Characterization of perioperative androgen profiles in men with bladder cancer undergoing radical cystectomy

BackgroundPrior studies have demonstrated declines in androgen levels in men with cancer and patients undergoing anesthesia and surgery. In this study, we hypothesized that decreased serum androgen levels are prevalent in male patients undergoing radical cystectomy (RC) for bladder cancer and that it persists in the postoperative period. We characterized perioperative androgen hormonal profiles and examined for associated changes indicative of sarcopenia on computed tomography scans in men undergoing RC.MethodsWe implemented a prospective observational trial in men with newly diagnosed non-metastatic bladder cancer undergoing RC. Baseline pre-operative total testosterone (TT), free testosterone (FT), and luteinizing hormone (LH) were obtained on morning lab draws with 30 days of surgery. TT and FT were then repeated on postoperative days (POD) 2, 3, 30, and 90. The threshold for normal TT was defined as >300 ng/dl, consistent with the AUA Guidelines for Evaluation and Management of Testosterone Deficiency. We evaluated postoperative changes in weight and psoas muscle cross-sectional area using computed tomography scans to assess for sarcopenic changes.ResultsUnivariable statistical analysis was performed. 25 patients were enrolled. The mean patient age was 68.9 years. The mean pre-operative TT was 308 ng/dl, and 12/23 (52.5%) patients had low testosterone. Mean TT onPOD 2 and 3 were 166 ng/dl and 161 ng/dl, respectively (range 24–345). 19/20 (95%) of men who had morning lab draws had decreased TT. The mean TT at 30 days was 253 ng/dl with 37.5% of men having low TT. Mean TT at 90 days was 306 ng/dl. The mean FT levels were 43 ng/dl, 29.25 ng/dl, 28.2 ng/dl, 40.89 ng/dl, and 42.62 ng/dl at baseline, POD 2, POD 3, POD 30, and POD 90, respectively. Mean LH at baseline was 9.9 IU/L. Average weight loss at 30- and 90- days postop was -4.29 and -4.38 kilograms, respectively. Weight loss was persistent with only 3/23 (13%) returning to their presurgery weight by 90 days. Despite significant declines in weight and perioperative TT, no significant differences in psoas muscle cross-sectional area were observed (net change -92 mm², P= 0.13)ConclusionsPerioperative disruption of androgen levels is prevalent in men undergoing RC. Our trial demonstrates a pre-op, immediate postop, 30- and 90-day postoperative prevalence of low TT of 52%, 95%, 63%, and 37.5%, respectively. Significant changes in baseline weight were noted, although no significant changes in psoas muscle cross-sectional area were observed, limiting conclusions regarding a link between changes in androgens and sarcopenia in this setting.     

Primary hyperoxaluria diagnosed after kidney transplant: A review of the literature and case report of aggressive renal replacement therapy and lumasiran to prevent allograft loss

Primary hyperoxaluria type 1 is a rare inherited disorder caused by abnormal liver glyoxalate metabolism leading to overproduction of oxalate, progressive kidney disease, and systemic oxalosis. While the disorder typically presents with nephrocalcinosis, recurrent nephrolithiasis, and/or early chronic kidney disease, the diagnosis is occasionally missed until it recurs after kidney transplant. Allograft outcomes in these cases are typically very poor, often with early graft loss. Here we present the case of a child diagnosed with primary hyperoxaluria type 1 after kidney transplant who was able to maintain kidney function, thanks to aggressive renal replacement therapy as well as initiation of a new targeted therapy for this disease. This case highlights the importance of having a high index of suspicion for primary hyperoxaluria in patients with chronic kidney disease and nephrocalcinosis/nephrolithiasis or with end stage kidney disease of uncertain etiology, as initiating therapies early on may prevent poor outcomes.     

Human Papillomavirus Vaccination and Pap Smear Rates Among Burmese Refugee Girls in a Healthcare System in Omaha,Nebraska

Journal of Community Health - While human papilloma virus (HPV) vaccinations and Pap smear screenings are known to improve the survival rates and incidence of cervical cancer, refugee populations...     

