Activation of TLR9-dependent p38MAPK pathway in the pathogenesis of primary Sjögren's syndrome in NOD/Ltj mouse.

OBJECTIVE: The objective of this study was to investigate the potential role of Toll-like receptor 9-dependent p38 MAPK signaling pathway in the pathogenesis of primary Sjögren's syndrome (pSS) in NOD/Ltj mouse, aiming to identify an ideal target therapy model for human pSS. METHODS: NOD/Ltj mice were chosen as a model of pSS. The Toll-like receptor 9 and p-p38 MAPK double-positive peripheral blood mononuclear cells (PBMCs) of 4-, 5-, 8-, 10-, and 15-week-old NOD/Ltj mouse were analyzed by flow cytometry. The expressions of Toll-like receptor 9 and p-p38 MAPK in the submandibular gland (SMG) were also examined by immunohistochemistry. The change of stimulated salivary flow rate was dynamically measured, and the histopathology of SMG was evaluated by hematoxylin and eosin stain. RESULTS: The stimulated salivary flow rate in NOD/Ltj was reduced to 50-60% of the flow rate of control mice since the fifth week onwards. The Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs in both groups increased gradually from 5 weeks, peaked at 8 weeks and then gradually decreased at 10 weeks, yet the percentage of Toll-like receptor 9 and p-p38MAPK double-positive PBMCs in 5-, 8-, and 10-week-old NOD/Ltj mouse was significantly increased compared with those in control subjects. After the 10th week onwards, there were no significant differences in the Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs between NOD/Ltj mice and controls. Immunohistochemical staining showed that Toll-like receptor 9 was positive in the acinar epithelium cells and infiltrating lymphocytes in NOD/Ltj mice. p-p38 MAPK was detected in infiltrating lymphocytes and few ductal or acinar epithelium cells adjacent to infiltrating lymphocytes in NOD/Ltj mice. CONCLUSIONS: From the fifth week till the tenth week, Toll-like receptor 9 and p-p38 MAPK double-positive PBMCs were significantly increased in NOD/Ltj mice, accompanied with reduced stimulated salivary flow rate and Toll-like receptor 9 or p-p38 MAPK positive infiltrating lymphocytes observed in the SMG of NOD/Ltj mouse. Our results indicated that activation of Toll-like receptor 9-depended p38 MAPK signal pathway in PBMCs was an early event in pSS which made NOD/Ltj as an ideal therapy model to test the treatment effects of p38 MAPK or Toll-like receptor 9 inhibitors on pSS.

Treatment of symptomatic polycystic liver disease: transcatheter super-selective hepatic arterial embolization using a mixture of NBCA and iodized oil.

BACKGROUND: Surgical therapy for symptomatic polycystic liver disease (PLD) is effective but has substantial mortality and morbidity. Minimally invasive options such as laparoscopic fenestration, percutaneous cyst aspiration with or without injection of a sclerosing solution have had disappointing results. Because the hepatic cysts in autosomal dominant polycystic kidney disease (ADPKD) patients are mostly supplied from hepatic arteries but not from portal veins, therefore, transcatheter arterial embolization (TAE) of the hepatic artery branches that supply major hepatic cysts can lead to shrinkage of the cyst and liver size. AIM: The purpose of this study was to evaluate the safety and effectiveness of TAE using a mixture of N-butyl-2-cyanoacrylate (NBCA) and iodized oil for massive PLD in ADPKD patients. METHODS: From February 2007 to March 2011, a total of 21 patients with symptomatic PLD underwent super-selective hepatic TAE with the mixture of NBCA and iodized oil. The patients consisted of 17 women and 4 men (age range 36-64 years, average age 48.8 years). All patients underwent contrast-enhanced computed tomography (CT) of the liver before TAE, and at every 3 months for the first year after TAE and at 6-monthly intervals thereafter. Laboratory data, including routine blood tests and liver enzymes, were collected before and 1, 3, 7, and 14 days, 1, 3, 6, and 12 months after TAE. RESULTS: Technical success was achieved in all cases. No serious complications were experienced. The mean follow-up period was 34 ± 20 months (range 12-60 months). At follow-up of 6-12 months, symptoms notably improved in 18 (85.7%) of 21 patients, and these patients experienced further relief of the symptoms during the follow-up period. TAE failed to benefit in 3 patients (14.3%). No patient complained of worsening of the symptoms after the procedure. At follow-up CT, the total liver volume and total intra-hepatic cyst volume decreased significantly (p < 0.001) compared with pre-TAE in 18 (85.7%) of 21 patients at 12 months after TAE. The total liver volume decreased from 8270 ± 3016 to 6120 ± 2680 cm(3) and the total intra-hepatic cyst volume decreased from 7120 ± 3070 to 4530 ± 2600 cm(3). Mild elevation of the liver enzymes was shown in patients at 1-14 days after TAE but returned to the normal range within 1 month. CONCLUSION: The mixture of NBCA and iodized oil is an acceptable embolic agent for embolization of the hepatic artery branches that supply the hepatic cysts in ADPKD patients. This technique is an option for patient with highly symptomatic PLD who are not candidates for surgical treatment.

Interventional embolization of giant thoracic tumors before surgical resection.

