Comparative study between different modalities of treatment of HCV in new era of direct acting antiviral drugs [DAAs] in Aswan Governorate

Background: Hepatitis C virus [HCV] infection is considered a national progressing problem that threatens the life of Egyptian people as Egypt has the highest prevalence of HCV infection in the world with prevalence rates of 14.7 % of the adult population. HCV infection causes chronic hepatic inflammation and severe liver diseases, such as liver cirrhosis and hepatocellular carcinoma. Currently, HCV is curable, unlike HIV and HBV. Goals of therapy are to eradicate HCV infection to prevent hepatic cirrhosis, decompensation of cirrhosis, hepatocellular carcinoma [HCC] and death. End point of therapy: undetectable HCV RNA in a sensitive assay [<15 Iu /ml] 12 weeks sustained virological response [SVR12] and 24 weeks [SVR24] after the end of treatment

Aim of the Work: To assess the efficacy of DAAs in the treatment of HCV in Aswan Governorate; and to compare between the different combinations of DAAs +/- ribavirin +/-interferon which were available during the study period as regards efficacy and possible side effects in each treatment combination

Patients and Methods: This retrospective study was conducted in Aswan Fever Hospital, Aswan Hospital Health Insurance and Tropical Medicine Department Ain Shams University. Study population: Patients with chronic hepatitis C who received treatment in the period from January 2015 to July 2016. Group I: Triple therapy [Sofosbuvir + Ribavirin + Interferon] for 3 months. Group II: Sofosbuvir + Ribavirin for 6 months. Group III: Sofosbuvir + Simeprevir for 3 months. Group IV: Sofosbuvir + daclatasvir +/- Ribavirin for 3 months

Results: In Group I SVR was 74.3% ,Group II SVR was 60% ,Group III SVR was 85.7% and Group IV SVR was 100%

Conclusion: This is a large real-life report of the use of very low-cost generic medications for treating HCV-G4 within the largest treatment programme worldwide. The use of entirely generic SOF DCV combination with or without generic RBV was well tolerated and associated with high response rate in patients with different stages of liver disease. This can be an example for other countries of similar limited resources for managing their patients with HCV

Effects of Ramadan fasting on Muslim patients with liver cirrhosis: a comparative study

Background: Patients with liver cirrhosis seem to be at increased risk of complications during fasting. This study aimed to assess the effect of Ramadan fasting on liver functions and portal hemodynamics among patients with liver cirrhosis in comparison with healthy subjects

Materials and Methods: Participants were divided into three groups. Group I: patients with liver cirrhosis who fasted during Ramadan [n = 34], group II: patients with cirrhosis who did not fast [n = 8], and group III: healthy volunteers who fasted [n = 30]. This study was done from May 2017 to July 2017 and the month of Ramadan began on May 27th to June 26th, 2017. Portal hemodynamics were evaluated by portal vein diameter, congestion index [CI], and portal flow velocity. Laboratory investigations were determined before, during, and after Ramadan as an indicator of the changes in the liver functions

Results: There were no dropouts during the study. Among the three groups, portal vein parameters showed statistically non-significant differences. Model for End-Stage Liver Disease [MELD] score and serum albumin levels showed a significant difference when the group I and II compared separately to group III [P = 0.000], while there were no differences between group I and group II [P = 0.6 and 0.57, respectively]. For portal vein CI, there was a significant difference between the patients with cirrhosis [fasting; group I and non-fasting; group II] and healthy subjects [group III] [p = 0.000], while the CI did not change significantly between the groups I and II [p = 0.54]

Conclusions: Patients with cirrhosis showed changes in their liver functions and portal hemodynamics irrespective of their fasting status and these differences were more pronounced in portal vein CI, MELD score, and serum albumin when compared with healthy subjects

relationship between expression of Toll-like receptor 4 in chronic hepatitis C patients and different stages of liver fibrosis

Aim: The objective of this work is to find out whether there is a relation between the expression of TLR4 and fibrosis progression in chronic HCV patients

Background: Toll-like Receptor 4 [TLR4] is a pattern recognition receptor whose activation results in the production of several pro-inflammatory cytokines

Methods: Fifty patients with chronic HCV were included. They were divided into group A: 40 patients [F1-F4] and group B [control group] which included ten patients [F0] based on fibroscan value. All patients were exposed to clinical and laboratory evaluations preliminary to antiviral therapy, assessment of TLR4 mRNA by Real Time- PCR

