Cryoglobulinaemic vasculitis: classification and clinical and therapeutic aspects

Cryoglobulinaemia may cause cutaneous vasculitis and glomerulonephritis, potentially leading to end stage renal failure. An important proportion of cryoglobulinaemias are secondary to hepatitis C virus infection. Emerging antiviral treatment options offer a chance for causal therapy of these cases of cryoglobulinaemia. This review summarises the classification and clinical and therapeutic aspects of cryoglobulinaemic vasculitis and glomerulonephritis

Fibroblast growth factor receptor 4 single nucleotide polymorphism Gly388Arg in head and neck carcinomas

BACKGROUND Head and neck squamous cell carcinoma (HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases (RTKs) and members of the fibroblast growth factor receptors (FGFR)-family. Single-nucleotide polymorphism (SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC. AIM To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted. METHODS Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany. Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP. Patients' clinical data with a minimum follow-up of 5 syears were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis. RESULTS Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high" (+++) in 74 (26%), "intermediate" (++) in 103 (36.3%), and "low" (+) in 107 (36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors (33.8%), 84 of them (29.6%) having a heterozygous and 12 (4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage (P < 0.004), local metastasis (P < 0.0001) and reduced disease-free survival (P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival (P < 0.003). CONCLUSION In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention

Ewing sarcoma of the mandible mimicking an odontogenic abscess – a case report

Ewing sarcoma (ES) of the mandible is rare and can be mistaken for inflammation of dental origin. We present a 24-year old male patient which underwent radical tumour surgery and primary reconstruction with a microvascular osteoseptocutaneous free fibular flap as well as postoperative adjuvant chemotherapy. Incomplete osseous tumour resection required a second intervention. This case report recapitulates the clinical and histopathological findings in oral ES, demonstrates its sometimes difficult diagnosis and discusses the (dis-)advantages of primary osseous reconstruction in ablative tumour surgery

Curative resection of a primarily unresectable acinar cell carcinoma of the pancreas after chemotherapy

<p>Abstract</p> <p>Background</p> <p>Acinar cell carcinoma (ACC) represents only 1–2% of pancreatic cancers and is a very rare malignancy. At the time of diagnosis only 50% of the tumors appear to be resectable. Reliable data for an effective adjuvant or neoadjuvant treatment are not available.</p> <p>Case presentation</p> <p>A 65-year old male presented with obstructive jaundice and non-specific upper abdominal pain. MRI-imaging showed a tumor within the head of the pancreas concomitant with Serum-Lipase and CA19-9. During ERCP, a stent was placed. Endosonographic fine needle biopsy confirmed an acinar cell carcinoma. Laparotomy presented an locally advanced tumor with venous infiltration that was consequently deemed unresectable. The patient was treated with five cycles of 5-FU monotherapy with palliative intention. Chemotherapy was well tolerated, and no severe complications were observed. Twelve months later, the patient was in stable condition, and CT-scanning showed an obvious reduction in the size of the tumor. During further operative exploration, a PPPD with resection of the portal vein was performed. Histopathological examination gave evidence of a diffuse necrotic ACC-tumor, all resection margins were found to be negative. Eighteen months later, the patient showed no signs of recurrent disease.</p> <p>Conclusion</p> <p>ACC responded well to 5-FU monochemotherapy. Therefore, neoadjuvant chemotherapy could be an option to reduce a primarily unresectable ACC to a point where curative resection can be achieved.</p

Altered plasticity of the parasympathetic innervation in the recovering rat submandibular gland following extensive atrophy

Adult rat submandibular glands have a rich autonomic innervation, with parasympathetic and sympathetic nerves working in synergy rather than antagonistically. Ligation of the secretory duct rapidly causes atrophy and the loss of most acini, which are the main target cell for parasympathetic nerves. Following deligation, there is a recovery of gland structure and function, as assessed by autonomimetic stimulation. This study examines whether the parasympathetic nerves reattach to new target cells to form functional neuro-effector junctions. Under recovery anaesthesia, the submandibular duct of adult male rats was ligated via an intra-oral approach to avoid damaging the chorda-lingual nerve. Four weeks later, rats were either killed or anaesthetized and the ligation clip removed. Following a further 8 weeks, both submandibular ducts were cannulated under terminal anaesthesia. Salivary flows were then stimulated electrically (chorda-lingual nerve at 2, 5 and 10 Hz) and subsequently by methacholine (whole-body infusion at two doses). Glands were excised, weighed and divided for further in vitro studies or fixed for histological examination. Ligation of ducts caused 75% loss of gland weight, with the loss of most acinar cells. Of the remaining acini, only 50% were innervated despite unchanged choline acetyltransferase activity, suggesting few parasympathetic nerves had died. Following deligation, submandibular glands recovered half their weight and had normal morphology. Salivary flows from both glands (per unit of gland tissue) were similar when evoked by methacholine but greater from the deligated glands when evoked by nerve stimulation. This suggests that parasympathetic nerves had reattached to new target cells in the recovered glands at a greater ratio than normal, confirming reinnervation of the regenerating gland

