Effect of Pravastatin on Kidney Function in Patients with Dyslipidemia and Type 2 Diabetes Mellitus: A Multicenter Prospective Observational Study.

INTRODUCTION: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice. METHODS: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety. RESULTS: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks. CONCLUSION: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. TRIAL REGISTRATION NUMBER: NCT05107063 submitted October 27, 2021.

Changes in the glymphatic system before and after dialysis initiation in patients with end-stage kidney disease.

INTRODUCTION: The aims of this study were to evaluate 1) glymphatic system function in patients with end-stage kidney disease (ESKD) before initiating dialysis compared to healthy controls, and 2) changes in the glymphatic system function after kidney replacement therapy including dialysis in patients with ESKD using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. MATERIALS AND METHODS: This study was prospectively conducted at a single hospital. We enrolled 14 neurologically asymptomatic patients who first initiated hemodialysis or peritoneal dialysis for ESKD and 17 healthy controls. Patients had magnetic resonance imaging scans before initiating dialysis and again 3 months after initiating dialysis and the DTI-ALPS index was calculated. We compared the DTI-ALPS index before and after the initiation of dialysis and compared the DTI-ALPS index between the patients with ESKD and healthy control. RESULTS: There were differences in the DTI-ALPS index between ESKD patients before initiating dialysis and healthy controls (1.342 vs. 1.633, p = 0.003). DTI-ALPS index between ESKD patients before initiating dialysis and those after dialysis were not different (1.342 vs. 1.262, p = 0.386). There was a positive correlation between DTI-ALPS index and phosphate (r = 0.610, p = 0.020) in patients with ESKD. CONCLUSION: We confirmed the presence of glymphatic dysfunction in patients with ESKD. However, there was no difference in the glymphatic system before and after dialysis initiation. This finding may be related to uremic toxins that are not removed by dialysis in patients with ESKD. This study can be used for the development of pathophysiology of patients with ESKD.

Delayed exacerbation of COVID-19 pneumonia in vaccinated kidney transplant recipients receiving immunosuppressants: a case series.

Coronavirus disease 2019 (COVID-19) increases the risk of mortality and hospitalization in immunocompromised patients, including kidney transplant recipients (KTRs) receiving immunosuppressants. Several vaccines for COVID-19 have been developed and proven effective in decreasing the incidence of COVID-19 and the rate of progression to severe COVID-19. However, breakthrough infections have also been reported in vaccinated patients. We report cases from our center of delayed exacerbated pneumonia from COVID-19 in vaccinated KTRs receiving immunosuppressants. Of the 900 KTRs who had been vaccinated for COVID-19 and were followed up at our center from January 1, 2022, to April 30, 2022 (during the Omicron variant outbreak), 126 contracted COVID-19 (incidence rate, 14%). Thirty-four (27%) in this group were hospitalized due to COVID-19. Twenty patients did not have pneumonia but had symptoms of upper respiratory tract infection or diarrhea, which improved with conservative treatment. Nine of the 14 patients with pneumonia had delayed onset or exacerbated pneumonia 1 week after their COVID-19 diagnosis. They were treated with remdesivir, and most recovered. One patient died due to progressive pneumonia and pneumothorax. It is important that KTRs who are taking immunosuppressants be observed closely and for a prolonged period after a COVID-19 diagnosis, irrespective of their COVID-19 vaccination status.

The Study of a Validated Assessment Scale for a Localized Submental Fat Volume.

BACKGROUND: This aim of this study was to develop an objective tool for rating submental fat applied to Koreans. METHODS: The study was conducted between April 2019 and October 2019. A total of 92 subjects were enrolled in the study. Clinical photos of the subjects were categorized using validated CR-SMFRS by three plastic surgeons and one dermatologist. The categorized photos were then shown to six different plastic surgeons for evaluation. RESULTS: The Cohen's kappa value for the six raters were 0.830, 0.742, 0.703, 0.907, 0.862, and 0.793 with statistical significance (p < 0.001). ICC value was between 0.860 and 0.966 (p < 0.001). Since the Cohen's value and ICC were above 0.6 for all raters, the ratings performed by all six raters were used in the analysis. The ICC values between raters were between 0.899 and 0.902. CONCLUSIONS: We came up with a set of reference photos that can be used for submental fat rating scale applicable to Korean subjects. LEVEL OF EVIDENCE: II.

