Sclerosing encapsulating peritonitis after living donor liver transplantation: a case successfully treated with tamoxifen: report of a case

Sclerosing encapsulating peritonitis (SEP) is a rare cause of bowel obstruction. It is difficult to diagnose and the prognosis is poor. This report describes a case of SEP after living donor liver transplantation that was successfully treated with tamoxifen. A 56-year-old male, that had received a liver transplant for hepatitis C virus-related hepatocellular carcinoma 5 years earlier, was admitted with continuous abdominal pain and nausea. He had increased C-reactive protein levels and white blood cell count, and underwent laparotomy 5 days after hospitalization. The surgical findings showed ascites and SEP of the small bowel. An attempt to peel off the adhesions was stopped because there was a strong risk of intestinal tract damage. Tamoxifen treatment was initiated for SEP after surgery. The patient’s symptoms gradually improved and he was able to resume feeding. He had been symptom-free for over 3 years at the last follow-up.     

TGF-β1 Promotes Lymphangiogenesis during Peritoneal Fibrosis

Peritoneal fibrosis (PF) causes ultrafiltration failure (UFF) and is a complicating factor in long-term peritoneal dialysis. Lymphatic reabsorption also may contribute to UFF, but little is known about lymphangiogenesis in patients with UFF and peritonitis. We studied the role of the lymphangiogenesis mediator vascular endothelial growth factor-C (VEGF-C) in human dialysate effluents, peritoneal tissues, and peritoneal mesothelial cells (HPMCs). Dialysate VEGF-C concentration correlated positively with the dialysate-to-plasma ratio of creatinine (D/P Cr) and the dialysate TGF-β1 concentration. Peritoneal tissue from patients with UFF expressed higher levels of VEGF-C, lymphatic endothelial hyaluronan receptor-1 (LYVE-1), and podoplanin mRNA and contained more lymphatic vessels than tissue from patients without UFF. Furthermore, mesothelial cell and macrophage expression of VEGF-C increased in the peritoneal membranes of patients with UFF and peritonitis. In cultured mesothelial cells, TGF-β1 upregulated the expression of VEGF-C mRNA and protein, and this upregulation was suppressed by a TGF-β type I receptor (TGFβR-I) inhibitor. TGF-β1–induced upregulation of VEGF-C mRNA expression in cultured HPMCs correlated with the D/P Cr of the patient from whom the HPMCs were derived (P<0.001). Moreover, treatment with a TGFβR-I inhibitor suppressed the enhanced lymphangiogenesis and VEGF-C expression associated with fibrosis in a rat model of PF. These results suggest that lymphangiogenesis associates with fibrosis through the TGF-β–VEGF-C pathway.The decrease in ultrafiltration capacity that is associated with the high peritoneal solute transport that is observed after prolonged peritoneal dialysis (PD) treatment is a major reason for its discontinuation.^1–4 Several studies have shown that a higher peritoneal solute transport rate is associated with reduced survival of PD patients.^1,2,5 The characteristic features of chronic peritoneal damage in PD treatment are associated with submesothelial fibrosis and neoangiogenesis.^6,7 Analyses of the surface peritoneum showed no significant changes in vessel density with duration of PD.^6,8 In addition, the vessel density in patients with ultrafiltration failure (UFF) was significantly higher than the vessel density in normal individuals or non-PD patients, but it was not higher than the vessel density in patients undergoing PD.⁶ These findings suggest that factors other than increased vascular density may be involved in disease states associated with increased transport of peritoneal membranes. In addition, the relationship between peritoneal fibrosis and UFF remains obscure.Blood capillaries have a continuous basal lamina with tight interendothelial junctions and are supported by pericytes and smooth muscle cells. In contrast, lymphatic capillaries are thin-walled with a wide lumen and do not contain pericytes or basement membrane. The structures of lymphatic vessels are suitable for the removal of tissue fluid, cells, and macromolecules from the interstitium.^9–11 If lymphangiogenesis develops in the peritoneal membrane, absorption of the PD fluid could be increased and lead to UFF. An increase in the number of lymphatic vessels has recently been reported in several disease conditions, including tumor metastasis,^12–15 chronic respiratory inflammatory diseases,^16–18 wound healing,¹⁹ and renal transplant rejection.^20,21 We recently reported that lymphangiogenesis had developed in tubulointerstitial fibrosis of human renal biopsy specimens,²² and we also reported the mechanisms of lymphangiogenesis in rat unilateral ureteral obstruction models.²³The lymphatic absorption rate, which is measured by the rate at which intraperitoneally administered radioactive serum albumin or macromolecule dextran 70 disappears, is significantly higher in patients with UFF, and lymphatic reabsorption is considered to be one of the causes of UFF.^24–27 However, the results from these clinical approaches have been controversial.^28,29 In addition, little is known about the pathology and the process of lymphangiogenesis in patients with UFF and peritonitis.In this study, we investigated lymphangiogenesis and the expression of vascular endothelial growth factor-C (VEGF-C), which is a potentially important mediator of lymphangiogenesis, in human peritoneal tissues, PD effluent, and peritoneal mesothelial cells. We also explored VEGF-C induction by TGF-β1 in the human mesothelial cell line (Met-5A) and cultured human peritoneal mesothelial cells (HPMCs) from the spent PD effluent of patients with varying rates of peritoneal transport. Finally, we explored the relationship between peritoneal fibrosis and lymphangiogenesis in rats that were administered chlorhexidine gluconate (CG) into the abdominal cavity, which provides a model of chemically induced peritoneal inflammation/fibrosis.^30–32 This work is the first report to show that lymphangiogenesis is linked to the peritoneal fibrosis that is often associated with a high peritoneal transport rate.     

