Complications of an uncovered metallic tracheal stent managed by veno-venous extracorporeal membrane oxygenation: a case report.

Airway stents are primarily inserted for the management of airway obstruction associated with an inoperable malignancy and are rarely indicated in benign disease. We outline the complications associated with tracheal stents and describe the use of veno-venous extracorporeal membrane oxygenation (V-V ECMO) to facilitate open tracheal surgery in an apnoeic patient who had an uncovered metallic tracheal stent left in place for an inappropriately long period. Computerised tomography imaging of the neck and thorax provided information for operative planning and described of the stent in addition to the extensive granulation tissue at the distal end of the stent. Veno-venous extracorporeal membrane oxygenation was used to facilitate open tracheal surgery, removal of the tracheal stent and formation of a surgical tracheostomy. Prolonged use of an uncovered metallic airway stent in younger patients with benign disease may lead to the stent being difficult to remove. There may be an accumulation of granulation tissue with the risk of airway obstruction.

Intracorporeal vs extracorporeal anastomosis following neoplastic right hemicolectomy resection: a systematic review and meta-analysis of randomized control trials.

PURPOSE: While minimally invasive surgery is the preferred approach for right hemicolectomy, the choice of anastomotic technique is still debated. Both intracorporeal (ICA) and extracorporeal anastomosis (ECA) are described, with conflicting reports on safety and efficacy seen. This study aimed to examine impact of ICA and ECA on outcomes in right hemicolectomy. METHODS: A meta-analysis of randomized control trials (RCT) was performed. The primary outcome was overall morbidity. The secondary outcomes included both perioperative and post-operative outcomes. RESULTS: Four RCTs were included incorporating 399 patients (199 patients (49.9%) ICA Vs 200 (50.1%) ECA). There was no significant difference in overall morbidity (RR 0.79, 95% CI 0.43, 1.48, p = 0.47), anastomotic leak (RR 1.34, 95% CI 0.58, 3.13, p = 0.5) or surgical site infections (RR 0.53, 95% CI 0.17, 1.64, p = 0.27). ICA patients had a significantly less post-operative ileus (RR 0.53, 95% CI 0.3-0.94, p = 0.03) quicker return to first flatus (WMD - 0.71, 95% CI - 1.12, 0.31, p = 0.0005), first bowel motion (WMD - 0.53, 95% CI - 0.69, - 0.37, p < 0.00001) and first meal (WMD - 0.68, 95% CI - 1.33, - 0.03, p = 0.04). Pain scores were significantly better for ICA patients on POD 3 (WMD - 0.76, 95% CI - 1.23, - 0.28, p = 0.002), POD 4 (WMD - 0.90, 95% CI - 1.71, - 0.09, p = 0.03) and POD 5 (WMD - 0.67, 95% CI - 1.22, - 0.13, p = 0.01). Length of hospital stay was similar (WMD - 0.46, 95% CI - 1.14, 0.22, p = 0.19). CONCLUSION: ICA is associated with a quicker return to normal physiological function with equivalent post-operative morbidity. Both ECA and ICA are safe and feasible for restoring normal bowel continuity.

Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients.

BACKGROUND: Abiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity. PATIENTS AND METHODS: This is a monocentric prospective observational study in mCRPC patients treated with ABI. The plasmatic concentration of ABI at steady state was measured using liquid chromatography with fluorescence detection. The primary objective was to study the relationship between mean ABI plasma exposure (ABI Cmin) and 3-month PSA response. RESULTS: From 2012 to 2016, 61 mCRPC patients were eligible for pharmacokinetic/pharmacodynamic assessment. Thirty-eight patients experienced PSA response (62%, [confidence interval {CI} 95% 50-78]). In univariate analysis, ABI Cmin was 1.5-fold higher in responders: 12.0 ng/mL (CI 95% 9.4-15.6) versus 8.0 ng/mL (CI 95% 5.8-11.6; P = 0.0015). In multivariate analysis, only ABI Cmin was independently associated with PSA response (odds ratio = 1.12 [CI 95% 1.01-1.25], P = 0.004). By receiver operating characteristic analysis, the optimal threshold for ABI Cmin was 8.4 ng/mL. Progression-free survival (PFS) was significantly higher in patients with ABI Cmin above 8.4 ng/mL (hazard ratio 0.55, [CI 95% 0.31-0.99], 12.2 [CI 95% 9.2-19.5] versus 7.4 [CI 95% 5.5-14.7] months otherwise, P = 0.044). CONCLUSIONS: We showed that ABI trough concentration correlates with PSA response and PFS. Moreover, we could determine a cut-off value of plasmatic concentration for PSA response. Altogether, ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients.

