Benign Inflammation Research Articles

449 The Efficiency of Non-surgical Therapies for the Treatment of Mortons Neuroma: A Systematic Review

INTRODUCTION: Morton’s neuroma or Intermetatarsal neuroma is a benign inflammation of the peripheral nerves in the feet causing sharp, burning metatarsalgia and significant morbidity while walking, running, etc. It occurs more in females because tight shoe styles put pressure on the nerve. METHODS: Keyword search of “Morton’s Neuroma”, “treatment”, “conservative” and “non-surgical” was conducted across MEDLINE, EMBASE, and Cochrane databases. Two cohort studies and seven Randomised Controlled Trials were included for review following PRISMA guidelines. These studies were reviewed for pain relief, functionality, and limitations of each procedure. RESULTS: Methylprednisolone injections were proved to reduce the Visual Analog Scale score with >50% cases showing no difficulty in functional daily activity at 9 months post-procedure. Short-term relief was achieved by alcohol and capsaicin injections independently. Modifications in the shoe insole indicated better functionality and analgesia compared to a flat insole but combined with steroids it showed better outcomes. Extracorporeal shockwave therapy provided relief for up to 3 months compared to radiofrequency ablation which provided relief for a longer period. CONCLUSIONS: Although these procedures show statistically significant changes, they are not without limitations. Well-designed randomized controlled trials looking into the avenues for radiofrequency ablation and shockwave therapies as opposed to surgical excision of neuromas are vital.

Post-COVID-19 Infection Tietze’s Syndrome in a Young Adult Patient

Tietze syndrome is a benign inflammation of one or more of the costal cartilages. The condition is characterized by tenderness and painful swelling of the anterior (front) chest wall at the costochondral (rib to cartilage), sternocostal (cartilage to sternum), or sternoclavicular (clavicle to sternum) junctions. We describe a previously healthy 35 years old gentleman with repeated presentations to the emergency department (ED) with left-sided chest and sternoclavicular pain on a background of recent asymptomatic COVID-19 infection. Labs and imaging subsequently confirmed the diagnosis of Tietze’s syndrome. Anti-inflammatory medications and colchicine eventually led to uneventful recovery. This case highlights how Tietze’s syndrome — a disorder that is potentially self-limiting, can cause recurrent hospital admission and should be a differential diagnosis of chest pain related to COVID-19. Bangladesh J Medicine 2023; 34(2): 155-159

S2898 A Unique and Challenging Presentation of Abdominal Pain in Patient of Gastric Bypass Anatomy

Introduction: We are presenting an interesting and challenging case of chronic abdominal pain in a patient of gastric bypass surgery. This patient required Endoscopic ultrasound (EUS) directed transgastric Endoscopy (EDGE) for diagnosis and management of pyloric stenosis in a patient with Roux-en-Y gastric bypass anatomy. Case Description/Methods: 61 years old female presented to emergency department with worsening upper abdominal pain for last 2 years. Patient has history of Roux-en-Y gastric bypass surgery in 2002. Patient had multiple prior evaluations with endoscopies and imaging without any significant etiology identified. She underwent repeat endoscopy with finding of a short gastric pouch and normal-appearing gastrojejunal anastomosis and jejunal limbs. An upper gastrointestinal series and small-bowel follow-through showed normal anatomy. A computed tomography of the abdomen significantly distended bypassed stomach (BS) with fluid. Upon further discussion with Radiology, there was abnormal thickening and elongation of the gastric pylorus noted. Subsequently, an EUS directed transgastric endoscopy was performed revealing significantly dilated BS. An AXIOS stent was placed between gastric pouch and BS in order to decompress as well as gaining access to pyloric channel. Tract was dilated and entered with regular gastroscope. Excessive amount of fluid was aspirated from stomach. A severe friable stenosis found at pylorus. This was only traversed with XP190N gastroscope with outer diameter of 5.4mm. Pathology showed benign inflammation. Repeat EGD was performed through the established tract. Pyloric stricture was then dilated up to 12 mm. Patient was subsequently discharged in stable condition and followed up in clinic. She reported significant improvement in symptoms. Discussion: Despite its overall benefit, there are multiple complications associated with Roux-en-Y gastric bypass. EDGE procedure has been routinely performed in order to gain access to biliary tract. Options to gain access to BS include laparoscopic assisted endoscopy versus surgical exploration. EDGE not only provided therapeutic benefit of decompressing significantly distended excluded stomach but also provided access for examining pyloric channel stenosis/thickening concerning for inflammation or neoplasm. After confirming benign nature, repeated endoscopy was performed for dilation. To our knowledge, this is among first few cases of minimally invasive management of gastric outlet obstruction in patient with gastric bypass anatomy.

