Pathological Findings of the Antral and Pyloric Smooth Muscle in Patients with Gastroparesis-Like Syndrome Compared to Gastroparesis: Similarities and Differences.

BACKGROUND: Gastroparesis (GP)-like syndrome presents with the symptoms of GP but without delayed gastric emptying (GE). Whether GP-like syndrome is part of a spectrum of GP is not clear. This study aimed to compare the histopathological features of antral and pyloric smooth muscle tissue in GP and GP-like syndrome. METHODS: Full-thickness antral and/or pyloric biopsies were obtained from 37 GP and 18 GP-like syndrome patients who underwent abdominal surgery to place a gastric electrical stimulator or jejunal feeding tube and/or pyloroplasty. The tissues were stained with H&E, C-Kit, and trichrome. Based on previous control data, an interstitial cells of Cajal (ICC) count of <10 per high power field in the antrum and/or pylorus was considered depletion. Baseline total symptom score (TSS) was recorded. RESULTS: Twenty-four GP and 7 GP-like patients had pyloric biopsies. Pyloric ICC loss was observed in 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients (p < 0.01). Fibrosis was detected in the pyloric tissue of 20/24 (83.3%) GP and 2/7 (28.6%) GP-like patients who had pyloric trichrome staining (p < 0.01). Seventeen out of 24 (70.8%) GP patients with pyloric biopsies had concomitant pyloric ICC loss and fibrosis, while only one GP-like patient had ICC loss and simultaneous pyloric fibrosis. GP patients had a greater TSS compared to GP-like patients. In GP patients, those with pyloric ICC loss had a greater TSS compared to those with normal ICC. GP patients with pyloric fibrosis had a higher TSS compared to those without pyloric fibrosis. CONCLUSIONS: Compared to GP-like patients, the pyloric histopathological findings of ICC loss and fibrosis are common in GP and predict a greater symptom score. These pathological findings might be considered as markers of "pyloric dysfunction" and explain delayed GE in GP.

The Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Hispanics Undergoing Endoscopy Is Infrequent Compared to Caucasians: A Cross-Sectional Study.

INTRODUCTION: The prevalence of eosinophilic esophagitis (EoE), a chronic, immune-mediated, clinicopathologic, inflammatory disorder, has been well described in the pediatric and adult Caucasian population but not as well studied in the Hispanic population. The major aims of this study are to determine the prevalence and gene expression profile of EoE in these populations. METHODS: This is a retrospective cohort study of patients from two institutions predominantly serving a Hispanic population. Patients included at Los Angeles County Hospital (LACH) had an esophagogastroduodenoscopy (EGD) and esophageal biopsies performed for evaluation of dysphagia and/or food impaction, while patients included from the University Hospital Medical Center of El Paso (UHMCEP) had an EGD and esophageal biopsies performed for any appropriate clinical indication. Gene expression analysis which has been shown to accurately diagnose EOE in Caucasians was performed for 9 patients at UHMCEP to determine its accuracy in Hispanics. RESULTS: At LACH, 234 patients were included in the study of whom 155 (66.3%) were Hispanic and 22 (9.4%) were Caucasian. 3.2% of the Hispanic patients and 9.1% of the Caucasian patients were diagnosed with EOE with threefold difference. At UHMCEP 1700 patients were included of whom 1350 (79.4%) were Hispanic and 179 (10.5%) were Caucasian. 0.96% of the Hispanic patients and 7.26% of the Caucasian patients were diagnosed with EOE with a sevenfold difference. Gene expression accurately diagnosed EOE in a small number of both Hispanics and Caucasians who underwent analysis. CONCLUSIONS: Hispanic patients at LAC and UMHCEP had a significantly lower prevalence of EOE as compared to Caucasians at these two institutions and a lower prevalence as compared to Caucasians with EOE previously reported in the literature. Gene expression analysis, which has previously been shown to accurately diagnose EOE in Caucasian patients, accurately diagnosed EOE in a small sample of this Hispanic population. Based on this similar gene expression, other factors such as environmental, ethnic, and cultural causes should be investigated to explain the markedly lower prevalence of EOE in Hispanics.

