Azoles de antes y ahora: una revisión / Azoles of then and now: a review

Resumen Los azoles son fármacos que inhiben la enzima 14α-esteroldemetilasa, impidiendo la unión de ergosterol; esto altera la estructura y función de la pared celular fúngica. Especialmente el grupo de los triazoles: fluconazol, itraconazol, voriconazol, posaconazol e isavuconazol, son una alternativa farmacológica para el tratamiento de la enfermedad fúngica invasora causada por Aspergillus spp, Candida spp, Cryptococcus spp, patógenos emergentes como los Mucorales, y de micosis endémicas como las ocasionadas por Histoplasma spp y Coccidioides spp. Los efectos adversos de los triazoles son menos frecuentes comparados con los ocasionados por anfotericina B, un antifúngico de uso común para estas micosis. Los principales efectos adversos de los triazoles son hepáticos, gastrointestinales y cardiovasculares como la prolongación del intervalo QT. Las interacciones farmacológicas son usuales y se presentan con moléculas que usan sustratos del citocromo CYP3A4, lo que incluye anti-retrovirales, anti-tuberculosos e inmunomoduladores. En este trabajo se revisan la historia, características farmacológicas y los ensayos clínicos que evidencian su eficacia clínica en los diferentes escenarios clínicos.

Abstract The azoles are drugs that inhibit the 14α-sterol-demethylase enzyme preventing the binding of ergosterol, altering the functionality and structure of the fungal cell wall. Especially the group of triazoles: fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole, are a pharmacological alternative for the treatment of the invasive fungal disease, caused by Aspergillus spp, Candida spp, Cryptococcus spp, by emerging pathogens for example, the Mucoral and finally of endemic mycosis as those caused by Histoplasma spp. and Coccidioides spp. The adverse effects of the triazoles are less frequent compared to those caused by amphotericin B, the main ones being hepatics, gastrointestinals and cardiovasculars, such as the prolongation of the QT interval. The pharmacological interactions are common and occur with molecules that use the substrates of the CYP3A4 cytochrome, for example: antiretroviral, anti-tuberculous and immunomodulators. The history, pharmacological characteristics and clinical trials are reviewed.

The distance from the peroneal tendons sheath to the sural nerve at the posterior tip of the fibula decreases from proximal to distal.

PURPOSE: The aim of this study is to compare the distance from the peroneal tendons sheath to the sural nerve in different points proximally and distally to the tip of the fibula. METHODS: Ten fresh-frozen lower extremities were dissected to expose the nerves and tendons. Having the posterior tip of the fibula as a reference, the distance between the tendons sheath and the sural nerve was measured in each point with a tachometer with three independent different observers. Two measures were taken distally at 1.5 and 2 cm from fibula tip and 3 measures were performed proximally at 2, 3, and 5 cm from fibula tip. Data were described using means, standard deviations, medians, and minimum and maximum values. RESULTS: The average distance between distance between the fibula tip and sural nerve is 16.6 ± 4.4 mm. The average distance between peroneal tendons sheath and the sural nerve at 5 cm, 3 cm, and 2 cm from the proximal fibular tip was 29.6 ± 3.2 mm, 24.2 ± 3.6 mm, and 19.7 ± 2.7 mm, respectively. The average distance between the peroneal tendons sheath and the sural nerve at 2 cm and 1.5 cm distal to fibular tip was 9.1 ± 3.5 mm and 7.8 ± 3.3 mm, respectively. CONCLUSION: The distance from the peroneal tendons sheath to the sural nerve decreases from proximal to distal. As the distance between the peroneal tendons sheath and the sural nerve decreases from proximal to distal, performing the tendoscopy portal more distally would increase the risk of nerve iatrogenic injury.

Role of 18F-FDG PET/CT vs CT-scan in patients with pulmonary metastases previously operated on for colorectal liver metastases.

