Baicalein and Αlpha-Tocopherol Inhibit Toll-like Receptor Pathways in Cisplatin-Induced Nephrotoxicity.

Cisplatin (CP) is a conventional chemotherapeutic agent with serious adverse effects. Its toxicity was linked to the stimulation of oxidative stress and inflammation. As a result, this study explored the protective effect of baicalein and alpha-tocopherol in nephrotoxicity induced by cisplatin. Until receiving an intraperitoneal injection of CP (3 mg/kg BW), rats were given baicalein orally 100 mg/kg for seven days or/and a single intraperitoneal injection of α-tocopherol 250 mg/kg. Renal function was tested to explore whether baicalein and α-tocopherol have any beneficial effects; blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA) content, antioxidant activity biomarkers and histopathology of renal tissue, oxidative stress biomarkers, inflammatory response markers, and histopathological features of kidney architecture were measured. Cisplatin treatment resulted in extreme renal failure, as measured by high serum creatinine and BUN levels and severe renal changes. Cisplatin therapy resulted in increased lipid peroxidation and decreased glutathione and superoxide dismutase levels, reflecting oxidative stress. Upon treatment with α-tocopherol, baicalein, and combined therapy, there was augmentation in the antioxidant status as well as a reduction in IL-6, NF-κB, TNF, TLR2, and TLR4 and a significant increase in Keap-1 and NRF-2. The combined treatment was the most effective and the nearest to the normal status. These findings suggest that baicalein and α-tocopherol may be useful in preventing cisplatin-induced nephrotoxicity.

Thyroid-Stimulating Hormone Favors Runx2-Mediated Matrix Mineralization in HOS and SaOS2 Cells: An In Vitro and In Silico Approach.

Osteoporosis is a skeletal disease that is both systemic and silent characterized by an unbalanced activity of bone remodeling leading to bone loss. Rising evidences demonstrate that thyroid stimulating hormone (TSH) has an important role in the regulation on the metabolism of bone. However, TSH regulation on human osteoblast essential transcriptional factors has not been identified. Current study examined the role of TSH on human osteoblastic Runx2 expression and their functional genes by in vitro and in slico analysis. Human osteoblast like (HOS and SaoS-2) cells were cultured with DMEM and treated with hTSH at the concentration of 0.01 ng/mL and 10 ng/mL. After treatment, osteoblastic Runx2 and IGF-1R beta expression were studied using RT-PCR and western blot analysis. TSH treatment induced osteoblastic essential transcriptional factor, Runx2 in HOS and SaOS2 cells on 48 h duration and elevated the expression of IGF-IR ß gene and Protein in SaoS-2 cells. TSH also promotes Runx2 responsive genes such as ALP, Collagen and osteocalcin in SaOS2 cells on day 2 to day 14 of 10 ng/mL of treatment and favors' matrix mineralization matrix in these cells. In addition, TSH facilitated human osteoblastic cells to mineralize their matrix confirmed by day 21 of alizarin red calcium staining. In silico study was performed to check CREB and ELK1 interaction with Runx2. Results of in silico analysis showed that TSH mediated signalling molecules such as CREB and ELK1 showed interaction with Runx2 which involve in osteobalstic gene expression and differentiation. Present findings confirm that TSH promotes Runx2 expression, osteoblastic responsive genes and bone matrix formation.

Repurposing of quinoline alkaloids identifies their ability to enhance doxorubicin-induced sub-G0/G1 phase cell cycle arrest and apoptosis in cervical and hepatocellular carcinoma cells.

The ability of quinoline alkaloids (cinchonine, cinchonidine, quinine, and quinidine) to sensitize different human cancer cell lines to doxorubicin (DOX)-induced cell death was evaluated. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the alkaloids ability to enhance DOX-induced apoptosis was explored using Western blotting analysis. Also, flow cytometry was applied to analyze cell fractions in the different cell cycle phases. All alkaloids showed a significant enhancement of DOX-induced cell death in HeLa and HepG2 cell lines. The chemosensitizing activity of the quinoline alkaloids was attributed to the induction of apoptosis as indicated by splitting of caspase-3 and its substrate poly (ADP-ribose) polymerase (PARP). In addition, there was an increase in the cell fractions in sub-G0/G1 phase in case of DOX combination with the alkaloids. This study proves the ability of the quinoline alkaloids to enhance DOX-induced apoptotic cell death in human cervical and hepatocellular carcinoma cells.