A Brachial Artery Pseudoaneurysm Treated with a Bifurcated Y-Shaped Artificial Vessel Graft.

Brachial artery aneurysms are rare diseases that may be caused by infection or trauma. We report a case of a 71-year-old man who presented with a mass in his right antecubital fossa that increased in size slowly over time. Three years ago, the patient underwent ascending and total-arch replacement with artificial vessel graft to treat aortic root and ascending aorta aneurysm. Preoperative physical examination of right upper extremity showed a nonpulsatile mass with normal pulse of axillary, brachial, and radial arteries. The mass was removed and brachial artery reconstruction was done initially using saphenous vein graft. Two months later, the patient revisited with recurrent pseudoaneurysm, involving the bifurcation point of brachial artery. Aneurysm was totally resected and the brachial artery was reconstructed by interposition graft using a bifurcated GORE-TEX artificial vessel graft. The patient healed without complication and no recurrence was observed. Artificial vessel graft is an available option for reconstruction, and revascularization of vessel defect after excision of brachial artery aneurysm may involve bifurcation point.

Characteristics and surgical outcomes of cleft palate in kabuki syndrome: a case series of 11 patients.

OBJECTIVE: A significant number of patients with KS have cleft palate (CP) or submucous cleft palate (SMCP) and show delayed speech development. However, few reports have discussed the characteristics of CP in KS and the outcomes of postoperative speech development. The purpose of this study was to investigate the characteristics and surgical outcomes of CP in patients with KS, and to discuss the importance of the diagnosis of CP or SMCP. METHODS: We conducted a retrospective study on patients with clinically diagnosed KS who underwent palatoplasty. Clinical and surgical data were collected from patients' medical records, and velopharyngeal function was evaluated using nasopharyngoscopy and speech analysis. RESULTS: In 11 cases, 5 patients had CP (45.5%) and 6 had SMCP (54.5%). Four patients who were genetically tested had a pathogenic variant of KMT2D. Seven of nine patients (77.8%) who underwent conventional palatoplasty showed velopharyngeal insufficiency and hypernasality. All patients who underwent pharyngeal flap surgery achieved velopharyngeal competency. Statistical analysis revealed a statistically significant difference in postoperative results between non-syndromic and KS patients. CONCLUSION: Patients with SMCP may be more common than previously reported. The results showed that it is difficult to produce optimal results with conventional palatoplasty; therefore, pharyngeal flap surgery should be considered as a treatment to obtain favorable results. Pharyngeal flap surgery in patients with KS should be carefully designed based on speech evaluation and nasopharyngoscopic findings.

The effect of delayed breast reconstruction after unilateral mastectomy on spine alignment.

BACKGROUND: Mastectomy in patients with breast cancer causes spinal deformities. We evaluated the effect of delayed breast reconstruction in post-mastectomy patients on spine alignments. METHODS: The study included 68 patients who underwent delayed breast reconstruction by three plastic surgeons in a single tertiary hospital. We measured proximal thoracic (PT), main thoracic (MT), and thoracolumbar (TL) Cobb angles and coronal spinal balance from chest or whole spine radiographs. RESULTS: The median changes in the PT and MT Cobb angles were -0.33 and -0.34 degrees, respectively. The change in TL Cobb angle and coronal spinal balance were only measured in 29 patients with available spine radiographs. The median change in TL Cobb angle and coronal spinal balance were -0.69 degrees and 3.75 mm, respectively. The median preoperative and postoperative PT Cobb angles were 1.75 and 1.24 degrees. The difference between preoperative and postoperative PT Cobb angles was statistically insignificant (P=0.036). The median preoperative and postoperative MT Cobb angles were 1.32 and 1.09 degrees, respectively. The difference between preoperative and postoperative MT Cobb angles was statistically insignificant (P=0.221). CONCLUSIONS: Delayed breast reconstruction did not result in clinically significant improvement in mastectomy-induced spinal deformity. This finding should be considered when choosing between immediate and delayed breast reconstruction.

