A Retrospective Review of Bovine Artery Graft Patency: A Single-Site Study.

BACKGROUND: The hemodialysis-dependent population is increasing in the United States. Dialysis access complications are a significant source of morbidity and mortality for patients with end-stage renal disease. A surgically created autogenous arteriovenous fistula has been the gold standard for dialysis access. However, for patients who are not candidates for arteriovenous fistula, arteriovenous grafts using various conduits have widely been used. In this study, we report the outcomes of bovine carotid artery (BCA) grafts for dialysis access at a single institution and compare these results to those for polytetrafluoroethylene (PTFE) grafts. METHODS: A single-institution, retrospective review of all patients undergoing surgical placement of a bovine carotid artery graft for dialysis access from 2017-2018 was performed under an institutional review board-approved protocol. The primary, primary-assisted, and secondary patency were calculated for the whole cohort and results determined based on gender, body mass index (BMI), and indication for use. Comparison was performed to PTFE grafts at same institution from 2013 to 2016. RESULTS: One hundred and twenty two patients were included in this study. Seventy four patients had a BCA graft placed while 48 had a PTFE graft placed. . The mean age was 59.7 ± 13.5 years in the BCA group, 55.8 ± 14.5 in the PTFE group, and the mean BMI was 29.8 ± 9.2 kg/m2 in the BCA group and 28.1 ± 9.7 in the PTFE group. Comparison of the comorbidities present in BCA/PTFE groups included hypertension (92%/100%), diabetes (57%/54%), congestive heart failure (28%/10%), lupus (5%/7%), and chronic obstructive pulmonary disease (4%/8%). The various configurations were reviewed (BCA/PTFE): interposition/access salvage (40.5%/13%), axillary-axillary (18.9%, 7%), brachial-basilic (5.4%, 6%), brachial-brachial (4.1%, 4%), brachial-cephalic (1.4%, 0%), axillary-brachial (1.4%, 0%), brachial-axillary (23%, 62%), and femoral-femoral (5.4%, 6%). Overall, 12-month primary patency was 50% in the BCA group and 18% in the PTFE group (P = 0.001). Twelve-month primary-assisted patency was 66% in the BCA group and 37% in the PTFE group (P = 0.003). Twelve-month secondary patency was 81% in the BCA group and 36% in the PTFE group (P = 0.07). When comparing BCA graft survival probability among male and female gender, males had better primary-assisted patency (P = 0.042). Secondary patency among the 2 genders was similar. There was no statistically significant difference in primary, primary-assisted, and secondary patency of BCA grafts between different BMI groups and indication for use. The average patency of a bovine graft was 17.8 ± 8 months. Sixty one percent of the BCA grafts needed intervention with 24% needing multiple interventions. There was an average of 7 ± 5 months to first intervention. The infection rate was 8.1% in the BCA group and 10.4% in the PTFE group with no statistical difference. CONCLUSIONS: Primary and primary-assisted patency rates at 12 months in our study were higher than those for PTFE at our institution. There was higher primary-assisted patency of BCA grafts among males at 12 months compared to PTFE. Obesity and indication for BCA graft use did not appear to affect patency in our population.

miR-24 Inhibition Increases Menin Expression and Decreases Cholangiocarcinoma Proliferation.