Antitumor Activity of Nitazoxanide against Colon Cancers: Molecular Docking and Experimental Studies Based on Wnt/ß-Catenin Signaling Inhibition.

In colon cancer, wingless (Wnt)/ß-catenin signaling is frequently upregulated; however, the creation of a molecular therapeutic agent targeting this pathway is still under investigation. This research aimed to study how nitazoxanide can affect Wnt/ß-catenin signaling in colon cancer cells (HCT-116) and a mouse colon cancer model. Our study included 2 experiments; the first was to test the cytotoxic activity of nitazoxanide in an in vitro study on a colon cancer cell line (HCT-116) versus normal colon cells (FHC) and to highlight the proapoptotic effect by MTT assay, flow cytometry and real-time polymerase chain reaction (RT-PCR). The second experiment tested the in vivo cytotoxic effect of nitazoxanide against 1,2-dimethylhydrazine (DMH) prompted cancer in mice. Mice were grouped as saline, DMH control and DMH + nitazoxanide [100 or 200 mg per kg]. Colon levels of Wnt and ß-catenin proteins were assessed by Western blotting while proliferation was measured via immunostaining for proliferating cell nuclear antigen (PCNA). Treating HCT-116 cells with nitazoxanide (inhibitory concentration 50 (IC50) = 11.07 µM) revealed that it has a more cytotoxic effect when compared to 5-flurouracil (IC50 = 11.36 µM). Moreover, it showed relatively high IC50 value (non-cytotoxic) against the normal colon cells. Nitazoxanide induced apoptosis by 15.86-fold compared to control and arrested the cell cycle. Furthermore, nitazoxanide upregulated proapoptotic proteins (P53 and BAX) and caspases but downregulated BCL-2. Nitazoxanide downregulated Wnt/ß-catenin/glycogen synthase kinase-3ß (GSK-3ß) signaling and PCNA staining in the current mouse model. Hence, our findings highlighted the cytotoxic effect of nitazoxanide and pointed out the effect on Wnt/ß-catenin/GSK-3ß signaling.

Surgical Loupe at 4.0× Magnification in Pancreaticoduodenectomy-Does It Affect the Surgical Outcomes? A Propensity Score-Matched Study.

BACKGROUND: There is paucity of data about the impact of using magnification on rate of pancreatic leak after pancreaticoduodenectomy (PD). The aim of this study was to show the impact of using magnifying surgical loupes 4.0× EF (electro-focus) on technical performance and surgical outcomes of PD. PATIENTS AND METHOD: This is a propensity score-matched study. Thirty patients underwent PD using surgical loupes at 4.0× magnification (Group A), and 60 patients underwent PD using the conventional method (Group B). The primary outcome was postoperative pancreatic fistula. Secondary outcomes included operative time, intraoperative blood loss, postoperative complications, mortality, and hospital stay. RESULTS: The total operative time was significantly longer in the loupe group ( P = .0001). The operative time for pancreatic reconstruction was significantly longer in the loupe group ( P = .0001). There were no significant differences between both groups regarding hospital stay, time to oral intake, total amount of drainage, and time of nasogastric tube removal. Univariate and multivariate analyses demonstrated 3 independent factors of development of postoperative pancreatic fistula: pancreatic duct <3 mm, body mass index >25, and soft pancreas. CONCLUSION: Surgical loupes 4.0× added no advantage in surgical outcomes of PD with regard to improvement of postoperative complications rate or mortality rate.

Predictors of long-term survival after pancreaticoduodenectomy for peri-ampullary adenocarcinoma: A retrospective study of 5-year survivors.

