Serum cystatin C (SCysC) and serum creatinine (SCr) are two biomarkers used in common practice to estimate the glomerular filtration rate (GFR). For SCysC and SCr to be used in a given population, normal values need to be determined to better assess patients. This study aimed to determine SCysC and SCr reference intervals (RIs) in a Cameroonian adult population and factors susceptible of influencing them.
Vilazodone is an FDA approved medication used to treat major depressive disorder. The authors describe two cases of accidental vilazodone exposure in toddlers who presented with symptoms similar to amphetamine exposure and also with unexplained positive amphetamine urine immunoassay drug screens. Given a lack of published data on cross-reactivity of vilazodone and its metabolites with drug of abuse screening tests, the authors investigated drug of abuse immunoassay cross-reactivity of vilazodone and metabolites using computational and empirical approaches.
Studies on malignant melanoma have largely focused on Caucasian populations due to higher incidence in lighter-skinned individuals. While there is a well developed body of literature describing melanoma in African-Americans, much less is known about melanoma in black Africans. Prior reports have suggested that it is reportedly extremely rare in black Africans who are considered to mostly have the acral lentiginous subtype. However, an accurate understanding of melanoma in this part of the world is hindered by the very limited nature of prior publications. The aim of this study was to determine the epidemiological profile, anatomical distribution and histopathological features of melanoma presenting in Africans at a tertiary referral hospital in Malawi.
BACKGROUND:EGFR and HER2 overexpression has been reported to play important roles in colorectal cancer (CRC) development and metastasis. Ovarian metastasis is rare yet is one of the most malignant metastases of CRC, but very few studies have focused on its biological features. This study aimed to investigate the expression of EGFR and HER2 in ovarian metastases of CRC and to reveal their clinical significance. METHODS:The expression of HER2 and EGFR in both primary tumours and ovarian metastases was analysed by immunohistochemistry (IHC) in 31 CRC patients with ovarian metastases as well as in the primary tumours of 26 CRC patients with non-ovarian metastases. The overall survival time was calculated with a Kaplan-Meier survival curve and compared with a log-rank test. RESULTS:HER2 positivity in primary tumours was significantly higher in patients with ovarian metastases than in those with non-ovarian metastases (54.5% vs. 36.4%, P < 0.05). The EGFR-positive rate in primary lesions was not significantly different between patients with ovarian metastases and those with non-ovarian metastases (63.6% vs. 58.3%, P > 0.05). HER2 expression was not correlated with age, primary tumour site, tumour differentiation, tumour diameter or vascular cancer embolus (P > 0.05). The positive rates of HER2 and EGFR in ovarian metastases were 44.8 and 69.0%, respectively. HER2 expression in ovarian metastases was correlated with peritoneal metastasis and bilateral ovarian metastasis (P < 0.05) but not with age, synchronous or metachronous ovarian metastases and the primary tumour site (P > 0.05). There was no significant correlation between EGFR expression and the clinicopathological features in ovarian metastases (P > 0.05). CRC patients with HER2-positive ovarian metastases showed a shortened overall survival time compared to that of CRC patients with HER2-negative metastases (17.0 ± 5.2 vs. 32.0 ± 8.3 months). CONCLUSION:Our studies revealed that EGFR and HER2 are highly expressed in the primary tumours and metastases of CRC patients with ovarian metastases. HER2 positivity may be a negative prognostic predictor in patients with ovarian metastases.
The overexpression of HER2 is associated with worse prognosis of breast cancer which responds favourably to anti-HER2 therapy. The objective of this study was to determine the frequency of HER2 and its association with clinicopathologic factors in breast cancer in Ivory Coast.
