Immune microenvironment of hepatocellular carcinoma,intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma: Relationship with histopathological and molecular classifications

Tumor tissue is composed of tumor cells and tumor stroma. Tumor stroma contains various immune cells and non-immune stromal cells, forming a complex tumor microenvironment which plays pivotal roles in regulating tumor growth. Recent successes in immunotherapies against tumors, including immune checkpoint inhibitors, have further raised interests in the immune microenvironment of liver carcinoma. The immune microenvironment of tumors is formed because of interactions among tumor cells, immune cells and non-immune stromal cells, including fibroblasts and endothelial cells. Different patterns of immune microenvironment are observed among different tumor subtypes, and their clinicopathological significance and intertumor/intratumor heterogeneity are being intensively studied. Here, we review the immune microenvironment of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and liver metastasis of colorectal adenocarcinoma, focusing on its histopathological appearance, clinicopathological significance, and relationship with histological and molecular classifications. Understanding the comprehensive histopathological picture of a tumor immune microenvironment, in addition to molecular and genetic approaches, will further potentiate the effort for precision medicine in the era of tumor-targeting immunotherapy.     

Clinicopathological features,diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to “interval cancers” and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.     

Association of the time to first epinephrine administration and outcomes in out-of-hospital cardiac arrest: SOS-KANTO 2012 study

Objective

This study assessed the association between the timing of first epinephrine administration (EA) and the neurological outcomes following out-of-hospital cardiac arrests (OHCAs) with both initial shockable and non-shockable rhythms.

Clinical effect of LM-001, prostaglandin synthetic inhibitor, on pain from urinary tract stone and vesical urgency after operation of the bladder or prostate

Clinical effect of LM-001, a prostaglandin synthetic inhibitor developed from a drug delivery system, was evaluated in 54 patients with pain from urinary tract stones (stone pain) and 32 with vesical urgency after an operation on bladder or prostate. LM-001, felbinac ethyl incorporated in lipid microsphere, wes intravenously administered at the onset of stone pain or vesical urgency. Of 54 with stones and 32 with urgency, 53 and 29 were eligible for response, respectively. The symptoms improved or disappeared in some cases just after the administration and in the majority of patients within 15 minutes, in 49 of 53 patients with stone pain. Further, the effectiveness lasted over 24 hours in 26 of the 49 responding to this agent. On one hand, improvement or disappearance of vesical urgency was recognized in 25 of 29 patients, and the effectiveness was observed shortly after injection in 16 and lasted over 24 hours in 13 cases. Toxicities of this drug were investigated in 54 patients with stone pain and 32 with urinary urgency. Side effects consisted of pain at the injection site in 4, a slight fall of blood pressure in 1, slight visual disturbance in 1, body heat sensation in 1, leukocytosis in 3 and elevation of alkaline phosphatase in 1. These symptoms were transient and disappeared without use of any agent. LM-001 is concluded to be a useful drug for controlling stone pain and vesical urgency since an immediate effect, long durability and high response rates were obtained without severe side     

Bending and torsion fractures in long bones (a mechanical and radiologic assessment of clinical cases).

Long bone injuries in clinical cases are studied by comparison of roentgenograms with a rational mechanical analysis of the injuries. Fractures produced by torsional loads have a spiral shape with a smooth and even surface. Fractures induced by bending loads have uneven and rugged fracture surfaces perpendicular to the bone axis. Long bones are weak in torsion but strong in tensile stress produced by bending. This result corresponds to the clinical fact that a large direct external force is needed to produce a transverse fracture while a spiral fracture is produced by a relatively small torque.     

Treatment of HTLV-I-associated myelopathy with high-dose intravenous gammaglobulin

Summary Fourteen patients with HTLV-1-associated myelopathy were treated with high-dose intravenous gammaglobulin (IVGG). Ten received 10 g/day of IVGG and 4 received 400 mg/kg of body-weight/day of IVGG for 5 consecutive days. Improvement of spastic paraparesis was observed in 10 within 7 days of the commencement of IVGG. The therapeutic effects were sustained for more than 3 weeks in some patients. There were no side effects. Analysis of factors of relevance to the clinical improvement with IVGG showed that the beneficial response was preferentially found in patients having a high CSF titre of anti-HTLV-I antibodies, a high CSF IgG level and a marked brain MRI abnormality.     

Comparison of factors related to hospitalization versus home care of elderly

This study was done to identify factors affecting present hospitalization versus home care in 4,578 elderly subjects representing 87.1% of the elderly population living in S. city near Osaka. Subjects or their families were asked by interviews regarding the age of the subjects, the kind of persons living together in the family unit, the kind of housing, the number of rooms in the family dwelling, and health conditions. Subjects were also asked whether he or she could walk unassisted and whether home care would be preferred in case of an illness. Among the 153 hospitalized subjects, ability to walk, age, and the number of rooms were all significant factors, in decreasing order. Among the 1,193 persons who preferred home care in case of an illness, the number of rooms, age, ability to walk, and the size of the family unit were all significant factors, in decreasing order. Among subjects who could not walk unassisted, the number of rooms was the main factor determining their admission and not preferring home care if their condition worsened. Thus, although the ability to walk is the major factor among the factors we investigated, housing conditions are also important if home care is to be possible.