In Silico Screening of Chlorogenic Acids from Plant Sources against Human Translocase-I to Identify Competitive Inhibitors to Treat Diabetes.

Chlorogenic acids (CHLs) are known to competitively bind to translocase-I (T1) of the glucose-6-phosphatase (G6 Pase) system, thereby inhibiting the transport of glucose-6-phosphate (G6P). This competitive binding results in a consequential reduction in blood sugar levels. In this study, steered molecular dynamics (SMD) simulation is employed to investigate the interaction between T1 and G6P, aiming to gain insights into the binding dynamics and diffusion process of G6P through T1. A database comprising 41 CHLs sourced from various plants was developed, subjected to minimization, and screened against T1 through conventional docking methods. The docked conformations were fed into a newly developed customized scoring method incorporating contact-based weights to assess the binding affinities that systematically rank and identify the most effective competitive inhibitors. Among the screened CHLs, 1-methoxy 3,5-dicaffeoylquinic acid, 3,4 dicaffeoyl quinic acid, and 3,4,5-tricaffeoylquinic acid stood out as the top three inhibitors, showcasing crucial atomic interactions with key residues within the binding pocket of T1, and these CHLs are sourced from readily available plants, diminishing reliance on coffee as the predominant CHL source. Along with the devised scoring function, which serves as a valuable tool for virtual screening and lead optimization in drug development, this study also marks a pioneering effort as it involves the modeling of the human translocase and unravels the mechanism of binding and diffusion of G6P within human T1, providing valuable insights into the structural prerequisites for successfully inhibiting the G6P system, laying the foundation for a rational approach to drug design. This research contributes to the progress of drug discovery strategies focused on the G6P system, presenting potential therapeutic avenues for addressing metabolic disorders linked to an impaired glucose metabolism.

Towards universal synthetic heterotrophy using a metabolic coordinator.

Engineering the utilization of non-native substrates, or synthetic heterotrophy, in proven industrial microbes such as Saccharomyces cerevisiae represents an opportunity to valorize plentiful and renewable sources of carbon and energy as inputs to bioprocesses. We previously demonstrated that activation of the galactose (GAL) regulon, a regulatory structure used by this yeast to coordinate substrate utilization with biomass formation during growth on galactose, during growth on the non-native substrate xylose results in a vastly altered gene expression profile and faster growth compared with constitutive overexpression of the same heterologous catabolic pathway. However, this effort involved the creation of a xylose-inducible variant of Gal3p (Gal3pSyn4.1), the sensor protein of the GAL regulon, preventing this semi-synthetic regulon approach from being easily adapted to additional non-native substrates. Here, we report the construction of a variant Gal3pMC (metabolic coordinator) that exhibits robust GAL regulon activation in the presence of structurally diverse substrates and recapitulates the dynamics of the native system. Multiple molecular modeling studies suggest that Gal3pMC occupies conformational states corresponding to galactose-bound Gal3p in an inducer-independent manner. Using Gal3pMC to test a regulon approach to the assimilation of the non-native lignocellulosic sugars xylose, arabinose, and cellobiose yields higher growth rates and final cell densities when compared with a constitutive overexpression of the same set of catabolic genes. The subsequent demonstration of rapid and complete co-utilization of all three non-native substrates suggests that Gal3pMC-mediated dynamic global gene expression changes by GAL regulon activation may be universally beneficial for engineering synthetic heterotrophy.

Structure, dynamics, and molecular inhibition of the Staphylococcus aureus m1A22-tRNA methyltransferase TrmK.