Custom-Made Nasal Retainer Using Latex Nelaton Urine Catheter After the Cheiloplasty.

Nasal retainers are common tools used in managing patients with cleft lip. The significance of nasal retainer in preventing nostril collapse or stenosis to maintain a symmetrical nose after the surgical procedures is already well known. We came up with a way to create a nasal retainer using a latex nelaton catheter. Custom-made nasal retainer using latex nelaton catheter was used postoperatively on a 10-month-old infant with median cleft lip after cheiloplasty. In postoperative day 7, her nostrils were large enough for premade silicone nasal retainer to fit. She was discharged with instructions given to use the retainer for 6 months. Custom-made nasal retainer can be used as an alternative to premade nasal retainers for patients with wide columella or small nostril cavities, or who cannot afford premade retainers.

Retrospective multicenter cohort analysis of 621 cases of BellaGel silicone breast implants with study of physicochemical properties and surface topography.

This study aimed to assess the effectiveness and safety of BellaGel implants after implantation in Asian women and inform surgeons of another option for use in breast augmentation and reconstruction. This study was conducted in eight hospitals from November 27, 2015 to April 30, 2018. All patients underwent augmentation mammoplasty or implant-based breast reconstruction with BellaGel implants. Complication rates were compared between groups, and the cumulative hazard function was compared using the Kaplan-Meier survival analysis. Implants were grouped by surface type, and the cumulative hazard functions of total complication cases were compared. The biomechanical properties of the BellaGel implant and other company representative implants were tested using a mechanical testing machine, and surface topography was analyzed using a 3D laser scanning confocal microscope. There was a significant difference in the incidence of complications between the reconstruction (17.1%) and augmentation (4.7%) groups, but no significant difference in the complication rates of each group. There was no difference in the reoperation or revision rates between the groups. The log rank test showed a statistically significant difference in cumulative hazard function between the groups. Among the three types of implants (smooth, textured, and microtextured), the microtextured type had the lowest complication rate. The BellaGel microtexture implant had the highest maximal tensile load and displacement value. The BellaGel and Silksurface implants had the highest stored energy, although there was no significant difference. BellaGel implants can serve as a criterion for the selection of safe and effective implants among currently available implants.

BellaGel breast implant: 6-Year results of a prospective cohort study.

BACKGROUND: This is the first clinical study conducted among Asian women using breast implants manufactured by an Asian company. Four-year data regarding the safety and efficacy of BellaGel breast implants have already been published, and we now report 6-year data. METHODS: This study was designed to take place over 10 years. It included 103 patients who underwent breast reconstruction or augmentation using BellaGel breast implants. The rates of implant rupture and capsular contracture were measured and analyzed to evaluate the effectiveness of the breast implant. RESULTS: At patients' 6-year postoperative visits, the implant rupture and capsular contracture rates were 1.15% and 2.30%, respectively. The implant rupture rate was 3.77% among reconstruction cases and 0% among augmentation cases. The capsular contracture rate was 5.66% among reconstruction cases and 0.83% among augmentation cases. CONCLUSIONS: The 6-year data from this planned 10-year study suggest that the BellaGel cohesive silicone gel-filled breast implant is an effective and safe medical device that can be used in breast reconstruction and augmentation.

Allograft dysfunction and parenchymal necrosis associated with renal artery stenosis and perigraft hematoma after kidney transplantation.

Transplant renal artery stenosis (TRAS) is one cause of allograft dysfunction. TRAS causes parenchymal necrosis and graft insufficiency. Herein, we report the case of a 40-year-old female with end-stage renal disease due to immunoglobulin A nephropathy, who underwent kidney transplantation with her elder sister. The surgery was successful and the allograft showed primary graft function. At postoperative day (POD) 2, urine output decreased sharply. We checked a non-enhanced abdominal computed tomography scan which showed subcapsular and pelvic cavity hematomas. She underwent hematoma removal surgery with renal upper polar capsulotomy. Bleeding control was successful, but her serum creatinine was 5.4 mg/dL. At POD 25, abdomen magnetic resonance angiography showed significant stenosis at the anastomosis site between the graft renal artery and the recipient's internal iliac artery. Then, percutaneous transluminal angioplasty was implemented. Significant stenosis (>80%) was detected at the anastomotic site and a 5-mm stent was inserted at stenotic lesion with post-stent balloon angioplasty using a 5-mm balloon catheter. The renal arterial diameter and blood flow were normalized. At postoperative 5 months, a 99mTc dimercaptosuccinic acid scan showed multiple focal radioisotope defects. At 54 months after renal transplantation, her serum creatinine level was 4.0 mg/dL and her glomerular filtration rate was 13 mL/min/1.73 m2. Hence, we report that TRAS can cause parenchymal necrosis and allograft dysfunction.

