Does Surgical Removal of the Thymus Have Deleterious Consequences?

The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the development of autoimmune diseases and cancer. Recently, a concern has been raised about deleterious consequences of the surgical removal of thymic tissue, including for patients who undergo thymectomy for myasthenia gravis (MG) or resection of a thymoma. This review adopts a multidisciplinary approach to scrutinize the evidence concerning the long-term risks of cancer and autoimmunity postthymectomy. We conclude that for patients with acetylcholine receptor antibody-positive MG and those diagnosed with thymoma, the removal of the thymus offers prominent benefits that well outweigh the potential risks. However, incidental removal of thymic tissue during other thoracic surgeries should be minimized whenever feasible.

Clinicopathological study of surgically treated non-neoplastic diseases of the pancreas with special reference to autoimmune pancreatitis.

PURPOSE: After the popularization of serum immunoglobulin G4 (IgG4) measurement and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in our institute, surgical resection for non-neoplastic diseases of the pancreas became less common. Although the incidence of such false-positive cases was clarified in the 10-year period after the introduction of these measures (2009-2018), these data were not compared with the 30 years before 2009 (1979-2008). This study was performed to determine the percentage of autoimmune pancreatitis (AIP) that was included during the latter period and how the numbers of false-positive cases differed between the two periods. METHODS: From 1979 to 2008, 51 patients had clinical suspicion of pancreatic carcinoma (false-positive disease). Among these 51 patients, 32 non-alcoholic patients who had tumor-forming chronic pancreatitis (TFCP) were clinically, histologically, and immunohistochemically compared with 11 patients who had TFCP during the latter 10-year period. RESULTS: Retrospective IgG4 immunostaining of false-positive TFCP revealed 14 (35.0%) cases of AIP in the former 30 years versus 5 (45.5%) in the latter 10 years. There were 40 (5.9%) cases of TFCP among 675 patients in the former 30 years and 11 (0.9%) among 1289 patients in the latter 10 years. CONCLUSIONS: When the TFCP ratio of pancreatic resections and the AIP ratio of false-positive TFCPs were compared between the two periods, the TFCP ratio was 5.9% versus 0.9% and the AIP ratio was 35.0% versus 45.5%, respectively. It can thus be speculated that IgG4 measurement and EUS-FNA are absolutely imperative for the diagnosis of TFCP.

Surgery in Autoimmune Pancreatitis.

INTRODUCTION: Autoimmune pancreatitis (AIP) is a disease that may mimic malignant pancreatic lesions both in terms of symptomatology and imaging appearance. The aim of the present study is to analyze experiences of surgery in patients with AIP in one of the largest European cohorts. PATIENTS AND METHODS: We performed a single-center retrospective study of patients diagnosed with AIP at the Department of Abdominal Diseases at Karolinska University Hospital in Stockholm, Sweden, between January 2001 and October 2020. RESULTS: There were 159 patients diagnosed with AIP, and among them, 35 (22.0%) patients had surgery: 20 (57.1%) males and 15 (42.9%) females; median age at surgery was 59 years (range 37-81). Median follow-up period after surgery was 50 months (range 1-235). AIP type 1 was diagnosed in 28 (80%) patients and AIP type 2 in 7 (20%) patients. Malignant and premalignant lesions were diagnosed in 8 (22.9%) patients for whom AIP was not the primary differential diagnosis, but in all cases, it was described as a simultaneous finding and recorded in retrospective analysis in histological reports of surgical specimens. CONCLUSIONS: Diagnosis of AIP is not always straightforward, and in some cases, it is not easy to differentiate it from the malignancy. Surgery is generally not indicated for AIP but might be considered in patients when suspicion of malignant/premalignant lesions cannot be excluded after complete diagnostic workup.

Role of tonsillectomy and adenoidectomy in parental satisfaction of treatments for PANDAS.

