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.

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.

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 (AU)

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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.

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.

Effect of weight loss induced by gastric bypass on proinflammatory interleukin-18, soluble tumour necrosis factor-alpha receptors, C-reactive protein and adiponectin in morbidly obese patients.

OBJECTIVE: Interleukin-18 (IL-18) is a potent proinflammatory cytokine whose role in human obesity has recently been suggested. The aim of our study was to analyse in morbidly obese patients undergoing gastric bypass, the relationship of IL-18 with insulin resistance and with proinflammatory cytokines (tumour necrosis factor-alpha receptors, sTNFR), C-reactive protein (CRP) and with adiponectin. DESIGN: Observational and prospective study. PATIENTS: Sixty-five morbidly obese patients, aged 45 +/- 8.9 years, were studied before and 12 months after gastric bypass. MEASUREMENTS: We analysed plasma concentrations of IL-18, sTNFR, CRP and adiponectin. RESULTS: Plasma concentrations of sTNFR2, IL-18 and CRP were decreased and adiponectin significantly increased after bypass surgery. In the multiple regression analysis, preoperative values of IL-18 remained significantly associated with preoperative triglycerides (beta = 0.47, P = 0.005) and TNFR2 (beta = 0.47, P = 0.004). R(2) for the model = 0.38. Postoperative IL-18 concentrations in the multiple regression analysis were significantly associated with postoperative homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.092, P = 0.019) and triglycerides (beta = 0.40, P = 0.036). R(2) for the model = 0.46. IL-18 did not correlate with body mass index, fat mass, fat-free mass or body fat. No relationship was either found between adiponectin and IL-18, TNFR1 and -2 and CRP. CONCLUSIONS: Massive weight loss induced by gastric bypass reduces IL-18, TNFR2 and CRP. IL-18 might be a marker of the chronic inflammatory process underlying insulin resistance but its lack of association with anthropometric and body composition parameters does not support a major secretion by human adipocytes. IL-18 and sTNFR1 and -2 do not play a main role in the inhibition of the secretion of adiponectin.

Modulation of K+-evoked [3H]-noradrenaline release from rat and human brain slices by gabapentin: involvement of KATP channels.

To elucidate the mechanism of action of the anticonvulsant gabapentin (GBP), we compared its effects on K+-evoked [3H]-noradrenaline ([3H]-NA) release from rat hippocampal and human neocortical slices with those of the KATP channel opener pinacidil and the Na+ channel blockers phenytoin, carbamazepine and lamotrigine. Rat hippocampal and human neocortical slices were loaded with [3H]-NA and superfused. [3H]-NA release was evoked by increasing the extracellular [K+] from 3 to 15 mM. GBP decreased [3H]-NA release from rat hippocampal with a pIC50 of 5.59 and a maximum inhibition of 44%. Concentration-dependent inhibition was also seen in human neocortical slices (39% inhibition with 100 microM GBP). These inhibitory effects were antagonized by the KATP channel antagonist glibenclamide, yielding a pA2 of 7.50 in the rat. The KATP channel opener pinacidil (10 microM), like GBP, decreased [3H]-NA release from rat hippocampal slices by 27% and this effect was also antagonized by glibenclamide. In human neocortical slices the inhibition by pinacidil (10 microM) was 31%. Although phenytoin (10 microM), carbamazepine (100 microM) and lamotrigine (10 microM) also decreased [3H]-NA release (by 25%, 57% and 22%, respectively), glibenclamide did not antagonize the effects of these classical Na+ channel blockers. These findings suggest that GBP inhibits K+-evoked [3H]-NA release through activation of KATP channels. To establish whether the KATP channels under investigation were located on noradrenergic nerve terminals or on other neuronal elements, the effects of GBP were compared in the absence and in the presence of tetrodotoxin (TTX 0.32 microM) throughout superfusion. Since the functional elimination of the perikarya of interneurons by TTX reduced the inhibitory effect of GBP, the KATP channels mediating the effect of GBP may be located on nerve terminals, probably on both noradrenergic and glutamatergic nerve endings.

