Intrahepatic cholangiocarcinoma: current management and emerging therapies.

INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is a malignancy with an increasing incidence and a high-case fatality. While surgery offers the best hope at long-term survival, only one-third of tumors are amenable to surgical resection at the time of the diagnosis. Unfortunately, conventional chemotherapy offers limited survival benefit in the management of unresectable or metastatic disease. Recent advances in understanding the molecular pathogenesis of iCCA and the use of next-generation sequencing techniques have provided a chance to identify 'target-able' molecular aberrations. These novel molecular therapies offer the promise to personalize therapy for patients with iCCA and, in turn, improve the outcomes of patients. Area covered: We herein review the current management options for iCCA with a focus on defining both established and emerging therapies. Expert commentary: Surgical resection remains as an only hope for cure in iCCA patients. However, frequently the diagnosis is delayed till advanced stages when surgery cannot be offered; signifying the urge for specific diagnostic tumor biomarkers and targeted therapies. New advances in genomic profiling have contributed to a better understanding of the landscape of molecular alterations in iCCA and offer hope for the development of novel diagnostic biomarkers and targeted therapies.

Regular Formal Evaluation Sessions are Effective as Frame-of-Reference Training for Faculty Evaluators of Clerkship Medical Students.

BACKGROUND: Face-to-face formal evaluation sessions between clerkship directors and faculty can facilitate the collection of trainee performance data and provide frame-of-reference training for faculty. OBJECTIVE: We hypothesized that ambulatory faculty who attended evaluation sessions at least once in an academic year (attendees) would use the Reporter-Interpreter-Manager/Educator (RIME) terminology more appropriately than faculty who did not attend evaluation sessions (non-attendees). DESIGN: Investigators conducted a retrospective cohort study using the narrative assessments of ambulatory internal medicine clerkship students during the 2008-2009 academic year. PARTICIPANTS: The study included assessments of 49 clerkship medical students, which comprised 293 individual teacher narratives. MAIN MEASURES: Single-teacher written and transcribed verbal comments about student performance were masked and reviewed by a panel of experts who, by consensus, (1) determined whether RIME was used, (2) counted the number of RIME utterances, and (3) assigned a grade based on the comments. Analysis included descriptive statistics and Pearson correlation coefficients. KEY RESULTS: The authors reviewed 293 individual teacher narratives regarding the performance of 49 students. Attendees explicitly used RIME more frequently than non-attendees (69.8 vs. 40.4 %; p < 0.0001). Grades recommended by attendees correlated more strongly with grades assigned by experts than grades recommended by non-attendees (r = 0.72; 95 % CI (0.65, 0.78) vs. 0.47; 95 % CI (0.26, 0.64); p = 0.005). Grade recommendations from individual attendees and non-attendees each correlated significantly with overall student clerkship clinical performance [r = 0.63; 95 % CI (0.54, 0.71) vs. 0.52 (0.36, 0.66), respectively], although the difference between the groups was not statistically significant (p = 0.21). CONCLUSIONS: On an ambulatory clerkship, teachers who attended evaluation sessions used RIME terminology more frequently and provided more accurate grade recommendations than teachers who did not attend. Formal evaluation sessions may provide frame-of-reference training for the RIME framework, a method that improves the validity and reliability of workplace assessment.

Clinical relevance of mold culture positivity with and without recurrent wound necrosis following combat-related injuries.

