Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior.

BACKGROUND: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. METHODS: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. RESULTS: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. CONCLUSIONS: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner.

Circulating miRNA Expression Is Inversely Correlated with Tumor Tissue or Sentinel Lymph Nodes in Estrogen Receptor-Positive Early Breast Cancer Patients.

The deregulation of microRNAs (miRNAs) is associated with the various steps of the metastatic process. In addition, circulating miRNAs are remarkably stable in peripheral blood, making them ideal noninvasive biomarkers for disease diagnosis. Here, we performed a proof-of-principle study to determine whether tumor-tissue-derived miRNAs are traceable to plasma in ER-positive early breast cancer patients. We performed RNA-sequencing on 30 patients for whom plasma, sentinel lymph nodes (SLNs) and tumor tissue were available. We carried out differential expression, gene ontology and enrichment analyses. Our results show that circulating miRNAs are inversely expressed compared with tumor tissue or SLNs obtained from the same patients. Our differential expression analysis shows the overall downregulation of circulating miRNAs. However, the expression of miR-643a-3p and miR-223 was up-regulated in patients with positive SLNs. Furthermore, gene ontology analysis showed the significant enrichment of biological processes associated with the regulation of epithelial cell proliferation and transcriptional regulation commonly involved in the promotion of metastases. Our results suggest the potential role of several circulating miRNAs as surrogate markers of lymph node metastases in early breast cancer patients. Further preclinical and clinical studies are required to understand the biological significance of the most significant miRNAs and to validate our results in a larger cohort of patients.

Low-Density Lipoprotein Receptor Is a Key Driver of Aggressiveness in Thyroid Tumor Cells.

We previously described the role of low-density lipoprotein (LDL) in aggressiveness in papillary thyroid cancer (PTC). Moreover, the MAPK signaling pathway in the presence of BRAF V600E mutation is associated with more aggressive PTC. Although the link between MAPK cascade and LDL receptor (LDLR) expression has been previously described, it is unknown whether LDL can potentiate the adverse effects of PTC through it. We aimed to investigate whether the presence of LDL might accelerate the oncogenic processes through MAPK pathway in presence or absence of BRAF V600E in two thyroid cell lines: TPC1 and BCPAP (wild-type and BRAF V600E, respectively). LDLR, PI3K-AKT and RAS/RAF/MAPK (MEK)/ERK were analyzed via Western blot; cell proliferation was measured via MTT assay, cell migration was studied through wound-healing assay and LDL uptake was analyzed by fluorometric and confocal analysis. TPC1 demonstrated a time-specific downregulation of the LDLR, while BCPAP resulted in a receptor deregulation after LDL exposition. LDL uptake was increased in BCPAP over-time, as well as cell proliferation (20% higher) in comparison to TPC1. Both cell lines differed in migration pattern with a wound closure of 83.5 ± 9.7% after LDL coculture in TPC1, while a loss in the adhesion capacity was detected in BCPAP. The siRNA knockdown of LDLR in LDL-treated BCPAP cells resulted in a p-ERK expression downregulation and cell proliferation modulation, demonstrating a link between LDLR and MAPK pathway. The modulation of BRAF-V600E using vemurafenib-impaired LDLR expression decreased cellular proliferation. Our results suggest that LDLR regulation is cell line-specific, regulating the RAS/RAF/MAPK (MEK)/ERK pathway in the LDL-signaling cascade and where BRAF V600E can play a critical role. In conclusion, targeting LDLR and this downstream signaling cascade, could be a new therapeutic strategy for PTC with more aggressive behavior, especially in those harboring BRAF V600E.

Biliary Tree Cysts and Surgical Treatment: Outcomes in a Multicentric Study.

