Cardiovascular risk and white matter lesions after endocrine control of Cushing's syndrome.

OBJECTIVE: Cushing's syndrome (CS) is associated with high cardiovascular risk. White matter lesions (WML) are common on brain magnetic resonance imaging (MRI) in patients with increased cardiovascular risk. AIM: To investigate the relationship between cardiovascular risk, WML, neuropsychological performance and brain volume in CS. DESIGN/METHODS: Thirty-eight patients with CS (23 in remission, 15 active) and 38 controls sex-, age- and education-level matched underwent a neuropsychological and clinical evaluation, blood and urine tests and 3Tesla brain MRI. WML were analysed with the Scheltens scale. Ten-year cardiovascular risk (10CVR) and vascular age (VA) were calculated according to an algorithm based on the Framingham heart study. RESULTS: Patients in remission had a higher degree of WML than controls and active patients (P<0.001 and P=0.008 respectively), which did not correlate with cognitive performance in any group. WML severity positively correlated with diastolic blood pressure (r=0.659, P=0.001) and duration of hypertension (r=0.478, P=0.021) in patients in remission. Both patient groups (active and in remission) had higher 10CVR (P=0.030, P=0.041) and VA than controls (P=0.013, P=0.039). Neither the 10CVR nor the VA correlated with WML, although both negatively correlated with cognitive function and brain volume in patients in remission (P<0.05). Total brain volume and grey matter volume in both CS patient groups were reduced compared to controls (total volume: active P=0.006, in remission P=0.012; grey matter: active P=0.001, in remission P=0.003), with no differences in white matter volume between groups. CONCLUSIONS: Patients in remission of Cushing's syndrome (but not active patients) have more severe white matter lesions than controls, positively correlated with diastolic pressure and duration of hypertension. Ten-year cardiovascular risk and vascular age appear to be negatively correlated with the cognitive function and brain volume in patients in remission of Cushing's syndrome.

Effect of calcineurin inhibitors in the outcome of liver transplantation in hepatitis C virus-positive recipients.

BACKGROUND: There is a paucity of good studies evaluating the impact of calcineurin inhibitors on posttransplantation outcome in hepatitis C virus (HCV)-infected liver transplant (LT) recipients. METHODS: We sought to determine whether there are differences on posttransplantation survival and histologic recurrence in HCV-LT recipients based on initial immunosuppression (IS) by conducting a prospective study comparing tacrolimus (Tac) versus cyclosporine-based IS in patients undergoing LT between 2001 and 2007. Protocol liver biopsies were performed. RESULTS: Baseline characteristics (demographics, liver function at LT, genotype distribution, donor, surgery, and IS except for the type of calcineurin inhibitor) did not differ between groups. Severe disease (defined as bridging fibrosis, cirrhosis, cholestatic hepatitis, or allograft loss or death because of recurrent disease in the first year) was present in 67 of 253 (26.5%) and was equally distributed in the CsA and Tac groups (27% vs. 26%; P=0.68). Two thirds of protocol biopsies performed at 1 year showed some fibrosis without differences between CsA and Tac groups (75% vs. 70%). Advanced fibrosis (bridging fibrosis and cirrhosis) was diagnosed in 30% CsA and 24.5% Tac patients (P=NS). No differences in survival at 1 and 7 years were observed (83% and 67% vs. 78% and 64%, respectively, P=0.4). In summary, in patients undergoing LT for HCV-related liver disease, posttransplantation outcome is not related to the calcineurin inhibitor used.

[Indications and results of liver retransplantation: experience with 1181 patients at the University Hospital La Fe]. / Indicaciones y resultados de retrasplante hepático: experiencia del hospital universitario La Fe (1.181 pacientes).

