Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia

We report here that loss of the Sprouty2 gene (also known as Spry2) in mice resulted in enteric nerve hyperplasia, which led to esophageal achalasia and intestinal pseudo-obstruction. Glial cell line-derived neurotrophic factor (GDNF) induced hyperactivation of ERK and Akt in enteric nerve cells. Anti-GDNF antibody administration corrected nerve hyperplasia in Sprouty2-deficient mice. We show Sprouty2 to be a negative regulator of GDNF for the neonatal development or survival of enteric nerve cells.     

Factors influencing joint-preserving operations in the treatment of the late stages of osteoarthritis of the hip

Between November 1983 and December 1992, 136 hips (119 patients) with coxarthritis were operated on using joint-preserving techniques based on the rationale of Pauwels' osteotomy. The criterion for selection was a patient in whom the height of the joint space in the weight-bearing area of the hip was less than 1 mm. The mean age at operation was 48 years and the mean follow-up 109 months (60 to 171). Hips were categorised using Bombelli's classification of osteoarthritis, into atrophic and non-atrophic types. The endpoint was defined as that at which the height of the joint space became less than 1 mm again. The Kaplan-Meier curve showed that the rate of survival of the non-atrophic group was significantly better than that of the atrophic group. Cox's proportional hazard model indicated that the factors influencing the results of joint-preserving operations included Bombelli's classification, postoperative incongruence of the joint and the height of the joint space.     

Exposure to 1-bromopropane causes ovarian dysfunction in rats.

Although 1-bromopropane has been used in chemical and electronic industries as an alternative to ozone layer-depleting solvents, its toxicity on female reproductive organs has not been fully elucidated. The aim of this experiment was to determine the effect of 1-bromopropane on female reproductive function in rats. Forty female Wistar rats were divided into four equal groups. Each group was exposed daily to 0, 200, 400, or 800 ppm of 1-bromopropane for eight h a day. After exposure for 7 weeks, all rats in the 800-ppm group became seriously ill and were sacrificed during the 8th week. The other dose groups were exposed for 12 weeks. In the 800-ppm group, but not in the other two exposed groups, body weight was significantly less than the control at each time point from 2 to 7 weeks after the beginning of exposure. Tests of vaginal smears showed a significant increase in the number of irregular estrous cycles with extended diestrus in the 400- and 800-ppm groups. Histopathological examination of the ovary showed a significant dose-dependent reduction of the number of normal antral follicles and a decrease in the number of normal growing follicles in the 400-ppm group. No significant change was found in plasma concentrations of LH or FSH in any group when compared with the control. Our results indicate that 1-bromopropane can induce a dose-dependent ovarian dysfunction in nonpregnant female rats associated with disruption in follicular growth process.     

Number of aberrant crypt foci in the rectum is a useful surrogate marker of colorectal adenoma recurrence

Aim: Endoscopic screening and removal of colorectal adenomas can reduce the incidence of colorectal cancer. However, given the possibility of adenoma recurrence, surveillance colonoscopy is currently recommended after the initial screening and removal of colorectal adenomas. Aberrant crypt foci (ACF) have been shown to serve as a reliable surrogate marker of colorectal carcinogenesis. In this study, the relationship between the number of ACF at the initial endoscopic polypectomy and the likelihood of colorectal adenoma recurrence after polypectomy were investigated. Methods: High‐magnification chromoscopic colonoscopy was performed in 82 subjects who underwent endoscopic polypectomy to identify ACF in the lower rectum. Surveillance colonoscopy was then performed 3 years after the baseline polypectomy at Yokohama City University Hospital. Results: The number of ACF was greater in patients who showed adenoma recurrence (7.88 ± 6.35) than in those who did not (2.19 ± 2.95) (P < 0.001). Receiver–operating curve analysis showed that the number of ACF was a highly specific predictor of the risk of adenoma recurrence. Conclusions: This is the first study conducted to investigate the relationship between the number of ACF after endoscopic polypectomy and the likelihood of recurrence of colorectal adenomas. These results suggest that the number of ACF is a useful predictor of the likelihood of colorectal adenoma recurrence.     

