Ultrasound-Guided Interstitial Brachytherapy in the Treatment of Advanced Vaginal Recurrences from Cervical and Endometrial Carcinoma

BACKGROUND: In advanced vaginal recurrences of cervical and endometrial carcinomas therapeutic options are rare because of preceding therapy. PATIENTS AND METHODS: 23 patients developing advanced vaginal recurrences of cervical and endometrial carcinomas were included. 15 patients started with external-beam therapy to the pelvis and eight patients after preceding radiotherapy underwent brachytherapy alone. All patients had ultrasound-guided implantation of transvaginal or transperineal interstitial needles for brachytherapy. Median prescribed total dose was 64 Gy. RESULTS: 18 patients (78%) achieved complete remission. Six patients are alive without tumor and one with tumor after a median follow-up of 64 months. 14 patients died of tumor and two of intercurrent disease. 5-year disease-specific survival and local control rate were 43% and 47%, respectively, in patients with complete remission. Univariate analysis found time to relapse > 2 years, initial diameter < or = 4 cm, initial volume < 15 cm(3), no extension to the pelvic side wall, volume before brachytherapy < 7.5 cm(3), brachytherapy coverage index > 0.8, and prescribed total dose > 64 Gy being positive predictors for local control and survival. CONCLUSION: The use of ultrasound guidance for placement of interstitial needles in template-based brachytherapy of advanced recurrent gynecologic malignancies is a feasible, safe, and cheap method with encouraging results. Today, ultrasound imaging can be also used to some extent for treatment planning which requires further development. Patient- and treatment-related prognostic factors can be defined.     

Respiratory failure with diffuse patchy lung infiltrates: an unusual presentation of squamous cell carcinoma

The case history is presented of a patient with squamous cell carcinoma of the lung with diffuse bilateral pulmonary shadowing mimicking bronchioloalveolar cell carcinoma which led to type I respiratory failure.     

Neural connections between the hypothalamus and the liver

After receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon-like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species-dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus-pancreas axis, the hypothalamus-adrenal axis, and the hypothalamus-pituitary axis. In the hypothalamus-pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus-adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamus-pituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections.     

Primary care funding, contract status, and outcomes: an observational study

BACKGROUND: The introduction of the Quality and Outcomes Framework (QOF) provides a quantitative way of assessing quality of care in general practice. We explore the achievements of general practice in the first year of the QOF, with specific reference to practice funding and contract status. AIM: To determine the extent to which differences in funding and contract status affect quality in primary care. DESIGN OF STUDY: Cross-sectional observational study using practice data obtained under the Freedom of Information Act 2000. SETTING: One hundred and sixty-four practices from six primary care trusts (PCTs) in England. METHOD: Practice data for all 164 practices were collated for income and contract status. The outcome measure was QOF score for the year 2004-2005. All data were analysed statistically. RESULTS: Contract status has an impact on practice funding, with Employed Medical Services (EMS) and Personal Medical Services (PMS) practices receiving higher levels of funding than General Medical Services (GMS) practices (P<0.001). QOF scores also vary according to contract status. Higher funding levels in EMS practices are associated with lower QOF scores (P=0.04); while GMS practices exhibited the opposite trend, with higher-funded practices achieving better quality scores (P<0.001). CONCLUSION: GMS practices are the most efficient contract status, achieving high quality scores for an average of pound 62.51 per patient per year. By contrast, EMS practices are underperforming, achieving low quality scores for an average of pound 105.37 per patient per year. Funding and contract status are therefore important factors in determining achievement in the QOF.     

Prognostic value of the combined assessment of proliferating cell nuclear antigen immunostaining and nuclear DNA content in invasive human mammary carcinomas

The expression of theS-phase associated, nuclear protein proliferating cell nuclear antigen (PCNA) was investigated in routinely paraffin-embedded surgical specimens from 209 breast cancer patients. Cytometric DNA assessments were performed on fine-needle aspirates, upon which the primary diagnosis of breast cancer had been based. The mean clinical follow-up was 16 years (range 13–20 years). The percentage of PCNA immunoreactive tumour cells ranged between less than 5 to 60% (mean value 13.34%). There was a direct association between PCNA expression, high histological tumour grade (p<0.01), and DNA aneuploidy (p=0.009). In a subgroup of 22 patients with near-diploid DNA distribution patterns the PCNA expression yielded additional prognostic information. Patients with tumours of near-diploid DNA histograms and more than 20% of PCNA immunoreactive neoplastic cells had a significantly worse clinical course, than patients with neardiploid tumours containing less than 20% PCNA immunoreactive cells (p=0.0001). In contrast, the PCNA immunoreactivity did not yield additional prognostic information for patients with distinctly diploid or highly aneuploid tumour variants. In a multivariate analysis comprising all 209 patients, nodal status (p<0.01), tumour size (p<0.01), and DNA ploidy (p<0.01) were found to have significant prognostic effect. The findings indicate that carcinomas characterised by high proliferative activity and near-diploid DNA distribution patterns can show rapid tumour progression. The combined assessment of the PCNA immunoreactivity and of the nuclear DNA content in routinely processed surgical specimens of breast cancer patients appears to be of prognostic value.     

