The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.

The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.

Superior capsular reconstruction of irreparable rotator cuff tear using autologous hamstring graft. / Reconstrucción de la cápsula superior en las roturas irreparables del manguito mediante injerto autógeno de isquiotibiales.

OBJECTIVE: The aim of this study was to investigate the clinical results and radiographic findings after superior capsular reconstruction (SCR) of postero-superior symptomatic irreparable rotator cuff tears (PSIRCT) using a new SCR technique using autologous hamstring graft MATERIAL AND METHODS: From 2014 to 2016, 8 shoulders of 8 patients (mean age 59.6 years) with PSIRCT underwent SCR using autologous hamstring graft. Physical examination, X-ray and MRI were performed before the surgery and 12 months after it. A descriptive analysis was performed of the variables, and the non-parametric test of signs comparing the measurements taken before the operation and 12 months after it. RESULTS: We found an improvement in the Constant test from 49 before the SCR to 77.25 one year after the operation. The mean active flexion significantly increased from 99.3° to 142.5°. The mean preoperative AH distance increased from 5.25 (range from 3 to 7) before surgery to 8.18 (range from 6 to 10.5) after the SCR. There were no tears of the graft during follow-up. CONCLUSION: SCR with a hamstring graft improves the function of the shoulder in PSIRCT, and is an alternative technique for treating these injuries without closing the door to other types of surgery.

Contribution of early SPECT/CT to 99mTc-MIBI double phase scintigraphy in primary hyperparathyroidism: Diagnostic value and correlation between uptake and biological parameters.

AIM: To evaluate the value of 99mTc-MIBI double-phase scintigraphy (DPS) and early SPECT/CT in the pre-surgical assessment of patients with primary hyperparathyroidism (PHPT). Also, to calculate the correlation between uptake and some biological parameters. MATERIAL AND METHODS: Forty patients with PHPT were included: 37 solitary adenomas, 1 hyperplasia, and 2 double adenomas. Fifteen patients had ectopic glands. DPS and early SPECT/CT were acquired in all patients. Ultrasound was performed in 31/40. All patients underwent surgery, intra-operative iPTH measurements, and histopathological examinations. Qualitative DPS uptake was assessed and correlated to pre-surgical calcium, iPTH levels, gland weight, and maximum diameter. RESULTS: In the planar study, there were 23 positive cases, 8 doubtful, and 9 negatives. With the SPECT/CT, 8/9 negatives cases were located. All doubtful cases were confirmed as positives. Gland location improved in 16 cases (12 ectopic). DPS+SPECT/CT failed to detect a solitary adenoma and at least one gland in three cases of multiglandular disease (MGD). The sensitivity by patient was: DPS 72.5%, DPS+SPECT/CT 90%, and ultrasound 42%. Ultrasound and scintigraphy (DPS+SPECT/CT) were concordant in 16/31 patients. For the rest of them, scintigraphy proved correct in 14/15, and both techniques failed in one case. There was a significant correlation between level of uptake and iPTH level, gland weight, and maximum diameter. CONCLUSION: Early SPECT/CT improves sensitivity and the locating of parathyroid pathological glands and increases diagnostic confidence. iPTH level, glandular size, and weight are related to the qualitative assessment of 99mTc-MIBI uptake in early DPS.

Genetic structure of a phytophagous mite species affected by crop practices: the case of Tetranychus urticae in clementine mandarins.

Tetranychus urticae Koch is a cosmopolitan mite considered as the most polyphagous species among spider mites. This mite is a key pest of clementine mandarins in Eastern Spain, where Spanish clementine production concentrates. Crop management practices can affect the population dynamics of this mite and, consequently, its impact on the orchard. Microsatellite markers were used to study mite population genetics from two commercial orchards which had been managed differently following Integrated Pest Management (IPM) or Organic Pest Management (OPM) schemes during four consecutive years. A multiplex system including 20 microsatellite loci was designed specifically and allowed an efficient and inexpensive genotyping of individual mites. We found that the IPM population had a stronger fluctuation of population structure and higher genetic diversity compared to OPM population. Thus, our study concludes that crop management has an impact on the population genetics of T. urticae which may be related to the alternation of some acaricides under IPM.

Evaluation by SPECT-CT of an incidental finding of a thymoma and breast cancer in a myocardial perfusion SPECT with 99mTc-MIBI.