Results: Twenty-eight males and 22 females with a mean age 28.9 +/- 6.1 years. The mean TLR4 expression is 11.2 +/- 7.4 folds, TLR4 expression in F0 group is 2.8 +/- 1.9, in F1 group 4.8 +/- 1.5, F2 group 10.2 +/- 2.5, F3 group 16.8 +/- 1.5 and in F4 21.3 +/- 3.6 folds [p<0.001]. TLR4 showed a positive correlation with age, fibrosis stage, HCV RNA, serum transaminases, total bilirubin and prothrombin time, a negative correlation with platelet count and serum albumin. Fibrosis progression was independently associated with TLR4 expression [beta=0. 648, P<0.0001], RNA [beta= 0.160, P =0.001] and platelet count [beta= -0.248, P = 0.004]

Conclusion: The expression of TLR4 is highly correlated with the fibrosis progression; TLR4 may be a potential target for drugs to limit the progression of fibrosis

Is diffusion weighted imaging adding value in diagnosis of focal hepatic lesions? Experience in 50 patients

Diffusion weighted imaging [DWI] offers molecular information that complements the morphologic information obtained with conventional magnetic resonance imaging [MRI] and can reflect the functions and structures of the body without trauma. To assess the role of DWI as a routine sequence in a MRI study to help in differentiating liver lesions. The study included 50 patients referred to do a MRI study to diagnose and/or to confirm the ultrasonographic or CT findings of focal hepatic lesions. The examination was done on 1.5T superconducting magnet MRI machines; Philips Gyroscan Intera version 12.1.1.2 [Best, The Netherlands] and Siemens Magnetom Avanto [Erlangen, Germany] machine. All studied patients had a focal hepatic lesion either on top of cirrhotic liver or non cirrhotic liver. DWI was found to be helpful with the routine MRI sequences to reach the diagnosis. The final diagnosis was confirmed by histopathological examination or follow up. A cutoff value of ADC for benign lesions was found to be 1.25 x 10[-3] mm[2]/s. DWI should be included as a basic sequence in the routine MRI study of the liver as it helps in diagnosis and so reaching a final diagnosis or at least trying to narrow the list of differential diagnosis

Lymphocytes DNA content, p53, C-MYC and BCL-2 as predictive markers in childhood with acute lymphoblastic leukemia

Cell cycle parameters as well as apoptotic and tumor markers directly control cell growth. DNA ploidy and S phase fraction, apoptosis fraction in addition to apoptotic inducer [p53, c-myc] and antiapoptotic marker [Bcl-2] were investigated in childhood with acute lymphoblastic leukemia [ALL] leukemia as a predictive markers represented in survival data. This study included 70 children with [ALL]; 38 males and 32 females; of median age 5 years. Event free survival [EFS] and overall survival [OS] were estimated for all studied cases. Cell cycle and apoptotic parameters as well as p53, c-myc and Bcl-2 were analyzed using FACS caliber flow cytometer in the lymphocyte cells of peripheral blood. Aneuploidy constituted 33% of studied cases. The median overall survival [OS] showed higher significant values when S% was <4.5%, and DNA index was >/= 0.94 and p53 was < 70.87, whereas it showed no significant difference related to G0/G1%, G2/M% and aneuploidy%. The median event free survival [EFS] showed significant higher value at Bcl-2 >/= 81.5 but with no significance related to other cell cycle parameters as well as p53 and c-myc. These data suggest that DNA index, S phase fraction, p53 and BcI-2 may be useful as a predictive markers that help patients' stratification and adjusting protocols of ALL therapy

Concurrent cisplatin / radiation followed by adjuvant cisplatin / paclitaxel in treatment of patients with stage IB grade 3,IC and IIA endometrial carcinoma

Postoperative radiotherapy [RT] is the most commonly used adjuvant treatment in high risk endometrial carcinoma [HREC], it reduces the incidence of pelvic relapses but doesn't improve survival. This study was conducted to evaluate the efficacy and safety of concomitant weekly cisplatin and postoperative RT in HREC [stages IB grade 3, 1C and IIA] followed by adjuvant cisplatin and weekly paclitaxel. Eighteen patients with pathologically confirmed endometrial carcinoma were enrolled in this study. All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy [TAH-BSO] and surgical staging. Five patients [28%], 4 patients [22%] and 9 patients [50%] presented with stages IB grade 3, 1C and IIA respectively. All patients received cisplatin once weekly during the 6 weeks of RT. After the chemo-radiation course, 4 additional adjuvant courses of cisplatin and paclitaxel were administered. Between May 2000 and March 2002, a total of 18 patients with pathologically confirmed endometrial carcinoma, presented to Radiation Oncology and Nuclear Medicine Department, Ain Shams University Hospitals, were enrolled in this study. Their median age was 59 years. No severe toxicity was encountered during concomitant chemoradiation. Grade 3 hematological toxicities, leucopenia, neutropenia and anemia were recorded in one patient [5.6%] each during adjuvant chemotherapy. Two patients [11%] relapsed with distant metastases and one patient [5.6%] developed pelvic recurrence. Median time to progression was 67 months. Five year disease free survival and the 5 year overall survival were 89% [95%, CI: 74-100]. Concomitant cisplatin and postoperative RT followed by adjuvant cisplatin and weekly paclitaxel is safe and acceptable treatment in patients with HREC. This study verifies the feasibility of this treatment to potentially reduce the incidence of local and distant relapses in order to improve survival. Randomized phase III studies with large number of patients are necessary to evaluate the benefits of this approach