Re-thinking benign inflammation of the lactating breast: A mechanobiological model.

Despite the known benefits of breastfeeding for both infant and mother, clinical support for problems such as inflammation of the lactating breast remains a research frontier. Breast pain associated with inflammation is a common reason for premature weaning. Multiple diagnoses are used for inflammatory conditions of the lactating breast, such as engorgement, blocked ducts, phlegmon, mammary candidiasis, subacute mastitis, mastitis and white spots, which lack agreed or evidence-based aetiology, definitions and treatment. This is the first in a series of three articles which review the research literature concerning benign lactation–related breast inflammation. This article investigates aetiological models. A complex systems perspective is applied to analyse heterogeneous and interdisciplinary evidence elucidating the functional anatomy and physiology of the lactating breast; the mammary immune system, including the human milk microbiome and cellular composition; the effects of mechanical forces during lactation; and the interactions between these. This analysis gives rise to a mechanobiological model of breast inflammation, in which very high intra-alveolar and intra-ductal pressures are hypothesized to strain or rupture the tight junctions between lactocytes and ductal epithelial cells, triggering inflammatory cascades and capillary dilation. Resultant elevation of stromal tension exerts pressure on lactiferous ducts, worsening intraluminal backpressure. Rising leucocyte and epithelial cell counts in the milk and alterations in the milk microbiome are signs that the mammary immune system is recruiting mechanisms to downregulate inflammatory feedback loops. From a complex systems perspective, the key mechanism for the prevention or treatment of breast inflammation is avoidance of excessively high intra-alveolar and intra-ductal pressures, which prevents a critical mass of mechanical strain and rupture of the tight junctions between lactocytes and ductal epithelial cells.

Re-thinking benign inflammation of the lactating breast: Classification, prevention, and management.

Despite the known benefits of breastfeeding for both infant and mother, clinical support for problems such as benign inflammation of the lactating breast remain a research frontier. Breast pain associated with inflammation is a common reason for premature weaning. Multiple diagnoses are used for benign inflammatory conditions of the lactating breast which lack agreed or evidence-based aetiology, definitions, and treatment. This article is the second in a three-part series. This second review analyses the heterogeneous research literature concerning benign lactation-related breast inflammation from the perspectives of the mechanobiological model and complexity science, to re-think classification, prevention, and management of lactation-related breast inflammation. Benign lactation-related breast inflammation is a spectrum condition, either localized or generalized. Acute benign lactation-related breast inflammation includes engorgement and the commonly used but poorly defined diagnoses of blocked ducts, phlegmon, mammary candidiasis, subacute mastitis, and mastitis. End-stage (non-malignant) lactation-related breast inflammation presents as the active inflammations of abscess, fistula, and septicaemia, and the inactive condition of a galactocoele. The first preventive or management principle of breast inflammation is avoidance of excessively high intra-alveolar and intra-ductal pressures, which prevents strain and rupture of a critical mass of lactocyte tight junctions. This is achieved by frequent and flexible milk removal. The second preventive or management principle is elimination of the mechanical forces which result in high intra-alveolar pressures. This requires elimination of conflicting vectors of force upon the nipple and breast tissue during milk removal; avoidance of focussed external pressure applied to the breast, including avoidance of lump massage or vibration; and avoidance of other prolonged external pressures upon the breast. Three other key preventive or management principles are discussed. Conservative management is expected to be effective for most, once recommendations to massage or vibrate out lumps, which worsen micro-vascular trauma and inflammation, are ceased.