We present a case of a 78-year-old female with effort angina. A myocardial perfusion SPECT (MPS) showed increased tracer uptake in two synchronic tumor lesions, a thymoma and a breast cancer. This case highlights the contribution of SPECT-CT in the characterization of these findings and its essential role in rapid decision-making. The patient underwent surgery of both lesions that had gone undetected prior to the conduction of the MPS.

Inflammatory myofibroblastic tumor of the esophagus treated by endoscopy.

Inflammatory myofibroblastic tumors are rare lesions that have been described in virtually every organ including the gastrointestinal tract. The esophagus is an extremely unusual site for these tumors, with only a few cases described in the literature. Surgery has been the most common therapeutic approach used for the resection of these lesions. In the present case, a patient diagnosed with an inflammatory myofibroblastic tumor of the upper esophagus was reported, and it was successfully removed by endoscopy with no complications.

Frequencies of -308G/A (TNFA) and -509C/T (TGFB1) polymorphisms in sickle cell anemia patients from Brazil.

Sickle cell anemia is an affection that causes chronic inflammation, with consequences for vaso-occlusion, oxidative stress and cytokine production. Genetic polymorphisms in markers involved in this process can modulate the inflammatory response, including polymorphisms -308G/A of TNFA (tumor necrosis factor alpha) and -509C/T of TGFB1 (transforming growth factor beta 1), reported to increase TNF-α and TGF-ß1 production, respectively. Changes in the cytokine balance are important risk factors for clinical events; consequently, we examined the frequencies of these polymorphisms in 240 Brazilian sickle cell anemia patients from southeast Brazil. PCR-RFLP was used to detect these polymorphisms. The -509C/T (TGFB1) polymorphism was more frequent than -308G/A (TNFA), with allelic frequency of 0.3 for the mutant allele T (TGFB) agaist 0.1 for the mutant allele A (TNFA). These allelic frequencies are similar to those known from populations with ethnicity similar to the Brazilian population. Inheritance of these polymorphisms does not seem to be associated with that of the Hb S mutation; however, this information could be useful in analyses of specific clinical characteristics of sickle cell anemia.

SPECT-CT in the localization of an ectopic retropharyngeal parathyroid adenoma as a cause for persistent primary hyperparathyroidism.

A common cause for surgical failure of primary hyperparathyroidism (pHPT) is the non-detection of an ectopic adenoma during the intervention. We present a case of a patient with pHPT in whom an ectopic gland was found in the right retropharyngeal space by means of a double phase (99m)Tc-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) scintigraphy and early SPECT-CT after several surgeries and imaging tests. The addition of a tomography to the planar scintigraphy increases its sensitivity and improves pathological parathyroid glands localization. The hybrid imaging is sometimes essential to obtain surgical success, as in the case of ectopic adenomas.

Lipid-based drug delivery systems for cancer treatment.

It is a fact that chemotherapy agents have little specificity for cancer cells, this leading to low concentrations into the tumor interstititum and severe side effects on healthy tissues. The formulation of lipid-based nanomedicines against cancer has been hypothesized to improve drug localization into the tumor tissue and to increase the anticancer efficacy of concentional drugs, while minimizing their systemic adverse effects. In this review, special attention is devoted to the analysis of the state-of-the-art in the development of lipid-based drug carriers against cancer. Specifically, the most significant in vitro and in vivo results on the use of niosomes, liposomes, and solid lipid nanoparticles are revised. It is concluded that biodistribution profiles of chemotherapy agents can be controlled by their loading to such nanoplatforms. Lipid-based nanomedicines offer an interesting approach to the delivery of anticancer drugs to brain tumors, and to reverse multi-drug resistance of cancer cells. Finally, a deep evaluation of the applicability of drug delivery strategies in the formulation of lipid-based nanoplatforms is carried out. They involve active drug targeting (including ligand-mediated delivery, and stimuli-sensitive carriers), and passive drug targeting (through the enhanced permeability and retention effect) to tumors.

Maternal caffeine intake during gestation and lactation down-regulates adenosine A1 receptor in rat brain from mothers and neonates.