In vitro characterization of the hematopoietic system in pediatric patients with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) has been recognized as a hematologic neoplasia that originates at the level of a primitive lymphoid stem/progenitor cell. To date, however, the biology of the hematopoietic system in this disorder is still not fully understood. In the present study, we have determined the progenitor cell content (including myeloid, erythroid and multipotent progenitors) in 14 children with ALL and followed the proliferation kinetics of these cells in Dexter-type long-term marrow cultures. We have also characterized some aspects related to the composition and function of the hematopoietic microenvironment developed in vitro. All patients included in this study showed extremely reduced levels of progenitor cells (median of 6.2% of the levels found in normal marrow). Proliferation of these cells in long-term cultures was markedly deficient, since they showed very low numbers - compared to normal cultures - and reached undetectable levels after only a few weeks. Regarding the microenvironment developed in vitro, whereas normal marrow samples contained a median of 8 fibroblastic progenitors/10(5) marrow cells and the stromal cell layers developed in culture contained a median of 341000 adherent cells per well, ALL marrow samples showed no fibroblastic progenitors and the numbers of adherent cells were 21% of those in normal cultures. Interestingly, the levels of TNFalpha and IL-6 in ALL culture supernatants were significantly increased, compared to normal cultures. Bone marrow samples from all 14 children were also analyzed once they reached a complete clinical and hematological remission. Myeloid, erythroid and multipotent progenitor cell levels were significantly increased, compared to patients at diagnosis, and proliferation of myeloid progenitors in long-term cultures was also improved. In contrast, proliferation of erythroid progenitors showed no difference to that in cultures from patients at diagnosis. The numbers of fibroblastic progenitors and adherent cells were significantly increased, compared to patients at diagnosis, and TNFalpha and IL-6 levels returned to normal. In summary, in the present study, we have demonstrated significant in vitro alterations of the hematopoietic system, both in terms of its composition and function, in pediatric patients with ALL. Importantly, most of these alterations are corrected, at least partially, after chemotherapy.

Long-term proliferation in vitro of hematopoietic progenitor cells from children with congenital bone marrow failure: effect of rhGM-CSF and rhEPO.

We have characterized the proliferation kinetics of hematopoietic cells in long-term marrow cultures (LTMC) from five normal children and seven children with congenital bone marrow failure (four with Fanconi anemia [FA] and three with congenital pure red cell aplasia [PRCA]). Total nonadherent and adherent cells, as well as nonadherent progenitors, were determined weekly in the presence or in the absence of rhGM-CSF (10 ng/ml) or rhEPO (3 U/ml). As compared to normal LTMC, hematopoiesis was drastically reduced in cultures from FA patients. Myeloid and erythroid progenitor cells reached undetectable levels after only 3 and 1 weeks of culture, respectively. This was observed even in cultures supplemented with rhGM-CSF, in which no response to this cytokine occurred. In LTMC from PRCA children, the growth of erythroid and multipotent progenitors was also drastically reduced. Myelopoiesis, on the other hand, showed normal levels during the first three weeks of culture; however, from week 4, there was a significant decrease in the levels of both progenitor and mature cells, reaching undetectable levels several weeks before normal cells did. Response to rhGM-CSF and rhEPO was transient and deficient. Our results suggest that in FA, alterations at the level of primitive progenitor cells are so severe that myeloid, erythroid and multipotent progenitors are unable to proliferate in LTMC, even in the presence of rhGM-CSF. In patients with PRCA the erythroid arm of hematopoiesis is preferentially affected and addition of rhGM-CSF and/or rhEPO to these cultures had little or no effect on erythroid cell production. Interestingly, myelopoiesis in this culture system was deficient as well and response to rhGM-CSF was defective, suggesting that the myeloid lineage is also altered in congenital PRCA.

Characterization of the alpha(2)-adrenoceptor subtype, which functions as alpha(2)-autoreceptor in human neocortex.

The pharmacological properties of the alpha(2)-adrenergic receptors regulating the release of norepinephrine were investigated in human neocortex. Slices were preincubated with [(3)H]norepinephrine, superfused under blockade of transmitter reuptake, and stimulated electrically. First, the autoinhibitory circuit of [(3)H]norepinephrine release was analyzed quantitatively by estimation of the K(d) of norepinephrine at the alpha(2)-autoreceptor (10(-7.99) M), the concentration of the endogenous transmitter causing this autoinhibition at a stimulation frequency of 3 Hz (10(-7.61) M), and the maximum inhibition obtainable through the autoreceptor (83%). Second, antagonist pK(b) values of nine antagonists were determined by using their pEC(50) values (negative logarithms of antagonist concentrations that increased the electrically evoked overflow of tritium by 50%) against the release-inhibiting effect of the endogenous transmitter. When compared with binding or functional data from the literature, the pK(b) values correlated best with the antagonist affinities at alpha(2A) binding sites. In contrast, the correlations with alpha(2B), alpha(2C), and alpha(2D) sites were not as good. It is concluded that in human neocortex prejunctional autoreceptors are alpha(2A).

Efficacy and safety of an early discharge protocol in low-risk patients with upper gastrointestinal bleeding.

PURPOSE: The outcome of patients with upper gastrointestinal hemorrhage is greatly influenced by recurrence of bleeding, but it may be possible to identify patients who have a low risk for rebleeding, and can be discharged after a short hospitalization. To examine the effect of an early discharge protocol (length of hospital stay < or =3 days), we conducted a 2-year prospective study in patients with upper gastrointestinal bleeding at low risk for rebleeding, as selected by clinical and endoscopic criteria. METHODS: During the first year of the study, patients were managed according to the standard criteria by any of six surgical teams (control period). During the second year, patients were managed by only one surgical team under the early discharge protocol guidelines (study period). RESULTS: Overall, 488 of 942 (52%) patients were considered as low risk. Early discharge was achieved in 26 of 230 (11%) patients in the control period and in 191 of 258 (74%) in the study period (P <0.001). Age and number of compensated comorbidities did not affect the rate of early discharge. Length of hospital stay was reduced from (mean +/- SD) 6 +/- 2.7 days (control period) to 3 +/- 2.3 days (study period, P <0.001). No differences were observed in rates of rebleeding, need for surgery, readmission or mortality. By contrast, no differences in lengths of stay were observed during that time period among patients admitted with coronary artery disease, colorectal cancer, or acute pancreatitis. CONCLUSION: Most patients with upper gastrointestinal bleeding who are at low risk for rebleeding can be discharged early, leading to important cost savings.