Anaesthetic management of patients with severe sepsis.

Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

Effect of intraoperative intravenous crystalloid infusion on postoperative nausea and vomiting after gynaecological laparoscopy: comparison of 30 and 10 ml kg(-1).

BACKGROUND: I.V. fluid administration has been shown to reduce postoperative nausea and vomiting (PONV). The optimum dose is unknown. We tested the hypothesis that administration of i.v. crystalloid of 30 ml kg(-1) would reduce the incidence of PONV compared with 10 ml kg(-1) of the same fluid. METHODS: A total of 141 ASA I female patients undergoing elective gynaecological laparoscopy were randomized, in double-blind fashion, to receive either 10 ml kg(-1) (n=71; CSL-10 group) or 30 ml kg(-1) (n=70; CSL-30 group) of i.v. compound sodium lactate (CSL). RESULTS: In the first 48 h after anaesthesia, the incidence of vomiting was lower in the CSL-30 group than in the CSL-10 group (8.6% vs 25.7%, P=0.01). Anti-emetic use was less in the CSL-30 group at 0.5 h (2.9% vs 14.3%, P=0.04). The incidence of severe nausea was significantly reduced in the treatment group at awakening (2.9% vs 15.7%, P=0.02), 2 h (0.0% vs 8.6%, P=0.04) and cumulatively (5.7% vs 27.1%, P=0.001). The numbers needed to treat to prevent vomiting, severe nausea and antiemetic use in the first 48 h were 6, 5 and 6, respectively. CONCLUSION: I.V. administration of CSL 30 ml kg(-1) to healthy women undergoing day-case gynaecological laparoscopy reduced the incidence of vomiting, nausea and anti-emetic use when compared with CSL 10 ml kg(-1).

Loss of Bcl-2 expression in Barrett's dysplasia and adenocarcinoma is associated with tumor progression and worse survival but not with response to neoadjuvant chemoradiation.

Esophageal adenocarcinoma arising on a background of Barrett's esophagus is increasing in incidence. A molecular understanding of both the progression of Barrett's esophagus and the factors determining the response of adenocarcinoma to neoadjuvant therapy is required, and this study focused on the role of proteins regulated by the bcl-2 family of genes, which are important regulators of programmed cell death (apoptosis). In total, 48 patients (36 men, 12 women) with Barrett's adenocarcinoma were studied. All patients received preoperative chemoradiotherapy followed by surgery. Bcl-2, bax and bcl-x protein expression were detected by standard avidin-biotin peroxidase method. Bcl-2, bax and bcl-x expression were detected in 84%, 80%, and 76%, respectively, of normal squamous mucosa. An increasing degree of dysplasia in Barrett's mucosa both before and after chemoradiotherapy was significantly associated with a reduction of bcl-2 expression (P = 0.03 and 0.009, respectively). Bcl-2 expression was significantly associated with tumor differentiation (P = 0.03) and a trend towards earlier T stage (P = 0.08), but not with nodal status. Pre-therapeutic bcl-2, bax and bcl-x protein expression (27%, 75%, and 87.5%, respectively) were not associated with tumor response or resistance to therapy. Bcl-2-positive patients had a significantly improved survival compared with bcl-2-negative tumors. A significant reduction of bcl-2 expression is associated with the progression of Barrett's mucosa to adenocarcinoma. Bcl-2 expression was associated with improved survival. Preoperative chemoradiotherapy induces expression of bax and bcl-x protein. The pretreatment expression of bcl-2 and related proteins did not predict response or resistance to neoadjuvant chemoradiotherapy, suggesting that regulators of apoptosis alone do not determine the response of Barrett's adenocarcinoma to neoadjuvant therapy.

Spontaneous and inducible apoptosis in oesophageal adenocarcinoma.

