Aberrant hormone production from ovarian neoplasms: Strategies for diagnosis and therapy

Syndromes involving peptide or nonsex steroid hormone secretion due to aberrantly located tumors are rare. We report a collected series of 16 patients with ectopic hormone production from ovarian neoplasms, including 3 patients recently encountered at our institution as well as 13 additional cases identified in the recent literature. These tumors included 2 insulin-producing ovarian carcinoids, 1 ACTH-producing pituitary adenoma within a benign ovarian cystic teratoma, 2 cortisol-producing ovarian neoplasms, 8 gastrin-producing ovarian cystadenomata or cystadenocarcinomata, and 3 thyroxine-producing ovarian strumal carcinoids. All patients presented with syndromes of hormone excess. Only 62% of all tumors were localized preoperatively. Following ovarian resection, 87% of patients remained disease-free with a median follow-up period of 1.5 years. In addition to ovariectomy, 8 additional unnecessary ablative procedures were performed in 7 patients. These included distal pancreatectomy, pancreaticoduodenectomy, adrenalectomy, total gastrectomy, selective vagotomy, and subtotal thyroidectomy. Failure to localize the ovarian neoplasm preoperatively was associated with a significantly higher risk of subsequent unnecessary ablative procedures. Because of the potential for the ovary to act as a source of aberrant hormone secretion, we recommend complete preoperative evaluation of the pelvis in female patients presenting with nonlocalizable endocrine tumors.

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Resumen Los síndromes relacionados con la secreción de péptidos o de hormonas esteroideas no sexuales por tumores de ubicación aberrante ocurren infrecuentemente. En este artículo reportamos una serie de 16 pacientes con producción hormonal ectópica por neoplasmas ováricos, la cual incluye 3 pacientes vistos recientemente en nuestra institución y 13 identificados en la literatura médica de los últimos años. El grupo incluye 2 carcinoides ováricos productores de insulina, 1 adenoma pituitario productor de ACTH, 2 neoplasmas ováricos productores de cortisol, 8 cistadenomas o cistadenocarcinomas ováricos productores de gastrina, y 3 carcinoides ováricos estrumales productores de tiroxina. Todas las pacientes se presentaron con síndromes de exceso hormonal. En sólo el 62% de los tumores se pudo establecer la ubicación anatómica en la fase preoperatoria. Después de realizada la resección del ovario, 87% de las pacientes permanecieron libres de enfermedad en el período de seguimiento, que fue de 1.5 años en promedio. Además de la resección ovárica, se practicaron otros 8 procedimientos adicionales innecesarios en 7 pacientes. Estos incluyeron pancreatectomía distal, pancreatoduodenectomía, adrenalectomía, gatrectomía total, vagotomía selectiva, y tiroidectomía subtotal. La falla en la localización preoperatoria del neoplasma ovárico apareció asociada con un riesgo aumentado de ulteriores procedimientos quirúrgicos innecesarios. En vista de la potencialidad del ovario de actuar como fuente de secreción hormonal aberrante, nosotros recomendamos una completa evaluación de la pelvis en las pacientes femeninas en quienes se diagnostiquen tumores endocrinos no localizables.

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Résumé Les syndromes concernant la sécrétion d'hormones peptidique ou stéroïde nonsexuelle due à des tumeurs ectopiques sont rares. Nous rapportons une série de 16 patientes avec une production d'hormone ectopique provenant de néoplasmes ovariens, comprenant 3 patientes récemment soignées dans notre établissement ainsi que 13 cas supplémentaires relevés dans la littérature récente. Ces tumeurs comprennent 2 tumeurs carcinoïdes ovariennes productrices d'insuline, 1 adénome hypophysaire producteur d'ACTH à l'intérieur d'un tératome cystique ovarien bénin, 2 néoplasmes ovariens producteurs de cortisol, 8 cystadénomes ou cystadénocarcinomes ovariens producteurs de gastrine, et 3 carcinoïdes ovariens strumaux producteurs de thyroxine. Toutes les patientes avaient des syndromes d'hyperproduction hormonale. Soixante-deux pour cent seulement des tumeurs avaient été localisées en préopératoire. Après ovariectomie, 87% des patientes étaient apparamment sans récidive avec un suivi médian d'un an et demi. Cependent, outre l'ovariectomie, 8 interventions supplémentaires non nécessaires ont été accomplis chez 7 patientes. Celles-ci comprenaient: pancréatectomie distale, duodénopancréatectomie, surrénalectomie, gastrectomie totale, vagotomie sélective, et thyroïdectomie subtotale. L'impossibilité de localiser le néoplasme ovarien en période préopératoire était associée à un risque notoirement plus grand de faire une résection inutile. Compte tenu de la possibilité pour l'ovaire de se comporter en producteur de sécrétion ectopique d'hormone, nous recommandons un examen complet préopératoire du bassin chez les femmes se présentant avec des tumeurs endocrines non localisables.

