Blood Cells, Molecules, and Diseases

Predictors of autoimmune hemolytic anemia in beta-thalassemia patients with underlying red blood cells autoantibodies Publication date: November 2019 Source: Blood Cells, Molecules, and Diseases, Volume 79 Author(s): Monia Ben Khaled, Monia Ouederni, Nessrine Sahli, Nawel Dhouib, Ahmed Ben Abdelaziz, Samia Rekaya, Ridha Kouki, Houda Kaabi, Hmida Slama, Fethi Mellouli, Mohamed Bejaoui Abstract In beta-thalassemia patients, erythrocyte autoantibodies can remain silent or lead to Autoimmune Hemolytic Anemia (AIHA).The aim of this study was to identify predictors of AIHA in beta-thalassemia patients with positive Direct Antiglobulin Test (DAT), in Tunisia. This longitudinal prognosis study was carried out on beta-thalassemia patients with a positive confirmed DAT. Predictors of AIHA were identified the Kaplan-Meier method. A Cox model analysis was used to identify independent predictors. Among 385 beta thalassemia patients, 87 developed positive DAT (22.6%). Autoimmune hemolytic anemia was occurred in 25 patients. Multivariate analysis showed that AIHA was independently associated with beta-thalassemia intermedia and similar family history of AIHA. Splenectomy in patients with positive DAT was independently associated with an increased risk of AIHA (HR = 6.175, CI: 2.049–18.612, p < 0.001). The risk of developing AIHA was higher during the first 72 transfusions. Autoimmune hemolytic anemia was significantly associated with polyspecific DAT (anti-complement and anti-IgG), blood group AB and prior alloimmunization. Whereas transfusion by phenotypic and leukoreduced blood was a protective factor. In summary, splenectomy after autoimmunization, prior alloimmunization, DAT specificity (IgG with complement), thalassemia intermedia, AB blood group and family history of AIHA were strongly associated with AIHA. Leukoreduced blood transfusion had a proven preventive role.

Serum calprotectin: A circulating biomarker of the inflammatory state in Philadelphia-negative myeloproliferative neoplasms Publication date: November 2019 Source: Blood Cells, Molecules, and Diseases, Volume 79 Author(s): Ivan Krečak, Filip Krečak, Velka Gverić-Krečak, Iva Bilandžija, Pavle Rončević, Ksenija Fumić, Josip Batinić, Nadira Duraković, Maja Radman

Evaluation of double heptamer-type sgRNA as a potential therapeutic agent against multiple myeloma Publication date: November 2019 Source: Blood Cells, Molecules, and Diseases, Volume 79 Author(s): Tatsuya Ishikawa, Arisa Haino, Takashi Ichiyanagi, Mineaki Seki, Masayuki Nashimoto Abstract Emergence of drug-resistant mutations in the course of myeloma cell evolution and subsequent relapse of myeloma appears to be currently inevitable in most patients. To remedy this situation, we are trying to develop therapeutic small guide RNAs (sgRNAs) based on tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing), an RNA-mediated gene expression control technology. We designed two sets of double heptamer-type sgRNA, which target the human BCL2 mRNA. Both sets of double heptamer-type sgRNA reduced viability of human myeloma cell lines, RPMI-8226 and KMM-1. We also performed a mouse xenograft experiment to examine how the double heptamer-type sgRNA DHa1(BCL2)/DHa2(BCL2) can reduce the growth of KMM-1 cells in vivo. Median survival periods of the sgRNA cohorts were greater than that of the control cohort by 11–43 days. Furthermore, we designed two sets of double heptamer-type sgRNA, which target the human CCND1 mRNA, and both sets synergistically reduced RPMI-8226 cell viability.

Mechanism underlying N-(3-oxo-dodecanoyl)-L-homoserine lactone mediated intracellular calcium mobilization in human platelets Publication date: November 2019 Source: Blood Cells, Molecules, and Diseases, Volume 79 Author(s): Vivek Kumar Yadav, Pradeep Kumar Singh, Deepmala Sharma, Sunil Kumar Singh, Vishnu Agarwal Abstract Acyl-homoserine lactones (AHLs), are the key autoinducer molecules that mediate Pseudomonas aeruginosa associated quorum sensing. P. aeruginosa produces two types of AHLs; N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12 HSL) and N-butyryl-L-homoserine lactone (C4 HSL). AHLs are not only regulating the virulence gene of bacteria but also influence the host cell functions by interkingdom signaling. In this study, we explored the mechanism of AHLs induced calcium mobilization in human platelets. We found that 3-oxo-C12 HSL but not C4 HSL induces intracellular calcium release. 3-oxo-C12 HSL induced calcium mobilization was majorly contributed from the dense tubular system (DTS). Furthermore, 3-oxo-C12 HSL also stimulates the store-operated Ca2+ entry (SOCE) in platelet. Intracellular calcium rise was significantly lowered in rotenone, and bafilomycin pre-treated platelets suggesting partial involvement of mitochondria and acidic vacuoles. The significant effect of 3-oxo-C12 HSL on calcium mobilization can alter the platelet functions that might results in thrombotic disorders in individuals infected with P. aeruginosa.

Phenazine methosulphate-treated red blood cells activate NF-κB and upregulate endothelial ICAM-1 expression Publication date: November 2019 Source: Blood Cells, Molecules, and Diseases, Volume 79 Author(s): Rani Kaliyaperumal, Jianhe Wang, Herbert J. Meiselman, Björn Neu Abstract Although enhanced Red Blood Cell (RBC) - Endothelial Cell (EC) interaction, as well as RBC induced EC activation, have been extensively studied in several RBC-linked pathologies, the specific individual effects of oxidatively modified RBC on EC activation has not yet been documented. However, increasing evidence in both experimental and clinical studies suggests that oxidatively modified RBC could be considered potential pathogenic determinants in several acute and chronic diseases displaying systemic oxidative stress. Therefore, the present study aimed to explore the specific effects of oxidized RBC interaction with endothelial cells on intracellular signaling pathways that promote EC activation. RBC were exposed to oxidative stress induced by phenazine methosulphate (PMS). It is shown that the interaction of oxidatively modified RBC with cultured human umbilical vein endothelial cells (HUVEC) results in: a) EC activation as indicated by the increased surface expression of intercellular adhesion molecule −1 (ICAM-1); b) the activation of transcription factor NF-κB, an indicator of cellular oxidant stress. These results emphasize the specific contribution of oxidatively modified RBC interaction to EC activation and their possible pathological role in vascular diseases and oxidative stress.

No increased cerebrovascular involvement in adult beta-thalassemia by advanced MRI analyses Publication date: September 2019 Source: Blood Cells, Molecules, and Diseases, Volume 78 Author(s): Andrea Gerardo Russo, Sara Ponticorvo, Immacolata Tartaglione, Martina Caiazza, Domenico Roberti, Andrea Elefante, Maddalena Casale, Rosanna Di Concilio, Angela Ciancio, Elisa De Michele, Antonietta Canna, Mario Cirillo, Silverio Perrotta, Fabrizio Esposito, Renzo Manara Abstract Beta-thalassemia-related anemia and chronic hypercoagulative state are supposed to cause cumulative cerebrovascular damage with consequent parenchymal/vascular changes and functional impairment. However, recent conventional MRI/MR-angiography investigations failed to show an increased cerebrovascular involvement in beta-thalassemia patients managed according to current treatment guidelines, in spite of significantly decreased full-scale IQ scores. We therefore investigated those patients and controls by means of advanced quantitative MRI analyses (based on magnetization transfer and diffusion tensor imaging) searching for signs of possible cerebrovascular injuries undetected by conventional MRI/MR-angiography. The 3 T-MRI study protocol included diffusion tensor imaging and 3D-multi-echo FLASH sequences for magnetization transfer analysis. Whole-brain voxel-based analyses showed that magnetization transfer, fractional anisotropy, and mean, radial and axial diffusivity do not differ between healthy controls and beta-thalassemia patients (considered as a whole group or as distinct transfusion dependent and non-transfusion dependent subgroups). No correlation emerged between all the considered MRI metrics and cognitive findings (full-scale IQ) or the main clinical and laboratory data. According to our findings, adult neurologically-asymptomatic beta-thalassemia patients (regardless of clinical severity) do not seem to present an increased disease-related cerebrovascular vulnerability compared to healthy controls downsizing the need of regular brain MRI monitoring, at least when the current treatment guidelines are followed.

EPO-R+ myelodysplastic cells with ring sideroblasts produce high erythroferrone levels to reduce hepcidin expression in hepatic cells Publication date: September 2019 Source: Blood Cells, Molecules, and Diseases, Volume 78 Author(s): Shogo Miura, Masayoshi Kobune, Hiroto Horiguchi, Shohei Kikuchi, Satoshi Iyama, Kazuyuki Murase, Akari Goto, Hiroshi Ikeda, Kohichi Takada, Koji Miyanishi, Junji Kato Abstract Recently, a new erythroid regulator, erythroferrone (ERFE), which downregulates hepatic hepcidin production, has been identified. However, the relationship between ERFE and abnormal iron metabolism in MDS is unclear. In this study, we examined the level of ERFE mRNA during ex vivo erythroid differentiation using cord blood CD34+ cells and we further analyzed whether ERFE could be produced by MDS cells using a public database (GSE58831). ERFE mRNA was increased during normal erythroid differentiation. An analysis of GSE58831 indicated that ERFE expression in bone marrow (BM) MDS cells was higher than that in healthy volunteer (HV)–derived BM cells. ERFE expression significantly and positively correlated with the expression of erythropoietin (EPO) receptors (EPO-R), ALAS2 (5'-Aminolevulinate Synthase 2), STEAP3 (STEAP family member 3) and the presence of ring sideroblasts or the SF3B1 mutation. These results suggest that EPO-R+ MDS cells with ring sideroblasts or an SF3B1 mutation produce high levels of ERFE that may be associated with a reduction in hepcidin.

