Helicobacter pylori infection and eradication outcomes among Vietnamese patients in the same households: Findings from a non-randomized study

Objective Familial transmission can possibly influence the infection and treatment of Helicobacter pylori. This study aimed to describe the prevalence of H. pylori infection and outcomes of eradication treatment among Vietnamese patients who live in the same households. Methods We conducted a prospective cohort study of Vietnamese household members with upper gastrointestinal complaints. Participants received esophagogastroduodenoscopy and H. pylori testing. The H. pylori-positive patients were treated and asked to return for follow-up within 4 months. To explore factors associated with H. pylori infection at baseline, we performed multilevel logistic regression to account for the clustering effect of living in the same households. To explore factors associated with eradication failure, we used Poisson regression with robust variance estimation to estimate the risk ratio. Results The prevalence of H. pylori infection was 83.5% and highest among children <12 years old (92.2%) in 1,272 patients from 482 households. There were variations in H. pylori infection across households (intraclass correlation = 0.14, 95% confidence interval (CI) 0.05, 0.33). Children aged <12 years had higher odds of H. pylori infection (odds ratio = 3.41, 95%CI 2.11, 5.50). At follow-up, H. pylori was eradicated in 264 of 341 patients (77.4%). The risk of eradication failure was lower for the sequential regimen with tetracycline. Conclusion H. pylori infection was common among people living in the same households. Eradication success for H. pylori was higher for the tetracycline sequential regimen. More research should be focused on how family factors influence H. pylori infection and on eradication treatment.

Primary Systemic Therapy for HER2/Neu-Positive Operable Breast Cancer Increases the Number of Breast-Conserving Surgery and Disease-Free Survival: Retrospective Cohort Analysis at Single Institution

Objective The aim of this study was to evaluate the efficacy and cardiotoxicity profile, and to reduce the extend of breast cancer surgery in primary systemic therapy (PST) HER2/neu–positive operable breast cancer patients. Materials and Methods A total of 152 patients diagnosed from 2010 to 2015 were included in the study. The PST consisted of a sequential regimen of taxanes and anthracyclines plus trastuzumab. The clinical and pathological responses and the type of breast cancer surgery were evaluated and correlated with clinical and biological factors. The cardiotoxicity profile and long-term benefits were analyzed. Results The median patient age was 47 (37–67) years, with T2 and T3 67 (44.1%) and 85 (55.9%), respectively. Axillary lymph node breast cancer at diagnosis N0 was 104 (68.4%) and N1 and N2 were 28.9% and 2.6%, respectively. A total of 95.7% of patients had nonspecific type of breast cancer, 67% of tumors were hormonal receptor–negative, 75.5% were grade III, 100% Ki67 > 20%, and 90% of tumors were confirmed to be HER2/neu–positive through immunohistochemistry. Following PST, pathological complete response (pCR) rate was achieved in 44.7% evaluable patients. The pCR rate was higher in HR-negative (93.1% vs. 6.9%) cancer and in grade III (86.2%) than in grade I and II (13.8%) cancer; only 75.5% of complete response (CR) on ultrasound and magnetic resonance imaging were also CR on pathology results. Breast conserving surgery was performed in 41.4%. Regarding type of chemotherapy, there were no significant differences between chemotherapy with anthracycline backbone or taxanes to achieved pathological complete response. Despite that, we were unable to demonstrate an association between pCR and better DFS with p = 0.096; HR 5.7 95.0% CI (0.73–45.52). Patients who are hormonal receptor positive tend to have lower disease-free survival (DFS) than those who are hormonal receptor negative; HR = 6.34, 95.0% CI (1.54–26.00) and p = 0.010. Five years DFS was higher for those who achieved pCR compare with those who did not. Even in this research we failed to show it is statistically significant. Conclusion A sequential regimen of taxanes and anthracyclines plus trastuzumab was effective with high pCR rates and increases the possibility to do breast conservation surgery and had tolerable cardiotoxicity profile.

Impact of Local Liver Irradiation Concurrent Versus Sequential with Lenvatinib on Pharmacokinetics and Biodistribution

Concurrent and sequential regimens involving radiotherapy (RT) and lenvatinib were designed with off-target or stereotactic body radiation therapy (SBRT) doses in a freely moving rat model to evaluate the effect of RT on the pharmacokinetics (PK) of lenvatinib. Liver RT concurrent with lenvatinib decreased the area under the concentration–time curve of lenvatinib concentration (AUClenvatinib) by 51.1% with three fractions of 2 Gy (RT2Gy×3f’x, p = 0.03), and 48.9% with RT9Gy×3f’x (p = 0.03). The AUClenvatinib increased by 148.8% (p = 0.008) with RT2Gy×3f’x, and 68.9% (p = 0.009) with RT9Gy×3f’x in the sequential regimen compared to the concurrent regimen. There were no differences in the AUClenvatinib between RT2Gy×3f’x and RT9Gy×3f’x in the concurrent or sequential regimen. Both the RT2Gy×3f’x and RT9Gy×3f’x concurrent regimens markedly decreased the biodistribution of lenvatinib in the heart, liver, lung, spleen, and kidneys, which ranged from 31% to 100% for RT2Gy×3f’x, and 11% to 100% for RT9Gy×3f’x, compared to the sham regimen. The PK and biodistribution of lenvatinib can be modulated by simultaneous off-target irradiation and SBRT doses. The timing of lenvatinib administration with respect to RT, impacted the PK and biodistribution of the drug. Additionally, off-target and SBRT doses had a similar ability to modulate the effect of systemic therapy.

