According to the current AJCC staging system, the T stage of distal extrahepatic bile duct carcinoma (EBD) is classified according to the extent of the tumor within or beyond the bile duct wall. However many invasive carcinoma accompany stromal desmoplasia that obscure lower boundary of bile duct wall; it is frequently difficult to clearly define the extent of tumors using the current T classification system. In this study, we validated an alternative T classification system by depth of invasion (DoI; T1: < 5 mm, T2: 5 to 12 mm, and T3: ≥ 12 mm). Specifically, we evaluated DoI in 114 cases of distal EBD carcinoma using digital scan images to achieve more objective measurements of tumor DoI. In addition, we evaluated the effect of the number of metastatic lymph nodes (LNs) as well as the number of total examined LNs on the survival rate in the same patient group, and performed a comparative analysis of these data to assess patient survival. We also analyzed 114 cases of distal EBD carcinoma using the current T and N classification of the AJCC staging system (7th edition). The T stage of the current AJCC staging system was not associated with significant differences in patient survival, especially between T2 and T3. However, T staging by DoI was associated with statistically significant differences in patient survival (P < 0.001 in DoI-1, P = 0.002 in DoI-2). With respect to N stage, we divided patients into 3 tiers comprising class 1 (no nodal metastasis), class 2 (1–3 nodal metastases), and class 3 (4 or more nodal metastases). In 3-tier classification analysis, the median survival times for classes 1, 2, and 3 were 79.2, 28.8, and 10.9 months, respectively. The difference in survival among the 3 classes was statistically significant (P < 0.001). We found the cut-off value of 11 LNs (1 to 10 vs ≥ 11) for N0 stage showed most significant difference (P = 0.007). We think at least 11 LNs should be examined for more accurate evaluation of N stage in distal EBD carcinoma. We propose an alternative T classification using DoI and 3-tier sub-classification of N stage for distal EBD carcinoma.

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Recent studies suggest that dysregulated innate immunity plays an important role in the pathogenesis of immunoglobulin A nephropathy (IgAN). The interleukin-20 subfamily and its receptor, interleukin-22 receptor alpha-1 (IL-22R1), were recently identified as immunomodulators in human diseases, acting as mediators of mucosal host defense. However, the potential role of IL-22R1 in the pathogenesis of IgAN has not been explored. In the current study, 194 patients with IgAN and 287 normal controls were genotyped for coding polymorphisms of the IL-22R1 gene and the association between the polymorphisms and IgAN was investigated. Local expression of IL-22R1 was examined in patients with IgAN and healthy controls using immunohistochemistry. Our case-control analysis showed that genotypes of rs3795299 were associated with childhood IgAN. Individuals with the CC genotype of rs3795299 had about 3-fold reduced risk of IgAN compared with those with the GG genotype in the codominant model (P=0.0028) and those with the genotypes containing the G allele (GG or GC) in the recessive model (P=0.002). After Bonferroni correction, the association between the rs3795299 CC genotype and reduced risk of developing IgAN remained significant. Furthermore, the renal expression of IL-22R1 was significantly higher in healthy controls compared with subjects with IgAN. Our data suggest that the CC genotype of rs3795299 polymorphism in the IL-22R1 gene is associated with the reduced risk of IgAN, and this genetic association was supported by the higher renal expression of IL-22R1 in healthy controls compared with patients with IgAN.

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We recently reported the downregulation of osteoprotegerin expression in primary colorectal carcinoma and its significant association with aggressive oncogenic behavior, which suggest that this process contributes to colorectal carcinoma development and progression. In this study, we used immunohistochemical staining to evaluate osteoprotegerin expression in 81 colorectal liver metastasis tissue samples and investigated its possible association with the clinicopathological characteristics and outcomes of patients with colorectal liver metastasis. These tissues exhibited significantly reduced expression of osteoprotegerin compared to primary colorectal carcinomas and normal colorectal mucosa. This reduced expression was significantly associated with the extent of colorectal liver metastasis, including multiplicity of metastatic tumors, involvement of the bilateral hepatic lobes, and higher histological grade. In addition, reduced osteoprotegerin expression was an independent significant predictor of recurrent liver metastasis and prognostic factor for reduced patient survival. These findings suggest that osteoprotegerin expression may be a novel predictor of recurrent liver metastasis and a prognostic biomarker in patients with colorectal liver metastasis. Patients harboring colorectal liver metastasis with reduced osteoprotegerin expression should be carefully monitored after hepatic resection for colorectal liver metastasis to enable early detection of potentially resectable metastatic recurrences.

Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time × group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age-and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time × group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers; however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.