Long-Term Seizure Outcome following Resective Surgery for Epilepsy: To Be or Not to Be Completely Cured?

Surgical intervention is expected to improve the quality of life in patients with intractable epilepsy by providing adequate seizure control. Although many previous studies showed various rates of seizure freedom, definite conclusions have not yet been made regarding outcomes. In order to clarify the long-term postoperative outcome for a period up to 10 years, a retrospective review of our patients was performed longitudinally by using the survival analysis method. The postoperative state of epilepsy in 76 patients who underwent resection surgery was assessed based on Engel’s criteria. In addition, Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom. In this patient group, abnormal lesion were detected by MRI in 70 out of 76 cases, and the ictal onset zone was finally identified within temporal lobe in 51 cases. The most favorable outcome, defined as Engel Class Ia, was observed in 26 (37%), 24 (40%), and 18 (41%) cases at 2, 5, and 10 years after surgery, respectively. The Kaplan-Meier survival curve in the overall group estimated the probability of seizure freedom as 75% (95% confidence interval [CI] 70–80%), 67% (62–72%), and 51% (45–57%) at 2, 5, and 10 years follow up, respectively. Half of all seizure recurrences occurred within the first 2 postoperative years. In this study, we showed that long-term favorable outcome of seizure control following resection surgery can be achieved in more than half of the patients.     

Clinical significance of IgG deposition in the glomerular mesangial area in patients with IgA nephropathy

Background

Immunoglobulin (Ig) A nephropathy (IgAN) is characterized by mesangial deposits of IgA1 and C3, often with co-deposits of IgG. We attempted to clarify the clinical significance of mesangial IgG deposition in patients with IgAN.

Methods

We retrospectively reviewed 57 patients who were diagnosed with IgAN on the basis of pathological examination of renal biopsy specimens obtained between October 2006 and December 2010. Subjects were divided into two groups: IgA+IgG deposition (IgA-IgG) group (n = 29) and IgA deposition alone (IgA) group (n = 28). The study outcome was complete remission (CR), defined as negative proteinuria by dipstick urinalysis and urinary erythrocytes of less than 1–4/high-power field.

Results

Proteinuria was greater in the IgA-IgG group than the IgA group (1.1 ± 0.8 vs. 0.7 ± 0.6 g/day, Mann–Whitney U test, P = 0.042). Capillary wall IgA deposits were noted more frequently in the IgA-IgG group than the IgA group (59 vs. 11 %, Fisher’s exact test, P = 0.014). During the median follow-up period of 33.3 months (range 6–55 months) in the 57 patients, we observed CR in 24 cases (42.1 %). After the start of treatment, urinary abnormalities disappeared earlier in the IgA group than in the IgA-IgG group (log rank test, P = 0.012). Cox’s regression model showed that IgG deposition reduced the hazard ratio for CR (hazard ratio 0.35; 95 % confidence interval 0.14–0.82, P = 0.014). Therefore, IgG deposition is a risk factor for persistent urinary abnormalities.

