Using (1,3)-ß-D-glucan concentrations in serum to monitor the response of azole therapy in patients with eumycetoma caused by Madurella mycetomatis.

INTRODUCTION: (1,3)-ß-D-glucan is a panfungal biomarker secreted by many fungi, including Madurella mycetomatis, the main causative agent of eumycetoma. Previously we demonstrated that (1,3)-ß-D-glucan was present in serum of patients with eumycetoma. However, the use of (1,3)-ß-D-glucan to monitor treatment responses in patients with eumycetoma has not been evaluated. MATERIALS AND METHODS: In this study, we measured (1,3)-ß-D-glucan concentrations in serum with the WAKO (1,3)-ß-D-glucan assay in 104 patients with eumycetoma treated with either 400 mg itraconazole daily, or 200 mg or 300 mg fosravuconazole weekly. Serial serum (1,3)-ß-D-glucan concentrations were measured at seven different timepoints. Any correlation between initial and final (1,3)-ß-D-glucan concentrations and clinical outcome was evaluated. RESULTS: The concentration of (1,3)-ß-D-glucan was obtained in a total of 654 serum samples. Before treatment, the average (1,3)-ß-D-glucan concentration was 22.86 pg/mL. During the first 6 months of treatment, this concentration remained stable. (1,3)-ß-D-glucan concentrations significantly dropped after surgery to 8.56 pg/mL. After treatment was stopped, there was clinical evidence of recurrence in 18 patients. Seven of these 18 patients had a (1,3)-ß-D-glucan concentration above the 5.5 pg/mL cut-off value for positivity, while in the remaining 11 patients, (1,3)-ß-D-glucan concentrations were below the cut-off value. This resulted in a sensitivity of 38.9% and specificity of 75.0%. A correlation between lesion size and (1,3)-ß-D-glucan concentration was noted. CONCLUSION: Although in general (1,3)-ß-D-glucan concentrations can be measured in the serum of patients with eumycetoma during treatment, a sharp decrease in ß-glucan concentration was only noted after surgery and not during or after antimicrobial treatment. (1,3)-ß-D-glucan concentrations were not predictive for recurrence and seem to have no value in determining treatment response to azoles in patients with eumycetoma.

Epidemiological cut-off values for itraconazole and ravuconazole for Madurella mycetomatis, the most common causative agent of mycetoma.

BACKGROUND: Eumycetoma is a neglected tropical disease. It is a chronic inflammatory subcutaneous infection characterised by painless swellings which produce grains. It is currently treated with a combination of itraconazole and surgery. In an ongoing clinical study, the efficacy of fosravuconazole, the prodrug of ravuconazole, is being investigated. For both itraconazole and ravuconazole, no clinical breakpoints or epidemiological cut-off values (ECV) to guide treatment are currently available. OBJECTIVE: To determine tentative ECVs for itraconazole and ravuconazole in Madurella mycetomatis, the main causative agent of eumycetoma. MATERIALS AND METHODS: Minimal inhibitory concentrations (MICs) for itraconazole and ravuconazole were determined in 131 genetically diverse clinical M. mycetomatis isolates with the modified CLSI M38 broth microdilution method. The MIC distributions were established and used to determine ECVs with the ECOFFinder software. CYP51A sequences were sequenced to determine whether mutations occurred in this azole target gene, and comparisons were made between the different CYP51A variants and the MIC distributions. RESULTS: The MICs ranged from 0.008 to 1 mg/L for itraconazole and from 0.002 to 0.125 mg/L for ravuconazole. The M. mycetomatis ECV for itraconazole was 1 mg/L and for ravuconazole 0.064 mg/L. In the wild-type population, two CYP51A variants were found for M. mycetomatis, which differed in one amino acid at position 499 (S499G). The MIC distributions for itraconazole and ravuconazole were similar between the two variants. No mutations linked to decreased susceptibility were found. CONCLUSION: The proposed M. mycetomatis ECV for itraconazole is 1 mg/L and for ravuconazole 0.064 mg/L.