OBJECTIVE: There is currently no conclusive scientific evidence available regarding the role of the 18F-FDG PET/CT for detecting pulmonary metastases from colorectal cancer (PMCRC) in patients operated on for colorectal liver metastases (CRLM). In the follow up of patients who underwent surgery for CRLM, we compare CT-scan and 18F-FDG PET/CT in patients with PMCRC. METHODS: We designed the study prospectively performing an 18F-FDG PET/CT on all patients operated on for CRLM where the CT-scan detected PMCRC during the follow up. We included patients who were operated on for PMCRC because the histological findings were taken as a control rather than biopsies. RESULTS: Of the 101 pulmonary nodules removed from 57 patients, the CT-scan identified a greater number (89 nodules) than the 18F-FDG PET/CT (75 nodules) (p < 0.001). Sensitivity was greater with the CT-scan (90 vs 76%, respectively) with a lower specificity (50 vs 75%, respectively) than with the 18F-FDG PET/CT. There were no differences between positive-predictive value and negative-predictive value. The 18F-FDG PET/CT detected more pulmonary nodules in four patients (one PMCRC in each of these patients) and more extrapulmonary disease in six patients (four mediastinal lymph nodes, one retroperitoneal lymph node and one liver metastases) that the CT-scan had not detected. CONCLUSION: Although CT-scans have a greater capacity to detect PMCRC, the 18F-FDG PET/CT could be useful in the detection of more pulmonary and extrapulmonary disease not identified by the CT-scan. Advances in knowledge: We tried to clarify the utility of 18F-FDG PET/CT in the management of this subpopulation of patients.

La Problemática Familiar y la Migración de los Adolescentes / Family Problems and Migration of Adolescents

Resumen: Este artículo aborda la problemática familiar, su relación con la migración de los padres y el deseo de migrar o no de los adolescentes de 12 a 18 años, en la comunidad rural de San Mateo Ozolco, municipio de Calpan, en el estado de Puebla, México. Se inició la investigación con un estudio exploratorio, a través de entrevistas a 10 informantes clave; se aplicó el Instrumento de Problemas Familiares a 121 estudiantes de secundaria y bachillerato. La población se dividió para su estudio considerando sus intenciones de migrar o no migrar, permitiendo con esto una diferenciación de las familias, después se relacionó con la problemática familiar, asimismo se dividió la población en hijos de padres migrantes y no migrantes para poder ver su correspondencia con los problemas familiares. Los resultados indican que la interacción familiar negativa y la agresión familiar, están influyendo en la decisión de migración de los adolescentes.

Abstract: This article deals with family issues, its relationship between the migration of parents and the adolescents' desire to migrate or not in the rural community of San Mateo Ozolco in state of Puebla, Mexico. Research began with an exploratory study, through interviews with 10 key informants; the Family Problems Instrument was applied to 121 middle and high school students. The population was divided for further detail, considering the intentions to migrate or not, allowing a differentiation between families and their relationship to family problems. Also, the population was divided into children of migrant and non migrant parents to see their correspondence with family problems. The results indicate that the Family Negative interaction and the Family Aggression are influencing the migration decision of adolescents.

Outcome of strict patient selection for surgical treatment of hepatic and pulmonary metastases from colorectal cancer.

BACKGROUND: Surgery is currently the only potentially curative treatment for hepatic or pulmonary metastases from colorectal cancer. However, the benefit of surgery and the criteria for the inclusion of patients developing hepatic and pulmonary metastases are not well defined. OBJECTIVE: The aim of this study was to describe the outcome for patients who undergo surgery for both hepatic and pulmonary metastases from colorectal cancer, to present a set of preoperative criteria for use in patient selection, and to analyze potential prognostic factors related to survival. DESIGN: This was an observational study with retrospective analysis of data collected with a prospective protocol. SETTINGS: This investigation was conducted at a tertiary centre. PATIENTS: Between January 1996 and January 2010, of 319 patients who underwent surgery for hepatic metastases from colorectal cancer, 44 also had resection of pulmonary metastases. A set of strict selection criteria established by a panel of liver surgeons, chest surgeons, oncologists, and radiologists was used. MAIN OUTCOME MEASURES: Survival was estimated with the Kaplan-Meier method, and univariate analyses were performed to evaluate potential prognostic factors for survival, including variables related to patient, primary tumour, hepatic, and pulmonary metastases and chemotherapy. RESULTS: The 44 patients received a total of 53 pulmonary resections: 36 patients had 1, 7 patients had 2, and 1 patient had 3 resections. There was no postoperative mortality and the morbidity rate after pulmonary resection was 1.8%. No patient was lost to follow-up. Overall survival was 93% at 1 year, 81% at 3 years, and 64% at 5 years. Factors related to poor prognosis in the univariate analysis were presence of more than 1 pulmonary metastasis (p = 0.04), invasion of the surgical margin (p = 0.006), and administration of neoadjuvant chemotherapy (p = 0.01 for hepatic metastases and p = 0.02 for pulmonary metastases). LIMITATIONS: The study was limited by its observational nature and the relatively small number of patients. CONCLUSION: In patients with hepatic and pulmonary metastases from colorectal cancer selected according to strict inclusion criteria, surgical treatment performed in a specialized center is a safe option that offers prolonged survival.

