Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Background and Objectives: We investigated whether extra-pulmonary vein (PV) ablation targeting a high maximal slope of the action potential duration restitution curve (Smax) improves the rhythm outcome of persistent atrial fibrillation (PeAF) ablation. Methods: In this open-label, multi-center, randomized, and controlled trial, 178 PeAF patients were randomized with 1:1 ratio to computational modeling-guided virtual Smax ablation (V-Smax) or empirical ablation (E-ABL) groups. Smax maps were generated by computational modeling based on atrial substrate maps acquired during clinical procedures in sinus rhythm. Smax maps were generated during the clinical PV isolation (PVI). The V-Smax group underwent an additional extra-PV ablation after PVI targeting the virtual high Smax sites. Results: After a mean follow-up period of 12.3±5.2 months, the clinical recurrence rates (25.6% vs. 23.9% in the V-Smax and the E-ABL group, p=0.880) or recurrence appearing as atrial tachycardia (11.1% vs. 5.7%, p=0.169) did not differ between the 2 groups. The postablation cardioversion rate was higher in the V-Smax group than E-ABL group (14.4% vs. 5.7%, p=0.027). Among antiarrhythmic drug-free patients (n=129), the AF freedom rate was 78.7% in the V-Smax group and 80.9% in the E-ABL group (p=0.776). The total procedure time was longer in the V-Smax group (p=0.008), but no significant difference was found in the major complication rates (p=0.497) between the groups. Conclusions Unlike a dominant frequency ablation, the computational modeling-guided V-Smax ablation did not improve the rhythm outcome of the PeAF ablation and had a longer procedure time.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population.METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis.RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence.CONCLUSION: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.
Antiviral Agents ; Carcinoma, Hepatocellular ; Cohort Studies ; DNA ; Follow-Up Studies ; Half-Life ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B ; Hepatitis ; Humans ; Immunoglobulins ; Korea ; Liver Transplantation ; Liver ; Organ Transplantation ; Polymerase Chain Reaction ; Recurrence ; Transplants

Purpose: Currently, trastuzumab plus chemotherapy is the standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic gastric cancer (mGC) or esophagogastric junction cancer. However, it is not clear whether the prognosis of HER2-positive mGC treated with trastuzumab plus chemotherapy is better than that of HER2-negative mGC treated with chemotherapy as the first-line therapy. Methods: We performed a retrospective study comparing the prognosis of mGC according to first-line treatment with trastuzumab plus chemotherapy or chemotherapy only, at the Korea Cancer Center Hospital from 2011 to 2018. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate survival analyses. Results: The median overall survival of trastuzumab group was 26.1 months and that of chemotherapy group was 14.8 months (P=0.047). Trastuzumab group had a longer median progression-free survival than chemotherapy group (23.4 vs. 9.2 months, P=0.026). By univariate analysis, sex, age, World Health Organization (WHO) histology, HER2 status, primary tumor site, extent of disease, number of lesions, number of metastatic, measurability of disease, prior gastrectomy, and chemotherapy group are statistically significant. Using multivariate analysis, number of lesions, number of metastatic, prior gastrectomy, and trastuzumab group (hazard ratio, 0.594; 95% confidence interval, 0.384–0.921; P=0.020) were found to be independent prognostic factors of overall survival. Conclusion The result suggests prognosis of HER2-positive mGC treated by trastuzumab plus chemotherapy could be better than that of HER2-negative mGC treated by chemotherapy only. Well-designed prospective cohort studies are needed to confirm the results of this study. HER2 testing should be performed routinely in all patients newly diagnosed with mGC.

Purpose: Currently, trastuzumab plus chemotherapy is the standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic gastric cancer (mGC) or esophagogastric junction cancer. However, it is not clear whether the prognosis of HER2-positive mGC treated with trastuzumab plus chemotherapy is better than that of HER2-negative mGC treated with chemotherapy as the first-line therapy. Methods: We performed a retrospective study comparing the prognosis of mGC according to first-line treatment with trastuzumab plus chemotherapy or chemotherapy only, at the Korea Cancer Center Hospital from 2011 to 2018. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate survival analyses. Results: The median overall survival of trastuzumab group was 26.1 months and that of chemotherapy group was 14.8 months (P=0.047). Trastuzumab group had a longer median progression-free survival than chemotherapy group (23.4 vs. 9.2 months, P=0.026). By univariate analysis, sex, age, World Health Organization (WHO) histology, HER2 status, primary tumor site, extent of disease, number of lesions, number of metastatic, measurability of disease, prior gastrectomy, and chemotherapy group are statistically significant. Using multivariate analysis, number of lesions, number of metastatic, prior gastrectomy, and trastuzumab group (hazard ratio, 0.594; 95% confidence interval, 0.384–0.921; P=0.020) were found to be independent prognostic factors of overall survival. Conclusion The result suggests prognosis of HER2-positive mGC treated by trastuzumab plus chemotherapy could be better than that of HER2-negative mGC treated by chemotherapy only. Well-designed prospective cohort studies are needed to confirm the results of this study. HER2 testing should be performed routinely in all patients newly diagnosed with mGC.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population. METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis. RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence. CONCLUSION Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.