Co-inheritance of Southeast Asian Ovalocytosis (SAO) and G6PD deficiency associated with acute hemolysis in a Thai patient Publication date: Available online 11 July 2019 Source: Blood Cells, Molecules, and Diseases Author(s): Kannadit Prayongratana, Vip Viprakasit

Pediatric cerebral sinovenous thrombosis: Optimal treatment may differ by etiology Publication date: Available online 11 July 2019 Source: Blood Cells, Molecules, and Diseases Author(s): Adriana Gonzalez Torriente, Lisa R. Sun

Conjugate prodrug AN-233 induces fetal hemoglobin expression in sickle erythroid progenitors and β-YAC transgenic mice Publication date: Available online 9 July 2019 Source: Blood Cells, Molecules, and Diseases Author(s): Aluya R. Oseghale, Xingguo Zhu, Biaoru Li, Kenneth R. Peterson, Abraham Nudelman, Ada Rephaeli, Hongyan Xu, Betty S. Pace Abstract Pharmacologic induction of fetal hemoglobin (HbF) is an effective strategy for treating sickle cell disease (SCD) by ameliorating disease severity. Hydroxyurea is the only FDA-approved agent that induces HbF, but significant non-responders and requirement for frequent monitoring of blood counts for drug toxicity limit clinical usefulness. Therefore, we investigated a novel prodrug conjugate of butyric acid (BA) and δ-aminolevulinate (ALA) as a potential HbF inducing agent, using erythroid precursors and preclinical β-YAC mouse model. We observed significantly increased γ-globin gene transcription and HbF expression mediated by AN-233 in K562 cells. Moreover, AN-233 stimulated mild heme biosynthesis and inhibited expression of heme-regulated eIF2α kinase involved in silencing γ-globin expression. Studies using primary erythroid precursors generated from sickle peripheral blood mononuclear cells verified the ability of AN-233 to induce HbF, increase histone H3 and H4 acetylation levels at the γ-globin promoter and reduce erythroid precursor sickling by 50%. Subsequent drug treatment of β-YAC transgenic mice confirmed HbF induction in vivo by AN-233 through an increase in the percentage of HbF positive red blood cells and HbF levels measured by flow cytometry. These data support the potential development of AN-233 for the treatment of SCD.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Clinical Nuclear Medicine

Unexpected Lymphatic Drainage of the Treated Breast This case highlights the use of lymphoscintigraphy with SPECT/CT in patients with previous chest and/or axillary surgery. A 67-year-old woman with a history of left breast carcinoma treated with lumpectomy and radiotherapy, and a second lumpectomy of the ipsilateral breast for a second breast carcinoma, underwent a lymphoscintigraphy for a new left breast lesion. Planar images visualized an alternative lymphatic drainage to the contralateral axilla and to the left paravertebral area. SPECT/CT confirmed sentinel nodes in both stations. Received for publication January 23, 2019; revision accepted May 26, 2019. Conflicts of interest and sources of funding: none. Correspondence to: Richard Raghoo, MD, Department of Radiology, Section Nuclear Medicine, C2-P, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. E-mail: r.raghoo@lumc.nl. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Imaging Characteristics of Coexisting Primary Pulmonary Carcinoid Tumor and Multiple Myeloma on 18F-FDG and 68Ga-DOTATATE PET/CT A 69-year-old man with recurrent multiple myeloma underwent FDG PET/CT evaluation. A pulmonary nodule without higher-than-background FDG avidity was later biopsied as a low-grade neuroendocrine tumor. On further 68Ga-DOTATATE PET/CT evaluation of patient's neuroendocrine tumor, the lytic myeloma lesions revealed only mild DOTATATE avidity while the primary pulmonary neuroendocrine tumor showed intense DOTATATE uptake. The distinct imaging characteristics of different primary malignancies correlated with their underlying different pathology. Received for publication May 2, 2019; revision accepted May 28, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Dr. Yang Lu, Department of Nuclear Medicine Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, 1400 Pressler Unit Number: 1483 Houston, TX 77030. E-mail: ylu10@mdanderson.org. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Added Value of Myocardial Blood Flow Quantification and Calcium Scoring During CZT SPECT Myocardial Perfusion Imaging for Coronary Artery Disease Screening Dedicated cadmium-zinc-telluride cardiac cameras have been shown to provide accurate measurements of absolute myocardial blood flow and flow reserve when PET is not available. We report the case of a 66-year-old woman who underwent 1-day stress/rest myocardial perfusion imaging (MPI) for coronary artery disease (CAD) screening. Relative MPI analysis was normal, whereas low-dose CT showed high calcium score. Myocardial blood flow and flow reserve were strongly impaired in all territories. Coronary angiography confirmed extended CAD. Flow parameters derived from cadmium-zinc-telluride SPECT MPI acquisition and calcium scoring can improve diagnostic accuracy and confidence of CAD. Received for publication March 17, 2019; revision accepted May 27, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Matthieu Bailly, MD, Service de Médecine Nucléaire, CHR Orleans, 14 Avenue de l'Hopital, 45100 Orleans, France. E-mail: matthieu.bailly@chr-orleans.fr. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Nivolumab-Induced Pneumonitis in Patient With Metastatic Melanoma Showing Complete Remission on 18F-FDG PET/CT A 49-year-old patient with metastatic melanoma was treated with nivolumab (Opdivo). An early 18F-FDG PET/CT after 2 cycles showed a progressive metabolic disease. A 4-month optimal follow-up 18F-FDG PET/CT showed a complete metabolic response. The treatment was stopped after 22 cycles because of immunotherapy-related pneumonitis. After discontinuation of treatment, PET/CT examinations demonstrated a metabolic complete remission during 2 years. The metabolic pattern on early PET was suggestive of pseudoprogression, which is a rare phenomenon reflecting an activation of inflammatory cells within the tumor microenvironment causing lesions to increase in size and to accumulate FDG until a sufficient immune response is developed. Received for publication March 13, 2019; revision accepted May 29, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Micheline Razzouk-Cadet, MD, Department of Nuclear Medicine, Centre Hospitalier Universitaire de Nice, Archet, 151, Route de Saint-Antoine de Ginestière 06200 Nice Cedex 3, France. E-mail: razzouk-cadet.m@chu-nice.fr. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Incidental Finding of Acute Lymphocytic Leukemia in a Prostate-Specific Membrane Antigen PET/CT PSMA PET/CT is known to show uptake in various benign and malignant processes. The following PSMA PET/CT was performed for prostate carcinoma staging (Gleason 3 + 4 left apex; PSA 5.8). It shows incidental diffuse PSMA marrow uptake, not typical for prostate metastatic disease. No treatment had been commenced at the time of the scan. Serology and bone marrow biopsy showed B-cell acute lymphocytic leukemia. Focal PSMA uptake in the right ischium was correlated with a T1 hypointense lesion on a previous MRI and was convincing for a skeletal metastasis. Alternative diagnoses in diffuse skeletal PSMA uptake need therefore to be considered. Received for publication December 27, 2018; revision accepted May 31, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Christian Acksteiner, Dr Med, FRANZCR, South Coast Radiology, Locked Bag 1000, Mermaid Beach, Queensland 4218 Australia. E-mail: christian.acksteiner@gmail.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

In Vivo Microbial Targeting of 99mTc-Labeled Human β-Defensin-3 in a Rat Model of Infection Objective Differentiation of infection from aseptic inflammation represents a major clinical issue. None of the commercially available compounds (labeled granulocytes, antigranulocyte antibodies, 67Ga-citrate, labeled immunoglobulin G, 18F-FDG) is capable of this differentiation, producing a nonnegligible false-positive rate. Recently, our group reported on a reliable labeling procedure of the antimicrobial peptide human β-defensin 3 (HBD-3) with 99mTc. The aim of this study was to evaluate in vivo 99mTc-HBD-3 uptake in a rat model of infection. Methods Recombinant HBD-3 was radiolabeled with 99mTc. Radiolabeling yield and specific activity of the compound were calculated. Chromatographic behavior and biological activity of 99mTc-HBD-3 were also assessed. An experimental model involving Staphylococcus aureus–induced infection and carrageenan-induced aseptic inflammation was performed in 5 Wistar rats. Serial planar scintigraphic acquisitions were performed from 15 to 180 minutes after 99mTc-HBD-3 intravenous administration. Radiotracer uptake was evaluated qualitatively and semiquantitatively as a target-to-nontarget ratio. Results Radiolabeling yield of 99mTc-HBD-3 was 70% with a specific activity of 6 to 8 MBq/μg. A significant and progressive 99mTc-HBD-3 uptake was observed in the site of S. aureus–induced infection, with a maximum average target-to-nontarget ratio of 5.7-fold higher in the infection site compared with an inflammation site observed at 140 minutes. Conclusions In vivo imaging with 99mTc-HBD-3 in a rat model of S. aureus–induced infection demonstrated favorable uptake in the infection site compared with sterile inflammation and background. These promising results, together with previous ex vivo uptake and toxicity assessment, suggest the potential of 99mTc-HBD-3 as a novel agent for specific infection imaging. Received for publication May 17, 2019; revision accepted May 31, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Giulia Anna Follacchio, MD, Nuclear Medicine Unit, Department of Radiology, Oncology and Human Pathology, AOU Policlinico "Umberto I," Sapienza University of Rome, 324, Viale Regina Elena, 00161, Rome, Italy. E-mail: giuliaanna.follacchio@uniroma1.it. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Quality and Safety in Healthcare, Part LV: Leadership to prevent burnout and increase joy Leadership is very important to reduce burnout and promote happiness in the healthcare workplace. Whereas burnout and unhappiness lead to doctor turnover, more errors, more accidents, and decreased patient satisfaction, joy in the workplace results in better patient care, enhanced engagement and productivity, and more profitability for the healthcare organization. Many leadership characteristics are critical including integrity, putting the well-being of others first, being fair, standing for important principles, being a good role model, being an excellent communicator, encouraging new ideas and adopting them when feasible, and loving people. Conflicts of interest and sources of funding: none declared. Received for publication May 27, 2019; revision accepted June 1, 2019. Correspondence to: Jay A. Harolds, MD, Division of Radiology and Biomedical Imaging, College of Human Medicine, Michigan State University, Advanced Radiology Services, PC, 3264 North Evergreen Dr. NE, Grand Rapids, MI 49525. E-mail: harolds112@cox.net. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.nuclearmed.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

