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Objectives This study sought to report P-wave morphology (PWM) from a series of paraseptal (PS) atrial tachycardia (AT), revise then prospectively evaluate a simplified PWM algorithm against a contemporary consecutive cohort with focal AT. Background The 2006 PWM algorithm was useful in predicting the origin of focal AT. An updated algorithm was developed given advances in multipolar 3-dimensional mapping, potential limitations of PWM in separating PS sites, and a renewed interest in the P-wave in mapping non–pulmonary vein triggers. Methods The PWM from a consecutive series of 67 patients with PS AT were analyzed. PS sites included were coronary sinus ostium, perinodal, left and right septum, septal tricuspid annulus, superior mitral annulus, and noncoronary cusp. Next the P-wave algorithm was revised and prospectively evaluated by 3 blinded assessors. Results The P-wave for PS sites was neg/pos (n = 50), iso/pos (n = 10), or isoelectric (n = 4) in lead V1 (96%). The P-wave algorithm was modified and prospectively applied to 30 consecutive patients with focal AT who underwent successful ablation. Foci (n = 30) originated from the right atrium (33.3%), left atrium (30%), and PS (36.7%). Using the PW algorithm, the correct anatomic location was identified in 93%. Incorrect interpretation of the terminal positive P-wave component (n = 3) and initial negative P-wave deflection (n = 1) in lead V1 misidentified 4 paraseptal cases. Conclusions The revised PWM algorithm offers a simplified and accurate method of localizing the responsible site for focal AT. The P-wave remains an important first step in mapping atrial arrhythmias.

Background Electrocardiographic (ECG) criteria have been proposed to localize the site of origin of outflow region ventricular arrhythmias (VAs). Many factors influence the QRS morphology of VAs and may limit the accuracy of these criteria. Objective The purpose of this study was to assess the accuracy of ECG criteria that differentiate right from left outflow region VAs and localize VAs within the aortic sinus of Valsalva (ASV). Methods One hundred one patients (mean age 52 ± 16 years; 55 [54%] women) undergoing catheter ablation of right ventricular outflow tract (RVOT) or ASV VAs with a left bundle branch block, inferior axis morphology were studied. ECG measurements including V2 transition ratio, transition zone index, R-wave duration index, R/S amplitude index, V2S/V3R index, V1–3 QRS morphology, R-wave amplitude in the inferior leads were tabulated for all VAs. Comparisons were made between the predicted site of origin using these criteria and the successful ablation site. Results Patients had successful ablation of 71 RVOT and 38 ASV VAs. For the differentiation of RVOT from ASV VAs, the positive predictive values and negative predictive values for all tested ECG criteria ranged from 42% to 75% and from 71% to 82%, respectively, with the V2S/V3R index having the largest area under the curve of 0.852. Morphological QRS criteria in leads V1 through V3 did not localize ASV VAs. The maximum R-wave amplitude in the inferior leads was the sole criterion demonstrating a significant difference between right ASV, right-left ASV commissure, and left ASV sites. Conclusion ECG criteria for differentiating right from left ventricular outflow region VAs and for localizing ASV VAs have a limited accuracy.

Multiple ECG algorithms exist to localize outflow tract PVCs. They can be invaluable in pre-procedure planning and patient counseling. We describe a case where the published algorithm for PVC localization did not predict the site of origin and successful ablation site. This case highlights the strengths and limitations of established ECG PVC localization algorithms.

Recently, Muhlemann et al. (2018) and Krause-Kyora et al. (2018) discovered 15 ancient Hepatitis B virus (aHBV) sequences dating back to the Neolithic age (NA) and the Bronze age (BA). Being published simultaneously, neither of these studies could include sequences from the other for analyses. In the present research, aHBV sequences from these studies were collective re-analysed with reference to a comprehensive database comprising extant HBV diversity to understand their relatedness and role in the evolution of extant HBV diversity. Present analyses revealed several interesting findings on distribution, dispersal, phylogenetic and recombinational relatedness of ancient HBV to extant genotypes, which were not recognized previously. Several interesting recombination patterns were observed, which corroborated well with ancient human migration, shown by the human genetic studies. Present analyses suggest that comparable to the replacement of the Neolithic European farmer associated Y chromosome haplogroups by haplogroups associated with the steppe people during Steppe migration, HBV genotype associated with the early Neolithic European farming cultures was also replaced by the ancestral HBV genotype A probably carried by the migrating steppe people, and a variant of this genotype is the prevalent HBV genotype in contemporary European populations. Additionally, based on recent literature, this research also indicates that HBV genotype divergence estimates proposed by Muhlemann et al., and others cannot sufficiently explain distribution of certain extant HBV genotypes. Hence, an alternative possibility to explain long distance and trans-oceanic distribution of phylogenetically related HBV genotypes was reviewed and discussed in the light of currently available knowledge. Through this manuscript, novel and important findings of the present analyses are communicated.