A study of biliary microbiota in patients with biliary tract disease

Biliary tract disease is associated with many factors: genes, environment, infection, etc. The current changes in biliary flora are thought to be involved in the formation of many gastrointestinal tract diseases. Therefore we want to investigate whether the biliary tract disease has a certain correlation with biliary microecology, and to detect specific strains. Patients who were diagnosed with pancreaticobiliary cancer or benign inflammation were enrolled in this study. Mucosa from specimen or bile samples from endoscopic retrograde cholangiopancretography was utilized to collect for DNA extraction and 16S rRNA gene sequencing, followed by analysis of bile microbiota composition. A total of 52 adults were enrolled, of whom 8 with pancreaticobiliary cancer, 13 with acute inflammation, and 31 with chronic inflammation. We found that pancreaticobiliary cancer patients and bening inflammation patients shared similar stable and permanent dominant species and showed apparent differences in their biliary microbial composition and gene function. We discovered that Lactobacillaceae may potentially play a role in pancreaticobiliary cancer progression. Our data suggested that changes in the microbiota between pancreaticobiliary cancer and benign inflammation may help deepen our understanding of the complex spectrum of different microbiotas involved in the development of pancreaticobiliary cancer.

The effect of Gestational Diabetes Mellitus on the fetal compartment

In indicated preterm births such a Gestational Diabetes Mellitus (GDM), little is known about the role of the amnion membranes. Investigating the role of amnion membrane inflammation in response GDM may suggest novel pathophysiologic mechanisms. We hypothesize that increased GDM inflammatory mediators may weaken the amnion membrane predisposing them to infection. Maternal and fetal serum and amnion membrane biopsies were collected from 20 GDM and 38 normoglycemic subjects (control) who underwent elective cesarean sections. Cytokines and adipokines were evaluated in serum and amnion culture supernatant samples. Amnion membrane biopsies from GDM and control subjects were studied: fresh frozen for RNA analysis for Toll-like receptor expression; cultured with LPS to test membrane permeability, and inflammation LPS + anti-TLR4 for testing mechanism. GDM was associated with higher fetal serum leptin (p = 0.004) and IL-10 (p = 0.04) compared to controls. Amnion membrane explants from GDM had higher levels of IL-6 (p = 0.019), and lower expression of Claudin-4 (p = 0.007) and increased permeability (p = 0.046) compared to controls. GDM membranes treated with LPS showed an increased expression of IL-10 (p = 0.013); IL-6 (p = 0.004) and TNF-α (p = 0.0005) but did not affect membrane permeability. LPS and anti-TLR4 antibody treatment reduced the production of TNF-α in controls (p = 0.03) and GDM (p = 0.007) compared to LPS alone. Fetal inflammatory response seems more balanced in GDM and does not impact membrane permeability function even with an infectious stimulus. Light fetal membrane inflammatory response may explain lack of preterm labor in GDM. Concluding, benign inflammation in the membranes may not be harmful for pregnancy maintenance.

Neonatale subcutane vetnecrose met opvolging van de hypercalciëmie

Subcutaneous fat necrosis of the newborn with follow-up of the hypercalcemia A thirteen-day-old boy is diagnosed with subcutaneous fat necrosis of the newborn after the appearance of erythematous, subcutaneous plaques on the right shoulder. This rare, usually self-limiting cutaneous disease is mainly diagnosed in term and postterm infants. The diagnosis is confirmed by a skin biopsy. Various etiological hypotheses are suggested, although the exact pathogenesis needs to be elucidated. The disease might be associated with several maternal and foetal predisposing factors, including therapeutic hypothermia at birth as part of hypoxic ischemic encephalopathy. It is a benign inflammation of the subcutaneous adipocytes that can be accompanied by life-threatening complications, such as hypercalcemia and thrombocytopenia. The latter requires rigorous follow-up and, in some cases, also treatment. The skin damage should only be treated symptomatically with analgesia.

Time Difference of Arrival on Contrast-Enhanced Ultrasound in Distinguishing Benign Inflammation From Malignant Peripheral Pulmonary Lesions.