The enzyme m1A22-tRNA methyltransferase (TrmK) catalyzes the transfer of a methyl group to the N1 of adenine 22 in bacterial tRNAs. TrmK is essential for Staphylococcus aureus survival during infection but has no homolog in mammals, making it a promising target for antibiotic development. Here, we characterize the structure and function of S. aureus TrmK (SaTrmK) using X-ray crystallography, binding assays, and molecular dynamics simulations. We report crystal structures for the SaTrmK apoenzyme as well as in complexes with methyl donor SAM and co-product product SAH. Isothermal titration calorimetry showed that SAM binds to the enzyme with favorable but modest enthalpic and entropic contributions, whereas SAH binding leads to an entropic penalty compensated for by a large favorable enthalpic contribution. Molecular dynamics simulations point to specific motions of the C-terminal domain being altered by SAM binding, which might have implications for tRNA recruitment. In addition, activity assays for SaTrmK-catalyzed methylation of A22 mutants of tRNALeu demonstrate that the adenine at position 22 is absolutely essential. In silico screening of compounds suggested the multifunctional organic toxin plumbagin as a potential inhibitor of TrmK, which was confirmed by activity measurements. Furthermore, LC-MS data indicated the protein was covalently modified by one equivalent of the inhibitor, and proteolytic digestion coupled with LC-MS identified Cys92 in the vicinity of the SAM-binding site as the sole residue modified. These results identify a cryptic binding pocket of SaTrmK, laying a foundation for future structure-based drug discovery.

In-depth Sequence-Function Characterization Reveals Multiple Pathways to Enhance Enzymatic Activity.

Deep mutational scanning (DMS) has recently emerged as a powerful method to study protein sequence-function relationships but it has not been well-explored as a guide to enzyme engineering and identifying pathways by which their catalytic cycle may be improved. We report such a demonstration in this work using a Phenylalanine ammonia-lyase (PAL), which deaminates L-phenylalanine to trans-cinnamic acid and has widespread application in chemo-enzymatic synthesis, agriculture, and medicine. In particular, the PAL from Anabaena variabilis (AvPAL*) has garnered significant attention as the active ingredient in Pegvaliase®, the only FDA-approved drug treating classical Phenylketonuria (PKU). Although an extensive body of literature exists on the structure, substrate-specificity, and catalytic cycle, protein-wide sequence determinants of function remain unknown, as do intermediate reaction steps that limit turnover frequency, all of which has hindered rational engineering of these enzymes. Here, we created a detailed sequence-function landscape of AvPAL* by performing DMS and revealed 112 mutations at 79 functionally relevant sites that affect a positive change in enzyme fitness. Using fitness values and structure-function analysis, we picked a subset of positions for comprehensive single- and multi-site saturation mutagenesis and identified combinations of mutations that led to improved reaction kinetics in cell-free and cellular contexts. We then performed QM/MM and MD to understand the mechanistic role of the most beneficial mutations and observed that different mutants confer improvements via different mechanisms, including stabilizing transition and intermediate states, improving substrate diffusion into the active site, and decreasing product inhibition. This work demonstrates how DMS can be combined with computational analysis to effectively identify significant mutations that enhance enzyme activity along with the underlying mechanisms by which these mutations confer their benefit.

Evaluation of dentifrices of complementary and alternative medicinal systems on plaque formation and gingivitis: A randomized controlled clinical trial.

BACKGROUND: Bio-film formation is a natural process in the oral environment, but needs to be controlled through regular brushing in order to prevent the development of caries and periodontal diseases. MATERIAL AND METHODS: A wide variety of dentifrices of complementary and alternative medicinal systems are available in the market which claims superior plaque control. A randomized controlled double-blinded concurrent parallel clinical trial was conducted with the objective to evaluate and compare the clinical effectiveness of three commercially available dentifrices of complementary and alternative medicine systems with that of a placebo dentifrice on Gingival Index (GI) and Plaque Index (PI) scores after 15, 30, 45 and 60 days of usage among 80 adults aged 35-44 years. RESULTS: The mean GI scores reduced by 29.19 %, 22.28 %, 32.43 % and 10.33 % in the herbal dentifrice, homeopathic dentifrice, conventional dentifrice, and placebo dentifrice groups by the end of the study period. Highest reduction of 33.5% and 34.87 % in PI scores were seen in the herbal and conventional dentifrice. This reduction was statistically significant (p=0.001). CONCLUSIONS: The herbal dentifrice tested in the present study has demonstrated anti-gingivitis and anti-plaque efficiency equivocal to the conventional dentifrice. The homeopathic dentifrice was as good as a placebo. Key words:CAM dentifrices, Homeopathic dentifrice, plaque, gingivitis, tooth brushing.