BACKGROUND: Invasive fungal wound infections (IFIs) are a recognized threat for personnel who sustain combat-related blast trauma in Afghanistan. Blast trauma, particularly when dismounted, has wounds contaminated with organic debris and potential for mold infection. Trauma-associated IFI is characterized by recurrent wound necrosis on serial debridement with histologic evidence of invasive molds and/or fungal culture growth. Wounds with mold growth but lacking corresponding recurrent necrosis present a clinical dilemma of whether to initiate antifungal treatment. Our objective was to assess the clinical significance of fungal culture growth without recurrent wound necrosis. METHODS: US military personnel wounded during combat in Afghanistan (June 2009 to August 2011) were assessed for growth of mold from wound cultures and/or histopathologic evidence of IFI. Identified patients were stratified based on clinical wound appearance (with/without recurrent necrosis), and the resultant groups were compared for injury characteristics, clinical management, and outcomes. RESULTS: A total of 96 patients were identified: 77 with fungal elements on histopathology and/or fungal growth plus recurrent wound necrosis and 19 with fungal growth on culture but no wound necrosis after initial debridements. Injury patterns and severity were similar between the groups. Patients with recurrent necrosis had more frequent fevers and leukocytosis during the first 2 weeks after injury, and the majority received antifungal therapy compared with only three patients (16%) without recurrently necrotic wounds. Overall, patients without recurrent wound necrosis had significantly less operative procedures (p = 0.02), shorter stay in the intensive care unit (p < 0.01), and lower rates of high-level amputations (5% vs. 20%) and deaths (none vs. 8%) despite no or infrequent antifungal use. CONCLUSION: The finding of molds on wound culture among patients with blast trauma in the absence of recurrently necrotic wounds on serial debridement does not require systemic antifungal chemotherapy. LEVEL OF EVIDENCE: Therapeutic study, level IV. Prognosti/epidemiologic study, level III.

Effect of early screening for invasive fungal infections in U.S. service members with explosive blast injuries.

BACKGROUND: An outbreak of invasive fungal infections (IFI) began in 2009 among United States servicemen who sustained blast injuries in Afghanistan. In response, the military trauma community sought a uniform approach to early diagnosis and treatment. Toward this goal, a local clinical practice guideline (CPG) was implemented at Landstuhl Regional Medical Center (LRMC) in early 2011 to screen for IFI in high-risk patients using tissue histopathology and fungal cultures. METHODS: We compared IFI cases identified after initiation of the CPG (February through August 2011) to cases from a pre-CPG period (June 2009 through January 2011). RESULTS: Sixty-one patients were screened in the CPG period, among whom 30 IFI cases were identified and compared with 44 pre-CPG IFI cases. Demographics between the two study periods were similar, although significantly higher transfusion requirements (p<0.05) and non-significant trends in injury severity scores and early lower extremity amputation rates suggested more severe injuries in CPG-period cases. Pre-CPG IFI cases were more likely to be associated with angioinvasion on histopathology than CPG IFI cases (48% versus 17%; p<0.001). Time to IFI diagnosis (three versus nine days) and to initiation of antifungal therapy (seven versus 14 days) were significantly decreased in the CPG period (p<0.001). Additionally, more IFI patients received antifungal agent at LRMC during the CPG period (30%) versus pre-CPG period (5%; p=0.005). The CPG IFI cases were also prescribed more commonly dual antifungal therapy (73% versus 36%; p=0.002). There was no statistical difference in length of stay or mortality between pre-CPG and CPG IFI cases; although a non-significant reduction in crude mortality from 11.4% to 6.7% was observed. CONCLUSIONS: Angioinvasive IFI as a percentage of total IFI cases decreased during the CPG period. Earlier diagnosis and commencement of more timely treatment was achieved. Despite these improvements, no difference in clinical outcomes was observed compared with the pre-CPG period.

Risk factors associated with invasive fungal infections in combat trauma.

BACKGROUND: In recent years, invasive fungal infections (IFI) have complicated the clinical course of patients with combat-related injuries. Commonalities in injury patterns and characteristics among patients with IFI led to the development of a Joint Trauma System (JTS) clinical practice guideline (CPG) for IFI management. We performed a case-control study to confirm and further delineate risk factors associated with IFI development in combat casualties with the objective of generating data to refine the CPG and promote timelier initiation of treatment. METHODS: Data were collected retrospectively for United States (U.S.) military personnel injured during deployment in Afghanistan from June 2009 through August 2011. Cases were identified as IFI based upon wound cultures with fungal growth and/or fungal elements seen on histology, in addition to the presence of recurrent wound necrosis. Controls were matched using date of injury (±3 mo) and injury severity score (±10). Risk factor parameters analyzed included injury circumstances, blood transfusion requirements, amputations after first operative intervention, and associated injuries. Data are expressed as multivariate odds ratios (OR; 95% confidence interval [CI]). RESULTS: Seventy-six IFI cases were identified from 1,133 U.S. military personnel wounded in Afghanistan and matched to 150 controls. Parameters associated significantly with the development of IFI multivariate analysis were blast injuries (OR: 5.7; CI: 1.1-29.6), dismounted at time of injury (OR: 8.5; CI: 1.2-59.8); above the knee amputations (OR: 4.1; CI: 1.3-12.7), and large-volume packed red blood cell (PRBC; >20 U) transfusions within first 24 h (OR: 7.0; CI: 2.5-19.7). CONCLUSIONS: Our analysis indicates that dismounted blast injuries, resulting in above the knee amputations, and requirement of large volume PRBC transfusions are independent predictors of IFI development. These data confirm all the preliminary risk factors, except for genitalia/perineal injuries, utilized by JTS in their IFI CPG. Model validation is necessary for further risk factor specification.