IntroductionWorldwide, the incidence and mortality of lung cancer are at the highest levels, and the most lesions are located in the lung periphery. Despite extensive screening and diagnosis, the pathologic types of peripheral pulmonary lesions (PPLs) are difficult to diagnose by noninvasive examination. This study aimed to identify a novel index—time difference of arrival (TDOA)—to discriminate between benign inflammation and malignant PPLs.MethodsUsing contrast-enhanced ultrasound (CEUS), we retrospectively analyzed 96 patients with PPLs who had undergone biopsy to confirm the pathologic types. All data were collected from Dazhou Central Hospital between December 2012 and July 2019. The parameters of CEUS were analyzed by two assistant chief physicians of ultrasound diagnosis. Area under the receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the diagnostic ability of different indices.ResultsWe found that the TDOA significantly distinguished benign inflammation from malignant lesions. The TDOA was markedly increased in patients with malignant lesions than benign inflammation lesions (P < 0.001). Compared with conventional time-intensity curve (TIC) indices, TDOA showed high diagnostic accuracy (area under the curve = 0.894). Moreover, conventional diagnostic indices did not affect the diagnostic performance of TDOA by adjusting the receiver operating characteristic curve.ConclusionTDOA is feasible for the diagnosis of benign inflammation and malignant PPLs.

16S rDNA microbiome composition pattern analysis as a diagnostic biomarker for biliary tract cancer

BackgroundThe aim of this study is to investigate the composition of microbiota in biliary tract cancer patients and healthy adults by metagenome analysis and evaluate its potential values as biomarkers for biliary tract cancer.MethodsPatients who were diagnosed with biliary tract cancer or benign inflammation were enrolled in this study. The control group consisted of healthy adults who presented with no history of significant medical issues. We isolated bacteria-derived extracellular vesicles in the plasma. The microbiome composition was investigated with 16S rDNA metagenome analysis. We evaluated each microbiome to ensure suitability for the biliary tract cancer prediction model.ResultsA total of 155 patients were included in this study: 24 patients with diagnosed biliary tract cancers, 43 diagnosed with cholecystitis or cholangitis, and 88 healthy adults. The microbiome composition pattern of the biliary tract cancer differed from the microbiome composition pattern seen in healthy adult group in beta diversity analysis. The percent composition of microbiota was found to be different from the phylum to genus level. Differences in the composition of the Bifidobacteriaceae and Pseudomonaceae families and Corynebacteriaceae Corynebacterium, Oxalobacteraceae Ralstonia and Comamonadaceae Comamonas species may be used to develop predictive models for biliary tract cancer.ConclusionBiliary tract cancer patients have altered microbiome composition, which represents a promising biomarker to differentiate malignant biliary tract disease from normal control group.

Human urothelial bladder cancer generates a clonal immune response: The results of T-cell receptor sequencing

BackgroundHigh T-cell receptor (TCR) repertoire clonality is associated with clinical response to immune checkpoint blockade in bladder cancer. ObjectiveTo determine if TCR repertoire is more clonal in tumors than in benign inflammation. MethodsWe prospectively identified 12 patients with bladder lesions undergoing transurethral resection. Specimens were collected at time of transurethral resection and stored at −80C. DNA was extracted and high throughput DNA sequencing of the CDR3 region of the TCR beta chain using the immunoSEQ assay (Adaptive Biotechnologies) was performed. T-cell fraction, clonal dominance, and maximum frequency of TCR clone were assessed. ResultsOf the 12 bladder lesions resected, 3 of 12 were cT0, 3 of 12 were cTa, 3 of 12 were cT1, and 3 of 12 were cT2 or greater. The median number of T cells in urothelial carcinoma specimens (UC+) and benign (UC−) specimens was 5,569 and 25,872, respectively. The number of unique TCRs sequenced in UC+ and UC− specimens was 3,069 and 9,680, respectively. The median tumor infiltrating lymphocyte percentage in UC+ and UC− specimens was 2% and 12%, respectively. The UC+ specimens demonstrated clonality as evidenced by identification of a specific T-cell clone being present in up to 17% of the total tumor infiltrating lymphocyte pool, in contrast to 2% among UC− specimens. ConclusionsPrimary urothelial tumors contain clonally expanded T-cell populations. These data support the hypothesis that bladder tumors induce an antigen-driven immunogenic host response, in contrast to the benign inflammatory response, which does not appear to demonstrate any T-cell clonal dominance.