Objectives This study sought to establish a mapping and ablation strategy to target intramural ventricular arrhythmias (VAs) by identifying the precise arrhythmia site of origin (SOO). Background Radiofrequency ablation of intramural VAs is challenging because the arrhythmia origin is difficult to localize. Methods In 83 consecutive patients with intramural VAs, a stepwise mapping approach was performed: ablation targeted directly the SOO when possible followed by the closest adjacent anatomical structure when necessary. If the SOO could not be identified, the earliest endocardial breakout sites were ablated. Safety and procedural outcomes between patients in whom the SOO could and could not be identified were compared. Results The SOO was identified in 19 of 83 (23%) patients, and radiofrequency ablation was effective in eliminating VAs in all 19 (100%) patients by ablation at the SOO alone (n = 3), at the SOO and an anatomically adjacent area (n = 7), or at an anatomically adjacent area alone (n = 9). Breakout site mapping and ablation in the remaining 64 patients in whom the SOO was not identified was effective in 43 of 64 patients, which was significantly less than in patients in whom the SOO was identified (67% vs. 100%; p Conclusions Identification of the SOO was associated with a successful ablation procedure by either targeting the SOO directly or targeting an adjacent anatomical structure. Ablation at the breakout sites of intramural VAs has a lower efficacy than when the SOO can be directly targeted.

The latest WHO classification cleanly divides gastrointestinal neuroendocrine neoplasms into neuroendocrine tumor (NET; well-differentiated, any grade) and neuroendocrine carcinoma (NEC; poorly differentiated, high-grade by definition), along with mixed neuroendocrine-non-neuroendocrine neoplasms. NECs are always aggressive, with multiple mutations; they are treated with chemotherapy. NETs have widely different presentations, behavior, and management depending on site of origin. Esophageal examples are vanishingly rare. Most gastric and appendiceal tumors are indolent, as are many colonic and rectal tumors. The duodenum is home to some unusual variants of NET, and jejunal/ileal NETs frequently metastasize, which impacts their staging and clinical management.

Aims Assess the minimal number of ECGI leads needed to obtain a good spatial resolution. Methods We enrolled 20 patients that underwent ablation of premature ventricular or atrial contractions using Carto and ECGI with AMYCARD. We evaluated the agreement regarding the site of origin of the arrhythmia between the ECGI and Carto, the area and diameter of the earliest activation site obtained with the ECGI (EASa and EASd). Based on previous studies with pacemapping, we considered a good spatial resolution of the ECGI when the EASd measured on the isopotential map was less than 18 mm. In presence of agreement the ECGI was reprocessed: a) with half the number of electrode bands (8 leads per electrode band) and b) with 6 electrode bands. Results The initial map was obtained with 23 (22-23) electrode bands per patient, corresponding to 143 (130-170) leads. Agreement rate was 85%, the median EASa and EASd were: 0.7 (0.5-1.3) cm2 and 9 (8-13) mm. With half the number of electrode bands including 73 (60-79) leads, agreement rate was 80%, the EASa and EASd were: 2.1 (1.5-6.2) cm2 and 16 (14 -28) mm. With only six electrode bands using 38 (30-42) leads, agreement rate was 55%, EASa and EASd were: 4.0 (3.3-5.0) cm2 and 23 (21-25) mm. The number of leads was a predictor of agreement with a good spatial resolution, OR (95% CI) of 1.138 (1.050–1.234), p = .002. According to the ROC curve, the minimal number of leads was 74 (AUC 0.981; 95% CI: 0.949–1.00, p Conclusion Reducing the number of leads was associated with a lower agreement rate and a significant reduction of spatial resolution. However, the number of leads needed to achieve a good spatial resolution was less than the maximal available.

This review serves as a primer on contemporary neuroendocrine neoplasm classification, with an emphasis on gastroenteropancreatic well-differentiated neuroendocrine tumors. Topics discussed include general features of neuroendocrine neoplasms, general neuroendocrine marker immunohistochemistry, the distinction of well-differentiated neuroendocrine tumor from pheochromocytoma/paraganglioma and other diagnostic mimics and poorly differentiated neuroendocrine carcinoma from diagnostic mimics, the concepts of differentiation and grade and the application of Ki-67 immunohistochemistry to determine the latter, the various WHO classifications of neuroendocrine neoplasms including the 2019 WHO classification of gastroenteropancreatic tumors, organ-specific considerations for gastroenteropancreatic well-differentiated neuroendocrine tumors, immunohistochemistry to determine site of origin in metastatic well-differentiated neuroendocrine tumor of occult origin, immunohistochemistry in the distinction of well-differentiated neuroendocrine tumor G3 from large cell neuroendocrine carcinoma, and, finally, required and recommended reporting elements for biopsies and resections of gastroenteropancreatic neuroendocrine epithelial neoplasms.