Patient specific tumor growth prediction using multimodal images.

Personalized tumor growth model is valuable in tumor staging and therapy planning. In this paper, we present a patient specific tumor growth model based on longitudinal multimodal imaging data including dual-phase CT and FDG-PET. The proposed Reaction-Advection-Diffusion model is capable of integrating cancerous cell proliferation, infiltration, metabolic rate and extracellular matrix biomechanical response. To bridge the model with multimodal imaging data, we introduce Intracellular Volume Fraction (ICVF) measured from dual-phase CT and Standardized Uptake Value (SUV) measured from FDG-PET into the model. The patient specific model parameters are estimated by fitting the model to the observation, which leads to an inverse problem formalized as a coupled Partial Differential Equations (PDE)-constrained optimization problem. The optimality system is derived and solved by the Finite Difference Method. The model was evaluated by comparing the predicted tumors with the observed tumors in terms of average surface distance (ASD), root mean square difference (RMSD) of the ICVF map, average ICVF difference (AICVFD) of tumor surface and tumor relative volume difference (RVD) on six patients with pathologically confirmed pancreatic neuroendocrine tumors. The ASD between the predicted tumor and the reference tumor was 2.4±0.5mm, the RMSD was 4.3±0.4%, the AICVFD was 2.6±0.6%, and the RVD was 7.7±1.3%.

Prospective evaluation of the clinical utility of 18-fluorodeoxyglucose PET CT scanning in patients with von hippel-lindau-associated pancreatic lesions.

BACKGROUND: The natural history of pancreatic neuroendocrine neoplasms (PNENs) in patients with Von Hippel-Lindau (VHL) disease is poorly defined. Management of patients with PNENs is challenging because there are no reliable preoperative criteria to detect malignant lesions, and the majority of resected tumors are found to be benign. The aim of this study was to determine whether 18-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) uptake predicts growth and detects malignant VHL-associated PNENs. STUDY DESIGN: We performed a prospective study of 197 patients with VHL-associated pancreatic lesions. Clinical and imaging characteristics were analyzed to study the associations between FDG-PET uptake, tumor growth, and the development of metastatic disease. RESULTS: One hundred nine of 197 patients had solid pancreatic lesions and underwent both CT and (18)FDG-PET scanning, which identified 165 and 144 lesions, respectively. Metastatic disease was detected by (18)FDG-PET in 3 patients in whom it was not detected by CT scan and suggested non-neoplastic disease in 3 patients. Maximum standardized uptake values (SUV) on (18)FDG-PET correlated with tumor size on CT (r = 0.47, p < 0.0001), and an increase in SUVmax was associated with tumor growth (r = 0.36, p = 0.0062). No association was seen between (18)FDG-PET uptake and age, VHL genotype, or serum chromogranin A levels. CONCLUSIONS: Scanning with FDG-PET identifies metastatic disease not detected by CT scan and avoids resection of non-PNEN lesions that have no malignant potential in patients with VHL-associated PNENs. It should be considered as a valuable functional imaging modality in the clinical management of patients with VHL-associated PNENs.

Assessment of tumor growth in pancreatic neuroendocrine tumors in von Hippel Lindau syndrome.

