A National Referral Service for Paediatric Brachytherapy: An Evolving Practice and Outcomes Over 13 Years.

AIMS: Most children requiring radiotherapy receive external beam treatment and few have tumours suitable for brachytherapy. No paediatric radiotherapy centre will treat enough patients from its own normal catchment population for expertise in brachytherapy to be developed and sustained. Following discussion and agreement in the national paediatric radiotherapy group, a service for paediatric brachytherapy in the UK has been developed. We report the process that has evolved over more than 10 years, with survival and functional outcome results. MATERIALS AND METHODS: Since 2009, potential patients have been referred to the central paediatric oncology multidisciplinary team meeting, where imaging, pathology and treatment options are discussed. Since 2013, the National Soft Tissue Sarcoma Advisory Panel has also reviewed most patients, with the principal aim of advising on the most suitable primary tumour management for complex patients. Clinical assessment and examination under anaesthetic with biopsies may be undertaken to confirm the appropriateness of brachytherapy, either alone or following conservative surgery. Fractionated high dose rate brachytherapy was delivered to a computed tomography planned volume after implantation of catheters under ultrasound imaging guidance. Since 2019, follow-up has been in a dedicated multidisciplinary clinic. RESULTS: From 2009 to 2021 inclusive, 35 patients (16 female, 19 male, aged 8 months to 17 years 6 months) have been treated. Histology was soft-tissue sarcoma in 33 patients and carcinoma in two. The treated site was pelvic in 31 patients and head and neck in four. With a median follow-up of 5 years, the local control and overall survival rates are 100%. Complications have been few, and functional outcome is good. CONCLUSION: Brachytherapy is effective for selected paediatric patients, resulting in excellent tumour control and good functional results. It is feasible to deliver paediatric brachytherapy at a single centre within a national referral service.

Bond strength of zirconia ceramics applied with a pH-cycling modeland different repair methods.

PURPOSE: To evaluate the shear bond strength of yttria-stabilized zirconia (YSZ) ceramics based on the type of surface treatment, repair kit, and aging method used. METHODS: YSZ ceramic blocks (N = 120) measuring 6 mm x 8 mm x 8 mm were randomly and equally divided into three groups for different surface treatments: (a) surface treatments recommended by the manufacturer (control), (b) air abrasion, and (c) Er:YAG laser. After surface treatment, either the Cimara intraoral ceramic repair kit or the Bisco intraoral repair kit were used on the samples. A resin composite was incrementally applied to the treated surfaces and light cured. Repaired samples were aged using either thermocycling or pH cycling. A shear bond strength test was conducted on all samples, and failure patterns were examined under a stereomicroscope. Data were analyzed using three-way ANOVA, Kruskal-Wallis, Mann-Whitney U, and Bonferroni corrected paired comparison tests. RESULTS: Interactions were found between aging methods, surface treatments, and repair kits, as well as between repair kits and surface treatments (P< 0.05). Although there was no statistically significant difference in bond strength values between the air abrasion and control groups in the thermal cycle (P= 0.053) and pH cycle (P= 0.104) for the Cimara repair kit, the bond strength values of the Er:YAG laser groups were statistically significant (P< 0.001). For the Bisco intraoral repair kit, there was a statistically significant difference in bond strength values between surface treatments in both aging methods (Plt; 0.001). All groups showed 100% adhesive failure. CLINICAL SIGNIFICANCE: The results of this study indicate the recommended use of the pH cycle aging method and primers containing carboxylic acid monomer and MDP for the repair of YSZ ceramics.

Diagnosis and treatment of mesenteric tumours.

