Utility of Molecular Analysis of Peritoneal Fluid in Staging Laparoscopy of Advanced Esophagogastric Junction and Gastric Cancer Prior to Neoadjuvant Treatment.

PURPOSE: Molecular analysis of peritoneal fluid in staging laparoscopy of gastric cancer is performed to improve the detection of free intraperitoneal tumor cells. Nevertheless, its significance is controversial, especially in patients with negative cytology but positive molecular analysis. The aim of this study was to analyze the sensitivity of molecular analysis and its prognostic value. METHODS: A retrospective analysis from April 2011 to October 2019 was performed. Cytology (Cyt) and molecular analysis were analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) of the carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) tumor makers. RESULTS: During the study period, 138 staging laparoscopies were performed. Macroscopic carcinomatosis was found in 12.3%. Of the remaining 87.7%, 9.9% were Cyt + and 11.6% were Cyt- RT-PCR + . Of the latter, 9 responded to chemotherapy and underwent radical surgery. The sensitivity of cytology and molecular analysis was 0.70 and 0.76, respectively (p = 0.67). The 2-year overall survival (OS) of Cyt- RT-PCR + vs. Cyt + was similar (p = 0.1). The 2-year OS of Cyt-RT-PCR + subgroup who underwent radical surgery vs. Cyt-RT-PCR- patients was similar (p = 0.69), but disease-free survival was shorter in the first group (p = 0.005). CONCLUSION: Our results show that the sensitivity of molecular analysis is similar to that of cytology. The prognostic value of positive molecular analysis was similar to positive cytology in terms of 2-year overall survival, except in the subgroup of operated patients in whom the overall survival was similar to that of those with a negative molecular analysis, albeit with a shorter disease-free survival.

Survey of glaucoma surgical preferences among glaucoma specialists in Spain.

PURPOSE: To evaluate the spectrum of glaucoma surgery undertaken among members of the Spanish Glaucoma Society (SEG). METHODS: A 10 question web-based anonimous survey was mailed through the Annals of the Spanish Glaucoma Society to all its members on January, February and July 2019 to determine their preferred surgical approach. MAIN OUTCOME MEASURES: Age, type of Glaucoma, surgery undertaken, type of anti-scarring strategy and prothesis introduced for the last 10 surgeries since the survey was received. The surgeon experience was registered in years of practice. RESULTS: A total of 97 SEG members across the country answered the survey. Sixty-two (63.4%) responders had more than 10 years of experience. Primary open angle glaucoma was the most frequent type of glaucoma (60.6%). The most popular surgery was deep-sclerectomy (37.3%) followed by trabeculectomy (17,6%) and the collagen microshunt (XEN® Allergan Inc., Irvine, CA) (14.1%). Glaucoma drainage device (GDD) was used in 10.5% of the cases. Up to 21.7% of surgeries were reinterventions, where GDD was used in 27.3% and trabeculectomy in 20.3% of the cases. Glaucoma surgery was combined with phacoemulsification in 47.3% of the eyes. Mitomycin C (MMC) was used in 54,8% of the cases, collagen matrix (Ologen®, Aeon Astron Corporation, Taipei, Taiwan) was used alone in 8.2% of the cases and in 13,7% combined with MMC. MMC was used in a soaked sponge in 79% of cases (concentrations of 0.02% in 99% and 0.04% in 1%) and in 21% of cases MMC was injected subconjunctivally (concentrations of 0,01% in 81% and 0.02% in 19%). CONCLUSIONS: Although the glaucoma surgeon performs a wide range of surgical techniques, deep sclerectomy remains the most widely used surgical technique in Spain. Combined cataract and glaucoma surgery is performed almost in half of the patients and MMC is the most frequently selected antifibrotic agent, alone or combined with collagen matrix. The new minimal invasive surgical techniques represent the 20% of the total.

Gastric and Small Intestine Gist: Results of 156 Cases in 20 Years.

