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Zakiyah Kadry

Publications and source records attributed to Zakiyah Kadry.

15 recordsLinked to original sources
PubMed2005

Immunosuppression in liver transplantation: beyond calcineurin inhibitors.

Although calcineurin inhibitors (CNIs) remain the mainstay of immunosuppression in liver transplantation (LTX), their long-term toxicity significantly contributes to morbidity and mortality. The elucidation of mechanisms of alloimmunity and leukocyte migration have provided novel targets for immunosuppression development. The toxicities of these agents differ from that of the CNI and act additively or synergistically. CNI avoidance protocols in LTX have not been achieved routinely; however, pilot trials have begun to delineate the limitations and promises of such approaches. CNI-sparing protocols appear to be much more promising in balancing the early need for minimizing rejection while tapering doses and minimizing long-term toxicity.

Adrenal Cortex Hormones↗
PubMed2004

Does the novel PET/CT imaging modality impact on the treatment of patients with metastatic colorectal cancer of the liver?

OBJECTIVE: To compare the diagnostic value of contrast-enhanced CT (ceCT) and 2-[18-F]-fluoro-2-deoxyglucose-PET/CT in patients with metastatic colorectal cancer to the liver. BACKGROUND: Despite preoperative evaluation with ceCT, the tumor load in patients with metastatic colorectal cancer to the liver is often underestimated. Positron emission tomography (PET) has been used in combination with the ceCT to improve identification of intra- and extrahepatic tumors in these patients. We compared ceCT and a novel fused PET/CT technique in patients evaluated for liver resection for metastatic colorectal cancer. METHODS: Patients evaluated for resection of liver metastases from colorectal cancer were entered into a prospective database. Each patient received a ceCT and a PET/CT, and both examinations were evaluated independently by a radiologist/nuclear medicine physician without the knowledge of the results of other diagnostic techniques. The sensitivity and the specificity of both tests regarding the detection of intrahepatic tumor load, extra/hepatic metastases, and local recurrence at the colorectal site were determined. The main end point of the study was to assess the impact of the PET/CT findings on the therapeutic strategy. RESULTS: Seventy-six patients with a median age of 63 years were included in the study. ceCT and PET/CT provided comparable findings for the detection of intrahepatic metastases with a sensitivity of 95% and 91%, respectively. However, PET/CT was superior in establishing the diagnosis of intrahepatic recurrences in patients with prior hepatectomy (specificity 50% vs. 100%, P = 0.04). Local recurrences at the primary colo-rectal resection site were detected by ceCT and PET/CT with a sensitivity of 53% and 93%, respectively (P = 0.03). Extrahepatic disease was missed in the ceCT in one third of the cases (sensitivity 64%), whereas PET/CT failed to detect extrahepatic lesions in only 11% of the cases (sensitivity 89%) (P = 0.02). New findings in the PET/CT resulted in a change in the therapeutic strategy in 21% of the patients. CONCLUSION: PET/CT and ceCT provide similar information regarding hepatic metastases of colorectal cancer, whereas PET/CT is superior to ceCT for the detection of recurrent intrahepatic tumors after hepatectomy, extrahepatic metastases, and local recurrence at the site of the initial colorectal surgery. We now routinely perform PET/CT on all patients being evaluated for liver resection for metastatic colorectal cancer.

Colorectal Neoplasms↗
PubMed2003

Living donor liver transplantation and tolerance: a potential strategy in cholangiocarcinoma.

BACKGROUND: Donor-specific immune tolerance has been reported in isolated cases of kidney transplantation associated with bone marrow transplantation. The following is a description of a living donor liver transplantation for a hilar cholangiocarcinoma in a previous recipient of an allogeneic bone marrow transplant. METHOD: A right hemi-liver transplantation was performed using a liver allograft obtained from the same previous bone marrow donor. A neoadjuvant chemo-irradiation protocol was implemented before the procedure. Because of the presence of full chimerism, no immunosuppression has been necessary for the last 22 months. RESULTS: Liver graft function has remained excellent, and a magnetic resonance imaging scan at one and a half years has shown no tumor recurrence. A control liver biopsy at 1 year showed no rejection. CONCLUSIONS: Neoadjuvant chemo-irradiation therapy and removal of all immunosuppression after liver transplantation formed the basic structure of this approach. Additional benefits provided by living donor liver transplantation included limitation of tumor progression by diminishing the pretransplantation waiting time, radical excision of the tumor through a complete hepatectomy, and optimal timing of the transplant procedure within a neoadjuvant chemo-irradiation protocol.

