Do not get stumped: multimodality imaging findings of early and late post-cholecystectomy complications.

Cholecystectomy is the most performed intra-abdominal surgical procedure in the US, with 1.2 million performed annually, and is predominantly performed laparoscopically. Although largely safe, laparoscopic cholecystectomy results in higher rates of abdominal symptoms consisting of abdominal pain and dyspepsia, which may persist or recur, collectively known as post-cholecystectomy syndrome. This article aims to (1) provide an overview of post-cholecystectomy syndrome with an emphasis on biliary complications and emergent imaging findings, (2) illustrate the spectrum of imaging findings of early and late post-cholecystectomy complications, (3) enumerate the role of various imaging modalities in evaluating post-cholecystectomy complications and address the role of selective trans-catheter coil embolization in managing bile leaks, and (4) discuss pearls and pitfalls in imaging following cholecystectomy. While common first-line imaging modalities for post-cholecystectomy complications include CT and sonography, ERCP and MRCP can delineate the biliary tree with greater detail. Scintigraphy has a higher sensitivity and specificity than CT or sonography for diagnosing bile leak and may preclude the need for ERCP. Post-operative complications include biliary duct injury or leak, biliary obstruction, remnant gallbladder/cystic duct stones and inflammation, biliary dyskinesia, papillary stenosis, and vascular injury. Subtle cases resulting in lethal outcomes, such as hemorrhage from the gallbladder bed without major vessel injury, have also been described. Cases presented will include biliary complications such as post-cholecystectomy stump cholecystitis, nonbiliary complications such as subcapsular hematoma, and normal post-surgical findings such as oxidized regenerated cellulose. Post-operative biliary complications can cause significant morbidity and mortality, and thus familiarity with the expected post-surgical appearance of the gallbladder fossa and biliary tract, as well as understanding the spectrum of complications and associated multimodality imaging findings, are essential for emergency radiologists and those practicing in the acute care setting to direct appropriate patient management. Furthermore, many of the postoperative complications can be managed by noninvasive percutaneous interventional procedures, from drain placement to cystic artery and cystic duct stump embolization.

Blunt thoracic trauma: role of chest radiography and comparison with CT - findings and literature review.

In the setting of acute trauma where identification of critical injuries is time-sensitive, a portable chest radiograph is broadly accepted as an initial diagnostic test for identifying benign and life-threatening pathologies and guiding further imaging and interventions. This article describes chest radiographic findings associated with various injuries resulting from blunt chest trauma and compares the efficacy of the chest radiograph in these settings with computed tomography (CT). Common chest radiographic findings in blunt thoracic injuries will be reviewed to improve radiologic identification, expedite management, and improve trauma morbidity and mortality. This article discusses demographic information, mechanism of specific injuries, common imaging findings, imaging pearls, and pitfalls and exhibits several classic imaging findings in blunt chest trauma. Thoracic structures commonly injured in blunt trauma that will be discussed in this article include vasculature structures (aortic trauma), the heart (cardiac contusion, pericardial effusion), the esophagus (esophageal perforation), pleural space and airways (pneumothorax, hemothorax, bronchial injury), lungs (pulmonary contusion), the diaphragm (diaphragmatic rupture), and the chest wall (flail chest). Chest radiography plays an important role in the initial evaluation of blunt chest trauma. While CT imaging has a higher sensitivity than chest radiography, it remains a valuable tool due to its ability to provide rapid diagnostic information in time-sensitive trauma situations and is ubiquitously available in the trauma bay. Familiarity with the gamut of injuries that may occur as well as identification of the associated chest radiograph findings can aid in timely diagnoses and prompt management in the setting of acute blunt chest trauma.

Beyond acute cholecystitis-gallstone-related complications and what the emergency radiologist should know.

The purpose of this study is to emphasize the imaging features of complications of gallstones beyond the cystic duct on ultrasound (US), enhanced and nonenhanced computed tomography (CECT and NECT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP). This article includes a brief overview of gallstone imaging and emerging trends in the detection of gallstones. This review article will highlight complications of gallstones, including choledocholithiasis, gallstone pancreatitis, acute cholangitis, Mirizzi syndrome, cholecystobiliary and cholecystoenteric fistulas, and gallstone ileus. Imaging findings and limitations of US, CT, MRI, and ERCP will be discussed. The review article will also briefly discuss the management of each disease. The presence of gallstones beyond the level of the cystic duct can lead to a spectrum of diseases, and emergency radiologists play a critical role in disease management by providing a timely diagnosis. Documenting the location of a gallstone within the common bile duct (CBD) in symptomatic cholelithiasis and the presence of acute interstitial edematous pancreatitis and/or ascending cholangitis plays a pivotal role in disease management. Establishing the presence of ectopic gallstones and biliary-enteric fistulae has a significant role in directing patient management.

