Although chemotherapy with oral S-1and oxaliplatin (SOX) plus bevacizumab (bev) is safe and feasible for patients with advanced or recurrent colorectal cancer, it is difficult to achieve a complete response (CR) using only chemotherapy. A 67-year-old man underwent endoscopic mucosal resection and additional sigmoidectomy (D2 dissection) for submucosal invasive sigmoid colon cancer. Multiple liver metastases were diagnosed 1.5 years later, and chemotherapy with SOX + bev was initiated. Computed tomography (CT) after the end of the third course revealed reduced liver recurrence. Liver metastases could not be identified using CT after the end of the sixth course. Grade 1peripheral neuropathy was the only side effect of this regimen. Subsequently, the chemotherapy regimen was changed to oral S-1. CT evaluation revealed that there was no recurrence at 6 months after the regimen change.
With the increase of elderly population, orthopaedic surgeons need to deal with the diseases related to aging, such as joint disorders and fragility fractures. The number of total joint replacements, for example, is two times more than it was 10 years ago. With these backgrounds, the Japanese Orthopaedic Association (JOA) has proposed the concept of locomotive syndrome; conditions under which the elderly have been receiving care services due to problems of the locomotive organs. To prevent geriatric or disuse syndrome, JOA is currently providing the care‒prevention programs such as the loco-check and loco-training. Recent advances in the orthopaedic fields were cited in this review article, including the topics of new biomaterials, regenerative medicine of cartilage, spinal cord injury and computer assisted orthopaedic surgery. These new technologies and knowledge are changing or have potential to change the future orthopedic medical care.
Surgical treatment for heart failure includes coronary artery bypass grafting to ischemic heart disease, valvular disease surgery such as mitral valvuloplasty, left ventricular restoration, ventricular assist device (VAD), and heart transplantation. In addition, HeartSheet which is regenerative medicine using autologous skeletal myoblast sheets has been started from the spring of 2016. Formal insurance reimbursement of implantable LVAD was obtained in April 2011, and the life prognosis of patients with severe heart failure improved markedly. However, the indication for implantable LVAD is limited to bridge use for heart transplantation. Implantable LVAD cannot be implanted in patients over 65 years old under health insurance because the adaptive age of heart transplantation in Japan is under 65 years old. It is a problem that the indication of implantable LVAD is identical to that of heart transplantation. Clinical trial of destination therapy is in progress for the purpose of optimizing the implantable LVAD indication. I strongly pray that VAD treatment including destination therapy (DT) and transplant medical treatment based on good intentions will be accepted socially as general treatment.
We have focused on the role of innate immunity during the formation oföchoroidal neovascularization (CNV) -related diseasesù. Inflammation affects the formation and the progression of various vitreoretinal diseases. We performed a comprehensive analysis of inflammatory immune mediators in the vitreous fluids with diabetic macular edema, proliferative diabetic retinopathy, branch retinal vein occlusion, central retinal vein occlusion and rhegmatogenous retinal detachment. The concentrations of 20 soluble factors (nine cytokines, six chemokines, and five growth factors) were measured simultaneously by multiplex bead analysis system. Out of 20 soluble factors, three factors : interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all groups of vitreoretinal diseases compared with control group. According to the correlation analysis in the individual patientʼs level, these three factors that were simultaneously increased, did not show any independent upregulation in all the examined diseases. We also elucidated the role of natural killer (NK)T cells, which restricted CD1 molecule and participate in the innate immune response, in laser-induced experimental CNV. We examined CNV formation in independent two NKT cell-deficient mice, either CD1 knockout (KO) mice or Ja18 KO mice, and found that both KO mice showed significant reduction of experimental CNV. During the clinical process of CNV-related diseases, not only CNV formation, subretinal scaring is thought to be another important step. We thus established the experimental model of subretinal scaring by injecting peritoneal exudating macrophages into subretinal space. Subretinal fibrous tissue was observed by fundus scope in PEC-inoculated mice after seven days. The tissue was consisted of monotonous and low cell-density area, which expressed a-SMA with collagen synthesis. Because PEC-inoculated MCP-1 KO mice showed less amount of glial residual, not only exogenous macrophages, but also intrinsic macrophages are critical. Activated macrophages directly induced myofibrotic changes in RPE cells in vitro.
