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.

An exploratory, randomized, parallel-group, open-label, relative bioavailability study with an additional two-period crossover food-effect study exploring the pharmacokinetics of two novel formulations of pexmetinib (ARRY-614).

BACKGROUND: Pexmetinib (ARRY-614) is a dual inhibitor of p38 mitogen-activated protein kinase and Tie2 signaling pathways implicated in the pathogenesis of myelodysplastic syndromes. Previous clinical experience in a Phase I dose-escalation study of myelodysplastic syndrome patients using pexmetinib administered as neat powder-in-capsule (PIC) exhibited high variability in pharmacokinetics and excessive pill burden, prompting an effort to improve the formulation of pexmetinib. METHODS: A relative bioavailability assessment encompassed three parallel treatment cohorts of unique subjects comparing the two new formulations (12 subjects per cohort), a liquid oral suspension (LOS) and liquid-filled capsule (LFC) and the current clinical PIC formulation (six subjects) in a fasted state. The food-effect assessment was conducted as a crossover of the LOS and LFC formulations administered under fed and fasted conditions. Subjects were divided into two groups of equal size to evaluate potential period effects on the food-effect assessment. RESULTS: The geometric mean values of the total plasma exposures based upon area-under-the-curve to the last quantifiable sample (AUClast) of pexmetinib were approximately four- and twofold higher after administration of the LFC and LOS formulations, respectively, than after the PIC formulation, when the formulations were administered in the fasted state. When the LFC formulation was administered in the fed state, pexmetinib AUClast decreased by <5% compared with the fasted state. After administration of the LOS formulation in the fed state, pexmetinib AUClast was 34% greater than observed in the fasted state. CONCLUSION: These results suggest that the LFC formulation of pexmetinib may achieve greater exposures with lower doses due to the greater bioavailability compared to the PIC, and remain unaffected by coadministration with food.

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.

[Nutritional support and risk factors of appearance of enterocutaneous fistulas]. / Soporte nutricional y factores de riesgo de aparición de fístulas enterocutáneas.

INTRODUCTION: Among the different factors described, nutritional support has been associated to prevention and management of enterocutaneous fistulae (ECF). OBJECTIVES: To assess the influence that the parameters related to nutritional, clinical status, and surgical variables have on the occurrence of ECF. METHODS: An observational case/control retrospective study was performed on patients admitted to the General and Digestive Surgery Department. The parameters analyzed were: diagnosis, body mass index (BMI), pathologic personal history, number of surgical interventions (SI) and complications (previous infection, bleeding, and ischemia). In patients with SI, we analyzed: number and type of SI, time until onset of nutritional support, and type of nutritional support. We performed a multiple logistic uni- and multivariate regression analysis by using the SPSSv.19.0 software. RESULTS: The primary diagnoses related to the occurrence of ECF were pancreatic pathology (OR = 5.346) and inflammatory bowel disease (IBD) (OR = 9.329). The surgical variables associated to higher prevalence of ECF emergency SI (OR = 5.79) and multiple SI (OR = 4.52). Regarding the nutritional variables, the late onset of nutrition (more than three days after SI) was associated to the occurrence of ECF (OR = 3.82). CONCLUSIONS: In surgical patients, early nutritional support , independently of the route of administration, decreases the occurrence of fistulae. Pancreatic pathology, IBD, emergency SI, and multiple SI were associated to higher prevalence of ECF. The variable hyponutrition appears as a risk factor that should be confirmed in further studies.

Tensile and shear properties of fingernails as a function of a changing humidity environment.

The mechanical properties of fingernails are important because of their impact in preventing damage and in maintaining their appearance. In particular, knowing the effect of local environmental conditions can tell us how they might best be protected. In order to better understand this, tensile tests were carried out to characterise the properties of fingernails at different relative humidities. Cyclic tests were also conducted to investigate the ability of the structure to recover deformation at different moisture contents. Torsional tests were performed to determine the shear modulus of the keratinous matrix material which binds together the fibrous components of the fingernails. This enabled an analysis of how the material may resist bending, torsion and permanent deformation in a natural environment. In particular, it is shown that at low relative humidity the nails are more brittle, and at high moisture contents they are more flexible. Increasing relative humidity lowers torsional stiffness much more than tensile stiffness, suggesting that moisture plasticises the matrix rather than affecting the fibres. The twist to bend ratio is minimised at 55% RH, close to the natural condition of nails which should minimise susceptibility to torsional damage due to plasticisation and a disruption of the matrix material binding the keratin fibres.

