Necrotic Components Research Articles

The Role of Laparoscopic Necrosectomy in the Era of Minimally Invasive Treatment for Necrotizing Pancreatitis: A Case Series and Review of the Literature

Purpose: Despite the recent increasing application of minimally invasive techniques to treat necrotizing pancreatitis, few reports on laparoscopic necrosectomy have appeared. The aim of the present study was to evaluate the role played by laparoscopic necrosectomy in treatment of necrotizing pancreatitis. We review our own experience and the relevant literature. Methods: All patients undergoing laparoscopic necrosectomy at Seoul National University Bundang Hospital from March 2005 to January 2016 were included in the study. Data on patient demographics, CT severity index score, American Society of Anesthesiologists’ score, preoperative procedures, operative methods, operation time, estimated blood loss, postoperative complications, and length of hospital stay were retrospectively analyzed. We also performed an up-to-date review of the relevant literature. Results: Laparoscopic necrosectomy was performed on four patients with infective pancreatic necrosis that was inadequately treated by percutaneous drainage. A transgastrocolic, transmesocolic, or retrocolic approach was used. The median time from diagnosis to operation was 57 days (range, 34~109 days) and the median operation time 203 min (range, 180~255 min). There was no operative mortality. The necrotic tissue was successfully removed in a single operation in three of the four patients. Three patients experienced postoperative complications, including pleural effusion and recurrence of necrosis. The median postoperative hospital stay was 39 days (range, 16~99 days). Conclusion: Laparoscopic necrosectomy is safe and effective when used to treat necrotizing pancreatitis. Such treatment is especially useful for patients with solid, necrotic pancreatic components that are not removed by percutaneous or endoscopic drainage.

Necrotic liver induces pyroptosis through Caspase-1 in eosinophils

Abstract During sterile inflammatory reactions damage associated molecular patterns (DAMPS) are released from necrotic cells and recruit immune cells to the sites of tissue injury. We found that necrotic liver homogenates, when injected intraperitoneally, can recruit large numbers of immune cells. Among these immune cells were activated eosinophils. Eosinophils are polymorphonuclear leukocytes typically found within tissues of the gastrointestinal and respiratory tracts. While eosinophils are well known to accumulate in the lungs of asthmatics or in response to helminths and parasites, several studies have shown the presence of eosinophils in liver biopsies of drug-induced liver injury, chronic hepatitis C and liver fibrosis. The prevalence of eosinophilic infiltrates in the liver points to a correlation between infiltration and disease outcome. Our results demonstrated eosinophil activation upon exposure to necrotic liver components. Exposure to necrotic liver cells induced eosinophil degranulation as measured by expression of CD107a and eosinophil peroxidase release as measured by ELISA. Further study of eosinophil activation during necrotic liver exposure showed IL-1β and IL-18 release as well as cell death. All of these responses were dependent upon caspase-1 activation. Caspase-1 mediated cell death accompanied by IL-1β and IL-18 release are hallmarks of pyroptosis, an inflammatory cell death pathway. We verified eosinophil pyroptosis in vivo using a liver fibrosis model involving Schistosoma mansoni infected mice. Eosinophils extracted from S. mansoni infected livers showed caspase-1 activation and cytokine release indicating that these cells undergo pyroptosis in vivo in response to hepatocyte injury.

Weekly response assessment of involved lymph nodes to radiotherapy using diffusion-weighted MRI in oropharynx squamous cell carcinoma.