PURPOSE: Gastric and small intestine are the most common gastrointestinal stromal tumors (GISTs). There are few studies of patients who underwent surgical treatment with disparate findings. We aimed to evaluate the differences between groups and the risk factors for recurrence and mortality. METHODS: A retrospective study of 96 gastric and 60 small intestine GIST was performed between 1995 and 2015. Both groups were compared in terms of clinicopathologic features, morbidity, recurrence, and mortality. Statistical analysis was performed with SPSS®. RESULTS: Eighty-one gastric GISTs and 56 small intestine GISTs underwent surgical treatment. Gastrointestinal bleeding was the most common cause of emergency surgery being more frequent in gastric GIST (P = 0.009); however, emergency surgery was indicated more frequently in the small intestinal GIST (P = 0.004) and was mostly due to perforation (P = 0.009). With a median follow-up of 66.9 (39.7-94.8) months, 28 (20.4%) patients had recurrence. A mitotic index > 5 (P ≤ 0.001) and the intestinal location (P = 0.012) were significantly associated to recurrence. Tumor size > 15 cm (P = 0.001) and an age of ≥ 75 years (P = 0.014) were associated to mortality. On univariate analysis, higher mean values of Ki-67 were associated to higher mortality (P = 0.0032). Small intestine GIST presented lower disease-free survival (DFS) than that of gastric GIST (65.7% vs 90.8%) with P = 0.003. The overall survival (OS) of gastric and small intestine GIST was 74.7% and 71.6%, respectively (P = 0.68). CONCLUSION: Small intestine GIST received emergency surgery more frequently showing lower DFS and same OS than that of gastric GIST. We found that Ki-67 could be a prognostic factor. Further studies are necessary to assess whether Ki-67 is a prognostic risk factor for GISTs.

Evaluation of data quality in the Spanish EURECCA Esophagogastric Cancer Registry.

BACKGROUND: Although the number of nationwide clinical registries in upper gastrointestinal cancer is increasing, few of them perform regular clinical audits. The Spanish EURECCA Esophagogastric Cancer Registry (SEEGCR) was launched in 2013. The aim of this study was to assess the reliability of the data in terms of completeness and accuracy. METHODS: Patients who were registered (2014-2017) in the online SEEGCR and underwent esophagectomy or gastrectomy with curative intent were selected for auditing. Independent teams of surgeons visited each center between July 2018 and December 2019 and checked the reliability of data entered into the registry. Completeness was established by comparing the cases reported in the registry with those provided by the Medical Documentation Service of each center. Twenty percent of randomly selected cases per hospital were checked during on-site visits for testing the accuracy of data (27 items per patient file). Correlation between the quality of the data and the hospital volume was also assessed. RESULTS: Some 1839 patients from 19 centers were included in the registry. The mean completeness rate in the whole series was 97.8% (range 82.8-100%). For the accuracy, 462 (25.1%) cases were checked. Out of 12,312 items, 10,905 were available for verification, resulting in a perfect agreement of 95% (87.1-98.7%). There were 509 (4.7%) incorrect and 35 (0.3%) missing entries. No correlation between hospital volume and the rate of completeness and accuracy was observed. CONCLUSIONS: Our results indicate that the SEEGCR contains reliable data.

A real-life analysis on the indications and prognostic relevance of perioperative chemotherapy in locally advanced resectable gastric adenocarcinoma.

