Mohammad Khalifeh

Comparative Pharmacokinetics and Metabolic Pathway of Gemcitabine During Intravenous and Intra-arterial Delivery in Unresectable Pancreatic Cancer Patients

AbstractBackground: To study the pharmacokinetics and clinical outcome of gemcitabine (2′-2′-difluoro-deoxcytidine [dFdC]) during intra-arterial versus intravenous delivery in locally advanced and regionally metastatic pancreatic cancer. Patients and methods: Seven patients with unresectable pancreatic cancer received escalating intra-arterial doses of gemcitabine ranging from 800 to 1400 mg/m2, after selective embolisation of all pancreatic blood supply, except for the tumour-feeding arteries. Four patients received intravenous gemcitabine (control). Venous blood samples at different time intervals were taken throughout 270 minutes for pharmacokinetic analyses of gemcitabine and its inactive metabolite 2′-2′-difluorodeoxyuridine (dFdU). Results: Pharmacokinetic data revealed differences in plasma concentrations between intra-arterial and intravenous delivery routes. The plasma concentration-time curve of gemcitabine during and after cessation of intra-arterial pancreatic target administration through the proximal splenic artery showed a profile with an area under the plasma concentration-time curve from 0 to 270 minutes (intra-arterial 29.0 + 0.4 vs intravenous 331.0 + 2.7 ng · min/mL; p < 0.0001) and peak plasma concentration (intra-arterial 1.1 + 0.2 vs intravenous 7.6 + 2.0 ng/mL; p < 0.0001) significantly lower than that for the corresponding systemic intravenous route. A plot of In (% of dose) versus time showed a bi-compartmentalised metabolic model for intravenous administration of gemcitabine, one indicating rapid conversion of gemcitabine to dFdU, and another at a significantly lower affinity resulting in no conversion. Hence, this could be the main reason why dFdU was not detected in the systemic circulation during pancreatic intra-arterial target delivery. Furthermore, during intravenous administration a pseudo first-order rate constant (≈0.20 min-1) for in vivo conversion of gemcitabine to dFdU was estimated, indicating a rapid cellular deamination which was not shown in the intra-arterial route. Clinically, one patient had a partial response and six patients had a stable disease after intra-arterial administration of gemcitabine. The median time to disease progression was 4 months and the median overall survival was 5 months. One patient survived for 26 months. No grade III or IV toxicity was documented. Conclusion: Intra-arterial administration of gemcitabine has a major advantage related to reduced toxicity as increasing the dose through this administration route will eventually result in pancreatic cellular drug target delivery prior to systemic availability. Despite the low number of patients recruited, the clinical results are encouraging and this approach should be tested in a randomised study.

Penetrating trauma to the abdominal vessels

Between January 1975 and December 1989, 1860 patients were admitted to the American University of Beirut Medical Centre with abdominal injuries. Their mean age was 23 years. Of these patients 107 had vascular injuries (an incidence of 6%). Bullets were the most common injurious agents (72%), followed by shrapnel (22%). There were 28 arterial and 113 venous injuries. All patients presented to the emergency unit within 5 h of injury (mean 45 min) and were surgically explored. The overall mortality rate was 36.5%. Patients who were haemodynamically stable had a better outcome than those who presented in shock (P < 0.005). The major cause of death was haemorrhage from uncontrolled bleeding. Two subgroups with a higher mortality were identified: patients with inferior vena caval injury associated with a liver injury had a mortality rate of 78.5%, and those with vascular injury associated with pelvic fracture had a mortality rate of 57% (P < 0.05). Abdominal vascular injuries have a high mortality rate, especially if the inferior vena cava is involved or associated pelvic fractures are present. Prompt resuscitation and control of bleeding are the key to an improved salvage rate.

Penetrating missile embolisation

The present case report is that of a 13-year-old boy, who was admitted to the Emergency Unit at the American University of Beirut Medical Center (AUBMC), with a bullet injury to the right upper quadrant with no exist. Chest X-ray and KUB failed to reveal the bullet and there was no evidence of haemo- or pneumothorax. X-ray of both thighs showed the bullet at the level of the right groin. The bullet penetrated the liver, diaphragm and pericardium. It entered through the left ventricle and embolised through the arterial circulation to the right superficial femoral artery. Included in this report is a review and analysis of patients with missile embolisation, who were treated at the AUBMC over the last 10 years.

Testicular metastasis from primary rectal carcinoma

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Inferior vena cava obstruction in Budd-Chiari syndrome: successful treatment by radiological stenting followed by a portosystemic shunt

Surgical decompression by a portosystemic shunt in Budd-Chiari syndrome depends on the caval state. Obstruction of the inferior vena cava (IVC) precludes such an operation due to the risk of reduced blood flow across the shunt and subsequent thrombosis. Similar risks are encountered in more complicated operations such as mesoatrial shunt. We report a patient with Budd-Chiari syndrome in whom obstruction of the intrahepatic IVC by a hypertrophied caudate lobe of the liver precluded the construction of a standard portocaval shunt. A two-step procedure with preoperative radiological stenting of the narrowed IVC followed by a portocaval shunt was successfully performed. This is the fifth case reported in the literature of such an approach.

Gallstone pancreatitis in children: atypical presentation and review

Pancreatitis in children is less common than in adults and is mostly related to trauma, infection and anatomical anomalies. Gallstone pancreatitis is an even rarer entity in infants and children. We present an unusual case of gallstone pancreatitis in a 17- month-old girl who presented with jaundice of 1 month duration. The laboratory studies showed conjugated hyperbilirubinaemia with associated acute pancreatitis and pseudo-hyponatraemia secondary to the markedly elevated lipid profile. Further evaluations revealed obstruction at the Ampulla of Vater with no evidence of a choledochal cyst and no mass lesion seen in the pancreas. The patient initially underwent urgent decompressive cholecystostomy with intraoperative cholecystography. When the biochemical parameters improved, the patient underwent formal cholecystectomy with common bile duct exploration, extraction of multiple impacted stones in the ampullary region and Fogarty balloon sphincterotomy. The post-operative course was uneventful. Conclusion:Acute gallstone pancreatitis in children may present as jaundice or abdominal pain. Recognition, early diagnosis and surgical intervention are the mainstay for a good outcome.