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Fourth-Generation Progestins Inhibit 3β-Hydroxysteroid Dehydrogenase Type 2 and Modulate the Biosynthesis of Endogenous Steroids.

Thu, 06/22/2017 - 16:59
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Fourth-Generation Progestins Inhibit 3β-Hydroxysteroid Dehydrogenase Type 2 and Modulate the Biosynthesis of Endogenous Steroids.

PLoS One. 2016;11(10):e0164170

Authors: Louw-du Toit R, Perkins MS, Snoep JL, Storbeck KH, Africander D

Abstract
Progestins used in contraception and hormone replacement therapy are synthetic compounds designed to mimic the actions of the natural hormone progesterone and are classed into four consecutive generations. The biological actions of progestins are primarily determined by their interactions with steroid receptors, and factors such as metabolism, pharmacokinetics, bioavailability and the regulation of endogenous steroid hormone biosynthesis are often overlooked. Although some studies have investigated the effects of select progestins on a few steroidogenic enzymes, studies comparing the effects of progestins from different generations are lacking. This study therefore explored the putative modulatory effects of progestins on de novo steroid synthesis in the adrenal by comparing the effects of select progestins from the respective generations, on endogenous steroid hormone production by the H295R human adrenocortical carcinoma cell line. Ultra-performance liquid chromatography/tandem mass spectrometry analysis showed that the fourth-generation progestins, nestorone (NES), nomegestrol acetate (NoMAC) and drospirenone (DRSP), unlike the progestins selected from the first three generations, modulate the biosynthesis of several endogenous steroids. Subsequent assays performed in COS-1 cells expressing human 3βHSD2, suggest that these progestins modulate the biosynthesis of steroid hormones by inhibiting the activity of 3βHSD2. The Ki values determined for the inhibition of human 3βHSD2 by NES (9.5 ± 0.96 nM), NoMAC (29 ± 7.1 nM) and DRSP (232 ± 38 nM) were within the reported concentration ranges for the contraceptive use of these progestins in vivo. Taken together, our results suggest that newer, fourth-generation progestins may exert both positive and negative physiological effects via the modulation of endogenous steroid hormone biosynthesis.

PMID: 27706226 [PubMed - indexed for MEDLINE]

Solitary adrenal metastasis from early-stage dedifferentiated endometrial carcinoma: CT findings and review of the literature.

Thu, 06/22/2017 - 16:59
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Solitary adrenal metastasis from early-stage dedifferentiated endometrial carcinoma: CT findings and review of the literature.

J Obstet Gynaecol. 2016 10;36(7):881-882

Authors: Mouka V, Tsili AC, Messinis T, Papoudou-Bai A, Kamina S, Argyropoulou MI

PMID: 27624653 [PubMed - indexed for MEDLINE]

Nonsurgical options to treat giant-cell tumors of the head and neck: A case report and brief review of the literature.

Thu, 06/22/2017 - 16:59
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Nonsurgical options to treat giant-cell tumors of the head and neck: A case report and brief review of the literature.

Ear Nose Throat J. 2016 Jul;95(7):E29-34

Authors: Rasband-Lindquist AN, Lindquist JD, Larsen CG, Thiessen A, Girod D

Abstract
Central giant-cell granulomas (CGCGs) are relatively uncommon. When they do occur, they typically arise in the mandible and maxilla. Some lesions are more destructive than others, and the destructive subtype has a tendency to recur. Unfortunately, there is no reproducible way to differentiate aggressive from nonaggressive subtypes. Treatment of CGCG has historically been based on surgical curettage or wide local excision. However, surgery has been associated with significant morbidity, disfigurement, and expense, as well as a high recurrence rate. Pharmacologic treatments-either as an alternative or an adjunct to surgery-have been shown to yield acceptable results. These agents include intralesional and/or systemic corticosteroids, bisphosphonates, calcitonin, and interferon alfa. These options are typically less expensive than surgery, and they are associated with few side effects, which makes them potentially more desirable. We report the case of a 36-year-old woman with a CGCG who was successfully treated with a combination of an intralesional steroid and an oral steroid over a period of 5 months. As evidenced by this case, medical management can be effective for tumor regression in treating CGCG of the head and neck, and it is ultimately associated with less morbidity and is less costly. To the best of our knowledge, no randomized controlled studies have been published on this topic. Such a study would be welcome, particularly considering the presence of both aggressive and nonaggressive subtypes of CGCG. We also briefly review the literature.

