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Biomedical subjects

Gaetano Ciancio

Publications and source records attributed to Gaetano Ciancio.

At least 19 recordsLinked to original sources

Surgical management of renal cell carcinoma with tumor thrombus in the renal and inferior vena cava: the University of Miami experience in using liver transplantation techniques.

OBJECTIVES: Renal cell carcinoma (RCC) with tumor thrombus in the inferior vena cava (IVC) poses a challenge to the surgeon due to the potential for massive hemorrhage and tumor thromboemboli. We developed a technique for safe resection of these tumors through a transabdominal approach, without recourse to cardiopulmonary bypass (CPB). MATERIALS AND METHODS: From August 1997 to February 2005, 66 patients underwent resection of a RCC with tumor thrombus in the IVC. The extent of the tumor thrombus was renal in 13, infrahepatic in 7; retrohepatic in 38; and intra-atrial in 8 patients. RESULTS: Mean operative time was 6.16+/-0.32 hours. The estimated blood loss ranged from 200 cc to 16,000 cc, with a mean of transfusions being 3.56+/-0.94 U. CBP was required in only 3 patients. Three patients (4.5%) died in the immediate postoperative period. Median follow-up among the 56 survivors was 7.1 months. Six patients died due to metastasis and 1 died of a cause unrelated to the cancer. The estimated actuarial survival at 36 months was 66%. CONCLUSIONS: An aggressive surgical approach is the only hope for curing patients having RCC with a tumor thrombus in the IVC. The extent of dissection is predicated on the extent and level of tumor thrombus. Our surgical approach uses liver transplant techniques to mobilize the liver off the IVC and to separate the IVC from the posterior abdominal wall. This maneuver provides excellent exposure and enables safe vascular control of the IVC.

Adult↗

A randomized long-term trial of tacrolimus/sirolimus versus tacrolimums/mycophenolate versus cyclosporine/sirolimus in renal transplantation: three-year analysis.

BACKGROUND: We report three-year (interim) effects of combining sirolimus (Siro) vs. mycophenolate mofetil (MMF) as adjunctive therapy with calcineurin inhibitors (CI) in renal transplantation in the three different CI-based regimens. METHODS: Between May 2000 and December 2001, 150 recipients of deceased donor (DD) and living donor (LD) kidney transplants were randomized into three groups (n=50/group): Group A (Tacro/Siro), Group B (Tacro/MMF) and Group C (CsA/Siro). This report details drug dosing and monitoring, protocol discontinuance, biopsy-proven rejection, graft failure, other adverse events, and death at 36 months postoperatively. RESULTS: Actual patient and graft survival respectively in Group A was 90% and 82%, in Group B was 92% and 88%, and in Group C was 96% and 88% (not significant). Biopsy-confirmed acute rejection incidents showed a trend in favor of Group B (10%) vs. Group A (26%) and Group C (20%) combined (P=0.07). The geometric mean */SE serum creatinine concentration and arithmetic mean +/- SE Cockroft-Gault creatinine clearance calculations, respectively, were 1.39*/1.1 and 72.8+/-4.3 for Group A, 1.36*/1.1 and 72.1+/-4.1 for Group B, and 1.60*/1.1 and 61.8+/-3.8 for Group C, a statistically favorable difference for Group B over Group C (P=0.04). There was also less de novo development of posttransplant diabetes mellitus and lipid disorders in Group B vs. A and C (P<0.04). CONCLUSIONS: This three-year (interim) analysis has indicated a trend towards better graft function, fewer endocrine disorders, and fewer acute rejection episodes comparing adjunctive MMF and Tacro vs. Siro and Tacro or Siro and CsA, in the dosages used.

Adolescent↗

Bone marrow-induced tolerance in the era of pancreas and islets transplantation.

Enormous progress has been made in the field of solid organ adaptation recently because of the improvement in immunosuppression. Although powerful immunosuppressive drugs decrease the rate of acute rejection significantly, the long-term functional graft survival and tolerance induction remains poor. Chronic rejection is the main cause of graft failure. An electronic search was performed for articles on chimerism, tolerance, and immunologic perspectives of islet and pancreas transplantation along with referrals to our experience. Infusion of donor bone marrow-derived cells to create a chimeric state continue to be tested in clinical protocols intended to induce specific immunologic tolerance. The proposed mechanisms of immunologic engagement and the emergence of a tolerant state through mixed chimerism include central depletion of alloreactive cells, induction of T-cell anergy, and generation of suppressor cells by interactions between donor and host cells. In this setting, depletion of recipient T cells by different strategies and subsequent repopulation by donor hematopoietic cells after donor bone marrow infusion are prerequisites for tolerance induction. Many efforts have aimed to establish mixed chimerism along with tolerance in solid organ transplantation including pancreas and islets to facilitate engraftment. A review of the more important advances in the field and the future prospects combined with our experience to induce tolerance in the clinic and the laboratory is presented in this article.

