Infrapopliteal Peripheral Vascular Interventions for Claudication are Performed Frequently in the USA and Are Associated with Poor Long Term Outcomes.

OBJECTIVE: Infrapopliteal peripheral vascular interventions (PVIs) for claudication are still performed in the USA. This study aimed to evaluate whether infrapopliteal PVI is associated with worse long term outcomes than isolated femoropopliteal PVI for treatment of claudication. METHODS: A retrospective analysis of fee for service claims in a national administrative database was conducted using 100% of the Medicare fee for service claims between 2017 and 2019 to capture all Medicare beneficiaries who underwent an index infra-inguinal PVI for claudication. Hierarchical Cox proportional hazards models were performed to assess the association of infrapopliteal PVI with conversion to chronic limb threatening ischaemia (CLTI), repeat PVI, and major amputation. RESULTS: In total, 36 147 patients (41.1% female; 89.7% age ≥ 65 years; 79.0% non-Hispanic White race) underwent an index PVI for claudication, of whom 32.6% (n = 11 790) received an infrapopliteal PVI. Of these, 61.4% (n = 7 245) received a concomitant femoropopliteal PVI and 38.6% (n = 4 545) received an isolated infrapopliteal PVI. The median follow up time was 3.5 years (interquartile range 2.7, 4.3). Patients receiving infrapopliteal PVI had a higher three year cumulative incidence of conversion to CLTI (26.0%; 95% confidence interval [CI] 24.9 - 27.2% vs. 19.9%; 95% CI 19.1 - 20.7%), repeat PVI (56.0%; 95% CI 54.8 - 57.3% vs. 45.7%; 95% CI 44.9 - 46.6%), and major amputation (2.2%; 95% CI 1.8 - 2.6% vs. 1.3%; 95% CI 1.1 - 1.5%) compared with patients receiving isolated femoropopliteal PVI. After adjusting for patient and physician level characteristics, the risk of conversion to CLTI (adjusted hazard ratio [aHR] 1.31, 95% CI 1.23 - 1.39), repeat PVI (aHR 1.12, 95% CI 1.05 - 1.20), and major amputation (aHR 1.72, 95% CI 1.42 - 2.07) remained significantly higher for patients receiving infrapopliteal PVI. An increasing number of infrapopliteal vessels treated during the index intervention was associated with increasingly poor outcomes (p < .001 for trend). CONCLUSION: Infrapopliteal PVI for claudication is associated with worse long term outcomes relative to isolated femoropopliteal PVI.

Infrapopliteal Endovascular Interventions for Claudication Are Associated with Poor Long-Term Outcomes in Medicare-Matched Registry Patients.

BACKGROUND: There are limited data supporting or opposing the use of infrapopliteal peripheral vascular interventions (PVI) for the treatment of claudication. OBJECTIVES: We aimed to evaluate the association of infrapopliteal PVI with long-term outcomes compared with isolated femoropopliteal PVI for the treatment of claudication. METHODS: We conducted a retrospective analysis of all patients in the Medicare-matched Vascular Quality Initiative database who underwent an index infrainguinal PVI for claudication from January 2004-December 2019 using Cox proportional hazards models. RESULTS: Of 14,261 patients (39.9% female; 85.6% age ≥65 years, 87.7% non-Hispanic white) who underwent an index infrainguinal PVI for claudication, 16.6% (N=2,369) received an infrapopliteal PVI. The median follow-up after index PVI was 3.7 years (IQR 2.1-6.1). Compared to patients who underwent isolated femoropopliteal PVI, patients receiving any infrapopliteal PVI had a higher 3-year cumulative incidence of conversion to CLTI (33.3% vs. 23.8%; P<0.001); repeat PVI (41.0% vs. 38.2%; P<0.01); and amputation (8.1% vs. 2.8%; P<0.001). After risk-adjustment, patients undergoing infrapopliteal PVI had a higher risk of conversion to CLTI (aHR 1.39, 95% CI, 1.25-1.53); repeat PVI (aHR 1.10, 95% CI, 1.01-1.19); and amputation (aHR 2.18, 95% CI, 1.77-2.67). Findings were consistent after adjusting for competing risk of death; in a 1:1 propensity-matched analysis; and in subgroup analyses stratified by TASC disease, diabetes, and end-stage kidney disease. CONCLUSIONS: Infrapopliteal PVI is associated with worse long-term outcomes than femoropopliteal PVI for claudication. These risks should be discussed with patients.

