Epidermal growth factor receptor system plays a central hepato-protective and pro-regenerative role in liver. Transforming growth factor-α (TGF-α) is an important autocrine growth regulator of hepatocytes that plays a role in development of hepatocellular carcinoma (HCC) among patients with chronic hepatitis C (CHC). This study was done on 40 core liver biopsies from patients with CHC, 20 liver specimens from HCC cases on top of CHC as well as five normal controls. All were immunohistochemically stained with epidermal growth factor receptor (EGFR) and TGF-α antibodies. Some selected HCC cases were submitted for FISH technique to detect EGFR gene alteration. By immunohistochemistry EGFR and TGF-α were overexpressed in HCC and cirrhotic cases compared to CHC cases without cirrhosis. Also, their expression was stronger in CHC cases with higher grades of activity and stages of fibrosis compared to lower ones. FISH positive results for EGFR were detected in 33.3% of the examined HCC cases. EGFR and TGF-α can be used as predictive markers for activity, fibrosis, and carcinogenesis in CHC patients. Overexpression of EGFR in HCC patients can be promising in selecting those who can get benefit from anti-EGFR target therapy.

Hyperacute soft tissue infection is an uncommon infectious entity, which mostly affects immunocompromised individuals, mainly diabetics and poses difficult diagnostic and therapeutic management decisions. This study addresses the presentation, evaluation and management of 37 diabetic patients with acute necrotizing fasciitis treated throughout the period between August 1993 and July 2006 by the main author. Extremities, trunk and perineum were the most commonly involved sites with an incidence of 35%, 30% and 27%, respectively. All patients presented with cellulitis, which was associated with oedema in 75.6% of cases, skin gangrene in 59% of cases and brown ecchymotic patches in 30% of cases. Skin vesicles, tenderness and crepitations were present in 13.5%, 11% and 11% of cases, respectively. Streptococci, Staphylococci and E coli were the most commonly encountered organisms, which affected 70% of cases, either alone or in combination. Anaemia and hypoalbuminaemia were the most commonly encountered laboratory findings in 75.6% and 84% of cases, respectively. The mortality rate in the 37 patients included in this study was 43% (16 cases); in 11 of them the infection was located in the trunk and perineum. Once necrotizing fasciitis is suspected, exploration of the fascia is mandatory with pathological assessment of tissue specimens. Radical debridement of the affected area, maintenance of adequate nutritional support and systemic antibiotic therapy should be implemented at once in order to reduce mortality and insure safe recovery of patients.

Introductionα-Smooth muscle actin (α-SMA)-positive hepatic stellate cells (HSCs) are pericytes responsible for fibrosis in chronic liver injury. The glial fibrillary acidic protein (GFAP), commonly expressed by astrocytes in the central nervous system, is expressed in vivo in the liver in a subpopulation of quiescent stellate cells. The reports concerning GFAP expression in human liver are still conflicting. The aim of the study is investigation the utility of GFAP compared to α-SMA as an indicator of early activated HSCs, in predicting fibrosis in chronic hepatitis C (CHC) patients.Material and methodsWith immunohistochemistry and a semi-quantitative scoring system, the expressions of α-SMA and GFAP on HSCs in liver biopsies from patients with pure CHC (n = 34), hepatitis C virus-induced cirrhosis (n = 24), mixed CHC/schistosomiasis (n = 11) and normal controls (n = 10) were analysed.ResultsThe immunoreactivity of α-SMA and GFAP in perisinusoidal, periportal and pericentral areas was assessed. α-Smooth muscle actin and GFAP-positive HSCs were significantly increased in all diseased groups compared with normal controls. In pure CHC with or without cirrhosis, perisinusoidal α-SMA-positive HSCs were predominant in relation to GFAP-positive cells. On the other hand, GFAP-positive cells were predominant in the group of schistosomiasis as compared with the other diseased groups. It was noticed that expression of GFAP on perisinusoidal HSCs in CHC patients sequentially decreased with the progression of fibrosis.ConclusionsGlial fibrillary acidic protein could represent a more useful marker than α-SMA of early activation of HSCs in CHC patients and seems to be an early indicator of hepatic fibrogenesis.

BackgroundHypersensitivity pneumonitis (HP) is a common diffuse parenchymal lung disease in Egypt which can be difficult to recognize due to the dynamic symptoms & associated environmental factors.MethodsForty-three Egyptian patients were enrolled in this study, presenting with dyspnea and cough, predominant ground-glass opacity (GGO) in high-resolution computed tomography (HRCT) where lung biopsy was needed to establish the diagnosis.ResultsThe age range was 15 to 60 years. Females represented 90.7% (39 patients) while 9.3% (4 patients) of our patients were males. History of contact with birds was detected in 9 (20.9%) patients. Most of our patients (60.5%) didn’t have exposure history, and only 8 patients (18.6%) were living in geographic areas in Egypt that are known for the exposure to environmental etiologic factors (cane sugar exhaust fumes). The most common HRCT pattern was GGO with mosaic parenchyma in 18 patients (41.86%), followed by GGO with centrilobular nodules in 9 patients (20.93%), then isolated diffuse GGO in 5 patients (11.62%), GGO with traction bronchiectasis in 4 patients (9.3%), GGO with consolidation in 3 patients (6.97%), GGO with reticulations in 2 patients (4.65%), and GGO with cysts in 2 patients (4.65%). The most common histologic finding was isolated multinucleated giant cells in 38 patients (88.3%) commonly found in airspaces (24 patients) and less commonly in the interstitium (14 patients), followed by interstitial pneumonia and cellular bronchiolitis in 36 patients (83.7% each), interstitial ill-formed non-necrotizing granulomas in 12 patients (27.9%), fibrosis in 10 patients (23.2%), and organizing pneumonia pattern in 4 patients (9.3%).ConclusionThe diagnosis of HP presenting with predominant GGO pattern in HRCT requires a close interaction among clinicians, radiologists, and pathologists. Some environmental and household factors may be underestimated as etiologic factors. Further environmental and genetic studies are needed especially in patients with negative exposure history.

