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Nermin Halkic

Publications and source records attributed to Nermin Halkic.

At least 19 recordsLinked to original sources

Molecular and immunological evaluation of the expression of cancer/testis gene products in human colorectal cancer.

Tumor-specific gene products, such as cancer/testis (CT) antigens, constitute promising targets for the development of T cell vaccines. Whereas CT antigens are frequently expressed in melanoma, their expression in colorectal cancers (CRC) remains poorly characterized. Here, we have studied the expression of the CT antigens MAGE-A3, MAGE-A4, MAGE-A10, NY-ESO-1 and SSX2 in CRC because of the presence of well-described HLA-A2-restricted epitopes in their sequences. Our analyses of 41 primary CRC and 14 metastatic liver lesions confirmed the low frequency of expression of these CT antigens. No increased expression frequencies were observed in metastatic tumors compared to primary tumors. Histological analyses of CRC samples revealed heterogeneous expression of individual CT antigens. Finally, evidence of a naturally acquired CT antigen-specific CD8(+) T cell response could be demonstrated. These results show that the expression of CT antigens in a subset of CRC patients induces readily detectable T cell responses.

Antigens, Neoplasm↗

Laparoscopic management of appendicitis and symptomatic cholelithiasis during pregnancy.

BACKGROUND: Laparoscopic surgery during pregnancy is a challenging procedure that most surgeons are reluctant to perform. The objective of this study was to evaluate whether laparoscopic appendectomy and cholecystectomy is safe in pregnant women. The management of these situations remains controversial. We report a single center study describing the successful management of 16 patients during pregnancy. METHODS: More than 3,356 laparoscopic procedures were performed in our institutions between May 1990 and June 2005. Sixteen of these patients were operated on in the second and third trimester between 22 and 32 weeks of estimated gestational age. We performed 11 laparoscopic appendectomies and 5 laparoscopic cholecystectomies. We also reviewed the management and operative technique used in these patients. RESULTS: In this study, the laparoscopic appendectomy or cholecystectomy was performed successfully in all patients. Three patients were in their second trimester, weeks 22, 23, and 25, and 13 were in the third trimester, weeks 27 (three patients), 28 (five patients), 31 (three patients), and 32 (two patients). No maternal or fetal morbidity occurred. Open laparoscopy was performed safely in all patients and all patients delivered healthy babies. CONCLUSION: From our experience laparoscopic management of appendicitis and biliary colic during pregnancy is safe, however the second trimester is preferable for laparoscopic cholecystectomy. Pregnancy is not a contraindication to the laparoscopic approach to appendicitis or symptomatic cholelithiasis. We believe that laparoscopic operations, when performed by experienced surgeons, are safe and even preferable for the mother and the fetus.

Appendectomy↗

Gene expression in human hepatocytes in suspension after isolation is similar to the liver of origin, is not affected by hepatocyte cold storage and cryopreservation, but is strongly changed after hepatocyte plating.

Isolated primary human hepatocytes are a well accepted system for evaluating pharmacological and toxicological effects in humans. However, questions remain regarding how culturing affects the liver-specific functions of the hepatocytes. In addition, cryopreservation could also potentially affect the differentiation state of the hepatocytes. The first aim of the present study was to compare gene expression in freshly isolated primary hepatocytes to that of the liver of origin and to evaluate the expression changes occurring after cryopreservation/thawing, both when maintained in suspension and after plating. The second aim of the present study was to evaluate gene expression in hepatocytes after cold storage of suspensions up to 24 h compared with freshly isolated hepatocytes in suspension. Our results show that the gene expression in freshly isolated human hepatocytes in suspension after isolation is similar to that of the liver of origin. Furthermore, gene expression in primary human hepatocytes in suspension is not affected by hepatocyte cold storage and cryopreservation. However, the gene expression is profoundly affected in monolayer cultures after plating. Specifically, gene expression changes were observed in cultured relative to suspensions of human hepatocytes that are involved in cellular processes such as phase I/II metabolism, basolateral and canalicular transport systems, fatty acid and lipid metabolism, apoptosis, and proteasomal protein recycling. An oxidative stress response may be partially involved in these changes in gene expression. Taken together, these results may aid in the interpretation of data collected from human hepatocyte experiments and suggest additional utility for cold storage and cryopreservation of hepatocytes.

Cell Separation↗

Agenesis of the gallbladder: a dangerously misdiagnosed malformation.