68Ga–Prostate-Specific Membrane Antigen-11 PET/CT: Incidental Finding of a Vestibular Schwannoma A 77-year-old man with newly diagnosed prostate adenocarcinoma with a total prostate-specific antigen level of 6.4 ng/mL and Gleason score 7 (4 + 3) was referred to 68Ga–prostate-specific membrane antigen-11 (PSMA) PET/CT for initial staging. An intense focal PSMA uptake was shown in the right peripheral zone of the prostate gland consistent with the primary tumor. Additionally, PET/CT demonstrated a PSMA-avid soft tissue mass in the left cerebellopontine angle. The patient had a history of left-sided sensorineural hearing loss. Received for publication March 15, 2019; revision accepted June 2, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Göksel Alçin, MD, Istanbul Egitim ve Arastirma Hastanesi, Nukleer Tip Kliniği, Org. Nafiz Gurman Cad, Samatya, Kocamustafapasa, Fatih 34098 Istanbul, Turkey. E-mail: gokselalcin@hotmail.com.tr. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

18F-Fluorocholine PET/CT in the Prediction of Molecular Subtypes and Prognosis for Gliomas Aim To study the association of metabolic features of 18F-fluorocholine in gliomas with histopathological and molecular parameters, progression-free survival (PFS) and overall survival (OS). Methods Prospective multicenter and nonrandomized study (Functional and Metabolic Glioma Analysis). Patients underwent a basal 18F-fluorocholine PET/CT and were included after histological confirmation of glioma. Histological and molecular profile was assessed: grade, Ki-67, isocitrate dehydrogenase status and 1p/19q codeletion. Patients underwent standard treatment after surgery or biopsy, depending on their clinical situation. Overall survival and PFS were obtained after follow-up. After tumor segmentation of PET images, SUV and volume-based variables, sphericity, surface, coefficient of variation, and multilesionality were obtained. Relations of metabolic variables with histological, molecular profile and prognosis were evaluated using Pearson χ2 and t test. Receiver operator caracteristic curves were used to obtain the cutoff of PET variables. Survival analysis was performed using Kaplan-Meier and Cox regression analysis. Results Forty-five patients were assessed; 38 were diagnosed as having high-grade gliomas. Significant differences of SUV-based variables with isocitrate dehydrogenase status, tumor grade, and Ki-67 were found. Tumor grade, Ki-67, SUVmax, and SUVmean were related to progression. Kaplan-Meier analysis revealed significant associations of SUVmax, SUVmean, and multilesionaly with OS and PFS. SUVmean, sphericity, and multilesionality were independent predictors of OS and PFS in Cox regression analysis. Conclusions Metabolic information obtained from 18F-fluorocholine PET of patients with glioma may be useful in the prediction of tumor biology and patient prognosis. Received for publication March 21, 2019; revision accepted June 2, 2019. All the authors confirm that the article is not under consideration for publication elsewhere. All ethical standards were complied with. Conflicts of interest and sources of funding: JPB and VMP-G were partially funded by the Ministerio de Economía y Competitividad/FEDER, Spain (grant number MTM2015-71200-R), Junta de Comunidades de Castilla-La Mancha (grant number SBPLY/17/180501/000154) and James S. Mc. Donnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer (Collaborative awards 220020560 and 220020450). All other authors declare no conflicts of interest. Research involving human participants and/or animals: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study. Correspondence to: Ana María García Vicente, MD, PhD, Nuclear Medicine Department, University General Hospital, C/ Obispo Rafael Torija, s/n 13005 Ciudad Real, Spain. E-mail: angarvice@yahoo.es. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

FDG-PET/CT Demonstrates Splenic Angiosarcoma Bone Marrow Metastasis Some patients with splenic angiosarcoma initially manifest thrombocytopenia owing to hypersplenism or tumor-related bone marrow fibrosis. The diagnosis of bone marrow metastasis in patients with splenic angiosarcoma is challenging, as the presentation mimics idiopathic thrombocytopenic purpura or primary myelofibrosis. Our case showed diffuse FDG uptake in the vertebral bodies, sacroiliac bone, humerus, femur, and clavicles. It was pathologically diagnosed as bone marrow metastasis of splenic angiosarcoma. We believe that the heterogeneous FDG accumulation in the bone marrow, although nonspecific, can be useful for the diagnosis of the bone marrow metastasis in patients with splenic angiosarcoma. Received for publication March 13, 2019; revision accepted June 2, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Hiroaki Takahashi, MD, Faculty of Medicine, Department of Diagnostic and Interventional Radiology, University of Tsukuba, 1-1-1, Tennoudai, Tsukuba, Ibaraki, 305-8575, Japan. E-mail: h.1982.takahashi@gmail.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Applied Immunohistochemistry & Molecular Morphology

Comparison of Dako HercepTest and Ventana PATHWAY Anti-HER2 (4B5) Tests and Their Correlation With Fluorescent In Situ Hybridization in Breast Carcinoma Objectives: We compared the performance of two Food and Drug Administration–approved HER2 immunohistochemistry (IHC) tests: HercepTest (Dako) and PATHWAY anti-HER2 (4B5) (Ventana). Materials and Methods: In total, 180 invasive breast carcinomas previously tested by both HercepTest and fluorescent in situ hybridization (FISH) were retested with 4B5. Three pathologists scored the HER2 IHC using the 2013 American Society of Clinical Oncology/College of American Pathologists guidelines. The HER2 IHC results were correlated with FISH. Results: Among 135 equivocal cases by HercepTest, 100 (74.1%) were negative by 4B5. Among 45 positive HercepTest cases 9 (20%) were equivocal by 4B5. Among 135 equivocal HercepTest results, 100 (74.1%) were nonamplified, 18 (13.3%) equivocal, and 17 (12.6%) amplified by FISH. Among the 45 positive results with HercepTest, 2 (4.5%) were nonamplified and 1 (2.2%) was equivocal by FISH. All 37 positive and 3 negative by 4B5 cases were amplified by FISH. The absolute interobserver agreement was high for both tests (Fleiss kappa=0.838 for HercepTest and 0.771 for 4B5). Conclusions: PATHWAY anti-HER2 (4B5) significantly reduced the number of equivocal results that require additional testing. Although HercepTest was positive in a small number of HER2 nonamplified cases, 4B5 failed to detect 3 cases that were interpreted as positive by FISH, all with nonclassic or low levels of amplification.

Identification of "Double Hit" Lymphomas Using Updated WHO Criteria: Insights From Routine MYC Immunohistochemistry in 272 Consecutive Cases of Aggressive B-Cell Lymphomas Aggressive lymphomas with MYC and BCL2 and/or BCL6 translocations ("double hit" lymphomas, DHL) represent a distinct diagnostic category in the updated World Health Organization (WHO) classification. The diagnostic yield of MYC immunohistochemistry (IHC) for the identification of DHL is currently uncertain. MYC IHC was performed in 272 consecutive cases of aggressive B-cell lymphoma, and results correlated with fluorescence in situ hybridization (FISH) for MYC translocations. Among 156 patients with IHC and FISH data, MYC IHC identified MYC translocations with 89% sensitivity, 38% specificity, 92% negative predictive value, and 29% positive predictive value. Three of 15 (20%) of DHL were MYC IHC negative. One case contained a MYC translocation detectable IGH/MYC fusion probes but not MYC break-apart probes. A subset of DHL lack MYC protein expression, and recognition of this subset of cases requires FISH testing. These results provide an appropriate diagnostic algorithm for implementation of 2016 WHO diagnostic criteria.

A Survey of Somatic Mutations in 41 Genes in a Cohort of T-Cell Lymphomas Identifies Frequent Mutations in Genes Involved in Epigenetic Modification Here, we utilize a high throughput sequencing panel that covers several genes known to be recurrently mutated in certain T-cell lymphoma subtypes as well as genes frequently mutated in other hematolymphoid malignancies, including myeloid neoplasms. This panel was applied to formalin-fixed, paraffin-embedded tissue from 84 biopsies from 78 patients selected for this study. The biopsies included ones a with a diagnosis of T-cell lymphoma (n=79), including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n=26) and angioimmunoblastic T-cell lymphoma (AITL; n=13), as well as 5 cases of atypical T-cell proliferations. KMT2C and KMT2D, which code for proteins involved in histone modifications, were the 2 most frequently mutated genes in our cohort and were altered across a range T-cell lymphomas. Mutations in TET2 and DNMT3A, which are involved in regulating DNA methylation, were also found in a variety of T-cell lymphoma categories. The RHOA G17V mutation that is frequently found in AITL was identified 5 of 13 (40%) cases of AITL and in 3 of 26 (12%) cases of PTCL-NOS, but not in biopsies involved by other T-cell proliferations. Our study adds to the already significant evidence from other investigators that, among T-cell lymphomas, the RHOA G17V variant is specific for AITL and PTCL-NOS. In contrast, variants in epigenetic modifier genes do not appear to be particularly specific for T-cell lymphoma subcategories evaluated in our study.

The Amount of Melanin Influences p16 Loss in Spitzoid Melanocytic Lesions: Correlation With CDKN2A Status by FISH and MLPA Aims: The risk assessment of spitzoid lesions is one of the most difficult challenges in dermatopathology practice. In this regard, the loss of p16 expression and the homozygous deletion of CDKN2A, have been pointed in the literature as reliable indicators of high risk. However, these findings are poorly reproducible, and the molecular bases underlying the loss of p16 expression remain unclear. We aimed to identify the underlying events causing loss of CDKN2A/p16 in spitzoid tumors. Materials and Methods: We evaluated the immunohistochemical expression of p16, and the presence of CDKN2A genetic alterations detected through fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA), in a series of 130 Spitz nevi, 20 atypical spitzoid tumors, and 11 spitzoid melanoma. Results: We found a significant loss of p16 expression in cases with high amount of melanin content in the 3 groups (P<0.000001) and a similar proportion of p16-negative cases in the group of Spitz nevi and atypical spitzoid tumors. MLPA allowed the recognition of CDKN2A microdeletions, which correlated with p16 loss (P=0.01). MLPA and FISH were more accurate than immunohistochemistry to detect CDKN2A alterations; although contrary to MLPA, FISH fails to recognize CDKN2A microdeletions. Conclusions: According to our results, p16 expression may be useful in the study of cases with atypical features and low melanin content, but it has no value in highly pigmented spitzoid lesions.