Time course of necrosis/apoptosis and neovascularization during experimental gastric conditioning.

Apoptosis, necrosis and neovascularization are three processes that occur during ischemic preconditioning in a range of organs. In the stomach, the effect of this preconditioning (the delay phenomenon) has helped to improve gastric vascularization prior to esophagogastric anastomosis after esophagectomy. Here we present a sequential study of the histological recovery of the gastric fundus and the phenomena of apoptosis, necrosis and neovascularization in an experimental model of partial gastric ischemia. Partial gastric devascularization was performed by ligature of the left gastric vessels in Sprague-Dawley rats. Rats were assigned to groups in accordance with their evaluation period: control, 1, 3, 6, 10, 15 and 21 days. Histological analysis, caspase-3 activity, DNA fragmentation and vascular endothelial cell proliferation (Ki-67) were measured in tissue samples after sacrifice. After 24 h of partial gastric ischemia, rates of apoptosis and necrosis were higher in the experimental groups than in controls. Tissue injury was higher 3 and 6 days post-ischemia. From day 10 after partial gastric ischemia, apoptosis and necrosis started to decrease, and on days 15 and 21 showed no differences in relation to controls. Neovascularization began between days 1 and 3, reaching its peak at 15 days after ischemia and coinciding with complete histological recovery. Both necrosis and apoptosis play a role in tissue injury during the first days after partial gastric ischemia. After 15 days, the evolution of both the histology and the neovascularization suggested that this is the optimal time for performing gastric transposition.

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.

Results of the management of upper gastrointestinal bleeding from gastroesophageal varices.

INTRODUCTION: The management of upper gastrointestinal bleeding caused by rupture of gastric and/or esophageal varices in patients with liver cirrhosis must focus on the initial control of the haemorrhage avoiding further worsening of an already poor liver function and the prevention of early relapsing bleeding. Therapeutic options include endoscopic, pharmacological and surgical methods. MATERIAL AND METHODS: Prospective study of the results obtained after the follow-up of 90 bleeding episodes in a total of 54 patients, 35 men and 19 women, with a mean age of 58 years (range 32-77), to which a therapeutic protocol for acute bleeding secondary to portal hypertension was applied over a 22-months period. Patient classification according to Child-Pugh upon admission was 57% Child A, 34% Child B and 9% Child C. RESULTS: Mean hospital length of stay was 9 days (2-50). Of the 90 bleeding episodes, 15 were early relapsing bleeding episodes (16.7%). Twelve patients died (mortality rate of 22.2% by patients and 13.4% by bleeding episodes). Twelve emergency surgical procedures were performed because of the persistence of haemorrhage. Forty one per cent of patients were readmitted because of relapsing bleeding at least once during the follow-up period. CONCLUSIONS: Management of upper gastrointestinal bleeding due to gastroesophageal varices in patients with liver cirrhosis requires a combined therapy in order to attain maximum effectiveness in acute haemorrhagic episodes and to address all potential later consequences. Such therapy should be provided in a hospital fully equipped and with specialists in this pathology. Based on our experience, emergency surgery as rescue treatment for persistent or short-term relapsing bleeding should be restricted to patients with good hepatic function because of its high morbidity and mortality.

Prognostic factors for mortality in left colonic peritonitis: a new scoring system.

