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.

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.

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.

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.

Retroperitoneal fibrosis after chemo-radiotherapy for cervical cancer: A case report.

Retroperitoneal fibrosis (RPF) is a rare disease characterized by proliferation of fibro-inflammatory tissue in the retroperitoneum. Multiple studies have reported on the idiopathic cases of the disease, but reports of RPF secondary to irradiation are very limited. Herein, we report the case of a 47-year-old woman who complained of lower abdominal pain 14 months after chemo-radiotherapy for cervical cancer. Computed tomography showed a soft-tissue mass spreading in the presacral space. Biopsy of the lesion revealed fibro-inflammatory tissue without malignancy. Retrospective imaging findings showed that the lesion was consistent with the irradiation field. We diagnosed the patient with RPF caused by radiotherapy. We started oral administration of prednisolone at a dose of 30 mg/day. After 3 months, scans showed a remarkable reduction in lesion size. Prednisolone was tapered to a maintenance dose of 5 mg/day, which is ongoing. The patient is doing well with no recurrence to date.

Long-term results after open repair of inflammatory infrarenal aortic aneurysms.

OBJECTIVE: The objective of this study was to investigate the long-term outcome after open repair of inflammatory infrarenal aortic aneurysms. METHODS: A total of 62 patients (mean age, 68.9 ± 8.8 years; 91.9% male) undergoing open surgery for inflammatory aortic aneurysm from 1995 until 2014 in a high-volume vascular center were retrospectively evaluated. The patients' demographics, preoperative and postoperative clinical characteristics, imaging measurements, and procedural data were collected. Study end points were preoperative and postoperative sac diameter, evolution of periaortic fibrosis and development of hydroureteronephrosis detected by computed tomography (CT) scan, and mortality and morbidity after 30 days and at the time of maximum follow-up. RESULTS: The mean abdominal aortic aneurysm diameter was 67.3 ± 16.7 mm. A total of 30 patients (48.4%) were asymptomatic, 27 patients (43.5%) were symptomatic, and 5 patients (8.1%) were treated for ruptured aneurysm. In 25 patients (40.3%), an aorta-aortic tube graft was implanted; in 37 patients (59.7%), an aortic bifurcation graft was used. Median operating time was 208 minutes (range, 83-519 minutes). Median aortic clamping time was 31 minutes (range, 14-90 minutes); in 25 patients (40.3%), suprarenal aortic cross-clamping was necessary. Hydroureteronephrosis was preoperatively diagnosed by CT scan in 16 patients (25.8%), with the need for a ureteral stent in 11 patients (17.7%). Aneurysm- and procedure-associated 30-day mortality was 11.3% (n = 7), with septic multiple organ failure in four patients and cardiac arrest in three patients. The overall perioperative complication rate was 33.9% (n = 21 patients). Median follow-up was 71.0 months (range, 0.2-231.6 months). At 1 year, 2 years, 4 years, and 6 years, overall survival was 83.4%, 79.6%, 79.6%, and 72.6%, respectively. Six patients (9.7%) required a reintervention during follow-up, predominantly aneurysm related and caused by aortoenteric fistula and graft infection (three of five patients). Median maximum thickness of preoperative perianeurysmal inflammation on CT was 10 mm (range, 2-22 mm), which decreased in 15 of 16 (94%) patients with available postoperative CT scans. Postoperative median thickness of perianeurysmal inflammation on CT was 6 mm (range, 0-13 mm). Hydroureteronephrosis persisted in two of nine (22.2%) patients at the end of follow-up. CONCLUSIONS: Surgery in patients with inflammatory abdominal aortic aneurysms is associated with a substantial amount of perioperative complications. After surgery, the perianeurysmal inflammation decreases in most patients on follow-up CT. However, because the inflammatory process does not totally resolve, patients require lifelong surveillance for hydroureteronephrosis and development of aortoenteric fistulas.

Urological manifestations of the disease related to immunoglobulin G4. / Manifestaciones urológicas de la enfermedad relacionada con la inmunoglobulina G4

Immunoglobulin G4 related disease (IgG4-RD) is a fibro-inflammatory disease of unknown etiology, characterized by lesions in the form of tumors, elevated serum IgG4 levels, plasma cells with significant IgG4 infiltration, accompanied by phlebitis obliterans and fibrosis. This disease usually has multiorgan disease, including pancreas, biliary tract, salivary glands, peri orbital tissues, kidneys, lungs, lymph nodes and retro peritoneum. IgG4-RD mainly affects men with a predominance of age by young adults until old age. The clinical manifestations of IgG4-RD, depend mainly on the organs affected and the response to steroids. His forecast is not yet clear. Within the affected urogenital organs can be observed kidney, retroperitoneum, ureter, bladder, urachus, testis/epididymis, paratesticular region, prostate and urethra.