BACKGROUND AND PURPOSE: Perioperative chemotherapy (periCTX) based on the "MAGIC" scheme has become a standard treatment in Europe for locally advanced oesophagogastric cancer. We assessed implementation and long-term oncological outcomes of MAGIC periCTX for locally advanced gastric cancer. METHODS: Population-based cohort study of all patients with locally advanced gastric cancer undergoing surgical resection with curative intent in Catalonia and Navarra (the first two autonomous communities included in the EURECCA Upper GI Spanish Working Group) between January 2011 and December 2013. The main variable was the percentage of patients treated with MAGIC periCTX. Kaplan-Meier analysis and Cox proportional hazards model were used to assess the survival benefit of periCTX. RESULTS: Among 814 patients, 217 (26.6%) received periCTX (especially patients more likely to receive it: aged < 70 years, with proximal tumors, low anesthetic risk, and cT3-4/cN+ clinical stage). 35% did not complete perioperative chemotherapy, with no relationship with age. PeriCTX showed no effect on postoperative morbimortality. Histological tumor regression was more often absent or poor (38.2%) than total or almost total (27.8%), although clinico-pathological lymph-node downstaging was higher than expected by staging inaccuracy (38.7% vs. 24.2%). PeriCTX was associated with a better survival only in cT3-4 and cN+ patients, showing less prognostic relevance than optimal oncological surgery with D2 lymphadenectomy. CONCLUSIONS: Only 26.6% of locally advanced resectable gastric cancer patients received PeriCTX. Pathological response was poor, although some degree of nodal downstaging was observed. Survival benefit of periCTX was limited to cT3-4 and cN+ patients, being less relevant than D2 lymphadenectomy.

Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System.

Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain (ClearColi) was engineered to produce polyhydroxybutyrate beads displaying the core antigen on their surface (Beads-Core) and their immunogenicity was evaluated in BALB/c mice. Immunization with Beads-Core induced gamma interferon (IFN-γ) secretion and a functional T cell immune response against the HCV Core protein. With the aim to target broad T and B cell determinants described for HCV, Beads-Core mixed with HCV E1, E2, and NS3 recombinant proteins was also evaluated in BALB/c mice. Remarkably, only three immunization with Beads-Core+CoE1E2NS3/Alum (a mixture of 0.1 µg Co.120, 16.7 µg E1.340, 16.7 µg E2.680, and 10 µg NS3 adjuvanted in aluminum hydroxide [Alum]) induced a potent antibody response against E1 and E2 and a broad IFN-γ secretion and T cell response against Core and all coadministered antigens. This immunological response mediated protective immunity to viremia as assessed in a viral surrogate challenge model. Overall, it was shown that engineered biopolyester beads displaying foreign antigens are immunogenic and might present a particulate delivery system suitable for vaccination against HCV.

Multidisciplinary cancer care may impact on the postoperative mortality and survival of patients with oesophageal and oesophagogastric junction cancer: a retrospective cohort study.

BACKGROUND: Modern management of Oesophageal and oesophagogastric junction (OGJ) cancers requires a multidisciplinary approach, which was implemented at our health centre in 2005. This study aimed to assess the impact of this change on clinical outcomes. METHODS: A retrospective cohort study was conducted, covering all patients treated for oesophageal and OGJ cancer at the cancer centre established by the Bellvitge University Hospital and Catalonian Institute of Oncology, over two time periods, i.e. 2000-2004 and 2005-2008. Descriptive and multivariate analyses were performed using survival at 1 and 3 years as dependent variables. RESULTS: Between 1 January 2000 and 31 December 2008, 586 patients were included. Number of patients with unknown stage at diagnosis was significantly reduced. Preoperative strategies at the oesophageal location clearly increased in the recent period. A multidisciplinary approach resulted in a significant reduction in surgical mortality (11.8 vs. 2 %) in the period 2005-2008. Analysis restricted to patients undergoing surgery with curative intent indicated a significant increase in 1- and 3-year survival in the latter period (68.4 vs. 89.8 and 38.2 vs. 57.1 %, respectively). Multivariate analysis showed that variables associated with improved survival were: age; tumour stage; radical intent of treatment (surgery and radical combined chemoradiotherapy); and therapeutic strategy. CONCLUSION: Better selection of patients for therapy together with improved staging resulted in a significant improvement in 1- and 3-year survival in cases undergoing surgery with curative intent. These changes would support the adoption of a multidisciplinary approach to clinical decision-making in cases of oesophageal and OGJ cancer.

Current knowledge on oxidative stress in hepatic ischemia/reperfusion.