Even though caffeine can be excreted in breast milk, few studies have analyzed the effect of maternal caffeine consumption during lactation on neonatal brain. In the present work pregnant rats were treated daily with 1 g/L of caffeine in their drinking water during pregnancy and/or lactation and the effect on adenosine A(1) receptor in brains from both lactating mothers and 15 days-old neonates was assayed using radioligand binding and real time PCR assays. Mothers receiving caffeine during gestational period developed motor activation in gestational days 8-10 which was associated with a significant decrease of total adenosine A(1) receptor number (84%). A similar decrease was detected in mothers treated with caffeine during lactation (76%) and throughout gestation and lactation (73%); this was accompanied by a significant decrease in mRNA level coding adenosine A(1) receptor (28%). In male neonates, adenosine A(1) receptor was also decreased after chronic caffeine exposure during gestation (80%), lactation (76%) and gestation plus lactation (80%). In female neonates, adenosine A(1) receptor tended to decrease in response to caffeine exposure although no significant variations were found. No variation in the level of mRNA coding adenosine A(1) receptor was detected in neonates in any case. Concerning adenosine A(2A) receptor, radioligand binding assays revealed that this receptor remains unaltered in maternal and neonatal brain in response to caffeine exposure. However, caffeine consumption during gestation and lactation evoked a significant decrease in mRNA level coding A(2A) receptor (32%) in mothers' brain.

Patient-reported outcomes in a phase III, randomized study of sunitinib versus interferon-{alpha} as first-line systemic therapy for patients with metastatic renal cell carcinoma in a European population.

BACKGROUND: The purpose of this study is to evaluate the impact on the health-related quality of life (HRQoL) of sunitinib versus interferon-alpha (IFN-alpha) treatment in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: In all, 304 mRCC patients (European cohort) were randomized 1 : 1 to receive sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off) or IFN-alpha (9 million units s.c. injection three times/week). The following questionnaires were completed (days 1 and 28 per cycle): Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index and the EuroQol Group's EQ-5D self-report questionnaire (EQ-5D). Results correspond to an ongoing trial with progression-free survival time as primary end point, and patients were still being followed up. Data were analyzed using repeated measures mixed effects models (MEMs) that allow the inclusion of initial differences and uncompleted repeated measures, with the assumption of data missing at random. Six-cycle results were included. RESULTS: Results consistently showed that patients in sunitinib group experienced statistically significantly milder kidney-related symptoms, better cancer-specific HRQoL and general health status (in social utility scores) during the study period as measured by these patient-reported outcome end points. No statistical differences between groups were found on the FACT-G physical well-being subscale or the EQ-5D VAS values. CONCLUSIONS: Results from MEM showed the sunitinib's benefit on HRQoL compared with IFN-alpha.

[Pleural effusion after spinal fixation surgery in patients with traumatic spinal cord injury]. / Derrame pleural tras cirugía de fijación espinal en pacientes con lesión medular traumática.

The present study was designed with to determine the prevalence of pleural effusion after posterior approach for spinal fixation in patients with traumatic spinal fracture with underlying spinal cord lesion. The study included 20 patients over two years. The postoperative monitoring has been done in the Intensive Care Unit and have been practiced complementary examinations control, including chest x-ray study. The prevalence of pleural effusion was 75%, the time of diagnosis was within the first 48 hours after the operation. The pleural effusion does not preference for either side, and has generally been small claims. Only 4 patients it has been need drainage due to respiratory symptoms restrictive, and the outcome have been favourable in rest of the cases at conservative treatment.

p63 protein expression in high risk diffuse large B-cell lymphoma.

BACKGROUND: p63 gene is a p53 homologue that encodes proteins with transactivation, DNA-binding and tetramerisation domains. The isoforms TAp63 and TAp73 transactivate p53 target genes and induce apoptosis, whereas the isoforms DeltaNp63 and DeltaNp73 lack transactivation and might have dominant-negative effects in p53 family members. p63 is expressed in germinal centre lymphocytes and can be related to the development of the lymphoma, but the prognostic significance of its expression in the survival of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. AIMS: To determine whether quantitative immunohistochemical (IHC) analysis of p63 protein expression correlates with CD10 antigen, Bcl-6 antigen and IRF4 antigen expression and to determine whether p63 is a surrogate predictor of overall survival in high-intermediate and high risk DLBCL populations. METHODS: CD10, Bcl-6 and IRF4 expression were retrospectively evaluated by IHC in 73 samples of high-intermediate and high risk DLBCL and were used to divide the lymphomas into subgroups of germinal centre B-cell-like (GCB) and activate B-cell-like (ABC) DLBCL. Similarly, p63 expression was evaluated by IHC and the results were compared with subgroups of DLBCL origin and with the survival rates for these patients. RESULTS: p63 was expressed in more than 50% of malignant cells in 11 patients and did not show correlation with subgroups of GCB-like DLBCL or ABC-like DLBCL, but p63(+) patients had better disease-free survival (DFS) than those who were negative (p = 0.01). CONCLUSIONS: p63(+) high-intermediate and high risk DLBCL patients have a better DFS than negative cases.

