Breaking the Mucin Barrier: A New Affinity Chromatography-Mass Spectrometry Approach to Unveil Potential Cell Markers and Pathways Altered in Pseudomyxoma Peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal mucinous carcinomatosis with largely unknown underlying molecular mechanisms. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapeutic option; however, despite its use, recurrence with a fatal outcome is common. The lack of molecular characterisation of PMP and other mucinous tumours is mainly due to the physicochemical properties of mucin. RESULTS: This manuscript describes the first protocol capable of breaking the mucin barrier and isolating proteins from mucinous tumours. Briefly, mucinous tumour samples were homogenised and subjected to liquid chromatography using two specific columns to reduce mainly glycoproteins, albumins and immunoglobulin G. The protein fractions were then subjected to mass spectrometry analysis and the proteomic profile obtained was analysed using various bioinformatic tools. Thus, we present here the first proteome analysed in PMP and identified a distinct mucin isoform profile in soft compared to hard mucin tumour tissues as well as key biological processes/pathways altered in mucinous tumours. Importantly, this protocol also allowed us to identify MUC13 as a potential tumour cell marker in PMP. CONCLUSIONS: In sum, our results demonstrate that this protein isolation protocol from mucin will have a high impact, allowing the oncology research community to more rapidly advance in the knowledge of PMP and other mucinous neoplasms, as well as develop new and effective therapeutic strategies.

Factors associated with the deterioration of intrinsic capacity in older people in Mexico and Colombia.

Background: Intrinsic capacity (IC) is defined as "all the physical and mental attributes possessed by the older person." This concept has gained momentum in recent years because it provides insights into the changes in the functional capacity of individuals during their life. This study examined common factors associated with IC decline among older adults in Mexico and Colombia. Methods: This cross-sectional, correlational study included 348 community-dwelling older adults. Sociodemographic, clinical, and family conditions were assessed as possible associated factors, and IC was analyzed across five domains: cognitive, locomotor, psychological, vitality (malnutrition through deficiency and excess), and sensory (visual and auditory). Parametric and non-parametric statistical analyses were performed. Results: The common factors associated with impairment according to domain were family dysfunctionality (cognitive domain); myocardial infarction, family dysfunctionality, age >80 years, home occupation, and not having a partner (locomotor domain); dysfunctional family and risk of falls (psychological domain); age >80 years and not having a partner (malnutrition by deficiency domain); age 60-79 years, walking <7,500 steps/day, and peripheral vascular disease (malnutrition by excess domain); risk of falling and being female (visual sensory domain); risk of falling (auditory sensory domain); and dysfunctional family and risk of falling (total intrinsic capacity). Conclusion: Both populations had common sociodemographic, clinical, and familial factors that directly affected total IC stocks and their domains.

Laparoscopic versus open approach for interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced epithelial ovarian cancer: a matched comparative study.

BACKGROUND: The use of the laparoscopic approach for the treatment of carcinomatosis from epithelial ovarian cancer (EOC) is controversial. The aim of this study was to compare the short-term outcomes of both laparoscopic and open approach for interval CRS+HIPEC in a matched cohort of patients with advanced EOC. METHODS: A retrospective analysis of a prospectively maintained database including 254 patients treated with interval CRS-HIPEC between January 2016 and December 2021 was performed. Patients with primary disease and limited carcinomatosis (PCI ≤ 10) were selected. A comparative analysis of patients treated by either open (O-CRS-HIPEC) or the laparoscopic (L-CRS-HIPEC) approach was conducted. Overall survival (OS), disease-free survival (DFS), and perioperative outcomes were analysed. RESULTS: Fifty-three patients were finally selected and enrolled into two comparable groups in this study. Of these, 14 patients were treated by interval L-CRS-HIPEC and 39 by interval O-CRS-HIPEC. The L-CRS-HIPEC group had a shorter hospital stay (5.6 ± 1.9 vs. 9.7 ± 9.8 days; p < 0.001) and a shorter time to return to systemic chemotherapy (4.3 ± 1.9 vs. 10.3 ± 16.8 weeks; p = 0.003). There were no significant differences in postoperative complications between both groups. The 2-year OS and DFS was 100% and 62% in the L-CRS-HIPEC group versus 92% and 60% in the O-CRS-HIPEC group, respectively (p = 0.96; p = 0.786). CONCLUSION: This study suggests that the use of interval L-CRS-HIPEC for primary advanced EOC is associated with shorter hospital stay and return to systemic treatment while obtaining similar oncological results compared to the open approach. Further prospective research is needed to recommend this new approach for these strictly selected patients.

