Propensity score matching analysis of laparoscopic surgery vs. open approach in 4 297 adult patients with acute appendicitis, acute cholecystitis or gastrointestinal tract perforation: a prospective multicentre study of nationwide outcomes.

BACKGROUND AND AIMS: Previous studies indicated that laparoscopic surgery could improve postoperative outcomes in acute appendicitis, acute cholecystitis, perforated gastroduodenal ulcer, or acute diverticulitis, but some reported opposite results or differences in the magnitude of improvement. A contemporary analysis using propensity score matching that compares outcomes is lacking. METHODS: Over a 6-month period, 38 centres (5% of all public hospitals) attending emergency general surgery patients on a 24 h, 7 days a week basis, enroled all consecutive adult patients who underwent laparoscopic surgery or open approach. RESULTS: The study included 2 645 patients with acute appendicitis [32 years (22-51), 44.3% women], 1 182 with acute cholecystitis [65 years (48-76); 46.7% women], and 470 with gastrointestinal tract perforation [65 years (50-76); 34% women]. After propensity score matching, hospital stays decreased in acute appendicitis [open, 2 days (2-4); lap, 2 days (1-4); P <0.001], acute cholecystitis [open, 7 days (4-12); lap, 4 days (3-6); P <0.001], and gastrointestinal tract perforation [open, 11 days (7-17); lap, 6 days (5-8.5); P <0.001]. A decrease in 30-day morbidity was observed in acute appendicitis (open, 15.7%; lap, 9.7%; P <0.001), acute cholecystitis (open, 41%; lap, 21.7%; P <0.001), and gastrointestinal tract perforation (open, 45.2%; lap, 23.5%; P <0.001). A decrease in 30-day mortality was found in acute cholecystitis (open, 8.8%; lap, 2.8%; P =0.013) and gastrointestinal tract perforation (open, 10.4%; lap, 1.7%; P =0.013). CONCLUSIONS: This clinically based, multicentre study suggests that an initial laparoscopic approach could be considered not only in patients with acute appendicitis or acute cholecystitis but also in patients with a perforation of the gastrointestinal tract.

Textbook outcome among patients undergoing enhanced recovery after liver transplantation stratified by risk. A single-center retrospective observational cohort study.

BACKGROUND & AIMS: Liver transplantation (LT) is one of the most complex surgical procedures. Enhanced recovery after surgery (ERAS) aims to reduce the risk of postoperative complications. When patients achieve all desirable outcomes after a procedure, they are considered to have experienced a textbook outcome (TO). METHODS: Two cohorts of patients undergoing low (n = 101) or medium risk (n = 15) LT were identified. The remaining patients (n = 65) were grouped separately. The ERAS protocol included pre-, intra-, and post-operative steps. TO was defined as the absence of complications, prolonged length of hospital stays, readmission and mortality during the first 90 days. RESULTS: One third of patients who underwent ERAS after LT experienced a TO. On multivariable analysis, age (OR, 1.05 [95% CI, 1.01-1.09]; P = .02), and having hepatocellular carcinoma (OR, 2.83 [95% CI, 1.37-6.03]; P = .005) were individually associated with a greater probability of achieving a TO. Belonging to the cohorts of medium risk or outside the selection criteria was associated with a lower probability of achieving a TO (OR, 0.46 [96% CI, 0.22-0.93]; P = .03). Patients less likely to experience TO required more hospital resources. Patients who achieved TO were more likely to remain free of chronic kidney disease (achieved TO, 83.8% [82.7-85.6]; failed TO, 67.9% [66.9-70.2]; P < .05). Tacrolimus dose and trough levels were similar. CONCLUSIONS: A novel finding of our study is that short and medium-term kidney function is better preserved in patients who experience a TO. Better kidney function of patients who achieve TO is not due to lower tacrolimus dosage.

Enhanced recovery after low- and medium-risk liver transplantation. A single-center prospective observational cohort study.