OBJECTIVE: To examine caregiver satisfaction with treatments for pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS) and how symptom frequency changes over time. METHODS: A list was created for PANDAS subjects seen at the Georgetown Pediatric Otolaryngology clinic from 2015 to 2018. Questionnaires were distributed to caregivers able to be contacted; 62% responded (n = 60). Subjects were placed in groups based on treatments reported: tonsillectomy and adenoidectomy (T&A, n = 28), T&A and intravenous immunoglobulin (IVIG, n = 22), or nonsurgical treatment(s) (n = 10). Caregivers reported frequencies for each of 10 associated symptoms from time of treatment to 12 months and also expressed their satisfaction with treatment. RESULTS: Patients were treated with antibiotics (n = 60, 100%), T&A (83.3%), IVIG (40%), Rituximab (15%), steroids (20%), and/or plasma exchange (10%). Caregivers for 66% (n = 33) of surgical patients identified T&A as the most effective treatment, and 80% would choose the operation again. No difference in median caregiver satisfaction level was found among the groups (n = 0.196). There was no significant difference in frequency for any of the symptoms (all p > 0.05) except choreiform movement (p = 0.0296). CONCLUSION: Caregivers reported a decreasing frequency of symptoms over time regardless of treatment and had no difference in satisfaction. T&A was the most preferred treatment and the most impactful on symptoms for surgical patients. Given the challenges of immunologic therapies, T&A in combination with antibiotics should be considered as an early intervention for PANDAS.

The mechanisms of cellular crosstalk between mesenchymal stem cells and natural killer cells: Therapeutic implications.

Mesenchymal stem cells (MSCs) are mesenchymal precursors of various origins, with well-known immunomodulatory effects. Natural killer (NK) cells, the major cells of the innate immune system, are critical for the antitumor and antiviral defenses; however, in certain cases, they may be the main culprits in the pathogenesis of some NK-related conditions such as autoimmunities and hematological malignancies. On the other hand, these cells seem to be the major responders in beneficial phenomena like graft versus leukemia. Substantial data suggest that MSCs can variably affect NK cells and can be affected by these cells. Accordingly, acquiring a profound understanding of the crosstalk between MSCs and NK cells and the involved mechanisms seems to be a necessity to develop therapeutic approaches based on such interactions. Therefore, in this study, we made a thorough review of the existing literature on the interactions between MSCs and NK cells with a focus on the underlying mechanisms. The current knowledge herein suggests that MSCs possess a great potential to be used as tools for therapeutic targeting of NK cells in disease context and that preconditioning of MSCs, as well as their genetic manipulation before administration, may provide a wider variety of options in terms of eliciting more specific and desirable therapeutic outcomes. Nevertheless, our knowledge regarding the effects of MSCs on NK cells is still in its infancy, and further studies with well-defined conditions are warranted herein.

Non-Myasthenia Gravis Immune Syndromes and the Thymus: Is There a Role for Thymectomy?

Thymectomy has long been considered, performed, and discussed for many different nonmyasthenic immune syndromes. Thymectomy is now an established treatment for MG, and has been performed for other immune syndromes with varying degrees of improvement. Although numerous reports document immune syndromes' association with thymoma, few address the role of thymectomy in symptom resolution. This review assesses thymectomy in the various nonmyasthenic immune syndromes for which it has been tried. Based on this review, it seems appropriate to revisit a more active role for thymectomy in pure red cell aplasia, pemphigus, rheumatoid arthritis, autoimmune hemolytic anemia, and ulcerative colitis.

Safety analysis in patients with autoimmune disease receiving allogeneic mesenchymal stem cells infusion: a long-term retrospective study.

