Jens C. Rückert

Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum / necrophorum

Background Acute appendicitis is a local intestinal inflammation with unclear origin. The aim was to test whether bacteria in appendicitis differ in composition to bacteria found in caecal biopsies from healthy and disease controls. Methods and patients We investigated sections of 70 appendices using rRNA-based fluorescence in situ hybridisation. Four hundred caecal biopsies and 400 faecal samples from patients with inflammatory bowel disease and other conditions were used as controls. A set of 73 group-specific bacterial probes was applied for the study. Results The mucosal surface in catarrhal appendicitis showed characteristic lesions of single epithelial cells filled with a mixed bacterial population (‘pinned cells’) without ulceration of the surroundings. Bacteria deeply infiltrated the tissue in suppurative appendicitis. Fusobacteria (mainly Fusobacterium nucleatum and necrophorum) were a specific component of these epithelial and submucosal infiltrates in 62% of patients with proven appendicitis. The presence of Fusobacteria in mucosal lesions correlated positively with the severity of the appendicitis and was completely absent in caecal biopsies from healthy and disease controls. Main faecal microbiota represented by Bacteroides, Eubacterium rectale (Clostridium group XIVa), Faecalibacterium prausnitzii groups and Akkermansia muciniphila were inversely related to the severity of the disease. The occurrence of other bacterial groups within mucosal lesions of acute appendicitis was not related to the severity of the appendicitis. No Fusobacteria were found in rectal swabs of patients with acute appendicitis. Conclusions Local infection with Fusobacterium nucleatum/necrophorum is responsible for the majority of cases of acute appendicitis.

Thoracic Epidural Anesthesia Combined with General Anesthesia: The Preferred Anesthetic Technique for Thoracic Surgery

Thoracic epidural anesthesia (TEA) combined with general anesthesia (GA) as well as total-IV anesthesia (TIVA) are both established anesthetic managements for thoracic surgery. We compared them with respect to hypoxic pulmonary vasoconstriction, shunt fraction and oxygenation during one-lung ventilation. Fifty patients, ASA physical status II-III undergoing pulmonary resection were randomly allocated to two groups. In the TIVA group, anesthesia was maintained with propofol and fentanyl. In the TEA group, anesthesia was maintained with TEA (bupivacaine 0.5%) combined with low-dose concentration 0.3–0.5 vol% of isoflurane (end-tidal). Changing from two-lung ventilation to one-lung ventilation caused a significant increase in cardiac output (CO) in the TIVA group, whereas no change was observed in the TEA group. One-lung ventilation caused significant increases in shunt fraction in both groups which was associated per definition with a significant decrease in Pao2 in both groups but Pao2 remained significantly increased in the TEA group (P < 0.05). We conclude that both anesthetic regimens are safe intraoperatively. However, TEA in combination with GA did not impair arterial oxygenation to the same extent as TIVA, which might be a result of the changes in CO. Therefore, patients with preexisting cardiopulmonary disease and impaired oxygenation before one-lung ventilation might benefit from TEA combined with GA.

Thoracoscopic Thymectomy with the da Vinci Robotic System for Myasthenia Gravis

Complete thymectomy (Thx) is a crucial part of treatment for myasthenia gravis (MG) and thymoma. The discussion about the necessity of radical, complete Thx and reduced invasiveness has led to no less than 14 different surgical approaches for Thx. The latest development is robotic‐assisted surgery. Though its impact on minimally invasive surgery is not yet clear, it seems to be most promising for surgery in remote, narrow anatomical regions like the mediastinum. One hundred six consecutive robotic‐assisted thymectomies (rThx) with the da Vinci robotic surgical system were performed between January 2003 and April 2007 in a prospective single‐center study. Postoperative morbidity was recorded according to the Myasthenia Gravis Foundation of America (MGFA) classification. With zero mortality, the overall postoperative morbidity rate was 2%. The cumulative complete stable remission rate of MG was > 40% for all patients, and there was no statistical difference as compared to non‐thymomatous MG patients. The cumulative rate of minimal manifestations (MM0–MM3) according to the MGFA classification showed a postoperative improvement in quality of life for most of the patients. The da Vinci robotic system allowed for technical refinements of the well‐defined operation technique of thoracoscopic Thx (tThx). From the technical point of view, rThx has advantages for mediastinal dissection. rThx had a shorter learning curve. There might be better outcome results for rThx in MG patients, as compared with nonrobotic tThx. Therefore, rThx is a promising technique for minimally invasive Thx.