BACKGROUND: Preoperative embolization of tumors is a well-established procedure that has been successfully applied in various clinical situations. Preoperative embolization can reduce the vascularity of tumors resulting in a clearer operative field, less difficult dissection, decreased blood loss, and, in some cases, a decrease in tumor size. However, few studies have been conducted regarding the preoperative embolization of giant thoracic tumors. PURPOSE: To examine the effectiveness and safety of interventional embolization of giant thoracic tumors before surgical resection. MATERIAL AND METHODS: A total of 14 consecutive patients with giant thoracic tumors received angiography and the feeding arteries of the tumors were embolized using polyvinyl alcohol (PVA) particles and gelatin sponges 1 day before surgical resection. The patient records were retrospectively reviewed and data regarding diagnoses, embolization, and surgical resection were recorded. RESULTS: Angiography revealed the feeding arteries of the tumors to be characterized by multiple branches and thickened vessel trunks with abnormal distal branches superimposed of the tumor shadow. Embolization was successfully without complications in all patients, and all feeding vessels of each tumor were occluded. Embolization reduced the severity of bleeding during surgery and decreased the difficulty of resection of the tumor. No intraoperative or postoperative complications occurred. CONCLUSION: Interventional embolization is a safe and efficient method to facilitate the surgical resection of giant thoracic tumors.

[Ovarian artery supply is one of the factors affecting the interventional therapeutic efficacy of pelvic tumors].

OBJECTIVE: To evaluate the efficacy and safety of transcatheter arterial embolization (TAE) of the ovarian arteries (OA) additionally supplying the tumor of pelvic cavity. METHODS: TAE of OA was performed in 63 patients with a pelvic tumor additionally supplied by the OA. The mean age of those patients was 43.6 years (range, 16 - 66 years). In this series, there were 28 cervical carcinomas, 22 uterus fibroids, 6 ovarian cancers, 3 choriocarcinomas, 2 uterine sarcomas, 1 fibrosarcoma, and 1 rectal carcinoma infiltrating the uterus and adnexa. Emergency TAE was performed in 8 patients due to colporrhagia. The embolization materials consisted of polyvinyl alcohol particles (PVA) in 24 patients, gelatin sponge particles in 10 cases, PVA + gelatin sponge particles in 26; and PVA + gelatin sponge particles + microcoils in 3 cases. RESULTS: The OA embolization was successfully performed in all the 63 cases, including bilateral in 19 cases and unilateral in 44 cases (left 27, right 17). No complications related to the procedure were observed. Bleeding from the vagina in 8 patients ceased immediately after supplemental OA embolization, and no re-bleeding occurred in any of them during their hospital stay. CONCLUSION: Pelvic tumors may be supplied additionally by the ovarian arteries. Therefore, routine internal iliac artery/uterine artery chemoembolization or embolization may not effectively cure the tumors. Ovarian artery angiography should be routinely performed before interventional treatment. A supplementary selective ovarian artery chemoembolization or embolization is safe and effective in the management of pelvic tumors with additional blood supply from the ovarian arteries.

Transarterial Embolization for Treatment of Symptomatic Polycystic Liver Disease: More than 2-year Follow-up.

BACKGROUND: Currently, treatment of symptomatic polycystic liver disease (PLD) is still a challenging problem, especially for these patients who are not feasible for surgery. Minimally invasive options such as laparoscopic fenestration and percutaneous cyst aspiration with sclerotherapy demonstrated disappointing results due to multiple lesions. Because the cysts in PLD are mostly supplied from hepatic arteries but not from portal veins, transcatheter arterial embolization (TAE) of the hepatic artery branches that supply the major hepatic cysts can lead to shrinkage of the cyst and liver size, relieve symptoms, and improve nutritional status. This study aimed to evaluate the effectiveness of TAE with a mixture of N-butyl-2-cyanoacrylate (NBCA) and iodized oil for patients with severe symptomatic PLD during a more than 2-year follow-up. METHODS: Institutional review board had approved this study. Written informed consent was obtained from all patients. From February 2007 to December 2014, twenty-three patients (20 women and 3 men; mean age, 49.0 ± 14.5 years) infeasible for surgical treatments underwent TAE. Changes in the abdominal circumferences, volumes of intrahepatic cysts, hepatic parenchyma volume, and whole liver, clinical symptoms, laboratory data, and complications were evaluated after TAE. RESULTS: Technical success was achieved in all cases. No procedure-related major complications occurred. The median follow-up period after TAE was 48.5 months (interquartile range, 30.0-72.0 months). PLD-related severe symptoms were improved remarkably in 86% of the treated patients; TAE failed to benefit in four patients (four patients did not benefit from TAE). The mean maximum abdominal circumference decreased significantly from 106.0 ± 8.0 cm to 87.0 ± 15.0 cm (P = 0.021). The mean intrahepatic cystic volume reduction rates compared with pre-TAE were 36% at 12 months, 37% at 24 months, and 38% at 36 months after TAE (P < 0.05). The mean liver volume reduction rates were 32% at 12 months, 31% at 24 months, and 33% at 36 months (P < 0.05). CONCLUSIONS: TAE with the mixture of NBCA and iodized oil appears to be a safe and effective treatment method for patients with symptomatic PLD, especially for those who are not good candidates for surgical treatments, to improve both hepatic volume and hepatic cysts volume.

Function of the parotid gland in juvenile recurrent parotitis: a case series.

Our aim was to find out how the parotid gland functions in 44 patients with juvenile recurrent parotitis, and to assess the value of measuring the serum amylase activity. Clinical and personal details were recorded, and all patients had their serum amylase activity measured together with sialography during the chronic phase. The function of the gland was classified by sialographic images. The chi square test and Spearman's rank correlation coefficient were used in the statistical analyses. There was a significant association between the degree of glandular function and serum amylase activity (p=0.014). The patients with unilateral and bilateral disease differed significantly in their degree of glandular function (p=0.020), those with bilateral disease having poorer function. There were no significant correlations between other clinical variables and glandular function. Serum amylase activity is an important diagnostic variable in juvenile recurrent parotitis, and poor parotid function reflects the severity of the disease.