Pituitary metastases: presentation and outcomes from a pituitary center over the last decade.

PURPOSE: Highlight and characterize manifestations, diagnostic/management approaches and outcomes in a contemporary cohort of patients with pituitary metastases (PM) from a large European pituitary center-over 10 years. METHODS: Retrospective review of PM cases between 1/2009 and 12/2018. Clinical, laboratory, imaging data at PM detection and during follow-up were analysed. RESULTS: 18 cases were identified (14 females; median age at diagnosis 61.5 years). Most common primary malignancies were lung (39%) and breast (32%). Most frequent presenting manifestation was visual dysfunction (50%). Gonadotrophin, ACTH, TSH deficiency were diagnosed in 85%, 67%, 46% of cases, respectively; diabetes insipidus (DI) was present in 17%. 33% of cases were detected during investigation for symptoms unrelated to PM. PM management included radiotherapy (44%), transsphenoidal surgery (17%), transsphenoidal surgery and radiotherapy (6%) or monitoring only (33%). One-year survival was 49% with median survival from PM detection 11 months (range 2-47). CONCLUSIONS: In our contemporary series, clinical presentation of PM has evolved; we found increased prevalence of anterior hypopituitarism, decreased rates of DI and longer survival compared with older literature. Increased availability of diagnostic imaging, improvements in screening and recognition of pituitary disease and longer survival of patients with metastatic cancer may be contributing factors.

Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature.

AIMS: Following stereotactic radiosurgery (SRS), brain metastases initially increase in size in up to a third of cases, suggesting treatment failure. Current imaging using structural magnetic resonance imaging (MRI) cannot differentiate between tumour recurrence and SRS-induced changes, creating difficulties with patient management. Combining multiparametric MRI techniques, which assess tissue physiological and metabolic information, has shown promise in answering this clinical question. MATERIALS AND METHODS: Multiparametric MRI techniques, including spectroscopy, diffusion and perfusion imaging, were used for the differentiation of radiation-related changes and tumour recurrence after SRS for intracranial metastases in six cases. All patients presented with enlargement of the treated lesion, an increase in perilesional brain oedema and aggravation or appearance of neurological signs and symptoms from 7 to 29 weeks after primary treatment. RESULTS: Multiparametric imaging helped to differentiate features of tumour progression (n = 4) from radiation-related changes (n = 2). A low apparent diffusion coefficient (ADC) <1000 × 10-6 mm2/s, high relative cerebral blood volume (rCBV) ratio > 2.1, high choline:creatine (Cho:Cr) ratio > 1.8 suggested tumour recurrence. A high ADC > 1000 × 10-6 mm2/s, low rCBV ratio < 2.1, Cho:Cr ratio < 1.8 suggested SRS-induced radiation changes. Multiparametric MRI diagnosis was confirmed by histology or radiological and clinical follow-up. CONCLUSION: Multiparametric MRI was helpful in the early identification of radiation-related changes and tumour recurrence and may be useful for monitoring treatment changes in intracranial neoplasms after SRS treatment.

Feasibility of Dose-escalated Hypofractionated Chemoradiation in Human Papilloma Virus-negative or Smoking-associated Oropharyngeal Cancer.

AIMS: Oropharyngeal squamous cell carcinoma (OPSCC) can be divided into favourable and poor prognostic groups by association with human papilloma virus (HPV) and smoking. This study prospectively investigated a dose-intensified schedule in poor/intermediate prognosis OPSCC. MATERIALS AND METHODS: Patients with p16/HPV-negative or p16-positive N2b OPSCC with a greater than 10 pack-year smoking history were eligible. Patients were planned to receive 64 Gy in 25 fractions with cisplatin. The primary end point was absence of grade 3 mucositis at 3 months. RESULTS: Fifteen patients were recruited over 14 months. All patients completed a minimum of 2 years of follow-up. All patients completed full-dose radiotherapy within a median treatment time of 32 days (31-35). Grade 3 mucositis was absent in all patients at 3 months. There was one grade 4 toxicity event due to cisplatin (hypokalaemia). Complete response rates at 3 months were 100% and 93% for local disease and lymph nodes, respectively. One patient developed metastatic disease and subsequently died. Overall survival at 2 years was 93% (95% confidence interval 61-99%). CONCLUSIONS: The schedule of 64 Gy in 25 fractions with concomitant chemotherapy is tolerable in patients with poor and intermediate prognosis OPSCC.