anatomical study of the ulnar artery in the hand in humans

Owing to the diverse applications of the ulnar artery in reconstructive surgery and the use of the radial artery in coronary bypass grafts, the study of the perforators and anastomotic branches of these arteries is becoming nowadays an issue of great importance. Is to study the ulnar artery in the lower forearm and hand. Ten upper limbs were injected with red latex and dissected to identify the perforators and anastomotic branches of the ulnar artery. It was found that the dorsal branch of the ulnar artery gave three branches: ascending and medial giving several perforators to the skin of the medial side of the forearm and a descending branch joining the dorsal carpal branch of the radial artery and the termination of the anterior interosseous artery to form the dorsal carpal arch. Palmar carpal arches were found in 50% of specimens; they were formed by the palmar carpal branches of the ulnar and radial arteries, the recurrent branch of the deep palmar arch and a branch from the anterior interosseous artery. Four types of the superficial palmar arch were found while deep palmar arch was found in all specimens and was classified into three types. There were always a significant anastomosis between the ulnar and radial arteries in the hand and this is essential for flap reconstruction and bypass grafts

Primary gastrointestinal non-Hodgkin's lymphoma [PGI NHL]: management and outcome

Sixty-four patients with PGI NHL were included in this study. The study outlined the clinicopathological features, modalities of diagnosis and treatment, outcome and variables affecting the overall survival. The stomach was involved in 36 cases and intestinal lymphoma was implicated in 28 cases. Stage IIE was the commonest stage. The predominant histological type was high-grade. The overall survival in all cases was 63% at 30 months according to the Kaplan Meier method. The stage of the disease, extension of resection, site of the lesion whether gastric or intestinal and achievement of complete remission [CR] were found to affect the overall survival

Adjuvant cisplatin with concurrent radiation therapy for resectable locally advanced carcinoma of head and neck

This randomized prospective study was performed to evaluate the efficacy and toxicity of postoperative concomitant chemoradiation for patients with locally advanced [stages III and IV] but operable squamous cell carcinoma of head and neck region. Eligible patients had completely resected tumor and histological evidence of extracapsular spread of metastatic lymph node or positive surgical margins. The patients were randomized to receive postoperatively either conventional radiotherapy alone [60 Gy] or concomitant cisplatin [100 mg/m2] on day 1, 22 and 43 and radiotherapy [60 Gy]. A total of 37 patients were entered into this study. At a median follow up of 23.7 months in both groups, the locoregional failure rates at 2 years were 50% and 36.8% in radiotherapy and chemoradiotherapy arms, respectively. The difference was not statistically significant. Although the incidence of distant metastasis was reduced by the addition of chemotherapy but it was not statistically significant. The 2-year disease free survival and overall survival were 38.9% and 50% in radiotherapy group compared with 52.6% and 57.9% in chemoradiotherapy group. The differences were not statistically significant. The chemotherapy was satisfactorily well tolerated and did not affect the ability to deliver the radiotherapy. The most common treatment related toxicity was mucositis, in the combined group, 5 patients [26%] developed severe mucositis that necessitated treatment interruption versus only 2 patients [11%] in the RT group. The study concluded that postoperative concomitant cisplatin and radiotherapy for patients with high risk resectable locally advanced head and neck carcinoma improves the locoregional control, together with improvement in both the 2-year disease free and overall survival. This seems to be true despite of not reaching the 5% level of significance, which may be due to the relatively small sample size

Cisplatin and paclitaxel concomitant with radiotherapy in locally recurrent cancer cervix

