Unplanned splenectomy during oesophagectomy does not affect survival.

OBJECTIVE: There are limited and conflicting data available concerning the incidence of inadvertent splenectomy and its impact on the outcome in patients who have undergone oesophagectomy. The aim of this study is to identify the factors associated with a likelihood of inadvertent splenectomy and its influence on early and long-term outcome in patients having oesophagectomy for oesophageal carcinoma. METHODS: A consecutive series of 738 oesophagectomies performed between 1991 and 2004 was analysed. In our practice, the spleen was removed only if damaged intraoperatively. Routine chemo- and immunoprophylaxis would subsequently be used. Multivariate analysis with logistic and Cox models determined significant variables. RESULTS: Of the 738 oesophagectomies, 48 (6.5%) had splenectomy. Neoadjuvant chemotherapy was administered to a minority of patients; none subsequently had splenectomy. There were significant differences between types of operation (Ivor-Lewis 18 (9.0%), left thoracolaparotomy 14 (9.9%) and left thoracophrenotomy 15 (3.9%), p=0.01). Splenectomy was more common with advanced N stage disease (OR=0.44 [0.20-0.95]; p=0.04). Splenectomy resulted in more blood transfusions (median, 2 units vs 0 units; p=0.03) more anastomotic leaks (7 [14.6%] vs 42 [6.1%]; p=0.02) but not an increase in pulmonary complications (p=0.64) or in-hospital mortality (1 [4.6%] vs 37 [5.4%]; p=0.30). Splenectomy did not significantly affect median survival (551 [332-770] days vs 627 [554-700] days; p=0.63). CONCLUSION: Although inadvertent splenectomy increased the morbidity of oesophagectomy, it did not impair survival. Type of operation and advanced N stage are important risks for splenectomy. Though best avoided, most of the consequences of splenectomy can be managed. An unexpected relationship between splenectomy and anastomotic leaks needs further investigation.     

The relationship between evaluative research and audit.

Evaluative research and audit are distinct activities with different goals. However, they are interrelated in four ways: research provides a basis for defining good-quality care for audit purposes; audit can provide high-quality data for nonexperimental evaluative research; research into the effectiveness and cost-effectiveness of audit is needed to establish the value of different interventions; and, in common with other research areas, evaluative research needs to be audited to ensure high-quality work is performed. Recognition of the unique and interrelated roles of research and audit will be of benefit to both endeavours.     

Modulation of carcinogenicity in 1,2,3,4-tetrahydro-7,12- dimethylbenz[a]anthracene (THDMBA) by fluorine substitution: crystal structures of the 5- and 6-fluoro regioisomers.

1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene (THDMBA) is an animal carcinogen which lacks an aromatic bay-region and shows promise as a model to investigate non-classical mechanisms of carcinogenesis. The fluorine-substituted derivatives at positions 5 and 6 on the B-ring exhibit a striking range of oncogenic potential wherein the 6F-THDMBA is twice as potent as the parent carcinogen, but the 5F-THDMBA is virtually inactive. To study structure-reactivity relationships for these fluorine regioisomers, we have determined the three-dimensional structures of the compounds by single-crystal X-ray diffraction. These crystal structures are the first such to be reported for any monofluoro anthracene (or pyrene) derivative. The partially-reduced A-ring exists in both enantiomeric half-chair conformers in the crystalline state, and the compounds have quasi-planar anthracene ring systems which exhibit a right-handed twist in the 'beta'-conformer, with the expected opposite twist in the other. A complete analysis of bond lengths, bond angles and torsion angles is presented. Preliminary electrostatic potentials have been derived from the X-ray data sets, and the results indicate significant differences in potential between 5F- and 6F-THDMBA at positions near the partially reduced bay region. Such results are likely to be of importance in the understanding of metabolic activation to reactive intermediates capable of bonding covalently to DNA.     

The effect of 5-lipoxygenase inhibition on blood-brain barrier permeability in experimental brain tumors.

To determine if leukotrienes are important mediators of vascular permeability in brain tumors, the effect of 5-lipoxygenase inhibitors on blood-tumor barrier permeability in rats harboring HK Walker 256 brain tumors was examined using quantitative autoradiography with alpha-14C-aminoisobutyric acid. The 5-lipoxygenase enzyme converts arachidonic acid to leukotrienes. Three 5-lipoxygenase inhibitors were utilized: BW755C, nordihydroguaiaretic acid, and AA-861. All three 5-lipoxygenase inhibitors significantly decreased vascular permeability both within the tumors and in brain adjacent to tumor. This suggests that capillary permeability in and adjacent to tumors is influenced by endogenous leukotrienes and that leukotrienes play an important role in brain tumor edema.     

Hormone receptors in vestibular schwannomas

Summary The possibility that steroid hormones play a role in vestibular schwannoma proliferation has been suggested by a number of investigators. There is conflicting information about the presence of steroid hormone receptors in these tumors. The aim of this study was to examine the expression of androgen, progesterone, glucocorticoid and estrogen receptor messenger ribonucleic acid levels (mRNA) in twenty-one vestibular schwannomas by either Northern blot analysis or the polymerase chain reaction (PCR).Glucocorticoid receptor mRNA was expressed in all twentyone tumors examined. Only two male specimens were positive for androgen receptor mRNA expression by PCR-Southern blot analysis. Thirty-three percent of the schwannomas (7/21) showed a strong band for progesterone receptor mRNA by PCR-Southern blot analysis; there were an equal number of males and females in this group. Estrogen receptor mRNA levels were undetectable in all tumors examined by PCR-Southern blot analysis. These studies suggest that the pattern of steroid receptor expression is different in schwannomas than in meningiomas. Individual vestibular schwannomas need to be examined for their steroid receptor mRNA expression mRNA expression to know whether they will be responsive.     

Oral hypoglycemic agents. Pyrimido[1,2-a]indoles and related compounds.

A series of pyrimido[1,2-a]indoles were synthesized and studied for their hypoglycemic activity following oral administration at a standard dose of 100 mg/kg to fed rats. The effect of 10-alkoxyalkyl, 10-alkyl, 10-aryl, and 3,3-dialkyl substitution on the activity of 10-hydroxypyrimido[1,2-a]indoles was investigated. Relative potencies of a number of the most active compounds were defined by three-point dose-response studies. The most potent compounds were those with either 3,3-dimethyl substituents, compounds 21, 22, and 38, or 3,3-spirocyclohexane substituents, compounds 39 and 49. 10-Aminopyrimido[1,2-a]indoles were in general less active than the 10-hydroxy analogues, and potency was further decreased by derivatizing the 10-amino group. The most potent 10-amino derivatives were 57 and 58.     

A comparison of midazolam with trimeprazine as an oral premedicant for children

The effect of oral premedication was investigated in a double-blind, randomised trial in 85 children undergoing tonsillectomy and/or adenoidectomy. Orally administered midazolam 0.5 mg.kg⁻¹ given 30 min pre-operatively was compared with trimeprazine 2 mg.kg⁻¹ given 90 min pre-operatively and a placebo preparation. Compliance, sedation and ease of induction were assessed as were the duration and quality of recovery. Following premedication with midazolam none of the patients was anxious, crying or distressed on leaving the ward, compared with 2/28 in the trimeprazine group and 5/28 in the placebo group (p =0.0007). More patients were calm and quiet on arrival in the anaesthetic room following midazolam than following trimeprazine, with both premedicant agents comparing favourably with placebo. There was no significant difference between the three groups in the time to recovery or the sedation score on discharge to the ward. Midazolam is a safe and effective oral premedicant for children.