BACKGROUND: The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing, but only a subset of these heterogeneous tumors will progress to malignant disease, which is associated with a poor prognosis. Currently, there are limited data on the natural history of these tumors and it is difficult to determine which patients require surgical intervention because the risk of metastatic disease cannot be accurately determined. STUDY DESIGN: We conducted a prospective study of 87 patients with von Hippel Lindau syndrome-associated solid pancreatic lesions to determine the natural history of these tumors with biochemical testing, follow-up anatomic and functional imaging, and advanced imaging analysis, with a median follow-up of 4 years. RESULTS: Approximately 20% of consecutive tumor measurements during follow-up were decreased in size and 20% showed no change. This included 2 of 4 surgically proven malignant tumors, which had a net decrease in tumor size over time. Tumor volume, as derived from greatest diameter and volumetric measurements, showed good correlation to pathology tumor measurement of surgically resected tumors (Spearman rank correlation ρ = 0.72, p = 0.0011, and ρ = 0.83, p < 0.0001, respectively). Tumor density measurement had an inverse relationship with tumor size (Spearman rank correlation -0.22, p = 0.0047). A tumor density cutoff of 200 was 75% specific for malignant tumors. CONCLUSIONS: Pancreatic neuroendocrine tumors demonstrate a nonlinear growth pattern, which includes periods of no growth and apparent decrease in size by imaging. These growth patterns are variable and are not associated with tumor grade and malignancy. Tumor density, as measured in this cohort, may offer a specific diagnostic tool for malignant disease.

Utility of intraoperative parathyroid hormone monitoring in patients with multiple endocrine neoplasia type 1-associated primary hyperparathyroidism undergoing initial parathyroidectomy.

BACKGROUND: Intraoperative parathyroid hormone monitoring (IOPTH) is a widely used adjunct for primary hyperparathyroidism (pHPT). However, the benefit of IOPTH in familial pHPT, such as in multiple endocrine neoplasia type I (MEN1), remains unclear. METHODS: We performed a retrospective analysis of 52 patients with MEN1-associated pHPT undergoing initial parathyroidectomy with IOPTH monitoring at our institution. Parathyroid hormone (PTH) levels were measured before skin incision and 10 min after resection of the last parathyroid gland. Variables analyzed included percent drop of PTH from baseline and the final PTH level compared to the normal reference range (RR). RESULTS: A total of 52 patients underwent initial subtotal parathyroidectomy with IOPTH. An IOPTH decrease cutoff of ≥75 % from baseline had the highest biochemical cure rate (87 %). In the remaining 13 % who met this cutoff, all had persistent pHPT, with ≥90 % drop of PTH from baseline. The remaining patients, who did not meet the ≥75 % cutoff, were cured. Follow-up was available for three of four patients with final IOPTH levels above the RR: one had persistent pHPT, two had hypoparathyroidism (50 %). When a postresection PTH level was within the RR, 88 % of patients were cured. While considered cured from pHPT, 7 % of patients in this group developed permanent hypoparathyroidism. When the final PTH level dropped below the RR, 28 % developed permanent hypoparathyroidism. CONCLUSIONS: A cutoff in IOPTH decrease of ≥75 % from baseline has the highest biochemically cure rate in patients with pHPT associated with MEN1. However, a 75 % cutoff in IOPTH decrease does not exclude persistent pHPT. The absolute IOPTH value does not accurately predict postoperative hypoparathyroidism.

Altered PTEN, ATRX, CHGA, CHGB, and TP53 expression are associated with aggressive VHL-associated pancreatic neuroendocrine tumors.

Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome in which 8-17 % of germline mutation carriers develop pancreatic neuroendocrine tumors (PNETs). There is limited data on prognostic markers for PNETs other than Ki-67, which is included in the World Health Organization classification system. Recently, specific genes and pathways have been identified by whole exome sequencing which may be involved in the tumorigenesis of PNETs and may be markers of disease aggressiveness. The objective of this study was to identify molecular markers of aggressive disease in VHL-associated PNETs. The protein expression of eight genes (PTEN, CHGA, CHGB, ATRX, DAXX, CC-3, VEGF, and TP53) was analyzed in PNETs by immunohistochemistry and compared to clinical data, VHL genotype, functional imaging results, and pathologic findings. Subcellular distribution of phosphatase and tensin (PTEN), chromogranin A (CHGA), and alpha thalassemia/mental retardation syndrome X-linked (ATRX) were significantly different by WHO classifications (p ≤ 0.05). There was decreased PTEN nuclear to cytoplasmic ratio (p < 0.01) and decreased CHGA nuclear expression (p = 0.03) in malignant samples as compared to benign. Lower cytoplasmic chromogranin B (CHGB) expression (p = 0.03) was associated with malignant tumors and metastasis. Higher nuclear expression of PTEN was associated with VHL mutations in exon 3 (p = 0.04). Higher PTEN and CHGB expression was associated with higher FDG-PET avidity (p < 0.05). Cytoplasmic expression of CC-3 was associated with higher serum chromogranin A levels (ρ = 0.72, p = 0.02). Lastly, greater cytoplasmic expression of p53 was associated with metastasis. Our findings suggest that altered PTEN, ATRX, CHGA, and CHGB expression are associated with aggressive PNET phenotype in VHL and may serve as useful adjunct prognostic markers to Ki-67 in PNETs.

Multimodal image driven patient specific tumor growth modeling.

Personalized tumor growth model using clinical imaging data is valuable in tumor staging and therapy planning. In this paper, we build a patient specific tumor growth model based on longitudinal dual phase CT and FDG-PET. We propose a reaction-advection-diffusion model integrating cancerous cell proliferation, infiltration, metabolic rate and extracellular matrix biomechanical response. We then develop a scheme to bridge our model with multimodal radiologic images through intracellular volume fraction (ICVF) and Standardized Uptake Value (SUV). The model was evaluated by comparing the predicted tumors with the observed tumors in terms of average surface distance (ASD), root mean square difference (RMSD) of the ICVF map, the average ICVF difference (AICVFD) of tumor surface and the tumor relative volume difference (RVD) on six patients with pathologically confirmed pancreatic neuroendocrine tumors. The ASD between the predicted tumor and the reference tumor was 2.5 +/- 0.7 mm, the RMSD was 4.3 +/- 0.6%, the AICVFD was 2.6 +/- 0.8%, and the RVD was 7.7 +/- 1.9%.

Association of type-O blood with neuroendocrine tumors in multiple endocrine neoplasia type 1.

CONTEXT: The ABO blood type system describes the expression of human blood group antigens found on both erythrocytes and normal tissue throughout the body. We recently reported an association between O blood type and the manifestation of pancreatic neuroendocrine tumors in a cohort of patients with Von Hippel-Lindau syndrome. OBJECTIVE: The aim of the study was to determine whether there is an association of ABO blood type with the development of neuroendocrine tumors in patients with multiple endocrine neoplasia, type 1 (MEN-1). DESIGN: A retrospective analysis of 105 patients with MEN-1 was performed. Demographic, clinical, and biochemical data were analyzed by ABO blood type. Fisher's exact test was used to determine association between ABO blood type and manifestation of neuroendocrine tumor. RESULTS: Demographic and clinical characteristics were similar amongst blood type cohorts. We found an association between O blood type and the manifestation of a primary neuroendocrine tumor of the gastrointestinal tract, lung, pancreas, and thymus in patients with MEN-1 (P = 0.01). Sixteen of 17 (94%) metastatic tumors had type-O blood, compared to 32 of 43 (74%) with a benign tumor who had non-O blood type. CONCLUSIONS: Our findings suggest an association between O blood type and the manifestation of a primary neuroendocrine tumor in patients with MEN-1. Prospective clinical studies are warranted to see whether patient blood type status may be a useful addition to current screening and surveillance practices.

Adrenal histologic findings show no difference in clinical presentation and outcome in primary hyperaldosteronism.