Influenza A Viruses Target Type II Pneumocytes in the Human Lung

Abstract Background. Highly pathogenic avian H5N1 influenza viruses preferentially infect alveolar type II pneumocytes in human lung. However, it is unknown whether this cellular tropism contributes to high viral virulence because the primary target cells of other influenza viruses have not been systematically studied. Methods. We provide the first comparison of the replication, tropism, and cytokine induction of human, highly pathogenic avian influenza A virus subtype H5N1 and other animal influenza A viruses in primary human lung organ cultures. Results. Subytpe H5N1 and human-adapted subtype H1N1 and H3N2 viruses replicated efficiently in the lung tissue, whereas classic swine and low-pathogenicity avian viruses propagated only poorly. Nevertheless, all viruses examined were detected almost exclusively in type II pneumocytes, with a minor involvement of alveolar macrophages. Infection with avian viruses that have a low and high pathogenicity provoked a pronounced induction of cytokines and chemokines, while human and pandemic H1N1-2009 viruses triggered only weak responses. Conclusions. These findings show that differences in the pathogenic potential of influenza A viruses in the human lung cannot be attributed to a distinct cellular tropism. Rather, high or low viral pathogenicity is associated with a strain-specific capacity to productively replicate in type II pneumocytes and to cope with the induced cytokine response.

Comparison of robotic and nonrobotic thoracoscopic thymectomy: A cohort study

OBJECTIVE Radical thymectomy has become more popular in the comprehensive treatment of myasthenia gravis. Minimally invasive techniques are increasingly used for thymectomy. The most recent development in robotic thoracoscopic surgery has been successfully applied for mediastinal pathologies. To establish robotic technique as a standard, the results of high-volume centers and comparison with traditional surgery are mandatory. METHODS In a retrospective cohort study, the results of 79 thoracoscopic thymectomies (October 1994 to December 2002) were compared with the results of 74 robotic thoracoscopic thymectomies (January 2003 to August 2006). Data from both series were collected prospectively. In both groups, all patients had myasthenia gravis. Both cohorts were compared with respect to severity of disease, gender, age, histology, and postoperative morbidity. All patients were analyzed for quantification of improvement of disease according to the Myasthenia Gravis Foundation of America. RESULTS There were no differences in age distribution and severity of myasthenia gravis. The dominant histologic finding was follicular hyperplasia of the thymus in both groups with a significantly higher percentage in the thoracoscopic thymectomy series (68% vs 45%, P < .001). After a follow-up of 42 months, the cumulative complete remission rate of myasthenia gravis for robotic and nonrobotic thymectomy was 39.25% and 20.3% (P = .01), respectively. CONCLUSIONS There is an improved outcome for myasthenia gravis after robotic thoracoscopic thymectomy compared with thoracoscopic thymectomy.

Emerging Human Middle East Respiratory Syndrome Coronavirus Causes Widespread Infection and Alveolar Damage in Human Lungs

Acknowledgment: The authors are grateful to Rosalind Simmonds, the staff within the Nuclear Medicine and Histopathology Department at Addenbrooke’s Hospital, and the Wellcome Trust Clinical Research Facility, Cambridge. They acknowledge the help of the Histopathology Departments at the Royal Brompton and Princess Alexandra Hospitals. They also thank the Cambridge Biomedical Research Centre and BRC Core Biochemistry Assay Laboratory and acknowledge the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. The study was approved by Cambridgeshire Research Ethics Committee (09/H0308/ 119) and the Administration of Radioactive Substances Advisory Committee of the UK (83/3130/25000).