Menin (MEN1) is a tumor-suppressor protein in neuroendocrine tissue. Therefore, we tested the novel hypothesis that menin regulates cholangiocarcinoma proliferation. Menin and miR-24 expression levels were measured in the following intrahepatic and extrahepatic cholangiocarcinoma (CCA) cell lines, Mz-ChA-1, TFK-1, SG231, CCLP, HuCCT-1, and HuH-28, as well as the nonmalignant human intrahepatic biliary line, H69. miR-24 miRNA and menin protein levels were manipulated in vitro in Mz-ChA-1 cell lines. Markers of proliferation and angiogenesis (Ki-67, vascular endothelial growth factors A/C, vascular endothelial growth factor receptors 2/3, angiopoietin 1/2, and angiopoietin receptors 1/2) were evaluated. Mz-ChA-1 cells were injected into the flanks of nude mice and treated with miR-24 inhibitor or inhibitor scramble. Menin expression was decreased in advanced CCA specimens, whereas miR-24 expression was increased in CCA. Menin overexpression decreased proliferation, angiogenesis, migration, and invasion. Inhibition of miR-24 increased menin protein expression while decreasing proliferation, angiogenesis, migration, and invasion. miR-24 was shown to negatively regulate menin expression by luciferase assay. Tumor burden and expression of proliferative and angiogenic markers was decreased in the miR-24 inhibited tumor group compared to controls. Interestingly, treated tumors were more fibrotic than the control group. miR-24-dependent expression of menin may be important in the regulation of nonmalignant and CCA proliferation and may be an additional therapeutic tool for managing CCA progression.

α7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile Duct-Ligated Mice.

α7-nAChR is a nicotinic acetylcholine receptor [specifically expressed on hepatic stellate cells (HSCs), Kupffer cells, and cholangiocytes] that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. Bile duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition. Immunofluorescence was performed to assess colocalization of α7-nAChR with bile ducts (costained with CK-19) and HSCs (costained with desmin). The mRNA expression of α7-nAChR, Ki-67/PCNA (proliferation), fibrosis genes (TGF-ß1, fibronectin-1, Col1α1, and α-SMA), and inflammatory markers (IL-6, IL-1ß, and TNF-α) was measured by real-time PCR. Biliary TGF-ß1 and hepatic CD68 (Kupffer cell marker) expression was assessed using IHC. α7-nAChR immunoreactivity was observed in both bile ducts and HSCs and increased following BDL. α7-nAChR-/- BDL mice exhibited decreased (i) bile duct mass, liver fibrosis, and inflammation, and (ii) immunoreactivity of TGF-ß1 as well as expression of fibrosis genes compared to WT BDL mice. α7-nAChR activation triggers biliary proliferation and liver fibrosis and may be a therapeutic target in managing extrahepatic biliary obstruction.

Inhibition of microRNA-24 increases liver fibrosis by enhanced menin expression in Mdr2-/- mice.

BACKGROUND: Liver transplantation remains the primary treatment for primary sclerosing cholangitis (PSC). Mdr2-/- mice provide a reliable in vivo model of PSC and develop characteristic biliary inflammation and fibrosis. We tested the hypothesis that the tumor suppressor protein menin is implicated in the progression of liver fibrosis and that menin expression can be regulated in the liver via microRNA-24 (miR-24). MATERIALS AND METHODS: Menin expression was measured in human PSC and Mdr2-/- mice. Twelve-week-old FVB/NJ wild-type (WT) and Mdr2-/- mice were treated with miR-24 Vivo-Morpholino to knockdown miR-24 expression levels. Liver fibrosis was evaluated by Sirius Red staining and quantitative polymerase chain reaction (qPCR) for genes associated with liver fibrosis, such as fibronectin 1, collagen type 1 alpha 1, transforming growth factor-ß1 (TGF-ß1), and α-smooth muscle actin. Studies were also performed in vitro using immortalized murine cholangiocyte lines treated with miR-24 hairpin inhibitor and mimic. RESULTS: Menin gene expression was increased in Mdr2-/- mice and late-stage human PSC samples. Treatment of FVB/NJ WT and Mdr2-/- mice with miR-24 Vivo-Morpholino increased menin expression, which correlated with increased expression of fibrosis genes. In vitro, inhibition of miR-24 also significantly increased the expression of fibrosis genes. CONCLUSIONS: Inhibition of miR-24 increases menin and TGF-ß1 expression, subsequently increasing hepatic fibrosis in FVB/NJ WT and Mdr2-/- mice. Modulation of the menin/miR-24 axis may provide novel targeted therapies to slow the progression of hepatic fibrosis into cirrhosis in PSC patients by altering TGF-ß1 expression.