Isolated agenesis of the gallbladder is a rare anomaly, often asymptomatic. However, one patient out of four presented with right upper abdominal pain, nausea, and fatty food intolerance. The condition is frequently mistaken with an excluded or sclero-atrophic gallbladder, regardless of the imaging modality used. Consequently, AG often leads to unnecessary and potentially dangerous laparoscopic surgery as described in a few case reports over the last 10 years. The aim of this study is to clarify the diagnostic and therapeutic approach of this unusual pathology. Two cases seen in our institutions were retrospectively reviewed, together with a review of the American and European literature. During laparoscopy, the absence of normal anatomical structures and the impossibility of pulling on the gallbladder to expose and dissect the triangle of Callot increases the risk of iatrogenic injury to biliary or portal structures. Depending on the experiment of the surgeon in laparoscopic procedure, this has to be taken into account to decide a conversion to laparotomy. A high index of suspicion is necessary when interpreting the radiological images. In case of doubt, a MRI-cholangiography is mandatory. Because of possible inherited transmission, relatives with a history of biliary symptoms should be investigated.

Abdominal Pain↗

[Hepatocellular carcinoma: a multidisciplinary approach].

The treatment of the hepatocellular carcinoma (HCC) is multidisciplinary. Hepatic transplantation offers the best chances of survival for patients with hepatic cirrhosis and HCC. However the indications for transplantation are limited. For patients that do not qualify for liver transplantation, surgical excision and percutaneous ablative treatment can also be curative. Five years survival then reaches 50%. The choice of treatment is based upon the patient's clinical state, the hepatic function and the cancer clinical stage. Follow-up is crucial as recurrences can be treated by following similar algorithms. The efficacy of oncological adjuvant and neoadjuvant treatment is not yet proved.

Algorithms↗

Naturally acquired MAGE-A10- and SSX-2-specific CD8+ T cell responses in patients with hepatocellular carcinoma.

Immunotherapy is being proposed to treat patients with hepatocellular carcinoma (HCC). However, more detailed knowledge on tumor Ag expression and specific immune cells is required for the preparation of highly targeted vaccines. HCC express a variety of tumor-specific Ags, raising the question whether CTL specific for such Ags exist in HCC patients. Indeed, a recent study revealed CTLs specific for two cancer-testis (CT) Ags (MAGE-A1 and MAGE-A3) in tumor infiltrating lymphocytes of HCC patients. Here we assessed the presence of T cells specific for additional CT Ags: MAGE-A10, SSX-2, NY-ESO-1, and LAGE-1, which are naturally immunogenic as demonstrated in HLA-A2(+) melanoma patients. In two of six HLA-A2(+) HCC patients, we found that MAGE-A10- and/or SSX-2-specific CD8(+) T cells naturally responded to the disease, because they were enriched in tumor lesions but not in nontumoral liver. Isolated T cells specifically and strongly killed tumor cells in vitro, providing evidence that these CTL were selected in vivo for high avidity Ag recognition. Therefore, besides melanoma, HCC is the second solid human tumor with clear evidence for in vivo tumor recognition by T cells, providing the rational for specific immunotherapy, based on immunization with CT Ags such as MAGE-A10 and SSX-2.

Aged↗

Percutaneous extraction of retained biliary T-tubes: a new technique.

Retained T-tubes are rare complications after biliary surgery. The authors present three cases of retained T-tubes in patients with transplanted liver that could not be removed by a standard manual traction. The authors describe a new simple percutaneous method that allows removal of these T-tubes without complication.

Adult↗

Portal vein embolization with N-butyl cyanoacrylate before partial hepatectomy in patients with hepatocellular carcinoma and underlying cirrhosis or advanced fibrosis.

PURPOSE: To describe the safety, complications, and liver regeneration associated with the left liver after embolization of the right portal vein (PV) in patients with hepatocellular carcinoma (HCC) developed in the setting of advanced liver fibrosis and cirrhosis. MATERIALS AND METHODS: Forty patients (31 men, nine women; mean age, 62 years) with HCC underwent PV embolization over a 4-year period. Embolization was performed from a left PV percutaneous access with use of n-butyl cyanoacrylate (NBCA) mixed with iodized oil. Computed tomography (CT) volumetry was performed before and 1 month after PV embolization to measure the left lobe volume as well as the functional liver ratio defined by the ratio between the left lobe and the total liver volume minus tumoral volume. PV pressure and liver enzyme levels were compared before and 1 month after the procedure and complications were registered. Factors potentially affecting regeneration (age, sex, diabetes, chemoembolization, functional liver ratio before PV embolization, and Knodell histologic score) were evaluated by one-way and stepwise regression analysis. RESULTS: PV embolization could be achieved successfully in all cases. Two patients had partial PV thrombosis on the 1-month follow-up CT and two patients developed transient ascites after PV embolization. The left lobe volume increase was 41% +/- 32% after PV embolization and the functional liver ratio increased from 28% +/- 10% to 36% +/- 10% (P < .0001). Hypertrophy of the left lobe was greater in patients with a low functional liver ratio before PV embolization and those with an F3 fibrosis score. Other factors had no influence on left lobe regeneration. CONCLUSION: PV embolization with use of NBCA is feasible in patients with advanced fibrosis and cirrhosis. Hypertrophy of the left lobe of the liver after PV embolization has a statistically significant correlation with lower functional liver ratio and lower degrees of fibrosis.

