Perioperative Oral Administration of Cystine and Theanine Enhances Recovery After Distal Gastrectomy

Background: It has been reported that cystine and theanine, amino acids related to glutathione synthesis, have immunomodulatory effects, such as suppressing inflammation after strenuous exercise. In this study, we examined the effects of oral administration of cystine and theanine during the perioperative period as a pilot study. Methods: Forty‐three cases of distal gastrectomy for cancer conducted in our department were assigned to the cystine and theanine group (CT group) or to the placebo control group (P group), and a randomized, single‐blind, parallel‐group study was then performed. Cystine (700 mg) and theanine (280 mg) or a placebo was administered to participants for 10 continuous days (4 days before to 5 days after surgery). Changes in pre‐ and postoperative interleukin (IL)–6, C‐reactive protein (CRP), albumin, white blood cell (WBC) count, neutrophil count, total lymphocyte count, resting energy expenditure (REE), and body temperature were compared and examined. Results: Ten patients were excluded, leaving 33 patients in the study. The CT group had significantly lower IL‐6 values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD 4), and body temperatures (POD 5) than the P group (P < .05). In addition, REE in the P group peaked on day 1 (1.14 ± 0.16 [pre‐ and postoperative ratio]), whereas the CT group did not show any increase on POD 1 (0.99 ± 0.21, P < .05 vs P group). Conclusions: This study suggests that oral administration of cystine and theanine during the perioperative period may alleviate postgastrectomy inflammation and promote recovery after surgery.     

ANALYSIS OF PROGNOSTIC FACTORS IN PATIENTS WITH GASTRIC VARICES AFTER ENDOSCOPIC TREATMENT

Background: The prognostic factors, including gastric variceal bleeding itself, in patients with gastric varices (GV) after endoscopic treatment remain unclear. The aim of this study was to analyze prognostic factors in patients with GV after endoscopic treatment as well as to evaluate safety and efficacy of our endoscopic treatment. Patients and Methods: This study enrolled 115 patients who underwent endoscopic treatment for GV between October 1988 and December 2003 using cyanoacrylate and 5% ethanolamine oleate. Successful hemostasis, recurrence rates, rebleeding rates, survival rates, complications and prognostic factors after the treatment were retrospectively reviewed. Results: Treatment sessions for GV were performed 3.4 ± 2.5 times. All cases, including 14 emergency cases, were treated successfully. The cumulative recurrence rates at 1, 3 and 5 years after the treatment were 7.0%, 15.6% and 20.0%, respectively, and the cumulative rebleeding rates at 1, 3 and 5 years were 3.5%, 8.7% and 14.8%, respectively. The overall survival rates were 78.3%, 63.7% and 51.5% at 1, 3 and 5 years, respectively. Grade B or C in Child–Pugh classification, emergency or elective cases, and association with hepatocellular carcinoma were identified as significant negative prognostic factors after endoscopic treatment by multivariate analysis. Although several complications were observed, there was no mortality. Conclusions: Grade B or C in Child–Pugh classification, emergency or elective situation, and association with hepatocellular carcinoma are negative prognostic factors after endoscopic treatment.     

Selection of Deep Brain Stimulation Candidates in Private Neurology Practices: Referral May Be Simpler than a Computerized Triage System

