Syed A. Jaffar Kazmi

Passive biaxial mechanical properties and in vivo axial pre-stretch of the diseased human femoropopliteal and tibial arteries.

Surgical and interventional therapies for atherosclerotic lesions of the infrainguinal arteries are notorious for high rates of failure. Frequently, this leads to expensive reinterventions, return of disabling symptoms or limb loss. Interaction between the artery and repair material likely plays an important role in reconstruction failure, but data describing the mechanical properties and functional characteristics of human femoropopliteal and tibial arteries are currently not available. Diseased superficial femoral (SFA, n = 10), popliteal (PA, n = 8) and tibial arteries (TA, n = 3) from 10 patients with critical limb ischemia were tested to determine passive mechanical properties using planar biaxial extension. All specimens exhibited large nonlinear deformations and anisotropy. Under equibiaxial loading, all arteries were stiffer in the circumferential direction than in the longitudinal direction. Anisotropy and longitudinal compliance decreased distally, but circumferential compliance increased, possibly to maintain a homeostatic multiaxial stress state. Constitutive parameters for a four-fiber family invariant-based model were determined for all tissues to calculate in vivo axial pre-stretch that allows the artery to function in the most energy efficient manner while also preventing buckling during extremity flexion. Calculated axial pre-stretch was found to decrease with age, disease severity and more distal arterial location. Histological analysis of the femoropopliteal artery demonstrated a distinct sub-adventitial layer of longitudinal elastin fibers that appeared thicker in healthier arteries. The femoropopliteal artery characteristics and properties determined in this study may assist in devising better diagnostic and treatment modalities for patients with peripheral arterial disease.

Nonlinear Mechanical Behavior of The Human Common, External, and Internal Carotid Arteries In Vivo

BACKGROUND The mechanical environment and properties of the carotid artery play an important role in the formation and progression of atherosclerosis in the carotid bifurcation. The purpose of this work was to measure and compare the range and variation of circumferential stress and tangent elastic moduli in the human common (CCA), external (ECA), and internal (ICA) carotid arteries over the cardiac cycle in vivo. METHODS Measurements were performed in the surgically exposed proximal cervical CCA, distal ECA, and distal ICA of normotensive patients (n = 16) undergoing carotid endarterectomy. All measurements were completed in vivo over the cardiac cycle in the repaired carotid bifurcation after the atherosclerotic plaque was successfully removed. B-mode Duplex ultrasonography was used for measurement of arterial diameter and wall thickness, and an angiocatheter placed in the CCA was used for concurrent measurement of blood pressure. A semiautomatic segmentation algorithm was used to track changes in arterial diameter and wall thickness in response to blood pressure. These measurements were then used to calculate the variation of circumferential (hoop) stresses, tangent elastic moduli (the slope of the stress-strain curve at specified stresses), and strain-induced stiffness of the arterial wall (stiffening in response to the increase of intraluminal blood pressure) for each patient. RESULTS The diameter and wall thickness of the segments (CCA, ECA, and ICA) of the carotid bifurcation were found to decrease and strain-induced stiffness to increase from proximal CCA to distal ECA and ICA. The circumferential stress from end-diastole (minimum pressure) to peak-systole (maximum pressure) varied nonlinearly from 25 ± 7 to 63 ± 23 kPa (CCA), from 22 ± 7 to 57 ± 19 kPa (ECA), and from 28 ± 8 to 67 ± 23 kPa (ICA). Tangent elastic moduli also varied nonlinearly from end-diastole to peak-systole as follows: from 0.40 ± 0.25 to 1.50 ± 2.05 MPa (CCA), from 0.49 ± 0.34 to 1.14 ± 0.52 MPa (ECA), and from 0.68 ± 0.31 to 1.51 ± 0.69 MPa (ICA). The strain-induced stiffness of CCA and ECA increased more than 3-fold and the stiffness of ICA increased more than 2.5-fold at peak-systole compared with end-diastole. CONCLUSIONS The in vivo mechanical behavior of the three segments of the carotid bifurcation was qualitatively similar, but quantitatively different. All three arteries--CCA, ECA and ICA--exhibited nonlinear variations of circumferential stress and tangent elastic moduli within the normal pressure range. The variability in the properties of the three segments of the carotid bifurcation indicates a need for development of carotid models that match the in vivo properties of the carotid segments. Finally, the observed nonlinear behavior of the artery points to the need for future vascular mechanical studies to evaluate the mechanical factors of the arterial wall over the entire cardiac cycle.

