Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: The first evidence.

OBJECTIVES: Cytokeratins (CKs) are mainly expressed in epithelial carcinomas and are valuable for making diagnoses and identifying metastatic status. Changes in the expression of individual CKs in certain carcinoma may be relevant to establishing a prognosis. However, the prognostic significance of CKs in head and neck squamous cell carcinoma (HNSCC) remains elusive. Herein, we investigated the diverse and unique expression patterns of Cytokeratin 13 (CK13) and Cytokeratin 17 (CK17) and assessed the role of CK17 as a predictor for HNSCC metastasis and prognosis. METHODS: CK13 and CK17 expressions were evaluated using immunohistochemical tissue microarray (TMA) analysis with 106 patients of HNSCC. To clarify the characterisation of CK17 expression with respect to its ability in predicting metastatic disease, an in vitro study of cells migration/invasion assays was conducted. Furthermore, the correlation of CK17 expression to clinicopathologic variables and prognosis was analyzed using a serial statistical method. RESULTS: CK13 was predominately expressed in non-cancerous tissues and was lost in HNSCC. Decreasing expression of CK17 correlated with cancerous cell migration and invasion (P < .0001) in an in vitro study. CK17 expression was lower in the N1 and N2 nodal metastases category compared to the N0 stage. Moreover, Kaplan-Meier survival analyses showed that a lower CK17 expression was associated with a poorer survival connotation in HNSCC patients (P < .05) with 10-year follow-up. CONCLUSION: Our findings provide the first evidence that CK17 under-expression might be a potential predictor of nodal metastasis and adverse prognosis.

Decrease of FGF receptor (FGFR) and interstitial fibrosis in the kidney of streptozotocin-induced diabetic rats.

Fibrosis is the final disorder of end-stage renal disease. Activation of fibroblast growth factor (FGF) 23-klotho axis could suppress renal fibrosis in mice. Also, a marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats). However, relation of FGF in renal fibrosis remained unclear. This study was aimed to screen the effect of hyperglycemia on FGF receptor (FGFR) and fibrosis in kidney of rats with diabetic nephropathy and investigate this potential mechanism in cultured Madin-Darby Canine Kidney (MDCK) epithelial cells. STZ rats were used to treat with insulin or phloridzin at the dose sufficient to correct hyperglycemia for understanding the changes of renal dysfunction. The cultured MDCK cells were also used to treat with high glucose, hydrogen peroxide, or tiron in addition to transfection of siRNA to silence the klotho. Both insulin and phloridzin reversed fibrosis and FGFR expressions in kidney of STZ rats. It was confirmed in high glucose-exposed MDCK cells. However, klotho failed to modify the level of FGFR in MDCK cells. Meanwhile, FGFR was restored by tiron in MDCK cells and in diabetic rats without changing blood glucose. In conclusion, interstitial fibrosis and decreased FGFR expression are observed in the kidney of diabetic rats. This change is reversed by tiron without the correction of blood glucose. Also, klotho has no effect on expression of FGFR. Thus, decrease of oxidative stress is useful for the recovery of FGFR expression and improvement of renal fibrosis in type-1 like diabetic rats.

Rosiglitazone is effective to improve renal damage in type-1-like diabetic rats.

A marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats) showing diabetic nephropathy. It has been documented that klotho is the target gene of PPARγ. However, the effect of PPARγ agonist on klotho expression in kidney of STZ rats remains obscure. Thus, we used rosiglitazone (TZD) as PPARγ agonist to investigate the effect on renal dysfunction in STZ rats. Treatment of TZD reversed the lower levels of PPARγ, klotho, and FGFR1 expressions in kidneys of STZ rats without the correction of hyperglycemia. Also, renal functions and structural defeats were improved by TZD treatment. Taken together, oral administration of TZD may improve STZ-induced diabetic nephropathy due to restoration of the expression of klotho axis through an increase in PPARγ expression without changing blood glucose in rats.

Mediation of AMP kinase in the increase of glucose uptake in L6 cells induced by activation of imidazoline I-2 receptors.

