Unique manifestations of catecholamine release in malignant pheochromocytoma: an experience within an inpatient palliative care unit.

PubMed

Coupe, Nicholas Anthony; Lacey, Judith; Sanderson, Christine

2012-05-01

Malignant pheochromocytoma is a rare disorder. We describe the case of a 41-year-old female with disseminated metastatic pheochromocytoma who was admitted for ongoing palliative and supportive care within an inpatient palliative care unit. Predominant symptoms included severe gastrointestinal pseudo-obstruction and orthostatic hypotension Pseudo-obstruction management included percutaneous enterogastric and percutaneous enterojejunostomy tubes for gastric decompression and delivery of nutrition, respectively. Debilitating symptoms of orthostatic hypotension were mitigated with judicious fluid balance and appropriate use of adrenergic blocking agents. The potential for metoclopramide to worsen symptoms also was a significant component of management. The case presents rare features of this unusual disease and is unique for its setting within the confines of a palliative care unit. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

[Complete hormonal and metabolic response after iodine-131 metaiodobenzylguanidine treatment in a patient diagnosed of malignant pheochromocytoma].

PubMed

García Alonso, M P; Balsa Bretón, M A; Paniagua Correa, C; Castillejos Rodríguez, L; Rodríguez Pelayo, E; Mendoza Paulini, A; Ortega Valle, A; Penín González, J

2013-01-01

Radiolabeled metaiodobenzylguanidine is an analogue of norepinephrine used to localize tumors that express the neurohormone transporters, specifically those derived from the neural crest having a neuroendocrine origin. It is also used to treat non-surgical metastases derived from them. A review of the literature revealed symptomatic improvements associated to a decrease in hormone levels in a significant percentage of patients after (131)I-MIBG treatment. However, complete tumor remission has been described only in very few cases and hardly ever when bone metastases exist. We present a case of a patient diagnosed of malignant pheochromocytoma who achieved complete hormonal and metabolic response after (131)I-MIBG treatment (600 mCi) in spite of the presence of bone metastases. Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

Angiogenesis and Vascular Architecture in Pheochromocytomas

PubMed Central

Favier, Judith; Plouin, Pierre-François; Corvol, Pierre; Gasc, Jean-Marie

2002-01-01

Angiogenesis is a critical step in tumor growth and metastatic invasion. We here report the study of the vascular status of 10 benign and 9 malignant pheochromocytomas. We examined the vascular architecture after immunostaining endothelial cells (CD34) and vascular smooth muscle cells (α-actin) and identified a vascular pattern characteristic of malignant lesions. To define a gene expression profile indicative of the invasive phenotype, we studied by in situ hybridization the expression of genes encoding several pro- and anti-angiogenic factors [hypoxia-inducible factor (HIF-1α), EPAS1, vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins and their receptor Tie2, five genes of the endothelin system, and thrombospondin 1]. A semiquantitative evaluation of the labeling revealed an induction of genes encoding EPAS1, VEGF, VEGFR-1, VEGFR-2, endothelin receptor, type B (ETB) and endothelin receptor, type A (ETA) in malignant pheochromocytomas as compared to benign tumors. These differences were observed in tumor cells, in endothelial cells, or in both. Quantification by real-time reverse-transcriptase polymerase chain reaction showed an increase of EPAS1, VEGF, and ETB transcripts of 4.5-, 3.5-, and 10-fold, respectively, in malignant versus benign tumors. Furthermore, we observed a strong correlation between the expression of EPAS1 and VEGF in tumoral tissue and between EPAS1 and ETB in endothelial cells. Altogether, our observations show that analysis of angiogenesis provides promising new criteria for the diagnosis of malignant pheochromocytomas. PMID:12368197

Utility of GATA3 in the differential diagnosis of pheochromocytoma.

PubMed

Perrino, Carmen M; Ho, Alex; Dall, Christopher P; Zynger, Debra L

2017-09-01

GATA3 is a relatively new immunohistochemical marker which shows consistent nuclear expression in a variety of tumours, including breast and urothelial carcinoma. The staining pattern of GATA3 in adrenal lesions is not well established. We aim to describe the expression of GATA3 in adrenal tumours and determine if there is differential staining between pheochromocytoma and adrenal cortical carcinoma. A retrospective search was performed to identify 74 adrenal lesions which were tested immunohistochemically for GATA3 expression. GATA3 was negative in 90% of adrenal cortical carcinoma. In contrast, pheochromocytomas were frequently positive (71%), including benign pheochromocytoma, pheochromocytoma with features concerning for malignancy, malignant (metastatic) pheochromocytoma and composite pheochromocytoma with ganglioneuroma. Metastatic lung adenocarcinoma in the adrenal gland had occasional (36%) expression, while metastatic clear cell renal cell carcinoma in the adrenal gland did not express GATA3. As the most common pitfall in diagnosing adrenal cortical carcinoma is mistaking it for pheochromocytoma or vice versa, GATA3 may be useful in narrowing the differential diagnosis as a part of a panel of immunohistochemical markers. However, occasional GATA3 expression in the most common source of metastases within the adrenal gland, metastatic pulmonary adenocarcinoma, may confound the diagnosis due to the overlapping expression with pheochromocytoma and other carcinomas. © 2017 John Wiley & Sons Ltd.

Hypertensive crisis secondary to pheochromocytoma.

PubMed

Greenleaf, Christopher E; Griffin, Laura A; Shake, Jay G; Orr, Wayne S

2017-07-01

Pheochromocytoma is an uncommon tumor of the adrenal glands that can present with headaches, sweating, palpitations, and paroxysmal hypertension. Pheochromocytoma crisis can lead to cardiomyopathy, pulmonary edema, and even total circulatory collapse. We describe a patient with hypoxic respiratory failure requiring extracorporeal membrane oxygenation to stabilize until the pheochromocytoma was discovered and treated.

Pheochromocytoma/Paraganglioma: Review of perioperative management of blood pressure and update on genetic mutations associated with pheochromocytoma

PubMed Central

Fishbein, Lauren; Orlowski, Robert; Cohen, Debbie

2015-01-01

Pheochromocytomas and paragangliomas are rare tumors with high morbidity, due to excessive catecholamine secretion, even though the majority of tumors are benign. The use of perioperative blockade regimens, together with improved surgical techniques, has greatly impacted the perioperative morbidity associated with these tumors. The old dogma of the “tumor of tens” no longer holds true. For example, at least one-third of all pheochromocytomas and paragangliomas are hereditary with mutations in one of ten well characterized susceptibility genes, and one-quarter of all tumors are malignant. This review will focus on the perioperative management of pheochromocytoma and paragangliomas and the clinical implications of the associated genetic mutations. PMID:23730992

Predictors of malignancy in patients with pheochromocytomas/paragangliomas: Asian Indian experience

PubMed Central

Sarathi, Vijaya; Kasaliwal, Rajeev; Pandit, Reshma; Goroshi, Manjunath; Malhotra, Gaurav; Dalvi, Abhay; Bakshi, Ganesh; Bhansali, Anil; Rajput, Rajesh; Shivane, Vyankatesh; Lila, Anurag; Bandgar, Tushar; Shah, Nalini S

2016-01-01

Background and aims Malignant transformation of pheochromocytomas/paragangliomas (PCC/PGL) is a rare occurrence, and predictive factors for the same are not well understood. This study aims to identify the predictors of malignancy in patients with PCC/PGL. Materials and methods We performed a retrospective analysis of 142 patients with either PCC or PGL registered at our institute between 2000 and 2015. Records were evaluated for clinical parameters like age, gender, familial/syndromic presentation, symptomatic presentation, biochemistry, size, number and location of tumours and presence of metastases and mode of its diagnosis. Results Twenty patients were found to have metastases; 13 had metastases at diagnosis and seven during follow-up. Metastases were detected by radiology (CT-neck to pelvis) in 11/20 patients (5/13 synchronous and 6/7 metachronous), 131I-metaiodobenzylguanidine in five (2/12 synchronous and 3/6 metachronous) patients and 18F-flurodeoxyglucose PET/CT in 15 (12/12 synchronous and 3/3 metachronous) patients. Malignant tumours were significantly larger than benign tumours (8.3 ± 4.1 cm, range: 3–22 cm vs 5.7 ± 2.3 cm, range: 2–14 cm, P = 0.0001) and less frequently metanephrine secreting. On linear regression analysis, tumour size and lack of metanephrine secretion were the independent predictors of malignancy. Conclusions Patients with primary tumour size >5.7 cm and lack of metanephrine secretory status should be evaluated for possible malignancy not only at diagnosis but also in the postoperative period. As compared to CT and 131I-MIBG scan, 18F-flurodeoxyglucose PET/CT analyses are better (sensitivity: 100%) for the diagnosis of metastases in our study. PMID:27852633

Molecular and Therapeutic Advances in the Diagnosis and Management of Malignant Pheochromocytomas and Paragangliomas

PubMed Central

Lowery, Aoife J.; Walsh, Siun; McDermott, Enda W.

2013-01-01

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies. PMID:23576482

Unusual presentation of pheochromocytoma: thirteen years of anxiety requiring psychiatric treatment.

PubMed

Alguire, Catherine; Chbat, Jessica; Forest, Isabelle; Godbout, Ariane; Bourdeau, Isabelle

2018-01-01

Pheochromocytoma is a rare tumor of the adrenal gland. It often presents with the classic triad of headache, palpitations and generalized sweating. Although not described as a typical symptom of pheochromocytoma, anxiety is the fourth most common symptom reported by patients suffering of pheochromocytoma. We report the case of a 64 year old man who had severe anxiety and panic disorder as presenting symptoms of pheochromocytoma. After 13 years of psychiatric follow-up, the patient was diagnosed with malignant pheochromocytoma. After surgical resection of his pheochromocytoma and his hepatic metastases, the major panic attacks completely disappeared, the anxiety symptoms improved significantly and the psychiatric medications were stopped except for a very low maintenance dose of venlafaxine. We found in our cohort of 160 patients with pheochromocytoma 2 others cases of apparently benign tumors with severe anxiety that resolved after pheochromocytoma resection. These cases highlight that pheochromocytoma should be included in the differential diagnosis of refractory anxiety disorder. Anxiety and panic disorder may be the main presenting symptoms of pheochromocytoma.The diagnosis of pheochromocytoma should be excluded in cases of long-term panic disorder refractory to medications since the anxiety may be secondary to a catecholamine-secreting tumor.Surgical treatment of pheochromocytoma leads to significant improvement of anxiety disorders.

Molecular markers of paragangliomas/pheochromocytomas

PubMed Central

Zaretsky, Andrew R; Alekseev, Boris Y; Pokrovsky, Anatoly V; Golovyuk, Alexander L; Melnikova, Nataliya V; Stepanov, Oleg A; Kalinin, Dmitry V; Moskalev, Alexey A; Krasnov, George S; Dmitriev, Alexey A; Kudryavtseva, Anna V

2017-01-01

Paragangliomas/pheochromocytomas comprise rare tumors that arise from the extra-adrenal paraganglia, with an incidence of about 2 to 8 per million people each year. Approximately 40% of cases are due to genetic mutations in at least one out of more than 30 causative genes. About 2530% of pheochromocytomas/paragangliomas develop under the conditions of a hereditary tumor syndrome a third of which are caused by mutations in the VHL gene. Together, the gene mutations in this disorder have implicated multiple processes including signaling pathways, translation initiation, hypoxia regulation, protein synthesis, differentiation, survival, proliferation, and cell growth. The present review contemplates the mutations associated with the development of pheochromocytomas/paragangliomas and their potential to serve as specific markers of these tumors and their progression. These data will improve our understanding of the pathogenesis of these tumors and likely reveal certain features that may be useful for early diagnostics, malignancy prognostics, and the determination of new targets for disease therapeutics. PMID:28187001

Retroperitoneoscopic adrenalectomy in pheochromocytoma

PubMed Central

Hisano, Marcelo; Vicentini, Fabio Carvalho; Srougi, Miguel

2012-01-01

Since the first laparoscopic adrenalectomy, the technique has evolved and it has become the standard of care for many adrenal diseases, including pheochromocytoma. Two laparoscopic accesses to the adrenal have been developed: transperitoneal and retroperitoneal. Retroperitoneoscopic adrenalectomy may be recommended for the treatment of pheochromocytoma with the same peri-operative outcomes of the transperitoneal approach because it allows direct access to the adrenal glands without increasing the operative risks. Although technically more demanding than the transperitoneal approach, retroperitoneoscopy can shorten the mean operative time, which is critical for cases with pheochromocytoma where minimizing the potential for intra-operative hemodynamic changes is essential. Blood loss and the convalescence time can be also shortened by this approach. There is no absolute indication for either the transperitoneal or retroperitoneal approach; however, the latter procedure may be the best option for patients who have undergone previous abdominal surgery and obese patients. Also, retroperitoneoscopic adrenalectomy is a good alternative for treating cases with inherited pheochromocytomas, such as multiple endocrine neoplasia type 2A, in which the pheochromocytoma is highly prevalent and frequently occurs bilaterally. PMID:22584723

Intracranial Epidural Metastases of Adrenal Pheochromocytoma: A Rare Entity.

PubMed

Boettcher, Lillian B; Abou-Al-Shaar, Hussam; Ravindra, Vijay M; Horn, Jeffrey; Palmer, Cheryl Ann; Menacho, Sarah T

2018-06-01

Pheochromocytomas are uncommon neuroendocrine tumors of the adrenal medulla. Malignant behavior is seen in approximately 10% of these lesions, evidenced by distant metastasis to sites without chromaffin tissue. Here we report a rare case of intracranial epidural metastases of an adrenal pheochromocytoma in a 24-year-old man. The patient originally presented at age 10 years with adrenal pheochromocytoma and subsequently developed extensive metastatic bone and lung disease. He was monitored in the intervening years until recent imaging demonstrated an enlarging right parietal mass. On surgical resection of the parietal lesion, the tumor was highly vascularized and confined to the epidural space. To the best of our knowledge, this is the first reported case of metastatic epidural spread of pheochromocytoma without concomitant subdural or intraparenchymal extension. Copyright © 2018 Elsevier Inc. All rights reserved.

Metastatic pheochromocytoma: clinical, genetic, and histopathologic characteristics

PubMed Central

Zelinka, Tomáš; Musil, Zdeněk; Dušková, Jaroslava; Burton, Deborah; Merino, Maria J; Milosevic, Dragana; Widimský, Jiří; Pacak, Karel

2011-01-01

Background Pheochromocytomas are tumors arising from chromaffin tissue located in the adrenal medulla associated with typical symptoms and signs which may occasionally develop metastases, which are defined as the presence of tumor cells at sites where these cells are not found. This retrospective analysis was focused on clinical, genetic, and histopathologic characteristics of primary metastatic versus primary benign pheochromocytomas. Materials and methods We identified 41 subjects with metastatic pheochromocytoma and 108 subjects with apparently benign pheochromocytoma. We assessed dimension and biochemical profile of the primary tumor, age at presentation, and time to develop metastases. Results Subjects with metastatic pheochromocytoma presented at a significantly younger age (41.4±14.7 vs. 50.2±13.7 years; P<0.001), with larger primary tumors (8.38±3.27 cm vs. 6.18±2.75 cm; P<0.001) and secreted more frequently norepinephrine (95.1% vs. 83.3 %; P=0.046) compared to subjects with apparently benign pheochromocytomas. No significant differences were found in the incidence of genetic mutations in both groups of subjects (25.7 % in the metastatic group and 14.7 % in the benign group; P=0.13). From available histopathologic markers of potential malignancy, only necrosis occurred more frequently in subjects with metastatic pheochromocytoma (27.6 % vs. 0 %; P<0.001). The median time to develop metastases was 3.6 years with the longest interval 24 years. Conclusions In conclusion, regardless of a genetic background, the size of a primary pheochromocytoma and age of its first presentation are two independent risk factors associated with the development of metastatic disease. PMID:21692797

Pheochromocytoma during Pregnancy

MedlinePlus

... foods high in tyramine (such as red wine, chocolate, and cheese). Tests that examine the blood and ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

Pheochromocytoma

MedlinePlus

Pheochromocytoma Overview A pheochromocytoma (fee-o-kroe-moe-sy-TOE-muh) is a rare, usually noncancerous (benign) tumor that develops in an adrenal ... it can affect both. If you have a pheochromocytoma, the tumor releases hormones that cause either episodic ...

The many faces of pheochromocytoma.

PubMed

Ghayee, H K; Wyne, K L; Yau, F S; Snyder, W H; Holt, S; Gokaslan, S Tunc; Nwariaku, F

2008-05-01

To recognize and manage pheochromocytomas in unusual settings. Three case reports are presented with clinical, biochemical, imaging, and operative findings. The pitfalls in diagnosis of pheochromocytomas and management are addressed. We begin with a 27-yr-old gravida 2, para 1 Caucasian woman with unexplained tachycardia and hypertension during a routine pre-natal visit at 30 weeks estimated gestational age. Urinary studies revealed elevated catecholamines. Magnetic resonance imaging localized a 6.6-cm right adrenal mass with features consistent with a pheochromocytoma. She was medically managed with phenoxybenzamine and propranolol until 35 weeks, after which she underwent a combined Cesarean section, and open right adrenalectomy. Another patient, a 36-yr-old African-American woman presented to a hospital in cardiac arrest, with elevated serum troponins, and underwent cardiac catheterization, which revealed normal coronary arteries. A computed tomography (CT) scan revealed a left adrenal mass and CT-guided biopsy was consistent with a pheochromocytoma, although prior studies were negative. Finally, we present a 49-yr-old Caucasian woman who had a right adrenalectomy 10 yr prior and presented to the clinic with fluctuating blood pressures, headaches, and palpitations. Further testing revealed she had a recurrent metastatic pheochromocytoma. The challenges behind treating these patients are further explored. Antenatal diagnosis of pheochromocytoma, though challenging, is associated with lower maternal and fetal morbidity and mortality. The differential diagnosis for cardiac arrest in the presence of normal coronary arteries should include a pheochromocytoma. Finally, treatment with iodinated metaiodobenzylguanidine may be a therapeutic option for those patients with metastatic pheochromocytomas.

Pheochromocytoma in neurofibromatosis type 1 during pregnancy.

PubMed

Remón-Ruiz, Pablo; Aliaga-Verdugo, Alberto; Guerrero-Vázquez, Raquel

2017-02-01

Pregnant women with neurofibromatosis type 1 (NF-1) have increased complications during gestation, including hypertensive disorders that are sometimes caused by pheochromocytoma. Pheochromocytoma is an extremely rare condition during pregnancy, and the main clinical manifestation is hypertension. If not properly treated, pheochromocytoma has high maternal and fetal mortality rates. Early recognition and adequate clinical management before delivery have led to better outcomes in the last few decades. Despite the association of NF-1 and pheochromocytoma, there are few clinical reports of these two conditions in pregnant patients. We present a rare case of pheochromocytoma diagnosed during pregnancy in a patient with NF-1, and we describe the treatment and the obstetric and fetal outcomes. We also review other medical conditions related to NF-1 that complicated this patient's pregnancy.

[Pheochromocytoma in 8-year observation at a single endocrinological center in Wroclaw].

PubMed

Bednarek-Tupikowska, Grazyna; Bucyk, Barbara; Daroszewski, Jacek; Bidzińska-Speichert, Bozena; Bohdanowicz-Pawlak, Anna; Szymczak, Jadwiga; Bednorz, Włodzimierz; Podgórski, Franciszek; Zareba-Bogdał, Elzbieta; Kuliczkowska-Płaksej, Justyna; Lenarcik, Agnieszka; Filus, Alicja; Kałuzny, Marcin; Kubicka, Eliza; Syrycka, Joanna; Tupikowska, Małgorzata; Lizurej, Oskar; Bolanowski, Marek; Milewicz, Andrzej

2009-01-01

Pheochromocytoma is rare tumor with a highly variable clinical presentation. This report provides clinical picture, efficiency of diagnostics and treatment of pheochromocytoma in 8-years in the endocrinological center in Wroclaw. The records of 37 patients with pheochromocytoma were identified, who were treated in 2000-2007 in the Department of Endocrinology, Diabetology and Isotope Treatment in Wroclaw. There were 23 women (age 23-75 year) and 14 men (age 17-74). We studied frequency of clinical signs, usefulness of diagnostic methods and efficacy of treatment. The duration of the clinical history ranged from 2 months to 16 years. The most frequent symptoms were: hypertension paroxysmal and constant, palpitations, headache, sweating and anxiety. The most sensitive diagnostic method was increased concentration of urinary metanephrine in 24-hour urine. Computed tomography was the most widely used method for tumor localization. Adrenal pheochromocytoma was detecting by CT in all patients, predominated in right adrenal, in 1 case in urinary bladder. Surgery caused remission of hypertension in 59%, improvement in 26.8%, and no changes in 13.9% of patients. Malignancy was reported in 2 cases, 1 woman died after surgery. MEN 2A occur in 21.6%. The diagnosis of pheochromocytma is usually made after long duration of the disease. The study confirms that clinical presentation of pheochromocytoma is variable and nonspecific, this finding makes the diagnosis very difficult. The most typical symptom is paroxysmal hypertension, which is present only in 40%, other symptoms are nonspecific. The measurement of 24-hour urinary metanephrines was the best indicator. CT was almost always successful in localizing the tumor. Patients with pheochromocytoma should be consider for other endocrine diseases especially medullary carcinoma, primary hyperparathyroidism and other component of MEN 2A.

Is Preoperative Biochemical Testing for Pheochromocytoma Necessary for All Adrenal Incidentalomas?

PubMed Central

Jun, Joo Hyun; Ahn, Hyun Joo; Lee, Sangmin M.; Kim, Jie Ae; Park, Byung Kwan; Kim, Jee Soo; Kim, Jung Han

2015-01-01

Abstract This study examined whether imaging phenotypes obtained from computed tomography (CT) can replace biochemical tests to exclude pheochromocytoma among adrenal incidentalomas (AIs) in the preoperative setting. We retrospectively reviewed the medical records of all patients (n = 251) who were admitted for operations and underwent adrenal-protocol CT for an incidentally discovered adrenal mass from January 2011 to December 2012. Various imaging phenotypes were assessed for their screening power for pheochromocytoma. Final diagnosis was confirmed by biopsy, biochemical tests, and follow-up CT. Pheochromocytomas showed similar imaging phenotypes as malignancies, but were significantly different from adenomas. Unenhanced attenuation values ≤10 Hounsfield units (HU) showed the highest specificity (97%) for excluding pheochromocytoma as a single phenotype. A combination of size ≤3 cm, unenhanced attenuation values ≤ 10 HU, and absence of suspicious morphology showed 100% specificity for excluding pheochromocytoma. Routine noncontrast CT can be used as a screening tool for pheochromocytoma by combining 3 imaging phenotypes: size ≤3 cm, unenhanced attenuation values ≤10 HU, and absence of suspicious morphology, and may substitute for biochemical testing in the preoperative setting. PMID:26559265

Pheochromocytoma of urinary bladder - a case report.

PubMed

Sharma, Shaleen; Gokhro, Sunil; Sharma, K K; Sadasukhi, T C

2007-08-01

Pheochromocytomas are catecholamine producing neuroendocrine tumours. Bladder involvement with pheochromocytoma is rare that usually presents with hypertension, hematuria and syncope often related to voiding. Clinical manifestation may be inconsistent and high index of suspicion is required for accurate diagnosis. We report a case, who presented with gross intermittent hematuria and mild elevation of pulserate and bloodpressure. Patient was adequately treated with partial cystectomy.

Igf-I regulates pheochromocytoma cell proliferation and survival in vitro and in vivo.

PubMed

Fernández, María Celia; Venara, Marcela; Nowicki, Susana; Chemes, Héctor E; Barontini, Marta; Pennisi, Patricia A

2012-08-01

IGFs are involved in malignant transformation and growth of several tissues, including the adrenal medulla. The present study was designed to evaluate the impact of IGF-I on pheochromocytoma development. We used a murine pheochromocytoma (MPC) cell line (MPC4/30) and an animal model with a reduction of 75% in circulating IGF-I levels [liver-IGF-I-deficient (LID) mice] to perform studies in vitro and in vivo. We found that, in culture, IGF-I stimulation increases proliferation, migration, and anchorage-independent growth, whereas it inhibits apoptosis of MPC cells. When injected to control and to LID mice, MPC cells grow and form tumors with features of pheochromocytoma. Six weeks after cell inoculation, all control mice developed sc tumors. In contrast, in 73% of LID mice, tumor development was delayed to 7-12 wk, and the remaining 27% did not develop tumors up to 12 wk after inoculation. LID mice harboring MPC cells and treated with recombinant human IGF-I (LID+) developed tumors as controls. Tumors developed in control, LID, and LID+ mice had similar histology and were similarly positive for IGF-I receptor expression. The apoptotic index was higher in tumors from LID mice compared with those from control mice, whereas vascular density was decreased. In summary, our work demonstrates that IGF-I has a critical role in maintaining tumor phenotype and survival of already transformed pheochromocytoma cells and is required for the initial establishment of these tumors, providing encouragement to carry on research studies to address the IGF-I/IGF-I receptor system as a target of therapeutic strategies for pheochromocytoma treatment in the future.

Pheochromocytoma

MedlinePlus

... this page: //medlineplus.gov/ency/article/000340.htm Pheochromocytoma To use the sharing features on this page, please enable JavaScript. Pheochromocytoma is a rare tumor of adrenal gland tissue. ...

Pheochromocytoma Crisis With Severe Cyclic Blood Pressure Fluctuations in a Cardiac Pheochromocytoma Patient Successfully Resuscitated by Extracorporeal Membrane Oxygenation

PubMed Central

Zhou, Xiang; Liu, Dawei; Su, Longxiang; Long, Yun; Du, Wei; Miao, Qi; Li, Fang; Jin, Zhengyu; Zeng, Zhengpei; Luo, Ailun; Huang, Yuguang

2015-01-01

Abstract Cardiac pheochromocytoma is relatively rare. Few reports describe the intraoperative and postoperative progression of patients experiencing a life-threatening pheochromocytoma crisis treated with extracorporeal membrane oxygenation (ECMO). A 35-year-old man was referred to our facility for paroxysmal hypertension with a 10-year history of sweating, headaches, cardiac palpitations, and postexercise dyspnea. The patient initially underwent urine catecholamine measurement and an isotope scan, somatostatin receptor scintigraphy, and 18F-fluorodeoxyglucose positron emission tomography/computer tomography (CT), which indicated a multiple, cardiac pheochromocytoma. Echocardiography, cardiac magnetic resonance imaging (MRI), CT reconstruction, and a coronary CT angiography revealed several lesions at the aortic root and along the cardiac vasculature. Multifocal cardiac pheochromocytoma was diagnosed and pheochromocytoma crisis with severe cyclic blood pressure fluctuation occurred during surgery. Surgical resection of multiple pheochromocytomas in the right medial carotid sheath, mediastinum between the main and pulmonary arteries, and between the abdominal aorta and inferior vena artery was performed. To ensure cardiac perfusion and avoid severe circulatory fluctuation, the cardiac paraganglioma resection was prioritized. After resecting the cardiac pheochromocytoma, a severe pheochromocytoma crisis with rapid cyclic blood pressure fluctuation developed. ECMO and intraaortic balloon pump (IABP) were initiated to stabilize circulation and perfusion. Phenoxybenzamine, norepinephrine, epinephrine, and fluid resuscitation were administered to support cardiovascular function. The magnitude of blood pressure fluctuation steadily decreased with treatment. IABP was discontinued after 3 days, and ECMO was discontinued after 16 days. The patient was discharged 3 months postoperatively. This case indicates that mechanical life support with ECMO is a valuable option for

Stages of Pheochromocytoma and Paraganglioma

MedlinePlus

... foods high in tyramine (such as red wine, chocolate, and cheese). Tests that examine the blood and ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

Pigmented Pheochromocytoma: an Unusual Variant of a Common Tumor.

PubMed

Kakkar, Aanchal; Kaur, Kavneet; Kumar, Tarun; Cherian, Libin Babu; Kaushal, Rohit; Sharma, Mehar Chand; Dhar, Anita; Seth, Amlesh; Jain, Deepali

2016-03-01

Pheochromocytoma is a neuroendocrine tumor arising from the adrenal medulla. A number of variants of pheochromocytoma are known; however, pigmented pheochromocytoma is extremely rare, with only few cases reported in literature. We report the cases of two patients with pigmented pheochromocytoma. Case 1 was a 28-year-old female who presented with complaints of breathlessness, palpitations, and anxiety for 5 years, which had worsened over the last 8 months. Computed tomography (CT) abdomen showed a right suprarenal mass. Case 2 was that of an 18-year-old girl who presented with similar complaints and was diagnosed with hypertension. CT abdomen showed bilateral adrenal masses. Urinary vanillyl mandelic acid was raised in both patients. Sections examined from all three tumors showed cells arranged in Zellballen pattern, separated by thin fibrovascular septae. Tumor cells showed moderate to marked nuclear pleomorphism in case 1. Mitoses were, however, not seen. There was no evidence of capsular or vascular invasion. Many of the tumor cells showed intracytoplasmic black pigment, which was positive for Fontana-Masson and was bleach-labile, confirming it as melanin. Hemosiderin deposition was also identified. Large areas of hemorrhagic necrosis were seen in case 1. Tumor cells were immunopositive for chromogranin and synaptophysin, while they were negative for HMB-45. Electron microscopy was performed. A final diagnosis of pigmented pheochromocytoma was rendered in both cases. Pigmented pheochromocytoma is a very rare tumor, which needs to be differentiated from other pigmented tumors like malignant melanoma of adrenal gland and pigmented adrenal adenoma. Histochemistry and immunohistochemistry help in making this distinction.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

PubMed Central

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-01-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

PubMed

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-09-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

Genetics Informs Precision Practice in the Diagnosis and Management of Pheochromocytoma.

PubMed

Neumann, Hartmut P H; Young, William; Krauss, Tobias; Bayley, Jean-Pierre; Schiavi, Francesca; Opocher, Giuseppe; Boedeker, Carsten; Tirosh, Amit; Castinetti, Frederic; Ruf, Juri; Beltsevich, Dmitry; Walz, Martin K; Groeben, Harald; Von Dobschuetz, Ernst; Gimm, Oliver; Wohllk, Nelson; Pfeifer, Marija; Lourenço, Delmar Muniz; Peczkowska, Mariola; Patocs, Attila; Ngeow, Joanne; Makay, Ozer; Shah, Nalini; Tischler, Arthur S; Leijon, Helena; Pennelli, Gianmaria; Villar Gómez de Las Heras, Karina; Links, Thera P; Bausch, Birke; Eng, Charis

2018-05-24

Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the 10 known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers, and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally-invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment, and surveillance of this rare neoplasm.

Nationwide review of hormonally active adrenal tumors highlights high morbidity in pheochromocytoma.

PubMed

Parikh, Punam P; Rubio, Gustavo A; Farra, Josefina C; Lew, John I

2017-07-01

Adrenal adenomas are benign tumors often discovered incidentally, and >70% are hormonally inactive. The remaining subset may produce excess aldosterone, cortisol, or catecholamine. Perioperative outcomes after adrenalectomy for such "hormonally active" tumors remain unclear. This study examines in-hospital outcomes after unilateral adrenalectomy for hormonally active tumors. A retrospective review was performed using the Nationwide Inpatient Sample (2006-2011) to identify patients undergoing unilateral adrenalectomy for hormonally active or inactive tumors. Malignant adrenal tumors were excluded. Demographics, comorbidities, and postoperative complications were evaluated by univariate analysis, using two-tailed Chi-square and t-tests and multivariate logistic regression. Of 27,312 patients who underwent adrenalectomy, 78% (n = 21,279) had hormonally inactive and 22% (n = 6033) had hormonally active adrenal tumors. Among the latter, 65% (n = 4000) had primary hyperaldosteronism (Conn's syndrome), 33% (n = 1996) had hypercortisolism (Cushing's syndrome), and 1.4% (n = 85) had pheochromocytoma. Patients with pheochromocytoma had higher rate of comorbidities including congestive heart failure, chronic lung disease, and malignant hypertension compared with remaining hormonally active tumors (12% versus 4%, 18% versus 11%, 6% versus 2%; P < 0.01). For patients with pheochromocytoma versus other hormonally active tumors, mean length of stay was 5 versus 3 d and total in-hospital cost was $50,000 versus $41,000 (P < 0.01). On multivariate analysis, pheochromocytoma had an independently higher risk for intraoperative blood transfusion (4.2, 95% confidence interval [CI] 2.4-7.2), postoperative cardiac (7.6, 95% CI 2.8-20.2), and respiratory (1.9, 95% CI 1.0-3.3) complications. Patients with pheochromocytoma have high rates of preoperative comorbidities, postoperative cardiopulmonary complications, and longer and more costly hospitalizations. Such high

Treatment Option Overview (Pheochromocytoma and Paraganglioma)

MedlinePlus

... foods high in tyramine (such as red wine, chocolate, and cheese). Tests that examine the blood and ... cause signs or symptoms are treated with drug therapy. Drug therapy begins when pheochromocytoma or paraganglioma is ...

Pheochromocytoma and Paraganglioma: Overview

MedlinePlus

... Family Lodge Children's Inn Frequently Asked Questions Overview Pheochromocytoma Pheochromocytoma is a rare endocrine tumor originating in ... abdomen, or pelvis. Who Should Be Examined for Pheochromocytoma? Patients with very difficult-to-control hypertension Patients ...

Pheochromocytoma in Urologic Practice

PubMed Central

Waingankar, Nikhil; Bratslavsky, Gennady; Jimenez, Camilo; Russo, Paul; Kutikov, Alexander

2016-01-01

Context Pheochromocytoma is regularly encountered in urological practice and requires a thoughtful and careful clinical approach. Objective To review clinical aspects of management of pheochromocytoma in urologic practice. Evidence Acquisition A systematic review of English-language literature was performed through year 2015 using the Medline database. Manuscripts were selected with consensus of the coauthors and evaluated using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. Evidence Synthesis Findings and recommendations of the evaluated manuscripts are discussed with an emphasis on the description of presentation, diagnosis, evaluation, and perioperative care. Conclusion In addition to surgical expertise, appropriate management of pheochromocytoma in urologic practice requires nuanced understanding of pathophysiology, genetics, and endocrinological principles. When skillfully managed, the vast majority of patients with pheochromocytoma should expect an excellent prognosis. Patient Summary In this article we review the clinical approach to patients with pheochromocytoma, a tumor that stems from the innermost part of the adrenal gland and that often secretes excessive amounts of powerful hormones such as noradrenaline and adrenaline. Significant expertise is required to appropriately manage patients with these tumors. Take Home Message In addition to surgical expertise, appropriate management of pheochromocytoma in urologic practice requires nuanced understanding of pathophysiology, genetics, and endocrinological principles. When skillfully managed, vast majority of patients with pheochromocytoma should expect an excellent prognosis. PMID:28078330

Coexistence of pheochromocytoma with uncommon vascular lesions

PubMed Central

Kota, Sunil Kumar; Kota, Siva Krishna; Meher, Lalit Kumar; Jammula, Sruti; Panda, Sandip; Modi, Kirtikumar D.

2012-01-01

Background: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. Materials and Methods: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. Results: Of the 50 patients with pheochromocytoma, 7 (14%) had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. Conclusion: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis. PMID:23226643

Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma.

PubMed

Jasim, Sina; Suman, Vera J; Jimenez, Camilo; Harris, Pamela; Sideras, Kostandinos; Burton, Jill K; Worden, Francis Paul; Auchus, Richard J; Bible, Keith C

2017-08-01

Pheochromocytomas and paragangliomas (Pheo/PGL) are rare, vascular, sometimes malignant endocrine tumors. Case reports indicate the activity of vascular endothelium growth factor receptor-targeted kinase inhibitors in these cancers. To assess the antitumor activity and tolerability of pazopanib in progressive malignant Pheo/PGL. This multicenter Phase II trial (MC107C) enrolled individuals  ≥18 years old with disease progression ≤ 6 months prior to registration, Eastern Cooperative Oncology Group PS 0-2, and measurable disease (response evaluation criteria in solid tumors 1.0). Pazopanib was administered in 28-day cycles, with the regimen ultimately being as follows: cycle 1: 400 mg daily on days 1-14, cycle 2: 800 mg daily on days 1-14, and then cycle 2 + : 800 mg daily on all days. The study was halted due to poor accrual. Seven patients were enrolled (05/2011-11/2014). One patient withdrew consent prior to treatment, leaving six evaluable patients. Treatment was discontinued, due to the following reasons: disease progression (4); withdrawal (1); and grade 4 (Takotsubo) cardiomyopathy (1). The median number of cycles administered was 4 (range: 2-29, total: 49). Four patients had >1 dose reduction due to the following reasons: fatigue (1), abnormal liver tests (2), hypertension and (Takotsubo) cardiomyopathy (1), and headaches (1). Common severe (Common Terminology Criteria for Adverse Events v3.0 grades 3-5) toxicities were as follows: hypertension (3/6), (Takotsubo) cardiomyopathy (2/6), diarrhea (1/6), fatigue (1/6), headache (1/6), and hematuria (1/6). One confirmed partial response was observed in PGL (17%, duration 2.4 years); median progression-free survival and overall survival were 6.5 and 14.8 months, respectively. Pazopanib has activity in Pheo/PGL requiring more study; optimal alpha- and beta-blockade are imperative pre-therapy in patients with secretory tumors, as risk of hypertension and cardiomyopathy are potentially life

Unexpected visitor on FDG PET/CT--brown adipose tissue (BAT) in mesentery in a case of retroperitoneal extra-adrenal pheochromocytoma: is the BAT activation secondary to catecholamine-secreting pheochromocytoma?

PubMed

Joshi, Prathamesh Vijay; Lele, Vikram Ramchandra

2012-05-01

Fused positron emission tomography-computed tomography (PET/CT) technology has enabled the determination that nonmalignant fluorodeoxyglucose (FDG) uptake is observed in brown adipose tissue (BAT). FDG uptake in BAT is a known potential source of false-positive interpretations for PET. The typical locations of BAT include neck, supraclavicular area, mediastinum, and paravertebral intercostal spaces. Examples of atypical locations for BAT include posterior neck, left paratracheal area, axillae, perirenal area, and retrocrural area. We report PET/CT findings in a young male patient with malignant retroperitoneal extra-adrenal pheochromocytoma, who demonstrated FDG uptake in BAT at multiple locations including mesenteric BAT. We also propose catecholamine-secreting pheochromocytoma as a possible cause of BAT activation in our case.

Loss of neurofibromatosis type 1 (NF1) gene expression in pheochromocytomas from patients without NF1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geist, R.T.; Gutmann, D.H.; Moley, J.F.

The neurofibromatosis type 1 (NF1) gene encodes a tumor suppressor protein, termed neurofibromin. Loss of NF1 gene expression has been reported in Schwann cell tumors (neurofibrosarcomas) from patients with NF1 as well as malignant and neuroblastomas from patients without NF1. Previously, we demonstrated the lack of neurofibromin expression in six pheochromocytomas from patients with NF1, suggesting that neurofibromin loss is associated with the progression to neoplasia in pheochromocytomas in these patients. The lack of NF1 gene expression in NF1 patient pheochromocytomas supports the notion that neurofibromin might be an essential regulator of cell growth in these cells. To determine whethermore » NF1 gene expression is similarly altered in pheochromocytomas from patients without NF1, twenty pheochromocytomas were examined for the presence of NF1 RNA by reverse-transcribed PCR (RT-PCR). Lack of NF1 gene expression was documented in four of these twenty tumors (20%) which corresponds to previously reported numbers for malignant melanomas and neuroblastomas in non-NF1 patients. Of these twenty pheochromocytomas, one of four sporadic tumors, one of ten tumors from patients with MEN2A, one of four tumors from patients with MEN2B, and one of two tumors from patients with von Hippel-Lindau syndrome demonstrated loss of NF1 gene expression. In all cases, the quality and quantity of tumor RNA was determined by RT-PCR amplification using primers which amplify cyclophilin RNA. We previously demonstrated that these tumors do not harbor activating mutations of the N-ras, K-ras or H-ras proto-oncogenes. These results suggest that loss of NF1 gene expression is frequently associated with the progression to neoplasia in tumors derived from adrenal medullary tissue in patients without clinical manifestations of neurofibromatosis and supports the notion that neurofibromin is a tumor suppressor gene product involved in the pathogenesis of a wide variety of tumor types.« less

[Composite pheochromocytoma: A rare adrenal tumor].

PubMed

Robinet, Gwladys; Rioux-Leclercq, Nathalie; Manunta, Andréa; Mathieu, Romain; Tissier, Frédérique; Peyronnet, Benoit; Kammerer-Jacquet, Solène-Florence

2017-04-01

Composite pheochromocytoma is a rare tumor of the adrenal medulla composed of pheochromocytoma and neuroblastic tumor. We report the case of a composite pheochromocytoma detected in a patient with neurofibromatosis type 1. A 61-year-old male patient presented occasional sweats with palpitation and moderate high blood pressure. Urinary catecholamine level was increased. CT scan showed a heterogeneous tumor limited to the adrenal gland. Histologically, the tumor showed two components: pheochromocytoma and ganglioneuroma and was diagnosed as a composite pheochromocytoma. This tumor is particularly associated with neurofibromatosis type 1, the NF1 germline gene mutation may be involved in its physiopathology. Composite pheochromocytoma is a rare tumor whose pheochromocytoma component is suspected clinically but the final diagnosis is assessed by pathological examination. Prognosis is still difficult to establish due to the rarity of these tumors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Pheochromocytoma Multisystem Crisis Behaving Like Interstitial Pneumonia: An Autopsy Case

PubMed Central

Nomoto, Yohta; Kawano, Kiyoshi; Fujisawa, Naoki; Yoshida, Keiko; Yamashita, Tomoko; Makita, Naoki; Takeshita, Hiroaki; Kamimori, Kimio; Yanagi, Shiro; Yoshiyama, Minoru

2017-01-01

Pheochromocytoma multisystem crisis is a rare and life-threatening disease that is associated with numerous symptoms and which is also difficult to diagnose. We herein report an autopsy case of a 61-year-old man who died due to pheochromocytoma multisystem crisis. The patient complained of vomiting and breathlessness. Computed tomography showed a shadow-like region with a similar appearance to interstitial pneumonia. The patient was diagnosed with takotsubo cardiomyopathy induced by severe lung disease based on the results of echocardiography and coronary angiography. The patient was treated for interstitial pneumonia. However, his condition rapidly deteriorated and he died 6 hours after arrival. We were later informed of his extremely high catecholamine serum levels. We found pheochromocytoma with hemorrhage at autopsy. The patient's lungs showed acute passive congestion with edema and extravasation. PMID:28090043

Robot-assisted partial cystectomy of a bladder pheochromocytoma.

PubMed

Kang, Sung Gu; Kang, Seok Ho; Choi, Hoon; Ko, Young Hwii; Park, Hong Seok; Cheon, Jun

2011-01-01

Pheochromocytoma of the urinary bladder is an unusual tumor that typically presents with hypertensive crises related to micturition. We report here an unusual case of bladder pheochromocytoma that was treated by robotic-assisted laparoscopic partial cystectomy. A 35-year-old male patient presented with headache and hypertension related to micturition. The patient, who had a 3.5 × 4 cm solitary bladder tumor in the bladder dome, underwent robot-assisted partial cystectomy. The whole procedure was successfully performed using the robot without conversion to open surgery. The total operative time was 120 min and the estimated blood loss was 30 ml. Copyright © 2011 S. Karger AG, Basel.