Molecular detection of human papillomavirus-16 among Sudanese patients diagnosed with squamous cell carcinoma and salivary gland carcinoma.

OBJECTIVE: Human papillomavirus (HPV) gained momentum as a potential etiological factor for many types of cancers. Therefore, the aim of this study was to assess the prevalence of HPV-16 infection among Sudanese patients diagnosed with Squamous Cell Carcinoma (SCC) and Salivary Gland Carcinoma. A descriptive, hospital-based study was conducted. 150 formalin-fixed paraffin-embedded blocks were collected. RESULTS: The study population included a total of 150 patients aged between 18 to 87 years with a mean age of 48.8 ± 11.9 years. Based on gender, females constituted 46.7% while males constituted 53.3%. The 150 patients were classified into 40 (26.0%) esophageal, 30 (20.0%) nasopharyngeal, 18 (12.0%) conjunctival, 18 (12.0%) tongue 12 (8.0%) laryngeal, 8 (5.3%) lip, 6 (4.0%) oropharyngeal, 6 (4.0%) mucoepidermoid, and 6 (4.0%) adenoid cystic, and 6 (4.0%) myoepithelial carcinomas. Odds ratio for male and female diagnosed with carcinoma was 1.025 [0.439-2.394, 95% CI]. Molecular detection of HPV-16 revealed a prevalence of 26 (17.3%) patients were positive for HPV-16. According to cancer diagnosis, esophageal SCC patients showed a high proportion of HPV-16; 14/40 (35.0%). A statistically significant difference was seen for the distribution of HPV-16 positive patients based on cancer diagnosis, P value 0.001.

Immunohistochemical expression of PAX-8 in Sudanese patients diagnosed with malignant female reproductive tract tumors.

OBJECTIVES: Paired box protein-8 (PAX-8) immunohistochemical expression can be used as a diagnostic marker for epithelial cells tumors. This study aimed at investigating the immunohistochemical expression of PAX-8 among Sudanese females diagnosed with cervical, endometrial, and ovarian cancers between December 2017 and May 2019 by studying their Formalin-fixed paraffin embedded blocks. RESULTS: Sixty patients diagnosed with female reproductive tract cancers were included who aged 58.7 ± 6.9 years (range, 43-71). Cervix was the most common cancer site in 51/60 (85%) patients. Regarding cancer stage, there was 17 (28%) and 14 (23%) of the study population had stage 3B and 2B, respectively. The histopathological diagnosis included 20 (44%), 13 (29%), and 12 (27%) poorly, moderately, and well differentiated cervical squamous cell carcinoma (SCC) as well as 11 (73%), 2 (13%), 1 (7%), and 1 (7%) endometrial adenocarcinoma, metastatic adenocarcinoma, endocervical adenocarcinoma, and ovarian mucinous cyst adenocarcinoma, respectively. PAX-8 was positively expressed in 9 endometrial adenocarcinoma, 1 endocervical adenocarcinoma and 1 ovarian mucinous cyst adenocarcinoma, 2 poorly, and 1 moderately differentiated SCC. All patients diagnosed with well differentiated SCC and metastatic adenocarcinoma showed no expression of PAX-8. A statistically significant was seen for PAX-8 expression and the different histopathological diagnosis, P value < 0.001.

Prevalence of Helicobacter pylori among Sudanese patients diagnosed with colon polyps and colon cancer using immunohistochemistry technique.