BACKGROUND: Primary hyperaldosteronism is most commonly due to a solitary cortical adenoma. Thus, some surgeons have suggested a subtotal adrenalectomy is a reasonable approach when a mass can be identified. On the other hand, adrenal vein sampling (AVS) is being used more frequently to distinguish patients with unilateral disease for adrenalectomy, even if a discrete mass is not identified on axial imaging. In these cases, surgical pathology may reveal a cortical adenoma, a cortical adenoma with hyperplasia, or cortical hyperplasia. The goal of this study was to compare the presentation and outcome among patients undergoing adrenalectomy and found to have different histologic features. METHODS: We performed a retrospective analysis of 136 patients with primary hyperaldosteronism. A total of 95 patients had an adrenalectomy for unilateral disease. The preoperative clinical and laboratory, and postoperative outcome of the three aforementioned histologic groups were compared. RESULTS: A total of 95 patients underwent an adrenalectomy. We found no significant difference in age, gender, body mass index, duration of hypertension, number of antihypertensive medications, serum aldosterone level, serum renin level, or adrenal vein sampling ratios among the three histologic categories. We also found no significant difference among the three categories in postoperative cure rate. CONCLUSION: The rate of unilateral hyperplasia in patients with primary hyperaldosteronism (16%) is likely higher than previously reported, which may be due to the increasing use of AVS. The clinical presentation and outcome of patients regardless of the histologic findings are similar. Our data also suggests that subtotal adrenalectomy would not be appropriate in patients with primary hyperaldosteronism.

Long-term outcomes of combat casualties sustaining penetrating traumatic brain injury.

BACKGROUND: Previous studies have documented short-term functional outcomes for patients sustaining penetrating brain injuries (PBIs). However, little is known regarding the long-term functional outcome in this patient population. Therefore, we sought to describe the long-term functional outcomes of combat casualties sustaining PBI. METHODS: Prospective data were collected from 2,443 patients admitted to a single military institution during an 8-year period from 2003 to 2011. PBI was identified in 137 patients and constitute the study cohort. Patients were stratified by age, Injury Severity Score (ISS) and admission Glasgow Coma Scale (aGCS) score. Glasgow Outcome Scale (GOS) scores were calculated at discharge, 6 months, 1 year and 2 years. Patients with a GOS score of 4 or greater were considered to have attained functional independence (FI). RESULTS: The mean (SD) age of the cohort was 25 (7) years, mean (SD) ISS was 28 (9), and mean (SD) aGCS score was 8.8 (4.0). PBI mechanisms included gunshot wounds (31%) and blast injuries (69%). Invasive intracranial monitoring was used in 80% of patients, and 86.9% of the study cohort underwent neurosurgical intervention. Complications included cerebrospinal fluid leak (8.3%), venous thromboembolic events (15.3%), meningitis (24.8%), systemic infection (27.0%), and mortality (5.8%). The cohort was stratified by aGCS score and showed significant improvement in functional status when mean discharge GOS score was compared with mean GOS score at 2 years. For those with aGCS score of 3 to 5 (2.3 [0.9] vs. 2.9 [1.4], p < 0.01), 32% progressed to FI. For those with aGCS score of 6 to 8 (3.1 [0.7] vs. 4.0 [1.2], p < 0.0001), 63% progressed to FI. For those with aGCS score of 9 to 11 (3.3 [0.5] vs. 4.3 [0.8], p < 0.0001), 74% progressed to FI. For those with aGCS score of 12 to 15 (3.9 [0.7] vs. 4.8 [0.4], p < 0.00001), 100% progressed to FI. CONCLUSION: Combat casualties with PBI demonstrated significant improvement in functional status up to 2 years from discharge, and a large proportion of patients sustaining severe PBI attained FI. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Association of type O blood with pancreatic neuroendocrine tumors in Von Hippel-Lindau syndrome.