Recent work using radioactive tracer indicates that activation of imidazoline I2 receptor (I2R) by guanidinium derivatives may increase the glucose uptake in the skeletal muscle. However, the effect of I2R activation on nonradioactive glucose uptake is still unknown. The ability of glucose uptake in cultured L6 cells is then determined using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) as a fluorescence indicator. The changes in 5'-AMP-activated protein kinase (AMPK) expression were also identified by Western blot analysis. In the present study, 2-(2-benzofuranyl)-2-imidazoline (2-BFI) is used to stimulate I2R while 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) is applied to activate AMPK directly. Both compounds can increase 2-NBDG in L6 cells in a concentration-dependent manner. Meanwhile, compound C at concentrations sufficient to inhibit AMPK blocked this increase of glucose uptake by 2-BFI or AICAR. However, only 2-BFI-induced glucose uptake action was dose-dependently blocked by BU224, a specific I2R antagonist, in L6 cells. Moreover, AMPK phosphorylation was markedly increased by 2-BFI or AICAR in L6 cells. Similarly, only the effect of 2-BFI was attenuated by BU224 in L6 cells. Thus, we suggest that AMPK is mediated in I2R activation for increase of glucose uptake in the skeletal muscle cell and I2R will be a new target for diabetic therapy.

Stimulatory effect of allantoin on imidazoline I1 receptors in animal and cell line.

Allantoin is known as the agonist of imidazoline receptor, especially the I2 subtype. Effect of allantoin on imidazoline I1 receptor (I1R) relating to reduction of blood pressure and its merit in steatosis are still obscure. Also, farnesoid X receptor (FXR) plays an important role in lipid homeostasis related to I1R activation. Thus, we administered allantoin into high fat diet (HFD)-fed mice showing hypertriglyceridemia and hypercholesterolemia. Allantoin significantly improved hyperlipidemia in HFD mice after 4 weeks of administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I1R activation, attenuated the action of allantoin. In addition, in cultured HepG2 cells, allantoin increased the expression of farnesoid X receptor (FXR). The allantoin-induced FXR expression was blocked by efaroxan. Similar changes were observed in the expressions of FXR-targeted genes. Otherwise, allantoin also lowered systolic blood pressure (SBP) in HFD mice that can be blocked by efaroxan. Taken together, allantoin has an ability to activate I1R for improvement of metabolic disorders.

Ovarian carcinomatosis presenting as bilateral inguinal hernia: a brief report.

The differential diagnosis for what may seem an inguinal hernia may be complex, as lateral pain may be of many types of origin. We report the case of a 48-year-old female patient who presented with a history of painful, progressively protruding soft bulging masses over the bilateral inguinal area and a 20-year history of head cancer and hepatitis B virus. Pathological analysis, gynecological ultrasound and abdominal computed tomography scan were required to make final determination. Final diagnosis was Stage IV ovarian carcinomatosis, which responded to chemotherapy. Initial diagnosis of inguinal hernia should not rule out other potential diagnoses, particularly in complex cases with other risk factors.

Factors affecting clinical and therapeutic outcomes of patients with juvenile rheumatoid arthritis.

OBJECTIVE: To investigate clinical features, medications, and therapeutic responses of juvenile rheumatoid arthritis (JRA) among Taiwanese children. METHODS: A retrospective chart review was conducted among all children newly diagnosed with JRA at the National Taiwan University Hospital between 1996 and 2001. RESULTS: Forty boys and 30 girls were enrolled in the study. The mean follow-up was 45 months. Oligoarticular onset was the most common type. A bimodal distribution of age at onset was observed, with peaks at 4 and 10 years. All patients received non-steroidal anti-inflammatory drugs (NSAIDs); 27 (39%) received corticosteroids, and 44 (63%) had second-line drugs during the first course of treatment. Forty-three patients (69%) achieved clinical remission after a mean of 14.8 months of medication, and 19 (31%) were drug-dependent. The major factors related to the failure of first remission were human leukocyte antigen B27 (HLA-B27), high C-reactive protein (CRP) level, and thrombocytosis at diagnosis. CONCLUSION: There are different phenotypic features among Taiwanese children with JRA. Factors related to the failure of first remission were HLA-B27, high CRP level, and thrombocytosis at diagnosis.

Wound healing effects of porcine placental extracts on rats with thermal injury.