Purpose:Patients with cancers of oropharynx have a favorable prognosis and are an ideal candidate for adaptive therapy. A replan to improve coverage or escalate/de-escalate dose based on morphological information alone may not be adequate as the grossly involved lymph nodes (LNs) of a subset of these patients tend to become cystic and often do not regress. Functional adaptation may be a better approach when considering replanning for these patients. The purpose of this study was to evaluate the weekly trends in treatment related morphological and physiological changes for these LNs using diffusion-weighted MRI (DW-MRI) and evaluate its implications for adaptive replanning.Methods:Ten patients with histologically proven oropharynx HNSCC undergoing concurrent chemoradiation were analyzed in this study. MR imaging protocol included axial T1w, T2w, and DW-MRI using a 3 T Philips MR scanner. The patients were scanned weekly in radiation treatment planning position using a 16 element phased-array anterior coil and a 44 element posterior coil. A total of 65 DWI and T2w scans were analyzed. DWI was performed using an optimized single-shot echo planar imaging sequence (TR/TE = 5000/65 ms, slice thickness = 5 mm; slices = 28; b values = 0 and 800 s/mm2). Quantification of the DW-MRI images was performed by calculating the apparent diffusion coefficient (ADC). T2w and DWI scans were imported into the Eclipse treatment planning system and gross tumor volumes (GTVs) corresponding to grossly involved LNs were contoured on each axial slice by physician experts. An attempt was made to remove any cystic or necrotic components so that the ADC analysis was of viable tumor only. A pixel-by-pixel fit of signal intensities within the GTVs was performed assuming monoexponential behavior. From each GTV histogram mean, median, standard deviation, skewness, and kurtosis were calculated. Absolute and percent change in weekly ADC histogram parameters and percent change in T2w GTV were also calculated.Results:For all nodes, an immediate change in ADC was observed during first 2–3 weeks after which ADC values either continued to increase or plateaued. A few nodal volumes had a slightly decreased ADC value during later weeks. Percent increase in median ADC from weeks 1 to 6 with respect to baseline was 14%, 25%, 41%, 42%, 45%, and 58%. The corresponding change in median T2 volumes was 8%, 10%, 16%, 22%, 40%, and 42%, respectively. The ADC distribution of the viable tumors was initially highly kurtotic; however, the kurtosis decreased as treatment progressed. The ADC distribution also showed a higher degree of skewness in the first 2 weeks, progressively becoming less skewed as treatment progressed so as to slowly approach a more symmetric distribution.Conclusions:Physiological changes in LNs represented by changes in ADC evaluated using DW-MRI are evident sooner than the morphological changes calculated from T2w MRI. The decisions for adaptive replanning may need to be individualized and should be based primarily on tumor functional information. The authors’ data also suggest that for many patients, week 3 maybe the optimal time to intervene and replan. Larger studies are needed to confirm their findings.

Hepatocellular carcinoma: IVIM diffusion quantification for prediction of tumor necrosis compared to enhancement ratios

PurposeTo correlate intra voxel incoherent motion (IVIM) diffusion parameters of liver parenchyma and hepatocellular carcinoma (HCC) with degree of liver/tumor enhancement and necrosis; and to assess the diagnostic performance of diffusion parameters vs. enhancement ratios (ER) for prediction of complete tumor necrosis. Patients and methodsIn this IRB approved HIPAA compliant study, we included 46 patients with HCC who underwent IVIM diffusion-weighted (DW) MRI in addition to routine sequences at 3.0T. True diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (PF) and apparent diffusion coefficient (ADC) were quantified in tumors and liver parenchyma. Tumor ER were calculated using contrast-enhanced imaging, and degree of tumor necrosis was assessed using post-contrast image subtraction. IVIM parameters and ER were compared between HCC and background liver and between necrotic and viable tumor components. ROC analysis for prediction of complete tumor necrosis was performed. Results79 HCCs were assessed (mean size 2.5cm). D, PF and ADC were significantly higher in HCC vs. liver (p<0.0001). There were weak significant negative/positive correlations between D/PF and ER, and significant correlations between D/PF/ADC and tumor necrosis (for D, r 0.452, p<0.001). Among diffusion parameters, D had the highest area under the curve (AUC 0.811) for predicting complete tumor necrosis. ER outperformed diffusion parameters for prediction of complete tumor necrosis (AUC>0.95, p<0.002). ConclusionD has a reasonable diagnostic performance for predicting complete tumor necrosis, however lower than that of contrast-enhanced imaging.

Pituitary Apoplexy.

Pituitary apoplexy, a rare clinical syndrome secondary to abrupt hemorrhage or infarction, complicates 2%-12% of pituitary adenomas, especially nonfunctioning tumors. Headache of sudden and severe onset is the main symptom, sometimes associated with visual disturbances or ocular palsy. Signs of meningeal irritation or altered consciousness may complicate the diagnosis. Precipitating factors (increase in intracranial pressure, arterial hypertension, major surgery, anticoagulant therapy or dynamic testing, etc) may be identified. Corticotropic deficiency with adrenal insufficiency may be life threatening if left untreated. Computed tomography or magnetic resonance imaging confirms the diagnosis by revealing a pituitary tumor with hemorrhagic and/or necrotic components. Formerly considered a neurosurgical emergency, pituitary apoplexy always used to be treated surgically. Nowadays, conservative management is increasingly used in selected patients (those without important visual acuity or field defects and with normal consciousness), because successive publications give converging evidence that a wait-and-see approach may also provide excellent outcomes in terms of oculomotor palsy, pituitary function and subsequent tumor growth. However, it must be kept in mind that studies comparing surgical approach and conservative management were retrospective and not controlled.