Conclusion

Mesangial IgG deposition is associated with more severe clinical features in patients with IgAN.     

Differences in vertebral,tibial, and iliac cancellous bone metabolism in ovariectomized rats

Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3 days to 26 weeks postoperatively. The trabeculae were thicker in the LV, where bone metabolism was less active than at other sites, and numerous fine trabeculae were observed in the tibia, where bone metabolism was more active. The iliac bone structure and metabolism were intermediate between those of the tibia and LV. Ovariectomy induced lower bone volume and higher bone metabolism in all skeletal sites, but the changes were greatest and occurred earliest in the tibia, followed by the iliac bone and then LV. Ovariectomy caused changes in bone metabolic markers, which occurred earlier than those in bone tissue. Activation frequency (Ac.f) increased after ovariectomy. At week 26 in ovariectomized rats, Ac.f was highest in the tibia (3.13 N/year) but similar between iliac bone (0.87 N/year) and LV (1.39 N/year). Ac.f is reportedly 0.3–0.4 N/year in the iliac bone of postmenopausal women, suggesting that bone turnover in rats is several times higher than in humans. The reference values reported here are useful for translating experimental results from rats to humans.     

Antibody‐mediated rejection after ABO‐incompatible pediatric living donor liver transplantation for propionic acidemia: A case report

We herein present the case of a four‐yr‐old boy with PA who developed AMR after ABO‐incompatible LDLT despite undergoing B cell desensitization using rituximab. Although the CD19+ lymphocyte count decreased to 0.1% nine days after the administration of rituximab, he developed a high fever which was accompanied by arthralgia due to a streptococcal infection 13 days after rituximab prophylaxis. After the clearance of the infection, he underwent ABO‐incompatible LDLT 36 days after the administration of rituximab. The CD19+ lymphocyte count just prior to LDLT was 1.2%. He developed AMR five days after LDLT, and the antidonor‐type IgM and IgG antibody titers increased to 1:1024 and 1:1024, respectively. He was treated by plasma exchange, IVIG, steroid pulse therapy, and rituximab re‐administration; however, his liver dysfunction continued. Despite intensive treatment, he died due to complicated abdominal hernia, acute renal failure, and ARDS. This case suggests that a streptococcal infection may induce the activation of innate immune responses; thus, additional desensitization therapy should be considered prior to ABO‐incompatible LDLT if B cell reactivation is suspected.     

Characterization and diagnostic use of a recombinant single-chain antibody specific for the gp116 envelop glycoprotein of Yellow head virus

Yellow head virus (YHV) is an invertebrate nidovirus that can cause mass mortality of the cultured Penaeus monodon shrimp. A single-chain variable fragment (scFv) antibody directed against the gp116 envelop glycoprotein of YHV was constructed from hybridomas. Variable heavy (V(H)) and light (V(L)) chain genes were amplified from cDNA using antibody-specific primers, linked to generate a full-length gene via a standard peptide linker, ligated into the pET28a expression vector and transformed into E. coli. The expressed insoluble scFv antibody was solubilized, purified using immobilized metal affinity chromatography and rapid refolded; final yield 1-1.5 mg/l. Solid-phase non-competitive enzyme-linked immunosorbent assay (non-competitive ELISA) determined the affinity constant (K(A)) to be 3.34+/-0.38 x 10(8)l/mol. The sensitivity and specificity of scFv antibody was demonstrated by ELISA, dot blot and Western blot analysis. The detection limit determined by dot blot and indirect ELISA was 9 ng and 45 ng of purified YHV, respectively. Dot-blot assays revealed that the scFv antibody could detect YHV-infected shrimp at 24h post-infection and did not cross-react with White spot syndrome virus (WSSV) and Taura syndrome virus (TSV) proteins. The scFv antibody therefore might find application in rapid, simple and sensitive diagnostic tests to detect YHV in farmed shrimp.