This review is based on a presentation given at the Hans Popper Hepatopathology Society companion meeting at the 2019 United States and Canadian Academy of Pathology Annual Meeting. It presents updates on the diagnosis and classification of neuroendocrine neoplasms, with an emphasis on the role of immunohistochemistry. Neuroendocrine neoplasms often present in liver biopsies as metastases of occult origin. Specific topics covered include 1. general features of neuroendocrine neoplasms, 2. general neuroendocrine marker immunohistochemistry, with discussion of the emerging marker INSM1, 3. non-small cell carcinoma with (occult) neuroendocrine differentiation, 4. the WHO Classification of neuroendocrine neoplasms, with discussion of the 2019 classification of gastroenteropancreatic neoplasms, 5. use of Ki-67 immunohistochemistry, 6. immunohistochemistry to assign site of origin in neuroendocrine metastasis of occult origin, 7. immunohistochemistry to distinguish well-differentiated neuroendocrine tumor G3 from poorly differentiated neuroendocrine carcinoma, 8. lesions frequently misdiagnosed as well-differentiated neuroendocrine tumor, and 9. required and recommended data elements for biopsies and resections with associated immunohistochemical stains. Next-generation immunohistochemistry, including lineage-restricted transcription factors (e.g., CDX2, islet 1, OTP, SATB2) and protein correlates of molecular genetic events (e.g., p53, Rb), is indispensable for the accurate diagnosis and classification of these neoplasms.

Background Data regarding the successful ablation site of idiopathic outflow tract (OT) ventricular arrhythmias (VAs) in the modern era of mapping and ablation are limited. Methods and results Over a 4-year period, a total of 309 patients underwent detailed activation mapping of OT VAs including the right ventricular outflow tract (RVOT), the left ventricular outflow tract (LVOT) and the aortic cusps (AC), and the coronary venous system. 244 cases were successfully ablated at the index procedure (78.9%). The successful ablation site was more frequently located at the LVOT/ACs (51.6%) followed by RVOT (36.2%). In particular, the ACs was the predominant successful ablation site of idiopathic OT VAs (46.7%). An epicardial site of origin was predictor of ablation failure (p Conclusions The ACs is the predominant successful ablation site of idiopathic OT VAs. Take-home message The aortic cusps are the predominant successful ablation site of idiopathic idiopathic outflow tract ventricular arrhythmias.

Most benign tumors of the larynx are epithelial in origin, with nearly 85% being laryngeal papilloma. Nonepithelial laryngeal tumors are uncommon and more than 50% of these are malignant. Therefore, benign nonepithelial solid tumors of the larynx are quite rare. The management of these tumors varies based on the site of origin, specific pathology, tumor size, and risk for malignant transformation. Most are ultimately treated with complete surgical excision, although the potential response of the tumor to adjuvant therapy may play a role in decision making. In this article, general approaches to surgical excision of these benign nonepithelial laryngeal tumors is discussed.

Imaging plays an active role in the surveillance of gastrointestinal stromal tumours (GISTs). Risk stratification schemes, based on size, mitotic count, and anatomical site of origin of the GIST, help in planning preoperative and postoperative imaging strategies especially in determining the frequency and duration of surveillance; however, there is no clear consensus on the optimal imaging strategies in patients with GISTs who are completely cured by surgery and patients who are at risk of recurrence. In addition, current surveillance protocols depend on the resectability of the primary tumour and presence of metastatic disease. The objective of this article is to provide a comprehensive review of the role of the different imaging methods for surveillance of GISTs, focusing on the guidelines recommended by National Comprehensive Cancer Network and European Society of Medical Oncology - European Network for Rare adult solid Cancers, and to propose practical guidelines for surveillance of GISTs for various risk categories.

Neuroendocrine tumors (NETs) are rare neoplasms whose incidence is increasing. NETs constitute a heterogeneous group of tumors. Their clinical features, functional properties, and clinical course are different on the basis of their site of origin. Due to the heterogeneity of these tumors, a coordinated multidisciplinary approach is required in these patients. However, medical doctor encounters many difficulties when providing care for patients with NETs. This review provides an overview of the state of the art of zebrafish model in the cancer research with a main focus on NETs.

High-grade serous (HGSC) stands apart from the other ovarian cancer histotypes in being the most frequent, in occurring as part of a genetic predisposition in a significant proportion of cases, and in having the poorest clinical outcomes. Although the pathologic diagnosis of HGSC is now made with high accuracy, there remain areas of disagreement regarding viewpoints on tissue site of origin and designation of primary site, with impact on staging in low-stage cases, as well as difficulties in reproducible and clinically relevant reporting of HGSC in specimens taken after neoadjuvant chemotherapy. These areas are discussed in the current article.