Functional genomics analysis reveals a MYC signature associated with a poor clinical prognosis in liposarcomas.

Liposarcomas, which are malignant fatty tumors, are the second most common soft-tissue sarcomas. Several histologically defined liposarcoma subtypes exist, yet little is known about the molecular pathology that drives the diversity in these tumors. We used functional genomics to classify a panel of diverse liposarcoma cell lines based on hierarchical clustering of their gene expression profiles, indicating that liposarcoma gene expression profiles and histologic classification are not directly correlated. Boolean probability approaches based on cancer-associated properties identified differential expression in multiple genes, including MYC, as potentially affecting liposarcoma signaling networks and cancer outcome. We confirmed our method with a large panel of lipomatous tumors, revealing that MYC protein expression is correlated with patient survival. These data encourage increased reliance on genomic features in conjunction with histologic features for liposarcoma clinical characterization and lay the groundwork for using Boolean-based probabilities to identify prognostic biomarkers for clinical outcome in tumor patients.

EUS-guided FNA biopsy of the muscularis propria of the antrum in patients with gastroparesis is feasible and safe.

BACKGROUND AND AIMS: EUS-guided FNA biopsies of the muscularis propria of the gastric wall in patients with gastroparesis could replace the routine use of surgical full-thickness biopsies for assessing the loss of the interstitial cells of Cajal (ICCs) and cellular infiltrates in the myenteric plexus. We investigated the efficacy and safety of EUS-guided FNA biopsies of the muscularis propria of the gastric antrum in gastroparesis and compared the tissue with a surgically obtained full-thickness biopsy specimen in the same patient. METHODS: This was a prospective, nonrandomized, feasibility trial. Patients with gastroparesis who were undergoing gastric neurostimulator placement were enrolled. Patients had a gastric wall measurement by radial EUS in the body and antrum of the stomach followed by linear EUS examination and FNA of the muscularis propria in the antrum by using a 19-gauge core needle. Within 24 hours, a full-thickness biopsy specimen of the antrum was obtained surgically during neurostimulator placement. Endoscopic and surgical specimens were compared for tissue morphology, number of ICCs (c-kit stain) and enteric neurons (S-100 stain), and fibrosis (trichome) for each patient. The correlation coefficient of the ICC count per high-power field was used to compare both specimens. Continuous data were compared by using a t test. RESULTS: Eleven patients (10 female, 1 male), with a mean age of 40.6 years, were enrolled in the trial. EUS-guided core biopsies were successful in obtaining sufficient tissue for the histologic assessment of ICCs in 9 patients (81%) and for the myenteric plexus in 6 patients (54%). There was a good correlation coefficient (0.65) when both surgical and endoscopic groups were compared for the loss of ICCs. Mild serosal bruising and/or localized hematoma formations were noted at the sites of EUS biopsies, but there were no serosal tears, perforations, or adverse effects on the hospitalization and outcomes. CONCLUSIONS: EUS-guided FNA of the gastric muscularis propria in patients with gastroparesis is safe and provides adequate tissue for full histologic assessment. (Clinical trial registration number: NCT01916460.).

Rare Association of Severe Cryptococcal and Tuberculosis in Central Nervous System in a case of Sarcoidosis.

Sarcoidosis is a multisystem noncaseating granulomatous disease with a propensity for lung, eye, and skin which recently have been proposed that mycobacterium tuberculosis may contribute in its pathogenesis, and rarely involves central nervous system (CNS). Despite CD4+ lymphocytopenia, sarcoidosis by itself does not increase risk of opportunistic infections other than cryptococcosis. Nonetheless, simultaneous association of CNS cryptococcosis and tuberculosis infection remains extremely rare event in immunocompetent states, and has not been reported in sarcoidosis yet. We here presented such a case in a 42 years old man, a known case of sarcoidosis with diagnostic and therapeutic difficulties were encountered in a fourteen-month-long hospitalization period.

Imaging of fat-containing lesions of the breast: a pictorial essay.