XANTHOGRANULOMATOUS CYSTITIS PRESENTING AS HEMATURIA: A CASE REPORT AND REVIEW OF LITERATURE

Xanthogranulomatous cystitis (XC) is a rare benign chronic granulomatous inflammation of the urinary bladder of unknownetiology. Here, we report a rare case of XC in a 54-year-old man who presented with painless hematuria and frequent urinationfor the past 3 years. His urine culture and sensitivity were positive for Escherichia coli with significant colony count. Contrastenhancedcomputed tomography showed diffusely thickened urinary bladder with no definitive mass. The patient was subjected toother investigations including cystoscopy and biopsy. All the above investigations confirmed the entity to be XC. An endoscopicresection was performed and he was started on a sulfamethoxazole-trimethoprim combination. The patient was asymptomatic at3-month follow-up.

T-cell receptor sequencing of bladder tumor infiltrating lymphocytes to reveal a clonal immune response.

437 Background: High T cell receptor (TCR) repertoire clonality is associated with clinical response to immune checkpoint blockade in bladder cancer (Funt et al ASCO 2016). We hypothesized that T cell repertoire is more clonal in tumors than in benign inflammation. Methods: After obtaining IRB approval, we prospectively identified 12 patients with bladder lesions at Montefiore Medical Center/Albert Einstein College of Medicine undergoing transurethral resection of bladder tumor (TURBT). Specimens collected at the time of TURBT were stored at -80C. After DNA extraction, high throughput sequencing of the CDR3 region of the TCR beta chain using the ImmunoSEQ assay (Adaptive Biotechnologies) was performed. Various parameters such as T infiltrating lymphocyte (TIL) percentage, total productive rearrangements, unique productive rearrangements, and maximum frequency of TCR clone were assessed. Results: 9/12 specimens were malignant (UC+) and 3/12 specimens were benign (UC-). There was an even distribution of specimens across all pathologic stages: 3/12 were T0, 3/12 were Ta, 3/12 were T1, and 3/12 were T2 or greater. The median number of T cells sequenced in UC+ and UC- specimens was 5,569 and 25,872 respectively. The median number of unique TCR rearrangements sequenced in UC+ and UC- specimens was 3,069 and 9,680, respectively. The median TIL percentage in UC+ and UC- specimens was 2% and 12%, respectively. The UC+ specimens demonstrated clonality as indicated by maximum productive frequency of up to 17% as opposed to a maximum productive frequency of 2% in UC- specimens. Conclusions: Primary urothelial tumors contain clonally expanded T cell populations that are not present in benign urothelium. Our data supports the hypothesis that bladder tumors induce a clonal T cell host response against tumor derived antigens. In contrast, benign inflammatory response does not appear to demonstrate any T cell clonal dominance. Future studies to identify tumor specific antigens that contribute to clonal expansion and predict therapeutic efficacy of immunotherapy will be of clinical significance.

S100P is associated with proliferation and migration in nasopharyngeal carcinoma.

In the present study, the function of S100 calcium binding protein P (S100P) in the C666-1 nasopharyngeal carcinoma (NPC) cell line was examined. The levels of S100P protein in NPC tissues were analyzed using immunohistochemistry, and small interfering RNA silenced S100P expression in C666-1 cells. Subsequently, cell proliferation, colony formation, migration and wound-healing assays were performed in order to assess whether the knockdown of S100P was able to influence the biological behavior of C666-1 cells. The expression levels of the receptor for advanced glycation end products (RAGE) were analyzed using a western blot following the inhibition of S100P. The immunohistochemistry results revealed that S100P was elevated in expression in 45/78 (57.7%) of patients with NPC, as compared with 5/30 (16.7%) of patients with benign inflammation. The S100P protein levels correlated with the rates of proliferation and migration in C666-1 cells. Additionally, reduced S100P expression levels altered a series of intracellular events, including the downregulation of epidermal growth factor receptor, cluster of differentiation (CD) 44, matrix metalloproteinase (MMP) 2 and MMP9 protein expression. In addition, RAGE expression was downregulated in the S100P silenced C666-1 cells, as detected by western blot analysis. These data suggest that S100P is important during the development and progression of nasopharyngeal cancer. Therefore, S100P may provide a novel treatment target for NPC.