Computed tomography (CT) is the imaging modality of choice for evaluating mediastinal masses detected by radiography or clinical presentation. However, CT results can often be indeterminate. Thoracic magnetic resonance (MR) imaging is a noninvasive way to characterize mediastinal lesions, site of origin, and involvement of adjacent structures by providing higher soft tissue contrast than CT, with superior tissue characterization and higher diagnostic specificity. Thoracic MR imaging of mediastinal masses can increase diagnostic certainty, reduce the number of surgical interventions, and improve clinical decision making. In this review article, current imaging techniques and clinical applications of MR imaging as a problem-solving tool for assessing mediastinal masses in pediatric patients are discussed.

The 12-lead electrocardiograph (ECG) is of critical importance both in the diagnosis of wide complex tachycardia and in the further classification, characterisation and management of ventricular arrhythmias. With its diligent application and interpretation, remarkable precision can be achieved in the localisation of the site of origin of ventricular arrhythmias and this may have major implications in the care of these patients. This review discusses the technical, anatomic and mechanistic basis of ECG interpretation in ventricular arrhythmias.

It has long been recognized that the bone marrow is the primary site of origin for circulating monocytes that may later become macrophages in atherosclerotic lesions. However, only in recent times has the complex relationship among the bone marrow, monocytes/macrophages, and atherosclerotic plaques begun to be understood. Moreover, the systemic nature of these interactions, which also involves additional compartments such as extramedullary hematopoietic sites (i.e., spleen), is only just becoming apparent. In parallel, progressive advances in imaging and cell labeling techniques have opened new opportunities for in vivo imaging of monocyte/macrophage trafficking in atherosclerotic lesions and at the systemic level. In this Part 3 of a 4-part review series covering the macrophage in cardiovascular disease, the authors intersect systemic biology with advanced imaging techniques to explore monocyte and macrophage dynamics in the cardiovascular system, with an emphasis on how events at the systemic level might affect local atherosclerotic plaque biology.

Primary hepatic leiomyosarcoma is a rare primary mesenchymal tumor of the liver requiring exclusion of any other primary site of origin and histological and immunohistochemical exclusion of other hepatic/extrahepatic tumors with spindle cell morphology. Only about 70 cases are reported in the English literature and many of these tumors have predisposing conditions in the form of immunosuppression or associated malignancies. The occurrence of this tumor in the immunocompetent individual is also known. Histomorphology of this tumor shows a spindle cell lesion which needs to be distinguished from other spindle cell lesions of this region. The main diagnostic challenge of this tumor lies in its rarity, lack of awareness and morphological mimickers in the given site. A complete range of immunohistochemical markers is required to distinguish the lesion from its close morphological mimickers. Here, we discuss a case of primary hepatic leiomyosarcoma in an adult female patient with detailed histomorphological differentials and respective immunoprofiles.

The surface ECG is a valuable mapping tool in patients with idiopathic and scar-related ventricular arrhythmias (VAs). A detailed analysis of 12-lead ECG can provide useful information in localizing the VA site of origin. This might help tailoring the ablation strategy to optimize procedural duration, increase the probability of success, and prevent complications. The aim of this article is to review the ECG features of both idiopathic and scar-related VAs and discuss their potential implications for optimizing the ablation strategy.

Pathologists use immunohistochemistry is their day-to-day practices to assist in distinguishing site of origin of metastatic carcinomas. Here, the work-up is discussed neuroendocrine carcinomas, squamous cell carcinomas and adenocarcinomas with particular attention to tumor incident rates and predictive values of the best-performing immunohistochemical markers.

PURPOSE/OBJECTIVE(S): Incident learning is key to developing and maintaining quality and safety in healthcare. This work aims to quantify how submissions to our incident learning system and contributing factors for events have changed in the time of COVID. MATERIALS/METHODS: Events from our incident learning system were analyzed for the 11 months pre-COVID (March 1, 2019 - January 31, 2020) and compared to 11 months during COVID (March 1, 2020 - January 31, 2021). Descriptive statistics were used to evaluate and compare the reporting rate, incident severity, contributing factors, and where in patient pathway the incident originated and was caught. RESULTS: See Table. CONCLUSION: During COVID the number of reported incidents, particularly incidents reaching the patient, markedly declined. This is perhaps related to a decline in the number of treatments delivered during COVID and the presence of new COVID-related workflows. The site of origin of the incidents was similar pre- vs. during-COVID. However, the locations where incidents were caught (detected) shifted to more near-'end of the line' safeguards (e.g., pre-RT Physics and RTT chart checks & write-up), suggesting a potential degradation of safeguards present earlier in the process (e.g., pre-RT peer review, Dosimetry pre-RT check). Communication, hand-offs, and cross-coverage were more likely to be contributing factors during COVID which is most likely attributable to people working virtually/remotely during the pandemic. This emphasizes the need to reduce inter-provider variations, and consistent standards for communication and treatment.