Characterization and Plasma Measurement of the WE-14 Peptide in Patients with Pheochromocytoma

PubMed Central

Guillemot, Johann; Guérin, Marlène; Thouënnon, Erwan; Montéro-Hadjadje, Maité; Leprince, Jérôme; Lefebvre, Hervé; Klein, Marc; Muresan, Mihaela; Anouar, Youssef; Yon, Laurent

2014-01-01

Granins and their derived peptides are valuable circulating biological markers of neuroendocrine tumors. The aim of the present study was to investigate the tumoral chromogranin A (CgA)-derived peptide WE-14 and the potential advantage to combine plasma WE-14 detection with the EM66 assay and the existing current CgA assay for the diagnosis of pheochromocytoma. Compared to healthy volunteers, plasma WE-14 levels were 5.4-fold higher in patients with pheochromocytoma, but returned to normal values after surgical resection of the tumor. Determination of plasma CgA and EM66 concentrations in the same group of patients revealed that the test assays for these markers had an overall 84% diagnostic sensitivity, which is identical to that determined for WE-14. However, we found that WE-14 measurement improved the diagnostic sensitivity when combined with the results of CgA or EM66 assays. By combining the results of the three assays, the sensitivity for the diagnosis of pheochromocytoma was increased to 95%. In fact, the combination of WE-14 with either CgA or EM66 test assays achieved 100% sensitivity for the diagnosis of paragangliomas and sporadic or malignant pheochromocytomas if taken separately to account for the heterogeneity of the tumor. These data indicate that WE-14 is produced in pheochromocytoma and secreted into the general circulation, and that elevated plasma WE-14 levels are correlated with the occurrence of this chromaffin cell tumor. In addition, in association with other biological markers, such as CgA and/or EM66, WE-14 measurement systematically improves the diagnostic sensitivity for pheochromocytoma. These findings support the notion that granin-processing products may represent complementary tools for the diagnosis of neuroendocrine tumors. PMID:24523932

Hereditary Pheochromocytoma.

PubMed

Santos, Pedro; Pimenta, Tiago; Taveira-Gomes, Antonio

2014-08-01

Pheochromocytomas (PHEO) and paragangliomas (PGL) are rare neuroendocrine tumors with an estimated occurrence of 2 to 5 patients per million per year and an incidence of about 1 per 100 000 in the general population. These tumors may arise sporadically or be associated to various syndromes, namely multiple endocrine neoplasia type 2, neurofibromatosis type 1, Von Hippel-Lindau syndrome, and hereditary paraganglioma-pheochromocytoma syndromes. This article aims to review the current epidemiology, pathogenesis, clinical presentation, and genetic aspects of syndromes associated with hereditary PHEO/PGL. The literature research, conducted at PubMed database, included review articles, published from February 2009 to February 2014, written in English or Portuguese, using as query: "Hereditary AND Pheochromocytoma." These tumors can be part of a myriad hereditary conditions that are not yet fully understood. Nevertheless, important systemic symptoms and even fatal outcomes can occur. Knowledge of these hereditary conditions can ensure a more efficient detection, treatment, and even prevention of these neuroectodermal tumors, thus new tests and studies should be conducted. © The Author(s) 2014.

[Nuclear medicine diagnosis of pheochromocytoma].

PubMed

Farahati, J; Reiners, C

1997-01-01

The synthesis of radioiodinated meta-iodobenzylguanidine (MIBG), a physiologic norepinephrine analog, was first accomplished by a group from the University of Michigan. Since the first report of the detection of pheochromocytoma with MIBG in humans, there have been several studies about the role of this agent in the diagnosis of pheochromocytoma and neuroblastoma. With a sensitivity of about 90% and a specificity of nearly 100% MIBG has been shown to be a reliable diagnostic tool for the detection and follow-up of pheochromocytoma.

Pheochromocytoma and haemophilia: an unusual combination.

PubMed

Jebasingh, K F; Koshy, T G; Paul, T V; Paul, M J; Abraham, D; Viswabandya, A

2009-02-01

We report pheochromocytoma and haemophilia occurring in a 19-year-old South Indian man. To the best of our knowledge, this case is the first of its kind to be reported in the medical literature. The patient had bilateral adrenal pheochromocytomas with an extradrenal pheochromocytoma on the left side, and was successfully operated on after optimal preoperative blood pressure control and factor VIII support.

Adrenergic crisis due to pheochromocytoma - practical aspects. A short review.

PubMed

Juszczak, Kajetan; Drewa, Tomasz

2014-01-01

The definitive therapy in case of pheochromocytoma is complete surgical resection. Improper preoperative assessment and medical management generally places the patient at risk for complications, resulting from an adrenergic crisis. Therefore, it is crucial to adequately optimize these patients before surgery. Optimal preoperative medical management significantly decreases morbidity and mortality during the tumor resection. This review addresses current knowledge in pre- and intraoperative assessment of a patient with pheochromocytoma. Before surgery the patient is conventionally prepared with α-adrenergic blockade (over 10-14 days) and subsequently, additional β-adrenergic blockade is required to treat any associated tachyarrhythmias. In preoperative assessment, it is obligatory to monitor arterial blood pressure, heart rate, and arrhythmias and to restore the blood volume to normal. In conclusion, due to the pathophysiological complexity of a pheochromocytoma, the strict cooperation between the cardiologist, endocrinologist, surgeon and the anaesthesiologist for an uneventful outcome should be achieved in patients qualified for the surgical removal of such a tumor.

[Urgent laparoscopic adrenalectomy in acute crisis caused by pheochromocytoma].

PubMed

Bereczky, Bíborka; Madách, Krisztina; Gál, János; István, Gábor; Sugár, István; Ondrejka, Pál; Vörös, Attila

2014-06-01

Authors present the case of a 30-year-old female patient, who was admitted to the ICU because of hypertensive crisis accompanied by chest complains, cardiac decompensation, progrediating short of breath and unconsciousness. Despite the quick examinations and the prompt treatment multi-organ failure developed 3 days after admission. Investigations revealed the underlying cause, which was a left-sided suprarenal neoplasm. Hence, multidisciplinary decision was made to carry out a laparoscopic adrenalectomy urgently. The histology examination of the removed neoplasm was pheochromocytoma. In the postoperative period the condition of the patient gradually improved, her symptoms and complains settled, and finally she was discharged in a healthy condition. The diagnosis of a pheochromocytoma is a difficult task, the symptoms and complains caused by it can simulate many other illnesses. The acute crisis caused by pheochromocytoma usually can be treated conservatively, but in more severe cases with impending multi-organ failure an urgent operative treatment can be unavoidable. Though the operative risk is relatively high, the correct intra- and postoperative treatment with a quick laparoscopic procedure can be effective.

The coexistence of renal artery stenosis and pheochromocytoma.

PubMed Central

Hill, F S; Jander, H P; Murad, T; Diethelm, A G

1983-01-01

The coexistence of renal artery stenosis and pheochromocytoma has been recognized since 1958 and a total of 36 patients reported. This article provides an additional patient with an extra adrenal pheochromocytoma and fibrous bands constricting the left renal artery. Hypertension was confirmed to occur from both excess catecholamine production and hyperreninemia from the left kidney. Surgical removal of the functioning paraganglioma and correction of the renal artery stenosis restored the postoperative plasma catecholamine, renin, and blood pressure to normal. A literature review confirmed the coexistence of these two lesions but failed to provide a common etiology to explain the pathophysiology encountered. However, when the two diseases occur simultaneously, both must be diagnosed accurately and treated in a definitive manner. Images Figs. 1a and b. Figs. 2a and b. PMID:6830355

A Case Report of Cystic Pheochromocytoma.

PubMed

Junejo, Shoaib Z; Tuli, Sandeep; Heimann, David M; Sachmechi, Issac; Reich, David

2017-07-25

BACKGROUND Pheochromocytoma is a rare catecholamine-producing tumor with an estimated incidence of less than 0.1% in the global population. We present a case of cystic pheochromocytoma that was diagnosed as an incidental finding. The patient presented with abdominal pain and had a history of hypertension. CASE REPORT A 64-year-old man with hypertension presented with a clinical history of intermittent abdominal pain for one year. He denied sweating, palpitations, headache or back pain. He was found to have an elevated blood pressure of 170/90 and no palpable abdominal mass. Contrast-enhanced computed tomography (CT) imaging of the abdomen and pelvis were performed that showed cystic mass measuring 9 cm in diameter arising from the left adrenal gland with contrast-enhancing mural nodules. Magnetic resonance imaging (MRI) confirmed the cystic nature of the mass. Laboratory analysis showed an elevated plasma normetanephrine (NMN) of 1,087 pg/ml and metanephrine (MN) of 372 pg/ml; 24-hour urine showed elevated levels of NMN and MN, 3,002 mg/24 h and 1,596 mg/24 h, respectively. Given the laboratory and radiologic findings, a diagnosis of cystic pheochromocytoma was made. After controlling blood pressure with the alpha-blocker, doxazosin, the patient was hydrated and scheduled for an elective adrenalectomy. The histopathology of the excised adrenal gland was consistent with a cystic pheochromocytoma. CONCLUSIONS Cystic pheochromocytoma is a very rare tumor that may present without symptoms. The clinical course of cystic pheochromocytoma is similar to that of solid pheochromocytoma. Early surgical intervention is recommended, following blood pressure control with an alpha-blocker, and adequate hydration.

Max Schottelius: Pioneer in Pheochromocytoma

PubMed Central

Tischler, Arthur S.; Schmid, Kurt W.; Leijon, Helena; Eng, Charis; Neumann, Hartmut P. H.

2017-01-01

First descriptions of diseases attract tremendous interest because they reveal scientific insight even in retrospect. Max Schottelius, the pathologist contributing the first histological description of pheochromocytoma, remains anonymous. We reviewed the description by Schottelius and weighed the report in modern context. Schottelius described the classical diagnostic elements of pheochromocytoma, including the brown appearance after exposure to chromate-containing Mueller’s fixative. This color change, known as chromaffin reaction, results from oxidation of catecholamines and is reflected in the name pheochromocytoma, meaning dusky-colored chromate-positive tumor. Thus Schottelius performed the first known histochemical contribution to diagnosis, which is today standard with immunohistochemistry for chromogranin. PMID:29264546

Pheochromocytoma and Paraganglioma—Health Professional Version

Cancer.gov

Pheochromocytomas and extra-adrenal paragangliomas are rare tumors arising from neural crest tissue that develops into sympathetic and parasympathetic paraganglia throughout the body. Find evidence-based information on pheochromocytoma and paraganglioma treatment, research, and genetics.

Pheochromocytoma crisis is not a surgical emergency.

PubMed

Scholten, Anouk; Cisco, Robin M; Vriens, Menno R; Cohen, Jenny K; Mitmaker, Elliot J; Liu, Chienying; Tyrrell, J Blake; Shen, Wen T; Duh, Quan-Yang

2013-02-01

Pheochromocytoma crisis is a feared and potentially lethal complication of pheochromocytoma. We sought to determine the best treatment strategy for pheochromocytoma crisis patients and hypothesized that emergency resection is not indicated. Retrospective cohort study (1993-2011); literature review (1944-2011). Tertiary referral center. There were 137 pheochromocytoma patients from our center and 97 pheochromocytoma crisis patients who underwent adrenalectomy from the literature. Medical management of pheochromocytoma crisis; adrenalectomy. Perioperative complications, conversion, and mortality. In our database, 25 patients (18%) presented with crisis. After medical stabilization and α-blockade, 15 patients were discharged and readmitted for elective surgery and 10 patients were operated on urgently during the same hospitalization. None underwent emergency surgery. Postoperatively, patients who underwent elective surgery had shorter hospital stays (1.7 vs 5.7 d, P = 0.001) and fewer postoperative complications (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) and were less often admitted to the intensive care unit (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) in comparison with urgently operated patients. There was no mortality. Review of the literature (n = 97) showed that crisis patients who underwent elective or urgent surgery vs emergency surgery had less intraoperative (13 of 31 [42%] vs 20 of 25 [80%], P < 0.001) and postoperative complications (15 of 45 [33%] vs 15 of 21 [71%], P = 0.047) and a lower mortality (0 of 64 vs 6 of 33 [18%], P = 0.002). Management of patients presenting with pheochromocytoma crisis should include initial stabilization of the acute crisis followed by sufficient α-blockade before surgery. Emergency resection of pheochromocytoma is associated with high surgical morbidity and mortality.

Pheochromocytoma of the urinary bladder: a systematic review of the contemporary literature

PubMed Central

2013-01-01

Background Pheochromocytoma (paraganglioma) of the urinary bladder is a rare tumor. Herein we sought to review the contemporary literature on pheochromocytomas of the urinary bladder in order to further illustrate the presentation, treatment options and outcomes of patients diagnosed with these tumors. Methods A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database and using the search terms “paraganglioma, pheochromocytoma, bladder.” This search resulted in the identification of 186 articles published between January 1980 and April 2012 of which 80 articles were ultimately included in our analysis. Results Pheochromocytomas usually occurred in young adult Caucasians (mean age, 43.3 years; range,11–84 years). According to the literature, the most common symptoms and signs of pheochromocytomas of the urinary bladder were hypertension, headache, and hematuria. Of the 77 cases that commented on catecholamine production, 65 patients had biochemically functional tumors. Approximately 20% of patients were treated by transurethral resection alone, 70% by partial cystectomy and 10% by radical cystectomy. The 75 patients with follow-up information had a mean follow-up of 35 months. At the time of last follow-up, 15 (14.2%) had disease recurrence, 10 (9.4%) had metastasis, and 65 (61.3%) were alive. Conclusions Pheochromocytomas of the urinary bladder tend to be functional and occur mostly in young adult Caucasians. Patients with localized tumors have an extremely favorable prognosis and may be managed by less aggressive modalities, whereas patients with metastatic disease have a significant reduction in survival rates despite aggressive treatment. PMID:23627260

A rare cause of hypertension in children: intrathoracic pheochromocytoma.

PubMed

Singh, Jaswinder; Rana, Sandeep Singh; Sharma, Rajeshwar; Ghai, Babita; Puri, G D

2008-07-01

Mediastinal pheochromocytomas account for only a small fraction of mediastinal tumors. Most commonly, these tumors are located in posterior mediastinum. Increasing number of cases of pheochromocytomas is being reported from middle mediastinum. Excision of mediastinal paraganglioma is often hazardous because of its rich blood supply and tendency to involve surrounding structures. It can be a big challenge to manage asymptomatic cases of pheochromocytoma intraoperatively. It is imperative that these patients receive adequate alpha adrenergic and if necessary beta adrenergic blockade. Adequate preoperative preparation with alpha and beta blockers may not prevent serious intraoperative hypertension. We report a case of posterior mediastinal pheochromocytoma which was biochemically active preoperatively. We review the presentation, diagnosis and management of intrathoracic pheochromocytomas including cardiac pheochromocytomas.

Pheochromocytoma diagnosed pathologically with previous negative serum markers.

PubMed

Heavner, Matthew G; Krane, Louis S; Winters, Shira M; Mirzazadeh, Majid

2015-10-01

Patients presenting with adrenal masses require workup with catecholamine or metabolite measurements to rule out pheochromocytoma. There is a select portion of patients with marker negative pheochromocytoma. The aim of this study is to compare patient characteristics and presentations between marker positive and marker negative tumors. We performed an IRB-approved retrospective chart review of 88 cases of pheochromocytoma excised at our institution from 1995 to 2013. We considered any abnormal elevation in diagnostic test to be marker-positive. Seventy-eight cases had laboratory results available. Among these, seven had no elevations in laboratory testing. There was no difference in age or tumor size, but marker-negative patients had higher BMI than marker-positive patients. Marker negative patients were more likely to present with vertigo/dizziness (P = 0.003). Neither was more likely to have a genetic syndrome associated with risk of pheochromocytoma. Marker-negative pheochromocytoma is uncommon, representing 9% of cases in our series. Of patients with adrenal masses or presentation suggesting catecholamine excess with normal labs, those with vertigo/dizziness may warrant a metaiodobenzylguanidine scan or repeat testing to avoid missing pheochromocytoma. Clinicians may need a high degree of suspicion for pheochromocytoma in patients with negative testing and elevated BMI. © 2015 Wiley Periodicals, Inc.

Localization and prediction of malignant potential in recurrent pheochromocytoma/paraganglioma (PCC/PGL) using 18F-FDG PET/CT.

PubMed

Fikri, Ahmad Saad Fathinul; Kroiss, A; Ahmad, A Z F; Zanariah, H; Lau, W F E; Uprimny, C; Donnemiller, E; Kendler, D; Nordin, A J; Virgolini, I J

2014-06-01

To our knowledge, data are lacking on the role of 18F-FDG PET/CT in the localization and prediction of neuroendocrine tumors, in particular the pheochromocytoma/paraganglioma (PCC/PGL) group. To evaluate the role of 18F-FDG PET/CT in localizing and predicting the malignant potential of PCC/PGL. Twenty-three consecutive patients with a history of PCC/PGL, presenting with symptoms related to catecholamine excess, underwent 18F-FDG PET/CT. Final confirmation of the diagnosis was made using the composite references. PET/CT findings were analyzed on a per-lesion basis and a per-patient basis. Tumor SUVmax was analyzed to predict the dichotomization of patient endpoints for the local disease and metastatic groups. We investigated 23 patients (10 men, 13 women) with a mean age of 46.43 ± 3.70 years. Serum catecholamine levels were elevated in 82.60% of these patients. There were 136 sites (mean SUVmax: 16.39 ± 3.47) of validated disease recurrence. The overall sensitivities for diagnostic CT, FDG PET, and FDG PET/CT were 86.02%, 87.50%, and 98.59%, respectively. Based on the composite references, 39.10% of patients had local disease. There were significant differences in the SUVmax distribution between the local disease and metastatic groups; a significant correlation was noted when a SUVmax cut-off was set at 9.2 (P<0.05). In recurrent PCC/PGL, diagnostic 18F-FDG PET/CT is a superior tool in the localization of recurrent tumors. Tumor SUVmax is a potentially useful predictor of malignant tumor potential. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

PubMed

Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

1990-09-01

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Predictors of recurrence in pheochromocytoma.

PubMed

Press, Danielle; Akyuz, Muhammet; Dural, Cem; Aliyev, Shamil; Monteiro, Rosebel; Mino, Jeff; Mitchell, Jamie; Hamrahian, Amir; Siperstein, Allan; Berber, Eren

2014-12-01

The recurrence rate of pheochromocytoma after adrenalectomy is 6.5-16.5%. This study aims to identify predictors of recurrence and optimal biochemical testing and imaging for detecting the recurrence of pheochromocytoma. In this retrospective study we reviewed all patients who underwent adrenalectomy for pheochromocytoma during a 14-year period at a single institution. One hundred thirty-five patients had adrenalectomy for pheochromocytoma. Eight patients (6%) developed recurrent disease. The median time from initial operation to diagnosis of recurrence was 35 months. On multivariate analysis, tumor size >5 cm was an independent predictor of recurrence. One patient with recurrence died, 4 had stable disease, 2 had progression of disease, and 1 was cured. Recurrence was diagnosed by increases in plasma and/or urinary metanephrines and positive imaging in 6 patients (75%), and by positive imaging and normal biochemical levels in 2 patients (25%). Patients with large tumors (>5 cm) should be followed vigilantly for recurrence. Because 25% of patients with recurrence had normal biochemical levels, we recommend routine imaging and testing of plasma or urinary metanephrines for prompt diagnosis of recurrence. Copyright © 2014 Elsevier Inc. All rights reserved.

Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas and paragangliomas.

PubMed

Yao, Li; Schiavi, Francesca; Cascon, Alberto; Qin, Yuejuan; Inglada-Pérez, Lucia; King, Elizabeth E; Toledo, Rodrigo A; Ercolino, Tonino; Rapizzi, Elena; Ricketts, Christopher J; Mori, Luigi; Giacchè, Mara; Mendola, Antonella; Taschin, Elisa; Boaretto, Francesca; Loli, Paola; Iacobone, Maurizio; Rossi, Gian-Paolo; Biondi, Bernadette; Lima-Junior, José Viana; Kater, Claudio E; Bex, Marie; Vikkula, Miikka; Grossman, Ashley B; Gruber, Stephen B; Barontini, Marta; Persu, Alexandre; Castellano, Maurizio; Toledo, Sergio P A; Maher, Eamonn R; Mannelli, Massimo; Opocher, Giuseppe; Robledo, Mercedes; Dahia, Patricia L M

2010-12-15

Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P = 2.7 × 10(-4)) and/or with familial disease (5 of 20 samples; P = .005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P = .54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. Germline mutations of FP/TMEM127 were associated with pheochromocytoma but

[Hypertension, catecholamine hypersecretion and potential for metastasis: recent progress in the pathophysiology and genetics of pheochromocytoma and paraganglioma].

PubMed

Plouin, Pierre-François; Amar, Laurence; Gimenez-Roqueplo, Anne-paule

2015-01-01

Pheochromocytomas and paragangliomas are catecholamine-secreting tumors usually associated with arterial hypertension. They can contribute to acute cardiovascular events. Ten to 15 percent of tumors are metastatic. Autosomal dominant gene alterations are present in more than a third of cases. The secretory phenotype and the risk of malignancy are driven by the presence of gene mutations, specifically in the subunits of succinate dehydrogenase. Recent advances in genomics have clinical implications for family screening, biological follow-up, prediction of the risk of recurrence, and therapeutic options in cases with malignant recurrence.

Clevidipine for hypertension treatment in pheochromocytoma surgery.

PubMed

Luis-García, C; Arbonés-Aran, E; Teixell-Aleu, C; Lorente-Poch, L; Trillo-Urrutia, L

2018-04-01

Pheochromocytoma is a catecholamine-producing tumour and laparoscopic adrenalectomy is its treatment of choice. During pneumoperitoneum insufflation and tumour handling there is a high risk of massive catecholamine release and hypertensive crisis. After tumour excision, severe arterial hypotension is a common effect, due to relative vasodilation and the residual effect of antihypertensive drugs. We report the case of a patient with pheochromocytoma who was treated with laparoscopic adrenalectomy. During surgical manipulation there was a sudden hypertensive peak that could be controlled quickly with clevidipine infusion. After tumour resection, clevidipine perfusion was stopped and there were no arterial hypotension episodes. Clevidipine is a new intravenous calcium antagonist with rapid onset of action and short half-life that has no residual effect and does not produce arterial hypotension after tumour resection. For these reasons, it can be a first-choice drug for this kind of surgery. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Novel Preclinical Testing Strategies for Treatment of Metastatic Pheochromocytoma

DTIC Science & Technology

2012-09-01

Treatment of Metastatic Pheochromocytoma PRINCIPAL INVESTIGATOR: Arthur S. Tischler...Treatment of Metastatic Pheochromocytoma 5a. CONTRACT NUMBER W81XWH-11-1-0670 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Pheochromocytomas (PCC) are catecholamine-producing neuroendocrine tumors. Up to 30% give

Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention.

PubMed

Bausch, Birke; Schiavi, Francesca; Ni, Ying; Welander, Jenny; Patocs, Attila; Ngeow, Joanne; Wellner, Ulrich; Malinoc, Angelica; Taschin, Elisa; Barbon, Giovanni; Lanza, Virginia; Söderkvist, Peter; Stenman, Adam; Larsson, Catharina; Svahn, Fredrika; Chen, Jin-Lian; Marquard, Jessica; Fraenkel, Merav; Walter, Martin A; Peczkowska, Mariola; Prejbisz, Aleksander; Jarzab, Barbara; Hasse-Lazar, Kornelia; Petersenn, Stephan; Moeller, Lars C; Meyer, Almuth; Reisch, Nicole; Trupka, Arnold; Brase, Christoph; Galiano, Matthias; Preuss, Simon F; Kwok, Pingling; Lendvai, Nikoletta; Berisha, Gani; Makay, Özer; Boedeker, Carsten C; Weryha, Georges; Racz, Karoly; Januszewicz, Andrzej; Walz, Martin K; Gimm, Oliver; Opocher, Giuseppe; Eng, Charis; Neumann, Hartmut P H

2017-09-01

Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head

An unusual cause of autonomic dysreflexia: pheochromocytoma in an individual with tetraplegia.

PubMed

Armenti-Kapros, Brenda; Nambiar, Prabhakaran K; Lippman, H Robert; Levy, James R

2003-01-01

Autonomic dysreflexia (AD) is a frequent, serious acute syndrome that occurs in patients with spinal cord lesions at level T6 and above. The syndrome is caused by massive sympathetic discharge that is triggered by a noxious stimulus below the level of the spinal cord lesion. Pheochromocytomas are rare tumors that present with symptoms similar to AD. Case Report. A 50-year-old man with C7 American Spinal Injury Association scale A tetraplegia presented with episodes of severe headaches and paroxysmal hypertension. He was diagnosed with AD. Despite resolving bladder and bowel problems, he continued to have hypertensive episodes. A CT scan of the abdomen revealed a heterogeneous left adrenal mass. Further workup revealed significantly elevated serum and 24-hour urinary catecholamines. Clonidine failed to fully suppress the markedly elevated concentrations of serum catecholamines. These biochemical findings were consistent with the diagnosis of pheochromocytoma. Prior to surgery, the patient was treated with alpha-receptor blockers and volume expansion with intravenous fluids. A left adrenalectomy was performed. The surgical specimen revealed that the adrenal gland was expanded by a spherical mass. The pathologic report was benign pheochromocytoma of the left adrenal gland. Clinical symptoms and hypertensive episodes resolved following adrenalectomy. To our knowledge, this is the first reported case of a pheochromocytoma in an individual with spinal cord injury.

Utility of plasma free metanephrines in diagnosis of factitious pheochromocytoma.

PubMed

Chidakel, Aaron R; Pacak, Karel; Eisenhofer, Graeme; Lawrence, Jennifer E; Ayala, Alejandro R

2006-01-01

To report a case of epinephrine-induced factitious pheochromocytoma in a young woman with a past medical history of Conn's syndrome. We present a case report with clinical and laboratory details, review related reports in the literature, and demonstrate the usefulness of plasma free metanephrine levels in facilitating the diagnosis of factitious pheochromocytoma. A 34-year-old woman was admitted to our hospital for confirmation and localization of an occult pheochromocytoma. After thorough investigation, we discovered that the patient was surreptitiously injecting epinephrine in order to induce symptoms and signs consistent with a pheochromocytoma. Analysis of the patient's biochemical profile during and between her catecholaminergic crises revealed plasma epinephrine and free metanephrine levels that would be highly unusual for a patient with a pheochromocytoma. This case illustrates the utility of implementing the ratio of plasma epinephrine to free metanephrine levels in distinguishing factitious from organic pheochromocytoma.

[Significance of 3-methoxytyramine urine measurement in the diagnosis of pheochromocytomas and paragangliomas: about 28 patients].

PubMed

Le Jacques, Aurélien; Abalain, Jean-Hervé; Le Saos, Fabienne; Carré, Jean-Luc

2011-01-01

Measurement of catecholamines derivatives is used to diagnose tumors such as pheochromocytomas and paragangliomas. Despite the low incidence of these diseases, their diagnosis is essential because of potentially lethal episodes of malignant hypertension related to an inappropriate secretion of catecholamines by these tumors. The catecholamines derivatives include 3-methoxytyramine, normetanephrine and metanephrine, assayed in urine or plasma. The significance of the measurement of urinary 3-methoxytyramine was addressed by analysing the records of 28 patients aged 25 to 84 years with isolated elevation of this derivative, with non-pathological urinary rates of metanephrine and normetanephrine, that might help suspect a catecholamine inappropriate secretion. In these situations, no pheochromocytoma or paraganglioma was diagnosed. This study, after discussing possible biases in the clinical care and diagnosis approach of these patients, raises the question of the relevance of this assay in the diagnostic management of these diseases.

PHEOCHROMOCYTOMA: A CATECHOLAMINE AND OXIDATIVE STRESS DISORDER

PubMed Central

Pacak, Karel

2012-01-01

-oncogene activation, tumor suppressor gene inactivation, DNA damage, and genomic instability. Since the mitochondria serves as the main source of prooxidants, any mitochondrial impairment leads to severe oxidative stress, a major outcome of which is tumor development. In terms of cancer pathogenesis, pheochromocytomas and paragangliomas represent tumors where the oxidative phosphorylation defect due to the mutation of succinate dehydrogenase is the cause, not a consequence, of tumor development. Any succinate dehydrogenase pathogenic mutation results in the shift from oxidative phosphorylation to aerobic glycolysis in the cytoplasm (also called anaerobic glycolysis if hypoxia is the main cause of such a shift). This phenomenon, also called the Warburg effect, is well demonstrated by a positive [18F]-fluorodeoxyglycose positron emission tomography scan. Microarray studies, genome-wide association studies, proteomics and protein arrays, metabolomics, transcriptomics, and bioinformatics approaches will remain powerful tools to further uncover the pathogenesis of these tumors and their unique markers, with the ultimate goal to introduce new therapeutic options for those with metastatic or malignant pheochromocytoma and paraganglioma. Soon oxidative stress will be tightly linked to a multistep cancer process in which the mutation of various genes (perhaps in a logistic way) ultimately results in uncontrolled growth, proliferation, and metastatic potential of practically any cell. Targeting the mTORC, IGF-1, HIF and other pathways, topoisomerases, protein degradation by proteosomes, balancing the activity of protein kinases and phosphatases or even synchronizing the cell cycle before any exposure to any kind of therapy will soon become a reality. Facing such a reality today will favor our chances to “beat” this disease tomorrow. PMID:21615192

Pheochromocytoma, diagnosis and treatment: Review of the literature.

PubMed

Farrugia, F A; Martikos, G; Tzanetis, P; Charalampopoulos, A; Misiakos, E; Zavras, N; Sotiropoulos, D

2017-07-01

We conducted an extensive review of the literature and tried to cite the most recent recommendations concerning the pheochromocytoma (PHEO). Pub Med and Google Scholar databases were searched systematically for studies concerning pheochromocytomas (intra-adrenal paragangliomas) from 1980 until 2016. Bibliographies were searched to find additional articles. More than four times elevation of plasma fractionated metanephrines or elevated 24-h urinary fractionated metanephrines are keys to diagnosing pheochromocytoma. If the results are equivocal then we perform the clonidine test. If we have not done it already, we preferably do a CT scan and/or an MRI scan. The patient needs pre-treatment with α1-blockers at least 10-14 days before operation. Alternatives or sometimes adjuncts are Calcium Channels Blockers and/or β-Blockers. Several familial syndromes are associated with PHEO and genetic testing should be considered. The biggest problem for pheochromocytoma is to suspect it in the first place. Elevated metanephrines establish the diagnosis. With the proper preoperative preparation the risks during operation and the postoperative period are minimal. If there is a risk of the hereditable mutation, it is strongly suggested that all the patients with pheochromocytoma need clinical genetic testing.

Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.

PubMed

Mannelli, Massimo; Castellano, Maurizio; Schiavi, Francesca; Filetti, Sebastiano; Giacchè, Mara; Mori, Luigi; Pignataro, Viviana; Bernini, Gianpaolo; Giachè, Valentino; Bacca, Alessandra; Biondi, Bernadette; Corona, Giovanni; Di Trapani, Giuseppe; Grossrubatscher, Erika; Reimondo, Giuseppe; Arnaldi, Giorgio; Giacchetti, Gilberta; Veglio, Franco; Loli, Paola; Colao, Annamaria; Ambrosio, Maria Rosaria; Terzolo, Massimo; Letizia, Claudio; Ercolino, Tonino; Opocher, Giuseppe

2009-05-01

The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. We examined 501 consecutive patients with pheochromocytomas and/or paragangliomas (secreting or nonsecreting). Complete medical and family histories, as well as the results of clinical, laboratory, and imaging studies, were recorded in a database. Patients were divided into different groups according to their family history, the presence of lesions outside adrenals/paraganglia considered syndromic for VHL disease, MEN2, and NF1, and the number and types of pheochromocytomas and/or paragangliomas. Germ-line mutations in known susceptibility genes were investigated by gene sequencing (VHL, RET, SDHB, SDHC, SDHD) or diagnosed according to phenotype (NF1). In 160 patients younger than 50 yr with a wild-type profile, multiplex ligation-dependent probe amplification assays were performed to detect genomic rearrangements. Germline mutations were detected in 32.1% of cases, but frequencies varied widely depending on the classification criteria and ranged from 100% in patients with associated syndromic lesions to 11.6% in patients with a single tumor and a negative family history. The types and number of pheochromocytomas/paragangliomas as well as age at presentation and malignancy suggest which gene should be screened first. Genomic rearrangements were found in two of 160 patients (1.2%). The frequency of the hereditary forms of pheochromocytoma/paraganglioma varies depending on the family history and the clinical presentation. A positive family history and an accurate clinical evaluation of patients are strong indicators of which genes should be screened first.

Hypertensive crisis due to contrast-enhanced computed tomography in a patient with malignant pheochromocytoma.

PubMed

Nakano, Sachiko; Tsushima, Yoshito; Taketomi-Takahashi, Ayako; Higuchi, Tetsuya; Amanuma, Makoto; Oriuchi, Noboru; Endo, Keigo

2011-07-01

A 63-year-old man underwent computed tomography (CT) using intravenous low-osmolar iodine contrast medium (LOCM) 6 days after undergoing high-dose (131)I-MIBG therapy for metastatic pheochromocytoma. Immediately after the CT examination, his blood pressure increased to 260/160 mmHg (from 179/101 mmHg before the examination). Phentolamine mesilate was administered, and the blood pressure rapidly went back to normal. Although hypertensive crisis after administration of LOCM is rare, this case suggests that high-dose (131)IMIBG therapy may be a risk factor for hypertensive crisis after administration of intravenous LOCM.

Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention

PubMed Central

Schiavi, Francesca; Ni, Ying; Welander, Jenny; Patocs, Attila; Ngeow, Joanne; Wellner, Ulrich; Malinoc, Angelica; Taschin, Elisa; Barbon, Giovanni; Lanza, Virginia; Söderkvist, Peter; Stenman, Adam; Larsson, Catharina; Svahn, Fredrika; Chen, Jin-Lian; Marquard, Jessica; Fraenkel, Merav; Walter, Martin A.; Peczkowska, Mariola; Prejbisz, Aleksander; Jarzab, Barbara; Hasse-Lazar, Kornelia; Petersenn, Stephan; Moeller, Lars C.; Meyer, Almuth; Reisch, Nicole; Trupka, Arnold; Brase, Christoph; Galiano, Matthias; Preuss, Simon F.; Kwok, Pingling; Lendvai, Nikoletta; Berisha, Gani; Makay, Özer; Boedeker, Carsten C.; Weryha, Georges; Racz, Karoly; Januszewicz, Andrzej; Walz, Martin K.; Gimm, Oliver; Opocher, Giuseppe; Eng, Charis; Neumann, Hartmut P. H.

2017-01-01

Importance Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. Objective To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. Design, Setting, and Patients This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. Main Outcomes and Measures Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. Results Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation

Evaluation of quantitative parameters for distinguishing pheochromocytoma from other adrenal tumors.

PubMed

Ohno, Youichi; Sone, Masakatsu; Taura, Daisuke; Yamasaki, Toshinari; Kojima, Katsutoshi; Honda-Kohmo, Kyoko; Fukuda, Yorihide; Matsuo, Koji; Fujii, Toshihito; Yasoda, Akihiro; Ogawa, Osamu; Inagaki, Nobuya

2018-03-01

Adrenal tumors are increasingly found incidentally during imaging examinations. It is important to distinguish pheochromocytomas from other adrenal tumors because of the risk of hypertensive crisis. Although catecholamines and their metabolites are generally used to diagnose pheochromocytoma, false-positive test results are common. An effective screening method to distinguish pheochromocytoma from adrenal incidentalomas is needed. We analyzed 297 consecutive patients with adrenal incidentalomas. Our findings included 162 non-functioning tumors, 47 aldosterone-producing adenomas, 26 metastases, 22 cases of subclinical Cushing's syndrome, 21 pheochromocytomas, 12 cases of Cushing's syndrome, and 7 adrenocortical cancers. We checked quantitative parameters such as age, blood, and urine catecholamines and their metabolites, neuron-specific enolase, size and computed tomography (CT) attenuation values. Among catecholamine-related parameters, the sum of urine metanephrine and normetanephrine (urineMNM) levels produced the highest area under the receiver operating characteristic curve regarding discrimination of pheochromocytoma from other lesions. Size and CT attenuation values also differed significantly. However, size was correlated with catecholamine levels. CT attenuation was not correlated with other factors. The optimal thresholds were 19 Hounsfield units (HU) for CT attenuation (sensitivity, 100%; specificity, 60%) and 0.43 mg/24 h for urineMNM (sensitivity, 89%; specificity, 96%). No pheochromocytomas were evident when CT attenuation values were under 19 HU. Even in adrenal tumors with CT attenuation values ≥ 19 HU, when urineMNM was < 0.43 mg/24 h, the frequency of pheochromocytoma was only 4.3%, when urineMNM was ≥ 0.43 mg/24 h, the frequency of pheochromocytoma was 93% and when urineMNM was > 0.77 mg/24 h the frequency of pheochromocytoma was 100%. CT attenuation value and urineMNM represented the most useful combination for

Retroperitoneal composite pheochromocytoma-ganglioneuroma : a case report and review of literature

PubMed Central

2013-01-01

Abstract Composite pheochromocytoma/paraganglioma is a rare tumor with elements of pheochromocytoma/paraganglioma and neurogenic tumor. Most were located in the adrenal glands, and extra-adrenal composite pheochromocytoma is extremely rare. Only 4 cases in the retroperitoneum have been described in the online database PUBMED. Here, we report a case of retroperitoneal extra-adrenal composite pheochromocytoma and review the related literature. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1700539911908679 PMID:23587063

[Pheochromocytoma and cardiogenic failure: an indication for emergency adrenalectomy].

PubMed

Vandwalle, J; Spie, R; Jarry, G; Agaesse, V; Petit, J; Saint, F

2010-07-01

To identify cardiogenic failure or cardiogenic shock associated with pheochromocytoma diagnosis and emergency adrenalectomy. Update this unusual presentation of pheochromocytoma. Between 1998 and 2009, 119 adrenalectomies were performed in our department, among which 19 cases for pheochromocytoma. We reported three cases with cardiogenic failure or cardiogenic shock associated with emergency adrenalectomy. Patients were 36, 41 and 67 years old. The elapsed time between cardiogenic failure and surgery was 0, 7 and 19 days. The first diagnosis was a viral myocarditis in those three cases. The diagnosis of adrenal pheochromocytoma was done in a second step by the association of adrenal tumour on abdominal CT scan and detection of significantly elevated plasma/urine catecholamine. Severe systolic dysfunction with low ejection fraction was associated in all cases. Cardiac function was quickly restored after adrenalectomy. Cardiac emergency associated with pheochromocytoma is an unusual clinical presentation. When diagnosis fails to be performed, patients have a very poor prognosis. According to a review of the sparse literature, only early recognition and emergency adrenalectomy can improve the outcome. Copyright 2010. Published by Elsevier Masson SAS.

Sensitivity and positive predictive value of CT, MRI and 123I-MIBG scintigraphy in localizing pheochromocytomas: a prospective study.

PubMed

Lumachi, Franco; Tregnaghi, Alberto; Zucchetta, Pietro; Cristina Marzola, Maria; Cecchin, Diego; Grassetto, Gaia; Bui, Franco

2006-07-01

To establish a standardized non-invasive imaging protocol for patients with pheochromocytoma undergoing surgery. A series of 32 consecutive patients (16 men, 16 women; median age 43 years, range 15-71 years) with biochemically confirmed pheochromocytoma underwent computed tomography (CT) scanning, magnetic resonance imaging (MRI) and meta-[I]iodobenzylguanidine (MIBG) whole-body scintigraphy prior to adrenalectomy or excision of extra-adrenal tumour (paraganglioma). At final pathology no malignant pheochromocytomas were found. The tumour was right-sided in 16 (50%) patients, left-sided in 13 (41%), extra-adrenal (sympathetic ganglia, upper abdomen) in two (6%) and bilateral in one (3%) patient. Overall, the median greatest diameter (size) of the tumour was 35 mm (range, 15-90 mm). The sensitivity of CT, MRI and MIBG scintigraphy was 90%, 93% and 91%, and the specificity was 93%, 93% and 100%, respectively. The three patients with false negative scintigraphy had an intra-adrenal tumour, ranging from 20 to 50 mm in size. The presence of necrosis within the mass might justify the lack of significant uptake of radiopharmaceutical in two patients, and the small size (15 mm) of the mass in the other. There were two false positive results with both CT and MRI, and no false positive MIBG scintigraphy, which had the highest (100%) positive predictive value. The combination of MRI+MIBG scintigraphy reached 100% sensitivity and positive predictive value. Our data suggest that this imaging protocol should be used in all patients with biochemically confirmed pheochromocytoma.

The spectrum of pheochromocytoma in hypertensive patients with neurofibromatosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalff, V.; Shapiro, B.; Lloyd, R.

We have found an appreciable number of pheochromocytomas in patients with neurofibromatosis and concurrent hypertension (ten of 18 cases). At diagnosis, the patient age range was 15 to 62 years, the clinical appearance of the neurofibromatosis did not predict who would and who would not have pheochromocytomas, but the age at diagnosis was helpful in that our younger patients tended to have causes of hypertension other than pheochromocytoma. However, several causes of hypertension may coexist. The biochemical findings were highly diagnostic. The pheochromocytomas secreted epinephrine as well as norepinephrine and resided in or next to the adrenal gland. Where pheochromocytomamore » is the cause of hypertension, its resection generally results in a better control of hypertension than that obtained in patients whose BPs were elevated from other unknown causes.« less

Robotic management of pheochromocytoma of the vesicoureteric junction.

PubMed

Nayyar, Rishi; Singh, Prabhjot; Gupta, Narmada P

2010-01-01

Pheochromocytoma of the urinary bladder is rare, presenting usually with hypertension, hematuria and syncopal attacks. Such cases have usually been managed with open or laparoscopic partial cystectomy. We present a case of bladder pheochromocytoma that had unusual presenting symptoms, a paraneoplastic manifestation and was successfully managed with robotic technique.

Bilateral pheochromocytoma during the postpartum period.

PubMed

Wattanachanya, Lalita; Bunworasate, Udomsak; Plengpanich, Wanee; Houngngam, Natnicha; Buranasupkajorn, Patinut; Sunthornyothin, Sarat; Shotelersuk, Vorasuk; Snabboon, Thiti

2009-12-01

Pheochromocytoma manifesting during pregnancy is uncommon but it is responsible for a high maternal and fetal mortality rate, especially when unrecognized. Most cases of pheochromocytoma are sporadic but they can be part of hereditary autosomal dominant syndromes. We describe a case of bilateral pheochromocytoma in a term-pregnant patient with a previous history of medullary thyroid carcinoma (MTC). Her genetic study revealed a heterozygous mutation, c.1900T>C, in the RET proto-oncogene which confirmed the diagnosis of multiple endocrine neoplasia type 2A (MEN2A). Unrecognized, the tumors caused a crisis with fatal outcome in the mother during the postpartum period. This event might have been prevented if the tumor had been detected previously. MEN2A affected pregnancy is an unusual condition. This syndrome should be suspected when a pregnant patient has a history of MTC. Early detection and appropriate management can prevent serious maternal and fetal complications. We also reviewed the literature of MEN2A-affected pregnancies.