Conservative management of scrotal pyoceles - A case series and literature review.

STUDY OBJECTIVE: We describe the common presenting signs and symptoms, treatment modalities, and outcomes of acutely presenting scrotal pyoceles. METHODS: We conducted a retrospective chart review of all adult patients treated for ultrasound-confirmed scrotal pyoceles between 2010 and 2020 at two sites within the [redacted]. Vitals at presentation, microbiology, and inpatient courses including antibiotic treatment and surgical procedures were collected. RESULTS: A total of 360 scrotal ultrasounds were reviewed identifying 15 patients with pyoceles, 11 patients presenting to the emergency department and 4 hospitalized patients. The most common chief complaint was testicular pain (67%). Only seven patients (47%) met SIRS criteria upon presentation. All patients were initially treated with broad-spectrum antibiotics and observation; 11 (73%) responded to this management alone, while four patients (27%) required surgical drainage due to persistent infection. No patients contracted Fournier's gangrene. CONCLUSION: This study reports the largest published database of scrotal pyoceles to date and describes our clinical approach to management. While pyoceles have traditionally been treated aggressively with surgical drainage, this case series suggests that most patients improve with broad-spectrum antibiotic treatment and observation alone, requiring surgical drainage if infection persists. Future investigations including multi-institutional data will be necessary to validate our institution's approach.

Practice patterns surrounding the use of tibial interventions for claudication in the Medicare population.

OBJECTIVE: At present, no data are available to support the use of tibial interventions in the treatment of claudication. We characterized the practice patterns surrounding tibial peripheral vascular interventions (PVIs) for patients with claudication in the United States. METHODS: Using 100% Medicare fee-for-service claims from 2017 to 2019, we conducted a retrospective analysis of all patients who underwent an index PVI for claudication. Patients with any previous PVI, acute limb ischemia, or chronic limb-threatening ischemia in the preceding 12 months were excluded. The primary outcome was the receipt or delivery of tibial revascularization during an index PVI for claudication, defined as tibial PVI with or without concomitant femoropopliteal PVI. Univariable comparisons and multivariable hierarchical logistic regression were used to assess the patient and physician characteristics associated with the use of tibial PVI for claudication. RESULTS: Of 59,930 Medicare patients who underwent an index PVI for claudication between 2017 and 2019, 16,594 (27.7%) underwent a tibial PVI (isolated tibial PVI, 38.5%; tibial PVI with concomitant femoropopliteal PVI, 61.5%). Of the 1542 physicians included in our analysis, the median physician-level tibial PVI rate was 20.0% (interquartile range, 9.1%-37.5%). Hierarchical logistic regression suggested that patient-level characteristics associated with tibial PVI for claudication included male sex (adjusted odds ratio [aOR], 1.23), increasing age (aOR, 1.30-1.96), Black race (aOR, 1.47), Hispanic ethnicity (aOR, 1.86), diabetes (aOR, 1.36), no history of hypertension (aOR, 1.12), and never-smoking status (aOR, 1.64; P < .05 for all). Physician-level characteristics associated with tibial PVI for claudication included early-career status (aOR, 2.97), practice location in the West (aOR, 1.75), high-volume PVI practice (aOR, 1.87), majority of practice in an ambulatory surgery center or office-based laboratory setting (aOR, 2.37), and physician specialty. The odds of vascular surgeons performing tibial PVI were significantly lower compared with radiologists (aOR, 2.98) and cardiologists (aOR, 1.67; P < .05 for all). The average Medicare reimbursement per patient was dramatically higher for physicians performing high rates of tibial PVI (quartile 4 vs quartile 1-3, $12,023.96 vs $692.31 per patient; P < .001). CONCLUSIONS: Tibial PVI for claudication was performed more often by nonvascular surgeons in high-volume practices and high-reimbursement settings. Thus, a critical need exists to reevaluate the indications, education, and reimbursement policies surrounding these procedures.

Clinical Outcomes of Percutaneous Biliary Endoscopy: A 7-Year Single-Institution Experience.