Animals↗

En bloc mobilization of the inferior vena cava and large hypervascular right renal tumors with or without inferior vena cava thrombus: Posterior ligation of the renal artery.

We describe our approach of posterior ligation of the renal artery during resection of large hypervascular right renal tumors. This technique uses en bloc mobilization of the inferior vena cava and renal tumor to ligate the renal artery at its origin from the aorta. In our experience, the use of this posterior approach for renal artery ligation is safe and effective, even with large renal tumors with multiple collaterals and/or lymph nodes making the identification of the renal artery difficult.

Aged↗

Adrenocortical carcinoma with tumor thrombus in the right hepatic vein.

Adrenocortical carcinoma is an unusual neoplasm with very poor prognosis. Patients present with an abdominal mass often exceeding 5 cm or as a functional tumor. Computed tomography is effective to demonstrate the neoplasm as an inhomogeneous adrenal lesion with irregular margins, and magnetic resonance imaging is helpful to visualize invasion into large vessels as well. Reported herein is a case of large adrenocortical carcinoma with tumor thrombus extending into the right hepatic vein.

Adrenal Cortex Neoplasms↗

Reactivation of dormant cutaneous Leishmania infection in a kidney transplant patient.

BACKGROUND: Leishmaniasis is an infection caused by a protozoan parasite belonging to genus Leishmania and transmitted by the Phlebotomus sandfly. Clinical presentations of infection include visceral, cutaneous, and mucocutaneous forms. Leishmaniasis is endemic in Africa, Asia, Europe, South America, and southern part of North America. This infection is extremely rare in the US and is mostly found among travelers coming from endemic areas. Cases of cutaneous and visceral leishmaniasis have been reported in organ transplant recipients in endemic areas. CASE REPORT: We describe a case of cutaneous leishmaniasis in a kidney transplant patient, originally from Bolivia, who resides in the area known to be non-endemic for leishmaniasis and who is known not to travel within or outside of the US after the transplantation. RESULTS: Histologic examination of cutaneous lesion revealed extensive subcutaneous lymphohistiocytic inflammation with clusters of amastigote within histiocytes. CONCLUSION: To our knowledge, this is the first case of cutaneous leishmaniasis in a kidney transplant patient residing in the US in an area known to be non-endemic for leishmaniasis, probably after reactivation of a previously dormant infection acquired outside of the US at least 9 months prior to developing clinical symptoms.

Amphotericin B↗

Efficacy of alemtuzumab in organ transplantation: current clinical status.

An overview of the past 5 years of clinical renal transplantation would include progress in (i) the development of protocols with new induction agents (non-depleting versus depleting monoclonal and polyclonal antibodies) designed to reduce the incidence and severity of acute rejection, (ii) the attempt to reduce calcineurin inhibitor short- and long-term nephrotoxicity, and (iii) the attempt to reduce immunosuppression overall if an immunoregulatory state ('tolerance') against donor alloantigens could be achieved. One such induction agent is the humanized anti-CD52 monoclonal antibody alemtuzumab (Campath-1H), which depletes T cells (most potently), as well as B cells and other lymphoid subsets, and may decrease the dosage or need for concurrent maintenance immunosuppressive agents.

Alemtuzumab↗

Review of major clinical trials with mycophenolate mofetil in renal transplantation.

Mycophenolate mofetil (MMF) was approved for the prevention of acute rejection following renal transplantation based on the results of three groundbreaking, large, clinical trials that demonstrated a significantly reduced risk of acute rejection in patients receiving MMF when compared with those receiving placebo or azathioprine. These three multicenter, prospective, double-blind trials performed at 55 transplant centers on three continents were the largest immunosuppressive drug trials ever attempted and the first prospective, randomized, double-blind trials ever performed in transplantation. These pivotal trials established a foundation for widespread acceptance of MMF in combination with cyclosporine and steroids as a maintenance regimen for renal transplant patients. The findings of these initial trials that led to the approval of MMF for renal transplantation, including long-term follow-up data, will be reviewed in this paper. The expanding scope of major trials of MMF, including trials in pediatric patients, combination regimens with novel induction therapies or other maintenance agents, and trials in special patient populations such as those at high immunological risk or with deteriorating kidney function, will also be discussed.