PMID: 27434482 [PubMed - indexed for MEDLINE]

Epidemiologic, Clinicopathologic, Diagnostic, and Management Challenges of Pityriasis Rubra Pilaris: A Case Series of 100 Patients.

Thu, 06/22/2017 - 16:59
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Epidemiologic, Clinicopathologic, Diagnostic, and Management Challenges of Pityriasis Rubra Pilaris: A Case Series of 100 Patients.

JAMA Dermatol. 2016 Jun 01;152(6):670-5

Authors: Ross NA, Chung HJ, Li Q, Andrews JP, Keller MS, Uitto J

Abstract
IMPORTANCE: Pityriasis rubra pilaris (PRP) is a rare papulosquamous disorder with limited epidemiologic and clinicopathologic data. Little information is available on long-term outcomes, comorbidities, and treatment efficacy.
OBJECTIVE: To evaluate objective and subjective disease experience metrics from the perspectives of patients and clinicians.
DESIGN, SETTING, AND PARTICIPANTS: One hundred patients with a putative diagnosis of PRP and who elected to participate completed a comprehensive survey, followed by acquisition of their medical records, including histopathology slides and reports. The data were analyzed separately from the health care clinician and the patient perspectives. Two academic dermatologists examined clinical notes, pathology reports, and photographs, confirming diagnoses via predetermined criteria. Patients were categorized into 4 levels of diagnostic certainty to allow stratification of the findings for subgroup analysis. Patients with a diagnosis of PRP were solicited through patient support organization websites.
MAIN OUTCOMES AND MEASURES: Clinical outcomes, unexpected association of comorbidities, and efficacy (or lack of it) of various treatment modalities.
RESULTS: Among the 100 patients, 50 were diagnosed as having classic, unquestionable PRP. The patients were a median of 61 years old (range, 5-87 years), and 46% were female. Fifty were categorized as level 1 diagnostic certainty, 15 as level 2, 30 as level 3, and 5 as level 4. Of the level 1 patients, 13 (26%) were correctly diagnosed at initial presentation; diagnosis was delayed, on average, by 29 months (range, 0.25-288 months; median, 2 months); and 27 (54%) having undergone 2 or more biopsies. At enrollment, PRP symptoms had persisted in 36 patients (72%) for an average of 58 months (range, 1-300 months; median, 30 months). Thirty-one patients (62%) had comorbidities, including hypothyroidism (20%). Nearly all patients (98%) received some form of therapy. Patients cited topical emollients, corticosteroids, and salicylic acid along with oral retinoids, methotrexate, and tumor necrosis factor inhibitors as most helpful.
CONCLUSIONS AND RELEVANCE: Pityriasis rubra pilaris remains a challenging diagnosis without established and specific treatment. Our data highlight new potential avenues for research with therapeutic perspective.

PMID: 26963004 [PubMed - indexed for MEDLINE]

Adrenal and thyroid metachronous metastases from renal cell carcinoma.

Thu, 06/22/2017 - 16:59
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Adrenal and thyroid metachronous metastases from renal cell carcinoma.

Endocrine. 2016 Jul;53(1):335-6

Authors: Taguchi T, Karashima T, Terada Y

PMID: 26611247 [PubMed - indexed for MEDLINE]

AN INDIVIDUALIZED APPROACH TO THE EVALUATION OF CUSHING SYNDROME.

Thu, 06/15/2017 - 14:02

AN INDIVIDUALIZED APPROACH TO THE EVALUATION OF CUSHING SYNDROME.

