Deleterious and ethnic-related BRCA1/2 mutations in tissue and blood of Egyptian colorectal cancer patients and its correlation with human papillomavirus.

This study aimed to identify BRCA1/2 mutational patterns in the tissue and blood of Egyptian colorectal cancer (CRC) patients and to study the possible correlation of this mutational pattern with Human papillomavirus (HPV) infection. Eighty-two colonoscopic biopsies and forty-six blood samples were collected from Egyptian CRC patients, as well as blood samples of age and sex-matched healthy controls (n = 43) were enrolled. The libraries were performed using Qiaseq Human BRCA1 and BRCA2 targeted DNA panel and sequenced via Ion proton sequencer. Also, the CRC tissues were subjected to conventional PCR targeting the HPV Late 1 (L1) region. Our analysis revealed that the BRCA-DNA damage pathway had been altered in more than 65% of the CRC patients. Comparing tissue and blood samples from CRC patients, 25 somatic mutations were found exclusively in tissue, while 41 germline mutations were found exclusively in blood. Additionally, we identified 23 shared BRCA1/2 pathogenic (PVs) mutations in both blood and tissue samples, with a significantly higher frequency in blood samples compared to tissue samples. The most affected exon in BRCA1 was exon 10, while the most affected exons in BRCA2 were 11, 14, 18, 24, and 27 exons. Notably, we revealed an ethnic-related cluster of polymorphism variants in our population closely related to South Asian and African ethnicities. Novel PVs were identified and submitted to the ClinVar database. HPV was found in 23.8% of the CRC tissues, and 54% of HPV-positive cases had somatic BRCA1/2 PVs. The results of this research point to a possible connection between infection with HPV and BRCA1/2 mutations in the occurrence of colorectal cancer in the Egyptian population, which has a mixed ethnic background. Our data also indicate that liquid biopsy (blood samples) may be more representative than tissue samples for detecting BRCA1/2 mutations. These findings may have implications for cancer screening and the development of personalized, targeted therapies, such as PARP inhibitors, which can effectively target BRCA1/2 mutations.

Respiratory indications for ECMO: focus on COVID-19.

Extracorporeal membrane oxygenation (ECMO) is increasingly being used for patients with severe respiratory failure and has received particular attention during the coronavirus disease 2019 (COVID-19) pandemic. Evidence from two key randomized controlled trials, a subsequent post hoc Bayesian analysis, and meta-analyses support the interpretation of a benefit of ECMO in combination with ultra-lung-protective ventilation for select patients with very severe forms of acute respiratory distress syndrome (ARDS). During the pandemic, new evidence has emerged helping to better define the role of ECMO for patients with COVID-19. Results from large cohorts suggest outcomes during the first wave of the pandemic were similar to those in non-COVID-19 cohorts. As the pandemic continued, mortality of patients supported with ECMO has increased. However, the precise reasons for this observation are unclear. Known risk factors for mortality in COVID-19 and non-COVID-19 patients are higher patient age, concomitant extra-pulmonary organ failures or malignancies, prolonged mechanical ventilation before ECMO, less experienced treatment teams and lower ECMO caseloads in the treating center. ECMO is a high resource-dependent support option; therefore, it should be used judiciously, and its availability may need to be constrained when resources are scarce. More evidence from high-quality research is required to better define the role and limitations of ECMO in patients with severe COVID-19.

Recurrent cutaneous basal cell carcinoma after surgical excision: A retrospective clinicopathological study.

Background: Recurrence of basal cell carcinoma (BCC) after complete surgical excision is rarely reported. Risk factors for this negative outcome are not well-studied. We present the clinical and histological features of recurrent BCCs in our institution. Methods: All patients between January 2016 to December 2020 whose primary BCCs were excised with free surgical margins according to the histopathology report, and represented later with local recurrence were included. The medical files were retrieved to record patient's age, sex, sun exposure, tumor site, size, clinical diagnosis, histopathology variant of primary lesion, least free margin distance of the original lesion, and recurrence time. Results: Eighteen patients (11 males and 7 females ranged between 50 and 75 years old) fulfilled the inclusion criteria; all of their lesions were located in head and neck regions. The mean recurrence time was 31.2 months (11-86) and the histological variant was the same of primary in 17/18 patients. Primary tumors showed nodular subtype in 77.8% of patients and 55.6% of the primary tumors were less than 15 mm in diameter. Sun exposure history was given by 77.8% of patients while the rest of patients had non-significant exposure. All recurrent excised lesions were of free margin less than 4 mm. Conclusion: We found that the primary tumors of all studied recurrent BCCs were excised with surgical margins less than 4 mm. We recommend follow up for all excised BCCs either those of low or high risk histological variants. Tumor size does not appear a considerable risk factor for local recurrence.