Temperature, which is one of the most relevant abiotic factors affecting seed germination, is strongly influenced by local site conditions. Here, we collected seeds of Hypericum balearicum, an endemic shrub of the Balearic Islands, from 11 sites of Mallorca. We investigated variations in final germination percentage (FGP), germination rate (t50) and germination timing (t0) of seeds from different provenances according to the local conditions of each location (here classified in mountain, coast and valley environment) under a range of temperature treatments (12–24 oC). An environmental data logger was installed in three of the sites to determine the temperature variability for each environment. Hypericum balearicum germinates in the optimal temperature range of Mediterranean plants. FGP was neither affected by temperature treatments nor by the site of origin (environment). However, the coast environment showed higher t50 and t0 values in all temperatures tested compared to mountain and valley, especially at low temperatures compared to mountain environment and at low and high temperatures compared to valley environment. These differences among environments were consistent with the temperature parameters recorded in each environment. Overall, this study demonstrates the importance of taking into account local temperature conditions effects in germination in order to know how plants will respond to environmental changes.

Metastatic colorectal cancers (mCRCs) are clinically heterogeneous, but the genomic basis of this variability remains poorly understood. We performed prospective targeted sequencing of 1134 CRCs. We identified splice alterations in intronic regions of APC and large in-frame deletions in CTNNB1, increasing oncogenic WNT pathway alterations to 96% of CRCs. Right-sided primary site in microsatellite stable mCRC was associated with shorter survival, older age at diagnosis, increased mutations, and enrichment of oncogenic alterations in KRAS, BRAF, PIK3CA, AKT1, RNF43, and SMAD4 compared to left-sided primaries. Left-sided tumors frequently had no identifiable genetic alteration in mitogenic signaling, but exhibited higher mitogenic ligand expression. Our results suggest different pathways to tumorigenesis in right- and left-sided microsatellite stable CRC that may underlie clinical differences.

The relevance of the temporal relationship between a unipolar electrogram (UEGM) and a bipolar electrogram (BEGM) in determining the site of origin (SOO) of focal arrhythmias has been largely demonstrated.We sought to demonstrate that a negative concordance in the initial forces of these EGMs is also helpful in predicting the SOO of premature ventricular contractions (PVCs).Mapping and radiofrequency (RF) ablation were performed in 41 patients with symptomatic PVCs in the absence of structural heart disease. Simultaneous recordings of the minimally filtered (0.5-500 Hz) UEGM and filtered BEGM (30-500 Hz) were analyzed at 247 mapping sites, where RF was attempted. EGMs of 63 mechanically induced PVCs were separately analyzed as a validation group. All ablation sites had a QS pattern in the UEGM. Acute PVC suppression was defined as a complete disappearance of ventricular ectopic beats after a 60-second pulse of RF.RF ablation obtained PVC suppression (RF+) in 33 of 247 sites (13.3%). A negative concordance pattern (NCP) during the initial 20 ms of both UEGM and BEGM was observed in 31 of 33 (94%) RF+ sites compared with 10 of 214 (4%)RF- sites (P.0001). The NCP criterion demonstrated to be an additional powerful predictor of acute RF success with sensitivity, specificity, positive predictive value, and negative predictive value of 94%, 95%, 76%, and 99%, respectively. Similarly to RF+ sites, the NCP was observed in 60 of 63 sites (95.2%) in the mechanical PVC group.An NCP in both UEGM and BEGM may be an additional criterion that helps to localize the SOO of focal ventricular arrhythmias.

The neocortex is the site of origin of several forms of acquired epilepsy. Here we provide a brief review of experimental models that were recently developed to study neocortical epileptogenesis as well as some major results obtained with these methods. Most of neocortical seizures appear to be nocturnal and it is known that neuronal activities reveal high levels of synchrony during slow-wave sleep. Therefore, we start the review with a description of mechanisms of neuronal synchronization and major forms of synchronized normal and pathological activities. Then, we describe three experimental models of seizures and epileptogenesis: ketamine-xylazine anesthesia as feline seizure triggered factor, cortical undercut as cortical penetrating wound model and neocortical kindling. Besides specific technical details describing these models we also provide major features of pathological brain activities recorded during epileptogenesis and seizures. The most common feature of all models of neocortical epileptogenesis is the increased duration of network silent states that up-regulates neuronal excitability and eventually leads to epilepsy.

