Diagnosis Of Chronic Inflammation Research Articles

Diagnostic Challenges during Inflammation and Cancer: Current Biomarkers and Future Perspectives in Navigating through the Minefield of Reactive versus Dysplastic and Cancerous Lesions in the Digestive System.

In the setting of pronounced inflammation, changes in the epithelium may overlap with neoplasia, often rendering it impossible to establish a diagnosis with certainty in daily clinical practice. Here, we discuss the underlying molecular mechanisms driving tissue response during persistent inflammatory signaling along with the potential association with cancer in the gastrointestinal tract, pancreas, extrahepatic bile ducts, and liver. We highlight the histopathological challenges encountered in the diagnosis of chronic inflammation in routine practice and pinpoint tissue-based biomarkers that could complement morphology to differentiate reactive from dysplastic or cancerous lesions. We refer to the advantages and limitations of existing biomarkers employing immunohistochemistry and point to promising new markers, including the generation of novel antibodies targeting mutant proteins, miRNAs, and array assays. Advancements in experimental models, including mouse and 3D models, have improved our understanding of tissue response. The integration of digital pathology along with artificial intelligence may also complement routine visual inspections. Navigating through tissue responses in various chronic inflammatory contexts will help us develop novel and reliable biomarkers that will improve diagnostic decisions and ultimately patient treatment.

Interface Hepatitis over Grade 2 May Differentiate Chronic Inflammation Associated with CHB from NAFLD in the Early Stage.

Background Patients with chronic hepatitis B (CHB) concomitant with nonalcoholic fatty liver disease (NAFLD) are increasing. Objectives To identify pathological features that can be used to differentiate between chronic inflammation caused by CHB and that caused by NAFLD. Methods Patients with CHB (n = 31) needing antiviral treatment, NAFLD (n = 50), or CHB-NAFLD (n = 51) who underwent biopsy were retrospectively enrolled. Pathological characteristics of chronic inflammation were evaluated using the METAVIR scoring system. The rates of three pathological characteristics were first compared in patients with NAFLD and those with CHB, then compared after fibrosis matching, and were finally compared in CHB-NAFLD patients with different viral loads. Results The rates of interface hepatitis over grade 2 and fibrosis over grade 2 were significantly higher in the CHB group than in the NAFLD group (100% vs. 4% and 80.6% vs. 22%; both P < 0.0001), while no significant difference was observed in the rate of lobular inflammation over grade 2 between the two groups. After fibrosis matching, in patients with F0–2 fibrosis, the rate of interface hepatitis over grade 2 in CHB was significantly higher than that in NAFLD (100% vs. 0%; P < 0.0001). In CHB-NAFLD patients with F0–2 fibrosis, the rate of interface hepatitis over grade 2 in cases with a high viral load was significantly higher than cases with a low viral load (66.6% vs. 0%; P < 0.0001). The rate of lobular inflammation showed no difference between groups. Conclusion Interface hepatitis over grade 2 can be used for the differential diagnosis of chronic inflammation associated with CHB or NAFLD in the early stage.

Heterogeneity in esophageal and gastric cardia precursor progression during six-year endoscopic surveillance after population-based screening in a Chinese high-risk region.

BackgroundThe study was conducted to examine esophageal and gastric cardia precursor progression.MethodsAfter population‐based baseline screening, 145 precursor and 335 chronic inflammation cases were endoscopically surveyed for six years.ResultsSurveillance of interval and baseline diagnoses for 18 severe dysplasia (SD) cases later detected were: 13, 23, 39, and 44 months since a diagnosis of chronic inflammation in four cases; 6, 6, 6, 11, 13, 16, 16, and 23 months since mild dysplasia (mD) diagnoses in eight; and 6, 9, 10, 13, 18, and 48 months since moderate dysplasia (MD) diagnoses in six. Rates for 11 carcinoma in situ (Cis) cases later detected were: 7 and 18 months since basal cell hyperplasia (Bch) diagnoses in two; and 6, 6, 9, 13, 13, 18, 35, 44, and 50 months since MD diagnoses in nine. In 10 cancer cases later detected, rates were: 6, 6, 7, 18, 19, 34, 36, and 48 months since SD diagnoses in eight cases with submucosal carcinoma; 46 months since MD diagnosis in a T 2 N 0 M 0 carcinoma case; and 52 months since Bch diagnosis in another T 2 N 0 M 0 case.ConclusionEsophageal and gastric cardia precursors are heterogeneous. Male gender, advanced age, family history of upper gastrointestinal cancer, and multifocal dysplasia are significant independent predictors for progression, and Bch/mD, MD, and SD constitute three distinctive entities regarding the risk of cancer.

Obesity promotes oxidative stress and exacerbates sepsis-induced brain damage.

