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In rheumatoid arthritis (RA), ACPA (anti-citrullinated protein/peptide antibody) is elevated with high specificity, and clinically, anti-CCP (cyclic citrullinated peptide) antibody is widely used for diagnosis of RA. It is thought ACPAs are produced with genetic background such as HLA-DR, environmental factors such as periodontal disease and smoking, however, the pathogenic role of ACPA in RA has not been elucidated. These were showed immune complexes including ACPA or ACPA itself promoted inflammatory cytokine production such as TNF. PADs (peptidylarginine deiminases) were expressed and citrullinated proteins existed in RA synovium. ACPAs were deposited on the site of citrulline in CD68 positive cells of RA synovium. The damage of bone and cartilage is observed in RA. It was also suggested that deposition of ACPAs caused osteoclastogenesis and bone loss. We introduce several findings about the pathogenic role of ACPA in RA.

Purpose: To compare pro re nata (PRN) intravitreal injections of aflibercept (IVA) and ranibizumab (IVR) in patients with treatment naïve age-related macular degeneration (AMD)., Material and Methods: We analyzed 42 eyes that receive 3 times monthly IVA as introduction phase and subsequently received PRN retreatment at the recurrence. As the control, 56 eyes received the same IVR treatments as the IVA criteria. We statistically analyzed chronological changes of VA and the first recurrence following introduction phase by comparing the findings of the 2 groups., Results: There was no difference in the IVA and the IVR in baseline visual acuity (VA) and the mean number of injections during 12 months. Compared to the IVR, the IVA showed better improved VA from baseline at each time point, especially, there was a statistically significant difference in 6 months after introduction (p = 0.041). The IVA proved to have a shorter period until the first recurrence and a lower remission maintenance rate following introduction phase than the IVR. The improvement of VA above 0.2 logMAR was significantly related to cases involving polypoidal choroidal vasculopathy, greatest linear dimension and baseline VA., Conclusions: The improvement of VA in anti-VEGF therapy for AMD was influenced by the disease type or pathology rather than the choice of therapeutic agents.

We evaluated the clinical significance of indoleamine 2,3-dioxygenase (IDO) during fulvestrant therapy for aromatase inhibitor (AI)-resistant metastatic breast cancer. IDO activity can be measured by the tryptophan (Trp)/kynurenine (Kyn) ratio. Trp and Kyn were measured with high performance liquid chromatography (HPLC). Patients with AI resistant metastatic breast cancer had a 28.6% response rate to fulvestrant therapy, and the clinical benefit rate was 76.2%. AI-resistant metastatic breast cancer patients with distant metastases had a lower serum Trp/Kyn level than patients who had local recurrences. During fulvestrant therapy, IDO activity significantly decreased in the fulvestrant responder group compared to that in the fulvestrant non-responder group. During fulvestrant therapy, the IDO activity correlated with the number of metastatic lesions. These results suggest that measuring the Trp/Kyn ratio is useful for evaluating immunological metastatic status during endocrine therapy.

We hypothesized that a large number of circulating tumor cells(CTCs)may be isolated from samples obtained by using the leukapheresis procedures that are utilized to collect peripheral blood mononuclear cells for dendritic cell vaccine therapy. We utilized the CellSearch System to determine the number of CTCs in samples obtained by using leukapheresis in 7 patients with colorectal cancer, 5 patients with breast cancer, and 3 patients with gastric cancer. In all patients, a large number of CTCs were isolated. The mean number of CTCs per tumor was 17.1(range 10-34)in colorectal cancer, 10.0(range 2-27)in breast cancer, and 24.0(range 2-42)in gastric cancer. We succeeded in culturing the isolated CTCs from 7 patients with colorectal cancer, 5 patients with breast cancer, and 3 patients with gastric cancer. In conclusion, compared to conventional methods, a large number of CTCs can be obtained by using leukapheresis procedures. The molecular analyses of the CTCs isolated by using this method should be promising in the development of personalized cancer treatments.

We report a 37-year-old patient with latent tuberculosis infection who received isoniazid (INH) antituberculosis chemoprophylaxis. However, he developed fever and productive cough 3 weeks after treatment. Chest radiography and computed tomography showed bilateral infiltrative shadows in upper fields. Bronchoalveolar lavage fluid revealed a high proportion of eosinophils, and histological examination of biopsied lung tissue showed interstitial thickening with eosinocyte infiltration. Based on these findings, the patient was diagnosed with drug-induced eosinophilic pneumonia. His febrile condition and dry cough resolved after discontinuation of INH. Chest X-rays showed improvement of infiltrative shadows. This case report highlights the potential for INH-induced pneumonitis during the course of antituberculosis chemoprophylaxis.