Urothelial Papilloma of the Urinary Bladder: A Case Report and Literature Review of a Rare Entity.

Urothelial papilloma is a rare benign neoplasm composed of a delicate fibrovascular core covered by normal urothelium. In this report, we present a case of an incidentally detected endovesical papillary growth in ultrasound scan (USS) during a routine check-up, suggestive of bladder tumor which was also suggested by CT urography. The tumor was initially managed with transurethral resection and immediate intravesical instillation of mitomycine C 40 mg. The histopathologic assessment of the specimen concluded that the growth was "urothelial papilloma with no atypia or malignancy." Although papilloma is unequivocally benign, it can recur; recurrences can be multiple and can occur years after the initial diagnosis occasionally with progression to carcinoma, hence long-term surveillance is essential. Our case was followed up for a year with no signs of recurrence or progression and long-term surveillance will be done annually.

Recurrent malignant solitary fibrous tumor of the scalp: a case report and literature review.

Solitary fibrous tumor (SFT) is a rare type of mesenchymal neoplasm that first was discovered in the pleura but can also affect the peritoneum, lungs, mediastinum, and skin. Cutaneous malignant SFT is an extremely rare tumor that resembles dermatofibrosacoma protuberance (DFSP) histologically and immunohistochemically. Herein, we describe a case of malignant SFT that presented as a recurrent mass on the scalp. The first lesion was totally excised one year before recurrence and was diagnosed as a DFSP based on the histopathology and cluster of differentiation 34 immunostaining positivity. Re-examination of the previously examined specimen was considered. Activator of transcription 6 positivity was also detected in the tissue, confirming the diagnosis of a recurrent malignant SFT rather than DFSP. There was no evidence of recurrence, locoregional, or distant metastases at six months after lesion removal with a safety margin.

Clinical characteristics, risk factors and diagnostic outcomes of patients presented with indeterminate biliary stricture: A multicenter study.

Background and aim: Indeterminate biliary stricture (IBS) is a frequently encountered clinical problem. In this study, we aimed to highlight the clinical characteristics, risk factors and diagnostic outcomes of patients presented with indeterminate biliary stricture. Method: A Retrospective multicenter study included all patients diagnosed with IBS in the participating centers between 2017 and 2021. Data regarding IBS such as presentations, patient characteristics, diagnostic and therapeutic modalities were collected from the patients' records and then were analyzed. Results: Data of 315 patients with IBS were retrospectively collected from 7 medical centers with mean age: 62.6 ± 11 years, females: 40.3% and smokers: 44.8%. For diagnosing stricture; Magnetic resonance imaging/Magnetic resonance cholangiopancreatography (MRI/MRCP) was the most frequently requested imaging modality in all patients, Contrast enhanced computerized tomography (CECT) in 85% and endoscopic ultrasound (EUS) in 23.8%. Tissue diagnosis of cholangiocarcinoma was achieved in 14% only. The used therapeutic modalities were endoscopic retrograde cholangiopancreatography (ERCP)/stenting in 70.5%, percutaneous trans-hepatic biliary drainage (PTD): 17.8%, EUS guided drainage: 0.3%, and surgical resection in 8%. The most frequent type of strictures was distal stricture in 181 patients, perihilar in 128 and intrahepatic in 6. Distal strictures had significant male predominance, with higher role for EUS for diagnosis and higher role for ERCP/stenting for drainage, while in the perihilar strictures, there was higher role for CECT and MRI/MRCP for diagnosis and more frequent use of PTD for drainage. Conclusion: Indeterminate biliary stricture is a challenging clinical problem with lack of tissue diagnosis in most of cases mandates an urgent consensus diagnostic and treatment guidelines.