Background Advanced gastric cancers are usually associated with incurable conditions for which systemic treatments are indicated. Recent studies suggest that circulating cell-free plasma DNA of tumour origin (tDNA) is a promising non-invasive biomarker that can be used to predict the prognosis and monitor the efficacy of systemic treatments in patients with certain types of cancer. We conducted a pilot study to analyse the potential role of tDNA as a biomarker in patients with advanced gastric cancer. Methods We included 30 patients with locally advanced unresectable or metastatic gastric cancer. We obtained samples (10 mL of total blood) from each patient every 3 months and performed concomitant CT until disease progression or death. Total cell-free circulating DNA (cfDNA) samples were measured using GeneQuant RNA/DNA Calculator-Amersham Pharmacia Biotech (Biochrom) Ltd. The cfDNA was used to evaluate the ALU DNA sequences 247 and 115. The level of tDNA was calculated from the ratio of the expression of ALU DNA sequences and the concentration of total cell-free DNA. We utilized the RECIST criteria 1.1 to evaluate the tumour response. Results Patients with advanced gastric cancer had significantly higher concentrations of cfDNA compared with normal controls ( p = 0.00015), which allowed us to conclude that the cfDNA in the patients originated from the tumour. We did not find any significant correlation between the level of tDNA and OS or tumour response. However, after the first cycles of chemotherapy (at 3 months), we observed that patients with lower tDNA levels had significantly longer DFS compared with those with higher levels (Cox Regression p = 0.0228). Conclusions At 3 months after the beginning of chemotherapy, the tDNA levels are correlated with DFS in patients with advanced gastric cancer who receive systemic chemotherapy. tDNA may be a specific, non-invasive and cost effective new biomarker for these patients.
The identification of implant wear particles and non-implant related particles and the characterization of the inflammatory responses in the periprosthetic neo-synovial membrane, bone, and the synovial-like interface membrane (SLIM) play an important role for the evaluation of clinical outcome, correlation with radiological and implant retrieval studies, and understanding of the biological pathways contributing to implant failures in joint arthroplasty. The purpose of this study is to present a comprehensive histological particle algorithm (HPA) as a practical guide to particle identification at routine light microscopy examination.
Background: Primary hepatic neuroendocrine carcinoma (PHNEC) is extremely rare. The diagnosis of PHNEC remains challenging-partly due to its rarity, and partly due to its lack of unique clinical features. Available treatment options for PHNEC include surgical resection of the liver tumor(s), radiotherapy, liver transplant, transcatheter arterial chemoembolization (TACE), and administration of somatostatin analogues. Case presentation: We report two male PHNEC cases and discuss the diagnosis and treatment options. Both cases presented with abdominal pain; case two also presented with symptoms of jaundice. The initial diagnosis for both cases was poorly differentiated grade 3 small-cell neuroendocrine carcinoma, based on imaging characteristics and the pathology of liver biopsies. Final diagnoses of PHNEC were arrived at by ruling out non-hepatic origins. Case one presented with a large tumor in the right liver lobe, and the patient was treated with TACE. Case two presented with tumors in both liver lobes, invasions into the left branch of hepatic portal vein, and metastasis in the hepatic hilar lymph node. This patient was ineligible for TACE and was allergic to the somatostatin analogue octreotide. This limited treatment options to supportive therapies such as albumin supplementation for liver protection. Patient one and two died at 61 and 109 days, respectively, following initial hospital admission. Conclusions: We diagnosed both cases with poorly differentiated grade 3 small-cell PHNEC through imaging characteristics, immunohistochemical staining of liver biopsies, and examinations to eliminate non-hepatic origins. Neither TACE nor liver protection appeared to significantly extend survival time of the two patients, suggesting these treatments may be inadequate to improve survival of patients with poorly differentiated grade 3 small-cell PHNEC. The prognosis of poorly differentiated grade 3 small-cell PHNEC is poor due to limited and ineffective treatment options.
BackgroundListeria monocytogenes is a bacterium present in some food products. It is rarely the cause of Rhombencephalitis in immunocompetent patients.Case presentationWe report a case of an immunocompetent patient, presenting with progressive perioral numbness and dizziness. Despite treatment with antiplatelet drugs, antiviral medication, antibiotics and corticosteroids for a wide differential diagnosis, the patient deteriorated tremendously. Eventually the patient died of Listeria rhombencephalitis, most likely due to the late diagnosis and concomitant late initiation of antibiotics combined with badly timed and inappropriate corticosteroid prescription.ConclusionEarly adequate antibiotic treatment is essential in Listeria rhombencephalitis and corticosteroid therapy should be avoided when Listeriosis is suspected.
