Clinical Characteristics of Retroperitoneal Fibrosis Patients at a Tertiary Hospital in Japan.

Retroperitoneal fibrosis (RPF) is a rare cause of hydronephrosis and progressive renal dysfunction with unidentified origin. RPF is categorized into idiopathic RPF with/without immunoglobulin G4 (IgG4)-related disease (IgG4-RD), and secondary RPF. Identifying the underlying cause is challenging and often associated with delayed diagnosis or therapeutic interventions. We investigated RPF's clinical characteristics based on different etiologies and factors that may help distinguish the underlying causes. We analyzed the cases of 49 patients with RPF that was radiographically diagnosed at our institution (2008-2022). The cohort was 77.6% males; 75.5% had idiopathic RPF and 24.5% had secondary RPF. Among the idiopathic patients, 54.1% had IgG4-RD. The patients were likely to have abdominal pain, lower back pain/lumbago, and constitutional symptoms including generalized fatigue and fever. The idiopathic patients were likely to have higher serum IgG4 and IgG levels and lower serum C3 levels compared to secondary RPF. The IgG4-RPF patients were likely to have higher serum IgG4 levels and lower serum C-reactive protein, ferritin, and C3 levels compared to the idiopathic RPF patients without IgG4-RD. These findings might reflect underlying systemic inflammatory responses. Comprehensive laboratory testing, including serum inflammatory markers and immunological panels, is recommended for radiologically diagnosed RPF patients.

3D Laparoscopic Ureterolysis for Retroperitoneal Fibrosis Secondary to Radical Hysterectomy and Radiation Treatment for Cervical Cancer: Results from the Oncological Institute, Cluj Napoca

Background: Ureterolysis represents the surgical treatment for retroperitoneal fibrosis. The aim of the study was to review the outcomes of patients who had undergone radical hysterectomy and radiotherapy for cervical cancer that later developed retroperitoneal fibrosis, for whom 3D laparoscopic ureterolysis was performed in our department and to review current published studies. Methods: We present a series of cases consisting of 6 patients with secondary retroperitoneal fibrosis. In all cases, the intervention was performed by the same surgeon from the Oncological Institute “Prof. Dr. Ion Chiricuț㔠Cluj-Napoca, Romania. We carried out a literature review, searching in the PubMed and MEDLINE studies published between 2000 and 2021 relevant to the matter and a total of 12 papers were selected. We reviewed the functional outcomes of patients that underwent minimally invasive ureterolysis. Results: 3D laparoscopic ureterolysis was performed in 6 patients. Mean operative time was 166 minutes and mean blood loss was 203 mL. No surgery required conversion. Five patients showed good functional results after ureteral stent removal. In one case, the patient developed acute pyelonephritis and the ureteral stents were kept. Conclusions: Laparoscopic ureterolysis for retroperitoneal fibrosis secondary to operated and radiation-treated cervical cancer represents one of the most complex and challenging surgeries in the urological field (AU)

A Review on The Role of Environmental Exposures in IgG4-Related Diseases.

PURPOSE OF REVIEW: Immunoglobulin G4-related diseases (IgG4-RDs) are immune-mediated fibroinflammatory multisystemic conditions identified by the presence of tumefactive lesions with a rich infiltrate of IgG4-positive plasma cells, and often by a high IgG4 serum concentration. IgG-RDs have a prevalence of at least 1 case every 100,000 persons, and they are mostly diagnosed after age 50, with a male to female ratio of about 3:1. IgG4-RD pathophysiology is still uncertain: it has been proposed that both genetic predisposition and chronic environmental exposures may play a role by triggering abnormal immune activation that perpetuates the disease. The purpose of this review is to summarize the evidences supporting the hypothesis that certain environmental/occupational exposures can trigger IgG4-RDs, focusing on the possible role of asbestos in an emerging IgG4-RD called idiopathic retroperitoneal fibrosis (IRF). RECENT FINDINGS: Although some studies suggested a relationship between tobacco smoking and IgG4-RD risk, occupational exposures seem to have the most interesting effects. Positive history of blue-collar work increases the risk of developing an IgG4-RD, and mineral dusts and asbestos were the most strongly associated industrial compounds. Asbestos has been found to be a risk factor for IRF years before its classification as IgG4-RD, and later in two large case-control studies. In the most recent one, conducted on 90 patients and 270 controls, asbestos exposure conferred an increased IRF risk, quantified by odds ratios from 2.46 to 7.07. Further structured studies including serum IgG4 evaluation should be conducted to clarify the effect of asbestos on patients with confirmed diagnosis of IgG4-related IRF. Environmental exposures, especially of occupational origin, appear to play a role in the development of different types of IgG-RDs. In particular, although first suggested very recently, the relationship between asbestos and IRF deserves to be explored in more structured studies, especially because of the biological plausibility of the role of asbestos in IRF pathogenesis.