Improving Minimally Invasive Adrenalectomy: Selection of Optimal Approach and Comparison of Outcomes.

INTRODUCTION: Minimally invasive adrenalectomy is commonly performed by either a transperitoneal laparoscopic (TLA) or posterior retroperitoneoscopic (PRA) approach. Our group described the technique for robot-assisted PRA (RAPRA) in 2010. Few studies are available that directly compare outcomes between the available operative approaches. We reviewed our results for minimally invasive adrenalectomy using the three different approaches over a 10-year period. METHODS: Between January 2005 and April 2015, 160 minimally invasive adrenalectomies were performed. Clinicopathologic data were prospectively collected and retrospectively analyzed. The primary endpoints evaluated were operative time, blood loss, length of stay (LOS), and morbidity. RESULTS: The study included 67 TLA, 76 PRA, and 17 RAPRA procedures. Tumor size for PRA/RAPRA was smaller than for patients undergoing TLA (2.38 vs 3.6 cm, p ≤ 0.0001). Procedure time was shorter for PRA versus TLA (133.3 vs 152.8 min, p = 0.0381), as was LOS (1.85 vs 2.82 days, p = 0.0145). Procedure time was longer in RAPRA versus TLA/PRA (177 vs 153/133 min, p = 0.008), but LOS was significantly decreased (1.53 vs 2.82/1.85 days, p = 0.004). CONCLUSIONS: Minimally invasive adrenalectomy is associated with expected excellent outcomes regardless of approach. In our series, the posterior approach is associated with decreased operative time and LOS. Robotic technology provides potential advantages for the surgeon at the expense of more complex setup requirements and costs. Further study is required to demonstrate clear benefit of one surgical approach. Utilization of the entire spectrum of available operative techniques can allow for selection of the optimal approach based on individual patient factors.

Management of the Parathyroid Glands During Preventive Thyroidectomy in Patients With Multiple Endocrine Neoplasia Type 2.

OBJECTIVES: Patients with multiple endocrine neoplasia type 2 (MEN2) have mutations in the RET protooncogene and virtually all of them will develop medullary thyroid carcinoma. Family members identified by genetic testing are candidates for preventive thyroidectomy. Management of the parathyroids during thyroidectomy is controversial. Some experts advocate total parathyroidectomy with autotransplantation, whereas others recommend preserving the parathyroids in situ. METHODS: Between 1993 and 2000, we performed preventive thyroidectomies on 50 patients with MEN2A (group A). All patients had a central neck dissection (CND) combined with total parathyroidectomy and autotransplantation of parathyroid slivers to the nondominant forearm or to the neck. Between 2003 and the present, we performed 102 preventive thyroidectomies attempting to preserve the parathyroid glands in situ with an intact vascular pedicle (group B). Individual parathyroids were autotransplanted only if they appeared nonviable or could not be preserved intact. Central neck dissection was done only if the serum calcitonin was greater than 40 pg/mL. RESULTS: Permanent hypoparathyroidism occurred in 3 (6%) of 50 patients in group A, compared with 1 (1%) of 102 patients in group B (P = 0.1). After total thyroidectomy, no patient in either group developed permanent recurrent laryngeal nerve injury or hyperparathyroidism. Immediate postoperative serum calcitonin levels were in the normal range (<5 pg/mL) in 100 of 102 patients in group B. No patients in either group have died. Oncologic follow-up of patients in group B is in progress. CONCLUSIONS: In patients with MEN2A treated by preventive total thyroidectomy routine total parathyroidectomy with autotransplantation and CND gives excellent long-term results. However, preservation of the parathyroids in situ during preventive thyroidectomy combined with selective CND based on preoperative basal serum calcitonin levels is an effective and safe alternative that results in a very low incidence of hypoparathyroidism.

A novel method for the management of post-thyroidectomy or parathyroidectomy hematoma: a single-institution experience after over 4,000 central neck operations.