BACKGROUND: ABO blood type antigens are expressed not only on human red blood cells, but also throughout the gastrointestinal tract and in normal pancreatic tissue. Previous studies have identified an association between ABO blood type and various malignancies. We analyzed the association of ABO blood type with pancreatic neuroendocrine tumors (PNETs) in a high-risk cohort of patients with Von Hippel-Lindau (VHL) syndrome. METHODS: A retrospective review was performed of 798 patients with VHL syndrome. Blood type was confirmed for 181 patients. Fisher's exact test and Mehta's modification to Fisher's exact test were used to test for an association between ABO blood type and manifestations of VHL syndrome. RESULTS: We found a strong trend for association between O blood type and pancreatic disease manifestation in patients with VHL syndrome (P = 0.047). More importantly, there was a significant association of O blood type with solid pancreatic lesions consistent with PNETs (P = 0.0084). Patients with solid pancreatic lesions who met criteria for surgical resection at the National Institutes of Health also had a higher rate of O blood type than those who did not require surgery (P = 0.051). CONCLUSIONS: Our findings suggest an association between O blood type and pancreatic manifestation of disease in patients with VHL syndrome, especially for PNETs. Screening and surveillance approaches for pancreatic lesions in patients with VHL syndrome should also consider patient blood type. The possibility of A, B, H misexpression in PNETs should also be explored to determine whether the serologic association with disease translates into a relationship with tissue pathology.

Clinical utility of functional imaging with ¹8F-FDOPA in Von Hippel-Lindau syndrome.

CONTEXT: Von Hippel-Lindau (VHL) syndrome is an inherited cancer syndrome in which patients are at risk of developing multiple tumors in different organs. 6-L-¹8F-fluorodihydroxyphenylalanine (¹8F-FDOPA) positron emission tomography (PET) is a relatively new metabolic imaging tracer proposed for the use of localizing sites of neuroendocrine tumors. There are limited data on the clinical utility of using ¹8F-FDOPA PET for identifying neuroendocrine tumors in a high-risk population such as VHL. OBJECTIVE: The aim of this prospective study was to evaluate the clinical utility of ¹8F-FDOPA PET in patients with VHL-related tumors. DESIGN: Radiological findings were prospectively collected from four imaging modalities: computed tomography, magnetic resonance imaging (MRI), ¹8F-fluorodeoxyglucose PET, and ¹8F-FDOPA PET. ¹8F-FDOPA PET findings were compared with those from other imaging modalities, as well as with clinical and laboratory data, and pathology findings if patients underwent an operation. RESULTS: In 52 patients with VHL, 390 lesions were identified by computed tomography (n = 139), MRI (n = 117), ¹8F-fluorodeoxyglucose PET (n = 94), and ¹8F-FDOPA PET (n = 40). ¹8F-FDOPA PET identified 20 pancreatic and 20 extrapancreatic tumors, including lesions in the adrenal gland (n = 11), kidney (n = 3), liver (n = 4), lung (n = 1), and cervical paraganglioma (n = 1). These tumor sites were not seen by conventional imaging studies in 9.6% of patients and 4.4% of lesions. Seven of eight patients who had an ¹8F-FDOPA PET-positive lesion underwent resection, and pathology showed a neuroendocrine tumor. Four of 10 patients with positive adrenal uptake had elevated catecholamine levels, and six of 10 patients had a discrete mass on axial imaging. CONCLUSIONS: ¹8F-FDOPA PET is a useful complementary imaging study to detect neuroendocrine tumors in patients with VHL undergoing surveillance, especially in those suspected to have adrenal pheochromocytoma or unusual ectopic locations.

Emergent management of postpartum hemorrhage for the general and acute care surgeon.

BACKGROUND: Postpartum hemorrhage is one of the rare occasions when a general or acute care surgeon may be emergently called to labor and delivery, a situation in which time is limited and the stakes high. Unfortunately, there is generally a paucity of exposure and information available to surgeons regarding this topic: obstetric training is rarely found in contemporary surgical residency curricula and is omitted nearly completely from general and acute care surgery literature and continuing medical education. METHODS: The purpose of this manuscript is to serve as a topic specific review for surgeons and to present a surgeon oriented management algorithm. Medline and Ovid databases were utilized in a comprehensive literature review regarding the management of postpartum hemorrhage and a management algorithm for surgeons developed based upon a collaborative panel of general, acute care, trauma and obstetrical surgeons' review of the literature and expert opinion. RESULTS: A stepwise approach for surgeons of the medical and surgical interventions utilized to manage and treat postpartum hemorrhage is presented and organized into a basic algorithm. CONCLUSION: The manuscript should promote and facilitate a more educated, systematic and effective surgeon response and participation in the management of postpartum hemorrhage.