Pheochromocytoma with inferior vena cava thrombosis: An unusual association.

PubMed

Kota, Sunil K; Kota, Siva K; Jammula, Sruti; Meher, Lalit K; Modi, Kirtikumar D

2012-04-01

Pheochromocytomas have been described in association with vascular abnormalities like renal artery stenosis. A 48-year-old man was admitted to our hospital with the complaints of headache, sweating, anxiety, dizziness, nausea, vomiting and hypertension. For last several days, he was having a dull aching abdominal pain. Abdominal computed tomography (CT) revealed the presence of a left adrenal pheochromocytoma. An inferior vena cava (IVC) venogram via the right jugular vein demonstrated occlusion of the IVC inferior to the right atrium. Surgical removal of pheochromocytoma was done, followed by anticoagulant treatment for IVC thrombosis, initially with subcutaneous low molecular weight heparin, and then with oral warfarin, resulting in restoration of patency. To the best of our knowledge, the occurrence of pheochromocytoma in IVC thrombosis has not been reported so far from India. Possible mechanisms of such an involvement are discussed.

Systematic genetic screening in a prospective group of Danish patients with pheochromocytoma

PubMed Central

Hansen, Morten Steen Svarer; Jacobsen, Niels; Frederiksen, Anja Lisbeth; Lund, Lars; Andersen, Marianne Skovsager; Glintborg, Dorte

2017-01-01

Recent guidelines recommend consideration of genetic screening in all newly diagnosed patients with pheochromocytoma. Patients diagnosed with pheochromocytoma in the Region of Southern Denmark during 2006–2013 without previously recognized monogenetic etiology were offered genetic screening for mutations in the VHL, RET, SDHB, SDHC, and SDHD genes. A total of 41 patients were included, and genetic data were available in 35. In four of the 35 patients, a pathogenic variant was identified prior to the diagnosis of pheochromocytoma (von Hippel–Lindau disease, n=2; neurofibromatosis type 1, n=2). The patients carrying a genetic mutation were all younger than 45 years at time of diagnosis of pheochromocytoma, two patients presented with bilateral tumors, and one patient had a positive family history of pheochromocytoma. Genetic screening of the remaining 31 patients did not identify any mutations. The sporadic cases had a median age of 58 years (range 33–80 years). Three of 31 sporadic cases (ages 60, 69, and 76 years at time of diagnosis) presented with bilateral adrenal tumors, one patient had multiple adrenal tumors in both adrenal glands, and no patients had a positive family history of pheochromocytoma. Of the 31 patients, 24 (68.6%) were diagnosed with pheochromocytoma due to evaluation of an adrenal incidentaloma. In conclusion, monogenetic etiology was identified in four of 35 (11.4%) patients diagnosed with pheochromocytoma. PMID:28721348

Systemic antibiotics for treating malignant wounds.

PubMed

Ramasubbu, Darshini A; Smith, Valerie; Hayden, Fiona; Cronin, Patricia

2017-08-24

Malignant wounds are a devastating complication of cancer. They usually develop in the last six months of life, in the breast, chest wall or head and neck regions. They are very difficult to treat successfully, and the commonly associated symptoms of pain, exudate, malodour, and the risk of haemorrhage are extremely distressing for those with advanced cancer. Treatment and care of malignant wounds is primarily palliative, and focuses on alleviating pain, controlling infection and odour from the wound, managing exudate and protecting the surrounding skin from further deterioration. In malignant wounds, with tissue degradation and death, there is proliferation of both anaerobic and aerobic bacteria. The aim of antibiotic therapy is to successfully eliminate these bacteria, reduce associated symptoms, such as odour, and promote wound healing. To assess the effects of systemic antibiotics for treating malignant wounds. We searched the following electronic databases on 8 March 2017: the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library, 2017, Issue 3), Ovid MEDLINE, Ovid Embase and EBSCO CINAHL Plus. We also searched the clinical trial registries of the World Health Organization (WHO) International Clinical Trials Registry Platform (apps.who.int/trialsearch) and ClinicalTrials.gov on 20 March 2017; and OpenSIGLE (to identify grey literature) and ProQuest Dissertations & Theses Global (to retrieve dissertation theses related to our topic of interest) on 13 March 2017. Randomised controlled trials that assessed the effects of any systemic antibiotics on malignant wounds were eligible for inclusion. Two review authors independently screened and selected trials for inclusion, assessed risk of bias and extracted study data. A third reviewer checked extracted data for accuracy prior to analysis. We identified only one study for inclusion in this review. This study was a prospective, double-blind cross

Unusual case of pheochromocytoma presenting with diabetic ketoacidosis.

PubMed

Sedhai, Yub Raj; Reddy, Kruthika; Patel, Dhruvan; Lozada, James A

2016-10-19

Pheochromocytoma is a rare catecholamine-secreting tumour that arises from chromaffin cells in the adrenal medulla or extra-adrenal sympathetic ganglia. It classically presents with paroxysmal headaches, hypertension, palpitations and sweating related to catecholamine excess. Diabetes is reported to be present in approximately one-third of patients with pheochromocytoma; however, diabetic ketoacidosis is an extremely rare complication. We present a case of an African-American male aged 30 years who initially presented with diabetic ketoacidosis and hypertensive urgency whose blood pressure and glycaemic control improved remarkably following tumour excision. We will discuss this unusual presentation of pheochromocytoma along with a management approach for such adrenal incidentalomas. 2016 BMJ Publishing Group Ltd.

Changes in Body Mass Index in Pheochromocytoma Patients Following Adrenalectomy.

PubMed

Spyroglou, Ariadni; Adolf, Christian; Hahner, Stefanie; Quinkler, Marcus; Ladurner, Roland; Reincke, Martin; Beuschlein, Felix

2017-03-01

Catecholamine excess from pheochromocytoma results in cardiovascular symptoms such as arterial hypertension and tachycardia and induces metabolic alterations including glucose intolerance and increase in resting metabolic rate. The objective of our study was to investigate the effect of surgical cure of pheochromocytoma on body-mass-index and the correlation of body-mass-index changes to preoperative endocrine parameters. Pheochromocytoma patients from the Munich ENSAT Registry were matched (1:2) for age and gender to patients from the German Conn's Registry, who had undergone surgery for aldosterone-producing-adenomas. Thereby, 43 pheochromocytoma patients (17 males/26 females) and 86 aldosterone-producing-adenoma patients were analyzed for body-mass-index, blood pressure, and catecholamine levels before and one year after adrenalectomy. Seventy-four percent of pheochromocytoma patients were hypertensive preoperatively and 48% one year postoperatively. Systolic blood pressure did not differ significantly in pre- and postoperative measurements whereas diastolic blood pressure was significantly reduced over time. Moreover, pheochromocytoma patients gained body weight (p<0.001) one year following adrenalectomy accompanied by significant increases in body-mass-index, whereas aldosterone-producing adenoma patients displayed a slight weight loss. Despite weight gain, diagnosis of diabetes mellitus dropped from 9 of 43 investigated pheochromocytoma patients at baseline to 4 at follow-up. A significant correlation between body-mass-index changes to the preoperative catecholamine levels was found only for urinary normetanephrines. These data suggest that normalization of chronic catecholamine excess by adrenalectomy is associated with an increase in body-mass-index, which is more pronounced in patients with high preoperative levels of urinary normetanephrines. © Georg Thieme Verlag KG Stuttgart · New York.

Histopathological analysis of spontaneous large necrosis of adrenal pheochromocytoma manifested as acute attacks of alternating hypertension and hypotension: a case report.

PubMed

Ohara, Nobumasa; Uemura, Yasuyuki; Mezaki, Naomi; Kimura, Keita; Kaneko, Masanori; Kuwano, Hirohiko; Ebe, Katsuya; Fujita, Toshio; Komeyama, Takeshi; Usuda, Hiroyuki; Yamazaki, Yuto; Maekawa, Takashi; Sasano, Hironobu; Kaneko, Kenzo; Kamoi, Kyuzi

2016-10-12

Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Hypertension secondary to pheochromocytoma is often paroxysmal, and patients occasionally present with sudden attacks of alternating hypertension and hypotension. Spontaneous, extensive necrosis within the tumor that is associated with catecholamine crisis is an infrequent complication of adrenal pheochromocytoma, but its pathogenesis remains unclear. A 69-year-old Japanese man developed acute-onset episodic headaches, palpitations, and chest pains. During the episodes, both marked fluctuations in blood pressure (ranging from 40/25 to 300/160 mmHg) and high plasma levels of catecholamines were found simultaneously. Radiological findings indicated a 4-cm left adrenal pheochromocytoma. These episodic symptoms disappeared within 2 weeks with normalization of plasma catecholamine levels. Two months later, the patient underwent adrenalectomy. Microscopic examinations revealed pheocromocytoma with a large central area of coagulative necrosis. The necrotic material was immunohistochemically positive for chromogranin A. Granulation tissue was adjacent to the necrotic area, accompanied by numerous hemosiderin-laden macrophages and histiocytes with vascular proliferation. Viable tumor cells, detected along the periphery of the tumor, demonstrated pyknosis, and the Ki-67 labeling index was 2 % in the hot spot. No embolus or thrombus formation was found in the resected specimen harboring the whole tumor. The Pheochromocytoma of the Adrenal gland Scaled Score was 2 out of 20. The patient's postoperative course was unremarkable for > 7 years. Presumed causal factors for the extensive necrosis of adrenal pheochromocytoma in previously reported cases include hemorrhage into the tumor, hypotension induced by a phentolamine administration, embolic infarction, high intracapsular pressure due to malignant growth of the tumor, and catecholamine-induced vasoconstriction. In the present case, histopathological

An unusual case of hematemesis and epistaxis caused by a pheochromocytoma.

PubMed

Ugur, Kader; Girgin, Mustafa; Bahcecioglu, İbrahim Halil; Artas, Hakan; Selcuk Simsek, Fikri; Aydin, Suleyman

2018-01-01

Pheochromocytoma is a rare catecholamine-secreting neoplasm that is the cause of hypertension in <0.2% of patients with hypertension. We encountered an unusual case of pheochromocytoma involving hematemesis and epistaxis episodes with accompanying hypertensive attacks. Venous ectasia was detected in the esophagus. Abdominal magnetic resonance imaging revealed an adenoma in the left adrenal region. The present case illustrates that pheochromocytoma can mimic different clinical conditions.

Pheochromocytoma, papillary thyroid carcinoma.

PubMed

Nasser, Tariq; Qari, Faiza

2009-08-01

A 53-year-old woman presented with labile and difficult to control hypertension on 3 different anti-hypertensive medications. Abdominal computed tomography and ultrasonography of the thyroid gland showed a 1.8 cm thyroid nodule. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum thyroid stimulating hormone and free thyroxine, calcitonin, carcinoembryonic antigen, intact parathyroid hormone, and calcium levels were within normal limits. A 24-hour urine metanephrine showed significant elevation in urine metanephrine of approximately 3 times the upper limit of normal, and the result of 131I-metaiodobenzyleguanjdjne (131I-MIBG) scintigraphy confirmed that the adrenal mass was pheochromocytoma. Right adrenalectomy and total thyroidectomy were performed. The final pathology was pheochromocytoma and papillary thyroid carcinoma. An analysis of c-ret porto-oncogene mutation yielded a negative result. This unusual association of 2 tumors represents a new entity.

Robotic versus laparoscopic adrenalectomy for pheochromocytoma.

PubMed

Aliyev, Shamil; Karabulut, Koray; Agcaoglu, Orhan; Wolf, Katherine; Mitchell, Jamie; Siperstein, Allan; Berber, Eren

2013-12-01

Although initial reports demonstrated the safety and feasibility of robotic adrenalectomy (RA), there are scant data on the use of this approach for pheochromocytoma. The aim of this study is to compare perioperative outcomes and efficacy of RA versus laparoscopic adrenalectomy (LA) for pheochromocytoma. Within 3 years, 25 patients underwent 26 RA procedures for pheochromocytoma. These patients were compared with 40 patients who underwent 42 LA procedures before the start of the robotic program. Data were retrospectively reviewed from a prospectively maintained, IRB-approved adrenal database. Demographic and clinical parameters at presentation were similar between the groups, except for a larger tumor size in the robotic group. In both groups, skin-to-skin operative time, estimated blood loss less, and intraoperative hemodynamic parameters were similar. The conversion to open rate was 3.9 % in the robotic and 7.5 % in the laparoscopic group (p = .532). There was no morbidity or mortality in the robotic group; morbidity was 10 % (p = .041) and mortality 2.5 % in the laparoscopic group. The pain score on postoperative day 1 was lower, and the length of hospital stay shorter in the robotic group (1.2 ± .1 vs. 1.7 ± .1 days, p = .036). To our knowledge, this is the first study comparing robotic versus laparoscopic resection of pheochromocytoma. Our results show that the robotic approach is similar to the laparoscopic regarding safety and efficacy. The lower morbidity, less immediate postoperative pain, and shorter hospital stay observed in the robotic approach warrant further investigation in future larger studies.

Precision medicine in pheochromocytoma and paraganglioma: current and future concepts.

PubMed

Björklund, P; Pacak, K; Crona, J

2016-12-01

Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with PPGL have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics-based taxonomy, PPGL can be divided into three different clusters characterized by: Krebs cycle reprogramming with oncometabolite accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling pathway with increased tumour cell proliferation, invasiveness and migration (group 1b); and aberrant kinase signalling causing a pro-mitogenic and anti-apoptotic state (group 2). Categorization into these clusters is highly dependent on mutation subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes and outcomes have been described. Genetic screening tests have a documented benefit, as different PPGL syndromes require specific approaches for optimal diagnosis and localization of various syndrome-related tumours. Genotype-tailored treatment options, follow-up and preventive care are being investigated. Future new developments in precision medicine for PPGL will mainly focus on further identification of driver mechanisms behind both disease initiation and malignant progression. Identification of novel druggable targets and prospective validation of treatment options are eagerly awaited. To achieve these goals, we predict that collaborative large-scale studies will be needed: Pheochromocytoma may provide an example for developing precision medicine in orphan diseases that could ultimately aid in similar efforts for other rare conditions. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Extra-adrenal pheochromocytoma: an unusual cause of deep vein thrombosis.

PubMed

Stevenson, Susan; Ramani, Vijay; Nasim, Akhtar

2005-09-01

We report a case of extra-adrenal pheochromocytoma within the organ of Zuckerkandl that presented initially with a left iliofemoral deep venous thrombosis (DVT). At the time of presentation, the DVT was thought to be idiopathic as no underlying cause was detected. Subsequently, because of a series of medical events, the patient was further investigated. This led to a diagnosis of extra-adrenal pheochromocytoma. We discuss the management of patients presenting with DVT, the nature of pheochromocytoma within the organ of Zuckerkandl, and problems relating to its diagnosis.

Unenhanced CT imaging is highly sensitive to exclude pheochromocytoma: a multicenter study.

PubMed

Buitenwerf, Edward; Korteweg, Tijmen; Visser, Anneke; Haag, Charlotte M S C; Feelders, Richard A; Timmers, Henri J L M; Canu, Letizia; Haak, Harm R; Bisschop, Peter H L T; Eekhoff, Elisabeth M W; Corssmit, Eleonora P M; Krak, Nanda C; Rasenberg, Elise; van den Bergh, Janneke; Stoker, Jaap; Greuter, Marcel J W; Dullaart, Robin P F; Links, Thera P; Kerstens, Michiel N

2018-05-01

A substantial proportion of all pheochromocytomas is currently detected during the evaluation of an adrenal incidentaloma. Recently, it has been suggested that biochemical testing to rule out pheochromocytoma is unnecessary in case of an adrenal incidentaloma with an unenhanced attenuation value ≤10 Hounsfield Units (HU) at computed tomography (CT). We aimed to determine the sensitivity of the 10 HU threshold value to exclude a pheochromocytoma. Retrospective multicenter study with systematic reassessment of preoperative unenhanced CT scans performed in patients in whom a histopathologically proven pheochromocytoma had been diagnosed. Unenhanced attenuation values were determined independently by two experienced radiologists. Sensitivity of the 10 HU threshold was calculated, and interobserver consistency was assessed using the intraclass correlation coefficient (ICC). 214 patients were identified harboring a total number of 222 pheochromocytomas. Maximum tumor diameter was 51 (39-74) mm. The mean attenuation value within the region of interest was 36 ± 10 HU. Only one pheochromocytoma demonstrated an attenuation value ≤10 HU, resulting in a sensitivity of 99.6% (95% CI: 97.5-99.9). ICC was 0.81 (95% CI: 0.75-0.86) with a standard error of measurement of 7.3 HU between observers. The likelihood of a pheochromocytoma with an unenhanced attenuation value ≤10 HU on CT is very low. The interobserver consistency in attenuation measurement is excellent. Our study supports the recommendation that in patients with an adrenal incidentaloma biochemical testing for ruling out pheochromocytoma is only indicated in adrenal tumors with an unenhanced attenuation value >10 HU. © 2018 European Society of Endocrinology.

A giant cystic pheochromocytoma mimicking liver abscess an unusual presentation - a case report.

PubMed

Sarveswaran, Venugopal; Kumar, Surees; Kumar, Amit; Vamseedharan, Muthukumar

2015-01-01

Giant cystic pheochromocytoma is a rare neuroendocrine tumor. The possibility of cystic pheochromocytoma should be considered for any peri-adrenal mass even in absence of characteristic symptoms and negative biochemical analysis. The key in the management of a case of cystic pheochromocytoma is the preoperative suspicion and the intraoperative crisis management.

Tetralogy of Fallot with pheochromocytoma: an unusual therapeutic challenge.

PubMed

Balakrishnan, Gautam; Ravikumar, Ratnagiri; Rao, Suresh; Balakrishnan, Komarakshi R

2013-08-01

An adult with unoperated tetralogy of Fallot diagnosed simultaneously with pheochromocytoma is extremely rare. This poses obvious diagnostic and therapeutic challenges. A 29-year-old woman with these conditions was successfully operated on for both diseases in the same hospitalization. There is some interesting speculation regarding the association of pheochromocytoma with uncorrected cyanotic congenital heart disease.

Recurrence of non-cardiogenic pulmonary edema and sustained hypotension shock in cystic pheochromocytoma.

PubMed

Dai, Jin; Chen, Shen-Jie; Yang, Bing-Sheng; Lü, Shu-Min; Zhu, Min; Xu, Yi-Fei; Chen, Jie; Cai, Hong-Wen; Mao, Wei

2017-05-01

Pheochromocytoma is a rare neuroendocrine tumor which derives from chromaffin cells of the adrenal gland or relevant to sympathetic nerves and ganglia. The clinical features of pheochromocytoma are various. Paroxysmal episodes of serious hypertension, headache, palpitation, and diaphoresis are the typical manifestations (Bravo, 2004). Hypotension shock, pulmonary edema, and acute coronary syndrome induced by pheochromocytoma are uncommon (Malindretos et al., 2008; Batisse-Lignier et al., 2015). In this study, we present a rare case of cystic pheochromocytoma causing recurrent hypotension shock, non-cardiogenic pulmonary edema, and acute coronary syndrome, and the possible mechanisms are discussed.

[Subclinical adrenal diseases: silent pheochromocytoma and subclinical Addison's disease].

PubMed

Thuillier, P; Kerlan, V

2012-10-01

The silent pheochromocytoma, a hidden form of pheochromocytoma, exposes the patient to an increased risk of mortality if the diagnosis is not established on time. Biological diagnosis of pheochromocytoma can be difficult. Catecholamine secretion is dependent on tumor size and a large number of physiological, pharmacological, lifestyle modifications and sampling conditions influence the measurement of urinary and plasma metanephrines. The prevalence of pheochromocytoma is 2% among adrenal incidentaloma smaller than 3 cm (2/3 of tumors). Recent studies suggest the almost zero risk of pheochromocytoma among these tumors if they are hypodense (<10 housefield units) on adrenal tomography. Addison's disease is a pathology affecting about 1 in 8000. Immunopathology is still unknown, but some elements advocated the hypothesis of a predominant cell-mediated immunity in particular Interferon-gamma production by CD4 T lymphocytes in the presence of an epitope from the 21-hydroxylase, as well as IgG1 subtype produced by activated B lymphocytes, autoantibodies do appear to be a simple marker of the disease. Subclinical Addison's disease is defined by the presence of anti-21-hydroxylase autoantibodies, without clinical symptoms. It evolves faster to the clinical phase in young subjects, male, having high levels of autoantibodies and with an initially impaired adrenal function. Dosage of ACTH, plasma renin active, and basal cortisol and after Synacthen allow to discriminate the subjects with low or high risk of evolution and establish an appropriate monitoring. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Increased uptake of [123I]-meta-iodobenzylguanidine and [18F]-dopamine in mouse pheochromocytoma cells and tumors after treatment with the histone deacetylase inhibitors romidepsin and trichostatin A

PubMed Central

Martiniova, Lucia; Perera, Shiromi M.; Brouwers, Frederieke M.; Alesci, Salvatore; Abu-Asab, Mones; Marvelle, Amanda F.; Kiesewetter, Dale O.; Thomasson, David; Morris, John C.; Kvetnansky, Richard; Tischler, Arthur S.; Reynolds, James C; Fojo, A. Tito; Pacak, Karel

2014-01-01

Purpose [131I]-meta-iodobenzylguanidine ([131I]-MIBG) is the most commonly employed treatment for metastatic pheochromocytoma and paraganglioma; however, its success is limited. Its efficacy depends on the [131I]-MIBG concentration reached within the tumor through its uptake via the norepinephrine transporter and retention in neurosecretory granules. Purpose is to enhance [123I]-MIBG uptake in cells and liver pheochromocytoma tumors. Experimental Design We report the in vitro effects of two histone deacetylase (HDAC) inhibitors, romidepsin and trichostatin A, on increased uptake of [3H]-norepinephrine and [123I]-MIBG in mouse pheochromocytoma (MPC) cells, and the effect of romidepsin on [18F]-fluorodopamine and [123I]-MIBG uptake in a mouse model of metastatic pheochromocytoma. The effects of both inhibitors on norepinephrine transporter activity were assessed in MPC cells by [123I]-MIBG uptake studies with and without the transporter blocking agent desipramine and the vesicular blocking agent reserpine. Results Both HDAC inhibitors increased [3H]-norepinephrine, [123I]-MIBG, and [18F]-fluorodopamine uptake through the norepinephrine transporter in MPC cells. In vivo, inhibitor treatment resulted in increased uptake of [18F]-fluorodopamine and in pheochromocytoma liver metastases as measured by maximal standardized uptake values on PET imaging (p < 0.001). Analysis of biodistribution after inhibitor treatment confirmed the PET results in that uptake of [123I]-MIBG was significantly increased in liver metastases (p < 0.05). Therefore, HDAC inhibitor treatment increased radioisotope uptake in MPC cells in vitro and in liver metastases in vivo, through increased norepinephrine transporter activity. Conclusion These results suggest that HDAC inhibitors could enhance the therapeutic efficacy of [131I]-MIBG treatment in patients with malignant pheochromocytoma. PMID:21098082

Recurrence of non-cardiogenic pulmonary edema and sustained hypotension shock in cystic pheochromocytoma*#

PubMed Central

Dai, Jin; Chen, Shen-jie; Yang, Bing-sheng; Lü, Shu-min; Zhu, Min; Xu, Yi-fei; Chen, Jie; Cai, Hong-wen; Mao, Wei

2017-01-01

Pheochromocytoma is a rare neuroendocrine tumor which derives from chromaffin cells of the adrenal gland or relevant to sympathetic nerves and ganglia. The clinical features of pheochromocytoma are various. Paroxysmal episodes of serious hypertension, headache, palpitation, and diaphoresis are the typical manifestations (Bravo, 2004). Hypotension shock, pulmonary edema, and acute coronary syndrome induced by pheochromocytoma are uncommon (Malindretos et al., 2008; Batisse-Lignier et al., 2015). In this study, we present a rare case of cystic pheochromocytoma causing recurrent hypotension shock, non-cardiogenic pulmonary edema, and acute coronary syndrome, and the possible mechanisms are discussed. PMID:28471119

Management of pheochromocytoma: old ideas and new drugs.

PubMed

Domi, R; Laho, H

2012-01-01

Pheochromocytoma presents a challenge to the surgery team because of its clinical features and implications. The patient must be treated before the surgery until a stable hemodynamically state is achieved. The preoperative treatment includes α2-short acting adrenergic blocking and β-blocker agents. The most crucial intraoperative moments are induction of anesthesia and hemodynamic oscillations. An adequate preoperative preparation, modern anesthetic drugs, good collaboration between the surgeons and the anesthesiologists, and postoperative care decrease the rate of complications and improve the outcome. This review aims to discuss all the possible pharmacological strategies of perioperative management of phoechromocytoma, focusing on new drugs and treatments.

Pheochromocytoma and pregnancy: A case report and review.

PubMed

Santos, Davi Rettori Pardo Dos; Barbisan, Cinthia Callegari; Marcellini, Claudio; dos Santos, Rubia Marina Vieira Rettori

2015-01-01

Pheochromocytoma is a catecholamine-producing adrenal tumor, being a rare cause of hypertension in pregnancy. It's prevalence in hypertensive patients is 0.2%, and 0.002% of pregnancies. We follow hypertensive pregnant 24 year old on her third pregnancy, admitted to 33 weeks with hypertensive emergency cesarean section indicated by fetal distress evolving with acute pulmonary edema in the post-partum period. Indicated laparoscopy after 13 days for acute abdominal pain, with no significant finding. In the postoperative, due a severe and resistant hypertension, suspected of pheochromocytoma and confirmed by biochemical tests and imaging. Performed unilateral adrenelectomia with cure of hypertension. The pathology and immunohistochemistry confirmed the diagnosis. We conclude that atypical cases of hypertension in pregnancy should be investigated early and differentiated pre-eclampsia. Despite the low prevalence, pheochromocytoma in pregnancy increases fetal maternal morbidity and mortality and the early recognition and treatment drastically change their outcome.

Diagnosis of pheochromocytoma in the setting of Parkinson disease.

PubMed

Mehta, Shyamal H; Prakash, Rajan; Prisant, L Michael; Isales, Carlos M; Morgan, John C; Williams, Hadyn; Sethi, Kapil D

2009-06-01

A 59-year-old man with a 7-year history of Parkinson disease (PD) presented with episodes of sudden, severe headaches with neck pain, tachycardia, sweating and pallor. During these episodes, the patient showed marked elevations in blood pressure, regardless of posture. This was unusual, given that he had no prior history of hypertension. The array of symptoms raised suspicions of pheochromocytoma, but diagnosis was challenging, as the standard diagnostic biochemical tests were confounded by dopaminergic medications. Further work-up revealed left adrenal medullary hyperplasia. Several reports exist of pseudopheochromocytoma in patients on dopaminergic therapy, but this is the first documented case of pheochromocytoma syndrome due to adrenal medullary hyperplasia in a patient with PD. This case highlights the challenges of performing a diagnostic work-up in a PD patient with symptoms suggestive of pheochromocytoma, and illustrates the utility of (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission CT in making a diagnosis.Investigations. Physical examination, laboratory tests, abdominal MRI scan, abdominal (123)I-MIBG scan, abdominal (18)F-fluorodeoxyglucose PET scan. Pheochromocytoma syndrome due to adrenal medullary hyperplasia.Management. Surgical excision of the left adrenal gland.

Pheochromocytoma of the Urinary Bladder - A Case Report of an Unusual Presentation.

PubMed

Nerli, Rajendra B; Magdum, Prasad V; Patil, Amey Y; Devraju, Shishir; Hiremath, M B

2015-09-01

Urinary bladder pheochromocytoma is rare. We report a case of bladder pheochromocytoma presenting with practically no obvious clinical symptoms in an adolescent who had undergone repair of mitral valve disease.

Persistent Hiccups-An Unusual Presentation of Bilateral Pheochromocytoma without Syndromic Association: A Case Report.

PubMed

Aherrao, Nitin; Kumar, Nilesh; Gambhir, Indarajeet Singh; Kishore, Dhiraj; Singh, Suryakumar; Mishra, Abhinandan; Anand, Aravind

2012-01-01

Pheochromocytoma is a rare catecholamine-producing tumor arising from chromaffin tissue in the adrenal medulla, occurring in less than 0.2 percent of patients with hypertension. The mean age at diagnosis is about 40 years. Pheochromocytomas are commonly inherited as features of multiple endocrine neoplasia type 2 or several other pheochromocytoma-associated syndromes and have variable clinical presentation. Among the presenting symptoms, episodes of palpitations, headaches, and profuse sweating are typical and constitute a classic triad. We report a case of a 17-year-old male patient with rare bilateral pheochromocytoma presenting with persistent hiccups for 4 months and blurring of vision for 1 week, later followed by hypertensive crisis. There was neither family history of pheochromocytoma nor any classic symptoms. Patient was diagnosed with bilateral pheochromocytoma without any syndromic association. But still this patient needs to be followed for future development of medullary carcinoma of thyroid because it could be an initial presentation of MEN 2A/2B/VHL syndromes. Our paper highlights the importance of maintaining a high level of suspicion for persistent hiccups and careful clinical screening for hypertension even in absence of associated syndromes of pheochromocytoma and classical symptoms to achieve prompt diagnosis and to avoid improper management.

Unusual clinical manifestation of pheochromocytoma in a MEN2A patient.

PubMed

Guerrieri, M; Filipponi, S; Arnaldi, G; Giovagnetti, M; Lezoche, E; Mantero, F; Taccaliti, A

2002-01-01

A case of unusual clinical manifestation of pheochromocytoma in a type 2A multiple endocrine neoplasia (MEN2A) patient is presented. A 27-year-old man affected by MEN2A syndrome, complaining of anxiety and depression, was admitted in our Division. Past medical history included a total thyroidectomy for medullary carcinoma in 1985, and left adrenalectomy for pheochromocytoma in 1994. Blood pressure was 130/ 85 mmHg without orthostatic hypotension and pulse rate was 72 beats/min. Laboratory data revealed thyroid hormones and carcinoembryonic antigen (CEA) in the normal range and high basal serum calcitonin levels (158 pg/ml). Plasma catecholamines and vanillylmandelic acid resulted in normal levels but epinephrine/norepinephrine ratio was elevated (0.65). The glucagon stimulation test showed positive clinical and biochemical response. Magnetic resonance imaging (MRI) and meta-iodobenzylguanidine (MIBG) scintiscan confirmed the presence of bilateral adrenal masses. Bilateral adrenalectomy by laparoscopic anterior approach was performed. Histology was consistent with adrenal pheochromocytomas. After surgical approach, psychiatric findings disappeared and did not recur at follow-up in spite of no medication for two years. In conclusion, bilateral pheochromocytoma is more frequent in MEN2A syndrome and probably understimated if the follow-up is not prolonged. In these cases clinical features are often aspecific and basal hormonal data may be normal in a great number of patients. Therefore long-term observation is justified in these patients. Pheochromocytoma was described as the "great mimic" for the numerous subjective manifestations. Differential diagnosis among typical features of neuropsychiatric disorders and pheochromocytoma must be considered.

Tyrosine hydroxylase is activated and phosphorylated at different sites in rat pheochromocytoma PC 12 cells treated with phorbol ester and forskolin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tachikawa, E.; Tank, A.W.; Weiner, D.H.

1986-03-01

The effects of phorbol ester (4..beta..-phorbol, 12..beta..-myristate, 13..cap alpha..-acetate; TPA), an activator of Ca/sup + +//phospholipid-dependent protein kinase (PK-C), and forskolin, which stimulates adenylate cyclase and cyclic AMP-dependent protein kinase (cAMP-PK), on the activation and phosphorylation of tyrosine hydroxylase (TH) in rat pheochromocytoma (PC 12) cells were examined. Incubation of the cells with TPA (0.01-1 ..mu..M) or forskolin (0.01-0.1 ..mu..M) produces increases in activation and phosphorylation of TH in a concentration-dependent manner. The stimulatory effects of TPA are dependent on extracellular Ca/sup + +/ and are inhibited by pretreatment of the cells with trifluoperazine (TFP). The effects of forskolin aremore » independent of Ca/sup + +/ and are not inhibited by TFP. In cells treated with forskolin, the time course of the increase in cAMP correlates with the increases in TH activity and phosphorylation. cAMP levels do not increase in cells treated with TPA. There is an increase in the phosphorylation of only one tryptic phosphopeptide derived from TH in cells treated with either forskolin or TPA. The peptide phosphorylated in TPA-treated cells exhibits different elution characteristics on HPLC from that in forskolin-treated cells. The authors conclude that TH in PC 12 cells is phosphorylated on different sites by cAMP-PK and PK-C. Phosphorylation of either of these sites is associated with enzyme activation.« less

A Case of a Composite Adrenal Medullary Tumor of Pheochromocytoma and Ganglioneuroma Masquerading as Acute Pancreatitis

PubMed Central

Choi, Eun-Kyoung; Kim, Wan-Ho

2006-01-01

Composite adrenal medullary tumors, composed of both pheochromocytoma and ganglioneuroma, are extremely rare, as are pheochromocytomas masquerading as acute relapsing pancreatitis. We recently experienced a case of a 48-year-old male with both these phenomena. The patient complained of an acute onset of intense abdominal discomfort. At the same time, pancreatic enzymes were increased in concentration. An abdominal computed tomographic scan revealed an enlarged pancreas and a 3-cm left adrenal incidentaloma. Biochemical and 131I-MIBG scintigraphic findings were compatible with a pheochromocytoma. Yet, he had no clinical manifestations suggesting pheochromocytoma. An adrenalectomy was performed and a composite adrenal medullary tumor of pheochromocytoma and ganglioneuroma was confirmed during a pathologic examination. This case illustrates two points: 1) acute abdominal intense discomfort and hyperamylasemia may be unusual presentations of pheochromocytomas; and 2) the possibility of the pheochromocytoma, albeit rare, should be considered when a relapsing pancreatitis of uncertain etiology develops. PMID:16913447

Spontaneous rupture of pheochromocytoma and its clinical features: a case report.

PubMed

Maruyama, Mayumi; Sato, Haruhiro; Yagame, Mitsunori; Shoji, Sunao; Terachi, Toshiro; Osamura, Robert Yoshiyuki

2008-09-20

Rupture of adrenal pheochromocytoma is extremely rare and can be lethal because of dramatic changes in the circulation. We describe a 58-year-old Japanese man who suffered rupture of a pheochromocytoma. The patient was referred to our hospital because of severe hypertension (256/127 mmHg) and a left adrenal tumor. T2-weighted magnetic resonance imaging showed high signal intensity in the 50-mm left adrenal tumor. Endocrinological examinations showed elevated plasma and urinary catecholamine levels. These findings suggested that the left adrenal tumor was a pheochromocytoma. Phentolamine mesilate was administered intravenously. This resulted in a decrease of the systolic blood pressure to 100 mmHg. On the third hospital day, the patient complained of left back pain, and abdominal computed tomography showed rupture of the pheochromocytoma. Pulmonary congestion and effusion, and paralytic small-intestinal ileus occurred. Blood pressure was controlled, small-intestinal decompression was done with a Miller-Abbot tube, and body water was controlled by fluid replacement. After the general condition of the patient had became stable, laparoscopic adrenalectomy was performed. Phentolamine mesilate is a useful α-adrenergic blocker. However, care is needed with its administration, because rupture of pheochromocytoma may be related to a decrease in blood pressure induced by phentolamine mesilate.

Risk factors for hypertensive attack during pheochromocytoma resection

PubMed Central

Kwon, Se Yun; Lee, Kyung Seop; Lee, Jun Nyung; Ha, Yun-Sok; Choi, Seock Hwan; Kim, Hyun Tae; Kim, Tae-Hwan; Yoo, Eun Sang

2016-01-01

Purpose We aimed to retrospectively evaluate the risk factors for hypertensive attack during adrenalectomy in patients with pheochromocytoma. Despite the development of newer surgical and anesthetic techniques for the management of pheochromocytoma, intraoperative hypertensive attack continues to present a challenge. Materials and Methods Data from 53 patients diagnosed with pheochromocytoma at Kyungpook National Uriversity Medical Center between January 2000 and June 2012 were retrospectively analyzed. The subjects were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack. A univariate analysis was conducted, and a multivariate logistic regression analysis was also performed. Results In the univariate analysis, systolic blood pressure at presentation, preoperative hormonal status (including epinephrine, norepinephrine, vanillylmandelic acid, and metanephrine levels in a 24-hour urine sample), tumor size, and postoperative systolic blood pressure were significantly associated with the development of hypertensive attack. In the multivariate analysis, preoperative epinephrine level and tumor size were independent factors that predicted hypertensive attack. The highest odds ratio for tumor size (2.169) was obtained at a cutoff value of 4.25 cm and the highest odds ratio for preoperative epinephrine (1.020) was obtained at a cutoff value of 166.3 µg/d. Conclusions In this study, a large tumor size and an elevated preoperative urinary epinephrine level were risk factors for intraoperative hypertensive attack in patients with pheochromocytoma. PMID:27194549

Pheochromocytoma presenting with rhabdomyolysis and acute renal failure: a case report.

PubMed

Celik, Huseyin; Celik, Ozlem; Guldiken, Sibel; Inal, Volkan; Puyan, Fulya Oz; Tugrul, Armagan

2014-02-01

Rhabdomyolysis ranges from an asymptomatic illness with elevated creatine kinase levels to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure, and disseminated intravascular coagulation. The most common causes are crush injury, overexertion, alcohol abuse, certain medicines, and toxic substances. A number of electrolyte abnormalities and endocrinopathies, including hypothyroidism, thyrotoxicosis, diabetic ketoacidosis, nonketotic hyperosmolar state, and hyperaldosteronism, cause rhabdomyolysis. Rhabdomyolysis and acute renal failure are unusual manifestations of pheochromocytoma. There are a few case reports with pheochromocytoma presenting rhabdomyolysis and acute renal failure. Herein, we report a case with pheochromocytoma crisis presenting with rhabdomyolysis and acute renal failure.

Incidence of Second Malignancies Among Patients Treated With Proton Versus Photon Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Christine S., E-mail: chungc1@sutterhealth.org; Yock, Torunn I.; Nelson, Kerrie

2013-09-01

Purpose: Proton radiation, when compared with photon radiation, allows delivery of increased radiation dose to the tumor while decreasing dose to adjacent critical structures. Given the recent expansion of proton facilities in the United States, the long-term sequelae of proton therapy should be carefully assessed. The objective of this study was to compare the incidence of second cancers in patients treated with proton radiation with a population-based cohort of matched patients treated with photon radiation. Methods and Materials: We performed a retrospective cohort study of 558 patients treated with proton radiation from 1973 to 2001 at the Harvard Cyclotron inmore » Cambridge, MA and 558 matched patients treated with photon therapy in the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry. Patients were matched by age at radiation treatment, sex, year of treatment, cancer histology, and site. The main outcome measure was the incidence of second malignancies after radiation. Results: We matched 558 proton patients with 558 photon patients from the Surveillance, Epidemiology, and End Results registry. The median duration of follow-up was 6.7 years (interquartile range, 7.4) and 6.0 years (interquartile range, 9.3) in the proton and photon cohorts, respectively. The median age at treatment was 59 years in each cohort. Second malignancies occurred in 29 proton patients (5.2%) and 42 photon patients (7.5%). After we adjusted for sex, age at treatment, primary site, and year of diagnosis, proton therapy was not associated with an increased risk of second malignancy (adjusted hazard ratio, 0.52 [95% confidence interval, 0.32-0.85]; P=.009). Conclusions: The use of proton radiation therapy was not associated with a significantly increased risk of secondary malignancies compared with photon therapy. Longer follow-up of these patients is needed to determine if there is a significant decrease in second malignancies. Given the limitations of the

Cushing's syndrome due to ectopic CRH secretion by adrenal pheochromocytoma accompanied by renal infarction.

PubMed

Bayraktar, F; Kebapcilar, L; Kocdor, M A; Asa, S L; Yesil, S; Canda, S; Demir, T; Saklamaz, A; Seçil, M; Akinci, B; Yener, S; Comlekci, A

2006-09-01

Ectopic production of corticotropin-releasing hormone (CRH) by a pheochromocytoma is an infrequent cause of Cushing's syndrome. We report the case of a 43-year-old man with Cushing's syndrome due to a CRH-producing adrenal pheochromocytoma. The patient had clinical and biochemical evidence of hypercortisolism in conjunction with high ACTH levels and non-suppressible serum cortisol levels on low-dose and high-dose dexamethasone suppression testing. In addition to these clinical features of one month's duration, the patient developed symptoms of pheochromocytoma including headache, hypertension that was resistant to conventional therapy and excessive sweating. Biochemical testing confirmed elevated 24-hour urinary catecholamines and metabolites. Abdominal CT revealed a 4.5 x 4 x 3.5 cm mass in the left adrenal gland. He underwent elective left adrenalectomy. Light microscopic and immunochemical studies revealed a pheochromocytoma that contained immunoreactive CRH and was negative for ACTH. Plasma ACTH and dexamethasone supression tests normalized after surgery. This is an unusual case of a CRH-secreting pheochromocytoma. This was complicated by renal infarction, illustrating further the complexity of Cushing's syndrome in a patient with pheochromocytoma caused by CRH hypersecretion.

Unusual Long Survival with a Giant Invasive Pheochromocytoma of an Incompatible Patient.

PubMed

Nar, Asli

2018-03-13

Pheochromocytomas (PHEOs) are rare neuroendocrine tumors and about 2-13% of PHEOs are malignant. Predicting malignancy in PHEO cases with invasion but without metastasis is still controversial in the literature. This study presents an unusual long survival with a giant invasive PHEO in an incompatible patient and a review of the literature. In 1989, a 23-year-old female patient was operated for a giant adrenal mass with a pathological final diagnosis of PHEO. Information to the patient's family was provided about the short life span of the patient in the postoperative period because the tumor could not be totally resected. The patient started using regular antihypertensive drugs only after 1994. In 1994, 3700 mBq 131-I-metaiodobenzylguanidine (MIBG) treatment was given. Since then, no specific treatment was administered for PHEO due to patient incompatibility. She was diagnosed with type 2 diabetes mellitus at the age of 40 years and had a cerebrovascular accident due to hypertension at the age of 42. New abdominal computed tomography (CT) showed a right-sided 75 x 37 mm irregular and heterogeneous mass lesion extending inferiorly from the diaphragmatic crus level located in the right adrenal locus compatible with local recurrence. There was no I-123-MIBG uptake. She refused to have advanced workup and further treatment options. Malignant PHEOs reduce overall survival as a consequence of excessive catecholamine release, large tumor burden, and malignancy-related complications. Currently, the treatment of a malignant PHEO still has difficulties for both patients and doctors. Main treatment options for malignant PHEOs are primarily surgical excision. The effect of radionuclide therapy on survival time still remains to be determined. Efforts should be made to identify clinical, biochemical, and pathological criteria for malignancy and to develop new therapies in these patients with malignancy. The clinical course of malignant PHEOs is remarkably variable. Disease

PHEOCHROMOCYTOMA: AN ENDOCRINE STRESS MIMICKING DISORDER

PubMed Central

Kantorovich, Vitaly; Eisenhofer, Graeme; Pacak, Karel

2008-01-01

Pheochromocytoma is an endocrine tumor that can uniquely mimic numerous stress-associated disorders, with variations in clinical manifestations resulting from different patterns of catecholamine secretion and actions of released catecholamines on physiological systems. PMID:19120142

Differentiating pheochromocytoma from lipid-poor adrenocortical adenoma by CT texture analysis: feasibility study.