Liver transplantation for hilar cholangiocarcinoma.

The most appropriate treatment for Klatskin tumor (KT) with a curative intention is multimodal therapy based on achieving resection with tumour-free margins (R0 resections) combined with other types of neoadjuvant or adjuvant treatment (the most important factor affecting KT survival is the possibility of R0 resections, achieving 5-year survival rate of 40%-50%). Thirty to forty percent of patients with KT are inoperable and present a 5-year survival rate of 0%. In irresectable non-disseminated KT patients, using liver transplantation without neoadjuvant treatment, the 5-year survival rate increase to 38%, reaching 50% survival in early stage. In selected cases, with liver transplantation and neoadjuvant treatment (chemotherapy and radiotherapy), the actuarial survival rate is 65% at 5 years and 59% at 10 years. In conclusion, correct staging, neoadjuvant treatment, living donor and priority on the liver transplant waiting list may lead to improved results.

[Liver transplantation increases R0 resection and survival of patients with a non-disseminated unresectable Klatskin tumour]. / El trasplante hepático aumenta la resecabilidad R0 y la supervivencia de los pacientes con tumor de Klatskin irresecable no diseminado.

INTRODUCTION: There are no established indications for Liver transplant (LT) in patients with a Klatskin tumour (KT) due to the differences in the published results. OBJECTIVE: To report on our patients who have non-disseminated unresectable KT and who were given a LT, and to compare results with those of patients who have had tumour resection and those who have not. PATIENTS AND METHOD: We have treated 75 patients diagnosed with KT. The mean age was 62 + or - 11 years (range: 38-88 years) and 50 were males (66%). Twenty patients were inoperable. Of the 55 patients who underwent surgery: tumour resection (TR) was performed in 29 cases; there was no tumour dissemination in 11 unresectable cases and therefore these patients were added to the LT waiting list and the remaining 15 unresectable cases had tumour dissemination and remained on palliative treatment. RESULTS: In the LT group there was no postoperative mortality (during the first month) and the survival rate was 95%, 59% and 36% with a disease-free survival of 75%, 40% and 20%; whereas the patients given RT had a survival rate of 80%, 52% and 38% at 1, 3 and 5 years, with a disease-free survival of 65%, 35% and 19%, without any differences compared to the LT group. Patients with unresectable tumour left on palliative therapy had a lower survival than the unresectable who underwent LT (p<0.001). CONCLUSIONS: In patients with non-disseminated unresectable KT, LT has a similar survival to that obtained in cases with resectable R0 liver resection. LT improves the survival rate achieved using palliative treatment in patients with non-disseminated unresectable KT.

[Chemical embolisation before laparoscopic hepatic resection in early hepatocellular carcinoma in cirrhotic patients]. / Quimioembolización previa a la resección hepática laparoscópica en el carcinoma hepatocelular precoz en pacientes cirróticos.

