It is extensively documented that tumor hypoxia contributes to the failure of chemotherapy and radiotherapy. Recent evidence suggests that hypoxia is also closely involved in the resistance to immunotherapy. In this review, we highlight how immune cells that are essential for the maximized immunotherapy efficacy, including cytotoxic T cells, dendritic cells, and natural killer cells, can adapt to tumor hypoxia. We then outline previous attempts targeting tumor hypoxia (for example, modulators of tumor cell oxygen consumption, perfusion modulators, hypoxia-activated prodrugs, hypoxia-inducible factor inhibitors, and hypoxia-responsive chimeric antigen receptor T cells) discussing how these approaches have resulted in an improvement of the antitumor response to immunotherapy in preclinical or clinical settings. Lastly, we review various non-invasive techniques to detect the tumor hypoxia and immune responses. We believe that an integration of the biological knowledge of immune cell adaptation to tumor hypoxia with the cutting edge non-invasive imaging technologies may ultimately allow us not only to select for patients who would benefit the most from the immunotherapy but also to monitor their responses in a real-time manner so that we can offer them an optimal personalized medicine in the clinic.

BACKGROUND: In response to growing concerns about the health effects of quasi-millimeter waves (qMMW) used in 5th-generation wireless systems, conservative whole-body exposure thresholds based on indirect evidence have been proposed. The guidelines define a whole-body average specific absorption rate (WBA-SAR) of 4 W/kg which causes a 1 °C increase in core temperature, as the operational threshold for adverse health effects. To address the lack of direct evidence, we recently reported that a 30-minute exposure to qMMW at 4.6 W/kg resulted in a 1 °C increase in rat core temperature. Here, we further analyzed the near-threshold stress response for the first time, using biological samples from the aforementioned and additional experiments. METHODS: A total of 59 young Sprague-Dawley rats (240-322 g) were exposed to 28 GHz for 40 minutes at WBA-SARs of 0, 3.7, and 7.2 W/kg, under normal (22.5 °C, 45-55% humidity), and heat (32 °C, 70% humidity) conditions. Rats were restrained in acrylic holders for dose control. We repeatedly measured serum and urinary biomarkers of stress response, aggregated the data, and analyzed them using a single statistical mixed model to subtract the effects of sham exposure and between-subject variation. RESULTS: Sham exposure induced stress responses, suggesting an effect of restraint. After the subtraction of the sham exposure effect, 28 GHz appeared to induce stress responses as evidenced by elevated serum-free corticosterone 1 or 3 days after the exposure, which was more evident in animals with a change in rectal temperature exceeding 1 °C. Urinary-free catecholamines demonstrated an inhibitory property of 28 GHz frequency exposure on the stress response as evidenced by noradrenaline on the day of exposure. Heat exposure enhanced this effect, suggesting a possible role of noradrenaline in heat dissipation by promoting cutaneous blood flow, a notion supported by the correlation between noradrenaline levels and tail surface temperature, a critical organ for heat dissipation. CONCLUSIONS This study is the first to demonstrate that qMMW whole-body exposure can alter the stress response as indicated by corticosterone and noradrenaline at near-threshold levels. Our findings may provide insight into the biological basis of the whole-body exposure thresholds in the international guidelines.
Animals ; Rats ; Rats, Sprague-Dawley ; Male ; Restraint, Physical ; Stress, Physiological/radiation effects* ; Corticosterone/blood* ; Biomarkers/blood* ; Microwaves/adverse effects*

Health support activities for residents were held three times during a period from June, 2016 to November, 2017. The residents registered in order to participate through 11 community pharmacies. Participant’s blood pressure values were measured at the venue of health support activities by pharmacists. The blood pressure values in 66 of the 106 participants were analyzed, excluding 40 participants receiving medical treatment. The rate of participants with hypertension, systolic blood pressure (SBP)≧140 mmHg or diastolic blood pressure (DBP)≧90 mmHg, was 32% (21／66). Of those with hypertension, 43% (9／21) had hypertension of a high risk level, SBP≧160 mmHg or DBP≧100 mmHg. Pharmacists provided lifestyle counseling and encouraged them to make changes in order to achieve tighter blood pressure control. The data of their blood pressure values were provided to community pharmacies for continuing support of their blood pressure control. With the pharmacist’s support, the median value of blood pressure of participants who had hypertension decreased in the second event. In addition, 50% (3／6) of participants who attended the second event with hypertension of high risk level, visited the hospital for a consultation with a doctor after getting pharmacist’s advice. These results indicate that greater access to community pharmacists improved blood pressure control of residents with hypertension. However, there were many residents who consider it difficult to use pharmacies without a prescription. Hence, friendly relationship to residents on their utilizing pharmacies is needed for providing them lifestyle counseling such as preventing hypertension by pharmacists.