Multireader evaluation of radiologist performance for COVID-19 detection on emergency department chest radiographs.

BACKGROUND: Chest radiographs (CXR) are frequently used as a screening tool for patients with suspected COVID-19 infection pending reverse transcriptase polymerase chain reaction (RT-PCR) results, despite recommendations against this. We evaluated radiologist performance for COVID-19 diagnosis on CXR at the time of patient presentation in the Emergency Department (ED). MATERIALS AND METHODS: We extracted RT-PCR results, clinical history, and CXRs of all patients from a single institution between March and June 2020. 984 RT-PCR positive and 1043 RT-PCR negative radiographs were reviewed by 10 emergency radiologists from 4 academic centers. 100 cases were read by all radiologists and 1927 cases by 2 radiologists. Each radiologist chose the single best label per case: Normal, COVID-19, Other - Infectious, Other - Noninfectious, Non-diagnostic, and Endotracheal Tube. Cases labeled with endotracheal tube (246) or non-diagnostic (54) were excluded. Remaining cases were analyzed for label distribution, clinical history, and inter-reader agreement. RESULTS: 1727 radiographs (732 RT-PCR positive, 995 RT-PCR negative) were included from 1594 patients (51.2% male, 48.8% female, age 59 ± 19 years). For 89 cases read by all readers, there was poor agreement for RT-PCR positive (Fleiss Score 0.36) and negative (Fleiss Score 0.46) exams. Agreement between two readers on 1638 cases was 54.2% (373/688) for RT-PCR positive cases and 71.4% (679/950) for negative cases. Agreement was highest for RT-PCR negative cases labeled as Normal (50.4%, n = 479). Reader performance did not improve with clinical history or time between CXR and RT-PCR result. CONCLUSION: At the time of presentation to the emergency department, emergency radiologist performance is non-specific for diagnosing COVID-19.

Complications of cholecystitis: a comprehensive contemporary imaging review.

Acute cholecystitis is a common cause of right upper quadrant pain in patients presenting to the emergency department. Ultrasound, computed tomography, HIDA scans, and magnetic resonance imaging are increasingly utilized to evaluate suspected cases. The prognosis of acute cholecystitis is usually excellent with timely diagnosis and management. However, complications associated with cholecystitis pose a considerable challenge to the clinician and radiologist. Complications of acute cholecystitis may result from secondary bacterial infection or mural ischemia secondary to increased intramural pressure. The recognized subtypes of complicated cholecystitis are hemorrhagic, gangrenous, and emphysematous cholecystitis, as well as gallbladder perforation. Acute acalculous cholecystitis is a form of cholecystitis that occurs as a complication of severe illness in the absence of gallstones or without gallstone-related inflammation. Complicated cholecystitis may cause significant morbidity and mortality, and early diagnosis and recognition play a pivotal role in the management and early surgical planning. As appropriate utilization of imaging resources plays an essential role in diagnosis and management, the emergency radiologist should be aware of the spectrum of complications related to cholecystitis and the characteristic imaging features. This article aims to offer a comprehensive contemporary review of clinical and cross-sectional imaging findings of complications associated with cholecystitis. In conclusion, cross-sectional imaging is pivotal in identifying the complications related to cholecystitis. Preoperative detection of this complicated cholecystitis can help the care providers and operating surgeon to be prepared for a potentially more complicated procedure and course of recovery.

Pancreatic Trauma: Imaging Review and Management Update.

