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Karim Boudjema

Publications and source records attributed to Karim Boudjema.

27 records · Page 2Linked to original sources

Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma.

The high rate of recurrence after surgical resection of hepatocellular carcinoma (HCC) is a major therapeutic challenge. Postoperative injection of 131-iodine-labeled lipiodol (131I-Lip) into the hepatic artery has been proposed as adjuvant treatment (Lau et al.). We analyzed 2 retrospective series of matched patients treated in our unit before and after addition of 131I-Lip adjuvant therapy to our standard surgical strategy. Thirty-eight patients who had undergone surgical resection of HCC after January 1999 were given adjuvant intra-arterial injection of 131I-Lip after surgery. These patients were matched with 38 other patients who had undergone surgical resection only between January 1997 and January 1999. The frequency of recurrences, disease-free rates, and overall survival rates were compared. The 2 groups were similar for clinical, biologic, or histologic parameters studied and Cancer Liver Italian Program scores. There were 15 recurrences in the group without adjuvant treatment and 9 in the group with 131I-Lip adjuvant treatment. The 1-, 2-, and 3-year disease-free survival rates (+/-95% confidence interval) were different (P <.02): 94.7% +/- 3.6%, 83.7% +/- 6.1%, and 68.4% +/- 9.7%, respectively, in the 131I-Lip group versus 73.7% +/- 7.1%, 54.3% +/- 8.2%, and 41.5% +/- 10.5% in the surgery group. The 1-, 2-, and 3-year survival rates (+/-95% confidence interval) also were different (P <.02): 94.7% +/- 3.6%, 91.7% +/- 4.6%, and 91.7% +/- 4.6%, respectively, in the 131I-Lip group versus 94.7% +/- 3.6%, 71.3% +/- 7.8%, and 49.9% +/- 10% in the surgery group. In conclusion, this retrospective analysis supports the promising contribution of postoperative injection of 131I-Lip after resection of HCC. A randomized study including more patients would be necessary to confirm its contribution to therapeutic management.

Aged↗

C/EBPalpha regulates hepatic transcription of hepcidin, an antimicrobial peptide and regulator of iron metabolism. Cross-talk between C/EBP pathway and iron metabolism.

Originally identified as a gene up-regulated by iron overload in mouse liver, the HEPC gene encodes hepcidin, the first mammalian liver-specific antimicrobial peptide and potential key regulator of iron metabolism. Here we demonstrate that during rat liver development, amounts of HEPC transcripts were very low in fetal liver, strongly and transiently increased shortly after birth, and reappeared in adult liver. To gain insight into mechanisms that regulate hepatic expression of hepcidin, 5'-flanking regions of human and mouse HEPC genes were isolated and analyzed by functional and DNA binding assays. Human and mouse HEPC promoter-luciferase reporter vectors exhibited strong basal activity in hepatoma HuH-7 and mouse hepatocytes, respectively, but not in non-hepatic U-2OS cells. We found that CCAAT/enhancer-binding protein alpha (C/EBPalpha) and C/EBPbeta were respectively very potent and weak activators of both human and mouse promoters. In contrast, co-expression of hepatocyte nuclear factor 4alpha (HNF4alpha) failed to induce HEPC promoter activity. By electrophoretic mobility shift assay we demonstrated that one putative C/EBP element found in the human HEPC promoter (-250/-230) predominantly bound C/EBPalpha from rat liver nuclear extracts. Hepatic deletion of the C/EBPalpha gene resulted in reduced expression of HEPC transcripts in mouse liver. In contrast, amounts of HEPC transcripts increased in liver-specific HNF4alpha-null mice. Decrease of hepcidin mRNA in mice lacking hepatic C/EBPalpha was accompanied by iron accumulation in periportal hepatocytes. Finally, iron overload led to a significant increase of C/EBPalpha protein and HEPC transcripts in mouse liver. Taken together, these data demonstrate that C/EBPalpha is likely to be a key regulator of HEPC gene transcription and provide a novel mechanism for cross-talk between the C/EBP pathway and iron metabolism.

Animals↗

Treatment of hepatocellular carcinoma (HCC) with systemic chemotherapy combining epirubicin, cisplatinum and infusional 5-fluorouracil (ECF regimen).