PubMed

Zhang, Gu-Mu-Yang; Shi, Bing; Sun, Hao; Jin, Zheng-Yu; Xue, Hua-Dan

2017-09-01

To investigate the feasibility of using CT texture analysis (CTTA) to differentiate pheochromocytoma from lipid-poor adrenocortical adenoma (lp-ACA). Ninety-eight pheochromocytomas and 66 lp-ACAs were included in this retrospective study. CTTA was performed on unenhanced and enhanced images. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curve (AUC) was calculated for texture parameters that were significantly different for the objective. Diagnostic accuracies were evaluated using the cutoff values of texture parameters with the highest AUCs. Compared to lp-ACAs, pheochromocytomas had significantly higher mean gray-level intensity (Mean), entropy, and mean of positive pixels (MPP), but lower skewness and kurtosis on unenhanced images (P < 0.001). On enhanced images, these texture-quantifiers followed a similar trend where Mean, entropy, and MPP were higher, but skewness and kurtosis were lower in pheochromocytomas. Standard deviation (SD) was also significantly higher in pheochromocytomas on enhanced images. Mean and MPP quantified from no filtration on unenhanced CT images yielded the highest AUC of 0.86 ± 0.03 (95% CI 0.81-0.91) at a cutoff value of 34.0 for Mean and MPP, respectively (sensitivity = 79.6%, specificity = 83.3%, accuracy = 81.1%). It was feasible to use CTTA to differentiate pheochromocytoma from lp-ACA.

Association of pheochromocytoma and ganglioneuroma: unusual finding in neurofibromatosis type 1.

PubMed

Mezitis, Spyros G E; Geller, Mauro; Bocchieri, Elisa; Del Pizzo, Joseph; Merlin, Scott

2007-10-01

To report a rare case of association of pheochromocytoma and ganglioneuroma in an asymptomatic patient with neurofibromatosis type 1 (NF1) and to discuss the importance of annual biochemical and imaging studies. We present the clinical, laboratory, and pathology findings in a 41-year-old woman with NF1 and review the pertinent literature. A 41-year-old woman with NF1 presented for a routine gynecologic examination, at which time a right adrenal mass (4 by 3 cm) was discovered by abdominal ultrasonography and confirmed by abdominal computed tomographic scans and magnetic resonance imaging. The patient was normotensive and complained only of discrete essential tremors. Biochemical studies showed a serum epinephrine level of 195 pg/mL (normal, <100) and a 24-hour urine epinephrine excretion of 55 microg (normal, <20), findings consistent with pheochromocytoma. Metaiodobenzylguanidine scintigraphy revealed uptake in the right adrenal gland, with no evidence of metastatic lesions. Before surgical treatment, the patient received an alpha-adrenergic antagonist for 30 days. Laparoscopic excision of the right adrenal gland yielded excellent postoperative results. Surgical pathology revealed a multinodular mass composed of pheochromocytoma and ganglioneuroma. In patients with NF1 (von Recklinghausen's disease), a tumor consisting of pheochromocytoma and ganglioneuroma is rare and may be more aggressive than pheochromocytoma alone. An asymptomatic catecholamine-producing tumor may cause substantial morbidity and mortality, especially in patients who are undergoing surgical intervention or are under other stressors. The current guidelines for managing patients with NF1 are an annual history and physical examination. Because of the increased prevalence of pheochromocytoma and ganglioneuroma in patients with NF1, and the potential associated adverse effects, we emphasize the importance of periodic clinical evaluation with biochemical testing and imaging studies.

Acute coronary syndrome-like presentation with prolonged QT interval: an unusual case of pheochromocytoma.

PubMed

Ozyuncu, Nil; Akturk, Sevinc; Tan Kurklu, Turkan Seda; Erol, Cetin

2016-09-26

Pheochromocytoma is a rare adrenal gland tumour, usually alerting the physician by causing hypertensive tachycardic attacks. Patients with pheochromocytoma can rarely present with clinical signs similar to acute coronary syndrome. QT interval prolongation and ST segment changes due to pheochromocytoma have also been reported in the literature in a few case reports. We report a patient who had been admitted to the emergency department with chest pain, ischaemic ECG changes and marked QT prolongation. Despite a normal coronary angiogram, we observed that the QT interval and ST segment morphologies had changed during the hospitalisation period. Adrenal adenoma was diagnosed incidentally on abdominal CT scan, and the final diagnosis was pheochromocytoma. The tumour was successfully excised and the patient is now symptom free. When there is lack of a typical clinical picture, the diagnosis of pheochromocytoma might be challenging. It is also very crucial, since misdiagnosis can be life-threatening. 2016 BMJ Publishing Group Ltd.

Unusual association of adrenal pheochromocytoma and para-aortic neurofibroma in pregnancy.

PubMed

Moretti, A; Minuto, M; Berti, P; Bernini, G P; Mannelli, M; Miccoli, P

2006-09-01

The association of pheochromocytoma (PHEO) and pregnancy is uncommon and life threatening for both the fetus and the mother. Early diagnosis and treatment is essential to decrease maternal and fetal mortality and to differentiate the disease from the more common pre-eclampsia. While medical treatment should be started immediately after diagnosis, the timing of surgical treatment is still debated. We describe the case of a 27-yr-old woman in the 18th week of pregnancy who showed a biochemical pattern typical of PHEO and, by imaging studies, 2 tumors with the same characteristics: the first localized on the right adrenal gland, the second at the right renal hilum. The patient underwent surgery because of suspicion of malignant PHEO with local metastasis, while histology revealed a rare association of a solitary PHEO and para-aortic neurofibroma, both tumors embryologically deriving from a common cell precursor.

Hypertensive crisis in pregnancy due to a metamorphosing pheochromocytoma with postdelivery Cushing's syndrome.

PubMed

Langton, Katharina; Gruber, Matthias; Masjkur, Jimmy; Steenblock, Charlotte; Peitzsch, Mirko; Meinel, Jörn; Lenders, Jacques; Bornstein, Stefan; Eisenhofer, Graeme

2018-01-01

Pheochromocytomas in pregnancy are rare but potentially lethal. Even rarer is the combination of pheochromocytoma in pregnancy with subsequent development of ectopic Cushing's syndrome. We report a 36-year-old woman, previously diagnosed with essential hypertension, who developed severe hypertension in pregnancy complicated by insulin-dependent gestational diabetes. A cesarean section was performed at 32 weeks following a hypertensive crisis after routine administration of betamethasone. Postnatal persistence of signs and symptoms of catecholamine excess led to the diagnosis of a left adrenal pheochromocytoma. Between diagnosis and planned tumor removal, the patient developed signs and symptoms of Cushing's syndrome (facial edema and hirsutism, myopathy and fatigue). Biochemical testing confirmed hypercortisolism with extremely elevated levels of plasma adrenocorticotropin, urinary cortisol and multiple steroids of a plasma panel that were all normal at previous testing. The previously noradrenergic tumor also started producing epinephrine. Histopathological examination confirmed the pheochromocytoma, which was also immunohistochemically positive for adrenocorticotropin. Full post-surgical recovery was sustained with normal blood pressure and biochemical findings after one year. This report not only underlines the chameleon behavior of pheochromocytoma but also illustrates its potential for a metamorphosing presentation. Corticosteroid administration in pregnancy requires a cautious approach in patients with hypertension.

[Analysis of a series pheochromocytoma cases over 15 years].

PubMed

Rojo Alvaro, J; Toni, M; Ollero, Md; Pineda, Jj; Munárriz, P; Anda, E

2012-01-01

The pheochromocytoma is a catecholamine secreting tumour derived from chromaffin cells of the sympathetic nervous system. Eighty to eighty-five percent of these tumours are localized in the adrenal medulla. When pheocromocytomas are found outside the adrenal gland they are referred to as extra-adrenal pheochromocytomas or paragangliomas. The diagnosis is confirmed by elevation of catecholamines and the metanephrines in blood plasma and urine. Localization of the tumour should be done following biochemical diagnosis by means of CT scan and/or MRI. The treatment of choice is tumour resection by laparoscopic surgery. A review was made of all patient medical histories diagnosed with pheochromocytoma confirmed by the pathology reports of Pathological anatomy of the Navarre hospital Complex (Anatomía patológica del Complejo hospitalario de Navarra A y B) between 1996 to 2010. Descriptive analysis was made using the IBM SPSS statistics program. Our series consists of 43 patients diagnosed with pheochromocytoma over a span of 15 years. The average age on presentation was 47 years. Among the younger patients specific genetic syndromes were found. Computerized tomography was the most widely used method of localization. Contradictory results were found regarding perioperative medical management protocols. All pheocromocytoma tumours in this series were benign. It is advisable to carry out a genetic study on patients under twenty. The biochemical indicators with the greatest diagnostic sensitivity were the levels of normetanephrine and metanephrine in urine. Surgery was the only treatment option.

Case Report: A giant but silent adrenal pheochromocytoma – a rare entity

PubMed Central

Munakomi, Sunil; Rajbanshi, Saroj; Adhikary, Prof Shailesh

2016-01-01

Herein we report a rare entity of a giant adrenal pheochromocytoma in a fifty-year-old male presenting with a vague abdominal pain. A computerised tomogram of the abdomen revealed a well-defined  left supraadrenal giant lesion with no evidence of invasion to surrounding structures.The patient underwent surgical excision without any untoward postoperative events. Histopathological study revealed a benign pheochromocytoma. This report highlights the importance of acknowledging the fact that sometimes a giant adrenal pheochromocytoma can present with paucity of clinical  signs and symptoms.Thorough investigations and a multidisciplinary team approach may lead  to a better outcome in these patients. PMID:27785358

Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

PubMed

Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

2014-03-01

Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

MANAGEMENT OF ENDOCRINE DISEASE: Outcome of adrenal sparing surgery in heritable pheochromocytoma.

PubMed

Castinetti, F; Taieb, D; Henry, J F; Walz, M; Guerin, C; Brue, T; Conte-Devolx, B; Neumann, H P H; Sebag, F

2016-01-01

The management of hereditary pheochromocytoma has drastically evolved in the last 20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von Hippel-Lindau (VHL) mutation carriers who are followed regularly, but these mutations induce major morbidities if total bilateral adrenalectomy is performed. Cortical sparing adrenal surgery may be proposed to avoid definitive adrenal insufficiency. The surgical goal is to leave sufficient cortical tissue to avoid glucocorticoid replacement therapy. This approach was achieved by the progressive experience of minimally invasive surgery via the transperitoneal or retroperitoneal route. Cortical sparing adrenal surgery exhibits <5% significant recurrence after 10 years of follow-up and normal glucocorticoid function in more than 50% of the cases. Therefore, cortical sparing adrenal surgery should be systematically considered in the management of all patients with MEN2 or VHL hereditary pheochromocytoma. Hereditary pheochromocytoma is a rare disease, and a randomized trial comparing cortical sparing vs classical adrenalectomy is probably not possible. This lack of data most likely explains why cortical sparing surgery has not been adopted in most expert centers that perform at least 20 procedures per year for the treatment of this disease. This review examined recent data to provide insight into the technique, its indications, and the results and subsequent follow-up in the management of patients with hereditary pheochromocytoma with a special emphasis on MEN2. © 2016 European Society of Endocrinology.

Failure of MIBG scan to detect metastases in SDHB-mutated pediatric metastatic pheochromocytoma.

PubMed

Sait, Sameer; Pandit-Taskar, Neeta; Modak, Shakeel

2017-11-01

123 I-meta-iodo benzyl guanidine (MIBG) scans are considered the gold standard imaging in neuroblastoma; however, flouro deoxy glucose positron emission tomography (FDG-PET) scans have increased sensitivity in adults with pheochromocytoma/paraganglioma. We describe a pediatric patient initially considered to have localized neuroblastoma based on anatomical imaging and 123 I-MIBG scan, but subsequent investigations revealed germline succinate dehydrogenase complex iron sulfur subunit B (SDHB) mutation-associated pheochromocytoma with multiple FDG-avid skeletal metastases. We then compared 123 I-MIBG and FDG-PET scans in children with metastatic pheochromocytoma/paraganglioma. FDG-PET was superior to 123 I-MIBG scan for the detection of skeletal metastases (median number of skeletal lesions detected 10 [range 1-30] vs. 2 [range 1-26], respectively; P = 0.005 by t-test). FDG-PET should be considered the functional scan of choice in children with pheochromocytoma/paraganglioma. © 2017 Wiley Periodicals, Inc.

Old, New, and Emerging Immunohistochemical Markers in Pheochromocytoma and Paraganglioma.

PubMed

Cheung, Veronica K Y; Gill, Anthony J; Chou, Angela

2018-05-19

The evolution of genetic research over the past two decades has greatly improved the understanding of pheochromocytomas and paragangliomas. It is now accepted that more than one third of pheochromocytoma and paragangliomas arise in the context of syndromic disease, usually hereditary. The genetic profile of these tumors also has important prognostic implications which may help guide treatment. Accompanying the changing molecular landscape is the development of new immunohistochemical markers. Initially used in assisting with diagnosis, immunohistochemical markers have now become an important adjunct to screening programs for inherited conditions and subsequently as prognostic markers. The accessibility and efficiency of immunohistochemistry bring pathologists to the forefront in triaging patients based on tumor genotype-phenotype. In this review, we provide an update on the role of immunohistochemistry in the diagnosis of pheochromocytomas and paragangliomas, as an adjunct to assessment for hereditary disease and finally as a potential tool to assist risk stratification.

Pheochromocytoma Screening Initiation and Frequency in von Hippel-Lindau Syndrome

PubMed Central

Aufforth, Rachel D.; Ramakant, Pooja; Sadowski, Samira M.; Mehta, Amit; Trebska-McGowan, Katarzyna; Nilubol, Naris; Pacak, Karel

2015-01-01

Context: Patients with von Hippel-Lindau (VHL) syndrome have a 25–30% chance of developing pheochromocytoma. Although practice guidelines recommend biochemical and radiological screening every 1–2 years for pheochromocytoma in patients with VHL, there are limited data on the optimal age and frequency for screening. Objective: Our objective was to determine the earliest age of onset and frequency of contralateral and recurrent pheochromocytomas in patients with VHL syndrome. Methods: This is a retrospective analysis of a prospective cohort of patients with VHL enrolled in a natural history study. Results: A total of 273 patients diagnosed with VHL were enrolled in a natural history clinical study. Thirty-one percent (84) were diagnosed with pheochromocytoma. The mean age of diagnosis was 28.8 ± 13.9 years. The earliest age at diagnosis was 5.5 years. Median follow-up for the cohort was 116.6 months (range, 0.1–613.2). Ninety-nine percent (83) of patients underwent adrenalectomy. Fifty-eight and 32% of patients had metanephrines and/or catecholamines elevated more than two times and more than four times the upper limit of normal, respectively. Twenty-five percent (21) of pheochromocytomas were diagnosed in pediatric patients younger than 19 years of age, and 86% and 57% of pediatric patients had an elevation more than two times and more than four times upper limit of normal, respectively. Eight patients had a total of nine recurrences. The median age at recurrence was 33.5 years (range, 8.8–51.9). Recurrences occurred as short as 0.5 years and as long as 39.7 years after the initial operation. Conclusions: Our findings among VHL pediatric patients supports the need for biochemical screening starting at age 5 with annual lifelong screening. PMID:26451910

Longitudinal plasma metanephrines preceding pheochromocytoma diagnosis: a retrospective case-control serum repository study.

PubMed

Olson, S W; Yoon, S; Baker, T; Prince, L K; Oliver, D; Abbott, K C

2016-03-01

Plasma metanephrines (PMN) are highly sensitive for diagnosis of pheochromocytoma, but the natural history of PMN before pheochromocytoma diagnosis has not been previously described. The aim of the study was to compare the progression of PMN before pheochromocytoma diagnosis to matched healthy and essential hypertension disease controls. A retrospective case-control Department of Defense Serum Repository (DoDSR) study. We performed a DoDSR study that compared three longitudinal pre-diagnostic PMN for 30 biopsy-proven pheochromocytoma cases to three longitudinal PMN for age, sex, race, and age of serum sample matched healthy and essential hypertension disease controls. Predominant metanephrine (MN) or normetanephrine (NMN) production was identified for each case and converted to a percentage of the upper limit of normal to allow analysis of all cases together. PMN were measured by Quest Diagnostics. The predominant plasma metanephrine (PPM) was >100 and 300% of the upper limit of normal a median of 6.6 and 4.1 years before diagnosis respectively. A greater percentage of pheochromocytoma patients had a PPM >100 and >300% of the upper limit of normal compared with combined healthy and essential hypertension disease controls <2, 2-8, and >8 years prior to diagnosis. For patients with a baseline PPM 90-300% of the upper limit of normal, a 25% rate of rise per year was 100% specific for pheochromocytoma. PPMs elevate years before diagnosis which suggests that delayed diagnoses are common. For mild PMN elevations, follow-up longitudinal PMN trends may provide a highly specific and economical diagnostic tool. © 2016 European Society of Endocrinology.

Superficial ocular malignancies treated with strontium-90 brachytherapy: long term outcomes.

PubMed

Laskar, Siddhartha; Gurram, Lavanya; Laskar, Sarbani Ghosh; Chaudhari, Suresh; Khanna, Nehal; Upreti, Rituraj

2015-10-01

The incidence of conjunctival malignancies is less than 1%. Though surgical excision remains the mainstay of treatment, the incidence of positive surgical margins and local recurrence rates are high, which is approximately up to 33% in negative margins and 56% in positive margins. Radiotherapy reduces the risk of recurrence in these cases. Brachytherapy using β emitters such as strontium-90 ((90)Sr) is an ideal treatment technique for these tumors with the advantage of treating only a few millimeters of tissue while sparing the underlying normal eye. We report the long term outcomes in the form of local control and late sequelae of patients with conjunctival malignancies treated with (90)Sr applicator brachytherapy. During 1999-2013, 13 patients with conjunctival tumors, treated using (90)Sr brachytherapy were analyzed. Brachytherapy was either in a post-operative adjuvant or in a recurrent setting. Local control (LC), disease free survival (DFS), overall survival (OS), and late sequelae were evaluated. The median age at presentation was 47 years (range: 11-71 years). Thirteen patients with 15 tumors were treated. The commonest histology was squamous cell carcinoma. The median dose was 44 Gy over 11 fractions. The median follow up of all the patients was 51 months (range: 3-139 months). The median follow up of patients with carcinoma only was 64 months with a LC and DFS of 90.9% at 5 years. None of the patients developed ≥ grade II Radiation Therapy Oncology Group (RTOG) acute toxicities. One patient developed a focal scar and another developed corneal opacification at the limbus. Vision was not impaired in any of the patients. Strontium-90 brachytherapy used in early invasive conjunctival malignancies as an adjunct to surgery in primary and recurrent settings, results in optimal disease control and ocular functional outcomes.

Superficial ocular malignancies treated with strontium-90 brachytherapy: long term outcomes

PubMed Central

Gurram, Lavanya; Laskar, Sarbani Ghosh; Chaudhari, Suresh; Khanna, Nehal; Upreti, Rituraj

2015-01-01

Purpose The incidence of conjunctival malignancies is less than 1%. Though surgical excision remains the mainstay of treatment, the incidence of positive surgical margins and local recurrence rates are high, which is approximately up to 33% in negative margins and 56% in positive margins. Radiotherapy reduces the risk of recurrence in these cases. Brachytherapy using β emitters such as strontium-90 (90Sr) is an ideal treatment technique for these tumors with the advantage of treating only a few millimeters of tissue while sparing the underlying normal eye. We report the long term outcomes in the form of local control and late sequelae of patients with conjunctival malignancies treated with 90Sr applicator brachytherapy. Material and methods During 1999-2013, 13 patients with conjunctival tumors, treated using 90Sr brachytherapy were analyzed. Brachytherapy was either in a post-operative adjuvant or in a recurrent setting. Local control (LC), disease free survival (DFS), overall survival (OS), and late sequelae were evaluated. Results The median age at presentation was 47 years (range: 11-71 years). Thirteen patients with 15 tumors were treated. The commonest histology was squamous cell carcinoma. The median dose was 44 Gy over 11 fractions. The median follow up of all the patients was 51 months (range: 3-139 months). The median follow up of patients with carcinoma only was 64 months with a LC and DFS of 90.9% at 5 years. None of the patients developed ≥ grade II Radiation Therapy Oncology Group (RTOG) acute toxicities. One patient developed a focal scar and another developed corneal opacification at the limbus. Vision was not impaired in any of the patients. Conclusions Strontium-90 brachytherapy used in early invasive conjunctival malignancies as an adjunct to surgery in primary and recurrent settings, results in optimal disease control and ocular functional outcomes. PMID:26622243

Localization and molecular forms of galanin in human adrenals: elevated levels in pheochromocytomas.

PubMed

Bauer, F E; Hacker, G W; Terenghi, G; Adrian, T E; Polak, J M; Bloom, S R

1986-12-01

Galanin immunoreactivity was measured by RIA, using antibodies directed against both the non-C- and C-terminal positions of porcine galanin, in tissue extracts of normal adrenals and pheochromocytomas and also in the plasma of normal subjects and patients with pheochromocytomas. No C-terminal galanin-like immunoreactivity was detected in plasma or tissue, suggesting differences in the amino acid sequence of human compared with porcine galanin. A non-C-terminally directed antibody was, therefore, used to characterize human galanin immunoreactivity by gel permeation chromatography and reverse phase high pressure liquid chromatography and to localize it by immunocytochemistry. The galanin content of whole adrenal gland was 2.6 +/- 0.9 (+/- SEM) pmol/g (n = 5). In contrast, however, pheochromocytomas had much greater concentrations (21 +/- 2.3 pmol/g; n = 16). Gel chromatography and reverse phase high pressure liquid chromatography revealed 2 molecular forms of galanin immunoreactivity with identical elution positions in both normal adrenals and tumors. The concentration of galanin in plasma from both normal subjects and pheochromocytoma patients was below the detection limit of the assay (less than 10 pmol/liter). Using immunocytochemistry, galanin was localized to scattered cells or clusters of tumor cells in 5 of 11 pheochromocytomas and only a few chromaffin cells and cortical nerve fibers in normal adrenals.

Pembrolizumab in Treating Patients With Malignant Mesothelioma

ClinicalTrials.gov

2018-03-01

Biphasic Mesothelioma; Epithelioid Mesothelioma; Peritoneal Malignant Mesothelioma; Pleural Biphasic Mesothelioma; Pleural Epithelioid Mesothelioma; Pleural Malignant Mesothelioma; Pleural Sarcomatoid Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Sarcomatoid Mesothelioma

Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma.

PubMed

Comino-Méndez, Iñaki; Gracia-Aznárez, Francisco J; Schiavi, Francesca; Landa, Iñigo; Leandro-García, Luis J; Letón, Rocío; Honrado, Emiliano; Ramos-Medina, Rocío; Caronia, Daniela; Pita, Guillermo; Gómez-Graña, Alvaro; de Cubas, Aguirre A; Inglada-Pérez, Lucía; Maliszewska, Agnieszka; Taschin, Elisa; Bobisse, Sara; Pica, Giuseppe; Loli, Paola; Hernández-Lavado, Rafael; Díaz, José A; Gómez-Morales, Mercedes; González-Neira, Anna; Roncador, Giovanna; Rodríguez-Antona, Cristina; Benítez, Javier; Mannelli, Massimo; Opocher, Giuseppe; Robledo, Mercedes; Cascón, Alberto

2011-06-19

Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.

Spontaneous ruptured pheochromocytoma: an unusual case report and literature review.

PubMed

Jee, Ye Seob

2017-09-01

Ruptured pheochromocytoma is a rare disease. Its mortality rate is up to 31%-50%. Proper management of ruptured pheochromocytoma remains unclear. A 44-year-old male patient visited our Emergency Department and presented with abrupt onset of left flank pain. His blood pressure was 190/140 mmHg with purse rate of 130 beats/min. CT scan showed 8.1 × 5.6-cm-sized heterogeneously mass with rupture on the left retroperitoneal space and active bleeding. His symptom of abdominal pain was aggravated. Follow-up laboratory analysis revealed elevated WBC count and decreased hemoglobin 2 hours after admission. Emergency laparotomy was performed. We resected the ruptured left retroperitoneal mass and hemostasis. Pathologic exams revealed adrenal pheochromocytoma with rupture. Although our patient was alive, according to literature review, mortality rate of emergency operation without medical management is higher than elective operation after blood pressure control with either medical or interventional methods such as transcatheter arterial embolization.

Severe polyuria after the resection of adrenal pheochromocytoma.

PubMed

Tobe, Musashi; Ito, Keiichi; Umeda, Shun; Sato, Akinori; Adaniya, Noriaki; Tanaka, Yuji; Hayakawa, Masamichi; Asano, Tomohiko

2010-12-01

A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary β2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date. © 2010 The Japanese Urological Association.

The importance of pheochromocytoma case detection in patients with neurofibromatosis type 1: A case report and review of literature.

PubMed

Tate, Joshua M; Gyorffy, Janelle B; Colburn, Jeffrey A

2017-01-01

Neurofibromatosis type 1 is a complex, multi-system genetic disorder that is associated with an increased prevalence of pheochromocytoma and paraganglioma compared to the general population, 1.0%-5.7% versus 0.2%-0.6%, respectively. A delay in pheochromocytoma and paraganglioma diagnosis or undiagnosed pheochromocytoma and paraganglioma, as seen in normotensive and asymptomatic patients, may portend a significant morbidity and mortality risk due to excess catecholamine secretion. Currently, there are no generally accepted guidelines of screening for pheochromocytoma and paragangliomas in asymptomatic individuals of this population with approaches and practices varying considerably between physicians. Emerging data suggest benefit in routine pheochromocytoma and paraganglioma screening of all individuals with neurofibromatosis type 1. Herein, we present a case to highlight how routine case detection screening would have identified pheochromocytoma earlier in an active duty military member.

Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone.

PubMed

Kim, Beom-Jun; Kwak, Mi Kyung; Ahn, Seong Hee; Kim, Hyeonmok; Lee, Seung Hun; Song, Kee-Ho; Suh, Sunghwan; Kim, Jae Hyeon; Koh, Jung-Min

2017-08-01

Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable. To clarify the link between the sympathetic nervous system and the skeleton in humans. Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly. This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption. Copyright © 2017 Endocrine Society

Orthostatic hypotension as an unusual clinical manifestation of pheochromocytoma: a case report.

PubMed

Bortnik, Miriam; Occhetta, Eraldo; Marino, Paolo

2008-08-01

Pheochromocytoma is a rare endocrine tumor which can have a highly variable presentation related to increased catecholamine secretion. We report the case of a 74-year-old man in whom recurrent episodes of syncope due to orthostatic hypotension were the only clinical manifestations of this challenging entity. Diagnosis of pheochromocytoma was achieved by biochemical test samples and computed tomography scans. Surgical excision of the tumor resulted in clinical improvement with normalization of catecholamine concentrations and no more episodes of orthostatic hypotension during a follow-up of 24 months. Although rare, pheochromocytoma may frequently cause disorders of orthostatic tolerance; because of its meaningful implications, screening for this entity should be considered in case of recurrent syncopal episodes due to new-onset orthostatic hypotension.

Controlling Tumor Progression with Cyclophosphamide, Vincristine, and Dacarbazine Treatment Improves Survival in Patients with Metastatic and Unresectable Malignant Pheochromocytomas/Paragangliomas.

PubMed

Asai, Shiko; Katabami, Takuyuki; Tsuiki, Mika; Tanaka, Yasushi; Naruse, Mitsuhide

2017-04-01

Evidence has not been established to support that combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) improves survival in patients with malignant pheochromocytoma and paraganglioma (M-PPGL). To investigate the efficacy of CVD for this disease, we retrospectively analyzed data of 23 patients with metastatic and unresectable M-PPGL (mean age, 41.7 ± 15.4 years) who received at least 2 cycles of this regimen. The follow-up period after initiation of CVD ranged from 0.3 to 13.7 years, with a median of 3.3 years. CVD therapy achieved a complete tumor response (CR) in 1 patient (4%), a partial response (PR) in 5 (22%), stable disease (SD) in 5 (22%), and progressive disease (PD) in 13 (52%), respectively. All of the responders (CR and PR) but 6% of the non-responders (SD and PD) showed substantial biochemical improvement. The progression-free survival period in the responders was significantly longer than in the non-responders (p < 0.01). Although the overall survival and survival after the diagnosis of M-PPGL were longer in the responders than the non-responders, the difference was not statistically significant (p = 0.08). The progression-free and overall survival period were significantly longer in the non-progression group (CR, PR, and SD) than in the progression group (PD) (1.7 ± 3.3 vs. 0.3 ± 0.3 years, p < 0.01, and 4.6 ± 3.6 vs. 2.0 ± 3.7 years, p = 0.01, respectively). It is therefore suggested that CVD chemotherapy could be useful in controlling tumor progression and improving survival in patients with metastatic and progressive M-PPGL.

Adrenal cortical oncocytoma mimicking pheochromocytoma.

PubMed

Kiriakopoulos, Andreas; Papaioannou, Dimitrios; Linos, Dimitrios

2011-01-01

Adrenal tumors present with clinical features and signs unique to their specific hormonal hypersecretion. However, there have been cases in which the clinical expression has been in conflict with the histologic features of the tumor. In this communication we report an unusual clinical presentation of an adrenal cortical tumor with histologic features of an oncocytoma that clinically mimicked a pheochromocytoma. A 49-year old man was referred to our Unit due to type B aortic dissection and a mass of the left adrenal gland. Computed tomography and magnetic resonance imaging confirmed the presence of aortic dissection extending from the left subclavian artery to both iliac arteries and also revealed a 6 cm tumor on the left adrenal gland. Preoperative endocrine evaluation showed a near tenfold increase of urinary vanillylmandelic acid (VMA) and metanephrine values. Transperitoneal laparoscopic adrenalectomy was successfully performed. The adrenal tumor proved to be an adrenal cortical neoplasm with histologic features of oncocytoma. Although the case of an adrenal cortical adenoma clinically mimicking a pheochromocytoma has been described in the literature, to the best of our knowledge, there has been no previous report of an adrenal cortical neoplasm with predominant features of oncocytoma.

Risk of second malignancies in patients with early-stage classical Hodgkin's lymphoma treated in a modern era.

PubMed

LeMieux, Melissa H; Solanki, Abhishek A; Mahmood, Usama; Chmura, Steven J; Koshy, Matthew

2015-04-01

Second malignancies remain an issue affecting morbidity and mortality in long-term survivors of early stage Hodgkin's lymphoma (HL). We undertook this study to determine if treatment in the modern era resulted in decreased second malignancies. Patients diagnosed with stage I-II cHL between 1988 and 2009 who received radiation therapy (RT) were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Freedom from second malignancy (FFSM) was estimated using the Kaplan-Meier method. Univariate analysis (UVA) was performed using the Log-Rank test, and included age, gender, year of diagnosis, and stage. Multivariable analysis (MVA) was performed using Cox Proportional Hazards modeling. The study cohort included 8807 patients. The median age at diagnosis was 32 years (range: 2-85). The majority of patients had stage II disease (n = 6044, 69%), 597 (7%) had extranodal involvement (ENI), and 1925 (22%) had B symptoms. Median follow-up for the entire cohort was 7.2 years (range: 0-22). Five hundred twenty-three (6%) patients developed a second malignancy. Median latency to second malignancy was 5.8 years (range: 0.1-21.5). Of the 523 patients that developed a second malignancy, 228 (44%) occurred in the first 5 years, 139 (27%) were diagnosed between years 5-10, and 156 (30%) beyond 10 years. The 10 year FFSM for patients treated between 1988 and 1999 was 93.0% versus 95.1% for patients treated between 2000 and 2009 (P = 0.04), On MVA, treatment between 2000 and 2009 was associated with a HR for second malignancy of 0.77 (95% Confidence Interval: 0.62-0.96, P = 0.02) compared to the treatment between 1988 and 1999. Our analysis suggests that in patients treated with RT for stage I or II cHL, treatment prior to 2000 had a slightly higher risk of second malignancy compared to treatment in 2000 and later. Further studies, with longer follow-up of patients treated in the modern era are needed to confirm these findings. © 2015 The Authors. Cancer Medicine

Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain.

PubMed

Li, Xiao; Li, Guoqi; Wu, Shaoling; Zhang, Baiyu; Wan, Qing; Yu, Ding; Zhou, Ruijun; Ma, Chao

2014-07-08

Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

A rare presentation of pheochromocytoma in pregnancy: a case report.

PubMed

Ghalandarpoor-Attar, Seyedeh Noushin; Ghalandarpoor-Attar, Seyedeh Mojgan; Borna, Sedigheh; Ghotbizadeh, Fahimeh

2018-02-09

Early diagnosis of pheochromocytoma and its proper management can lessen its mortality and morbidity. This case report describes a 24-year-old pregnant woman with an unusual presentation of pheochromocytoma. An Iranian 24-year-old primigravid woman from Kordistan province was referred to our center with left flank pain at 37 weeks of gestation. She had a history of gestational diabetes mellitus since the 12th week of gestation which was managed by insulin administration. She also had a history of pulsatile bi-temporal headache for 2 years prior to her referral to us. She underwent complete abdominal and pelvic ultrasound imaging for her flank pain. This examination revealed a heterogeneous mass of 119 × 87 × 79 mm above her left kidney, highly suspicious of being an adrenal-originating tumor. Subsequently, we consulted an endocrinologist. She underwent abdominopelvic magnetic resonance imaging and her 24-hour urine metanephrine, normetanephrine, and vanillylmandelic acid were assessed. Finally, the diagnosis of pheochromocytoma was confirmed. She underwent a cesarean section and adrenal mass excision at the 40th week of gestation. This timely diagnosis resulted in her proper management and good maternal and neonatal treatment outcomes. Our patient had pheochromocytoma during pregnancy. She had no complaints about hypertension before or during pregnancy until giving birth to her child; her only symptoms were a vague left flank pain, gestational diabetes, and headaches for the past 2 years. The unusual symptom of flank pain led to timely diagnosis and a good treatment outcome.

Pheochromocytoma and paraganglioma

PubMed Central

Kantorovich, Vitaly; Pacak, Karel

2016-01-01

Pheochromocytoma is a very special kind of tumor full of duplicity. On the one hand it represents its own microworld with unique clinical, biochemical and pathological features, while on the other it constitutes a tremendously significant part of whole body system, playing a vital role for practically every organ system. It has a very special character – sometimes like a child it can be sweet and predictable, while at times it can behave like a deadly wild beast, crashing and tearing everything on its path in a fierce rage. It also consists of the amazingly intelligent neuroendocrine cells that possess a magical ability to make miraculous substances of many kinds. But most of all, it is a system that is able to drive our curiosity and the itch of “Cogito, ergo sum” to limitless depths and year by year it still amazes us with new and unexpected discoveries that move our understanding of multiple pathways and metabolic events closer to the ultimate truth. Recent discoveries of succinate dehydrogenase (SHD) and prolyl hydroxylase (PHD) mutations, for example, propelled our understanding of neuroendocrine tumorigenesis as a whole, as well as physiology of mitochondrial respiratory chain and phenomenon of pseudohypoxia in particular. Good old discoveries make their way from dusty repositories to shine with new meaning, appropriate for the current level of knowledge. This acquired wisdom makes us better physicians – knowing the specific expression makeup of catecholamine transporters, GLUTs and SRIFs allows for better tailored imaging and therapeutic manipulations. There are still long ways to go, keeping in mind that pheochromocytoma is but so very special, and we are optimistic and expect many great things to come. PMID:20541673

Pheochromocytoma and Paraganglioma Treatment (PDQ®)—Patient Version

Cancer.gov

Pheochromocytoma and paraganglioma treatment is usually surgery and drug therapy. Chemotherapy, radiation therapy, targeted therapy, ablation, and embolization can be used for disease that has spread or come back. Learn more in this expert-reviewed summary.

Tetralogy of Fallot and pheochromocytoma in a situs inversus totalis: An unusual association

PubMed Central

Tapia-Orihuela, Rubén Kevin Arnold; Huaringa-Marcelo, Jorge; Loja-Oropeza, David

2016-01-01

Introduction: Situs inversus totalis is an uncommon anomaly which exist a complete transposition of organs and it’s occasionally associated with congenital heart diseases, such as tetralogy of fallot. Pheochromocytoma is a rare neuroendocrine tumor with an annual incidence of 2-8 cases per million people and for years has been studied its relationship with the hypoxic pathway. Case Report: A 29 year old male with a history of tetralogy of fallot corrected at 10 years and situs inversus totalis. He was admitted to hospital with a progressive story of four months of constipation, palpitations, headache, dyspnea and sweating. Physical examination revealed a thinned man with peripheral cyanosis, clubbing and signs of decompensated congestive heart failure as hepatomegaly, legs edema, multifocal systodiastolic murmurs, abdominal distension and jugular venous distention. The echocardiogram shows severe right ventricular dysfunction and severe pulmonary hypertension. Furthermore, abdominal computed tomography shows right adrenal mass. Elevated metanephrines and catecholamines confirmed the diagnosis of pheochromocytoma. Surgical removal is decided and preoperative management begins with alpha-adrenergic blockade, however the patient had a hemodynamic decompensation with an unfavorable evolution. Discussion: In conclusion, there are few reports of cyanotic congenital heart disease with pheochromocytoma. Several studies show a significant association between both of them due to chronic hypoxia leads sustained hyperresponsiveness in adrenal medulla and it would cause the tumor. Special preoperative management of pheochromocytoma is recommended when there underlying heart disease and congestive heart failure. We present the first international report of tetralogy of fallot and pheochromocytoma in a patient with situs inversus totalis. PMID:27777699

Tetralogy of Fallot and pheochromocytoma in a situs inversus totalis: An unusual association.

PubMed

Tapia-Orihuela, Rubén Kevin Arnold; Huaringa-Marcelo, Jorge; Loja-Oropeza, David

2016-01-01

Introduction: Situs inversus totalis is an uncommon anomaly which exist a complete transposition of organs and it's occasionally associated with congenital heart diseases, such as tetralogy of fallot. Pheochromocytoma is a rare neuroendocrine tumor with an annual incidence of 2-8 cases per million people and for years has been studied its relationship with the hypoxic pathway. Case Report: A 29 year old male with a history of tetralogy of fallot corrected at 10 years and situs inversus totalis. He was admitted to hospital with a progressive story of four months of constipation, palpitations, headache, dyspnea and sweating. Physical examination revealed a thinned man with peripheral cyanosis, clubbing and signs of decompensated congestive heart failure as hepatomegaly, legs edema, multifocal systodiastolic murmurs, abdominal distension and jugular venous distention. The echocardiogram shows severe right ventricular dysfunction and severe pulmonary hypertension. Furthermore, abdominal computed tomography shows right adrenal mass. Elevated metanephrines and catecholamines confirmed the diagnosis of pheochromocytoma. Surgical removal is decided and preoperative management begins with alpha-adrenergic blockade, however the patient had a hemodynamic decompensation with an unfavorable evolution. Discussion: In conclusion, there are few reports of cyanotic congenital heart disease with pheochromocytoma. Several studies show a significant association between both of them due to chronic hypoxia leads sustained hyperresponsiveness in adrenal medulla and it would cause the tumor. Special preoperative management of pheochromocytoma is recommended when there underlying heart disease and congestive heart failure. We present the first international report of tetralogy of fallot and pheochromocytoma in a patient with situs inversus totalis.

Intraoperative hypertensive crisis secondary to an undiagnosed pheochromocytoma during orthognathic surgery: a case report.

PubMed

Bouchard, Carl; Chiniara, Gilles; Valcourt, Annie-Claude

2014-04-01

Increased blood pressure (BP) during orthognathic surgery may result in excessive blood loss, poor surgical field visualization, and longer surgical time and require blood transfusion. When uncontrollable high BP is encountered in an otherwise healthy patient during orthognathic surgery, the diagnosis of pheochromocytoma should be considered. Pheochromocytomas are rare neuroendocrine tumors of the chromaffin cells of the adrenal medulla or extra-adrenal paraganglia (sympathetic ganglia) that secrete catecholamine. They are present in approximately 0.05 to 0.2% of hypertensive patients. Patients can present with hypertension, tachycardia, headaches, and diaphoresis. The clinical presentation may vary and a wide spectrum of nonspecific symptoms may be encountered. The elevated BP can be intermittent (40%) or permanent (60%). About 10% of pheochromocytomas are hereditary and they can be a feature of multiple endocrine neoplasia type 2. This report describes the case of a 29-year-old patient with a large pheochromocytoma of the right adrenal gland undiagnosed before orthognathic surgery. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Is biochemical screening for pheochromocytoma in adrenal incidentalomas expressing low unenhanced attenuation on computed tomography necessary?

PubMed

Sane, T; Schalin-Jäntti, C; Raade, M

2012-06-01

Pheochromocytomas are characterized by a high attenuation value on unenhanced computed tomography (CT). It is not known whether pheochromocytoma could be ruled out as a cause of adrenal incidentalomas on the basis of unenhanced attenuation values only. We retrospectively evaluated the outcome of routine biochemical screening for pheochromocytoma in a series of adrenal incidentalomas in relationship to the unenhanced attenuation values on CT. An unenhanced CT was available in 174 of 184 patients with 214 adrenal incidentalomas. All patients were screened for pheochromocytoma with 24-h urinary metanephrines and normetanephrines and for hypercortisolism (1 mg dexamethasone test and ACTH). Hypertensive patients were screened for aldosterone overproduction (aldosterone to renin ratio and 24 h urinary aldosterone). The results were compared between incidentalomas with high [≥10 Hounsfield units (HU)] and low (<10 HU) unenhanced attenuation values. One hundred forty-six incidentalomas in 115 patients had an unenhanced HU less than 10. None of these patients had elevated 24-h fractionated urinary metanephrines or normetanephrines suggesting pheochromocytoma. Sixty-eight incidentalomas in 59 patients had an unenhanced HU of 10 or greater, and nine (15.2%) of these patients had surgically and histologically verified pheochromocytoma. Incidentalomas with a HU of 10 or greater were significantly larger (2.6 ± 1.5 vs. 2.3 ± 1.2 cm; P < 0.001), more often functional (27.9 vs. 8.9%, P < 0.001), and more often operated (44.1 vs. 10.2%; P < 0.001) than those with a Hounsfield unit less than 10. The results of this study indicate that routine biochemical screening of pheochromocytoma in small homogenous adrenal incidentalomas characterized by an unenhanced Hounsfield unit value less than 10 HU may not be necessary.