PURPOSE: To evaluate safety and effectiveness of percutaneous biliary endoscopy (PBE) performed on patients ineligible for surgery or endoscopic retrograde cholangiopancreatography. MATERIALS AND METHODS: Retrospective review was conducted for all patients who underwent PBE at a single academic institution between June 2013 and February 2020; 39 patients underwent 58 choledochoscopy sessions, and 21 patients underwent 48 cholecystoscopy sessions. Choledochoscopy indications included stone removal (23 of 39 patients) or biliary stenosis evaluation (19 of 39 patients). Cholecystoscopy indications included calculous cholecystitis (18 of 21 patients) and symptomatic cholelithiasis (3 of 21 patients). Technical success, procedural and fluoroscopy times, and tube-free survival were assessed. RESULTS: For all PBEs performed for stone clearance, using disposable endoscopes led to shorter mean ± SD procedural (128.7 minutes ± 56.2 vs 240.2 minutes ± 184.6; P < .01) and fluoroscopy times (10.7 minutes ± 7.9 vs 16.5 minutes ± 12.0; P = .01) than using reusable endoscopes. Increasing institutional experience was associated with reduced procedural time (ß = -56.73; P < .001). Choledochoscopy technical success was 94.8% with 1 adverse event of bile duct perforation with bile leak requiring drainage. For patients with choledocholithiasis, biliary drains were removed in 14 (60.9%) patients, with a mean tube-free survival of 22.1 months ± 23.8. For cholecystoscopy, technical success was 93.8% with no adverse events. Cholecystostomy tubes were removed in 15 (71.4%) patients, with a mean tube-free survival of 7.5 months ± 8.8. CONCLUSIONS: This study supports PBE as a safe and feasible option for nonsurgical patients or those with altered anatomy precluding endoscopic retrograde cholangiopancreatography. Moreover, PBE may result in tube-free survival.

Radiofrequency Ablation versus Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma Awaiting Liver Transplant: An Analysis of the Scientific Registry of Transplant Recipients.

PURPOSE: To evaluate differences in waitlist mortality and dropout in liver transplant candidates with hepatocellular carcinoma (HCC) who undergo radiofrequency (RF) ablation versus transarterial chemoembolization (TACE). MATERIAL AND METHODS: From 2004 to 2013, 11,824 patients with HCC in the Scientific Registry of Transplant Recipients who underwent RF ablation or TACE were included and followed until December 31, 2019, or 5 years, whichever came first, and were stratified by the Milan criteria. Competing risk and Cox regression analyses to compare waitlist mortality and dropout were performed using adjusted hazard ratios (asHRs, with RF ablation group as reference). Regression models were adjusted for age, race, sex, calculated Model for End-Stage Liver Disease score, tumor size, and number. RESULTS: There was no difference in waitlist mortality and dropout for patients outside the Milan criteria (n = 1,226) who underwent TACE (19.2%) or RF ablation (19.0%) (asHR, 0.91; 95% CI, 0.79-1.03). There was also no difference for patients inside the Milan criteria (n = 10,598) in waitlist mortality/dropout (TACE 13.4% vs RF ablation 12.9%) (asHR, 1.29; 95% CI, 0.79-2.09). A subgroup analysis within the Milan criteria demonstrated no difference between TACE and RF ablation treatments in patients with a single tumor of ≤3 cm (asHR, 0.92; 95% CI, 0.77-1.10), with a single tumor of >3 cm (asHR, 1.03; 95% CI, 0.79-1.34), or with >1 tumor (asHR, 0.89; 95% CI, 0.72-1.09). CONCLUSIONS: Using the national registry data, no difference was found in waitlist mortality and dropout for transplant candidates with HCC who received TACE versus RF ablation.

Single-Use versus Reusable Endoscopes for Percutaneous Biliary Endoscopy with Lithotripsy: Technical Metrics, Clinical Outcomes, and Cost Comparison.

PURPOSE: To compare procedure and fluoroscopy time, technical and clinical success, and costs between single-use and reusable endoscopes in patients undergoing percutaneous biliary endoscopy (PBE) with lithotripsy. MATERIAL AND METHODS: Thirty-four patients (67 procedures) were retrospectively included in the study. The patients were treated with PBE for gallstone removal from October 24, 2014, to February 12, 2020, using reusable (28 procedures) or single-use (39 procedures) endoscopes. The procedure time, fluoroscopy time, technical success rate (accessing the biliary system and locating the gallstone), clinical success rate (at least partial gallstone removal), complication rate, and cost of use were compared between the procedures. RESULTS: The mean (± standard deviation) procedure time was not significantly different between single-use (136 minutes ± 45) and reusable endoscopes (136 minutes ± 51) (P = .47). The mean fluoroscopy time was significantly shorter for single-use endoscopes (11 minutes ± 8.4) than for reusable endoscopes (18 minutes ± 12) (P = .01). When comparing single-use versus reusable endoscopes, the technical success (95% [n = 37] vs 93% [n = 26]) and the clinical success (90% [n = 35] vs 75% [n = 21]) rates were not significantly different (both, P > .05). Only 1 complication was noted in the reusable endoscope group (P = .42). The cost per case was lower for single-use ($1,500) than for reusable ($3,987) endoscope procedures, primarily due to differences in capital costs and repair costs. CONCLUSIONS: Single-use endoscopes offer the potential for lower patient radiation exposure and lower cost per case, which may reduce the financial barriers to offering PBE in interventional radiology practices. The clinical and technical success rates did not differ by endoscope type.