Sepsis is a severe clinical syndrome in which a system-wide inflammatory response follows initial attempts to eliminate pathogens. It is not novel that in sepsis the brain is one of the first organs affected which causes an increase in morbidity and mortality and its consequences may be exacerbated when associated with a diagnosis of chronic inflammation, such as in obesity. Thus, the aim of the present study is to evaluate the susceptibility to brain damage after sepsis in obese rats. During two months, Wistar rats, 60 days, 250-300g received hypercaloric nutrition to induce obesity. Sepsis was submitted to the cecal ligation and perforation (CLP) procedure and sham-operated rats was considered control group. The experimental groups were divided into Sham + Eutrophic, Sham + Obesity, CLP + Eutrophic and CLP + Obesity. Twelve and twenty four hours after surgery the blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the hippocampus, cortex and prefrontal cortex. The data indicate that in obese rats subjected to sepsis occurs an increase of BBB permeability in different brain regions compared to eutrophic septic rats. This alteration reflected an increase of MPO activity, concentration of nitrite/nitrate, oxidative damage to lipids and proteins and an imbalance of SOD and CAT especially 24 hours after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate or accelerate the sepsis-induced damage in rat brain.

Diagnostic value of computed tomography-guided percutaneous lung biopsy for malignant lung tumors

To explore the diagnostic efficiency of percutaneous lung biopsy for malignant lung tumors under the guidance of computed tomography (CT). The clinical data of 623 patients undergoing CT-guided percutaneous lung biopsy at Department of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University from January 2010 to November 2012 were analyzed to examine the influencing factors for the occurrences of pneumothorax and hemoptysis, including patient age, gender, site of puncture, tumor location and size, depth and number of puncture, chronic obstructive pulmonary disease (COPD) and doctor's clinical experience. A total of 623 cases were recruited. There were 410 male and 213 female with an average age of 60 ± 11 (15-87) years. Among them, 618 were diagnosed as malignant lung tumors with a positive rate of 99.2%. Pathological classifications were adenocarcinoma (n = 387, 62.1%), squamous carcinoma (n = 166, 26.6%), small cell lung cancer (n = 30, 4.8%), undifferentiated cancer (n = 18, 2.9%) adenosquamous carcinoma (n = 2, 0.3%), sarcomatoid carcinoma (n = 6, 0.9%), leiomyosarcoma (n = 3, 0.5%), neuroendocrine carcinoma (n = 2, 0.3%), low differentiated carcinoid (n = 1, 0.2%), cribriform carcinoma (n = 1, 0.2%), malignant lymphoma (n = 1, 0.2%) and metastatic renal cell carcinoma (n = 1, 0.2%) respectively. Another 5 patients (0.8%) had an initial diagnosis of chronic inflammation according to their pathological features of lung punctures. Their definite diagnoses were lung squamous cell carcinoma (n = 3), adenocarcinoma (n = 1) and small cell carcinoma (n = 1) respectively. The major complications were pneumothorax and hemoptysis. Among 73 cases of pneumothorax (n = 73, 11.7%), 65 cases (n = 65, 10.4%) of mild pneumothorax (lung compression < 20%) were cured by sufficient oxygen inhalation and repose while 8 cases (1.3%) suffered lung compression ≥ 75% recovered via closed thoracic drainage. Eighty-four patients (13.5%) suffered from the complications of slight or self-limited hemoptysis with blood-tinged sputum. The symptoms of hemoptysis disappeared after oral hemostatic or other treatments. Another 5 patients (0.8%) suffered from moderate hemoptysis (100-500 ml) and their symptoms disappeared after rest or an intravenous infusion of haemostatic. None of them died of massive hemoptysis or biopsy. The occurrence of pneumothorax was significantly correlated with the diameter of lesions ( ≤ 2 cm) (P = 0.006), depth of needle (>3 cm) (P = 0.044), number of puncture needles ( ≥ 3 needles) (P = 0.025), inadequate clinical experience of puncturing doctors (P = 0.003) and COPD (P = 0.036); the occurrence of hemoptysis was obviously correlated with the diameter of lesions ( ≤ 2 cm) (P = 0.031), depth of needle (>3 cm) (P = 0.018), number of puncture needles ( ≥ 3 needles) (P = 0.015) and inadequate clinical experience of puncturing doctors (P = 0.014). However, the relationship was unremarkable between the occurrences of pneumothorax and hemoptysis and patient gender, age, sites of puncture and tumor location. With a high diagnostic value, CT-guided percutaneous lung biopsy is both safe and effective for malignant lung tumors.

Abstract A37: Low-density protein array reveals inflammation associated serum-autoantibody profile in prostate cancer.