Ventricular Tachycardia and Resembling Acute Coronary Syndrome During Pheochromocytoma Crisis

PubMed Central

Li, Shi-jun; Wang, Tao; Wang, Lin; Pang, Zhan-qi; Ma, Ben; Li, Ya-wen; Yang, Jian; Dong, He

2016-01-01

Abstract Pheochromocytomas are neuroendocrine tumors, and its cardiac involvement may include transient myocardial dysfunction, acute coronary syndrome (ACS), and even ventricular arrhythmias. A patient was referred for evaluation of stuttering chest pain, and his electrocardiogram showed T-wave inversion over leads V1 to V4. Coronary angiography showed 90% stenosis in the mid-left anterior descending coronary artery (LAD), which was stented. Five days later, the patient had ventricular tachycardia, and severe hypertension, remarkable blood pressure fluctuation between 224/76 and 70/50 mm Hg. The patient felt abdominal pain and his abdominal ultrasound showed suspicious right adrenal gland tumor. Enhanced computed tomography of adrenal gland conformed that there was a tumor in right adrenal gland accompanied by an upset level of aldosterone. The tumor was removed by laparoscope, and the pathological examination showed pheochromocytoma. After the surgery, the blood pressure turned normal gradually. There was no T-wave inversion in lead V1-V4. Our case illustrates a rare pheochromocytoma presentation with a VT and resembling ACS. In our case, the serious stenosis in the mid of LAD could be explained by worsen the clinical course of myocardial ischemia or severe coronary vasospasm by the excessive amounts of catecholamines released from the tumor. Coronary vasospasm was possible because he had no classic coronary risk factors (e.g. family history and smoking habit, essential hypertension, hyperglycemia and abnormal serum lipoprotein, high body mass index). Thus, pheochromocytoma was missed until he revealed the association of his symptoms with abdominalgia. As phaeochromocytomas that present with cardiovascular complications can be fatal, it is necessary to screen for the disease when patients present with symptoms indicating catecholamine excess. PMID:27057898

[How to screen for pheochromocytoma, primary aldosteronism and Cushing's syndrome].

PubMed

Meyer, Patrick

2009-01-07

Pheochromocytoma, primary aldosteronism and Cushing's syndrome are uncommon disorders and are difficult to diagnose because laboratory tests lack validation and specificity. Despite these limitations, practice guidelines are proposed to standardize the screening procedure. The most reliable method to diagnose pheochromocytoma is the measurement of plasmatic and/or urinary metanephrines and normetanephrines depending on the pre-test probability of the disease. The approach for detection of primary aldosteronism is based on the aldosterone-renin ratio under standard conditions. Finally, three tests are available to establish the diagnosis of Cushing's syndrome: 24-h urinary free cortisol excretion, low-dose dexamethasone suppression test and the recent and promising late evening salivary cortisol.

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population.

PubMed

Brain, Keith L; Kay, Jonathan; Shine, Brian

2006-11-01

Despite the rarity of pheochromocytoma, diagnosis is important because of the dangers of uncontrolled severe hypertension and the availability of very effective surgical treatment. Urinary or plasma catecholamines or catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, and sex may better predict tumors in populations with a low pretest probability. We retrospectively studied outcomes of an unselected population (1819 patients) referred to a tertiary hospital laboratory for urinary metanephrine testing and investigated the usefulness of some simple derivative measures for detecting pheochromocytoma. We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range. We then compared pheochromocytoma prediction by the use of products of these normalized measures with the gold standard of biopsy-confirmed tumor. The product of the excretion of normalized metanephrine (nMAD) and normalized normetanephrine (nNMT) (nMAD.nNMT) was a highly sensitive (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%. ROC curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. The test for nMAD.nNMT gave higher sensitivity and specificity than the tests for either substance alone. The test for nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pretest probability.

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population

PubMed Central

Brain, Keith L.; Kay, Jonathan; Shine, Brian

2009-01-01

Background Despite the rarity of pheochromocytoma, the dangers of uncontrolled severe hypertension and the very effective surgical treatment of this condition mean that diagnosis is important. Urinary or plasma catecholamines or catecholamine-derivatives are commonly used to screen for pheochromocytomas prior to imaging. This study investigates whether derived measures obtained from 24-hour urinary metanephrine results, patient age and sex can better predict tumors in populations with a low pre-test probability. Methods This study takes a pragmatic approach by retrospectively studying the outcomes of an unselected population referred for urinary metanephrine testing (1819 patients) to a tertiary hospital laboratory, and investigates the usefulness of some simple derivative measures for detecting pheochromocytoma. Urinary 24-hour excretion of metanephrine, normetanephrine and 3-methoxytyramine were normalized by dividing by an age- and sex- specific reference range. The ability of products of these normalized measures to predict pheochromocytomas was assessed, compared to a gold standard of biopsy-confirmed tumor. Results The normalized product of urinary metanephrine and normetanephrine excretion (nMAD.nNMT) proved to be a highly sensitive (100%) and specific (99.1%) measure yielding a positive predictive value 82%. Receiver-operator characteristic curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. nMAD.nNMT gave higher sensitivity and specificity than either test alone. Conclusion We suggest that nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pre-test probability. PMID:16990424

Diverse proportion in composite pheochromocytoma-ganglioneuroma may induce varied clinical symptom: comparison of two cases

PubMed Central

Zhang, Bu-Yi; Zhao, Mingfei; Li, Baizhou; Zhang, Jian-Min

2015-01-01

Composite pheochromocytoma-ganglioneuroma is extremely rare. We described two cases of composite pheochromocytomas in the adrenal medullar. Case 1 was a 70-year-old male presenting with lower abdominal pain and normal blood electrolytes. Case 2 was a 48-year-old female with palpitation and back tenderness. Biochemical investigations showed hypocalcium, hypokalemia and high level of vma. The histological images and the immunohistochemical staining demonstrated the two cases composed of pheochromocytoma and ganglioneuromoma components. Ganglioneuroma component in case 2 accounted for more proportion than that in case 1. We speculated that the varied clinical symptoms were related with the diverse proportions in composite pheochromocytome-ganglioneuroma. PMID:26823896

Cardiovascular collapse after labetalol for hypertensive crisis in an undiagnosed pheochromocytoma during cesarean section.

PubMed

Kuok, Chi-Hang; Yen, Chia-Rong; Huang, Chong-Sin; Ko, Yuan-Pi; Tsai, Pei-Shan

2011-06-01

Pheochromocytoma is a catecholamine-producing tumor but rarely delayingly diagnosed until during pregnancy. We reported a pregnant woman who underwent emergent cesarean section because of intrauterine growth retardation, oligohydramnios, and hypertension. The existence of an undiagnosed pheochromocytoma was suspected by the unusual hemodynamic response to spinal anesthesia, abdominal compressions, and operative stimulus. Hypertensive crisis occurred during the operation and she was sent to the intensive care unit for postoperative care. In the intensive care unit, cardiovascular collapse occurred after nonselective β-adrenergic blockade. Unexpected hypertensive crisis during the perioperative period should alert clinicians to the possibility of a pheochromocytoma. For the treatment of choice, nonselective β-adrenergic blockade should not be used before the α-blockade. Copyright © 2011. Published by Elsevier B.V.

Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells.

PubMed

Pasquali, Daniela; Rossi, Valentina; Conzo, Giovanni; Pannone, Giuseppe; Bufo, Pantaleo; De Bellis, Annamaria; Renzullo, Andrea; Bellastella, Giuseppe; Colao, Annamaria; Vallone, Gianfranco; Bellastella, Antonio; Sinisi, Antonio A

2008-06-01

Surgery is the primary therapy for pheochromocytoma (PHEO), a catecholamine-producing tumor. Benign and malignant PHEO could develop recurrences, and the intraoperative risk of recurrent PHEO is an important unresolved issue. Non-surgical treatments of PHEO recurrence would therefore better prepare patients for reintervention as well as provide them with palliative management. We investigated the effects of the new somatostatin analog (pasireotide) SOM230 versus octreotide (OCT) in primary PHEO cell cultures (Pheo-c). Pheo-c from six benign surgical samples were set up and characterized by immunocytochemistry. Real-time PCR, using both PHEO tissues and Pheo-c, showed different levels of somatostatin receptor(1-5) mRNA expression. Cells treated with various doses of OCT or SOM230 for 48 and 72 h were analyzed to assess their effects on cell proliferation and apoptosis and catecholamine levels. Even if reduction of cell viability was observed in Pheo-c treated for 48 h with either OCT or SOM230 and this effect increased after 72 h, a more significant inhibition of cell growth as well as a significantly higher induction of apoptosis was seen in Pheo-c treated with SOM230 versus OCT. In particular, apoptosis in Pheo-c was detected after 48 h and was associated with increased expression and activation of caspase-3 and cleaved poly(ADP-ribose) polymerase. OCT 10(-6) M and SOM230 10(-7) M significantly reduced catecholamine levels. Our results indicate that while both OCT and SOM230 modulate cell growth and apoptosis and catecholamine levels in Pheo-c through specific receptors, SOM230 is more effective. This improves our knowledge on the mechanism of SOM230 action in PHEO and supports a possible therapeutic use in benign PHEO recurrence.

An unusual case of back pain: A large Pheochromocytoma in an 85 year old woman.

PubMed

Karumanchery, Roopa; Nair, Jagdish R; Hakeem, Abdul; Hardy, Robert

2012-01-01

Low back ache is a common complaint in the elderly and in the absence of red flag symptoms can be easily dismissed as benign. Pheochromocytoma presenting as back pain is unusual and to our knowledge, only two previous cases have been reported in the literature with back pain as the 'only' presenting symptom. We illustrate the case of an 85 year-old woman who presented with a 6 month history of back pain due to a very large Pheochromocytoma. This was incidentally picked up during a routine Lumbar spine plain radiograph and was noted to be a large Pheochromocytoma occupying the whole of the left abdomen. She required an open adrenalectomy to remove the large left adrenal tumour weighing 2.3 kg. Pheochromocytoma can present as a mimic of musculoskeletal conditions and hence due care should be exercised in assessing such presentations both in the young and elderly patients. Our patient is different from the other reported cases, as she is an 85 year-old and 'back pain' can be easily dismissed without investigating in such age groups, thereby missing serious conditions.

Pheochromocytoma and Paraganglioma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Pheochromocytoma and paraganglioma treatment is usually surgery, however, preoperative medical preparation is critical. Palliative care for metastatic disease may include chemotherapy, radiation therapy, targeted therapy, and other modalities. Get detailed information in this clinician summary.

An Unusual Right-sided Suprarenal Accessory Spleen Misdiagnosed as an Atypical Pheochromocytoma.

PubMed

Xia, Zenan; Zhou, Zhien; Shang, Zhiyuan; Ji, Zhigang; Yan, Weigang

2017-12-01

Compared with left suprarenal splenosis, a right suprarenal accessory spleen is more likely to be misdiagnosed as an adrenal tumor because of its extreme rarity. Especially when splenosis mimics an atypical pheochromocytoma, preoperative diagnosis may become more difficult and elusive. Herein we report the case of a female patient with a right suprarenal mass, which was suspected to be an atypical pheochromocytoma based on a history of the classic triad and positive somatostatin receptor scintigraphy, but histopathology suggested a final diagnosis of right suprarenal splenosis. Copyright © 2017 Elsevier Inc. All rights reserved.

99mTc-HYNIC-TOC scintigraphy is superior to 131I-MIBG imaging in the evaluation of extraadrenal pheochromocytoma.

PubMed

Chen, Libo; Li, Fang; Zhuang, Hongming; Jing, Hongli; Du, Yanrong; Zeng, Zhengpei

2009-03-01

In this investigation, the efficacy of scintigraphy using (99m)Tc-labeled hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) in the evaluation of extraadrenal pheochromocytoma was assessed and compared with (131)I-labeled metaiodobenzylguanidine (MIBG) imaging. Ninety-seven patients who were suspected of having pheochromocytoma but showed no definite adrenal abnormalities on CT were evaluated by both (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging. The results were compared with pathology findings or clinical follow-up. Of 58 patients proven to be without pheochromocytoma, (99m)Tc-HYNIC-TOC and (131)I-MIBG imaging excluded 56 and 58 patients, respectively, rendering a specificity of 96.6% for (99m)Tc-HYNIC-TOC imaging and 100% for (131)I-MIBG imaging. In the evaluation of adrenal pheochromocytoma (14 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 50% and 85.7%, respectively. However, in the evaluation of extraadrenal pheochromocytomas (25 patients), the sensitivity of (99m)Tc-HYNIC-TOC scintigraphy and (131)I-MIBG imaging was 96.0% and 72.0%, respectively. (99m)Tc-HYNIC-TOC scintigraphy is more sensitive than (131)I-MIBG imaging in the detection of extraadrenal pheochromocytomas.

PHEOCHROMOCYTOMA: IMPLICATIONS IN TUMORIGENESIS AND THE ACTUAL MANAGEMENT

PubMed Central

Shah, Urvi; Giubellino, Alessio; Pacak, Karel

2012-01-01

Pheochromocytomas and paragangliomas are rare neuroendocrine catecholamine producing tumors with varied clinical presentations, biochemistries and genetic makeup. These features outline the complexity and the difficulties in studying and understanding the oncogenesis of these tumors. The study of families with genetically inherited mutations in pheochromocytoma susceptibility genes has greatly enhanced our understanding of the pathophysiology and mechanisms of oncogenesis of the disease, and consequently changed our clinical approach. Several molecular pathways and mutations in their important regulatory proteins have been identified. Such mutations are responsible for the dysregulation of metabolic pathways involved in oxygen and nutrient sensing, apoptosis regulation, cell proliferation, migration and invasion. The knowledge derived from the study of these pathways will be fundamental in the future clinical management of these patients. As a rare disease that often masks its clinical presentation, the diagnosis is frequently missed and a high level of suspicion is required. Management of this disease requires a multidisciplinary team approach and has been discussed along with advances in its treatment. PMID:22691888

Pheochromocytoma: implications in tumorigenesis and the actual management.

PubMed

Shah, U; Giubellino, A; Pacak, K

2012-06-01

Pheochromocytomas and paragangliomas are rare neuroendocrine catecholamine producing tumors with varied clinical presentations, biochemistries and genetic makeup. These features outline the complexity and the difficulties in studying and understanding the oncogenesis of these tumors. The study of families with genetically inherited mutations in pheochromocytoma susceptibility genes has greatly enhanced our understanding of the pathophysiology and mechanisms of oncogenesis of the disease, and consequently changed our clinical approach. Several molecular pathways and mutations in their important regulatory proteins have been identified. Such mutations are responsible for the dysregulation of metabolic pathways involved in oxygen and nutrient sensing, apoptosis regulation, cell proliferation, migration and invasion. The knowledge derived from the study of these pathways will be fundamental in the future clinical management of these patients. As a rare disease that often masks its clinical presentation, the diagnosis is frequently missed and a high level of suspicion is required. Management of this disease requires a multidisciplinary team approach and will be discussed along with advances in its treatment.

Nonclassic presentation of pheochromocytoma: difficulties in diagnosis and management of the normotensive patient.

PubMed

Gonzalez-Pantaleon, Adalberto D; Simon, Barbara

2008-01-01

To report an unusual presentation of pheochromocytoma along with challenges in diagnosis and management. We report a clinical case history and describe diagnostic methods and pitfalls. The preoperative medical preparation in a normotensive patient is described. A 33-year-old man fell off a ladder, resulting in C6 paraplegia. After C7-T1 laminectomy, he was transferred to a rehabilitation center where he reported lightheadedness, shortness of breath, and chest pain during therapy sessions. A left adrenal mass was incidentally discovered during the workup to rule out a pulmonary embolism. He reported no history of hypertension, and no elevated blood pressure readings had been documented. Magnetic resonance imaging of the adrenal glands showed a well-defined left adrenal mass measuring 3.9 x 3.2 x 3.3 cm, which was hyperintense on T2-weighted images. Twenty-four hour urinary catecholamine concentrations were unremarkable; urinary metanephrines were markedly elevated. During hospital admission, blood pressure was in the low to normotensive range, requiring a cautious approach to alpha-adrenergic blockade and surgical preparation. He under-went uneventful laparoscopic left adrenalectomy; surgical pathology was consistent with pheochromocytoma. This case illustrates a nonclassic presentation of pheochromocytoma and demonstrates that urinary catecholamines alone are not sufficient for a biochemical diagnosis of large pheochromocytomas. Preoperative preparation in normotensive patients can be achieved with alpha-adrenergic blockade, hydration, and liberal salt intake.

Pheochromocytoma in MEN 2A syndrome. Study of 54 patients.

PubMed

Rodriguez, Jose M; Balsalobre, Maria; Ponce, Jose L; Ríos, Antonio; Torregrosa, Nuria M; Tebar, Javier; Parrilla, Pascual

2008-11-01

Pheochromocytoma occurs in nearly 50% of MEN 2A (multiple endocrine neoplasia, type 2A) cases. Many issues related to this tumor are still the subject of debate: the diagnostic management in patients who have had positive genetic study results (RET mutation), variations related to mutation, the best surgical option, and the real relapse rate during long-term follow-up. The aim of this study is to present our experience with this unusual disease, looking for answers to some of these questions. Of 169 patients belonging to 19 MEN 2A families, 54 (32%) presented with pheochromocytoma. The following variables have been studied: (1) clinical and diagnostic data [age, mutation, clinical features, results of catecholamines and catabolites in a 24-h urine sample, computerized tomography (CT) scan and iodine-131 meta-iodobenzylguanidine (MIBG) scintigraphy results, and the means of diagnostic, clinical, or genetic screening]; (2) surgical treatment; and (3) follow-up and recurrence. The mean follow-up time was 92.5 months (range: 12-120 months). The mean age of the 54 patients was 37.9 years (range: 14-71 years); 33 were women. Most (96.3%) mutations were found in exon 11. The most frequent mutations were Cys634Tyr (in 33 cases [61.1%]) and Cys634Arg (in 14 [25.9%]). The diagnosis of pheocromocytoma was made after the diagnosis of MTC in 26 cases (48.2%), simultaneously in 21 (38.9%), and prior in the 7 remaining cases (12.9%). At the time of diagnosis 28 patients (51.8%) were asymptomatic and 26 (48.2%) had clinical features related to pheochromocytoma. In 6 patients (11.1%), the values of catecholamines and catabolites in urine were normal. In the cases with high values, the most useful isolated determination was that of metanephrines (82%), followed by adrenaline (76%). The CT scan did not provide a correct diagnosis in 6 patients with bilateral lesions, and one patient with a bilateral tumor was not diagnosed by MIBG. The combination of CT scan and MIBG diagnosed 100

[Adrenalectomy after snowboard fall. A pheochromocytoma becomes clinically apparent in an unusual way].

PubMed

Gramann, T; Stamm, B; Buchmann, P

2007-04-01

A 33-year-old snowboarder fell and underwent radiological examination, which was suspicious for a vertebral body fracture. Accidentally we found a tumour of the left suprarenal gland. Two days after the fall, he developed a hypertensive crisis with peak blood pressure levels up to 280/120 mmHg. Further endocrinologic testing indicated a pheochromocytoma which was confirmed by post-operative histology. The fall is supposed to have activated the pheochromocytoma. The course of examinations and significance of the tumour are described.

Rhabdomyolysis and acute myoglobinuric renal failure in a patient with bilateral pheochromocytoma following open pyelolithotomy.

PubMed

Anaforoglu, Inan; Ertorer, M Eda; Haydardedeoglu, Filiz E; Colakoglu, Tamer; Tokmak, Naime; Demirag, Nilgun G

2008-04-01

Rhabdomyolysis is an unusual manifestation of pheochromocytoma. Early diagnosis and prompt management are crucial, as it may have life-threatening consequences. This is the case of a 19-year-old man with bilateral pheochromocytoma complicated with rhabdomyolysis and acute myoglobinuric renal failure after surgery for nephrolithiasis. A massive catecholamine release during the procedure manifested itself as a hypertensive crisis, producing severe vasoconstriction and thereby provoking ischemia of the patient's muscle tissue. This insult resulted in rhabdomyolysis and acute myoglobinuric renal failure. After making sure that all necessary medical precautions were performed, including blood pressure stabilization with alpha receptor blockade and adequate fluid replacement, the patient successfully underwent a bilateral cortex-sparing medullar adrenalectomy. The operation specimen was reported as pheochromocytoma.

ADC histogram analysis for adrenal tumor histogram analysis of apparent diffusion coefficient in differentiating adrenal adenoma from pheochromocytoma.

PubMed

Umanodan, Tomokazu; Fukukura, Yoshihiko; Kumagae, Yuichi; Shindo, Toshikazu; Nakajo, Masatoyo; Takumi, Koji; Nakajo, Masanori; Hakamada, Hiroto; Umanodan, Aya; Yoshiura, Takashi

2017-04-01

To determine the diagnostic performance of apparent diffusion coefficient (ADC) histogram analysis in diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiating adrenal adenoma from pheochromocytoma. We retrospectively evaluated 52 adrenal tumors (39 adenomas and 13 pheochromocytomas) in 47 patients (21 men, 26 women; mean age, 59.3 years; range, 16-86 years) who underwent DW 3.0T MRI. Histogram parameters of ADC (b-values of 0 and 200 [ADC 200 ], 0 and 400 [ADC 400 ], and 0 and 800 s/mm 2 [ADC 800 ])-mean, variance, coefficient of variation (CV), kurtosis, skewness, and entropy-were compared between adrenal adenomas and pheochromocytomas, using the Mann-Whitney U-test. Receiver operating characteristic (ROC) curves for the histogram parameters were generated to differentiate adrenal adenomas from pheochromocytomas. Sensitivity and specificity were calculated by using a threshold criterion that would maximize the average of sensitivity and specificity. Variance and CV of ADC 800 were significantly higher in pheochromocytomas than in adrenal adenomas (P < 0.001 and P = 0.001, respectively). With all b-value combinations, the entropy of ADC was significantly higher in pheochromocytomas than in adrenal adenomas (all P ≤ 0.001), and showed the highest area under the ROC curve among the ADC histogram parameters for diagnosing adrenal adenomas (ADC 200 , 0.82; ADC 400 , 0.87; and ADC 800 , 0.92), with sensitivity of 84.6% and specificity of 84.6% (cutoff, ≤2.82) with ADC 200 ; sensitivity of 89.7% and specificity of 84.6% (cutoff, ≤2.77) with ADC 400 ; and sensitivity of 94.9% and specificity of 92.3% (cutoff, ≤2.67) with ADC 800 . ADC histogram analysis of DW MRI can help differentiate adrenal adenoma from pheochromocytoma. 3 J. Magn. Reson. Imaging 2017;45:1195-1203. © 2016 International Society for Magnetic Resonance in Medicine.

Meta-ethnography to understand healthcare professionals’ experience of treating adults with chronic non-malignant pain

PubMed Central

Seers, Kate; Barker, Karen L

2017-01-01

Objectives We aimed to explore healthcare professionals’ experience of treating chronic non-malignant pain by conducting a qualitative evidence synthesis. Understanding this experience from the perspective of healthcare professionals will contribute to improvements in the provision of care. Design Qualitative evidence synthesis using meta-ethnography. We searched five electronic bibliographic databases from inception to November 2016. We included studies that explore healthcare professionals’ experience of treating adults with chronic non-malignant pain. We used the GRADE-CERQual framework to rate confidence in review findings. Results We screened the 954 abstracts and 184 full texts and included 77 published studies reporting the experiences of over 1551 international healthcare professionals including doctors, nurses and other health professionals. We abstracted six themes: (1) a sceptical cultural lens, (2) navigating juxtaposed models of medicine, (3) navigating the geography between patient and clinician, (4) challenge of dual advocacy, (5) personal costs and (6) the craft of pain management. We rated confidence in review findings as moderate to high. Conclusions This is the first qualitative evidence synthesis of healthcare professionals’ experiences of treating people with chronic non-malignant pain. We have presented a model that we developed to help healthcare professionals to understand, think about and modify their experiences of treating patients with chronic pain. Our findings highlight scepticism about chronic pain that might explain why patients feel they are not believed. Findings also indicate a dualism in the biopsychosocial model and the complexity of navigating therapeutic relationships. Our model may be transferable to other patient groups or situations. PMID:29273663

Thyrotoxic and pheochromocytoma multisystem crisis: a case report.

PubMed

Suzuki, Kodai; Miyake, Takahito; Okada, Hideshi; Yamaji, Fuminori; Kitagawa, Yuichiro; Fukuta, Tetsuya; Yasuda, Ryu; Tanaka, Yoshihito; Okamoto, Haruka; Nachi, Sho; Doi, Tomoaki; Yoshida, Takahiro; Kumada, Keisuke; Yoshida, Shozo; Ushikoshi, Hiroaki; Toyoda, Izumi; Ogura, Shinji

2017-06-23

Thyrotoxic crisis and pheochromocytoma multisystem crisis are rare, life-threatening, emergency endocrine diseases with various clinical manifestations. Here we report a case of a patient who simultaneously developed thyrotoxic crisis and pheochromocytoma multisystem crisis and required intensive cardiovascular management. A 60-year-old Asian man experienced nausea and vomiting, and subsequently developed dyspnea and cold sweats while farming. His serum free thyroxine, free triiodothyronine, and thyrotropin receptor antibody levels were elevated at 2.9 ng/dL, 7.2 pg/dL, and 4.7 IU/L, respectively. Serum thyrotropin levels were suppressed at less than 0.01 μIU/mL. Thyroid echography demonstrated no thyroid swelling (23 × 43 mm). A whole body computed tomography was performed for systemic evaluation. This revealed exophthalmos and a mass of size 57 × 64 mm in the anterior pararenal space. Based on these findings, we made an initial diagnosis of thyrotoxic crisis secondary to exacerbation of Grave's hyperthyroidism. Treatment was begun with an iodine agent at a dose of 36 mg/day, thiamazole at a dose of 30 mg/day, and hydrocortisone at a dose of 300 mg daily for 3 consecutive days. To control tachycardia, continuous intravenously administered propranolol and diltiazem infusions were given. At the same time, small doses of doxazosin and carvedilol were used for both alpha and beta adrenergic blockade. On hospital day 5, his blood pressure and serum catecholamine concentrations (adrenalin 42,365 pg/mL, dopamine 6409 pg/mL, noradrenalin 72,212 pg/mL) were still high despite higher beta blocker and calcium channel blocker doses. These findings contributed to the diagnosis of pheochromocytoma multisystem crisis with simultaneous thyrotoxic crisis. We increased the doses of doxazosin and carvedilol, which stabilized his hemodynamic status. On hospital day 16, metaiodobenzylguanidine scintigraphy showed high accumulation in the right adrenal gland tumor

Pitfalls in genetic analysis of pheochromocytomas/paragangliomas-case report.

PubMed

Canu, Letizia; Rapizzi, Elena; Zampetti, Benedetta; Fucci, Rossella; Nesi, Gabriella; Richter, Susan; Qin, Nan; Giachè, Valentino; Bergamini, Carlo; Parenti, Gabriele; Valeri, Andrea; Ercolino, Tonino; Eisenhofer, Graeme; Mannelli, Massimo

2014-07-01

About 35% of patients with pheochromocytoma/paraganglioma carry a germline mutation in one of the 10 main susceptibility genes. The recent introduction of next-generation sequencing will allow the analysis of all these genes in one run. When positive, the analysis is generally unequivocal due to the association between a germline mutation and a concordant clinical presentation or positive family history. When genetic analysis reveals a novel mutation with no clinical correlates, particularly in the presence of a missense variant, the question arises whether the mutation is pathogenic or a rare polymorphism. We report the case of a 35-year-old patient operated for a pheochromocytoma who turned out to be a carrier of a novel SDHD (succinate dehydrogenase subunit D) missense mutation. With no positive family history or clinical correlates, we decided to perform additional analyses to test the clinical significance of the mutation. We performed in silico analysis, tissue loss of heterozygosity analysis, immunohistochemistry, Western blot analysis, SDH enzymatic assay, and measurement of the succinate/fumarate concentration ratio in the tumor tissue by tandem mass spectrometry. Although the in silico analysis gave contradictory results according to the different methods, all the other tests demonstrated that the SDH complex was conserved and normally active. We therefore came to the conclusion that the variant was a nonpathogenic polymorphism. Advancements in technology facilitate genetic analysis of patients with pheochromocytoma but also offer new challenges to the clinician who, in some cases, needs clinical correlates and/or functional tests to give significance to the results of the genetic assay.

Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors

ClinicalTrials.gov

2016-06-09

Extensive Stage Small Cell Lung Cancer; Hereditary Paraganglioma; Male Breast Cancer; Malignant Paraganglioma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pheochromocytoma; Recurrent Prostate Cancer; Recurrent Renal Cell Cancer; Recurrent Small Cell Lung Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Regional Pheochromocytoma; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage III Uterine Sarcoma; Stage IIIA Breast Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Endometrial Carcinoma; Stage IV Neuroendocrine Carcinoma of the Skin; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Thyroid Gland Medullary Carcinoma

Cardiogenic shock with basal transient left ventricular ballooning (Takotsubo-like cardiomyopathy) as first presentation of pheochromocytoma.

PubMed

Di Palma, Gisella; Daniele, Gian P; Antonini-Canterin, Francesco; Piazza, Rita; Nicolosi, Gian L

2010-07-01

Pheochromocytoma is a rare tumor that produces a distant effect by secretion of catecholamines. This tumor usually presents with hypertension and palpitations but it may also cause cardiogenic shock because of catecholamine-induced myocardial dysfunction. We describe a rare case of Takotsubo-like cardiomyopathy as first manifestation of pheochromocytoma with an unusual onset characterized by severe hypotension and transient basal left ventricular ballooning ('inverted' Takotsubo-like cardiomyopathy).

Ectopic ACTH syndrome due to pheochromocytoma: case report and review of the literature.

PubMed Central

Forman, B. H.; Marban, E.; Kayne, R. D.; Passarelli, N. M.; Bobrow, S. N.; Livolsi, V. A.; Merino, M.; Minor, M.; Farber, L. R.

1979-01-01

A 51-year-old female was diagnosed preoperatively to have a pheochromocytoma producing ACTH. This diagnosis was based upon her paroxysmal hypertension, hyperpigmentation, and hypokalemia. Elevated levels of serum and urine corticosteroids, plasma ACTH, urinary VMA, and catecholamines fell after a right adrenal pheochromocytoma was removed. Subsequently this tumor was found to have a high content of ACTH. Review of the literature indicates a mortality rate of 57% for this syndrome. Proper preoperative recognition and management can result in total cure. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:222080

Adrenal tuberculosis after a pheochromocytoma: a misleading tumoral presentation.

PubMed

Hiéronimus, S; Bernard, J-L; Chevallier, P; Chevallier, A; Chyderiotis, G; Fenichel, P; Landraud, L

2007-06-01

Adrenal gland involvement could account for 6% of active tuberculosis. The diagnosis of this extrapulmonary form of tuberculosis is difficult, especially when presenting as unilateral adrenal tumor. This report describes an unusual case of adrenal tuberculosis presenting as a tumor occurring shortly after surgical removal of an adrenal pheochromocytoma located in the opposite gland, in a 63-year-old woman with a previous history of breast cancer. At initial presentation, the patient suffered from symptomatic paroxysmal hypertension. A pheochromocytoma in the left adrenal was diagnosed and resected. One year later, while physical examination and biological parameters were unremarkable, an enhanced adrenal computed tomography (CT) scan showed a right adrenal mass mimicking the CT features of the resected pheochromocytoma. A peripheral tissular rim delineating a central hypodensity characterized this tumor. Magnetic resonance imaging (MRI) showed the same findings on gadolinium-enhanced T1-weighted slices, while the mass was not seen on T2-weighted images. No tumoral signal loss was observed on out of phase images when using the in phase-out of phase T1-weighted sequence. Because of the tumoral evolution and the uncertainty of the nature of that lesion, the patient underwent a second adrenalectomy. Definitive diagnosis was provided by culture of tissue sample, which resulted in the identification of Mycobacterium tuberculosis. In an era of tuberculosis resurgence, this unusual case underscores the necessity of keeping in mind adrenal tuberculosis as a possible differential diagnosis in adrenal tumors of uncertainty nature. It stresses the importance of culture of biopsy tumor, whenever feasible, to avoid unnecessary operations. In the near future, interferon-gamma assay could be a valuable means to recognize extrapulmonary forms of tuberculosis.

Mucosal Malignant Melanoma of the Head and Neck Treated by Carbon Ion Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yanagi, Takeshi; Mizoe, Jun-etsu; Hasegawa, Azusa

2009-05-01

Purpose: To evaluate the efficacy of carbon ion radiotherapy for mucosal malignant melanoma of the head and neck. Methods and Materials: Between 1994 and 2004, 72 patients with mucosal malignant melanoma of the head and neck were treated with carbon ion beams in three prospective studies. Total dose ranged from 52.8 GyE to 64 GyE given in 16 fixed fractions over 4 weeks. Clinical parameters including gender, age, Karnofsky index, tumor site, tumor volume, tumor status, total dose, fraction size, and treatment time were evaluated in relation to local control and overall survival. Results: The median follow-up period was 49.2more » months (range, 16.8-108.5 months). Treatment toxicity was within acceptable limits, and no patients showed Grade 3 or higher toxicity in the late phase. The 5-year local control rate was 84.1%. In relation to local control, there were no significant differences in any parameters evaluated. The 5-year overall and cause-specific survival rates were 27.0% and 39.6%, respectively. For overall survival, however, tumor volume ({>=}100 mL) was found to be the most significant prognostic parameter. Of the patients who developed distant metastasis, 85% were free from local recurrence. Conclusion: Carbon ion radiotherapy is a safe and effective treatment for mucosal malignant melanoma of the head and neck in terms of high local control and acceptable toxicities. Overall survival rate was better than in those treated with conventional radiotherapy and was comparable to that with surgery.« less

Expression of Extracellular Signal-regulated Kinase 5 and Ankyrin Repeat Domain 1 in Composite Pheochromocytoma and Ganglioneuroblastoma Detected Incidentally in the Adult Adrenal Gland

PubMed Central

Suenaga, Shinta; Ichiyanagi, Osamu; Ito, Hiromi; Naito, Sei; Kato, Tomoyuki; Nagaoka, Akira; Kato, Tomoya; Yamakawa, Mitsunori; Obara, Yutaro; Tsuchiya, Norihiko

2016-01-01

Composite pheochromocytoma (cPC) is extremely rare, arising in the adrenal medulla as a mixture of PC and other tumors of neural origin. We herein report on a case of adrenal incidentaloma post-operatively diagnosed as cPC with ganglioneuroblastoma (GNBL). The PC component had 7 points on the PASS, a Ki-67 index of 5.1%, a focal absence of sustentacular cells, and no genetic aberrations in succinate dehydrogenase subunit B. The GNBL component exhibited no N-myc amplification. Tumor cells of both components were stained positively for extracellular signal-regulated kinase 5 and ankyrin repeat domain 1. The aberrant activation of growth signaling may play a role in the marginal malignancy of cPC. PMID:27980262

The RET p.G533C mutation confers predisposition to multiple endocrine neoplasia type 2A in a Brazilian kindred and is able to induce a malignant phenotype in vitro and in vivo.

PubMed

Oliveira, Mariana N L; Hemerly, Jefferson P; Bastos, André U; Tamanaha, Rosana; Latini, Flavia R M; Camacho, Cléber P; Impellizzeri, Anelise; Maciel, Rui M B; Cerutti, Janete M

2011-09-01

We have previously described a p.G533C substitution in the rearranged during transfection (RET) oncogene in a large family with medullary thyroid carcinoma. Here, we explore the functional transforming potential of RET p.G533C mutation. Plasmids expressing RET mutants (p.G533C and p.C634Y) and RET wild type were stable transfected into a rat thyroid cell line (PCCL3). Biological and biochemical effects of RET p.G533C were investigated both in vitro and in vivo. Moreover, we report the first case of pheochromocytoma among the RET p.G533C-carriers in this Brazilian family and explore the RET mutational status in DNA isolated from pheochromocytoma. Ectopic expression of RET p.G533C and p.C634Y activates RET/MAPK/ERK pathway at similar levels and significantly increased cell proliferation, compared with RET wild type. We additionally show that p.G533C increased cell viability, anchorage-independent growth, and micronuclei formation while reducing apoptosis, hallmarks of the malignant phenotype. RET p.G533C down-regulates the expression of thyroid specific genes in PCCL3. Moreover, RET p.G533C-expressing cells were able to induce liver metastasis in nude mice. Finally, we described two novel RET variants (G548V and S556T) in the DNA isolated from pheochromocytoma while they were absent in the DNA isolated from blood. Our in vitro and in vivo analysis indicates that this mutation confers a malignant phenotype to PCCL3 cells. These findings, in association with the report of first case of pheochromocytoma in the Brazilian kindred, suggest that this noncysteine mutation may be more aggressive than was initially considered.

Bilateral pheochromocytoma associated with paraganglioma and papillary thyroid carcinoma: report of an unusual case.

PubMed

Yang, Jeong Hoon; Bae, Sung Jin; Park, Sanghui; Park, Hyun-Kyung; Jung, Hye Seung; Chung, Jae Hoon; Min, Yong-Ki; Lee, Myung-Shik; Kim, Kwang-Won; Lee, Moon-Kyu

2007-04-01

A 42-year old woman presented with headache, palpitation and facial flushing. Ultrasonograms and computed tomograms revealed tumors in both of the adrenal glands, anterior aspect of the inferior vena cava, and the right lobe of the thyroid gland. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum calcitonin, CEA, intact PTH and calcium levels were within normal limits. Markedly elevated levels of urinary normetanephrine and vanillylmandelic acid, and the result of 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy indicated that both adrenal masses were pheochromocytoma. Bilateral adrenalectomy, paracaval mass removal and total thyroidectomy together with central lymph node dissection were performed. The final pathological diagnosis was bilateral adrenal pheochromocytoma, paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia. Analysis of the RET proto-oncogene mutation, von Hippel Lindau mutation, succinate dehydrogenase subunit B mutation, and succinate dehydrogenase subunit D mutation yielded negative results. The relationship of these lesions could not be determined. This is the first report of a combination of bilateral pheochromocytoma, abdominal paraganglioma, papillary thyroid carcinoma and either parathyroid adenoma or hyperplasia without hyperparathyroidism.

Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma.

PubMed

Sisson, James C; Giordano, Thomas J; Avram, Anca M

2012-04-01

Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.

Anti-tumor effects of peptide analogs targeting neuropeptide hormone receptors on mouse pheochromocytoma cells.

PubMed

Ziegler, C G; Ullrich, M; Schally, A V; Bergmann, R; Pietzsch, J; Gebauer, L; Gondek, K; Qin, N; Pacak, K; Ehrhart-Bornstein, M; Eisenhofer, G; Bornstein, S R

2013-05-22

Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor with currently no effective treatment. Peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by various anti-tumor peptide analogs. The present study carried out on mouse pheochromocytoma cells (MPCs) and a more aggressive mouse tumor tissue-derived (MTT) cell line revealed that these cells are characterized by pronounced expression of the somatostatin receptor 2 (sst2), growth hormone-releasing hormone (GHRH) receptor and the luteinizing hormone-releasing hormone (LHRH) receptor. We further demonstrated significant anti-tumor effects mediated by cytotoxic somatostatin analogs, AN-162 and AN-238, by LHRH antagonist, Cetrorelix, by the cytotoxic LHRH analog, AN-152, and by recently developed GHRH antagonist, MIA-602, on MPC and for AN-152 and MIA-602 on MTT cells. Studies of novel anti-tumor compounds on these mouse cell lines serve as an important basis for mouse models of metastatic pheochromocytoma, which we are currently establishing. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pheochromocytoma as a rare cause of hypertension in a 46 X, i(X)(q10) turner syndrome: a case report and literature review.

PubMed

Shin, Ji Yeon; Kim, Bo Hyun; Kim, Young Keum; Kim, Tae Hwa; Kim, Eun Heui; Lee, Min Jin; Kim, Jong Ho; Jeon, Yun Kyung; Kim, Sang Soo; Kim, In Joo

2018-05-10

Cardiovascular disease (CVD) presents the most serious health problems and contributes to the increased mortality in young women with Turner syndrome. Arterial hypertension in Turner syndrome patients is significantly more prevalent than that in a general age-matched control group. The aetiology of hypertension in Turner syndrome varies, even in the absence of cardiac anomalies and obvious structural renal abnormalities. Pheochromocytoma is an extremely rare cause among various etiologies for hypertension in patients with Turner syndrome. Here, we reported a pheochromocytoma as a rare cause of hypertension in Turner syndrome patient. A 21-year-old woman who has diagnosed with Turner syndrome with a karyotype of 46,X,i(X)(q10) visited for hypertension and mild headache. Transthoracic echography (TTE) showed no definite persistent ductus arteriosus shunt flow and cardiac valve abnormalities. Considering other important secondary causes like pheochromocytoma, hormonal studies were performed and the results showed increased serum norepinephrine, serum normetanephrine, and 24 h urine norepinephrine. We performed an abdominal computed tomography (CT) to confirm the location of pheochromocytoma. Abdominal CT showed a 1.9 cm right adrenal mass. I-131 meta-iodobenzylguanidine (MIBG) scintigraphy showed a right adrenal uptake. Laparoscopic adrenalectomy was performed and confirmed a pheochromocytoma. After surgery, blood pressure was within normal ranges and postoperative course was uneventful, and no recurrence developed via biochemical tests and abdominal CT until 24 months. Our case and previous literatures suggest that hypertension caused by pheochromocytoma which is a rare but important and potentially lethal cause of hypertension in Turner syndrome. This case underlines the importance of early detection of pheochromocytoma in Turner syndrome. Clinicians should keep in mind that pheochromocytoma can be a cause of hypertension in patients with Turner syndrome.

Novel and evolving therapies in the treatment of malignant phaeochromocytoma: experience with the mTOR inhibitor everolimus (RAD001).

PubMed

Druce, M R; Kaltsas, G A; Fraenkel, M; Gross, D J; Grossman, A B

2009-09-01

Phaeochromocytoma and paraganglioma are rare neuroendocrine tumours (NETS). They may be benign or malignant but the pathological distinction is mainly made when metastases are present. Available treatments in the form of surgery, chemotherapy, and radionuclide therapy may improve symptoms and biochemical markers, but the results for the control of tumour bulk are less favourable. Furthermore, responses to treatment are frequently short-lived. This short review outlines the main molecular and histological features of malignant phaeochromocytoma and the difficulties in differentiating between benign and malignant disease. We list current therapies used for malignant pheochromocytoma; however, these generally achieve relatively low success rates. Hence, there is a need for new and more effective therapies. In vitro studies have implicated the PI3/Akt/mTOR pathway in the pathogenesis of malignant NETS, including phaeochromocytoma. Everolimus (RAD001, Novartis UK) is a compound that inhibits mTOR (mammalian Target Of Rapamycin) signalling. We have used RAD001 in four patients with progressive malignant paraganglioma/phaeochromocytoma in addition to other therapies (with institutional approval for compassionate use), and evaluated the effects of this treatment. We outline these four cases and review the theoretical background for this therapy, although the outcomes were relatively disappointing.

Pheochromocytoma in a Pregnant Woman With Prior Traumatic Aortic Injury.