Sequential vs concurrent adjuvant chemotherapy of anthracycline and taxane for operable breast cancer

Background Whether a sequential or concurrent regimen of anthracyclines and taxanes is superior for breast cancer is controversial. We compared the efficacy of two regimens in patients with operable breast cancer based on all relevant published data of phase III randomized controlled trials. Methods A comprehensive literature search on PubMed, Web of Science, Embase, ScienceDirect, Google Scholar, and ClinicalTrials.gov databases was performed up to May 2020. Meta-analysis was performed to evaluate the different efficacy on disease-free survival (DFS) and overall survival (OS) for the two chemotherapy regimens. Subgroup analyses were further carried out in terms of node status and anthracycline selection. Results Compared to the concurrent regimen, the sequential regimen did not improve the DFS or OS in the population studied. Subgroup analysis showed that in node-positive patients, the sequential regimen had better DFS, but not OS, than the concurrent regimen. In sequential regimen, patients who received doxorubicin and taxanes had improved DFS and OS than patients who were administered epirubicin and taxanes. Furthermore, for patients who received doxorubicin and taxanes, compared to the sequential regimen, fewer cycles (4 cycles) of concurrent treatment resulted in a worse DFS and OS, which can be rescued by more cycles (6 cycles). Conclusions The sequential regimen of anthracyclines and taxanes for patients with operable breast cancer did not yield a significant benefit in DFS or OS over the concurrent regimen. The sequential regimen, however, provided a better DFS than concurrent regimen for node-positive patients. Interestingly, further subgroup analysis showed that for node-positive patients who were given doxorubicin and taxanes, more cycles (6 cycles) of the concurrent regimen may rescue the efficacy for fewer cycles (4 cycles).

Sequential vs concurrent adjuvant chemotherapy for operable breast cancer: A meta-analysis

Background: Whether a sequential or concurrent regimen of anthracyclines and taxanes is superior for breast cancer is controversial. We compared the efficacy of two regimens in patients with operable breast cancer based on all relevant published data of phase III randomized controlled trials.Methods: A comprehensive literature search on PubMed, Web of Science, Embase, ScienceDirect, Google Scholar and clinicaltrials.gov databases was performed up to May 2020. Meta-analysis was performed to evaluate the different efficacy on disease free survival (DFS) and overall survival (OS) for the two chemotherapy regimens. Subgroup analyses were further carried out in terms of node status and anthracycline selection.Results: Compared to the concurrent regimen, sequential regimen did not improve the DFS or OS in the population studied. Subgroup analysis showed that in node-positive patients, the sequential regimen had better DFS, but not OS, than the concurrent regimen. In sequential regimen, patients who received doxorubicin and taxanes had improved DFS and OS than patients who were administered epirubicin and taxanes. Furthermore, for patients who received doxorubicin and taxanes, compared to the sequential regimen, fewer cycles (4 cycles) of concurrent treatment resulted in a worse DFS and OS, which can be rescued by more cycles (6 cycles). Conclusions: The sequential regimen of anthracyclines and taxanes for patients with operable breast cancer did not yield a significant benefit in DFS or OS over the concurrent regimen. The sequential regimen, however, provided a better DFS than concurrent regimen for node-positive patients. Interestingly, further subgroup analysis showed that for node-positive patients who were given doxorubicin and taxanes, more cycles (6 cycles) of the concurrent regimen may rescue the efficacy for fewer cycles (4 cycles).

Efficacy Of Three Different Regimens In Eradication Of Helicobacter Pylori Infection In Nepalese Patients Of Gandaki Region

Background: Helicobacter pylori (H. pylori) is associated with the pathogenicity of gastro-duodenal ulcers and gastric cancers. Combination of several antimicrobial therapies and regimens have been advised for H. pylori treatment. But, resistance to various antibiotics regimens are being documented worldwide. The present study was undertaken to study the efficacy of commonly used 3 different regimens for eradication of H.pylori infection in Nepalese patients. Methods: A cross-sectional, hospital based study comprising of 405 subjects, was conducted. Each study patient underwent upper gastro-intestinal endoscopy followed by rapid urease test or histopathology from the biopsy sample for H. pylori detection. Patients were randomly subjected to 3 different H. pylori eradication regimen. After 4 weeks of therapy, patients were re-evaluated for persistence of H. pylori infection either by repeat UGI endoscopy followed by RUT or C14- Urea Breadth Test. Data analysis was done by SPSS 20. Results: Mean age of the patients was 34.4±8.72 years (M: F=1.5:1) with male predominance. H. pylori eradication rate was only 65.9% in patients using standard triple regimen using Amoxicillin, Clarithromycin and PPI (Group A). Eradication rate was greater (77.8%) with Levofloxacin based regimen (Group B) and 83.3%. with sequential regimen containing Amoxicillin followed by Clarithromycin and Tinidazole with PPI (Group C). Conclusion: The study demonstrates that the current standard Amoxicillin and Claritrhromycin based triple regimen has lowest eradication rate followed by levofloxacin based regimen. The sequential regimen was the most efficacious among the 3 different regimens for H. pylori eradication.