A prospective comparison of common toxicity criteria adverse events Version 3 and 4 in assessing oral mucositis for oral and oropharyngeal carcinoma.

BACKGROUND AND PURPOSE: Oral mucositis is an expected complication of radiotherapy in the management of carcinoma of the head and neck. The Common Terminology Criteria for Adverse Events (CTCAE) Version 3 (V3) and related systems based on mucosal appearance have been used in clinical trials historically. More recently, Version 4 (V4) which is based on patient symptoms has been employed. This study compares the use of V3 and V4 in the grading of mucositis in patients undergoing radiotherapy with or without concurrent systemic therapy for carcinoma of the oral cavity and oropharynx. METHODS: Oral mucositis was graded prospectively in patients receiving radiotherapy with or without concurrent systemic therapy using both V3 and V4. Grading was recorded during and after completion of therapy. RESULTS: Between November 2014 and November 2015, 555 measurements were taken from 73 patients. Mucositis scores were equal in both versions in 327 (59%) measurements. Significant differences between V3 and V4 were seen in patients receiving cetuximab-based concurrent therapy (p < 0.001) and beyond 8 weeks from the start of radiotherapy (p = 0.004). CONCLUSION: Differences in grading of mucositis scored by V3 and V4 are frequent. Relationships between biologically effective dose and rates of grade 3 mucositis have historically been based on mucosal appearances. It is not known whether the same relationships apply when mucositis is graded based on symptomatic grading systems. Both V3 and V4 should be used in clinical trials to improve understanding of mucositis and its relationship to quality of life and late mucosal toxicity.

Can radiobiological parameters derived from squamous cell carcinoma of the head and neck be used to predict local control in anal cancer treated with chemoradiation?

OBJECTIVES: Parameters have been derived in head and neck cancer to account for the additional biological effective dose provided by synchronous chemotherapy. The purpose of this study was to establish whether such parameters could be used to predict local control differences in anal cancer. METHODS: In anal cancer two randomised trials of radiotherapy vs chemoradiotherapy and two trials randomising between different synchronous chemotherapy regimens were identified. To predict differences in local control between the arms of the first two studies, a global value of 9.3 Gy for the chemotherapy biologically effective dose was employed. For the last two trials, values specific to differing chemotherapy schedules were derived. These values were added to the calculated biological effective dose for the radiotherapy component in order to predict local control outcomes in anal cancer trials. RESULTS: The predicted difference in local control using the global value of 9.3 Gy for the addition of synchronous chemotherapy in the trials of radiotherapy vs radiotherapy and synchronous chemotherapy was 24.6% compared with the observed difference of 21.4%. Using schedule-specific values for the contribution of chemotherapy, the predicted differences in local control in the two trials of differing synchronous chemotherapy schedules were 7.2% and 12% compared with the observed 18% and 0%. CONCLUSION: The methods initially proposed require modification to result in adequate prediction. If the decreased cisplatin dose intensity employed in anal cancer is modelled, more satisfactory predictions for such trials can be achieved. ADVANCES IN KNOWLEDGE: This revised modelling may be hypothesis generating.

Protein cross-linking in food.

The aims of this paper are (1) to probe the relationship between molecular structure and protein cross-linking ability for a range of small molecules; (2) to establish whether this relationship holds within a food matrix; and (3) to test the impact of Maillard cross-linking on food functionality, particularly texture, in wheat- and soy-based food systems. A variety of molecules were obtained, either commercially or via organic synthesis. Cross-linking ability was tested using our standard model system, employing ribonuclease A and analyzing the results by SDS-PAGE. Molecules of varying reactivity were tested in wheat- and soy-based products, and the changes in functionality were correlated with changes in protein cross-linking. No simple relationship was found between molecular structure and ability to cross-link ribonuclease. Only the most reactive reagents were able to cross-link within the food matrix. Nevertheless, a low degree of cross-linking was shown to have significant consequences on the properties of wheat- and soy-based foods, suggesting that the Maillard reaction may represent a means to control food texture.