BACKGROUND: Pancreaticoduodenectomy (PD) is the standard curative treatment for periampullary tumors. The aim of this study is to report the incidence and predictors of long-term survival (≥ 5 years) after PD. METHODS: This study included patients who underwent PD for pathologically proven periampullary adenocarcinomas. Patients were divided into 2 groups: group (I) patients who survived less than 5 years and group (II) patients who survived ≥ 5 years. RESULTS: There were 47 (20.6%) long-term survivors (≥ 5 years) among 228 patients underwent PD for periampullary adenocarcinoma. Patients with ampullary adenocarcinoma represented 31 (66.0%) of the long-term survivors. Primary analysis showed that favourable factors for long-term survival include age < 60 years old, serum CEA < 5 ng/mL, serum CA 19-9 < 37 U/mL, non-cirrhotic liver, tumor size < 2 cm, site of primary tumor, postoperative pancreatic fistula, R0 resection, postoperative chemotherapy, and no recurrence. Multivariate analysis demonstrated that CA 19-9 < 37 U/mL [OR (95% CI) = 1.712 (1.248-2.348), P = 0.001], smaller tumor size [OR (95% CI )= 1.335 (1.032-1.726), P = 0.028] and Ro resection [OR (95% CI) = 3.098 (2.095-4.582), P < 0.001] were independent factors for survival ≥ 5 years. The prognosis was best for ampullary adenocarcinoma, for which the median survival was 54 months and 5-year survival rate was 39.0%, and the poorest was pancreatic head adenocarcinoma, for which the median survival was 27 months and 5-year survival rate was 7%. CONCLUSIONS: The majority of long-term survivors after PD for periampullary adenocarcinoma are patients with ampullary tumor. CA 19-9 < 37 U/mL, smaller tumor size, and R0 resection were found to be independent factors for long-term survival ≥ 5 years.

Impact of bone-marrow-derived mesenchymal stem cells on adriamycin-induced chronic nephropathy.

OBJECTIVES: To study the effects of bone-marrow-derived mesenchymal stem cells (BM-MSCs) on adriamycin (ADR)-induced chronic nephropathy in rats. METHODS: 60 male Sprague-Dawley rats were distributed among 3 groups (20 rats each): (i) the negative control group, which was normal rats that received saline (vehicle); (ii) the positive control (ADR) group, which was rats that received 2 intravenous injections of ADR into the penile vein at 14 day intervals without treatment, and (iii) the MSC group, which were rats treated as for the ADR group that were also given 2 intravenous injections of MSCs (5 days after each ADR injection). RESULTS: ADR caused a significant reduction in animal body mass, survival rate, hemoglobin (Hb) content, serum albumin, and renal GSH, and significantly increased serum levels of triglycerides, cholesterol, urinary protein excretion and kidney injury molecule-1 (KIM-1), renal MDA, as well as caspase-3 expression and glomerular and tubulointerstitial damage compared with the negative control group. MSC treatment failed to improve animal survival rate, body mass, Hb level, proteinuria, or hypoalbuminemia; however, it mildly improved the serum BUN, hyperlipidemia, caspase-3 expression, urinary levels of KIM-1, renal oxidative stress markers, and glomerular and tubulointerstitial damage score. CONCLUSION: administration of BM-MSCs during induction of ADR nephropathy provides partial protection, which could be due to improvements in the levels of of endogenous antioxidants, reduction of apoptosis, and maintenance of the integrity of the glomerular membrane.

Prognostic factors affecting survival after pancreaticoduodenectomy for pancreatic adenocarcinoma (single center experience).

BACKGROUND: Pancreatic cancer is considered to have the worst prognosis of the periampullary carcinomas. This retrospective study was to determine prognostic factors for survival after pancreaticoduodenectomy in patients had pancreatic carcinoma. METHODS: We retrospectively studied all patients who underwent PD for pancreatic adenocarcinoma originating from the head, neck or uncinate process from January 1996 to January 2011 in our center. Preoperative variables, intraoperative variables and postoperative variables were collected. RESULTS: The study included 480 patients (282 males and 198 females with a median age of 53 years. At the time of analysis, 180 (37.5%) patients were still alive. The median survival was 19 months. This corresponded to a 1-, 3-, and 5-year actuarial survival of 44 %, 20%, and 15% respectively. Mass size less than 2 cm (P=0.0001), lymph node ratio (P=0.0001), safety margin (P=0.0001), perineural, perivascular infiltration, age above 60 years (P=0.03), gender, preoperative bilirubin, SGPT, liver status, pre and postoperative CEA, CA19- 9 (P=0.0001) were significant predictors of survival. CONCLUSION: Mass size less than 2 cm, lymph node ratio, safety margin, perineural, perivascular infiltration, age above 60 years, gender, liver status, pre and postoperative CEA, CA19-9 are important predictors of survival in patients undergoing PD for pancreatic cancer.