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Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.     

Tolerance of Pseudomonas aeruginosa to killing by ciprofloxacin, gentamicin and imipenem in vitro and in vivo

In the rat croton oil pouch model, treatment with ciprofloxacin, gentamicin or imipenem caused a sharp reduction in the numbers of Pseudomonas aeruginosa when applied 24 h after infection but treatment had little or no effect when delayed until 48 h after infection. Surviving bacteria from treated animals were fully susceptible on subculture in vitro. Between 24 h and 48 h after infection there was an increase in the concentration of magnesium and a decrease in the concentration of oxygen but no significant change in the pH of the pouch fluid. In-vitro, the MBC of gentamicin was increased four-fold by the addition of magnesium ions and eight-fold under anaerobic conditions whereas these variables had no significant effect upon the MBC of ciprofloxacin and imipenem. However, cells of P. aeruginosa incubated in batch culture for 4, 24 and 48 h became progressively more tolerant to killing by all three drugs. We conclude that the tolerance of P. aeruginosa in vivo was only partly explained by biochemical changes at the site of infection. The stationary growth phase was associated with progressive tolerance to killing by ciprofloxacin, gentamicin and imipenem both in vivo and in vitro.     

High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects and in vitro assessment in p-glycoprotein expressing cell lines.

Twenty-six patients with relapsed or drug-resistant cancer were treated with a combination of oral etoposide (300 mg day-1 for 3 days) and high-dose oral tamoxifen as a potential modulator of drug resistance (480 or 720 mg day-1 for 6 days beginning 3 days before etoposide). One patient with relapsed high-grade lymphoma and one with adenocarcinoma of unknown primary site has a partial response. Toxicity consisting of nausea, vomiting and subjective dizziness, unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum levels of tamoxifen averaged 3-3.5 microM on day 4 of all courses of treatment at both 480 and 720 mg day-1. N-desmethyltamoxifen levels were lower than tamoxifen during the first course (2 microM) but increased to equal tamoxifen levels during the second course. Didesmethyltamoxifen levels remained below 1 microM. In vitro, both tamoxifen and the standard modulator of multidrug resistance, verapamil, produced minor enhancement of etoposide cytotoxicity in the MCF-7 wt cell line but produced no enhancement with any other cell line. High, intermittent doses of tamoxifen can be given with acceptable toxicity and produce serum levels that have been shown to modulate drug resistance in vitro. In vitro, however, such levels have no significant effect on etoposide cytotoxicity towards a range of wild-type and MDR cell lines.     

Reducing arrhythmias associated with central venous catheter insertion or exchange.

A recent study demonstrated that the incidence of new arrhythmias occurring during central venous catheter insertion or exchange was 41% atrial and 25% ventricular arrhythmias (12% couplets or greater). Over-insertion of the guidewire, causing direct stimulation to the right side of the heart, has been postulated to be the causative factor. A new technique that allows the operator to control the length of guidewire inserted was developed. With this technique on a population of hospitalized patients, similar to those in the previous study, the incidence of atrial arrhythmias decreased to 32% and the incidence of ventricular arrhythmias to 6% (single premature ventricular contractions only). Although this new technique has limitations, there was a dramatic improvement in the incidence of cardiac arrhythmias. These results indicate a need for modifications in the available equipment to avoid the infrequent but life-threatening complication of malignant arrhythmia.     

Relationships between health and culture in Polynesia – A review

This review of journal articles and book chapters discusses the health beliefs characteristic of Polynesia and reveals several themes. These are: commonality in health conceptualisations across the cultures of the region which differ from the conceptualisations of biomedicine; the role of the relational self, traditional living and communalism in understanding health; the place of spirituality and religion in health and illness causation; and pluralism and pragmatism in health-seeking behaviour. Suggestions are made as to how awareness of key ideas might contribute to effective planning of health promotion and intervention activities.     

Normalized protein catabolic rate versus serum albumin as a nutrition status marker in pediatric patients receiving hemodialysis.