BACKGROUND: Perforating lesions of the colon affect a heterogeneous group of patients, often elderly, and usually present as abdominal emergencies, with high morbidity and mortality. The aims of this study were to assess the prognostic value of specific factors in patients with left colonic peritonitis and to evaluate the utility of a scoring method that allows one to define groups of patients with different mortality risks. STUDY DESIGN: Between January 1994 and December 1999, 156 patients (77 men and 79 women), with a mean (SD) age of 63.2 years (15.5 years) (range 22 to 87 years), underwent emergency operation for a distal colonic perforation. Intraoperative colonic lavage was the first choice operation and it was performed in 74 patients (47.4%). There were three alternative procedures: the Hartmann operation was performed in 69 patients (44.2%), subtotal colectomy in 9, and colostomy in 4 patients. We analyzed specific variables for their possible relation to death including gender, age, American Society of Anesthesiologists (ASA) score, immunocompromised status, etiology, and degree of peritonitis, preoperative organ failure, time (hours) between hospital admission and surgical intervention, and degree of temperature elevation (38 degrees C). Univariate relations between predictors and outcomes (death) were analyzed using logistic regression. Multivariate logistic regression analysis was used to assess the prognostic value of combinations of the variables. Significant factors identified in univariate and multivariate logistic regression analyses were used to define a left colonic Peritonitis Severity Score (PSS). Factors that were significant only in univariate analysis scored 2 points if present and 1 if not. Variables significant in multivariate analysis were scored from 1 to 3 points. Patients were randomly split into two groups, one to calculate the scoring system and the other to validate it. RESULTS: Overall postoperative mortality rate was 22.4%. Septic-related mortality was observed in 24 patients (15.4%). Age, peritonitis grade, ASA score, immunocompromised status, and ischemic colitis were significant for postoperative death in univariate analysis. But only ASA score and preoperative organ failure were significantly associated with postoperative mortality in multivariate logistic regression analysis. The PSS, as defined in this study, was related to outcomes of patients. Mortality rate increased from 0%, when PSS was 6 points (minimum possible score), to 100% in patients with a PSS of 13 (maximum possible PSS = 14). CONCLUSIONS: Left colonic peritonitis continues to have a persistently high mortality in patients with septic complications. ASA score and preoperative organ failure are the only factors that are significantly associated with mortality in the multivariate analysis. The PSS classification may help uniformly define the mortality risk of patients with distal large bowel peritonitis, and may help to increase the comparability of studies carried out at different centers.

Role of resection and primary anastomosis of the left colon in the presence of peritonitis.

BACKGROUND: Classically a primary colonic anastomosis is not performed in the presence of left colonic peritonitis. Recently there has been a trend towards resection and anastomosis in selected patients, but no prospective study concerning the safety of this approach has been published. The objective of this study was to define the role of intraoperative colonic lavage with resection and primary anastomosis (RPA) in left colonic peritonitis, and to evaluate the differences in outcome in patients with diffuse or localized peritonitis. METHODS: Between January 1994 and December 1998, 127 patients underwent emergency operation for a distal large bowel perforation. RPA was the operation of choice and was performed in 61 patients, 38 with localized and 23 with diffuse peritonitis. Septic shock, faecal peritonitis, immunocompromised status and American society of Anesthesiologists grade IV were contraindications to the one-stage procedure. Alternative operations used in high-risk patients were Hartmann's procedure in 55 patients, subtotal colectomy in eight and colostomy in three. RESULTS: There were two deaths (3 per cent) among 61 patients treated by RPA and one (2 per cent) case of clinical anastomotic dehiscence. Overall morbidity was 39 per cent and the overall mean(s.d.) hospital stay was 18(15) days. No statistical differences were observed between patients with localized and diffuse peritonitis treated by RPA. CONCLUSION: RPA may be the operation of choice in selected patients with left colonic diffuse peritonitis.

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.

Vascular occlusion in hepatic resections in cirrhotic rat livers: an experimental study in rats.