Extensive full thickness abdominal wall reconstruction using anterolateral thigh compound flap modifications.

PURPOSE: Abdominal wall reconstruction is challenging, which demands adequate skin coverage and structural support. The anterolateral thigh (ALT) flap including fascial portion can be useful in such cases. METHODS: Retrospective chart review of five patients that underwent complex abdominal wall defects reconstruction with ALT free flaps with fascia lata was conducted. Patient age ranged from 49 to 69 years (average: 57.4). The etiology of defects was infected liposuction site, small bowel perforation, esophageal cancer, diverticulum perforation, and Hartmann operation. The average size of the defect was 17.4 × 10 cm (9 × 9 ~ 21 × 18). Single-stage reconstruction using ALT flaps based on the lateral circumflex femoral artery was done in all patients. Exposed intestines were successfully covered and reinforced utilizing fascial component. RESULTS: The average size of the flap was 17.4 × 8 cm (9 × 9 cm ~25 × 10 cm). One partial flap necrosis, venous congestion, and infection occurred. These complications were treated successfully. During the follow-up (12-96 months, mean: 63), all patients achieved functional stabilization and returned to normal activities. CONCLUSION: ALT flap combined with its fascial component is useful for abdominal wall. It can be a reliable option in cases of intestinal exposure.

Long-term Survival Analysis of Kidney Transplant Recipients Receiving Mizoribine as a Maintenance Immunosuppressant: A Single-Center Study.

BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressant and is widely used in Asia. However, most studies on MZR have been performed in Japan, and there remains a lack of reports on long-term use in other countries. The purpose of this study is to evaluate the efficacy and safety of MZR's use in Korean kidney transplant recipients by observing their clinical courses and analyzing their long-term patent and graft survival rates. METHODS: We studied 129 subjects who had received MZR as a maintenance immunosuppressant since January 2000. Our analysis was based on the patients' medical records from January 2000 to December 2017. RESULTS: The overall survival rates of the kidney transplant recipients were 100% at 1 year, 99.1% at 5 years, 96.8% at 10 years, and 92.5% at 15 years. The graft survival rates were 100% at 1 year, 98.3% at 5 years, 93.2% at 10 years, and 82.2% at 15 years. There were differences in the recipient survival and graft survival rates according to the kidney donor and the use of renal replace therapy before transplant. There were no differences in the survival rates according to the MZR dose, the type of underlying disease, or other clinical factors. CONCLUSIONS: The use of low doses of MZR as a maintenance immunosuppressant could be an effective means of ensuring relatively good long-term patient and graft survival rates in cases of kidney transplant.

Efficacy and Safety of Ultra-Low-Dose Valganciclovir Chemoprophylaxis for Cytomegalovirus Infection in High-Risk Kidney Transplantation Patients.

