Acute airway obstruction in a patient with achalasia.

Megaesophagus resulting from achalasia is a rare but serious cause of acute airway obstruction. We treated achalasia in a 52-year-old woman with acute respiratory distress and stridor. Chest X-ray and endoscopy showed a marked dilatation of the cervical esophagus with a large amount of undigested food. Emergency suction of the food through a nasogastric tube led to decompression of the esophagus and the immediate relief of respiratory symptoms. These findings suggest a dysfunction of the upper esophageal sphincter as a possible mechanism. As this exceptional complication of achalasia is fatal, a wider appreciation is required.

Triple therapy with ecabet sodium, amoxicillin and lansoprazole for 2 weeks as the rescue regimen for H. pylori infection.

BACKGROUND/AIM: Ecabet sodium has an anti-H. pylori effect. We assessed the efficacy of ecabet sodium in the rescue therapy for the eradication of H. pylori. METHODS: A total of 74 patients with failed eradication of H. pylori after triple therapy with lansoprazole 30 mg bid, amoxicillin 750 mg bid and clarithromycin 200 mg bid were enrolled. They were randomly assigned to the three treatment groups as follows: LAC, lansoprazole 30 mg + amoxicillin 750 mg + clarithromycin 200 mg bid for 1 week; LAC2E, lansoprazole 30 mg bid + amoxicillin 750 mg bid + clarithromycin 200 mg bid + ecabet sodium 2 g bid for 1 week; and LA2E, lansoprazole 30 mg bid + amoxicillin 750 mg bid + ecabet sodium 2 g bid for 2 weeks. Eradication of H. pylori was assessed by the 13C-urea breath test after treatment. RESULTS: Eradication rates in intention-to-treat and per-protocol analyses were 20.0% (95% CI: 6.8-40.7) and 20.0% (6.8-40.7) with LAC, respectively, and 16.0% (4.5-36.1) and 17.4% (5.0-38.8) with LAC2E. In contrast, respective rates with LA2E were 75% (53.3-90.2) and 85.7% (63.7-97.0), which were significantly higher than those with LAC (p<0.001 for both ITT and PP) and LAC2E (p<0.001 for both ITT and PP). CONCLUSION: Triple therapy with ecabet sodium, lansoprazole and amoxicillin for 2 weeks was effective as the rescue therapy after failure of the standard clarithromycin-based regimen.

Gastroesophageal reflux-associated chronic cough in an adolescent and the diagnostic implications: a case report.

A 15-year-old girl was referred with a 2-year history of perennial non-productive cough, which had been preceded by Mycoplasma pneumoniae pneumonia and subsequent asthma. Symptoms were only partially responsive to anti-asthma treatment including an inhaled corticosteroid and a leukotriene receptor antagonist. The patient's BMI was 27.8; she had gained over 10 kg in the previous two years. Typical symptoms of gastroesophageal reflux disease were not evident except for belch. Coughing worsened on eating and rising from bed. Although esophagography failed to disclose reflux esophagitis, esophageal pH monitoring revealed significant acid reflux. Asthma was considered well controlled. Treatment with the proton-pump inhibitor rabeprazole resulted in disappearance of cough. Frequency Scale for the Symptoms of Gastroesophageal reflux disease (FSSG) score, a questionnaire evaluating the symptoms of gastroesophageal reflux disease, was initially high but normalized after treatment. Capsaicin cough sensitivity also diminished with treatment.Chronic cough due to gastroesophageal reflux disease has been considered rare in adolescents, but this condition might be increasing in line with the recent trend in adults. Clinical features of gastroesophageal reflux disease-associated cough typical for adult patients and a specific questionnaire for evaluating gastroesophageal reflux disease validated in adults may also be useful diagnostic clues in adolescents.

[Bernstein test].

It is almost 50 years ago, when L.M. Bernstein and L.A. Baker wrote a paper on esophageal pain created by intra-luminal acid infusion. Their main purpose was to distinguish the chest pain due to esophagitis from cardiac pain. As former experiments had failed to show the direct roll of acid on chest pain, esophageal pain observed in esophagitis patients had been thought to be the result of esophageal wall extension. Bernstein showed that acid itself could cause chest pains in not only endoscopically positive esophagitis patients but also in pseudoesophagitis patients as Bernstein called. The simple and effective method he developed during his trial was called as Bernstein test with respect. Nowadays, more than half of the patients who suffer GERD symptoms are diagnosed as non-erosive reflux disease (NERD). Effective management of NERD is one of the most anticipated fields in the clinical upper GI treatment, and for that purpose, selecting the group of patients who are sensitive to acid is especially important. In this paper, I will describe about this Bernstein's "old but up-to-date" original paper in detail and consider its present-day interpretation. It has become obvious recently that acid is not the only cause of the esophageal pain of NERD patients. But, the importance of acid in NERD is still not small. Both as the theoretical basis of acid induced esophageal pain and as clinical method of measuring acid sensitivity in esophagus, Bernstein test should be recalled frequently and improved further.

