Purpose: Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. Materials and Methods: The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. Results: Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). Conclusion The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

Purpose: The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC). Materials and Methods: In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety. Results: Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates. Conclusion Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

Purpose: We aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC). Materials and Methods: We retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3-4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys. Results: The median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman’s nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA). Conclusion Tumor extension to renal vessels or the IVC and Fuhrman’s nuclear grade IV were the independent risk factors associated with LRR after RN for pT3-4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.

Objectives: It is important that inflammatory bowel disease (IBD) patients adhere to their prescribed medication regimens to avoid the repeat exacerbations, complications, or surgeries associated with this disorder. However, there are few studies on medication adherence in patients with IBD, especially in Asian populations. So, we analyzed the factors associated with medication adherence in Korean IBD patients. Methods: Patients who had been diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) more than 6 months previously and receiving oral medications for IBD were enrolled. Medication adherence was measured using the Medical Adherence Reporting Scale (MARS-5), a self-reported medication adherence measurement tool. Results: Among 207 patients in the final study population, 125 (60.4%) had CD and 134 (64.7%) were men. The mean age was 39.63 years (SD, 13.16 years) and the mean disease duration was 10.09 years (SD, 6.33 years). The mean medication adherence score was 22.46 (SD, 2.86) out of 25, and 181 (87.4%) patients had score of 20 or higher.In multiple linear regression analysis, self-efficacy (β=0.341, P<0.001) and ≥3 dosing per day (β=–0.192 P=0.016) were revealed to be significant factors associated with medication adherence. Additionally, there was a positive correlation between self-efficacy and medication adherence (r=0.312, P<0.001). However, disease related knowledge, depression, and anxiety were not significantly associated with medication adherence. Conclusion To improve medication adherence among patients with IBD, a reduction in the number of doses per day and an improved self-efficacy will be helpful.

Background/Aims: Self-expandable metal stents (SEMSs) can be applied to relieve colorectal obstruction secondary to incurable primary colorectal cancer or extracolonic malignancy. We aimed to identify factors associated with clinical success and the reintervention-free survival (RFS) after palliative stenting. Methods: Cases of palliative SEMS placement between 2005 and 2019 were retrieved from the institutional database and reviewed retrospectively. Logistic regression and log-rank testing followed by Cox proportional hazard analyses were performed to investigate the predictors of the clinical success of palliative stenting and factors associated with RFS, respectively. Results: A total of 593 patients underwent palliative stenting for malignant colonic obstruction (MCO). The technical and clinical success rates were 92.9% and 83.5%, respectively. Peritoneal carcinomatosis was a predictor of clinical failure (odds ratio, 0.33; 95% confidence interval [CI], 0.17 to 0.65) in the multivariate analysis. Peritoneal carcinomatosis (hazard ratio [HR], 2.48; 95% CI, 1.69 to 3.64) and stent expansion >90% on day 1 (HR, 1.62; 95% CI, 1.05 to 2.50) were associated with a shorter RFS. Neither clinical success nor RFS was associated with extracolonic malignancy. Re-obstruction, stent migration, and perforation were responsible for most reinterventions after clinically successful palliative stenting. Conclusions In patients requiring palliative stenting for MCO, peritoneal carcinomatosis was associated with both clinical failure and short RFS. Stent expansion >90% on postprocedural day 1 was another predictor of a short RFS after clinically successful stenting. A large prospective study is warranted to establish factors associated with RFS after successful palliative stenting for MCO.

Background/Aims: Self-expandable metal stents (SEMSs) can be applied to relieve colorectal obstruction secondary to incurable primary colorectal cancer or extracolonic malignancy. We aimed to identify factors associated with clinical success and the reintervention-free survival (RFS) after palliative stenting. Methods: Cases of palliative SEMS placement between 2005 and 2019 were retrieved from the institutional database and reviewed retrospectively. Logistic regression and log-rank testing followed by Cox proportional hazard analyses were performed to investigate the predictors of the clinical success of palliative stenting and factors associated with RFS, respectively. Results: A total of 593 patients underwent palliative stenting for malignant colonic obstruction (MCO). The technical and clinical success rates were 92.9% and 83.5%, respectively. Peritoneal carcinomatosis was a predictor of clinical failure (odds ratio, 0.33; 95% confidence interval [CI], 0.17 to 0.65) in the multivariate analysis. Peritoneal carcinomatosis (hazard ratio [HR], 2.48; 95% CI, 1.69 to 3.64) and stent expansion >90% on day 1 (HR, 1.62; 95% CI, 1.05 to 2.50) were associated with a shorter RFS. Neither clinical success nor RFS was associated with extracolonic malignancy. Re-obstruction, stent migration, and perforation were responsible for most reinterventions after clinically successful palliative stenting. Conclusions In patients requiring palliative stenting for MCO, peritoneal carcinomatosis was associated with both clinical failure and short RFS. Stent expansion >90% on postprocedural day 1 was another predictor of a short RFS after clinically successful stenting. A large prospective study is warranted to establish factors associated with RFS after successful palliative stenting for MCO.

