Cancer is the primary cause of deaths in Japan. Both cancer metastasis and relapse are the major issues, which have not been overcome until now. Cancer cells preferentially metastasize from the primary tumor to the distant target organs. Especially, carcinomas originating from the breast and prostate preferentially metastasize to the bone. However, the mechanism underlying bone-tropic metastasis has been unclear for long time. In recent years, metastatic niches, which are microenvironments that support both metastasis and relapse of cancer, are proposed. These niches are formed before or after the arrival of cancer cells to the distant target organs. In this review, I focus on the bone metastatic niche and introduce the mechanisms underlying bone-tropic metastasis induced by the bone metastatic niche regulators. In the pre-metastatic phase, primary tumor-derived pre-metastatic niche regulators, such as receptor tyrosine kinase MET and lysyl oxidase, can induce the pre-metastatic niche to support metastatic growth of cancer in the bone. However, post-metastatic niche regulators, such as VCAM-1, TGF-β, PGE2, IL-6, and periostin, were produced after the arrival of a minor population of cancer cells, such as cancer stem cells, and supported tumor dormancy, relapse, and bone lesions. Taken together, the bone-tropic metastasis may be accomplished by the cell-to-cell interaction between cancer cells and host cells forming the bone metastatic niche through the bone metastatic niche regulators. In the future, development of novel molecular medicines targeting the bone metastatic niche regulators would be desirable to prevent the formation of metastatic niches in the bone.
Two topics, insulin autoimmune syndrome and early-onset diabetes care, have been selected for the final lecture in the Tokyo Women's Medical University (TWMU).
Insulin autoimmune syndrome (IAS), or Hirata's disease, first described by Hirata in 1971, is characterized by fasting hypoglycemia without evidence of exogenous insulin administration, high concentration of total serum immune reactive insulin, and the presence of high titer autoantibodies against native human insulin in serum. Other characteristics associated with IAS are the high frequencies of HLA-DR4 positivity, the prevalence of IAS in Japan, and the intake of drugs containing sulfhydryl compounds before IAS onset. We found that IAS showed a strong association with HLA-DR4 (mostly with DRB1*04:06, less frequently with DRB1*04:03 or DRB1*04:07), which encode glutamate at position 74 in the HLA-DR beta molecules, and is presumed to be essential to the production of polyclonal insulin autoantibodies in IAS.
As part of a physicians' professional duty of care for early-onset diabetes patients, the staff at our clinic aim to provide high-quality care for these patients with early-onset DM to improve treatment outcomes. Patients with type 1 diabetes were found to have a better prognosis compared to those attending other clinics, which suggests an improved care system at TWMU diabetes center.
Purpose: This study was undertaken to clarify the clinical significance of dysplasia graded according to the Ministry of Health, Labour and Welfare study group classification (none, UC-I, IIa, IIb, or III) in patients with ulcerative colitis (UC).
Subjects and Methods: We analyzed the clinical features, colonoscopy findings, incidence of malignancy, and risk factors for malignancy in 420 UC patients who underwent colonoscopy at our hospital. These patients were stratified by the histopathological grade of dysplasia at initial biopsy. We focused on the clinical course and the factors associated with malignancy in patients with UC-III dysplasia (severe dysplasia) during the observation period.
Results: The median observation period of the 420 patients was 7 years. Endoscopy generally showed a significant increase of elevated lesions as the grade of dysplasia increased. The incidence of malignancy increased along with the grade of dysplasia. Patients with UC-IIa or higher dysplasia had a significantly higher incidence of malignancy compared to those with UC-I or no dysplasia (p<0.05). Juvenile onset of UC and inflammatory polyps were significantly associated with malignancy. During the observation period, UC-III dysplasia was detected in 29 patients. Among them, 8 patients (27.6 %) developed cancer, with the median period until detection of UC-IV being 2.5 months.
Conclusion: Careful follow-up by surveillance colonoscopy is required for patients with UC-IIa or higher dysplasia. Early detection of dysplasia (suggesting the presence of precancerous lesions), inflammatory polyps, and juvenile onset are useful for predicting a higher risk of colitis cancer.