Comparative Analysis of the Biaxial Mechanical Behavior of Carotid Wall Tissue and Biological and Synthetic Materials Used for Carotid Patch Angioplasty

Patch angioplasty is the most common technique used for the performance of carotid endarterectomy. A large number of patching materials are available for use while new materials are being continuously developed. Surprisingly little is known about the mechanical properties of these materials and how these properties compare with those of the carotid artery wall. Mismatch of the mechanical properties can produce mechanical and hemodynamic effects that may compromise the long-term patency of the endarterectomized arterial segment. The aim of this paper was to systematically evaluate and compare the biaxial mechanical behavior of the most commonly used patching materials. We compared PTFE (n  =  1), Dacron (n  =  2), bovine pericardium (n  =  10), autogenous greater saphenous vein (n  =  10), and autogenous external jugular vein (n  =  9) with the wall of the common carotid artery (n  =  18). All patching materials were found to be significantly stiffer than the carotid wall in both the longitudinal and circumferential directions. Synthetic patches demonstrated the most mismatch in stiffness values and vein patches the least mismatch in stiffness values compared to those of the native carotid artery. All biological materials, including the carotid artery, demonstrated substantial nonlinearity, anisotropy, and variability; however, the behavior of biological and biologically-derived patches was both qualitatively and quantitatively different from the behavior of the carotid wall. The majority of carotid arteries tested were stiffer in the circumferential direction, while the opposite anisotropy was observed for all types of vein patches and bovine pericardium. The rates of increase in the nonlinear stiffness over the physiological stress range were also different for the carotid and patching materials. Several carotid wall samples exhibited reverse anisotropy compared to the average behavior of the carotid tissue. A similar characteristic was observed for two of 19 vein patches. The obtained results quantify, for the first time, significant mechanical dissimilarity of the currently available patching materials and the carotid artery. The results can be used as guidance for designing more efficient patches with mechanical properties resembling those of the carotid wall. The presented systematic comparative mechanical analysis of the existing patching materials provides valuable information for patch selection in the daily practice of carotid surgery and can be used in future clinical studies comparing the efficacy of different patches in the performance of carotid endarterectomy.

Extranodal marginal zone lymphoma of the dura mater with IgH/MALT1 translocation and review of literature.

Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma involving brain, intraocular structures and spinal cord, without evidence of systemic disease. The majority of PCNSLs are diffuse large B-cell type. We encountered a rare case of primary dural marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) with extension into the brain in a 59-year-old man. A magnetic resonance imaging scan showed a 22-mm tumor located in the left posterior temporal lobe extending from the dura. Histopathology revealed a lymphoplasmacytic infiltration of the dura and the brain parenchyma in a perivascular pattern. Immunohistochemical and in situ hybridization studies showed a B-cell phenotype with kappa light chain restriction. Fluorescent in situ hybridization study showed a t(14;18)(q32;q21) with immunoglobulin heavy-chain/MALT1 fusion. The molecular study for immunoglobulin heavy-chain gene rearrangement by polymerase chain reaction showed a clonal gene rearrangement.

Effects of Carotid Artery Stenting on Arterial Geometry

BACKGROUND The role of carotid artery stenting (CAS) for the treatment of carotid artery disease continues to evolve, despite higher stroke and restenosis risks for CAS compared with conventional open endarterectomy. Understanding the effects of CAS on arterial geometry, which strongly influence hemodynamics and wall mechanics, can assist in better stratifying the inherent risk of CAS to individual patients. STUDY DESIGN Fifteen consecutive patients undergoing CAS had pre- and post-stenting CT angiograms. These images were used to reconstruct the 3-dimensional geometries of the bilateral carotid arteries from their origin to the skull base. Quantitative assessment of the carotid bifurcation angle, cross-sectional area, tortuosity and artery length, were compared pre- and post-stenting. Plaque volume and calcification were also measured. Mathematical models were devised to determine the mechanisms of CAS-induced geometric changes, and their mechanical and hemodynamic significances. RESULTS Major and moderate changes in arterial tortuosity and elongation were seen in 5 (33%) patients. Characteristics most associated with the development of CAS-induced geometric changes were stenoses located in the internal carotid artery distal to the carotid bulb, circumferential distribution of plaque, and plaque calcification. Modeling did not demonstrate substantial alterations in wall shear stress due to geometric changes, but did show considerable increases in arterial wall axial stress. CONCLUSIONS Carotid artery stenting can produce geometric changes to the artery that promote favorable conditions for complications and recurrent disease. Patients with circumferential, highly calcified plaques that are located relatively distal in the internal carotid artery are most likely to have post-stenting geometric changes.