PURPOSE: To reveal clinical and diagnostic findings in patients with mesenteric tumours and to give an insight into the follow-up of these patients. BACKGROUND: Primary tumours of the mesentery are very infrequent. These tumours are cystic or solid and show benign or malignant clinical behaviour. In this article, we report clinical and radiological findings from eight cases of mesenteric tumours. PATIENTS AND METHODS: This study included eight patients with mesenteric tumours who underwent computed tomography in the Department of General Surgery, Baskent University, between December 2003 and April 2007. RESULTS: Three mesenteric tumours were solid and five had cystic patterns. Seven were excised totally on laparotomy and one was excised on laparoscopy. None of the patients showed malignant progression. CT showed mesenteric cysts in only two cases, but failed to show solid tumours: the pre-operative diagnosis was made accurately in just (2/8) 25% of the patients. CONCLUSIONS: It can be concluded that pre-operative CT is generally helpful, but inconclusive in an accurate diagnosis of mesenteric tumours. Surgery is required to make a definitive diagnosis of mesenteric tumours and to avoid complications.

Expression of vascular endothelial growth factor (VEGF), hypoxia inducible factor 1 alpha (HIF-1alpha), and transforming growth factors beta1 (TGFbeta1) and beta3 (TGFbeta3) in gestational trophoblastic disease.

The aim of this study was to investigate the relationship between the expression of vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta1 and TGF-beta3), and hypoxia inducible factor 1 alpha (HIF-1alpha) in gestational trophoblastic diseases to highlight the possible histogenesis. Twenty-one partial hydatidiform moles (PHM), 19 complete hydatidiform moles (CHM), 13 choriocarcinomas, and 20 nonhydropic spontaneous abortions (control group) were evaluated with immunohistochemistry using VEGF, HIF-1alpha, TGFbeta1, and TGFbeta3. The extent of immunohistochemical positivity (0%=0, 1-24%=1, 25-49%=2, 50-74%=3, and greater than 75%=4) and intensity (no staining=0, weak staining=1, medium staining=2, and strong staining=3) were recorded. The expression of VEGF in spontaneous abortions and choriocarcinoma was higher than the expression in PHM and CHM. HIF-1alpha was strongly expressed in the choriocarcinomas compared to the other subgroups. Nonhydropic spontaneous abortions (control group) showed the highest TGFbeta1 expression levels among the case subgroups, followed by PHM, CHM, and choriocarcinoma (p<0.001). The expression of TGFbeta3 was seen in all groups, but the highest level of expression was observed in both CHM and choriocarcinoma. We conclude that higher levels of VEGF, HIF-1alpha, and TGFbeta3 expression in choriocarcinoma might be involved in the development of trophoblastic diseases.

A case report of hemangioendothelioma of the hard palate.

Hemangioendothelioma is a rare vascular tumour with potential for malignancy that is intermediate between that of a benign hemangioma and a malignant angiosarcoma. This tumour occurs infrequently in the head and neck regions. In this report, we describe and discuss a case of hemangioendothelioma that originated in the hard palate of a 49-year-old woman.

Three siblings with juvenile hyaline fibromatosis.

Juvenile hyaline fibromatosis (JHF) is an extremely rare hereditary genetic disease of autosomal recessive transmission that is characterized by large cutaneous tumors commonly involving the scalp, papulonodular skin lesions, flexural joint contractures, gingival hyperplasia, and osteolytic bone lesions. JHF is usually diagnosed in young infants and in children younger than 5 years, and the lesions characteristic of this disorder consist of fibrous tissue and homogenous amorphous eosinophilic hyaline material. We report the case of a 9-year-old girl with severe gingival hyperplasia, nasal enlargement, mild osteoporosis, and multiple papulonodular skin lesions. Her two brothers (7 and 13 years of age, respectively) were also diagnosed as having JHF. In the patient described in this report, the maintenance of oral hygiene after gingivectomy enabled the continued resolution of gingival hyperplasia, although skin lesions recurred and nasal overgrowth persisted.

Microvessel density, VEGF expression, and tumor-associated macrophages in breast tumors: correlations with prognostic parameters.

Angiogenesis plays an important role in tumor growth, metastasis, and prognosis. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen and acts on the angiogenic stimulation of human neoplasias. In infiltrative ductal carcinoma (IDC), VEGF expression is correlated with high vascularity. Tumor-associated macrophages (TAMs) contribute to tumor proliferation, progression and angiogenesis and have a complex role in tumor biology. In this study, the correlations between microvessel density (MVD), VEGF expression, and TAMs and their relations to clinicopathological parameters such as tumor size, metastatic lymph node, mitotic activity index (MAI) and tumor grade were investigated in 48 cases of IDC and 30 infiltrative lobular carcinoma (ILC) cases. MVD showed a significant positive correlation with TAMs, VEGF, metastatic lymph nodes, tumor size and grade in IDC (P < 0.001). In ILC, MVD and tumor size were positively correlated (P = 0.003), while MVD was not correlated with VEGF, TAMs, MAI, metastatic lymph nodes, and grade. These findings are suggestive of angiogenesis stimulation in IDCs by VEGF, driving the macrophages into the tumor area. MVD and TAMs were found to be important prognostic factors in IDCs. On the other hand, however, VEGF did not contribute to angiogenesis in ILCs, and MVD and TAMs did not have any prognostic significance. These results suggest the involvement of factors not related to VEGF in the angiogenesis of lobular carcinoma.

Parotid duct cyst: a case report.

Salivary gland cysts can be benign or malignant. Salivary duct cysts are benign tumours that occur mainly in the parotid gland and represent 10% of all salivary gland cysts. We report the case of a 48-year-old man who presented with a painless preauricular mass on the right side. Superficial parotidectomy was performed based on magnetic resonance imaging (MRI). Histopathologic examination of the specimen revealed a parotid duct cyst. Here we report clinical features, diagnosis, and treatment of the case as well as a review of the literature.

An unusual case of port site metastasis after laparoscopic cholecystectomy in a renal transplant patient: a case report.

Port site metastasis after laparoscopy is a rarely seen intraabdominal malignancy independent of tumor stage. We present an unusual case of port site adenocarcinoma metastasis from unknown origin following laparoscopic cholecystectomy. A 52-year-old woman with a previous renal transplant underwent a laparoscopic cholecystectomy for symptomatic cholelithiasis. Six months later, she was admitted to the hospital with a complaint of a mass at the four trocar sites. A biopsy from the port sites led to the diagnosis of adenocarcinoma metastasis. Port site metastasis after laparoscopic cholecystectomy is seen especially after gallbladder cancer, and less frequently after intraabdominal malignancy independent of tumor stage. Our patient illustrated that port site metastasis probably spread from an undetected cancer site of an early stage intraabdominal tumor. Immunosuppression may have increased the likelihood of tumor seeding at the port sites.

Nurses' views on their involvement in euthanasia: a qualitative study in Flanders (Belgium).

BACKGROUND: Although nurses worldwide are confronted with euthanasia requests from patients, the views of palliative care nurses on their involvement in euthanasia remain unclear. OBJECTIVES: In depth exploration of the views of palliative care nurses on their involvement in the entire care process surrounding euthanasia. DESIGN: A qualitative Grounded Theory strategy was used. SETTING AND PARTICIPANTS: In anticipation of new Belgian legislation on euthanasia, we conducted semistructured interviews with 12 nurses working in a palliative care setting in the province of Vlaams-Brabant (Belgium). RESULTS: Palliative care nurses believed unanimously that they have an important role in the process of caring for a patient who requests euthanasia, a role that is not limited to assisting the physician when he is administering life terminating drugs. Nurses' involvement starts when the patient requests euthanasia and ends with supporting the patient's relatives and healthcare colleagues after the potential life terminating act. Nurses stressed the importance of having an open mind and of using palliative techniques, also offering a contextual understanding of the patient's request in the decision making process. Concerning the actual act of performing euthanasia, palliative care nurses saw their role primarily as assisting the patient, the patient's family, and the physician by being present, even if they could not reconcile themselves with actually performing euthanasia. CONCLUSIONS: Based on their professional nursing expertise and unique relationship with the patient, nurses participating as full members of the interdisciplinary expert team are in a key position to provide valuable care to patients requesting euthanasia.

Perioperative anxiety and postoperative behavioural disturbances in children: comparison between induction techniques.

BACKGROUND AND OBJECTIVE: This study was designed to determine if subhypnotic propofol reduces postoperative behavioural disturbances in children undergoing sevoflurane induction compared with intravenous propofol induction for elective adenoidectomy and tonsillectomy. METHODS: Following Ethics Committee approval and parental informed consent, ASA I-II, 120 children (2-10 yr) were recruited. Parents were not allowed to accompany their child. Unpremedicated children were randomly allocated to groups receiving inhalation induction with sevoflurane, 2-2.5 mg kg-1 intravenous propofol induction or inhalation induction with sevoflurane followed by subhypnotic dose of propofol (1 mg kg-1). Anaesthesia was maintained with 2-4% sevoflurane, O2 and N2O. Anxiety on arrival to operating theatre, at anaesthesia induction and 30 min after emergence was assessed. Parents completed a state-trait anxiety inventory test preoperatively and a post hospitalization behaviour questionnaire a week later to assess children's postoperative behavioural disturbances. Kruskal-Wallis test, Wilcoxon signed rank sum test, Bonferroni's test, Paired t-test, t-test, Pearson and Spearman's rank correlation test, chi2-test were used for statistical analysis. RESULTS: The anxiety level at induction was high in all groups (P < 0.05). There was no difference between groups in respect to anxiety at other measurement times. A relation between preoperative anxiety level and postoperative behavioural disturbances was determined (P < 0.05). Some behavioural disturbances as nightmare/night fear and desire of sleeping with parents were rarely seen in intravenous propofol induction group (P < 0.05). CONCLUSION: Addition of subhypnotic dose of propofol to sevoflurane induction did not reduce the incidence of postoperative behavioural disturbances.

Case report: solid-pseudopapillary tumour of the pancreas associated with dorsal agenesis.

Solid-pseudopapillary tumour of the pancreas is a rare benign or low-grade malignant epithelial tumour; its association with pancreatic dorsal agenesis has been reported only once before. We present the radiological and histological findings of a case of pancreatic solid-pseudopapillary tumour associated with total pancreatic dorsal agenesis. A 49-year-old woman presented with abdominal pain radiating to the back for several months. Radiological findings showed absence of the dorsal pancreas and an 8 cm x 6 cm diameter tumour arising from the head of the pancreas. She underwent successful complete resection of the tumour. Histopathology revealed a diagnosis of solid-pseudopapillary tumour.

Radiological findings of primary retroperitoneal synovial sarcoma.

Synovial sarcomas are most commonly localized in the extremities, especially the lower thigh and knee areas. Retroperitoneal synovial sarcoma is very rare. We describe the radiological and pathological findings of an adult retroperitoneal synovial sarcoma.

Gallbladder adenosquamous cell carcinoma: report of two cases.

Adenocarcinoma is the usual histological presentation of the very rare gallbladder carcinoma. Adenosquamous cell carcinoma accounts for less than 3.5% of gallbladder carcinomas, and is characterised by invasive growth, a reduced tendency for lymph node metastasis, an increased tendency for hepatic infiltration or liver metastasis, and a poorer prognosis than adenocarcinoma. We present two cases. The first patient presented to our institution with increased bilirubin levels and dilated intra- and extrahepatic bile ducts. Adenosquamous carcinoma of the gallbladder was diagnosed on the post-operative pathological specimen. After surgery, bilirubin levels decreased, but hepatic metastases occurred that did not respond to conventional chemotherapy. The second patient was admitted to our hospital with jaundice and abdominal pain. Abdominal computed tomography (CT) imaging showed marked thickening of the gallbladder with direct extension of a mass into the left liver lobe. Cytology specimens obtained with an endoscopic retrograde cholangiopancreatography (ERCP) procedure revealed a malignant epithelial tumour. The patient underwent surgery but the tumour was incompletely resected. A regimen of oral UFT (Tegafur + uracil) chemotherapy was begun. Serum bilirubin levels increased due to occlusion in the surgical area 15 weeks after the start of chemotherapy.

Inhibition of nitrosylation, nitration, lymphocyte proliferation, and gene expression in acute and delayed cardiac allograft rejection by an orally active dithiocarbamate.

Dithiocarbamate derivatives sequester metals such as iron and may have benefits in inflammatory diseases. We examined the actions of a new dithiocarbamate-based oral formulation, NOX-700, on protein modification by nitric oxide (NO), gene expression, and lymphocyte proliferation in a model of acute and delayed cardiac rejection. Chronic treatment with NOX-700 prolonged graft survival. In combination with low-dose cyclosporine (CsA), NOX-700 produced a synergistic action to prolong graft survival. NOX-700 decreased myocardial heme nitrosylation. A single bolus injection with NOX-700 in untreated recipients did not decrease heme nitrosylation but normalized NO metabolites and caused the formation of a mononitrosyl iron complex indicating NO scavenging in vivo. NOX-700 alone given with CsA inhibited protein nitration. NOX-700 or CsA each alone decreased intragraft inflammatory cell infiltration. NOX-700 also potentiated the CsA-induced inhibition of splenocyte proliferation ex vivo stimulated by concanavalin A. In splenocytes derived from treated rats but stimulated ex vivo in a mixed lymphocyte response (MLR), interferon-gamma and cyclin D3 gene expression was inhibited by NOX-700 suggesting down-regulation of lymphocyte activation and proliferation by in vivo treatment. These studies suggest that NOX-700 is protective in cardiac rejection, in part, by scavenging of NO and by limiting lymphocyte activation infiltration.

A possible regulatory role for the metal-binding domain of CadA, the Listeria monocytogenes Cd2+-ATPase.

Using the baculovirus/Sf9 expression system, we produced CadA and DeltaMBD, a metal-binding domain, truncated CadA. Both proteins had the expected properties of P-type ATPases: ATP-induced Cd2+ accumulation, Cd2+-sensitive ATP and Pi phosphorylation and ATPase activity. DeltaMBD displayed lower initial transport velocity as well as lower maximal ATPase activity than CadA. MBD truncation flattened the Cd2+ dependence of the ATPase activity and increased apparent Cd2+ affinity, suggesting a positive cooperativity between MBD and membranous transport sites. We propose that occupancy of MBD by Cd2+ modulates CadA activity.

Antidepressant drugs inhibit a glial 5-hydroxytryptamine transporter in rat brain.

We assessed the role of glial cells in the uptake of serotonin (5-hydroxytryptamine, 5-HT). Primary cultures of rat and mouse cortical astrocytes took up and deaminated 5-HT. The antidepressants citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine and sertraline inhibited this process. The presence of the mRNAs for the 5-HT transporter and monoamine oxidase-A (MOA-A) was established in cultured astrocytes and in adult rat brain areas with (midbrain and brainstem) and without (frontal cortex) serotonergic cell bodies after reverse transcription-polymerase chain reaction and hybridization with probes complementary to the cloned neuronal 5-HT transporter and MAO-A. To examine in vivo the role of astrocytes in the elimination of 5-HT from the extracellular brain space, 5-HT was perfused through dialysis probes implanted in the frontal cortex of conscious rats and its concentration was measured at the probe outlet. Tissue 5-HT recovery was dose-dependently inhibited by the concurrent perfusion of citalopram, fluoxetine and paroxetine, showing that it essentially measured uptake through the high-affinity 5-HT transporter. Rats lesioned with 5,7-dihydroxytryptamine (5,7-DHT; 88% reduction of tissue 5-HT) displayed tissue 5-HT recovery slightly higher than sham-operated rats (55 +/- 2 vs. 46 +/- 3%, P < 0.001), a finding perhaps attributable to the astrogliosis induced by 5,7-DHT denervation. Rats lesioned with 6-hydroxydopamine showed tissue 5-HT uptake similar to controls, suggesting negligible reuptake of 5-HT by catecholaminergic terminals. These results are consistent with the presence of a glial component of 5-HT uptake in the rodent brain, sensitive to antidepressants, which takes place through a 5-HT transporter very similar or identical to that present in neurons.