Introduction: Ventricular septal perforation (VSP) after acute myocardial infarction (AMI) is often complicated by a worsening of rapid hemodynamics, thus remaining a poor prognostic emergency disease. In our department, during the repair of VSPs with lesions in the left anterior descending artery area, infarct lesions are pre-operatively detected with ECG synchronized contrast computed tomography, and the scope of approach and exclusion is determined. Furthermore, in order to prevent complications of residual shunt, a double patch exclusion technique (DPET) is used in combination to preserve left ventriclar function.
Materials: We identified two consecutive VSP patients who underwent this procedure from September to December 2015. There was an average of five days between AMI and the onset of VSP, and an average of one day between onset of VSP and surgery.
Results: All cases were extubated on the day after surgery and intra-aortic balloon pump assistance was also withdrawn. Without perioperative complications, patients were able to leave the intensive care unit, on average, 6.5 days post-operation. Early postoperative echocardiographic and magnetic resonance angiography showed good left ventricular wall contraction except at the infarcted area, with no evidence of residual shunt.
Conclusion: The use of the double patch exclusion technique prevents residual shunt more effectively that in cases without, and it is thought that it is useful for maintaining postoperative cardiac function.
Objective: Patients with ruptured abdominal aortic aneurysms (AAA) are often treated via open repair despite the existence of endovascular aortic repair (EVAR), a less invasive and widely accepted approach beneficial for elective AAA patients. We aimed to evaluate the early clinical results of EVAR of ruptured AAA in emergency setting.
Methods: Patients with ruptured AAA who underwent emergency EVAR between January 2012 and March 2017 were included in this study. There were 16 men and 9 women (mean age, 76.4±9.6 years). Six patients were hemodynamically unstable with a systolic blood pressure of ≤70 mmHg before procedure. Two patients required the insertion of aortic occlusion balloons, preoperatively. In all cases, preoperative computed tomography (CT) was performed, which revealed a mean AAA maximum diameter, proximal neck length, and proximal neck diameter of 71.4±11.4 mm, 22.5±17.8 mm, and 23.0±3.8 mm respectively.
Results: There were no intraoperative deaths, the early mortality rate was 8 %, and the technical success rate was 96 %. No patient underwent open surgery, all participants underwent EVAR with bifurcated graft, and 3 underwent concomitant coil embolization of the internal iliac artery. One case showed type I endoleak on intraoperative digital subtraction angiogram and postoperative enhanced CT. Postoperatively, 2 patients had abdominal compartment syndrome, 1 needed dialysis, 7 required prolonged ventilator use. Aneurysm sac shrinkage was seen in 13 patients on postoperative CT examination.
Conclusion: EVAR for ruptured AAA is feasible and relatively safe. Our early clinical findings suggest that it could be considered the first-line therapy in ruptured AAA with favorable anatomy.
A 72-year-old woman with no abdominal surgery presented with a sudden-onset pain in the left lumber region accompanied by nausea and vomiting. Computed tomography confirmed a cluster of dilated small bowel loops with ischemic change near the posterior side of the transverse colon and to the left of the Treitz ligament. This cluster had a sac-like-appearance. The patient was diagnosed with small bowel obstruction caused by a left paraduodenal hernia and emergency surgery was performed. The hernia sac was found between the anterior and posterior lobes of the descending mesocolon. We resected the herniated small intestine with ischemic change and closed the hernia orifice. On the 10th day after the surgery, the patient was discharged without any complication. Recently improvements in imaging techniques have enabled early diagnosis of paraduodenal hernia, thus helping avoid intestinal resection in most cases. In our case although the patient had no peritoneal irritation sign and slight inflammation at the time of preoperative diagnosis, the intestine already had accompanying ischemic change. Therefore, it is crucial to perform an emergency surgical intervention as soon as possible even if the patient has minor symptoms. We herein report a case of a left paraduodenal hernia needed intestinal resection in spite of preoperative diagnosis.