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Short-course versus long-course neoadjuvant chemoradiotherapy in patients with rectal cancer: preliminary results of a randomized controlled trial

  • Aghili, Mahdi;Khalili, Nastaran;Khalili, Neda;Babaei, Mohammad;Farhan, Farshid;Haddad, Peiman;Salarvand, Samaneh;Keshvari, Amir;Fazeli, Mohammad Sadegh;Mohammadi, Negin;Ghalehtaki, Reza
    • Radiation Oncology Journal
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    • v.38 no.2
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    • pp.119-128
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    • 2020
  • Purpose: Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods: In this clinical trial we recruited patients with rectal adenocarcinoma located from 5 cm to 15 cm above the anal verge. Patients in group I (short-course) received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/㎡ from day 1-5 twice daily and oxaliplatin 50 mg/㎡ on day 1 once daily). Patients in group II (long-course) received a total dose of 50-50.4 Gy/25-28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/㎡ twice daily. Both groups underwent consolidation chemotherapy followed by delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results: In this preliminary report on complications and pathological response, 66 patients were randomized into two study groups. Mean duration of radiotherapy in the group II (long-course) was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the shortcourse and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment-related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group except one grade 4 hematologic toxicity that was seen in group II. Within one month of surgery, no significant difference was seen regarding grade ≥3 postoperative complications (p = 0.333). Conclusion: For patients with rectal cancer located at least 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy.

Effect of Daily and Alternate Day Feeding Regimens on Growth and Food Utilization by Juvenile Flounder Paralichtys olivaceus (일일 및 격일 습사료 공급방법이 육성 넙치의 성장과 영양소 이용효율에 미치는 영향)

  • 김정대;신승훈;조구긴;이상민
    • Journal of Aquaculture
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    • v.15 no.1
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    • pp.15-21
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    • 2002
  • Two groups of juvenile flounders (90 g/each) were fed on moist pellet feed thrice a day for a period of 8 weeks; the first group, reared in 4 circular (6m $\times$ 0.8 m) tanks (1200 flounders/tank), was fed daily (ED) and the second one on alternate days (EO). There was no significant difference in growth and feed conversion ratio (FCR) between these groups. There was also no difference in chemical composition, except in lipid, which was significantly higher (4.1%) in the ED group than the EO group (3.4%). Food intake and gain in the whole body nitrogen (N) were higher in the ED group but there was no significant difference between these groups in N retention; they excreted almost equal amount (114 vs 112 g) of N. Although phosphorus intake was significantly different between these groups, the flounders retained equal amount (0.5 g) of P in their body and excreted also equal amount (27.6 vs 26.0 g/kg weight gain) of p. Energy intake (2528 kJ) of the ED group was higher than that (2116 kJ) of the EO group. However, there was no significant difference in their energy retention efficiency. Clearly, alternate day feeding regimen led to more efficient utilization of food by the juvenile flounder.

Clinical Response to Etoposide Plus Carboplatin and Topotecan Chemotherapy in Small Cell Lung Cancer (소세포폐암에 대한 Etoposide와 Carboplatin 병합요법과 Topotecan 화학요법의 효과)

  • Park, Kyung Hwa;Cho, Gye Jung;Ju, Jin Young;Son, Chang Young;Wi, Jeong Ook;Kim, Kyu Sik;Kim, Yu Il;Lim, Sung Chul;Kim, Young Chul;Park, Kyung Ok
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.4
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    • pp.415-428
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    • 2003
  • Background : This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. Methods : One hundred and ten patients with previously untreated SCLC received etoposide($100mg/m^2$ i.v., day 1 to 3) and carboplatin($300mg/m^2$ i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan($1.5mg/m^2$) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). Results : One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). Conclusion : The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.