Immunohistochemical localization of pepsinogen A and C containing cells in Barrett's oesophagus

Summary No data are available on the localization of Pepsinogen A (PGA=PG I) and Pepsinogen C (PGC=PG II) positive cells in Barrett's epithelium. Endoscopic biopsy specimens were taken from the columnar epithelium from 23 patients (n=93), and in addition from the cardia from eight healthy control subjects (n=38). The tissue was stained by the immunoperoxidase technique with specific anti-pepsinogen antisera, and double immunostained for PGA and PGC. In the Barrett's epithelium PGA was found in 28 out of 93 biopsy specimens (30.1%) and PGC in 55 out of 93 (59.1%). Chief cells always stained both for PGA and PGC, while clear mucous cells were often PGA– and PGC+. PGA+ and PGC+ cells were found each in 100% of the biopsy specimens with fundic type epithelium, in 21.7% and 70.7% of biopsy specimens with junctional type, in 0% and 26.1% of biopsy specimens with specialized epithelium and in 12.5% and 43.5% of biopsy specimens with mixed junctional/specialized features respectively. Dysplastic epithelium stained always negatively with both anti-pepsinogen antisera. In most control cardia biopsy specimens PGA as well as PGC were demonstrable; occasionally clear mucous glands were PGA– and PGC+.It is concluded that pepsinogen-containing cells can be accurately identified in the Barrett's epithelium; their presence seems related to the histological cell type. Identification of pepsinogen positive cells may contribute to a more accurate morphological classification of the Barrett's epithelium.Presented in part at the Annual Meeting of the American Gastroenterological Association, San Francisco, May 1986     

Antithrombotic properties of trillium coated connectors

Trillium coating (Medtronic Inc., Minneapolis, MN) offers, in addition to the presence of heparin, endothelium-like properties of its negatively charged surface. Its thromboresistant properties on coated connectors are tested here and compared with uncoated standard connectors, as well as with the Carmeda BioActive surface (CBAS) heparin surface coating. A partial cardiopulmonary bypass bovine model (body weight 68 +/- 5 kg) was selected, and the surfaces were exposed to the blood stream (pump flow 3.5 L/min) for up to 350 minutes without systemic heparinization. Thereafter, another set of samples was exposed to stagnant blood for 20 minutes. Besides hemodynamic, hematologic, and biochemical analyses, the macroscopic appearance of 45 blood exposed surface samples were graded semiquantitatively on a scale of 0 to 10: no macroscopic deposits = grade 0, one spot (1 mm diameter) = grade 1, two spots = grade 2, five or more spots = grade 5, 10% of the surface covered with clots = grade 6, 100% covered = grade 10. When exposed to blood flow, Trillium and CBAS coatings showed a statistically significant (p = 0.03) better thromboresistance (score: 0 +/- 0 for both) than uncoated connectors (score: 0.8 +/- 1.5) in this nonheparinized model. The same holds true when the connectors were exposed to stagnant blood (score: 0 +/- 0 for both coatings vs 4.3 +/- 2.8 for controls; p = 0.03). Therefore, Trillium coating exhibits significant antithrombotic properties that outperform standards for connectors used in clinical perfusion.     

Assessment of donor liver steatosis: pathologist or automated software?

Steatosis in donor liver biopsy specimens has been shown to correlate with graft dysfunction after orthotopic liver transplantation. This 2-part (laboratory pilot, clinical retrospective) study compared the traditional interpretation of steatosis by a pathologist with an automated measurement determined by an image analysis system. In our pilot study, Sprague-Dawley rats were studied prospectively by feeding them a choline-deficient diet for up to 7 days. In our clinical group, data from 49 consecutive recipients of cadaveric liver transplantation were reviewed retrospectively. In both studies, the percentages of microvesicular fat, macrovesicular fat, and total fat content within liver biopsy specimens were determined by an automated image analysis software program and a pathologist using the same set of slides. The association between fat content of the donor liver and patient survival and graft survival, along with levels of aspartate aminotransferase, alanine aminotransferase, prothrombin time, and total bilirubin after transplantation, were also examined in the clinical study. A direct correlation was observed between levels of macrovesicular fat determined by a pathologist and the automated software using livers from rats fed a choline-deficient diet and livers from deceased donors. A significant association was observed between macrovesicular fat content in the donor liver biopsy and graft survival by both techniques. We conclude that an image analysis system can be used to automate the determination of fat content in liver biopsy specimens, and that its findings correlate with both the visual interpretation by a pathologist and graft survival. Further study is needed to determine the role of an automated technique in the evaluation of donor livers for transplantation.