Endocr Pract. 2017 Jun;23(6):726-737

Authors: Sharma ST, AACE Adrenal Scientific Committee

Abstract
Cushing syndrome (CS) is caused by chronic exposure to excess glucocorticoids. Early recognition and treatment of hypercortisolemia can lead to decreased morbidity and mortality. The diagnosis of CS and thereafter, establishing the cause can often be difficult, especially in patients with mild and cyclic hypercortisolism. Surgical excision of the cause of excess glucocorticoids is the optimal treatment for CS. Medical therapy (steroidogenesis inhibitors, medications that decrease adrenocorticotropic hormone [ACTH] levels or glucocorticoid antagonists) and pituitary radiotherapy may be needed as adjunctive treatment modalities in patients with residual, recurrent or metastatic disease, in preparation for surgery, or when surgery is contraindicated. A multidisciplinary team approach, individualized treatment plan and long-term follow-up are important for optimal management of hypercortisolemia and the comorbidities associated with CS.
ABBREVIATIONS: ACTH = adrenocorticotropic hormone; BIPSS = bilateral inferior petrosal sinus sampling; CBG = corticosteroid-binding globulin; CD = Cushing disease; CRH = corticotropin-releasing hormone; CS = Cushing syndrome; Dex = dexamethasone; DST = dexamethasone suppression test; EAS = ectopic ACTH syndrome; FDA = U.S. Food & Drug Administration; HDDST = high-dose DST; IPS/P = inferior petrosal sinus to peripheral; MRI = magnetic resonance imaging; NET = neuroendocrine tumor; PET = positron emission tomography; UFC = urinary free cortisol.

PMID: 28614036 [PubMed - in process]

Texture analysis of FDG PET/CT for differentiating between FDG-avid benign and metastatic adrenal tumors: efficacy of combining SUV and texture parameters.

Thu, 06/15/2017 - 14:02
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Texture analysis of FDG PET/CT for differentiating between FDG-avid benign and metastatic adrenal tumors: efficacy of combining SUV and texture parameters.

Abdom Radiol (NY). 2017 Jun 13;:

Authors: Nakajo M, Jinguji M, Nakajo M, Shinaji T, Nakabeppu Y, Fukukura Y, Yoshiura T

Abstract
PURPOSE: To retrospectively investigate the SUV-related and texture parameters individually and in combination for differentiating between F-18-fluorodeoxyglucose (FDG)-avid benign and metastatic adrenal tumors with PET/CT.
METHODS: Thirteen benign adrenal tumors (BATs) and 22 metastatic adrenal tumors (MATs) with a metabolic tumor volume (MTV) > 10.0 cm(3) and SUV ≥ 2.5 were included. SUVmax, MTV, total lesion glycolysis, and four textural parameters [entropy, homogeneity, intensity variability (IV), and size-zone variability] were obtained. These parameters were compared between BATs and MATs using Mann-Whitney U test, and the diagnostic performance was evaluated by the area under the curve (AUC) values derived from the receiver operating characteristic analysis. The diagnostic value of combining SUV and texture parameters was examined using a scoring system.
RESULTS: MATs showed significantly higher SUVmax (p = 0.004), entropy (p = 0.013), IV (p = 0.006), and lower homogeneity (p = 0.019) than BATs. The accuracies for diagnosing MATs were 82.9, 82.9, 85.7, and 71.4% for SUVmax, entropy, IV, and homogeneity, respectively. No significant differences in AUC were found among these parameters (p > 0.05 each). When each parameter was scored as 0 (negative for malignancy) and 1 (positive for malignancy) according to each threshold criterion and the four parameter summed scores 0, 1, and 2 were defined as benignity and 3 and 4 as malignancy, the sensitivity and specificity and accuracy to predict MATs were 100% (22/22), 84.6% (11/13), and 94.3% (33/35), respectively, with 0.97 of the AUC.
CONCLUSION: The combined use of SUVmax and texture parameters has a potential to significantly increase the diagnostic performance to differentiate between large FDG-avid BATs and MATs.

PMID: 28612161 [PubMed - as supplied by publisher]

Relative Adrenal Insufficiency is Associated with the Clinical Outcome in Patients with Stable Decompensated Cirrhosis.

Thu, 06/15/2017 - 14:02
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Relative Adrenal Insufficiency is Associated with the Clinical Outcome in Patients with Stable Decompensated Cirrhosis.

Ann Hepatol. 2017 Aug 01;16(4):584-590

Authors: Cholongitas E, Goulis I, Pagkalidou E, B Haidich A, K A Karagiannis A, Nakouti T, Pipili C, Oikonomou T, Gerou S, Akriviadis E