Immunogenicity and Safety of a Two Doses of Hepatitis A Vaccine(VAQTATM) in Healthy Children and Adolescents (건강한 소아와 청소년에 대한 A형 간염(VAQTATM) 2회 접종시 면역원성 및 안전성에 대한 연구)

  • Lee, Jin Soo;Park, Ji Ho;Sohn, Young Mo
    • Pediatric Infection and Vaccine
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    • v.8 no.2
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    • pp.160-167
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    • 2001
  • Purpose : To assess the immunogenicity, safety, and tolerability of hepatitis A vaccine ($VAQTA^{TM}$) in healthy children and adolescents. Methods : Eligible subjects aged 2 to 17 years received 25 U/0.5 mL of $VAQTA^{TM}$ intramuscularly at 0 and 24 week schedule. Bleeds were obtained prior to vaccination and 4 weeks after the second dose to ascertain serostatus. To detect antibody to HAV after vaccination with an inactivated HA vaccine, a modification of the $Abbott^{(R)}$ HAVAB kit was used. Sample with titers ${\geq}10$ mIU/mL were considered seroconverted. Adverse experiences were monitored. Results : 102 subjects(54 male, 48 female) were enrolled. The mean age was $6.8{\pm}3.5$ years. Two subjects were seropositive, two were lost of follow up. 88 subjects were available for a per protocol analysis and 90 for all subjects with serology after the second dose, and ten withdral. All subjects(95% CI, 94.8~100) seroconverted. Geometric mean titers was 7,991.1(95% CI, 6,481.1~9,852.7) with very little difference in per protocol analysis and all subjects analysis. Adverse experiences to $VAQTA^{TM}$ were generally mild and transient. Conclusion : The pediatric two-dose regimen of $VAQTA^{TM}$ was found to be highly immunogenic, generally well tolerated and resulted in 100% seroconversion. Regarding Korea is in transition from a high to low risk region resulting in a paradox increase of clinical disease and disease burden, routine vaccination should be considered in order to control hepatitis A effectively.

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Efficacy and Safety Profile of TS-1 or TS-1/CDDP in Patients with Advanced Gastric Cancer (진행성 위암환자에 있어 TS-1 또는 TS-1/CDDP의 항암효과 및 안정성)

  • Ha,, Tae-Kyung;Kwon, Sung-Joon
    • Journal of Gastric Cancer
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    • v.6 no.3
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    • pp.139-145
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    • 2006
  • Purpose: Although several chemotherapy regimens used against advanced gastric cancer (AGC) have been studied extensively in an attempt to further improve the prognosis of patients, to date, no standard chemo-therapeutic regimens have been established. The aim of this study was to determine the anti-tumor efficacy and safety of TS-1 or TS-1 plus cisplatin (CDDP). Material and Methods: We treated 78 patients with AGC either with $80\;mg/m^{2}$ of TS-1 for 28 days, which was followed by a 2-week rest, or with $80\;mg/m^{2}$ of TS-1 for 21 days and $80\;mg/m^{2}$ of CDDP on day 8 every 5 weeks. Results: Tumor response rates in the neoadjuvant chemotherapy group and in the recurrent or post-palliative surgery group were 87.5% and 32.4%, respectively, and they were 28.6% and 48.4%, respectively, in the TS-1 group and the TS-1 plus CDDP group. The survival rates in the recurrent and the post-palliative surgery group were significantly different according to the degree of tumor response (P=0.0016), but the one-year survival rates according to the kinds of regimens (TS-1 or TS-1/CDDP group) were not significantly different. The incidences of grade 3 or 4 adverse effects in the TS-1 and the TS-1/CDDP groups were 14.3% and 36.8%, respectively. Conclusion: The anti-tumor efficacy and safety of TS-1 and TS-1 plus CDDP in Korean patients with AGC seemed to be high with modest adverse effects, thus suggesting the possible use of this regimen as a standard chemotherapy for gastric cancer.