Antitumor effect of a small-molecule inhibitor of KRASG12D in xenograft models of mucinous appendicular neoplasms.

Pseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive surgery, aimed at removing all visible tumors. However, a high percentage of patients relapse, with subsequent progression and death. Recently, there has been an increase in therapies that target mutated oncogenic proteins. In this sense, KRAS has been reported to be highly mutated in PMP, with KRASG12D being the most common subtype. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in a high-grade PMP xenograft mouse model carrying a KRASG12D mutation. The results obtained in this work showed a profound inhibition of tumor growth, which was associated with a reduction in cell proliferation, an increase in apoptosis, and a reduction in the MAPK and PI3K/AKT/mTOR signaling pathways. In conclusion, these results demonstrate the high potency and efficacy of MRTX1133 in KRASG12D-PMP tumors and provide a rationale for clinical trials.

Normothermic Regional Perfusion in Controlled Donation After Circulatory Determination of Death Simultaneous Pancreas - Kidney Transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation is the optimal treatment for patients with type 1 diabetes and renal failure. The use of pancreas grafts from donation after circulatory death (DCD), using normothermic regional perfusion (NRP), is still marginal worldwide, mainly due to possible additional risks of graft dysfunction and complications compared with grafts from donors after brain death. METHODS: Case series of patients who underwent simultaneous pancreas-kidney transplantation after DCD-NRP between January 2018 and September 2022. This study evaluated early postoperative grafts and survival outcomes. RESULTS: Four patients were included. One patient lost the pancreatic graft due to arterial thrombosis requiring transplantectomy. Another patient required a laparotomy due to hemoperitoneum. Overall, 1-year pancreas and kidney graft survival was 75% and 100%, respectively. One patient developed a lymphoma during the follow-up. CONCLUSION: The use of pancreas grafts from DCD after NRP preservation is safe and feasible. Comparative studies with donors after brain death grafts and larger series are required to confirm the feasibility of DCD-NRP pancreas transplantation.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Urothelial Origin: a Case Report and Literature Review.

Introduction: Urothelial carcinomas (UC) are the fourth most common tumours. Approximately, 50% of patients with invasive bladder cancer relapse after radical cistectomy (RC). In this report, we present the case of peritoneal carcinomatosis from bladder UC treated with cytoreductive surgery plus the administration of hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). Case Presentation: A 34-year-old woman diagnosed with high-grade bladder cancer with peritoneal recurrence in 2017. She underwent cytoreductive surgery followed by HIPEC with mitomycin C. Histopathological results showed metastases from UC in the left ovary and right diaphragmatic peritoneum. In 2021, the patient underwent surgery after treatment with atezolizumab for abdominal wall recurrence. Today, the patient is alive and free of tumor recurrence 12 months after the last surgery. Discussion: Despite advances in surgical technique and patient selection, the risk of relapse remains high among patients with muscle-invasive bladder cancer. We face the case of a young female patient with local, peritoneal, and lymphatic recurrence of bladder cancer after RC who had a partial response to chemotherapy. The possibility of CRS + HIPEC is offered by the surgical oncology unit, referent in the management of peritoneal carcinomatosis. Surgery is capable of resecting residual tumor in patients with a partial response or who have been erroneously underdiagnosed. Conclusion: CRS + HIPEC might be a valid option to be considered in well-selected patients and to be performed in reference units. There is a need for more collaborative clinical trials and prospective studies addressing the role of surgery in patients with metastatic bladder cancer.

Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer: A Phase 3 Randomized Clinical Trial.

