Systematic review and meta-analysis of endoscopic submucosal dissection versus transanal endoscopic microsurgery for large noninvasive rectal lesions

Background

For almost 30 years, transanal endoscopic microsurgery (TEM) has been the mainstay treatment for large rectal lesions. With the advent of endoscopic submucosal dissection (ESD), flexible endoscopy has aimed at en bloc R0 resection of superficial lesions of the digestive tract. This systematic review and meta-analysis compared the safety and effectiveness of ESD and full-thickness rectal wall excision by TEM in the treatment of large nonpedunculated rectal lesions preoperatively assessed as noninvasive.

Methods

A systematic review of the literature published between 1984 and 2010 was conducted (Registration no. CRD42012001882). Data were integrated with those from the original databases requested from the study authors when needed. Pooled estimates of the proportions of patients with en bloc R0 resection, complications, recurrence, and need for further treatment in the ESD and TEM series were compared using random-effects single-arm meta-analysis.

Results

This review included 11 ESD and 10 TEM series (2,077 patients). The en bloc resection rate was 87.8 % (95 % confidence interval [CI] 84.3–90.6) for the ESD patients versus 98.7 % (95 % CI 97.4–99.3 %) for the TEM patients (P < 0.001). The R0 resection rate was 74.6 % (95 % CI 70.4–78.4 %) for the ESD patients versus 88.5 % (95 % CI 85.9–90.6 %) for the TEM patients (P < 0.001). The postoperative complications rate was 8.0 % (95 %, CI 5.4–11.8 %) for the ESD patients versus 8.4 % (95 % CI 5.2–13.4 %) for the TEM patients (P = 0.874). The recurrence rate was 2.6 % (95 % CI 1.3–5.2 %) for the ESD patients versus 5.2 % (95 % CI 4.0–6.9 %) for the TEM patients (P < 0.001). Nevertheless, the rate for the overall need of further abdominal treatment, defined as any type of surgery performed through an abdominal access, including both complications and pathology indications, was 8.4 % (95 % CI 4.9–13.9 %) for the ESD patients versus 1.8 % (95 % CI 0.8–3.7 %) for the TEM patients (P < 0.001).

Conclusions

The ESD procedure appears to be a safe technique, but TEM achieves a higher R0 resection rate when performed in full-thickness fashion, significantly reducing the need for further abdominal treatment.     

SIRPα on CD11c+ cells induces Th17 cell differentiation and subsequent inflammation in the CNS in experimental autoimmune encephalomyelitis

Signal regulatory protein α (SIRPα) is expressed predominantly on type 2 conventional dendritic cells (cDC2s) and macrophages. We previously showed that mice systemically lacking SIRPα were resistant to experimental autoimmune encephalomyelitis (EAE). Here, we showed that deletion of SIRPα in CD11c⁺ cells of mice (Sirpa^ΔDC mice) also markedly ameliorated the development of EAE. The frequency of cDCs and migratory DCs (mDCs), as well as that of Th17 cells, were significantly reduced in draining lymph nodes of Sirpa^ΔDC mice at the onset of EAE. In addition, we found the marked reduction in the number of Th17 cells and DCs in the CNS of Sirpa^ΔDC mice at the peak of EAE. Whereas inducible systemic ablation of SIRPα before the induction of EAE prevented disease development, that after EAE onset did not ameliorate the clinical signs of disease. We also found that EAE development was partially attenuated in mice with CD11c⁺ cell-specific ablation of CD47, a ligand of SIRPα. Collectively, our results suggest that SIRPα expressed on CD11c⁺ cells, such as cDC2s and mDCs, is indispensable for the development of EAE, being required for the priming of self-reactive Th17 cells in the periphery as well as for the inflammation in the CNS.     

A unique mitovirus from Glomeromycota,the phylum of arbuscular mycorrhizal fungi

Arbuscular mycorrhizal (AM) fungi that belong to the phylum Glomeromycota associate with most land plants and supply mineral nutrients to the host plants. One of the four viral segments found by deep-sequencing of dsRNA in the AM fungus Rhizophagus clarus strain RF1 showed similarity to mitoviruses and is characterized in this report. The genome segment is 2,895 nucleotides in length, and the largest ORF was predicted by applying either the mold mitochondrial or the universal genetic code. The ORF encodes a polypeptide of 820 amino acids with a molecular mass of 91.2 kDa and conserves the domain of the mitovirus RdRp superfamily. Accordingly, the dsRNA was designated as R. clarus mitovirus 1 strain RF1 (RcMV1-RF1). Mitoviruses are localized exclusively in mitochondria and thus generally employ the mold mitochondrial genetic code. The distinct codon usage of RcMV1-RF1, however, suggests that the virus is potentially able to replicate not only in mitochondria but also in the cytoplasm. RcMV1-RF1 RdRp showed the highest similarity to the putative RdRp of a mitovirus-like ssRNA found in another AM fungus, followed by RdRp of a mitovirus in an ascomycotan ectomycorrhizal fungus. The three mitoviruses found in the three mycorrhizal fungi formed a deeply branching clade that is distinct from the two major clades in the genus Mitovirus.     

