Immunohistochemical study of the muscularis externa of the esophagus in achalasia patients.

The etiology of achalasia is believed to be the neuropathy associated with chronic inflammation of the nerve plexus, but the cause of plexus inflammation is unknown. The purpose of this study was to evaluate the pathophysiology of achalasia by examining the muscularis externa of the esophagus. We used the muscularis externa of the esophagus of 62 patients with achalasia (median 44 years, male : female 32:30) who underwent surgical treatment (achalasia group) and of 10 patients (median 65.5 years, male : female 9:1) who underwent esophagectomy for thoracic esophageal cancer (control group) to perform immunohistochemical staining with S-100, CD43, c-kit (CD117), n-NOS, vasoactive intestinal polypeptide (VIP), and ubiquitin. The cell counts that were positive for S-100, n-NOS, VIP, and ubiquitin were significantly lower in the achalasia group compared with the control group (P < 0.001, P= 0.001, P < 0.001, and P= 0.001, respectively). There were no statistically significant differences with respect to CD43 and c-kit staining (P= 0.586 and P= 0.209, respectively). In conclusion, the pathophysiology of achalasia is therefore considered to be an impaired production of NO and VIP, which both affect interstitial cell of Cajal and smooth muscles, and this impairment is therefore considered to play a role in the pathophysiology of achalasia.

[Anti-reflux procedure].

We introduced surgical indication, laparoscopic technique and procedure, management after surgery, and postoperative complication for gastroesophageal reflux diseases (GERD). Several points of laparoscopic fundoplication for GERD are shown below. 1) Exposure of abdominal esophagus: downward exposure is recommended in order to avoid postoperative dysphagia like achalasia. 2) Dissection of short gastric vessels: this procedure warrant free tension of gastric fundus at fundoplication. 3) Crural repair: create appropriate size of hiatus. 4) Fundoplication: we should do shoe shine maneuver and drop test to confirm free tension of fundus. 5) Shoulder stitch and anchor stitch: this procedure are needed to avoid dislocation of gastric fundus.

Cerebral microembolisation during radiofrequency ablation of lung tumours: detection by carotid duplex ultrasound.

The aim of this study was to investigate the appearance of microbubbles during radiofrequency ablation (RFA) of lung tumours. Eight consecutive patients (mean age, 73.1 years; 3 men and 5 women; 10 malignant lesions; mean lesion size, 24.8 mm) who underwent RFA of lung tumours using internally cooled single electrodes were enrolled. During the RFA procedure, the right internal carotid artery was continuously monitored by duplex ultrasound. High-intensity transient signals (HITS) that occurred in the Doppler blood flow waveform were taken to indicate microbubbles. 21 RFA applications were performed for the 10 lesions. HITS were observed in 19 of 21 RFA applications; the mean frequency in a single application was 10+/-13.3. A statistical correlation was seen between the duration of energy deposition and the number of HITS, and between tumour size and the number of HITS. Microbubbles were detected in all patients in the late phase of the first session of RFA.

Prediction of recurrence after laparoscopic fundoplication for erosive reflux esophagitis based on anatomy-function-pathology (AFP) classification.

BACKGROUND: The usefulness of the anatomy-function-pathology (AFP) score was examined to evaluate its prediction of recurrence after laparoscopic fundoplication for erosive reflux esophagitis. METHODS: Of the patients undergoing laparoscopic fundoplication for erosive reflux esophagitis of Los Angeles classification grade A or higher from December 1994 to December 2004, 107 who underwent preoperative barium esophagogram, pH monitoring, and endoscopy were selected as subjects. The AFP score was calculated by A, F, and P factor grades of the AFP classification. By comparing patients with and without recurrence, the usefulness of the AFP score for predicting recurrence was examined. RESULTS: Reflux esophagitis recurred in seven patients. No significant difference in age, sex, or A or F factor was observed between the groups, whereas a significant difference was observed in the P factor (p = 0.008). On the other hand, the mean AFP score in the recurrence group was 16.9 +/- 5.3, whereas that in the nonrecurrence group was 8.9 +/- 5.3 (p = 0.0021). Among the patients with a score of 17 points or more (n = 23), recurrence was found in 6 patients (26%). On the other hand, among the patients with a score lower than 17 points (n = 84), recurrence was found in 1 patient, but not in the remaining 83 patients (1%). Sensitivity was thus 85.7% (95% confidence interval [CI], 42.1-99.6), and specificity was 83% (95% CI, 74.2-89.8). The positive predictive value was 26.1% (95% CI, 10.2-48.4), and the negative predictive value was 98.8% (95% CI, 93.5-99.9). Multiple logistic regression analysis was performed, and receiver operating characteristics curves were obtained. The area under the curve for the AFP score was 0.8457, whereas that for the P factor was 0.7907 (p = 0.0045), suggesting that the AFP score may more accurately predict recurrence than the P factor. CONCLUSION: The AFP score may be useful for predicting postoperative recurrence. If surgery is performed when the AFP score is lower than 17 points, the likelihood of postoperative recurrence is expected to be very low.