La enfermedad relacionada con la inmunoglobulina G4 (ER-IgG4) es una enfermedad fibroinflamatoria de etiología desconocida, la cual se caracteriza por presentar lesiones en forma de tumoraciones, concentraciones séricas aumentadas de IgG4 y células plasmáticas con una infiltración importante de IgG4, junto con flebitis obliterante y fibrosis. Esta enfermedad suele tener afección multiorgánica, incluyendo el páncreas, el tracto biliar, las glándulas salivares, los tejidos periorbitarios, los riñones, los pulmones, los ganglios linfáticos y el retroperitoneo. La ER-IgG4 afecta principalmente a hombres, con un predominio de edad por los adultos jóvenes y hasta la vejez. Las manifestaciones clínicas de la ER-IgG4 dependen principalmente de los órganos afectados y de la respuesta a los esteroides. Su pronóstico aún no es del todo claro. Dentro de los órganos urogenitales afectados pueden incluirse el riñón, el retroperitoneo, el uréter, la vejiga, el uraco, el testículo/epidídimo, la región paratesticular, la próstata y la uretra.

Abdominal Pain in the Presence of Small Abdominal Aortic Aneurysms: If in Doubt, Cut It Out!

Although small (<5 cm) abdominal aortic aneurysms (AAA) have been associated with symptoms and indication for intervention scarcely, the clinicians should never exclude such potential association especially in the absence of other overt pathological findings. In such cases, a surgical exploration with consequent intervention, if feasible, should be justified to prevent a detrimental evolution in a dubious scenario. In this article, we present 2 cases of patients with small AAA presenting with severe abdominal pain. In the absence of other solid clinical and radiological pathological findings, both patients underwent laparotomy where an inflammatory small AAA was identified and subjected either to resection and restoration with a tube graft or secondary endovascular repair because the periaortic fibrosis precluded the open repair. The characteristics and rationale of treatment modalities are exemplified and discussed.

Idiopathic retroperitoneal fibrosis and its overlap with IgG4-related disease.

Retroperitoneal fibrosis (RPF) is a rare disease characterised by fibrous tissue proliferation in the retroperitoneum, with encasement of the ureters and large vessels of the abdomen as the most destructive of potentially severe complications. It can either be idiopathic, or secondary to infections, malignancies, or the use of certain drugs. The idiopathic form accounts for approximately 75% of the cases, and is usually responsive to immunosuppressive therapy. In recent years, the emergence of a new clinical entity, IgG4-related disease (IgG4-RD), shed light on many fibro-inflammatory disorders once thought to be separate clinical entities, although frequently associated in the so-called multifocal fibrosclerosis. Among these, together with sclerosing pancreatitis and cholangitis, pseudotumour of the orbit, idiopathic mediastinal fibrosis and other conditions, is idiopathic retroperitoneal fibrosis (IRF). Both IRF and IgG4-RD can be associated with a wide variety of disorders, usually governed by immune-mediated (and particularly auto-immune) mechanisms. In our review, we discuss the clinical and therapeutic challenges IRF presents to the internist, as well as the meaning of its recent inclusion in the IgG4-RD spectrum from a clinical practice standpoint.

Clinical signs of fibrosis in small intestinal neuroendocrine tumours.

BACKGROUND: In patients with small intestinal neuroendocrine tumours (SI-NETs), serotonin and other cytokines released from tumour cells may induce fibrosis, leading to carcinoid heart disease and abdominal fibrotic reactions. The aim of this study was to assess the prevalence, clinical complications and management of this reaction in the abdomen. METHODS: This was a retrospective cohort study of patients with SI-NETs diagnosed between 1985 and 2015. Clinical data, outcomes, radiological findings, and surgical and radiological interventions were reviewed. RESULTS: A total of 824 patients were diagnosed with SI-NETs in the study interval. Clinically significant abdominal signs and symptoms of fibrosis occurred in 36 patients. Of these, 20 had critically symptomatic central mesenteric fibrosis causing obstruction of mesenteric vessels, and 16 had retroperitoneal fibrosis causing obstructive uropathy with hydronephrosis. Extensive fibrosis causing mesenteric vessel obstruction and/or obstructive uropathy was more often associated with symptomatic and advanced disease encompassing lymph node metastases in the mesenteric root, para-aortic lymph node metastases, as well as liver metastases and peritoneal carcinomatosis. Palliative intervention in terms of superior mesenteric vein stenting or resection of central mesenteric metastases and/or percutaneous nephrostomy and J stent treatment was beneficial in the majority of the patients. CONCLUSION: Extensive abdominal fibrosis associated with clinically significant symptoms of intestinal ischaemia and/or obstructive uropathy was linked to advanced disease in patients with SI-NETs. Prompt recognition and minimally invasive intervention was effective in disease palliation.