Traumatic injuries of the pancreas are uncommon and often difficult to diagnose owing to subtle imaging findings, confounding multiorgan injuries, and nonspecific clinical signs. Nonetheless, early diagnosis and treatment are critical, as delays increase morbidity and mortality. Imaging has a vital role in diagnosis and management. A high index of suspicion, as well as knowledge of the anatomy, mechanism of injury, injury grade, and role of available imaging modalities, is required for prompt accurate diagnosis. CT is the initial imaging modality of choice, although the severity of injury can be underestimated and assessment of the pancreatic duct is limited with this modality. The time from injury to definitive diagnosis and the treatment of potential pancreatic duct injury are the primary factors that determine outcome following pancreatic trauma. Disruption of the main pancreatic duct (MPD) is associated with higher rates of complications, such as abscess, fistula, and pseudoaneurysm, and is the primary cause of pancreatic injury-related mortality. Although CT findings can suggest pancreatic duct disruption according to the depth of parenchymal injury, MR cholangiopancreatography and endoscopic retrograde cholangiopancreatography facilitate direct assessment of the MPD. Management of traumatic pancreatic injury depends on multiple factors, including mechanism of injury, injury grade, presence (or absence) of vascular injury, hemodynamic status of the patient, and associated organ damage. ©RSNA, 2020 See discussion on this article by Patlas.

A parametric ribcage geometry model accounting for variations among the adult population.

The objective of this study is to develop a parametric ribcage model that can account for morphological variations among the adult population. Ribcage geometries, including 12 pair of ribs, sternum, and thoracic spine, were collected from CT scans of 101 adult subjects through image segmentation, landmark identification (1016 for each subject), symmetry adjustment, and template mesh mapping (26,180 elements for each subject). Generalized procrustes analysis (GPA), principal component analysis (PCA), and regression analysis were used to develop a parametric ribcage model, which can predict nodal locations of the template mesh according to age, sex, height, and body mass index (BMI). Two regression models, a quadratic model for estimating the ribcage size and a linear model for estimating the ribcage shape, were developed. The results showed that the ribcage size was dominated by the height (p=0.000) and age-sex-interaction (p=0.007) and the ribcage shape was significantly affected by the age (p=0.0005), sex (p=0.0002), height (p=0.0064) and BMI (p=0.0000). Along with proper assignment of cortical bone thickness, material properties and failure properties, this parametric ribcage model can directly serve as the mesh of finite element ribcage models for quantifying effects of human characteristics on thoracic injury risks.

Inter-radiologist agreement for CT scoring of pediatric splenic injuries and effect on an established clinical practice guideline.

BACKGROUND: The American Pediatric Surgical Association (APSA) advocates for the use of a clinical practice guideline to direct management of hemodynamically stable pediatric spleen injuries. The clinical practice guideline is based on the CT score of the spleen injury according to the American Association for the Surgery of Trauma (AAST) CT scoring system. OBJECTIVE: To determine the potential effect of radiologist agreement for CT scoring of pediatric spleen injuries on an established APSA clinical practice guideline. MATERIALS AND METHODS: We retrospectively analyzed blunt splenic injuries occurring in children from January 2007 to January 2012 at a single level 1 trauma center (n = 90). Abdominal CT exams performed at clinical presentation were reviewed by four radiologists who documented the following: (1) splenic injury grade (AAST system), (2) arterial extravasation and (3) pseudoaneurysm. Inter-rater agreement for AAST injury grade was assessed using the multi-rater Fleiss kappa and Kendall coefficient of concordance. Inter-rater agreement was assessed using weighted (AAST injury grade) or prevalence-adjusted bias-adjusted (binary measures) kappa statistics; 95% confidence intervals were calculated. We evaluated the hypothetical effect of radiologist disagreement on an established APSA clinical practice guideline. RESULTS: Inter-rater agreement was good for absolute AAST injury grade (kappa: 0.64 [0.59­0.69]) and excellent for relative AAST injury grade (Kendall w: 0.90). All radiologists agreed on the AAST grade in 52% of cases. Based on an established clinical practice guideline, radiologist disagreement could have changed the decision for intensive care management in 11% (10/90) of children, changed the length of hospital stay in 44% (40/90), and changed the time to return to normal activity in 44% (40/90). CONCLUSION: Radiologist agreement when assigning splenic AAST injury grades is less than perfect, and disagreements have the potential to change management in a substantial number of pediatric patients.

A statistical skull geometry model for children 0-3 years old.