OBJECTIVE: The aim of this study was to evaluate the safety of mesenchymal stem cell infusion in patients with autoimmune diseases. METHODS: A total of 404 patients with autoimmune diseases who received mesenchymal stem cell infusion between 2007 and 2016 were included in this study. Adverse events in these patients were collected, mainly including infections and malignancies. Sources of information included hospitalization records and data from outpatient visits and each follow-up. RESULTS: The mean follow-up period of all patients was 43.4 ± 25.9 months (range 1-109). Majority of stem cells were from the umbilical cord. The most common indications for mesenchymal stem cell infusion were systemic lupus erythematosus, Sjögren's syndrome, and systemic sclerosis. The median age at infusion was 38.7 ± 15.7 years. The 5-year and 8-year survival rates were 90.4% and 88.9%, respectively. Median follow-up of survivors was 45.1 ± 25.7 months. The incidence rate of infections was 29.5% (119/404), and that of serious infections was 12.9% (52/404). Five patients (1.2%) experienced malignancies. Deaths occurred in 45 patients, and transplantation-related mortality was 0.2%. The most common causes of deaths in our study were disease relapse and complications associated with the underlying disease. CONCLUSION: Autoimmune disease is an emerging indication for mesenchymal stem cell infusion. Our data shows that mesenchymal stem cell infusion is a safe therapy for patients with autoimmune diseases. The incidences of adverse events, whether infections or malignancies, are acceptable in these patients. TRIAL REGISTRATION: ClinaicalTrials.gov, NCT00698191 . Registered 17 June 2008-Retrospectively registered.

Progressive Encephalomyelitis with Rigidity and Myoclonus Resolving after Thymectomy with Subsequent Anasarca: An Autopsy Case.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is an autoimmune disorder involving the brainstem and spinal cord and is sometimes associated with thymoma. We encountered a 75-year-old woman with typical PERM features, glycine receptor antibody, and thymoma. Her neurologic symptoms improved after thymectomy, but she unexpectedly developed anasarca with massive pleural effusions and hypoalbuminemia and finally succumbed to death. The autopsy showed edema and mononuclear infiltration in the pleura but no neuropathological findings typical of PERM. Effective treatment of PERM can reverse the neuropathological signs of encephalomyelitis. The autoimmune nature of anasarca is possible but not proven.

Immunoglobulin G Subclass 4-Related Lymphoplasmacytic Thoracic Aortitis in a Patient with Acute Type A Aortic Dissection.

Immunoglobulin G subclass 4-related disease (IgG4-RD) is a recently recognized systemic inflammatory disease characterized by an elevated serum IgG4 level and an IgG4-positive lymphocyte infiltrate mainly in exocrine tissues. Previous reports documented IgG4-RD in several cardiovascular disorders. We present a case of type A aortic dissection associated with IgG4-RD. A 52-year-old man diagnosed with a type A aortic dissection was referred for surgical treatment. He underwent emergency hemiarch reconstruction with a prosthetic graft. His postoperative recovery was uncomplicated. Histopathologic examination of his aortic tissue showed marked adventitial thickening with fibrosis and an IgG4-positive plasma cell infiltrate. He was diagnosed with type A aortic dissection incidentally complicated by IgG4-RD. The relationship between IgG4-RD and the pathogenesis of aortic dissection remains unknown and requires further investigation.

Autoimmune Progesterone Dermatitis Presenting as Stevens-Johnson Syndrome.

BACKGROUND: Autoimmune progesterone dermatitis is an uncommon disease presenting with cyclical skin eruptions corresponding with the menstrual cycle luteal phase. Because symptoms are precipitated by rising progesterone levels, treatment relies on hormone suppression. CASE: A 22-year-old nulligravid woman presented with symptoms mistaken for Stevens-Johnson syndrome. A cyclic recurrence of her symptoms was noted, and the diagnosis of autoimmune progesterone dermatitis was made by an intradermal progesterone challenge. After 48 months, she remained refractory to medical management and definitive surgical treatment with bilateral oophorectomy was performed. CONCLUSION: Autoimmune progesterone dermatitis is a challenging diagnosis owing to its rarity and variety of clinical presentations. Treatment centers on suppression of endogenous progesterone and avoidance of exogenous triggers. When these modalities fail, surgical management must be undertaken.

Long-Standing Isolated Autoimmune Hypothalamitis Diagnosed with Endoscopic Transventricular Biopsy.