UNLABELLED: Liver retransplantation (LrT) is the only therapeutic option for irreversible failure of a hepatic graft and accounts for 2.9%-24.0% of all liver transplantations (LT). It is technically difficult and has a high level of immediate morbidity and a lower survival than primary LT. Our aim was to determine the rate of LrT and its indications, morbidity, post-operative mortality and actuarial survival in the retransplanted patient. PATIENTS AND METHOD: A historical cohort study of 1181 patients transplanted between 1991 and 2006. RESULTS: Of the 1260 LT performed, 79 were LrT. At the time of the first LT there were no differences between those patients and those that did not require an LrT. The LrT rate was 6.3% and the most frequent causes were: hepatic artery thrombosis (31.6%), recurrence of cirrhosis due the HVC (30.4%) and primary graft (21.5%). The ischemia times, perfusion syndrome and hepatic congestion were no different between the primary LT and the LrT. On the other hand, red cell transfusions were higher in LrT (6.3+/-4.9 vs. 3.5+/-3.0 units, P<0.001). The post-operative morbidity and morbidity (up to 30 days after the LT) was higher in retransplanted patients (68.4% vs. 57.0%, P=0.04 and 25.3% vs. 10.9%, P<0.001; respectively). The actuarial survival at 1 and 5 years was 83% and 69% in those without LrT, 71% and 61% in early LrT and 64% and 34% in delayed LrT (P<0.001). CONCLUSIONS: Despite the increased morbidity and mortality of LrT, it appears that this treatment alternative is still valid in those patients with an early loss of the liver graft. On the other hand, when the graft loss is delayed, it needs to be defined, what would be the minimum acceptable results to indicate LrT and which patients could benefit from this treatment.

Remote cerebral hematomas in patients treated with intravenous rt-PA.

The frequency, clinical presentation, radiological features, and prognosis of remote cerebral hematomas (rPH) are not well known. We report our experience in patients treated with intravenous rt-PA. We reviewed our database of consecutive patients treated at our hospital from 1999 to 2008. We used the inclusion/exclusion criteria of the ECASS-2 study from 1999 to 2003, and the criteria of the SITS-MOST study since 2004. A follow-up CT scan was obtained in all of the patients within the first 36 h of treatment. Cerebral hemorrhagic complications were classified as hemorrhagic infarction (HI-1/HI-2) and parenchymal hematoma (PH-1/PH-2). The rPH was defined as any extra-ischemic hemorrhagic lesion observed in the follow-up CT. A favorable outcome was defined as a score 0-1 on the Rankin scale at 3 months. We treated 210 patients (mean age 67.6 +/- 12.4 years, 56% were men). The median initial NIHSS score was 14. Patients with rPH (n = 7) had a mean age of 72.4 +/- 7.5 years and 43% were men. The median initial NIHSS score was 15. Three patients had multifocal rPH; three patients had a single rPH and in one patient the rPH was associated with a PH-2. rPH were lobar in six patients and in brainstem in one patient, symptomatic in five patients and asymptomatic in two patients. The outcome was unfavorable in all of them; four deaths (57%) were recorded. Remote cerebral hemorrhage is an infrequent complication after rt-PA treatment (3.3%), it is usually lobar and symptomatic and has an uniformly unfavorable outcome.

Long-term results of neoadjuvant chemotherapy and combined chemoradiotherapy before surgery in the management of locally advanced oesophageal cancer: a single-centre experience.

INTRODUCTION: Neoadjuvant chemoradiotherapy before surgery is an option in the treatment of locally advanced resectable oesophageal cancer (EC). However toxicity is substantial and the improvement in overall survival (OS) with this approach is controversial. METHODS: This was a prospective, single-centre study of neoadjuvant chemotherapy and concomitant chemoradiotherapy with CDDP and 5-FU and 50.4 Gy of external radiotherapy before possible radical surgery in patients with locally advanced resectable EC. If surgery was not possible, a second-phase radiotherapy boost of 10 Gy and one cycle of modified dose chemotherapy were used. RESULTS: Seventy-three patients included between 1998 and 2007: 96% males, median age 61, 83% squamous cell carcinomas, 23% lower third tumours, 36% stage II and 54% stage III and 47% local lymph node involvement. Eighty-six percent completed the combined protocol. Main grade 3-4 toxicities: mucositis (19%) and infections (8%); 4 toxic deaths. Clinical response rates: complete response 54%, partial response 27%, stable disease 8%. Twenty-five patients proceeded to surgery, with radical resection in 24. Pathological response rate: complete response 32%, partial response 52%, progression 16%. There were 7 postoperative deaths and 16 of 34 patients that did not have surgery received the second-phase RT boost. Survival analysis: Median follow-up of 64 months (range 6-134 months). Median OS of 10.33 months. 2-year and 5-year OS of 22 and 16%. The only significant prognostic factor in OS is the clinical complete response rate: 13.9 vs. 7.7 months (p=0.0049). CONCLUSIONS: Our protocol offers a high rate of clinical activity although it is relatively toxic and seems to increase the postoperative mortality, which would blunt any small improvement in survival. The achievement of a complete response is a powerful prognostic factor.

Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Orthotopic liver transplantation (OLT) selection for patients with hepatocellular carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely adopted by the international community. The main aim of this study was to evaluate the survival rates and recurrence probabilities of a new proposal for criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden

Lessons learned from anatomic variants of the hepatic artery in 1,081 transplanted livers.

The aim of this study is to contribute our experience to the knowledge of the anatomic variations of the hepatic arterial supply. The surgical anatomy of the extrahepatic arterial vascularization was investigated prospectively in 1,081 donor cadaveric livers, transplanted at La Fe University Hospital from January 1991 to August 2004. The vascular anatomy of the hepatic grafts was classified according to Michels description (Am J Surg 1966;112:337-347) plus 2 variations. Anatomical variants of the classical pattern were detected in 30% of the livers (n=320). The most common variant was a replaced left artery arising from the left gastric artery (9.7%) followed by a replaced right hepatic artery arising from the superior mesenteric artery (7.8%). In conclusion, the information about the different hepatic arterial patterns can help in reducing the risks of iatrogenic complications, which in turn may result in better outcomes not only following surgical interventions but also in the context of radiological treatments.

Results of an organ preservation protocol with induction chemotherapy and radiotherapy in patients with locally advanced laryngeal carcinoma.

An alternative treatment in patients with advanced laryngeal carcinoma who are candidates for total laryngectomy is induction chemotherapy and radical radiotherapy in an organ preservation approach. We conducted a study to evaluate results of this treatment in patients with locally advanced laryngeal carcinoma, candidates for total laryngectomy, who were treated at a single institution between 1985 and 1997. During the study period, 224 began treatment with induction chemotherapy. Induction chemotherapy consisted of three cycles of cisplatin and 5-fluoruracil in the majority of cases. Four patients died as a consequence of complications associated with chemotherapy treatment. Subsequent treatment consisted of total laryngectomy in 79 patients and radical radiotherapy in 141. After radical radiotherapy, local control for patients who achieved a complete response after induction chemotherapy was 74%, significantly better than 57% in patients with a non-complete response (P=0.04). Considering the initial group of 224 patients, the frequency of organ preservation was 39%. Considering only the patients treated with induction chemotherapy and radiotherapy, the organ preservation frequency was 62%. In a multivariate study, only the response after induction chemotherapy was significantly related to organ preservation.

Hepatocellular carcinoma: Can it be considered a controversial indication for liver transplantation in centers with high rates of hepatitis C?

Hepatocellular carcinoma (HCC) is still considered a controversial indication for liver transplantation (LT), mainly because of long waiting times and underlying viral cirrhosis. The goal was to evaluate the outcome of LT in 104 patients with HCC and cirrhosis, mainly hepatitis C virus (HCV)-related, in a center with a short waiting time (median, 105 days). Four groups were formed according to the HCC and HCV status: HCV positive with HCC (group 1, n = 81), HCV negative with HCC (group 2, n = 23), HCV positive without HCC (group 3, n = 200), and HCV negative without HCC (group 4, n = 207). Predictive factors of tumor recurrence were demographics, tumor related (size or number of nodules, capsule, bilobar involvement, vascular or lymphatic invasion, clinical and pathologic TNM staging, pre-LT percutaneous ultrasound-guided ethanol injection or transarterial chemoembolization, alpha-fetoprotein levels), donor and surgery related, and year of transplantation. The same variables and "tumor recurrence (yes/no)" were applied to evaluate the effect on survival. The median follow up was 29 months (range, 0 to 104 months). Patient survival was 70% at 1 year and 59% at 5 years for group 1, 87% at 1 year and 77% at 5 years for group 2, 81% at 1 year and 64% at 5 years for group 3, and 88% at 1 year and 77% at 5 years for group 4 (P =.013). Survival was significantly lower in patients with HCC than in those without (74% and 63% versus 85% and 70%, at 1 and 5 years, respectively; P =.05). The causes of death in those with and without HCC were tumor recurrence (24%) and recurrent HCV (8%) versus sepsis (34%) and recurrent HCV (14%). HCC recurrence occurred in 12 patients (11.5%) at a median of 14 months (range, 3 to 60 months) with a probability increasing from 8% at 1 year to 16% at 5 years. In patients with HCC, tumor recurrence was associated with vascular invasion (P =.0004) by multivariate analysis; variables predictive of survival were donor old age (P =.01), viral-related etiology (P =.02), and tumor recurrence (P =.001). Although LT still remains an adequate indication for HCC in centers with high prevalence of HCV infection and short waiting times, both tumor and HCV-related recurrent diseases hamper significantly the outcomes of these patients.