Inflammatory and non-inflammatory inclusion body myositis

Summary In ten patients with inclusion body myositis (IBM) five muscular biopsies showed profuse inflammatory exudates and three showed a few scattered inflammatory cells with partial invasion in some muscle fibers. No inflammatory cells were seen in two cases. In all patients, histopathological, histomorphometric and immunocytochemical studies were performed. Immunocytochemistry for the class I and class II major histocompatibility complex gene product (MHC) was performed in all cases and in ten control muscles including: normal muscles [3], dermatomyositis [3], polymyositis [3], scleroderma [1]. In the five cases of IBM with inflammatory exudates, subsets of lymphocytes were analyzed with a panel of monoclonal antibodies against B cells, T4 cells, T8 cells, K and natural killer cells and macrophages. Some muscle fibers expressed class I MHC antigens in the inflammatory cases of IBM. These fibers were near the inflammatory exudates and occasionally showed a partial invasion. No expression of class I MHC was found in normal muscles and in non-inflammatory cases of IBM. The antigen which triggers the mononuclear cells in the inflammatory forms of IBM is probably not the filamentous inclusions in rimmed vacuoles. In other inflammatory myopathies, expression of class I MHC was present on all fibers in polymyositis, only in the perifascicular area in dermatomyositis and in scleroderma. It could be suggested that the term inclusion body muscle disease be applied to cases with rimmed vacuoles and IBM-like filaments without inflammatory cells.     

Total parenteral nutrition during acute pancreatitis: Clinical experience with 156 Patients

Over a 3-year period, 156 of 815 patients admitted to a single institution with acute pancreatitis received total parenteral nutrition (TPN) for 2,572 patient days. Seventy had simple acute pancreatitis (group I) and 86 (group II) developed local complex disease (pseudocyst, abscess, or necrotic gland). In groups I and II, respectively, days without oral intake (NPO) were 13.6±1.5 (SEM) and 24.0±2.1 (p<0.005), hospital days were 19.8±1.7 and 35.8±3.2 (p<0.005), and duration of TPN was 10.9 ±1.0 and 21.0±2.3 days (p<0.005). Thirty-three patients in group I and 53 in group II required exogenous insulin. Alteration of standard formulas was necessary in 87 patients, but cessation of therapy was necessary in only one instance. Twenty catheters were removed for suspected sepsis with only 3 confirmed cases. Fat-based formulas were well tolerated in 15% of patients. During TPN, body weight rose from 95.0±2.4% to 97.4±4.3% of ideal in group I and remained at 90.5±1.8% in group II. Albumin rose from 3.36±0.10 to 3.50±0.08 g/dl in group I and from 3.01±0.07 to 3.35±0.07 g/dl in group II. The entire cohort differed from 10 randomly chosen patients who did not receive TPN in terms of days NPO (2.8±0.3) and hospital days (5.5±0.6). Variables associated with prolongation of hospital stay and time NPO were number of prognostic criteria, local complex disease, and underlying chronic pancreatitis only in select groups. We conclude that during acute pancreatitis, TPN can be administered safely but with careful monitoring and we recommend early aggressive therapy in the subgroups noted above and when underlying malnutrition exists. In the borderline patient, TPN may be administered by peripheral vein until the severity of disease is manifest.

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Resumen En el curso de un período de 3 años, 156 de 815 pacientes hospitalizados en una sola institución por pancreatitis aguda recibieron nutrición parenteral total (NPT) durante 2,572 paciente-días. Setenta presentaban pancreatitis aguda simple (grupo I) y 86 (grupo II) desarrollaron enfermedad local complicada (pseudoquiste, absceso, o necrosis de la glándula). Las siguientes fueron las características de los grupos I y II, respectivamente: días sin ingesta oral (NPO) 13.6±1.5 (SEM) y 24.0±2.1 (p<0.005), días de hospitalización: 19.8±1.7 y 35.8±3.2 (p<0.005), y duración de la NPT: 10.9±1.0 y 21.0 ±2.3 días (p<0.005). Trienta y tres pacientes en el grupo I y 53 en el grupo II requirieron insulina exógena. Se requirió alterar la fórmula estándar en 87 pacientes, pero sólo fue necesario cesar la terapia en un caso. Veinte catéteres fueron retirados por sospecha de sepsis, pero sólo en 3 se confirmó. Las fórmulas a base de grasa fueron bien toleradas en 15% de los pacientes. En el curso de la NPT el peso corporal ascendió de 95.0±2.4% a 97.4±4.3% del peso ideal en el grupo I y se mantuvo a un 90.5±1.8% en el grupo II. La albúmina ascendió de 3.36±0.10 a 3.50±0.8 g/dl en el grupo I y de 3.01±0.07 a 3.35±0.07 g/dl en el grupo II. Toda la cohorte se diferenció de un grupo de 10 pacientes escogidos al azar que no recibieron NPT en términos del número de días NPO (2.8±0.3) y de días de hospitalización (5.5±0.6). Las variables que aparecieron asociadas con prolongación de la hospitalización y el tiempo NPO fueron el número de criterios de pronóstico, la enfermedad complicada, y la presencia de pancreatitis crónica subyacente sólo en grupos seleccionados. Nuestra conclusión es que en el curso de la pancreatitis aguda, la NPT puede ser administrada con seguridad pero bajo monitoría cuidadosa, y recomendamos terapia agresiva precoz en los subgrupos anotados anteriormente y cuando exista mal nutrición concomitante. En el paciente limitrofe se puede administrar la NPT por vía periférica hasta cuando la gravedad de la enfermedad se haga manifiesta.