Teratoma with Malignant Transformation: A Case Report with Pathological, Cytogenetic, and Immunohistochemistry Analysis

Background. Teratoma with malignant transformation (TMT) is rare and most commonly encountered in adult patient with germ cell tumor (GCT). Method. We report a rare case of testicular teratoma with metastatic TMT/embryonal rhabdomyosarcoma (ERMS). A 44-year-old man underwent right orchiectomy which revealed a malignant teratoma, he subsequently had right pneumonectomy with two pulmonary masses containing a high-grade embryonal rhabdomyosarcoma. The patient developed liver metastasis three months after initial diagnosis. He was treated with a chemotherapy regimen with vincristine, dactinomycin, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (VI) with complete resolution of his liver lesion. The tumors were examined with a battery of cytogenetic, immunohistochemical, and molecular assays. Results. The malignant cells were immunohistochemically positive for desmin, myogenin, and MyoD1. Molecular cytogenetics of embryonal rhabdomyosarcoma tissue revealed the presence of i(12p). The tumor expressed high level of TOPO2A, TOPO1, MRP1, MGMT, BCRP, ERCC1, RRM1, and TS. Conclusion. The activity of topoisomerase inhibitors and the potential usefulness of topoisomerase expression as biomarkers should be further tested in aprospective study.

A mathematical evaluation of hemodynamic parameters after carotid eversion and conventional patch angioplasty

Carotid endarterectomy has a long history in stroke prevention, yet controversy remains concerning optimal techniques. Two methods frequently used are endarterectomy with patch angioplasty (CEAP) and eversion endarterectomy (CEE). The objective of this study was to compare hemodynamics-related stress and strain distributions between arteries repaired using CEAP and CEE. Mathematical models were based on in vivo three-dimensional arterial geometry, pulsatile velocity profiles, and intraluminal pressure inputs obtained from 16 patients with carotid artery disease. These data were combined with experimentally derived nonlinear, anisotropic carotid artery mechanical properties to create fluid-structure interaction models of CEAP and CEE. These models were then used to calculate hemodynamic parameters thought to promote recurrent disease and restenosis. Combining calculations of stress and strain into a composite risk index, called the integral abnormality factor, allowed for an overall comparison between CEAP and CEE. CEE demonstrated lower mechanical stresses in the arterial wall, whereas CEAP straightened the artery and caused high stress and strain concentrations at the suture-artery interface. CEAP produced a larger continuous region of oscillatory, low-shear, vortical flow in the carotid bulb. There was a more than two-fold difference in the integral abnormality factor, favoring CEE. In conclusion, in a realistically simulated carotid artery, fluid-structure interaction modeling demonstrated CEE to produce less mechanical wall stress and improved flow patterns compared with CEAP. Clinical validation with larger numbers of individual patients will ultimately be required to support modeling approaches to help predict arterial disease progression and comparative effectiveness of reconstruction methods and devices.

Multifocal Histologically Malignant Epstein–Barr Virus–Associated Smooth Muscle Tumor in a Pediatric Transplant Patient With an Indolent Course

Epstein–Barr virus–associated smooth muscle tumors (EBV-SMTs) are rare lesions that occur in immunocompromised patients. Dural involvement appears to be less common in organ transplant recipients than in HIV patients. Due to the paucity of reported cases following organ transplantation, the natural history of these lesions is unclear. We describe an 8-year-old female who presented with adrenal, small bowel, and intracranial tumors 6 years following renal transplantation. Histopathological analysis revealed a highly cellular, mitotically active, smooth muscle neoplasm without necrosis. The tumor stained diffusely for smooth muscle actin and myosin. In situ hybridization for EBV-encoded RNA was diffusely positive. Following gross total resection, antiviral therapy, and a reduction in immunosuppression, the patient is tumor-free at 3 years follow-up. In patients with compromised immune systems, it is important to recognize this unique form of SMT because, even when there are multiple lesions, the prognosis may be excellent.

Metastases From Nested Variant Urothelial Carcinoma of the Urinary Bladder in Pancreatic Allograft Mimicking Graft Rejection

While not an uncommon tumor, urothelial carcinoma of the urinary bladder is rare in bladders draining pancreatic allografts. A case of urothelial carcinoma directly involving a pancreatic allograft with metastasis that occurred in a 49-year-old pancreas and kidney transplant recipient is described. Her initial clinical presentation and findings of CT scan of the abdomen suggested pancreatitis with features worrisome for rejection. A biopsy of her pancreatic allograft contained poorly differentiated carcinoma and cystoscopic biopsy disclosed an invasive high grade urothelial carcinoma arising in the background of extensive urothelial carcinoma in situ. Exploratory laparotomy revealed that the tumor invaded the right ovary and fallopian tube, cecum, and allograft with extensive retroperitoneal involvement. She underwent en bloc resection of distal ileum and cecum, resection of transplant pancreas, partial cystectomy, ileocolostomy anastomosis, and right salpingo-oophorectomy. Postoperatively, the patient was treated with four cycles of carboplatin and gemcitabine. She ultimately succumbed to her disease approximately 1 year after diagnosis. This case should alert physicians and radiologists to be aware of atypical presentation of urothelial carcinoma in bladder-drained pancreas grafts, the aggressiveness of such lesions, and the need for early biopsy to avoid diagnostic confusion with rejection. Keywords Bladder cancer; Nested variant of urothelial carcinoma; Pancreas and kidney transplantation