Abstract
BACKGROUND: The clinical impact of relative adrenal insufficiency (AI) on patients with stable decompensated cirrhosis (DeCi) has not been yet elucidated.
AIM: Explore the association between AI and outcome [death or liver transplantation (LT)] in patients with DeCi.
MATERIAL AND METHODS: Patients with DeCi presenting no active complication have been included. Clinical and laboratory data, including serum levels of corticosteroid-binding globulin (CBG), interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNFα) were recorded in each participant. Salivary cortisol (SC) and serum total cortisol (STC) were assessed at (T0) and 1 h (T60) after intravenous injection of 250 μg corticotropin.
RESULTS: 113 consecutive patients were totally tested. Median SC was 3.9 ng/mL and 15.5 ng/mL and median STC was 10.7 μg/dL and 22.7 μg/dL at T0 and T60 respectively. The patients with AI [group 1, n = 34 (30%)] had significantly lower systolic blood pressure (106 ± 12 vs. 113 ± 13 mmHg, p = 0.05), serum sodium (133 ± 7 vs. 137 ± 12 mEq/ L, p = 0.04), HDL (29.9 ± 14 vs. 38.6 ± 18 mg/dL, p = 0.034) and albumin (2.7 ± 0.5 vs. 3.1 ± 0.5 g/dL, p = 0.002), but higher direct bilirubin (median: 1.6 vs. 0.8 mg/dL, p = 0.029) compared to those without AI [group 2, n = 79 (70%)]. Moreover, group 1 patients presented more frequently past history of spontaneous bacterial peritonitis (SBP) [10/34 (29.4%) vs. 6/79 (7.5%), p = 0.002]. AI was significantly associated with death [HR = 2.65, 95% C.I.: 1.55 - 4.52, p = 0.003 over a follow up period of 12 (6-48) months.] Conclusions. The presence of AI in patients with stable DeCi predispose to obvious clinical implications since it is associated with circulatory dysfunction, previous history of SBP and worse survival.

PMID: 28611262 [PubMed - in process]

Respiratory motion of adrenal gland metastases: Analyses using four-dimensional computed tomography images.

Thu, 06/15/2017 - 14:02
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Respiratory motion of adrenal gland metastases: Analyses using four-dimensional computed tomography images.

Phys Med. 2017 Jun;38:54-58

Authors: Chen B, Hu Y, Liu J, Cao AN, Ye LX, Zeng ZC

Abstract
PURPOSE: To evaluate the respiratory motion of adrenal gland metastases in three-dimensional directions using four-dimensional computed tomography (4DCT) images.
METHODS: From January 2013 to May 2016, 12 patients with adrenal gland metastases were included in this study. They all underwent 4DCT scans to assess respiratory motion of adrenal gland metastases in free breathing state. The 4DCT images were sorted into 10 image series according to the respiratory phase from the end inspiration to the end expiration, and then transferred to FocalSim workstation. All gross tumor volumes (GTVs) of adrenal gland metastases were drawn by a single physician and confirmed by a second. Relative coordinates of adrenal gland metastases were automatically generated to calculate adrenal gland metastases motion in different axial directions.
RESULTS: The average respiratory motion of adrenal gland metastases in left-right (LR), cranial-caudal (CC), anterior-posterior (AP), 3-dimensional (3D) vector directions was 3.4±2.2mm, 9.5±5.5mm, 3.8±2.0mm and 11.3±5.3mm, respectively. The ratios were 58.6%±11.4% and 63.2%±12.5% when the volumes of GTVIn0% and GTV In100% were compared with volume of IGTV10phase. The volume ratio of IGTV10phase to GTV3D was 1.73±0.48.
CONCLUSIONS: Adrenal gland metastasis is a respiration-induced moving target, and an internal target volume boundary should be provided when designing the treatment plan. The CC motion of adrenal gland metastasis is predominant and >5mm, thus motion management strategies are recommended for patients undergoing external radiotherapy for adrenal gland metastasis.

PMID: 28610697 [PubMed - in process]

Retroperitoneal Ganglioneuroma Mimicking a Kidney Tumor. Case Report.

Thu, 06/15/2017 - 14:02
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Retroperitoneal Ganglioneuroma Mimicking a Kidney Tumor. Case Report.

