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Etiology of solitary extrapulmonary positron emission tomography and computed tomography findings in patients with lung cancer.

PURPOSE: The aim of this prospective study was to assess the incidence and the nature of solitary extrapulmonary [18F] fluorodeoxyglucose (FDG) accumulations in patients with non-small-cell lung cancer (NSCLC) staged with integrated positron emission tomography and computed tomography (PET/CT) and to evaluate the impact on management. PATIENTS AND METHODS: A total of 350 patients with NSCLC underwent whole-body PET/CT imaging. All solitary extrapulmonary FDG accumulations were evaluated by histopathology, further imaging, or clinical follow-up. RESULTS: PET/CT imaging revealed extrapulmonary lesions in 110 patients. In 72 patients (21%), solitary lesions were present. A diagnosis was obtained in 69 of these patients, including 37 (54%) with solitary metastases and 32 (46%) with lesions unrelated to the lung primary. Histopathologic examinations of these 32 lesions revealed a second clinically unsuspected malignancy or a recurrence of a previous diagnosed carcinoma in six patients (19%) and a benign tumor or inflammatory lesion in 26 patients (81%). The six malignancies consisted of carcinoma of the breast in two patients, and carcinoma of the orbit, esophagus, prostate, and non-Hodgkin's lymphoma in one patient each. Benign tumors and inflammatory lesions included eight colon adenomas, four Warthin's tumors, one granuloma of the lower jaw, one adenoma of the thyroid gland, one compensatory muscle activity due to vocal chord palsy, two occurrences of arthritis, three occurrences of reflux esophagitis, two occurrences of pancreatitis, two occurrences of diverticulitis, one hemorrhoidal inflammation, and one rib fracture. CONCLUSION: Solitary extrapulmonary FDG accumulations in patients with newly diagnosed lung cancer should be analyzed critically for correct staging and optimal therapy, given that up to half of the lesions may represent unrelated malignancies or benign disease.

Adult↗

Cushing's syndrome due to medullary thyroid carcinoma: diagnosis by proopiomelanocortin messenger ribonucleic acid in situ hybridization.

Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 micro g/d), epinephrine (66 micro g/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 micro g/dl and decreased to 12.9 and 4.5 micro g/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was -4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 micro g/d), epinephrine (0 micro g/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing's syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.

Adrenal Glands↗

Isolated skeletal involvement in Cushing's syndrome: response to therapy.

A 38-yr-old male presented with severe symptomatic osteopenia secondary to adrenal hyperfunction without any clinical expression of Cushing's syndrome. The predominantly axial distribution of his osteopenia and the presence of rib fractures healing with abundant callus formation, despite insignificant elevations in serum alkaline phosphatase, were characteristic of glucocorticoid excess syndromes. The histological features of the pretreatment bone biopsy were typical of those associated with excess glucocorticoids, namely decreased quantities of nonmineralized bone matrix, reflecting sites of bone formation, and an increase in the number of osteoclasts, indicating enhanced bone resorption. Six weeks after adrenalectomy, repeat bone biopsy revealed a marked increase in bone matrix synthesis and a significant decrease in bone resorption. These observations suggest that stimulators of skeletal turnover, like sodium fluoride, may be inappropriate in the initial treatment of steroid-induced osteopenia after surgical cure and that vitamin D and calcium therapy offers a more rational approach. Furthermore, the importance of the routine evaluation of adrenal function in any patient presenting with osteopenia is stressed, as well as the fact that relatively isolated skeletal involvement, classically described in micronodular adrenal disease, is not necessarily peculiar to a specific subset of the syndrome but may potentially attend any cause of glucocorticoid excess.

Adrenal Cortex Function Tests↗

Galactorrhea after prolonged traumatic coma: case report.

A 17-year-old girl suffered a traumatic acute subdural hematoma and rib fractures after a motor vehicle accident. Prolonged coma resulted, and significant galactorrhea began 4 weeks after the accident. The galactorrhea was treated successfully by the administration of 2-bromoergocryptine. The pathophysiology of this condition is discussed.

Adolescent↗

Case reports. 1. An autopsy case of fatal arrhythmia induced by injuries of the atrioventricular conduction system: a case report.