The use of neoadjuvant chemoradiotherapy prior to surgery in the treatment of oesophageal adenocarcinoma has increased in recent years, and up to 25% of patients will have a complete pathological response to the neoadjuvant therapy. Many patients will not respond, however, and the knowledge of molecular factors predicting response or resistance to chemoradiotherapy is required to enhance treatment results. An understanding of apoptosis and cell proliferation may be relevant and this study focused on apoptotic indices and cell-cycle related (Ki-67, p53 and bcl-2) protein expression in a cohort of 42 patients with primary oesophageal adenocarcinoma. We documented that apoptosis occurs among viable (proliferating) tumour cells in all adenocarcinoma cases examined in this study. Pre-operative chemoradiotherapy significantly increased apoptosis and significantly decreased cell proliferation (estimated by Ki-67 expression). Immunohistochemically detected p53 and bcl-2 gene products had no regulatory role in the apoptotic process. The cumulative expression of p53 protein is significantly associated with increasing proliferation activity. Evaluation of apoptosis in pre-treatment specimens may have potential utility in predicting the efficacy of treatment. Assessment of the tumours proliferation activity by Ki-67 expression might identify patients who are at risk of developing metastatic disease.

A common p73 polymorphism is associated with a reduced incidence of oesophageal carcinoma.

The incidence of oesophageal adenocarcinoma is rising; to date, no susceptibility genes have been identified. p73, a novel p53 homologue, maps to chromosome 1p36, a region commonly deleted in oesophageal cancers. p73 shares some p53-like activity, but in addition, may also play a role in gastrointestinal epithelial inflammatory responses. A non-coding p73 polymorphism (denoted AT or GC) may be functionally significant. We investigated whether this polymorphism might play a role in the aetiopathogenesis of oesophageal cancer. This was a case-control, retrospective study. 84 cases of oesophageal cancer (25 squamous and 59 adenocarcinoma) and 152 normal population controls were genotyped for this polymorphism. Informative cases were examined for p73 LOH within the tumour. AT/AT homozygotes were significantly less prevalent in the oesophageal cancer population (1/84 = 1.2%) compared to controls (15/152 = 9.9%) (P < 0.02), corresponding to an odds ratio of 0.11 (95% C.I. 0.02-0.6, P < 0.02), or 9-fold reduced risk. Moreover, AT/AT homozygotes were significantly less frequent in the cancer population than would be expected under the Hardy-Weinberg hypothesis (P = 0.0099). LOH at the p73 locus was observed in 37.8% (14/37) of the AT/GC heterozygotes studied; in all cases there was loss of the AT allele. Our findings indicate that p73 AT/AT homozygotes appear to be protected against the development of oesophageal cancer. Clinically, this observation could have implications in aiding identification of high-risk Barrett's oesophagus patients.

Specialized intestinal metaplasia: analysis of prevalence, risk factors and association with gastro-oesophageal reflux disease

AIMS: There is an increasing awareness that short (less than 3 cm) segments of Barrett's epithelium and macroscopically normal cardia epithelium may harbour specialized intestinal metaplasia (SIM), a premalignant phenotype. This was a prospective study of both the prevalence of SIM in an unselected population of patients attending for endoscopy, and the association of SIM with symptoms, lifestyle, medication, endoscopic oesophagitis and carditis. METHODS: Two hundred consecutive patients underwent endoscopy. Biopsies taken from just below the squamocolumnar junction were stained for SIM, and were analysed for carditis and Helicobacter pylori infection. A detailed questionnaire of symptoms, tobacco consumption and the use of proton pump inhibitors was completed. RESULTS: Forty-two patients (21 per cent) had SIM, 19 of 126 (15 per cent) in an endoscopically normal oesophagus, 15 of 63 (24 per cent) in a short segment of Barrett's epithelium and eight of 11 in classical Barrett's oesophagus. Comparative analysis between the SIM positive and negative groups with respect to potential risk factors is outlined below. Table 1. CONCLUSION: SIM is prevalent in patients undergoing endoscopy, does not correlate with symptoms or with H. pylori infection, but is significantly associated with endoscopic and pathological markers of gastro-oesophageal reflux.

Specialized intestinal metaplasia in patients with gastro-oesophageal reflux disease.

BACKGROUND: There is an increasing awareness that short (less than 3 cm) segments of Barrett's epithelium and macroscopically normal cardia epithelium may harbour specialized intestinal metaplasia (SIM), a premalignant phenotype. The prevalence of SIM was studied prospectively in an unselected population of patients attending for endoscopy, and the association of SIM with symptoms, lifestyle, medication, endoscopic oesophagitis and carditis was investigated. METHODS: Two hundred consecutive patients underwent endoscopy. Biopsies taken from just below the squamocolumnar junction were stained for SIM, and were analysed for carditis and Helicobacter pylori infection. A detailed questionnaire of symptoms, tobacco consumption and the use of proton pump inhibitors was completed. RESULTS: Forty-two patients (21 per cent) had SIM: 19 (15 per cent) of 126 in an endoscopically normal oesophagus, 15 (24 per cent) of 63 in a short segment of Barrett's epithelium and eight of 11 in classical Barrett's oesophagus. There was a significant association between SIM and carditis (P < 0.0001) and endoscopic oesophagitis (P = 0.03). CONCLUSION: SIM is prevalent in patients undergoing endoscopy, does not correlate with symptoms or H. pylori infection, but is significantly associated with endoscopic and pathological markers of gastro-oesophageal reflux.