Ischemia/reperfusion (I/R) injury associated with hepatic resections and liver transplantation remains a serious complication in clinical practice, despite several attempts to solve the problem. The redox balance, which is pivotal for normal function and integrity of tissues, is dysregulated during I/R, leading to an accumulation of reactive oxygen species (ROS). Formation of ROS and oxidant stress are the disease mechanisms most commonly invoked in hepatic I/R injury. The present review examines published results regarding possible sources of ROS and their effects in the context of I/R injury. We also review the effect of oxidative stress on marginal livers, which are more vulnerable to I/R-induced oxidative stress. Strategies to improve the viability of marginal livers could reduce the risk of dysfunction after surgery and increase the number of organs suitable for transplantation. The review also considers the therapeutic strategies developed in recent years to reduce the oxidative stress induced by hepatic I/R, and we seek to explain why some of them have not been applied clinically. New antioxidant strategies that have yielded promising results for hepatic I/R injury are discussed.

The Current Knowledge of the Role of PPAR in Hepatic Ischemia-Reperfusion Injury.

Strategies to improve the viability of steatotic livers could reduce the risk of dysfunction after surgery and increase the number of organs suitable for transplantation. Peroxisome proliferator-activated receptors (PPARs) are major regulators of lipid metabolism and inflammation. In this paper, we review the PPAR signaling pathways and present some of their lesser-known functions in liver regeneration. Potential therapies based on PPAR regulation will be discussed. The data suggest that further investigations are required to elucidate whether PPAR could be a potential therapeutic target in liver surgery and to determine the most effective therapies that selectively regulate PPAR with minor side effects.

Cyclin D1 interacts and collaborates with Ral GTPases enhancing cell detachment and motility.

Alterations in the levels of adhesion and motility of cells are critical events in the development of metastasis. Cyclin D1 (CycD1) is one of the most frequently amplified oncogenes in many types of cancers and it is also associated with the development of metastasis. Despite this, we still do not know which are all the relevant pathways by which CycD1 induces oncogenic processes. CycD1 functions can be either dependent or independent of the cyclin-dependent kinase Cdk4, and they affect several cellular aspects such as proliferation, cell attachment and migration. In this work, we reveal a novel function of CycD1 that fosters our understanding of the oncogenic potential of CycD1. We show that CycD1 binds to the small GTPases Ral A and B, which are involved, through exocyst regulation, in the progression of metastatic cancers, inducing anchorage-independent growth and cell survival of transformed cells. We show that CycD1 binds active Ral complexes and the exocyst protein Sec6, and co-localizes with Ral GTPases in trans-Golgi and exocyst-rich regions. We have also observed that CycD1-Cdk4 phosphorylates the Ral GEF Rgl2 'in vitro' and that CycD1-Cdk4 activity stimulates accumulation of the Ral GTP active forms. In accordance with this, our data suggest that CycD1-Cdk4 enhances cell detachment and motility in collaboration with Ral GTPases. This new function may help explain the contribution of CycD1 to tumor spreading.

Preoperative gastric conditioning in cervical gastroplasty.

To determine if ischemic conditioning of the stomach improves the morbidity, mortality, and the anastomotic failure in gastroplasties with cervical anastomosis. Analysis of all patients with indication for cervical gastroplasty during the period of study. In all cases, ischemic conditioning was performed by selective embolization. Anastomotic failure, morbidity, and mortality rates were studied. Thirty-nine consecutive patients were included. Angiography and selective embolization of the left gastric, right gastric, and splenic arteries were performed. Surgery was performed 2 weeks later. Four patients did not have a complete embolization; median hospital stay after conditioning was 1.24 ± 0.6 days. In two patients, surgery could not be completed. Of the 33 remaining, 29 had a posterior mediastinic gastroplasty and four through the anterior mediastinum. The most common morbidity was respiratory. Five patients had a reoperation and the mortality was 6%. One case of anastomotic leak was found (3%). The mean hospital stay was 17.5 days. Preoperative embolization is a technique with acceptable morbidity and a short hospital stay. In our experience it can reduce the incidence of the morbidity, mortality, and anastomotic leak in gastroplasties with cervical anastomosis. Prospective studies will be necessary to demonstrate the validity of this approach.