Nestin Expression in Spitzoid Lesions: An Immunohistochemical Characterization With Clinical and Dermoscopic Correlations Spindle or epithelioid melanocytic (Spitz) nevi usually affect children or adolescents and growth in the face or the lower extremities. Histologically, they may show cytoarchitectural atypia and mitotic figures that could represent diagnostic pitfalls with malignant melanoma. Atypical spitzoid tumors (AST) indicate lesions that microscopically show intermediate characteristics between benign nevi and malignant melanoma. Nestin expression has been evaluated in benign nevi and malignant melanoma, but no studies on its role in Spitz lesion have been elaborated so far. Our results indicate that Nestin could allow to discriminate between AST and malignant spiztoid melanoma; the typical dermoscopic pattern is also associated with benign nevi in contrast to the atypical pattern that accumunates AST and malignant spitzoid melanoma.

Cooperation of Indian Hedgehog and Vascular Endothelial Growth Factor in Tumor Angiogenesis and Growth in Human Hepatocellular Carcinomas, an Immunohistochemical Study The Hedgehog pathway was recently shown to be involved in vascular development and neovascularization in human embryogenesis and disease. However, the role of Hedgehog pathway in modulating tumor angiogenesis is still unexplored. In the current study, we investigated the expression of Indian Hedgehog (Ihh) and vascular endothelial cell growth factor (VEGF) in human hepatocellular carcinomas (HCCs) with immunohistochemical staining and compared the immunoreaction data with various clinicopathologic characteristics. Immunoreactivity of Ihh and VEGF proteins was observed in 61.5% (56/91) and 64.5% (59/91) cases of HCC tumor tissues, respectively, which was considerably higher than the adjacent nonmalignant tissues. Ihh protein was observed predominantly in the cytoplasm of the tumor cells with a staining pattern of which was sparse and dot-like, or circular around the cell membrane. VEGF protein was expressed heterogenously in the cytoplasm in tumor cells and was negative in peritumoral areas in all cases. CD34 showed diffuse staining in the tumor parenchyma in most HCC specimens. The association of expression of Ihh and VEGF with tumor size was statistically significant (P<0.05), but there was no significant association with other clinicopathologic parameters. Moreover, there was a significant association of the expressions of Ihh and VEGF proteins in HCC (r=0.6, P<0.0001), and of Ihh and CD34 staining (r=0.261, P=0.012). Our findings suggest that Ihh is involved in the development of HCC. These findings are also consistent with the concept that cooperation of Ihh and VEGF modulate HCC tumor angiogenesis and growth.

Patterns of Immunohistochemistry Utilization in Metastases to the Liver Immunohistochemistry (IHC) is a well-established morphology adjunct enabling pathologists to make accurate diagnoses. Metastases to the liver is a common scenario where pathologists may rely heavily on IHC in their interpretation. We conducted this study to audit the patterns of IHC utilization in malignant liver biopsies in 3 practice types (academic, community, and expert) as an initial step toward developing best practice guidelines. A total of 1100 specimens were analyzed and the association between the availability of history of other malignancies and the practice type on IHC utilization was studied. Community pathologists were twice as likely to use IHC and to use more markers per case than academic pathologists or the expert pathologist. When history of another malignancy was available, pathologists were not only 1.5 times more likely to use IHC but they also used more markers per case. IHC was still deemed necessary to reach the diagnosis in 67% of cases with a given history of other malignancy. This study described several variables for consideration in our effort to develop IHC utilization guidelines and its results quantify the variance noted among practice types.

SOFAT as a Putative Marker of Osteoclasts in Bone Lesions Secreted osteoclastogenic factor of activated T cells (SOFAT) is a novel activated human T-cell–secreted cytokine that induce osteoclastogenesis in a RANKL-independent manner. The aim of this study was to evaluate the immunohistochemical expression of SOFAT in intraosseous and extraosseous lesions. Thirty-two oral biopsies were divided into 2 groups: (1) intraosseous lesions—4 cases of cherubism, 5 central giant cell lesions, 3 osteoblastomas, 3 cementoblastomas, 2 periapical lesions and (2) extraosseous lesions—5 peripheral giant cell lesions, 5 cases of oral paracoccidioidomycosis, and 5 foreign body reactions. Immunohistochemistry was performed for SOFAT and tartrate-resistant acid phosphatase. Image analysis consisted of a descriptive evaluation of the immunohistochemical staining pattern observed. Tartrate-resistant acid phosphatase-positive lesions included those containing multinucleated giant cells (MGC) from both groups. SOFAT was positive in MGC of the intraosseous lesions group, except in periapical foreign body reactions as well as extraosseous lesions. SOFAT was shown to be a putative marker of osteoclasts, which proved useful to differentiate them from multinucleated macrophages. Osteoclast induction may be both dependent and independent from the RANK/RANKL/OPG pathway and independent from the bone microenvironment.

Novel Finding of Paired Box 5 (PAX5) Cytoplasmic Staining in Well-differentiated Rectal Neuroendocrine Tumors (Carcinoids) and Its Diagnostic and Potentially Prognostic Utility Although nuclear immunostaining for paired box protein (PAX5) is widely used in practice, its cytoplasmic localization has not been evaluated. Recently we encountered cytoplasmic granular PAX5 staining in rectal well-differentiated neuroendocrine tumor (WD-NET) in the absence of nuclear staining. We investigated the specificity of this staining pattern for rectal NET (n=21) in comparison with 108 NETs, 1 WD rectal NET with elevated proliferation (WD-NET G3), and 40 poorly differentiated neuroendocrine carcinomas from the gastrointestinal and pancreatobiliary tract and liver. Representative tumor sections were subject to immunohistochemical stain for PAX5 antibody. Immunohistochemistry for 3 L-cell markers, glucagon-like peptide 1 and 2, and peptide YY, was performed on all rectal and appendiceal NETs and all other NETs with cytoplasmic PAX5 staining. Cytoplasmic PAX5 staining was observed in 90% (19/21) of rectal NET, 27% (3/11) of appendiceal, 14% (2/14) of pancreatic, 7% (2/29) of lung, 25% (3/12) metastatic NET in the liver, and 100% (1/1) of renal NET. No PAX5 cytoplasmic staining was seen in all grades of NET in other organs, rectal WD-NET G3, and all neuroendocrine carcinoma. L-cell marker staining was observed in all 21 (100%) rectal, in 3 of 3 (100%) PAX5-positive, and 1 of 7 (14%) PAX5-negative appendiceal NET. Cytoplasmic PAX5 staining is specific for rectal carcinoids. The sensitivity and specificity of PAX5 to detect L-cell type rectal carcinoids is 90% (19/21) and 100% (21/21), respectively. Cytoplasmic localization of the PAX5 protein may be utilized as a surrogate marker to detect L-cell type rectal carcinoids.

Gastrointestinal Stromal Tumor With Multiple Primary Tyrosine Kinase Mutations—Clinicopathologic and Molecular Characterization A unique cohort of chemo-naive gastrointestinal stromal tumors (GISTs) with double-primary tyrosine kinase mutations was characterized particularly to determine whether coexistent mutations represent a single mutational event. Up to 2013, 4 UK centers reported 9 GISTs with 2 primary tyrosine kinase mutations. In each of 8 cases validated by next generation sequencing, both mutations were present in the same allele of the same exon (KIT exon 11 or 17, or PDGFRA exon 18). One case showed the second mutation only on some of the mutant alleles. Seven cases showed both mutations in all the reads, but in 2 cases, additional variants were found only in some reads. Clinicopathologic features of the 8 cases were similar to GISTs with single-primary mutations. When GIST genotyping rarely uncovers multiple tyrosine kinase variants in an exon, they occur in the same allele but are likely to represent separate mutational events and lack clinical significance.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Coronary Artery Disease

Beneficial effect of ticagrelor on microvascular perfusion in patients with ST-segment elevation myocardial infarction undergoing a primary percutaneous coronary intervention Background Ticagrelor significantly reduced the incidence of death, myocardial infarction, and stent thrombosis in patients with ST-segment elevation myocardial infarction (STEMI) intended for reperfusion with a primary percutaneous coronary intervention (pPCI). However, the effects of this drug on microvascular perfusion in patients presenting with STEMI have not been evaluated completely. Patients and methods A total of 298 patients presenting with STEMI were randomized to either ticagrelor 180 mg loading, followed by 90 mg twice daily, or clopidogrel 600 mg loading, followed by 75 mg daily. The primary endpoint was ST-segment resolution at 90 min after pPCI. The secondary endpoints included myocardial blush grade and corrected thrombolysis in myocardial infarction frame count after the procedure. Left ventricular ejection fraction and major adverse cardiac events (MACE) at the 1- and 6-month follow-up time points were also recorded. Results There were no significant differences between the two groups with respect to baseline characteristics. Ticagrelor administration resulted in a higher rate of completed ST-segment resolution (58.67 vs. 39.86%, P=0.001), higher myocardial blush grade (2.63±0.64 vs. 2.41±0.71, P=0.005), and lower corrected thrombolysis in myocardial infarction frame count (19.68±7.38 vs. 22.35±8.30, P=0.004). At 6 months, left ventricular ejection fraction was higher (55.01±8.44 vs. 52.34±9.05%, P=0.009) in the ticagrelor group. Kaplan–Meier analysis showed that MACE-free survival had also improved in the ticagrelor group during the 1- and 6-month follow-up time points. Conclusion Compared with clopidogrel, ticagrelor improves myocardial perfusion and left ventricular ejection fraction, and reduces the incidence of MACE for STEMI patients undergoing pPCI, with no significant increase in major bleeding.