Clinicopathological characteristics and outcomes of eosinophilic cystitis: A retrospective study.

BACKGROUND: Eosinophilic cystitis (EC) is a rare inflammatory urinary bladder disorder whose etiology, pathogenesis, and treatment are unknown. The work aims to evaluate the clinical manifestations, cystoscopic characteristics, pathological features, treatment, and clinical outcome of EC patients. MATERIALS AND METHODS: The clinical records and histopathology material of 22 patients diagnosed as EC during ten years were reviewed and analyzed for patient's age, sex, clinical data, cystoscopic features, biopsy procedures, treatment plan, follow-up, and prognosis. Frequencies, normality tests, descriptive statistics, and correlations were run. RESULTS: The mean age of patients was 46.5 + 17 years, 12 females and 10 males. Regarding the patient's complaints, dysuria was the most frequent main symptom, followed by hematuria. On cystoscopic examination, bladder mass was seen in 54.5% of patients. Six patients (27.3%) were associated with different allergic diseases; however peripheral eosinophilia was shown in two patients (9.1%). All cases revealed predominance of eosinophilic infiltration on microscopic examination. The most commonly used medications were corticosteroids for 72.7% of patients with tapering dose giving a significant improvement with a recorded recurrence in one patient after 12 months from the first lesion. CONCLUSIONS: No specific clinical presentation for EC patients and histopathology is the standard diagnostic tool. Medical treatment including corticosteroids was the first line with good prognosis, although recurrence remains a possibility which emphasizes the importance of patients' follow-up.

Effect of combination sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity; role of heme oxygenase-1.

BACKGROUND/AIM: Cisplatin-induced nephrotoxicity in large proportion of patients. The aim of this work is to clarify the effect of combination of sildenafil and gemfibrozil on cisplatin-induced nephrotoxicity either before or after cisplatin treatment and determination of nephrotoxicity predictors among the measured tissue markers. METHODS: Thirty two adult male albino rats were divided into four equal groups (G) GI control, GII received cisplatin, GIII received sildenafil and gemfibrozil before cisplatin, GIV received sildenafil and gemfibrozil after cisplatin. Creatinine and urea were measured and animals were sacrificed and kidney was taken for histopathology. The following tissue markers were measured, heme oxygenase-1 (HO-1) activity, reduced glutathione, quantitative (real-time polymerase chain reaction) RT-PCR for gene expression of tumor necrosis factor alpha (TNF-α) and endothelial nitric oxide synthase (ENOS) level. RESULTS: GII developed AKI demonstrated by significantly high urea and creatinine and severe diffuse (80-90%) tubular necrosis. TNF-α was highly and significantly elevated while the rest of tissue markers were significantly reduced in GI1 compared to other groups. GIV showed better results compared to GIII. There was a significant positive correlation between creatinine and TNF-α when combining GI and GII while there were significant negative correlation between creatinine and other tissue markers in same groups. Linear regression analysis demonstrated that HO-1 was the independent predictor of AKI demonstrated by elevated creatinine among GI and GII. CONCLUSIONS: Combination of sildenafil and gemfibrozil can be used in treatment of cisplatin-induced nephrotoxicity. HO-1 is a promising target for prevention and/or treatment of cisplatin-induced nephrotoxicity.

Thrombopoietin level in patients with chronic liver diseases.