Objective: The objective of this study is to compare a computerized deep brain stimulation (DBS) screening module (Comparing Private Practice vs. Academic Centers in Selection of DBS Candidates [COMPRESS], NeuroTrax Corp., Bellaire, TX, USA) with traditional triage by a movement disorders specialized neurologist as the gold standard. Methods: The COMPRESS consists of a combination of the Florida Surgical Questionnaire for Parkinson disease (FLASQ‐PD), a cognitive assessment battery provided by MindStreams® (NeuroTrax Corp.), and the Geriatric Depression Scale and the Zung Anxiety Self‐Assessment Scale. COMPRESS resulted in the classification of patients into three categories: “optimal candidate,”“probable candidate,” and “not a good candidate.” Similar categorical ratings made by a referring private practice neurologist and by a trained movement disorders specialist were compared with the ratings generated by COMPRESS. Results: A total of 19 subjects with Parkinson's disease were enrolled from five private neurological practices. The clinical impressions of the private practice neurologist vs. those of the movement disorders specialist were in agreement approximately half the time (10/19 cases). The movement disorders specialist and COMPRESS agreed on 15/19 cases. A further comparison between outcomes from the entire COMPRESS module and the FLASQ‐PD questionnaire by itself resulted in high agreement (18/19 cases in agreement). Conclusions: The COMPRESS agreed with an in‐person evaluation by a movement disorders neurologist approximately 80% of the time. The computerized COMPRESS did not provide any screening advantage over the short FLASQ‐PD paper questionnaire. Larger studies will be needed to assess the utility and cost effectiveness of this computerized triage method for DBS.     

Multiplexed genome editing by in vivo electroporation of Cas9 ribonucleoproteins effectively induces endometrial carcinoma in mice

Synergistic effects among multiple gene mutations are involved in cancer development and progression. However, developing genetically modified mouse models to analyze various combinations of mutations is extremely labor-intensive and time-consuming. To address these problems, we developed a novel method for in vivo multiplexed genome editing of the murine uterus to model human endometrial carcinoma (EMC). To do this, we injected a CRISPR-Cas9 ribonucleoprotein complex into the uterine cavity of adult female mice, followed by electroporation. Evaluation of reporter mice demonstrated that genome editing occurred specifically in uterine epithelial cells, which are the origin of EMCs. Simultaneous targeting of Pten/Trp53/Lkb1, or targeting of Pten/Lkb1 along with the Ctnnb1ΔEx3 mutation, resulted in efficient generation of invasive tumors in wild-type females within 3 months. This novel method will enable rapid and easy validation of many combinations of gene mutations that lead to endometrial carcinogenesis.     

Significance of immunohistochemical expression of estrogen receptors alpha and beta in squamous cell carcinoma of the esophagus.

PURPOSE: Possible significance of sex hormone estrogen as an antitumor therapeutic arm toward esophageal squamous cell carcinoma (ESCC) cells has been suggested. The aim of the current study was to clarify the clinicopathologic significance of an immunohistochemical expression of estrogen receptors alpha and beta (ER alpha and ER beta) in ESCC. EXPERIMENTAL DESIGN: Expression of ER alpha and ER beta were examined using an immunohistochemical methods in 73 paraffin-embedded sections collected from patients with ESCC who had been subjected to esophageal resection and digestive reconstruction without any preoperative induction therapy. RESULTS: Forty-seven (64.4%) ESCCs had a positive cytoplasmic expression of ER alpha and 21 (28.8%) ESCCs had a positive nuclear expression of ER beta. Univariate analysis showed that both positive ER alpha expression (P=0.0001) and negative ER beta expression (P=0.026) were unfavorable prognostic indicators in ESCC. Moreover, multivariate analysis showed that ER alpha-positive/ER beta-negative expression (P=0.003) and progression of tumor stage (P=0.014) were found to be independent unfavorable prognostic indicators in ESCCs. CONCLUSIONS: Immunohistochemical expression of ER alpha and ER beta were found to be observed in ESCC. Positive expression of ER alpha in addition to negative expression of ER beta proved to be an unfavorable independent prognostic indicator in ESCC.     

Prediction of anti-tumour effect of thermochemotherapy with in vitro thermochemosensitivity testing for non-small cell lung cancer.