Ticagrelor and microvascular perfusion in patients with acute myocardial infarction: hype or hope? No abstract available

Outcomes of a routine invasive strategy in elderly patients with non-ST-segment elevation myocardial infarction from 2005 to 2014: results from the PL-ACS registry Background Elderly patients (≥75 years old) with non-ST-segment elevation myocardial infarction (NSTEMI) represent a large subgroup of all cases. They are rarely included in randomized trials because of comorbidities and concerns about complications. Furthermore, invasive treatments are used less frequently in this patient group. The aim of this study was to analyze trends in invasive procedures and outcomes in elderly patients with NSTEMI from 2005 to 2014. Patients and methods We analyzed 68 978 elderly patients with NSTEMI enrolled in the prospective, nationwide Polish Registry of Acute Coronary Syndromes from 2005 to 2014. Results Elderly patients accounted for 34.9% of all patients with NSTEMI. There was an increase in the rate of coronary angiography from 19.1% in 2005–2007 to 83.5% in 2012–2014 among women (P<0.05) and from 26.0 to 87.5% among men (P<0.05). Simultaneously, there was an increase in percutaneous coronary intervention usage from 12.9% in 2005–2007 to 56.3% in 2012–2014 among women (P<0.05) and from 17.6 to 60.5% among men (P<0.05). On comparing the periods of 2005–2007 and 2012–2014, in-hospital mortality decreased considerably from 9.6 to 5.3% among women (P<0.05) and from 9.1 to 4.7% among men (P<0.05). In the same time period, the 12-month mortality ratio decreased: from 30.5 to 22.0% among women (P<0.05) and from 32.0 to 22.8% among men (P<0.05). In multivariate analysis, age was one of the most important factors associated with poorer outcome. With each increased decade of life, the outcomes worsened – the relative risk of mortality was 1.63 [95% confidence interval (CI): 1.59–1.68] for the in-hospital prognosis and 1.57 (95% CI: 1.55–1.59) for the 12-month prognosis. Invasive treatment strategy was the strongest factor associated with improved outcome, with a relative risk of 0.31 (95% CI: 0.29–0.33) for in-hospital mortality and 0.51 (95% CI: 0.49–0.52) for 12-month mortality, respectively. Conclusion Patients with NSTEMI benefit considerably from invasive procedures independent of age. In-hospital as well as 12-month outcomes in elderly patients improved markedly in the last decade as a result of the wide implementation of an invasive treatment strategy.

Characteristics and outcomes of patients with cancer presenting with acute myocardial infarction Background Limited data are available regarding the optimal management of patients with cancer in the acute myocardial infarction (AMI) setting. Patients and methods We studied consecutive patients with AMI included in a national registry (years 2010, 2016) with the diagnosis of past or active malignancy and followed them for 1 year. Results Our cohort consisted of 2937 cancer-naive patients and 152 patients with cancer, of whom 35% presented with active malignancies. Compared with cancer-naive patients, patients with cancer were older, with female predominance, and presented more often with a history of hypertension and chronic kidney disease (P<0.001 for all comparisons). The rate of ST-elevation AMI was comparable (P=0.067). GRACE score more than 140 was more common in the cancer group (P<0.001). Most patients with cancer were referred to coronary angiography, though less than cancer-naive patients (87 vs. 93%; P=0.004). The rate of percutaneous coronary intervention was similar (P=0.265). Propensity score matching demonstrated similar rates of in-hospital complications between groups, and no mortality or major cardiac adverse event differences were noted at 30 days. Moreover, short-term mortality was similar between patients with active versus past malignancies, and between patients with solid and nonsolid tumors. However, cancer in patients with AMI was found to predict an increased mortality risk at 1 year by multivariable analysis (hazard ratio=2.52; P<0.001). Conclusion Patients with cancer and AMI have a more complicated clinical presentation, yet their short-term prognosis is similar to cancer-naive patients. Nevertheless, 1-year outcome is worse.

Path analysis for key factors influencing long-term quality of life of patients following a percutaneous coronary intervention Objectives This cross-sectional study aimed to investigate the long-term quality of life (QOL) influencing of patients following a percutaneous coronary intervention (PCI) as well as its influencing factors. Patients and methods From June 2013 to April 2014, 428 PCI patients were enrolled in this questionnaire survey. The demographic and clinical data, Social Support Rating Scale, Medical Coping Modes Questionnaire, Social Disability Screening Schedule, and Short Form 36 Health Status Questionnaire were collected. Statistical analyses for data and path analyses for influencing factors were then carried out. Results PCI patients received considerable social support from family and society, and most PCI patients adopted negative coping styles (avoidance and acceptance-resignation). Approximately 70.3% of PCI patients had a serious functional defect, and 96.97% of patients had an average (79.91%) or better (17.06%) QOL. Multiple linear regression analysis showed that long-term QOL of PCI patients was correlated positively with social support and sleep quality, but correlated negatively with the acceptance-resignation coping style, social function defects, and number of adverse cardiac events. Path analysis further showed that social support, acceptance-resignation coping style, social function defects, number of adverse cardiac events, and sleep quality exerted important effects on long-term QOL of PCI patients in descending order. Conclusion Most PCI patients had an average medium-term or better long-term QOL. Social support, acceptance-resignation coping style, social function defects, number of adverse cardiac events, and sleep quality were key influencing factors.

Ultra-low-contrast angiography in patients with advanced chronic kidney disease and previous coronary artery bypass surgery Objective We sought to describe a technique for ultra-low-contrast angiography (ULCA) in patients with advanced chronic kidney disease (CKD) and previous coronary artery bypass surgery (CABG). Background Patients with advanced CKD and previous CABG are at high risk of developing contrast-induced nephropathy (CIN) because of the additional contrast often required to identify bypass grafts. Apart from hydration, reduced contrast administration is the only established method to minimize the risk of CIN. Patients and methods Ten patients underwent ULCA, whereby an intracoronary injection of saline and coronary guidewires were used instead of test injections of contrast for engagement of bypass grafts with catheters. Estimated glomerular filtration rate (eGFR) before and 30 days following angiography were recorded as was the need for renal replacement therapy 1 year after the procedure. Results All patients completed a diagnostic angiogram without complications. The median volume of contrast delivered was 13.5 ml (interquartile range: 10.5–17.8). The median eGFR was 18.3 ml/min/1.73 m2 (interquartile range: 16.5–28.2). There was no statistically significant difference in eGFR before the procedure and 30 days after the procedure (P=0.79). No patient required dialysis 30 days after the procedure. Two patients required initiation of dialysis at 1 year after the procedure. Conclusion In patients with advanced CKD and previous CABG, ULCA may be performed with high procedural success and without complications, minimizing the risk of CIN in these high-risk patients.

A novel safe method for treatment of giant coronary artery aneurysm: Wire Looping Technique No abstract available

Off-pump onlay-patch grafting using the left internal mammary artery for a diffusely diseased left anterior descending artery: in-hospital and mid-term outcomes Background The aims of this study were to evaluate the in-hospital and mid-term outcomes of the off-pump onlay-patch grafting procedure using the left internal mammary artery (LIMA) for a diffusely diseased left anterior descending artery (LAD) and to identify the risk factors for postoperative LIMA graft failure in a single-center retrospective study. Patients and methods A total of 63 patients (52 males, 65.7±9.0 years) undergoing LAD arteriotomy with or without concomitant endarterectomy, followed by reconstruction using LIMA onlay-patch at the time of off-pump coronary artery bypass grafting at our institute from January 2014 to December 2016 were reviewed. The operative mortality, major postoperative morbidity, follow-up all-cause mortality, major adverse cardiac events at follow-up, and postoperative LIMA graft patency were analyzed. The risk factors for postoperative LIMA graft failure on the basis of baseline and surgical characteristics were identified by multivariable logistic regression analysis. Results Eighteen (28.6%) patients underwent concomitant open LAD endarterectomy. The operative mortality rate was 1.6%. Major postoperative morbidity included perioperative myocardial infarction (3.2%), low cardiac output (1.6%), and reoperation for bleeding (1.6%). During the follow-up period of 24.2±9.5 months, all-cause mortality was 1.7% and the incidence of major adverse cardiac events was 6.8%. No repeat revascularization was recorded. In total, 88.1% of LIMA grafts showed FitzGibbon grade A patency determined by noninvasive coronary computed tomography angiography during follow-up. In addition, concomitant LAD endarterectomy and intraoperative LIMA graft flow were found to be independent risk factors for mid-term LIMA graft failure by multivariable logistic regression analysis (odds ratio=2.681, 95% confidence interval: 1.314–9.856, P=0.007 and odds ratio=0.932, 95% confidence interval: 0.791–0.976, P=0.021, respectively). Conclusion Revascularization of a diffusely diseased LAD using the off-pump LIMA onlay-patch technique results in encouraging clinical outcomes with favorable angiographic results. Concomitant LAD endarterectomy and intraoperative LIMA graft flow are associated with the risk of postoperative LIMA graft failure.

Traditional Chinese medicine training for cardiac rehabilitation: a randomized comparison with aerobic and resistance training Background The aim of this study was to investigate the efficacy and safety of different exercise regimens in the rehabilitation of patients with stable coronary heart disease. Patients and methods This study was a randomized controlled trial to screen 141 patients with stable coronary heart disease who were admitted to the General Administration of Sport of China Sports Medical Science Institute from January 2018 to September 2018. They were randomly divided into the aerobic and resistance training (ART) group for 12 weeks (36 cases), the traditional Chinese medicine training (TCMT) group 12 weeks (37 cases), and the control (CON) group (39 cases). We analyzed the baseline parameters of all participants and the 12-week exercise plate test parameters and related physical and body parameters. Result After 12 weeks of intervention, volume of oxygen (VO2), VO2/kg, metabolic equivalents, VO2/heart rate, stroke volume, and peaked grip strength and flexibility parameters of the ART group and the TCMT group were significantly higher than those of the control group (P<0.05). Resting heart rate of the TCMT group was significantly lower than the CON group, but there was no significant difference between the ART and CON groups (P>0.05). Ventilation/VO2 of the TCMT group was significantly higher than that of the CON group. BMI of the ART group was significantly lower than that of the TCMT group and the CON group, and body fat mass of the TCMT group was significantly smaller than that of the ART group, but there was no difference between the TCMT group and the CON group for BMI and body fat mass. Conclusion Both ART and TCMT can improve the cardiopulmonary aerobic exercise capacity and physical fitness of patients with stable coronary heart disease. Although the degree of improvement is different, they all have certain effects on the rehabilitation of patients with stable coronary heart disease and the application is safe.