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Résumé Pendant une période de 3 ans, 156 des 815 patients admis pour pancréatite aiguë ont reçu une alimentation parentérale totale (APT), soit en tout 2,572 jours patient. Soixante dix patients (groupe I) avaient une pancréatite simple et 86 (groupe II) avaient aussi une maladie locale complexe (pseudokyste, abcès ou nécrose du pancréas). La durée du jeûne était respectivement de 13.6±1.5 (ET) et de 24.0±2.1 (p<0.005), la durée moyenne de séjour était respectivement de 19.8±1.7 et de 35.8 ±3.2 (p<0.005) alors que la durée d'APT était respectivement de 10.9±1.0 et de 21.0±2.3 jours (p<0.005). Trente-trois patients dans le groupe I et 53 dans le groupe II avaient besoin d'insuline exogène. Un changement dans la formule standard a été nécessaire chez 87 patients mais l'APT n'a du être arrêté complètement que chez un patient seul. Vingt cathéters ont été enlevés avec suspicion de sepsis, confirmée cependant dans 3 cas seulement. Les compositions à base de lipides ont été bien tolérées chez 15% des patients. Pendant l'APT, le poids du corps s'est élevé de 95.0±2.4% à 97.4±4.3% du poids idéal chez les patients du groupe I et est resté à 90.5±1.8% chez ceux du groupe II. L'albumine s'est élevée de 3.36±0.10 à 3.50 ±0.08 g/dl dans le groupe I et de 3.01±0.07 à 3.35±0.07 g/dl dans le groupe II. La durée du jeûne (2.8±0.3) et la durée moyenne de séjour (5.5±0.6) de l'ensemble des patients différaient de ces mêmes données chez 10 autres patients choisis au hasard. Les facteurs associés avec un séjour hospitalier prolongé et sans alimentation orale étaient le nombre de critères pronostiques, l'existence de complications locales, et de pancréatite chronique sous-jacente chez certains patients. Nous concluons que pendant la pancréatite aiguë, l'APT peut être administrée sans danger sous contrôle permanent et nous conseillons un traitement agressif et précoce dans le sous groupe mentionné plus haut ou quand existe un état de nutrition déficient. Chez le patient limite, on peut se contenter d'APT par une veine périphérique tant que des signes de gravité ne se manifestent pas.

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Presented at the Société Internationale de Chirurgie in Toronto, Ontario, Canada, September, 1989.     

Phase II study of intravenous adenosine 5''-triphosphate in patients with previously untreated stage IIIB and Stage IV non-small cell lung cancer

Fifteen patients with Stage IIIB or IV non-small cell lung cancer gave informed consent to receive three or more 96-hour infusions of ATP at a dose of 50 mcg/kg/min or higher to determine whether ATP has antineoplastic activity against this tumor type and to better define the spectrum of toxicity for ATP given as a single agent. There were no objective complete or partial responses observed. The median survival of the overall group was 187 days and the median time to tumor progression was 113 days. The major toxic side effects were chest pain and dyspnea, leading to the cessation of treatment in 5 patients. We conclude that ATP at this dose and schedule of administration is an inactive agent in patients with advanced non-small cell lung cancer.