Laparoscopic Heller myotomy and Dor fundoplication for the treatment of achalasia. Assessment in relation to morphologic type.

BACKGROUND: The significance of laparoscopic Heller myotomy and Dor fundoplication (LHD) for the treatment of achalasia in relation to the severity of the lesion has not been sufficiently assessed. METHODS: Of patients who were diagnosed with achalasia from August 1994 to February 2004, 55 individuals who underwent LHD served as subjects. The therapeutic effects of LHD were assessed in terms of operation time, intraoperative complications, postoperative hospital stay, and symptom improvement in relation to morphologic type (spindle type, Sp; flask type, Fk; and sigmoid type, Sig). Degree of symptomatic improvement was classified into four grades: excellent, good, fair, and poor. RESULTS: Breakdown of morphologic type was as follows: Sp, n = 29; Fk, n = 18; and Sig, n = 8. Excluding one patient for whom conversion to open surgery was required, median average operation time for 54 patients was 160 min. As to intraoperative complications, esophageal mucosal perforation was seen in nine of the 55 patients (16%); however, conversion to open surgery could be avoided by suturing the affected area. Moreover, intraoperative bleeding of at least 100 g was seen in five of the 55 patients (9%), with one Fk patient requiring conversion to open surgery and transfusion. Median postoperative hospital stay was 8 days. Degree of dysphagia relief was excellent in 45 patients (83%), good in eight patients (15%), and fair in one patient (2%). Excellent improvement was obtained in 90%, 88%, and 50% in Sp, Fk, and Sig patients, respectively. Reflux esophagitis was seen in two patients, and was treated with a proton pump inhibitor. CONCLUSIONS: The results of the present study suggest that classification of morphologic type is a useful parameter in predicting postoperative outcome in achalasia. In order to achieve excellent symptomatic relief, surgery for achalasia should be recommended for but not limited to Sp and Fk types.

New strategy for acute necrotizing pancreatitis: Continuous Regional Arterial Infusion (CRAI) therapy.

Acute pancreatitis is an autodigestive disease, of which protease inhibition has been the focus of experimental and clinical research. Different from Europe and the United States, protease inhibitors are often applied in the treatment of acute pancreatitis in Japan. However, in clinical settings, the effect of protease inhibitors on acute pancreatitis is still controversial. Continuous Regional Arterial Infusion (CRAI) of protease inhibitors and antibiotics therapy were developed in Japan and it has been demonstrated that CRAI therapy has beneficial effects on severe acute necrotizing pancreatitis. In the Japanese clinical guidelines for the treatment of acute pancreatitis, published in 2003, CRAI therapy is still classified as a special therapy. However, a Randomized Controlled Trial for CRAI therapy has started and CRAI therapy is expected to become a new standard therapy for severe acute pancreatitis. CRAI therapy is aimed at preventing the progression of pancreatic inflammation and pancreatic infection. CRAI therapy can decrease the mortality rate and the frequency of pancreatic infection in severe acute pancreatitis, but it should be started as soon as possible after the onset of acute pancreatitis.

Hand-assisted laparoscopic and thoracoscopic surgery (HALTS) in radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.

AIM: To prove the feasibility of hand-assisted laparoscopic and thoracoscopic surgery (HALTS) for radical esophagectomy with three-field lymphadenectomy to thoracic esophageal cancer. METHODS: Esophagectomy with three-field lymphadenectomy was performed using HALTS in 19 patients with thoracic esophageal cancer without distant metastasis. Five patients had chemo-radiotherapy prior to surgery. RESULTS: All operations were completed successfully without the need for open surgery. Mean surgical time was 476+/-58 min, and mean blood loss during surgery was 343+/-184 mL. All patients started tube feeding and were moved from the intensive care unit to the general surgery ward the day after surgery. Discharge occurred a median of 10 days after surgery. Fifteen patients could return to full time jobs from 8 to 62 days after surgery (median 22 days) and from 1 to 35 days after discharge (median 9 days). Other three could return to daily activities at home soon as well. No major complications occurred, except one anastomotic leak. In terms of lung function, %FEV(1) was not changed whereas %VC was reduced significantly 1 month after surgery. All but two recurrences have been healthy without a relapse for a mean of 289 days. CONCLUSIONS: These results suggest that HALTS may be a useful surgical technique to reduce the invasiveness of conventional radical esophagectomy with three-field lymphadenectomy for thoracic esophageal cancer.