Pol J Radiol. 2017;82:283-286

Authors: Dąbrowska-Thing A, Rogowski W, Pacho R, Nawrocka-Laskus E, Nitek Ż

Abstract
BACKGROUND: Ganglioneuroma (GN) is a rare benign tumor arising from the neural crest cells. The reported incidence of GN is one per million population. As a primary retroperitoneal tumor, it constitutes only a small percentage of 0.72 to 1.6%. GN can arise de novo or as a result of maturation of a neuroblastoma either spontaneously or after chemotherapy. The most common location is the posterior paraspinal mediastinum, retroperitoneum, neck and adrenal gland. However, GN can potentially occur anywhere along the peripheral autonomic ganglion sites. Most ganglioneuromas are asymptomatic and found incidentally.
CASE REPORT: We present a case of retroperitoneal ganglioneuroma that mimicked renal mass on imaging. The tumor was incidentally discovered during an abdominal ultrasound examination 43-year-old male patient without clinical symptoms. Complete surgical resection was subsequently performed and histopathological examination of the retroperitoneal mass revealed GN.
CONCLUSIONS: Retroperitoneal ganglioneuroma is a rare bening tumor, generally asymptomatic, which grows slowly, and appears large when it is identified. Preoperative diagnosis can be challenging, particularly in asymptomatic case. Histopathological examination is currently the mainstay of diagnosis. In the case presented herein GN stricktly adjoined to the left kidney mimicking renal mass.

PMID: 28607627 [PubMed - in process]

Adrenal tumour bigger than 5 cm - what could it be? An analysis of 139 cases.

Thu, 06/15/2017 - 14:02
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Adrenal tumour bigger than 5 cm - what could it be? An analysis of 139 cases.

Endokrynol Pol. 2017 Jun 12;:

Authors: Cichocki A, Samsel R, Papierska L, Roszkowska-Purska K, Nowak K, Jodkiewicz Z, Kasperlik-Załuska A

Abstract
INTRODUCTION: There is an increasing number of adrenal being tumours discovered incidentally during imaging examinations performed for many different indications. Radiological findings suggesting adrenal pathology may be caused by true adrenal tumours or by other retroperitoneal masses. Generally, the larger the tumour, the higher the possibility of adrenal cancer.
MATERIAL AND METHODS: Analysis of our data - 139 operations performed over 11 years (2004-2014) in patients with tumours in the adrenal area larger than 5 cm.
RESULTS: The most common finding was adrenal cancer (25.2%), benign adenoma (24.5%), pheochromocytoma (12.9%), and metastatic cancer (10.1%). In total, there were 19 various histopathological diagnoses in this group.
CONCLUSION: Although adrenal cancer is the most likely diagnosis in large adrenal tumours, a broad spectrum of various adrenal and retroperitoneal tumours with size more than 5 cm can be found in such patients.

PMID: 28604945 [PubMed - as supplied by publisher]

Heart combined with adrenal multiple pheochromocytomas.

Thu, 06/15/2017 - 14:02
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Heart combined with adrenal multiple pheochromocytomas.

J Nucl Cardiol. 2017 Jun 07;:

Authors: Zhao SH, Liang S, Luo J, Mo HD, Jiang Y, Zhang MM, Yuan J

Abstract
Pheochromocytoma is a kind of rare tumor, occurring at any site in the sympathoadrenal system. Main lesions occur within the adrenal gland; only 1%-2% occur within the chest, and most of these are located in the posterior mediastinum. Intrapericardial pheochromocytoma is extremely rare in clinic, only about 100 cases have been reported in total in both the domestic and foreignliterature since Besterman et al. first reported in 1974. It is often difficult to diagnose and locate these tumors. Hence, we present here a case of adrenal combined with heart multiple pheochromocytomas and discuss about techniques contributed to diagnosis and localization.

PMID: 28593533 [PubMed - as supplied by publisher]

Long-term recurrence-free survival of adrenocortical cancer extending into the inferior vena cava and right atrium: Case report and literature review.

Thu, 06/15/2017 - 14:02
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Long-term recurrence-free survival of adrenocortical cancer extending into the inferior vena cava and right atrium: Case report and literature review.

Medicine (Baltimore). 2017 May;96(18):e6751

Authors: Alghulayqah A, Alghasab N, Amin T, Alkahtani N, Farhat R, Alzahrani AS

Abstract
CONTEXT: Adrenocortical cancer (ACC) is rare but frequently fatal malignancy. Tumor extension into the inferior vena cava signifies an advanced stage (stage III) of the disease and is frequently associated with high risk of recurrence and short-term survival.
OBJECTIVE: To present the surgical and medical management of an unusual case of ACC with IVC invasion up to the right atrium. He has the longest reported tumor-free survival of such a situation. We also reviewed and summarized the literature of similar cases.
PATIENT: We present a 15-year old boy who presented with an 11 cm ACC extending into the IVC up to the right atrium and causing the Budd Chiari syndrome. He had complete surgical excision under cardiopulmonary bypass of a large ACC followed by Mitotane adjunctive therapy for 5 years. He is alive and free of any clinical or radiological signs of recurrence 98 months after surgery. This is the longest tumor-free survival reported in the literature of similar cases.
CONCLUSION: Significant invasion of the IVC up to the right atrium by ACC should not preclude surgery with the intent of complete resection. Cardiopulmonary bypass significantly aids this surgical procedure and Mitotane therapy should be instituted postoperatively. Long-term free-survival is possible in such a situation.
LESSONS: our patient and the literature review strongly suggest that complete surgical extirpation is the primary choice for patients with ACC invading the IVC, including those reaching the right atrium.