CT and MRI features of pancreatic acinar cell carcinoma

Objective To identify the imaging features of pancreatic acinar cell carcinomas. Methods Eleven patients of pancreatic acinar cell carcinomas proven surgically and pathologically were included. We retrospectively evaluated the CT and MR findings including the location, size, shape, margin, necrosis , calcification, hemorrhage, enhancement degree, enhancement pattern, invasion to other organs, perilesional lymph nodes, metastasis, recurrence. Results The tumors were distributed in the head(n=4), body and tail(n=4),tail(n=3) of pancreas. The median tumor size was 97 mm(27 to 180 mm).Nine cases presented with a well-defined enhancing capsule. Tumor vessels could be seen in 9 cases.Seven cases were hypovascular while the other 4 were hypervascular. Different extents of necrosis could be seen in all masses as a swirling or cleft low density in the enhanced tumors, with an median of 10% (2% to 25%). The hypovascular masses more frequently demonstrated a lobulated tumor, heterogeneous enhancement pattern, with a larger necrotic component and were more common invasion to other organs. Conclusions Pancreatic acinar cell carcinoma typically presents as a sizable pancreatic mass with a well-defined enhancing capsule. Key words: Pancreatic neoplasms; Tomography, X-ray computed; Magnetic resonance imaging

Clinical and computed tomography imaging features of renal medullary carcinoma: A report of six cases.

Patients with renal medullary carcinoma (RMC) have a poor prognosis, usually due to late diagnosis. Computed tomography (CT) analysis may aid the differentiation between RMC and other types of renal cell carcinoma, in order to establish an accurate early diagnosis. There is a limited number of reports in the literature focusing on clinical and multi-slice CT (MSCT) imaging findings of RMC. Consequently, the present study aimed to characterize the clinical and MSCT imaging features of RMC. For this purpose, the MSCT imaging findings of 6 patients with RMC were retrospectively studied. The patients were subjected to MSCT in order to investigate the characteristics of the tumors, including location, size, density, calcification, cystic or solid appearance, capsule sign, enhancement pattern and presence of retroperitoneal lymph node metastasis. The tumors in the current study presented a mean diameter of 7.48±3.25 cm, and were observed to be solitary and heterogeneous with necrotic components. The majority of the tumors did not contain calcifications (5/6); displayed an ill-defined margin (4/6); were centered in the medulla; extended into the renal pelvis or peripelvic tissues (6/6); and did not exhibit a fibrous capsule. Localized caliectasis was observed in 3 of the 6 cases. The attenuation of the solid region of the RMC on unenhanced CT was equal to that of the renal cortex or medulla (42.3±2.7 vs. 40.7±3.6 and 41.2±3.9 Hounsfield units, respectively; P>0.05) while, on enhanced CT, the enhancement of the tumor was lower than that of the normal renal cortex and medulla during all phases (cortical phase, 52.6±4.8 vs. l99.5±9.7 and 72.7±6.4; medullary phase, 58.6±5.7 vs. 184.6±10.8 and 93.5±7.8; delayed phase, 56.8±6.1 vs. 175.7±8.5 and 96.5±7.9, respectively; P<0.05). In conclusion, RMC tends to be an infiltrative, ill-defined heterogeneous mass with intratumoral necrosis, which arises from the renal medulla, and displays lower enhancement than the renal cortex and medulla during all phases on enhanced CT. Despite its rarity in adults, RMC should be included in a differential diagnosis when CT imaging reveals these features.

Primary synovial sarcoma of the kidney: A case report.