PURPOSE: We investigated the clinical course of infants with congenital heart disease (CHD) who experienced thyroid dysfunction within 100 days of birth. METHODS: We performed retrospective medical reviews of 54 CHD patients (24 male patients) who underwent a thyroid function test (TFT) between January 2007 and July 2016. Data were collected on birth history, diagnosis of CHD, underlying chromosomal or genetic abnormalities, medication history, surgery, ventilator care, and exposure to iodine contrast media (ICM). Results of neonatal screening tests (NSTs) and TFTs were reviewed. RESULTS: A total of 36 patients (29 transient, 7 permanent) showed thyroid dysfunction. Among the seven patients with permanent hypothyroidism, three had an underlying syndrome, three showed abnormal NST results, and one was admitted to the intensive care unit for macroglossia and feeding cyanosis. We found that infants with transient thyroid dysfunction had a lower birth weight and were more commonly exposed to thyroid disrupting medication and/or ICM. However, these risk factors were not significant. A total of 8 patients with a history of ICM exposure showed thyroid dysfunction. Excluding 3 patients with elevated thyroid stimulating hormone before ICM exposure, 5 patients recovered from transient thyroid dysfunction. CONCLUSIONS: We observed thyroid dysfunction in two-thirds of CHD infants (53.7% transient, 13.0% permanent) who had risk factors and received TFT screening within 100 days, despite normal NSTs. Further studies with larger sample sizes are required to revise the criteria for TFT screening in CHD infants.
Birth Weight ; Contrast Media ; Cyanosis ; Diagnosis ; Heart ; Heart Defects, Congenital* ; Humans ; Hypothyroidism ; Infant* ; Infant, Newborn ; Intensive Care Units ; Iodine ; Macroglossia ; Male ; Mass Screening ; Neonatal Screening ; Parturition ; Reproductive History ; Retrospective Studies ; Risk Factors ; Sample Size ; Thyroid Function Tests ; Thyroid Gland* ; Thyrotropin ; Ventilators, Mechanical

beta-lapachone is a naturally occurring quinone that selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of beta-lapachone on the induction of apoptosis in human gastric carcinoma AGS cells. beta-lapachone significantly inhibited cellular proliferation, and some typical apoptotic characteristics such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells were observed in beta-lapachone-treated AGS cells. Treatment with beta-lapachone caused mitochondrial transmembrane potential dissipation, stimulated the mitochondria-mediated intrinsic apoptotic pathway, as indicated by caspase-9 activation, cytochrome c release, Bcl-2 downregulation and Bax upregulation, as well as death receptor-mediated extrinsic apoptotic pathway, as indicated by activation of caspase-8 and truncation of Bid. This process was accompanied by activation of caspase-3 and concomitant with cleavage of poly(ADP-ribose) polymerase. The general caspase inhibitor, z-VAD-fmk, significantly abolished beta-lapachone-induced cell death and inhibited growth. Further analysis demonstrated that the induction of apoptosis by beta-lapachone was accompanied by inactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. The PI3K inhibitor LY29004 significantly increased beta-lapachone-induced apoptosis and growth inhibition. Taken together, these findings indicate that the apoptotic activity of beta-lapachone is probably regulated by a caspase-dependent cascade through activation of both intrinsic and extrinsic signaling pathways, and that inhibition of the PI3K/Akt signaling may contribute to beta-lapachone-mediated AGS cell growth inhibition and apoptosis induction.
Apoptosis* ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cell Death ; Cell Proliferation ; Chromatin ; Cytochromes c ; Down-Regulation ; Humans ; Membrane Potentials ; Phosphatidylinositol 3-Kinase ; Poly(ADP-ribose) Polymerases ; Up-Regulation

BACKGROUND/AIMS: This study compared the therapeutic efficacy of endoscopic band ligation (EBL) with that of electrocoagulation for treating non-variceal, non-ulcer (NVNU) upper gastrointestinal (UGI) bleeding. METHODS: This study included 89 patients who underwent EBL and 56 patients in whom monopolar electrocoagulation was performed for NVNU UGI bleeding. The lesions treated were Mallory-Weiss tear in 91 patients, Dieulafoy's lesion in 42 patients and angiodysplasia in 12 patients. RESULTS: The initial hemostatic rate was 97% in the EBL group and 91% in the electrocoagulation group, but this was not statistically different. Rebleeding occurred in 5 of 89 patients (5.6%) in the EBL group and in 8 of 56 patients (14.3%) in the electrocoagulation group (p=0.07). Thrombocytopenia or prothrombin time prolongation was confirmed to be a significant risk factor for rebleeding. The rebleeding rate in the high risk group was significantly lower than in the EBL group (9% vs. 30%, respectively, p=0.03). The median procedure time was significantly shorter in the EBL group compared with that in the electrocoagulation group (median 5.6 minutes vs. 8.3 minutes, respectively, p=0.04). CONCLUSIONS: EBL and electrocoagulation are both effective for treating NVNU UGI bleeding, and EBL is especially safe and effective for the cases with a high risk for rebleeding.
Risk Factors