Ismail Matalka

Idiopathic Granulomatous Mastitis: Time to Avoid Unnecessary Mastectomies

Abstract:  Idiopathic granulomatous mastitis is a rare disease of the breast. Clinically and radiologically it may mimic breast carcinoma. Awareness of surgeons, pathologists, and radiologists is essential to avoid unnecessary mastectomies. Data regarding 24 patients with histologically confirmed idiopathic granulomatous mastitis treated at our center over 8 years were analyzed. The mean age of patients was 34.3 years. Breast lump was the most common presentation. The right breast was affected in 16 cases. Four patients were pregnant at the time of presentation. Lactation within 6 months of presentation was documented in four patients. Two patients used contraceptives pills. A clinical suspicion of malignancy was present in 17 cases. Mammography was performed in 16 patients and showed focal asymmetrical dense lesions in 9, well‐circumscribed opacity in 4, spiculated lesion in 1, and was normal in 2. Fine‐needle aspiration was performed in 17 patients, of which 2 were reported as malignant. Wide local excision was the mainstay of treatment. One patient underwent mastectomy upon clinical, mammographic, and repeated cytologic findings consistent with malignancy, and the final histology confirmed idiopathic granulomatous mastitis with no evidence of malignancy. Four patients developed recurrence after a mean follow‐up of 31.2 months. A greater awareness of the rare entity of idiopathic granulomatous mastitis is mandatory to avoid unnecessary mastectomies. Clinical, radiologic, and even cytologic findings are sometimes confused with malignancy. To the best of our knowledge, our patient who developed the disease at the age of 11 years is the youngest reported case. 

Helicobacter pylori genotypes identified in gastric biopsy specimens from Jordanian patients

BackgroundThe genetic diversity of Helicobacter pylori can be analyzed at two different levels: the genomic variation between strains originating from different individuals, and the variation in bacterial populations within an individual host. We reported for the first time the H. pylori genotypes in Jordanian patients with gastrointestinal diseases.MethodsUpper endoscopy was performed on 250 patients with symptoms of gastrointestinal diseases. Multiple gastric biopsy specimens were taken from the antrum. All the biopsies were tested by PCR for the H. pylori virulence genes vacA, cagA, and iceA, and 151 were tested by histology.ResultsThe biopsies positive for H. pylori by PCR were 110/250 (44%), and by histology 117/151 (77.5%), and these results were highly associated (P < 0.02). Analyses of virulence genes revealed that iceA2 (73.6%) was the predominant genotype, the vacAs2 allele was more frequently identified than the vacAs1 allele, while the cagA genotype was low (26.4%). The presence of certain genotypes might be associated with each other, but the presence of certain genotypes was not significantly associated with the age, or gender of the patient.ConclusionThe results illustrate the geographic nature of the genetic diversity of H. pylori, as the identified genotypes are similar to those reported in neighboring countries. This study provides a baseline data of H. pylori genotypes identified in gastric biopsy specimens from Jordan, serving as a powerful epidemiological tool for prospective investigations to better understand the genetic diversity of this pathogen.

Inhibition of MEK sensitizes paclitaxel-induced apoptosis of human colorectal cancer cells by downregulation of GRP78

Here we report that paclitaxel induces variable degrees of apoptosis in human colorectal cancer cells. Paclitaxel induces multiple arms of the endoplasmic reticulum stress response, including upregulation of the 78-kDa glucose-regulatory protein (GRP78) and eukaryotic initiation factor &agr; phosphorylation. Inhibition of the MEK/ERK pathway sensitized colorectal cancer cells to paclitaxel-induced apoptosis. A similar result was obtained by the inhibition of GRP78 using small interfering RNA molecules. Knockdown of MEK resulted in a significant downregulation of paclitaxel-induced upregulation of GRP78 indicating that activation of GRP78 is a downstream event of MEK/ERK pathway activation. These results indicate that GRP78 might be a novel mechanism underlying the resistance of colorectal cancer cells to microtubule-targeting drugs. A combination of compounds capable of suppressing GRP78 might be a golden approach for improving the effectiveness of taxanes.

Xanthogranulomatous Pyelonephritis: Analysis of 18 Cases

OBJECTIVE To review and evaluate patients with a clinicopathological diagnosis of xanthogranulomatous pyelonephritis (XGP) with emphasis on the diagnostic methods and the effect of socioeconomic status on disease severity. METHODS Data compiled from the previous history of the patients, clinical, laboratory, radioimaging findings, preoperative, operative, histopathological diagnosis and postoperative follow-up period were analysed. On the basis of presentation, XGP was classified as complicated and simple. RESULTS There were 18 cases of XGP. The clinical characteristics included: calculi or obstruction in the urinary tract, and damage to the kidney, complication of urinary tract infection, anaemia, increased erythrocyte sedimentation rate and liver dysfunction. All patients had diffuse XGP. Associated pathological findings such as psoas abscess, nephrocutaneous fistula, renocolonic fistula and paranephric abscess were found in 33.3% of cases. Eleven of 14 patients (78.6%) who were evaluated by computed tomography (CT) had the correct diagnosis made prior to nephrectomy. Urine culture was positive in 88.9% of patients and Proteus mirabilis was the most common organism. CONCLUSION Our experience with a small number of patients demonstrates that low socioeconomic status could be a risk factor in the development of complicated cases of XGP. CT is considered to be the best radiological test for correct preoperative diagnosis and evaluation of XGP. Nephrectomy and removal of all surrounding affected tissue proved to be curative for XGP.

FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population

Bladder cancer accounts for nearly 5% of all newly diagnosed cancers in Jordan, with a much higher frequency in males. Recent studies have shown that activating mutations in FGFR3 are the most common findings in non-invasive low grade bladder tumors. In this study, we, retrospectively, investigated a cohort of 121 bladder cancer patients with various grades and stages of the tumor for molecular changes in FGFR3. Overexpression of FGFR3 was observed in 49%, 34%, 15%, and 2% of pTa, pT1, pT2, and pT3 cases, respectively. Further, FGFR3 expression was positive in 45%, 26%, and 30% of G1, G2 and G3 cases, respectively. Mutational analysis of exons 7, 10 and 15 of FGFR3 identified four previously reported mutations, namely R248C (n=4; 10%), S249C (n=23; 59%), Y375C (n=7; 18%), G382R (n=4; 10%), and one novel mutation, G382E (n=1; 3%). Our results indicate that both mutations and overexpression of FGFR3 are correlated together, and are more prevalent in early stage (pTa and pT1) and low grade (G1 and G2) bladder tumors. Survival analysis showed no contribution of changes in FGFR3 on the patients survival. Multivariate Cox proportional hazards model analysis of overall survival for the following variables: age, gender, stage and grade of tumor, and FGFR3 (expression and mutation) revealed that age, stage and grade of tumor are independent predictors of overall survival in patients with bladder cancer. Our work is the first to address the molecular status of FGFR3 in Jordanian patients with bladder cancer, and provides further support for FGFR3 as a key player in the initiation of bladder tumors.

Skin cancer trends in northern Jordan.

Background  The Jordan Cancer Registry was established in 1996, since which time all cases of cancer have been reported and registered. We have used this registry to perform the first analysis of skin cancer in northern Jordan and to compare our findings with those of published reports from other regions.

Multi-drug resistance 1 genetic polymorphism and prediction of chemotherapy response in Hodgkin's Lymphoma

BackgroundThe human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility to cancer and response to chemotherapy. The C3435T Polymorphism of MDR1 gene was correlated with expression levels and functions of P-gp. Here, we studied the association between MDR1 C3435T polymorphism and susceptibility to Hodgkin lymphoma (HL) and patients response to ABVD chemotherapy regimen.Methodsa total of 130 paraffin embedded tissue samples collected from HL patients were analyzed to identify the C3435T polymorphism. As a control group, 120 healthy subjects were enrolled in the study. The C3435T Polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data analysis was carried out using the statistical package SPSS version 17 to compute all descriptive statistics. Chi-square and Fisher exact tests were used to evaluate the genotype distribution and allele frequencies of the studied polymorphism.Resultsthese studies revealed that the frequency of T allele was significantly higher in HL patients compared to the controls (P < 0.05). In addition, the frequency of CT and TT genotypes were also significantly higher in HL patients compared to the controls (P < 0.05). No association between C3435T polymorphism and response to ABVD was detected among HL patients (P > 0.05).Conclusionsthese results suggest that MDR1 C3435T polymorphism might play a role in HL occurrence; however this polymorphism is not correlated with the clinical response to ABVD.

Evaluation of BCL-6, CD10, CD138 and MUM-1 Expression in Diffuse Large B-Cell Lymphoma patients: CD138 is a Marker of Poor Prognosis

The diffuse large B-cell lymphoma (DLBCL) encompasses two major groups of tumors with uneven survival outcomes--germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB). In the present study, we investigated the expression of GCB markers (BCL-6 and CD10) and non-GCB markers (CD138 and MUM-1) in an effort to evaluate their prognostic value. Paraffin-embedded tumor biopsies of 46 Jordanian DLBCL patients were analyzed, retrospectively, by immunohistochemistry to investigate the expression of BCL-6, CD10, CD138 and MUM-1. In addition, survival curves were calculated with reference to marker expression, age, sex and nodal involvement. Positive expression of BCL-6, CD10, CD138 and MUM-1 was shown in 78%, 61%, 39% and 91% of the cases, respectively, that of BCL-6 being associated with better overall survival (p = 0.02), whereas positive CD138 was linked with poor overall survival (p = 0.01). The expression of CD10 and MUM-1 had no impact on the overall survival. Among the clinical characteristics studied, diagnosis at an early age, nodal involvement and maleness were associated with a higher overall survival for DLBCL patients. Our results underline the importance of BCL-6 as a marker of better prognosis and CD138 as a marker of poor prognosis for DLBCL patients.

INI1 (BAF 47) Immunohistochemistry is an Essential Diagnostic Tool for Children With Hepatic Tumors and Low Alpha Fetoprotein

Malignant rhabdoid tumor (MRT) of the liver is a rare malignancy with grave prognosis. This entity should be considered in the differential diagnosis of any aggressive liver tumor with low levels of alpha fetoprotein. We report 2 cases of hepatic MRT presenting in infancy. In these 2 cases, we show that loss of INI1 facilitates making the correct diagnosis of primary hepatic MRT utilizing BAF 47 (INI1 gene product) immunostains. Difficulty encountered in making this rare diagnosis, including the need for repeated biopsies, can be avoided if MRT is considered in the differential diagnosis early on and BAF 47 immunohistochemistry is ordered.

Quantitative assessment of liver fibrosis: a novel automated image analysis method

Abstract: Background: Semiquantitative staging of liver fibrosis is a highly subjective procedure and may lead to an uncertainty in judgment regarding the degree of severity and hence the progression of the disease.