Background Pace mapping (PM) is used to identify the origin of ventricular arrhythmias (VAs). For intramural VAs, the site of origin often cannot be reached and therefore PM is less accurate. Objective The purpose of this study was to assess the value of single- and dual-site pace maps to differentiate intramural from nonintramural VAs. Methods In 18 consecutive patients with idiopathic intramural VAs, pace mapping was performed at 2 breakthrough sites in adjacent anatomic structures. Twelve-lead electrocardiograms of the 2 pace maps were averaged in MATLAB and compared (correlation coefficient [CC]) with the targeted VA. Dual-site pace mapping was performed in a control group of 18 patients with nonintramural VAs at the sites of earliest electrical activation and a breakthrough site in an adjacent anatomic location. Results Dual-site pace maps had a higher CC than did best single-site pace maps (0.87 ± 0.1 vs 0.81 ± 0.16; P = .02) in patients with intramural VAs. At the site of origin, single-site pace maps had a higher CC than did dual-site pace maps obtained from adjacent anatomic locations (0.93 ± 0.04 vs 0.89 ± 0.05; P = .0004) in patients with nonintramural VAs. Sensitivity, specificity, positive predictive value, and negative predictive value of dual-site pace maps for identifying an intramural VA were 89%, 82%, 84%, 88%, and 86%, respectively. Furthermore, the receiver operating characteristic curve analysis revealed that a CC cutoff value of ≤0.86 for a single-site pace map best differentiated intramural from nonintramural VAs. Conclusion A higher CC value for a dual-site pace map obtained from the earliest breakthrough site as well as a CC cutoff value of ≤0.86 for a single-site pace map obtained from the site of earliest electrical activation can best differentiate intramural from nonintramural VAs.

Juvenile nasopharyngeal angiofibroma (JNA) is the most common benign tumor of the nasopharynx. For reasons unknown, this tumor is found almost always in male population. However, site of origin of JNA is still an enigma. Previously, JNA was considered to arise from the superior aspect of sphenopalatine foramen. Over last decade, the vidian canal was considered to be the more specific and likely site of origin. However, based on our observations, we believe this hypothesis to be anomalous as it does not explain major blood supply, pattern of skull base erosion in early stage of tumor and newer studies on electron microscopic and immunopathological findings. To explain these anomalies, we hypothesize the site of origin to be palato-vaginal canal.

Using isotopic ratio mass spectrometry (IRMS) measurements, this study analyzed samples of saffron originating from two distinct geographical regions. We then used the results to distinguish saffron of the two considered origins. δ13C data related to the crocin fractions in 48 saffron samples from Western Macedonia (Greece) and 48 samples from Khorasan Province (Iran) were correlated to an index derived from triacylglycerols. Isotopic data could clearly differentiate between samples from the two areas. The isotopic measurements were -28.3 to -26.9 for Greek samples, and -26.1 to -24.5 for Iranian samples. Another index, derived from a gas-chromatographic analysis of the triacylglycerols, successfully determined that the range of isotopic values that characterized Greek samples was 52% larger than the range that characterized Iranian samples. The application of statistical evaluations permitted us to identify the two groups of saffron with confidence and to accurately identify the site of origin of a saffron sample.

Background The earliest activation site (EAS) location in the septal right ventricular outflow tract (RVOT) could be an additional mapping data predictor of left ventricular outflow tract (LVOT) vs RVOT origin of idiopathic ventricular arrhythmias (VAs). Objective The purpose of this study was to assess the impact of EAS location in predicting LVOT vs RVOT origin. Methods Macroscopic and histologic study was performed in 12 postmortem hearts. Electroanatomic maps (EAMs) from 37 patients with outflow tract (OT) VA with the EAS in the septal RVOT were analyzed. Pulmonary valve (PV) was defined by voltage scanning after validation of voltage thresholds by image integration. EAM measurements were correlated with those of macroscopic/histologic study. Results A cutoff value of 1.9 mV discriminated between subvalvular and supravalvular positions (90% sensitivity, 96% specificity). EAS ≥1 cm below PV excluded RVOT site of origin (SOO). According to anatomic findings (distance PV–left coronary cusp=5 ± 3 vs PV–right coronary cusp=11 ± 5 mm), EAS–PV distance was significantly shorter in VAs arising from left coronary cusp than from the other LVOT locations (4.2 ± 5.4 mm vs 9.2 ± 7 mm; P = .034). The 10-ms isochronal longitudinal/perpendicular diameter ratio was higher in the RVOT vs the LVOT SOO group (1.97 ± 1.2 vs 0.79 ± 0.49; P = .001). An algorithm based on EAS–PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio predicted LVOT SOO with 91% sensitivity and 100% specificity. Conclusion An algorithm based on the EAS–PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio accurately predicts LVOT vs RVOT SOO in outflow tract VAs with EAS in the septal RVOT.

Background The caries lesion, the most commonly observed sign of dental caries disease, is the cumulative result of an imbalance in the dynamic demineralization and remineralization process that causes a net mineral loss over time. A classification system to categorize the location, site of origin, extent, and when possible, activity level of caries lesions consistently over time is necessary to determine which clinical treatments and therapeutic interventions are appropriate to control and treat these lesions. Methods In 2008, the American Dental Association (ADA) convened a group of experts to develop an easy-to-implement caries classification system. The ADA Council on Scientific Affairs subsequently compiled information from these discussions to create the ADA Caries Classification System (CCS) presented in this article. Conclusions The ADA CCS offers clinicians the capability to capture the spectrum of caries disease presentations ranging from clinically unaffected (sound) tooth structure to noncavitated initial lesions to extensively cavitated advanced lesions. The ADA CCS supports a broad range of clinical management options necessary to treat both noncavitated and cavitated caries lesions. Practical Implications The ADA CCS is available for implementation in clinical practice to evaluate its usability, reliability, and validity. Feedback from clinical practitioners and researchers will allow system improvement. Use of the ADA CCS will offer standardized data that can be used to improve the scientific rationale for the treatment of all stages of caries disease.