Synovial sarcoma (SS) is a soft-tissue tumor with a unique t(X;18)(p11.2;q11.2) chromosomal translocation that can be identified by polymerase chain reaction in tissue homogenates. Generally, the tumor occurs in the proximity of the joints. The current study presents the case of a 54-year-old female with primary SS (PSS) of the right kidney; this is an extremely rare tumor accounting for <2% of malignant renal carcinomas. The patient presented with an interrupted right flank pain of 20 years duration, with a precipitating factor of a hematuria of 8 days. Abdominal computerized tomography (CT) scan revealed a heterogeneous, unclear-marginated soft tissue arising in the upper pole of the right kidney with solid, necrotic components and heterogeneous enhancement. Renal cell carcinoma was diagnosed pre-operatively. A right nephrectomy was performed, and the patient is currently free of metastasis 12 months after the surgery. The current treatment for renal SS includes surgical resection and ifosfamide-based chemotherapy. To the best of our knowledge, <50 cases have been reported in the English literature. Urologists should be aware of the possibility of malignancy in cystic renal masses and consider a diagnosis of SS. Along with the case report, the current study presents a literature review on the diagnosis and treatment of PSS.

Primary tumor of thoracic vertebra: chondrosarcoma

A 46-year-old man who had a prior history of lung mass operation presented with back pain. On suspicion of recurrence physician performed thorax and mediastinal magnetic resonance imaging with contrast. A lobulated mass with cystic necrotic components on the T9 left paravertebral space that extended into the spinal column through the left neural foramen (Figs. 1 and 2) was found. Postcontrast images showed the heterogenous capsular enhancement. There was also a pleuralbased mass on the left lung lower lobe superior segment. [F]fluorodeoxyglucose positron emission tomography-computed tomography was performed to investigate metastasis. On positron emission tomography images, hypermetabolic focus (standardized uptake value max: 3.80) was seen in the left lung concordant with magnetic resonance imaging. Furthermore, the mass at the vertebral corpus and transverse process could be seen as increased fluorodeoxyglucose uptake (standardized uptake value max: 6.17) (Fig. 3). The patient underwent neurologic examination and the result was normal. He was operated and T9 corpectomy and T8–T10 posterior fixation-fusion were performed. Pathologically, the tumor was diagnosed as low-grade chondrosarcoma.

Prognostic value of the primary lesion apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma: a retrospective study of 541 cases.

The prognostic value of the primary lesion pretreatment apparent diffusion coefficient (ADC), which is obtained by diffusion-weighted magnetic resonance imaging (MR-DWI), remains unknown in nasopharyngeal carcinoma (NPC). Thus, to investigate whether the pretreatment ADC value as measured from the primary site on MR-DWI is an independent prognostic factor in NPC, we retrospectively reviewed a cohort of 541 patients with histologically-proven stage I-IVB NPC. All patients underwent MRI using a 3-Tesla system (Trio Tim; Siemens, Erlangen Germany). To calculate ADC, the primary lesion was designated on the ADC map at the level of the largest tumor diameter to cover most of the lesion, avoiding cystic or necrotic components. Median and mean (±SD) pretreatment ADC were 0.713 and 0.716 ± 0.079 × 10−3 mm2/s, respectively. Univariate and multivariate analysis confirmed high pretreatment ADC was a good prognostic factor for poor local relapse-free survival and disease-free survival. Furthermore, the area under the ROC curve for prediction of local failure significantly increased when pretreatment ADC was combined with T classification (P = 0.004). Thus, pretreatment ADC might provide useful information for predicting outcome and selecting high-risk patients appropriate for more aggressive therapy. Further studies are warranted to investigate the biological basis of this observation.

Magnetic Resonance Imaging Characteristics of Ovarian Clear Cell Carcinoma.