Impact of smoking on all-cause mortality and cardiovascular events in patients after coronary revascularization with a percutaneous coronary intervention or coronary artery bypass graft: a systematic review and meta-analysis Although cigarette smoking is an independent risk factor for cardiovascular disease, inconsistent results have been published in the literature on its impacts on the cardiovascular health of patients after coronary revascularization with a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). We performed a comprehensive electronic database search through July 2018. Studies reporting the risk estimates of all-cause mortality and cardiovascular outcomes in patients after coronary revascularization with PCI or CABG on the basis of smoking status were selected. Multivariate-adjusted relative risks (RRs) and 95% confidence intervals (CIs) were pooled using random-effects models with inverse variance weighting. Data from 37 records including 126 901 participants were finally collected. Overall, the pooled RR (95% CI) associated with cigarette smoking was 1.26 (95% CI: 1.09–1.47) for all-cause mortality, 1.08 (95% CI: 0.92–1.28) for major adverse cardiovascular events, 0.96 (95% CI: 0.69–1.35) for cardiovascular mortality and 1.15 (95% CI: 0.81–1.64) for myocardial infarction. The increased risk of all-cause mortality was also observed in former smokers compared with those who had never smoked (RR: 1.19; 95% CI: 1.03–1.38). Furthermore, the negative effects of cigarette smoking on all-cause mortality were also observed in most subgroups. Cigarette smoking has been shown to increase the likelihood of all-cause mortality in patients after coronary revascularization with PCI or CABG. Smoking cessation is essential for PCI or CABG patients to manage their coronary artery disease.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Diseases of the Colon & Rectum

Drs Julio Garcia-Aguilar and Emina Huang: Colorectal Surgeons Advancing the Science of Colorectal Diseases No abstract available

Evaluation and Management of Enterocutaneous Fistula Case Summary: A 36-year-old woman presents with an abscess at her midline wound 4 weeks following an ileocecectomy for Crohn's disease. After the abscess is incised, there is purulent drainage followed by the drainage of enteric contents; the output is 750 mL per 24 hours.

Expert Commentary on the Management of Enterocutaneous Fistula No abstract available

Abstracts Featured in This Issue: August 2019 No abstract available

Anatomic Distribution of Colorectal Adenocarcinoma in Young Patients BACKGROUND: The incidence of colorectal cancer has increased in the younger population. Studies show an increased prevalence of left-sided tumors in younger patients; however, exact anatomic distribution is not known. OBJECTIVE: We sought to determine the anatomic distribution of colorectal cancer in young patients and to calculate the proportion of tumors that would be within reach of a flexible sigmoidoscopy. DESIGN: The National Cancer Database (2004–2015) was used to identify patients with colorectal cancer. SETTINGS: This was a multicenter study using national data. PATIENTS: The study included 117,686 patients under the age of 50 years diagnosed with colorectal cancer and 1,331,048 patients over the age of 50 years diagnosed with colorectal cancer. MAIN OUTCOME MEASURES: The primary outcome was the proportion of left-sided tumors in patients under the age of 50 years. RESULTS: A total of 74.4% of patients under age 50 years and 56.1% of patients over age 50 years had left-sided colorectal cancer. LIMITATIONS: The study is a retrospective review and does not exclude young patients who developed colorectal cancer with familial syndromes with a colorectal cancer disposition. CONCLUSIONS: A total of 74.4% of colorectal cancers diagnosed before age 50 years are left sided. In light of recent changes to screening recommendations, distribution of disease in young patients is important to both provider and patient education and decision-making. See Video Abstract at http://links.lww.com/DCR/A966.

Predictive Factors for Bowel Dysfunction After Sphincter-Preserving Surgery for Rectal Cancer: A Single-Center Cross-sectional Study BACKGROUND: With increasing rates of sphincter preservation because of advances in preoperative chemoradiation, restoration of bowel continuity has become a main goal of rectal cancer treatment. However, in many patients, postoperative bowel dysfunction negatively affects the quality of life. OBJECTIVE: This study aimed to analyze predictors of bowel dysfunction after sphincter-preserving surgery in patients with rectal cancer. DESIGN: This was a cross-sectional study. SETTINGS: Assessment of bowel dysfunction was conducted between November 2015 and June 2017 at our institution. PATIENTS: A total of 316 patients with rectal cancer who underwent sphincter-preserving surgery between February 2009 and April 2017 and agreed with an interview for assessing bowel dysfunction were included. MAIN OUTCOME MEASURES: Bowel dysfunction was assessed with the Memorial Sloan Kettering Cancer Center Bowel Function Instrument and Wexner score. All the assessments were conducted face-to-face by the same interviewer. RESULTS: The median time interval between the restoration of bowel continuity and assessment was 10 months (interquartile range, 3–37), and the median total Memorial Sloan Kettering Cancer Center and Wexner scores were 65 (interquartile range, 58–73) and 6 (interquartile range, 0–11). The time interval was correlated with the Memorial Sloan Kettering Cancer Center scores (rho, 0.279) and Wexner scores (rho, –0.306). In a multivariate analysis, handsewn anastomosis and short time interval (≤1 year) were independently associated with poor bowel function (Memorial Sloan Kettering Cancer Center score ≤65). A short time interval (≤1 year), preoperative chemoradiation, and ileostomy were independently associated with major fecal incontinence (Wexner ≥8). LIMITATIONS: Selection bias may be inherent. CONCLUSIONS: Bowel function recovers with time after the restoration of bowel continuity. A short time interval, handsewn anastomosis, preoperative chemoradiation, and ileostomy were significantly associated with poor bowel function or major fecal incontinence. Surgeons should discuss postoperative bowel dysfunction and its predictive factors with the patients. See Video Abstract at http://links.lww.com/DCR/A930.

Risk of Invasive Anal Cancer in HIV-Infected Patients With High-Grade Anal Dysplasia: A Population-Based Cohort Study BACKGROUND: The progression rate and predictors of anal dysplastic lesions to squamous cell carcinoma of the anus remain unclear. Characterizing these parameters may help refine anal cancer screening guidelines. OBJECTIVE: This study aimed to determine the rate of progression of high-grade anal dysplasia to invasive carcinoma in HIV-infected persons. DESIGN: Using the Surveillance, Epidemiology, and End Results database linked to Medicare claims from 2000 to 2011, we identified HIV-infected subjects with incident anal intraepithelial neoplasia III. To estimate the rate of progression of anal intraepithelial neoplasia III to invasive cancer, we calculated the cumulative incidence of anal cancer in this cohort. We then fitted Poisson models to evaluate the potential risk factors for incident anal cancer. SETTINGS: This is a population-based study. PATIENTS: Included were 592 HIV-infected subjects with incident anal intraepithelial neoplasia III. MAIN OUTCOME MEASURES: The primary outcome measured was incident squamous cell carcinoma of the anus. RESULTS: Study subjects were largely male (95%) with a median age of 45.7 years. Within the median follow-up period of 69 months, 33 subjects progressed to anal cancer. The incidence of anal cancer was 1.2% (95% CI, 0.7%–2.5%) and 5.7% (95% CI, 4.0%–8.1%) at 1 and 5 years, following a diagnosis of anal intraepithelial neoplasia III. Risk of progression did not differ by anal intraepithelial neoplasia III treatment status. On unadjusted analysis, black race (p = 0.02) and a history of anogenital condylomata (p = 0.03) were associated with an increased risk of anal cancer incidence, whereas prior anal cytology screening was associated with a decreased risk (p = 0.04). LIMITATIONS: The identification of some incident cancer episodes used surrogate measures. CONCLUSIONS: In our population-based cohort of HIV-infected subjects with long-term follow-up, the risk of progression from anal intraepithelial neoplasia III to anal squamous cell carcinoma was higher than reported in other studies and was not associated with the receipt of anal intraepithelial neoplasia III treatment. See Video Abstract at http://links.lww.com/DCR/A933.

Emergency Surgery for Obstructive Colon Cancer in Elderly Patients: Results of a Multicentric Cohort of the French National Surgical Association BACKGROUND: Although elderly patients constitute most of the patients undergoing surgery for obstructed colon cancer, available data in the literature are very limited. OBJECTIVE: The purpose of this study was to assess the management and outcomes of elderly patients treated for obstructed colon cancer. DESIGN: This was a multicenter, retrospective cohort study. SETTINGS: Between 2000 and 2015, 2325 patients managed for an obstructed colon cancer in member centers of the French National Surgical Association were identified. Data were collected by each center on a voluntary basis after institutional approval. Bowel obstruction was defined clinically and confirmed by imaging. PATIENTS: Three age groups were defined, including patients <75 years, 75 to 84 years, and ≥85 years. MAIN OUTCOME MEASURES: Postoperative and oncologic results in elderly patients with an obstructed colon cancer were measured. Relative survival was calculated as the ratio of the overall survival with the survival that would have been expected based on the corresponding general population. INTERVENTIONS: A total of 302 patients (13%) underwent colonic stent insertion, and 1992 (87%) underwent surgery as emergency procedure. RESULTS: A total of 2294 patients were analyzed (<75 y, n = 1200 (52%); 75–84 y, n = 650 (28%); and ≥85 y, n = 444 (20%)). Elderly patients were more likely to be women (p < 0.0001), to have proximal colon cancer (p < 0.0001), and to have a higher incidence of comorbidities (p < 0.0001). The use of colonic stent or the type of surgery was identical regardless of age. In patients with resected colon cancer, elderly patients had less stage IV disease (p < 0.0001). The absence of tumor resection (p < 0.0001) and definitive stoma rate increased with age (p < 0.0001). Postoperative mortality and morbidity were significantly higher in elderly patients (p < 0.0001), but surgical morbidity was similar across age groups (p = 0.60). Postoperative morbidity was correlated to the 6-month mortality rate in elderly (p < 0.0001). Overall and disease-free survivals were significantly lower in more elderly patients (p < 0.0001) but relative survival was not (p = 0.09). LIMITATIONS: It is quite difficult to know how to interpret these data as a whole, given the inherent bias in the study population, lack of ability to stratify by performance status, and long study period duration. CONCLUSIONS: Elderly patients have high morbidity with lower survival in the highest age ranges of elderly subgroups. These data should be considered when deciding on an operative approach. See Video Abstract at http://links.lww.com/DCR/A964.

