Rapamycin and HIV Replication in Liver Transplant Recipients

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Treatment of wounds colonized by multidrug resistant organisms in immune-compromised patients: a retrospective case series.

Immune-compromised patients incur a high risk of surgical wound dehiscence and colonization by multidrug resistant organisms. Common treatment has been debridement and spontaneous secondary healing.All immune-compromised patients referred to our Institution between March 1, 2010 and November 30, 2011 for dehiscent abdominal wounds growing multidrug resistant organisms were treated by serial wound debridements and negative pressure dressing. They were primarily closed, despite positive microbiological cultures, when clinical appearance was satisfactory.Nine patients were treated by direct wound closure, five had been treated previously by secondary intention healing.According to our results, fast healing can be safely obtained by closure of a clinically healthy wound, despite growth of multidrug resistant organisms, even in immune-compromised patients

Surgical Approach for Long-term Survival of Patients With Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis of 434 Patients.

OBJECTIVES To examine the outcomes of a hepatectomy for intrahepatic cholangiocarcinoma (IHC) and to clarify the prognostic impact of a lymphadenectomy and the surgical margin. Large series of patients who were surgically treated for IHC are scarce. Thus, prognostic factors and long-term survival after resection of IHC remain uncertain. DESIGN Prospective study of patients who were surgically treated for IHC. Clinicopathologic, operative, and long-term survival data were analyzed. SETTING Prospectively collected data of all consecutive patients with pathologically confirmed IHC who had undergone liver resection with a curative intent at 1 of 16 tertiary referral centers were entered into a multi-institutional registry. PATIENTS All consecutive patients who underwent a hepatectomy with a curative intent for IHC (1990-2008) were identified from a multi-institutional registry. RESULTS A total of 434 patients were included in the analysis. Most patients underwent a major or extended hepatectomy (70.0%) and a systematic lymphadenectomy (62.2%). The incidence of lymph node metastases (overall, 36.9%) increased with increased tumor size, with 24.4% of patients with a small IHC (diameter 643 cm) having N1 disease. Almost one-third of patients required an additional major procedure to obtain a R0 resection in 84.6% of the cases. In these patients, the median time of survival was 39 months, and the 5-year survival rate was 39.8%. Lymph node metastases (hazard ratio, 2.21; P < .001), multiple tumors (hazard ratio, 1.50; P = .009), and an elevated preoperative cancer antigen 19.9 level (hazard ratio, 1.62; P = .006) independently predicted an adverse prognosis. Conversely, survival was not influenced by the width of a negative resection margin (P = .61). The potential survival benefit of a lymphadenectomy was assessed with the therapeutic value index, which was calculated to be 5.9 points. CONCLUSIONS Survival rates after a hepatectomy with a curative intent for IHC at tertiary referral centers exceed the survival rates reported in most study series in single institutions, which strengthens the value of an aggressive approach to radical resection. Lymph node metastases and multiple tumors are associated with decreased survival rates, but they should not be considered selection criteria that prevent other patients from undergoing a potentially curative resection. Lymphadenectomy should be considered for all patients

Kidney, kidney-pancreas and liver-kidney transplantation in HIV infected individuals: the Italian experience

Until a few years ago, HIV infection was considered an exclusion criteria for organ transplantation. However, more recently, because of the significant increase in life expectancy of HIV-infected persons with highly active antiretroviral therapy (HAART), kidney, kidney-pancreas, heart, lung and liver transplantation have been introduced in this patients population in several centers around the world. To evaluate the possible extension of the indications of kidney transplantation to HIV-infected individuals, the Italian National Centre for Transplantation has designed a protocol to be applied on a national basis. Inclusion criteria required a CD4 count ≥200/mm3 and undetectable HIV viral load for at least 3 months for patients on HAART.The program was voluntarily adopted by 4 transplant centres. From January 2006 through November 2007 a total of 13 HIV infected patients (9 male and 4 female, mean age 46.4 years, range 35-56) underwent cadaveric kidney transplantation (including two kidney-pancreas and two liver-kidney) after a median waiting time of 142 days (range 58-650). Median CD4 cells count at the time of transplantation was 449 (range 210-782) and the HIV-RNA was undetectable in all recipients. HAART was started in all recipients after transplantation and HIV-RNA remain undetectable in all patients. Five patients (38.4%) experienced an episode of biopsy proven acute rejection (steroid resistant in one). Drug-drug interactions between antiretrovirals and immunosuppressive agents required frequent dosage modifications. Graft and patient survival was 100% at a median follow-up of 161 days after transplantation (range 8-669). Despite the limited number of patients and the shortness of the follow-up, our study confirms excellent short term results of kidney transplantation in HIV-infected individuals

Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study

Abstract In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant

FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer

BACKGROUND: In patients with colorectal liver metastases (CLM) R0 resection significantly improves overall survival (OS). METHODS: In this report, we present the results of a phase II trial of FOLFOX6+bevacizumab in patients with non-optimally resectable CLM. Patients received six cycles of FOLFOX6+ five of bevacizumab. Patients not achieving resectability received six additional cycles of each. A PET-CT was performed at baseline and again within 1 month after initiating treatment. RESULTS: From September 2005 to July 2009, 21 patients were enrolled (Male/Female: 15/6; median age: 65 years). An objective response (OR) was documented in 12 cases (57.1%; complete responses (CRs): 3, partial response (PR): 9); one patient died from toxicity before surgery. Thirteen patients underwent radical surgery (61.9%). Three (23%) had a pathological CR (pCR). Six patients (46.1%) experienced minor postsurgical complications. After a median 38.8-month follow-up, the median OS was 22.5 months. Patients achieving at least 1 unit reduction in Standard uptake value (SUV)max on PET-CT had longer progression-free survival (PFS) (median PFS: 22 vs 14 months, P=0.001). CONCLUSIONS: FOLFOX6+bevacizumab does not increase postsurgical complications, yields high rates of resectability and pCR. Early changes in PET-CT seem to be predictive of longer PFS