River and groundwater nitrogen contamination caused by livestock production.

Water quality of rivers in Japanese domestic dairy and pig raising regions, as well as the groundwater in these regions, was investigated. Regarding the method of disposing livestock excreta, interview results from the livestock production farmers and the results of water quality analysis were evaluated. It is concluded that the rivers and the groundwater were contaminated due to inappropriate disposal methods of the livestock excreta. The concentrations of ammonium nitrogen and nitrate nitrogen in the rivers and groundwater were high. The sludge from the bottom of the rivers was also investigated and bacteria which are characteristic of excreta of dairy cattle and pigs were detected. The above pollutants were, therefore, considered to be of livestock origin.

Effect of a histamine H1 receptor antagonist on gastric endocrine cell proliferation induced by chronic acid suppression in rats.

The effect of histamine on gastrin cells and enterochromaffin-like cells has not yet been clarified. We investigated the influence of pyrilamine (a histamine H1 receptor antagonist) on serum gastrin level, gastrin cells, and enterochromaffin-like cells in rats with or without 4 weeks of famotidine treatment. The rats were divided into six groups: a control group, two pyrilamine groups (2mg/kg, or 20mg/kg, p.o.), a famotidine group (20mg/kg twice/daily i.m.), and two pyrilamine + famotidine groups. The serum gastrin concentration was determined, and gastrin cells and enterochromaffin-like cells were identified by the labeled streptavidin biotin complex method and counted. Hypergastrinemia, gastrin cell hyperplasia, and enterochromaffin-like cell hyperplasia were found after 4 weeks of famotidine treatment. Four weeks of treatment with pyrilamine alone did not affect the gastrin level, gastrin cells, or enterochromaffin-like cells in the rat stomach. When combined with famotidine, pyrilamine enhanced famotidine-induced hypergastrinemia, but it did not affect gastrin cell hyperplasia, and it significantly inhibited enterochromaffin-like cell hyperplasia. These results suggest that gastrin secretion and enterochromaffin-like cell proliferation may be regulated by histamine via the H1 receptor during acid suppression.

Effects of ecabet sodium on experimentally induced reflux esophagitis.

We investigated the effects of ecabet sodium on experimentally induced reflux esophagitis in rats. Three groups of rats, i.e., a control group, esophagitis group, and an ecabet sodium group (25mg/kg given twice daily) were used. The number of animals which developed esophagitis, the extent of the lesions, and the esophagitis lesion index were assessed 3 weeks after the start of the experiment, and the lesions were evaluated histopathologically. All nine surviving rats in the esophagitis group developed esophagitis, and the esophagitis lesion index was 32.6 +/- 7.2 (mean +/- SE) per animal. Histopathologically, thickening of the epithelium, elongation of papillae of the lamina propria into the epithelium, and infiltration of the lamina propria by lymphocytes, eosinophils, plasmacytes, and neutrophils, were observed. Interruption of the lamina of the muscularis mucosae was also observed, and there was marked proliferation of collagen fibers in the submucosa and lamina propria. In the ecabet sodium group, esophagitis developed in five of the nine surviving animals (55.6%), but the esophagitis lesion index was 1.89 +/- 0.73 per animal, which was significantly lower than that in the esophagitis group. The histopathological changes in the rats which developed esophagitis were milder in the ecabet sodium group than in the esophagitis group. These results suggest that ecabet sodium could be useful for the prevention of reflux esophagitis.

Establishment of surgically induced chronic acid reflux esophagitis in rats.

BACKGROUND: The purpose of the study was to establish an animal model of chronic acid reflux esophagitis which could be used for further investigations of the pathophysiology of reflux esophagitis. METHODS: Esophagitis was produced by ligating the transitional region between the forestomach and the glandular portion with a 2-0 silk thread and covering the duodenum near the pylorus ring with a small piece of an 18Fr Nélaton catheter. The histologic features of the esophagus were examined, and the survival rate of these animals was investigated. Moreover, the effects of lansoprazole on this model was studied. RESULTS: The 3-week survival rate was 90%, and esophagitis was noted in all rats. Esophagitis was found 2 or 3 cm above the esophagogastric junction in most cases and at 4.0+/-2.3 sites per animal. Histopathologically, there were increased thickness of the esophageal epithelium, elongation of the lamina propria papillae, which extended upward into the epithelium, marked inflammatory cell infiltration, interruption of the lamina muscularis mucosae, and increase of collagen fibers in the lamina propria and submucosa. These signs were in accord with the histologic features of typical chronic esophagitis. No signs of esophagitis were observed, except in one animal, in the rats given 1 mg/kg/day of lansoprazole. CONCLUSIONS: This experimental rat model is considered useful as a model of chronic acid-type esophagitis for the evaluation of the pathophysiology of reflux esophagitis and the evaluation of drug efficacy.

