Placebo controlled evaluation of Xilei San,a herbal preparation in patients with intractable ulcerative proctitis

Background and Aim: Topical mesalamine or corticosteroid has shown efficacy in patients with ulcerative proctitis, but patients often become refractory to these interventions. Xilei San is a herbal preparation with evidence of anti‐inflammatory effects. We evaluated the efficacy of topical Xilei San in ulcerative proctitis patients. Methods: In a double blind setting, 30 patients with intractable ulcerative proctitis despite ≥ 4 weeks of topical mesalamine or corticosteroid were randomly assigned to True (n = 15) and placebo (n = 15). Patients in True received suppository Xilei San (0.1 g/dose per day of Xilei San), the other 15 received placebo suppository. The initial efficacy was evaluated on day 14. Primary endpoint of the trial was avoiding relapse during 180 days, relapse meant recurrence of active disease. Riley's index was applied for endoscopic and histological evaluations, while patients' quality of life was evaluated by an inflammatory bowel disease questionnaire. Results: On day 14, the number of patients who achieved remission, clinical activity index ≤ 4 in True was significantly higher versus placebo (P < 0.04). Likewise, at day 180, an 81.8% of patients in True were without relapse versus 16.7% in placebo (P < 0.001). Further, significant endoscopic (P < 0.01), histological (P < 0.02) and inflammatory bowel disease questionnaire (P < 0.04) improvements were observed in True, but not in placebo. Conclusions: This is the first controlled investigation showing significant clinical and endoscopic efficacy for Xilei San in patients with intractable ulcerative proctitis. Topical Xilei San was well tolerated, and was without safety concerns.     

Endoscopically proven case of rapid esophagogastric variceal progression and rupture as a result of portal hypertension with liver sarcoidosis

Sarcoidosis is a multi‐systemic disease of unknown etiology that results in the development of non‐caseating epithelioid granulomas. The liver is the third most frequently involved organ after the lymph nodes and the lungs. Most cases of liver sarcoidosis do not present with symptoms and involve minimal liver dysfunction, but some cases display progression to portal hypertension and liver cirrhosis, and finally to liver failure. The mechanism and the risk of progression in liver sarcoidosis are still unknown because of the diagnostic difficulty associated with this condition, and because follow‐up examinations can only be done in an invasive manner. Here, we present an informative case of liver sarcoidosis with rapid progression of esophagogastric varices. Four months prior to the definitive diagnosis, no signs of varices were observed on endoscopy, and developmentof esophagogastric varices, rapid progression, and eventual rupture occurred in a short period of time. A liver biopsy, carried out after endoscopic sclerotherapy, revealed that granulomas primarily affected the portal area without fibrotic and cirrhotic changes, which is considered a primary cause of portal hypertension and esophagogastric varices. Following the liver biopsy, the patient was given systemic steroids and is currently receiving outpatient care. Thus, we should consider the possibility that liver sarcoidosis, even in the absence of cirrhotic changes, can cause serious events such as esophagogastric variceal rupture following rapid progression as a result of portal hypertension.     

Negative regulation of cell motile and invasive activities by lysophosphatidic acid receptor-3 in colon cancer HCT116 cells

Lysophosphatidic acid (LPA) mediates a wide range of biological responses with G protein-coupled transmembrane receptors (LPA receptors). So far, at least six types of LPA receptors (LPA receptor-1 (LPA₁) to LPA₆) have been identified. Recently, it has been reported that LPA₃ indicates opposite effects on cellular functions of cancer cells. In the present study, to assess a biological role of LPA₃ on cell migration ability of colon cancer cells, we generated LPA receptor-3 (LPAR3) knockdown (HCT-sh3-3) cells from HCT116 and measured cell motile and invasion activities. In motility assay with a cell culture insert, HCT-sh3-3 cells showed significantly high cell motile activity, compared with control cells. For invasion assay, the filter was coated with Matrigel. The invasive activity of HCT-sh3-3 cells was significantly higher than that of control cells. Furthermore, we also examined the effects of LPAR3 knockdown on the interaction between colon cancer cells and endothelial F-2 cells. When F-2 cells were cultured with serum-free DMEM containing a supernatant from HCT-sh3-3 cells, the cell growth rate and migration activity of F-2 cells were significantly stimulated, associating with the elevated expressions of vascular endothelial growth factor (VEGF)-A and VEGF-C genes in HCT-sh3-3 cells. These results suggest that LPA₃ may act as a negative regulator on cell motile and invasive abilities of colon cancer HCT116 cells.     