BackgroundThe development of molecular techniques to estimate the risk of breast cancer recurrence has been a significant addition to the suite of tools available to pathologists and breast oncologists. It has previously been shown that immunohistochemistry can provide a surrogate measure of tumor recurrence risk, effectively providing a less expensive and more rapid estimate of risk without the need for send-out. However, concordance between gene expression-based and immunohistochemistry-based approaches has been modest, making it difficult to determine when one approach can serve as an adequate substitute for the other. We investigated whether immunohistochemistry-based methods can be augmented to provide a useful therapeutic indicator of risk.MethodsWe studied whether the Oncotype DX breast cancer recurrence score can be predicted from routinely acquired immunohistochemistry of breast tumor histology. We examined the effects of two modifications to conventional scoring measures based on ER, PR, Ki-67, and Her2 expression. First, we tested a mathematical transformation that produces a more diagnostic-relevant representation of the staining attributes of these markers. Second, we considered the expression of BCL-2, a complex involved in regulating apoptosis, as an additional prognostic marker.ResultsWe found that the mathematical transformation improved concordance rates over the conventional scoring model. By establishing a measure of prediction certainty, we discovered that the difference in concordance between methods was even greater among the most certain cases in the sample, demonstrating the utility of an accompanying measure of prediction certainty. Including BCL-2 expression in the scoring model increased the number of breast cancer cases in the cohort that were considered high certainty, effectively expanding the applicability of this technique to a greater proportion of patients.ConclusionsOur results demonstrate an improvement in concordance between immunohistochemistry-based and gene expression-based methods to predict breast cancer recurrence risk following two simple modifications to the conventional scoring model.
Background: Urinary schistosomiasis is a common parasitic disease in endemic countries. Case presentation: We report the case of a patient who was on a working trip to Mauritania. This parasitosis, suspected in the presence of hematuria and the notion of stay in an endemic zone, was confirmed by the presence of Schistosoma heamatobium eggs during the histological examination of the bladder biopsy performed after cystoscopy, highlighting a bilharzial granuloma and of course, the diagnosis was confirmed by the presence of eggs during the direct examination of the freshly collected urine. Conclusions: It should be pointed out that the diagnosis of schistosomiasis must be evoked with the association of hematuria and the particular inflammatory aspect of the vesical mucosa and, of course, the notion of stay in an endemic zone.
Background: to evaluate the intraobserver and interobserver reproducibility of cervical cytopathology according to previous knowledge of whether patients received radiotherapy (RT) treatment or not. Methods: The study analyzed a sample of 95 cervix cytological slides; 24 with cytological abnormalities (CA) and presence of RT; 21 without CA and presence of RT; 25 without CA and without previous RT; 25 with CA and without previous RT. Two cytopathology (CP) evaluations of the slides were carried out. For the first CP reevaluation, the cytotechnologist was blinded for the information of previous RT. For the second CP re-evaluation, the cytotechnologist was informed about previous RT. The results were analyzed through inter and intraobserver agreement using the unweighted and weighted kappa. Results: Post radiotherapy effects were identified in 44.4% of cases that undergone previous pelvic RT. The agreement for RT status was 66.32% (unweighted K = 0.31, 95%CI: 0.13; 0.49, moderate agreement). The intraobserver agreement, regarding the cytological diagnoses, regardless of radiotherapy status, was 80.32% (weighted K = 0.52, 95%CI: 0.34; 0.68). In no RT group, the intraobserver agreement was 70% (weighted K = 0.47, 95%CI: 0.27;0.65) and in patients that received RT, the intraobserver agreement was 84.09% (unweighted K = 0.37, 95%CI: 0.01;0.74). The interobserver agreement between cytopathology result (abnormal or normal) in the group with RT, considering normal and abnormal CP diagnosis was 14.0% and 12.5%, respectively. There was no association between the cytological alterations and the median time between the end of RT and the cytological diagnosis. Conclusion: This study showed that RT has an important impact in CP diagnosis because the agreement, also in interobserver and intraobserver analysis, had high discrepancy in patients that received RT. Also, demonstrated that it is difficult to recognize the presence of RT in cytological slides when this information is not provided.