Selective expansion of donor‐derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome

IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.     

Effects of dietary fiber on vascular calcification by repetitive diet-induced fluctuations in plasma phosphorus in early-stage chronic kidney disease rats

Vascular calcification progresses under hyperphosphatemia, and represents a risk factor for cardiovascular disease in chronic kidney disease (CKD) patients. We recently indicated that phosphorus (P) fluctuations also exacerbated vascular calcification in early-stage CKD rats. Dietary fiber intake is reportedly associated with cardiovascular risk. This study investigated the effects of dietary fiber on vascular calcification by repeated P fluctuations in early-stage CKD rats. Unilateral nephrectomy rats were used as an early-stage CKD model. For 36 days, a P fluctuation (LH) group was fed low-P (0.02% P) and high-P (1.2% P) diets alternating every 2 days, and a P fluctuation with dietary fiber intake (LH + F) group was fed low-P and high-P diets containing dietary fiber alternating every 2 days. The effect on vascular calcification was measured calcium content. Effects on uremic toxin were measured levels of indoxyl sulfate (IS) and investigated gut microbiota. The LH + F group showed significantly reduced vessel calcium content compared to the LH group. Further, dietary fiber inhibited increases in blood levels of IS after intake of high-P diet, and decreased uremic toxin-producing intestinal bacteria. Dietary fiber may help suppress progression of vascular calcification due to repeated P fluctuations in early-stage CKD rats by decreasing uremic toxin-producing intestinal bacteria.     

Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels

The aim of this study was to clarify the relationship between human leukocyte antigen DR allele distribution and the degree of liver cell injury of hepatitis C virus (HCV) carriers in Japan. The subjects, 68 HCV carriers, were divided into two groups according to the laboratory data and liver histology. Those in the asymptomatic carrier group (n = 19) had normal ALT levels persistently for 8–153 months (mean 25.7 months) and were diagnosed histologically as normal liver, nonspecific reactive hepatitis or chronic persistent hepatitis. Those in the chronic active hepatitis group (n = 49) had elevated ALT levels and were diagnosed histologically with chronic active hepatitis. The human leukocyte antigen DR alleles of all subjects were defined using the polymerase chain reaction restriction fragment length polymorphism method. The expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane were also examined in 14 patients from each group using an indirect immunohistochemical method. The frequency of DR13 (42.1%) in the asymptomatic carrier group was significantly higher (Pc < 0.003) than that of the chronic active hepatitis group (4.1%). There were no significant differences for the other DR alleles. The frequencies of expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane of the asymptomatic carrier group were significantly less than those of the chronic hepatitis group (64% vs. 100% P < 0.05, 29%; vs. 71% P < 0.05, respectively), although there was no significant difference in the serum HCV-RNA titer between the two groups (10^6.4±1.1 vs. 10^6.5±0.7 copies/mL). These results demonstrate that the cellular immune response of the asymptomatic carrier group is less activated than the response of the chronic active hepatitis group and that HLA DR13 may be closely associated with this low activity of hepatitis among HCV carriers. © 1996 Wiley-Liss, Inc.     

Birt‐Hogg‐Dubé syndrome‐associated renal cell carcinoma: Histopathological features and diagnostic conundrum

Birt‐Hogg‐Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene. Most cases of BHD syndrome‐associated RCC (BHD‐RCC) are less aggressive than sporadic clear cell RCC and multifocal. Therefore, it is critical to distinguish BHD‐RCC from its sporadic counterparts to identify and monitor affected families and to preserve renal function for as long as possible. The World Health Organization/International Society of Urological Pathology consensus classification defined distinct entities for certain hereditary RCC; however, BHD‐RCC was not included in this classification. Although the clinical features and molecular mechanisms of BHD‐RCC have been investigated intensively over the last two decades, pathologists and urologists occasionally face difficulties in the diagnosis of BHD‐RCC that require genetic testing. Affected patients usually have miscellaneous benign disorders that often precede renal carcinogenesis. In the present review, we summarize the current understanding of the histopathological features of BHD‐RCC based on our epidemiological studies of Japanese families and a literature review. Pathological diagnostic clues and differential diagnosis of BHD‐RCC from other hereditary RCC are also briefly discussed.