Feeding, drinking, and temperature responses of chickens to intracerebroventricular histamine.

The present study examines the effects of intracerebroventricular injections of histamine (HA) and two HA antagonists, the H(1) receptor antagonist chloropheneramine maleate (CM) and the H(2) receptor antagonist cimetidine (CIM), on food and water consumption and body temperature in chickens. Single-Comb White Leghorns (SCWL) and broiler cockerels were utilized for these experiments. The first pair of experiments consisted of intracerebroventricular injections of HA and its effects on food and water consumption. HA was infused at dosages of 0, 25, 50, and 100 microg/10 microl of artificial cerebrospinal fluid (aCSF). HA significantly decreased food and water intake in a dose-dependent manner. The second pair of experiments examined the effects of HA on water intake while birds had no access to feed. Water intake was not significantly affected by intracerebroventricular injections of HA. The next pair of experiments examined the effects of HA on body temperature. In SCWL, body temperature was not affected by HA until 165 min postinjection when HA decreased temperature in a quadratic dose-response with maximum hypothermia being achieved at a dose of 25 microg. In contrast, HA increased body temperature in broilers beginning at 75 min postinjection. In the final series of experiments, the anorexia induced by HA was attenuated in SCWL and broilers with pretreatment of either CM or CIM. These results suggest that HA has an anorexigenic effect in SCWL and broiler cockerels, and this effect is mediated by both H(1) and H(2) receptors. Water intake is not directly affected by the intracerebroventricular injection of HA. Whereas HA increased body temperature in broilers, the response in SCWL is equivocal.

Leptin-induced decrease in food intake in chickens.

The effect of intracerebroventricular (i.c.v.) injection of leptin was investigated using broiler and Single Comb White Leghorn (SCWL)-type chickens. These represent relatively fast- and slow-growing birds, respectively. The i.c.v. injection of leptin decreased food intake in both broilers and Leghorns in a dose-dependent manner. The most efficacious dose appeared to be 10 microg in both types of chickens. Water intake was generally not affected by leptin, indicating that this effect was not due to general malaise. It appears that leptin can act within the central nervous sytstem of birds to decrease food intake.

Mothers' perceptions of the quality of their infants' back transfer.

OBJECTIVE: To describe mothers' experiences with back transfer of their infants from a neonatal intensive-care unit (NICU) to a community hospital (CH). DESIGN: Descriptive correlational study. PARTICIPANTS: One hundred forty-three mothers whose infants were back transferred from regional NICUs to 1 of 20 Level I or Level II CHs. MAIN OUTCOME MEASURES: Quality of back transfer was measured by the NICU/CH Transfer Quality Scale developed by the investigators. Overall level of stress related to back transfer was also measured. RESULTS: More positive experiences with the NICU component of back transfer were related to fewer perceived differences in physician practice between NICUs and CH settings and fewer infant problems after transfer (R2 = 8.1%, p = .007). More positive experiences with the CH component of back transfer were related to fewer perceived differences in nursing and medical practices between settings; fewer infant problems after transfer; and more sources of pretransfer preparation (R2 = 33.4%, p < .0001). Lower levels of overall stress associated with transfer were related to fewer infant problems after transfer and greater lengths of stay in the NICU (R2 = 8.8%, p = .01). CONCLUSION: Results support the need for consistency of care and coordinated approaches to back transfer.

Mothers' perceptions of the quality of their infants' back transfer: pilot study results.

This pilot study was designed to test an instrument measuring mothers' perceptions of the quality of the back-transfer experience from a neonatal intensive care unit in a tertiary medical center to a community hospital. Forty-one mothers completed a questionnaire that contained the 24-item NICU/Community Hospital Transfer Quality Scale, a 1-item measure of stress associated with the overall experience, and other variables that might affect the transfer experience. Transfer quality was strongly correlated with the overall stress of the transfer (r = .61, p < .001). That is, the higher the perceived transfer quality, the less stress the mother associated with the transfer. This instrument had a test-retest reliability of r = .82 (p < .001, n = 23) and a Chronbach's alpha of .84. Comments made by mothers indicated that communication with health care providers is a very important but sometimes inadequately addressed component of the transfer experience. Nurses can play a key role in facilitating communication between the family and health care providers in both the tertiary and community settings. Four goals for enhancing communication between parents and health care providers are described.