OBJECTIVES: Infection with the bacteria Helicobacter pylori has been classified as class one carcinogen associated with increasing susceptibility of gastritis and gastric carcinoma. This study is aiming at investigating the prevalence of H. pylori among colon polyps and colon cancer patients. A descriptive cross-sectional hospital-based study was conducted between February and June 2017. Sixty-nine formalin-fixed paraffin blocks collected from colon polyps and colon cancer patients to detect H. pylori using immunohistochemistry technique. RESULTS: Of the 69 patients included in the study, 39 (56.5%) males and 30 (43.5%) were females, their age ranged from 21 to 80 years with a mean age of 47.1 ± 19.7. Of the 69 colon polyps and colon cancer patients, 44 (63.8%) were diagnosed as adenocarcinoma, 10 (14.5%) colitis, 15 (21.7%) juvenile polyposis syndrome. The results of immunohistochemistry technique showed the presence of 16 (23.2%) positive patients for H. pylori infection. Of these 16, 13 (81.3%) patients were diagnosed with adenocarcinoma and 3 (18.7%) patients were diagnosed with juvenile polyps. The results of H. pylori detection among the different colon polyps and colon cancer patients were showing a statistically significant association for H. pylori infection and adenocarcinoma, P value 0.028.

Immunohistochemical expression of Cyclin D1 among Sudanese patients diagnosed with benign and malignant prostatic lesions.

OBJECTIVES: Prostate cancer (PC) is common cancer worldwide. Several markers have been developed to differentiate between benign prostatic hyperplasia (BPH) from PC. A descriptive retrospective hospital-based study aimed at determining the expression of Cyclin D1 in BPH and PC. The study took place at different histopathology laboratories in Khartoum state, Sudan, from December 2016 to January 2019. Formalin-fixed paraffin-embedded blocks were sectioned and fixed in 3-aminopropyltriethoxysilane coated slides incubated into primary antibody for Cyclin D1. The assessment of immunoreactivity of Cyclin D1 of each section was done using the Gleason scoring system. RESULTS: A total of 153 males' prostate sections included in this study, of them, 120 (78.4%) were PC, and 33 (21.6%) were BPH. Their age ranged from 45 to 88 years, mean age was 66.19 ± 8.599. 142 (92.8%) did not have a family history of PC, while 11 (7.2%) patients reported having a family history. The Gleason scoring showed a total of 81 (52.9%) patients with high-grade and 39 (25.5%) with low-grade. 118 (97.5%) patients had PC showed positive results for Cyclin D1, while BPH was 3 (2.5%). P value < 0.001. Cyclin D1 staining was associated with high-grade Gleason score and perineural invasion, P value 0.001.

Erratum to: Molecular Detection of Epstein - Barr virus in Nasopharyngeal Carcinoma among Sudanese population.

[This corrects the article DOI: 10.1186/s13027-016-0104-7.].

Molecular Detection of Epstein - Barr virus in Nasopharyngeal Carcinoma among Sudanese population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx that varies significantly from other cancers of the head and neck in its occurrence, causes, clinical behavior, and treatment. NPC caused by an interaction between infection with EBV and environmental and genetic factors, encompasses a multistep oncogenic process. The frequency of Epstein-Barr virus EBV among nasopharyngeal carcinoma is well known worldwide, however, in the Sudan there is barely a published data. The aim of this study was to detect Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC) biopsies obtained from Sudanese patients using Polymerase Chain reaction. METHODS: This is a descriptive, retrospective hospital based study, conducted at the National Center for ENT diseases and the Faculty of Medical Laboratory Science, University of Khartoum, Khartoum City, Sudan. Archival blocks were obtained from 82 patients diagnosed as having nasopharyngeal carcinoma were molecularly examined for the presence of Epstein-Barr virus. RESULTS: Eighty two Paraffin fixed tissue sections were examined for the presence of the virus using PCR, EBV was identified in 51/ 82 (62.2 %) samples and couldn't be identified in 31/ 82 (37.8 %) tissue samples. Out of the 51 infected samples, 33/51 (64.7 %) were found among males and 18/27 (66.7 %) were found among females. CONCLUSION: The present study is providing strong evidence supporting the general association of EBV infection in NPC among Sudanese patients.