Background: Biliary tree cysts (BTCs) represent an either localized or multifocal abnormal dilatation of the biliary tree, which entails an increased risk of acute cholangitis and cholangiocarcinoma (2.5%-16%). Its incidence in Western countries is ∼1/100.000-1/150.000, being more frequent in Asia (1/1.000). These cysts are usually classified according to Todani classification, which is based on site and morphology of cysts. Patients and Methods: This is a retrospective multicentric descriptive study of patients surgically treated for BTCs. From 2005 to 2018, 25 cases were collected between Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) and Ospedale San Paolo (Savona, Italy). Clinical presentation was characterized by abdominal pain, jaundice, fever, and sometimes weight loss. Eight patients presented Todani type I, 1 patient Todani type II, 3 patients Todani III, 1 patient Todani type IV, and 12 patients Todani type V. Results: Among the 25 surgically treated patients, 12 patients underwent liver resection, 7 patients underwent resection of the extrahepatic biliary tree, 3 patients underwent BTC removal through a duodenotomy, 1 patient underwent resection of the extrahepatic biliary tree and liver resection, and 2 patients underwent pancreatoduodenectomy. Overall 30-day morbidity rate was 20%, and 90-day mortality was 0%. Pathologic examination confirmed diagnosis of cholangiocarcinoma in 5 patients (20%). After a median follow-up of 59 months, 20 patients are alive and in good conditions, whereas 50% of patients with cholangiocarcinoma died for disease progression. Conclusions: Surgical treatment for BTCs is associated with acceptable postoperative outcomes, with moderate morbidity and null mortality rates. Moreover, the risk of developing cholangiocarcinoma is still high that prompts surgical treatment once diagnosis is made.

Circulating microRNAs in Early Breast Cancer Patients and Its Association With Lymph Node Metastases.

MicroRNAs have emerged as important regulators of the metastatic process. In addition, circulating miRNAs appear to be surprisingly stable in peripheral blood making them ideal noninvasive biomarkers for disease diagnosis. Here, we performed a proof-of-principle study to investigate the expression profile of circulating miRNAs and their association with the metastatic lymph node status in early breast cancer patients. Sentinel lymph node status was detected by one-step nucleic acid (OSNA) analysis. We performed RNA-sequencing in 16 plasma samples and validated the results by qPCR. Gene Ontology term enrichment and KEGG pathway analyses were carried out using DAVID tools. We found16 differentially expressed miRNAs (q < 0.01) in patients with positive SLNs. Fourteen miRNAs were down-regulated (miR-339-5p, miR-133a-3p, miR-326, miR-331-3p, miR-369-3p, miR-328-3p, miR-26a-3p, miR-139-3p, miR-493-3p, miR-664a-5p, miR-146a-5p, miR-323b-3p, miR-1307-3p and miR-423-3p) and 2 were up-regulated (miR-101-3pand miR-144-3p). Hierarchical clustering using differentially expressed miRNAs clearly distinguished patients according to their lymph node status. Gene ontology analysis showed a significant enrichment of biological processes associated with the regulation of the epithelial mesenchymal transition, cell proliferation and transcriptional regulation. Our results suggest the potential role of several circulating miRNAs as surrogate markers of lymph node metastases in early breast cancer patients. Further validation in a larger cohort of patients will be necessary to confirm our results.

What to do when the parathyroid gland is not found during a transcervical exploration?

The most frequent cause of suboptimal results in a parathyroid adenoma resection is an ectopic location, mainly in the anterior mediastinum. These cases may not always be resected through a traditional cervical access. We present 2 cases of primary hyperparathyroidism who underwent an unsuccessful bilateral cervical exploration due to parathyroid tissue located inside the thymic gland. A video-assisted thoracoscopic surgery thymectomy with intraoperative determination of blood parathormone levels was performed. A 50% reduction of intraoperatory parathyroid hormone blood from the highest basal level at 5 and 10 min after resection was obtained. Final pathological results showed an intra-thymic parathyroid adenoma in the first patient and an intra-thymic focus of parathyroid hyperplasia in the second patient. In conclusion, video-assisted thoracoscopic surgery thymectomy could be the optimal approach to resect ectopic parathyroid adenomas located in the anterior mediastinum.

LDL, HDL and endocrine-related cancer: From pathogenic mechanisms to therapies.

Cholesterol is essential for a variety of functions in endocrine-related cells, including hormone and steroid production. We have reviewed the progress to date in research on the role of the main cholesterol-containing lipoproteins; low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and their impact on intracellular cholesterol homeostasis and carcinogenic pathways in endocrine-related cancers. Neither LDL-cholesterol (LDL-C) nor HDL-cholesterol (HDL-C) was consistently associated with endocrine-related cancer risk. However, preclinical studies showed that LDL receptor plays a critical role in endocrine-related tumor cells, mainly by enhancing circulating LDL-C uptake and modulating tumorigenic signaling pathways. Although scavenger receptor type BI-mediated uptake of HDL could enhance cell proliferation in breast, prostate, and ovarian cancer, these effects may be counteracted by the antioxidant and anti-inflammatory properties of HDL. Moreover, 27-hydroxycholesterol a metabolite of cholesterol promotes tumorigenic processes in breast and epithelial thyroid cancer. Furthermore, statins have been reported to reduce the incidence of breast, prostate, pancreatic, and ovarian cancer in large clinical trials, in part because of their ability to lower cholesterol synthesis. Overall, cholesterol homeostasis deregulation in endocrine-related cancers offers new therapeutic opportunities, but more mechanistic studies are needed to translate the preclinical findings into clinical therapies.