BACKGROUND: Cervical hematoma is a rare but serious complication of thyroid and parathyroid surgery that has historically required inpatient monitoring. With improved surgical technique and experience, operations are being performed increasingly as outpatient procedures. Therefore, a safe and systematic approach to cervical exploration of a postoperative hematoma needs to be defined. METHODS: From 1996 to 2013, a retrospective review was performed of 4,140 thyroid and parathyroid operations. Surgical outcomes data were recorded, specifically including the occurrence of a cervical hematoma, time interval to presentation, and methods of management. RESULTS: A total of 18 patients (0.43 %) developed a postoperative cervical hematoma that required surgical intervention. The occurrence of hematoma was 0.66 % (n = 11) for bilateral thyroid procedures, 0.21 % (n = 3) for unilateral thyroid procedures, and 0.13 % (n = 1) for parathyroid procedures. There were 3 (1.69 %) patients who had combined unilateral thyroid and parathyroid procedures and developed hematomas. Emergent bedside decompression was required for only two patients, both of whom suffered respiratory arrest in the postoperative anesthesia recovery unit. The remaining 16 patients were explored in the operating room, utilizing initial local anesthesia in the semi-upright position in 11 patients (69 %). CONCLUSIONS: From our experience, hematomas that caused significant airway compromise leading to respiratory arrest occurred in the postoperative anesthesia recovery room, and hematoma presentation after this time did not require emergent bedside decompression. Hematoma, when it occurs, can otherwise be managed safely in the operating room after inpatient or outpatient procedures using initial local anesthesia with the patient in the semi-upright position for hematoma evacuation.

Loss of tumor suppressor menin expression in high grade cholangiocarcinomas.

BACKGROUND: MEN1, which codes for the protein menin, is a tumor suppressor in neuroendocrine tissue. In cholangiocarcinoma (CCA) cell lines the overexpression of menin decreased proliferation, angiogenesis, migration, and invasion in vitro and in xenografts, but its expression in CCA tumor tissue samples is not established. OBJECTIVE: Determine whether the expression of menin correlates with disease progression in patient samples of CCA in a tissue microarray (TMA) by immunohistochemical (IHC) staining. RESULTS: IHC analysis of 97 biopsies revealed that low-grade tumors (Grade I) exhibited intense, diffuse, finely granular nuclear menin immunoreactivity with a pronounced linear perinuclear pattern (mean IHC score = 2.00), whereas high-grade tumors (Grade III) mostly lacked such staining (mean IHC score = 0.35). Collectively, there was a significant inverse association between tumor grade and menin staining (P = 0.0005). We also found a significant association between fibrosis status and menin staining, in that, 81.2% (56/69) of patients without fibrosis had no menin staining, whereas 92.9% (26/28) patients with fibrosis exhibited menin staining (P < 0.0001). No association was found between fibrosis status and grade. Overall, menin expression is inversely associated with tumor grade and positively associated with fibrosis status.

A Rare Case of Pure Primary Large Cell Neuroendocrine Carcinoma of the Gallbladder.

Primary large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is a rare malignancy which is often associated with non-LCNEC histologic components. Histologically "pure" LCNECs of the gallbladder are exceedingly rare with only 15 cases reported in the medical literature. Clinically, LCNECs present with abdominal pain and jaundice and follow an aggressive course with patients surviving a median of 15 months following initial diagnosis. To our knowledge, we present the 16th case of a histologically pure LCNEC in a 62-year-old African American male who was successfully treated surgically. After discharge, he was subsequently lost to follow-up. Due to the extreme rarity of such disease entity, accurate diagnosis and proper management are essential for the best clinical outcome.

Matrix metalloproteinase-activated anthrax lethal toxin inhibits endothelial invasion and neovasculature formation during in vitro morphogenesis.