Adult↗
PubMed2003

Right living donor hepatectomy in the presence of celiac artery stenosis.

BACKGROUND: Incidental celiac artery stenosis has been cited as an exclusion criterion for adult donor right hepatectomy. METHODS: We report our experience involving right donor hepatectomy performed in the presence of isolated high-grade (greater than 80%) celiac trunk stenosis in two young healthy and asymptomatic adult living liver donors. RESULTS: The immediate postoperative course was complicated by a superficial wound infection in one patient and a transient median nerve palsy caused by intraoperative positioning, which spontaneously resolved, in the second patient. Both were discharged within 7 to 10 days postoperatively. They are doing well at 1 year follow-up without any complaints and have both returned to 100% full employment. CONCLUSIONS: Our results show that right donor hepatectomy can be safely performed in the presence of significant celiac artery stenosis. However, careful long-term follow-up will be required to monitor for any future progression of mesenteric vascular disease.

Adult↗
PubMed2003

A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning.

OBJECTIVE: To evaluate the protective effects of ischemic preconditioning in a prospective randomized study involving a large population of unselected patients and to identify factors affecting the protective effects. SUMMARY BACKGROUND DATA: Ischemic preconditioning is an effective protective strategy in several animal models. Protection has also been suggested in a small series of patients undergoing a hemihepatectomy with 30 minutes of inflow occlusion. Whether preconditioning confers protection in other types of liver resection and longer periods of ischemia is unknown. Therefore, we conducted a prospective randomized study to evaluate the impact of ischemic preconditioning in liver surgery. METHODS: A total of 100 unselected patients undergoing major liver resection (> bisegmentectomy) under inflow occlusion for at least 30 minutes were randomized during surgery to either receive or not receive an ischemic preconditioning protocol (10 minutes of ischemia followed by 10 minutes of reperfusion). Univariate and multivariate analyses were performed to identify independent factors affecting the protective effects of ischemic preconditioning. ATP contents in liver were measured as a possible mechanism of protection. RESULTS: Both groups (n = 50 in each) were comparable regarding age, gender, duration of inflow occlusion, and resected liver volumes. Postoperative serum transaminase levels were significantly lower in preconditioned than in control patients (median peak AST 364 U/L vs. 520 U/L, P = 0.028; ALT 406 vs. 519 U/L, P = 0.049). Regression multivariate analysis revealed an increased benefit of ischemic preconditioning in younger patients, in patients with longer duration of inflow occlusion (up to 60 minutes), and in cases of lower resected liver volume (<50%). Patients with steatosis were also particularly protected by ischemic preconditioning. ATP content in liver tissue was preserved by ischemic preconditioning in young but not older patients. CONCLUSIONS: This study establishes ischemic preconditioning as a protective strategy against hepatic ischemia in humans. The strategy is particularly effective in young patients requiring a prolonged period of inflow occlusion, and in the presence of steatosis, and is possibly related to preservation of ATP content in liver tissue. Other strategies are needed in older patients.

Adult↗
PubMed2002

Living donor liver transplantation in patients with portal vein thrombosis: a survey and review of technical issues.

BACKGROUND: Unlike cadaveric liver transplantation, current attitudes in living donor liver transplantation (LDLT) quote increased risk factors in the potential recipient such as retransplantation, multiple previous surgeries, or preexisting recipient portal vein thrombosis (PVT) as absolute or relative contraindications to this procedure. METHODS: An international survey was performed to examine the attitude of transplant teams relative to LDLT in the setting of preexisting PVT in the potential recipient. A questionnaire was sent to a total of 80 transplant centers performing LDLT in the United States, Europe, Canada, Japan, Southeast Asia, and Australia. RESULTS: A response was obtained from 47 transplant centers (59% response rate). This included 2146 LDLT procedures that combined both left and right lobe allografts. The incidence of acute preexisting recipient PVT was 18 (0.8%) and of chronic PVT was 26 (1.2%). Thrombectomy was performed in 28 (64%), a jump graft in 13 (29.5%), and a combination of both thrombectomy and a jump graft in 2 (4.5%) cases. With reference to the presence of preexisting PVT in the potential recipient, 5 centers considered this to be an absolute contraindication (10.7%), 24 centers as a relative contraindication (51%), and 18 as not being a contraindication (38.3%) to LDLT. CONCLUSIONS: The overall response to our questionnaire reflected a cautious attitude within the transplant community. Ethical criteria pertaining to risk undertaken by a healthy donor in situations of higher recipient morbidity risk does seem to impact on the decision to undertake LDLT in this group of patients.