MicroRNA-1291 Is Associated With Locoregional Metastases in Patients With Early-Stage Breast Cancer.

Evidence that microRNAs (miRNAs) regulate the various steps of metastasis is increasing. Several studies have looked at the miRNA expression profile in primary breast tumors but few have compared primary tumor and sentinel lymph node (SLN) metastasis. We correlated the expression of miRNAs with the SLN status and the outcome of axillary lymph node dissection (ALND) in 60 patients with early breast cancer. We profiled the expression of miRNAs in paired breast tumor samples and SLNs using the NextSeq500 Illumina platform and key findings were validated by qPCR. MultiMiR Bioconductor and Reactome pathways analysis were performed to identify target genes and signaling pathways affected by altered expressed miRNAs. Our results show that nine miRNAs were differentially expressed in tumor tissues (q ≤ 0.05). In tumor samples, a 13.5-fold up-regulation of miR-7641-2 (q < 0.001) and a 2.9-fold down-regulation of miR-1291 (q < 0.001) were associated with tumors with positive SLNs. However, only down-regulation of miR-1291 (q = 0.048) remained significant in paired SLNs samples. Interestingly, a 10.5 up-regulation of miR-1291 in SLNs samples was associated with additional axillary lymph node involvement (q < 0.001). The enrichment analyses showed that canonical and non-canonical WNT pathways and negative regulation of various receptor tyrosine kinases signaling pathways were targets of miR-1291 and supports the role of miR-1291 as a tumor suppressor gene (TSG). Further studies are warranted to investigate the use of miR-1291 as a surrogate biomarker of SLN node metastasis in patients with early-stage breast cancer.

Laparoscopic liver resection of the Spiegel lobe by a left-sided approach preserving an accessory left hepatic artery.

BACKGROUND: Caudate lobe of the liver can be divided in three portions: Spiegel lobe, paracaval portion and caudate process [1]. The anatomy of the caudate lobe and its proximity to major vascular structures makes this operation a difficult resection, especially for laparoscopic liver surgery [2]. For that reason the Iwate criteria proposed to classify this surgery at the "2nd International Consensus Conference on Laparoscopic Liver Resection" as intermediate or advanced difficulty depending on the type of resection, and the size of the tumor [3]. For tumors located in the Spiegel lobe, the left side approach is preferred [4]. METHODS: We present a 69-year-old woman with liver metastasis from previously resected sternal condrosarcoma on 30/05/2017. A unique recurrence in the caudate lobe was found on computed tomography and magnetic resonance imaging on April 2019. RESULTS: A Spiegel lobe resection with left side approach preserving an accessory left hepatic artery was performed. A resection of the artery was planned if the preservation was not possible. The operative time was 180 min and the total Pringle time was 30 min. Patient was discharged at the 4 postoperative day and there were no postoperative complications CONCLUSIONS: Laparoscopic liver resection of the caudate lobe for condrosarcoma liver metastasis is feasible and safe. Left approach seems the best option for Spiegel lobe resections even in patients with accessory left hepatic artery.

Risk factors for open conversion of lateral transperitoneal laparoscopic adrenalectomy: retrospective cohort study of the Spanish Adrenal Surgery Group (SASG).