Expression of the REG IV gene in ulcerative colitis.

The regenerating gene (REG) IV gene was isolated from a cDNA library of ulcerative colitis (UC) tissues. However, its role in the pathophysiology of UC and subsequent development of colitic cancer is still unclear. We investigated the expression of the REG IV gene in UC and colitic cancer tissues and examined whether cytokines or growth factors are responsible for REG IV gene expression and whether REG IV gene induction affects cell growth and apoptosis in colon cancer cells. The expressions of REG IV and growth factor genes in UC tissues were analyzed by real time reverse transcription-polymerase chain reaction. The effects of cytokines and growth factors on REG IV gene expression were examined in SW403 cells by Northern blot analysis. The effects of REG IV gene induction on cell growth and H(2)O(2)-induced apoptosis were examined in DLD-1 cells by MTT and TUNEL assays, respectively. REG IV mRNA was strongly expressed in inflamed epithelium and in dysplasias and cancerous lesions in UC tissues. The level of REG IV mRNA expression was correlated with that of basic fibroblast growth factor (bFGF) as well as hepatocyte growth factor (HGF) mRNA expression in UC tissues. The REG IV gene expression in SW403 colon cancer cells was enhanced by stimulation with transforming growth factor-alpha, epidermal growth factor, bFGF, and HGF. REG IV gene induction promoted cell growth and conferred resistance to H(2)O(2)-induced apoptosis in DLD-1 cells. The REG IV gene is inducible by growth factors and may function as a growth promoting and/or an antiapoptotic factor in the pathophysiology of UC.

Involvement of cyclooxygenase-2 in gastric mucosal hypertrophy in gastrin transgenic mice.

Gastrin promotes gastric mucosal growth, and hypergastrinemia induces gastric mucosal hypertrophy. Recently, it has been reported that gastrin induces cyclooxygenase-2 (COX-2) in human gastric and colorectal cancer cell lines. However, whether COX-2 is involved in gastrin-induced gastric mucosal growth in vivo is unknown. We investigated the role of COX-2 in gastrin-induced gastric mucosal hypertrophy using gastrin transgenic mice. Hypergastrinemic mice [mice with mutated gastrin under the control of the beta-actin promoter (ACT-GAS mice)] received the COX-2 inhibitor celecoxib (0, 200, or 500 mg/kg of diet) from 5 wk of age and were killed at 16 or 24 wk. Some ACT-GAS mice received celecoxib from 16 wk and were killed at 24 wk. Eighty-week-old ACT-GAS mice without celecoxib treatment were also examined. The thickness of the gastric mucosa, cell populations, COX-2 expression, and PGE(2) levels were evaluated. All ACT-GAS mice showed gastric mucosal hypertrophy, and four of six 80-wk-old ACT-GAS mice developed gastric cancer. COX-2 was expressed in interstitial cells of the hypertrophic gastric mucosa and gastric cancers. Moreover, PGE(2) levels in the gastric mucosa of ACT-GAS mice were significantly higher than those of normal mice. With treatment with celecoxib, PGE(2) levels, the gastric mucosal thickness, and the number of total gastric cells per gastric gland of ACT-GAS mice were significantly decreased. The decrease in gastric mucosal thickness was caused by a reduction of foveolar hyperplasia. The thickness of glandules and the number of Ki67-positive cells were not significantly changed. In conclusion, COX-2 contributes to gastrin-induced mucosal hypertrophy of the stomach.

STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells.

Signal transduction and activator of transcription 3(STAT3) signaling is constitutively activated in various tumors, and is involved in cell survival and proliferation during oncogenesis. There are few reports, however, on the role of STAT3 signaling in gastric cancer. The aim of the present study was to clarify the role of STAT3 signaling in apoptosis and cellular proliferation in gastric cancer. Here we reported that STAT3 was constitutively activated in various human gastric cancer cells and its inhibition by ectopic dominant-negative STAT3 or Janus kinase inhibitor, tyrphostin AG490, induced apoptosis. Furthermore, STAT3 inhibition markedly decreased survivin expression, and forced expression of survivin rescued AGS cells from apoptosis induced by STAT3 inhibition. Although some reports demonstrated that the PI3K/Akt pathway regulates survivin expression, inhibition of the PI3K/Akt pathway did not affect survivin expression in AGS and MKN1 cells. Finally, activated form of STAT3, Tyr-705 phospho-stat3, was found in the nucleus of cancer cells in 11 of 40 (27.5%) human gastric cancer specimens. These findings suggest that constitutively activated STAT3 signaling supports gastric cancer cell survival in association with survivin expression.2004

Resection for hepatocellular carcinoma with duodenal invasion: report of a case.