Imaging Manifestations and Interventional Treatments for Hereditary Hemorrhagic Telangiectasia.

Hemorrhagic hereditary telangiectasia (HHT) is a rare autosomal dominant disorder that causes multisystem vascular malformations including mucocutaneous telangiectasias and arteriovenous malformations (AVMs). Clinical and genetic screening of patients with signs, symptoms, or a family history suggestive of HHT is recommended to confirm the diagnosis on the basis of the Curaçao criteria and prevent associated complications. Patients with HHT frequently have epistaxis and gastrointestinal bleeding from telangiectasias. Pulmonary AVMs are common right-to-left shunts between pulmonary arteries and veins that can result in dyspnea and exercise intolerance, heart failure, migraine headaches, stroke or transient ischemic attacks, brain abscesses, or in rare cases, pulmonary hemorrhage. Primary neurologic complications from cerebral AVMs, which can take on many forms, are less common but particularly severe complications of HHT. Multimodality imaging, including transthoracic echocardiography, Doppler US, CT, and MRI, is used in the screening and initial characterization of vascular lesions in patients with HHT. Diagnostic angiography is an important tool in characterization of and interventional treatments for HHT, particularly those in the lungs and central nervous system. A multidisciplinary approach to early diagnosis, treatment, imaging, and surveillance at high-volume HHT Centers of Excellence is recommended. Although a variety of idiopathic, traumatic, or genetic conditions can result in similar clinical and imaging features, the Curaçao criteria are particularly useful for the proper diagnosis of HHT. Imaging and treatment options are reviewed, with a focus on screening, diagnosis, and posttreatment findings, with the use of updated international guidelines. Online supplemental material is available for this article. ©RSNA, 2021.

Increasing Consulting Fee Payments to Interventional Radiologists in the United States From Industry, 2014 to 2018: Analysis of the Open Payments Database.

PURPOSE: To evaluate trends in consulting fees from industry to US-based interventional radiologists from 2014 to 2018. METHODS: Payments to interventional radiologists from January 1, 2014, to December 31, 2018, were analyzed from the CMS Open Payments Database. Payment type, total consulting fee payments per year and total payment per physician, and aggregate payments per company were analyzed before and after adjustment for outliers. RESULTS: Over the 5-year period, a total of $79.8 million was paid from industry to interventional radiologists, of which $17.6 million (22.1%) represented consulting fees. Per physician, the median total yearly amount paid as consulting fees was $5,050. Consulting fees increased from a total of $2.8 million per year in 2014 to $4.6 million per year in 2018 (+65%). After adjustment for outliers, consulting fee payments rose from $1.8 million to $3.5 million (+94%). The number of physicians paid each year increased from 156 to 219 physicians and the median payment increased from $4,327 to $5,419. Before ($5,118,966) and after adjustment, Sirtex Medical Inc paid the highest total aggregate consulting fee payments per year to self-identified interventional radiologists. After expansion to include both interventional and diagnostic radiologists by specialty type, Merck Sharp & Dohme Corp ($21,505,861) and Pfizer Inc ($11,798,255) followed by Sirtex Medical Inc ($8,276,818) paid the highest total aggregate in consulting fees. CONCLUSION: Total consulting fees to interventional radiologists increased between 2014 and 2018 by 65%, driven by both the increased number of physicians paid consulting fees and the increased average payment amount.

When More Is Better: Underused Advanced Imaging Exams That Can Improve Outcomes and Reduce Cost of Care.

