Lipomatous Soft Tissue Masses: Challenging the Paradigm of Routine Preoperative Biopsy.

BACKGROUND: Lipomatous masses are the most common soft tissue tumors. While the majority are benign lipomas, it is important to identify those masses that are malignant prior to excision. Current guidelines recommend core needle biopsy (CNB) for all lipomatous masses larger than 3-5 cm. The objective of this study was to determine if routine preoperative CNB based on mass size is necessary, or if radiographic features can guide the need for CNB. MATERIALS AND METHODS: Patients who underwent excision of extremity or truncal lipomatous masses at a single institution from October 2014 to July 2017 were retrospectively reviewed. By protocol, preoperative imaging was routinely obtained for all masses larger than 5 cm. High-risk radiographic features (intramuscular location, septations, nonfat nodules, heterogeneity, and ill-defined margins) and surgical pathology were evaluated to determine patients most likely to benefit from preoperative CNB. RESULTS: Of 178 patients, 2 (1.1%) had malignant tumors on surgical pathology. All masses smaller than 5 cm were benign and, if imaging was obtained, had two or fewer high-risk radiographic features. Both of the patients with malignant tumors had masses larger than 5 cm, preoperative imaging that showed at least four high-risk radiographic features, and underwent CNB prior to excision. CONCLUSIONS: The overall rate of malignancy is very low. The results of this study suggest that lipomatous masses smaller than 5 cm without concerning clinical characteristics do not require preoperative imaging or CNB. Conversely, lipomatous masses larger than 5 cm should undergo routine MRI with subsequent CNB if multiple high-risk radiographic features are present.

TKS5-positive invadopodia-like structures in human tumor surgical specimens.

Invadopodia, cancer cell protrusions with proteolytic activity, are functionally associated with active remodeling of the extracellular matrix. Here, we show that the invadopodia-related protein TKS5 is expressed in human pancreatic adenocarcinoma lines, and demonstrate that pancreatic cancer cells depend on TKS5 for invadopodia formation and function. Immunofluorescence staining of human pancreatic cancer cells reveals that TKS5 is a marker of mature and immature invadopodia. We also analyze the co-staining patterns of TKS5 and the commonly used invadopodia marker Cortactin, and find only partial co-localization of these two proteins at invadopodia, with a large fraction of TKS5-positive invadopodia lacking detectable levels of Cortactin. Whereas compelling evidence exist on the role of invadopodia as mediators of invasive migration in cultured cells and in animal models of cancer, these structures have never been detected inside human tumors. Here, using antibodies against TKS5 and Cortactin, we describe for the first time structures strongly resembling invadopodia in various paraffin-embedded human tumor surgical specimens from pancreas and other organs. Our results strongly suggest that invadopodia are present inside human tumors, and warrants further investigation on their regulation and occurrence in surgical specimens, and on the value of TKS5 antibodies as pathological research and diagnostic tools.

Detection of probable dementia cases in undiagnosed patients using structured and unstructured electronic health records.

BACKGROUND: Dementia is underdiagnosed in both the general population and among Veterans. This underdiagnosis decreases quality of life, reduces opportunities for interventions, and increases health-care costs. New approaches are therefore necessary to facilitate the timely detection of dementia. This study seeks to identify cases of undiagnosed dementia by developing and validating a weakly supervised machine-learning approach that incorporates the analysis of both structured and unstructured electronic health record (EHR) data. METHODS: A topic modeling approach that included latent Dirichlet allocation, stable topic extraction, and random sampling was applied to VHA EHRs. Topic features from unstructured data and features from structured data were compared between Veterans with (n = 1861) and without (n = 9305) ICD-9 dementia codes. A logistic regression model was used to develop dementia prediction scores, and manual reviews were conducted to validate the machine-learning results. RESULTS: A total of 853 features were identified (290 topics, 174 non-dementia ICD codes, 159 CPT codes, 59 medications, and 171 note types) for the development of logistic regression prediction scores. These scores were validated in a subset of Veterans without ICD-9 dementia codes (n = 120) by experts in dementia who performed manual record reviews and achieved a high level of inter-rater agreement. The manual reviews were used to develop a receiver of characteristic (ROC) curve with different thresholds for case detection, including a threshold of 0.061, which produced an optimal sensitivity (0.825) and specificity (0.832). CONCLUSIONS: Dementia is underdiagnosed, and thus, ICD codes alone cannot serve as a gold standard for diagnosis. However, this study suggests that imperfect data (e.g., ICD codes in combination with other EHR features) can serve as a silver standard to develop a risk model, apply that model to patients without dementia codes, and then select a case-detection threshold. The study is one of the first to utilize both structured and unstructured EHRs to develop risk scores for the diagnosis of dementia.