Health Surveys↗
PubMed2002

Cost-effectiveness of cadaveric and living-donor liver transplantation.

BACKGROUND: Cadaveric liver transplantation (5-year survival >80%) represents the standard of care for end-stage liver disease (ESLD). Because the demand for cadaveric organs exceeds their availability, living-donor liver transplantation has gained increasing acceptance. Our aim was to assess the marginal cost-effectiveness of cadaveric and living-donor orthotopic liver transplantation (OLT) in adults with ESLD. METHODS: Using a Markov model, outcomes and costs of ESLD treated (1) conservatively, (2) with cadaveric OLT alone, and (3) with cadaveric OLT or living-donor OLT were computed. The model was validated with published data. The case-based scenario consisted of data on all 15 ESLD patients currently on our waiting list (3 women, 12 men; median age, 48 years [range, 33-59 years]) and on the outcome of all OLT performed for ESLD at our institution since 1995 (n=51; actuarial 5-year survival 93%). Living-donor OLT was allowed in 15% during the first year of listing; fulminant hepatic failure and hepatocellular carcinoma were excluded. RESULTS: Cadaveric OLT gained on average 6.2 quality-adjusted life-years (QALYs) per patient compared with conservative treatment, living-donor OLT, an additional 1.3 QALYs compared with cadaveric OLT alone. Marginal cost-effectiveness of a program with cadaveric OLT alone and a program with cadaveric and living-donor OLT combined were similar (E 22,451 and E 23,530 per QALY gained). Results were sensitive to recipient age and postoperative survival rate. CONCLUSIONS: Offering living-donor OLT in addition to cadaveric OLT improves survival at costs comparable to accepted therapies in medicine. Cadaveric OLT and living-donor OLT are cost-effective.

Adult↗
PubMed2002

Cold ischemia decreases liver regeneration after partial liver transplantation in the rat: A TNF-alpha/IL-6-dependent mechanism.

New strategies of partial liver transplantation such as cadaveric split or living related liver transplantation have been developed to overcome organ shortage. Thus, studies on the ability of small partial grafts to regenerate to normal size while maintaining adequate function have become important. Here, we evaluated the effects of cold preservation on hepatocyte proliferation and function in a novel model of partial liver transplantation in rats. Lewis rats subjected to 70% liver resection (control) were compared with rats that underwent total hepatectomy and 30% partial liver transplantation (recipient). Livers were preserved at 4 degrees C for 30 minutes, 10 hours, or 16 hours in University of Wisconsin solution. Seventy percent liver resection was associated with 100% survival, whereas 30-minute, 10-hour, and 16-hour preservation before 30% transplantation resulted in 80%, 40%, and 20% animal survival, respectively. Prolonged time of cold preservation (10 and 16 hours) was associated with a dramatic decrease of all markers of regeneration (P <.05). Tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) levels were also significantly decreased in recipient rats compared with the control group. Finally, pretreatment of recipients with recombinant IL-6 (rIL-6) normalized all markers of regeneration and significantly improved survival in the 10-hour group (90% vs. 40%; P <.05). In conclusion, sustained periods of cold preservation significantly impaired TNF-alpha and IL-6 production, the regenerative ability of the liver, and animal survival. rIL-6 reversed impaired regeneration in the 10-hour cold ischemia group and suggests a primary role of nonparenchymal cells in modulating hepatocyte proliferation in the ischemic liver.

Animals↗
PubMed2002

New treatments with curative intent for metastatic colorectal liver cancer.

Although surgical resection is the mainstay of therapy in metastatic colorectal liver cancer, < 10 - 15% of patients are suitable for resection. In addition, recurrence rates after resection may reach 75% in the first 2 years, of which 50% involve local recurrences in the liver. This has provided an impetus for the development of neoadjuvant and adjuvant protocols in the treatment of this malignancy, techniques concentrating on improving the residual liver functional reserve, as well as local tumour ablative therapies using radiofrequency and cryotherapy. A multimodal interdisciplinary approach is a pre-requisite when treating secondary liver tumours from colorectal cancer and should be concentrated in centres of reference. The development of such innovative modalities as preoperative downstaging in the absence of extrahepatic tumour disease, local tumour control and new adjuvant therapies has expanded the patient population thus providing the opportunity to treat patients with large or advanced stage colorectal liver tumours. The following is a review of some of the approaches currently being evaluated in the treatment of colorectal liver metastases.

Antineoplastic Agents↗