Appropriate use of resources is a tenet of care transformation efforts, with a national campaign to reduce low-value imaging. The next level of performance improvement is to bolster evidence-based screening, imaging surveillance, and diagnostic innovation, which can avert more costly, higher-risk elements of unnecessary care like emergent interventions. Clinical scenarios in which underused advanced imaging can improve outcomes and reduce total cost of care are reviewed, including abdominal aortic aneurysm surveillance, coronary artery disease diagnosis, and renal mass characterization. Reliable abdominal aortic aneurysm surveillance imaging reduces emergency surgery and can be driven by radiologists incorporating best practice standardized recommendations in imaging interpretations. Coronary computed tomography angiography in patients with stable and unstable chest pain can reduce downstream resource use while improving outcomes. Preoperative 99mTc-sestamibi single-photon emission computed tomography (SPECT) reliably distinguishes oncocytoma from renal cell carcinoma to obviate unnecessary nephrectomy. As technological advances in diagnostic, molecular, and interventional radiology improve our ability to detect and cure disease, analyses of cost effectiveness will be critical to radiology leadership and sustainability in the transition to a value-based reimbursement model.

Vertebroplasty and kyphoplasty in the USA from 2004 to 2017: national inpatient trends, regional variations, associated diagnoses, and outcomes.

BACKGROUND: To explore the national inpatient trends, regional variations, associated diagnoses, and outcomes of vertebral augmentation (vertebroplasty and kyphoplasty) in the USA from 2004 to 2017. METHODS: Data from the National Inpatient Sample were used to study hospitalization records for percutaneous vertebroplasty and kyphoplasty. Longitudinal projections of trends and outcomes, including mortality, post-procedural complications, length of stay, disposition, and total hospital charges were analyzed. RESULTS: Following a period of decreased utilization from 2008 to 2012, hospitalizations for vertebroplasty and kyphoplasty plateaued after 2013. Total hospital charges and overall financial burden of hospitalizations for vertebroplasty and kyphoplasty increased to a peak of $1.9 billion (range $1.7-$2.2 billion) in 2017. Overall, 8% of procedures were performed in patients with a history of malignancy. In multivariable modeling, lung cancer (adjusted OR (aOR) 2.6 (range 1.4-5.1)) and prostate cancer (aOR 3.4 (range 1.2-9.4)) were associated with a higher risk of mortality. The New England region had the lowest frequency of routine disposition (14.1±1.1%) and the lowest average hospital charges ($47 885±$1351). In contrast, 34.0±0.8% had routine disposition in the West Central South region, and average hospital charges were as high as $99 836±$2259 in the Pacific region. The Mountain region had the lowest number of procedures (5365±272) and the highest mortality rate (1.2±0.3%). CONCLUSION: National inpatient trends of vertebroplasty and kyphoplasty utilization remained stable after a period of decline from 2008 to 2012, while the financial burden of hospitalizations increased. Despite recent improvements in outcomes, significant regional variations persisted across the USA.

Risk Factors for Complications Requiring Interventional Radiological Treatment After Hepatectomy.

PURPOSE: To identify perioperative factors that are significantly associated with complications requiring interventional radiology (IR) treatment after hepatectomy. METHODS: We retrospectively reviewed data from 11,243 patients in the USA who underwent hepatectomy from 2014 to 2016 using the National Surgical Quality Improvement Program database. Data on the following IR procedures were extracted: abscess drain placement, endovascular treatment for bleeding, and postoperative percutaneous biliary drain (PBD) placement up to 30 days postoperatively. Patients' clinical and intraoperative factors were examined. Population, univariate, and multivariable analyses were performed. P < 0.05 was considered significant. RESULTS: A total of 704 patients (6%) required IR treatment postoperatively, and 10,539 patients (94%) did not. On multivariable analysis, biliary reconstruction was a significant predictor of postoperative abscess drain placement (hazard ratio (HR), 3.5; 95% confidence interval (CI) 1.8, 6.5; P < .001), endovascular treatment for bleeding (HR, 3.3; 95% CI 1.4, 7.8 P = .006), and postoperative PBD placement (HR, 2.9; 95% CI 1.9, 4.2; P < .001). Compared with hepatectomy without biliary reconstruction, hepatectomy with biliary reconstruction was associated with significantly higher rates of complications treated with IR procedures (26% vs. 4.9%) and death within 30 days (6.0% vs. 1.2%) (both, P < .001). CONCLUSION: Biliary reconstruction is a strong predictor of the need for postoperative IR treatment after hepatectomy. One in four patients who underwent biliary reconstruction required IR treatment of a complication during the first 30 days after hepatectomy.

Evaluation of Serial Chest Radiographs of High-Altitude Pulmonary Edema Requiring Medical Evacuation from South Pole Station, Antarctica: From Diagnosis to Recovery.