Evaluation of stresses on mandible bone and prosthetic parts in fixed prosthesis by utilizing CFR-PEEK, PEKK and PEEK frameworks.

Fixed prostheses are appropriate treatment solutions for edentulous patients. In fixed prostheses, following "All on four", titanium frameworks are commonly used to support the implants. However, the limitations of titanium have prompted researchers to search for alternative materials (e.g. polymers). This study applied finite element investigation to evaluate the stress distribution in the parts of fixed prosthesis and the surrounding bone tissue, using polymeric frameworks in place of titanium, and different densities of spongy bone. As, the success of fixed prosthesis was predicted to be influenced also by bone quality, particularly spongy bone density. Fixed prosthesis was constructed on edentulous mandible, then different frameworks (CFR-PEEK 60%, CFR-PEEK 30%, PEKK, and PEEK) were stimulated instead of titanium, under 300N unilateral and bilateral forces. Three densities of spongy bone were stimulated which are normal, low and high. The choice of framework material depended on the density of spongy bone. Moreover, PEEK framework showed the lowest stress values on bone tissues and the highest stress values on mucosa. All frameworks could be used in the fixed prosthesis, in the cases of normal and high densities of spongy bone. In low-density case, soft frameworks (PEKK and PEEK) were recommended to reduce the stresses generated on bone tissues.

Metformin suppresses LRG1 and TGFß1/ALK1-induced angiogenesis and protects against ultrastructural changes in rat diabetic nephropathy.

Diabetic nephropathy (DN) has high prevalence and poor prognosis which make it a research priority for scientists. Since metformin, a hypoglycaemic drug, has been found to prolong the survival of mice with DN. This study aims at investigating the molecular mechanisms leading to DN in rats and to explore the role of leucine-rich α-2-glycoprotein-1 (LRG1), activin-like kinase1 (ALK1), and transforming growth factor-ß (TGFß1) in the pathologic alterations seen in DN. The aim was also extended to explore the protective action of metformin against DN in rats and its influence on LRG1and ALK1/TGFß1 induced renal angiogenesis. 24 male rats were used. Rats were assigned as, the vehicle group, the diabetic control group and diabetic + metformin (100 and 200 mg/kg) groups. Kidney samples were processed for histopathology, immunohistochemistry and biochemical analysis. Bioinformatic analysis of studied proteins was done to determine protein-protein interactions. Metformin reduced serum urea and creatinine significantly, decreased the inflammatory cytokine levels and reduced LRG1, TGFß1, ALK1 and vascular endothelial growth factor (VEGF) proteins in rat kidneys. Bioinformatic analysis revealed interactions between the studied proteins. Metformin alleviated the histopathological changes observed in the diabetic rats such as the glomerular surface area and increased Bowman's space diameter. Metformin groups showed decreased VEGF immunostaining compared to diabetic group. Metformin shows promising renoprotective effects in diabetic model that was at least partly mediated by downregulation of LRG1 and TGFß1/ALK1-induced renal angiogenesis. These results further explain the molecular mechanism of metformin in DN management.

Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury-Insight into Oxidative Injury/Inflammation/Apoptosis Modulation.

In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium-glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-κB and TNF-α expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune-histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury.

Synthesis and characterization of berberine-loaded chitosan nanoparticles for the protection of urethane-induced lung cancer.

Lung cancer is one of the most common types of malignant tumors of the respiratory system and has the highest rates of incidence and mortality of malignant tumors. This study aimed to synthesize and characterize berberine-loaded chitosan nanoparticles (BBR-COSNPs) and to evaluate their protective effects against urethane-induced lung cancer. Forty male albino mice were divided into four groups, with the first serving as a negative control and the other three groups were injected intraperitoneally with urethane (1 mg/kg b.w) each other day for 1 week then group 2 was served as a positive control, however, groups 3 and 4 were treated orally with a daily dose of BBR or BBR-COSNPs (75 mg/kg b.w) for 10 consecutive weeks. Blood and lung tissue samples are collected for laboratory assay. The BBR-COSNPs were spherical, with an average particle size of 45.56 nm and zeta potential of 39.82 1.82 mV. The in vivo data demonstrated that mice given urethane alone had a significant increase in MDA, NO, NF-κB level, HIF1-α, and COX-2-positive expression in the lung tissue and serum VEGFR2, ALT, AST, urea, and creatinine accompanied with a significant decrease in GSH, SOD, caspase 9 in the lung tissue and serum BAX. Co-treatment with BBR-COSNPs suppressed lung cancer growth and promoted apoptosis by modulating serum BAX and lung caspase 9 gene expressions. In addition, BBR-COSNPs inhibited tumor angiogenesis by reduction in levels of serum VEGFR2 and lung HIF 1 gene expression. It is possible to conclude that BBR-COSNPs can be used in oral administration formulations for lunganticancer therapy.