PMID: 28471969 [PubMed - indexed for MEDLINE]

Hypo- or conventionally fractionated radiotherapy combined with chemotherapy in patients with limited stage small cell lung cancer.

Thu, 06/15/2017 - 14:02
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Hypo- or conventionally fractionated radiotherapy combined with chemotherapy in patients with limited stage small cell lung cancer.

Radiat Oncol. 2017 Mar 11;12(1):51

Authors: Zhang J, Fan M, Liu D, Zhao KL, Wu KL, Zhao WX, Zhu ZF, Fu XL

Abstract
BACKGROUND: Previous data from our institution showed that hypofractionated thoracic radiotherapy (HypoTRT) with concurrent etoposide/platinum chemotherapy yielded favorable survival in patients with limited-stage small cell lung cancer (LS-SCLC). The present study retrospectively compared the survival outcomes, failure patterns and toxicities between groups of LS-SCLC patients treated with conventionally fractionated thoracic radiotherapy (ConvTRT) or HypoTRT combined with chemotherapy.
METHODS: Medical records of LS-SCLC patients between January 2010 and December 2013 at Fudan University Shanghai Cancer Center were retrospectively reviewed. All patients treated with chemotherapy and ConvTRT (2 Gy per fraction daily, DT ≥ 56 Gy) or HypoTRT (2.5 Gy per fraction daily, DT = 55 Gy) were eligible for analysis. Progression-free survival (PFS) and overall survival (OS) were generated for different populations using the Kaplan-Meier method and compared using the log-rank test. Comparisons of failure patterns and toxicity were analyzed using the χ (2) test.
RESULTS: A total of 170 patients treated with HypoTRT (n = 69) or ConvTRT (n = 101) were eligible for analysis. The median PFS and OS were 13.7 and 25.3 months, respectively, in the ConvTRT cohort, which was similar to the HypoTRT cohort (PFS 18.2 months, p = 0.991, and OS 27.2 months, p = 0.698), with a median follow-up of 30 months. Multivariate analysis revealed that PCI and TNM stage were prognostic factors for PFS and that PCI was prognostic for OS. The patterns of failure (stratified by local-regional recurrence, distant metastasis or both as first relapse) were similar between the dose cohorts (p = 0.693, p = 0.330, p = 0.572). Distant metastasis remained the main failure pattern. The brain was the most frequent remote failure site, followed by bone, liver and adrenal gland. PCI improved the 2-year survival rate from 46.1% to 70.0% and the 2-year PFS rate from 20.9% to 45.3%, respectively (p < 0.001). Grade ≥3 esophagitis and pneumonitis occurred in 9.9% and 11.9%, respectively, of the patients in the ConvTRT cohort and in 11.6% and 10.0%, respectively, of those in the HypoTRT cohort (p = 0.815).
CONCLUSION: This retrospective analysis demonstrated that HypoTRT or ConvTRT combined with etoposide/platinum chemotherapy yielded statistically similar survival, treatment failure outcomes, and toxicity profiles. PCI correlated with improved PFS and OS.

PMID: 28283034 [PubMed - indexed for MEDLINE]

Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.

Thu, 06/15/2017 - 14:02
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Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.

J Physiol Pharmacol. 2016 Dec;67(6):919-932

Authors: Mokra D, Kosutova P, Balentova S, Adamkov M, Mikolka P, Mokry J, Antosova M, Calkovska A

Abstract
Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO2 1.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1β, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and improved lung functions in a lavage model of ALI. These findings suggest a potential of therapy with inhaled budesonide also for patients with ARDS.

PMID: 28195073 [PubMed - indexed for MEDLINE]

Short-term effectiveness of golimumab for ulcerative colitis: Observational multicenter study.

Thu, 06/15/2017 - 14:02
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Short-term effectiveness of golimumab for ulcerative colitis: Observational multicenter study.