Importance: Peritoneal metastasis in patients with locally advanced colon cancer (T4 stage) is estimated to recur at a rate of approximately 25% at 3 years from surgical resection and is associated with poor prognosis. There is controversy regarding the clinical benefit of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. Objective: To assess the efficacy and safety of intraoperative HIPEC in patients with locally advanced colon cancer. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial was conducted in 17 Spanish centers from November 15, 2015, to March 9, 2021. Enrolled patients were aged 18 to 75 years with locally advanced primary colon cancer diagnosed preoperatively (cT4N02M0). Interventions: Patients were randomly assigned 1:1 to receive cytoreduction plus HIPEC with mitomycin C (30 mg/m2 over 60 minutes; investigational group) or cytoreduction alone (comparator group), both followed by systemic adjuvant chemotherapy. Randomization of the intention-to-treat population was done via a web-based system, with stratification by treatment center and sex. Main Outcomes and Measures: The primary outcome was 3-year locoregional control (LC) rate, defined as the proportion of patients without peritoneal disease recurrence analyzed by intention to treat. Secondary end points were disease-free survival, overall survival, morbidity, and rate of toxic effects. Results: A total of 184 patients were recruited and randomized (investigational group, n = 89; comparator group, n = 95). The mean (SD) age was 61.5 (9.2) years, and 111 (60.3%) were male. Median duration of follow-up was 36 months (IQR, 27-36 months). Demographic and clinical characteristics were similar between groups. The 3-year LC rate was higher in the investigational group (97.6%) than in the comparator group (87.6%) (log-rank P = .03; hazard ratio [HR], 0.21; 95% CI, 0.05-0.95). No differences were observed in disease-free survival (investigational, 81.2%; comparator, 78.0%; log-rank P = .22; HR, 0.71; 95% CI, 0.41-1.22) or overall survival (investigational, 91.7%; comparator, 92.9%; log-rank P = .68; HR, 0.79; 95% CI, 0.26-2.37). The definitive subgroup with pT4 disease showed a pronounced benefit in 3-year LC rate after investigational treatment (investigational: 98.3%; comparator: 82.1%; log-rank P = .003; HR, 0.09; 95% CI, 0.01-0.70). No differences in morbidity or toxic effects between groups were observed. Conclusions and Relevance: In this randomized clinical trial, the addition of HIPEC to complete surgical resection for locally advanced colon cancer improved the 3-year LC rate compared with surgery alone. This approach should be considered for patients with locally advanced colorectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02614534.

Learning curve for minimal invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) procedures.

PURPOSE: The benefits of the minimally invasive approach for performing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) have been described previously, associating an early recovery with similar oncologic outcomes in patients with limited peritoneal carcinomatosis. Currently, no studies are focusing on the learning curve for this emerging procedure. This study aimed to evaluate the L-CRS + HIPEC learning curve and its knock-on effect on the perioperative outcomes. METHODS: We identified all consecutive unselected patients who underwent L-CRS + HIPEC by a single surgeon between April 2016 and January 2022 (n = 51). Patients who underwent risk-reducing CRS + HIPEC (PCI = 0) or initial conversion due to an intraoperative PCI > 10 were excluded from the final analysis. To evaluate the learning curve, perioperative data were analysed using the cumulative sum (CUSUM) analysis. RESULTS: Twenty-six patients were included in the final analysis. Major morbidity occurred in one patient (3.8%). The difficulty of the L-CRS + HIPEC procedures was categorised as low in 23.1% (n = 6), intermediate in 19.2% (n = 5), and advanced in 57.7% (n = 15). The mean length of hospital stay was 5.4 ± 1.5 days. No patient had a conversion to open surgery. The learning curve was divided into two distinct phases: the learning phase (1-14) and the consolidation phase (15-26). A significant decrease in the operative time (375 ± 103.1 vs 239.2 ± 63.6 min) was observed with no differences in complexity, the number of peritonectomy procedures, or morbidity. CONCLUSION: L-CRS + HIPEC is a complex procedure that must be performed in a high-volume and experienced oncologic unit, requiring a learning curve to achieve the consolidation condition, which could be established after 14 procedures.

Calidad percibida en adultos mayores sobre el proceso de vacunación contra la Covid-19 en Jalisco, México / Perceived quality in older adults about the vaccination process against covid-19 in Jalisco, Mexico