A 65-year-old woman died three days after being involved in a traffic accident, following an episode of ventricular fibrillation. She was diagnosed as having suffered cardiac contusion, liver contusion, mediastinal hematoma and rib fracture on admission. Her electrocardiogram showed complete right bundle branch block, complete atrioventricular block, and right axis deviation. Aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and creatine kinase-MB were found to be elevated on biochemical blood analysis. These findings recovered and her condition appeared to improve daily. At autopsy, epicardial and intramyocardial haemorrhage were macroscopically seen in the posterior wall of the bilateral ventricles. On microscopic examination, there was evidence of fresh haemorrhage and coagulative necrosis with inflammatory reaction in the ordinary myocardium and adipose tissue around the atrioventricular node, which had spread to the proximal portion of the His' bundle. It is considered that these findings caused ventricular fibrillation to occur, and that the cause of death in this case was myocardial contusion due to blunt thoracic injury. This case would indicate that myocardium nearby atrioventricular junction is vulnerable to external force. Moreover, it would seem that fatal arrhythmia occasionally occurs during the follow-up stage, despite the lack of any significant clinical findings.

Accidents, Traffic↗

Metabolic bone disease after chronic antacid administration in an infant.

OBJECTIVE: To describe a case of hypophosphatemia and metabolic bone disease (MBD) due to aluminum-containing antacids. CASE SUMMARY: An 8-month-old white boy was brought to the emergency department due to irritability and pain with movement. Upon examination, the infant was irritable, unable to bear weight, had palpable clavicular bony lesions, point tenderness of the hips, and poor head control. The infant had lost several developmental milestones over the past 4 months (eg, ability to roll over) and had decreased appetite and minimal weight gain. Skeletal survey revealed multiple rib fractures, osteoporosis, and Ricketts. Hypophosphatemia (2.3 mg/dL; normal 3.2-6.3) and an elevated serum aluminum level (14 microg/L, normal 0-9) were noted. Past medical history was positive for gastroesophageal reflux. He had been started on ranitidine and aluminum hydroxide (1/2 teaspoonful per 6-ounce bottle) at 2 months of age. The infant's formula contained elevated aluminum levels. Further investigation showed that 1/2 tablespoonful instead of 1/2 teaspoonful of antacid had been added to each 6-ounce formula bottle for the prior 6 months; only 1 month of antacid therapy had been recommended. An objective causality assessment revealed a probable adverse drug event. DISCUSSION: Phosphate-binding substances such as aluminum-containing antacids can bind large amounts of phosphorus, causing hypophosphatemia and MBD. CONCLUSIONS: We report this case to increase awareness of the risk of hypophosphatemia and MBD (likely aluminum related) with use of over-the-counter aluminum-containing antacids in pediatrics, as well as the hazards of prescribing doses in "spoonful" units.

Aluminum Hydroxide↗

Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation.

A significant proportion of patients will be long-term survivors of bone marrow transplantation (BMT) and little is known about their risk of late bony complications. We therefore evaluated bone mineral density (BMD) prior to BMT, post-transplantation changes in BMD, and mechanisms of bone loss in long-term survivors. We performed two analyses. The first was a cross-sectional study of 83 consecutive BMT patients (38 F, 45 M), examining the relationship between BMD and bone turnover, measured immediately prior to transplantation, and a number of disease and patient variables. The second was a prospective study of 39 patients (19F, 20 M) followed for a median of 30 months (range 5-64 months) following either allogeneic (allo, n = 29) or autologous (auto, n = 10) BMT to determine if bone loss was related to treatment of graft versus host disease (GVHD) with glucocorticoids and cyclosporine A, high bone turnover rates, or hypogonadism. Auto BMT recipients acted as a control group for effects of GVHD therapy on BMD. Prior to BMT, spinal and femoral neck (FN) BMDs were 8.6% and 14% lower in female auto BMT recipients than in female allo BMT recipients, respectively (p = 0.12 and p = 0. 003). Urinary bone resorption markers were higher than in normal gender- and age-matched control subjects. Patients treated previously with glucocorticoids also had 8% lower FN BMD. Glucocorticoid-pretreated women with amenorrhoea had lower lumbar spine (LS) and FN BMDs than eumenorrheic women and women receiving HRT. Post-allo BMT, patients lost 11.7% of FN BMD compared with a nonsignificant decrease of 1.1% post-auto BMT (p < 0.001). Spinal BMD and total body bone mineral content (TBBMC) decreased by 3.9% and 3.5%, respectively, post-allo, compared with an increase (1.5%, p = 0.03) or nonsignificant decrease (-3.7%, p = NS), respectively, post-auto BMT. Post-allo BMT bone loss correlated best with the cumulative prednisolone dose at the LS and FN, and with average daily prednisolone dose for TBBMC. At the spine, the rate of bone loss was 4%/10 g of prednisolone, while the rate of bone loss at the FN was greater (9%/10 g of prednisolone). Bone loss was also negatively related to the duration of cyclosporine therapy for GVHD and baseline deoxypyridinoline concentrations. Avascular necrosis of the femoral head occurred in four, and vertebral and rib fractures occurred in one of the allo BMT patients, but in no auto BMT patients. In conclusion, BMT recipients are at risk of osteoporosis secondary to bone loss associated with their underlying illness and/or chemotherapy, particularly in female autograft recipients, and in allograft recipients secondary to GVHD and its treatment.