PubMed

Malinowski, Ann Kinga; Maxwell, Cynthia; Sermer, Mathew; Rubin, Barry; Gandhi, Shital; Silversides, Candice K

2015-11-01

Pheochromocytoma, a catecholamine-producing tumor seldom encountered in pregnancy, is often heralded by nonspecific symptoms and undue mortality with delayed diagnosis. The presence of an aortic pseudoaneurysm poses a management challenge given the risk of aortic rupture amplified by hypertensive events. A 30-year-old woman, gravida 3 para 1, presented at 23 6/7 weeks of gestation with vomiting, chest pain, and severe hypertension. Investigation revealed adrenal pheochromocytoma and pseudoaneurysm at the site of a previous aortic injury. Prazosin and phenoxybenzamine achieved α-blockade with subsequent addition of labetalol for β-blockade. Concerns for aortic dissection led to endovascular aortic repair at 30 2/7 weeks of gestation. A female neonate was delivered by urgent cesarean delivery for persistent postprocedure fetal bradycardia. An adrenalectomy followed with near-immediate symptom resolution. Mother and neonate remain well. The case underscores the necessity of a meticulous approach to hypertension management and the pivotal role of diligent multidisciplinary collaboration to achieve a safe outcome.

Pheochromocytoma: clinical review based on a rare case in adolescence

PubMed Central

Alface, Marisa Maibel; Moniz, Patricia; Jesus, Susana; Fonseca, Cândida

2015-01-01

Pheochromocytomas are rare tumours originating in chromaffin cells, representing 0.1–1% of all secondary hypertension (HT) cases. The majority are benign and unilateral, characterised by the production of catecholamines and other neuropeptides. Mainly located in the adrenal gland, they are more frequent between the 3rd and 5th decades of life; however, 10–25% can be associated with genetic familial syndromes (multiple endocrine neoplasia type 2 (MEN 2), type 1 neurofibromatosis and Von-Hippel-Landau disease in younger ages. The authors present a rare case of secondary HT due to a pheochromocytoma in a 15-year-old patient, whose metanephrine assay confirmed the diagnosis, and abdominal ultrasound and CT localised the tumour in the adrenal gland. HT was controlled with α and β blockers, with posterior retroperitoneal laparoscopic surgical intervention and subsequent resolution of HT. Age and concomitant hyperparathyroidism compelled genetic testing for the exclusion of MEN 2, which was negative. PMID:26243750

A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: 
A Case Report and Literature Review

PubMed Central

Mula-Abed, Waad-Allah S.; Ahmed, Riyaz; Ramadhan, Fatima A.; Al-Kindi, Manal K.; Al-Busaidi, Noor B.; Al-Muslahi, Hilal N.; Al-Lamki, Mohammad A.

2015-01-01

A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The patient’s history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine) and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold) which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold), consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario. PMID:26421121

A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: 
A Case Report and Literature Review.

PubMed

Mula-Abed, Waad-Allah S; Ahmed, Riyaz; Ramadhan, Fatima A; Al-Kindi, Manal K; Al-Busaidi, Noor B; Al-Muslahi, Hilal N; Al-Lamki, Mohammad A

2015-09-01

A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The patient's history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine) and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold) which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold), consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario.

Pheochromocytoma-Induced Atrial Tachycardia Leading to Cardiogenic Shock and Cardiac Arrest: Resolution with Atrioventricular Node Ablation and Pacemaker Placement

PubMed Central

Bajaj, Mandeep; Cunningham, Glenn R.

2014-01-01

Pheochromocytoma should be considered in young patients who have acute cardiac decompensation, even if they have no history of hypertension. Atrioventricular node ablation and pacemaker placement should be considered for stabilizing pheochromocytoma patients with cardiogenic shock due to atrial tachyarrhythmias. A 38-year-old black woman presented with cardiogenic shock (left ventricular ejection fraction, <0.15) that did not respond to the placement of an intra-aortic balloon pump. A TandemHeart® Percutaneous Ventricular Assist Device was inserted emergently. After atrioventricular node ablation and placement of a temporary pacemaker, the TandemHeart was removed. Computed tomography of the abdomen revealed a pheochromocytoma. After placement of a permanent pacemaker, the patient underwent a right adrenalectomy. This is, to our knowledge, the first reported case of pheochromocytoma-induced atrial tachyarrhythmia that led to cardiogenic shock and cardiac arrest unresolved by the placement of 2 different ventricular assist devices, but that was completely reversed by radiofrequency ablation of the atrioventricular node and the placement of a temporary pacemaker. We present the patient's clinical, laboratory, and imaging findings, and we review the relevant literature. PMID:25593537

Pheochromocytoma presenting with Takotsubo syndrome.

PubMed

Marcovitz, Pamela A; Czako, Peter; Rosenblatt, Solomon; Billecke, Scott S

2010-10-01

The clinical presentation of Takotsubo syndrome, or apical ballooning syndrome, resembles an extensive anterolateral myocardial infarction with chest pain symptoms and electrocardiographic ST-elevation or T-wave inversion noted in most patients. However, coronary arteries are invariably found to be normal or to display minimal atherosclerotic disease despite modest elevation of cardiac enzymes. Since most cases of Takotsubo syndrome occur after intense physical and/or emotional stress, catecholamine surge appears to be a common underlying mechanism. We present a case of Takotsubo syndrome, which presented with unusual symptoms and was found to be caused by pheochromocytoma. A sudden rise in blood pressure moments after completion of echocardiographic stress testing aided in uncovering the diagnosis. ©2010, Wiley Periodicals, Inc.

Magnesium sulphate and (123)I-MIBG in pheochromocytoma: Two useful techniques for a complicated disease.

PubMed

Vendrell, M; Martín, N; Tejedor, A; Ortiz, J T; Muxí, À; Taurà, P

2016-01-01

Pheochromocytoma is a tumour of the chromaffin tissue. It may, through catecholamine release, have deleterious effects on myocardial structure. A 48-year-old woman with a history of hypertension and type II diabetes mellitus (ASA II) was diagnosed of pheochromocytoma-induced myocarditis, which caused severe cardiogenic shock, with an ejection fraction of 20%. Extreme blood pressure swings required aggressive therapy with vasoactive drugs (norepinephrine and dopamine) and an intra-aortic balloon pump, despite which severe haemodynamic instability persisted. Finally, the use of magnesium sulphate allowed for cardiovascular stabilization and weaning off vasoactive drugs prior to surgery. (123)I-metaiodobenzylguanidine scintigraphy helps not only to functionally confirm tumour tissue, but also to assess severity and prognosis of cardiac failure. Prognosis of pheochromocytoma-induced heart failure can be very poor. The use of these two well-known and relatively simple 'tools' for treatment and prognosis is a helpful option to keep in mind. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Incidence of second primary malignancies and related mortality in patients with imatinib-treated chronic myeloid leukemia.

PubMed

Gugliotta, Gabriele; Castagnetti, Fausto; Breccia, Massimo; Albano, Francesco; Iurlo, Alessandra; Intermesoli, Tamara; Abruzzese, Elisabetta; Levato, Luciano; D'Adda, Mariella; Pregno, Patrizia; Cavazzini, Francesco; Stagno, Fabio; Martino, Bruno; La Barba, Gaetano; Sorà, Federica; Tiribelli, Mario; Bigazzi, Catia; Binotto, Gianni; Bonifacio, Massimiliano; Caracciolo, Clementina; Soverini, Simona; Foà, Robin; Cavo, Michele; Martinelli, Giovanni; Pane, Fabrizio; Saglio, Giuseppe; Baccarani, Michele; Rosti, Gianantonio

2017-09-01

The majority of patients with chronic myeloid leukemia are successfully managed with life-long treatment with tyrosine kinase inhibitors. In patients in chronic phase, other malignancies are among the most common causes of death, raising concerns on the relationship between these deaths and the off-target effects of tyrosine kinase inhibitors. We analyzed the incidence of second primary malignancies, and related mortality, in 514 chronic myeloid leukemia patients enrolled in clinical trials in which imatinib was given as first-line treatment. We then compared the observed incidence and mortality with those expected in the age- and sex-matched Italian general population, calculating standardized incidence and standardized mortality ratios. After a median follow-up of 74 months, 5.8% patients developed second primary malignancies. The median time from chronic myeloid leukemia to diagnosis of the second primary malignancies was 34 months. We did not find a higher incidence of second primary malignancies compared to that in the age- and sex-matched Italian general population, with standardized incidence ratios of 1.06 (95% CI: 0.57-1.54) and 1.61 (95% CI: 0.92-2.31) in males and females, respectively. Overall, 3.1% patients died of second primary malignancies. The death rate in patients with second primary malignancies was 53% (median overall survival: 18 months). Among females, the observed cancer-related mortality was superior to that expected in the age- and sex-matched Italian population, with a standardized mortality ratio of 2.41 (95% CI: 1.26 - 3.56). In conclusion, our analysis of patients with imatinib-treated chronic myeloid leukemia did not reveal a higher incidence of second primary malignancies; however, the outcome of second primary malignancies in such patients was worse than expected. Clinicaltrials.gov: NCT00514488, NCT00510926. Copyright© 2017 Ferrata Storti Foundation.

Different values of urinary fractionated metanephrines after unilateral adrenalectomy for pheochromocytoma according to time intervals after surgery.

PubMed

Cho, Yoon Y; Kim, Young N; Kim, Jung-Han; Jeong, Byong C; Lee, Soo-Youn; Kim, Jae H

2017-01-01

Background After adrenalectomy, urinary fractionated metanephrine concentrations are expected to be reduced. However, there are few studies suggesting cut-offs for adrenalectomy patients. Methods Urinary metanephrine and normetanephrine concentrations in adrenalectomy patients and two controls were compared and hormonal concentrations were evaluated via time intervals after surgery. Results The median urinary metanephrine level after unilateral adrenalectomy was lower than that of the non-pheochromocytoma controls but comparable to healthy controls. Urinary normetanephrine concentrations did not differ between adrenalectomy patients and non-pheochromocytoma controls, although both group had levels higher than those of healthy controls. The median urinary normetanephrine level in the immediate postoperative period was higher than in the later period. Conclusions Urinary metanephrine concentrations were lower after adrenalectomy, but urinary normetanephrine concentrations were not changed compared with the non-pheochromocytoma controls. However, urinary normetanephrine concentrations in the patient group were higher than levels in the heathy controls.

[Hereditary pheochromocytoma--a family affected by von Hippel-Lindau disease].

PubMed

Mertl, J; Rovný, A; Krepelová, A; Prásek, J

2003-07-01

The authors present a case of a 37 year old male (proband) with a 13 year history of progressive sight impairment leading to blindness and a 4 year history of a mild hypertension. He was incidentally found to have large adrenal tumors after an ultrasound kidney examination. The tumors were confirmed with CT scan and magnetic resonance imaging. A bilateral pheochromocytoma was biochemically demonstrated and successfully removed. The eye diagnosis of angiomatosis retinae von Hippel-Lindau was ascertained after a search of the patient files in other medical departments, which led to a family screening. Proband's brother, having hypertension and a history of a cerebellar astrocytoma operation, was also diagnosed with CT scan to have a bilateral pheochromocytoma. Unfortunately, at the same time he was found to have a large irremovable neuroendocrine pancreatic carcinoma, which caused complications and his eventual death. Both proband and his brother were affected by the same CGG(Arg167)->CAG(Gln) mutation in the exon 3 of the VHL gene. Other living and examined family members were not affected, which was confirmed by negative genetic testing. One year after the pheochromocytoma operation, proband was diagnosed to have a retroperitoneal tumor left to the aorta, clinically silent, with slightly and non-constantly elevated urine norepinephrine and normetanephrine. Metaiodobenzylguanidine scintigraphy showed that it was a paraganglioma. The old CT and magnetic resonance picture review demonstrated that the tumor had already been present at the time of the operation. It was surgically removed and histologically verified. It is a pity that proband had not been sent by his ophthalmologist for an endocrine examination when the eye diagnosis was determined. Affection of the family would have been discovered earlier, and proband's brother might have possibly been saved.

Pulmonary complications in patients with haematological malignancies treated at a respiratory ICU.

PubMed

Ewig, S; Torres, A; Riquelme, R; El-Ebiary, M; Rovira, M; Carreras, E; Raño, A; Xaubet, A

1998-07-01

Patients with haematological malignancies developing severe pulmonary complications have a poor outcome, especially after bone-marrow transplantation (BMT). We studied the aetiology, the yield of different diagnostic tools, as well as the outcome and prognostic factors in the corresponding population admitted to our respiratory intensive care unit (RICU). Overall, 89 patients with haematological malignancies and pulmonary complications treated within a 10 yr period were included. The underlying malignancies were predominantly acute leukaemia and chronic myeloid leukaemia (66/89, 74%). Fifty-two of 89 (58%) patients were bone marrow recipients. An aetiological diagnosis could be obtained in 61/89 (69%) of cases. The aetiology was infectious in 37/89 (42%) and noninfectious in 24/89 (27%). Blood cultures and cytological examinations of bronchoalveolar lavage fluid were the diagnostic tools with the highest yield (13/43 (30%) and 13/45 (29%) positive results, respectively). Necropsy results were coincident with results obtained during the lifetime in 43% of cases with infectious and 60% with noninfectious aetiologies. Overall mortality was 70/89 (79%), and 47/52 (90%) in transplant recipients. The requirement of mechanical ventilation, BMT, and an interval <90 days of BMT prior to ICU admission were independent adverse prognostic factors. The outcome in this patient population was uniformly poor. It was worst in bone marrow recipients developing pulmonary complications <90 days after transplantation and requiring mechanical ventilation. Decisions about intensive care unit admission and mech-anical ventilation should seriously consider the dismal prognosis of these patients.

Excessive Catecholamine Secretion and the Activation of the Renin-Angiotensin-Aldosterone-System in Patients with Pheochromocytoma: A Single Center Experience and Overview of the Literature.

PubMed

Haase, Matthias; Dringenberg, Till; Allelein, Stephanie; Willenberg, Holger S; Schott, Matthias

2017-10-01

Catecholamines stimulate renin-secretion in the juxtaglomerular cells of the kidney and a number of case reports suggest an association between pheochromocytoma and activation of the RAAS. Therefore, it could be asked whether patients suffering from pheochromocytoma with high concentrations of circulating catecholamines present with oversecretion of renin and aldosterone. We identified twelve patients with excessive catecholamine secretion due to pheochromocytoma and compared them to a group of twelve patients with essential hypertension (EH) with regard to the activation of the renin-angiotensin-aldosterone-system (RAAS). The PubMed database was screened for studies that investigate the association between pheochromocytoma and activation of the RAAS. The plasma concentrations of metanephrines (19.9-fold) and normetanephrines (29.5-fold) were significantly higher in the pheochromocytoma group than in the EH group. Renin and aldosterone levels were 1.3-fold and 1.6-fold higher, respectively, as compared to the EH group, whereas the differences were not statistically significant. There was no significant correlation between plasma metanephrine or normetanephrine levels and the plasma renin concentration (r s =0.077, r s =0.049, respectively) in our patients. The data from our institution and from review of literature suggest that an association between pheochromocytoma in the context of high plasma catecholamine levels and activation of the RAAS is present. However, results have not been consistent. Thus, other causes of RAAS-activation should be considered also in the presence of pheochromocytoma or reinvestigation for aldosteronism should be offered to such patients after removal of the catecholamine-producing tumour. © Georg Thieme Verlag KG Stuttgart · New York.

Validation of pathological grading systems for predicting metastatic potential in pheochromocytoma and paraganglioma

PubMed Central

Koh, Jung-Min; Ahn, Seong Hee; Kim, Hyeonmok; Kim, Beom-Jun; Sung, Tae-Yon; Kim, Young Hoon; Hong, Suck Joon; Song, Dong Eun

2017-01-01

Purpose The Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP) was proposed for predicting the metastatic potential of pheochromocytoma and paraganglioma to overcome the limitations of the Pheochromocytoma of the Adrenal Scaled Score (PASS). However, to date, no study validating the GAPP has been conducted, and previous studies did not include mutations in the succinate dehydrogenase type B (SDHB) gene in the score calculation. In this retrospective cohort study, we validated the prediction ability of GAPP and assessed whether it would be improved by inclusion of the loss of SDHB immunohistochemical staining. Methods We divided the tumors into non-metastatic and metastatic groups based on the presence of synchronous or metachronous metastases. The GAPP score and PASS at the initial operation were measured. Moreover, we combined some GAPP parameters with the immunohistochemical staining of SDHB to obtain a modified GAPP (M-GAPP) score. Results Metastasis occurred in 15/72 (20.8%) patients, with a mean follow-up of 43.5 months. Loss of SDHB staining was more frequent (P = 0.044) in the metastatic group. The GAPP score (P = 0.006), PASS (P = 0.003), and M-GAPP score (P<0.001) were all higher in the metastatic group. Twelve of 40 (30.0%) moderately or poorly differentiated tumors, as defined by the GAPP score, and 12/34 (35.3%) tumors with a PASS ≥4 were metastatic. Conversely, 10/19 (52.6%) tumors with an M-GAPP score ≥3 were metastatic. The area under the curve of the M-GAPP score (0.822) was significantly higher than that of the GAPP (0.728) (P = 0.012), but similar to that of the PASS (0.753) (P = 0.411). The GAPP (P = 0.032) and M-GAPP scores (P = 0.040), but not PASS (P = 0.200), negatively correlated with metastasis-free survival. Conclusion The GAPP was validated, and M-GAPP, a combination of some GAPP parameters and loss of SDHB staining, might be useful for the prediction of the metastatic potential of pheochromocytoma and paraganglioma

Use of the Esophageal Doppler Machine to help guide the intraoperative management of two children with pheochromocytoma.

PubMed

Hack, Henrik

2006-08-01

The anesthetic management of pheochromocytoma has been based upon the intraoperative control of blood pressure and fluid balance following adequate preoperative preparation. This can be difficult, especially in the presence of significant comorbidity such as cardiac or renal dysfunction. Two cases of children with pheochromocytoma are reported where the introperative management of fluid balance and blood pressure control were guided by measurement of changes in descending aortic blood flow using an esophageal Doppler probe. The advantages of such a technique compared with more invasive monitors are discussed.

Pheochromocytoma presenting as an acute coronary syndrome complicated by acute heart failure: The challenge of a great mimic.

PubMed

Sanna, Giuseppe Damiano; Talanas, Giuseppe; Fiore, Giuseppina; Canu, Antonella; Terrosu, Pierfranco

2016-10-01

Pheochromocytoma is a rare neuroendocrine tumor with a highly variable clinical presentation. The serious and potentially lethal cardiovascular complications of these tumors are related to the effects of secreted catecholamines. We describe a case of a 50-year-old woman urgently admitted to our hospital because of symptoms and clinical and instrumental findings consistent with an acute coronary syndrome complicated by acute heart failure. Urgent coronary angiography showed normal coronary arteries. During her hospital stay, the recurrence of episodes characterized by a sudden increase in blood pressure, cold sweating, and nausea allowed us to hypothesize a pheochromocytoma. The diagnosis was confirmed by elevated levels of urinary catecholamines and by the finding of a left adrenal mass on magnetic resonance imaging. The patient underwent left adrenalectomy. Therefore, the initial diagnosis was critically reappraised and reviewed as a cardiac manifestation of a pheochromocytoma during catecholaminergic crisis.

Pheochromocytoma of the Organ Zuckerkandl.

PubMed

Lee, C; Chang, E; Gimenez, J; McCarron, R

2017-01-01

Pheochromocytomas (PCCs);, or intra-adrenal paragangliomas (PGLs);, are neuroendocrine tumors arising within the adrenal medulla. Extra-adrenal paragangliomas may arise in the sympathetic or parasympathetic paraganglia and more rarely in other organs. One of the most common extra-adrenal sites is in the organ of Zuckerkandl, a collection of chromaffin cells near the origin of the inferior mesenteric artery or near the aortic bifurcation. The following is a case of a patient with resistant hypertension secondary to an extra-adrenal paraganglioma in the organ of Zuckerkandl. The patient is a 43 year old man with a history of depression, type 2 diabetes mellitus, and hypertension who was sent to the emergency department by his primary care physician for severely elevated blood pressures. Patient also had diaphoresis, tachycardia, and a new, fine tremor of his left hand. Upon presentation, the patient's blood pressure was 260/120 mmHg with a heart rate of 140 beats per minute. Plasma fractionated metanephrines sent on admission revealed significantly elevated levels of total plasma metanephrines (2558 pg/mL);, free metanephrine (74 pg/ml); and free normetanephrine (2484pg/mL);. An I-123 metaiodobenzylguanidine (MIBG); scan showed abnormal uptake in the lower abdomen at the level of the aortic bifurcation. Patient was started on alpha-blockade, with subsequent addition of a beta-blocker prior to surgery. Patient underwent surgical removal of the tumor with pathology consistent with a paraganglioma. Pheochromocytomas and paragangliomas are responsible for approximately 0.5 percent of cases of secondary hypertension. Many different biochemical markers have been used to aid in the diagnosis of PCC/PGL including plasma catecholamines, plasma metanephrines, urine fractionated metanephrines, urine catecholamines, total metanephrines and vanillymandellic acid. Definitive management of a PCC and PGL involves surgical removal of the tumor. Finally, there should be a discussion

Exercise-induced nausea and vomiting: another sign and symptom of pheochromocytoma and paraganglioma.

PubMed

King, Kathryn S; Darmani, Nissar A; Hughes, Marybeth S; Adams, Karen T; Pacak, Karel

2010-06-01

A cohort of nine patients, mostly young adults, presented with a new sign/symptom of pheochromocytoma/paraganglioma: exercise-induced nausea and vomiting. The aims of this article are to introduce this sign/symptom and offer a possible hypothesis for the observation. Following a 2000 report from a paraganglioma patient experiencing exercise-induced nausea and vomiting, we began asking patients about instances of nausea and vomiting with exercise. A total of nine patients, 4.4% of our pheochromocytoma/paraganglioma population, presented with reports of exercise-induced nausea and vomiting, initially with moderate-to-intense levels of exercise, at the first presentation of their disease. All of these patients reported a cessation of exercise-induced nausea and vomiting following the removal of their primary tumor. Two patients with metastatic disease to the lungs reported a recurrence of exercise-induced nausea and vomiting. The majority of patients studied were young adults with mean onset age of 19.4 years (range of 9-51 years) and the mean age of diagnosis being 24.1 years (range of 11-53 years). Exercise-induced nausea and vomiting should be considered a sign/symptom of pheochromocytoma/paraganglioma and should be addressed in the clinical evaluation of these patients, especially in young adults. Whether exercise-induced elevated catecholamine levels could account for the induced nausea and vomiting via activation of adrenergic receptors in the area postrema remains to be established.

ACTION OF 50 HZ MAGNETIC FIELDS ON NEURITE OUTGROWTH IN PHEOCHROMOCYTOMA CELLS

EPA Science Inventory

This study tests the capacity of 50-Hz magnetic and electric fields to stimulate neurite outgrowth in PC-12D cells, a cell line which originated from a pheochromocytoma in rat adrenal medulla. he cells were plated on collagen-coated plastic petri dishes and exposed to sinusoidal ...

[Analysis of laboratory data of 155 patients with pheochromocytoma-paraganglioma syndrome diagnosed during the past 20 years].

PubMed

Balog, Beatrice; Tőke, Judit; Róna, Kálmán; Szücs, Nikolette; Igaz, Péter; Pusztai, Péter; Sármán, Beatrix; Gláz, Edit; Kiss, Róbert; Patócs, Attila; Rácz, Károly; Tóth, Miklós

2015-04-19

Laboratory diagnosis of pheochromocytoma-paraganglioma syndrome has been markedly improved during the past two decades. Retrospective assessment of diagnostic utility of urinary catecholamines and their metabolites as well as serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine, Semmelweis University. Urinary catecholamines and metabolites were measured using high-performance liquid chromatography with electrochemical detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had hereditary background) and in 170 non-pheochromocytoma patients used as controls. Serum chromogranin A was measured by immunoradiometry. Sensitivity (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r = 0.618, p<0.0001, respectively). These data confirm the diagnostic utility of urinary catecholamines and their metabolites. Urinary normetanephrine and serum chromogranin A may help to estimate tumour mass and probably tumour progression.

Update on Modern Management of Pheochromocytoma and Paraganglioma.

PubMed

Lenders, Jacques W M; Eisenhofer, Graeme

2017-06-01

Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine. To minimize false-positive test results particular attention should be paid to pre-analytical sampling conditions. In addition to anatomical imaging by computed tomography (CT) or magnetic resonance imaging, new promising functional imaging modalities of photon emission tomography/CT using with somatostatin analogues such as ⁶⁸Ga-DOTATATE (⁶⁸Ga-labeled DOTA(0)-Tyr(3)-octreotide) will probably replace ¹²³I-MIBG (iodine-123-metaiodobenzylguanidine) in the near future. As nearly half of all pheochromocytoma patients harbor a mutation in one of the 14 tumor susceptibility genes, genetic testing and counseling should at least be considered in all patients with a proven tumor. Post-surgical annual follow-up of patients by measurements of plasma or urinary metanephrines should last for at least 10 years for timely detection of recurrent or metastatic disease. Patients with a high risk for recurrence or metastatic disease (paraganglioma, young age, multiple or large tumors, genetic background) should be followed up lifelong. Copyright © 2017 Korean Endocrine Society.

Metastatic Pheochromocytoma/Paraganglioma Related to Primary Tumor Development in Childhood or Adolescence: Significant Link to SDHB Mutations

PubMed Central

King, Kathryn S.; Prodanov, Tamara; Kantorovich, Vitaly; Fojo, Tito; Hewitt, Jacqueline K.; Zacharin, Margaret; Wesley, Robert; Lodish, Maya; Raygada, Margarita; Gimenez-Roqueplo, Anne-Paule; McCormack, Shana; Eisenhofer, Graeme; Milosevic, Dragana; Kebebew, Electron; Stratakis, Constantine A.; Pacak, Karel

2011-01-01

Purpose To present data on the high rate of SDHB mutations in patients with metastatic pheochromocytoma/paraganglioma whose initial tumor presentation began in childhood or adolescence. Patients and Methods From 2000 to 2010, 263 patients with pheochromocytoma/paraganglioma were evaluated through the National Institutes of Health (NIH), Bethesda, MD. Of the 263 patients, 125 patients were found to have metastatic disease; of these 125 patients, 32 patients presented with a tumor before 20 years of age. An additional 17 patients presented with a tumor before 20 years of age but demonstrated no development of metastatic disease. Genetic testing for mutations in the VHL, MEN, and SDHB/C/D genes was performed on patients without previously identified genetic mutations. Results Of the 32 patients who presented with metastatic disease and had their primary tumor in childhood or adolescence, sequence analysis of germline DNA showed SDHB mutations in 23 patients (71.9%), SDHD mutations in three patients (9.4%), VHL mutations in two patients (6.3%), and an absence of a known mutation in four patients (12.5%). The majority of these 32 patients (78.1%) presented with primary tumors in an extra-adrenal location. Conclusion The majority of patients with metastatic pheochromocytoma/paraganglioma who presented with a primary tumor in childhood/adolescence had primary extra-adrenal tumors and harbored SDHB mutations. Except for primary tumors located in the head and neck where SDHD genetic testing is advised, we recommend that patients who present with metastatic pheochromocytoma/paraganglioma with primary tumor development in childhood or adolescence undergo SDHB genetic testing before they undergo testing for other gene mutations, unless clinical presentation or family history suggests a different mutation. PMID:21969497

Treatment with Sunitinib for Patients with Progressive Metastatic Pheochromocytomas and Sympathetic Paragangliomas

PubMed Central

Ayala-Ramirez, Montserrat; Chougnet, Cecile N.; Habra, Mouhammed Amir; Palmer, J. Lynn; Leboulleux, Sophie; Cabanillas, Maria E.; Caramella, Caroline; Anderson, Pete; Al Ghuzlan, Abir; Waguespack, Steven G.; Deandreis, Desirée

2012-01-01

Context: Patients with progressive metastatic pheochromocytomas (PHEOs) or sympathetic paragangliomas (SPGLs) face a dismal prognosis. Current systemic therapies are limited. Objectives: The primary end point was progression-free survival determined by RECIST 1.1 criteria or positron emission tomography with [18F]fluorodeoxyglucose/computed tomography ([18F]FDG-PET/CT), in the absence of measurable soft tissue targets. Secondary endpoints were tumor response according to RECIST criteria version 1.1 or FDG uptake, blood pressure control, and safety. Design: We conducted a retrospective review of medical records of patients with metastatic PHEO/SPGL treated with sunitinib from December 2007 through December 2011. An intention-to-treat analysis was performed. Patients and Setting: Seventeen patients with progressive metastatic PHEO/SPGLs treated at the Institut Gustave-Roussy and MD Anderson Cancer Center. Interventions: Patients treated with sunitinib. Results: According to RECIST 1.1, eight patients experienced clinical benefit; three experienced partial response, and five had stable disease, including four with predominant skeletal metastases that showed a 30% or greater reduction in glucose uptake on [18F]FDG-PET/CT. Of 14 patients who had hypertension, six became normotensive and two discontinued antihypertensives. One patient treated with sunitinib and rapamycin experienced a durable benefit beyond 36 months. The median overall survival from the time sunitinib was initiated was 26.7 months with a progression-free survival of 4.1 months (95% confidence interval = 1.4–11.0). Most patients who experienced a clinical benefit were carriers of SDHB mutations. Conclusion: Sunitinib is associated with tumor size reduction, decreased [18F]FDG-PET/CT uptake, disease stabilization, and hypertension improvement in some patients with progressive metastatic PHEO/PGL. Prospective multi-institutional clinical trials are needed to determine the true benefits of sunitinib. PMID

Torsade de pointes in a case of pheochromocytoma--an unusual presentation of an uncommon disease.

PubMed

Roshan, John; George, Oommen K; Vineet, S; George, Paul V; Jose, V Jacob

2004-01-01

We report the case of a middle aged lady with dilated cardiomyopathy, presenting with recurrent syncope due to torsade de pointes. Further evaluation revealed that she had a pheochromocytoma which caused the arrhythmia.

Incompletely treated malignancies of the major salivary gland: Toward evidence-based care.

PubMed

Tam, Samantha; Sandulache, Vlad C; Metwalli, Kareem A; Rock, Crosby D; Eraj, Salman A; Sheu, Tommy; El-Naggar, Adel K; Fuller, Clifton D; Weber, Randal S; Lai, Stephen Y

2018-05-07

Unexpected malignancy is common in major salivary gland tumors due to variability of workup, creating challenging treatment decisions. The purpose of this study was to define treatment-related outcomes for patients with incompletely treated major salivary gland tumors. A retrospective cohort study was completed of patients with incompletely treated major salivary gland tumors. Tumor burden at presentation was established and treatment categorized. The Cox Proportional Hazards model was used to determine predictors of survival and failure. Of the 440 included patients, patients with gross residual or metastatic disease had a worse overall survival (OS; P < .001). Presentation status was an independent predictor of OS on multivariate analysis (gross residual disease adjusted hazard ratio [HR adjusted ] 2.55; 95% confidence interval [CI] 1.20-5.30; metastatic disease HR adjusted 9.53; 95% CI 3.04-27.06). Failure to achieve gross total resection during initial surgery resulted in worse OS. Adequate preoperative planning is required for initial surgical management to optimize tumor control and survival. © 2018 Wiley Periodicals, Inc.

Pheochromocytoma diagnosed after anticoagulation for atrial fibrillation ablation procedure: a giant in disguise.

PubMed

Galvão Braga, Carlos; Ribeiro, Sílvia; Martins, Juliana; Arantes, Carina; Ramos, Vítor; Primo, João; Magalhães, Sónia; Correia, Adelino

2014-04-01

Pheochromocytoma is a rare catecholamine-producing tumor, discovered incidentally in 50% of cases. We present the case of a 44-year-old male with a history of paroxysmal palpitations. Baseline ECG, transthoracic echocardiogram and ECG stress test showed no relevant alterations. Paroxysmal atrial fibrillation was detected on 24-hour Holter ECG. After antiarrhythmic therapy, the patient remained symptomatic, and was accordingly referred for electrophysiological study and atrial fibrillation ablation. Anticoagulation was initiated before the procedure. After ablation and still anticoagulated, he complained of hematospermia. The abdominal and pelvic imaging study showed a 10-cm left adrenal mass, predominantly cystic, compatible with pheochromocytoma, which was confirmed after biochemical tests (increased urine metanephrines and plasma catecholamines). Metaiodobenzylguanidine scintigraphy scanning confirmed localized disease in the adrenal gland, excluding other uptake foci. Following appropriate preoperative management, surgical resection of the giant mass was performed successfully and without complications. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Second Malignant Neoplasms in Childhood Cancer Survivors Treated in a Tertiary Paediatric Oncology Centre.

PubMed

Lim, Jia Wei; Yeap, Frances Sh; Chan, Yiong Huak; Yeoh, Allen Ej; Quah, Thuan Chong; Tan, Poh Lin

2017-01-01

Introduction : One of the most feared complications of childhood cancer treatment is second malignant neoplasms (SMNs). This study evaluates the incidence, risk factors and outcomes of SMNs in a tertiary paediatric oncology centre in Singapore. Materials and Methods : A retrospective review was conducted on patients diagnosed with childhood cancer under age 21 and treated at the National University Hospital, Singapore, from January 1990 to 15 April 2012. Case records of patients with SMNs were reviewed. Results : We identified 1124 cases of childhood cancers with a median follow-up of 3.49 (0 to 24.06) years. The most common primary malignancies were leukaemia (47.1%), central nervous system tumours (11.7%) and lymphoma (9.8%). Fifteen cases developed SMNs, most commonly acute myeloid leukaemia/myelodysplastic syndrome (n = 7). Median interval between the first and second malignancy was 3.41 (0.24 to 18.30) years. Overall 20-year cumulative incidence of SMNs was 5.3% (95% CI, 0.2% to 10.4%). The 15-year cumulative incidence of SMNs following acute lymphoblastic leukaemia was 4.4% (95% CI, 0% to 8.9%), significantly lower than the risk after osteosarcoma of 14.2% (95% CI, 0.7% to 27.7%) within 5 years ( P <0.0005). Overall 5-year survival for SMNs was lower than that of primary malignancies. Conclusion : This study identified factors explaining the epidemiology of SMNs described, and found topoisomerase II inhibitor use to be a likely risk factor in our cohort. Modifications have already been made to our existing therapeutic protocols in osteosarcoma treatment. We also recognised the importance of other risk management strategies, including regular long-term surveillance and early intervention for detected SMNs, to improve outcomes of high risk patients.

Increased adenosine triphosphate production by peripheral blood CD4+ cells in patients with hematologic malignancies treated with stem cell mobilization agents.

PubMed

Manga, Kiran; Serban, Geo; Schwartz, Joseph; Slotky, Ronit; Patel, Nita; Fan, Jianshe; Bai, Xiaolin; Chari, Ajai; Savage, David; Suciu-Foca, Nicole; Colovai, Adriana I

2010-07-01

Hematopoietic stem cell (HSC) transplantation is an important therapeutic option for patients with hematologic malignancies. To explore the immunomodulatory effects of HSC mobilization agents, we studied the function and phenotype of CD4(+) T cells from 16 adult patients with hematologic malignancies undergoing HSC mobilization treatment for autologous transplantation. Immune cell function was determined using the Immuknow (Cylex) assay by measuring the amount of adenosine triphosphate (ATP) produced by CD4(+) cells from whole blood. ATP activity measured in G-CSF-treated patients was significantly higher than that measured in healthy individuals or "nonmobilized" patients. In patients treated with G-CSF, CD4(+) T cells were predominantly CD25(low)FOXP3(low), consistent with an activated phenotype. However, T-cell depletion did not abrogate ATP production in blood samples from G-CSF-treated patients, indicating that CD4(+) myeloid cells contributed to the increased ATP levels observed in these patients. There was a significant correlation between ATP activity and patient survival, suggesting that efficient activation of CD4(+) cells during mobilization treatment predicts a low risk of disease relapse. Monitoring immune cell reactivity using the Immuknow assay may assist in the clinical management of patients with hematologic malignancies and optimization of HSC mobilization protocols. Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

DIFFERENTIAL MODULATION OF CATECHOLAMINES BY CHLOROTRIAZINE HERBICIDES IN PHEOCHROMOCYTOMA (PC12) CELLS IN VITRO

EPA Science Inventory

Differential modulation of catecholamines by chlorotriazine herbicides in pheochromocytoma (PC12) cells in vitro.

Das PC, McElroy WK, Cooper RL.

Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599, USA.

Epidemiological, wildlife, and lab...

POTENTIAL MECHANISMS RESPONSIBLE FOR CHLOROTRIAZINE-INDUCED ALTERATIONS IN CATECHOLAMINES IN PHEOCHROMOCYTOMA (PC12) CELLS

EPA Science Inventory

ABSTRACT

Potential Mechanisms Responsible for Chlorotriazine-induced Changes in Catecholamine Metabolism in Pheochromocytoma (PC12) Cells*
PARIKSHIT C. DAS1, WILLIAM K. McELROY2 , AND RALPH L. COOPER2+
1Curriculum in Toxicology, University of North Carolina, Chape...

High penetrance of pheochromocytoma associated with the novel C634Y/Y791F double germline mutation in the RET protooncogene.

PubMed

Toledo, Rodrigo A; Wagner, Simona M; Coutinho, Flavia L; Lourenço, Delmar M; Azevedo, Juliana A; Longuini, Viviane C; Reis, Mariana T A; Siqueira, Sheila A C; Lucon, Antonio M; Tavares, Marcos R; Fragoso, Maria C B V; Pereira, Adelaide A; Dahia, Patricia L M; Mulligan, Lois M; Toledo, Sergio P A

2010-03-01

Previous studies have shown that double RET mutations may be associated with unusual multiple endocrine neoplasia type 2 (MEN 2) phenotypes. Our objective was to report the clinical features of patients harboring a previously unreported double mutation of the RET gene and to characterize this mutation in vitro. Sixteen patients from four unrelated families and harboring the C634Y/Y791F double RET germline mutation were included in the study. Large pheochromocytomas measuring 6.0-14 cm and weighing up to 640 g were identified in the four index cases. Three of the four tumors were bilateral. High penetrance of pheochromocytoma was also seen in the C634Y/Y791F-mutation-positive relatives (seven of nine, 77.7%). Of these, two cases had bilateral tumors, one presented with multifocal tumors, two cases had large tumors (>5 cm), and one case, which was diagnosed with a large (5.5 x 4.5 x 4.0 cm) pheochromocytoma, reported early onset of symptoms of the disease (14 yr old). The overall penetrance of pheochromocytoma was 84.6% (11 of 13). Development of medullary thyroid carcinoma in our patients seemed similar to that observed in patients with codon 634 mutations. Haplotype analysis demonstrated that the mutation did not arise from a common ancestor. In vitro studies showed the double C634Y/Y791F RET receptor was significantly more phosphorylated than either activated wild-type receptor or single C634Y and Y791F RET mutants. Our data suggest that the natural history of the novel C634Y/Y791F double mutation carries a codon 634-like pattern of medullary thyroid carcinoma development, is associated with increased susceptibility to unusually large bilateral pheochromocytomas, and is likely more biologically active than each individual mutation.

[Malignant tumors of thyroid gland].

PubMed

Uhliarová, B; Bugová, G; Hajtman, A

2015-01-01

The incidence of thyroid cancer has been increasing. The aim of this work was to determine risk factors, diagnostic methods and extent of surgical treatment of malignant goiter. The authors retrospectively analyzed patients who were surgically treated for thyroid disease at the Department of Otorhinolaryngology, Head and Neck Surgery, Comenius University, Jessenius Faculty of Medicine, Teaching Hospital in Martin, Slovakia, from the January 1st, 2006 to December 31st, 2013, for thyroid disease. The incidence, risk factors of malignant thyroid tumors, indication for surgery and its complications were evaluated. A total of 1,620 adult patients were surgically treated for thyroid disease at the Department of ENT, Head and Neck Surgery, CU JMF, UH in Martin, Slovakia, between 2006- 2013. Malignant tumors were identified in 238 patients (15%). Microcarcinoma (incidentally detected malignant tumor 1 cm) occurred in 78 cases (5%). Malignant thyroid tumor was more common in younger patients (p = 0.002). Newly created and larger nodules positively correlated with the occurrence of malignancy (p = 0.003, p = 0.041, resp.). Gender, family history of thyroid disorder, previous radiation therapy, and previous malignancy did not affect the incidence of malignant tumor of thyroid gland. High sensitivity and specificity in the dia-gnosis of malignant thyroid nodule was observed using aspiration cytology (75%, 97%, resp.) and intraoperative histopathological examination (88%, 100%, resp.). Malignant tumor of thyroid gland is more common in younger patients with newly developed nodule. The risk factors of malignancy increase with the size of the thyroid nodule. Aspiration cytology and peroperative histopathology have high sensitivity and specificity in the dia-gnosis of malignant thyroid tumor; therefore, they should be a standard method in the dia-gnosis of nodular goiter. The method of choice in the treatment of thyroid malignancy is total thyroidectomy.

[Gynecological malignant tumor related multiple primary malignant neoplasms: clinical analysis of 30 cases].

PubMed

Shi, Li; Zhou, Shulin; Jiang, Yi; Wan, Yicong; Ma, Jingjing; Fu, Shilong; Cheng, Wenjun

2014-03-01

To investigate the clinical features of gynecological malignant tumor related multiple primary malignant neoplasms (MPMN). Apply retrospective and comprehensive analysis to the clinical data of 30 patients with gynecological malignant tumor related MPMN. Synchronous MPMN were found in 9 patients. Their average age was 50.2 years old and their median age was 49 years old. The neoplasms were located at ovary, uterus, cervix, breast and intestine. Metachronous MPMN were found in 21 patients. Their average age was 57.7 and their median age was 57 years old. The median interval between the first and the second primary malignant neoplasm was 4.0 years. The neoplasms were located at breast, ovary, uterus, gastrointestinal tract, uterine cervix, lung etc. In 30 cases, 26 of them were treated by surgical operation and further adjunctive treatment of chemotherapy and (or) radiotherapy was conducted as per the neoplasm staging and its pathological results. The rest 4 patients (first primary malignant neoplasms were excised from 3 of them and another one was not treated by surgical operation) received adjunctive treatment of chemotherapy and (or) radiotherapy. Followed ups, which varied from 6 to 60 months, were made to 29 patients and 20 out of the 29 were alive.5-year survival rate of patients with gynecological malignant tumor related MPMN was 47.8%, 2-year survival rate was 73.9%, and 1-year survival rate was 88.6%. Pay more attention to the patients with gynecological malignant tumor related MPMN, examine the high-risk patients with malignant tumor comprehensively, identify whether it is recurrence, metastasis or new growth of malignant neoplasm, and further ensure early diagnosis and proper treatment, avoiding misdiagnosis and missed diagnosis.

MAX mutations status in Swedish patients with pheochromocytoma and paraganglioma tumours.

PubMed

Crona, Joakim; Maharjan, Rajani; Delgado Verdugo, Alberto; Stålberg, Peter; Granberg, Dan; Hellman, Per; Björklund, Peyman

2014-03-01

Pheochromocytoma (PCC) and Paraganglioma are rare tumours originating from neuroendocrine cells. Up to 60% of cases have either germline or somatic mutation in one of eleven described susceptibility loci, SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, EPAS1, RET, NF1, TMEM127 and MYC associated factor-X (MAX). Recently, germline mutations in MAX were found to confer susceptibility to PCC and paraganglioma (PGL). A subsequent multicentre study found about 1% of PCCs and PGLs to have germline or somatic mutations in MAX. However, there has been no study investigating the frequency of MAX mutations in a Scandinavian cohort. We analysed tumour specimens from 63 patients with PCC and PGL treated at Uppsala University hospital, Sweden, for re-sequencing of MAX using automated Sanger sequencing. Our results show that 0% (0/63) of tumours had mutations in MAX. Allele frequencies of known single nucleotide polymorphisms rs4902359, rs45440292, rs1957948 and rs1957949 corresponded to those available in the Single Nucleotide Polymorphism Database. We conclude that MAX mutations remain unusual events and targeted genetic screening should be considered after more common genetic events have been excluded.