Epithelial myoepithelial carcinoma (EMC) is a rare low-grade biphasic tumour of salivary gland. Most common site of origin is the parotid gland with female predominance. We present a case of a 51-year-old male patient with symptomless slow-growing 2-year-old lump on the floor of the mouth. Histopathological diagnosis is corroborative with tubular variant of epithelial myoepithelial carcinoma. The floor of the mouth is the rare site for this tumour. In this literature, we intend to discuss the clinical and pathological aspect of EMC located on the floor of the mouth.

Vascular leiomyosarcomas are extremely rare, and involve veins 5 times more often than arteries. In the lower extremity, the great saphenous vein is the most frequent site of origin. We report the case of a healthy 45-year-old patient who presented with a painless mass located proximally in the right thigh in line with the great saphenous vein. At surgery, the treatment consisted of wide local excision. Histopathological studies confirmed mass as leiomyosarcoma. In light of this report, we draw attention to this rare disease, though with a poor prognosis.

Prediction of site of origin of ventricular arrhythmias (VA) prior to ablation is important for procedural prognostication, risk assessment and preparation. We used noninvasive electrocardiographic mapping (ECM) to identify the origin of outflow tract VAs (OTVA). We included patients with OTVA

Immunohistochemistry (IHC) has broad applications in neoplastic gastrointestinal surgical pathology. Although classically used as a diagnostic tool, IHC increasingly provides prognostic and predictive information. This review highlights 11 key uses of IHC (Box 1). Emphasis is placed on specific clinical applications and qualitative aspects of interpretation. Common pitfalls are specifically highlighted. The potential application of emerging markers is discussed in relation to several of the 11 topics. In many instances, an immunostain serves as a surrogate for specific molecular genetic events. Survey of relevant articles forms the evidence basis for this review.

Immunohistochemistry has come to occupy a key position among the armamentarium of tools pathologists apply to the evaluation of lung and pleural neoplasms. This technique uses antibodies that bind to specific antigens, usually proteins, enabling microscopic detection of the antigens. Over the last several decades, an impressive array of antibodies has become commercially available, and many of these antibodies have become integrated into the routine practice of pathology. Evaluation of tissue or cytology samples with these antibodies can facilitate determination of tumor type and site of origin. Comments citing results of immunohistochemical staining with these antibodies frequently appear in pathology reports and may be difficult to translate for those less familiar with the technique. This review presents, in two parts, common diagnostic applications of immunohistochemistry with information about strategies taken for frequently encountered differential diagnostic scenarios. This article is the second of the two parts and focuses on immunohistochemical approaches to differentiating primary pulmonary from metastatic adenocarcinomas, mesotheliomas from carcinomas, and various types of spindle cell neoplasms. Potential future directions involving therapeutic and prognostic biomarkers are also discussed.

► Most solitary fibrous tumors (SFTs) are benign tumors, but some behave more aggressively. ► Correlation between pathologic grading and clinical behavior is poor but immunohistochemical profiles may be of use. ► Most disease is limited to site of origin, but complete surgical resection with follow-up is the standard of care.

Immunohistochemistry has come to occupy a key position among the armamentarium of tools pathologists apply to the evaluation of lung and pleural neoplasms. This technique uses antibodies that bind to specific antigens, usually proteins, enabling microscopic detection of the antigens. Over the last several decades, an impressive array of antibodies has become commercially available, and many of these antibodies have become integrated into the routine practice of pathology. Evaluation of tissue or cytology samples with these antibodies can facilitate determination of tumor type and site of origin. Comments citing results of immunohistochemical staining with these antibodies frequently appear in pathology reports and may be difficult to translate for those less familiar with the technique. This review presents, in two parts, common diagnostic applications of immunohistochemistry, with information about strategies taken for frequently encountered differential diagnostic scenarios. This, the first of two parts, offers a basic overview of the technique and discusses its applications in the diagnosis of common primary lung carcinomas.

SummaryWe report a case of cardiac memory following recurrent episodes of monomorphic idiopathic ventricular tachycardia and explain how it could be helpful in localizing the site of origin of the arrhythmia.

The lateral ventricle is a deep-seated cavity, overlayed by a cortical mantle which contains eloquent areas, especially on the dominant hemisphere, and surrounded by the optic radiations. The surgical approach requires a thorough preoperative reflexion based on magnetic resonance imaging, in order to understand the site of origin and the vascular pedicles of the tumor. Surgical approaches to the frontal horn, temporal horn and atrium are successively described.