Adult↗

Risk factors for early onset pneumonia in trauma patients.

STUDY OBJECTIVES: The aim of the study was to identify risk factors for early onset pneumonia (EOP) in trauma patients, in order to seek possible intervention strategies. STUDY POPULATION: Participants included 124 consecutive trauma patients admitted to a general intensive care unit (ICU) of a university hospital from December 1990 to February 1992 inclusive. DATA COLLECTION: The following data were prospectively collected for each patient: demographics, severity of trauma according to the abbreviated injury scale (AIS), severity of coma according to the Glasgow coma scale (GCS), presence of pneumothorax, pulmonary contusion, rib fractures, hemothorax, and mechanical ventilation. All patients were monitored daily during the ICU stay for the onset of pneumonia, sepsis syndrome, septic shock, and adult respiratory distress syndrome (ARDS). Criteria for the diagnosis of pneumonia were: core temperature of greater than 38.3 degrees C, a WBC count of 10,000 cells/mm3, purulent tracheobronchial secretions, a worsening of pulmonary gas exchange, and persistent pulmonary infiltrates. All patients with suspected pneumonia underwent quantitative bronchoalveolar lavage (BAL) as well as blood cultures; BAL cultures were considered positive when they showed bacterial growth greater than 1 x 10(5) colony-forming unit (cfu)/ml, or less than 10(5), but with the same microorganism isolated in blood cultures. Pneumonia occurring within the first 96 h after trauma was considered EOP. DATA ANALYSIS: A stepwise logistic regression analysis was carried out in order to identify factors independently associated with an increased risk of EOP and late onset pneumonia (LOP). RESULTS: Overall mortality was 43.5 percent: mortality increased by age and AIS score. Forty one patients (33.1 percent) developed pneumonia: 26 (63.4 percent) were EOP and 15 (36.6 percent) were LOP. In the univariate analysis, an age greater than 40 years, the presence of pulmonary contusion, AIS of more than 4 for thorax and of more than 9 for abdomen, and the absence of mechanical ventilation (MV) during the first 4 days of hospitalization or MV lasting less than 24 h were significantly associated with an increased risk of acquiring EOP. Logistic regression analysis showed that the strongest risk factor for EOP was a combined severe abdominal and thoracic trauma, which increased the risk of EOP by 11 times; an age of more than 40 years and MV of less than 24 h during the first 4 days of hospitalization were also independent risk factors for EOP. Factors associated with LOP were an AIS score of more than 4 for abdomen and a length of MV of more than 5 days. CONCLUSION: In a trauma population, a combined severe abdominal and thoracic trauma represents a major risk factor for EOP. Mechanical ventilation administered during the first days after trauma seems to reduce the risk of EOP. As reported in previous studies, mechanical ventilatory support lasting more than 5 days is associated with an increased risk of LOP.

Abbreviated Injury Scale↗

Thorax and lung injuries arising from the two earthquakes in Turkey in 1999.

STUDY OBJECTIVE: To make a descriptive analysis of the frequency and the type of thorax and lung injuries among the casualties of the two devastating earthquakes that occurred in Turkey in 1999. DESIGN: Records of the hospitalized patients injured in the earthquakes were examined retrospectively. RESULTS: Among the total of 356 hospitalized patients, 21 (9.7%) in the Izmit earthquake and 6 (7.6%) in the Duzce earthquake had thorax and lung injuries. Pneumothorax and rib fractures were the two most frequent pathologies and accounted for 50% and 33.3% of the injuries, respectively. CONCLUSION: Approximately 10% of the casualties of a great earthquake may be expected to have thorax and lung injuries, and traumatic chest diseases should be considered in planning the medical response strategies.

Adolescent↗

Complete heart block following therapeutic irradiation of the left side of the chest.

Two female patients had received therapeutic irradiation of the left side of the chest for adenocarcinoma of the left breast and 18 and 23 years later, respectively, developed atrioventricular block. Both patients had early and late cutaneous reactions, as well as fibrosis of the left lung, lymphedema of the left arm, and pathologic rib fractures but had no signs of recurrence of the carcinoma. One patient developed signs of congestive heart failure while the electrocardiogram revealed second and third degree atrioventricular block; subsequent pacemaker implantation relieved the congestive heart failure. In the second patient, fatigue was the only symptom leading to the diagnosis of transient second and third degree atrioventricular block; this symptom subsided after pacemaker implantation. Based on reports of radiation-induced cardiac damage, it is assumed that the heart block in these two patients might have been due to postirradiation fibrosis of the atrioventricular node, either direct or mediated by fibro-occlusive changes in the coronary vessels.