Abstract Background: Chronic prostatic inflammation of the prostate is one of the main reasons for false positive serum PSA tests in prostate cancer screening. In addition there is accumulating evidence that an inflammatory microenvironment may support the development of malignancy and the progression to metastatic disease. Easy accessible and non-invasive indicators for prostate inflammation would be very helpful for a biopsy decision after an elevated PSA test result. However, at present, the histological examination of prostate biopsies remains the only way for identification of prostatic inflammation. The finding that cancer is immunogenic and that patients are able to elicit and potentially amplify an immune response against their tumor antigens suggests that autoantibodies serve as non-invasive serum biomarkers for prostate cancer diagnosis. Consequently, autoantibodies may also be capable of detecting differential disease progression grades -e.g. inflammatory states- enabling a more specific and individualized treatment in cancer therapy. In the present study, we aimed to find new non-invasive biomarkers for the diagnosis of prostatic inflammation in prostate cancer. Methods: Seventy prostate cancer tissue samples derived from radical prostatectomy were classified into two groups (high/low inflammation) according to the amount of tissue infiltrating lymphocytes. Clinical parameters including PSA, fPSA, GSC, prostate weight, prostate volume, tumor size, age and CRP were controlled for equal distribution amongst the two groups. The corresponding blood serum samples were analyzed using a low density protein array (microarray) containing 4012 prostate cancer associated and inflammation related recombinant proteins. Statistical comparison of the serum autoantibody profile in the two groups was used to identify differentially expressed biomarkers. Finally, specificity of candidate autoantibody markers was validated by immunohistochemical detection of corresponding autoantigens in prostate tissue. Results: Autoantibodies against 165 antigens were found to be differentially expressed in the high compared to the low inflammation group. 30 out of these proteins have recently been identified to be associated with prostate cancer. The identified autoantibody profile discriminated between prostate cancer patients bearing high or low inflammation in prostate tissue with a ROC curve AUC of 0.71. Out of the top ranked autoantibodies, three candidate proteins were selected due to their differential expression and significant up-regulation in serum samples of the high inflammation group: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Immunohistochemical analysis showed that targets of all three autoantibody candidates are expressed in epithelial prostate cells. Remarkably, the highest staining intensity was detected in tissue infiltrating lymphocytes in both high and low inflammation samples. Conclusion: The presented data evaluates the possible use of serum autoantibody markers as non-invasive indicators for the diagnosis of chronic inflammation in prostate cancer. The polyclonal immune response to aberrant proteins in heterogeneous diseases such as cancer and autoimmunity favors the development of autoantibody markers with potential specificities to detect disease subtypes and disease progression grades. We provide evidence for an inflammation specific antibody profile and verify the expression of three biomarker candidates in prostate tissue. Citation Format: Bettina Schlick, Petra Massoner, Angelika Luecking, Christof Saifarth, Georg Schaefer, Klaus Marquart, Peter Amersdorfer, Peter Schulz-Knappe, Helmut Klocker. Low-density protein array reveals inflammation associated serum-autoantibody profile in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A37.

Postoperative Inflammation as the Presenting Sign of Latent Syphilis

Purpose: To describe an unusual case of latent syphilis that presented with postoperative inflammation. Methods: Case report. Results: A 62-year-old African American woman developed persistent postoperative inflammation following cataract surgery. Despite a regimen of topical corticosteroid, the inflammation did not settle. A uveitic workup indicated that the patient had latent syphilis. She was referred to Infectious Disease and the inflammation resolved with intravenous penicillin. Conclusions: Postoperative inflammation has not previously been reported as the first sign of latent syphilis. This report underscores the importance of considering syphilis in the differential diagnosis of chronic inflammation, including the postoperative period.

Vestibulectomy for Vulvar Vestibulitis

At the Mayo Clinic, vulvar vestibulitis is treated with vestibulectomy consisting of simple excision of the vulvar vestibule as described by Bomstein and Kaufman. The authors conducted a review of the medical records of their patients who underwent vestibulectomy between 1986 and 2002, and identified 45 who met the definition of vestibulitis described by Friedrich: 1) focal, reproducible points in the vestibule exquisitely tender to light touch; 2) coincident focal area of erythema; and 3) a history of superficial dyspareunia or severe pain on attempted vaginal entry. In addition, a pathologic diagnosis of chronic inflammation only was required. Participants were interviewed by phone at least 6 months after surgery and asked to rate their pre- and postoperative symptoms on a scale from none (0) to 15. Forty-two patients were available for inclusion in the analysis. Their median age was 29 years. On average, women had experienced symptoms of vulvar vestibulitis for 40.7 months (range, 6-240 months) before surgery. There were no diagnoses of psychiatric problems or major medical problems at the time of treatment. Thirty-eight women reported at least a substantial improvement in their symptoms of vulvar vestibulitis. These patients had an average preoperative score of 8.9 (range, 3-13) and an average postoperative score of 1.3 (range, 0-8) (P <0.01). Four women had no improvement in symptoms. Their average pre- and postoperative scores were 7.0 (range, 3-10) and 7.3 (range, 6-10), respectively.