Propensity Score Adjusted Comparison of Pelviperineal Morbidity With and Without Omentoplasty Following Abdominoperineal Resection for Primary Rectal Cancer BACKGROUND: Abdominoperineal resection is associated with a high incidence of perineal complications, and whether this is reduced by an omentoplasty is still unclear. OBJECTIVE: This study aimed to investigate the impact of omentoplasty on pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer. DESIGN: This was a retrospective comparative cohort study using propensity score analyses to reduce potential confounding. SETTING: The study was undertaken in 2 teaching hospitals and 1 university hospital. PATIENTS: Patients who underwent abdominoperineal resection for primary rectal cancer between 2000 and 2017 were included. MAIN OUTCOME MEASURES: The main end points were primary perineal wound healing at 30 days and overall and specific pelviperineal morbidity until the end of the study period. RESULTS: Among 254 included patients, 106 had an omentoplasty. The primary perineal wound healing rate at 30 days was similar for omentoplasty and no omentoplasty (65% vs 60%; p = 0.422), also after adjusting for potential confounding by propensity score analysis (OR, 0.89; 95% CI, 0.45–1.75). Being free from any pelviperineal complication at 6 months (75% vs 79%; p = 0.492), absence of any pelviperineal morbidity until 1 year (54% vs 49%; p = 0.484), and incidence of persistent perineal sinus (6% vs 10%; p = 0.256) were also similar in both groups. The unadjusted higher perineal hernia rate after omentoplasty (18% vs 7%; p = 0.011) did not remain statistically significant after regression analysis including the propensity score (OR, 1.34; 95% CI, 0.46–3.88). Complications related to the omentoplasty itself were observed in 8 patients, of whom 6 required reoperation. LIMITATIONS: This study was limited by the retrospective and nonrandomized design causing some heterogeneity between the 2 cohorts. CONCLUSION: In this multicenter study using propensity score analyses, the use of omentoplasty did not lower the incidence or the duration of pelviperineal morbidity in patients undergoing abdominoperineal resection for rectal cancer, and omentoplasty itself was associated with a risk of reoperation. See Video Abstract at http://links.lww.com/DCR/A918.

How Reliable Is CT Scan in Staging Right Colon Cancer? BACKGROUND: The observation of inferior oncologic outcomes after surgery for proximal colon cancers has led to the investigation of alternative treatment strategies, including surgical procedures and neoadjuvant systemic chemotherapy in selected patients. OBJECTIVE: The purpose of this study was to determine the accuracy of CT staging in proximal colon cancer in detecting unfavorable pathologic features that may aid in the selection of ideal candidates alternative treatment strategies, including extended lymph node dissection and/or neoadjuvant chemotherapy. DESIGN: This was a retrospective consecutive series. SETTINGS: Trained abdominal radiologists from 2 centers performed a blinded review of CT scans obtained to locally stage proximal colon cancer according to previously defined prognostic groups, including T1/2, T3/4, N+, and extramural venous invasion. CT findings were compared with histopathologic results as a reference standard. Unfavorable pathologic findings included pT3/4, pN+, or extramural venous invasion. PATIENTS: Consecutive patients undergoing right colectomy in 2 institutions between 2011 and 2016 were retrospectively reviewed from a prospectively collected database. MAIN OUTCOME MEASURES: T status, nodal status, and extramural venous invasion status comparing CT with final histologic findings were measured. RESULTS: Of 150 CT scans reviewed, CT failed to identify primary cancer in 18%. Overall accuracy of CT to identify unfavorable pathologic features was 63% with sensitivity, specificity, positive predictive value, and negative predictive value of 63% (95% CI, 54%–71%), 63% (95% CI, 46%–81%), 87% (95% CI, 80%–94%) and 30% (95% CI, 18%–41%). Only cT3/4 (55% vs 45%; p = 0.001) and cN+ (42% vs 58%; p = 0.02) were significantly associated with correct identification of unfavorable features at final pathology. CT scans overstaged and understaged cT in 23.7% and 48.3% and cN in 28.7% and 53.0% of cases. LIMITATIONS: The study was limited by its retrospective design, relatively small sample size, and heterogeneity of CT images performed in different institutions with variable equipment and technical details. CONCLUSIONS: Accuracy of CT scan for identification of pT3/4, pN+, or extramural venous invasion was insufficient to allow for proper identification of patients at high risk for local recurrence and/or in whom to consider alternative treatment strategies. Locoregional overstaging and understaging resulted in inappropriate treatment strategies in <48%. See Video Abstract at http://links.lww.com/DCR/A935.

Benign
 
Identification of Collagenolytic Bacteria in Human Samples Screening Methods and Clinical Implications for Resolving and Preventing Anastomotic Leaks and Wound Complications
Guyton, Kristina L.; Levine, Zoe C.; Lowry, Ann C.; More
Diseases of the Colon & Rectum. 62(8):972-979, August 2019.

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BACKGROUND:
Bacteria that produce collagen-digesting enzymes (collagenolytic bacteria) have been shown to play a critical and previously unappreciated role in anastomotic leak pathogenesis by breaking down host tissue extracellular matrix proteins. Detection of these bacteria is labor intensive, and no screening method currently exists.

OBJECTIVES:
We evaluated a rapid screening method developed to detect the presence of these collagenolytic bacteria in clinical samples, such as drain fluid, anastomotic tissue, or feces.

DESIGN:
We compared a new method of detecting collagenolytic bacterial species with a previously used technique using samples from a murine experimental model and then demonstrated the utility of this screening method in samples from patients with anastomotic complications.

SETTINGS:
All of the laboratory work and previous murine experiments were performed in Dr Alverdy's laboratory at the University of Chicago under institutional review board–approved protocols.

PATIENTS:
Samples from patients with challenging wound complications were provided by participating clinicians with verbal patient consent. Given the small number of patients, this was determined to be institutional review board exempt.

MAIN OUTCOME MEASURES:
Whether this analysis can influence patient management and outcomes will require additional study.

RESULTS:
This screening method detects numerous strains of bacteria with collagenolytic properties, including the collagenolytic species that have been implicated previously in anastomotic leak. Once collagenolytic strains are identified, they can be speciated and tested for antibiotic resistance using standard laboratory techniques.

LIMITATIONS:
This study is limited by the small number of patient samples tested.

CONCLUSIONS:
We demonstrated the potential applicability of this assay to evaluate rare and complex anastomotic complications that often require analysis beyond standard culture and sensitivity assays. Future applications of this method may allow the development of strategies to prevent anastomotic leak related to collagenolytic bacteria. See Video Abstract at http://links.lww.com/DCR/A962 .

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Anorectal
 
Drainage Seton Versus External Anal Sphincter–Sparing Seton After Rerouting of the Fistula Tract in the Treatment of Complex Anal Fistula A Randomized Controlled Trial
Omar, Waleed; Alqasaby, Abdallah; Abdelnaby, Mahmoud; More
Diseases of the Colon & Rectum. 62(8):980-987, August 2019.

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BACKGROUND:
Complex anal fistula is one of the challenging anorectal conditions. Several treatments have been proposed for complex anal fistula, yet none proved to be ideal.

OBJECTIVE:
This randomized trial aimed to assess the efficacy of external anal sphincter–sparing seton in comparison with the conventional drainage seton in the treatment of complex anal fistula.

DESIGN:
This was a prospective, randomized, single-blind controlled study.

SETTINGS:
The study was conducted at the Colorectal Surgery Unit of Mansoura University Hospitals.

PATIENTS:
Adult patients of both sexes with complex anal fistula were recruited and evaluated with MRI before surgery.

INTERVENTIONS:
Patients were randomly divided into 2 groups; group 1 was treated with conventional drainage seton and group 2 was treated with external anal sphincter–sparing seton using a rerouting technique.

MAIN OUTCOME MEASURES:
The duration of healing, incidence of recurrence or persistence, postoperative pain, and complications including fecal incontinence were measured.

RESULTS:
Sixty patients (56 men) with a mean age of 43 years were included. Mean operation time in group 1 was significantly shorter than group 2 (29.8 ± 4.3 vs 43.8 ± 4.5 min; p < 0.0001). The mean pain score at 24 hours in group 1 was 8.1 ± 1.6 versus 5.3 ± 1.3 in group 2 ( p < 0.0001). Five patients (17%) in group 1 experienced complications versus 2 (7%) in group 2. All of the patients in group 1 required a second-stage fistulotomy versus 2 patients (7%) in group 2 ( p < 0.0001). Time to complete healing in group 1 was significantly ( p < 0.0001) longer than group 2 (103 ± 47 vs 46 ± 18 d). Four patients (13%) in group 1 and 1 patient (3%) in group 2 experienced persistence or recurrence of anal fistula ( p = 0.35).

LIMITATIONS:
This was a single-center study with relatively small numbers in each group.

CONCLUSIONS:
Patients treated with external anal sphincter–sparing seton after rerouting of the fistula tract achieved quicker healing and less postoperative pain than those with conventional drainage seton. Postoperative complication and recurrence rates were comparable in both groups. See Video Abstract at http://links.lww.com/DCR/A963 .

TRIAL REGISTRATION:
clinicaltrials.gov identifier: NCT03636997 ( https://clinicaltrials.gov/ct2/show/NCT03636997 ).

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Short-term Outcomes of Transanal Hemorrhoidal Dearterialization With Mucopexy Versus Vessel-Sealing Device Hemorrhoidectomy for Grade III to IV Hemorrhoids A Prospective Randomized Multicenter Trial
Trenti, Loris; Biondo, Sebastiano; Kreisler Moreno, Esther; More
Diseases of the Colon & Rectum. 62(8):988-996, August 2019.