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Multiple Daily Fractionated RT for Malignant Glioma (악성 성상세포종과 다형성 교아종 치료에 있어서 다분할 방사선 치료와 단순분할 방사선치료에 대한 성적비교)

  • Yang Kang Mo;Chang Hye Sook;Ahn Seoung Do;Choi Eun Kyung
    • Radiation Oncology Journal
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    • v.12 no.2
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    • pp.151-158
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    • 1994
  • Since Jan. 1992, authors have conducted a pilot study to treat malignant glioma with multiple daily fractionated(MDF) radiation therapy and this paper presents the outcome compared MDF to conventional factionated(CF) radiation therapy Between Sep. 1989 and Jan. 1993, forty three patients with high grade glioma of brain except brain stem glioma were treated: nineteen patients were treated with CF radiation therapy and 24 patients were treated with MDF radiation therapy. In CF radiation therapy, total dose was 6300cGy/35fx in 7 weeks, which 5040cGy was delivered to the initial target volume and 1260cGy to reduced target volume. And in MDF radiation therapy, total dose was 6400cGy/40fx in 4 weeks, which 3200cGy was delivered to the initial target volume as 160cGy 2 times daily 6hr apart. All patients had histologically confirmed anaplastic astrocytoma(AA) of glioblastoma multiforme (GBM) with stereotactic biopsy or craniotomy for subtotal or gross tumor resection. The range of follow-up was 7 months to 4 years with a median follow-up of 9 months. The Median survival from surgery was 9 months for all patients. The median survival was 9 months and 10 months for MDF group and CF group and 10 months and 9.5 months for glioblastoma multiforme and anaplastic astrocytoma, respectively. In 36 patients with follow-up CT scan or MRI scan, disease status was evaluated according to treatment groups, Four patients(GBM:3, AA:1) of 21 patients in MDF group, were alive with no evidence of disease, while none of patient was alive with no evidence of disease in CF group. The progression of disease had occurred in 20 patients, 11 patients and 9 patients in MDF group and CF group, respectively All of these patients showed in-field progression of disease, Four of 11 patients($27\%$) in MDF group showed the new leasion outside of the treatment field, while 5 of 9 patients($56\%$) in CF group. In our study the prognosis was not influenced by age, KPS, grade, extent of surgery and different fractional scheduled radiation therapy. Authors concluded that MDF regimen was well tolerated and shortened the treatment period from 7 weeks to 4 weeks without compromising results. We believe that further follow-up is needed to assess the role of MDF.

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The Associated Factors with Obesity-related Habits and Obesity index Change (비만관련 습관 및 비만도 변화에 영향을 미치는 관련요인 분석)

  • Gil, Mi-Kyeong
    • Journal of the Korean Society of School Health
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    • v.12 no.1
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    • pp.27-44
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    • 1999
  • Obesity in children is a major concern of public health. This study was performed to illuminate its effect on weight control program and the associated factors of obesity-related habits and obesity index in primary school obese children. Weight control program consisted of behavioral modification, nutrition education and exercise during 17 weeks. The sample consisted of treatment group(n=42) and control group(n=41). There was no statistical difference between the two groups in obesity index, socioeconomic status and grade. To assess the effects of weight control program, the subjects were given pre-test and post-test such as the measurement of anthropometric values and self-reporting questionnaire. This result of this study were as follows; 1. After weight control program was applied, there was a significant decrease in obesity index among the treatment group. Obesity-related habits score of the treatment group increased significantly, While there was not much difference between the pre-test and the post-test among the control group. But exercise habit didn't increase significantly in the both groups. 2. Correlation between obesity-related habits and obesity index were not evident. 3. After application of weight control program, the factors associated with change of eating habit were children's past experience of weight control, motivational change toward weight control program and friends' support for treatment group. The factors associated with change of exercise habit were post-test motivation score and friends' support. Motivational change toward weight control and pre-test self-efficacy of exercise behavior were counter-related to exercise habit. For change of other obesity-related habits, initial obesity index, motivational change, post-test self-efficacy score of exercise behavior and paternal educational status were closely associated. But post-test self-efficacy score of eating behavior was unrelated. 4. Only the factor of experience of weight control was associated with change of obesity index. 5. For the both groups, the factors associated with change of eating habits were post-test self-efficacy of eating behavior and family's support. The factors associated with change of exercise behavior were self-efficacy changes of exercise behavior and friends' support. The factors associated with change of other obesity-related habits were self-efficacy change of eating behavior. Initial obesity index was associated with change of obesity index. 6. The rate of dropouts from weight control program was 28.6% (12/42) in treatment group. Initial obesity index, other obesity-related habits except eating exercise habits, friend's support were associated with dropout. In conclusion, these results indicated that weight control program in primary school settings was effective. Direct exercise regimen and practice was demanded. In addition to the program itself, much of the success is dependent on the degree of motivation of the children involved and support provided by their parents and friends. Further study need to be performed under the condition that the weight control progrom is applied for a longer period.