Clinical Evaluation of Proclination of Lower Anterior Teeth during Alignment using a Single Width Bracket-A Pilot Study.

INTRODUCTION: The pre-adjusted brackets are available in various prescriptions and sizes; nevertheless there are still many controversies as to which pre-adjusted edgewise bracket offers the maximum clinical efficiency. AIM: This study was conducted to determine and compare the amount of lower incisor proclination during de-crowding if any of the Mini-Uni Twin Brackets with that of the standard double width brackets. MATERIALS AND METHODS: A total of 20 patients i.e., 10 patients in each group both males and females were randomly selected for the study from subjects seeking treatment, the selected samples were grouped as follows. Group I - Double Width Brackets (3M Unitek Gemini Series) 0.018" slot with Roth prescription. Group II - Mini Uni-Twin Bracket (3M Unitek) 0.018" slot with Roth prescription. RESULTS: The Mini-Uni Twin Brackets had statistically significant (p = 0.01) amount of proclination of the lower anteriors (0.8(o)± 0.3(o)) after de-crowding as compared to the standard Double Width Brackets and since the mean change in the Incisor Mandibular Plane Angle (IMPA) was lesser than 1(o), its clinical significance could be questionable. CONCLUSION: The Mini Uni Twin brackets are comparatively efficient in the lower anterior decrowding but further comparative clinical studies need to be performed on these Mini Uni Twin brackets, with an increase in the sample size and also the number of parameters to prove its total clinical efficiency.

Comparative Evaluation of the Etching Pattern of Er,Cr:YSGG & Acid Etching on Extracted Human Teeth-An ESEM Analysis.

INTRODUCTION: Etching of enamel and dentin surfaces increases the surface area of the substrate for better bonding of the tooth colored restorative materials. Acid etching is the most commonly used method. Recently, hard tissue lasers have been used for this purpose. AIM: The aim of the present study was to evaluate and compare the etching pattern of Er,Cr:YSGG and conventional etching on extracted human enamel and dentin specimens. MATERIALS AND METHODS: Total 40 extracted non-diseased teeth were selected, 20 anterior and 20 posterior teeth each for enamel and dentin specimens respectively. The sectioned samples were polished by 400 grit Silicon Carbide (SiC) paper to a thickness of 1.0 ± 0.5 mm. The enamel and dentin specimens were grouped as: GrE1 & GrD1 as control specimens, GrE2 & GrD2 were acid etched and GrE3 & GrD3 were lased. Acid etching was done using Conditioner 36 (37 % phosphoric acid) according to manufacturer instructions. Laser etching was done using Er,Cr:YSGG (Erbium, Chromium : Ytrium Scandium Gallium Garnet) at power settings of 3W, air 70% and water 20%. After surface treatment with assigned agents the specimens were analyzed under ESEM (Environmental Scanning Electron Microscope) at X1000 and X5000 magnification. RESULTS: Chi Square and Student "t" statistical analysis was used to compare smear layer removal and etching patterns between GrE2-GrE3. GrD2 and GrD3 were compared for smear layer removal and diameter of dentinal tubule opening using the same statistical analysis. Chi-square test for removal of smear layer in any of the treated surfaces i.e., GrE2-E3 and GrD2-D3 did not differ significantly (p>0.05). While GrE2 showed predominantly type I etching pattern (Chi-square=2.78, 0.05

0.10) and GrE3 showed type III etching (Chi-square=4.50, p<0.05). The tubule diameters were measured using GSA (Gesellschaft fur Softwareentwicklung und Analytik, Germany) image analyzer and the 't' value of student 't' test was 18.10 which was a highly significant result (p<.001). GrD2 had a mean dentinal tubule diameter of 2.78µm and GrD3 of 1.09µm. CONCLUSION: The present study revealed type I etching pattern after acid etching, while type III etching pattern in enamel after laser etching. The lased dentin showed preferential removal of intertubular dentin while acid etching had more effect on the peritubular dentin. No significant differences was observed in removal of smear layer between the acid etched and lased groups. Although diameter of the exposed dentinal tubules was lesser after lased treatment in comparison to acid etching, further long term in vivo studies are needed with different parameters to establish the usage of Er,Cr:YSGG as a sole etching agent.