High Dose Flamsa, CLAG or FLAG-Based Sequential Conditioning Regimen Followed By Allogeneic Hematopoietic Transplantation Results in Favorable Outcome for High Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Myeloproliferative Neoplasia Patients : A Multicenter Study in Singapore

Introduction: Allogeneic hematopoietic cell transplant (allo-HCT) is an effective consolidative treatment for patients with certain hematological malignancies and gives the best outcome when done in remission. However, patients with refractory acute myeloid leukemia (AML), certain forms of myeloproliferative neoplasia (MPN), and myelodysplastic syndrome (MDS) deemed unable to achieve remission with standard induction are often excluded from allo-HCT with conventional conditioning regimen as pre-transplant remission could not be achieved. Recently, a sequential transplant approach, as developed by the Munich group, comprising of intensive cytoreductive chemotherapy FLAMSA (fludarabine/amsacrine/cytarabine) to decrease leukemia cell burden shortly prior to conditioning regimen, had been successfully used for high-risk (HR) AML/MDS with promising results. Methods: We studied 56 patients (median age, 52 years; range 17-68) with HR AML (n=45), as defined by refractory, relapsed disease, secondary leukemia, complete remission with adverse-risk cytogenetics according to ELN criteria, or high/very high risk refined Disease Risk Index (DRI), MPN (n=2), and HR MDS (n=9) according to IPSS-R, undergoing allo-HCT using the sequential transplant approach in 2 transplant centers in Singapore between January 2009 and June 2020. The sequential transplant approach combined a cytoreductive chemotherapy, which consisted of either FLAMSA (n=17), FLAG +/- Ida [fludarabine/cytarabine/granulocyte colony stimulating factor (GCSF) +/- idarubicin] (n=23), or CLAG (clofarabine +/- cytarabine +/- GCSF) (n=15), followed by reduced intensity (RIC) (N=48) or myeloablative (MAC) (N=8) conditioning regimen. All patients received peripheral blood stem cell from matched related donors (N=30), mismatched related donors (N=3), matched unrelated donors (N=16), or mismatched unrelated donors (N=7). Post-grafting immunosuppression consisted of calcineurin inhibitor and mycophenolate mofetil in all patients. Thymoglobuline or post-transplant cyclophosphamide were added for GVHD prophylaxis in unrelated donor transplant and mismatched related donors, respectively. Results: The median time to neutrophil &gt; 1000/μL was 11 days (range, 8-19). With a median follow-up of 44 months (range, 1-123), the Kaplan-Meier estimate of overall (OS) and leukemia-free (LFS) survivals at 5 years were 49% (95% CI, 35-62) and 37% (95% CI, 23-52), respectively. The 2-years cumulative incidence of relapse and non-relapse mortality (NRM) were 47% (95% CI, 32-60) and 13% (95% CI, 6-24), respectively. Patients receiving FLAG or CLAG-based sequential regimen showed lower cumulative incidence of NRM (2-year cumulative incidence for NRM: 5% vs 29%; p=0.018), and similar relapse (2-year cumulative incidence for relapse: 49% vs 53%; p=0.64), as compared to patients given FLAMSA-based sequential regimen, resulting in a trend towards more favourable OS (5-year OS: 53% vs 41%; p=0.29) and LFS (5-year LFS: 46% vs 20%; p=0.08). In multivariable analysis, only refined DRI showed significant impact on OS (p=0.04), but has no significant impact on LFS, NRM, and relapse. The 5-year OS for patients with intermediate/high risk and very high risk DRI were 59% and 27%, respectively (p=0.017), and the corresponding 5-year LFS were 46%, and 20% (p=0.06), respectively (Figure 1 & Figure 2). The intensity of conditioning regimen did not significantly impact on OS, LFS, relapse, and NRM. Conclusions: Sequential transplant conditioning with FLAMSA, FLAG or CLAG followed by allo-HCT is an effective strategy in overcoming the dismal prognosis of HR AML, MDS and MPN, and enabling favourable long-term disease-free survival. More studies on effective strategies such as post-transplant maintenance therapy with prophylactic donor lymphocyte infusion, are needed to further eliminate the risk of relapse, without increasing risk of treatment related toxicity. Disclosures No relevant conflicts of interest to declare.