Mostafa A. Hamad

Laparoscopic cholecystectomy under spinal anesthesia with nitrous oxide pneumoperitoneum: a feasibility study.

Background: Spinal anesthesia has been successfully used to perform various laparoscopic procedures. However, laparoscopic cholecystectomy under spinal anesthesia has not been reported. Is this feasible? Methods: Ten successive laparoscopic cholecystectomies were performed under spinal anesthesia. The surgical technique was modified using nitrous oxide insufflation, lower levels of intraabdominal pressure, modified trocar sites, and minimal surgical manipulation. We used spinal anesthesia by intrathecal hyperbaric 10–12 mg bupivacaine with 10 µg fentanyl to give an anesthetic level at T8–T6. Results: The mean age was 39.3 years and there were four females. Only one patient was converted to general anesthesia due to intolerable shoulder pain. One patient vomited intraoperatively. Nine patients considered the procedure well tolerated under spinal anesthesia. The mean operative time was 47.4 min. Postoperatively, there were minimal pain and no vomiting. Conclusions: Laparoscopic cholecystectomy can be performed successfully under spinal anesthesia and is well tolerated.

Major biliary complications in 2,714 cases of laparoscopic cholecystectomy without intraoperative cholangiography: a multicenter retrospective study

BackgroundThe ongoing debate between routine and selective users of intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC) has not yet come to an end. Routine users argue that IOC decreases the rate of biliary complications such as bile duct injury, biliary leak and missed common bile duct (CBD) stones, a claim that selective users do not fully support. On the other hand, a third policy that was adopted by many other centers is performing LC without IOC. In this retrospective study, we are exploring the results of a relatively large multicenter series of LC without IOC regarding major biliary complications.MethodsWe performed a retrospective analysis of LC cases operated by experienced laparoscopic surgeons, without resorting to IOC, in four surgical units of university hospitals in Egypt during a 6-year period (January 2004 through December 2009). Excluded from the study were cases with positive predictors of CBD stones, namely, sonographically detected CBD dilatation and/or CBD stones, elevated bilirubin and/or alkaline phosphatase, persistent biliary pancreatitis, cholangitis, and those who had preoperative magnetic resonance cholangiography.ResultsOf the 2,955 cases of LC reviewed, 241 were excluded, leaving 2,714 cases enrolled in the study. Fifty-five cases (2%) were converted to open surgery. Five cases (0.18%) had major bile duct injuries requiring surgical repair. Postoperative bile leakage was encountered in seven cases (0.26%). Missed CBD stones were reported in six cases (0.22%). There was no perioperative mortality in the present study.ConclusionLC can be performed safely without the use of IOC, with acceptable low rates of biliary complications provided that proper detection of patients with silent CBD stones is done and facilities for pre- and postoperative endoscopic retrograde cholangiopancreatography are available.

Laparoscopic versus open cholecystectomy in patients with liver cirrhosis: a prospective, randomized study.

BACKGROUND Gallstones are more common in patients with liver cirrhosis than in healthy individuals. Higher morbidity and mortality were reported in cirrhotic patients with either laparoscopic or open cholecystectomy. The aim of this study was to compare laparoscopic and open cholecystectomy in cirrhotic patients with symptomatic cholelithiasis in a prospective, randomized manner. MATERIALS AND METHODS Thirty patients with symptomatic cholelithiasis associated with Child-Pugh class A or B liver cirrhosis were prospectively and randomly grouped equally to either laparoscopic or open cholecystectomy. The two groups were compared regarding operative time, morbidity, mortality, postoperative liver function, and hospital stay. RESULTS The two groups were comparable regarding demographic data, preoperative and postoperative Child-Pugh scoring, mean operative time (57.3 minutes for laparoscopic and 48.5 for open), and complications (33.3% for each). Hospital stay was shorter for the laparoscopic group. One conversion (6.7%) to open surgery was reported. No periopertive mortality occurred in either group. CONCLUSIONS For Child-Pugh class A and B cirrhotics, laparoscopic cholecystectomy is comparable to the open approach regarding operative time, morbidity, mortality, and effect on liver function, but with shorter hospital stay. Considering the other well-documented advantages of the laparoscopic approach, namely, less pain, earlier mobilization and feeding, and better cosmoses, laparoscopic cholecystectomy would be the first choice in cirrhotic patients.