Morbidity among long-term survivors after pancreatoduodenectomy for pancreatic adenocarcinoma.

BACKGROUND: Because pancreatoduodenectomy for pancreatic adenocarcinoma is focused on disease-free and overall survival, morbidity among long-term survivors is not well described. This study sought to evaluate outcomes for long-term survivors of pancreatic cancer after pancreatoduodenectomy. METHODS: The authors identified 29 patients from their prospectively collected database of patients with pancreatic adenocarcinoma who had undergone pancreatoduodenectomy and were without evidence of disease during at least 3 years of follow-up evaluation. Demographics, treatment, and pathologic characteristics were collected for review. Data with regard to long-term sequelae also were collected, focusing on those complications requiring additional procedures and on the development of metachronous cancers. RESULTS: The median follow-up period was 83 months, with 62 % of patients still alive. All patients received an R0 resection, and 34 % of the patients had N1 disease. For 42 % of the patients, no significant subsequent sequelae occurred. In the four remaining patients (14 %), ascites developed, requiring repeated paracentesis or Denver shunt, with a median time to development (MTD) of 63 months. Six patients (21 %) experienced a biliary stricture requiring stent placement (MTD, 56 months). One patient experienced portal venous thrombosis requiring a venous stent (MTD, 52 months), and four patients (14 %) experienced clinically significant ulcers (MTD, 52 months). With regard to metachronous cancers, two patients experienced subsequent lymphomas (MTD, 92 months). CONCLUSIONS: Long-term survivors among patients who undergo pancreatoduodenectomy for pancreatic adenocarcinoma can experience significant late sequelae, which often manifest more than 3 years after surgery. As such, continued follow-up evaluation and counseling are warranted.

Neoadjuvant chemoradiation and duration of chemotherapy before surgical resection for pancreatic cancer: does time interval between radiotherapy and surgery matter?

BACKGROUND: Neoadjuvant chemoradiation and chemotherapy provided for borderline or locally advanced, potentially resectable pancreatic adenocarcinoma improves resectability rates. Response to therapy is also an important prognostic factor. There are no data in the literature regarding optimal time interval or duration of chemotherapy after chemoradiation before surgery, and pathologic response rates. Using our database, we evaluated these relationships and the effect on overall and progression-free survival. METHODS: We retrospectively analyzed the records of 83 patients who underwent neoadjuvant chemoradiation for locally advanced, potentially resectable, and borderline resectable pancreatic cancers before definitive resection. We divided patients into three groups according to time interval between completion of chemoradiation and resection: group A (0-10 weeks), group B (11-20 weeks), and group C (>20 weeks). After chemoradiation, patients underwent ongoing chemotherapy before resection. Pathologic response was defined as major (>95% fibrosis), partial (50-94% fibrosis), or minor (<50% fibrosis). RESULTS: There were 56 patients in group A, 17 patients in group B, and 10 patients in group C. Patients in groups B and C were significantly more likely to experience a major response than group A (p < 0.013). Patients in group C had significantly increased median progression-free and overall survival (p < 0.05). Multivariable classification and regression tree analysis demonstrated pathologic response to be the only significant factor in overall survival. CONCLUSIONS: Patients who underwent a prolonged time interval after neoadjuvant chemoradiation with ongoing chemotherapy were more likely to have an improved pathologic response at time of surgical resection, which was associated with improved median overall survival.

The Utility of ACR TI-RADS in Predicting False-Negative Fine Needle Aspiration for Thyroid Cancer.

BACKGROUND: Thyroid nodule fine needle aspiration (FNA) biopsies are associated with a low false-negative rate. There is limited data regarding the predictive value of American College of Radiology Thyroid Imaging Reporting and Data System for false-negative FNA. METHODS: This single-center retrospective study evaluated 119 patients who underwent thyroidectomy. The association of TR category, along with other clinical variables, with false-negative FNA was evaluated. RESULTS: The overall false-negative rate of FNA was 10.8% (n = 9). False-negative FNAs were associated with younger age (mean 42 years vs 50.6 years, P = .04), larger nodule size (mean 4.4 cm vs 3.2 cm, P = .03), and a lower TR category (median 3 v 4, P = .01). DISCUSSION: Lower TR category, younger age, and larger nodule size were associated with false-negative FNA of thyroid nodules. These findings should be taken into context when counseling patients with thyroid nodules who have a benign FNA.