Dilation of both pancreatic duct and the common bile duct on computed tomography and magnetic resonance imaging scans in patients with or without obstructive jaundice.

OBJECTIVES: "Double-duct sign" (strictures in both common bile duct [CBD] and pancreatic duct [PD] with proximal dilation) on endoscopic retrograde cholangiopancreatography is considered suggestive of pancreatic malignancy. Dilation of CBD and PD is frequently noted on computed tomography/magnetic resonance imaging scans, sometimes found incidentally in patients without jaundice. The prevalence of malignancy in these patients is not established. METHODS: In this retrospective analysis, consecutive patients who underwent endoscopic ultrasound (EUS) at a tertiary care hospital from 2002 to 2006 for suspected pancreatic malignancy and had double-duct sign on imaging were included. We evaluated (1) prevalence of malignancy in patients with or without obstructive jaundice and (2) performance characteristics of EUS-fine-needle aspiration (FNA) in diagnosing malignancy in this setting. RESULTS: A final diagnosis of pancreatic malignancy was made in 142 (85.5%) of 166 patients with and 4 (5.9%) of 68 without obstructive jaundice (P < 0.005). The accuracy of EUS-FNA for diagnosing malignancy in patients with or without obstructive jaundice was 92.8% versus 98.5%. CONCLUSIONS: Dilation of both PD and CBD on computed tomography/magnetic resonance imaging scans is suggestive of pancreatic malignancy. The prevalence of malignancy, however, is markedly lower in patients without obstructive jaundice but is clinically significant and merits further diagnostic evaluation. Endoscopic ultrasound-FNA is highly accurate for diagnosing malignancy in this setting.

Small and potentially resectable focal pancreatic lesions noted on CT/MRI scans in nonjaundiced patients: likelihood of neoplasia and utility of EUS.

BACKGROUND: Management of small and potentially resectable "mass" lesions encountered on CT/MRI scans in patients without obstructive jaundice (ObJ) is rather empirical since there is scant data on likelihood of neoplasm to formulate treatment strategies. We evaluated (1) the prevalence of neoplasm and (2) performance characteristics of EUS-FNA for diagnosing neoplasm in above-mentioned subset of patients. PATIENTS: This is a retrospective analysis of 232 patients (without ObJ) with a focal pancreatic lesion, ≤ 25 mm and potentially resectable on CT/MRI who underwent EUS-FNA from 2002 to 2009. RESULTS: Seventy-five patients (32.3%, 95% CI 26.6, 38.6) were finally diagnosed to have a neoplasm. Four of 92 (4.3%) lesions ≤ 15 mm, 13 of 57(22.8%) lesions 16-20 mm, and 35 of 83 (42.1%) lesions 21-25 mm had an adenocarcinoma. Larger lesion size, older patient age, and h/o recent weight loss significantly increased the likelihood of adenocarcinoma. EUS-FNA had 98.2% overall accuracy and 98.1% NPV with no significant differences based on lesion size. CONCLUSIONS: In nonjaundiced patient with a potentially resectable pancreatic lesion ≤25 mm in size noted on CT/MRI scanning, EUS-FNA can provide useful adjunctive information to optimize the use of surgery and can potentially obviate the need for "wait and watch approach" with repeat imaging in their clinical management.

Predictors of axillary lymph node involvement in women with T3 breast cancers: analysis of 1988-2003 SEER data.