Role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in evaluating patients with pheochromocytoma.

PubMed

Bandopadhyaya, G P; Kumar, Abhishek; Kumari, Jyotsana

2015-01-01

The aim of this retrospective study was to evaluate role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in patients with pheochromocytoma. The patients with diagnosis of pheochromocytoma based on radiological and biochemical markers were retrospectively selected for the study. These patients had undergone both (131)I-MIBG scintigraphy and (18)F-DOPA PET/CT. The imaging findings were compared to patient histopathology reports, biochemical markers and clinical follow up whenever available to establish the diagnosis. (131)I-MIBG showed a sensitivity of 68% and specificity of 100%. (18)F-DOPA PET/CT showed a sensitivity of 82% and specificity of 100%. (18)F-DOPA was better at localizing and finding more no of lesions as compared to (131)I-MIBG scintigraphy. (18)F-DOPA also is a better study in evaluation of paragangliomas. (18)F-DOPA PET/CT seems to be a better modality in comparison to (131)I-MIBG scintigraphy in the evaluation of pheochromocytoma/paraganglioma. At this point both these tracers seem to have mutually additive role in these patients and essential investigations with diagnosis and follow-up of this disease.

Genetics of pheochromocytoma and paraganglioma: new developments.

PubMed

Pigny, P; Cardot-Bauters, C

2010-03-01

Since 2000, several new susceptibility genes for hereditary pheochromocytoma or paraganglioma have been discovered. The aim of this review is to highlight how these discoveries have improved our knowledge on the mode of inheritance of these tumors and also on their molecular pathogenesis. Concerning this specific point, we will show that the different key players of tumorigenesis can converge on two pathways, the first being the hypoxia/angiogenesis pathway and the second being the control of neural crest cell development pathway. Finally, practical issues are considered; for us, it would be preferable to apply easy-to-identify clinical predictors to preselect patients eligible for molecular testing in order to improve the efficiency of these high-cost tests. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

INFLUENCE OF 50-HZ ELECTRIC AND MAGNETIC FIELDS ON NEURITE OUTGROWTH IN PHEOCHROMOCYTOMA CELLS

EPA Science Inventory

This study describes the ability of electric and magnetic fields to substitute for nerve growth factor in the stimulation of trite growth in a subline of PC-12 cells, derived from a pheochromocytoma in rat adrenal medulla. he cells were plated on collagen-coated, 60-mm plastic di...

Second primary malignancies after treatment for malignant lymphoma

PubMed Central

Okines, A; Thomson, C S; Radstone, C R; Horsman, J M; Hancock, B W

2005-01-01

To determine the incidence and possible causes of second primary malignancies after treatment for Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL). A cohort of 3764 consecutive patients diagnosed with HL or NHL between January 1970 and July 2001 was identified using the Sheffield Lymphoma Group database. A search was undertaken for all patients diagnosed with a subsequent primary malignancy. Two matched controls were identified for each case. Odds ratios were calculated to detect and quantify any risk factors in the cases compared to their matched controls. Mean follow-up for the cohort was 5.2 years. A total of 68 patients who developed second cancers at least 6 months after their primary diagnosis were identified, giving a crude incidence of 1.89% overall: 3.21% among the patients treated for HL, 1.32% in those treated for NHL. Most common were bronchial, breast, colorectal and haematological malignancies. High stage at diagnosis almost reached statistical significance in the analysis of just the NHL patients (odds ratio=3.48; P=0.068) after adjustment for other factors. Treatment modality was not statistically significant in any analysis. High stage at diagnosis of NHL may be a risk factor for developing a second primary cancer. PMID:16106249

Ordering pattern and performance of biochemical tests for diagnosing pheochromocytoma between 2000 and 2008.

PubMed

Yu, Run

2009-01-01

To examine what tests are ordered by physicians for pheochromocytoma diagnosis and how those tests perform in modern clinical practice. In this case series, electronic medical records of patients seen between January 2000 and July 2008 at a large academic hospital in Los Angeles, California, were queried, and patients older than 15 years who underwent any 1 of 5 tests for pheochromocytoma (measurement of plasma catecholamines, plasma fractionated metanephrines, urinary catecholamines, urinary metanephrines, or urinary vanillylmandelic acid) were identified. Because testing was performed in various reference laboratories, test results were classified into 1 of 3 categories: (a) markedly elevated, (b) moderately elevated, or (c) normal. Patient demographics, clinical history, test results, imaging study findings, and pathology records were reviewed. A total of 3980 tests were ordered for 1898 patients. Pretest probability was 2.2% (based on 681 patients in whom pheochromocytoma was confirmed or excluded), and hypertension was the most common indication for testing. The number of patients tested and the number of tests ordered increased over the years. The ordering pattern stabilized since 2006 when urinary metanephrines, urinary catecholamines, and plasma metanephrines were ordered more frequently. Sensitivity was highest for urinary metanephrines and vanillylmandelic acid, specificity was highest for vanillylmandelic acid and urinary catecholamines, and positive likelihood ratio was highest for vanillylmandelic acid. Positive predictive value for markedly elevated test results was 39% to 83%, while that for moderately elevated test results was only 2% to 14%. Ordering pattern and test performance differ significantly from those recommended and reported by large centers. The best testing strategy should incorporate local experience. Categorizing test results as markedly elevated, moderately elevated, and normal is important for result interpretation.

Combined Inhibition of mTORC1 and mTORC2 Signaling Pathways Is a Promising Therapeutic Option in Inhibiting Pheochromocytoma Tumor Growth: In Vitro and In Vivo Studies in Female Athymic Nude Mice

PubMed Central

Bullova, Petra; Nölting, Svenja; Turkova, Hana; Powers, James F.; Liu, Qingsong; Guichard, Sylvie; Tischler, Arthur S.; Grossman, Ashley B.

2013-01-01

Several lines of evidence, including the recent discovery of novel susceptibility genes, point out an important role for the mammalian target of rapamycin (mTOR) signaling pathway in the development of pheochromocytoma. Analyzing a set of pheochromocytomas from patients with different genetic backgrounds, we observed and confirmed a significant overexpression of key mTOR complex (mTORC) signaling mediators. Using selective ATP-competitive inhibitors targeting both mTORC1 and mTORC2, we significantly arrested the in vitro cell proliferation and blocked migration of pheochromocytoma cells as a result of the pharmacological suppression of the Akt/mTOR signaling pathway. Moreover, AZD8055, a selective ATP-competitive dual mTORC1/2 small molecular inhibitor, significantly reduced the tumor burden in a model of metastatic pheochromocytoma using female athymic nude mice. This study suggests that targeting both mTORC1 and mTORC2 is a potentially rewarding strategy and supports the application of selective inhibitors in combinatorial drug regimens for metastatic pheochromocytoma. PMID:23307788

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

ClinicalTrials.gov

2018-06-27

Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma

Pheochromocytoma: The First Metabolic Endocrine Cancer

PubMed Central

Jochmanova, Ivana; Pacak, Karel

2016-01-01

Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics allowed us to take a closer look at the metabolic changes present in pheochromocytomas and paragangliomas (PHEOs/PGLs). These neuroendocrine tumors often exhibit dysregulation of mitochondrial metabolism, which is driven by mutations in genes encoding Krebs cycle enzymes or by activation of hypoxia signaling. Present metabolic changes are involved in processes associated with tumorigenesis, invasiveness, metastasis, and resistance to various cancer therapies. In this review, we discuss the metabolic nature of PHEOs/PGLs and how unveiling the metabolic disturbances present in tumors could lead to identification of new biomarkers and personalized cancer therapies. PMID:27742786

Performance of plasma free metanephrines measured by liquid chromatography-tandem mass spectrometry in the diagnosis of pheochromocytoma.

PubMed

Peaston, Robert T; Graham, Kendon S; Chambers, Erin; van der Molen, Jan C; Ball, Stephen

2010-04-02

Plasma free metanephrines have proved a highly sensitive biochemical test for the diagnosis of pheochromocytoma. We have developed and validated a simple, LC-MS/MS method to determine plasma metanephrines and compared the diagnostic efficacy of the method with an enzyme immunoassay procedure in 151 patients, 38 with histologically confirmed pheochromocytoma. Off-line solid phase extraction in a 96-well plate format was used to isolate metanephrines from 100-microL of plasma, followed by rapid separation with hydrophilic interaction chromatography. Mass spectrometry detection was performed in multiple-reaction monitoring mode using a tandem quadrupole mass spectrometer with positive electrospray ionization. Detection limits were <0.1nmol/l with method linearity up to 23.0nmol/L for normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT). Method comparison with an automated LC-MS/MS yielded Deming regression slopes of r=0.94 for NMN, r=0.98 for MN and r=0.94 for 3-MT. Method comparison with enzyme immunoassay revealed regression slope of r=1.28 (NMN) and 1.25 (MN) with values approximately 25% lower than LC-MS/MS. Plasma metanephrines by LC-MS/MS identified all 38 patients with phaeochromocytoma compared with 36 cases by immunoassay. Plasma metanephrines measured by LC-MS/MS are a reliable and sensitive test for the biochemical detection of pheochromocytoma. 2010 Elsevier B.V. All rights reserved.

Synchronous adrenocortical neoplasms, paragangliomas, and pheochromocytomas: syndromic considerations regarding an unusual constellation of endocrine tumors.

PubMed

LeBlanc, Melissa; Tabrizi, Mohsen; Kapsner, Patricia; Hanson, Joshua Anspach

2014-12-01

The most common clinical syndromes presenting with paragangliomas and/or pheochromocytomas as their endocrine components are multiple endocrine neoplasia type 2, neurofibromatosis, Von Hippel-Lindau syndrome, Carney-Stratakis syndrome, Carney triad, and the recently described hereditary paraganglioma syndrome. Only Carney triad is known to also present with adrenocortical adenomas, currently representing the only described syndrome in which all 3 of the aforementioned tumors are found together. In most cases, prototypical lesions of the triad such as gastrointestinal stromal tumor and pulmonary chondromas are also seen. We present a case of a young woman with synchronous paragangliomas, adrenal/extra-adrenal cortical neoplasms, and pheochromocytoma without genetic mutations for multiple endocrine neoplasia 2, Von Hippel-Lindau syndrome, neurofibromatosis, and succinate dehydrogenase. We speculate that this represents a previously undescribed presentation of Carney triad and, at the very least, indicates the need for monitoring for the development of other tumors of the triad. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypertensive emergency due to pheochromocytoma crisis complicated with refractory hemodynamic collapse.

PubMed

Hayıroğlu, Mert İlker; Yıldırımtürk, Özlem; Bozbay, Mehmet; Eren, Mehmet; Pehlivanoğlu, Seçkin

2015-12-01

Hypertensive emergency usually appears in older patients with previous recurrent episodes, and is among the most frequent admissions to emergency departments. A 29-year-old woman was referred to our clinic with the diagnosis of hypertensive emergency. The patient complained of severe headache, dyspnea, palpitation, diaphoresis, and confusion due to hypertensive encephalopathy. Her blood pressure was 250/150 mmHg on admission. At the referral hospital, the patient had undergone cranial CT because of her confused state and this excluded acute cerebral hemorrhage. Also at that hospital, thoracoabdominal CT for differential diagnosis depicted an adrenal mass with a necrotic core. After admission to our clinic, initial control of excessive blood pressure was not achieved despite high dose intravenous nitrate therapy. Thereafter intravenous esmolol treatment was initiated simultaneously with oral alpha blocker therapy in order to counterbalance the unopposed alpha adrenergic activity with beta blocker therapy. After 12 hours, sudden onset of hypotension developed and deepened despite IV saline, inotropic and vasopressor agents such as IV dopamine, noradrenaline and adrenaline. The patient died at the 24th hour due to hemodynamic collapse as a result of hyperadrenergic state due to possible pheochromocytoma crisis. This case is an exceptional example of hypertensive emergency secondary to fulminant pheochromocytoma crisis failing to respond to intensive antihypertensive treatment, and in which patient death was unavoidable due to uncontrolled excessive adrenergic activity which led to profound cardiogenic shock.

Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline.

PubMed

Lenders, Jacques W M; Duh, Quan-Yang; Eisenhofer, Graeme; Gimenez-Roqueplo, Anne-Paule; Grebe, Stefan K G; Murad, Mohammad Hassan; Naruse, Mitsuhide; Pacak, Karel; Young, William F

2014-06-01

The aim was to formulate clinical practice guidelines for pheochromocytoma and paraganglioma (PPGL). The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), seven experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, European Society of Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of the guidelines. The Task Force recommends that initial biochemical testing for PPGLs should include measurements of plasma free or urinary fractionated metanephrines. Consideration should be given to preanalytical factors leading to false-positive or false-negative results. All positive results require follow-up. Computed tomography is suggested for initial imaging, but magnetic resonance is a better option in patients with metastatic disease or when radiation exposure must be limited. (123)I-metaiodobenzylguanidine scintigraphy is a useful imaging modality for metastatic PPGLs. We recommend consideration of genetic testing in all patients, with testing by accredited laboratories. Patients with paraganglioma should be tested for SDHx mutations, and those with metastatic disease for SDHB mutations. All patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications. Preparation should include a high-sodium diet and fluid intake to prevent postoperative hypotension. We recommend minimally invasive adrenalectomy for most pheochromocytomas with open resection for most

Single-fraction stereotactic body radiation therapy for sinonasal malignant melanoma.

PubMed

Bourgeois, Daniel J; Singh, Anurag K

2015-03-01

A rare head and neck disease that may benefit from definitive or palliative stereotactic body radiation therapy (SBRT) is sinonasal malignant melanoma. These tumors can be very aggressive and often lead to severe epistaxis and significant mass effect. Results from only a handful of head and neck sinonasal malignant melanoma treated with SBRT are available in the current literature. The following reports on 2 cases of sinonasal malignant melanoma that recurred postoperatively and were subsequently treated at Roswell Park with SBRT. Both were treated with a single fraction of 15 Gy. Nearly instant relief of their chronic epistaxis and complete responses were seen in both patients. One patient is alive and free of disease 7 years after radiation. These patients with sinonasal malignant melanoma achieved symptomatic relief of severe bleeding and airway issues from single-fraction SBRT. SBRT should be considered as a treatment option in patients with unresectable sinonasal malignant melanoma. © 2014 Wiley Periodicals, Inc.

Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

ClinicalTrials.gov

2017-11-14

Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

The Genetic Basis of Pheochromocytoma and Paraganglioma: Implications for Management

PubMed Central

Shuch, Brian; Ricketts, Christopher J.; Pacak, Karol; Linehan, W. Marston

2015-01-01

Chromaffin cells are catecholamine-producing cells derived from neural crest tissue. Chromaffin tumors (ChT) are rare tumors arising from these cells and are divided into pheochromocytoma (PCC) arising from adrenal tissue and paraganglioma (PGL) arising from extra-adrenal ganglia. Previously, ∼10% were believed to be hereditary, but advances in genome sequencing has shown roughly 35% of apparently sporadic tumors have a hereditary component. In this review we describe both classic and newly discovered hereditary ChT syndromes and provide recommendations for genetic testing. In many cases the genes associated with these conditions are linked to common kidney cancer pathways familiar to urologic oncologists. PMID:24642075

Gastrointestinal surgical emergencies in patients treated for hemathological malignancies.

PubMed

Caronna, R; Cardi, M; Arcese, W; Iori, A P; Martelli, M; Catinelli, S; Mangioni, S; Corelli, S; Priore, F; Tarantino, E; Frantellizzi, V; Spera, G; Borrini, F; Chirletti, P

2005-01-01

Upper and lower gastrointestinal symptoms are major and serious complications in patients who undergo chemotherapy for hematological malignancies. Their most frequent causes are acute intestinal graft-versus-host disease (GVHD) after bone marrow transplant, infections, toxicity or preexisting gastrointestinal diseases. Mortality can reach 30-60% of cases. We report 15 cases operated on for abdominal emergencies: 3 severe gastrointestinal bleeding and 12 acute abdomen. We performed 10 bowel resections, one cholecystectomy, one splenectomy, two laparotomy with pancreatic debridement and peritoneal lavage, and one suture of perforated peptic ulcer. Operative mortality was 33.3% (5/15). Deaths have been reported only in the group of patients with acute abdomen. In all cases death was correlated to generalized sepsis related to immunosuppression. We believe that an aggressive approach, consisting of close monitoring and early laparotomy combined with vigorous supportive therapy, should be used when dealing with suspected gastrointestinal complications in patients with hematological malignancies.

Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer-Predisposing Mutations in Pheochromocytomas and Paragangliomas.

PubMed

Remacha, Laura; Comino-Méndez, Iñaki; Richter, Susan; Contreras, Laura; Currás-Freixes, María; Pita, Guillermo; Letón, Rocío; Galarreta, Antonio; Torres-Pérez, Rafael; Honrado, Emiliano; Jiménez, Scherezade; Maestre, Lorena; Moran, Sebastian; Esteller, Manel; Satrústegui, Jorgina; Eisenhofer, Graeme; Robledo, Mercedes; Cascón, Alberto

2017-10-15

Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes. Methylation profiling, metabolite assessment and additional analyses were also performed in selected cases. Results: One of the 11 tumors was found to carry a known cancer-predisposing somatic mutation in IDH1 A variant in GOT2 , c.357A>T, found in a patient with multiple tumors, was associated with higher tumor mRNA and protein expression levels, increased GOT2 enzymatic activity in lymphoblastic cells, and altered metabolite ratios both in tumors and in GOT2 knockdown HeLa cells transfected with the variant. Array methylation-based analysis uncovered a somatic epigenetic mutation in SDHC in a patient with multiple pheochromocytomas and a gastrointestinal stromal tumor. Finally, a truncating germline IDH3B mutation was found in a patient with a single paraganglioma showing an altered α-ketoglutarate/isocitrate ratio. Conclusions: This study further attests to the relevance of the Krebs cycle in the development of PCC and PGL, and points to a potential role of other metabolic enzymes involved in metabolite exchange between mitochondria and cytosol. Clin Cancer Res; 23(20); 6315-24. ©2017 AACR . ©2017 American Association for Cancer Research.

Unusual Differentiation to Pheochromocytoma-Like Cells in an Adrenal Neuroblastoma After Chemotherapy: A Case Report and Literature Review.

PubMed

Tatekawa, Yukihiro

2015-01-01

The authors present a case of 3-year-old female with Stage 4 neuroblastoma originating from the left adrenal gland. Biopsy of the left adrenal tumor showed neuroblastoma. After three courses of chemotherapy, the left adrenal gland including the left adrenal tumor was surgically removed. Pathological findings of the resected tumor revealed that most of the neuroblastoma tissues changed to pheochromocytoma-like cells. The tumor cells were arranged in well-defined nests surrounded by a delicate fibrovascular stroma and had granular eosinophilic cytoplasm, and round to oval nuclei. Immunohistological analysis of the biopsy samples showed strongly positive Ganglioside GD2-staining cells, whereas almost all of the tumor cells in the resected specimen were Ganglioside GD2-negative; cells were very weakly stained. The authors suggest that a part of the neuroblastoma in the left adrenal gland exhibited unusual differentiation toward pheochromocytic lineage Ganglioside GD2-negative neuroblastoma in a patient who had been treated with intensive chemotherapy.

Pembrolizumab in Treating Patients With HIV and Relapsed, Refractory, or Disseminated Malignant Neoplasms

ClinicalTrials.gov

2018-03-22

AIDS-Related Non-Hodgkin Lymphoma; Classical Hodgkin Lymphoma; HIV Infection; Locally Advanced Malignant Neoplasm; Metastatic Malignant Neoplasm; Recurrent Hepatocellular Carcinoma; Recurrent Hodgkin Lymphoma; Recurrent Kaposi Sarcoma; Recurrent Malignant Neoplasm; Recurrent Melanoma of the Skin; Recurrent Non-Hodgkin Lymphoma; Recurrent Non-Small Cell Lung Carcinoma; Refractory Hodgkin Lymphoma; Refractory Malignant Neoplasm; Solid Neoplasm; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7

Paraspinal tuberculosis mimicking malignancy.

PubMed

Alherabi, Ameen Z; Marglani, Osama A; Gazzaz, Malak J; Abbas, Mohammed M

2013-12-01

Tuberculosis (TB) of the paraspinal muscles is a rare clinical entity. We present a case of an 18-year-old, Saudi male patient presenting with the clinical picture of a paraspinal mass that turned out to be paraspinal TB. It originated from the paraspinal tissues and muscles, and invaded the C6 and C7 vertebrae. Initially, it was highly suspicious for malignancy. A biopsy confirmed the diagnosis of TB, and the patient was treated successfully with anti-TB therapy. It is important to be aware that paraspinal TB can mimic malignancy.

Clinical results of primary malignant musculoskeletal tumor treated by wide resection and recycling autograft reconstruction using liquid nitrogen.

PubMed

Paholpak, Permsak; Sirichativapee, Winai; Wisanuyotin, Taweechok; Kosuwon, Weerachai; Jeeravipoolvarn, Polasak

2015-06-01

To evaluate the clinical results of primary malignant musculoskeletal tumors treated with wide resection and recycling autograft reconstruction using liquid nitrogen. We reviewed 12 patients who had a primary malignant bone and soft tissue tumor treated by wide resection and recycling autograft reconstruction using liquid nitrogen between March 2006 and March 2013. The results were judged by recurrence, functional status and complications. Functional status was assessed according to the Musculoskeletal Tumor Society Score (MSTSS). Clinical failure was defined as need for reoperation in order to change the type of reconstruction or to amputate, and the presence of local recurrence. The most common tumor was osteosarcoma (eight cases) followed by Ewing's sarcoma (two cases). The tibia was the most frequently involved skeletal site (six cases) followed by the femur (three cases). The median follow-up period was 32 months. In 12 patients, 7 were still alive without recurrence. There were 3 clinical failures: 1 local recurrence and 2 graft complications at 28, 51 and 20 months after reconstruction, respectively. The main complication was infection (three cases). All osteotomy sites were radiographic unions, and the union time was 8.2 ± 2.7 months. The mean ± SD MSTSS score was 79% ± 11%; excellent functional results were achieved in seven patients. Recycling autograft reconstruction using liquid nitrogen had favorable clinical outcomes in terms of functional status and local recurrence. This reconstruction method, therefore, represents a reasonable alternative for limb salvage surgery. © 2014 Wiley Publishing Asia Pty Ltd.

Limbic encephalitis following immunotherapy against metastatic malignant melanoma

PubMed Central

Salam, Sharfaraz; Lavin, Timothy; Turan, Ayse

2016-01-01

Novel immunotherapies are increasingly being used to treat malignant melanoma. The use of such agents has been associated with triggering autoimmunity. However, there has been a paucity in reports of limbic encephalitis associated with these immunotherapies. Pembrolizumab, a monoclonal antibody against programmed cell death antigen (PD-1), is currently being trialled in the UK to treat malignant melanoma. We report a unique case of antibody-negative limbic encephalitis presenting 1 year after starting pembrolizumab, in the context of malignant melanoma. The patient presented with progressive cognitive decline. MRI of the brain revealed signal change within the limbic structures. Cerebrospinal fluid studies confirmed evidence of inflammation with raised white cell count and protein. We were able to prevent further progression of symptoms by stopping pembrolizumab and treating the patient instead with steroids. We advocate considering autoimmune neuroinflammation as a differential for neurological disorders presenting in patients receiving PD-1 antagonist treatment and immunotherapy in general. PMID:27009198

Constipation: an overlooked, unmanaged symptom of patients with pheochromocytoma and sympathetic paraganglioma.

PubMed

Thosani, Sonali; Ayala-Ramirez, Montserrat; Román-González, Alejandro; Zhou, Shouhao; Thosani, Nirav; Bisanz, Annette; Jimenez, Camilo

2015-09-01

Pheochromocytomas (PHs) and sympathetic paragangliomas (PGs) are tumors that produce catecholamines, predisposing patients to cardiovascular disease and gastrointestinal effects such as constipation. i) determine the prevalence of constipation, its risk factors, and its impact on survival; ii) identify whether a systematic combination of fiber, water, and laxatives was effective for treatment of constipation. We retrospectively studied 396 patients with PH/PG diagnosed in 2005-2014. The study population was patients with constipation as a presenting symptom; the control group was patients without constipation as a presenting symptom. The MD Anderson Symptom Inventory was used to assess constipation and quality of life. Twenty-three patients (6%) had constipation. Constipation was associated with headaches, palpitations, diaphoresis, weight loss, and excessive noradrenaline production (P<0.0001). Eighteen of these patients had non-metastatic primary tumors larger than 5 cm and/or extensive metastases. No statistically significant differences in age, sex, and genotype were noted between the study and control groups. In patients without metastases, resection of the primary tumor led to symptom disappearance. A systematic combination of fiber, water, and laxatives was associated with symptom improvement. Two patients who presented unmanaged constipation died because of sepsis from toxic megacolon. Constipation is a rare and potentially lethal complication in patients with PH/PGs. Severe constipation can be prevented by recognizing and treating mild symptoms. © 2015 European Society of Endocrinology.

Pheochromocytoma-paraganglioma: Biochemical and genetic diagnosis.

PubMed

Cano Megías, Marta; Rodriguez Puyol, Diego; Fernández Rodríguez, Loreto; Sención Martinez, Gloria Lisette; Martínez Miguel, Patricia

Pheochromocytomas and paragangliomas are tumours derived from neural crest cells, which can be diagnosed by biochemical measurement of metanephrine and methoxytyramine. Advances in genetic research have identified many genes involved in the pathogenesis of these tumours, suggesting that up to 35-45% may have an underlying germline mutation. These genes have a singular transcriptional signature and can be grouped into 2 clusters (or groups): cluster 1 (VHL and SHDx), involved in angiogenesis and hypoxia pathways; and cluster 2 (MEN2 and NF1), linked to the kinase signalling pathway. In turn, these genes are associated with a characteristic biochemical phenotype (noradrenergic and adrenergic), and clinical features (location, biological behaviour, age of presentation, etc.) in a large number of cases. Early diagnosis of these tumours, accompanied by a correct genetic diagnosis, should eventually become a priority to enable better treatment, early detection of complications, proper screening of family members and related tumours, as well as an improvement in the overall prognosis of these patients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Hemostasis and malignancy.

PubMed

Francis, J L; Biggerstaff, J; Amirkhosravi, A

1998-01-01

There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

Watery diarrhea, hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma

PubMed Central

Ikuta, Shin-ichi; Yasui, Chiaki; Kawanaka, Masahiro; Aihara, Tsukasa; Yoshie, Hidenori; Yanagi, Hidenori; Mitsunobu, Masao; Sugihara, Ayako; Yamanaka, Naoki

2007-01-01

Watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome caused by vasoactive intestinal polypeptide (VIP) -producing tumor only rarely occurs in patients with nonpancreatic disease. A 49-year-old woman was referred for evaluation of a right adrenal tumor incidentally diagnosed by abdominal ultrasound during the investigation of chronic watery diarrhea. Laboratory findings showed hypokalemia and excessive production of VIP and catecholamines. After surgical resection of the tumor, diarrhea subsided and both electrolytes and affected hormone levels normalized. Immunohistochemical examination confirmed a diagnosis of pheochromocytoma, which contained VIP-positive ganglion-like cells. We herein present the clinical and histogenetic implications of this rare clinical entity, with literature review. PMID:17729424

[Pheochromocytoma and paraganglioma in childhood: a report of 2 cases report].

PubMed

Mosquera Gorostidi, A; Justo Ranera, A; Zakirian Denis, S E; González Temprano, N; Sagaseta de Ilúrdoz Uranga, M; Molina Garicano, J

2015-01-01

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors in children and most of them are sporadic. However, they represent the most common endocrine tumor in childhood, and hereditary tumor syndromes are most relevant in these age. Advances in genetic, biochemistry and imaging techniques have revised the management of these tumors; thus A biochemical study should be always initiated once the clinical diagnosis is suspected, followed by imaging and molecular studies, particularly in the context of known familial disease. The diagnostic and therapeutic features are reviewed after the presentation of two clinical cases, where the second one is a patient with type 1 Neurofibromatosis. Copyright © 2014. Published by Elsevier Espana.

A large deletion in the succinate dehydrogenase B gene (SDHB) in a Japanese patient with abdominal paraganglioma and concomitant metastasis.

PubMed

Kodama, Hitomi; Iihara, Masatoshi; Nissato, Sumiko; Isobe, Kazumasa; Kawakami, Yasushi; Okamoto, Takahiro; Takekoshi, Kazuhiro

2010-01-01

Recently, mutations in nuclear genes encoding two mitochondrial complex II subunit proteins, Succinate dehydrogenase D (SDHD) and SDHB, have been found to be associated with the development of familial pheochromocytomas and paragangliomas (hereditary pheochromocytoma/paraganglioma syndrome: HPPS). Growing evidence suggests that the mutation of SDHB is highly associated with abdominal paraganglioma and the following distant metastasis (malignant paraganglioma). In the present study, we used multiplex ligation dependent probe amplification (MLPA) analysis to identify a large heterozygous SDHB gene deletion encompassing sequences corresponding to the promoter region, in addition to exon 1 and exon 2 malignant paraganglioma patient in whom previously characterized SDHB mutations were undetectable. This is the first Japanese case report of malignant paraganglioma, with a large SDHB deletions. Our present findings strongly support the notion that large deletions in the SDHB gene should be considered in patients lacking characterized SDHB mutations.

Essential Oils from the Medicinal Herbs Upregulate Dopamine Transporter in Rat Pheochromocytoma Cells.

PubMed

Choi, Min Sun; Choi, Bang-sub; Kim, Sang Heon; Pak, Sok Cheon; Jang, Chul Ho; Chin, Young-Won; Kim, Young-Mi; Kim, Dong-il; Jeon, Songhee; Koo, Byung-Soo

2015-10-01

The dopamine transporter (DAT) protein, a component of the dopamine system, undergoes adaptive neurobiological changes from drug abuse. Prevention of relapse and reduction of withdrawal symptoms are still the major limitations in the current pharmacological treatments of drug addiction. The present study aimed to investigate the effects of essential oils extracted from Elsholtzia ciliata, Shinchim, Angelicae gigantis Radix, and Eugenia caryophyllata, well-known traditional Korean medicines for addiction, on the modulation of dopamine system in amphetamine-treated cells and to explore the possible mechanism underlying its therapeutic effect. The potential cytotoxic effect of essential oils was evaluated in PC12 rat pheochromocytoma cells using cell viability assays. Quantification of DAT, p-CREB, p-MAPK, and p-Akt was done by immunoblotting. DAT was significantly reduced in cells treated with 50 μM of amphetamine in a time-dependent manner. No significant toxicity of essential oils from Elsholtzia ciliata and Shinchim was observed at doses of 10, 25, and 50 μg/mL. However, essential oils from A. gigantis Radix at a dose of 100 μg/mL and E. caryophyllata at doses of 50 and 100 μg/mL showed cytotoxicity. Treatment with GBR 12909, a highly selective DAT inhibitor, significantly increased DAT expression compared with that of amphetamine only by enhancing phosphorylation of mitogen-activated protein kinases (MAPK) and Akt. In addition, essential oils effectively induced hyperphosphorylation of cyclic-AMP response element-binding protein (CREB), MAPK, and Akt, which resulted in DAT upregulation. Our study implies that the essential oils may rehabilitate brain dopamine function through increased DAT availability in abstinent former drug users.

MALIGNANT PLEURAL MESOTHELIOMA TREATED IN CLINIC FOR PULMONARY DISEASES AND TUBERCULOSIS “PODHRASTOVI” IN TEN-YEAR PERIOD (FROM 1998 TO 2007)

PubMed Central

Čukić, Vesna; Ustamujić, Aida; Lovre, VLAdimir; Žutić, Hasan; Genjac, Sadika; Mašić - Zečević, Mína

2008-01-01

Malignant pleural mesothelioma (MPM) is the most common primary malign tumour of pleura. The aim of this study was to evaluate cases of MPM diagnosed and treated in Clinic for Pulmonary Diseases and Tuberculosis “Podhrastovi” during ten-year period (1998-2007). Study is retrospective. The patients were analysed according to age, sex, histopathologic type of the tumour, cantonal distribution in Federation of Bosnia and Herzegovina and regimen of treatment. MPM presented 0,72% (0-1,56% per year) of all hospitalised malignant patients, and the greatest number of registered cases was in the year of 2007. The series included 16 male (57,14%) and 12 female (42,86%). Cases over 64 years old were the most frequent (14-50%) than 45-54 years (7--25%). Histopathology types of hospitalised cases of MPM: epitheloid form (8- 28,57%); sarcomatoid form (2- 7,14 %); other forms (18-64,29%). The most patients came from Canton Sarajevo (12-42,86%); ZE-DO canton (8-28,57%) and the UNA-SANA canton (5-17,86%). The therapy applied: chemotherapy (11-39,29%); radiotherapy (3-10,71%); chemotherapy + radiotherapy (4-14,29%); symptomatic therapy (10-35,71 %). PMID:19125709

Rectification of Acetylcholine-Elicited Currents in PC12 Pheochromocytoma Cells

NASA Astrophysics Data System (ADS)

Ifune, C. K.; Steinbach, J. H.

1990-06-01

The current-voltage (I-V) relationship for acetylcholine-elicited currents in the rat pheochromocytoma cell line PC12 is nonlinear. Two voltage-dependent processes that could account for the whole-cell current rectification were examined, receptor channel gating and single receptor channel permeation. We found that both factors are involved in the rectification of the whole-cell currents. The voltage dependence of channel gating determines the shape of the I-V curve at negative potentials. The single-channel I-V relationship is inwardly rectifying and largely responsible for the characteristic shape of the whole-cell I-V curve at positive potentials. The rectification of the single-channel currents is produced by the voltage-dependent block of outward currents by intracellular Mg2+ ions.

Unusual presentation of pheochromocytoma with ischemic sigmoid colitis and stenosis.

PubMed

Tan, Florence; Thai, Ah Chuan; Cheah, Wei Keat; Mukherjee, J J

2009-10-01

A 45-year-old woman with poorly controlled hypertension and diabetes mellitus presented with left iliac fossa pain, constipation alternating with diarrhea, and weight loss. She had been diagnosed with idiopathic cardiomyopathy five years previously. Echocardiogram had shown a left ventricular ejection fraction (LVEF) of 35%; coronary angiogram was normal. Colonoscopy revealed sigmoid colitis with stenosis. Abdominal computed tomography revealed a 5 cm right adrenal tumor. Twenty-four hour urinary free catecholamines and fractionated metanephrine excretion values were elevated, confirming pheochromocytoma. Her colitis resolved after one month of adrenergic blockade. Repeat echocardiogram showed improvement of LVEF to 65%. After laparoscopic right adrenalectomy, the patient's hypertension resolved, and diabetic control improved. Timely management avoided further morbidity and potential mortality in our patient.

Second cancers and late mortality in Australian children treated by allogeneic HSCT for haematological malignancy.

PubMed

Nelson, A S; Ashton, L J; Vajdic, C M; Le Marsney, R E; Daniels, B; Nivison-Smith, I; Wilcox, L; Dodds, A J; O'Brien, T A

2015-02-01

We examined risk of second cancer and late mortality in a population-based Australian cohort of 717 pediatric allogeneic stem cell transplant (HSCT) recipients treated for a malignant disease during 1982-2007. Record linkage with population-based death and cancer registries identified 17 second cancers at a median of 7.9 years post HSCT; thyroid cancer being the most common malignancy (n=8). The cumulative incidence of second cancer was 8.7% at follow-up, and second cancers occurred 20 times more often than in the general population (standardised incidence ratio 20.3, 95% confidence interval (CI)=12.6-32.7). Transplantation using radiation-based conditioning regimens was associated with increased second cancer risk. A total of 367 patients survived for at least 2 years post HSCT and of these 44 (12%) died at a median of 3.1 years after HSCT. Relapse was the most common cause of late mortality (n=32). The cumulative incidence of late mortality was 14.7%. The observed rate of late mortality was 36 times greater than in the matched general population (standardised mortality ratio 35.9, 95% CI=26.7-48.3). Recipients who relapsed or who had radiation-based conditioning regimens were at higher risk of late mortality. Second cancers and late mortality continue to be a risk for pediatric patients undergoing HSCT, and these results highlight the need for effective screening and survivorship programs.

Concurrent bilateral pheochromocytoma and thoracic paraganglioma during pregnancy.

PubMed

Snabboon, Thiti; Plengpanich, Wanee; Houngngam, Natnicha; Buranasupkajorn, Patinut; Plengvidhya, Nattachet; Sereepapong, Wisan; Sunthornyothin, Sarat; Shotelersuk, Vorasuk

2010-04-01

Although hypertension occurring during pregnancies is not uncommon and its prognosis is generally excellent, some of its unusual causes can lead to catastrophic consequences, especially in undiagnosed cases. Here, we report a pregnant woman who presented with hypertension in her early pregnancy. It was subsequently found to be caused by bilateral pheochromocytoma. After removal of both tumors, catecholamine levels unexpectedly and unexplainably remained elevated. At 23 weeks of gestation, the fetus was found dead in utero. After the fetal death, additional studies were performed and revealed a thoracic paraganglioma. To our knowledge, this is the first report of a case of three catecholamine-producing tumors occurring concurrently during a pregnancy. Genetic analysis helped identify this unprecedented condition; the patient harbored a heterozygous missense mutation c.482G>A in exon 3 of the VHL gene, indicating von Hippel-Lindau syndrome. Physicians who care for hypertensive pregnant patients should be aware of this condition as its diagnosis would probably lead to a better outcome.

Subsequent Malignancies in Children Treated for Hodgkin's Disease: Associations With Gender and Radiation Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Constine, Louis S.; Department of Pediatrics, James P. Wilmot Cancer Center at University of Rochester, Rochester, NY; Tarbell, Nancy

2008-09-01

Purpose: Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. Methods and Materials: A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). Results: We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. Withmore » 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Conclusions: Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.« less

Subsequent malignancies in children treated for Hodgkin's disease: associations with gender and radiation dose.

PubMed

Constine, Louis S; Tarbell, Nancy; Hudson, Melissa M; Schwartz, Cindy; Fisher, Susan G; Muhs, Ann G; Basu, Swati K; Kun, Larry E; Ng, Andrea; Mauch, Peter; Sandhu, Ajay; Culakova, Eva; Lyman, Gary; Mendenhall, Nancy

2008-09-01

Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.

Preclinical Mouse Models of Neurofibromatosis

DTIC Science & Technology

2007-10-01

in NF1 and NF2 Patients. Persons with NF1 are predisposed to benign neurofibromas, optic nerve gliomas, and to specific malignant neoplasms ...anatomic location. The malignant neoplasms seen in NF1 patients include astrocytoma, malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, and...hematopoietic cells results in a progressive myeloproliferative disorder. Blood 2004; 103: 4243-4250. Reilly KM, Tuskan RG, Christy E, Loisel DA

Preclinical Mouse Models of Neurofibromatosis

DTIC Science & Technology

2006-10-01

Patients. Persons with NF1 are predisposed to benign neurofibromas, optic nerve gliomas, and to specific malignant neoplasms . Individuals with NF1...malignant neoplasms seen in NF1 patients include astrocytoma, malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, and juvenile...Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder. Proc Natl Acad Sci U S A 2004;101(2):597-602. 14. Chan IT, Kutok JL

Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2018-01-12

Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

Ewing's Sarcoma as a Second Malignancy in Long-Term Survivors of Childhood Hematologic Malignancies.

PubMed

Wolpert, Fabian; Grotzer, Michael A; Niggli, Felix; Zimmermann, Dieter; Rushing, Elisabeth; Bode-Lesniewska, Beata

2016-01-01

Modern multimodal treatment has significantly increased survival for patients affected by hematologic malignancies, especially in childhood. Following remission, however, the risk of developing a further malignancy is an important issue. The long-term estimated risk of developing a sarcoma as a secondary malignancy is increased severalfold in comparison to the general population. Ewing's sarcoma family encompasses a group of highly aggressive, undifferentiated, intra- and extraosseous, mesenchymal tumors, caused by several types of translocations usually involving the EWSR1 gene. Translocation associated sarcomas, such as Ewing sarcoma, are only rarely encountered as therapy associated secondary tumors. We describe the clinical course and management of three patients from a single institution with Ewing's sarcoma that followed successfully treated lymphoblastic T-cell leukemia or non-Hodgkin lymphoma. The literature on secondary Ewing's sarcoma is summarized and possible pathogenic mechanisms are critically discussed.

Localized malignant pleural mesothelioma: report of two cases.

PubMed

Tanzi, Silvia; Tiseo, Marcello; Internullo, Eveline; Cacciani, Giancarlo; Capra, Roberto; Carbognani, Paolo; Rusca, Michele; Rindi, Guido; Ardizzoni, Andrea

2009-08-01

Localized malignant pleural mesothelioma is very rare tumor disease. There are sporadic reports in the literature showing that this entity has a different biologic behavior compared with diffuse pleural mesothelioma. We report two cases of radically resected localized pleural malignant mesothelioma, with a previous history of asbestos exposure. Both cases showed a microscopic and immunohistochemical findings of malignant mesothelioma, biphasic and sarcomatoid lympho-histiocitoid variant type, respectively, without evidence of diffuse pleural spread. The first is very peculiar case of bilateral localized malignant pleural mesothelioma with complete response to chemotherapy and localized late recurrence, radically resected and treated with adjuvant radiotherapy. The second case revealed as a solitary localized mass, underwent a complete en bloc resection and adjuvant radiotherapy. Both cases demonstrate that the localized malignant mesothelioma should be distinguished from diffuse form and that complete resection is associated with good prognosis.

Risk of secondary malignancies after radiation therapy for breast cancer: Comprehensive results.

PubMed

Burt, Lindsay M; Ying, Jian; Poppe, Matthew M; Suneja, Gita; Gaffney, David K

2017-10-01

To assess risks of secondary malignancies in breast cancer patients who received radiation therapy compared to patients who did not. The SEER database was used to identify females with a primary diagnosis of breast cancer as their first malignancy, during 1973-2008. We excluded patients with metastatic disease, age <18 years, no definitive surgical intervention, ipsilateral breast cancer recurrence, or who developed a secondary malignancy within 1 year of diagnosis. Standardized incidence ratios and absolute excess risk were calculated using SEER*Stat, version 8.2.1 and SAS, version 9.4. There were 374,993 patients meeting the inclusion criteria, with 154,697 who received radiation therapy. With a median follow-up of 8.9 years, 13% of patients (49,867) developed a secondary malignancy. The rate of secondary malignancies was significantly greater than the endemic rate in breast cancer patients treated without radiation therapy, (O/E 1.2, 95% CI 1.19-1.22) and with radiation therapy (O/E 1.33, 95% CI 1.31-1.35). Approximately 3.4% of secondary malignancies were attributable to radiation therapy. The increased risk of secondary malignancies in breast cancer patients treated with radiation therapy compared to those without was significant regardless of age at breast cancer diagnosis (p < 0.01) and more pronounced with longer latency periods. There was an increased risk of secondary malignancies for breast cancer patients both with and without radiation therapy compared to the general population. There was an increased risk in specific sites for patients treated with radiation therapy. This risk was most evident in young patients and who had longer latency periods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insulinoma: A retrospective study analyzing the differences between benign and malignant tumors.