Laparoscopic sutured anastomosis of the bowel

Background: Even though the safety and efficacy of sutured anastomosis have been proved in open surgery, laparoscopic sutured anastomosis is rarely performed because it is difficult and time-consuming. We aim at description of a standardized technique for laparoscopic sutured anastomosis of the bowel and definition of its learning curve. Methods: Fifty-six laparoscopic sutured anastomoses of cow small intestine were performed in a laparoscopic simulator. In a survival animal trial, 10 end-to-end, 2 gastrojejunostomy, 2 cholecystojejunostomy, 2 colocolic, and one side-to-side anastomoses were performed, using the same technique. Results: In the survival cases, we had no leaks or obstruction, minimal adhesions, and only one stenotic gastrojejunostomy. The mean end-to-end anastomotic time was 50 min. The technique was suitable for most sites in the GIT. The learning phase required 40 anastomoses in the simulator. Conclusions: The described technique seems relatively fast, safe, and universal, and it needs about 40 anastomoses to be mastered.

In vitro and in vivo evaluation of biologically synthesized silver nanoparticles for topical applications: effect of surface coating and loading into hydrogels

In the present study, silver nanoparticles (AgNPs) were synthesized via biological reduction of silver nitrate using extract of the fungus Fusarium verticillioides (green chemistry principle). The synthesized nanoparticles were spherical and homogenous in size. AgNPs were coated with polyethylene glycol (PEG) 6000, sodium dodecyl sulfate (SDS), and β-cyclodextrin (β-CD). The averaged diameters of AgNPs were 19.2±3.6, 13±4, 14±4.4, and 15.7±4.8 nm, for PEG-, SDS-, and β-CD-coated and uncoated AgNPs, respectively. PEG-coated AgNPs showed greater stability as indicated by a decreased sedimentation rate of particles in their water dispersions. The antibacterial activities of different AgNPs dispersions were investigated against Gram-positive bacteria (methicillin-sensitive and methicillin-resistant Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) by determination of the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). MIC and MBC values were in the range of 0.93–7.5 and 3.75–15 µg/mL, respectively, which were superior to the reported values in literature. AgNPs-loaded hydrogels were prepared from the coated-AgNPs dispersions using several gelling agents (sodium carboxymethyl cellulose [Na CMC], sodium alginate, hydroxypropylmethyl cellulose, Pluronic F-127, and chitosan). The prepared formulations were evaluated for their viscosity, spreadability, in vitro drug release, and antibacterial activity, and the combined effect of the type of surface coating and the polymers utilized to form the gel was studied. The in vivo wound-healing activity and antibacterial efficacy of Na CMC hydrogel loaded with PEG-coated AgNPs in comparison to the commercially available silver sulfadiazine cream (Dermazin®) were evaluated. Superior antibacterial activity and wound-healing capability, with normal skin appearance and hair growth, were demonstrated for the hydrogel formulations, as compared to the silver sulfadiazine cream. Histological examination of the treated skin was performed using light microscopy, whereas the location of AgNPs in the skin epidermal layers was visualized using transmission electron microscopy.

Nanomedicine in management of hepatocellular carcinoma: Challenges and opportunities.

Hepatocellular carcinoma is the second leading cause of cancer deaths worldwide. It is characterized by unique features that can be utilized for selective and targeted therapy, which aids in preserving healthy tissues from deteriorating effects of traditional chemotherapeutics. In this minireview, a brief overview of recent drug delivery attempts for the management of hepatocellular carcinoma with the aid of nanomedical structures is presented. The beneficial impact of nanomaterials in terms of prolonged retention in blood and target sites, controlled biodistribution and improved stability of the encapsulated payloads, will be described, together with the possibility of incorporating more than one cargo into the same nanostructure. Incorporation of stimuli‐responsive components, decoration with targeting moieties and the use of molecularly targeted drugs for treatment of hepatocellular carcinoma are also highlighted.

Polyphosphoester nanoparticles as biodegradable platform for delivery of multiple drugs and siRNA

Delivery of multiple therapeutics and/or diagnostic agents to diseased tissues is challenging and necessitates the development of multifunctional platforms. Among the various strategies for design of multifunctional nanocarriers, biodegradable polyphosphoester (PPE) polymers have been recently synthesized via a rapid and simple synthetic strategy. In addition, the chemical structure of the polymer could be tuned to form nanoparticles with varying surface chemistries and charges, which have shown exceptional safety and biocompatibility as compared to several commercial agents. The purpose of this study was to exploit a mixture of PPE nanoparticles of cationic and neutral surface charges for multiple delivery of anticancer drugs (ie, sorafenib and paclitaxel) and nucleic acids (ie, siRNA). Cationic PPE polymers could efficiently complex siRNA, and the stability of the nanoparticles could be maintained in physiological solutions and upon freeze-drying and were able to deliver siRNA in vivo when injected intravenously in mice. Commercially available cationic polyethylenimine polymer had LD50 of ca. 61.7 mg/kg in mice, whereas no animal died after injection of the cationic PPE polymer at a dose of >130 mg/kg. Neutral PPE nanoparticles were able to encapsulate two hydrophobic drugs, namely, sorafenib and paclitaxel, which are commonly used for the treatment of hepatocellular carcinoma. Mixing the neutral and cationic PPE nanoparticles did not result in any precipitation, and the size characteristics of both types of nanoparticles were maintained. Hence, PPE polymers might have potential for the delivery of multiple drugs and diagnostic agents to diseased tissues via simple synthesis of the individual polymers and assembly into nanoparticles that can host several drugs while being mixed in the same administration set, which is of importance for industrial and clinical development.