INTRODUCTION: Valganciclovir (VGCV) prophylaxis of 900 mg twice daily for 6 months is recommended to prevent cytomegalovirus (CMV) infection, which is a major cause of decreased graft and patient survival in kidney transplant recipients. However, recent studies have shown the efficacy of 900 mg once daily for 3 to 6 months. Maintaining VGCV compliance is difficult because of high drug costs and side effects, such as thrombocytopenia and leukopenia. Therefore, we studied the efficacy of ultra-low dose, short-duration VGCV (450 mg every other day for 3 months) in preventing CMV infection in ABO-incompatible (ABOiKT) and deceased donor kidney transplant (DDKT) recipients. METHODS: We retrospectively reviewed the medical records of all kidney transplant patients > 18 years old treated at Bong Seng Memorial Hospital from June 2009 to July 2016 who received ultra-low-dose VGCV prophylaxis (450 mg every other day for 3 months). The review included 74 CMV seropositive donor/seropositive recipient (D+/R+) ABOiKT and 78 CMV D+/R+DDKT recipients. The primary outcome was occurrence of CMV infection. Secondary outcomes were graft and patient survival and hematologic side effects. RESULTS: Mean prophylaxis and follow-up were 3 and 98 months, respectively. CMV disease occurrence was significantly higher in DDKT than in ABOiKT (12 cases, 8.1%, vs 1 case, .7%, P < .01). There were no significant differences in patient survival rate, graft survival rate, or hematologic side effects between the groups. CONCLUSION: Ultra-low-dose VGCV prophylaxis to prevent CMV infection is effective in ABOiKT, but other treatment protocols are needed for DDKT patients.

Placement of tunneled cuffed catheter for hemodialysis: Micropuncture kit versus Angiocath IV catheter.

INTRODUCTION: Tunneled cuffed catheters provide stable, instantaneous, long-term intravenous access for hemodialysis. Because catheterization is often performed in emergency situations, speed and accuracy are emphasized. METHODS: We retrospectively compared the Micropuncture kit with the standard 18-gauge Angiocath IV catheter for tunneled cuffed catheter insertion in the right jugular vein. From June 2016 to May 2017, 31 tunneled cuffed catheters were successfully inserted via the Micropuncture kit and another 31 via the Angiocath IV catheter. All patients underwent the same ultrasound-guided procedure performed by a single experienced interventionalist. Procedure time was the time from draping of the patient to the completion of povidone dressing after the catheterization. In our center, the Angio Lab nurse maintains records, including procedure time and method for every procedure. All patient records were retrospectively tracked through electronic medical record review. The primary outcome was procedure time and the secondary outcomes were complications and cost-effectiveness. RESULTS: There were no significant differences in the patients' demographic data between the two groups. However, procedure time was significantly shorter in the Angiocath group than in the Micropuncture group (12.4 ± 3.5 vs 17.6 ± 6.9 min, p = 0.001); there were no serious complications, such as hemorrhage, pneumothorax, or hematoma, in both groups. Moreover, cost-effectiveness was better in the Angiocath group than in the Micropuncture group (0.34 vs 52 US$, p < 0.01). CONCLUSIONS: Using the Angiocath IV catheter can reduce procedure time and cost with no severe complications. Moreover, experienced practitioners can reduce the risk of complications when using Angiocath. There are several limitations to this study. First, it was retrospective; second, it was not randomized; and finally, it was conducted by only one experienced interventionalist.

Treatment of acute antibody-mediated rejection using bortezomib: a case report.

Here we report the successful treatment of acute antibody-mediated rejection (AMR) with bortezomib. Bortezomib rescue treatment was administered after a 42-year-old woman failed to respond to steroid pulse and plasmapheresis with intravenous immunoglobulin (IVIG). The patient underwent a second renal transplantation with a deceased donor kidney. She was treated pre-operatively with rituximab (200 mg/body) and underwent plasmapheresis twice (day-1 and operation day) because ELISA screening revealed that her pre-operative peak panel reactive antibody (PRA) composition was 100% class I and 100% class II and 15 times of cross-match positive history during the waiting period for transplantation. The patients received induction therapy with Simulect (an IL-2-blocking agent). A 1-hour protocol biopsy revealed C4d-positivity and mild peritubular capillary inflammation. This was suggestive of early AMR-associated changes. After transplantation, the patient underwent plasmaphereses (nine times) with low-dose IVIG (2 mg/kg). Despite this treatment regimen, serum creatinine levels increased to 3.4 mg/dL on post-transplant day 15. A second graft biopsy was performed, which showed overt AMR with glomerulitis, peritubular capillary inflammation and no C4d deposition. On post-operative day (POD) 22, treatment with four doses of bortezomib (1.3 mg/m(2) ) was initiated with the patient's consent. On POD 55, renal function had recovered and serum creatinine was 1.5 mg/dL. In summary, bortezomib was administered as a rescue treatment for a patient who developed AMR that was refractory to a combination of plasmaphereses with low-dose IVIG and preemptive administration of rituximab.