Creating an Optimal Learning Environment in the Operating Room: Lessons From the Soccer Field.

For trainees, the operating room (OR) often represents an educational sanctuary, where for a few hours they can focus on their craft, rather than on phone calls, pages, and the never-ending task of electronic health record documentation. The OR provides a unique opportunity for unfettered one-on-one time with an attending surgeon at their side, where they can learn the art of surgery without interruption. It is vitally important to maximize learning in the OR, yet evidence suggests that it is not always an ideal educational environment. Considering the recent excitement over the World Cup soccer tournament (full disclosure: the senior author is an Argentine immigrant and soccer fan), in this article, we provide evidence-based ideas and suggestions on how to optimize learning in the OR using some analogies from the soccer field.

Rapid MRI Abdomen for Assessment of Clinically Suspected Acute Appendicitis in the General Adult Population: a Systematic Review.

OBJECTIVES: To perform a systematic review on the use of magnetic resonance imaging (MRI) of the abdomen to evaluate clinically suspected appendicitis in the general adult population. We examined the diagnostic accuracy, the reported trends of MRI use, and the factors that affect the utility of MRI abdomen, including study duration and cost-benefits. METHODS: We conducted a systematic literature search on PubMed, MEDLINE, Embase, Web of Science, and Cochrane Library databases. We enrolled primary studies investigating the use of MRI in diagnosing appendicitis in the general adult population, excluding studies that predominantly reported on populations not representative of typical adult appendicitis presentations, such as those focusing on paediatric or pregnant populations. RESULTS: Twenty-seven eligible primary studies and 6 secondary studies were included, totaling 2,044 patients from eight countries. The sensitivity and specificity of MRI for diagnosing appendicitis were 96% (95% CI: 93-97%) and 93% (95% CI: 80-98%), respectively. MRI can identify complicated appendicitis and accurately propose alternative diagnoses. The duration of MRI protocols in each primary study ranged between 2.26 and 30 minutes, and only one study used intravenous contrast agents in addition to the non-contrast sequences. Decision analysis suggests significant benefits for replacing computed tomography (CT) with MRI and a potential for cost reduction. Reported trends in MRI usage showed minimal utilisation in diagnostic settings even when MRI was available. CONCLUSIONS: MRI accurately diagnoses appendicitis in the general adult population and improves the identification of complicated appendicitis or alternative diagnoses compared to other modalities using a single, rapid investigation.

Identifying probable dementia in undiagnosed Black and White Americans using machine learning in Veterans Health Administration electronic health records.

The application of machine learning (ML) tools in electronic health records (EHRs) can help reduce the underdiagnosis of dementia, but models that are not designed to reflect minority population may perpetuate that underdiagnosis. To address the underdiagnosis of dementia in both Black Americans (BAs) and white Americans (WAs), we sought to develop and validate ML models that assign race-specific risk scores. These scores were used to identify undiagnosed dementia in BA and WA Veterans in EHRs. More specifically, risk scores were generated separately for BAs (n=10K) and WAs (n=10K) in training samples of cases and controls by performing ML, equivalence mapping, topic modeling, and a support vector-machine (SVM) in structured and unstructured EHR data. Scores were validated via blinded manual chart reviews (n=1.2K) of controls from a separate sample (n=20K). AUCs and negative and positive predictive values (NPVs and PPVs) were calculated to evaluate the models. There was a strong positive relationship between SVM-generated risk scores and undiagnosed dementia. BAs were more likely than WAs to have undiagnosed dementia per chart review, both overall (15.3% vs 9.5%) and among Veterans with >90th percentile cutoff scores (25.6% vs 15.3%). With chart reviews as the reference standard and varied cutoff scores, the BA model performed slightly better than the WA model (AUC=0.86 with NPV=0.98 and PPV=0.26 at >90th percentile cutoff vs AUC=0.77 with NPV=0.98 and PPV=0.15 at >90th). The AUCs, NPVs, and PPVs suggest that race-specific ML models can assist in the identification of undiagnosed dementia, particularly in BAs. Future studies should investigate implementing EHR-based risk scores in clinics that serve both BA and WA Veterans.