Xanthogranulomatous prostatitis with benign prostatic hyperplasia: A rare combination

Xanthogranulomatous prostatitis is a rare benign granulomatous inflammation of the prostate. Only ten cases of such pathology have been reported in literature. Patients usually present with symptoms of lower urinary tract symptoms. It occasionally resembles other prostatic diseases such as prostatic carcinoma and abscess. Imaging techniques are not useful in the diagnosis of xanthogranulomatous prostatitis; hence, it is diagnosed only on the basis of histopathological examination of prostate.

Cancer stem cell-still an enigma in CTCL?

Abstract Cancer stem cells have created great excitement in the research community. The concept that tumours are maintained by their own stem cells has revolutionized cancer research since the 70's. At this decade mutation in oncogenes and tumour suppressor genes were found to cause most human cancers. This led to formulating a clonal evolution concept, stating "it is proposed that most neoplasms arise from a single cell of origin, and tumour progression results from a quiet genetic viability within the original clone, allowing sequential selection of a more aggressive sub-line" [1]. This article is protected by copyright. All rights reserved.

Biopsy-proven IgG4-related lung disease.

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve single or multiple organs. Biopsy-proven lung involvement of this disease is occasionally reported, but not well understood.MethodsPatients with the diagnosis of biopsy-proven IgG4-related lung disease (IgG4-RLD) from Peking Union Medical College Hospital between January 2011 and July 2015 were retrospectively analyzed. Age, sex, clinical symptoms, laboratory findings, pulmonary function test results, chest CT tests, positron emission tomography (PET) examinations, treatments and prognoses were retrieved from medical records and analyzed.ResultsSeventeen patients were included in this study (mean age: 44.8 ± 15.0 years). Ten patients were diagnosed via surgery, and 7 patients were diagnosed via percutaneous transthoracic core-needle lung biopsy. Extrapulmonary involvement was observed in only one patient. The clinical symptoms included cough, fever, dyspnea, chest pain and hemoptysis. The serum IgG4 concentration was elevated in 7/13 patients (mean: 1955 ± 1968 mg/L). The chest CT findings included mainly nodules and masses with spiculated borders, alveolar consolidations with air bronchograms, and ground glass opacities with or without reticular opacities. PET scans indicated increased standardized uptake values, and 7/8 patients were correctly diagnosed with benign inflammation. Corticosteroids and immunosuppressants were administered to 14/17 patients and effectively alleviated the disease.ConclusionsIn biopsy-proven IgG4-RLD, a normal serum IgG4 concentration is commonly seen, while extrapulmonary involvement is infrequent. Alveolar consolidation with air bronchograms is an important imaging finding of IgG4-RLD, which has not been emphasized before.

Spectrum of lesions encountered and accuracy of core needle biopsy of breast

Introduction: A wide spectrum of non-neoplastic and neoplastic lesions can affect the breast. Core needle biopsy (CNB) forms an integral part of the Triple test to evaluate breast lumps and is progressively replacing fine needle aspiration cytology(FNAC). The present study was planned to evaluate the accuracy of diagnosis and spectrum of lesions encountered on CNB. Methods: A retrospective analysis of CNB received over a two year period was done. CNBs were categorized using the UK National Health services breast screening programme (NHSBSP) guidelines and correlated with subsequent excision wherever available. Results: 68 CNB were received, 65/68 had a palpable lump. Malignant lesions(B5) were the most common (43%) followed by B1. Infiltrating duct Carcinoma (IDC- NST) was the most common malignancy. Proliferative and Non proliferative benign lesions, granulomatous and non-specific inflammation, Fibroadenoma and Phyllodes tumor were some of the other lesions seen. Overall concordance between CNB and final excision was 71.4%. 8/10 discordant CNB were from Category B1. For detection of malignancy overall sensitivity, specificity, positive predictive value( PPV), negative predictive value (NPV) and accuracy were 90.4%, 100%, 100%, 87.5% and 94.2% respectively. Sensitivity, specificity, PPV, NPV and accuracy in biopsies with more than 3 cores was 100%. Conclusion: A wide spectrum of lesions can be diagnosed on CNB and CNB is accurate, sensitive and specific for preoperative diagnosis. Study of more than three cores per biopsy and a multidisciplinary approach with clinicoradiologic correlation will improve overall sensitivity and NPV. Keywords: Core Needle Biopsy, Breast, Accuracy, Lesions

Little evidence for the effectiveness of chemiluminescence and autofluorescent imaging devices as oral cancer screening adjuncts.