Solid tumor growth is dependent on angiogenesis, the formation of neovasculature from existing vessels. Endothelial activation of the extracellular signal-regulated kinase 1/2, c-jun NH(2)-terminal kinase, and p38 mitogen-activated protein kinase pathways is central to this process, and thus presents an attractive target for the development of angiogenesis inhibitors. Anthrax lethal toxin (LeTx) has potent catalytic mitogen-activated protein kinase inhibition activity. Preclinical studies showed that LeTx induced potent tumor growth inhibition via the inhibition of xenograft vascularization. However, LeTx receptors and the essential furin-like activating proteases are expressed in many normal tissues, potentially limiting the specificity of LeTx as an antitumor agent. To circumvent nonspecific LeTx activation and simultaneously enhance tumor vascular targeting, a substrate preferably cleaved by the gelatinases class of matrix metalloproteinases (MMP) was substituted for the furin LeTx activation site. In vivo efficacy studies showed that this MMP-activated LeTx inhibited tumor xenografts growth via the reduced migration of endothelial cells into the tumor parenchyma. Here we have expanded on these initial findings by showing that this MMP-activated LeTx reduces endothelial proangiogenic MMP expression, thus causing a diminished proteolytic capacity for extracellular matrix remodeling and endothelial differentiation into capillary networks. Additionally, our data suggest that inhibition of the c-jun NH(2)-terminal kinase and p38, but not extracellular signal-regulated kinase-1/2, pathways is significant in the antiangiogenic activity of the MMP-activated LeTx. Collectively, these results support the clinical development of the MMP-activated LeTx for the treatment of solid tumors.

Primary splenic angiosarcoma.

Primary splenic angiosarcoma is a rare, aggressive malignant neoplasm arising from splenic vascular endothelium. A 70-year-old woman presented with shortness of breath and chest discomfort secondary to a left-sided pleural effusion. A thoracentesis revealed a reactive effusion suspicious for malignancy. Splenic enlargement with heterogeneous enhancement was identified on CT of the abdomen. Laboratory findings at initial presentation revealed mild anemia (10.5 g/dL) with normal platelets (300 × 109/L). Laparoscopic splenectomy was performed, and a primary splenic angiosarcoma was discovered. After 2 rounds of chemotherapy, a CT scan showed progressive disease with metastasis to the liver and lung. The patient's antineoplastic regimen was switched to Ifosfamide and Doxorubicin. She is currently alive with evidence of disease at 9 months but without further progression. Primary splenic angiosarcoma is almost universally fatal despite treatment. The best chance for survival is early diagnosis and prompt splenectomy prior to splenic rupture.

The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors.

This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.

Role of menin in neuroendocrine tumorigenesis.

The menin protein encoded by the MEN1 tumor suppressor gene is ubiquitously expressed and highly conserved evolutionarily. The combination of findings from current in vitro and in vivo studies has not yielded a comprehensive understanding of the mechanisms of menin's tumor suppressor activity or the specific role for menin in endocrine tumorigenesis, although its diverse interactions suggest possible pivotal roles in transcriptional regulation, DNA processing and repair and cytoskeletal integrity. This manuscript summarizes recent research findings including studies of global gene expression in MEN1-associated neuroendocrine tumors and pivotal changes in intracellular signaling pathways associated with neuroendocrine tumorigenesis. Finally, the clinical applications provided by the understanding of the effects of MEN1 gene mutations on neuroendocrine tumor development in patients with this familial cancer syndrome are discussed.

Influence of Adrenal Venous Sampling on Management in Patients with Primary Aldosteronism Independent of Lateralization on Cross-Sectional Imaging.