BACKGROUND: Placental extracts have been used as Chinese folk medicines to accelerate wound healing. However, the molecular mechanism of placental extracts on wound healing has not been identified. It is known that fibroblast growth factors (FGF) and transforming growth factors (TGF) are two key factors involved in wound healing. OBJECTIVES: To determine the molecular mechanism of placental extracts on wound healing. METHODS: The protein levels of both growth factors in rat skins with thermal injury were therefore studied to explore the molecular mechanism of placental extracts on wound healing. As cell proliferation is essential for wound healing, effects of placental extracts on fibroblast proliferation were also determined. RESULTS: As compared with the controls, the S phase of fibroblasts was significantly increased by 1.5-, 1.7- and 4.7-fold for 1, 10 and 30 mg mL(-1) of placental extracts, respectively. The increase of the S phase was not due to the minute amount of sex hormones in the placental extracts as the addition of equivalent amounts of hormones showed no increase of the S phase. In addition, a 2.5-fold increase of TGF-beta1 in wound skin biopsy was noticed with 30 mg mL(-1) of porcine placental extracts. The FGF levels in the wound skin receiving 30 mg mL(-1) of porcine placental extracts were also significantly increased compared with the controls. CONCLUSIONS: These ex vivo data support the observation that the application of 30 mg mL(-1) of placental extracts reduced the wound healing time by about 50%. To the best of our knowledge, this is the first report to explore the molecular mechanisms of porcine placental extracts on wound healing. These results may provide the insight into the potential use of porcine placental extracts as an alternative medicine for accelerating wound healing.

Prognostic value of nm23 expression in stage IB1 cervical carcinoma.

BACKGROUND: The purpose of this retrospective study was to evaluate the patterns of nm23 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare nm23 expression with clinicopathological findings and to assess its prognostic value. METHODS: Twenty-seven patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of nm23 was studied immunohistochemically, followed by amplification and direct sequencing of exons 4 and 5 of the nm23 gene. RESULTS: Overexpression of nm23 was detected in 18.5% of the tumors and low expression was seen in 33.3%, while negative expression was found in 48.1% of the tumors. Deep cervical stromal invasion (> or =1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when nm23 overexpression was observed (p = 0.0063). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessel, squamous cell carcinoma (> or =2 ng/ml) and nm23 overexpression had a significantly lower recurrence-free survival rate of the patients. None of the above factors was significant according to multivariate analysis. There were no mutations in exons 4 and 5 of the nm23 gene in stage IB1 squamous cell carcinoma of the uterine cervix. CONCLUSIONS: This study suggests that expression of nm23 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.

Choroidal infarction, anterior ischemic optic neuropathy, and central retinal artery occlusion from polyarteritis nodosa.

PURPOSE: Ocular ischemia from polyarteritis nodosa (PAN) is rare. The authors present a case of multifocal ocular infarction from PAN. METHODS AND RESULTS: A 70-year-old woman developed hand and foot numbness followed by intermittent blurred vision and binocular horizontal diplopia. Two weeks later, she suddenly lost vision in the right eye from a central retinal artery occlusion and then developed a left anterior ischemic optic neuropathy and bilateral triangular choroidal abnormalities consistent with infarction. Her erythrocyte sedimentation rate and C-reactive protein were elevated. Although giant cell arteritis was suspected, a multiple mononeuropathy was demonstrated by electromyogram and nerve conduction velocity studies. Biopsy specimens from her sural nerve and biceps muscle showed a necrotizing vasculitis with fibrinoid necrosis, consistent with PAN. CONCLUSIONS: Polyarteritis nodosa can produce ischemia of a variety of ocular structures, including the retina, choroid, and optic nerve. In our patient, all three structures were affected. To our knowledge, this is the first reported case of the triangular sign of Amalric in PAN.

Endoscopic comparison of the gastroduodenal safety and the effects on arachidonic acid products between meloxicam and piroxicam in the treatment of osteoarthritis.