Fat-containing breast lesions constitute a heterogeneous group of predominantly benign tumors and non-neoplastic conditions. The role of imaging is to distinguish leave-me-alone lesions from rarely occurring malignant fat-containing tumors that require histologic analysis. Correlating mammographic findings with appearance at ultrasonography often helps in identifying lesions that do not require further work-up. MRI can be valuable to confirm the presence of fat and characterize lesions indeterminate on conventional imaging. The purpose of this multimodality imaging review is to exemplify the radiologic appearances of common and uncommon fat-containing breast lesions to facilitate accurate diagnosis, avoid unnecessary interventions, and ensure appropriate management.

Brentuximab vedotin demonstrates an objective response in a patient with refractory CD30+ primary mediastinal B-cell lymphoma.

Diffuse large B-cell lymphomas (DLBCL) with MYC translocations combined with translocations involving BCL-2 or BCL-6 are referred to as double-hit lymphomas. These lymphomas are generally refractory to currently available therapies and have a poor prognosis. Primary mediastinal B-cell lymphoma (PMBL) is a rare subtype of DLBCL, which shares clinical, pathologic, and genetic similarities with classical Hodgkin's lymphoma. Unlike DLBCL, rearrangements involving MYC, BCL-2, and BCL-6 are typically absent in PMBL. We present a patient with PMBL who had increased gene copy numbers of MYC and BCL-2 along with increased protein expression of BCL-2 (c-Myc expression was about 15%-20% by immunostain). The disease was refractory to standard and salvage chemotherapies. The lymphoma, however, responded to brentuximab vedotin, a CD30-directed chemoimmunoconjugate.

Immune ontogeny and engraftment receptivity in the sheep fetus.

OBJECTIVE: The biologic explanation for fetal receptivity to donor engraftment and subsequent long-term tolerance following transplantation early in gestation is not known. We investigated the role fetal immune ontogeny might play in fetal transplantation tolerance in sheep. METHODS: Engraftment of allogeneic and xenogeneic HSC was determined 60 days following transplantation at different time points in sheep fetal gestation. Parallel analysis of surface differentiation antigen expression on cells from lymphoid organs of timed gestational age fetal sheep was determined by flow cytometry using available reagents. RESULTS: An engraftment window was identified after day 52 gestation lasting until day 71 (term gestation: 145 days). This period was associated with the expression of the leukocyte common antigen CD45 on all cells in the thymus. Double-positive and single-positive CD4 and CD8 cells began appearing in the thymus just prior (day 45 gestation) to the beginning of the engraftment window, while single-positive CD4 or CD8 cells do not begin appearing in peripheral organs until late in the engraftment period, suggesting deletional mechanisms may be operative. In concert, surface IgM-positive cells express CD45 in the thymus at day 45, with a comparable delay in the appearance of IgM/CD45 cells in the periphery until late in the engraftment window. CONCLUSIONS: These findings support a central role for the thymus in multilineage immune cell maturation during the period of fetal transplantation receptivity. Further, they suggest that fetal engraftment receptivity is due to gestational age-dependent deletional tolerance.

The beta adrenergic receptor antagonist propranolol alters mitogenic and apoptotic signaling in late stage breast cancer.

BACKGROUND: Substantial evidence supports the use of inexpensive ß-AR antagonists (beta blockers) against a variety of cancers, and the ß-AR antagonist propranolol was recently approved by the European Medicines Agency for the treatment of soft tissue sarcomas. Prospective and retrospective data published by our group and others suggest that non-selective ß-AR antagonists are effective at reducing proliferative rates in breast cancers, however the mechanism by which this occurs is largely unknown. METHODS: In this study, we measured changes in tumor proliferation and apoptosis in a late stage breast cancer patient treated with neoadjuvant propranolol. We expounded upon these clinical findings by employing an in vitro breast cancer model, where we used cell-based assays to evaluate propranolol-mediated molecular alterations related to cell proliferation and apoptosis. RESULTS: Neoadjuvant propranolol decreased expression of the pro-proliferative Ki-67 and pro-survival Bcl-2 markers, and increased pro-apoptotic p53 expression in a patient with stage III breast cancer. Molecular analysis revealed that ß-AR antagonism disrupted cell cycle progression and steady state levels of cyclins. Furthermore, propranolol treatment of breast cancer cells increased p53 levels, enhanced caspase cleavage, and induced apoptosis. CONCLUSION: Collectively, these data provide support for the incorporation of ß-AR antagonists into the clinical management of breast cancer, and elucidate a partial molecular mechanism explaining the efficacy of ß-AR antagonists against this disease.