Background: Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is distinctly rare. We report a patient with a uniquely biphasic LGNPPA; additionally, we review similar tumors reported in the literature. Case presentation: A 56-year-old man presented with an asymptomatic pedunculated tumor in the vault of the nasopharynx, at the junction of the nasal septum and the roof, which was discovered during screening for laryngeal cancer. To obtain a definitive diagnosis, the patient underwent endoscopic endonasal surgery under general anesthesia. Immunohistochemical analysis of the tumor revealed it to be an LGNPPA with a prominent spindle cell component. Conclusion: To our knowledge, this is the fourth reported LGNPPA exhibiting a spindle cell component and the second with a prominent pathological condition. The prognosis of LGNPPA is usually excellent. Therefore, it is important for clinicians to scrutinize the lesion's pathology to avoid unnecessary, disfiguring surgery.
Background p16 and p53 genes are frequently mutated in triple negative breast cancer & prognostic value of these mutations have been shown; however, their role as immunohistochemical overexpression has not been fully validated. Therefore we aimed to evaluate the association of p16 and p53 overexpression in triple negative breast cancer with various prognostic parameters. Methods Total 150 cases of triple negative breast cancers were selected from records of pathology department archives that underwent surgeries at Liaquat National hospital, Karachi from January 2008 till December 2013. ER, PR and Her2neu immunohistochemistry were re-performed to confirm triple negative status. p16 & p53 immunohistochemistry was performed on all cases and association with various clinicopathologic parameters was determined. Results Mean age of the patients involved in the study was 48.9 years. Most of the patients presented at stage T2 with a high mean ki67 index i.e. 46.9%. 42.7% of cases had nodal metastasis. Although 84% cases were of invasive ductal carcinoma; however a significant proportion of cases were of metaplastic histology (9.3%). Fifty-one percent (76 cases) of cases showed positive p53 expression while 49% (74 cases) were negative. Higher percentage of p53 expression was found to correlate with higher T stage, high ki67 index and higher nodal stage. On the other hand, strong intensity of p53 expression was positively correlated with higher tumor grade and ki67 index. Seventy-one percent (98 cases) of cases showed positive p16 expression, whereas 24.8% (34 cases) were negative and 3.6% (5 cases) showed focal positive p16 expression. However, no significant association was found between p16 expression and various clinical and pathologic parameters. Similarly, no significant association of either p16 or p53 over-expression was noted with recurrence status of patients. Conclusion On the basis of significant association of p53 over-expression with worse prognostic factors in triple negative breast cancer, therefore we suggest that more large scale studies are needed to validate this finding in loco-regional population. Moreover, high expression of p16 in triple negative breast cancer suggests a potential role of this biomarker in triple negative breast cancer pathogenesis which should be investigated with molecular based research in our population.
Background: The cutaneous nocardiosis remains a diagnostic challenge: similar clinical presentations as of cutaneous diseases with different etiology- and the inherent difficulty in cultivating the pathogen. Case presentation: Herein, we describe a case of primary cutaneous nocardiosis in a renal transplant recipient; treated with anti-tubercular drugs due to misdiagnosis of cutaneous tuberculosis. On clinical examinations, a few red erythematous papules with erosions and crusting seen, over prior surgery scar of renal transplant. Multiple basophilic colonies surrounded by neutrophilic abscesses and granulation tissue were seen on histopathological examinations. The presumptive identification was done by Ziehl-neelson staining, bacterial culture, biochemical interpretations, and susceptibility pattern of the isolates to antibiotics. Radiographic imaging of brain and lungs were normal; no feature of disseminated nocardiosis seen. After 3 months of an anti-microbial therapy i.e. TMP-SMX(sulfamethoxazole and trimethoprim); the patient underwent progressive changes no relapse noted; transplant function observed in a good state, found asymptomatic with limited side effects on a regular follow up till now. Conclusion: Cutaneous nocardiosis can occur in the renal-transplant patient. Therefore, a high degree of clinical suspicions, extensive clinical differentiation, early detection of the pathogen, apt selection of the antimicrobial therapy, correct dosing, and treatment duration is crucial for successful outcomes.