Our objective was to evaluate the efficacy, the gastroduodenal safety, and the effects on arachidonic acid products of meloxicam, a new acidic enolic non-steroidal anti-inflammatory drug which preferentially inhibits cyclo-oxygenase-2 over cyclo-oxygenase-1, versus piroxicam in patients with osteoarthritis of the knee. Meloxicam 7.5 mg or piroxicam 20 mg daily was administered for 4 weeks in this double-blind parallel-groups randomised study. The efficacy for pain relief of the two tested medications was assessed by means of visual analogue scale and other clinical parameters. Pre- and post-treatment endoscopies were performed, and the findings were scored and recorded. The gastric fluid was aspirated at each time and prostaglandin E2, thromboxane B2 and leukotriene B4 were determined by ELISA. There was no significant difference between the groups regarding the primary efficacy. Changes in endoscopic findings by means of Lanza score showed statistically significant differences between the two treatment groups in favour of meloxicam at all sites--gastric, duodenal and total. Within-group comparisons showed a statistically significant difference (worsening) in gastric and total score with piroxicam, but no significant difference with meloxicam. The frequency of clinically relevant cases (total score >2) also showed a statistically significant worsening in the piroxicam group. The better GI tolerability of meloxicam was also suggested by fewer adverse GI events and no withdrawals due to adverse events compared with piroxicam. The pre-/post-study gastric juice concentration of PGE2, TXB2, and LTB4 in the meloxicam group was 135.2 +/- 85.8/71.2 +/- 32.2, 116.3 +/- 81.7/99.4 +/- 107.5 and 388 +/- 321/223 +/- 98 pg/ml respectively. The pre-/post-study gastric juice concentration of PGE2, TXB2 and LTB4 in the piroxicam group was 105.7 +/- 43.1/68.2 +/- 34.9, 94.0 +/- 50.9/105.9 +/- 121.1 and 625 +/- 1574/828 +/- 1464 pg/ml, respectively. Both meloxicam and piroxicam significantly inhibited gastric PGE2 levels after 4 weeks' treatment; however, there was no difference between these two groups. Neither of these medications had an effect on TXB2. Only meloxicam inhibited LTB4 concentration significantly, and the between-groups difference was significant. Meloxicam 7.5 mg once daily had better gastrointestinal tolerability and an efficacy comparable to that of piroxicam 20 mg over 4 weeks in patients with osteoarthritis of the knee.

The sympathetic nervous system promotes carbon tetrachloride-induced liver cirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of regenerating hepatocytes.

Norepinephrine is considered to possess potent anti-apoptotic action in regenerating hepatocytes. To clarify the role of the sympathetic nervous system in apoptosis that occurs in chronic liver damage and following the promotion of liver cirrhosis, we studied a carbon tetrachloride (CCl4)-induced liver injury model, using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and chemically sympathectomized WKY. At 24 h after CCl4 administration. acute damage, characterized by vacuolated hepatocytes in the centrilobular zone, was greater in SHR than in WKY. This vacuolated change in WKY hepatocytes was significantly reduced by chemical sympathectomy with 6-hydroxydopamine (6-OHDA). After 48 h, the acute damage was dramatically improved in each animal, without significant differences between the three groups. In chronic damage after weekly repetition of CCl4 treatment for 4 weeks, fibrosis was evident in SHR, while in the other groups there was only scant fibrosis in the centrilobular zone. After 8 weeks' repetition of CCl4, liver cirrhosis was seen only in SHR. The incidence of apoptotic cells in areas of both acute and chronic damage in WKY, detected by terminal deoxynucleotidyl transferase-dUTP nick end labeling, was significantly increased in comparison with that in SHR, and was further increased by 6-OHDA pretreatment. In contrast, there was significantly greater enhancement of the growth of hepatocytes in SHR than in WKY in both acute and chronic damage. Moreover. hepatocyte growth kinetics in WKY was significantly inhibited after sympathectomy in acute injury, as evidenced by immunohistochemistry for proliferating cell nuclear antigen (PCNA). In vitro, the amount of hepatocellular apoptosis induced by transforming growth factor-beta1 was significantly decreased by incubation with norepinephrine. These findings suggest that the anti-apoptotic effect of the sympathetic nervous system increases cell growth kinetics and promotes liver cirrhosis in this animal model.

Role of hypothalamic neuropeptide Y (NPY) in the change of feeding behavior induced by repeated treatment of amphetamine.

Neuropeptide Y (NPY), an orexigenic peptide, is involved in the control of food intake. Repeated administration of amphetamine (AMPH), an anorectic agent, results in an anorectic effect on day 1 and a tolerant anorectic effect on the followings. In an attempt to know the role of hypothalamic NPY in these effects of AMPH, contents of hypothalamic NPY were determined by radioimmunoassay at first. In AMPH-treated groups, the contents of hypothalamic NPY decreased rapidly on day 1 but restored gradually to the normal level on the following days as observed in repeated AMPH. An involvement of hypothalamic NPY in the feeding change of repeated AMPH can thus be considered. Moreover, daily injection of NPY antisense oligonucleotide into brain (10 microg/10 microl/day, i.c.v.) to inhibit the gene expression of hypothalamic NPY were performed at 1 hour before daily 2 mg/kg AMPH. The reversion of food intake from the anorectic level to the normal level (tolerant anorexia) was abolished by this antisense pretreatment. It is suggested that hypothalamic NPY may play a role in the change of feeding behavior induced by repeated AMPH administration.