Results of using the recipient's splenic artery for arterial reconstruction in liver transplantation in 23 patients.

BACKGROUND: Arterial reconstruction is essential in liver transplantation. In some patients there may be an inadequate flow as a result of stenosis, intimal dissection, or anomalies of the hepatic artery. METHODS: This study analyzes our experience with 23 patients in whom arterial anastomosis was performed using the splenic artery due to the inadequacy of the hepatic artery. During the same period an aortoiliac conduit was used in 12 liver transplantations due to the same problem. RESULTS: No splenic infarction, pancreatitis, or other related complications were found. Artery thrombosis developed in only two patients in the aortoiliac conduit group. One- and three-year patient actuarial survival were 78% vs. 80% and 72% vs. 80%, respectively, for the splenic artery group and the aortoiliac conduit group. CONCLUSIONS: Anastomosis with the splenic artery is an alternative in liver transplantation and is particularly suitable when splenomegaly is present.

[Instrument to measure quality of life based on daily performance in pediatric patients with leukemia]. / Un instrumento para medir la calidad de vida por medio del desempeño diario en pacientes pediátricos con leucemia.

The objective of this study was to determine the validity of a questionnaire to measure daily performance as an evaluation of quality of life in pediatric leukemia patients. A questionnaire of the daily activities of a child according to Lickert's criteria was done. A pilot survey was performed in patients without a chronic or disabling disease in order to assess its validity. The impression of the medical attendance of each pediatric patient with leukemia, of their daily performance, was compared with the results of the instrument. A trained nurse applied the questionnaire to 60 mothers of patients (29 female/31 male) as outpatients during the clinical review. Fifteen questionnaires were applied twice to evaluate its consistency. According to the results, 77% of the patients were in remission. 15% in relapse, and 8% during induction to remission. The mean age of the patients was 9 = 3.6 years, ranging from 2-16 years. One hundred percent of the patients obtained a satisfactory grade greater than 35 points. In conclusion, the questionnaire identified adequately the level of the daily performance in addition to the specific affected areas of the patients with leukemia. Our findings are that their level of performance is satisfactory and is not affected because of the disease or the phase of the treatment.

[Granulocytopenia and fever in children with leukemia as indicator of quality of medical care]. / Granulocitopenia y fiebre en niños con leucemia como indicador de calidad de la atención médica.

OBJECTIVES: 1. To identify the quality degree of medical care in patients with acute leukaemia who had fever and granulocytopenia during the hospitalization period. 2. To establish the relationship between the medical care process and the results in this concern. DESIGN: Retrospective survey. STUDY AREA: Children's Hospital of the Mexican Institute of Social Security. STUDY SUBJECTS: Twenty three patients with acute leukaemia were studied. Also, hospitalization episode of these patients, in which they suffered fever and granulocytopenia, was randomly selected. MAIN MEASUREMENTS: Compliance of diagnostic and therapeutic process was measured during hospitalization, according to the protocolized recommendations made by consensus of the hospital expert group. In order to identify the quality degree of medical care, it was taken into account the protocol compliance besides the results observed in the patients. Results were assessed based on patients' survival to fever and granulocytopenia episode, as well as on fever's duration. The correlation was calculated by using Spearman's coefficient. RESULTS: The medical care quality of the hospital was "adequate" (85% on average). Compliance degree, including the total process was 71%; with diagnostic process 63%, and with therapeutic process 76%. The results observed in the patients were considered as "adequate" (89%). By evaluating individual cases, the medical care quality was considered excellent or adequate in 17 patients (74%) regular in five (22%) and poor in one (4%). Diagnostic process was adequate in 6 patients (26%) regular in 12 (53%) poor in three (13%) and very bad in two (8%). On the other hand, therapeutic process was excellent in 14 patients (60%) regular in one (4%) poor in six (26%) and very bad in two (9%). Results observed in 13 cases were excellent (57%) adequate in eight (35%) regular in one (4%) and very bad in one (4%). The relationship between process and result was 0.41 (P < 0.05) between diagnostic process and result 0.14 and, between therapeutic process and result 0.34. CONCLUSIONS: The medical care quality rendered to patients with leukaemia, who suffered a granulocytopenia episode and fever, was considered as adequate. Therapeutic recommendations were followed accurately, meanwhile, diagnostic process had a lower adherence. A positive relationship between process and result was observed.