Lack of a common or characteristic cytogenetic anomaly in solitary fibrous tumor.

Solitary fibrous tumor is a mesenchymal tumor that was initially described as a pleural-based lesion, but later was discovered in many other locations. The light-microscopic appearance of solitary fibrous tumor may overlap with other diagnostic entities; however, consistent tumor cell CD34 immunoreactivity is useful in establishing the diagnosis. Limited data suggest that solitary fibrous tumors are karyotypically diverse, and no common or characteristic anomaly has yet emerged for this entity. Cytogenetic analysis of two solitary fibrous tumors, one peritoneal and the other arising in the liver, revealed predominantly structural abnormalities in the former and numerical imbalances in the latter. Clonal karyotypic abnormalities were lacking in three additional solitary fibrous tumors.

Periodontal Regenerative Treatment of Intrabony Defects in the Esthetic Zone Using Modified Vestibular Incision Subperiosteal Tunnel Access (M-VISTA).

Periodontal regenerative treatment of intrabony defects in the esthetic zone often poses a significant challenge to clinicians. Various materials and techniques have been proposed to achieve periodontal regeneration. This article presents modified vestibular incision subperiosteal tunnel access (M-VISTA) for treatment of intrabony defects in the esthetic zone. Two cases were treated using the proposed approach with enamel matrix derivatives and demineralized freeze-dried bone allograft to optimize the regenerative outcomes without affecting the soft tissue profile in the esthetic zone. Two different indications were described with addition of acellular dermal matrix and specific suturing techniques based on each particular clinical scenario. Clinical and radiographic follow-up of 18 months revealed successful outcomes of the proposed minimally invasive approach with no postoperative gingival recession. Patient-centered outcomes were highlighted as another major consideration in periodontal regeneration.

Lip Repositioning with Vestibular Shallowing Technique for Treatment of Excessive Gingival Display with Various Etiologies.

Improvement of smile esthetics is a major goal of modern dentistry. Various treatment modalities have been proposed to correct excessive gingival display (EGD), depending on the identified etiologies. This study reports on the clinical and patient-centered outcomes of a novel lip repositioning technique with vestibular shallowing approach in the treatment of three types of EGD with varying etiologies. Periosteal fenestration with cicatrization (scarification) was performed at the mucogingival junction to ensure the stability of esthetic outcomes. Suspensory triangular sutures and extraoral tissue stabilization tapes were used to facilitate the cicatrization process during the healing phase of this novel technique. Postoperative clinical examination revealed 84% reduction in gingival display that remained stable for 13 to 16 months with a high level of patient satisfaction.

Thoracic Paraspinal Castleman Disease in a Young Mexican-American Man with Postcoital Hematuria.

BACKGROUND: Castleman disease (CD) is an uncommon disorder of deregulated lymphoproliferation with unicentric (UCD) and multicentric forms based on extent of nodal involvement. Gross resection with histopathologic analysis remains the gold standard for diagnosis of UCD and is curative in most cases. Symptomatic paraspinal UCD is a rare presentation with potentially dangerous complications, and its tendency to mimic more common spinal tumors presents a significant diagnostic challenge. CASE PRESENTATION: A 25-year-old Hispanic man with no past medical history was evaluated for a known left-sided paraspinal mass that was incidentally discovered during an emergency department work-up for hematuria. Computed tomography on initial presentation revealed a 5.3 cm × 3.3 cm × 4.8 cm heterogeneously enhancing left paraspinal mass adjacent to the T11 vertebral body with tonguelike extension into the T11-T12 neural foramen. Although he remained neurologically intact throughout most of the diagnostic work-up, an inconclusive biopsy, worsening hematuria, and late-onset radiculopathy with severe back pain prompted surgical intervention. Microscopic histomorphology was consistent with CD. He continued to have intermittent hematuria and dysuria postoperatively, but repeat computed tomography at 7 months confirmed no recurrence of the mass. CONCLUSIONS: Compared with previous reports, our case of postcoital hematuria and radiculopathy accompanying a paraspinal thoracic mass in a young Mexican-American man is a unique presentation. Awareness and early consideration of UCD in the work-up of a paraspinal mass may spare affected patients adverse and dangerous sequelae, such as spinal cord compression and excessive intraoperative hemorrhage.