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Effect of early chemoradiotherapy in patients with limited stage small cell lung cancer

  • Ha, In-Bong;Jeong, Bae-Kwon;Jeong, Hojin;Choi, Hoon-Sik;Chai, Gyu-Young;Kang, Myoung-Hee;Kim, Hoon Gu;Lee, Gyeong-Won;Na, Jae-Beom;Kang, Ki-Mun
    • Radiation Oncology Journal
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    • v.31 no.4
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    • pp.185-190
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    • 2013
  • Purpose: We evaluated the effect of early chemoradiotherapy on the treatment of patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods: Between January 2006 and December 2011, thirty-one patients with histologically proven LS-SCLC who were treated with two cycles of chemotherapy followed by concurrent chemoradiotherapy and consolidation chemotherapy were retrospectively analyzed. The chemotherapy regimen was composed of etoposide and cisplatin. Thoracic radiotherapy consisted of 50 to 60 Gy (median, 54 Gy) given in 5 to 6.5 weeks. Results: The follow-up period ranged from 5 to 53 months (median, 22 months). After chemoradiotherapy, 35.5% of the patients (11 patients) showed complete response, 61.3% (19 patients) showed partial response, 3.2% (one patient) showed progressive disease, resulting in an overall response rate of 96.8% (30 patients). The 1-, 2-, and 3-year overall survival (OS) rates were 66.5%, 41.0%, and 28.1%, respectively, with a median OS of 21.3 months. The 1-, 2-, and 3-year progression free survival (PFS) rates were 49.8%, 22.8%, and 13.7%, respectively, with median PFS of 12 months. The patterns of failure were: locoregional recurrences in 29.0% (nine patients), distant metastasis in 9.7% (three patients), and both locoregional and distant metastasis in 9.7% (three patients). Grade 3 or 4 toxicities of leukopenia, anemia, and thrombocytopenia were observed in 32.2%, 29.0%, and 25.8%, respectively. Grade 3 radiation esophagitis and radiation pneumonitis were shown in 12.9% and 6.4%, respectively. Conclusion: We conclude that early chemoradiotherapy for LS-SCLC provides feasible and acceptable local control and safety.

Altitude training as a powerful corrective intervention in correctin insulin resistance

