occurs in noninvasive proliferative lesions of the pancreas, a series of cases of ductal papillary hyperplasia, intraductal papillary neoplasia, and intraduct extensions of ductal adenocarcinoma were examined for activating mutations of Ki-ras at codons 12, 13, and 61 using polymerase chain reaction amplification. Specific mutations at Ki-ras codon 12 were found in 5 of 6 cases (83%) of intraduct extensions of carcinomas and in 12 of 16 (75%) invasive carcinomas. In cases with both intraductal and invasive components, the same mutation was identified in each. No mutations were found in 5 intraductal papillary neoplasms and 9 cases of ductal papillary hyperplasia. The authors conclude that Ki-ras activation at codon 12 is important in the tumorigenesis of ductal adenocarcinoma of the pancreas but is not required in the pathogenesis of ductal papillary hyperplasia or intraductal papillary neoplasm.

Chronic pancreatitis: evolution of the disease.

The aim of this study was to review the pathology of acute pancreatitis, resolving acute pancreatitis and chronic pancreatitis in order to find an answer to the unresolved question as to whether chronic pancreatitis is a primary disease or may be due to recurrent acute pancreatitis. Our series consisted of 71 pancreatic resection specimens and 15 autopsy pancreases from 8 patients with acute pancreatitis, 5 patients with pancreatitis 5-7 weeks prior to examination (resolving acute pancreatitis), and 66 patients with chronic pancreatitis. Peripancreatic and intrapancreatic fat necrosis was the key finding in acute pancreatitis. Organization of fat necrosis with early perilobular fibrosis and/or peripancreatic pseudocysts characterized the pancreas with resolving acute pancreatitis. Pseudocysts were present in 52% of pancreases with an early stage of chronic pancreatitis that was characterized by a focally accentuated fibrosis of the perilobular and, to a lesser degree, intralobular type. Marked fibrosis, ductal distortions and presence of intraductal calculi were the main features of advanced chronic pancreatitis. Pseudocysts were less frequent (36%) than in the early stage of the disease. On the basis of these findings it is suggested that acute pancreatitis, if it is severe and also affects the intrapancreatic fat deposits, may evolve into chronic pancreatitis.

Pseudocysts in chronic pancreatitis: a morphological analysis of 57 resection specimens and 9 autopsy pancreata.

The pathology of chronic pancreatitis is reviewed in order to study the histology and incidence of pseudocysts in relation to the degree of pancreatic fibrosis and calcification. The series consisted of 57 resection specimens (49 partial pancreatectomy specimens and 8 total pancreatectomy specimens) and 9 autopsy pancreata. The histology of cystic lesions observed in the specimens was found to be identical to that of pseudocysts in acute pancreatitis. In 19 of 57, there was concomitant occurrence of focal autodigestive (fat) necrosis and pseudocysts. Pseudocysts were more common in specimens with focal fibrosis and few calcifications (13/25) than in those with diffuse advanced fibrosis and numerous calcifications (15/41). The findings indicate that sequelae of acute pancreatitis are frequently present in chronic pancreatitis, particularly in an early stage when fibrosis is still focal and calcification rare. This suggests that chronic pancreatitis may result from relapses of severe acute pancreatitis. A pathogenetic concept that relates acute pancreatitis with chronic pancreatitis is proposed.

Histological typing of pancreatic and periampullary carcinoma.

In recent years, detailed histological, immunocytochemical and ultrastructural studies of pancreatic tumours have provided a system of classification of pancreatic cancer. This classification defines tumour entities with distinct clinicopathologic and prognostic features. Although ductal adenocarcinoma is the most commonly encountered tumour, rare types of pancreatic cancer must not be neglected because of their particular biological features.

Tissue characterization of atheromatous plaques: correlation between ultrasound image and histological findings.

Fifty-four atheromatous plaques of carotid arteries, obtained at autopsy, were scanned with a high-resolution real-time instrument, then histologically examined. Comparison between atherogenesis assessed first by histology then by ultrasonography allowed us to differentiate young from old plaques. An old plaque is characterized by a dense heterogeneous echo pattern and irregular borders or ulceration. Previous studies have shown a correlation between the presence of hemorrhage and ulceration of atheromatous plaques in the carotid, and the frequency of cerebral complications. Since these characteristics were mainly found in older plaques, we consider them to be the most important ones clinically.

Recurrent brachial plexus neuropathy and giant cell arteritis.

A 73-year-old women presented with a recurrent form of sporadic brachial plexus neuropathy, the so-called Parsonage and Turner syndrome. This diagnosis is based on clinical and electromyographic findings. Interestingly a biopsy of the temporal artery demonstrated a giant cell arteritis. The clinical picture started 2 weeks after an upper respiratory tract illness. The possible viral etiology of giant cell arteritis is considered. We think an immunological rather than ischemic disturbance may have caused the recurrent brachial plexus neuropathy. This case report suggests that giant cell arteritis be considered in the investigation of the Parsonage and Turner syndrome.

[Portal venous gas and necrotizing enterocolitis. Apropos of a case diagnosed by x-ray computed tomography]. / Aéroportie et entérocolite nécrosante. A propos d'un cas diagnostiqué par le scanner.

Hepatic portal vein gas is defined as the presence of gas in the portal system. Its presence is exceptional in adults and indicates severe disease. The prognosis depends on the cause of the pathology and not on the portal vein gas itself. We report the case of a patient with acute abdominal pain associated with vascular and neurological symptoms; abdominal C.T. scan revealed hepatic portal vein gas and supported the diagnosis of necrotizing enterocolitis.