Adult↗

Laparoscopic cholecystectomy as a day surgery procedure: implementation and audit of 136 consecutive cases in a university hospital.

Laparoscopic cholecystectomy (LC) has been routinely performed since 1989 at our institution, and patients were traditionally admitted for 2 days. In 1996 we implemented a protocol for LC as a day surgery procedure at our center. Although initially reported by others, it has not yet been introduced as routine in Switzerland. The objective of this prospective study was to determine acceptability and safety of LC as an outpatient procedure in a university hospital. Data were collected prospectively for 136 LCs between January 1996 and December 2001. Patients were selected for the study if they wanted to go home within less than 24 hours, had no previous jaundice, and had no anesthetic contraindication. Systematic preoperative liver function tests and hepatic ultrasonography were performed. All patients were admitted on the day of operation. LC was performed using a three-trocar technique. Systematic cholangiography was performed, and all the procedures were completed laparoscopically. There were no common bile duct explorations. Postoperative complications were the following: nausea in seven patients, a minor umbilical hematoma in two. According to patient preference, 101 (74%) were discharged after an overnight stay (less than 24 hours) and 32 (24%) on the same day. The unplanned admission rate was 2%, and none of the patients was subsequently readmitted. The reasons for unplanned admissions were two patients with persistent nausea and one patient for whom an overnight stay was scheduled who presented with a ruptured subcapsular hematoma of the liver. Altogether, 97% of the patients were satisfied with the care they received. Operative costs were not significantly different when comparing inpatient and outpatient LC. The main postoperative savings were in the postoperative costs. Our results confirm that LC as a day surgery procedure is safe, effective, and acceptable to patients and their relatives. These results were achieved by using selection criteria that considered not only the surgical pathology but also the individual and by using appropriate techniques and planned postoperative analgesia.

Adult↗

Recurrent cytomegalovirus disease, visceral leishmaniosis, and Legionella pneumonia after liver transplantation: a case report.

PURPOSE: Recurrent cytomegalovirus (CMV) disease is a frequent complication of liver transplantation. Visceral leishmaniosis in a transplant recipient is, on the other hand, extremely rare and only two cases of kala-azar have been described after liver transplantation. Immunosuppressed patients are known to be at risk of Legionella infection and the relationship between infection with this organism and hospital water supplies has been well described. These three diseases carry a high mortality rate. Our report examines the potential relationship between these complications. CLINICAL FEATURES: We describe the case of a liver transplant recipient who presented the three complications successively and survived. After reviewing the literature, we explore hypotheses linking these infections and discuss treatment strategies. CONCLUSIONS: In the patient described, infection with leishmania probably occurred months prior to the clinical presentation, a delay that matches the incubation period of kala-azar. The simultaneous onset of leishmaniosis and of a high CMV viremia may have been a coincidence. However, CMV infection has been shown to be an independent predictor of invasive fungal infection in liver transplant recipients. CMV does indeed have a suppressive effect on the humoral and cellular immune response in vitro as well as in vivo. The clinical manifestations of leishmaniosis may, therefore, have been precipitated in this patient by the additive immunosuppressive effect of antirejection drugs and CMV.

Anti-Bacterial Agents↗

Hepatic portal gas in adults: review of the literature and presentation of a consecutive series of 11 cases.

BACKGROUND: Hepatic portal venous gas (HPVG) in adults is a rare entity. The underlying pathologic condition is usually an intestinal ischemia, but it has been reported in association with a variety of conditions. HYPOTHESIS: Miscomprehension of the underlying pathologic conditions has led to some confusion in the literature concerning its etiology, diagnostic methods, and clinical consequences. SETTING: Centre Hospitalier et Universitaire Vaudois, Lausanne, Switzerland, and District Hospital of Morges, Morges, Switzerland. METHOD: Between February 1, 1995, and May 30, 2000, eleven cases of HPVG were treated. These cases were retrospectively reviewed, together with a review of the literature to define the clinical significance of HPVG, the role of the computed tomographic scan, and the necessity of performing systematic emergency exploratory surgery. RESULTS: Two groups have to be distinguished-those who have HPVG with associated pneumatosis intestinalis and those who have HPVG without associated pneumatosis intestinalis. When associated with pneumatosis intestinalis, the cause is usually an intestinal ischemia and in a symptomatic patient it justifies systematic exploratory surgery. An abdominal computed tomographic scan including lung window settings to better identify air in the bowel wall will distinguish between these 2 groups. Pneumatosis intestinalis and HPVG due to bowel ischemia do not allow prediction of the severity of bowel wall damage. CONCLUSIONS: The cause of HPVG without pneumatosis intestinalis is variable. Good knowledge of the possible causes combined with the clinical picture and the abdominal computed tomographic scan is required to correctly identify the underlying cause of HPVG and to avoid unnecessary surgery.

Adult↗