El adulto mayor (AM) percibe la calidad a partir de las acciones ejecutadas al momento de brindarle algún servicio de salud. El propósito fue identificar la calidad percibida por los adultos mayores durante el proceso para la aplicación de la vacuna contra la COVID-19. El estudio fue cuantitativo-descriptivo, transversal, N=14,508 AM, n=494, muestreo aleatorio, se utilizó estadística descriptiva; prueba U de Mann-Whitney y Chi-cuadrado de Pearson, fijando el valor de significancia de p=≤0.05. El estudio contempló los principios de Helsinki. La muestra se compuso de 494 AM. (58.5%) fueron mujeres y (41.5%) eran hombres. La edad mínima fue de 60 años y la máxima de 93 años. La primera causa de enfermedad que dijo padecer el AM fue la enfermedad hipertensiva (35.6%), a través de Chi-cuadrado de Pearson, se estableció que no existen diferencias estadísticamente significativas entre el sexo y enfermedad, sig. 0.293 (p= ≤0.05). 0.05), la percepción del AM sobre el trato recibido por parte del personal de enfermería, durante la aplicación de la vacuna lo describieron como bueno 312 (63.2%), sig.=0.002 (p= ≤0.05). Los AM manifiestan que el personal de enfermería brindó información sobre el proceso para la aplicación de la vacuna y refieren estar totalmente satisfechos 399 (92.4%), sig.=0.001 (p= ≤0.05). Los resultados son novedosos, ya que evidencian el reconocimiento de la calidad de las intervenciones que las enfermeras realizan al proporcionar el cuidado, y permiten identificar que los AM tuvieron buena percepción de calidad durante el proceso de vacunación y total satisfacción con el trato recibido por enfermería. (AU)

The older adult perceives the quality from the actions carried out at the time of providing a health service. The purpose was to identify the quality perceived by older adults during the process for the application of the COVID-19 vaccine, the study was quantitative descriptive, cross-sectional, N=14,508 AM, n=494, random sampling, descriptive statistics were used; Mann-Whitney U test and Pearson’s Chi-square, fixing the significance value of p=≤0.05. The Helsinki principles were applied. The sample consisted of 494 older adult (58.5%) were women and (41.5%) were men. The minimum age was 60 years, and the maximum was 93 years. The first cause of disease reported to suffer from participants was hypertensive disease (35.6%), through Pearson’s Chi-square, it was established that there are no statistically significant differences between sex and disease, sig. 0.293 (p= ≤0.05). 0.05), the perception of the participants about the treatment received by the nursing staff, during the application of the vaccine was described as good by 312 (63.2%), sig.=0.002 (p= ≤0.05).The older adult state that the nursing staff provided information on the process for the application of the vaccine and reported being totally satisfied 399 (92.4%), sig.=0.001 (p= ≤0.05). The results are novel since they show the recognition of the quality of the interventions that nurses carry out when providing care and allow to identify that the older adult had a good perception of quality during the vaccination process and total satisfaction with the treatment received by nursing. (AU)

Intraoperative oxygen tension and redox homeostasis in Pseudomyxoma peritonei: A short case series.

Introduction: Pseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment option is based on complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. However, the recurrence is frequent with subsequent progression and death. To date, most of the studies published in PMP are related to histological and genomic analyses. Thus, the need for further studies unveiling the underlying PMP molecular mechanisms is urgent. In this regard, hypoxia and oxidative stress have been extensively related to tumoral pathologies, although their contribution to PMP has not been elucidated. Methods: In this manuscript, we have evaluated, for the first time, the intratumoral real-time oxygen microtension (pO2mt) in the tumor (soft and hard mucin) and surrounding healthy tissue from five PMP patients during surgery. In addition, we measured hypoxia (Hypoxia Inducible Factor-1a; HIF-1α) and oxidative stress (catalase; CAT) markers in soft and hard mucin from the same five PMP patient samples and in five control samples. Results: The results showed low intratumoral oxygen levels, which were associated with increased HIF-1α protein levels, suggesting the presence of a hypoxic environment in these tumors. We also found a significant reduction in CAT activity levels in soft and hard mucin compared with healthy tissue samples. Discussion: In conclusion, our study provides the first evidence of low intratumoral oxygen levels in PMP patients associated with hypoxia and oxidative stress markers. However, further investigation is required to understand the potential role of oxidative stress in PMP in order to find new therapeutic strategies.

Intraoperative metabolic changes associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) causes considerable hemodynamic, respiratory, and metabolic changes during the perioperative period. OBJECTIVES: To evaluate metabolic changes associated with this procedure. Understanding perioperative factors and their association with morbidity may improve the perioperative management of patients undergoing this treatment. METHODS: A retrospective review of a prospectively maintained database was performed. All consecutive unselected patients who underwent CRS plus HIPEC between January 2018 and December 2020 (n = 219) were included. RESULTS: The mean age was 58 ± 11.7 years and 167 (76.3%) were female. The most frequent histology diagnosis was serous ovarian carcinoma 49.3% (n = 108) and colon carcinoma 36.1% (n = 79). Mean peritoneal cancer index was 14.07 ± 10.47. There were significant variations in pH, lactic acid, sodium, potassium, glycemia, bicarbonate, excess bases, and temperature (p < 0.05) between the pre-HIPEC and post-HIPEC periods. The closed HIPEC technique resulted in higher levels of temperature than the open technique (p < 0.05). Age, potassium level post-HIPEC potassium level, and pre-HIPEC glycemia were identified as prognostic factors for morbidity in multivariate analysis. CONCLUSION: The administration of HIPEC after CRS causes significant changes in internal homeostasis. Although the closed technique causes a greater increase in temperature, it is not related to higher morbidity rates. The patient's age, post-HIPEC potassium level, and pre-HIPEC glycemia are predictive factors for morbidity.