PurposeTo probe the magnetic resonance imaging (MRI) features of ovarian clear cell carcinoma (OCCC).MethodsThis study retrospectively collected MRI data for 21 pathology-confirmed OCCCs from 19 female patients. The MRI findings were analyzed to determine the tumor size, shape/edge, shape and number of protrusions within the cyst, cystic or necrotic components, signal intensity (SI) and enhancement features.ResultsThe age of the 19 patients ranged from 28 to 63 years (mean age: 53 years). Unilateral tumors were found in 17 patients (17/19, 89%); the average size of all tumors was 10.8 cm. The tumors on MRI were classified into two categories: (a) “cystic adnexal mass with solid protrusions” in 12 (57%) and (b) “solid adnexal mass with cystic areas or necrosis” in 9 (43%). For group a, high to very high SI was observed for most tumors (10/12, 83%) on T1-weighted images (T1WIs), and very high SI was observed on T2-weighted images (T2WIs) for all 12 tumors. Most solid protrusions were irregular and few in number and exhibited heterogeneous intermediate SI on T1WIs and T2WIs and prolonged enhanced SI in the contrast study. All 9 OCCCs in group b were predominantly solid masses with unequally sized necrotic or cystic areas in which some cysts were located at the periphery of the tumor (4/9, 44%). The solid components in all 9 tumors showed iso- or slightly high SI on T1WIs, heterogeneous iso-high SI on T2WIs and heterogeneous prolonged enhancement. According to FIGO classification, 14 tumors (14/19, 74%) were stages I-II, and 5 (5/19, 26%) were stages III-IV.ConclusionsOn MRI, OCCCs present as large unilateral multilocular or unilocular cystic masses with irregular intermediate SI solid protrusions or predominantly solid masses with cysts or necrosis at an early FIGO stage.

Abstract A41: Automated immunohistochemistry of phosphobiomarkers: Case study of MTOR (MLN0128) and PI3Kα (MLN1117) investigational inhibitors, single agent and in combination, on xenografts and mouse skin

Abstract Background: Immunohistochemistry provides visual context to protein modulation and is relied upon to elucidate mechanism of action, marker translocation and pharmacodynamics (PD) in drug discovery. Markers of the PI3K-MTOR pathway have been monitored in this way to aid in the clinical development of various inhibitors targeting this pathway. Here, assays were developed using preclinical xenograft PD studies to explore the feasibility of automated staining of pAKT 473, pS6, p4EBP1 and pRb. In preparation for clinical assessment of these markers in human skin samples; these markers were also examined in normal mouse skin. p4EBP1 was selected to examine the reproducibility of these automated assays and to explore the correlation between pathway inhibition in PD xenograft tissues and murine skin tissues. The automated staining technique was coupled with whole slide scanning and digital image analysis for quantitative comparison. Methods: Assays were chosen for evaluation based on known biology. FFPE PTEN-null breast cancer primary human tumor xenografts with high, medium and low biomarker expression, with companion skin samples, were selected for feasibility and reproducibility testing. Whole slide scanning and reproducibility analysis was executed using Aperio Scanscope XT and Spectrum software. Statistical analysis methods of mixed effect linear models and two sample t-tests were applied. Xenograft and skin samples from NCI-H1048 tumor bearing Nude mice treated with MTOR (MLN0128)and PI3Kα (MLN1117) investigational inhibitors were immunohistochemically stained for p4EBP1. Definiens object-based imaging software was used to isolate and analyze viable tumor area and exclude necrotic and stromal components in xenografts. A customized Definiens® algorithm was used on skin to identify the epithelial layer for analysis. Results: After evaluation, baseline biomarker expression in the xenograft and skin samples determined marker selection for future steps. Baseline p4EBP1 levels were high in both xenograft and skin. The reproducibility testing yielded consistent results in both xenograft and skin, validating autostaining use for PD studies. Phosphomarker p4EBP1 expression was inhibited after MLN0128 administration, with increased reduction after combination with MLN1117. Development of a novel analysis solution using Definiens software for skin samples permitted the area of interest to be restricted to the epithelial layer and excluded other epidermal features with similar morphometric characteristics. The p4EBP1 modulation was concordant between skin and tumor though more pronounced in skin, indicating that skin is a suitable surrogate tissue for determining modulation of this PI3K-MTOR pathway marker. Conclusions: Autostaining platforms provide reproducible results and stain consistently for PI3K-MTOR phosphomarkers on both xenografts and mouse skin samples. Utilizing p4EBP1, target effect was observed after MTOR and PI3Kα administration. This development and evaluation of the phosphobiomarker using automated staining technology and advanced image analysis supports preclinical PD assessment and combination clinical trials as well as influenced timepoint selection for clinical assessment. Citation Format: Anna Kreshock, Natalia Iartchouk, Yueying Cao, Jeffrey Szwaya, Feng Gao, Christopher Simpson, Evan Luongo, Kristine Burke, Esha Gangolli, Keisuke Kuida, Rachael Brake, Stephen Tirrell, Vaishali Shinde. Automated immunohistochemistry of phosphobiomarkers: Case study of MTOR (MLN0128) and PI3Kα (MLN1117) investigational inhibitors, single agent and in combination, on xenografts and mouse skin. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A41.