BACKGROUND & AIMS: Few studies have fully applied an enhanced recovery after surgery (ERAS) protocol to liver transplantation (LT). Our aim was to assess the effects of a comprehensive ERAS protocol in our cohort of low- and medium-risk LT patients. METHODS: The ERAS protocol included pre-, intra-, and post-operative steps. During the five-year study period, 181 LT were performed in our institution. Two cohorts were identified: low risk patients (n = 101) had a laboratory model for end-stage liver disease (MELD) score of 20 points or less at the time of LT, received a liver from a donor after brain death, and had a balance of risk score of 9 points or less; medium-risk patients (n = 15) had identical characteristics except for a higher MELD score (21-30 points). In addition, we analyzed the remaining patients (n = 65) who were transplanted over the same study period separately using the ERAS protocol. RESULTS: The low-risk cohort showed a low need for packed red blood cells transfusion (median: 0 units) and renal replacement therapy (1%), as well as a short length of stay both in the intensive care unit (13 h) and in the hospital (4 days); morbidity during one-year follow-up, and probability of surviving to one year (89.30%) and five years (76.99%) were in line with well-established reference data. Similar findings were observed in the medium-risk cohort. CONCLUSIONS: This single-center prospective observational cohort study provides evidence that ERAS is feasible and safe for low- and medium-risk LT.

Bacterial DNA translocation contributes to systemic inflammation and to minor changes in the clinical outcome of liver transplantation.

Bacterial (bact)DNA is an immunogenic product that frequently translocates into the blood in cirrhosis. We evaluated bactDNA clearance in patients undergoing liver transplantation (LT) and its association with inflammation and clinically relevant complications. We prospectively included patients consecutively admitted for LT in a one-year follow-up study. We evaluated bactDNA before and during the first month after LT, quantifying cytokine response at 30 days. One hundred patients were included. BactDNA was present in the blood of twenty-six patients undergoing LT. Twenty-four of these showed bactDNA in the portal vein, matching peripheral blood-identified bactDNA in 18 cases. Thirty-four patients showed bactDNA in blood during the first month after LT. Median TNF-α and IL-6 levels one month after LT were significantly increased in patients with versus without bactDNA. Serum TNF-α at baseline was an independent risk factor for bactDNA translocation during the first month after LT in the multivariate analysis (Odds ratio (OR) 1.14 [1.04 to 1.29], P = 0.015). One-year readmission was independently associated with the presence of bactDNA during the first month after LT (Hazard ratio (HR) 2.75 [1.39 to 5.45], P = 0.004). The presence of bactDNA in the blood of LT recipients was not shown to have any impact on complications such as death, graft rejection, bacterial or CMV infections. The rate of bactDNA translocation persists during the first month after LT and contributes to sustained inflammation. This is associated with an increased rate of readmissions in the one-year clinical outcome after LT.

aLicante sUrgical Community Emergencies New Tool for the enUmeration of Morbidities: a simplified auditing tool for community-acquired gastrointestinal surgical emergencies.

BACKGROUND: In a previous study, we found that Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) overpredicts morbidity risk in emergency gastrointestinal surgery. Our aim was to find a POSSUM equation adjustment. METHODS: A prospective observational study was performed on 2,361 patients presenting with a community-acquired gastrointestinal surgical emergency. The first 1,000 surgeries constituted the development cohort, the second 1,000 events were the first validation intramural cohort, and the remaining 361 cases belonged to a second validation extramural cohort. RESULTS: (1) A modified POSSUM equation was obtained. (2) Logistic regression was used to yield a statistically significant equation that included age, hemoglobin, white cell count, sodium and operative severity. (3) A chi-square automatic interaction detector decision tree analysis yielded a statistically significant equation with 4 variables, namely cardiac failure, sodium, operative severity, and peritoneal soiling. CONCLUSIONS: A modified POSSUM equation and a simplified scoring system (aLicante sUrgical Community Emergencies New Tool for the enUmeration of Morbidities [LUCENTUM]) are described. Both tools significantly improve prediction of surgical morbidity in community-acquired gastrointestinal surgical emergencies.

Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery.

