Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study).

BACKGROUND: Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. METHODS: This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. DISCUSSION: In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. TRIAL REGISTRATION: NCT03208621 . This trial was registered prospectively on June 30, 2017.

Systematic review: pharmacotherapy for high-output enterostomies or enteral fistulas.

BACKGROUND: High-output enterocutaneous fistula or enterostomies can cause intestinal failure. There is a wide variety of options in medical management of patients with high output. AIM: To systematically review the literature on available pharmacotherapy to reduce output and to propose an algorithm for standard of care. METHODS: Relevant databases were systematically reviewed to identify studies on pharmacotherapy for reduction in (high-) output enterostomies or fistula. Randomised controlled trials and within subjects controlled prospective trials were included. An algorithm for standard of care was generated based on the outcomes of the systematic review. RESULTS: Two studies on proton pump inhibitors, six on anti-motility agents, three on histamine receptor antagonists, one on an α2- receptor agonist and eight on somatostatin (analogues) were included. One study examined a proton pump inhibitor and a histamine receptor antagonist within the same patients. Overall, we found evidence for the following medical therapies to be effective: omeprazole, loperamide and codeine, ranitidine and cimetidine. On the basis of these outcomes and clinical experience, we proposed an algorithm for standard of care which consists of high-dose proton pump inhibitors combined with high-dose loperamide as the first step followed by addition of codeine in case of insufficient output reduction. So far, there is insufficient evidence for the standard use of somatostatin (analogues). CONCLUSIONS: The available evidence on the efficacy of medication to reduce enterostomy or enterocutaneous fistula output is hampered by low quality studies. We propose an algorithm for standard of care output reduction in these patients.

Results of streamlined regional ambulance transport and subsequent treatment of acute abdominal aortic aneurysms.

OBJECTIVE: To describe the triage of patients operated for non-ruptured and ruptured abdominal aortic aneurysms (AAAs) before the endovascular era. DESIGN: Retrospective single-centre cohort study. METHODS: All patients treated for an acute AAA between 1998 and 2001 and admitted to our hospital were evaluated in the emergency department for urgent AAA surgery. All time intervals, from the telephone call from the patient to the ambulance department, to the arrival of the patient in the operating theatre, were analysed. Intraoperative, hospital and 1-year survival were determined. RESULTS: 160 patients with an acute AAA were transported to our hospital. Mean (SD) age was 71 (8) years, and 138 (86%) were men. 34 (21%) of these patients had symptomatic, non-ruptured AAA (sAAA) and 126 patients had ruptured AAA (rAAA). All patients with sAAA and 98% of patients with rAAA were operated upon. For the patients with rAAA, median time from telephone call to arrival at the hospital was 43 min (interquartile range 33-53 min) and median time from arrival at the hospital to arrival at the operating room was 25 min (interquartile range 11-50 min). Intraoperative mortality was 0% for sAAA and 11% for rAAA (p = 0.042), and hospital mortality was 12% and 33%, respectively (p = 0.014). CONCLUSIONS: A multidisciplinary unified strategy resulted in a rapid throughput of patients with acute AAA. Rapid transport, diagnosis and surgery resulted in favourable hospital mortality. Despite the fact that nearly all the patients were operated upon, survival was favourable compared with published data.

The central role of monocytes in the pathogenesis of sepsis: consequences for immunomonitoring and treatment.

Despite important advances in critical care medicine during the last two decades, the mortality rate of sepsis has remained high, probably because the pathogenesis of sepsis is still incompletely understood. Recent studies have shown that sepsis is a bimodal entity. The first phase is characterized by the systemic release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and IL-8, and by activation of the complement and coagulation cascades. In the second phase, anti-inflammatory mediators such as transforming growth factor-beta (TGF-beta), IL-10 and prostaglandin E2 (PGE2) may be released in an effort to counteract ongoing inflammation. Depending whether the pro- or anti-inflammatory response predominates, sepsis results in a systemic inflammatory response syndrome (SIRS), or a compensatory anti-inflammatory response syndrome (CARS). So far, most efforts to intervene in the immunopathogenesis of sepsis have been directed at the pro-inflammatory response. None of these interventions has been shown to improve the prognosis of sepsis, possibly because many patients were already in a state in which anti-inflammatory responses dominated. Recently, it has been shown that decreased expression of HLA-DR on monocytes in patients with sepsis constitutes a marker for CARS. We suggest that HLA-DR expression on monocytes might constitute a useful indicator of the immunological status of the individual patient with sepsis and a guide for treatment. Patients with CARS, as manifested by low HLA-DR expression, might benefit from immunostimulants, while patients with SIRS and normal or high monocyte HLA-DR expression should receive treatment directed to interfere with pro-inflammatory pathways.