Clinical Features and Outcomes of Patients with Pancreaticobiliary Malignancies in Los Angeles County and Their Association with CA 19-9 Levels.

Although CA 19-9 is a commonly used tumor marker in the management of PBMs, the literature describing outcomes in patients with PBMs who have undetectable or low (hereinafter "low") CA 19-9 levels remains scarce. In this study, we sought to compare clinical features and outcomes in patients with PBMs and low CA 19-9 levels to those with normal and elevated CA 19-9 levels. METHODS: We retrospectively collected data on patients with biopsy-confirmed PBMs and stratified patients into categories based on their CA 19-9 level at diagnosis. Survival curves were estimated for patients in each of the three aforementioned CA 19-9 groups using the Kaplan-Meier method and compared using a Cox proportional hazards regression model. RESULTS: Of the 283 patients identified, 23 (8.1%) had low, 70 (24.7%) had normal, and 190 (67.1%) had elevated CA 19-9 levels. After controlling for sex, age, BMI, the presence of metastases at the time of diagnosis, and treatment with curative intent, the hazard ratio for death in the elevated CA 19-9 group compared to the low CA 19-9 group was 1.993 (95% CI 1.089-3.648; p = 0.025). CONCLUSION: The elevated CA 19-9 level compared to the low CA 19-9 level and the presence of metastases were associated with an increased hazard of death, while treatment with curative intent was associated with a decreased hazard of death.

Racial Disparities in Colorectal Cancer Care for Black Patients: Barriers and Solutions.

Racial disparities in colorectal cancer for Black patients have led to a significant mortality difference when compared to White patients, a gap which has remained to this day. These differences have been linked to poorer quality insurance and socioeconomic status in addition to lower access to high-quality health care resources, which are emblematic of systemic racial inequities. Disparities impact nearly every point along the colorectal cancer care continuum and include barriers to screening, surgical care, oncologic care, and surveillance. These critical faults are the driving forces behind the mortality difference Black patients face. Health care systems should strive to correct these disparities through both cultural competency at the provider level and public policy change at the national level.

The impact of waste reduction in general surgery operating rooms.

INTRODUCTION: Operating rooms are responsible for a significant burden of waste and negative environmental impact. This study aimed to reduce OR waste and improve both environmental impact and hospital cost savings. METHODS: The unused items in two standard single-use surgical packs were tracked for general surgery cases. A new pack was created excluding the most frequently unused items. The feasibility of the new pack was then tested, and a projected cost savings analysis was performed. RESULTS: A total of 35 general surgery operations were tracked using two standard packs ($89.51 or $93.68 per case, each 23.2 lbs). The new pack ($46.88 per case, 20.8 lbs) was then successfully used in nine cases. The projected cost-savings of substituting the new pack was $45,719 annually with a 2437 pounds annual waste reduction. CONCLUSIONS: Simple and feasible adjustments to standard single-use surgical packs can have a significant impact on waste reduction and cost-savings.

Patterns of gastric cancer metastasis in the United States.

BACKGROUND: Literature on the epidemiology of gastric cancer metastasis is limited, although outcomes are known to be poor. We describe patterns of gastric cancer metastasis and treatment in the United States. METHODS: Patients with metastatic gastric adenocarcinoma were identified in the NCDB from 2004 to 2016. We describe univariate associations between sites of metastasis and clinicopathologic characteristics and treatment modalities, using chi-square and Kruskal-Wallis tests. Overall survival was calculated using Kaplan-Meier estimation. RESULTS: 43% (n = 2028) of patients presented with peritoneal metastases, 26% (n = 1228) with liver metastases, 20% (n = 941) with distant nodes, and 11% (n = 552) with bone, brain or lung metastases. Compared to liver metastases, peritoneal metastases were more likely from an antral primary site (28% v. 16%); associated with signet ring histology (34% v. 6%); tumor grade of III/IV (85% vs. 60%) (p < 0.0001 for all). Isolated metastasis to distant lymph nodes had the longest median overall survival (7.6 months, p < 0.0001). CONCLUSIONS: Most patients with metastatic gastric cancer in the USA present with peritoneal disease. Predictors for peritoneal metastases include primary antral site, signet ring histology and higher tumor grades.

The Impact of Primary Care Physicians on the Surgical Presentation and Outcomes of Colorectal Cancer in Vulnerable Populations.