Background: In lacrimal gland, lymphomas and inflammatory lesions predominate. Primary epithelial tumours represent less than 30% of lacrimal gland lesions. Myoepithelial carcinoma of lacrimal gland is rare. To the best of our knowledge, only nine cases have been reported in the literature. This lesion presents diagnostic difficulties: non-specific clinical and radiological findings and histological polymorphism. This is well illustrated by the diagnostic pathology errors described in the literature. We report a new case of lacrimal myoepithelial carcinoma with a review of others published cases to try to assess clinico-pathological features and outcome whenever possible of this rare tumour. Case presentation: An 80-year-old Arabian female presented with a 2-month history of swelling over the right eyebrow, pain, proptosis of the right eye and diplopia. Computed tomography demonstrated an ill-defined, homogeneous, contrast-enhancing mass attached to the medial rectus. A biopsy was performed. Microscopic examination showed malignant spindle cells tumour, most consistently to sarcoma or sarcomatoid carcinoma. Immunohistochemical study was not possible because neoplastic material has been exhausted. Subsequently, total exenteration of the right orbit was performed. Immunohistochemical study revealed diffuse positive staining for pancytokeratin AE1/AE3, epithelial membrane antigen (EMA) and smooth muscle actin (SMA) and focal positivity for S100 protein. The lesion was immunonegative for desmin, h-cladesmon, CD34, Melan-A and HMB-45. The tumour was extending to the surgical margins. The patient was lost to follow-up until she developed local tumour progression 3 months after removal. The patient was again lost to follow-up and therefore did not receive any other treatment in our hospital. Conclusion: We present this rare tumour with an unusual location. The use of a complete immunohistochemical panel with epithelial and myoepithelial markers positivity helped us for classification of this poorly differentiated tumour.
Chronic lymphocytic leukemia (CLL) is a mature lymphoid neoplasm currently categorized as an indolent type of malignant lymphoma. CLL progresses slowly over years, but it eventually transforms to a more aggressive lymphoma such as the diffuse large B-cell (DLBCL) type, also known as Richter’s syndrome.
Helicobacter pylori antibody titters fall very slowly even after successful treatment. Therefore, tests detecting H. pylori antibody lack specificity and sensitivity. On the other hand, H. pylori stool antigen tests are reported as an alternative assay because of their reliability and simplicity. However, the comparative performance of H. pylori stool antigen tests for detecting the presence of the bacterium in clinical specimens in the study area is not assessed. Therefore, in this study we evaluated the performance of SD BIOLINE H. pylori Ag rapid test with reference to the commercially available EZ- STEP ELISA and SD BIOLINE H. pylori Ag ELISA tests.
Gastrointestinal stromal tumors (GIST) are the most common primary mesenchymal tumors of the digestive system. The assessment of their biological behavior still remains a scientific challenge. To date, there are no well-established biological prognostic markers of GIST. Our aim is to study the expression of the MDM2 oncoprotein in GIST through an immunohistochemical analysis.
Measuring expression profiles of inflammatory biomarkers is important in monitoring the polarization of immune responses; therefore, results should be independent of quantitation methods if they are to be accepted as validated clinical pathology biomarkers. To evaluate effects of differing quantitation methods, the seven major circulating Th1/Th2/Th17 cytokines interleukin 2 (IL-2), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), IL-4, IL-6, IL-10 and IL-17A were quantified in plasma of lipopolysaccharide (LPS)-treated mice with two different multiplex platforms.