World J Gastroenterol. 2016 Dec 21;22(47):10432-10439

Authors: Bosca-Watts MM, Cortes X, Iborra M, Huguet JM, Sempere L, Garcia G, Gil R, Garcia M, Muñoz M, Almela P, Maroto N, Paredes JM

Abstract
AIM: To evaluate the real-world effectiveness of golimumab in ulcerative colitis (UC) and to identify predictors of response.
METHODS: We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at week 0 and 14 with the physician's global clinical assessment (PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS database.
RESULTS: Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC (E2) and 70% had extensive UC (E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor (TNF) treatment naïve, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at week 14 (a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 μg/g, and 170.5 μg/g at week 14. Being anti-TNF treatment naïve was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of follow-up. Only three adverse effects (AEs) were observed during the study; all were mild and golimumab was not interrupted.
CONCLUSION: This real-life practice study endorses golimumab's promising results, demonstrating its short-term effectiveness and confirming it as a safe drug during the induction phase.

PMID: 28058024 [PubMed - indexed for MEDLINE]

Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability.

Thu, 06/15/2017 - 14:02
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Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability.

Ann Surg. 2017 Jan;265(1):197-204

Authors: Kim Y, Margonis GA, Prescott JD, Tran TB, Postlewait LM, Maithel SK, Wang TS, Glenn JA, Hatzaras I, Shenoy R, Phay JE, Keplinger K, Fields RC, Jin LX, Weber SM, Salem A, Sicklick JK, Gad S, Yopp AC, Mansour JC, Duh QY, Seiser N, Solorzano CC, Kiernan CM, Votanopoulos KI, Levine EA, Poultsides GA, Pawlik TM

Abstract
OBJECTIVE: To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC).
BACKGROUND: ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery.
METHODS: CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x).
RESULTS: One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%).
CONCLUSIONS: DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.

PMID: 28009746 [PubMed - indexed for MEDLINE]

Colorectal Cancer Liver Metastases and Concurrent Extrahepatic Disease Treated With Resection.

Thu, 06/15/2017 - 14:02
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Colorectal Cancer Liver Metastases and Concurrent Extrahepatic Disease Treated With Resection.

Ann Surg. 2017 Jan;265(1):158-165

Authors: Leung U, Gönen M, Allen PJ, Kingham TP, DeMatteo RP, Jarnagin WR, D'Angelica MI

Abstract
OBJECTIVE: The aim of the study was to evaluate outcomes after resection of colorectal liver metastases (CRLM) and concurrent extrahepatic disease (EHD), and to define prognostic factors.
BACKGROUND: There is increasing evidence to support resection of liver metastases and concurrent EHD in selected patients. Long-term survival data are lacking, and prognostic factors are not well defined.
METHODS: Retrospective review of 219 patients was undertaken between January 1992 and December 2012, who underwent hepatectomy for CRLM and resection of synchronous EHD. Survival outcomes were estimated by the Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed. A scoring system for prognostication was developed.
RESULTS: The median, 3, 5, and 10-year overall survival were 34.4 months, 49%, 28%, and 10%, respectively. Disease recurred in 185 patients (90.2%) at a median of 8 months. There were 8 actual 10-year survivors. The site of EHD affected survival, with portal, retroperitoneal nodes and multiple sites associated with the worst prognoses. The size of the largest CRLM, the number of CRLM, unfavorable site of EHD, and progression of CRLM on neoadjuvant therapy were associated with overall survival on univariate and multivariate analyses. Three variables, assigned 1 point each, were used to create an EHD risk score: largest CRLM greater than 3 cm, greater than 5 CRLM, and unfavorable site of EHD. The resulting score was prognostic of overall and recurrence-free survival.
CONCLUSIONS: Long-term survival is possible after resection of liver metastases and concurrent EHD, but true cure is rare. A proposed scoring system may identify patients most likely to benefit from surgery.

PMID: 28009741 [PubMed - indexed for MEDLINE]

Crohn's Disease Activity and Concomitant Immunosuppressants Affect the Risk of Serious and Opportunistic Infections in Patients Treated With Adalimumab.

Thu, 06/15/2017 - 14:02
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Crohn's Disease Activity and Concomitant Immunosuppressants Affect the Risk of Serious and Opportunistic Infections in Patients Treated With Adalimumab.