TH‐AB‐304‐09: A Patient‐Specific Heterogeneous Radiobiological Model for Glioblastoma Multiforme

Purpose:Gliomas tumors proliferate and invade healthy brain tissue rapidly, yielding short life expectancies. Radiation therapy is commonly used, but gliomas are known to be radio‐resistant, and almost always recur following treatment. Current radiotherapy protocols are based on the classic linear‐quadratic radiobiological model, assuming a homogeneous (one‐component) tumor. Gliomas are very heterogeneous, consisting of normoxic, hypoxic, and necrotic tissues, each responding differently to radiation. An enhanced linear‐quadratic model which takes into account the different responses of the heterogeneous tumor regions to radiation can guide treatment planning to optimize dose distributions to maximize the therapeutic effect.Methods:We used a set of differential equations to model the growth of glioma tumors. Our model expands on the one‐component model developed by (Rockne,2010) by including normoxic, hypoxic, and necrotic components and radiosensitivity values for each component. Proliferation and diffusion parameters are extracted by contouring the tumor on two sets of pre‐treatment MRIs and modeling it as a volume equivalent sphere.Results:We compared two examples of glioma tumors presented in (Rockne,2010) with our three component model and find better predictive capabilities for post‐RT tumor volumes using the three component model. In both cases, the one‐component model over predicts the effects of radiation on the tumor core, while the three‐component model more accurately fits the data by accounting for radioresistance of the hypoxic core. Additionally, we applied the model to a UCSF patient with a recurring tumor and use the model to predict time to fatal tumor burden.Conclusion:The three‐component model accurately matches tumor growth dynamics derived from MRIs for two example cases presented in literature, and one case from UCSF. Spatial information about hypoxic, necrotic, and normoxic cell densities are derived from the model providing information needed to more intelligently prescribe dose distributions tailored to a specific patient's tumor.[Rockne,et.al.,PhysMedBio,2010]

Impact of local endothelial shear stress on neointima and plaque following stent implantation in patients with ST-elevation myocardial infarction: A subgroup-analysis of the COMFORTABLE AMI–IBIS 4 trial

BackgroundNumerous studies have demonstrated an association between endothelial shear stress (ESS) and neointimal formation after stent implantation. However, the role of ESS on the composition of neointima and underlying plaque remains unclear. MethodsPatients recruited in the Comfortable AMI–IBIS 4 study implanted with bare metal stents (BMS) or biolimus eluting stents (BES) that had biplane coronary angiography at 13month follow-up were included in the analysis. The intravascular ultrasound virtual-histology (IVUS-VH) and the angiographic data were used to reconstruct the luminal surface, and the stent in the stented segments. Blood flow simulation was performed in the stent surface, which was assumed to represent the luminal surface at baseline, to assess the association between ESS and neointima thickness. The predominant ESS was estimated in 3-mm segments and was correlated with the amount of neointima, neointimal tissue composition, and with the changes in the underlying plaque burden and composition. ResultsForty three patients (18 implanted with BMS and 25 with BES) were studied. In both stent groups negative correlations were noted between ESS and neointima thickness in BMS (P<0.001) and BES (P=0.002). In BMS there was a negative correlation between predominant ESS and the percentage of the neointimal necrotic core component (P=0.015). In BES group, the limited neointima formation did not allow evaluation of the effect of ESS on its tissue characteristics. ESS did not affect vessel wall remodeling and the plaque burden and composition behind BMS (P>0.10) and BES (P>0.45). ConclusionsESS determines neointimal formation in both BMS and BES and affects the composition of the neointima in BMS. Conversely, ESS does not impact the plaque behind struts irrespective of stent type throughout 13months of follow-up.

Cocaine-Induced Pituitary Apoplexy and Panhypopituitarism

ABSTRACT Objective: Chronic cocaine use has been implicated in panhypopituitarism. Acute cocaine intoxication resulting in pituitary apoplexy and panhypopituitarism has not been reported in the literature. Methods: We hereby report a case of panhypopituitarism resulting from pituitary apoplexy induced by a single intranasal cocaine use. Results: A 54-year-old African American man presented with a week-long headache that started 2 hours after snorting a gram of cocaine. His physical exam was normal. His labs were suggestive of panhypopituitarism. Anti-neutrophil cytoplasmic antibodies were negative. Brain magnetic resonance imaging with and without contrast showed a large complex sellar mass with hemorrhagic and necrotic components. Surgical decompression was deferred due to normal visual acuity and absence of visual field defects. He received a stress dose of glucocorticoids followed by maintenance dose and was discharged on the glucocorticoid with levothyroxine replacement. The patient has been lost to f...