BACKGROUND: Laparoscopic adrenalectomy has become the standard of care for treating adrenal tumors. Conversion from laparoscopic adrenalectomy to an open approach during surgery may be necessary in some cases. This study aimed to identify the risk factors for open conversion of laparoscopic adrenalectomy. METHODS: Retrospective analysis of all consecutive patients undergoing lateral transperitoneal laparoscopic adrenalectomy in six endocrine surgery units of the Spanish Adrenal Surgery Group (SASG) between January 2005 and December 2017. Demographic, clinical, surgical, and histopathologic characteristics were recorded. Risk factors for conversion were assessed by logistic regression analysis. RESULTS: Of a total of 865 patients included in the study, 58 (6.7%) required conversion to open surgery. In the univariate analysis, factors associated with conversion from laparoscopic to open adrenalectomy were body mass index (BMI) ≥ 30 kg/m2 (P = 0.002), previous abdominal surgery (P = 0.015), tumor size > 5 cm (P = 0.001), and surgery for pheochromocytoma (P = 0.034). In the multivariate analysis, independent risk factors were BMI ≥ 30 kg/m2 [odds ratio (OR) 4.26, 95% confidence interval (CI) 2.81-8.75; P = 0.001], tumor size > 5 cm (OR 10.15, 95% CI 4.24-28.31; P < 0.001), and surgery for pheochromocytoma (OR 2.96, 95% CI 1.89-11.55; P = 0.015). CONCLUSIONS: Obesity, tumor size, and pheochromocytoma as the type of adrenal tumor were predictive factors for intraoperative conversion from laparoscopic to open adrenalectomy. Preoperative assessment of these characteristics should be valuable to clinicians in discussing conversion risk in patients and for surgical planning.

Cholesterol and 27-hydroxycholesterol promote thyroid carcinoma aggressiveness.

Cholesterol mediates its proliferative and metastatic effects via the metabolite 27-hydroxycholesterol (27-HC), at least in breast and endometrial cancer. We determined the serum lipoprotein profile, intratumoral cholesterol and 27-HC levels in a cohort of patients with well-differentiated papillary thyroid carcinoma (PTC; low/intermediate and high risk), advanced thyroid cancers (poorly differentiated, PDTC and anaplastic thyroid carcinoma, ATC) and benign thyroid tumors, as well as the expression of genes involved in cholesterol metabolism. We investigated the gene expression profile, cellular proliferation, and migration in Nthy-ori 3.1 and CAL-62 cell lines loaded with human low-density lipoprotein (LDL). Patients with more aggressive tumors (high-risk PTC and PDTC/ATC) showed a decrease in blood LDL cholesterol and apolipoprotein B. These changes were associated with an increase in the expression of the thyroid's LDL receptor, whereas 3-hydroxy-3-methylglutaryl-CoA reductase and 25-hydroxycholesterol 7-alpha-hydroxylase were downregulated, with an intratumoral increase of the 27-HC metabolite. Furthermore, LDL promoted proliferation in both the Nthy-ori 3.1 and CAL-62 thyroid cellular models, but only in ATC cells was its cellular migration increased significantly. We conclude that cholesterol and intratumoral accumulation of 27-HC promote the aggressive behavior process of PTC. Targeting cholesterol metabolism could be a new therapeutic strategy in thyroid tumors with poor prognosis.

Cross-Talk between Inflammatory Mediators and the Epithelial Mesenchymal Transition Process in the Development of Thyroid Carcinoma.

There is strong association between inflammatory processes and their main metabolic mediators, such as leptin, adiponectin secretion, and low/high-density lipoproteins, with the cancer risk and aggressive behavior of solid tumors. In this scenario, cancer cells (CCs) and cancer stem cells (CSCs) have important roles. These cellular populations, which come from differentiated cells and progenitor stem cells, have increased metabolic requirements when it comes to maintaining or expanding the tumors, and they serve as links to some inflammatory mediators. Although the molecular mechanisms that are involved in these associations remain unclear, the two following cellular pathways have been suggested: 1) the mesenchymal-epithelial transition (MET) process, which permits the differentiation of adult stem cells throughout the acquisition of cell polarity and the adhesion to epithelia, as well to new cellular lineages (CSCs); and, 2) a reverse process, termed the epithelial-mesenchymal transition (EMT), where, in pathophysiological conditions (tissue injury, inflammatory process, and oxidative stress), the differentiated cells can acquire a multipotent stem cell-like phenotype. The molecular mechanisms that regulate both EMT and MET are complex and poorly understood. Especially, in the thyroid gland, little is known regarding MET/EMT and the role of CCs or CSCs, providing an exciting, new area of knowledge to be investigated. This article reviews the progress to date in research on the role of inflammatory mediators and metabolic reprogramming during the carcinogenesis process of the thyroid gland and the EMT pathways.

Leiomyosarcoma of the Right Gonadal Vein: Review of the Approach and Prognostic in a Rare Case.