Energy homeostasis is maintained locally through parenchymal-stromal cell interaction and systemically through metabolic organ network. In obese adipose tissue, saturated fatty acids, which are released as a danger signal from hypertrophied adipocytes, stimulates a pathogen sensor TLR4 in the infiltrating macrophages, thus establishing a vicious cycle between adipocytes and macrophages to stimulate adipose tissue inflammation. Histologically, macrophages aggregate to constitute crown-like structures (CLS), where they are thought to scavenge the residual lipid droplets of dead adipocytes. Free fatty acids, when released from obese visceral fat depots, are transported in large quantities to the liver via the portal vein, where they are accumulated as ectopic fat, thus developing non-alcoholic fatty liver disease (NAFLD). There is a unique histological feature termed÷hepatic CLS (hCLS)øin the non-alcoholic steatohepatitis (NASH) liver, where macrophages aggregate to surround dead hepatocytes with large lipid droplets. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. Our data suggest that hCLS serves as an origin of hepatic inflammation and fibrosis during the progression from simple steatosis to NASH. Sodium glucose cotransporter 2 (SGLT2) inhibitors, an oral antidiabetic drug, promotes the urinaryexcretion of glucose by blocking its reabsorption in renal proximal tubules. Inhibition of SGLT2 lowers is expected to reduce body weight because of urinary calorie loss. Interestingly, SGLT2 inhibition improves hepatic steatosis in obese mice irrespective of body weight reduction. There is an inverse correlation between liver weight and adipose tissue weight in obese mice with SGLT2 inhibition, suggesting that SGLT2 inhibition induces the÷healthyøadipose tissue expansion and prevents ectopic fat accumulation in the liver. Our data suggest that seeing both the wood and trees is Required to understand the molecular mechanism of lifestyle-related diseases.
The immunohistological localization of peroxisome proliferator-activated receptor a (PPARa) and PPAR g was examined in 28 pilosebaceous units in 10 paraffin-embedded normal human skin specimens. Rabbit polyclonal antibody against human PPARa and monoclonal antibody against human PPARg were used as specific primary antibodies. The nuclear and cytoplasmic expression of PPARa was detected in basal to differentiated sebocytes. In contrast, the expression of PPARg was confined to nuclei of suprabasal to early-differentiated sebocytes. The nuclear PPARg expression was present only occasionally in the basal sebocytes. These results suggest that PPARa and PPARg are integral parts of sebocyte differentiation in human sebaceous glands.
Background: Although portal vein thrombosis in cirrhotic patients is frequently observed, the detailed process remains to be clarified, and the role of anticardiolipin antibody in the development of portal vein thrombosis has been controversial.
Case report: A 52-year-old man, who had been diagnosed with alcoholic cirrhosis of the liver, was admitted to our hospital suffering from dyspnea and ascites. Just after being diagnosed as having antiphospholipid antibody syndrome with lung thrombosis and delivering a positive result for the β 2-glycoprotein I-dependent anticardiolipin antibody, he sustained rupture of the esophageal varices with rapid development of portal vein thrombosis, which resolved under anticoagulant therapy. Two years later, he was admitted again on suspicion of thrombosis because of an elevation in the serum D-dimer level, and computed tomography showed portal and upper mesenteric vein thrombosis. Although immediate anticoagulant therapy resulted in complete recanalization, he suffered the same episode 2 months later, which occurred with re-elevation of the serum D-dimer level.
Conclusion: A positive finding of an anticardiolipin antibody in cirrhotic patients has been considered to be nonspecific and not related to the development of thrombus in the portal vein. This case, however, seems to indicate that cirrhotic patients with the β2-glycoprotein I-dependent anticardiolipin antibody should be regarded as being at high risk for portal vein thrombosis. Monitoring with the serum D-dimer was useful in detecting portal vein thrombosis in its early stage.
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