Impact of Remnant Lipoprotein on Coronary Plaque Components.

Intravascular ultrasound (IVUS) is a useful modality for visualizing atherosclerotic lesions in coronary arteries, not only for the degree of arterial luminal stenosis but also for the plaque composition within the vessel walls. We aimed to determine the relationship between the clinical parameters and coronary plaque characteristics evaluated by IVUS in patients with stable angina under medical treatment. Plaque measurements within the coronary arteries were collected by coronary angiography and iMAP-IVUS in 40 men with stable angina. The serum remnant-like cholesterol (RemL-C) was measured using homogeneous assays and serum adiponectin and omentin-1 levels were measured by enzyme-linked immunosorbent assays. The iMAP-IVUS analysis of the coronary arteries demonstrated that the plaque cross-sectional area (CSA) was 11.0±3.5 mm(2). Plaque CSA positively correlated with body mass index and negatively correlated with the serum adiponectin levels. Both areal and volumetric analyses of the plaque characteristics demonstrated that the serum RemL-C level was a positive determinant for %Necrosis and the negative determinant for %Fibrosis of the plaques. Neither serum high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol levels correlated with the proportion of any plaque components. Additionally, the RemL-C/triglyceride ratio positively correlated with %Lipid significantly in the areal analysis. Elevation of the serum RemL-C levels in the patients with stable angina may link to coronary plaque vulnerability, which is characterized by high necrotic and low fibrotic components.

Evaluation of guidewire artifact subtraction in quantitative and tissue analysis with intracoronary ultrasound and iMAPTM technology in patients presenting with acute coronary syndrome: an iWonder study subanalysis

BackgroundIntravascular ultrasound (IVUS) is the most widely used ancillary method in Interventional Cardiology, and its analysis depends on standards for acquisition, measurement and interpretation of the images. By associating tissue characterization, the artifact caused by the guidewire may overestimate the percentage of necrotic core in certain lesions, leading to misclassification of fibroatheroma. In this paper we described quantitative and tissue analysis effects resulting from subtracting the effect of guidewire artifact on atherosclerotic lesions in patients with acute coronary syndrome. MethodsTwenty-one patients with post-thrombolysis myocardial infarction were evaluated with grayscale IVUS and iMAPTM technology, totaling 76 lesions. ResultsGrayscale IVUS showed that the lesions had a mean length of 21.01 ± 18.03mm and revealed high plaque burden (52.07 ± 7.56%). The analysis by iMAPTM demonstrated that, after subtracting the guidewire artifact, there was a reduction of all tissue (necrotic, calcific, lipid and fibrotic) components, but more markedly in necrotic core (mean difference: 3.59%). In addition, after artifact subtraction 12.4% of the lesions that initially exhibited a necrotic core ≥ 10% ceased to be classified as fibroatheroma. ConclusionsAn atheroma analysis by iMAPTM technology showed that the guidewire artifact overestimated the tissue component of the necrotic core. This interference may change, in an erroneous and categorical way, the phenotypic characteristics of more stable and benign (fibrotic) lesions to potentially unstable lesions, for example, fibroatheromas, in a ratio of one out of ten patients.

Enhanced expression of hemoglobin scavenger receptor CD163 in accumulated macrophages within filtered debris between acute coronary syndromes and stable angina pectoris.