Classification of radiation effects for dose limitation purposes: history,current situation and future prospects

Radiation exposure causes cancer and non-cancer health effects, each of which differs greatly in the shape of the dose–response curve, latency, persistency, recurrence, curability, fatality and impact on quality of life. In recent decades, for dose limitation purposes, the International Commission on Radiological Protection has divided such diverse effects into tissue reactions (formerly termed non-stochastic and deterministic effects) and stochastic effects. On the one hand, effective dose limits aim to reduce the risks of stochastic effects (cancer/heritable effects) and are based on the detriment-adjusted nominal risk coefficients, assuming a linear-non-threshold dose response and a dose and dose rate effectiveness factor of 2. On the other hand, equivalent dose limits aim to avoid tissue reactions (vision-impairing cataracts and cosmetically unacceptable non-cancer skin changes) and are based on a threshold dose. However, the boundary between these two categories is becoming vague. Thus, we review the changes in radiation effect classification, dose limitation concepts, and the definition of detriment and threshold. Then, the current situation is overviewed focusing on (i) stochastic effects with a threshold, (ii) tissue reactions without a threshold, (iii) target organs/tissues for circulatory disease, (iv) dose levels for limitation of cancer risks vs prevention of non-life-threatening tissue reactions vs prevention of life-threatening tissue reactions, (v) mortality or incidence of thyroid cancer, and (vi) the detriment for tissue reactions. For future discussion, one approach is suggested that classifies radiation effects according to whether effects are life threatening, and radiobiological research needs are also briefly discussed.     

Long-term pulmonary function after major lung resection

The function of the remaining lungs after major lung resection may be a determinant of the early postoperative outcome, as well as the late postoperative quality of life of the patient. Thus, extensive efforts have been made to accurately estimate the postoperative pulmonary function using a variety of methods: the segment counting method is utilized in patients without parenchymal diseases, while the functional lung imaging technique may be useful in patients with heterogeneous anatomical lung diseases. The postoperative pulmonary function is influenced not only by the extent of parenchymal resection, but also by various other factors, such as the site of resection, the mode of thoracotomy, the severity of pulmonary emphysema and/or the postoperative progression of pulmonary fibrosis. Although thoracoscopic surgery or segmental resection can lessen the extent of chest wall damage or the extent of parenchymal resection compared with conventional operations, the resulting functional benefits do not last. Interestingly, the postoperative pulmonary function continues to improve during the first postoperative year as if the remaining lungs grow, although the cause(s) of this compensatory response of the remaining lungs remains unclear. Such an ability of the remaining lung to compensate for the lost lung function may eventually determine the late postoperative pulmonary function.     

Successful pregnancy after gonadotropin-releasing hormone analogue and hysteroscopic myomectomy in a woman with diffuse uterine leiomyomatosis

We report a patient with diffuse uterine leiomyomatosis, who wished to become pregnant. We performed hysteroscopic myomectomy after treatment with nafarelin acetate for 6 months. The patient conceived spontaneously soon after hysteroscopic myomectomy, and delivered a 2,798-g healthy baby.     

Does stress exacerbate liver diseases?

Although anecdotal comments on detrimental effects of psychosocial stress on liver diseases can be found even in the early literature, only recently has scientific evidence been reported. The present article reviewed such evidence to demonstrate how stress exacerbates liver diseases. A search of the literature from the last two decades was performed using MEDLINE by pairing ‘psychological stress’ with ‘liver’ or ‘hepatitis.’ Additional research was conducted by screening the bibliographies of articles retrieved in the MEDLINE search. The search results showed that the principal effectors of the activated hypothalamic–pituitary–adrenal (HPA) axis, glucocorticoids, can exert a facilitative effect on the hepatic inflammatory response and even increase the risk of developing hepatocellular carcinoma. For certain liver diseases, defective HPA axis activation, which probably contributed to the exacerbation of the liver disease, has been reported. The efferent sympathetic/adrenomedullary system mainly contributes to the stress‐induced exacerbation of liver diseases via its neurotransmitters, the catecholamines. In contrast, the efferent parasympathetic nervous system elicits an inhibitory effect on the development of hepatic inflammation. In conclusion, the pathophysiological interaction between stress and the liver appears to be regulated by the complex, dynamic networks of both the endocrine and autonomic nervous systems, which implies a further need for basic research into the involved mechanisms and for clinical evidence to apply psychosocial support to patients with chronic liver diseases.