BACKGROUND: Patients with primary aldosteronism undergo imaging of the adrenal glands after confirmation of the disease. Adrenal venous sampling (AVS) is a useful adjunct to imaging, and advocates believe that AVS should be performed before surgical management. Others argue that patients with unilateral lesions on imaging do not require AVS. Although AVS accuracy has been established, few studies have evaluated how AVS alters management. Our study aimed to determine how AVS affected management of these patients. STUDY DESIGN: Patient data were collected retrospectively from the electronic medical records at a single institution. Patients aged 18 years or older who underwent AVS with successful adrenal vein cannulation from 2007 to 2016 were included. The laterality of AVS was compared with laterality of preprocedural imaging for each patient. The management plan before AVS was determined by laterality on preprocedural imaging. The primary outcomes were management of primary aldosteronism, change in management compared with the plan before AVS, and antihypertensive medication use after therapy. RESULTS: Seventy-four patients had successful adrenal venous cannulation. Thirty-three (44.6%) patients had AVS lateralization that was concordant with preprocedural imaging. Forty-one (55.4%) patients had AVS lateralization that was non-concordant with preprocedural imaging. There was a change in management in 29 (39.2%) patients. CONCLUSIONS: Adrenal venous sampling can delineate the source of aldosterone hypersecretion, and often this is not concordant with cross-sectional imaging. We found that many patients avoided a potentially non-curative operation due to AVS. Adrenal venous sampling frequently alters the management of aldosteronomas and should be highly considered in patients before surgical intervention.

Central Lymph Node Dissection Improves Lymph Node Clearance in Papillary Thyroid Cancer Patients with Lateral Neck Metastases, Even after Prior Total Thyroidectomy.

The oncologic benefit of a central lymph node dissection (CLND) at the time of modified radical neck dissection (MRND) in patients with papillary thyroid cancer who have previously undergone a total thyroidectomy (TT) has not been studied. Patients with lateral cervical metastases were divided into two treatment groups: the concurrent cohort (TT with CLND and MRND), and the interval cohort (CLND and MRND after prior TT). Primary outcomes were lymph node metastases, skip metastases, level VI cancer recurrence, hypoparathyroidism and recurrent laryngeal nerve injury. Treatment groups consisted of 63 and 16 patients in the concurrent and interval groups, respectively. More central lymph nodes were removed (15.4 ± 8.4 to 10.1 ± 5.2 (P = 0.02)), but similar level VI lymph node metastasis occurred (92.0-93.8% (P = 0.99)) in the concurrent group compared with the interval group, respectively. Skip metastases were identified in only 7.6 per cent of patients. The incidence of level VI recurrence and recurrent laryngeal nerve injury was 1.2 per cent. Three patients developed hypoparathyroidism (3.7%). All permanent morbidities occurred in the concurrent group. CLND at the time of MRND for metastatic papillary thyroid cancer frequently identifies level VI metastases and can be done with low operative morbidity by experienced endocrine surgeons, even in patients who have undergone a prior TT.

Biliary epithelium: A neuroendocrine compartment in cholestatic liver disease.

Hepatic fibrosis is characterized by abnormal accumulation of extracellular matrix (ECM) that can lead to ductopenia, cirrhosis, and even malignant transformation. In this review, we examine cholestatic liver diseases characterized by extensive biliary fibrosis such as primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), polycystic liver disease (PLD), and MDR2-/- and BDL mouse models. Following biliary injury, cholangiocytes, the epithelial cells that line the bile ducts, become reactive and adopt a neuroendocrine phenotype in which they secrete and respond to neurohormones and neuropeptides in an autocrine and paracrine fashion. Emerging evidence indicates that cholangiocytes influence and respond to changes in the ECM and stromal cells in the microenvironment. For example, activated myofibroblasts and hepatic stellate cells are major drivers of collagen deposition and biliary fibrosis. Additionally, the liver is richly innervated with adrenergic, cholinergic, and peptidergic fibers that release neurohormones and peptides to maintain homeostasis and can be deranged in disease states. This review summarizes how cholangiocytes interact with their surrounding environment, with particular focus on how autonomic and sensory regulation affects fibrotic pathophysiology.

Reoperative central lymph node dissection for incidental papillary thyroid cancer can be performed safely: A retrospective review.