Coronary intraplaque hemorrhage up-regulates hemoglobin scavenger receptor CD163 expression on macrophages, and has an association with vulnerable plaque development. During percutaneous coronary intervention, mechanical plaque disruption exposes potentially embolic atheromatous contents from culprit plaque.In 37 patients with stable angina pectoris (SAP, n = 20) or acute coronary syndrome (ACS, n = 17), atherothrombotic debris was collected using a filter-based distal embolic protection device. We immunohistochemically determined CD14-positive macrophages and CD163-positive macrophages in filtered debris. We also examined the relation of CD14- and CD163-positive macrophages with culprit plaque volume and components evaluated with ultrasonic tissue characterization (VH-IVUS).The only significant difference in clinical characteristics between the two groups was in hs-CRP. In ACS, the percentage of CD14- and CD163-positive macrophages to the whole cells (%CD14 and %CD163, respectively) was significantly higher than that in SAP (20.1 ± 8.2 versus 8.8 ± 6.8%, P < 0.001 and 32.6 ± 18.9 versus 9.0 ± 3.8%, P < 0.001, respectively). In IVUS indices of culprit plaque, the remodeling index was significantly higher in ACS than in SAP. However, necrotic core component (%NC) in ACS was significantly higher than that in SAP. Furthermore, fibrotic component (%Fibrous) in ACS was significantly lower than that in SAP (56.1 ± 4.7 versus 60.1 ± 3.3%, P = 0.03). %CD14 and %CD163 had a significant positive correlation with %NC (%CD14: r = 0.40, P = 0.01 and %CD163: r = 0.45, P = 0.01), but only %CD163 was negatively correlated with %Fibrous (%CD163: r = -0.48, P = 0.01).These findings suggest that the presence of CD14- and CD163-positive macrophages may reflect plaque inflammation, NC expansion, and plaque vulnerability in patients with coronary heart disease.

Avaliação da subtração do artefato do fio‐guia na análise quantitativa e tecidual com ultrassom intracoronário e tecnologia iMAP® em pacientes com síndrome coronária aguda: subanálise do estudo iWonder

BackgroundIntravascular ultrasound (IVUS) is the most widely used ancillary method in Interventional Cardiology, and its analysis depends on standards for acquisition, measurement and interpretation of the images. By associating tissue characterization, the artifact caused by the guidewire may overestimate the percentage of necrotic core in certain lesions, leading to misclassification of fibroatheroma. In this paper we described quantitative and tissue analysis effects resulting from subtracting the effect of guidewire artifact on atherosclerotic lesions in patients with acute coronary syndrome. MethodsTwenty‐one patients with post‐thrombolysis myocardial infarction were evaluated with grayscale IVUS and iMAPTM technology, totaling 76 lesions. ResultsGrayscale IVUS showed that the lesions had a mean length of 21.01 ± 18.03mm and revealed high plaque burden (52.07 ± 7.56%). The analysis by iMAPTM demonstrated that, after subtracting the guidewire artifact, there was a reduction of all tissue (necrotic, calcific, lipid and fibrotic) components, but more markedly in necrotic core (mean difference: 3.59%). In addition, after artifact subtraction 12.4% of the lesions that initially exhibited a necrotic core ≥ 10% ceased to be classified as fibroatheroma. ConclusionsAn atheroma analysis by iMAPTM technology showed that the guidewire artifact overestimated the tissue component of the necrotic core. This interference may change, in an erroneous and categorical way, the phenotypic characteristics of more stable and benign (fibrotic) lesions to potentially unstable lesions, for example, fibroatheromas, in a ratio of one out of ten patients.

Endosonography guided management of pancreatic fluid collections

The revised Atlanta classification of acute pancreatitis was adopted by international consensus, and is based on actual local and systemic determinants of disease severity. The local determinant is pancreatic necrosis (sterile or infected), and the systemic determinant is organ failure. Local complications of pancreatitis can include acute peri-pancreatic fluid collection, acute necrotic collection, pseudocyst formation, and walled-off necrosis. Interventional endoscopic ultrasound (EUS) has been increasing utilized in managing these local complications. After performing a PubMed search, the authors manually applied pre-defined inclusion criteria or a filter to identify publications relevant to EUS and pancreatic collections (PFCs). The authors then reviewed the utility, efficacy, and risks associated with using therapeutic EUS and involved EUS devices in treating PFCs. Due to the development and regulatory approval of improved and novel endoscopic devices specifically designed for transmural drainage of fluid and necrotic debris (access and patency devices), the authors predict continuing evolution in the management of PFCs. We believe that EUS will become an indispensable part of procedures used to diagnose PFCs and perform image-guided interventions. After draining a PFC, the amount of tissue necrosis is the most important predictor of a successful outcome. Hence, it seems logical to classify these collections based on their percentage of necrotic component or debris present when viewed by imaging methods or EUS. Finally, the authors propose an algorithm for managing fluid collections based on their size, location, associated symptoms, internal echogenic patterns, and content.