Ultrahigh antibacterial efficacy of meropenem-loaded chitosan nanoparticles in a septic animal model

Antimicrobial resistance is one of the most significant health challenges worldwide. Meropenem is a broad spectrum beta-lactam antibiotic that possesses high activity against Gram-positive and Gram-negative bacteria. However, it has a short plasma half-life, and thus requiring frequent administration of high doses. For the first time, meropenem-loaded chitosan nanoparticles were prepared and evaluated as a potential tool to overcome antimicrobial resistance and to improve pharmacokinetics of the drug. Spherical nanosized particles were prepared and demonstrated ultrahigh encapsulation efficiency of meropenem (i.e. 76.3%). The nanoparticles could be stored in a freeze-dried powdered form while maintaining their physicochemical characteristics. In vitro, higher antibacterial activities of the drug-loaded nanoparticles were observed against methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae, as compared to the free drug. The nanoparticles were then tested in a septic rat model of Klebsiella pneumoniae and showed exceptional improvement of survival and bacterial clearance, as compared to the animals treated with the free drug. Hence, meropenem-loaded chitosan nanoparticles might have great potential for overcoming antimicrobial resistance.

Novel technique for biliary reconstruction using an isolated gastric tube with a vascularized pedicle: a live animal experimental study and the first clinical case

BackgroundBiliary tract reconstruction continues to be a challenging surgical problem. Multiple experimental attempts have been reported to reconstruct biliary defects with different materials and variable outcome. Our aim was to evaluate a new method for biliary reconstruction using an isolated pedicled gastric tube in a live animal trial and also to present the first clinical case.MethodsSeven mongrel dogs underwent biliary reconstruction using gastric tube harvested, completely separated from the greater curvature, and based on a vascularized pedicle with the right gastroepiploic vessels. The tube was interposed between the common bile duct (CBD) and the duodenum. Postoperative mortality, morbidity, liver functions, gross and microscopic histological picture were assessed. The first clinical case was also presented where, in a patient with post-cholecystectomy biliary injury, an isolated pedicled gastric tube was interposed between the proximal and distal ends of the CBD.ResultsOne dog did not recover from anesthesia and another one died postoperatively from septic peritonitis. Five dogs survived the procedure and showed uneventful course and no cholestasis. The mean anastomotic circumference was 4.8 mm (range 4-6) for CBD anastomosis and 6.2 mm (range 5-7) for duodenal anastomosis. Histologically, anastomotic sites showed good evidence of healing. In the first clinical case, the patient showed clinical and biochemical improvement. Endoscopic retrograde cholangiography was feasible and assured patent biliary anastomoses.ConclusionIn mongrel dogs, biliary reconstruction using pedicled gastric tube interposition between CBD and duodenum is feasible with satisfactory clinical results, anastomotic circumference and histological evidence of healing. The technique is also feasible in human and seems to be promising.

Poly(glycerol methacrylate)-based degradable nanoparticles for delivery of small interfering RNA

Abstract Nucleic acids therapeutic efficiency is generally limited by their low stability and intracellular bioavailability, and by the toxicity of the carriers used to deliver them to the target sites. Aminated poly(glycerol methacrylate) polymers are biodegradable and pH-sensitive polymers that have been used previously to deliver antisense oligonucleotide and show high transfection efficiency. The purpose of this study is to compare the efficiency and toxicity of aminated linear poly(glycerol methacrylate) (ALT) biodegradable polymer to the most commonly used cationic degradable (i.e. chitosan) and non-degradable (i.e. polyethylenimine (PEI)) polymers for delivery of short interfering RNA (siRNA). ALT, PEI and chitosan polymers were able to form nanosized particles with siRNA. Size, size-distribution and zeta-potential were measured over a wide range of nitrogen-to-phosphate (N/P) ratios, and the stability of the formed nanoparticles in saline and upon freeze-drying was also assessed. No significant cytotoxicity at the range of the tested concentrations of ALT and chitosan nanoparticles was observed, whereas the non-degradable PEI showed significant toxicity in huh-7 hepatocyte-derived carcinoma cell line. The safety profiles of the degradable polymers (ALT and chitosan) over non-degradable PEI were demonstrated in vitro and in vivo. In addition, ALT nanoparticles were able to deliver siRNA in vivo with significantly higher efficiency than chitosan nanoparticles. The results in the present study give evidence of the great implications of ALT nanoparticles in biomedical applications due to their biocompatibility, low cytotoxicity, high stability and simple preparation method.