Manifestaciones toracoabdominales de las enfermedades relacionadas con la inmunoglobulina G4 / Thoracoabdominal manifestations of immunoglobulin G4-related disease

Las enfermedades relacionadas con la IgG4 (ER-IgG4) son un conjunto de enfermedades inmunomediadas que, hasta no hace mucho tiempo, se consideraban como entidades individuales. Se ha demostrado la existencia de una clínica, una serología y una patogenia similares, por lo que, actualmente, se considera como una única enfermedad multisistémica. Su característica común es la infiltración de los tejidos afectados por células plasmáticas y linfocitos IgG4 positivos. Se han propuesto 3 criterios mayores para su diagnóstico, que son el clínico, el analítico y el anatomopatológico. El páncreas es el órgano que más se afecta en esta enfermedad, pudiendo simular un proceso tumoral. De ahí que se haya descrito una serie de signos que podrían hacernos sospechar que no se trata de una neoplasia (signo del halo, del conducto penetrante, ausencia de invasión vascular, etc.). El diagnóstico diferencial es importante de cara a evitar cirugías innecesarias (AU)

Immunoglobulin G4-related disease (IgG4-RD) comprises a group of immune-mediated diseases that, until recently, were considered separate entities. These entities have a similar clinical presentation, serological findings, and pathogenesis, so they are currently considered a single multisystemic disease. The common characteristic is the infiltration of involved tissues by plasma cells and lymphocytes that are positive for IgG4. Three major criteria have been proposed for the diagnosis of IgG4-RD: clinical, laboratory, and histological. The pancreas is the organ that is most affected by IgG4-RD, which can simulate a tumor. In this respect, a series of signs could help us suspect that the pancreatic findings do not reflect a tumor (halo sign, duct-penetrating sign, absence of vascular invasion, etc.). The differential diagnosis is important to avoid unnecessary surgical interventions (AU)

New-onset retroperitoneal fibrosis following COVID-19 mRNA vaccination: Coincidental or vaccine-induced phenomenon?

The Pfizer-BioNTech mRNA vaccine is a US Food and Drug Administration-approved coronavirus disease 2019 (COVID-19) vaccine. Although it is reported to be safe and effective, immune dysregulation leading to autoimmunity has become an area of concern. Retroperitoneal fibrosis (RPF) is an immune-mediated fibroinflammatory disease characterized by the deposition of fibrous tissues, primarily around the abdominal aorta and iliac arteries. Herein, we report a case of RPF following Pfizer BioNTech COVID-19 mRNA vaccination. To the best of our knowledge, there have been no published reports on RPF after COVID-19 mRNA vaccination. A 58-year-old woman with no history of autoimmune diseases presented with acute onset of epigastric pain 5 weeks after the second dose of the Pfizer-BioNTech vaccine. She had been diagnosed with stage I breast cancer 9 years ago and was in complete remission on admission. Abdominal computed tomography showed preaortic soft-tissue infiltration around the origin of the superior mesenteric artery but no evidence of breast cancer recurrence. Considering the temporal relationship between current symptoms and vaccination and the absence of other possible causes, she was diagnosed with RPF secondary to Pfizer-BioNTech vaccine-induced autoimmunity. This case may raise awareness of the possibility of RPF development following COVID-19 mRNA vaccination.

Retroperitoneal fibrosis as a postoperative complication following renal transplantation in cats.