BACKGROUND: Multiple socioeconomic and clinical factors have been implicated in the health disparities that exist amongst vulnerable populations with colorectal cancer. Efforts have been directed toward addressing these factors to improve outcomes. We evaluate the impact of primary care physicians (PCP) on the surgical presentation and outcomes of colorectal cancer at a safety-net hospital. METHODS: A retrospective chart review of 331 patients diagnosed with colorectal adenocarcinoma between 2014 and 2020 at a single-institution urban county medical center. RESULTS: The cohort was predominantly male (59%) and Hispanic (52.1%). Thirty-two percent of patients had a PCP at time of diagnosis. Patients with PCPs compared to those without PCPs had significantly lower rates of acute presentation (perforation or obstruction) (17.0 vs 38.1%, P < .001), higher rates of surgical resection (83.0 vs 70.7%, P = .016), and were less likely to have metastatic disease at presentation (20.4 vs 33.5%, P = .02). Overall, having a PCP also improved probability of survival (HR 1.36, P < .04). CONCLUSION: Having a PCP at the time of colorectal cancer diagnosis is associated with improved outcomes in a safety-net population, with significant differences in surgical presentation and resection.

Routine pre-operative Covid testing in elective surgeries: Is it worth it?

BACKGROUND: Pre-procedural COVID-19 testing in patients scheduled for elective cases have become routine to reduce the risk of COVID-19 exposure and pulmonary complications related to perioperative COVID-19 infection, and to reduce the use of specific hospital resources among other reasons. This study evaluates the efficacy of universal COVID-19 testing for elective procedures. METHODS: Single institution retrospective observational study from July 2020 through August 2021. RESULTS: There were a total of 499 unique patients who were scheduled for 581 surgeries or procedures. A total of 569 anterior nares reverse transcriptase polymerase chain reaction (RT-PCR) tests were completed before scheduled procedure. There were 2 (0.35%) positive COVID tests, both of whom were asymptomatic and unvaccinated at time of testing, and 13 (2.2%) cancelled cases overall. The total cost for labor and materials during this period was $19,738, with each RT-PCR test costing $34.69 and each true positive test costing $9,869. CONCLUSIONS: Given the low COVID-19 positivity in the elective procedural patient population, testing protocols for elective procedures should be re-evaluated as the pandemic evolves.

Determinants of Psychosocial Distress in Breast Cancer Patients at a Safety Net Hospital.

INTRODUCTION: Psychosocial distress screening of cancer patients is an American College of Surgeons Commission on Cancer mandate for accredited cancer programs. We evaluated psychosocial distress in breast cancer patients to characterize risk factors for high distress scores at a safety net hospital. MATERIALS AND METHODS: The psychosocial distress screening form includes a list of potential issues and a distress score scaled from 1 through 10. Psychosocial distress screening results were retrospectively analyzed, along with patient demographics and clinical data. Cochran-Mantel-Haenszel test was applied to identify predictors for high distress scores, which were defined as a score of 5 and greater. RESULTS: 775 distress screens were completed by 171 breast cancer patients. High distress scores were reported in 21.3%. Patients who had no evidence of disease at time of screening were less likely to report a high distress score compared to those who were newly diagnosed or in active treatment (odds ratio 0.51, 95% CI, 0.38-0.68, P< .0001). Patients with high distress scores were more likely to report concerns with insurance (29.1% vs. 7.6%, P< .0001), transportation (16.4% vs. 4.6%, P< .0001), housing (15.2% vs 2.1%, P< .0001), sadness/depression (63.6% vs. 14.1, P< .0001), and physical issues (89.1% vs. 52.8%, P< .0001). CONCLUSION: Status of cancer at time of screening, particularly newly diagnosed cancer and active treatment of cancer were associated with high distress scores in this patient group. While there should be an emphasis to ensure patients with these risk factors receive psychosocial distress screening, routine periodic screening for all patients should continue to be implemented to ensure quality cancer care.

Chondroitin Sulfate Proteoglycan 4 as a Marker for Aggressive Squamous Cell Carcinoma.