OBJECTIVE: To assess whether preoperative transarterial chemoembolisation (TACE) reduces haemorrhage during laparoscopic resection, thus making the Pringle manoeuvre unnecessary and avoiding any subsequent complications. PATIENTS AND METHODS: We present 3 cirrhotic Child A patients with early hepatocellular carcinoma, all of whom had been given the same treatment involving resection by laparoscopy and preoperative TACE of the segments to remove. All the nodules were located in the right hepatic lobe. One case was treated using total laparoscopic surgery and the two remaining cases were converted to the hand-assisted technique. In the first case we carried out bisegmentectomy VI-VII; in the second, segmentectomy VI plus radiofrequency of a second nodule in segment VII, and in the third case, segmentectomy V. RESULTS: There was no morbidity or mortality. Blood transfusion was not required by any of the patients; in fact blood losses were 100, 50 and 150 ml, respectively, and it was not necessary to carry out the Pringle manoeuvre. Surgical margin was greater than 1cm in the three cases and hospital stay was less than 3, 3 and 4 days, respectively. CONCLUSION: TACE prior to early hepatocellular carcinoma resection in cirrhotic patients seems to improve surgical safety with low blood losses without the use of the Pringle manoeuvre. Prospective random studies should be carried out on a larger number of patients in order to assess this technique.

A new approach to hand-assisted laparoscopic liver surgery.

BACKGROUND: The best type of laparoscopic approach in solid liver tumours (SLTs), whether total laparoscopic surgery or hand-assisted laparoscopic surgery (HALS), has not yet been established. Our objective is to present our experience with laparoscopic liver resections in SLTs performed by HALS using a new approach. METHODS: We performed 35 laparoscopic resections in SLTs, of which 26 were carried out using HALS (in 25 patients) and 21 patients had liver metastases of a colorectal origin (LMCRC) (1 patient had 2 resections), 1 metastasis from a neuroendocrine tumour of the pancreas, 1 hepatocarcinoma on a healthy liver, 1 primary hepatic leiomyosarcoma and 1 giant haemangioma. Mean follow-up was 22 months. OPERATION: One right hemihepatectomy, one left hemihepatectomy, five bisegmentectomies II-III, three bisegmentectomies VI-VII and 16 segmentectomies (five of S. VI, three of S. VIII; three of S. V; two of S. IVb; one of S. II; one of S. IV; and in the remaining case resection of S. III and VI plus resection of a metastasis in S. VIII). MAIN OUTCOME MEASURES: Morbidity and mortality, conversion to open procedure, intraoperative blood loss, intra- and postoperative transfusion, length of stay and survival. RESULTS: There were no intra- or postoperative deaths, nor were there any conversions. One patient presented with morbidity (3.8%) (liver abscess). Mean blood loss was 200 ml (range 0-600 ml). One patient required transfusion (3.8%). Mean operative time was 180 min (range 120-360 min). Mean length of hospital stay was 4 days (range 2-5 days). The actuarial survival rate of the patients at 36 months with liver metastases from colorectal carcinoma (LMCRC) was 80%. CONCLUSIONS: Liver resection with HALS reproduces the low morbidity and mortality rates and effectiveness (3-year survival) of open surgery in SLTs when indicated selectively.

[Right hepatectomy and left hepatectomy performed via hand-assisted laparoscopic surgery. Description of an original technique]. / Hepatectomía derecha e izquierda por laparoscopia asistida. Descripción de un abordaje original.

INTRODUCTION: Laparoscopic liver surgery in solid tumors presents a number of difficulties. This type of surgery is indicated especially in tumors of less than 5 cm located in the left lobe and in anterior segments of the right lobe. Access to posterior lesions of the right lobe (segments VII and VIII) and performing major regulated hepatectomies (more than 3 segments) are at present difficult for liver surgeons. OBJECTIVE: To present a regulated right hepatectomy (RH) and left hepatectomy (LH) performed via hand-assisted laparoscopic surgery (HALS) using an original technique. PATIENTS AND METHOD: RH was performed in a 70-year-old man with hepatic metastases from colorectal carcinoma (pT2N0M1 sigmoid adenocarcinoma). LH was performed in a 44-year-old woman with a 16-cm hemangioma that had shown tumoral growth. Dissection of the hepatic artery was performed between ligations, and the portal vein was sectioned between ligations or with a vascular endostapler. Division of the bile duct and suprahepatic veins was performed with a vascular endostapler. Parenchymal dissection was carried out with a harmonic scalpel and dissection of intrahepatic veins of over 3 mm was performed with a 10-mm Ligasure Atlas. RESULTS: The operating time for RH was 360 min, with no transfusion or complications, and length of hospital stay was 5 days. The operating time for LH was 240 min, requiring 2 U of blood, with no morbidity and a length of hospital stay of 4 days. CONCLUSIONS: HALS allows major liver resections to be performed with low morbidity and mortality and with the advantages of laparoscopic surgery.