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BACKGROUND:
Transanal hemorrhoidal dearterialization with mucopexy and vessel-sealing device hemorrhoidectomy seem to reduce postoperative pain compared with classic excisional hemorrhoidectomy, but whether one of them is superior remains unclear.

OBJECTIVE:
We compared transanal hemorrhoidal dearterialization with mucopexy and vessel-sealing device hemorrhoidectomy.

DESIGN:
This was a multicenter, randomized controlled trial.

SETTING:
The study was conducted at 6 Spanish centers.

PATIENTS:
Patients aged ≥18 years with grade III to IV hemorrhoids were included.

INTERVENTIONS:
Patients were randomly assigned to transanal hemorrhoidal dearterialization with mucopexy (n = 39) or vessel-sealing device hemorrhoidectomy (n = 41).

MAIN OUTCOME MEASURES:
Primary outcome was the mean postoperative number of days in which patients needed nonsteroidal anti-inflammatory drugs. Secondary outcomes were postoperative pain, 30-day morbidity, patient satisfaction, Vaizey score, hemorrhoid symptoms score, return to work, and quality of life.

RESULTS:
More patients were still taking analgesia in the vessel-sealing device hemorrhoidectomy group during the second postoperative week compared with the transanal hemorrhoidal dearterialization with mucopexy group (87.8% vs 53.8%; p = 0.002). For the transanal hemorrhoidal dearterialization with mucopexy group, analgesia consumption continued until day 10.1 (mean; SD = 7.22 d), whereas in the vessel-sealing device hemorrhoidectomy group it continued until day 15.2 (mean; SD = 8.70 d; p = 0.006). The mean daily average pain was similar during the first ( p = 0.900) and second postoperative weeks ( p = 0.265). Mean operative time was higher for the transanal hemorrhoidal dearterialization with mucopexy group versus the vessel-sealing device hemorrhoidectomy group (45 min; range, 40–60 vs 20 min; range, 15–41 min; p < 0.001). Postoperative complications rate, use of laxatives, patient satisfaction, Vaizey score, hemorrhoids symptoms score, return to work, and quality of life at 1 month after surgery were similar between groups.

LIMITATIONS:
The main limitation of this study was that the 2 groups did not contain equal numbers of grade III and IV hemorrhoids.

CONCLUSIONS:
Transanal hemorrhoidal dearterialization with mucopexy is associated with a shorter need for postoperative analgesia compared with vessel-sealing device hemorrhoidectomy. See Video Abstract at http://links.lww.com/DCR/A915 .

TRIAL REGISTRATION:
clinicaltrials.gov identifier: NCT02654249.

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Socioeconomic
 
Does Coffee Intake Reduce Postoperative Ileus After Laparoscopic Elective Colorectal Surgery? A Prospective, Randomized Controlled Study The Coffee Study
Hasler-Gehrer, Simone; Linecker, Michael; Keerl, Andreas; More
Diseases of the Colon & Rectum. 62(8):997-1004, August 2019.

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BACKGROUND:
Postoperative ileus after colorectal surgery is a frequent problem that significantly prolongs hospital stay and increases perioperative costs.

OBJECTIVE:
The aim was to evaluate the effect of standardized coffee intake on postoperative bowel movement after elective laparoscopic colorectal resection.

DESIGN:
This is a prospective randomized controlled trial that was conducted between September 2014 and December 2016.

SETTINGS:
This study was performed in a public cantonal hospital in Switzerland with accreditation for colon and rectum cancer surgery.

PATIENTS:
Patients who underwent elective colorectal surgery were included.

INTERVENTIONS:
Patients were randomly assigned either to the intervention group receiving coffee or the control group receiving tea. A total of 150 mL of the respective beverage was drunk 3 times per day every postoperative day until discharge.

MAIN OUTCOME MEASURES:
The primary end point was time to first bowel movement. Secondary end points included the use of laxative, insertion of a nasogastric tube, length of hospital stay, and postoperative complications.

RESULTS:
A total of 115 patients were randomly assigned: 56 were allocated to the coffee group and 59 to the tea group. After coffee intake, the first bowel movement occurred after a median of 65.2 hours versus 74.1 hours in the control group (intention-to-treat analysis; p = 0.008). The HR for earlier first bowel movement after coffee intake was 1.67 ( p = 0.009). In the per-protocol analysis, hospital stay was shorter in the coffee group (6 d in the coffee group vs 7 d in the tea group; p = 0.043).

LIMITATIONS:
The rate of protocol violation, mostly coffee consumption in the tea arm, was relatively high, even if patients were clearly instructed not to consume coffee if they were in the tea arm.

CONCLUSIONS:
Coffee intake after elective laparoscopic colorectal resection leads to faster recovery of bowel function. Therefore, coffee intake represents a simple and effective strategy to prevent postoperative ileus. See Video Abstract at http://links.lww.com/DCR/A955 .

TRIAL REGISTRATION:
clinicaltrials.gov identifier: NCT02469441.

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Antibiotics Versus No Antibiotics for Acute Uncomplicated Diverticulitis A Systematic Review and Meta-analysis
Desai, Madhav; Fathallah, Jihan; Nutalapati, Venkat; Saligram, Shreyas Less
Diseases of the Colon & Rectum. 62(8):1005-1012, August 2019.

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BACKGROUND:
Antibiotics are routinely used for diverticulitis irrespective of severity. Current practice guidelines favor against the use of antibiotics for acute uncomplicated diverticulitis.

OBJECTIVE:
We performed a systematic review and meta-analysis to examine the role of antibiotic use in an episode of uncomplicated diverticulitis.

DATA SOURCES:
PubMed/Medline, Embase, Scopus, and Cochrane were used.

STUDY SELECTION:
Eligible studies included those with patients with uncomplicated diverticulitis receiving any antibiotics compared with patients not receiving any antibiotics (or observed alone).

MAIN OUTCOME MEASURES:
Pooled odds rate of total complications, treatment failure, recurrent diverticulitis, readmission rate, sigmoid resection, mortality rate, and length of stay were measured.

RESULTS:
Of 1050 citations reviewed, 7 studies were eligible for the analysis. There were total of 2241 patients: 895 received antibiotics (mean age = 59.1 y; 38% men) and 1346 did not receive antibiotics (mean age = 59.4 y; 37% men). Antibiotics were later added in 2.7% patients who initially were observed off antibiotics. Length of hospital stay was not significantly different among either group (no antibiotics = 3.1 d vs antibiotics = 4.5 d; p = 0.20). Pooled rate of recurrent diverticulitis was not significantly different among both groups (pooled OR = 1.27 (95%, CI 0.90–1.79); p = 0.18). Rate of total complications (pooled OR = 1.99 (95% CI, 0.66–6.01); p = 0.22), treatment failure (pooled OR = 0.68 (95% CI, 0.42–1.09); p = 0.11), readmissions (pooled OR = 0.75 (95% CI, 0.44–1.30); p = 0.31). and patients who required sigmoid resection (pooled OR = 3.37 (95% CI, 0.65–17.34); p = 0.15) were not significantly different among patients who received antibiotics and those who did not. Mortality rates were 4 of 1310 (no-antibiotic group) versus 4 of 863 (antibiotic group).

LIMITATIONS:
Only 2 randomized controlled studies were available and there was high heterogeneity in existing data.

CONCLUSIONS:
This meta-analysis of current literature shows that patients with uncomplicated diverticulitis can be monitored off antibiotics.

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Perineal Hernia Repair With Mesh After Robotic Abdominoperineal Resection
Sapci, Ipek; Tiernan, Jim P.; Gorgun, Emre
Diseases of the Colon & Rectum. 62(8):1013, August 2019.

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Surgical Management of an Ileal J-Pouch-Anal Anastomosis Volvulus
Geers, Joachim; Bislenghi, Gabriele; D'Hoore, André; More
Diseases of the Colon & Rectum. 62(8):1014-1019, August 2019.

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BACKGROUND:
A restorative proctocolectomy with an IPAA is the surgical treatment of choice for medically refractory ulcerative colitis. Until now, a pouch volvulus has been considered a rare complication, only described in case reports and small case series. The aim of this technical note was to develop a standardized approach to allow a minimally invasive treatment.

TECHNIQUE:
First, an endoscopic decompression of the pouch is attempted. Subsequently, an exploratory laparoscopy is performed. If the endoscopic decompression was successful, a complete laparoscopic reduction is feasible. Once the integrity of the pouch is confirmed, a bilateral pouchopexy is performed, using multifilament interrupted sutures. Finally, the pouch patency is tested by pouchoscopy.

RESULTS:
Between December 2010 and December 2018, 151 minimally invasive restorative proctocolectomies with an IPAA were performed. Eighty-nine IPAAs were constructed with the mesentery positioned anteriorly, 35 posteriorly, and 27 on the right side. Three patients were diagnosed with an IPAA volvulus. All 3 of the patients were in the anterior group (3.4%) compared with 0 patients in the nonanterior group. One patient (33%) was treated laparoscopically, after a successful endoscopic reduction. In the other 2 cases, conversion to a laparotomy was needed because an endoscopic decompression could not be achieved.

CONCLUSION:
An endoscopic decompression was required to allow a laparoscopic treatment, and a bilateral pouchopexy was needed to avoid recurrence. This standardized approach might be a good treatment option, and we are awaiting additional follow-up to determine its long-term durability. In addition to the already described risk factors (minimally invasive technique, female sex, and low BMI), an anterior positioning of the pouch mesentery might be a potential risk factor as well for pouch volvulus. However, these observations should be carefully interpreted, considering the small number of cases.

 Selected Abstracts

Abridged Abstracts From the Medical Literature

Lee, Lawrence; Raman, Shankar; Keller, Deborah S.; More

Diseases of the Colon & Rectum. 62(8):1020-1023, August 2019.

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Diseases of the Colon & Rectum. 62(8):e410, August 2019.

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Alexandros Sfakianakis
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