BACKGROUND: Autoimmune hypothalamitis, which is among the causes of acquired central diabetes insipidus, has seldom been described in the literature. This condition is probably provoked by the production of anti-vasopressin-secreting cell antibodies and antihypothalamus antibodies and is often associated with pituitary or polyendocrine autoimmunity. Correct diagnosis and immediate treatment are essential to avoid the progression of the pathologic process. CASE DESCRIPTION: A woman diagnosed with central diabetes insipidus 12 years ago, who had panhypopituitarism and mild memory deficit, came to our attention. She refused radiologic studies. Magnetic resonance imaging performed in our unit showed a contrast-enhancing hypothalamic lesion. Lumbar puncture was negative for neoplastic markers. We decided to perform a biopsy of the lesion to obtain a histopathologic examination of the tissue and chose an endoscopic transventricular approach to reach the floor of the third ventricle. Autoimmune hypothalamitis was diagnosed and treatment with steroids and azathioprine was started. The lesion size decreased and was stable after 17 months of follow-up. CONCLUSIONS: The endoscopic transventricular approach has proved to be an effective and safe way to obtain tissue samples for histopathologic examination from a region that is usually difficult to reach; it also gives direct visualization of the lesion, which makes sampling easier. The lesion size decreased after treatment but no clinical improvement was detected, either on the cognitive or on the endocrinologic side.

Sialendoscopic management of autoimmune sialadenitis: a review of literature.

Autoimmune diseases of major salivary glands include Sjögren's syndrome and a complex of disorders classified as immunoglobulin G4-related diseases. These pathologies are characterised by an autoimmune reaction mediated by T-helper lymphocytes that targets the ducts of exocrine glands in Sjögren's syndrome and glandular parenchyma in immunoglobulin G4-related diseases. Immunoglobulin G4-related diseases represent recently introduced multi-organ diseases that also involve the salivary glands. However, the morbid conditions once known as Mikulicz's disease and Kuttner's tumour were recently considered as two variants of immunoglobulin G4-related diseases affecting the major salivary glands ( immunoglobulin G4-related sialadenitis). This review briefly summarises the pathogenesis and clinical features of autoimmune diseases of the major salivary glands, focusing on the diagnostic and therapeutic role of sialendoscopy.

Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia.

Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcγR expression were measured by flow cytometry on splenic macrophages. The major FcγR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcγR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2 weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcγRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcγR expression on splenic macrophages but decreases their phagocytic capabilities.

[A Case of an IgG4-Related Inflammatory Pseudotumor of the Liver Showing Enlargement That Was Difficult to Differentiate from Hepatic Cancer].

A 60-year-old man was admitted for a liver mass(S3), which rapidly increased in size during intraductal papillary mucinous neoplasm(IPMN)follow-up. Although EOB-MRIwas performed, the mass could not be accurately diagnosed as hepatic cancer. Thus, we performed a lateral segmentectomy. In the resected specimen, a solid tumor mass was clearly bound in segment 3 of the liver. Since histopathology revealed no malignant cells and many IgG4-positive cells, we confirmed the diagnosis as IgG4-related inflammatory pseudotumor of the liver. IgG4-related diseases occur in various organs in the body, and they are known to associate with autoimmune pancreatitis and sclerosing cholangitis, but an IgG4-related inflammatory pseudotumor of the liver is a rare disease. It is often difficult to distinguish from hepatic cancer and surgical resection is performed.

Laryngotracheal stenosis of autoimmune aetiology. / Estenosis laringotraqueales de etiología autoinmune.

Autoimmune origin ranks fifth in the etiologic classification of laryngotracheal stenosis. Wegener's disease is the autoimmune illness most associated with stenosis; however, there are other autoimmune diseases that may also be associated with it. A descriptive, retrospective study of 9 cases of laryngotracheal stenosis associated with autoimmune disease was carried out. There were 9 patients (8 females and 1 male) with an average age of 27.9 years. Four of the patients suffered from Wegener's disease, 1 from ulcerative colitis and 1 from purple vasculitis. The other 3 patients only had positive c-ANA. Endoscopic treatment was performed in 3 cases. The other 6 patients required open surgery. Respiratory results were acceptable. Based on our study, we feel that the immunological profiles should be studied in all patients with stenosis, given that not only Wegener's disease is linked to stenosis.