BACKGROUND: This study compares the pathological outcomes and operative morbidity for papillary thyroid cancer (PTC) patients undergoing a primary total thyroidectomy (TT) with central lymph node dissection (CLND), to those undergoing an interval CLND following a previous thyroid operation, or for the unsuspected diagnosis of PTC. METHODS: Single-institution, retrospective review of PTC patients from 2000 to 2015 was performed. Three treatment groups were identified: primary TT/CLND, interval prophylactic CLND, and interval therapeutic CLND. Primary outcome measures were number of lymph nodes removed, hypoparathyroidism and recurrent laryngeal nerve (RLN) injury. RESULTS: Results for 30 prophylactic and 35 therapeutic interval CLND were compared with 218 patients undergoing primary TT/CLND. Interval CLND was associated with similar rates of cervical metastases, complications, and a trend towards decreased lymph node recovery. CONCLUSION: Reoperative CLND for incidental PTC frequently identifies cervical lymph node metastases, potentially reduces recurrence, and can be performed with similar morbidity to a primary lymphadenectomy.

Needle biopsy of incidentally discovered adrenal masses is rarely informative and potentially hazardous.

INTRODUCTION: The role of fine needle aspiration (FNA) biopsy in patients with incidentally discovered adrenal masses is limited. However, image-guided biopsy continues to be performed in this setting, in some cases before biochemical workup. The purpose of this study was to review the value of FNA biopsy of adrenal masses in patients referred to a large university endocrine surgical practice. METHODS: Patients referred to the endocrine surgery service at our institutions from 1997 through 2006 for evaluation of an adrenal mass were identified and those who underwent needle biopsy were selected for analysis. RESULTS: Of the 347 patients evaluated for adrenal masses, 22 (6.3%) had undergone needle biopsy before referral. Clinical presentations were incidentaloma (n = 15), suspected metastasis (n = 4), and symptomatic large mass (n = 3). In 10 cases, a radiology report had either suggested a biopsy or stated that the mass was "amenable" to biopsy. In the 15 patients with incidentaloma, 12 (80%) had nondiagnostic biopsy results and 2 showed pheochromocytoma. Biopsies were diagnostic in 2 of 4 patients with suspected metastasis and in 1 of 3 patients with a large symptomatic mass. There were 3 biopsy-related complications: 1 liver hematoma, 1 hemothorax, and 1 duodenal hematoma. No biochemical testing for pheochromocytoma was performed before biopsy in 10 patients, 5 of whom were ultimately diagnosed with pheochromocytoma. Biopsy results did not alter clinical management in any of the 22 patients in this study. CONCLUSIONS: FNA biopsy is not useful in the diagnostic workup of patients with incidentally discovered adrenal masses and rarely alters management in patients with resectable adrenal metastases and primary adrenal malignancies. Furthermore, biopsy in this setting can also be potentially hazardous. Language that suggests biopsy of adrenal masses should be avoided in radiology reports.

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth.

PURPOSE: Cholangiocarcinoma (CCA) is a malignancy of the biliary epithelium that is associated with low five-year survival. The apelin receptor (APLNR), which is activated by the apelin peptide, has not been studied in CCA. The purpose of this study is to determine if inhibition of the apelin/APLNR axis can inhibit CCA growth. METHODS: Immunohistochemistry, rtPCR, immunofluorescence, flow cytometry, and ELISA was used to measure APLNR expression in human CCA cells and tissues. Mz-ChA-1 cells were treated with increasing concentrations of apelin and ML221, an APLNR antagonist. Expression of proliferative and angiogenic genes were measured via rtPCR. In vivo, Mz-ChA-1 cells were injected into the flanks of nu/nu mice, which were treated with ML221 (150 µg/kg) via tail vein injection. RESULTS: Expression of the apelin/APLNR axis was increased in CCA. In vitro, CCA proliferation and angiogenesis was inhibited by ML221 treatment. ML221 treatment significantly decreased tumor growth in nu/nu mice. CONCLUSION: The apelin/APLNR axis regulates CCA proliferation and angiogenesis. Inhibition of the apelin/APLNR axis decreases tumor growth in our xenograft model. Targeting APLNR signaling has the potential to serve as a novel, tumor directed therapy for CCA.