A 73-year-old man was admitted to our hospital on emergency for severe anemia. Upper gastrointestinal endoscopic study revealed a hemorrhagic ulcer in the duodenal bulb. He underwent endoscopic hemostasis. Abdominal ultrasonography and computed tomography showed a huge mass in segment 4 of the liver, growing into the extrahepatic space with direct invasion to the duodenal bulb. Extended left lobectomy and partial gastroduodenectomy was performed, because the endoscopic management of hemostasis was incomplete. He was discharged on the 30th postoperative day. Histopathologically, the tumor cells were moderately differentiated hepatocellular carcinoma with direct invasion to the duodenal mucosa. This report demonstrated the first case with a hepatocellular carcinoma with duodenal invasion, for which hepatic resection was performed successfully.

Differentiation-inducing factor-1 (DIF-1) inhibits STAT3 activity involved in gastric cancer cell proliferation via MEK-ERK-dependent pathway.

Differentiation-inducing factor-1 (DIF-1) is a chlorinated hexaphenone isolated from Dictyostelium. DIF-1 exhibits antitumor activity in several types of mammalian tumor cells, although the underlying mechanisms remain unknown. On the other hand, recent studies indicate that constitutively activated STAT3 acts as an oncogene and could be a target for antitumor drug. In the present study, we examined the effects of DIF-1 on proliferation of gastric cancer cell lines as well as on its signal transduction pathways, focusing mainly on STAT proteins. DIF-1 inhibited proliferation of gastric cancer cells. Western blot analysis and electrophoretic mobility shift assay showed that DIF-1 inhibited STAT3 activity in an MEK-ERK-dependent manner in gastric cancer cell lines, AGS and MKN28. Moreover, blockade of STAT3 activity by ectopic expression of dominant-negative STAT3 or the Janus kinase inhibitor, tyrphostin AG490, inhibited cell growth of AGS cells. These results suggest that STAT3 activity plays an important role for cell growth in AGS cells, and raises the possibility that inhibition of STAT3 activity is one of the mechanisms responsible for the antitumor effect of DIF-1 in these cells.

Prohormone convertase furin has a role in gastric cancer cell proliferation with parathyroid hormone-related peptide in a reciprocal manner.

We investigated the expression of parathyroid hormone-related peptide (PTHrP) and the relationship between PTHrP and its endoprotease furin in gastric cancer. PTHrP was colocalized with furin in 75% of gastric cancer tissues (six of eight) from patients with high serum PTHrP levels. PTHrP mRNA expression was confirmed in 67% of gastric cancer cell lines (four of six), whereas furin mRNA was detected in all six gastric cancer cell lines. In a cultured gastric cancer cell line, MKN28, mature PTHrP protein expression was markedly increased by transfection of furin cDNA. Furin cDNA-transfected MKN28 cells grew faster than did the mock controls. Moreover, furin mRNA expression in cultured gastric cancer cells was enhanced when PTHrP was added to the culture medium. These results suggest a link between PTHrP and furin in the regulation of gastric cancer cell growth. Furin might be involved not only in the production of the mature form of PTHrP, but also in promoting growth in gastric cancer cells.

Gastrin stimulates the growth of gastric pit cell precursors by inducing its own receptors.

Gastrin/CCK-B receptors (CCKB-Rs) are present on parietal and enterochromaffin-like cells in the gastric mucosa but not on pit cells in the proliferative zone. Because serum gastrin levels are well correlated with the growth of the gastric pit, we examined whether pit precursor cells express CCKB-Rs using hypergastrinemic transgenic mice and a mouse pit precursor cell line, GSM06. In situ hybridization indicated that CCKB-R mRNA was limited to the lower one-third of the mucosa in control mice, whereas it was faintly distributed along the mid- to low glandular region in the hypergastrinemic transgenic mouse mucosa. CCKB-R-positive midglandular cells appear to have a pit cell lineage; therefore, GSM06 cells were used for an [(125)I]gastrin binding study. [(125)I]gastrin bound to the membrane fraction of the GSM06 cells when precultured with gastrin. Gastrin dose dependently induced CCKB-R expression in GSM06 cells and stimulated their growth. Thus these findings suggest that gastrin directly stimulates the growth of the pit cell lineage by inducing its own receptor in pit cell precursors.