OBJECTIVES: The aim of this report was to describe the clinical signs, diagnostic imaging findings, surgical management, histopathological findings, outcome and possible risk factors for cats that developed retroperitoneal fibrosis (RPF) following renal transplantation. METHODS: Medical records of cats that underwent renal transplantation and developed clinically significant RPF between 1995 and 2019 were reviewed. RESULTS: Eighty-one cats underwent 83 renal transplantations. Of these 81 cats, six developed clinically significant RPF. For all six cats, renal transplantation was performed using cold organ preservation solution and ureteral papilla implantation. Immunosuppression protocol included ciclosporin and prednisolone. All cats had at least one subtherapeutic trough ciclosporin level (<250 ng/ml) in the postoperative period. Cats presented with moderate-to-severe azotemia 39-210 days following renal transplantation. Abdominal ultrasonography and contrast pyelography revealed various degrees of hydroureter and hydronephrosis of the transplanted kidney. Surgical examination revealed a layer of dense fibrous tissue surrounding the transplanted kidney, ureter and bladder resulting in ureteral obstruction. Ureteral obstruction was managed by reimplantation of the proximal ureter or renal pelvis to the bladder. Histopathologic examination of the fibrous tissue and affected portion of the distal ureter revealed fibrous connective tissue with lymphoplasmacytic infiltration and perivascular inflammation suggestive of an autoimmune type reaction. Of the six cats, two died within 5 days after revision surgery, two developed signs consistent with recurrent partial ureteral obstruction (40 and 41 days after revision), one was euthanized 6 years later for an unrelated disease and one was lost to follow-up. CONCLUSIONS AND RELEVANCE: The incidence of RPF in this population of cats was relatively low (7%), but still represents a significant cause of morbidity and mortality. The cause of RPF remains unknown, although investigation into suboptimal immunosuppression as a potential cause for local rejection reaction is warranted.

Retroperitoneal Fibrosis After Spinal Surgery: A Report of 2 Cases.

CASE: Retroperitoneal fibrosis (RPF) is a rare chronic fibroinflammatory disorder with typically unknown etiology (i.e., idiopathic). However, several causes have been identified, including retroperitoneal injury or inflammation. In this study, we describe 2 patients who developed RPF complicated by hydroureteronephrosis after (combined) anterior lower interbody fusion (ALIF) and posterior spine fusion. We also reviewed 6 additional cases from the literature of suspected RPF development after spinal surgery. In these cumulative 8 cases, ALIF was the common denominator. CONCLUSION: RPF may develop after ALIF and should be considered a potential longer term complication of this procedure.

Immunoglobulin G-4-Related Retroperitoneal Fibrosis.

Retroperitoneal fibrosis is caused by the replacement of normal retroperitoneal tissue with fibrosis. The majority of the cases are idiopathic, but some secondary causes include malignancy, infection, drugs, and radiotherapy. Immunoglobulin G-4 (IgG-4) related disease is a relatively newer disease and one of the rarer causes of retroperitoneal fibrosis. It usually involves the pancreas, lungs, kidneys, aorta lacrimal and salivary glands, or extrapancreatic bile duct. Elevated serum IgG-4 is the biomarker of the disease and its levels correlate with disease activity. High-dose glucocorticoid is the treatment of choice.

Idiopathic Retroperitoneal Fibrosis.

The world of surgery has been concerned with idiopathic retroperitoneal fibrosis (RPF) ever since 1948, when J. K. Ormond published the first case of ureteral stenosis following a retroperitoneal scleroinflammatory process due to unknown reasons. Until 1960, 82 such cases were reported in the literature. The authors present two new cases of RPF, located exclusively in the pelvic (subperitoneal) compartment of the retroperitoneal space. The literature on this subject is reviewed, current etiological theories are mentioned and treatment opportunities are discussed.

Idiopathic retroperitoneal fibrosis: an update for nephrologists.

Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications of IRF, which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. IRF may be isolated or develop in association with autoimmune diseases (e.g. Hashimoto's thyroiditis and psoriasis) and other fibro-inflammatory disorders (often within the spectrum of immunoglobulin G4-related disease), which suggests that it should be considered as a potentially systemic condition. IRF is an immune-mediated disease: genetic variants (e.g. human leukocyte antigen (HLA)-DRB1*03) and environmental agents (mainly exposure to asbestos and smoking) are strongly associated with an increased risk of developing the disease, while a complex network of chemokines (e.g. CXCL12 and C-C moti chemokine 11 (CCL11)) and cytokines [e.g. interleukin (IL)-6, IL-12 and IL-13] is likely to orchestrate the inflammatory response and simultaneously promote fibrosis. Glucocorticoids, alone or in combination with traditional immunosuppressants such as methotrexate and mycophenolate mofetil, are usually efficacious and promptly induce disease remission; however, up to 50% of patients relapse, thus requiring repeat immunosuppressive courses. Biologic drugs, namely rituximab, are being explored for the treatment of IRF. In addition to medical therapies, interventional procedures (mainly ureteral stenting) are required to relieve ureteral obstruction, whereas surgical ureterolysis is generally reserved to refractory cases. If appropriately treated, then the overall and renal prognosis of IRF are good, with <5% patients developing end-stage renal disease.