UNLABELLED: Thrombocytopenia and oxidative stress are the most frequent problems in patients with chronic liver diseases as viral cirrhosis and schistosomiasis. So, this study aimed to evaluate the role of thrombopoietin (TPO) on the occurrence of thrombocytopenia and in differentiation between these diseases. It also aimed to investigate the relation between TPO, oxidative stress and antioxidant status in these two types of chronic liver disease. So, We measured serum TPO level, lipid peroxide (MDA) and serum total antioxidant activity (TAO) in 40 patients with cirrhosis caused by hepatitis C virus and 37 patients with schistosomiasis from The Specialized Medical Hospital, Mansoura University. RESULTS: Both serum TPO level and serum TAO activity were significantly lower (p < 0.05) in thrombocytopenic patients with viral cirrhosis when compared to both non thrombocytopenic and control groups. In contrast, TPO level was within the normal range in the patients with scistosomiasis either thrombocytopenic or not. while serum TAO activity was significantly lower (p < 0.05) in both thrombocytopenic and non thrombocytopenic patients with schistosomiasis in comparison to control subjects with no significant difference between these two subgroups. Serum MDA concentration was increased significantly (p < 0.05) in all diseased groups when compared to controls with significant increase in thrombocytopenic patients as compared to non thrombocytopenic. CONCLUSION: TPO hypoproduction played a role in the pathogenesis and treatment of viral cirrhosis associated with thrombocytopenia. Also, total antioxidant activity and MDA are useful markers for monitoring patients with these chronic liver diseases.

Measurements of oxidative stress status and antioxidant activity in chronic leukaemia patients.

There is an interactive relationship between leukaemia and oxidative stress. Leukaemic cells produce larger amounts of reactive oxygen species (ROS) than non-leukaemic cells as they are under a continual state of oxidative siege. So, this study was performed on 20 patients with chronic leukaemia from the Oncology Centre, Mansoura University. We measured leucocytic H(2)O(2) concentrations and lipid peroxidation as serum malondialdehyde (MDA) concentration, serum total antioxidant activity, plasma ascorbic acid and dehydroascorbic acid concentrations, blood reduced glutathione concentration, haemolysate G6PD activity, blood catalase activity, serum superoxide dismutase (SOD) activity and serum anti-dsDNA concentration. We found that chronic leukaemia patients showed a significant increase (P < 0.05) in leucocytic H(2)O(2), serum MDA concentration and total antioxidant activity either before or after treatment as compared with control group. Also, there was a significant increase in the other parameters (glutathione, catalase and SOD) either before or after treatment, but we found a significant decrease in ascorbic acid concentration and G6PD activity. There was a significant increase in anti-dsDNA concentration either before or after treatment. It can be concluded that leukaemic patients produce larger amounts of ROS than non-leukaemic patients. Also, the increase in antioxidant activity in leukaemic patients is not high enough to counteract the harmful effects of free radicals. This scenario becomes worse after administration of chemotherapy.

Value of internerve tissue dissection during axillary lymphadenectomy for early breast cancer.

BACKGROUND: Breast cancer is one of the most commonly occurring malignancies in females in the Eastern Mediterranean Region. Axillary clearance is an integral part of the surgical treatment of breast cancer. Precise analysis of lymph node involvement for proper staging and adjuvant therapy is therefore necessary. During axillary dissection, lymph nodes at levels I, II and III are removed, while the important axillary structures ( axillary vein, long thoracic and thoracodorsal nerves ) are preserved. The latter two structures are particularly vulnerable to injury when dissecting the tissue between them ( the internerve tissue). PATIENTS AND METHODS: This study evaluates the necessity of dissecting the internerve tissue during axillary dissection in breast cancer surgery by reviewing the lymph node yield and metastasis rate in this tissue. This is a prospective non-randomized study, conducted on 50 female patients, who underwent axillary lymphadenectomy for breast cancer. The internerve tissue was excised separately after a routine axillary dissection. RESULTS: Twenty eight ( 56% ) of the 50 internerve specimens contained lymph nodes; the internerve nodes were positive for carcinoma in 5 patients ( 10%). In those 5 patients, metastasis was also found in some other axillary lymph nodes. There was no incidence of isolated metastasis in the internerve tissue nodes in absence of metastatic disease to other lymph nodes in the axilla. CONCLUSIONS: There is a significant incidence of lymph nodes ( 56% ) and axillary node metastases ( 10% ) in the tissue lying between the long thoracic and thoracodorsal nerves. Therefore, meticulous dissection and excision of this internerve tissue is strongly recommended in order to optimize decision making regarding adjuvant treatment and outcome in women with operable breast cancer. Key Words:Breast cancer - Axillary lymphadenectomy - Internerve tissue.