Energy and exergy assessment of new designed solar air heater of V-shaped transverse finned absorber at single- and double-pass flow conditions.

Flat plate solar collector is one of the main solar collectors that has a simple structure, reliable operation, large heat preoccupation area, and low cost. Its drawback is the low heat transfer between the working air and the absorber plate. A solar air heater of V-shaped transverse finned absorber having new designed absorber plate of lateral gaps and central holes to enhance its performance is investigated experimentally at single-pass and double-pass airflow conditions. Moreover, the energy and exergy assessment of its performance was studied and compared with traditional longitudinal finned heater having the same fin surface area and construction except for the absorber plate design. The study is investigated at air mass flow rates of 0.025, 0.05, and 0.075 kg/s. Findings show that the new heater achieves maximum outlet temperature rising of 28.2 °C at 0.025 kg/s and double-pass flow. Moreover, it has an average daily energy efficiency of 88.5%, 81.88%, and 61.3% at mass flow rates of 0.075, 0.05, and 0.025 kg/s with increments of 9.4%, 13.3%, and 9.66%, respectively, compared to the longitudinal finned heater. Additionally, it achieves exergy efficiencies of 2.5%, 2.1%, and 1.7% at mass flow rates of 0.025, 0.05, and 0.075 kg/s with increments 18%, 25.7%, and 18.2%, respectively, relative to longitudinal finned heater. Furthermore, the new heater design possesses greater energy efficiency comparing to former studied SAH designs.

Ingestion of mannose ameliorates thioacetamide-induced intrahepatic oxidative stress, inflammation and fibrosis in rats.

BACKGROUND AND AIMS: The monosaccharide mannose has gained recent interest for its beneficial effect against certain inflammatory disorders. Nevertheless, the influence of mannose on experimentally-induced liver fibrosis and the ensued inflammation is still not fully clear to date. MAIN METHODS: The current study investigated the outcomes of treating rats with mannose (0.2 ml of 20% w/v, oral gavage) 30 min before the twice weekly intoxication with thioacetamide (TAA) (200 mg/kg, intraperitoneal) for a total period of 8 weeks. KEY FINDINGS: The data indicated that mannose markedly dampened TAA-induced liver fibrosis, as indicated by lowering the fibrotic bridges shown by Masson's trichrome staining. This effect was consistent with reducing TAA-induced hepatocellular injury, as evidenced biochemically (serum ALT and AST activities) and pathologically (necroinflammation score). These hepatoprotective effects mediated by mannose were attributed to i) reversing TAA-induced rise in malondialdehyde (MDA) and decrease in reduced glutathione (GSH) expressions in the liver, ii) limiting TAA-induced release of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), iii) impairing TAA-induced activation of hepatic stellate cells by downregulating α-smooth muscle actin expression (α-SMA), and more importantly, iv) dampening TAA-induced fibrogenesis driven by transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF). SIGNIFICANCE: Mannose may be a valuable candidate for preventing oxidative stress, inflammation and fibrogenesis in the liver.

Application of the Box-Behnken design for the production of soluble curcumin: Skimmed milk powder inclusion complex for improving the treatment of colorectal cancer.