Short- and Long-Term Intestinal Complications After Combined Pancreas-Kidney Transplantation.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation is the treatment of choice in patients with type 1 diabetes and end-stage renal disease, because it improves survival and quality of life. Currently, enteric exocrine drainage is the most commonly used method. Intestinal complications continue to be a major cause of posttransplant morbidity despite improvements in surgical technique. This study analyzed early and late intestinal complications related to SPK transplantation. MATERIALS AND METHODS: We performed a retrospective analysis of 100 adult patients undergoing SPK transplantation between January 2009 and December 2019. We performed systemic venous drainage and exocrine enteric drainage with duodenojejunostomy. Statistical analysis was performed using SPSS v2. This study was performed in accordance with the Declaration of Istanbul and the 1964 Declaration of Helsinki. Informed consent was obtained from all participants involved in the study. RESULTS: Intestinal complications were reported in 18 patients. Ten patients (10%) had the following early intestinal complications including: ileus (n = 4), intestinal obstruction (n = 2), graft volvulus (n = 1), duodenal graft fistula (n = 1), and jejunal fistula after pancreas transplantation (n = 1). Two cases required relaparotomy: graft repositioning with Roux-en-Y conversion (n = 1) and Y-roux conversion (n = 1). Eight patients had repeated episodes of intestinal obstruction (8%), of whom 2 required surgery for resolution with 100% postoperative mortality. CONCLUSIONS: SPK transplantation with enteric drainage via duodenojejunostomy has a low rate of short- and long-term postoperative intestinal complications. Surgery in patients with recurrent intestinal obstruction has a high mortality risk and should be performed in reference transplant centers.

The Role of Intraperitoneal Intraoperative Chemotherapy with Paclitaxel in the Surgical Treatment of Peritoneal Carcinomatosis from Ovarian Cancer-Hyperthermia versus Normothermia: A Randomized Controlled Trial.

BACKGROUND: The treatment of ovarian carcinomatosis with cytoreductive surgery and HIPEC is still controversial. The effect and pharmacokinetics of the chemotherapeutics used (especially taxanes) are currently under consideration. METHODS: A phase II, simple blind and randomized controlled trial (NTC02739698) was performed. The trial included 32 patients with primary or recurrent ovarian carcinomatosis undergoing cytoreductive surgery (CRS) and intraoperative intraperitoneal chemotherapy with paclitaxel (PTX): 16 in hyperthermic (42-43 °C) and 16 in normothermic (37 °C) conditions. Tissue, serum and plasma samples were taken in every patient before and after intraperitoneal chemotherapy to measure the concentration of PTX. To analyze the immunohistochemical profile of p53, p27, p21, ki67, PCNA and caspase-3 and the pathological response, a scale of intensity and percentage of expression and a grouped Miller and Payne system were used, respectively. Perioperative characteristics and morbi-mortality were also analyzed. RESULTS: The main characteristics of patients, surgical morbidity, hemotoxicity and nephrotoxicity were similar in both groups. The concentration of paclitaxel in the tissue was higher than that observed in plasma and serum, although no statistically significant differences were found between the two groups. No statistically significant association regarding pathological response and apoptosis (caspase-3) between both groups was proved. There were no statistically significant differences between the normothermic and the hyperthermic group for pathological response and apoptosis. CONCLUSIONS: The use of intraperitoneal PTX has proven adequate pharmacokinetics with reduction of cell cycle and proliferation markers globally without finding statistically significant differences between its administration under hyperthermia versus normothermia conditions.

Ghrelin-Reactive Autoantibodies as Potential Modulators of Dysfunctional Eating Patterns in Women: An Exploratory Study.