Head injury is the leading cause of fatality and long-term disability for children. Pediatric heads change rapidly in both size and shape during growth, especially for children under 3 years old (YO). To accurately assess the head injury risks for children, it is necessary to understand the geometry of the pediatric head and how morphologic features influence injury causation within the 0-3 YO population. In this study, head CT scans from fifty-six 0-3 YO children were used to develop a statistical model of pediatric skull geometry. Geometric features important for injury prediction, including skull size and shape, skull thickness and suture width, along with their variations among the sample population, were quantified through a series of image and statistical analyses. The size and shape of the pediatric skull change significantly with age and head circumference. The skull thickness and suture width vary with age, head circumference and location, which will have important effects on skull stiffness and injury prediction. The statistical geometry model developed in this study can provide a geometrical basis for future development of child anthropomorphic test devices and pediatric head finite element models.

Development and Validation of Statistical Models of Femur Geometry for Use with Parametric Finite Element Models.

Statistical models were developed that predict male and female femur geometry as functions of age, body mass index (BMI), and femur length as part of an effort to develop lower-extremity finite element models with geometries that are parametric with subject characteristics. The process for developing these models involved extracting femur geometry from clinical CT scans of 62 men and 36 women, fitting a template finite element femur mesh to the surface geometry of each patient, and then programmatically determining thickness at each nodal location. Principal component analysis was then performed on the thickness and geometry nodal coordinates, and linear regression models were developed to predict principal component scores as functions of age, BMI, and femur length. The average absolute errors in male and female external surface geometry model predictions were 4.57 and 4.23 mm, and the average absolute errors in male and female thickness model predictions were 1.67 and 1.74 mm. The average error in midshaft cortical bone areas between the predicted geometries and the patient geometries was 4.4%. The average error in cortical bone area between the predicted geometries and a validation set of cadaver femur geometries across 5 shaft locations was 2.9%.

A statistical human rib cage geometry model accounting for variations by age, sex, stature and body mass index.

In this study, we developed a statistical rib cage geometry model accounting for variations by age, sex, stature and body mass index (BMI). Thorax CT scans were obtained from 89 subjects approximately evenly distributed among 8 age groups and both sexes. Threshold-based CT image segmentation was performed to extract the rib geometries, and a total of 464 landmarks on the left side of each subject׳s ribcage were collected to describe the size and shape of the rib cage as well as the cross-sectional geometry of each rib. Principal component analysis and multivariate regression analysis were conducted to predict rib cage geometry as a function of age, sex, stature, and BMI, all of which showed strong effects on rib cage geometry. Except for BMI, all parameters also showed significant effects on rib cross-sectional area using a linear mixed model. This statistical rib cage geometry model can serve as a geometric basis for developing a parametric human thorax finite element model for quantifying effects from different human attributes on thoracic injury risks.

Emergency radiology elective improves second-year medical students' perceived confidence and knowledge of appropriate imaging utilization.

RATIONALE AND OBJECTIVES: Given recent advances in and wider availability of complex imaging, physicians are expected to understand imaging appropriateness. We introduced second-year medical students to the American College of Radiology Appropriateness Criteria (ACR-AC) in an interactive case-based elective to demonstrate their use in imaging for common emergency department clinical complaints. MATERIALS AND METHODS: Prospective pre- and post-test design assessed second-year medical students' performance on case-based knowledge applications and self-assessed confidence related to ACR-AC guidelines compared to second-year students participating in a different concurrent radiology elective. Students participated in a 3-day elective covering the ACR-AC, comparative effective imaging, and risks associated with imaging radiation exposure, with outcomes of perceived confidence using a 5-point Likert scale and knowledge of ACR-AC using case-based multiple choice questions. Analysis included computing mean scores and assessing effect sizes for changes in knowledge. RESULTS: Before the elective, 24 students scored an average of 3.45 questions correct of 8 (43.1%). On course completion, students scored an average of 5.3 questions correct of the same questions (66.3%) (P < .001; effect size [Cohen's d] = 1.3940. In the comparison group, 12 students scored an average of 3.08 questions (38.5%) correctly pretest and 3.09 questions (38.6%) correctly post-test (P > .85; effect size = 0.008). Students' confidence in ordering appropriate imaging improved nearly 2-fold from a range of 1.9 to 3.2 (on a scale of 1.0 to 5.0) to a range of 3.7 to 4.5. CONCLUSIONS: Following a short radiology elective, second-year medical students improved their knowledge of appropriate image utilization and perceived awareness of the indications, contraindications, and effects of radiation exposure related to medical imaging.

Effects of BMI on the risk and frequency of AIS 3+ injuries in motor-vehicle crashes.