Purpose: There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. Materials and Methods: In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. Results: After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. Conclusions Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.

Purpose: There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. Materials and Methods: In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. Results: After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. Conclusions Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.

Objective: : Radiation is known to induce autophagy in malignant glioma cells whether it is cytocidal or cytoprotective.Dexamethasone is frequently used to reduce tumor-associated brain edema, especially during radiation therapy. The purpose of the study was to determine whether and how dexamethasone affects autophagy in irradiated malignant glioma cells and to identify possible intervening molecular pathways. Methods: : We prepared p53 mutant U373 and LN229 glioma cell lines, which varied by phosphatase and tensin homolog (PTEN) mutational status and were used to make U373 stable transfected cells expressing GFP-LC3 protein. After performing cell survival assay after irradiation, the IC50 radiation dose was determined. Dexamethasone dose (10 µM) was determined from the literature and added to the glioma cells 24 hours before the irradiation. The effect of adding dexamethasone was evaluated by cell survival assay or clonogenic assay and cell cycle analysis. Measurement of autophagy was visualized by western blot of LC3-I/LC3-II and quantified by the GFP-LC3 punctuated pattern under fluorescence microscopy and acridine orange staining for acidic vesicle organelles by flow cytometry. Results: : Dexamethasone increased cell survival in both U373 and LN229 cells after irradiation. It interfered with autophagy after irradiation differently depending on the PTEN mutational status : the autophagy decreased in U373 (PTEN-mutated) cells but increased in LN229 (PTEN wild-type) cells. Inhibition of protein kinase B (AKT) phosphorylation after irradiation by LY294002 reversed the dexamethasone-induced decrease of autophagy and cell death in U373 cells but provoked no effect on both autophagy and cell survival in LN229 cells. After ATG5 knockdown, radiation-induced autophagy decreased and the effect of dexamethasone also diminished in both cell lines. The diminished autophagy resulted in a partial reversal of dexamethasone protection from cell death after irradiation in U373 cells; however, no significant change was observed in surviving fraction LN229 cells. Conclusion : Dexamethasone increased cell survival in p53 mutated malignant glioma cells and increased autophagy in PTENmutant malignant glioma cell but not in PTEN-wildtype cell. The difference of autophagy response could be mediated though the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway.

PURPOSE: Treatment targeting immune checkpoint with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has demonstrated efficacy and tolerability in the treatment of metastatic urothelial carcinoma (mUC). We investigated the efficacy and safety of atezolizumab in mUC patients who failed platinum-based chemotherapy. MATERIALS AND METHODS: A retrospective study using the Samsung Medical Center cancer chemotherapy registry was performed on 50 consecutive patients with mUC treated with atezolizumab, regardless of their PD-L1(SP142) status, as salvage therapy after chemotherapy failure between May 2017 and June 2018. Endpoints included overall response rate (RR), progression-free survival (PFS), and safety. RESULTS: Among 50 patients, men constituted 76% and the median age was 68 years (range, 46 to 82 years). Twenty-three patients (46%) received atezolizumab as second-line therapy. PD-L1 (SP142) status IC0/1 and IC2/3 were found in 21 (42%) and 21 (42%) of patients, respectively; in eight patients (16%), PD-L1 (SP142) expression was not available. Atezolizumab was generally well tolerated, with pruritus and fatigue being the most commonly observed toxicities. As a result, partial response was noted in 20 patients (40%), with 12 (24%) stable diseases. RRwas higherin IC2/3 (62%) than in IC0/1 patients (24%, p=0.013). The median PFS was 7.4 months (95% confidence interval, 3.4 to 11.4 months). As expected, PFS also was significantly longer in IC2/3 patients than in IC0/1 (median, 12.7 vs. 2.1 months; p=0.005). PFS was not significantly influenced by age, sex, performance status, number of previous chemotherapy, site of metastases, or any of the baseline laboratory parameters. CONCLUSION: In this retrospective study, atezolizumab demonstrated clinically efficacy and tolerability in unselected mUC patients who failed platinum-based chemotherapy.
Disease-Free Survival ; Drug Therapy ; Fatigue ; Humans ; Male ; Neoplasm Metastasis ; Pruritus ; Retrospective Studies ; Salvage Therapy