Crohn's colitis: the fate of the rectum.

Previous reports suggest that up to 70% of patients undergoing surgery for Crohn's disease of the large bowel do not have gastrointestinal continuity restored and require a permanent ileostomy. In this study the experience with patients requiring surgical treatment of large bowel Crohn's disease is reviewed with particular reference to the management of the rectum. The records of 19 elective and 25 urgent colonic resections performed for large bowel Crohn's disease in 44 patients (16 males, 28 females; mean age 41 years, range 17-76) between 1983 and 1995 were reviewed. Staged proctectomy was performed in 5 of 12 patients who had colectomy for acute colitis and in one patient who had had an elective colectomy. Permanent ileostomy was required in 72% of patients with acute Crohn's colitis and 84% of patients who had elective surgery for large bowel Crohn's. Over 70% of patients having surgical treatment of Crohn's disease of the large bowel required permanent ileostomy. No cases of cancer developed in patients with retained rectal stumps.

Preoperative or postoperative diclofenac for laparoscopic tubal ligation.

We have compared the analgesic effects of diclofenac given before operation or immediately after operation in a randomized, double-blind, double-dummy study of 40 healthy female patients undergoing laparoscopic tubal ligation. Group 1 patients received diclofenac 75 mg as a 3-ml i.m. injection 1-2 h before operation and normal saline 3 ml i.m. immediately after surgery. Group 2 patients received normal saline 3 ml i.m. before operation and diclofenac 75 mg i.m. immediately after surgery. Outcome measures were patients' perception of pain on a visual analogue scale (VAS), verbal response scale (VRS), the number of patients who required postoperative morphine, time to first postoperative morphine injection and total dose of morphine given. VAS at 30 min and at 1, 3 and 6 h after operation were, respectively (median, interquartile range) 4.5 (2.3-6.0) vs 5.3 (2.8-7.8); 3.3 (2.3-5.0) vs 4.4 (3.0-5.8); 1.4 (0-2.3) vs 1.9 (0.8-3.0); 0.5 (0-1) vs 0.7 (0-1.3), (ns). VRS at 1 and 3 h after operation were, respectively, (median, interquartile range) 2.2 (1.5-3.0) vs 2.7 (2.0-4.0) and 0.8 (0-1.3) vs 0.9 (0-1.5) (ns). Sixteen patients in group 1 compared with 17 in group 2 required postoperative morphine. Time to first morphine administration and dose given were, respectively, (median, interquartile range) 50.6 (39-60) min vs 35.7 (20-49) min (P = 0.1) and 9.0 (5-10) mg vs 9.5 (7.5-10) (P = 0.9).(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: At Rotunda Hospital in Dublin, Ireland, a randomized double-blind, double-dummy study of 40 women undergoing laparoscopic tubal ligation was conducted to examine the preoperative and postoperative analgesic effects of 75 mg intramuscular (i.m.) diclofenac, a nonsteroidal anti-inflammatory drug. 20 women first received 75 mg diclofenac 1-2 hours before tubal ligation and normal saline right after the operation. The other 20 women received the same injections in the reverse order. As outcome measures, researchers used patients' perception of pain on a visual analogue scale (VAS), verbal response scale (VRS), number of patients who needed a postoperative 10 mg morphine injection, time to first postoperative morphine injection, and total dose of morphine administered. The median pain scores on VAS were essentially the same at 30 minutes and at 1, 3, and 6 hours after the operation. The median pain scores on VRS were also the same at 1 and 3 hours after the operation. The median dose of morphine was less than 10 mg in both groups. Four women in the first group and three women in the second group did not require analgesia. Even though the median time to first morphine injection was longer for the first group than the second group (50.6 vs. 35.7 min), the difference was not statistically significant (p = 0.1). These findings show that diclofenac does not provide pre-emptive analgesia in patients undergoing laparoscopic tubal ligation.