OBJECTIVE: To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery. BACKGROUND: EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients. METHODS: Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement. RESULTS: These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were provided: one (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement. CONCLUSIONS: EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.

Bacterial DNA translocation holds increased insulin resistance and systemic inflammatory levels in morbid obese patients.

BACKGROUND: Morbidly obese patients show several common comorbidities associated with immunological alterations such as a sustained low-level proinflammatory profile. Bacterial product translocation is frequent in inflammation-related diseases and may aggravate patients' clinical outcome. DESIGN: Consecutively admitted morbidly obese patients who presented indications for bariatric surgery were studied. Before surgery, patients were subjected to a modified fasting diet. Patients underwent surgery by sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. Clinical and analytical parameters were recorded. Blood samples were collected at baseline, at the end of a 3-month modified fasting period, and 3, 6, and 12 months after surgery. Serum cytokine and endotoxin levels were evaluated by flow cytometry and ELISA, respectively. Bacterial DNA was identified in blood by broad-range PCR of prokaryote 16SrRNA gene and partial sequencing analysis. RESULTS: Fifty-eight patients were included in the study. All patients showed a significantly reduced weight and body mass index at each time-point. Postoperative mortality was null. Bacterial DNA translocation rate was 32.8% (19 of 58) at baseline; 13.8% (8 of 58) after the modified fasting period; and 13.8% (8 of 58), 1.8% (1 of 58), and 5.2% (3 of 58) at 3, 6, and 12 months after surgery. Proinflammatory cytokines, serum endotoxin levels, and insulin resistance remained increased in patients with bacterial DNA despite weight loss and were individually affected by the appearance/clearance of bacterial DNA in blood. Multivariate analyses revealed bacterial DNA as an independent significant factor, explaining the systemic cytokine response and the insulin resistance levels in the studied population. CONCLUSION: Bacterial DNA translocation holds increased insulin resistance and systemic inflammatory levels in morbidly obese patients despite significant weight loss.

[Assessment of the surgical risk of 1,000 consecutive episodes using the POSSUM system. Comparison between elective and emergency gastrointestinal surgery]. / Evaluación del riesgo quirúrgico de 1.000 episodios consecutivos con el sistema POSSUM. Comparación entre cirugía gastrointestinal programada y urgente.

INTRODUCTION: The aim of the present study was to assess the predictive capacity of the POSSUM system in a Spanish university hospital, and to determine its behaviour in elective gastrointestinal surgery and compare it with emergency gastrointestinal surgery (operation < 24 hours). PATIENTS AND METHOD: A total of 1,000 surgical episodes corresponding to 909 patients who required hospital admission, operated on under general or loco-regional anaesthesia, either in the elective (n= 547 episodes) or the emergency setting (n= 453), were included in the study. RESULTS: The overall morbidity was 31.9% (32.8% in elective surgery; 30.7% in emergency surgery). The discriminatory capacity of the POSSUM scale, evaluated using receiver operating characteristic (ROC) curves, was higher for the Portsmouth variant of mortality (Area Under the Curve [AUC] = 0,92) than for morbidity (AUC= 0,74). The goodness of fit between the expected values using the POSSUM scale and those observed was reduced for morbidity (Hosmer-Lemeshow [H-L] = 164.1; p< 0.05). The POSSUM scale predicted a higher number of deaths than those observed, although the Portsmouth variant was better at predicting mortality. The goodness of fit for morbidity was better for elective gastrointestinal surgery (H-L= 27.7) than emergency gastrointestinal surgery (H-L= 177.3). The logistic regression analysis identified (besides the estimated risk using the POSSUM scale itself), surgical complexity, surgery type (elective, emergency), and age of patient, as significant predictive factors of morbidity and mortality. CONCLUSIONS: In a Spanish university hospital, the POSSUM system adequately predicts morbidity risk in elective gastrointestinal surgery, and over-estimates morbidity risk in emergency gastrointestinal surgery.