Acute myeloid leukemia with KMT2A-SEPT5 translocation: A case report and review of the literature.

Chromosomal rearrangement involving the KMT2A gene is one of the most common genetic alteration in acute myeloid leukemia. A total of 135 different KMT2A rearrangements have been identified, where 94 translocation partner genes are now characterized at the molecular level. Of these 94 translocation partner genes, 35 translocation partner genes occur recurrently, but only 9 specific gene fusions account for more than 90% of cases. Translocation of KMT2A with SEPT5 gene at 22q11.2 is rare, with few reported cases in the literature. In this report, we are presenting a case of KMT2A-SEPT5 fusion in de novo acute myeloid leukemia with t(11;22)(q23;q11.2) with a review of the literature.

A New Prognostication System for Dental Implants.

Given the popularity of dental implants, determining their prognosis is an integral component of dental practice. An accurate prognosis is crucial to development of an appropriate treatment plan and may require alterations as overall status or the status of implants or natural teeth change. The importance of an established set of factors for determining implant prognosis would be highlighted in dentist-patient communication and in interdisciplinary collaboration. The main objective of the proposed prognostication system is short- and long-term success of dental implants. The aim of this study was to review evidence-based prognostic factors including surgical, peri-implant, prosthetic, and overall considerations in implant dentistry and to propose a new prognostication system. A blind survey was taken by 67 prosthodontists, periodontists, and oral surgeons at three dental schools to assess the importance of each consideration based on clinical experience and available evidence. The results supported incorporation of the comprehensive review of evidence-based prognostic factors into the proposed dynamic system for dental implant prognostication.

Calcitonin-Negative Neuroendocrine Tumor of the Thyroid.

Neuroendocrine tumors (NETs) of the thyroid are rare; the most common type is medullary thyroid carcinoma (MTC). They are derived from parafollicular cells (C-cells) that usually express calcitonin, chromogranin, and carcinoembryonic antigen. Calcitonin-negative NETs of the thyroid are extremely rare, and the origin of these tumors is unclear. Whereas some believe that these tumors are from follicular cells, recent reports have shown expression of calcitonin gene-related peptide in these tumors, indicating parafollicular C-cell origin. Here, we report a case of calcitonin-negative NET of the thyroid in a 74-year-old woman, with review of the literature.

Dermatopathic Lymphadenitis Mimicking Breast Cancer with Lymphatic Metastasis: A Case Report and Discussion.

BACKGROUND Dermatopathic lymphadenitis is a rare benign lymphatic hyperplasia commonly associated with exfoliative or eczematoid dermatitis. Of interest, this condition can be confused with lymphatic metastasis in adults. CASE REPORT In this report, we describe the case of a 56-year-old woman diagnosed with left breast invasive ductal carcinoma in remission, who presented with dermatopathic lymphadenitis mimicking breast cancer recurrence. CONCLUSIONS Dermatopathic lymphadenitis is a benign entity that needs to be considered in the differential diagnosis of lymphadenopathy. Pursuing extensive workup in asymptomatic patients with a similar presentation and initial negative tests for malignancy recurrence is not recommended.

Spontaneous Rupture of the Uterine Artery in an Otherwise Normal Pregnancy.

Spontaneous rupture of a uterine artery in pregnancy is associated with a high rate of mortality. Although uterine artery rupture has been associated with postpartum hemorrhage, it is rarely found during pregnancy. Unfortunately, clinical signs and symptoms are usually vague and nonspecific. We report a case of a 36-year-old woman at 20 weeks gestation presenting with abdominal pain who was found to have a spontaneous uterine artery rupture. To our knowledge, this is the first case report demonstrating imaging findings in a patient with this condition. Our patient underwent successful ligation of the uterine vessel with preservation of both mother and fetus. We will discuss possible etiologies of uterine artery rupture during pregnancy, associated imaging findings, and management options.