An invasive adenocarcinoma of the accessory parotid gland: a rare example developing from a low-grade cribriform cystadenocarcinoma?

Low-grade cribriform cystadenocarcinoma (LGCCA) is a rare tumor of the salivary gland that exhibits clinically indolent behavior. In this paper, we present a case of invasive adenocarcinoma of the accessory parotid gland in a young male that exhibited histology suggestive of an association of LGCCA. A 27-year-old man presented with a subcutaneous tumor in his left cheek. The tumor was separated from the parotid gland and located on the masseter muscle. The tumor was resected, and the postoperative histological diagnosis was adenocarcinoma, not otherwise specified (ANOS). The tumor exhibited papillary-cystic and cribriform proliferation of the duct epithelium and obvious stromal infiltration. Some tumor nests were rimmed by myoepithelium positive for smooth muscle actin, p63, and cytokeratin 14, indicating the presence of intraductal components of the tumor. Tumor cells exhibited mild nuclear atypia, and some of them presented an apocrine-like appearance and had cytoplasmic PAS-positive/diastase-resistant granules and hemosiderin. Other cells had foamy cytoplasm with microvacuoles. Immunohistochemistry revealed that the almost all of the tumor cells were strongly positive for S-100. These histological findings suggest the possibility that ANOS might arise secondarily from LGCCA. This is an interesting case regarding the association between ANOS and LGCCA in oncogenesis

Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sjögren's syndrome

BACKGROUND: the classification criteria for primary Sjögren's syndrome (pSS) include a number of oral components. In this study we evaluated if salivary flow and composition as well as dental caries are oral markers of disease severity in pSS. METHODS: in 20 patients fulfilling the American-European Consensus criteria for pSS and 20 age-matched healthy controls whole and parotid saliva flow rates and composition, measures of oral dryness, scores of decayed, missing and filled tooth surfaces (DMFS), periodontal indices, oral hygiene, and dietary habits were examined. RESULTS: in pSS, salivary flow rates, pH, and buffer capacities were lower, and DMFS, salivary sodium and chloride concentrations higher than in the healthy controls. DMFS also correlated inversely to salivary flow rates and positively to oral dryness. Apart from slightly increased gingival index, and more frequent dental visits in pSS, the periodontal condition, oral hygiene or sugar intake did not differ between these two groups. In pSS, findings were correlated to labial salivary gland focus score (FS) and presence of serum-autoantibodies to SSA/SSB (AB). The patients having both presence of AB and the highest FS (>2) also had the highest salivary sodium and chloride concentrations, the lowest salivary phosphate concentrations, lowest salivary flow rates, and highest DMFS compared to those with normal salivary concentrations of sodium and chloride at a given flow rate. CONCLUSION: the salivary changes observed in some pSS patients reflect impaired ductal salt reabsorption, but unaffected acinar transport mechanisms, despite low salivary secretion. Our results suggest that changes in salivary flow and composition as well as dental caries may serve as potential markers of the extent of autoimmune-mediated salivary gland dysfunction in pSS. The study also indicates that the ductal epithelium is functionally affected in some pSS patients, which calls for future pathophysiological studies on the mechanisms underlying this impaired salt reabsorption

Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis

In primary Sjogren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-kappa B pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4(+) T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS. Salivary gland dysfunction is an important characteristic of primary Sjogren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell-immune cell interactions contribute to disease development and progression

The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands

This study developed an animal model of surgically wounded submandibular glands (SMGs) and investigated the effects of collagen gel with basic fibroblast growth factor (bFGF) on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF (bFGF group) or without bFGF (control group). In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day (AOD) 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, α-smooth muscle actin (αSMA), CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration