The neurotrophic tyrosine kinase receptor 1 (TrkA) is overexpressed in oesophageal squamous cell carcinoma.

Nerve growth factor (NGF) and its receptors, the neurotrophic receptor tyrosine kinase 1 (NTRK1/TrkA) and the common neurotrophin receptor (NGFR/p75NTR), are increasingly implicated in cancer progression, but their clinicopathological significance in oesophageal cancer is unclear. In this study, the expression of NGF, NTRK1 and NGFR were analysed by immunohistochemistry in a cohort of 303 oesophageal cancers versus 137 normal adjacent oesophageal tissues. Immunostaining was digitally quantified and compared to clinicopathological parameters. NGF and NGFR staining were found in epithelial cells and at similar levels between oesophageal cancers and normal oesophageal tissue. NGFR staining was slightly increased with grade (p=0.0389). Interestingly, NTRK1 staining was markedly higher in oesophageal squamous cell carcinoma (OR 2.31, 95%CI 1.13-4.38, p<0.0001) and significantly lower in adenocarcinoma (OR 0.50, 95%CI 0.44-0.63, p<0.0001) compared to normal oesophageal tissue. In addition, NTRK1 staining was decreased in grade 2 and grade 3 (OR 0.51, 95%CI 0.21-1.40, p<0.0001) compared to grade 1, suggesting a preferential involvement of this receptor in the more differentiated forms of oesophageal carcinomas. Together, these data point to NTRK1 as a biomarker and a candidate therapeutic target in oesophageal squamous cell carcinoma.

Clinicopathological Significance of Nerves in Esophageal Cancer.

Nerves are emerging promoters of cancer progression, but the innervation of esophageal cancer and its clinicopathologic significance remain unclear. In this study, nerves were analyzed by immunohistochemistry in a cohort of 260 esophageal cancers, including 40 matched lymph node metastases and 137 normal adjacent esophageal tissues. Nerves were detected in 38% of esophageal cancers and were more associated with squamous cell carcinomas (P = 0.04). The surrounding or invasion of nerves by cancer cells (perineural invasion) was detected in 12% of esophageal cancers and was associated with reduced survival (P = 0.04). Nerves were found to express the following receptors for nerve growth factor (NGF): neurotrophic receptor tyrosine kinase 1 and nerve growth factor receptor. An association was suggested between high production of NGF by cancer cells and the presence of nerves (P = 0.02). In vitro, NGF production in esophageal cancer cells was shown by Western blot, and esophageal cancer cells were able to induce neurite outgrowth in the PC12 neuronal cells. The neurotrophic activity of esophageal cancer cells was inhibited by anti-NGF blocking antibodies. Together, these data suggest that innervation is a feature in esophageal cancers that may be driven by cancer cell-released NGF.

Patient knowledge of the risks of post-splenectomy sepsis.

BACKGROUND: Splenectomy is associated with a lifelong increase in the risk of sepsis. The aim of this study was to determine the level of knowledge of patients who have undergone splenectomy within an Australian area health service. METHODS: Adults undergoing a splenectomy between 1994 and 2004 within the Hunter Area Health Service were invited to participate in the study. Consenting participants were contacted by telephone and a standardized questionnaire completed. RESULTS: More than 50% of participants displayed a good active knowledge of the risk of infection post-splenectomy and an understanding of the role of vaccinations in reducing the risk of infection. Few participants (11.3%) had standby antibiotics readily available. Knowledge of travel precautions and risk of sepsis following animal bites was poor. CONCLUSION: Although most participants displayed a good knowledge of infection risk post-splenectomy, deficiencies in knowledge were identified. We propose the development of a splenectomy protocol and patient briefing to improve patient education.

Acute management of hemodynamically unstable pelvic trauma patients: time for a change? Multicenter review of recent practice.

BACKGROUND: Hemorrhage-related mortality (HRM) associated with pelvic fractures continues to challenge trauma care. This study describes the management and outcome of hemodynamically unstable patients with a pelvic fracture, with emphasis on primary intervention for hemorrhage control and HRM. METHODS: Blunt trauma patients [Injury Severity Score (ISS) >or=16] with a major pelvic fracture (Abbreviated Injury Score, pelvis >or=3) and hemodynamic instability [admission systolic blood pressure (SBP) or=6 units of packed red blood cells (PRBCs)/24 hours) were included into a 48-month (ending in December 2003) multicenter retrospective study of 11 major trauma centers. Data are presented as the mean +/- SD. RESULTS: A total of 217 patients (mean age 41 +/- 19 years, 71% male, ISS 42 +/- 16) were studied. The admission SBP was 96 +/- 37 mmHg and the Glascow Coma Scale (GCS) 11 +/- 5. Patients received 4 +/- 2 liters of fluids including 4 +/- 4 units of PRBCs in the emergency room (ER). In total, 69 (32%) patients died, among whom the HRM was 19%; 29% of the deaths were due to pelvic bleeding. Altogether, 120 of the 217 (55%) patients underwent focused abdominal sonography for trauma (FAST) or diagnostic peritoneal aspiration (DPA) and diagnostic peritoneal lavage (DPL); 60 of the 217 (28%) patients were found to have pelvic binding in the ER. In all, 53 of 109 (49%) patients had no bleeding noted at laparotomy, 26 of 106 (25%) had no abdominal findings, and 15 of 53 (28%) had had no prior abdominal investigation (FAST/DPL/computed tomography). Angiography was positive in 48 of 58 (83%) patients. The HRM was highest in patients with laparotomy as the primary intervention (29%) followed by the angiography group (18%), the combined laparotomy/pelvic fixation group (16%), and the pelvic fixation-only group (10%). CONCLUSION: HRM associated with major pelvic trauma is unacceptably high especially in the laparotomy group. Hence, nontherapeutic laparotomy must be avoided, concentrating instead on arresting pelvic hemorrhage. Standards of care must be implemented and abided by.

Complications of biliary T-tubes after choledochotomy.

BACKGROUND: Traditional management of choledocholithiasis has been supraduodenal choledochotomy, duct exploration and insertion of a T-tube. This study reviews the complications associated with T-tube use and assesses whether laparoscopic procedures are associated with an increase in complications relating to T-tube use. METHODS: Case records from two large public hospitals in New South Wales (Australia) were analysed retrospectively for a 10-year period using a standardized data collection form. Morbidity, mortality and potential factors influencing the complication rate after choledochotomy and T-tube insertion were recorded. All complications were reviewed by an experienced biliary surgeon. RESULTS: T-tubes were inserted in 274 patients, with 42 patients (15.3%) experiencing a total of 60 complications relating to T-tube use. Morbidity occurring while the tube was in situ included fluid and electrolyte disturbance (five patients), sepsis (10 patients), premature dislodgement (three patients) and bile leakage (six patients). Complications resulting after planned tube removal included localized pain (13 patients), biliary peritonitis (seven patients), a prolonged biliary fistula (seven patients) and a late bile duct stricture (one patient). T-tube complications resulted in a prolonged hospital stay (19 days vs 13 days, P = 0.005), 10 additional abdominal operations and two deaths. Complications related to T-tubes were constant over the study period and were similar between laparoscopic and open cases (13.8% vs 15.5%, P = 0.81). CONCLUSIONS: Although this retrospective review is likely to have underestimated the incidence of T-tube complications, it has demonstrated significant morbidity associated with T-tube use. The incidence of these complications has been constant and is unrelated to a laparoscopic approach.