The aim of this study was to evaluate the tolerance of normothermic liver ischemia with different degrees of hepatic function in cirrhotic rats. Liver cirrhosis was induced by administering carbon tetrachloride (CCl4) in water solution to male Wistar rats. Hepatic function was graded using the plasma levels of antithrombin III, albumin, and bilirubin and the presence of ascites. Rats were distributed in four groups: noncirrhotic (control group), compensated cirrhosis (group A), decompensated cirrhosis (group B), and decompensated cirrhosis with ascites (group C). Groups A, B, and C were significantly different in all four parameters studied (P < .003). Subtotal liver ischemia was performed for periods of 0, 30, 45, 60, and 75 minutes. At the end of the procedure, the nonischemic lobes were resected. Postoperative evolution of alanine aminotransferase, aspartate aminotransferase, and bilirubin levels was also recorded. Survival rates after the same periods of ischemia were statistically different (P < .05): control group, 7 of 7 after 45 minutes (100%), 7 of 7 after 60 minutes (100%), and 4 of 9 after 75 minutes (44%); group A, 7 of 7 after 45 minutes (100%) and 1 of 7 after 60 minutes (14%); group B, 7 of 7 after 0 minutes (100%), 5 of 7 after 30 minutes (71%), and 1 of 7 after 45 minutes (14%); and group C, 0 of 5 after 0 minutes (0%) and 1 of 7 after 30 minutes (14%). No differences were found in the postoperative course of transaminases. However, bilirubin levels found 24 hours and 7 days after ischemia were significantly greater in cirrhotic rats, and this was directly related to the degree of hepatic insufficiency (P < .001). Histological examination of the livers exposed to CCl4 showed features of liver cirrhosis with ductal proliferation. The ischemia time tolerated by cirrhotic rat livers is shorter than the time tolerated by normal rats. Tolerance to hilar vascular occlusion depends on the degree of hepatic insufficiency. Rats with decompensated cirrhosis and ascites do not tolerate any surgical procedure.

Intraoperative colonic lavage and primary anastomosis in peritonitis and obstruction.

BACKGROUND: The surgical management of left colonic emergencies has evolved in the past few decades. Recently, there has been increasing interest in resection with primary anastomosis in selected cases. The aim of this study was to evaluate the differences in outcome in patients with peritonitis or obstruction treated by resection, on-table lavage and primary anastomosis of the left colon. METHODS: Between January 1992 and August 1995, 212 patients underwent emergency operation for a distal colonic lesion: 97 presented with peritonitis, 113 with obstruction and two with other indications. Intraoperative colonic lavage was performed in 37 patients with obstruction and in 24 with an acute intra-abdominal inflammatory process. RESULTS: The postoperative mortality rate was 5 per cent. The incidence of clinical anastomotic leakage was 5 per cent. Wound infection was observed in ten patients (16 per cent), more often in those with peritonitis (P = 0.03). The overall mean(s.d.) hospital stay was 15(9) days. CONCLUSION: Resection, on-table lavage and primary anastomosis constitute the operation of choice for selected patients with left colonic emergency.

[Surgical treatment of emergency pathology of the left colon]. / Tratamiento quirúrgico de la patología urgente del colon izquierdo.

The aim of this study was to evaluate the postoperative morbidity and mortality of patients with left colon disease that underwent emergency surgery. Intra-operative colonic irrigation (ICI) with primary anastomosis was used for unresectable lesions, faecal peritonitis, colon remnant associated lesions and poor performance status. The options included colostomy, Hartmann procedure or subtotal colectomy; 127 resections of left-sided large bowel were performed. In 56 cases the procedure was a Hartmann operation, in 38 cases subtotal colectomy and in 33 ICI. The most frequent complication was abdominal sepsis (29%). The overall mortality was 24%; 39% for the Hartmann procedure; 16% for subtotal colectomy and 6% for ICI. Our results suggest that ICI should be the first choice in patients with good performance status who undergo emergency surgery for left colon disease without faecal peritonitis or associated right colon lesions.

[Left hemicolectomy and intraoperative antegrade lavage in emergency surgery of the left colon]. / Hemicolectomía izquierda y lavado anterógrado peroperatorio en el tratamiento de la patología urgente del colon izquierdo.

We report our results with a left colonic resection and intraoperative antegrade colonic irrigation technique with primary anastomosis. Thirty five consecutive patients operated on in the Emergency Surgical Ward are presented. Twenty five with large bowel occlusion and 10 with sigma perforation. Anastomotic leakage (2 patients, 5.7%) and postoperative hospital stay (mean 15 days) were similar to cases of elective surgery. The intraoperative antegrade colonic irrigation technique has become the first choice in our Department to treat any patient with left colonic occlusion or perforation. Only patients with faecal peritonitis or ischemic colon were excluded.