OBJECTIVE: Determine the effects of BMI on the risk of serious-to-fatal injury (Abbreviated Injury Scale ≥ 3 or AIS 3+) to different body regions for adults in frontal, nearside, farside, and rollover crashes. DESIGN AND METHODS: Multivariate logistic regression analysis was applied to a probability sample of adult occupants involved in crashes generated by combining the National Automotive Sampling System (NASS-CDS) with a pseudoweighted version of the Crash Injury Research and Engineering Network database. Logistic regression models were applied to weighted data to estimate the change in the number of occupants with AIS 3+ injuries if no occupants were obese. RESULTS: Increasing BMI increased risk of lower-extremity injury in frontal crashes, decreased risk of lower-extremity injury in nearside impacts, increased risk of upper-extremity injury in frontal and nearside crashes, and increased risk of spine injury in frontal crashes. Several of these findings were affected by interactions with gender and vehicle type. If no occupants in frontal crashes were obese, 7% fewer occupants would sustain AIS 3+ upper-extremity injuries, 8% fewer occupants would sustain AIS 3+ lower-extremity injuries, and 28% fewer occupants would sustain AIS 3+ spine injuries. CONCLUSIONS: Results of this study have implications on the design and evaluation of vehicle safety systems.

Development, validation, and application of a parametric pediatric head finite element model for impact simulations.

In this study, a statistical model of cranium geometry for 0- to 3-month-old children was developed by analyzing 11 CT scans using a combination of principal component analysis and multivariate regression analysis. Radial basis function was used to morph the geometry of a baseline child head finite element (FE) model into models with geometries representing a newborn, a 1.5-month-old, and a 3-month-old infant head. These three FE models were used in a parametric study of near-vertex impact conditions to quantify the sensitivity of different material parameters. Finally, model validation was conducted against peak head accelerations in cadaver tests under different impact conditions, and optimization techniques were used to determine the material properties. The results showed that the statistical model of cranium geometry produced realistic cranium size and shape, suture size, and skull/suture thickness, for 0- to 3-month-old children. The three pediatric head models generated by morphing had mesh quality comparable to the baseline model. The elastic modulus of skull had a greater effect on most head impact response measurements than other parameters. Head geometry was a significant factor affecting the maximal principal stress of the skull (p = 0.002) and maximal principal strain of the suture (p = 0.021) after controlling for the skull material. Compared with the newborn head, the 3-month-old head model produced 6.5% higher peak head acceleration, 64.8% higher maximal principal stress, and 66.3% higher strain in the suture. However, in the skull, the 3-month-old model produced 25.7% lower maximal principal stress and 11.5% lower strain than the newborn head. Material properties of the brain had little effects on head acceleration and strain/stress within the skull and suture. Elastic moduli of the skull, suture, dura, and scalp determined using optimization techniques were within reported literature ranges and produced impact response that closely matched those measured in previous cadaver tests. The method developed in this study made it possible to investigate the age effects from geometry changes on pediatric head impact responses. The parametric study demonstrated that it is important to consider the material properties and geometric variations together when estimating pediatric head responses and predicting head injury risks.

Effects of osteoporosis on AIS 3+ injury risk in motor-vehicle crashes.

Older occupants in motor-vehicle crashes are more likely to experience injury than younger occupants. One possible reason for this is that increasing age is associated with increased prevalence of osteoporosis, which decreases bone strength. Crash-injury data were used with Bayes' Theorem to estimate the conditional probability of AIS 3+ skeletal injury given that an occupant is osteoporotic for the injury to the head, spine, thorax, lower extremities, and upper extremities. This requires the conditional probabilities of osteoporosis given AIS 3+ injury for each of the body regions, which were determined from analysis of the Crash Injury Research and Engineering Network database. It also requires information on probability of osteoporosis in the crash-involved population and the probabilities of AIS 3+ skeletal injury to different body regions in crashes. The latter probabilities were obtained from the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) database. The former was obtained by modeling the probability of osteoporosis in the US populations using data from the 2006 National Health Examination Nutrition Survey and applying this model to the estimate of the crash-involved population in NASS-CDS. To attempt to account for the effects of age on injury outcome that are independent of osteoporosis, only data from occupants who were 60 years of age or older were used in all analyses. Results indicate that the only body region that experiences a statistically significant change in fracture injury risk with osteoporosis is the spine, for which osteoporosis increases the risk of AIS 3+ fracture by 3.28 times, or from 0.41% to 1.34% (p<0.0001). This finding suggests that the increase in AIS 3+ injury risk with age for non-spine injuries is likely influenced by factors other than osteoporosis.