Resection of ectopic mediastinal parathyroid glands with the da Vinci® robotic system

Mediastinal ectopic parathyroid adenoma is a frequent cause of persistent or recurrent hyperparathyroidism, traditionally treated by open surgery. Thoracoscopic access is associated with reduced morbidity in mediastinal surgery. The aim of this study was to evaluate the feasibility and effectiveness of robot‐assisted dissection for mediastinal ectopic parathyroid glands.

The Novel Human Influenza A(H7N9) Virus Is Naturally Adapted to Efficient Growth in Human Lung Tissue

ABSTRACT A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients. IMPORTANCE Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to propagate. Robust replication of the H7N9 strain correlated with a low induction of antiviral beta interferon (IFN-β), and cell-based studies indicated that this is due to efficient suppression of the IFN response by the viral NS1 protein. Thus, explanted human lung tissue appears to be a useful experimental model to explore the determinants facilitating cross-species transmission of the H7N9 virus to humans. Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to propagate. Robust replication of the H7N9 strain correlated with a low induction of antiviral beta interferon (IFN-β), and cell-based studies indicated that this is due to efficient suppression of the IFN response by the viral NS1 protein. Thus, explanted human lung tissue appears to be a useful experimental model to explore the determinants facilitating cross-species transmission of the H7N9 virus to humans.

Primary Hepatic Neuroendocrine Tumor: Successful Hepatectomy in Two Cases and Review of the Literature

Background/Aims: Primary hepatic neuroendocrine tumor represents an extremely rare clinical entity with only very few cases having been reported to date. Methods: The case histories of 2 patients with presumably primary hepatic neuroendocrine tumor were analyzed and a complete follow-up obtained. The literature was reviewed to provide comprehensive data collection. Results: Both patients underwent partial hepatic resection. Histomorphologic diagnosis revealed a neuroendocrine tumor in both cases. Extensive preoperative as well as intra- and postoperative search for the primary tumor did not identify another site of neuroendocrine tumor tissue. Six and ten years after hepatic segmentectomy, the 2 patients are alive and show no clinical signs of malignancy. Their most recent thorough follow-up included computed tomography and somatostatin receptor scintigraphy. Neither a nonhepatic primary neuroendocrine tumor site nor recurrent disease was found in the 2 patients. The literature review resulted in a complete survey of all previously reported cases of primary hepatic neuroendocrine tumors. Conclusion: We conclude that the liver was the primary site of the neuroendocrine tumor in both patients. Radical surgery was successfully performed as the only treatment option with curative intention.

State of the Art of Robotic Thymectomy

BackgroundThymectomy is a widely accepted treatment for most cases of myasthenia gravis and essential for the treatment of thymoma. The development of a minimally invasive procedure for thymectomy resulted in a variety of approaches for surgery on the thymic gland. The use of thoracoscopy-based techniques has continued to increase, including the latest advance in this field, robotic thymectomy.MethodsWe review the rapid development and actual use of this approach by examining published reports, worldwide registries, and personal communications and by analyzing our database, which is the largest single-center experience and contains 317 thymectomies until 12/2012. The technical modifications of robotic thymectomy are also described.ResultsSince 2001, approximately 3,500 robotic thymectomies have been registered worldwide. Meanwhile, the results of approximately 500 thymectomy cases have been published. Robotic thymectomy is performed most frequently through a standardized unilateral three-trocar approach. All reports describe promising and satisfactory results for myasthenia gravis. For early-stage thymoma, robotic thymectomy is a technically sound and safe procedure with a very low complication rate and short hospital stay. Oncological outcome without recurrences is promising, but a longer follow-up is needed.ConclusionThe unilateral robotic technique can be considered an adequate approach for thymectomy, even with demanding anatomical configurations. Robotic thymectomy has spread worldwide over the last decade because of the promising results in myasthenia gravis and thymoma patients.