Vaccination against gonadotropin-releasing hormone (GnRH) using toxin receptor-binding domain-conjugated GnRH repeats.

A method for the preparation of an immunogen containing multiple copies of a self-peptide in linear alignment was designed in order to overcome the difficulty of inducing an immune response to poorly immunogenic peptide antigens. DNA fragments encoding multiple repeats of the self-peptide were generated by a new technique, termed template-repeated polymerase chain reaction (TR-PCR), which could be subcloned into an expression vector for production of peptide repeats as an immunogen. This approach was tested by constructing fusion proteins containing the receptor-binding domain of Pseudomonas exotoxin A and multiple copies of the 10-residue sequence of the peptide hormone gonadotropin-releasing hormone (GnRH). Immunization of female rabbits with the immunogen that contained the exotoxin receptor-binding domain and 12 copies of GnRH (PEIa-GnRH12) resulted in the generation of high-titer antibodies specific for GnRH. Although at equal molar basis of the GnRH moiety, the immunogen that contained single copy of GnRH (PEIa-GnRH1) induced low-titer anti-GnRH antibodies. These observations suggest that the presence of multiple peptide repeats is a key factor in eliciting an immune response. In addition, anti-GnRH antibodies effectively neutralized GnRH activity in vivo, as demonstrated by the degeneration of the ovaries in the injected rabbits. Because anti-GnRH antibody could be functionally analogous to GnRH antagonist, which has been used to treat patients with ovarian cancer, vaccination of PEIa-GnRH12 presents a potential therapeutic application for the treatment of GnRH-sensitive ovarian cancer.

Prognostic value of p53 expression in stage IB1 cervical carcinoma.

The purpose of this retrospective study was to evaluate the patterns of p53 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare p53 expression with clinicopathological findings, and to assess its prognostic value. 27 patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of p53 was studied immunohistochemically. Overexpression of p53 was detected in 33.3% of the tumors, low expression was seen in 11.1%, and negative expression was found in 55.6%. Deep cervical stromal invasion (> or = 1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when p53 overexpression was observed (p = 0.0315). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessels, squamous cell carcinoma antigen (> or = 2 ng/ml), and p53 overexpression had a significantly lower recurrence-free survival rate. None of these above factors obtained significance in the multivariate analysis. This study suggests that expression of p53 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.

Development of DNA delivery system using Pseudomonas exotoxin A and a DNA binding region of human DNA topoisomerase I.

Gene therapy is defined as the delivery of a functional gene for expression in somatic tissues with the intent to cure a disease. Thus, highly efficient gene transfer is essential for gene therapy. Receptor-mediated gene delivery can offer high efficiency in gene transfer, but several technical difficulties need to be solved. In this study, we first examined the DNA binding regions of the human DNA topoisomerase I (Topo I), using agarose gel mobility shift assay, in order to identify sites of noncovalent binding of human DNA Topo I to plasmid DNA. We identified four DNA binding regions in human DNA Topo I. They resided in aa 51-200, 271-375, 422-596, and 651-696 of the human DNA Topo I. We then used one of the four regions as a DNA binding protein fragment in the construction of a DNA delivery vehicle. Based on the known functional property of each Pseudomonas exotoxin A (PE) domain and human DNA Topo I, we fused the receptor binding and membrane translocation domains of PE with a highly positively charged DNA binding region of the N-terminal 198 amino acid residues of human DNA Topo I. The resulting recombinant protein was examined for DNA binding in vitro and transfer efficiency in cultured cells. The results show that this DNA delivery protein is a general DNA delivery vehicle without DNA sequence, topology, and cell-type specificity. The DNA delivery protein could be used to target genes of interest into cells for genetic and biochemical studies. Therefore, this technique can potentially be applied to cancer gene therapy.

Bcl-2 accelerates retinoic acid-induced growth arrest and recovery in human gastric cancer cells.