[Safety of a multiperforated catheter implanted in the surgical wound for the continuous infusion of local anaesthetics in post-operative analgesia]. / Seguridad de un catéter multiperforado implantado en la herida quirúrgica para la infusión continua de anestésicos locales en la analgesia post-operatoria.

OBJECTIVE: To evaluate the incidence of infection at the surgical site in patients who have a multiperforated catheter implant for continuous infusion of a local anaesthetic as a local analgesic. PATIENTS AND METHOD: An observational, descriptive and prospective study, of one month duration. It included 50 patients subjected to selective laparotomy in whom a multiperforated pre-peritoneal catheter was implanted for analgesia purposes (Painfusor®. Baxter). Patients with a surgical incision of less than 15 cm and/or ASA>III, were excluded from the study. RESULTS: The catheter was removed from all patients at 48 hours. An infection at the surgical site was present in 6% of the patients who had the catheter implanted, which was similar to the incidence in clean-contaminated surgery (5.5%; 95% CI: 3.4-8.7%). Colonisation of the catheter was observed in two patients, causing only one infection of the surgical site. CONCLUSIONS: The use of an in-situ pre-peritoneal catheter for post-surgical anaesthesia does not increase the risk of surgical site infection.

Treatment with 5-fluorouracil enhances radiosensitivity of the human pancreatic cancer cell line MiaPaCa-2.

BACKGROUND AND PURPOSE: Several clinical studies have suggested that the combination of radiation therapy and 5-fluorouracil (5-FU) may improve outcome of patients with pancreatic cancer. However, there are few experimental studies supporting this treatment. AIM OF THE STUDY: To examine the radiosensitivity of human pancreatic cancer cells and its modulation by 5-FU. MATERIAL AND METHODS: MiaPaCa-2, PANC-1 and NP-18 cells growing as monolayer culture were treated with radiation and 5-FU. In addition, 5-FU was studied administered either pre- or postradiation, both as pulse or continuous exposure. Cell survival was determined by the in vitro clonogenic assay. RESULTS: In MiaPaCa-2 cell line, both radiation and 5-FU alone reduced cell survival. The addition of 5-FU to radiation caused a significant net decrease of cell survival. Pulse exposure of 5-FU decreased survival after 2 Gy and mean inactivation dose by 1.64; continuous exposure decreased survival after 2 Gy and mean inactivation dose by about 2.4. Timing of 5-FU exposure did not modify survival. However, when adjusting for 5-FU killing effect and cell multiplicity, only continuous exposure significantly enhanced radiation cell killing. CONCLUSION: Both pulse and continuous exposure increase radiation cell killing, but only continuous exposure may radiosensitize MiaPaCa-2 cells.

Implantación ortotópica de fragmentos sólidos de cáncer de páncreas exocrino humano en ratones atímicos / Orthotopic solid human pancreatic cancer fragment implants in athimic rats

Introducción: el desarrollo de modelos experimentales de cáncer de páncreas exocrino es esencial para un mejor conocimiento de la enfermedad. El objetivo del presente trabajo ha sido implantar y perpetuar carcinomas de páncreas exocrino humano en el páncreas del ratón atímico (implantación ortotópica), estudiar su patrón de diseminación y las alteraciones en genes implicados en la tumorigénesis. Material y Métodos: Se implantaron, de forma ortotópica, fragmentos sólidos de 11 carcinomas de páncreas exocrino humano. Se analizó la presencia de mutaciones en los genes K-ras y p53, tanto en tumores primarios como en los tumores perpetuados. Resultados: Siete de 11 tumores implantados (63 por ciento) crecieron como ortoimplantes. En 4 tumores se evidenció diseminación a distancia (metástasis hepáticas, diseminación peritoneal, o metástasis en los ganglios linfáticos). El patrón de diseminación fue específico para cada tumor y reproducible a lo largo de múltiples pases. Los tumores primarios y los perpetuados compartían el mismo genotipo. Conclusiones: La implantación ortotópica de fragmentos sólidos de carcinomas de páncreas exocrino humano permite la perpetuación de tumores con distinto genotipo y la reproducción de diferentes patrones de crecimiento local y a distancia