Chondroitin sulfate (CS) proteoglycan 4 (CSPG4) is a cell surface proteoglycan that is currently under investigation as a marker of cancer malignancy, and as a potential target of anticancer drug treatment. CSPG4 acts as a driver of tumourigenesis by regulating turnover of the extracellular matrix (ECM) to promote tumour cell invasion, migration as well as inflammation and angiogenesis. While CSPG4 has been widely studied in certain malignancies, such as melanoma, evidence is emerging from global gene expression studies, which suggests a role for CSPG4 in squamous cell carcinoma (SCC). While relatively treatable, lack of widely agreed upon diagnostic markers for SCCs is problematic, especially for clinicians managing certain patients, including those who are aged or infirm, as well as those with underlying conditions such as epidermolysis bullosa (EB), for which a delayed diagnosis is likely lethal. In this review, we have discussed the structure of CSPG4, and quantitatively analysed CSPG4 expression in the tissues and pathologies where it has been identified to determine the usefulness of CSPG4 expression as a diagnostic marker and therapeutic target in management of malignant SCC.

A role for intestinal alkaline phosphatase in the maintenance of local gut immunity.

BACKGROUND AND AIMS: Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor known to dephosphorylate lipopolysaccharide (LPS); however, the role of IAP in the gut response to luminal bacteria remains poorly defined. We investigated immune responses of wild-type (WT) and IAP-knockout (IAP-KO) mice to LPS and Salmonella typhimurium challenges. METHODS: Cryostat sectioning and standard indirect immunohistochemical staining for major histocompatibility complex (MHC) class II molecules were performed on liver tissue from WT and IAP-KO mice. WT and IAP-KO mice were orally gavaged with S. typhimurium; bacterial translocation to mesenteric nodes, liver, and spleen was determined by tissue homogenization and plating. In other experiments, WT and IAP-KO mice received intraperitoneal injections of LPS, with subsequent quantification of complete blood counts and serum interleukin (IL)-6 by enzyme-linked immunosorbent assay (ELISA). WT and IAP-KO whole blood were plated and stimulated with LPS and Pam-3-Cys, followed by cytokine assays. RESULTS: Immunohistologic liver examinations showed increased expression of MHC class II molecules in IAP-KO mice. Following S. typhimurium challenge, WT mice appeared moribund compared with IAP-KO mice, with increased bacterial translocation. WT mice had >50% decrease (P<.005) in platelets and 1.8-fold (P<.05) increased serum IL-6 compared with IAP-KO mice in response to LPS injections. IAP-KO whole-blood stimulation with LPS and Pam-3-Cys resulted in increased IL-6 and tumor necrosis factor (TNF)-alpha secretion compared with WT. CONCLUSIONS: IAP-KO mice exhibit characteristics consistent with local LPS tolerance. Whole-blood response of IAP-KO mice did not reflect systemic tolerance. These data suggest that IAP is a local immunomodulating factor, perhaps regulating LPS-toll-like receptor 4 (TLR4) interaction between commensal microflora and intestinal epithelium.

Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase.

Intestinal alkaline phosphatase (IAP) is a small intestinal brush border enzyme that has been shown to function as a gut mucosal defense factor, but its precise mechanism of action remains unclear. We investigated the effects of IAP on specific bacteria and bacterial components to determine its molecular targets. Purulent fluid from a cecal ligation and puncture model, specific live and heat-killed bacteria (Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes), and a variety of proinflammatory ligands (LPS, CpG DNA, Pam-3-Cys, flagellin, and TNF) were incubated with or without calf IAP (cIAP). Phosphate release was determined by using a malachite green assay. The various fluids were applied to target cells (THP-1, parent HT-29, and IAP-expressing HT-29 cells) and IL-8 secretion measured by ELISA. cIAP inhibited IL-8 induction by purulent fluid in THP-1 cells by >35% (P < 0.005). HT29-IAP cells had a reduced IL-8 response specifically to gram-negative bacteria; >90% reduction compared with parent cells (P < 0.005). cIAP had no effect on live bacteria but attenuated IL-8 induction by heat-killed bacteria by >40% (P < 0.005). cIAP exposure to LPS and CpG DNA caused phosphate release and reduced IL-8 in cell culture by >50% (P < 0.005). Flagellin exposure to cIAP also resulted in reduced IL-8 secretion by >40% (P < 0.005). In contrast, cIAP had no effect on TNF or Pam-3-Cys. The mechanism of IAP action appears to be through dephosphorylation of specific bacterial components, including LPS, CpG DNA, and flagellin, and not on live bacteria themselves. IAP likely targets these bacterially derived molecules in its role as a gut mucosal defense factor.