Adolescent↗

A randomized trial of three renal transplant induction antibodies: early comparison of tacrolimus, mycophenolate mofetil, and steroid dosing, and newer immune-monitoring.

BACKGROUND: New trends in immunosuppression in clinical transplantation include the use of antibody induction agents in protocols that emphasize reduction or avoidance of steroids and calcineurin inhibitors. METHODS: In a randomized trial using three different antibody induction agents in 90 first renal transplant recipients from cadaver donors, group A received Thymoglobulin, group B received Alemtuzumab, and group C received Daclizumab. Maintenance immunosuppression included tacrolimus and mycophenolate in all three arms, and methylprednisolone in groups A and C only (standard clinical institutional practice). The targeted trough level of tacrolimus was between 8 and 10 ng/mL for groups A and C, respectively, with a targeted mycophenolate dose of 1 g twice daily. However, in group B, the target tacrolimus trough level was 4 to 7 ng/mL to reduce long-term nephrotoxicity, with 500 mg twice-daily doses of mycophenolate, without steroid maintenance. RESULTS: In this 15-month median postoperative interval report, there were no notable differences in demographics and patient and graft survivals. Acute rejection rates at 1 year were equivalent, that is, 5 of 30 in all three groups (16.6%). In group B, there was slightly lower renal function at 1 month, but no difference at 1 year. There was also significantly more leukopenia, but a greater percentage of T-regulatory cells and number of Fox-P3 mRNA copies by flow cytometry and semiquantitative polymerase chain reaction analysis, respectively, in group B. CONCLUSIONS: This preliminary analysis indicates that 80% of the patients in group B remained steroid-free 1 year postoperatively, with lower tacrolimus trough levels and no difference in other adverse events.

Adult↗

Campath-1H does not alter bone marrow cell regulatory function.

We have previously reported in laboratory volunteers (in vitro) and renal transplant recipients (ex vivo) that bone marrow cells (BMC) are potent downregulators of the immune response. Also, the use of alemtuzumab (Campath-1H, C1H) for immunodepletion is associated with the most potent lasting effects yet seen on T-cell immunity in renal transplantation. We questioned whether the administration of C1H to kidney allograft recipients of donor bone marrow cell (DBMC) infusions would lead to stronger or weaker immunoregulatory effects. Human BMC depleted of T cells (nT-BMC) were either untreated or treated with C1H and rabbit complement and compared for their ability to downregulate autologous or allogeneic T-cell responses and to generate T regulatory (T reg) cells. The proliferative responses to anti-CD3 monoclonal antibody of T cells derived from cocultures with C1H-treated or untreated autologous nT-BMC were equally suppressed, i.e., an equivalent alteration in CD3 complex signaling, not regained by the addition of interleukin 2. Adenosine triphosphate levels were also markedly reduced in T cells both from C1H-treated and untreated nT-BMC cocultures. The ability of C1H-treated or untreated nT-BMC to suppress autologous T-cell cytotoxic function was also equivalent, with a marked, but equivalent, capacity to induce CD4/CD25(high) T regs from CD3(+) cells, which effectively downregulated cytotoxic T cells. To mimic the clinical infusion of DBMC into (allogeneic) recipients, peripheral blood mononuclear cells were also cultured with allogeneic C1H-treated and untreated nT-BMC. T cells derived from these cultures secondarily stimulated with the same-donor mature antigen-presenting cells exhibited suppressed cytotoxicity by 85% and 54%, respectively. These in vitro studies suggest that C1H does not abrogate BMC immunoregulation and thus may allow its lympho-depleting effect to be synergistic.

Alemtuzumab↗

Renal cell carcinoma with tumor thrombus extending above diaphragm: avoiding cardiopulmonary bypass.