The main objective of this study was to develop a soluble product of the practically insoluble curcumin (CMN) to treat colorectal cancer more effectively than with pure CMN. To improve the solubility of CMN, various hydrophilic carriers of skimmed milk powder (SMP), polyvinylpyrrolidone (PVP), and mannitol (MNT) were utilized to prepare solid dispersion (SD) binary complexes. The prepared complexes were characterized in terms of their aqueous solubility and in vitro drug release and analyzed by Fourier transform infrared spectrophotometry, powder X-ray diffractometry, scanning electron microscopy, dynamic light scattering, and the novel dyeing test. Based on this characterization, the best SD complex was optimized using the Box-Behnken design (RSM-BBD). These results showed that the solubility of CMN was greatly improved in combination with SMP. The SD of CMN with SMP produced significantly improved solubility (0.646 ± 0.024 mg/ml) and dissolution (54.94 ± 3.21% at 5 min). Further, solid-state characterization revealed that the complex exhibited intermolecular inclusion of the drug and carrier. Also, the complex did not undergo any chemical modification owing to its amorphous form, and the novel dye test showed better coloring impact, indicating the solubility of CMN. The in vitro cytotoxicity of the complex showed that 50% inhibition (IC50) of SW480 and Caco-2 cells was achieved at a considerably lower concentration than that of pure CMN. Flow cytometry analysis confirmed that the cell cycle arrest was at G2/M phase (43.26% and 65.14%), and DNA fragmentation analysis investigation confirmed that the complex induced more DNA damage during apoptosis.

Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: A case-control study.

BACKGROUND/OBJECTIVE: The potential benefit of preoperative biliary drainage (PBD) on postoperative outcomes remains controversial. The aim of this study was to elucidate surgical outcomes of pancreaticoduodenectomy (PD) in patients with PBD and to show the impact of bilirubin level. METHODS: We retrospectively studied all patients who underwent PD in our center between January 2003 and June 2015. Patients were divided into: Group A (PBD) and Group B (no PBD). The primary outcome was the rate of postoperative complication. RESULTS: A total of 588 cases underwent PD. Group A included 314 (53.4%) patients while Group B included 274 (46.6%) patients. The overall incidence of complications and its severity were higher in Group A (p = 0.03 and p = 0.02). There was significant difference in the incidence of postoperative pancreatic fistula (p = 0.002), delayed gastric emptying (p = 0.005), biliary leakage (p = 0.04), abdominal collection (p = 0.04), and wound infection (p = 0.04) in Group A. The mean length of hospital stay was significantly longer in Group A than in Group B (12.86 ± 7.65 days vs. 11.05 ± 7.98 days, p = 0.01). No significant impact of preoperative bilirubin level on surgical outcome was detected. CONCLUSION: PBD before PD was associated with major postoperative complications and stent-related complications.

Genetic Polymorphisms of Fas/FasL Promoter Associated with Hepatitis C cirrhosis and HCC

Aim: The present study was performed to determine any associations of genetic polymorphisms of Fas/FasL promoter regions, at Fas670 and Fas1377 and FasL844, with hepatitis C cirrhosis and HCC, with a focus on severity of disease. Methods: Totals of 120 patients with cirrhosis and 101 with hepatocellular carcinoma (HCC) were enrolled. All had chronic HCV infection as indicated by positive anti-HCV antibodies and positive HCV RNA on real time PCR. One hundred healthy control subjects were also included in the study. Patients were subjected to full clinical, radiological and histopathological examinations. In addition to routine laboratory tests for liver function tests, Fas670 and Fas1377 and FasL844 genetic polymorphisms of Fas/FasL promoter regions were assessed by RFLP-PCR (restriction fragment length polymorphism with polymerase chain reaction). Results: Significant higher levels of the AG genotype in Fas670 and Fas1773 were observed in patients with cirrhosis and HCC (P=0.0001) as compared to control subjects. In addition, the CC genotype in FASL844 was also more common in patients (P=0.01). Furtehrmore, there was a significant association of substitution of A by G alleles in Fas670 and Fas1773 with advanced BCA staging (P=0.02, P=0.0001 respectively) and larger tumor size >5cm (P=0.01, P=0.0001 respectively) and in Fas670 with advanced pathological grading (P=0.0001). Moreover the CC genotype of FASL844 was significantly linked with advanced BCA, large tumor size >5cm and advanced pathological grading (P=0.0001). Conclusion: The findings of the present study highlight associations of genetic polymorphisms of promoter regions in Fas and Fas L with cirrhosis and HCC associated with chronic HCV. Support was also obtained for the conclusion that single nucleotide polymorphisms of the Fas/ FasL system impact on clinical and histopathological grading of HCCs. Further large scale studies are recommended for confirmation.