[Toward zero mortality in liver resection. Presentation of 200 consecutive cases]. / Hacia la mortalidad cero en las resecciones hepáticas. Presentación de 200 casos consecutivos.

INTRODUCTION: Liver resection (LR) morbidity and mortality rates have dropped in recent decades. Mortality is now below 5% and morbidity is less than 30%. Our objective was to present a series of 200 LRs without mortality and to analyze the factors that may be related to complications. PATIENTS AND METHOD: Between January 1996 and October 2003, 200 LRs were performed in 177 patients. The most common indication was liver metastases in 123 patients (61.5%), primary malignant liver tumors in 27 patients (13.5%), bile duct tumors in 27 patients (13.5%) and benign disease in 23 patients (11.5%). Fifty-one percent of the resections were performed under hemihepatic vascular control and 49% were resections of central segments, segmentary and atypical resections. We studied the association between morbidity and age, sex, previous comorbidity, liver status, indication for surgery, number of resections, major and minor resections, resection extended to other organs, type of vascular occlusion, transfusion requirements, operating time, length of hospital stay and experience of the surgical team. RESULTS: There was no postoperative mortality. The morbidity rate was 17.5% (35 patients) and the most common complications were biliary (8%). Morbidity was related to transfusion (transfused patients presented more complications) (P < .001). Transfusion was greater in major resections, the first 100 resections and prolonged operations. Among the segmentary resections the Pringle maneuver reduced transfusion requirements but this difference was not statistically significant. Morbidity decreased in the second 100 resections, without significant differences. CONCLUSION: LRs can be performed with low mortality and morbidity. Biliary complications and blood transfusion should be avoided whenever possible.

[Perforation of choledochal cyst in a 12-year-old boy]. / Perforación de quiste de colédoco en un varón de 12 años.

Choledochal cyst is a rare congenital malformation that presents in children and young adults and is more frequent in women. Early diagnosis is essential to avoid possible complications. The method of choice for the initial diagnosis is ultrasound. Treatment consists of complete resection of the cyst. We describe a case of perforation of a choledochal cyst in a 12-year-old boy.

[Liver transplantation in the management of unresectable bilateral neuroendocrine metastases]. / Trasplante hepático en metástasis hepáticas irresecables de origen neuroendocrino.

INTRODUCTION: Neuroendocrine tumors are rare neoplasms that present bilateral liver metastases at diagnosis. Because of the good initial results obtained, liver transplantation is considered as a potentially curative treatment. OBJECTIVE: Present our experience of the use of liver transplantation in the management of unresectable bilateral neuroendocrine metastases. PATIENTS AND METHODS: We retrospectively reviewed the medical records of eight patients (four men and four women), with a mean age of 45 years, who underwent liver transplantation due to bilateral neuroendocrine liver metastases between January 1996 and January 2005. The most frequent location of the primary tumor was the pancreas in five patients (one carcinoid, one gastrinoma and three non-functioning tumors). The remaining three tumors were located in the small bowel (two) and in the lung. RESULTS: Only one patient died due to technical complications related to the transplant, representing a mortality rate for the entire group of 14%. After a median follow-up of 3 years (range: 1 month-6 years), two patients died due to tumoral recurrence at 15 and 17 months, representing a tumoral recurrence rate of 33%. The survival rate at 1 and 3 years was 86% and 57%, respectively. CONCLUSIONS: Despite the initial promising results obtained with liver transplantation in the management of unresectable neuroendocrine liver metastases, our results indicate that careful patient selection is required. The key to obtaining good results is individualization of the indication for this procedure.

[Laparoscopic resection of solid liver tumors. Presentation of our experience]. / Resección de tumores hepáticos sólidos por laparoscopia. Presentación de nuestra experiencia.

