Synergistic deterioration of prognosis associated with decreased grip strength and hyporesponse to erythropoiesis-stimulating agents in patients undergoing hemodialysis.

INTRODUCTION: We examined the combined effect of erythropoietin (EPO) hyporesponsiveness and low handgrip strength (HGS) on the prognosis of patients undergoing hemodialysis (HD). METHODS: We recruited patients with chronic kidney disease (CKD) Stage 5, who were undergoing HD at our dialysis clinic between January 2015 and March 2015 (n = 182). Patients of ≥20 years of age and who had been undergoing HD for ≧3 months at enrollment were eligible for inclusion. Seven patients treated with epoetin-ß pegol were excluded. First, the erythropoietin resistance index (ERI) and HGS were measured. The patients were stratified by the ERI of 9.44 (U/kg/week/g/dL), and by the HGS of 28 kg for men and 18 kg for women. We then observed death and cardiovascular disease (CVD), composite endpoint (deaths or CVD) for a median of 2 years. RESULTS: A total of 175 patients (male, n = 122; female, n = 53; age, 34-92 years) were included in the analysis. During the observation period of 24 months, 57 events (14 deaths and 43 CVD) were observed. High ERI and low HGS were associated with a high incidence of endpoints compared to low ERI and high HGS. Among the four groups classified by ERI and HGS values, the highest risk group was the high ERI/low HGS group (HR: 4.20 95% CI 2.12-8.33). CONCLUSIONS: EPO hyporesponsiveness combined with low HGS were found to be significant predictors of a poor outcome, and the synergistic effects of the two factors had stronger predictive ability than either single factor.

Correction: Iron deficiency associates with deterioration in several symptoms independently from hemoglobin level among chronic hemodialysis patients.

[This corrects the article DOI: 10.1371/journal.pone.0201662.].

Iron deficiency associates with deterioration in several symptoms independently from hemoglobin level among chronic hemodialysis patients.

BACKGROUND: While iron deficiency (ID) is a frequent cause of anemia in hemodialysis patients, the clinical impact of ID without anemic level of hemoglobin remains unclear. As such, this study was designed to clarify the manifestations of ID itself in subjects on hemodialysis. METHODS: Maintenance hemodialysis patients achieving target hemoglobin levels (≥ 10.0g/dL) under treatment in our clinic were stratified for comparison from three perspectives: ID (transferrin saturation [TSAT] < 20% or ferritin < 100ng/mL) vs non-ID, level of TSAT (< or ≥ 20%), and level of serum ferritin concentration (< or ≥ 100ng/mL). The severity of frequent symptoms was determined by a self-rating symptom score questionnaire, and the rate of those with severe manifestations was calculated for each symptom. Significant difference was examined between groups; univariate and adjusted multivariate odds ratios and 95% confidence intervals were obtained by logistic regression. RESULTS: Among 154 subjects selected for analysis, the ratio of severe arthralgia and fatigue was significantly higher in the ID group (n = 94) compared to the non-ID group (n = 60), in both univariate and adjusted multivariate analyses. Moreover, in multivariate analysis, low TSAT was significantly associated with exacerbation of pain during vascular access puncture and intradialytic leg cramps, while low serum ferritin concentration was related to significant increase in severe arthralgia, fatigue, intradialytic headache and leg cramps. CONCLUSIONS: ID was identified as a risk factor regarding severity of several symptoms even without low hemoglobin level among chronic hemodialysis patients, and supplementation of iron was considered efficacious for improving critical symptoms affecting those undergoing maintenance dialysis.

p53 gene mutation and p53 protein overexpression in a patient with simultaneous double cancer of the gallbladder and bile duct associated with pancreaticobiliary maljunction.

Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. We present a case of simultaneous double cancer of the gallbladder and bile duct. A 77-year-old woman who had jaundice, intra- and extra-hepatic biliary ductal dilatation and a space-occupying lesion in the gallbladder and lower bile duct underwent pancreatoduodenectomy. The gallbladder cancer showed papillary carcinoma without mutation of the K-ras gene and with p53 non-sense mutation of CCA (Pro) to CA (Stop) on codon 301 in exon 8. The bile duct cancer revealed a well-differentiated adenocarcinoma without mutation of the K-ras gene and with p53 miss-sense mutation of GTG (Val) to GAG (Glu) on codon 272 in exon 8. There were no mutations of either the K-ras or p53 gene in non-cancerous epithelia. In contrast, only the mucosa of the common channel had p53 protein accumulation and high cell proliferation activity. Therefore, the genetic pathway might be the same in both the gallbladder and bile duct cancer, and a high potential for carcinogenesis might be present in the epithelium of the common channel in patients with PBM.

The VIO soft-coagulation system can prevent pancreatic fistula following pancreatectomy.

BACKGROUND/PURPOSE: The VIO soft-coagulation system (SC) is a new device for tissue coagulation. We hypothesized that this device would be an effective tool for sealing small pancreatic ducts, thus reducing pancreatic fistula following pancreatectomy. METHODS: To confirm whether the SC could be used to seal small pancreatic ducts, we measured the burst pressure in sealed ducts in mongrel dogs. Eight dogs underwent distal pancreatectomy, with the remnant stump coagulated by using the SC. The animals were necropsied on postoperative day 10. In a clinical trial, 11 patients who underwent pancreatoduodenectomy with SC treatment (SC group), and 24 patients who underwent pancreatoduodenectomy without SC treatment (non-SC group) were compared. RESULTS: In the experimental study, the burst-pressure test revealed that the SC had efficiently sealed the small pancreatic ducts. Histological examination revealed completely obstructed pancreatic ductal structures, ranging from large pancreatic ducts (diameter, 500 microm) to microscopic ducts. No pancreatic leakage was observed following distal pancreatectomy without main pancreatic duct (MPD) suturing in dogs that had an MPD diameter of less than 500 microm. In the clinical trial, pancreatic fistula developed in only one patient (9.1%) in the SC group, but a pancreatic fistula developed in five patients (20.8%) in the non-SC group. CONCLUSIONS: This novel technique using the SC is an effective procedure for preventing the development of pancreatic fistula following pancreatectomy.

Pathological features and surgical outcome of pancreaticobiliary maljunction without dilatation of the extrahepatic bile duct.

In cases of pancreaticobiliary maljunction without dilatation of the extrahepatic bile duct (undilated PBM), preventive cholecystectomy is performed because there is a high incidence of gallbladder cancer as compared to cases of PBM with dilatation of the extrahepatic bile duct (dilated PBM). However, it is still controversial whether resection of the extrahepatic bile duct should also be performed in patients with undilated PBM. Accordingly, we analyzed pathological findings, postoperative complications and a long-term prognosis in 19 patients with undilated PBM to clarify the possibility of the bile duct cancer. In undilated PBM, hyperplasia was significantly recognized in the gallbladder as compared to the bile duct (p=0.0238), while no significant differences were found in other epithelium. Atypical epithelium and hyperplasia in gallbladder mucosa of undilated PBM were significantly recognized as compared to cases of pancreas or biliary tract cancer without PBM (p=0.0035, p=0.0019, respectively), while no significant differences were recognized in any kind of epithelium of the bile duct. In 14 cases of undilated PBM with preservation of the extrahepatic bile duct, the postoperative observation period was from 1 year and 5 months to 18 years and 10 months (mean: 8.3 years). One of the 5 patients with gallbladder cancer died 2 years and 6 months after surgery due to the cancer recurrence, while the remaining 13 patients had no complications such as liver dysfunction, cholangitis or remnant bile duct cancer, and the patients have survived in good health. These findings indicate that preventive bile duct resection is not necessary in patients with undilated PBM.

Subphrenic bronchopulmonary foregut malformation with pulmonary-sequestration-like features.

A retroperitoneal bronchopulmonary foregut malformation in a 62-year-old man is reported. The lesion was composed of mature lung tissue with randomly distributed bronchial structures and ciliated epithelium-lined cysts, some of which were lined with gastric mucosa. The histological features of this lesion were of both pulmonary sequestration and a bronchogenic, or foregut, cyst, and thus were a unique example of bronchopulmonary foregut malformation with pulmonary differentiation. This case is important in understanding the pathogenesis of foregut anomalies (i.e. bronchopulmonary foregut malformations), which range from pulmonary sequestrations to bronchogenic cysts and foregut duplication cysts.

Immunohistochemical analysis of cyclooxygenase-2 and vascular endothelial growth factor in pancreaticobiliary maljunction.

Recent studies have elucidated that cyclooxygenase (COX)-2 is strongly related to cancer progression or development by means of its anti-apoptotic effect, enhancement of angiogenesis or decrease of cell-to-cell adhesive activity. However, there is no report on the relationship between COX-2 expression and angiogenesis in pancreaticobiliary maljunction (PBM). We examined the correlation between the overexpression of COX-2 and vascular endothelial growth factor (VEGF) in 65 lesions from 30 patients with PBM immunohistochemically. The positive expression of COX-2 was found in 20% of regenerative epithelium, 11.1% of hyperplasia without atypia, 86.4% of hyperplasia with mild atypia, 75% of dysplasia, and 75% of cancerous lesions. VEGF was highly expressed in 80% of regenerative epithelium, 27.8% of hyperplasia without atypia, 86.4% of hyperplasia with mild atypia, 66.7% of dysplasia, and 75% of cancerous lesions. The positive rate of both COX-2 and VEFG expression was significantly higher in hyperplasia with atypia, dysplasia and cancerous lesions than that in hyperplasia without atypia. In addition, there was a statistically significant correlation between COX-2 and VEGF overexpression among all lesions. In 6 of 8 patients of various histological types, both COX-2 and VEGF were stained in almost exactly the same locations. In addition, there were no significant differences between the degree of inflammatory cell infiltration in the surrounding stroma and the expression of COX-2 and VEGF, respectively. These results demonstrated a strong relationship between COX-2 and VEGF overexpression in PBM. Therefore, chemoprevention via the suppression of angiogenesis by means of COX-2 inhibitor may be effective in PBM.

Expression of cyclooxygenase-2 and vascular endothelial growth factor in pancreatic tumors.

Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) have been reported to be significantly related to carcinogenesis or progression of various cancers. However, there has been no report on the relation between COX-2 and VEGF overexpression in pancreatic tumors. We investigated the overexpression of COX-2 and VEGF immunohistochemically in intraductal papillary-mucinous tumors (IPMT) and invasive ductal carcinoma (IDC) and examined the relationship with clinicopathological factors and the correlation between these immunoactivities in IPMT and IDC. In IPMT, the positive rates of COX-2 overexpression were 0% in 10 areas of hyperplasia, 54.5% of adenoma, 83.3% of intraductal areas of adenocarcinoma, and 66.7% of invasive areas of adenocarcinoma. On the contrary, 47.8% of IDC were positive for COX-2 overexpression. The positive rates of VEGF in IPMT were 10% in areas of hyperplasia, 54.5% of adenoma, 66.7% of intraductal areas of adenocarcinoma and 66.7% of invasive areas of adenocarcinoma. However, in IDC it was 47.8%. Only lymph node metastasis correlated significantly with VEGF overexpression (p=0.04), while the other factors had no significant relationships with either COX-2 or VEGF overexpression. There was a statistically significant correlation between COX-2 and VEGF overexpression in IPMT (p<0.001), in 5 patients with adenoma of which both COX-2 and VEGF were stained in almost exactly the same locations. On the contrary, COX-2 and VEGF overexpression had no statistically significant relationship in IDC. In conclusion, we demonstrate evidence of COX-2 and VEGF overexpression in human pancreatic tumors. Chemoprevention via the suppression of angiogenesis by means of COX-2 inhibitor may be more effective in IPMT than in IDC, because of the strong correlation of both factors especially in IPMT.