An unknown primary tumor (UPT) is defined by the presence of a metastatic cancer without a known primary site of origin despite a standardized diagnostic workup. Clinically, UPTs show rapid progression and early dissemination, with signs and symptoms related to the metastatic site. The molecular bases of their biology remain largely unknown, with no evidence as to whether they represent a distinct biological entity. Immunohistochemistry remain the best diagnostic tool in term of cost-effectiveness, but the time-consuming "algorithmic process" it relies on has led to the application of new molecular techniques for the identification of the primary site of UPTs. For example, several microarray or miRNA classifications of UPTs have been used, with an accuracy in the prediction of the primary site as high as 90%. It should be noted that validating a prediction of tissue origin is challenging in these patients, since most of them will never have a primary site identified. Moreover, prospective studies to determine whether selection of treatment options based on such profiling methods actually improves patient outcome are still missing. In the last few years functional imaging (i.e. FDG-PET/CT) has gained a main role in the detection of the site of origin of UPTs and is currently recommended by the European Association of Nuclear Medicine. However, despite recent refinements in the diagnostic workup, the site of origin of UPT often remains elusive. As a consequence, treatment of patients with UPT is still empirical and inadequate.

Hairy polyps are rare benign tumors that are derived from 2 germ layers: ectoderm and mesoderm. Although location in the head and neck area is rare, the soft palate as the site of origin is even more unusual. The clinical presentation depends on the polyp's location and size. These masses can commonly cause respiratory and feeding difficulties. We present a case of a soft palate hairy polyp causing respiratory and feeding difficulties in a 6-month-old female infant and review the literature.

Patients presenting with frequent ventricular arrhythmias can have underlying myocardial inflammation as an inciting factor. We seek to determine whether the site of origin (SOO) of ventricular arrhythmias on 12 lead EKG correlate with areas of inflammation on FDG PET cardiac imaging in patients

Understanding the factors that influence escape responses can provide important insight into processes that permit coexistence between species. I tested whether learning shapes the expression and timing of escape behaviour of native lizards to invasive fire ants. Fence lizards survive encounters with fire ants by body twitching to remove stinging ants and fleeing the source of attack. I found that adult lizards from invaded sites body-twitched more frequently and fled sooner than did lizards from uninvaded sites, minimizing their exposure to envenomation. Juveniles' small size makes them more vulnerable to fire ants, and they fled rapidly from encounters, irrespective of their site of origin. A higher percentage of adult lizards body-twitched and fled, and they fled sooner, with repeated exposure to fire ants over 4 days, and lizards that had been repeatedly exposed to fire ants fled sooner than did control-conditioned lizards. These results suggest that adult lizards may learn to flee more rapidly after repeated encounters with fire ants. However, the percentage of lizards that performed this behaviour appeared to be driven by aspects of the testing procedure other than the presence of fire ants, as the percentage of lizards that fled or body-twitched in response to fire ants was not affected by prior fire ant conditioning. These results suggest that adult lizards cannot learn to show escape behaviour with repeated exposure to fire ants, but that they can optimize this behaviour by fleeing sooner. This study highlights the need to test alternative explanations rigorously for apparent learned behaviour.

Peroxisomes are one of numerous organelles in a eukaryotic cell; they are small, single-membrane-bound vesicles involved in cellular metabolism, particularly fatty acid degradation. Transport of metabolites and co-factors in and across the membrane is taken care of by specific transporters. Peroxisome formation and maintenance has been debated for a long time: opinions swinging from autonomous to ER-derived organelles. Only recently it has been established firmly that the site of origin of peroxisomes is the ER. It implies that a new branch of the endomembrane system is open to further characterization.

The lineage relationship between the blood cells found in the developmentally successive hematopoietic organs has remained elusive. In this issue of Immunity, Murayama et al. (2006) track the migration of nascent hematopoietic stem cells in zebrafish from their site of origin to a newly described intermediate location.

Every year, nearly 7500 patients in the United States are diagnosed with biliary tract cancer [1]. Although most of these cancers arise from the gallbladder, one third arise from the bile ducts. Biliary tract cancers have been divided traditionally into four categories based on the site of origin and the anatomic implications for management: intrahepatic, gallbladder, extrahepatic periampullary, and extrahepatic nonperiampullary. Biliary tract cancers that arise from the latter site of origin have been referred to as hilar or perihilar cholangiocarcinomas. Altmeier et al [2] and Klatskin [3] independently highlighted the clinical presentation and problems posed by perihilar cholangiocarcinoma (PCC). This article focuses on the surgical management of PCC and addresses the relevance of hepatic resection in the treatment of these tumors. The clinicopathology and patterns of spread of PCC are reviewed. The options for preoperative imaging, perioperative preparation, and outcomes related to the role of hepatic resection are assessed. It is hoped that this article provides clinical evidence that supports hepatic resection as an essential and efficacious component of the surgical management of PCC in selected patients.