[Non-fatal rupture of a cocaine packet in a man with the 'bodypacker' syndrome]. / Niet-fatale ruptuur van een cocaïnebolletje bij een man met 'bodypacker'-syndroom.

A 24-year-old patient was admitted to the intensive care unit because he had swallowed about 20 cocaine packets 48 hours before admission; he also complained of abdominal cramps, perspiration and dizziness. The patient reported that he had not defecated since swallowing the packets. Abdominal X-ray revealed only coprotasis. On conservative therapy with bowel irrigation, two packets were eliminated, after which a second abdominal X-ray revealed several cocaine packets in the colon. Four days afterwards, the cocaine packets in the colon had not progressed despite adequate bowel irrigation. The patient now showed signs of mild cocaine intoxication (hallucinations and tachycardia). It was therefore decided to perform a laparotomy. Via a sigmoidotomy, 7 intact packets were removed; another 3 had already ruptured and were empty. The rupture of 3 cocaine packets in this patient was probably not fatal because of the sedation with midazolam and because the patient had diarrhoea as a result of the extensive irrigation, so that a large proportion of the cocaine was probably not absorbed. This case also shows that the presence of foreign bodies cannot be established adequately by an abdominal X-ray if there is coprostasis.

Intraoperative motive for performing a laparoscopic appendectomy on a postoperative histological proven normal appendix.

BACKGROUND: Diagnostic laparoscopy is the ultimate tool to evaluate the appendix. However, the intraoperative evaluation of the appendix is difficult, as the negative appendectomy rate remains 12%-18%. The aim of this study is to analyze the intraoperative motive for performing a laparoscopic appendectomy of an appendix that was proven to be noninflamed after histological examination. METHODS: In 2008 and 2009, in five hospitals, operation reports of all negative laparoscopic appendectomies were retrospectively analyzed in order to assess the intraoperative motive for removing the appendix. RESULTS: A total of 1,465 appendectomies were analyzed with an overall negative appendectomy rate of 9% (132/1,465). In 57% (841/1,465), a laparoscopic appendectomy was performed, with 9% (n = 75) negative appendectomies. In 51% of the negative appendectomies, the visual assessment of the appendix was decisive in performing the appendectomy. In 33%, the surgeon was in doubt whether the appendix was inflamed or normal. In 4%, the surgeon was aware he removed a healthy appendix, and in 9%, an appendectomy was performed for different reasons. CONCLUSION: In more than half of the microscopic healthy appendices, the surgeon was convinced of the diagnosis appendicitis during surgery. Intraoperative laparoscopic assessment of the appendix can be difficult.

Low HLA-DR expression on peripheral blood monocytes predicts bacterial sepsis after liver transplantation: relation with prednisolone intake.

Bacterial sepsis remains a frequent complication after liver transplantation. We previously reported the results of a pilot study that suggested that low expression of HLA-DR on monocytes is a predictive marker for the occurrence of sepsis. We have studied the value of this marker in an additional cohort of patients, and have analyzed the relation of HLA-DR expression with the use of immunosuppressive agents. 20 adult liver transplantation patients were prospectively monitored during the first 4 weeks after transplantation. All were treated according to standard protocols. The percentage of monocytes expressing HLA-DR was measured by flow cytometry. In addition, the effects of incubation of monocytes with prednisolone in vitro on the expression of HLA-DR was determined in 7 healthy volunteers. Seven patients developed bacterial sepsis after a median 15 (range 10-20) days after transplantation. HLA-DR expression was significantly lower in these patients on days 7, 14, 21, and 28 after transplantation compared with non-septic patients. The percentage of HLA-DR positive monocytes was 30% or less, 3 (1-8) days before onset of sepsis. On day 7 after transplantation, HLA-DR expression on 50% or less of monocytes had a positive predictive value for sepsis of 71%, whereas the negative predictive value was 85%. Patients who developed sepsis received significantly more prednisolone. Incubation with prednisolone in vitro lowered the expression of HLA-DR in a dose-dependent manner. We conclude that low HLA-DR expression on monocytes is a marker for a high risk of subsequent sepsis in liver transplantation patients. This high risk may be (at least partly) related to the dose of prednisolone.