Retroperitoneal fibrosis in the military hospital of Morocco.

Retroperitoneal fibrosis (RPF) is a rare disease. It is characterized by the presence of fibro-inflammatory tissue involving retroperitoneal structures. The usual mode of presentation of this disease is with lumbar pain, kidney failure, and a biological inflammatory syndrome. The aim of our study is to describe the diagnostic, etiologic, therapeutic aspects and outcomes of RPF in a nephrology unit in Morocco. Twelve cases of RPF were included in our study. The mean age was 57 ± 10 years (32.70). Nine patients were male and three were female. Symptoms were highly variable, dominated by pain that was present in all patients. Venous compressive signs were described in four patients (33.3%), anuria in one patient (8.3%), and hematuria in two patients (16.6%). Laboratory examinations found an inflammatory syndrome in all patients and renal failure in nine patients (75%), with a mean serum creatinine at 35 mg/L ± 8.5. Diagnosis was suspected on the ultrasound data and confirmed by computed tomography or magnetic resonance imaging. RPF was idiopathic in nine patients (75%). It was secondary to aortic aneurysm in one patient (8.3%), Riedel's thyroiditis in one patient (8.3%), and drug induced in another patient (8.3%). All patients received surgical treatment along with corticosteroids. At six months, remission was achieved in nine patients, whereas three others had steroid resistance. These patients were treated by mycophenolate mofetil (MMF) at a dose of 2 g/day; two of them had intestinal intolerance to MMF and thus were treated by tamoxifen at a dose of 40 mg/day. At 24 months, they stabilized their renal function with incomplete regression of the fibrotic plate. No cases of recurrence were observed during the study period.

Current approach to diagnosis and management of retroperitoneal fibrosis.

Retroperitoneal fibrosis is characterized by fibrotic lesions around the abdominal aorta and common ileac artery causing ureteral obstruction. Secondary retroperitoneal fibrosis is associated with malignant disease, drugs, exposure to radiation and surgery. In contrast, the majority of retroperitoneal fibrosis is classified into idiopathic retroperitoneal fibrosis, for which immunological etiology has been suggested. Recently, idiopathic retroperitoneal fibrosis has been considered to be a spectrum of immunoglobulin G4-related disease, a systemic inflammatory disease, the concept of which has been developed during the past decade. In the management of retroperitoneal fibrosis, assessment of systemic lesions associated with immunoglobulin G4-related disease and the exclusion of secondary retroperitoneal fibrosis is mandatory. Histological examination of retroperitoneal lesions is desired for accurate diagnosis and management. Laparoscopic or open biopsy is often beneficial, although it is more invasive than needle biopsy. Treatment for idiopathic retroperitoneal fibrosis consists of meticulous glucocorticoid therapy based on that for immunoglobulin G4-related disease, which is expected to be highly effective. Ureteral obstruction is usually managed with conservative procedures, such as ureteral stenting or percutaneous nephrostomy. The goal of treatment for retroperitoneal fibrosis should be freedom from the stent/nephrostomy with withdrawal of the glucocorticoid in addition to salvage of renal function; however, conservative management does not always provide favorable outcomes. In contrast, aggressive surgical treatment, such as ureterolysis, can achieve the goal; however, the procedure is associated with high morbidity. Establishment of a consensus about treatment for idiopathic retroperitoneal fibrosis, including the optimal indications for the invasive surgical procedure and conservative management, is desired.

Cross-sectional pictorial review of IgG4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune disorder characterized by the infiltration of one or more organs with IgG4-positive plasma cells resulting in inflammatory lesions and fibrosis. Although the pancreas is the most commonly affected organ, involvement of extrapancreatic organs is an increasingly recognized manifestation of the disease. Patients may be asymptomatic and serum IgG4 concentrations may be elevated or normal. Treatment consists of glucocorticosteroid treatment, with excellent response. A definitive diagnosis requires histopathology with imaging playing a key role in avoiding treatment delays. This pictorial review will focus on the most current knowledge regarding IgG4-RD including its common and less common manifestations and the roles of multidetector CT, MRI and ultrasound in the diagnosis and management of suspected IgG4-RD. Knowledge of the varied imaging findings of this multi systemic disease is essential for radiologists to avoid misdiagnosis and assist with timely and effective treatment.