  • Chen, Shu-Man;Kuo, Chia-Hua
    • Korean Journal of Exercise Nutrition
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    • v.16 no.2
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    • pp.65-71
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    • 2012
  • Oxygen is the final acceptor of electron transport from fat and carbohydrate oxidation, which is the rate-limiting factor for cellular ATP production. Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate for the shortfall caused by reduced fatty acid oxidation [1]. Therefore, training at altitude is expected to strongly influence the human metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting diabetes or related metabolic problems. However, most people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness (AMS) and insulin resistance corresponding to a increased levels of the stress hormones cortisol and catecholamine [2]. Thus, less stringent conditions were evaluated to determine whether glucose tolerance and insulin sensitivity could be improved by moderate altitude exposure (below 4000 M). In 2003, we and another group in Austria reported that short-term moderate altitude exposure plus endurance-related physical activity significantly improves glucose tolerance (not fasting glucose) in humans [3,4], which is associated with the improvement in the whole-body insulin sensitivity [5]. With daily hiking at an altitude of approximately 4000 M, glucose tolerance can still be improved but fasting glucose was slightly elevated. Individuals vary widely in their response to altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity is not apparent in those individuals with low baseline DHEA-S concentration [6]. In addition, hematopoietic adaptation against altitude hypoxia can also be impaired in individuals with low DHEA-S. In short-lived mammals like rodents, the DHEA-S level is barely detectable since their adrenal cortex does not appear to produce this steroid [7]. In this model, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can still improve insulin sensitivity, secondary to an effective suppression of adiposity [8]. Genetically obese rats exhibit hyperinsulinemia (sign of insulin resistance) with up-regulated baseline levels of AMP-activated protein kinase and AS160 phosphorylation in skeletal muscle compared to lean rats. After prolonged hypoxia training, this abnormality can be reversed concomitant with an approximately 50% increase in GLUT4 protein expression. Additionally, prolonged moderate hypoxia training results in decreased diffusion distance of muscle fiber (reduced cross-sectional area) without affecting muscle weight. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on changing body composition. Conclusion: Prolonged moderate altitude hypoxia (rangingfrom 1700 to 2400 M), but not acute high attitude hypoxia (above 4000 M), can effectively improve insulin sensitivity and glucose tolerance for humans and antagonizes the obese phenotype in animals with a genetic defect. In humans, the magnitude of the improvementvaries widely and correlates with baseline plasma DHEA-S levels. Compared to training at sea-level, training at altitude effectively decreases fat mass in parallel with increased muscle mass. This change may be associated with increased perfusion of insulin and fuel towards skeletal muscle that favors muscle competing postprandial fuel in circulation against adipose tissues.

Seven-Day Bismuth-based Quadruple Therapy as an Initial Treatment for Helicobacter pylori Infection in a High Metronidazole Resistant Area

  • Vilaichone, Ratha-korn;Prapitpaiboon, Hatainuch;Gamnarai, Pornpen;Namtanee, Juraiwan;Wongcha-um, Arti;Chaithongrat, Supakarn;Mahachai, Varocha
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6089-6092
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    • 2015
  • Background: The prevalence of metronidazole-resistant H. pylori is almost 50% in Thailand which severely limits the use of this drug for eradication therapy. The aims of this study were to evaluate the efficacy and safety profiles of 7-day bismuth-based quadruple therapy including metronidazole as an initial treatment for H. pylori infection in a high metronidazole resistance area. Materials and Methods: This study was performed at Thammasat University Hospital and King Chulalongkorn Memorial Hospital during January 2009 to October 2010. Patients with non-ulcer dyspepsia (NUD) with active H. pylori infection were assigned to receive seven days of quadruple therapy (pantoprazole 40 mg bid, bismuth subsalicylate 1,048 mg bid, amoxicillin 1 gm bid and metronidazole 400 mg tid). H. pylori infection was defined as positive H. pylori culture or two positive tests (rapid urease test and histology). Antibiotic susceptibility test for metronidazole by Epsilometer test (E-test) was performed in all positive cultures. At least four weeks after treatment, $^{13}C$ urea breath test ($^{13}C-UBT$) was performed to confirm H. pylori eradication. Results: A total of 114 patients were enrolled in this study, 50 males and 64 females with a mean age of 49.8 years. All 114 patients had a diagnosis of NUD. Overall eradication as confirmed by negative $^{13}C-UBT$ was achieved in 94 out of 114 patients (82.5%). 44 patients had positive cultures and success for E-test. In vitro metronidazole resistance was observed in 22/44 (50%) patients. Eradication rate in patients with metronidazole resistant strains was 16/22 (72.7%) and 20/22 (90.1%) with metronidazole sensitive strains (72.7% vs 90.1%, p-value=0.12; OR=3.75 [95%CI=0.6-31.5]). Minor adverse reactions included nausea, bitter taste, diarrhea and black stools but none of the patients dropped out from the study. Conclusions: Initial treatment with 7-day bismuth-based quadruple therapy including metronidazole, amoxycillin and pantoprazole is highly effective and well tolerated for metronidazole-sensitive H. pylori infections. However, the efficacy markedly decline with metronidazole resistance. Longer duration of this regimen might be required to improve the eradication rate and larger multi-center studies are needed to confirm this hypothesis.