Adenocarcinoma↗

Clinical practice guidelines for the care and treatment of breast cancer: 16. Locoregional post-mastectomy radiotherapy.

OBJECTIVE: To provide information and recommendations to assist women with breast cancer and their physicians in making decisions regarding the use of locoregional post-mastectomy radiotherapy (PMRT). OUTCOMES: Locoregional control, disease-free survival, overall survival and treatment-related toxicities. EVIDENCE: This guideline is based on a review of all meta-analyses, consensus statements and other guidelines published between 1966 and November 2002. Searches of MEDLINE and CANCERLIT for English-language randomized controlled trials published between 1995 and November 2002 were also conducted to supplement the literature previously reviewed by the American Society of Clinical Oncology (ASCO) Health Services Research Committee panel in its published guideline. A nonsystematic review of the literature was continued through June 2003. RECOMMENDATIONS: Locoregional PMRT is recommended for women with an advanced primary tumour (tumour size 5 cm or greater, or tumour invasion of the skin, pectoral muscle or chest wall). Locoregional PMRT is recommended for women with 4 or more positive axillary lymph nodes. The role of PMRT in women with 1 to 3 positive axillary lymph nodes is unclear. These women should be offered the opportunity to participate in clinical trials of PMRT. Locoregional PMRT is generally not recommended for women who have tumours that are less than 5 cm in diameter and who have negative axillary nodes. Other patient, tumour and treatment characteristics, including age, histologic grade, lymphovascular invasion, hormone receptor status, number of axillary nodes removed, axillary extracapsular extension and surgical margin status, may affect locoregional control, but their use in specifying additional indications for PMRT is currently unclear. PMRT should encompass the chest wall and the supraclavicular, infraclavicular and axillary apical lymph node areas. To reduce the risk of lymphedema, radiation of the entire axilla should not be used routinely after complete axillary dissection of level I and II lymph nodes. A definite recommendation regarding the inclusion of the internal mammary lymph nodes in PMRT cannot be made because of limited and inconsistent data. The use of modern techniques in radiotherapy planning is recommended to minimize excessive normal tissue exposure, particularly to the cardiac and pulmonary structures. Common short-term side effects of PMRT, including fatigue and skin erythema, are generally tolerable and not dose-limiting. Severe long-term side effects, including lymphedema, cardiac and pulmonary toxicities, brachial plexopathy, rib fractures and secondary neoplasms, are relatively rare. The optimal sequencing of PMRT and systemic therapy is currently unclear. Regimens containing anthracyclines or taxanes should not be administered concurrently with radiotherapy because of the potential for increased toxicity. VALIDATION: The authors' original text was submitted for review, revision and approval by the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Subsequently, feedback was provided by 11 oncologists from across Canada. The final document was approved by the steering committee. SPONSOR: The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was convened by Health Canada. COMPLETION DATE: November 2003.

Breast Neoplasms↗

Osteopenic effects of MgSO4 in multiple pregnancies.

OBJECTIVE: To describe the effects of prolonged maternal treatment with MgSO4 in infants who were products of multiple pregnancies. STUDY DESIGN: Case series of infants presenting with osteopenia secondary to MgSO4 administration for preterm labor. RESULTS: Ten premature infants with hypermagnesemia (4.5+/-0.2 mg/dl), hypocalcemia (6.0 +/-0.3 mg/dl), and high serum alkaline phosphatase (574+/-96 U/l) underwent imaging studies that showed diffuse osteopenia of the long bones and probable rib fractures. All mothers had isolated premature labor, for which they were given MgSO4; (average dose 3.66+/-0.08 kg/ pregnancy over 10.0+/-0.5 weeks). On follow-up (to 9 months), all infants had complete or near complete resolution of the osteopenia. CONCLUSIONS: Premature infants who are exposed to large doses of MgSO4, especially those of multiple pregnancies, have an increased risk of developing hypocalcemia, osteopenia, and fractures. Our findings indicate that these infants should be identified at birth and managed prospectively.

Adult↗

The cause of infant and toddler subdural hemorrhage: a prospective study.