Graft rupture after high-dose intravenous immunoglobulin therapy in a renal transplant patient.

Cases of life-threatening thromboses in pulmonary, coronary, cerebral and peripheral vessels are associated with high-dose intravenous immunoglobulin (IVIg) therapy that is generally considered safe. We experienced a patient with a renal graft rupture that developed after high-dose IVIg was administered for desensitization. A needle biopsy performed 4 days prior to the rupture revealed the presence of glomerular thrombosis and mesangiolysis. The ruptured nephrectomy specimen contained renal infarction around the haemorrhagic segment and arterial wall thickening with intimal fibrosis. This might have contributed to rupturing associated with small arterial and glomerular arteriolar thrombi. This is the first case of a graft rupture as a complication of high-dose IVIg we have encountered.

The targeted inhibition of mitochondrial Hsp90 overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis.

Previous studies have reported that a Gamitrinib variant containing triphenylphosphonium (G-TPP) binds to mitochondrial Hsp90 and rapidly inhibits its activity, thus inducing the apoptotic pathway in the cells. Accordingly, G-TPP shows a potential as a promising drug for the treatment of cancer. A cell can die from different types of cell death such as apoptosis, necrosis, necroptosis, and autophagic cell death. In this study, we further investigated the mechanisms and modes of cell death in the G-TPP-treated Hep3B and U937 cell lines. We discovered that G-TPP kills the U937 cells through the apoptotic pathway and the overexpression of Bcl-2 significantly inhibits U937 cell death to G-TPP. We further discovered that G-TPP kills the Hep3B cells by activating necroptosis in combination with the partial activation of caspase-dependent apoptosis. Importantly, G-TPP overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. We also observed that G-TPP induces compensatory autophagy in the Hep3B cell line. We further found that whereas there is a Bcl-2-Beclin 1 interaction in response to G-TPP, silencing the beclin 1 gene failed to block LC3-II accumulation in the Hep3B cells, indicating that G-TPP triggers Beclin 1-independent protective autophagy in Hep3B cells. Taken together, these data reveal that G-TPP induces cell death through a combination of death pathways, including necroptosis and apoptosis, and overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. These findings are important for the therapeutic exploitation of necroptosis as an alternative cell death program to bypass the resistance to apoptosis.

Etoposide induces a mixed type of programmed cell death and overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells.

The Bcl-2 protein is known to exert not only anti-apoptotic but also anti-autophagic activities. Numerous studies have demonstrated that etoposide, which is one of the most widely used cancer chemotherapy agents, induces apoptotic cell death. However, the exact molecular mechanism leading to cell death by etoposide remains to be resolved. This study aimed to dissect the mode of cell death induced by etoposide in Hep3B hepatoma cells. Furthermore, this study was conducted to examine whether etoposide overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells. We observed that Hep3B cells treated with etoposide show not only apoptotic but autophagic phenotypes. Autophagy inhibition by 3-methyladenine (3MA) and caspase inhibition by zVAD-fmk effectively decreased autophagic and apoptotic phenotypes, respectively. However, either zVAD-fmk or 3MA only partially prevented cell death. These data indicate that etoposide concomitantly induces autophagic cell death and apoptosis in Hep3B cells. Importantly, etoposide can effectively induce cell death in Bcl-2-overexpressing Hep3B cells. Conversely, staurosporine, which exclusively induces apoptosis in Hep3B cells, did not efficiently induce cell death in Bcl­2­overexpressing Hep3B cells. Staurosporine-treated Hep3B cells also showed an autophagic phenotype. While autophagy is cell death-inducing in Hep3B cells treated with etoposide, it is cytoprotective in Hep3B cells treated with staurosporine. To this end, we observed that etoposide-induced mixed type of programmed cell death is associated with the dissociation of Bcl-2 from Beclin-1. Taken together, etoposide induces a mixed type of programmed cell death and overcomes the resistance conferred by Bcl-2 in Hep3B hepatoma cells.