Twenty-three eligible patients with locally recurrent cervical carcinoma after radical hysterectomy were treated with concomitant cisplatin/paclitaxel and radiation. Thechemotherapy regimen consisted of cisplatin [20 mg/m2] and paclitaxel [45 mg/m2 therapy] that were given every other week concomitantly with 65-70 Gy local pelvic irradiation over 7 weeks. Eight patients [34.8%] experienced grade 3-4 acute toxicity during treatment. Late morbidity was reported in 4 patients [17.4%]. The chemotherapy related morbidity included mainly hematological toxicity, nausea and vomiting and neurotoxicity. The radiation related morbidity included mainly skin reaction, prostatitis and cystitis. Objective response was achieved in 69.7% ofpatients [34.8% complete response and 34.8% partial response]. The median duration of follow up for whole group was 17.1 months. Sex patients [26.9%] were alive with no evidence of disease with a median survival of 30.6 months. The 2 year overall survival was 26.9%. Five patients [21.7%] developed distant metastases. There was a tendency towards better results for earlier initial stage of the disease, patients older than 50 years old, squamous cell carcinoma tumors, tumors < 5 cm, central pelvis tumors and disease free interval from initial surgery more than 1 year. The study concluded that concomitant cisplatin/paclitaxel and radiation is a safe and tolerable treatment with reasonable response rate and satisfying survival for locally recurrent cancer cervix. However, this regimen must be run on a larger number of patients with a longer follow up period to get significant predictors of the response and survival and to guide in identifying the subset of patients that may benefit from more aggressive therapy

Preoperative versus postoperative 5 FU-based chemoradiation in the management of resectable rectal carcinoma

Forty-eight patients with resectable rectal carcinoma [stages II and III] were randomized to receive either preoperative concomitant 2 cycles of 5-FU/LV and pelvic radiation followed 4-6 weeks later by surgery then additional 4 cycles of the same chemotherapy [group A = 23 patients] or the standard surgical procedure to be followed by 6 cycles of 5-FU/LV and concomitant pelvic irradiation during cycle 3 and 4 [group B = 25 patients]. In preoperative group, objective response was seen in 47.8% of patients 4 weeks after chemoradiation. The remaining patients had stable disease. Ten patients [43.5%] and 16 patients [64%] in preoperative group and postoperative group, respectively, underwent abdominoperineal resection [APR]; while 13 patients [56.5%] in preoperative group and 9 patients [36%] in postoperative group underwent sphincter saving surgery. Seven out of 17 patients [41%] in preoperative group who were initially candidates for APR saved their anal sphincter after preoperative chemoradiation, 85.7% of these patients had excellent to good sphincter function. No pathologic complete response had been recorded. Hematologic grade 3+ toxicity was recorded in 17.4% of patients in preoperative group and in 28% in postoperative group. Grade 3+ diarrhea was recorded in 17.4% in preoperative group and in 20% of patients in postoperative group. The differences were not statistically significant. Eight patients [34.8%] in preoperative group and 9 patients [36%] in postoperative group had one or more components of failure. The difference was not statistically significant. The 2-year overall survival was 69.6% in preoperative group and 72% in postoperative group. The 2-year disease free survival was 65.2% in preoperative group and 64% in postoperative group. The differences in survival and disease free survival between the two groups were not statistically significant. The study concluded that treatment with preoperative combined modality therapy, followed by surgery and postoperative chemotherapy in resectable rectal carcinoma is an attractive alternative to the standard postoperative combined modality therapy. The local control, survival rates and toxicity are comparable to postoperative combined modality therapy. Preoperative chemoradiation offers an additional potential advantage of sphincter preservation. This work needs to be confirmed on a larger number of patients with longer follow up

Concurrent temozolomide [TMZ] and irradiation for the management of high grade malignant glioma

This pilot study was conducted on 18 newly diagnosed patients with malignant glioma [11 patients with glioblastoma multiforme [GBM] and 7 patients with anaplastic astrocytoma [AA]] to assess the safety, tolerability and efficacy of concurrent administration of temozolomide [TMZ] and radiation. The eligible patients received 40 Gy [1.8 Gy/fraction, 1 fraction/day, 5 days/week] to the computed tomography [CT] or magnetic resonance imaging [MRI] enhancing lesion and surrounding edema with a 3 cm margin, then 20 Gy to a smaller volume including the contrast enhancing lesion plus 1-2 cm margin. Starting from the first day of radiation, the patients received oral TMZ [150 mg/m2] daily for 5 days and repeated every 28 days for two cycles. The study demonstrated the safety and efficacy of concurrent TMZ with radiation in newly diagnosed high grade gliomas and supported a further continued investigation of low daily dose TMZ with concurrent radiation, preferably with some cycles of TMZ as an adjuvant to radiation, in a multicenter phase III randomized trial containing a large number of patients and comparing this regimen with radiotherapy alone in newly diagnosed high-grade astrocytomas