PURPOSE: We tested the efficacy of a systemic chemotherapy regimen combining epirubicin, cisplatinum and infusional 5-fluorouracil (ECF) in a cohort of patients with hepatocellular carcinoma (HCC) who could not be given surgical, intraarterial or percutaneous treatment. PATIENTS AND METHODS: Between January 1998 and June 2000, 21 patients with metastatic and/or locally advanced HCC complicating a fibrous liver or a well-compensated (Child A) cirrhosis were given systemic chemotherapy with the ECF regimen. Tumor responses as assessed on CT scan and in terms of survival were studied. RESULTS: Patients completed a median of five chemotherapy courses. Overall tolerance was good but eight patients developed grade 3-4 toxicity, mainly hematological, and one patient experienced a grade 4 renal toxicity. Median survival was 10 months. Actuarial survivals (+/-SD) at 6 months, 1 year and 2 years were 90.2+/-9%, 70.3+/-10% and 24.6+/-19%, respectively. Of the 21 patients, 13 died, 12 from their tumor and 1 from treatment-related renal failure. There were only three objective responses (14.5%; CI95 1-28%) but one of these corresponded to a pathological complete response. The delay to tumor progression was 5.9+/-4.7 months. CONCLUSIONS: Systemic chemotherapy using the ECF regimen gave a poor response and low survival rates. It would appear reasonable to pursue the search for potentially efficacious chemotherapy protocols using other drug combinations.

Aged↗

Auxiliary partial orthotopic liver transplantation (APOLT) in the treatment of acute liver failure.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has been developed in order to benefit from the efficacy of orthotopic liver transplantation (OLT) in the treatment of fulminant hepatic failure (FHF), but to avoid the negative counterpart of OLT which is to eliminate the possibility of native liver (NL) regeneration and which consequently implies a life-long immunosuppression. METHODS: In our institution we performed 16 consecutive APOLTs in 15 patients between October 1992 and December 1999. Patients' mean age was 30 years (range 0.5-65 years). The causes of FHF were viral (HAV = 3; HBV = 3), drugs (n = 4), or others (n = 5). None of the patients had a history of chronic liver disease. The decision to transplant was taken when the patients met well-defined criteria. All but one of the patients were in a coma. RESULTS: Five patients died, 10 patients are alive (66.7%). Regeneration of the NL occurred in 11 of the 15 patients (73.3%) and in 8 of the 10 survivors. Six of these 8 patients have permanently stopped immunosuppressive therapy. These results can be favorably compared with those of OLT for FHF. In the European Transplant Registry, the survival rate is 57% at 5 years (2612 patients receiving OLT for FHF between 1988 and 1998). In our experience the survival rate is 59% at 5 years (42 patients receiving OLT for FHF between 1987 and 1999). CONCLUSIONS: APOLT is feasible in both adults and children; it rapidly restored liver function and reversed encephalopathy. Right APOLT seems more advisable since the right liver provides more functional hepatocytes; however, left APOLT harvested in an adult appears sufficient for a child. APOLT should be proposed only to patients with high chances of liver regeneration: age of recipient, etiology of liver failure, interval between onset of jaundice and occurrence of encephalopathy, and quality of liver graft are early prognostic indicators. Better results have been observed with younger patients (less than 40 years old) presenting with FHF (rather than subfulminant hepatic failure (SHF)) and due to HAV, HBV, or paracetamol.

Adolescent↗

Indication of liver transplantation in severe alcoholic liver cirrhosis: quantitative evaluation and optimal timing.

BACKGROUND/AIMS: The aim of our study was to evaluate the proportion of patients with severe alcoholic cirrhosis who would need orthotopic liver transplantation (OLT) and to determine the optimal delay to evaluate an abstinent patient for transplantation. METHODS: Survival without OLT, improvement in liver function and need for OLT were studied in all patients admitted in 1997 for a first episode of Child-Pugh C alcoholic cirrhosis. RESULTS: Twenty-six percent (19/74) of patients died during the initial hospitalization. The cumulative survival rates after 6 months and 1, 2 and 3 years were 56, 36, 35 and 24%, respectively. One liver transplantation (1.3%, 95% confidence interval 0.0-3.9) was performed for persisting liver failure despite abstinence. Improvement of the Child-Pugh score was observed within 3 months in 66% of the abstinent patients. OLT was indicated in four patients without liver improvement despite abstinence, but was contraindicated in three. CONCLUSIONS: Only a few patients with severe alcoholic cirrhosis undergo OLT, since most of them do not stop drinking and/or die soon, and those becoming abstinent often improve their liver function. OLT should be considered when improvement in liver function is lacking after 3 months of abstinence.

Adult↗

Squamous cell carcinoma arising in a hepatic forgut cyst.