BACKGROUND: Venous leiomyosarcoma is a mesenchymal tumour that represents 5-7% of soft tissue sarcomas. It originates in the smooth muscle cells of the vessel wall and is frequently located in the inferior vena cava. Primary leiomyosarcomas of the gonadal vein are rare, with only 10 cases reported in the literature. CASE REPORT: We present the case of a 51-year-old woman diagnosed with a right retroperitoneal mass by computed tomography (CT). The differential diagnosis was between a neurogenic tumour and a mesodermic tumour. The tumour was dissected from the vena cava and right ureter by laparoscopy without performing resection en bloc. Histologic examination of the surgical specimen showed a high-grade leiomyosarcoma of the right gonadal vein. The postoperative course was uneventful. Three cycles of chemotherapy with epirubicin-ifosfamide were performed. DISCUSSION AND CONCLUSIONS: Venous leiomyosarcoma is an aggressive tumour, and prognosis is poor due to haematogenous spread. No chemotherapy or radiotherapy has yet proven effective in improving survival, and complete surgical excision is currently considered to offer the best chance of cure. Despite the more conservative treatment approach used in the present case, the patient is alive three years after surgery and has a good quality of life. Although it was not used in this patient, the standard procedure for optimal survival is resection en bloc.

The proteomic 2D-DIGE approach reveals the protein voltage-dependent anion channel 2 as a potential therapeutic target in epithelial thyroid tumours.

We investigated the role of VDAC2 in human epithelial thyroid tumours using proteomic 2D-DIGE analysis and qRT-PCR. We found a significant up-regulation of VDAC2 in thyroid tumours and in thyroid tumour cell lines (TPC-1 and CAL-62). We did not detect overexpression of VDAC2 in a normal thyroid cell line (Nthy-ori 3-1). Silico analysis revealed that two proteins, BAK1 and BAX, had a strong relationship with VDAC2. BAK1 gene expression showed down-regulation in thyroid tumours (follicular and papillary tumours) and in TPC-1 and CAL-62 cell lines. Transient knockdown of VDAC2 in TPC-1 and CAL-62 promoted upregulation of the BAK1 gene and protein expression, and increased susceptibility to sorafenib treatment. Overexpression of the BAK1 gene in CAL-62 showed lower sorafenib sensitivity than VDAC2 knockdown cells. We propose the VDAC2 gene as a novel therapeutic target in these tumours.

A new time limited psychotherapy for BPD: preliminary results of a randomized and controlled trial.

INTRODUCTION: Psychic Representation focused Psychotherapy (PRFP) is a new time limited dynamic psychotherapy for the treatment of Borderline Personality Disorder. It is a psychodynamic technique based on brief psychoanalytic psychotherapy principles. It is manualized and designed to be applied in the framework of public health care services. A randomized and controlled study with a sample of 53 patients was conducted to assess PRFP efficacy. This work presents the results for the first 44 trial completers at termination of treatment. METHODS: Both groups, the experimental (n= 18) and control group (n= 26), received treatment as usual. The experimental group received an additional 20 (PRFP) sessions, conducted by four therapists with homogenous characteristics specifically trained in this technique. The main outcome variables measures were: Severity global index of SCL-90-R, Barrat Impulsivity Scale scores and Social Adaptation (SASS score). Baseline and final condition at termination was compared. CONCLUSIONS: Preliminary results showed significantly better outcomes for the experimental group in all the main variables measured and in most of the secondary ones. PRFP may represent an important contribution for the treatment of BPD patients. Follow-up assessment at 6 and 12 months is planned.

Complete axillary lymph node dissection versus clinical follow-up in breast cancer patients with sentinel node micrometastasis: final results from the multicenter clinical trial AATRM 048/13/2000.

BACKGROUND: It has been suggested that selective sentinel node (SN) biopsy alone can be used to manage early breast cancer, but definite evidence to support this notion is lacking. The aim of this study was to investigate whether refraining from completion axillary lymph node dissection (ALND) suffices to produce the same prognostic information and disease control as proceeding with completion ALND in early breast cancer patients showing micrometastasis at SN biopsy. METHODS: This prospective, randomized clinical trial included patients with newly diagnosed early-stage breast cancer (T<3.5 cm, clinical N0, M0) who underwent surgical excision as primary treatment. All had micrometastatic SN. Patients were randomly assigned to one of the two study arms: complete ALND (control arm) or clinical follow-up (experimental arm). Median follow-up was 5 years, recurrence was assessed, and the primary end point was disease-free survival. RESULTS: From a total sample of 247 patients, 14 withdrew, leaving 112 in the control arm and 121 in the experimental arm. In 15 control subjects (13%), completion ALND was positive, with a low tumor burden. Four patients experienced disease recurrence: 1 (1%) of 108 control subjects and 3 (2.5%) of 119 experimental patients. There were no differences in disease-free survival (p=0.325) between arms and no cancer-related deaths. CONCLUSIONS: Our results strongly suggest that in early breast cancer patients with SN micrometastasis, selective SN lymphadenectomy suffices to control locoregional and distant disease, with no significant effects on survival.