BACKGROUND:Bladder cancer represents the fifth most common malignancy worldwide and a major cause of cancer-related morbidity and death. Incidence and mortality rates have remained relatively constant over the past four decades. Urothelial bladder cancers have identified multiple risk factors.AIM:We aimed at evaluating the expression of the FGFR3 protein and gene amplification in the urothelial cells of neoplastic and non-neoplastic urothelial lesions of the urinary bladder, and correlation with tumour grade, stage and associated bilharziasis.MATERIAL AND METHODS:One hundred and five different urinary bladder lesions were studied, including 15 cystitis cases (9 bilharzial and 6 non-bilharzial cystitides), 75 urothelial carcinoma cases (18 bilharzial associated and 57 non-bilharzial associated) and 15 squamous cell carcinoma associated with bilharziasis, beside 5 control cases. Data concerning age, sex, tumour grade, stage, and associated bilharziasis were obtained. Each case was studied for FGFR3 expression, and FISH technique was applied on forty malignant cases that show high protein expression.RESULTS:The highest incidence of cystitis was in the fourth decade while of bladder cancer was in the seventh decade. Tumour grade was correlated significantly with tumour stage. FGFR3 correlates significantly with tumour grade, stage and with a bilharzial infestation. FGFR3 gene amplification was reported mainly in low grade and NNMBIC tumours.CONCLUSIONS:FGFR3 overexpression in malignant cases was significantly higher than in chronic cystitis. FGFR3 gene amplification was reported mainly in low grade and NNMBIC tumours. FGFR3 may be further studied as a subject for target therapy of bladder cancer.

Liver tissue engineering aims to create transplantable liver grafts that can serve as substitutes for donor's livers. One major challenge in creating a fully functional liver tissue has been to recreate the biliary drainage in an engineered liver construct through integration of bile canaliculi (BC) with the biliary ductular network that would enable the clearance of bile from the hepatocytes to the host duodenum. In this study, we show the formation of such a hepatic microtissue by coculturing rat primary hepatocytes with cholangiocytes and stromal cells. Our results indicate that within the spheroids, hepatocytes maintained viability and function for up to 7 days. Viable hepatocytes became polarized by forming BC with the presence of tight junctions. Morphologically, hepatocytes formed the core of the spheroids, while cholangiocytes resided at the periphery forming a monolayer microcysts and tubular structures extending outward. The spheroids were subsequently cultured in clusters to create a higher order ductular network resembling hepatic lobule. The cholangiocytes formed functional biliary ductular channels in between hepatic spheroids that were able to collect, transport, and secrete bile. Our results constitute the first step to recreate hepatic building blocks with biliary drainage for repopulating the whole liver scaffolds to be used as transplantable liver grafts.

Introduction: Overexpression of epidermal growth factor receptor (EGFR) has been described in several solid tumors including bladder cancer. Transforming growth factor alpha (TGFα) is frequently deregulated in neoplastic cells and plays a role in the development of bladder cancer. TGFα-EGFR ligand-receptor combination constitutes an important event in multistep tumorigenesis. Methods: This study was done on 30 bladder biopsies from patients with urothelial carcinoma, 15 with squamous cell carcinoma, 10 with cystitis and 5 normal control bladder specimens. All were immuohistochemically stained with EGFR and TGFα antibodies. Results: EGFR and TGFα were over-expressed in higher grades and late stages of bladder cancer. Moreover, they show higher expression in squamous cell carcinoma compared to urothelial carcinoma and in schistosomal associated lesions than in non-schistosomal associated lesions. Conclusion: EGFR and TGFα could be used as prognostic predictors in early stage and grade of bladder cancer cases, especially those with schistosomal association. In addition they can help in selecting patients who can get benefit from anti-EGFR molecular targeted therapy.

AIM:Prostate cancer (PCa) is the second most common cancers in men worldwide. Its incidence can be influenced by several risk factors including genetic susceptibility. Therefore the search for the expression of a certain gene (ERG) and its rearrangement could give us clues for proper identification of PCa. And the study of ERG expression and its comparison to FISH in Egyptian patients can show whether ERG immunophenotype could be used instead of FISH, as it is cheaper.MATERIALS AND METHODS:This study was performed on 85 cases of PCa, showing 30 cases with HGPIN and 30 cases of prostatic hyperplasia. All were immunohistochemistry stained using ERG monoclonal rabbit antihuman antibody was used (clone: EP111). FISH analysis was performed in 38 biopsies of PCa cases to detect TMRPSS2-ERG rearrangement using the FISH ZytoLight TriCheck Probe (SPEC TMRPSS2-ERG).RESULTS:ERG expression was found in 26% of PCa cases and 20% of HGPIN cases. FISH analysis showed fusion of 21 cases of PCa (out of 22 cases showing ERG immunoexpression).CONCLUSION:Our findings emphasise that only malignant and pre-malignant cells and not benign cells from the prostate stain positive. ERG expression may offer a simpler, accurate and less costly alternative for evaluation of ERG fusion status in PCa.