Background: Elderly patients with femoral neck fractures, particularly those with severe comorbidities or living in regions with limited medical resources, may experience delays in surgical treatment. Although the benefits of preoperative rehabilitation (prehabilitation) in hip arthroplasty have been reported, pain management remains a challenge. The pericapsular nerve group (PENG) block, known for its exceptional analgesic effect and motor function preservation, may be a promising intervention during prehabilitation in these patients. Case: We enrolled ten patients with Garden classification 3–4 femoral neck fractures scheduled for hip arthroplasty. After receiving a PENG block with 20 ml of 0.375% ropivacaine, all patients underwent initial prehabilitation sessions comprising 9 mobility levels, ranging from bed-sitting to walking. One patient was excluded due to experiencing high blood pressure during prehabilitation. Six of the nine remaining patients (66.7%) were successfully transferred from bed to wheelchair. Conclusions The PENG block enhanced prehabilitation for patients with femoral neck fractures undergoing hip arthroplasty.

OBJECTIVE: The aim of the study is to investigate recurrence of stage I epithelial ovarian cancer. METHODS: Six hundred two patients diagnosed with stage I epithelial ovarian cancer at 4 hospitals between 2000 and 2013 were retrospectively analyzed. Age, surgical procedure, substage, histologic type, adjuvant chemotherapy, recurrence, initial recurrence site (peritoneal dissemination [P], hematogenous recurrence [H], lymphogenous recurrence [L], and others [O]), and frequency of recurrence at each site were investigated retrospectively. RESULTS: Median age was 54 years and median follow-up was 60 months. The stage was IA in 180 cases (30%), IB in 8 (1%), IC1 in 247 (41%), IC2 in 63 (10%), and IC3 in 104 (17%). Systematic lymph node dissection including both pelvic and para-aortic lymph nodes was performed in 224 patients (37%), and 412 patients (68%) received adjuvant chemotherapy. Recurrence occurred in 70 patients (11.6%). The median time to recurrence was 18 months, and the stage was IA in 13 (19%), IB in 1 (1%), IC1 in 24 (34%), IC2 in 9 (13%), and IC3 in 23 (33%) cases. The numbers of recurrence at the P, H, L, and O sites, including overlapping cases, were 49 (70%), 18 (26%), 9 (13%), and 6 (9%), respectively, and recurrence by peritoneal dissemination in the pelvis occurred in 43 cases (61%). CONCLUSION: Recurrence of stage I epithelial ovarian cancer by peritoneal dissemination was frequent, especially in the pelvis. There is a need to elucidate the pathogenesis of peritoneal recurrence and to prepare a treatment strategy to prevent pelvic peritoneal recurrence.
Chemotherapy, Adjuvant ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Metastasis ; Neoplasm Seeding ; Ovarian Neoplasms* ; Pelvis ; Recurrence* ; Retrospective Studies*

An 8 year-old boy had a cardiac murmur pointed out on day three after birth and was given a diagnosis of ventricular septal defect (VSD). He underwent VSD patch closure at two months after birth. He was also found the having Loeys-Dietz syndrome on the basis of mutation of TGFBR2 and physical examination at the age of 2 years. He had been followed up at pediatrics clinic of our hospital since then, and was hospitalized for a 46.5-mm extension of valsalva sinus diameter and moderate aortic insufficiency. The aortic valve was three-cusped and had no abnormality. We performed valve-sparing aortic root replacement. He was discharged on day 18 after the operation without any problems in the postoperative course. Use of an artificial heart valve for the surgery of the aortic root lesion in childhood will probably cause reoperation in the future and difficulty in Warfarin anticoagulation control. A careful decision is needed in the choice of an operation method. Valve-sparing aortic root replacement is a useful operation for patients without aortic valve abnormality.