OBJECTIVE: To determine the frequency of child abuse and unintentional injury as a cause of infant and toddler subdural hemorrhage (SDH). METHODS: A prospective case series of a level I regional trauma center, regional children's hospital, and county medical examiner's office assessed consecutive children who were </=36 months old and had SDH. Children who had previously known hemorrhagic disease, previous neurosurgical procedure, previously recognized perinatal brain injury, meningitis, renal dialysis, and severe dehydration were excluded. Concurrent medical, retinal, skeletal, and social work abuse evaluation were measured. Etiologic assessment using predetermined criteria was conducted. RESULTS: From March 1995 through December 1998, 66 children were admitted with SDH. Abuse was confirmed in 39 (59%), unintentional injury in 15 (23%), and indeterminate cause in 12 (18%). The mean age of abused children was 8.7 +/- 8.1 months and of children with unintentional injuries was 19.1 +/- 10.0 months. The predominant presenting histories for abusive injury were a minor fall or no mechanism for 33 (84%) of 39 patients. All unintentional injuries resulted from a motor vehicle accident or other documented major trauma. Chronic or mixed acute and chronic SDH were found only in abused children (17 [44%] of 39) and in children whose injuries were indeterminate (8 [67%] of 12), not in children who were unintentionally injured (0 [0%] of 15). Long bone and/or rib fractures were found in 20 (51%) of 39 abused children but in only 1 unintentionally injured child. Retinal bleeding was present in 28 (72%) of 39 of the abused children. Only 1 of the 3 unintentionally injured children who had a retinal examination had bleeding, which was of the type associated with acute increased intracranial pressure. CONCLUSIONS: Nearly one fifth of infant and toddler SDH resulted from unintentional trauma. Of those without obvious unintentional trauma, 76% were corroborated to have been abused. Abused children were younger, more likely to have chronic SDH, and more likely to have multiple associated injuries. Their injury history usually was minor or absent.

Alaska↗

Hypophosphatemia associated with hypovitaminosis-D in Speke's gazelles (Gazella spekei).

Two juvenile male Speke's gazelles (Gazella spekei) at the St. Louis Zoo showed poor body condition, slowed growth, hunched stance, rough hair coat, and profound hypophosphatemia. The first gazelle was treated with parenteral phosphorous supplements but continued to deteriorate clinically and was euthanatized. The second gazelle had serum 25-hydroxyvitamin D levels of 0 nmol/L and was treated with i.m. injections of vitamin D. It died shortly after starting therapy. The only significant necropsy finding was multiple rib fractures in various stages of healing. Hypovitaminosis D has been confirmed in multiple Speke's gazelles in this collection, indicating possible deficiencies in the diet or in the amount of ultraviolet light available to the gazelles.

Animals↗

Adrenal hemorrhage in abused children: imaging and postmortem findings.

OBJECTIVE: Adrenal hemorrhage associated with child abuse has received little attention in published reports. We review imaging studies or pathologic findings of adrenal hemorrhage in five cases of proved child abuse. SUBJECTS AND METHODS: The imaging findings in three children with adrenal hemorrhage were analyzed retrospectively. All three had abdominal CT scans and skeletal radiographs. One also had abdominal sonograms and MR images. The pathologic findings in two other abused children with adrenal hemorrhage who died of head injuries were also studied. In all five cases, a history of trauma was not initially known; child abuse was later confirmed. RESULTS: Unilateral hemorrhage in the right adrenal gland was found in all patients. Enhanced CT scans of the abdomen showed a low-attenuation, oval mass separating the limbs of the adrenal gland. Sonograms in one case showed a small, heterogeneous mass in the right adrenal gland. MR images obtained 3 weeks later showed an area of high signal intensity within the right adrenal gland on both T1- and T2-weighted images, consistent with subacute hemorrhage. In both deceased children, autopsy showed hemorrhage in the right adrenal gland, mainly within the medulla with some extension beyond the capsule in one case. All five children had associated abdominal visceral injuries or rib fractures or both, on the same side as the hemorrhage. CONCLUSION: Imaging findings of adrenal hemorrhage are similar to those previously described in patients with accidental trauma. Pathologic sections of the gland reveal predominantly medullary involvement with hemorrhage. The presence of adrenal hemorrhage in a child should prompt a search for other associated injuries and raise the possibility of unsuspected trauma.

Adrenal Gland Diseases↗

Clinical follow-up of burn patients after long-term mechanical ventilation.

13 burn patients who had been treated for inhalation injuries (9), respiratory failure (3) or fractured ribs (1) were followed up after an average period of five years. Tracheal stenosis was found in five patients, increased pulmonary resistance in six patients. Even in patients who had sustained inhalation traumas there was only a minimal impairment of pulmonary function and physical work capacity.

Burns, Inhalation↗