INTRODUCTION: Laparoscopic liver resection (LLR) of solid liver tumors (SLT) has not become widespread due to technical problems, the risk of air embolism, and possible tumoral spread in malignant lesions. We present our experience of LLR in SLT. PATIENTS AND METHOD: Between January 2003 and May 2005, we performed the laparoscopic approach in 16 patients with SLT. Preoperative diagnosis was liver metastases from colorectal carcinoma in 11 patients and benign tumor in the remaining five patients. Five of the lesions were located in the left lobe, another 10 in the right lobe (two in S. V, four in S. VI and four in S. VII) and the remaining lesion was bilobar (S. III and VI). LLRs were performed by complete laparoscopic hepatectomy (CLH) (n=8) and assisted laparoscopic hepatectomy (ALH) (n=8). LLR was completed in 13 patients (81%). Surgical technique (n=13) consisted of three left lobectomies, one with partial resection of S. IV, three bisegmentectomies (two of S. VI and VII and one of S. III and IV, the latter associated with metastasectomy in S. VIII), five segmentectomies (one of S. II, two of S. V and two of S. VI, one of the latter associated with metastasectomy in S. VII) and two local resections of benign tumors. RESULTS: There was no intra- or postoperative mortality. With CLH the LLR was completed in five patients (62%), whereas with ALH there were no conversions. Only one of the 13 resected patients required transfusion. Seventeen nodules were excised in the 13 LLR, and 12 of 17 required the Pringle maneuver. The mean length of hospital stay was 4.9 days (3-14 days). Only one female patient (7.7%) developed an infected hematoma, requiring radiological drainage. CONCLUSION: LLR of benign SLTs shows all the advantages of laparoscopy. In the case of malignant lesions, greater experience is needed to confirm the safety and effectiveness of the open approach.

Laparoscopic iatrogeny of the hepatic hilum as an indication for liver transplantation.

The introduction of biliary laparoscopic surgery led to an increase in the incidence of liver hilum injuries. These types of lesions are very serious, because they can lead to secondary biliary cirrhosis or fulminant hepatic failure and the need for liver transplantation (LT). We present three cases of liver hilum injuries, which were treated with LT; one case was due to severe and persistent cholangitis, and two cases were due to fulminant hepatic failure. The world literature is also reviewed, and published cases of iatrogenic lesions of the liver hilum caused by laparoscopic surgery and requiring LT are presented. These iatrogenic lesions of the hepatic hilum are complex and technically demanding, due to their high morbidity and mortality and even the need for LT. In conclusion, these lesions must be always managed in centers with experience in hepatobiliary surgery.

Spanish experience in liver transplantation for hilar and peripheral cholangiocarcinoma.

OBJECTIVE: To assess the real utility of orthotopic liver transplantation (OLT) in patients with cholangiocarcinoma, we need series with large numbers of cases and long follow-ups. The aim of this paper is to review the Spanish experience in OLT for hilar and peripheral cholangiocarcinoma and to try to identify the prognostic factors that could influence survival. SUMMARY BACKGROUND DATA: Palliative treatment of nondisseminated irresectable cholangiocarcinoma carries a zero 5-year survival rate. The role of OLT in these patients is controversial, due to the fact that the survival rate is lower than with other indications for transplantation and due to the lack of organs. METHODS: We retrospectively reviewed 59 patients undergoing OLT in Spain for cholangiocarcinoma (36 hilar and 23 peripheral) over a period of 13 years. We present the results and prognostic factors that influence survival. RESULTS: The actuarial survival rate for hilar cholangiocarcinoma at 1, 3, and 5 years was 82%, 53%, and 30%, and for peripheral cholangiocarcinoma 77%, 65%, and 42%. The main cause of death, with both types of cholangiocarcinoma, was tumor recurrence (present in 53% and 35% of patients, respectively). Poor prognosis factors were vascular invasion (P < 0.01) and IUAC classification stages III-IVA (P < 0.01) for hilar cholangiocarcinoma and perineural invasion (P < 0.05) and stages III-IVA (P < 0.05) for peripheral cholangiocarcinoma. CONCLUSIONS: OLT for nondisseminated irresectable cholangiocarcinoma has higher survival rates at 3 and 5 years than palliative treatments, especially with tumors in their initial stages, which means that more information is needed to help better select cholangiocarcinoma patients for transplantation.