Pancreatic manifestations of von Hippel-Lindau disease-effect of imaging on clinical management.

OBJECTIVE: To assess the impact of imaging on pancreatic lesion management in von Hippel-Lindau disease (VHL). METHODS: We reviewed sequential computed tomography (CT) and magnetic resonance examinations (1997-2008) of 33 patients with VHL who had at least 1 pancreatic lesion. RESULTS: One hundred sixty-seven imaging studies demonstrated innumerable simple pancreatic cysts and 58 complex pancreatic masses: 24 were complex cystic and 34 were solid (30 small [2 cm]). Aggregate annual growth was significant in complex cystic and solid masses (mean, 0.39 cm/y [P = 0.006] and 0.14 cm/y [P = 0.045]). Solid mass growth differed by size (small: 0.06 cm/y [range, -0.09 to 0.31 cm/y]; large: 1.28 cm/y [range, 0-1.98 cm/y]). Thirteen masses were excised. No patient developed metastases. Arterial-phase CT improved (P = 0.0003) solid mass detection, but 28% of studies still underreported the total number. CONCLUSIONS: Most pancreatic masses in VHL do not require annual surveillance. Arterial-phase CT improves mass detection, but many masses remain prospectively missed.

A phase I study of interleukin 12 with trastuzumab in patients with human epidermal growth factor receptor-2-overexpressing malignancies: analysis of sustained interferon gamma production in a subset of patients.

PURPOSE: On the basis of preclinical studies, we hypothesized that interleukin (IL)12 would potentiate the antitumor actions of an antihuman epidermal growth factor receptor-2 (HER2) monoclonal antibody (trastuzumab). We conducted a Phase I trial to determine the safety and optimal biological dose of IL-12 when given in combination with trastuzumab. PATIENTS AND METHODS: Patients with metastatic HER2-positive malignancies received trastuzumab on day 1 of each weekly cycle. Beginning in week 3, patients also received intravenous injections of IL-12 on days 2 and 5. The IL-12 component was dose-escalated within cohorts of 3 patients (30, 100, 300, or 500 ng/kg). Correlative assays were conducted using serum samples and peripheral blood cells obtained during the course of therapy. RESULTS: Fifteen patients were treated, including 12 with HER2 2+ or 3+ breast cancer. The regimen was well tolerated with IL-12-induced grade 1 nausea and grade 2 fatigue predominating. Evaluation of dose-limiting toxicity and biological end points suggested that the 300 ng/kg dose was both the maximally tolerated dose and the optimal biological dose of IL-12 for use in combination with trastuzumab. Two patients with HER2 3+ breast cancer within the 500 ng/kg dose level experienced grade 1 asymptomatic decreases in left ventricular ejection fraction of 12% and 19% after 3 and 10 months of therapy, respectively. There was one complete response in a patient with HER2 3+ breast cancer metastatic to the axillary, mediastinal, and supraclavicular nodes, and 2 patients with stabilization of bone disease lasting 10 months and >12 months, respectively. Correlative assays showed sustained production of interferon (IFN)gamma by natural killer cells only in those patients experiencing a clinical response or stabilization of disease. Elevated serum levels of macrophage inflammatory protein-1alpha, tumor necrosis factor-alpha, and the antiangiogenic factors IFN-gamma inducible protein-10 and monokine induced by gamma were also observed in these patients. Patient genotyping suggested that a specific IFN-gamma gene polymorphism might have been associated with increased IFN-gamma production. The ability of patient peripheral blood cells to conduct antibody-dependent cellular cytotoxicity against tumor targets in vitro did not correlate with clinical response or dose of IL-12. CONCLUSIONS: The addition of IL-12 to trastuzumab therapy did not appear to enhance the efficacy of this antibody treatment. Sustained production of IFN-gamma and other cytokines were observed in three patients: One who exhibited a complete response and two others who had stabilization of disease lasting over 6 months. Given the small sample size and heterogeneity of the patient population, the effects of IL-12 on the innate immune response to trastuzumab therapy should be further explored in the context of a larger clinical trial.