The role of Bcl-2 as an anti-apoptotic protein has been well documented. In the present work, we present evidence that Bcl-2 may also be involved in cell growth regulation. SC-M1 is an unique cell line which responds to retinoic acid (RA) treatment with reversible growth arrest [Shyu, Jiang, Huang, Chang, Wu, Roffler and Yeh (1995) Eur. J. Cancer 31, 237-243]. In this study, when treated with RA, SC-M1/Bcl2 cells, which were generated by transfecting SC-M1 cells with bcl-2 DNA, were growth-arrested two days earlier than SC-M1/neo cells, which were generated by transfecting SC-M1 cells with vector DNA. This indicates that Bcl-2 accelerates RA-induced growth arrest. In addition to the accelerated growth arrest, RA-treated SC-M1/Bcl2 cells also recovered from growth arrest two days faster than SC-M1/neo cells after the removal of RA. Previously, we had identified the cyclin-dependent kinase inhibitor p21((WAF1/CIP1)) (p21) as a mediator of RA-induced growth arrest [Tsao, Li, Kuo, Liu and Chen (1996) Biochem. J. 317, 707-711]. In a search for the mechanism by which Bcl-2 affects growth regulation, we found that p21 gene expression was more prominent in SC-M1/Bcl2 cells than in SC-M1/neo cells in the presence of RA, but when RA was removed, p21 gene expression levels in SC-M1/Bcl2 cells were also reduced earlier than in SC-M1/neo cells. The present report is the first to show that Bcl-2 accelerates not only growth arrest but also recovery from growth arrest. Moreover, the close correlation between the effect of Bcl-2 on both RA-induced growth arrest and RA-induced p21 gene expression suggests the possibility that Bcl-2 affects cell growth through the mechanism of p21.

Tumor seeding of the jejunostomy site after transhiatal esophagectomy for esophageal carcinoma.

A 65-year-old male patient with squamous cell carcinoma of the esophagus had a transhiatal esophagectomy after a prophylactic tube jejunostomy. The tube was removed 3 weeks after surgery. Ten months later, a painless 2-cm abdominal mass was noted at the previous jejunostomy site. Subsequent segmental resection of the jejunum disclosed metastatic squamous cell carcinoma of the esophagus. It is possible that tumor seeding may develop at the jejunostomy site after transhiatal esophagectomy for esophageal carcinoma.

A multicenter study on eradication of Helicobacter pylori infection in patients with duodenal ulcer by lansoprazole-antibiotics combined therapy.

The aim of this prospective randomized multicenter study was to find out if there is one or several promising regimens containing lansoprazole with various combinations of antibiotics which have a high eradication rate of Helicobacter pylori, few side-effects, good patient compliance, and relative low cost if possible. Two hundred and ninety-seven patients with H. pylori positive duodenal ulcer were enrolled and randomly allocated into one of the five treatment groups: 1) group A: received lansoprazole 30 mg once daily for 2 weeks plus amoxicillin (AM) 500 mg and metronidazole (MZ) 500 mg twice daily for one week in the first week; 2) group B: the AM in group A was replaced by clarithromycin (CM) 250 mg; 3) group C: the MZ in group A was replaced by CM 250 mg; 4) group D: the AM and CM in group C was used for 2 wk; 5) group E: the CM in group D was doubled to 500 mg twice daily. All patients received endoscopies pre- and 4-6 weeks post termination of treatment. H. pylori was detected by culture, histology and rapid urease test (CLO test). 13C-urea breath test was performed if the patients refused the second endoscopy. The E-test was adopted to evaluate the MZ and CM resistance of H. pylori. Totally, 253 patients completed the study. The eradication rate of groups A, B, C, D and E were 75%, 80%, 78%, 92%, and 96%, respectively. The eradication rate of group E was significantly higher than that of groups A, B, or C. There were no significant differences of eradication rates between the groups D and E. Sixty-seven cases (28.8%) were MZ-resistant. The difference of eradication rates between MZ-S and MZ-R patients was significant in group A (85.3% vs. 42.9%) and in the combination of groups A and B (83.8% vs. 59.4%). Good compliance (defined as taking > 90% of medications) was seen in more than 90% of cases in each group. Triple therapy containing lansoprazole 30 mg once daily, AM 500 mg and CM 250 mg twice daily for two weeks is a promising regimen which reaches a high eradication rate, avoids MZ resistance, and has very good patient compliance at an acceptable cost.