OBJECTIVES: Renal cell carcinoma with a tumor thrombus extending into the supradiaphragmatic inferior vena cava (IVC) and right atrium represents a challenge to the surgical team. We describe a technique that can be used to resect these tumors safely through a transabdominal approach without recourse to cardiopulmonary bypass (CPB) or entry into the thoracic cavity. METHODS: Between May 1997 and August 2004, 59 patients (mean age 61 years) underwent surgical resection of a renal tumor extending into the IVC by techniques developed with the intention to avoid sternotomy and CPB. In 7 patients (12%), the tumor thrombus extended into the supradiaphragmatic IVC and right atrium. Complete surgical resection was successful through a transabdominal approach without CPB in all 7 of these patients. RESULTS: In the 7 patients who underwent the described technique, the median age was 71 years (range 51 to 80). The mean operative time was 7 hours, 47 minutes. The mean estimated blood loss was 2514 mL (range 500 to 6000). The mean number of blood units transfused was 4.7 (range 0 to 11). One patient died in the immediate postoperative period of cardiac arrhythmia. The median follow-up was 11.1 months, and 5 patients were disease free. CONCLUSIONS: In select cases, renal cell carcinoma extending into the supradiaphragmatic IVC and right atrium can be resected without the use of CPB. We describe our technique.

Aged↗

Renal cell cancer with invasive atrial tumor thrombus excised off-pump.

We report a case of a 50-year-old man with right renal cell cancer extending into the inferior vena cava, invading the right atrial wall, and Budd-Chiari syndrome. Because of the patient's coagulopathy and extensive venous collateralization, cardiopulmonary bypass and deep hypothermic circulatory arrest were avoided. Through an abdominal approach, the diaphragm was incised and the right atrium pulled into the abdomen and clamped. The invasive tumor thrombus was sharply excised off the atrial wall. If serious medical conditions do not permit the use of cardiopulmonary bypass, it is technically feasible to excise a wall-invasive atrial tumor thrombus off-pump.

Carcinoma, Renal Cell↗

Arterial reconstruction with donor iliac vessels during pancreas transplantation: an intraoperative approach to arterial injury or inadequate flow.

BACKGROUND: Outcome of pancreas transplantation (PTX) has improved because of use of novel immunosuppression and advances in surgical technique. It is not uncommon for severe atherosclerosis in patients with type 1 insulin-dependent diabetes mellitus or the presence of a previously transplanted organ to limit the options for vascular anastomosis. Herein we report the novel application of donor iliac arterial interposition grafts for arterial reconstruction in patients with severe iliac artery arteriosclerosis, and/or previous transplant who develop an arterial injury or stenosis during surgery. METHODS: In five patients undergoing PTX, the external iliac artery was severely atherosclerotic and/or occupied by a previous vascular anastomosis. In four of the five patients, an arterial intimal dissection became apparent. The external iliac artery was excised and reconstructed with donor iliac artery interposition graft (end-to-end anastomosis). Pancreas or kidney was engrafted onto this arterial interposition graft (end-to-side anastomosis). RESULTS: There was no operative morbidity related to this surgical approach. All grafts functioned well after transplantation. Distal lower extremities have no evidence of vascular insufficiency with mean follow-up of 26 months (7-45 months). CONCLUSION: This surgical technique is an acceptable option during PTX for the patient with severe iliac artery arteriosclerosis with intraoperative intimal dissection or stenosis, or perhaps those with challenging arterial access.

Adult↗

Resection of the abdominal inferior vena cava for complicated renal cell carcinoma with tumour thrombus.

OBJECTIVE: To describe our experience of excising the inferior vena cava (IVC) without a graft; en bloc resection of a renal cell carcinoma (RCC) with the renal vein and vena cava tumour thrombus and a segment of the entire abdominal IVC is technically feasible, but traditionally, after resection, attempts are made to restore continuity with the use of synthetic or homologous venous grafts. PATIENTS AND METHODS: Between May 1997 and September 2004, 60 patients (mean age 62 years) underwent surgical resection of a renal tumour with a thrombus extending into the IVC. To resect the entire evident tumour, excision of the affected portion of the IVC was required in three patients (5%); the IVC was not reconstructed. RESULTS: The three patients were aged 38, 39 and 74 years; the mean operative duration was 5.88 h, the mean (range) estimated blood loss was 833 (500-1000) mL, the mean number of blood units transfused was 3.3 (0-7) units, and the mean follow-up was 24 months. The course after surgery was uneventful; specifically, none of the patients had a venous thrombosis or a pulmonary embolus. CONCLUSIONS: RCC has a propensity to invade the renal vein and IVC. Occasionally the thrombus invades the wall of the IVC and complete removal requires excision of a circumferential portion of the IVC; this can be done safely without a graft.

Blood Loss, Surgical↗