BACKGROUND: We investigated characteristics associated with axillary lymph node (LN) status in patients with T3 breast cancers and hypothesized that LN status is an independent predictor of survival. METHODS: Characteristics associated with axillary LN metastasis among women with T3 breast cancers were identified from the 1988-2003 Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was breast cancer-specific mortality. Cox models were used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: A total of 12,778 patients with T3 breast cancers were analyzed (8201 LN+, 3695 LN-, 882 unknown). LN+ patients were more likely to be <50 y, married, and have ER+/PR+, grade 3 invasive ductal cancers (P<0.01 for each). Most patients underwent mastectomy (87.4%). Post-mastectomy radiation was more commonly used in LN+ patients (P<0.01). LN+ patients had higher breast cancer-specific mortality (36.2% versus 16.4%, P<0.01) and were more likely to die during the follow-up period (aHR = 2.87, 95% CI: 2.62-3.15) compared with LN- patients. CONCLUSIONS: Analysis of the SEER database indicated that several patient and tumor characteristics predict a higher likelihood of axillary LN involvement in patients with T3 breast cancers. LN status was an independent predictor of survival in women with T3 breast cancers.

Diagnostic value of EUS-FNA in patients suspected of having pancreatic cancer with a focal lesion on CT scan/MRI but without obstructive jaundice.

OBJECTIVE: Patients frequently present with suspected pancreatic neoplasm based on a focal pancreatic lesion on computed tomographic (CT) scan/magnetic resonance image (MRI) but without obstructive jaundice. We evaluated the performance characteristics of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in this patient subset. METHODS: This is a retrospective analysis of a prospective database and included patients who underwent EUS-FNA at a university hospital for a focal pancreatic lesion noted on CT/MRI. Patients were excluded if (1) they had obstructive jaundice or (2) the lesion appear (seem)ed cystic on CT/MRI. The main outcome measurements were (1) prevalence of pancreatic cancer and (2) performance characteristics of EUS-FNA for identifying malignancy. RESULTS: In the 213 study patients, a focal pancreatic lesion was identified in 173 patients by EUS. The final diagnosis included adenocarcinoma (n=89), neuroendocrine tumor (n=14), mucinous cystadenocarcinoma (n=1), solid pseudopapillary tumor (n=2), metastases (n=4), benign cyst (n=19), pseudocyst (n=9), abscess (n=4), chronic pancreatitis (n=32), and normal pancreas (n=39). Endoscopic ultrasound-guided FNA had an accuracy of 97.6% for diagnosing malignant neoplasm, with 96.6% sensitivity, 99.0% specificity, 96.2% negative predictive value, and 99.1% positive predictive value. CONCLUSIONS: Endoscopic ultrasound-guided FNA is highly accurate for diagnosing malignancy in patients with a focal pancreatic lesion on CT scan/MRI but without obstructive jaundice. Endoscopic ultrasound-guided FNA can potentially be used as a definitive diagnostic test in the management of these patients.

EUS/EUS-FNA for suspected pancreatic cancer: influence of chronic pancreatitis and clinical presentation with or without obstructive jaundice on performance characteristics.

BACKGROUND: The clinical utility of EUS-FNA is debated in patients with obstructive jaundice (ObJ) because of a very high pretest probability of pancreatobiliary malignancy (PBM) and biliary stent-induced inflammation that can potentially confound EUS-FNA diagnosis. EUS-FNA also has lower accuracy in patients with underlying chronic pancreatitis (CP). OBJECTIVE: Our purpose was to determine the clinical value of EUS-FNA for PBM diagnosis based on clinical presentation and presence of CP. DESIGN: Retrospective analysis of prospective database. SETTING: University hospital. PATIENTS: Patients who underwent EUS-FNA from 2002 to 2006 for suspected PBM based on (1) ObJ with biliary stricture or a mass lesion or (2) abnormal pancreatic imaging by CT/MRI: a focal pancreatic "mass" lesion; dilated pancreatic duct +/- common bile duct; or an enlarged head of pancreas. INTERVENTIONS: EUS was performed with a radial echoendoscope followed by a linear echoendoscope if a focal pancreatic lesion was identified. Fine-needle aspirates were assessed immediately by an attending cytopathologist. MAIN OUTCOME MEASUREMENTS: (1) Prevalence of cancer and (2) performance characteristics of EUS-FNA. RESULTS: PBM was diagnosed in 73.9% of patients with ObJ and biliary stricture or pancreatic mass, in 49.6% of patients with pancreatic mass, and in 7.0% of patients with an enlarged head of pancreas or dilated pancreatic duct +/- common bile duct. The prevalence of PBM was lower in all 3 presentations with associated CP. Both CP and presentation with ObJ lowered performance characteristics of EUS-FNA, but CP did so only in the subset of patients with ObJ. All except 1 false-negative diagnoses were due to cytologic misinterpretation. LIMITATION: Retrospective design. CONCLUSION: Among patients with suspected PBM, the accuracy of EUS-FNA is significantly lower only in a subset of patients with ObJ with underlying CP, largely as a result of difficulty in cytologic interpretation.