BACKGROUND: Protein-energy malnutrition occurs commonly in patients receiving hemodialysis (HD). Although serum albumin (sAlb) is recommended to monitor nutrition status in patients receiving HD, many processes unrelated to nutrition status can affect albumin concentrations. METHODS: We previously showed normalized protein catabolic rate (nPCR) to be superior to sAlb to reflect improvement in nutrition status in pediatric patients receiving maintenance HD after treatment with intradialytic parenteral nutrition for severe protein-energy malnutrition. We now compare nPCR and sAlb as nutrition status markers for pediatric patients on HD irrespective of current nutrition status. RESULTS: Forty-four patients comprising 840 months of HD provision were assessed. nPCR was higher for younger patients. Mean nPCR values were significantly lower for adolescent patients with persistent weight loss of at least 2% for at least 3 consecutive months versus patients without persistent weight loss (1.03 +/- 0.29 g/kg/d vs. 1.15 +/- 0.27 g/kg/d, P < .002), and the odds for developing persistent weight loss were four times greater for adolescent patients with nPCR less than 1 g/kg/d. No association between nPCR and weight loss was observed for younger patients. Mean sAlb levels were greater than 4 g/dL for all patient age groups and did not demonstrate a clinically significant difference between patients with or without weight loss. CONCLUSION: We suggest that nPCR may be useful for monthly nutrition status in adolescent patients receiving maintenance HD and that adolescents with nPCR less than 1 g/kg/d may be at increased risk for subsequent weight loss.     

Reconstructive options after temporal bone resection for squamous cell carcinoma.

Squamous cell carcinoma (SCC) of the temporal bone is a rare, aggressive and highly malignant tumour that requires specialised, multidisciplinary surgery for its treatment. Reconstruction of the defect is as crucial as the tumour ablation in terms of mortality and postoperative morbidity. METHODS: The experience of the East Anglian Skull Base Surgery Service from 1982 to 2004 in managing 42 consecutive patients (22 females; age range 37-80 years) undergoing extended and lateral temporal bone resection for SCC is presented. RESULTS: The overall 5-year survival was 31.0% (median follow up: 97 months) when both curative and palliative procedures were included. On multivariate analysis, the favourable prognostic factors were male sex, well-differentiated tumours and stage N(0) neck. The reconstructions in 38 patients were analysed. The majority (24/38) had free tissue transfer reconstructions and most of these were radial forearm free flaps. Later in the series, other free flap types such as anterolateral thigh flaps and lateral arm flaps were employed. Pedicled myocutaneous flaps and local flaps were also used. CONCLUSIONS: This paper analyses the outcomes of the various reconstructions and discusses the evolution of their care in our unit. The information obtained from the review of our data is extrapolated to offer guidance on the choice of reconstructive option in these patients.     

HP 818: A centrally acting analgesic with neuroleptic properties

HP 818 (1-benzoyl-6-fluoro-3-(1-methyl-4-piperidinyl)-1H-indazole) exhibits the profile of a potent nonnarcotic analgesic with neuroleptic properties. HP 818 blocks the effects of chemical (phenylquinone), pressure (tail clip), and radiant heat (tail flick) painful stimuli in mice (ED₅₀ values of 0.3, 1.2, and 4.1 mg/kg s.c., respectively). This compound displays antinociceptive activity by the subcutaneous, oral, and intravenous routes of administration. It is also effective in the shock titration assay in squirrel monkeys and in a model of surgically induced pain. The rank order of potency of HP 818 and several other standard compounds in these tests for analgesia was Innovar > fentanyl > HP 818 > codeine > droperidol. In addition to its antinociceptive effects, HP 818 possesses neuroleptic properties. It is active in the climbing mouse, pole climb avoidance, and intracranial self-stimulation assays (ED₅₀ values of 1.8, 1.7, and 2.5 mg/kg i.p., respectively). Moreover, HP 818 inhibits amphetamine- and apomorphine-induced stereotypy, indicative of D₂-dopaminergic blocking properties. HP 818, unlike typical neuroleptic agents, does not induce supersensitivity to the effects of apomorphine when administered chronically in mice. In contrast to the clinical standard neuroleptanalgesic Innovar, HP 818 (1.0–3.0 mg/kg i.v.) produces no significant cardiovascular or respiratory changes in the anesthetized dog. Thus, HP 818 is potentially an effective presurgical medication due to its nonnarcotic analgesic activity and sedative neuroleptic effects, along with its lack of limiting cardiorespiratory side effects.