Medline/PubMed. Primary studies where an optical device was used for investigation, screening or as a diagnostic tool for OSCC or OPMD were considered. Data were abstracted by two reviewers independently and the biological plausibility, technical feasibility and diagnostic performance assessed. Twenty-five studies were included, 13 involving the use of chemiluminescence and 12 using autofluorescence with some using both. Chemiluminescence showed sensitivity at detecting any OPMDs and oral cancer, but preferentially detects leukoplakia and may fail to spot red patches. The additive use of toluidine blue may improve specificity. Tissue autofluorescence is sensitive at detecting white, red and white and red patches, and the area of fluorescence visualisation loss often extends beyond the clinically visible lesion. However, in addition to OPMDs, it may detect erythematous lesions of benign inflammation resulting in false-positive test results. In agreement with previous reviews, there is inadequate evidence to draw valid conclusions on the effectiveness of chemiluminescence and autofluorescent imaging devices as screening adjuncts. There is limited evidence for their use in primary care, and these tools are better suited to specialist clinics in which there is a higher prevalence of disease and where experienced clinicians may better discriminate between benign and malignant lesions.

Abstract 4121: Immunohistochemical characterization of xenobiotic detoxification enzymes in normal mucosal epithelium, benign tumors and carcinomas of the nasal and nasopharyngeal regions

Abstract In a cDNA microarray analysis in nasopharyngeal cancer (NPC) patients, we found abundant RNA expression of a variety of phase I and II xenobiotic detoxification enzyme genes (CYP4B1, GSTA1, GSTA2, GSTA3, MAOB, ALDH1A1 &amp; NQO1) in the normal nasopharyngeal (NP) biopsy tissues but a lack of expression in the tumor tissues. Phase I and II detoxification enzyme systems are responsible for catabolism &amp; excretion of different types of hydrocarbon types of carcinogens (e.g. benzopyrene, benzoanthracene &amp; benzochrysane) present in burnt meat and tobacco smoke plus nitrosamine types of carcinogens (e.g. N-nitrosodibutylamine) present in Chinese styled salted fish, which are associated with NPC development. To further investigate the protein expression of these carcinogen detoxification enzymes, we performed immunohistochemical staining of the detoxification enzymes in tissue microarray (TMA) slides from nasopharynx and nasal regions containing 80 malignant carcinomas, 17 metatastic carcinomas, 42 benign tumors (papilloma and polyps), 12 hyperplasia and chronic inflammation and 45 normal NP or nasal tissues. GSTA3 was the enzyme with the strongest staining in the normal epithelium in 37 TMA cores but negative or weak staining was found in 63 cores of squamous cell carcinomas (SCC) (grades I, II or III) as well as undifferentiated carcinomas. Seventeen cores of metastatic NPC in lymph nodes also had weak/negative GSTA3 staining. This weak to negative staining of GSTA3 also occurred in limited numbers of rare malignant tumors in NP or nasal regions such as basal cell carcinomas, adenoid cystic carcinomas &amp; adenocarcinomas. In great contrast, 42 cores of benign tumors (30 cores of papillomas &amp; 12 cases of polyps) and 12 cores of hyperplasia and chronic inflammation all had significantly stronger staining of GSTA3 than malignant carcinomas although they were still weaker than that in normal mucosal epithelium. Expression of GSTA3 mainly resides in the outer epithelial layer facing the lumen of the nasopharynx (which is in direct contact with carcinogens) with the basal proliferative layer being negative. The differential expression of the detoxification enzymes in the normal epithelium versus malignant cancers enables us to hypothesize a role of these enzymes in protecting NP or nasal region from cancer development. High expression of the enzymes in benign tumors indicates another mechanism of tumor development which could be unrelated to carcinogen insults. Further cell functional analysis is ongoing to further investigate this point. Citation Format: Victor W.S. Ma, Yuen Ping Leung, Roger K.C. Ngan, Dora L.W. Kwong, Loretta Tse, Stephen C.K. Law, Timothy T.C. Yip. Immunohistochemical characterization of xenobiotic detoxification enzymes in normal mucosal epithelium, benign tumors and carcinomas of the nasal and nasopharyngeal regions. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4121. doi:10.1158/1538-7445.AM2014-4121