The endogenous sulfated pentapeptide phytosulfokine-alpha stimulates tracheary element differentiation of isolated mesophyll cells of zinnia

Dispersed zinnia (Zinnia elegans) mesophyll cells cannot differentiate into tracheary elements (TEs) at low cell density conditions even if auxin and cytokinin are present in the medium, indicating the involvement of intercellular interactions during the initiation and/or subsequent progresses in TE differentiation. When zinnia cells were incubated at a low density (2.5 x 10(4) cells mL(-1)) in TE-inductive medium in the presence of various concentrations of phytosulfokine (PSK)-alpha, which was originally identified as an intercellular signal peptide involved in cell proliferation, TE differentiation was strongly stimulated in a dose-dependent fashion; more than 35% of the living cells differentiated into TEs by 5 d of culture in the presence of 10 nM PSK-alpha. Enzyme-linked immunosorbent assay and mass spectroscopy confirmed that cultured zinnia cells produce nanomolar levels of PSKs under inductive conditions. These results suggest that PSK-alpha is a factor responsible for TE differentiation of zinnia mesophyll cells.

A case of granulocyte-colony stimulating factor producing gallbladder cancer.

Ever since the identification of the colony-stimulating factor (CSF), granulocyte-CSF (G-CSF)-producing tumors have often been reported, and have been attracting attention, especially in pulmonary cancer. However, there have been only a small number of reports of G-CSF-producing tumors in cases of gastrointestinal cancer, and only four cases of G-CSF-producing gallbladder cancer have been reported so far. Recently, we encountered a 73-yr-old man with G-CSF-producing gallbladder cancer. The leukocyte count in the peripheral blood increased to the maximum of 75,200/mm3 during the course of observation, and mature neutrophils accounted for 97% (segmented forms: 89%, band forms: 8%). The serum G-CSF concentration was high (129 pg/ml). The leukocyte count became normalized postoperatively, and the serum G-CSF concentration also decreased (50 pg/ml). The tumor was diagnosed as undifferentiated adenocarcinoma of the pleomorphic type on the histopathologic examination. Numerous tumor cells were stained with the anti-G-CSF antibody. Detailed findings of the patient are presented here together with some discussion of the literature.

Effect of pirenzepine on gastric endocrine cell kinetics during lansoprazole administration.

We studied the effect of pirenzepine on gastric secretion kinetics in rats in a hypochlorhydric state induced by lansoprazole, a proton pump inhibitor. Pirenzepine was administered intramuscularly at a dosage of 20 mg/kg twice daily; and lansorprazole, subcutaneously at 50 mg/kg once daily, both every day for 4 weeks. After the 4-week treatment, serum gastrin and plasma somatostatin levels were determined by radioimmunoassay. In addition, gastrin cells, somatostatin cells, and enterochromaffin-like cells were immunostained and counted. Serum gastrin levels were elevated, and gastrin and enterochromaffin-like cell numbers increased in the group on lansoprazole alone, compared with these values in the control group (which received distilled water). In the group on the lansoprazole and pirenzepine combination, serum gastrin levels decreased, and gastrin and enterochromaffin-like cell numbers were significantly decreased, compared with the respective variables in the group on lansoprazole alone, while the number of somatostatin cells increased in the group on the combination. Plasma somatostatin levels did not vary significantly in any group. It was thus demonstrated that pirenzepine corrects the abnormal gastric secretion kinetics resulting from treatment with lansoprazole alone, such as hypergastrinemia and gastrin and enterochromaffin-like cell hyperplasia.

Effects of enprostil on gastric endocrine secretion during chronic administration of lansoprazole.

We investigated changes in the secretory kinetics of gastric endocrine cells related to the administration of lansoprazole, and the effects of enprostil on these altered kinetics. Male Wistar-derived 8-week-old rats were allotted to a control group, a lansoprazole administration group, an enprostil administration group, and a lansoprazole + enprostil administration group. Lansoprazole (30 mg/kg once a day for 4 weeks) and enprostil (10 micrograms/kg twice a day for 4 weeks) were administered into the gastric lumen with a gastric tube. At this time, blood was collected and immunohistological staining of gastric endocrine cells was conducted to investigate the secretory kinetics. Lansoprazole administration induced hypergastrinemia, increase of gastrin cells, and increase of enterochromaffin-like cells. Enprostil administration induced increase of somatostatin cells. The group administered lansoprazole + enprostil exhibited significant decreases in serum gastrin level, total gastrin cell count, and total enterochromaffin-like cell count, compared with the group administered lansoprazole alone. These findings suggest that enprostil may ameliorate the alteration in gastric endocrine secretion produced by the chronic administration of lansoprazole.