Open Cholecystectomy Has a Place in the Laparoscopic Era: a Retrospective Cohort Study.

Laparoscopic cholecystectomy (LC) is considered the gold standard for treatment of symptomatic gallbladder stones and has replaced the traditional open cholecystectomy (OC). The aim of this study is to evaluate the proper indications of the primary OC and conversion from LC and their predictive factors. This study includes all patients who underwent cholecystectomy between January 2011 and June 2016, whether open from the start (group A), conversion from laparoscopic approach (group B), or laparoscopic cholecystectomy (group C). There were 3269 patients underwent cholecystectomy. LC was completed in 3117 (95.4%) patients. The overall conversion rate was 83 (2.5%). The main two causes of conversion were adhesion in 35 (42.2%) patients and unclear anatomy in 29 (34.9%) patients. Primary OC was indicated in 69 (2.1%) patients due to previous history of upper abdominal operations in 16 (23.2%) patients and anesthetic problem in 21 (30.4%) patients. Age >60 years, male sex, diabetic patients, history of endoscopic retrograde cholangiopancreatography, dilated common bile duct, gallbladder status, adhesion, and previous upper abdominal operation were demonstrated to be independent risk factors for OC. Open cholecystectomy still has a place in the era of laparoscopy. Conversion should not be a complication, but it represents a valuable choice to avoid an additional risk. Safe OC required training because of the causes of conversion, usually unsafe anatomy, occurrence of complications, or anesthetic problems, in order to prevent disastrous complications.

Surgical outcomes of pancreaticoduodenectomy in young patients: A case series.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex procedure for management periampullary neoplasms The aim of our work is to report the surgical outcomes after PD in young adult (YA) (<35 years) and to compare it to a adult patients who underwent PD. METHODS: We retrospectively analyzed the data of all patients who underwent PD in the period from January 1993 to December 2016. The primary outcome was the rate of total postoperative complications. Secondary outcomes included postoperative pathology, exocrine and endocrine function and survival rate. RESULTS: 58/975 patients (5.9%) were YA and the majority of them were females. The incidence of post-operative complications in the YA was comparable to that in the adult group. Delayed gastric emptying developed significantly in adult group than YA group (0.008). The overall survival was significantly higher in the YA (P = 0.0001). The most common pathology in the YA was adenocarcinoma (41.4%) and solid pseudopapillary tumor (SPT) (29.3%). No significant difference as regards postoperative pancreatic exocrine and endocrine function in both groups. CONCLUSION: PD in YA when performed in tertiary centers with good surgical experience is safe. The most common pathological diagnosis in the YA was adenocarcinoma followed by SPT.

Impact of obesity on surgical outcomes post-pancreaticoduodenectomy: a case-control study.

BACKGROUND: Obesity is a growing worldwide epidemic. There is association between obesity and pancreatic cancer risk. However, the impact of obesity on the outcome of pancreatoduodenectomy (PD) is controversial. The aim of this study was to elucidate effect of obesity on surgical outcomes of PD. STUDY DESIGN: A case-control study. PATIENT AND METHODS: We retrospectively studied all patients who underwent PD in our center between January 2000 and June 2012. Patients were divided into two groups; Group A (patients with BMI <25) and Group B (patients with BMI > 25). Preoperative demographic data, intraoperative data, and postoperative details were collected. RESULTS: Only 112/471 patients (25.9%) had BMI > 25. The median intraoperative blood loss was more in overweight patients (P = 0.06). The median surgical time in group B was significantly longer than that in group A (P = 0.003). The overall incidence of complications was higher in the overweight group (P = 0.001). The severity of complications was also higher in the overweight group (P = 0.0001). Postoperative pancreatic fistula (POPF) (P = 0.0001) and hospital mortality (P = 0.001) were significantly higher in overweight patients. Oral intake was significantly delayed in overweight patients in comparison to normal weight group (P = 0.02). Postoperative stay was significantly longer in overweight patients (P = 0.0001). CONCLUSION: PD is associated with an increased risk of postoperative morbidity in overweight patient. Overweight patients must not be precluded from undergoing PD. However, operative techniques and pharmacological prophylaxis to decrease POPF should be considered in overweight patients.