Clinical outcome in chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation: the experience of the Bone Marrow Transplantation Unit of FUNFARME/BRAZIL using FISH.

Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for follow-up of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units.

Magnetite/poly(alkylcyanoacrylate) (core/shell) nanoparticles as 5-Fluorouracil delivery systems for active targeting.

In this article, a reproducible emulsion polymerization process is described to prepare core/shell colloidal nanospheres, loaded with 5-Fluorouracil, and consisting of a magnetic core (magnetite) and a biodegradable polymeric shell [poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate), or poly(octylcyanoacrylate)]. The heterogeneous structure of these carriers can confer them both the possibility of being used as drug delivery systems and the responsiveness to external magnetic fields, allowing an active drug targeting without a concurrent systemic distribution. Zeta potential determinations as a function of ionic strength showed that the surface behaviour of the core/shell particles is similar to that of pure cyanoacrylate particles. The first magnetization curve of both magnetite and magnetite/polymer particles demonstrated that the polymer shell reduces the magnetic responsiveness of the particles, but keeps unchanged their ferrimagnetic character. Two drug loading mechanisms were studied: absorption or entrapment in the polymeric network, and surface adsorption. We found that the acidity of the medium had significant effects on the drug absorption per unit mass of polymer, and needs to be controlled to avoid formation of macroaggregates and to reach significant 5-Fluorouracil absorption. The type of polymer and the drug concentration are also main factors determining the drug incorporation to the core/shell particles. 5-Fluorouracil release evaluations showed a biphasic profile affected by the type of polymeric shell, the type of drug incorporation and the amount of drug loaded.

[Acute abdominal pain and mesenteric cyst: Presentation of a case.]. / Abdomen agudo y quiste de mesenterio: Presentación de un caso.

The cysts of mesentery (QM) are organizations whose embryological origin is multiple and the clinical presentation is not clear, in most of the times it is diagnosed of incidental form or by exclusion of other organizations.At least the third part is diagnosed before the 15 years of age, and tends to be of benign nature, but the recurrence she is high when no parched the surgical treatment the totality of the injury.Little series exist reported in Literature in the last years that try to classify and to know the behavior clinical the organization as well as the surgical findings and the histological types without being able to group series greater to 4 patients.The present work tries to inform on the findings ofa pediatric patient of 4 years of age that enter our hospital by a picture of acute abdomen whose diagnosis of certainty was of a QM and to make are vision of Literature in special in our country.

Poly(alkylcyanoacrylate) colloidal particles as vehicles for antitumour drug delivery: a comparative study.

Because of the fundamental importance of new therapeutic routes for cancer treatment, a number of systems based on colloidal particles as vehicles for the delivery of chemotherapeutic agents have been devised. The target is always to provide the proper dose of the antitumour agent only at the desired locus of action, thus reducing the unwanted side effects. The systems studied in this work are nanospheres of the biodegradable polymers poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate) and poly(octylcyanoacrylate), all suitable for parenteral administration, as vehicles for 5-fluorouracil, a well studied drug used for the treatment of solid tumours. Two loading methods have been analyzed: the first one is based on drug addition during the process of generation of the particles, by an anionic emulsion/polymerization procedure, and the subsequent drug trapping in the polymeric network. The second method is based on surface adsorption in already formed nanoparticles, after incubation in the drug solution. A detailed investigation of the capabilities of the polymer particles to load this drug is described. The main factors determining the drug incorporation to the polymer network were the type of monomer, the pH and the drug concentration. The release kinetics of 5-fluorouracil is found to be controlled by the pH of the release medium, the type of drug incorporation and the type of polymer.