We report the second case of squamous cell carcinoma arising in a hepatic foregut cyst (CHFC) in a 40-year-old woman. Microscopically, the lining of the cyst was composed of ciliated columnar epithelium, gastric and squamous epithelium. The squamous epithelium showed areas with dysplastic changes and other areas with carcinomatous transformation. In this congenital lesion, it was not surprising to find squamous and gastric mucosa because oesophagus, stomach, and tracheobronchic tree derive from the embryologic foregut. Squamous carcinoma might develop in a context of inflammation as in biliary cyst. In agreement with the first case described in the literature, this report also suggests that a large-sized symptomatic hepatic cyst should be excised.

Adult↗

Auxiliary liver transplantation and bioartificial bridging procedures in treatment of acute liver failure.

The aim of this review is to discuss the place of auxiliary liver transplantation (ALT) and other cellular based bridging procedures such as hepatocyte transplantation, ex vivo liver perfusion, and bioartificial livers, in the treatment of acute liver failure, vis à vis conventional orthotopic liver transplantation. Hepacocyte transplantation, and ex vivo pig or human liver perfusion are still experimental procedures. Bioartificial livers using human tumoral hepatocytes or porcine hepatocytes have been used in clinical situations as a bridge to transplantation, i.e. to gain the time required to find a high-quality graft for conventional or auxiliary liver transplantation. None of these techniques have yet proved capable of keeping a patient alive long enough for the native liver to recover. Conversely, ALT has been shown to be effective in the treatment of acute liver failure and now appears to be a satisfactory bridging procedure pending native liver (NL) regeneration. We report personal experience of 18 ALT procedures performed in 17 patients between October 1992 and December 1999. The ALT procedure was indicated when patients met criteria for conventional transplantation; it was ultimately selected when a fresh frozen biopsy of the NL did no show any fibrosis. Six patients died within the first 2 postoperative months. The remaining 11 patients are alive, with a follow-up ranging from 2 to 7 years. Regeneration of the NL occurred in 11 of the 17 patients (65%) and in 8 of the 11 survivors (72%), 6 of whom have permanently stopped immunosuppressive therapy. We conclude that liver failure should no longer be handled outside centers where all types of transplantation can be offered, and where innovative therapies such as hepatocyte transplantation and extracorporeal liver-assist devices are being developed and evaluated.

Adolescent↗

Arterial and vena caval resections combined with pancreaticoduodenectomy in highly selected patients with periampullary malignancies.

BACKGROUND/AIMS: To obtain a margin-negative resection and increase the indication for resection of periampullary malignancies, pancreaticoduodenectomy with a SM-PVR (superior mesenterico-portal vein resection) has been performed. However, an arterial resection, other vascular resections except SM-PVR (e.g., an inferior vena caval resection), or a metastatic tumor resection combined with pancreaticoduodenectomy has yet to be fully elucidated because of the high risk of postoperative complications and extremely poor long-term survival in patients undergoing these exceptional procedures. The present report focused on highly selected patients undergoing an arterial resection or a vena caval resection associated with pancreaticoduodenectomy. METHODOLOGY: Besides 31 patients with periampullary tumors undergoing pancreaticoduodenectomy associated with SM-PVR in our department, a group of 4 patients underwent arterial resections and another patient underwent pancreaticoduodenectomy combined with a resection of liver metastasis together with an inferior vena caval resection. These five patients were reported in the present study. RESULTS: A 27 year-old-woman presented pancreatic ductal adenocarcinoma of the pancreatic head and a liver metastasis in which involvements of the superior mesenterico-portal vein and the inferior vena cava were shown. Pancreaticoduodenectomy was performed with SM-PVR associated with a left hemihepatectomy combined with a segment 1 resection and an inferior vena caval resection. The patient did not present severe postoperative complications and experienced a good quality of life during 16 months after surgery. Four other patients underwent arterial resections. These arterial resections were performed only when a margin-negative resection was feasible. The superior mesenteric artery was resected and reconstructed with a Goretex graft in one patient. The right hepatic artery was resected and reconstructed with a saphenous graft in two patients. The other patient underwent a resection of the common hepatic artery and reconstruction was performed with the splenic artery. Three of the four patients presented postoperative complications but were conservatively treated. Two patients are still alive 25 months and 8 months after surgery. One patient died of sepsis 5 months after surgery, and the other died of cancer progression 19 months after surgery. CONCLUSIONS: The indication for retropancreatic arterial resection associated with pancreaticoduodenectomy should be carefully evaluated only when a margin-negative resection can be achieved. An appropriate bypass method of arterial reconstruction should be selected because a direct end-to-end anastomosis is not always feasible. Hepatectomy for metastases of pancreatic ductal carcinoma should be also regarded as an exceptional procedure.

Adenocarcinoma↗