Reversible gelation of rod-like viruses grafted with thermoresponsive polymers.

The synthesis and selected macroscopic properties of a new model system consisting of poly(N-isopropylacrylamide) (PNIPAM)-coated rod-like fd virus particles are presented. The sticky rod-like colloids can be used to study effect of particle shape on gelation transition, the structure and viscoelasticity of isotropic and nematic gels, and to make both open isotropic as well as ordered nematic particle networks. This model system of rod-like colloids, for which the strength of attraction between the particles is tunable, is obtained by chemically grafting highly monodisperse rod-like fd virus particles with thermoresponsive polymers, e.g. PNIPAM. At room temperature, suspensions of the resulting hybrid PNIPAM-fd are fluid sols which are in isotropic or liquid crystalline phases, depending on the particle concentration and ionic strength. During heating/cooling, the suspensions change reversibly between sol and gel state near a critical temperature of approximately 32 degrees C, close to the lower critical solution temperature of free PNIPAM. The so-called nematic gel, which exhibits a cholesteric feature, can therefore be easily obtained. The gelation behavior of PNIPAM-fd system and the structure of the nematic gel have been characterized by rheology, optical microscopy and small-angle X-ray scattering.

EUS and/or EUS-guided FNA in patients with CT and/or magnetic resonance imaging findings of enlarged pancreatic head or dilated pancreatic duct with or without a dilated common bile duct.

BACKGROUND: Incidental findings of an enlarged head of pancreas (HOP) or dilated pancreatic duct (PD) with or without a dilated common bile duct (CBD) on CT or magnetic resonance imaging (MRI), in patients without obstructive jaundice, raise suspicion for a pancreatic neoplasm, but their clinical significance has not been established. OBJECTIVE: To determine the prevalence of pancreatic neoplasm in this patient group. DESIGN: Retrospective analysis of a prospective database. SETTING: Tertiary-care university hospital. PATIENTS: Patients without obstructive jaundice at initial presentation, who underwent EUS and/or EUS-guided FNA (EUS-FNA) for an abnormal CT and/or MRI with an enlarged HOP (n = 67) or a PD with or without a dilated CBD (n = 43). The final diagnosis was based on definitive cytology, surgical pathology, and clinical follow-up. INTERVENTIONS: An EUS examination was performed by using a radial echoendoscopy followed by a linear echoendoscopy, if a focal pancreatic lesion was identified. Fine-needle aspirates were stained with Diff-Quik and Papanicolaou's methods, and were immediately assessed by an attending cytopathologist. MAIN OUTCOME MEASUREMENTS: (1) The prevalence of pancreatic neoplasms and (2) performance characteristics of EUS-FNA for identifying malignant neoplasm, in this patient group. RESULTS: In 110 study patients, the final diagnosis included adenocarcinoma (n = 7), pancreatic intraepithelial neoplasia (n = 1), neuroendocrine tumor (n = 1), tumor metastasis (n = 1), and benign cyst (n = 3). Thirty-two patients had EUS evidence of chronic pancreatitis, and, in the remaining 65 patients, the pancreas was normal. The accuracy of EUS and EUS-FNA for diagnosing pancreatic neoplasm in these patients was 99.1%, with 88.8% sensitivity, 100% specificity, 99% negative predicative value, and 100% positive predictive value. LIMITATION: A retrospective design and surgical confirmation in only a small number of study patients. CONCLUSION: A pancreatic neoplasm is seen in a clinically significant number of patients with "enlarged HOP" or "dilated PD with or without a dilated CBD" but without obstructive jaundice. EUS-FNA seems highly accurate for diagnosing pancreatic neoplasm in these patients.