Patterns of mental health service utilization in a general hospital and outpatient mental health facilities: analysis of 365,262 psychiatric consultations.

PURPOSE: Mental health is one of the priorities of the European Commission. Studies of the use and cost of mental health facilities are needed in order to improve the planning and efficiey of mental health resources. We analyze the patterns of mental health service use in multiple clinical settings to identify factors associated with high cost. SUBJECTS AND METHODS: 22,859 patients received psychiatric care in the catchment area of a Spanish hospital (2000-2004). They had 365,262 psychiatric consultations in multiple settings. Two groups were selected that generated 80% of total costs: the medium cost group (N = 4,212; 50% of costs), and the high cost group (N = 236; 30% of costs). Statistical analyses were performed using univariate and multivariate techniques. Significant variables in univariate analyses were introduced as independent variables in a logistic regression analysis using "high cost" (>7,263$) as dependent variable. RESULTS: Costs were not evenly distributed throughout the sample. 19.4% of patients generated 80% of costs. The variables associated with high cost were: age group 1 (0-14 years) at the first evaluation, permanent disability, and ICD-10 diagnoses: Organic, including symptomatic, mental disorders; Mental and behavioural disorders due to psychoactive substance use; Schizophrenia, schizotypal and delusional disorders; Behavioural syndromes associated with physiological disturbances and physical factors; External causes of morbidity and mortality; and Factors influencing health status and contact with health services. DISCUSSION: Mental healthcare costs were not evenly distributed throughout the patient population. The highest costs are associated with early onset of the mental disorder, permanent disability, organic mental disorders, substance-related disorders, psychotic disorders, and external factors that influence the health status and contact with health services or cause morbidity and mortality. CONCLUSION: Variables related to psychiatric diagnoses and sociodemographic factors have influence on the cost of mental healthcare.

[Surgical resection of liver metastases from colorectal carcinoma. Experience in Sant Pau Hospital]. / Resección quirúrgica de metástasis hepáticas de cáncer colorrectal. Experiencia del Hospital de Sant Pau.

INTRODUCTION: Surgical resection is the only available treatment that improves survival in patients with liver metastases from colorectal cancer, particularly when carried out by a multidisciplinary team. MATERIAL AND METHOD: We retrospectively analyzed a consecutive series of 116 patients who underwent 138 liver resections (65.4% minor and 35.5% major) for hepatic metastases from colorectal cancer between 1998 and 2004. In 34.5% of the patients, the lesions were synchronous. All patients were individually assessed by a multidisciplinary team. The mean number of metastases removed per patient was 2.43 (range: 1-10). The mean size of the largest tumor per patient was 40 mm (range: 12-90). In 67.3% of the patients, the primary tumor was at an advanced stage (III-IV). In 98% of the patients, the diagnosis was confirmed by helical computed tomography scans/magnetic resonance imaging and intraoperative ultrasonography. RESULTS: Postoperative morbidity was 31.2% and mortality was 2.2%. A mean of 2.7 units of blood was transfused per patient. Overall 5-year survival was 43.2% (median 50 months). Survival rates varied according to whether the patients had < 4 or > or = 4 colorectal liver metastases (50 and 43 months respectively), tumor size (more or less than 5 cm) (60 and 50.6 months respectively) and whether the site was monolobar or bilobar (60 and 43.11 months respectively). In 16 patients, recurrence of liver metastases led to 22 rehepatectomies. Overall 5-year survival was 36.7% (median 60 months) after the first rehepatectomy but was 36 and 12 months respectively after a second or third rehepatectomy. CONCLUSIONS: These results confirm that multidisciplinary decisions and interventions by specialist liver surgeons, as in our hospital, reduce postoperative morbidity and mortality and increase survival in patients requiring surgical removal of liver metastases from colorectal cancer.