Am J Gastroenterol. 2016 Dec;111(12):1806-1815

Authors: Osterman MT, Sandborn WJ, Colombel JF, Peyrin-Biroulet L, Robinson AM, Zhou Q, Lewis JD

Abstract
OBJECTIVES: Anti-tumor necrosis factor (TNF) drugs are commonly used to treat moderate-to-severe Crohn's disease (CD). Both the activity of CD and the concomitant immunosuppressants (corticosteroids and immunomodulators) used with anti-TNF drugs could increase the risk of infection. We determined the relative risk of serious and opportunistic infections associated with increasing disease activity and concomitant immunomodulators and corticosteroids in patients with CD treated with adalimumab.
METHODS: This pooled analysis identified incident treatment-emergent serious and opportunistic infections among patients with CD in clinical trials of adalimumab. Disease activity was assessed with the Crohn's Disease Activity Index (CDAI).
RESULTS: The analysis included 2,266 patients treated with adalimumab with median age 35 years. Higher disease activity was associated with significantly increased risks of both serious and opportunistic infections at 1 year, with each 100-point increase in CDAI associated with a >30% increased risk of each type of infection. Concomitant use of immunomodulators was associated with a significant >3-fold decreased risk of serious infection (hazard ratio (HR) 0.29 (0.08-0.98), P=0.045) by 1 year. Concomitant use of corticosteroids was associated with a significantly increased risk of serious infection by day 120 (HR 2.40 (1.33-4.35), P=0.004). Concomitant use of either category of immmunosuppressant was associated with numerically higher rates of opportunistic infection, 40% of which were due to herpes zoster, compared with adalimumab monotherapy.
CONCLUSIONS: Higher disease activity in CD is associated with significantly increased risks of both serious and opportunistic infections. In addition to corticosteroid-sparing strategies, consideration should be given to expanding herpes zoster vaccination guidelines to include younger patients.

PMID: 27670599 [PubMed - indexed for MEDLINE]

Surgical quality of minimally invasive adrenalectomy for adrenocortical carcinoma: a contemporary analysis using the National Cancer Database.

Thu, 06/15/2017 - 14:02
Related Articles

Surgical quality of minimally invasive adrenalectomy for adrenocortical carcinoma: a contemporary analysis using the National Cancer Database.

BJU Int. 2017 Mar;119(3):436-443

Authors: Maurice MJ, Bream MJ, Kim SP, Abouassaly R

Abstract
OBJECTIVES: To compare quality outcomes between open (OA) and minimally invasive (MIA) adrenalectomy for adrenocortical carcinoma (ACC).
PATIENTS AND METHODS: In the National Cancer Database, we identified 481 patients with non-metastatic ACC who underwent adrenalectomy from 2010 to 2013. OA and MIA were compared on positive surgical margin (PSM) and lymph node dissection (LND) rates (primary outcomes), and lymph node yield, length of stay (LOS), readmission, and overall survival (secondary outcomes). Using the intention-to-treat principle, minimally-invasive-converted-to-open cases were considered MIA. Logistic regression analysis was used to identify predictors of PSMs and LND. Associations between approach and the outcomes were further assessed by stage and tumour size.
RESULTS: Overall, 161 patients (33.5%) underwent MIA. MIA was used more commonly in older, comorbid patients; for smaller, localised tumours; and at lower-volume centres. In the intention-to-treat analysis, MIA independently predicted PSMs [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.6; P = 0.03) and no LND (OR 0.1, 95% CI 0.03-0.6; P = 0.01). On subgroup analysis, the association between MIA and PSMs only held true for pT3 disease (48.7% vs 26.7%, P = 0.01). A higher PSM rate was seen for tumours of ≥10 cm managed with MIA vs OA, but this difference was not significant (28.2% vs 18.5%, P = 0.16). Likewise, the association between MIA and no LND was only observed for male patients, tumours ≥10 cm, and cN0 disease. After excluding minimally-invasive-converted-to-open cases, the difference in PSM was less pronounced and non-significant (OR 1.8, 95% CI 0.9-3.4; P = 0.08). MIA was associated with significantly shorter median LOS (3 vs 6 days, P < 0.01) and non-significantly decreased readmissions (4.4% vs 8.8%, P = 0.08) compared to OA without any difference in lymph node yield or overall survival.
CONCLUSION: For organ-confined disease, MIA offers comparable surgical quality to OA, while expediting inpatient recovery. OA is associated with superior outcomes for locally advanced disease.

PMID: 27488744 [PubMed - indexed for MEDLINE]

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