A Pilot Study of Seamless Regeneration of Bone and Cartilage in Knee Joint Regeneration Using Honeycomb TCP

The knee joint is a continuous structure of bone and cartilage tissue, making it difficult to regenerate using artificial biomaterials. In a previous study, we succeeded in developing honeycomb tricalcium phosphate (TCP), which has through-and-through holes and is able to provide the optimum microenvironment for hard tissue regeneration. We demonstrated that TCP with 300 μm pore diameters (300TCP) induced vigorous bone formation, and that TCP with 75 μm pore diameters (75TCP) induced cartilage formation. In the present study, we regenerated a knee joint defect using honeycomb TCP. 75TCP and 300TCP were loaded with transforming growth factor (TGF)-β alone or bone morphogenic protein (BMP)-2+TGF-β with or without Matrigel and transplanted into knee joint defect model rabbits. 75TCP showed no bone or cartilage tissue formation in any of the groups with TGF-β alone and BMP-2+TGF-β with/without Matrigel. However, for 300TCP and BMP-2+TGF-β with or without Matrigel, vigorous bone tissue formation was observed in the TCP holes, and cartilage tissue formation in the TCP surface layer was continuous with the existing cartilage. The cartilage area in the TCP surface was larger in the group without Matrigel (with BMP-2+TGF-β) than in the group with Matrigel (with BMP-2+TGF-β). Therefore, honeycomb TCP can induce the seamless regeneration of bone and cartilage in a knee joint.     

Successful treatment of porocarcinoma with maxacalcitol and imiquimod

This is the first report of a case of porocarcinoma that was successfully treated with maxacalcitol and imiquimod.     

Japanese version of the international PROMs “Vail Hip Score”: Reliability,validity, and responsiveness according to the COSMIN checklist

BackgroundThis study aimed to develop a Japanese version of the international PROMs “Vail Hip Score (Vail10)” and to establish its reliability, validity, and responsiveness with COSMIN check-list.MethodsThe study was conducted from March 2016 to October 2017 and included 46 patients totaling 47 joints. Disorders included 30 cases of FAI (55%), 13 cases of DDH (28%), and 4 others (8%). We administered an identical set of PROMs (5 measures: Japanese-version iHOT12 (pilot draft), Japanese-version Vail10, Japanese-version Oxford Hip Score, JHEQ, and SF36) twice in these subjects. We determined interclass correlation coefficients for the first and second round [ICC(1,2)], as well as the Cronbach α coefficient for patient responses to each of the 10 items in Vail10. In addition, we determined Spearman rank correlation coefficients of Vail10, OHS, JHEQ, satisfaction VAS, the 8 subscales of SF36, and the 3 QOL summary scores.ResultsICC for the total score of all 10 items in Vail10 was 0.96. Cronbach α coefficient was 0.96. Bland-Altman plot analysis showed a solid agreement. Regarding the validity, Spearman rank correlation coefficients, only satisfaction VAS, and SF36 subscales of PF and BP had r > 0.45 (p < 0.01 in both administration rounds). The SDC (1.32) was smaller than the MIC (8.14).ConclusionsAfter developing the Japanese version of Vail10, we examined its Reliability, validity, and responsiveness by administering the measure to patients with acetabular labral tear. Correlations were strong and demonstrated the efficacy of the Japanese version of Vail10.     

Chronic eosinophilic pneumonia with subpleural curvilinear shadow

We report a rare case of chronic eosinophilic pneumonia with subpleural curvilinear shadow. CT scan showed a patchy consolidation in the bilateral upper lungs. In addition, subpleural curvilinear shadow was found in the bilateral upper lungs. A bronchoalveolar lavage obtained from the right middle lobe showed 25 % eosinophils. Although very rare, we should therefore keep in mind that patients, who have patchy consolidation with areas of subpleural curvilinear shadow in the bilateral upper lungs, may have chronic eosinophilic pneumonia.     

Ectopic gastric mucosa and pancreatic ducts in the rectum

A 68-year-old woman with fecal occult blood was referred to Dokkyo Medical School Hospital. Colonoscopy demonstrated a flat lesion in the rectum, and endoscopic mucosal resection of the lesion was performed. Histologic examination revealed that it contained ectopic gastric mucosa, which had a gastric foveolar and glandular mucinous phenotype, as demonstrated by immunohistochemistry. Moreover, the lesion also contained CA19-9- and CK7-positive pancreatic duct-like components in the submucosal layer. The present case is the first report to describe ectopic gastric mucosa and pancreatic ducts concurrently arising in the rectum.     

GROα promotes invasion of colorectal cancer cells

Growth-regulated oncogene α (GROα) is a chemokine that plays a role not only in inflammation, but also in tumorigenesis. Accumulating data suggest that GROα is involved in tumor development and invasion in various malignancies, such as melanoma and bladder cancer. However, the pathophysiological role of GROα in human colorectal cancers (CRCs) is still unknown. We examined the expression of GROα and its pathophysiological significance in human CRCs and investigated whether GROα promotes the invasive potential of colon cancer cells. Specimens of 62 primary CRCs were examined immunohistochemically for GROα, and the relationship between GROα expression and clinicopathological features was investigated. The mRNA expression of GROα and its receptor CXCR2 was examined in ten colon cancer cell lines using RT-PCR. The effect of GROα protein on invasive potential was investigated in DLD-1 and LoVo cells using a Matrigel invasion chamber assay. Forty-nine (79%) of the 62 CRCs showed positive immunoreactivity for GROα. GROα expression was significantly associated with tumor size, tumor stage, depth of invasion, LN metastasis and patient survival (P=0.021, P<0.0001, P=0.0033, P<0.0001, P=0.039, respectively). Expression of CXCR2 mRNA was detectable in all ten colon cancer cell lines examined, whereas expression of GROα mRNA was detectable in six. Treatment with GROα protein significantly increased the number of invasive cells. In conclusion, GROα may play a pivotal role in the invasion of human CRCs.     

Cluster microRNAs miR‐194 and miR‐215 suppress the tumorigenicity of intestinal tumor organoids

Tumor stem cells with self‐renewal and multipotent capacity play critical roles in the initiation and progression of cancer. Recently, a new 3‐D culture system known as organoid culture has been developed, allowing Lgr5‐positive stem cells to form organoids that resemble the properties of original tissues. Here we established organoids derived from intestinal tumors of Apc^min/+ mice and normal intestinal epithelia of C57BL/6J mice and investigated the roles of microRNA (miRNA) in intestinal tumor organoids. The results of microarray analyses revealed that expression of the cluster miRNAs, miR‐194 and miR‐215 was markedly suppressed in intestinal tumor organoids in comparison with organoids derived from normal intestinal epithelia. Enforced expression of miR‐194 resulted in inhibition of E2f3, a positive regulator of the cell cycle and growth suppression of intestinal tumor organoids. In addition, enforced expression of miR‐215 suppressed the cancer stem cell signature through downregulation of intestinal stem cell markers including Lgr5. These findings indicate that the miRNA cluster including miR‐194 and miR‐215 plays important roles in suppressing the growth and attenuating the stemness of intestinal tumor organoids.