Efficacy of enteral decontamination in the prevention of anastomotic dehiscence and pulmonary infection in esophagogastric surgery.

Our aim in this study is to evaluate the efficacy of decontamination of the high digestive tract in reducing the incidence of anastomotic dehiscence, pulmonary infection and mortality after resective gastro-esophageal surgery. A prospective randomized and double-blinded study was conducted in patients undergoing total gastrectomy for gastric cancer and esophagectomy for esophageal cancer. Two groups were studied: group A patients were given erythromycin + gentamicine + nistatine sulfate orally; group B patients were given placebo. Mortality, incidence of anastomotic dehiscence and incidence of pulmonary infection were the end points evaluated. One hundred and nine consecutive patients were randomized. Eighteen (16.5%) were excluded. From the 91 patients who were evaluated, 42 (46.2%) received an esophagectomy and 49 (53.8%) had a total gastrectomy. Esophagectomies showed: a 0% rate of anastomotic dehiscence in group A and 12.5% in group B, P = 0.176; a pulmonary infection rate of 22.2% in group A and 29.1% in group B, P = 0.443; and mortality rate was 0% in group A and 12.5% in group B, P = 0.176. After gastrectomy, anastomotic dehiscence rate was 4.5% in group A and 0% in group B, P = 0.449; pulmonary infection rate was 4.5% in group A and 11.1% in group B, P = 0.387 and mortality was 9% in group A and 0% in group B, P = 0.196. Decontamination protocol does not help in decreasing the incidence of anastomotic dehiscence, pulmonary infection and mortality in the present study. Nevertheless, there seems to be a tendency to low pulmonary infection after gastrectomy and esophagectomy and to improve the incidence of anastomotic dehiscence after esophagectomy. Further studies are needed to re-evaluate these findings.

[Effect of a mineralizing solution (Minersol) on acid solubility resistance of enamel]. / Determinación del efecto de la solución mineralizante (Minersol) sobre la resistencia del esmalte a la disolución ácida.

Degree of mineralization of enamel is one of the parameters mediating in its resistance to acid dissolution and at the stage of teething, the enamel is immature and, therefore, present a higher susceptibility to dental caries. This investigation was carried out with 38 preschool children (means = 5.5 years) and 19 children coursing second grade (means = 7.6 years). They were treated with 10 oral rinsing with mineralizing solution in order to evaluate its effect on enamel resistance to acid dissolution; colorimetric technique was used for such purpose. A study in vitro was also performed in impacted third molars extracted by surgery and to two halves of the clinical crowns of such molars the treatment was applied; the other two halves were taken as control. Increase of enamel resistance found was 18.6% in the study of preschool children and 34.6% in the children attending to second grade school. In both groups, 89.5% of the children increased enamel resistance and in the study in vitro increaser enamel was 14.9%.. It is concluded that the use of risings with mineralizing solution at the outbreak of permanent teething increase, significatively, enamel resistance, and that at the age of seven the enamel is still immature, thus its resistance to acid dissolution can be also increased using mineralizing solution.

Tuberculosis-associated hemophagocytic syndrome. A systemic process.

Virus-associated hemophagocytic syndrome has been recently identified as a benign, reactive histiocytic proliferation distinct from Rappaport's malignant hystiocytosis. Other etiologic agents, including different bacteria, have also been identified. Three autopsy cases of hemophagocytic syndrome associated to acute tuberculous sepsis are presented. Benign histiocytic proliferation with striking hemophagocytosis was present in a disseminated, multisystemic pattern in all three cases. A relationship between systemic histiocytic proliferation and an anergic status in these patients is suggested.

[Goldenhar's syndrome]. / Síndrome de Goldenhar

We are presenting five cases of Goldenhar's syndrome studied at the Clinical Genetics Unit of the Hospital Infantil of México. We do not know exactly the type of inheritance of this congenital malforamtion; in one of our cases, it seems to be related to advanced paternal age. We can consider the possibility of autosomal dominant neomutation.