Breast-feeding patterns of Montserratian women.

This article describes the breast-feeding patterns found on Montserrat by a survey that interviewed 69 mothers who delivered infants over a 13-month period, from March 1989 through March 1990. The results indicated that 94% of the women breast-fed these children for at least two weeks after delivery; that 70% were still breast-feeding at the time of the interview in March or April 1990; and that principal factors influencing early termination of breast-feeding were the age at which supplementary feeding was commenced and lack of maternal information about why babies appear to reject the breast.

Enhanced transforming activity of pSV2 plasmids in human cells depends upon the type of damage introduced into the plasmid.

When pSV2-gpt or pSV2-neo plasmids are introduced into human cells by calcium phosphate coprecipitation, the yield of stable transformants (Gpt+ or Neo+) is increased by irradiating the respective plasmid DNA in vitro with UV (254 nm). To identify specific lesions that can increase the transforming activity of plasmids in human cells we examined pSV2 plasmids containing different types of damage. Of the lesions tested, cyclobutane pyrimidine dimers produced the greatest increase, and can nearly fully account for the effect of 254 nm UV on transformation. The enhancement of transformation produced by UV was not altered by the additional treatment of the plasmid DNA with T4 endonuclease V, an enzyme that nicks DNA specifically at pyrimidine dimers. Treatment of plasmid DNA with osmium tetroxide to produce thymine glycols, or with acid and heat to produce apurinic sites did not affect transformation frequency. The enhancement occurred in all the human cell lines tested, whether they contained or not sequences homologous to those in the plasmids, and was independent of the repair capacity of the recipient cells.

Ventricular dilation after neonatal periventricular-intraventricular hemorrhage. Natural history and therapeutic implications.

Infants with periventricular-intraventricular hemorrhage (PV-IVH) were followed up with weekly ultrasound sector scans to define the natural history of late ventricular dilation (ie, dilation in excess of that seen at the time of diagnosis of PV-IVH). Infants fell into two groups: (1) posthemorrhagic hydrocephalus (PHH), dilation that produced an increase in occipitofrontal circumference greater than 2 cm per week and/or clinical symptoms of increased intracranial pressure; and (2) ventriculomegaly (VM), dilation that stabilized or reversed without producing these effects. The former was directly related to the severity of hemorrhage. The diameter of the lateral ventricle was significantly greater in PHH. In 26 of 48 infants at risk, late dilation developed: 14 had VM and 12 had PHH. Thus, late ventricular dilation stabilized or resolved spontaneously in 54%. Only three infants eventually required a ventriculoperitoneal shunt. Clinical changes in addition to ventricular size should be used in assessing the need for treatment of ventricular dilation after PV-IVH.

Surgical Operations in short-stay Hospitals United States-1968.

Out of the universe of 6,965 hospitals, 413 hospitals participated during all or part of the 1968 data year and approximately 210,000 abstracts of sample discharges were received and processed; A detailed description of the sample design, data collection procedures, and the estimation process may be found in appendix I. An estimated 28.1 million inpatients were discharged from the Nation's short-stay hospitals during 1968. Thirty-nine percent of these patients had one or more surgical operations or procedures as defined herein. The highest proportions of patients treated surgically in 1968 were in the Northeast and West Regions. Fifty-one percent of the nonobstetrical inpatients discharged from short-stay hospitals having 300-499 beds had one or more surgical operations. More than one-half of the inpatients under the age of 15 years were treated surgically, with. an average of 1.2 operations per surgical patient in that age group. Only 37 percent of the adult patients (15 and over) had an operation.However, adult patients accounted for 84 percent of the estimated volume of operations and procedures performed for inpatients discharged in 1968.