PURPOSE: We investigated whether it is possible to predict the antitumour effects of thermochemotherapy from the results of anticancer agent sensitivity testing. MATERIALS AND METHODS: We produced a nude mouse cancer model using 4 lung cancer cell lines. Animals were divided into 4 groups: Thermotherapy (HT group), chemotherapy (CT group), thermochemotherapy (HT+CT group), and no therapy (NT group). Comparison of in vivo and in vitro effects were performed using cisplatin (CDDP), doxorubicin (ADR) and vinorelbine (NVB). In vivo thermotherapy was performed using the Thermotron RF IV, and radiofrequency (RF) capacitative hyperthermia device that induces a localised temperature of 42.0 degrees C for 45 min. The collagen gel embedded culture drug sensitivity test (CD-DST) was used for in vitro chemosensitivity analysis of the anticancer agents. In vitro thermochemotherapy was performed using a modified CD-DST method, with the incubator set at 42.0 degrees for the first hour of the 24 hours drug exposure period. RESULTS: A good correlation was seen between in vivo and in vitro treated/control ratios (T/C%) in the HT group (R = 0.91, p = 0.09). Good correlations were also seen between in vivo and in vitro T/C in all cell lines in the CT group (R = 0.759, p = 0.09) and the HT+CT group (R = 0.65, p = 0.02). True positive rate was 87.5% (7/8), and true negative rate was 100% (4/4). Sensitivity, specificity and accuracy were 100% (7/7), 80% (4/5), and 91.7% (11/12) respectively. CONCLUSION: A modified CD-DST using an exposure temperature of 42 degrees C can be used to predict the antitumour effect of thermochemotherapy.     

Rapid and accurate method for delineating cancer lesions in laparoscopic colectomy using activated carbon injection

The aim of our study was to evaluate the clinical efficacy of preoperative injection of activated carbon in delineation of cancer location in laparoscopic colectomy. Activated carbon particles were injected during endoscopy into the normal colonic wall surrounding cancer lesions in five cases of early colon cancer, prior to laparoscopic surgery. The carbon-stained area was clearly recognizable as a blackened patch on the serosal surface of the colon. Using the carbon-stained area as a reference point, partial colectomies were successfully performed on all five patients. The preoperative injection of activated carbon assisted in the intraoperative delineation of early colonic cancer lesions. This method is recommended for the rapid and accurate delineation of early colonic cancers in laparoscopic surgery. © 1995 Wiley-Liss, Inc.     

Angiospermic Changes of Coronary Aneurysms in Kawasaki Disease

The fate of coronary aneurysms in Kawasaki disease or MCLS was examined by follow-up studies on 9 patients with multiple bilateral aneurysms in the coronary arteries demonstrated by coronary arteriography. Their ages at the time if first examination ranged from 0.3 to 11 years (mean, 4.1 years). The mean interval between the onset of acute illness and the initial examination was 15.8 months, and the mean interval between the first and second examination was 17.9 months. Eight of the nine patients received anticoagulants between examinations. The second coronary arteriogram showed morphologic changes of the aneueysm from the time of the first examination: changes were seen in the right coronary artery area in 8 patients (89%) and in the left coronary artery area in 7 patients. These morphologuic changes seemed to be mainly secondary to thrombus formation, calcification, stenosis and/or obstruction of the aneuryms. Thus, coronary aneuryms in Kawasaki disease were transformed despite the use of anticoagulants. It is considered that multiple large coronary aneurysms will not healed or disappear, but are simply transformed as a result of their thrombosis and/or calcification.     

Chemosensitivity test for unresectable non-small cell lung cancer

To choose the optimal chemotherapy regimens, we have employed a new chemosensitivity testing method, the collagen gel droplet embedded culture drug sensitivity test (CDDST) for patients with non-small cell lung cancer (NSCLC). This method requires fewer cancer cells(1 x 10(5) cells in 2 specimens biopsied by bronchoscopy) than conventional chemosensitivity tests and can be also used to assess cases of malignant effusion. Correlations between the in vitro and in vivo responses were: true positive ratio, 75.0% (21/28 patients); true negative ratio 85.0% (17/20 patients); and accuracy 79.2%. The median survival time (MST) of patients (n = 11) with unresectable NSCLC who were given optimal chemotherapy based on the results of the CDDST was 15.8 months and the MST of those (n = 16) who did not receive a sensitive agent was 5.6 months. There was a significant difference between these two groups (p = 0.0048, log-rank test). These results suggest that the CDDST is an effective method for chemosensitivity testing in unresectable NSCLC.