INTRODUCTION: Chest radiography is a diagnostic tool commonly used by medical providers to assess high-altitude pulmonary edema (HAPE). Although HAPE often causes a pattern of pulmonary edema with right lower lung predominance, previous research has shown that there is no single radiographic finding associated with the condition. The majority of research involves a retrospective analysis of chest radiographs taken at the time of HAPE diagnosis. Little is known about the radiographic progression of HAPE during treatment or medical evacuation. MATERIALS AND METHODS: Three sequential chest radiographs were obtained from two patients diagnosed with HAPE at the Amundsen-Scott South Pole Station, Antarctica, who required treatment and medical evacuation. Deidentified and temporally randomized images were reviewed in a blinded fashion by two radiologists. A score of 0 (normal lung) to 4 (alveolar disease) was assigned for each of the four lung quadrants for an aggregate possible score ranging from 0 to 16 for each radiograph. RESULTS: Patient 1's initial radiograph showed severe HAPE with an initial score of 13. Despite a rapid clinical improvement after medical evacuation, he continued to show multifocal radiographic evidence of disease in all the lung quadrants on day 1 (score of 11) and day 2 (score of 5). Patient 2's radiographs showed less severe disease at presentation (score of 6). Despite the need for continued treatment, his radiographs showed a rapid improvement, with radiographic score decreasing to 3 on day 1 and 1 on day 3. CONCLUSION: The chest radiographs showed serial improvement after medical evacuation in both patients. There was not a strong correlation between clinical symptoms and radiographic severity in subsequent images.

Surgical Residents as Certified Bilingual Speakers: A Quality Improvement Initiative.

BACKGROUND: The objective of this quality improvement initiative was to identify general surgery residents proficient in a non-English language and have each attempt the Clinician Cultural and Linguistic Assessment (CCLA) to become qualified bilingual staff speakers. METHODS: General surgery house staff were asked to self-identify as proficient in a language other than English. Fees for the certification examination were waived, and each resident was excused from clinical duties to complete the exam. McNemar's test was used for statistical analysis. RESULTS: All residents responded to the initial survey, with 18/65 reporting a non-English language proficiency. Of the 12 residents who sat for the CCLA exam, 9 (75.0%) passed, with 5 certifying in the most commonly spoken non-English languages at this institution. The number of certified residents increased from 1 to 10 (1.5 % to 15.4%, p = 0.004). CONCLUSION: Language barriers result in health care disparities for patients with limited English proficiency. This reproducible quality improvement initiative significantly increased the number of qualified bilingual speakers, while 25.0% of self-described proficient speakers did not demonstrate adequate language proficiency. These newly certified providers allow for increased language concordant care, which may be associated with improved outcomes.

Loss of VOPP1 overexpression in squamous carcinoma cells induces apoptosis through oxidative cellular injury.

The vesicular overexpressed in cancer prosurvival protein 1 (VOPP1) gene product (previously known as GASP and ECOP) has a poorly characterized functional role in cancer cells, although its expression levels are known to be elevated in many cancer types. To determine the role that VOPP1 has in human squamous cell carcinoma (SCC), a series of siRNA-mediated expression knockdown experiments were performed in carcinoma-derived model systems with confirmed endogenous VOPP1 overexpression (three SCC-derived cell lines: SCC-9, FaDu, and H2170, as well as the cervical adenocarcinoma HeLa cell line, which has been examined in relevant previous reports). The data indicate that VOPP1 knockdown induces cell death at 72 h post-transfection and this is caused by the induction of apoptosis via the intrinsic pathway. Analysis of microarray gene expression profiling showed that genes whose expression was affected by VOPP1 knockdown exhibited enrichment in annotations of oxidative stress and mitochondrial dysfunction. Reporters of reactive oxygen species (ROS) and mitochondrial membrane potential show that ROS levels become elevated and mitochondrial dysfunction occurs with VOPP1 knockdown at time points before the activation of effector caspases and cell death seen at later time points. Furthermore, the introduction of the antioxidant N-acetyl cysteine was able to abrogate the induction of apoptosis observed with VOPP1 knockdown in a dose-responsive manner. Reporter constructs for NF-κB-mediated transcription are not affected in SCC cell lines by VOPP1 knockdown. Taken together, these data support the hypothesis that VOPP1 overexpression in cancer participates in the control of the intracellular redox state, and that its loss leads to oxidative cellular injury leading to cell death by the intrinsic apoptotic pathway.