Intraductal US in evaluation of biliary strictures without a mass lesion on CT scan or magnetic resonance imaging: significance of focal wall thickening and extrinsic compression at the stricture site.

BACKGROUND AND OBJECTIVE: The clinical utility of intraductal US (IDUS) for evaluating biliary strictures has been limited because of a lack of easily recognized morphologic criteria to distinguish benign and malignant strictures. We studied the clinical value of 2 easily assessed IDUS findings: wall thickness and extrinsic compression at the stricture site. DESIGN AND SETTING: A retrospective, single-center study. PATIENTS AND METHODS: Forty-five patients without an identifiable mass on CT/magnetic resonance imaging, who underwent ERCP/IDUS for evaluation of biliary strictures were studied. IDUS pictures were reviewed specifically to measure wall thickness and to look for extrinsic compression at the stricture site. MAIN OUTCOME MEASUREMENTS AND RESULTS: The mean age of the patients was 64.2+/-13.3 years. Thirty patients had jaundice at presentation, and in 15 patients a stricture was suspected on imaging. The mean length of biliary strictures was 15.1+/-7.8 mm. Strictures were distal (distal common bile duct) in 25 patients and proximal (mid/proximal common bile duct or common hepatic duct) in 20 patients. Fourteen strictures were finally diagnosed to be malignant. Strictures in 20 patients were caused by extrinsic compression, and tissue diagnosis was readily obtained by EUS-FNA in all these patients. Of 25 strictures without extrinsic compression, 6 were malignant (wall thickness 9-16 mm) and 19 were benign (wall thickness

Periportal lymphadenopathy in patients without identifiable pancreatobiliary or hepatic malignancy.

BACKGROUND & AIMS: Enlarged periportal lymph nodes often are noticed during imaging of the upper abdomen. Malignant infiltration and enlargement of periportal nodes occur in patients with cancers of the liver, gallbladder, biliary tree, and pancreas and lymphoma. However, there are no published data on the significance and differential diagnosis of enlarged periportal lymph nodes in patients without the above mentioned cancers. METHODS: We searched our database for patients who (1) underwent endoscopic ultrasound for evaluation of enlarged periportal nodes or (2) were found to have enlarged periportal lymph nodes (> or =10 mm) during endoscopic ultrasound (EUS) examination. Patients with identifiable pancreatic, biliary, gallbladder, or liver cancers were excluded. EUS-guided fine-needle aspiration of one or more nodes was performed. RESULTS: Sixty-four patients with periportal lymph nodes 10-40 mm in size met the inclusion criteria. In 24 patients, enlarged periportal nodes were noted in the computerized tomography or magnetic resonance imaging scans. Fifty-one patients had multiple enlarged periportal nodes. Concomitantly, enlargement was seen in peripancreatic nodes (n = 14), celiac nodes (n = 14), and mediastinal nodes (n = 11). Twelve of the 64 patients (18.8%; 95% confidence interval, 9.2%-28.4%) had a malignant cause of enlarged periportal lymph nodes: 5 with metastatic carcinoma and 7 with non-Hodgkin's lymphoma. Significant cytologic findings in benign nodes included granulomas (n = 4) and lipogranulomatosis (n = 8). CONCLUSIONS: A significant number of patients with enlarged periportal lymph nodes without identifiable pancreatobiliary and liver cancer harbor malignancy and other identifiable pathologic processes. We recommend that these nodes be sampled with fine-needle aspiration at the time of EUS examination.