Purpose: To investigate the factors associated with recurrence following remission of at least 12 months after photodynamic therapy in patients with age-related macular degeneration (AMD)., Subjects and Methods: We analyzed 42 eyes with AMD in 41 patients who did not require additional treatment within 12 months of their photodynamic therapy (PDT). Additional treatment for recurrence beyond 12 months after the last PDT was required in 20 eyes in the recurrent group (n = 20). The remaining eyes (controls; n = 22) showed no recurrence during this period. We statistically analyzed the factors associated with recurrence by comparing the findings of the 2 groups., Results: Compared to the controls, the recurrent group showed significantly improved baseline visual acuity (VA) (p = 0.005), but required significantly more PDT applications to achieve remission (p = 0.010). Age (p = 0.026), multiple PDT sessions (p = 0.001), and high baseline VA (p = 0.003) were factors significantly related to the recurrence following remission maintenance with PDT for AMD (R = 0.63; R2 = 0.39; p < 0.0001)., Conclusions: Age, preoperative VA and number of PDT sessions were associated with a significant risk of recurrence after remission maintenance with PDT.

Prognosis of rheumatoid arthritis (RA) patients has significantly improved with the recent use of biologics targeting TNFα, IL-6, and co-stimulatory molecule. In US and Europe, clear therapeutic benefit of anti-CD20 antibodies is also confirmed. As a disease specific marker, rheumatoid factor and anti-citrullinated protein antibody are crucial in RA, although the pathology of them is not defined. Here we focus on glycolytic enzyme such as glucose-6-phospate isomerase, that is confirmed as arthritogenic in two different mouse models, and discuss about pathogenic relevance to RA.

A 35-year-old woman was admitted to our hospital for right upper quadrant pain and multiple liver tumor were detected by diagnostic imaging. Tumors located near the surface of the liver which accompanied capsular retraction. Diagnostic laparoscopy showed multiple white tone tumors with retraction of the adjacent liver capsule. Tumor targeted biopsy was performed. The pathologic diagnosis of epithelioid hemangioendothelioma (EHE) was made by the positive staining of factor VIII-related antigen. EHE tend to locate in peripheral and extend to the liver capsule. Therefore, we face difficulties in getting biopsy sample safely. Here we report a useful case of laparoscopic examination and biopsy in the diagnosis of EHE.

A 55-year-old man with advanced gastric cancer underwent total gastrectomy (T3N0M0, stage II , por, sig) in the USA. Following his return to Japan, the patient then suffered from a recurrence with ileus, bilateral hydronephrosis and ascites caused by peritoneal dissemination. Systemic chemotherapy of paclitaxel combined with 5-FU was performed, and after four cycles, ileus, bilateral hydronephrosis and ascites disappeared. S-1 monotherapy was started to maintain his QOL, but after five cycles, ileus of the transverse colon recurred. Colostomy was performed and systemic chemotherapy of paclitaxel combined with S-1 was performed. For 13 months, the patient's condition remained stable and he returned to society, but died 30 months after the first recurrence. This case suggests that paclitaxel-based chemotherapy is a promising treatment for gastric cancer with peritoneal dissemination.

Heterotopic ossification after spinal cord injury, most commonly affecting the hip, can represent a significant problem in function and mobility of the patient. Attempt of reduction by medication is unsatisfactory once it developed. In addition, surgical removal is often associated with infection and recurrence. Disodium etidronate is an agent effecting on prevention of development and prophylaxis of ossification.

Fifty-one patients with acute A, B, C, and non A-C hepatitis were studied. Alcoholic abusers and drug-induced hepatitis were excluded from non A-C hepatitis. Among 10 patients with acute non A-C hepatitis, 3 were positive for HGV-RNA by nested RT-PCR as primer of 5' non-coding region of HGV. Maximal s-ALT values in acute hepatitis G patients were significantly higher than those in acute hepatitis C(p < 0.05), but not different from those in acute hepatitis A and B. Although HGV-RNA was demonstrated after 9 years of onset of hepatitis in one patient, non of three patients took chronic course. In one patient, route of transmission was assumed to be blood transfusion.