Background : The Japanese Society for Dialysis Therapy in 2011 reports that the number of hemodialysis patients has been increasing and that there is an increase in long-term hemodialysis patients and the aging of hemodialysis induction. Therefore, it can be expected that the number of valve surgeries in chronic hemodialysis patients will increase. However, there are many problems between chronic hemodialysis and valve surgery. Objectives : To describe the results of valve surgery in chronic hemodialysis patients at our institution and evaluate the selection of prosthetic valve and associated problems. Methods : Between January 2001 and June 2011, a total of 29 patients on chronic hemodialysis including 3 patients for re-operation, underwent valve replacements. The average age was 67.3±9.3 years and 17 (65%) were men. The average dialysis duration was 7.9±6.4 years. The etiologies of renal failure were 8 for chronic glomerulonephritis (31%), 8 for nephrosclerosis (31%) and 3 for diabetic nephropathy (12%). Results : There were 2 (7.7%) in-hospital deaths, which resulted from ischemia of intestine and multiple organ failure due to heart failure. Twelve (46%) patients died during the follow-up period and the 5-year survival rate after surgery was as poor as another authors have reported previously (30.6%). However, the 5-year survival rate after hemodialysis introduction was 87.1%, which was better than the report of the Japanese Society for Dialysis Therapy in 2011 (60%). Average age was significantly higher in bioprosthetic valves than in mechanical valves (p=0.02). There was no significant difference in survival rate among mechanical and bioprosthetic valves (p=0.75). There was no significant difference in valve-related complication free rate among mechanical (27.5%) and bioprosthetic valves (23.4%) (p=0.9). Three patients with mechanical valves had cerebral hemorrhage, and 1 patient with bioprosthetic valve had structural valve deterioration. Conclusions : Surgical result of valvular disease in hemodialysis patients was as poor as another authors reported previously (5-year survival rate : 30.6%), but survival rate after hemodialysis introduction was not very poor (87.1%). There was no significant difference in survival rate among mechanical and bioprosthetic valves. Bioprosthetic valve has the risk of reoperation due to early structural valve deterioration, but there was no significant difference in valve-related complication free rates. Therefore, we should select prosthetic valve in consideration of individual cases.

We experienced a very rare case in a 26-year-old man who underwent surgery for bilateral atrial myxomas. Moreover, his initial symptoms were due to acute myocardial infarction, which strongly suggested coronary artery embolization. Transesophageal echocardiography revealed not only left atrial myxoma at posterior wall, but also right atrial myxoma at the fossa ovalis which had not been detected by transthoracic echocardiography. At surgery, both left and right atriotomy was performed and bilateral atrial myxomas were completely removed. We emphasized that transesophageal echocardiography was very useful in detecting the location of myxomas, and that surgical exploration of the right atrium would have been necessary even if left atrial myxomas had not existed at the atrial septum.

We evaluated the therapeutic results of cancers in the bile duct, the pancreas head region and the liver and cirrhosis.
The former two types were examined in a total of 49 cases: 10 cholecystocarcinomas, 18 cholangiocarcinomas, 6 papillocarcinomas, and 15 pancreas head cancers. Radical surgery was performed in only 9 cases: 1 cholecystocarcinoma, 1 cholangiocarcinoma, 5 papillocarcinomas and 2 pancreas head cancers. The surgical success rate was satisfactory 83%(5/6) for papillocarcinoma, yet showed 18.4% overall.
Liver cancer and cirrhosis were examined in 102 cases: 78 cirrhoses and 24 livercancers. Of the former, 15% were viral cirrhosis, 44% alcoholic, 1% specific and 40% unknown. Ofthe latter, 29% were viral liver cancer, 29% alcoholic and 42% unknown.
Treatment of these cancers, with the exception of one type, was unfavorable. To increase the surgical success rate, cancers will have to be discovered earlier using such recent, highly-advanced technological means as endoscopy, ultrasonography, angiography and computerized tomography. At the same time, radical surgery should be actively applied in a broader range of cases.
In cirrhosis, bleeding in the upper digestive tract and complicating liver cancer are increasing in frequency due to prolonged life expectancy. How to manage this increase remains subject for further study in the future.