Traction suture technique of the pericardium to suspend the heart for excellent exposure in abdominal-transhiatal approach

In this report, we describe our traction suture technique of the pericardium for suspension of the heart without hemodynamic instability to obtain excellent exposure in the abdominal-transhiatal approach (TH). Our technique is an application of deep pericardium stitches for off-pump coronary artery bypass surgery. In detail, the left hepatic lobe is detached at its triangular ligament from the diaphragm and is deflected to the right. Then, the tendinous portion of the diaphragm arching over the esophagus is incised upward in the midline until the pericardium is exposed. Pericardial fatty tissue was dissected. Three U-shaped sutures reinforced with a felt pledget are placed on the posterior aspect of the pericardium and diaphragm. A 15 Fr. flexible catheter is placed over both ends of the suture to avoid damage of the adjacent organs. Finally, the sutures are fixed to the drape of anterior wall of the patient to maintain good exposure.     

Comparison of endoscopic findings with symptom assessment systems (FSSG and QUEST) for gastroesophageal reflux disease in Japanese centres

Background and Aim: We compared endoscopic findings of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), a written questionnaire developed in Japan, to that for the questionnaire for the diagnosis of reflux esophagitis (QUEST) for the diagnosis of reflux esophagitis. Methods: We registered 475 patients with untreated symptoms of upper abdominal pain (male/female: 252/223, average age 52.4 ± 17.8 years). Subjects were assessed first with the FSSG and QUEST questionnaires, then by endoscopy, before allocation to a gastric ulcer (GU), duodenal ulcer (DU), gastroesophageal reflux disease (GERD) or functional dyspepsia (FD) group. Results: On the basis of the endoscopic findings the diagnoses for the 475 subjects were as follows: FD 52.2%, DU 7.6%, GU 7.8%, and GERD 32.4% (Grade M 10.1%, Grade A + B 20.2%, Grade C + D 2.3%). There was no difference between the FSSG and QUEST in sensitivity, specificity or accuracy for any condition. The FSSG score rose with increasing endoscopic severity of GERD, but there was no correlation between the QUEST score and endoscopic severity. The FSSG total score was inferior to QUEST in terms of distinguishing GERD from other conditions, but when only the questions relating to reflux symptoms were used, the FSSG was able to distinguish GERD from other conditions as well as QUEST. Conclusions: The FSSG score reflects the severity of the endoscopic findings of GERD.     

Thymidine phosphorylase and angiogenesis in early stage esophageal squamous cell carcinoma

Background

The relationship between thymidine phosphorylase (TP) and angiogenesis at the early stage of esophageal squamous cell carcinoma has been unclear.

Methods

Using 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer, microvessel density (MVD) was estimated using immunostaining for CD34 and CD105. TP expression was also evaluated in both cancer cells and stromal monocytic cells (SMCs). We then investigated the correlation between MVD and TP expression in both cancer cells and SMCs.

Results

On the basis of the above parameters, MVD was significantly higher in cancerous lesions than in normal squamous epithelium. In terms of CD34 and CD105 expression, MVD showed a gradual increase from normal squamous epithelium, to low-grade intraepithelial neoplasia, and then to M1 and M2 cancer, and M3 or deeper cancer. M1 and M2 cancer showed overexpression of TP in both cancer cells and SMCs. There was no significant correlation between TP expression in cancer cells and MVD estimated from CD34 (rS = 0.16, P = 0.21) or CD105 (rS = 0.05, P = 0.68) expression. Significant correlations were found between TP expression in SMCs and CD34-related (rS = 0.46, P < 0.001) and CD105-related (rS = 0.34, P < 0.01) MVD. In M3 or deeper cancers, there were no significant correlations between TP expression in cancer cells or SMCs and venous invasion, lymphatic invasion, and lymph node metastasis.

Conclusion

TP expression is activated in both cancer cells and stromal monocytic cells at the very early stage of ESCC progression. TP expression in SMCs, rather than in cancer cells, is significantly correlated with angiogenesis.