Dysfunctional eating patterns include alterations in experiencing and expressing hunger, appetite, and satiety, which may lead to eating disorders or obesity in the long term. Alterations in hormones such as ghrelin have been suggested to influence emotional eating in women with obesity. Ghrelin-reactive autoantibodies (autoAbs) are present both in healthy individuals and those with eating disorders and have been suggested to protect the hormone from degradation and preserve its functional activity. This study aimed to evaluate the relationship between IgG ghrelin-reactive autoAbs with dysfunctional eating patterns, subjective perception of stress, and body composition parameters in young women. This cross-sectional study included 82 women (age 21±2 years) classified according to body fat percentage. Dysfunctional eating patterns were measured with the Spanish version of the Three-factor Eating Questionnaire-R18, and perceived stress was measured with the Spanish version of the Perceived Stress Scale - 10. A validated in-house enzyme-linked immunosorbent assay was performed to measure IgG ghrelin-reactive autoAbs in its free, total, and immune complex fractions. Free IgG ghrelin-reactive autoAbs were positively correlated with weight, BMI, body fat percentage, waist, and hip circumference in women with very high body fat percentage. In this group, a negative correlation was observed between ghrelin immune complexes and uncontrolled eating. This exploratory research shows that IgG ghrelin-reactive autoAbs have a potential role in altered body composition parameters and appetite expression, such as uncontrolled eating in women with very high body fat. Further studies are required to clarify the role of IgG autoAbs in eating behavior.

Surgical treatment of vena cava leiomyosarcomas: Series of cases in a referral center and literature review.

BACKGROUND: Primary tumors of the inferior vena cava are rare tumors of mesenchymal origin. They arise from the smooth muscles of the vena cava wall. Due to its low prevalence, there are few definitive data on its treatment and prognosis. Its treatment is based on general oncological principles. METHODS: A series of 6 cases operated from 2010 to 2020 were analyzed. Different parameters related to the demographic characteristics, the tumor, the treatment received, and the results obtained in survival and morbidity were analyzed. In addition, a bibliographical review of the currently available evidence was carried out. RESULTS: Optimal surgical resection was accomplished in all patients with R0 in 4/6 and R1 in 2/6. The greatest morbidity occurred in a patient who died in the intraoperative period. Cavorraphy was performed in one patient and cavoplasty in 5/6 using cryopreserved graft in 3/6 and prothesis in 2/6. The 50% were still alive at the end of the follow-up (with a mean follow-up of 10.7 months). The mean survival was 11.3 ± 9.07 months. 3/6 patients presented hematogenous recurrences with a disease-free interval of 9 ± 2 months. CONCLUSION: The diagnosis and treatment of inferior vena cava leiomyosarcoma is still a challenge. Due to its low prevalence, it will be difficult to establish a totally standardized treatment and its approach is recommended in specialized centers. On the other hand, a multicentric study should be made to collect the most cases as possible in order to advance in the understanding of the approach to this disease.

Comparing the copper binding features of alpha and beta synucleins.

Amyloid aggregation of α-synuclein (AS) is one of the hallmarks of Parkinson's disease (PD). Copper ions specifically bind at the N-terminus of AS, accelerating protein aggregation. Its protein homolog ß-synuclein (BS) is also a copper binding protein, but it inhibits AS aggregation. Here, a comparative spectroscopic study of the Cu2+ binding properties of AS and BS has been performed, using electronic absorption, circular dichroism (CD) and electronic paramagnetic resonance (EPR). Our comparative spectroscopic study reveals striking similarities between the Cu2+ binding features of the two proteins. The Cu2+ binding site at the N-terminal group of BS protein, modeled by the BS (1-15) fragment is identical to that of AS; however, its rate of reduction is three times faster as compared to the AS site, consistent with BS having an additional Met residue in its Met1-Xn-Met5-Xn-Met10 motif. The latter is also evident in the cyclic voltammetry studies of the Cu-BS complex. On the other hand, the Cu2+ binding features of the His site in both proteins, as modeled by AS(45-55) and BS(60-70), are identical, indicating that the shift in the His position does not affect its coordination features. Finally, replacement of Glu46 by Ala does not alter Cu2+ binding to the His site, suggesting that the familial PD E46K mutation would not impact copper-induced aggregation. While further studies of the redox activity of copper bound to His50 in AS are required to understand the role of this site in metal-mediated aggregation, our study contributes to a better understanding of the bioinorganic chemistry of PD.