PubMed

Câmara-de-Souza, A B; Toyoshima, M T K; Giannella, M L; Freire, D S; Camacho, C P; Lourenço, D M; Rocha, M S; Bacchella, T; Jureidini, R; Machado, M C C; Almeida, M Q; Pereira, M A A

2018-04-01

Insulinoma is a rare pancreatic tumor and, usually, a benign disease but can be a malignant one and, sometimes, a highly aggressive disease. The aim of this study was to determine differences between benign and malignant tumors. Retrospective study of 103 patients with insulinoma treated in a tertiary center. It was analyzed demographic, clinical, laboratory, localization and histologic analysis of tumor and follow up data of subjects in order to identify differences between individuals benign and malignant disease. Almost all patients (87%) had a benign tumor and survival rates of 100% following pancreatic tumor surgery. Those with malignant tumors (13%) have a poor prognosis, 77% insulinoma-related deaths over a period of 1-300 months after the diagnosis with a survival rate of 24% in five years. The following factors are associated with an increased risk of malignant disease: duration of symptoms < 24 months, fasting time for the occurrence of hypoglycemia < 8 h, blood plasma insulin concentration ≥ 28 μU/mL and C-peptide ≥ 4.0 ng/mL at the glycemic nadir and tumor size ≥ 2.5 cm. Our data help to base the literature about these tumors, reinforcing that although insulinoma is usually a single benign and surgically treated neoplasia, the malignant one is difficult to treat. We highlight the data that help predict a malignancy behavior of tumor and suggest a long follow up after diagnosis in these cases. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

[Diode laser in "Malignant Glaucoma" treatment].

PubMed

Bresson Dumont, H; Ballereau, L; Lehoux, A; Santiago, P-Y

2006-05-01

Malignant glaucoma remains one of the most dramatic complications of ocular surgery. It can occur after glaucoma surgery but also after iridotomy, capsulotomy, or cataract extraction. However, the mechanisms remain unclear. to evaluate diode laser cyclodestruction as a complementary treatment in refractory malignant glaucoma. Seven women with malignant glaucoma with onset several months before (mean, 43 months; range, 12-96 months), in whom shallow anterior chamber and high IOP (25 mmHg +/- 5.5 treated with 2.86 +/- 0.9 topical and systemic medications) persisted despite prior surgical treatment (mean, 2; range, 1-5). Controlateral eyes had hyperopia (mean, +3.7 D, range, +1 to +6), five had shallow anterior chamber and high IOP. UBM detected plateau iris in four women. Seven eyes with malignant glaucoma and three controlateral eyes underwent cyclodestruction with diode laser (Viridis Twin Quantel Medical, laser, 810 nm), 22 burns around 270 degrees , 2 mm from the limbus for glaucomatous eyes and 15 inferior burns for controlateral eyes. Resolution of malignant glaucoma, with lower pressure (mean, 35%; range, 10%-70%), lower levels of medications (64%), final IOP at 13.2 mmHg (+/- 4.7), and deepening anterior chamber was achieved in all cases (mean follow-up, 18 months; range, 12-22). Cycloplegic topical treatment was stopped in 70% of cases. Diode laser cyclodestruction can help to resolve refractory malignant glaucoma. Larger UBM studies could help us to better understand the mechanisms of malignant glaucoma.

Application and assessment of Chinese arsenic drugs in treating malignant hematopathy in China.

PubMed

Hu, Xiao-mei; Liu, Feng; Ma, Rou

2010-08-01

Chinese arsenic drugs have been applied in Chinese medicine for several centuries. Beginning from 1970s, arsenic containing drugs have been generally used for the treatment of malignant hematologic diseases including acute promyelocytic leukemia, myelodysplastic syndrome, and multiple myeloma. No matter what ingredients of arsenic drugs were applied, either arsenic trioxide, arsenic disulfide, or arsenic containing Chinese herbal compositions including Qinghuang Powder and Realgar-Indigo naturalis formula, they all provided the distinct approaches for the management of malignant hematologic diseases, and good clinical efficacy was obtained with mild adverse reactions. Moreover, the mechanisms of action have been continually elucidated.

Ultrasound Evaluation of Thyroid Gland Pathologies After Radiation Therapy and Chemotherapy to Treat Malignancy During Childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lollert, André, E-mail: andre.lollert@unimedizin-mainz.de; Gies, Christina; Laudemann, Katharina

Purpose: The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations. Methods and Materials: Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and laboratory examinations throughmore » 2014 (median follow-up time: 48 months). Results: A relevant reduction of thyroid gland volume was significantly correlated with thyroid gland dose in univariate (P<.001) and multivariate analyses for doses above 2 Gy. Odds ratios were 3.1 (95% confidence interval: 1.02-9.2; P=.046) for medium doses (2-25 Gy) and 14.8 (95% confidence interval: 1.4-160; P=.027) for high doses (>25 Gy). Thyroid gland dose was significantly higher in patients with thyroid gland pathologies during follow-up (P=.03). Univariate analysis revealed significant correlations between hypothyroidism and thyroid gland dose (P<.001). Conclusions: Ultrasonographically detectable changes, that is, volume reductions, pathologies, and hypothyroidism, after malignancy treatment during childhood are associated with thyroid gland dose. Both ultrasonography and laboratory follow-up examinations should be performed regularly after tumor therapy during childhood, especially if the treatment included radiation therapy.« less

Ultrasound Evaluation of Thyroid Gland Pathologies After Radiation Therapy and Chemotherapy to Treat Malignancy During Childhood.

PubMed

Lollert, André; Gies, Christina; Laudemann, Katharina; Faber, Jörg; Jacob-Heutmann, Dorothee; König, Jochem; Düber, Christoph; Staatz, Gundula

2016-01-01

The purpose of this study was to evaluate correlations between treatment of malignancy by radiation therapy during childhood and the occurrence of thyroid gland pathologies detected by ultrasonography in follow-up examinations. Reductions of thyroid gland volume below 2 standard deviations of the weight-specific mean value, occurrence of ultrasonographically detectable thyroid gland pathologies, and hypothyroidism were retrospectively assessed in 103 children and adolescents 7 months to 20 years of age (median: 7 years of age) at baseline (1997-2013) treated with chemoradiation therapy (with the thyroid gland dose assessable) or with chemotherapy alone and followed by ultrasonography and laboratory examinations through 2014 (median follow-up time: 48 months). A relevant reduction of thyroid gland volume was significantly correlated with thyroid gland dose in univariate (P<.001) and multivariate analyses for doses above 2 Gy. Odds ratios were 3.1 (95% confidence interval: 1.02-9.2; P=.046) for medium doses (2-25 Gy) and 14.8 (95% confidence interval: 1.4-160; P=.027) for high doses (>25 Gy). Thyroid gland dose was significantly higher in patients with thyroid gland pathologies during follow-up (P=.03). Univariate analysis revealed significant correlations between hypothyroidism and thyroid gland dose (P<.001). Ultrasonographically detectable changes, that is, volume reductions, pathologies, and hypothyroidism, after malignancy treatment during childhood are associated with thyroid gland dose. Both ultrasonography and laboratory follow-up examinations should be performed regularly after tumor therapy during childhood, especially if the treatment included radiation therapy. Copyright © 2016. Published by Elsevier Inc.

How I treat influenza in patients with hematologic malignancies

PubMed Central

Casper, Corey; Englund, Janet

2010-01-01

The 2009 H1N1 influenza pandemic has heightened the interest of clinicians for options in the prevention and management of influenza virus infection in immunocompromised patients. Even before the emergence of the novel 2009 H1N1 strain, influenza disease was a serious complication in patients with hematologic malignancies receiving chemotherapy or undergoing hematopoietic cell transplantation. Here we review the clinical manifestations of seasonal and 2009 H1N1 influenza and discuss current diagnosis, antiviral treatment, and prophylaxis options. We also summarize infection control and vaccination strategies for patients, family members, and caregivers. PMID:20009037

Update on non-acquired immunodeficiency syndrome-defining malignancies.

PubMed

Chiao, Elizabeth Y; Krown, Susan E

2003-09-01

Since the introduction of highly active antiretroviral therapy (HAART), the natural history of human immunodeficiency virus (HIV) infection has changed. Early in the acquired immunodeficiency syndrome (AIDS) epidemic, epidemiologic studies showed that HIV-infected patients were at higher risk for developing specific AIDS-defining malignancies. More recent studies linking HIV/AIDS databases to cancer registries have shown that HIV-infected patients are also at higher risk of developing non-AIDS-defining malignancies. We review the most recent data regarding clinical presentation, pathology, and treatment outcomes for these non-AIDS-defining malignancies. Recent large cohort studies linking HIV/AIDS databases to cancer registries have shown that HIV-infected patients are also at higher risk of developing non-AIDS-defining malignancies. Besides anal cancer and Hodgkin disease, the cohort studies have identified other malignancies that appear to occur at a higher rate in the HIV-infected population as compared with the general population. These malignancies include lung cancer, skin cancer, germ cell tumors, leiomyosarcomas, cancers of the head and neck, conjunctival cancer, multiple myeloma, and leukemias. As the epidemiology of non-AIDS-defining malignancies continues to evolve, it is unclear whether the appropriate treatments and outcomes for these or other malignancies are changed for HIV-infected patients treated with HAART.

Unusual Asymptomatic Fluorodeoxyglucose Avid Pheochromocytoma in a Case of Myxoid Liposarcoma of the Extremity on 18-F Fluorodeoxyglucose Positron Emission Tomography-computed Tomography.

PubMed

Shivdasani, Divya; Singh, Natasha; Pereira, Melvika; Zade, Anand

2017-01-01

Sarcomas are a heterogeneous group of rare tumors and arise either from soft tissue or from bone. Soft-tissue sarcomas (STSs) initially metastasize to the lungs. Metastases to extrapulmonary sites such as liver, brain, and soft tissue distant from primary tumor usually develop later. However, cases with isolated adrenal metastasis without disseminated disease have been reported in literature. We present a case of primary myxoid liposarcoma of the lower limb, in which staging 18 -F fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan detected a suspicious FDG avid adrenal lesion which eventually on resection was diagnosed as asymptomatic pheochromocytoma. Pheochromocytomas have been reported to demonstrate FDG uptake mimicking metastasis. Hence, while interpreting FDG PET-CT scans in the context of STSs, both the extrapulmonary metastatic potential of aggressive histological subtypes of sarcoma and rare possibility of FDG avid coexistent benign tumor should be taken into consideration.

Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

PubMed

Nasu, K; Okamoto, M; Nishida, M; Takai, N; Narahara, H

2012-01-01

Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

Adrenalectomy

MedlinePlus

... One of the most common tumors is a pheochromocytoma , which can cause very high blood pressure Other ... to be treated. If you had surgery for pheochromocytoma, the outcome is usually good. Alternative Names Adrenalectomy; ...

Better Clinical Efficiency of TILs for Malignant Pleural Effusion and Ascites than Cisplatin Through Intrapleural and Intraperitoneal Infusion.

PubMed

Chu, Hongjin; Du, Fengcai; Gong, Zhaohua; Lian, Peiwen; Wang, Zhixin; Li, Peng; Hu, Baohong; Chi, Cheng; Chen, Jian

2017-08-01

To evaluate the clinical efficiency of tumor-infiltrating lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion. Thirteen patients with malignant pleural effusion and ascites were divided into a TIL-treated group and a cisplatin-treated group. Patients were given TILs or cisplatin, through intrapleural and intraperitoneal infusion respectively, after drainage of the malignant serous effusion by thoracentesis or abdominocentesis. The overall response rate and disease control rate of the TIL-treated group (33.33% and 83.33%) were higher than that of the cisplatin-treated group (28.57% and 71.43%). The progression-free survival for the TIL-treated group was significantly longer (p=0.002) and better than that of the cisplatin-treated group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated group and was clearly higher than that in the cisplatin-treated group. The use of TILs has a better clinical efficiency for malignant pleural effusion and ascites than cisplatin through intrapleural and intraperitoneal infusion without severe adverse effects. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Talazoparib and Temozolomide in Treating Younger Patients With Refractory or Recurrent Malignancies

ClinicalTrials.gov

2018-03-02

Adult Solid Neoplasm; Childhood Solid Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Malignant Solid Neoplasm; Refractory Central Nervous System Neoplasm

Pheochromocytoma/Paraganglioma: A Poster Child for Cancer Metabolism.

PubMed

Tevosian, Sergei G; Ghayee, Hans K

2018-05-01

Pheochromocytomas (PCCs) are tumors that are derived from the chromaffin cells of the adrenal medulla. Extra-adrenal PCCs called paragangliomas (PGLs) are derived from the sympathetic and parasympathetic chain ganglia. PCCs secrete catecholamines, which cause hypertension and have adverse cardiovascular consequences as a result of catecholamine excess. PGLs may or may not produce catecholamines depending on their genetic type and anatomical location. The most worrisome aspect of these tumors is their ability to become aggressive and metastasize; there are no known cures for metastasized PGLs. Original articles and reviews indexed in PubMed were identified by querying with specific PCC/PGL- and Krebs cycle pathway-related terms. Additional references were selected through the in-depth analysis of the relevant publications. We primarily discuss Krebs cycle mutations that can be instrumental in helping investigators identify key biological pathways and molecules that may serve as biomarkers of or treatment targets for PCC/PGL. The mainstay of treatment of patients with PCC/PGLs is surgical. However, the tide may be turning with the discovery of new genes associated with PCC/PGLs that may shed light on oncometabolites used by these tumors.

Intercellular crosstalk in human malignant melanoma.

PubMed

Dvořánková, Barbora; Szabo, Pavol; Kodet, Ondřej; Strnad, Hynek; Kolář, Michal; Lacina, Lukáš; Krejčí, Eliška; Naňka, Ondřej; Šedo, Aleksi; Smetana, Karel

2017-05-01

Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form multiple metastases. Consequently, the survival rate is poor. Therefore, emphasis in melanoma research is given on early diagnosis and development of novel and more potent therapeutic options. The malignant melanoma is arising from melanocytes, cells protecting mitotically active keratinocytes against damage caused by UV light irradiation. The melanocytes originate in the neural crest and consequently migrate to the epidermis. The relationship between the melanoma cells, the melanocytes, and neural crest stem cells manifests when the melanoma cells are implanted to an early embryo: they use similar migratory routes as the normal neural crest cells. Moreover, malignant potential of these melanoma cells is overdriven in this experimental model, probably due to microenvironmental reprogramming. This observation demonstrates the crucial role of the microenvironment in melanoma biology. Indeed, malignant tumors in general represent complex ecosystems, where multiple cell types influence the growth of genetically mutated cancer cells. This concept is directly applicable to the malignant melanoma. Our review article focuses on possible strategies to modify the intercellular crosstalk in melanoma that can be employed for therapeutic purposes.

Metachronous Multiple Primary Malignant Neoplasms of the Stomach and the Breast: Report of Two Cases With Review of Literature

PubMed Central

Karthikeyan, Vilvapathy Senguttuvan; Sistla, Sarath Chandra; Srinivasan, Ramachandran; Basu, Debdatta; Panicker, Lakshmi C.; Ali, Sheik Manwar; Rajkumar, Nagarajan

2014-01-01

Multiple primary malignant neoplasm is the occurrence of a second primary malignancy in the same patient within 6 months of the detection of first primary (synchronous), or 6 months or more after primary detection (metachronous). Multiple primary malignant neoplasms are not very frequently encountered in clinical practice. The relative risk for a second primary malignancy increases by 1.111-fold every month from the detection of the first primary malignancy in any individual. We present 2 patients treated for carcinoma of the breast who developed a metachronous primary malignancy in the stomach to highlight the rare occurrence of multiple primary malignant neoplasms. These tumors were histologically dissimilar, with distinct immunohistochemical parameters. The importance lies in carefully identifying the second primary malignancies, not dismissing them as metastases, and treating them accordingly. PMID:24444270

[Three cases of the malignant esophageal stenosis successfully treated with the Niti-S™ esophageal stent].

PubMed

Isohata, Noriyuki; Naritaka, Yoshihiko; Asaka, Shinichi; Shimakawa, Takeshi; Miyaki, Akira; Yamaguchi, Kentaro; Murayama, Minoru; Katsube, Takao; Ogawa, Kenji

2011-11-01

We herein report three cases of the malignant esophageal stenosis successfully treated with the Niti-S™ esophageal stent. CASE 1: The hilar lung cancer and its mediastinal lymph node metastasis pressed the esophagus extramurally and caused the marked stenosis. CASE 2: A metastatic lymph node along the left laryngeal nerve caused the stenosis of the trachea. A primary esophageal lesion located at the middle thoracic esophagus also caused the marked stenosis. At first, tracheal stent was placed because of dyspnea, and two weeks later, we placed an esophageal stent. Case 3: Esophageal cancer at lower thoracic esophagus after definitive radiation therapy caused the marked stenosis. Because of the stenosis of esophago-gastric junction( EGJ), we used an esophageal stent with a long cover in order to prevent a reflux into the esophagus. This new Niti-STM esophageal stent was easy to place at the stenosis without difficulty using a conventional device. The symptom was improved immediately for each case. We hope this new device will be used widely.

Cystic pancreatic tumors (CPT): predictors of malignant behavior.

PubMed

Javle, Milind; Shah, Pankaj; Yu, Jihnhee; Bhagat, Vishal; Litwin, Alan; Iyer, Renuka; Gibbs, John

2007-03-01

Due to widespread use of imaging studies, increasing cystic pancreatic tumor (CPT) cases are being detected. The diagnosis of malignancy in CPT cases requires pancreatectomy. Clinical and laboratory characteristics of CPT may predict underlying malignancy. CPT cases treated between 1994 and 2004 at our institution were included. Pseudocysts were excluded. Serous cystadenoma (SCA), mucinous cystadenoma (MCA), intrapapillary mucinous tumor, cystic endocrine tumor, and lymphoepithelial cysts were classified as benign or pre-malignant. Serous cystadenocarcinoma (SCACA), mucinous cystadenocarcinoma (MCACA), and adenocarcinoma (ACA) were classified as malignant. Thirty-five patients had histological confirmation. Median age was 65 years. Male/female ratio was higher in malignant group (P = 0.0284). Weight loss and abdominal mass were more prevalent in malignant group (P = 0.042 and 0.028, respectively). Malignant lesions were larger, associated with local invasion (superior mesenteric artery (SMA), superior mesenteric vein (SMV), portal vein (PV) complex or celiac encasement) and CA 19-9 elevation. On univariate analyses, local invasion (P = 0.0029), negative surgical intervention (P = 0.0010), presence of ACA (P = 0.0044), or malignant CPT (P = 0.0018) were associated with shorter survival. On a multivariate analysis, local invasion was associated with shorter survival [Hazard ratio (HR) = 4.322, P = 0.0218], while surgical intervention was associated with improved survival (HR = 0.179, P = 0.0124). Male sex, abdominal mass, weight loss, larger tumor size, local invasion, and elevated CA 19-9 were associated with malignant CPT.

RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

ClinicalTrials.gov

2015-09-28

Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma

Analysis of Pheochromocytoma (PC12) Membrane Potential under the Exposure to Millimeter-wave Radiation

NASA Astrophysics Data System (ADS)

Mizuno, M.; Hirata, A.; Kawase, K.; Otani, C.; Nagatsuma, T.

2004-08-01

Non-thermal effects of millimeter wave (MMW) on Pheochromocytoma (PC12) were studied by potential measurement with a voltage sensitive dye (DiBAC4(3)). Cells were irradiated at fixed frequencies of 30, 40, 60, 76GHz as well as sweeping frequency between 10 and 100 GHz by an MMW generator based on a uni-traveling-carrier photodiode (UTC-PD), the most widely tunable MMW source. However there were no significant changes in membrane potential between MMW-irradiated and control cells. The results suggest that MMW irradiation in the range from 10 to 100GHz appears to be safe for ordinary PC12 cells under non-thermal conditions.

Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features.

PubMed

Mazza, Alberto; Armigliato, Michela; Marzola, Maria Cristina; Schiavon, Laura; Montemurro, Domenico; Vescovo, Giorgio; Zuin, Marco; Chondrogiannis, Sotirios; Ravenni, Roberta; Opocher, Giuseppe; Colletti, Patrick M; Rubello, Domenico

2014-04-01

Pheochromocytoma (PH) and paraganglioma (PG) are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and the sympathetic ganglia, respectively. Although are unusual cause of hypertension (HT) accounting for at most 0.1-0.2 % of cases, they may lead to severe and potentially lethal hypertensive crisis due to the effects of the released catecholamines. However, both PH and PG may be asymptomatic as ~30 % of subjects are normotensive or have orthostatic hypotension and in these cases the 24 h ambulatory blood pressure (BP) monitoring is an important toll to diagnose and treat HT. HT treatment may be difficult when PH or PG occurs in pregnancy or in the elderly subjects and in these cases a multidisciplinary team is required. When surgical excision is mandatory the perioperative management requires the administration of selective α1-adrenergic blocking agents (i.e., doxazosin, prazosin or terazosin) followed by a β-adrenergic blockade (i.e., propranolol, atenolol). This latter should never be started first because blockade of vasodilatory peripheral β-adrenergic receptors with unopposed α-adrenergic receptor stimulation can lead to a further elevation of BP. Although labetalol is traditionally considered the ideal agent due to its α- and β-adrenergic antagonism, experimental studies do not support its use in this clinical setting. As second regimen, the administration of vasodilators as calcium channel blockers (i.e., nicardipine, nifedipine) may be required to control BP. Oral and sublingual short-acting nifedipine are potentially dangerous in patients with hypertensive emergencies and are not recommend. The latest evidences into the diagnosis and treatment of hypertensive crisis due to PH and PG are reviewed here.

Ribociclib and Everolimus in Treating Children With Recurrent or Refractory Malignant Brain Tumors

ClinicalTrials.gov

2018-03-09

Central Nervous System Embryonal Tumor, Not Otherwise Specified; Malignant Glioma; Recurrent Atypical Teratoid/Rhabdoid Tumor; Recurrent Childhood Ependymoma; Recurrent Diffuse Intrinsic Pontine Glioma; Recurrent Medulloblastoma; Refractory Diffuse Intrinsic Pontine Glioma

Antitumor effect of fibrin glue containing temozolomide against malignant glioma

PubMed Central

Anai, Shigeo; Hide, Takuichiro; Takezaki, Tatsuya; Kuroda, Jun-ichiro; Shinojima, Naoki; Makino, Keishi; Nakamura, Hideo; Yano, Shigetoshi; Kuratsu, Jun-ichi

2014-01-01

Temozolomide (TMZ), used to treat glioblastoma and malignant glioma, induces autophagy, apoptosis and senescence in cancer cells. We investigated fibrin glue (FG) as a drug delivery system for the local administration of high-concentration TMZ aimed at preventing glioma recurrence. Our high-power liquid chromatography studies indicated that FG containing TMZ (TMZ-FG) manifested a sustained drug release potential. We prepared a subcutaneous tumor model by injecting groups of mice with three malignant glioma cell lines and examined the antitumor effect of TMZ-FG. We estimated the tumor volume and performed immunostaining and immunoblotting using antibodies to Ki-67, cleaved caspase 3, LC3 and p16. When FG sheets containing TMZ (TMZ-FGS) were inserted beneath the tumors, their growth was significantly suppressed. In mice treated with peroral TMZ plus TMZ-FGS the tumors tended to be smaller than in mice whose tumors were treated with TMZ-FGS or peroral TMZ alone. The TMZ-FGS induced autophagy, apoptosis and senescence in subcutaneous glioma tumor cells. To assess the safety of TMZ-FG for normal brain, we placed it directly on the brain of living mice and stained tissue sections obtained in the acute and chronic phase immunohistochemically. In both phases, TMZ-FG failed to severely damage normal brain tissue. TMZ-FG may represent a safe new drug delivery system with sustained drug release potential to treat malignant glioma. PMID:24673719

Potentially malignant oral lesions: clinicopathological correlations

PubMed Central

Maia, Haline Cunha de Medeiros; Pinto, Najara Alcântara Sampaio; Pereira, Joabe dos Santos; de Medeiros, Ana Miryam Costa; da Silveira, Éricka Janine Dantas; Miguel, Márcia Cristina da Costa

2016-01-01

ABSTRACT Objective To determine the incidence of potentially malignant oral lesions, and evaluate and correlate their clinical and pathological aspects. Methods The sample consisted of cases clinically diagnosed as oral leukoplakia, oral erythroplakia, erythroleukoplakia, actinic cheilitis, and oral lichen planus treated at a diagnostic center, between May 2012 and July 2013. Statistical tests were conducted adopting a significance level of 5% (p≤0.05). Results Out of 340 patients, 106 (31.2%) had potentially malignant oral lesions; and 61 of these (17.9%) were submitted to biopsy. Actinic cheilitis was the most frequent lesion (37.5%) and the lower lip was the most affected site (49.6%). Among 106 patients in the sample, 48 (45.3%) reported nicotine consumption, 35 (33%) reported alcohol intake and 34 (32.1%) sun exposure while working. When clinical and histopathological diagnoses were compared, oral erythroplakia and atypical ulcer were the lesions that exhibited greater compatibility (100% each). Conclusion In most cases, clinical and histopathological diagnoses were compatible. An association between the occurrence of erythroplakia, leukoplakia and erythroleukoplakia with smoking was observed. Similarly, an association between actinic cheilitis and sun exposure was noted. Erythroleukoplakia presented the highest malignancy grade in this study. Finally, dental surgeons should draw special attention to diagnosis of potentially malignant oral lesions, choose the best management, and control the lesions to avoid their malignant transformation. PMID:27074232

Atezolizumab, Pemetrexed Disodium, Cisplatin, and Surgery With or Without Radiation Therapy in Treating Patients With Stage I-III Pleural Malignant Mesothelioma

ClinicalTrials.gov

2018-06-26

Biphasic Mesothelioma; Epithelioid Mesothelioma; Stage I Pleural Malignant Mesothelioma AJCC v7; Stage IA Pleural Malignant Mesothelioma AJCC v7; Stage IB Pleural Malignant Mesothelioma AJCC v7; Stage II Pleural Malignant Mesothelioma AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7

G2 accumulation and melanin overproduction in malignant melanocytes treated with a new nitrosourea.

PubMed

Buchdahl, C; Papon, J; Communal, Y; Bourges, M; Madelmont, J C

1998-12-01

Cystemustine (N'-(2-chloroethyl)-N-(2-(methylsulphonyl)ethyl)-N'-nitrosourea), a new anticancer chloroethylnitrosourea (CENU) is being tested in a phase II clinical trial of disseminated melanoma. The antitumour effect of this drug is mainly due to DNA damage in malignant melanocytes. Recently, we have shown that this damage can induce apoptosis in some melanoma cell lines. In others, apoptosis is not clearly observed, although there is a strong cytostatic effect. In this paper, we have characterized the cytological effect of cystemustine on murine malignant melanocytes (B16 cell line) which are resistant to apoptosis induced by this CENU. The results show that 3 days after cystemustine treatment, these melanocytes had accumulated in phase G2 of the cell cycle. There was then a strong morphological modification during a long cytostatic phase up to 30 days after treatment. During this cytostatic phase, there was uncontrolled DNA synthesis and marked swelling. Also, tyrosinase activity, melanin content and the number of mature melanosomes were greatly increased. These results suggest that when malignant melanocytes are not able to undergo apoptosis after treatment with CENU, they accumulate in G2 and this is followed by enhancement of melanogenesis.

Pituitary Adenoma With Paraganglioma/Pheochromocytoma (3PAs) and Succinate Dehydrogenase Defects in Humans and Mice

PubMed Central

Xekouki, Paraskevi; Szarek, Eva; Bullova, Petra; Giubellino, Alessio; Quezado, Martha; Mastroyannis, Spyridon A.; Mastorakos, Panagiotis; Wassif, Christopher A.; Raygada, Margarita; Rentia, Nadia; Dye, Louis; Cougnoux, Antony; Koziol, Deloris; Sierra, Maria de La Luz; Lyssikatos, Charalampos; Belyavskaya, Elena; Malchoff, Carl; Moline, Jessica; Eng, Charis; Maher, Louis James; Pacak, Karel; Lodish, Maya

2015-01-01

Context: Germline mutations in genes coding succinate dehydrogenase (SDH) subunits A, B, C, and D have been identified in familial paragangliomas (PGLs)/pheochromocytomas (PHEOs) and other tumors. We described a GH-secreting pituitary adenoma (PA) caused by SDHD mutation in a patient with familial PGLs. Additional patients with PAs and SDHx defects have since been reported. Design: We studied 168 patients with unselected sporadic PA and with the association of PAs, PGLs, and/or pheochromocytomas, a condition we named the 3P association (3PAs) for SDHx germline mutations. We also studied the pituitary gland and hormonal profile of Sdhb+/− mice and their wild-type littermates at different ages. Results: No SDHx mutations were detected among sporadic PA, whereas three of four familial cases were positive for a mutation (75%). Most of the SDHx-deficient PAs were either prolactinomas or somatotropinomas. Pituitaries of Sdhb+/− mice older than 12 months had an increased number mainly of prolactin-secreting cells and several ultrastructural abnormalities such as intranuclear inclusions, altered chromatin nuclear pattern, and abnormal mitochondria. Igf-1 levels of mutant mice tended to be higher across age groups, whereas Prl and Gh levels varied according to age and sex. Conclusion: The present study confirms the existence of a new association that we termed 3PAs. It is due mostly to germline SDHx defects, although sporadic cases of 3PAs without SDHx defects also exist. Using Sdhb+/− mice, we provide evidence that pituitary hyperplasia in SDHx-deficient cells may be the initial abnormality in the cascade of events leading to PA formation. PMID:25695889

Chemical pleurodesis for malignant pleural effusions.

PubMed

Walker-Renard, P B; Vaughan, L M; Sahn, S A

1994-01-01

To provide information about available agents for chemical pleurodesis. A MEDLINE search (1966 to October 1992) was conducted using the terms malignant pleural effusion and pleurodesis. All articles containing references to patients with recurrent, symptomatic, malignant pleural effusions treated with chemical pleurodesis were selected and reviewed for pleurodesis regimen, number of patients treated, success rate (complete response), and adverse effects. The agents studied included doxycycline, minocycline, tetracycline, bleomycin, cisplatin, doxorubicin, etoposide, fluorouracil, interferon-beta, mitomycin-c, Corynebacterium parvum, methylprednisolone, and talc. Independent extraction by three observers. Studies including a total of 1168 patients with malignant pleural effusions were reviewed for efficacy of the pleurodesis agent and studies including 1140 patients were reviewed for toxicity. Chemical pleurodesis produced a complete response in 752 (64%) of 1168 patients. The success rate of the pleurodesis agents varied from 0% with etoposide to 93% with talc. Corynebacterium parvum, the tetracyclines, and bleomycin had success rates of 76%, 67%, and 54%, respectively. The most commonly reported adverse effects were pain (265 of 1140, 23%) and fever (220 of 1140, 19%). Doxycycline and minocycline, with success rates of 72% and 86%, respectively, appear to be effective tetracycline-replacement agents in the few patients studied. Talc appears to be the most effective and least expensive agent; however, insufflation has the disadvantages of the expense of thoracoscopy and the usual need for general anesthesia. Bleomycin appears to be less effective than talc and the tetracyclines and is substantially more expensive.

Microenvironmental regulation of the progression of oral potentially malignant disorders towards malignancy

PubMed Central

Ai, Ruixue; Tao, Yan; Hao, Yilong; Jiang, Lu; Dan, Hongxia; Ji, Ning; Zeng, Xin; Zhou, Yu; Chen, Qianming

2017-01-01

Oral potentially malignant disorders (OPMD) develop in a complex tissue microenvironment where they grow sustainably, acquiring oral squamous cell carcinoma (OSCC) characteristics. The malignant tumor depends on interactions with the surrounding microenvironment to achieve loco-regional invasion and distant metastases. Unlike abnormal cells, the multiple cell types in the tissue microenvironment are relatively stable at the genomic level and, thus, become therapeutic targets with lower risk of resistance, decreasing the risk of OPMD acquiring cancer characteristics and carcinoma recurrence. However, deciding how to disrupt the OPMD and OSCC microenvironments is itself a daunting challenge, since their microenvironments present opposite capacities, resulting in diverse consequences. Furthermore, recent studies revealed that tumor-associated immune cells also participate in the process of differentiation from OPMD to OSCC, suggesting that reeducating stromal cells may be a new strategy to prevent OPMD from acquiring OSCC characteristics and to treat OSCC. In this review, we discuss the characteristics of the microenvironment of OPMD and OSCC as well as new therapeutic strategies. PMID:29113419

Mixed cortical adenoma and composite pheochromocytoma-ganglioneuroma: an unusual corticomedullary tumor of the adrenal gland.

PubMed

Lau, Sean K; Chu, Peiguo G; Weiss, Lawrence M

2011-06-01

Adrenal neoplasms composed of more than one cell type and demonstrating a mixed histologic appearance are exceedingly rare. We report the clinical and pathologic features of a morphologically distinctive tumor of the adrenal gland composed of cortical, chromaffin, and neural cells. Histologically, the tumor consisted of intermixed areas of proliferating cortical cells resembling adrenal cortical adenoma, neoplastic chromaffin cells consistent with pheochromocytoma, and a ganglioneuromatous stroma. The presence of the cortical, medullary, and neural components within the tumor was confirmed by immunohistochemical studies. The present case serves to broaden the morphologic spectrum of mixed tumors that may be encountered in the adrenal gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Emerging antibody-drug conjugates for treating lymphoid malignancies.

PubMed

Wolska-Washer, Anna; Robak, Pawel; Smolewski, Piotr; Robak, Tadeusz

2017-09-01

Antibody-drug conjugates (ADC) are monoclonal antibodies (Mabs) attached to biologically active drugs through specialized chemical linkers. They deliver and release cytotoxic agents at the tumor site, reducing the likelihood of systemic exposure and therefore toxicity. These agents should improve the potency of chemotherapy by increasing the accumulation of cytotoxic the drug within or near the neoplastic cells with reduced systemic effects. Areas covered: A literature review was conducted of the MEDLINE database PubMed for articles in English examining Mabs, B-cell receptor pathway inhibitors and immunomodulating drugs. Publications from 2000 through April 2017 were scrutinized. Conference proceedings from the previous five years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. Expert opinion: Newer ADCs show promise as treatment for several hematologic malignancies, especially lymphoma, multiple myeloma, and leukemia. However, definitive data from ongoing and future clinical trials will aid in better defining the status of these agents in the treatment of these diseases.

Precautionary measures reduce risk of definite neuroleptic malignant syndrome in newly typical neuroleptic-treated schizophrenia inpatients.

PubMed

Shiloh, Roni; Valevski, Avi; Bodinger, Liron; Misgav, Sagit; Aizenberg, Dov; Dorfman-Etrog, Pnina; Weizman, Abraham; Munitz, Hanan

2003-05-01

Neuroleptic malignant syndrome (NMS) is a potentially lethal antipsychotic drug (APD)-induced thermoregulatory disturbance. We hypothesized that several precautionary measures taken after administeration of APDs might prevent progression to definite NMS. The study group included 657 consecutively admitted drug-free schizophrenia inpatients who received various typical APDs for 28 days. Specific predefined precautionary measures were employed for this group. The comparison group (n=192) consisted of typical APD-treated schizophrenia inpatients in whom such precautionary measures were not imposed. The study group exhibited a significantly lower incidence of definite NMS (1/657=0.2% versus 4/192=2.1%; P=0.01, odds ratio=13.96; 95% confidence interval 1.55-125.63). Antipsychotics were discontinued in 28 patients (28/657=4.3%) from the study group due to NMS (n=1) or early detection of potential NMS-related signs (probable abortive NMS) (n=27). Our findings suggest that specific precautionary measures can effectively reduce the incidence of definite NMS by approximately one order in newly medicated schizophrenia inpatients.

Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK.

PubMed

Verganti, S; Berlato, D; Blackwood, L; Amores-Fuster, I; Polton, G A; Elders, R; Doyle, R; Taylor, A; Murphy, S

2017-01-01

Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease. © 2017 British Small Animal Veterinary Association.

The androgen receptor malignancy shift in prostate cancer.

PubMed

Copeland, Ben T; Pal, Sumanta K; Bolton, Eric C; Jones, Jeremy O

2018-05-01

Androgens and the androgen receptor (AR) are necessary for the development, function, and homeostatic growth regulation of the prostate gland. However, once prostate cells are transformed, the AR is necessary for the proliferation and survival of the malignant cells. This change in AR function appears to occur in nearly every prostate cancer. We have termed this the AR malignancy shift. In this review, we summarize the current knowledge of the AR malignancy shift, including the DNA-binding patterns that define the shift, the transcriptome changes associated with the shift, the putative drivers of the shift, and its clinical implications. In benign prostate epithelial cells, the AR primarily binds consensus AR binding sites. In carcinoma cells, the AR cistrome is dramatically altered, as the AR associates with FOXA1 and HOXB13 motifs, among others. This shift leads to the transcription of genes associated with a malignant phenotype. In model systems, some mutations commonly found in localized prostate cancer can alter the AR cistrome, consistent with the AR malignancy shift. Current evidence suggests that the AR malignancy shift is necessary but not sufficient for transformation of prostate epithelial cells. Reinterpretation of prostate cancer genomic classification systems in light of the AR malignancy shift may improve our ability to predict clinical outcomes and treat patients appropriately. Identifying and targeting the molecular factors that contribute to the AR malignancy shift is not trivial but by doing so, we may be able to develop new strategies for the treatment or prevention of prostate cancer. © 2018 Wiley Periodicals, Inc.

Apoptosis and injuries of heavy ion beam and x-ray radiation on malignant melanoma cell.

PubMed

Qin, Jin; Li, Sha; Zhang, Chao; Gao, Dong-Wei; Li, Qiang; Zhang, Hong; Jin, Xiao-Dong; Liu, Yang

2017-05-01

This study aims to investigate the influence of high linear energy transfer (LET) heavy ion ( 12 C 6+ ) and low LET X-ray radiation on apoptosis and related proteins of malignant melanoma on tumor-bearing mice under the same physical dosage. C57BL/6 J mice were burdened by tumors and randomized into three groups. These mice received heavy ion ( 12 C 6+ ) and X-ray radiation under the same physical dosage, respectively; their weight and tumor volumes were measured every three days post-radiation. After 30 days, these mice were sacrificed. Then, median survival time was calculated and tumors on mice were proliferated. In addition, immunohistochemistry was carried out for apoptosis-related proteins to reflect the expression level. After tumor-bearing mice were radiated to heavy ion, median survival time improved and tumor volume significantly decreased in conjunction with the upregulated expression of pro-apoptosis factors, Bax and cytochrome C, and the downregulated expression of apoptosis-profilin (Bcl-2, Survivin) and proliferation-related proteins (proliferating cell nuclear antigen). The results indicated that radiation can promote the apoptosis of malignant melanoma cells and inhibit their proliferation. This case was more suitable for heavy ion ( 12 C 6+ ). High LET heavy ion ( 12 C 6+ ) radiation could significantly improve the killing ability for malignant melanoma cells by inducing apoptosis in tumor cells and inhibiting their proliferation. These results demonstrated that heavy ion ( 12 C 6+ ) presented special advantages in terms of treating malignant melanoma. Impact statement Malignant melanoma is a malignant skin tumor derived from melanin cells, which has a high malignant degree and high fatality rate. In this study, proliferating cell nuclear antigen (PCNA) can induce the apoptosis of malignant melanoma cells and inhibit its proliferation, and its induction effect on apoptosis is significantly higher than low LET X-ray; hence, it is expected to

Functional adrenal cortex preservation: A good reason for posterior retroperitoneal endoscopic approach.

PubMed

Vidal, Óscar; Delgado-Oliver, Eduardo; Díaz Del Gobbo, Rafael; Hanzu, Felicia; Squarcia, Mattia; Martínez, Daniel; Fuster, David; Fondevila, Constantino

2018-05-24

Cortical-sparing adrenalectomy is a suitable treatment for hereditary and sporadic bilateral pheochromocytoma, in cases of low risk of malignancy, to reduce the possibility of adrenal insufficiency assuming the chance of local recurrence. The aim of the study is to analyze the functional results of partial adrenalectomy by retroperitoneal endoscopic approach in single-adrenal patients or patients requiring bilateral adrenalectomy. Prospective study between January 2015 and February 2016 including pheochromocytoma patients diagnosed with low risk of malignant mutations. All patients agreed to be included in the study. Experienced endocrine surgeons who have been trained in minimally invasive endocrine surgery performed the procedure using the same surgical technique. Demographic variables and clinical characteristics were collected, subsequently carrying out the descriptive analysis of the data. A total of 6 patients were registered, four associated with MEN type 2 syndrome and two in the context of VHL syndrome. Retroperitoneoscopic resection was performed without laparoscopic or open conversion and no postoperative complications; the average hospital stay was 2.5 days. Preservation of the functional cortex without corticosteroids was achieved in 5 (83%) of out 6 cases with a follow-up of 26.2 ± 6 months. Today, these 5 patients have a preserved adrenal function without hormone replacement. Cortical-sparing adrenalectomy by the retroperitoneal endoscopic approach, in expert hands, is safe and feasible for the treatment of hereditary and sporadic pheochromocytoma in a context of low malignancy, making it possible to avoid the need for corticoid replacement in most cases. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Impact of Surgical Resection of the Primary Tumor on Overall Survival in Patients With Metastatic Pheochromocytoma or Sympathetic Paraganglioma.

PubMed

Roman-Gonzalez, Alejandro; Zhou, Shouhao; Ayala-Ramirez, Montserrat; Shen, Chan; Waguespack, Steven G; Habra, Mouhammed A; Karam, Jose A; Perrier, Nancy; Wood, Christopher G; Jimenez, Camilo

2018-07-01

To determine whether primary tumor resection in patients with metastatic pheochromocytoma or paraganglioma (PPG) is associated with longer overall survival (OS). Patients with metastatic PPG have poor survival outcomes. The impact of surgical resection of the primary tumor on OS is not known. We retrospectively studied patients with metastatic PPG treated at the University of Texas, MD Anderson Cancer Center from January 2000 through January 2015. Kaplan-Meier analysis with log-rank tests was used to compare OS among patients undergoing primary tumor resection and patients not treated surgically. Propensity score method was applied to adjust for selection bias using demographic, clinical, biochemical, genetic, imaging, and pathologic information. A total of 113 patients with metastatic PPG were identified. Eighty-nine (79%) patients had surgery and 24 (21%) patients did not. Median OS was longer in patients who had surgery than in patients who did not [148 months, 95% confidence interval (CI) 112.8-183.2 months vs 36 months, 95% CI 27.2-44.8 months; P < 0.001].Fifty-three (46%) patients had synchronous metastases; of these patients, those who had surgery had longer OS than those who did not (85 months, 95% CI 64.5-105.4 months vs 36 months, 95% CI 29.7-42.3 months; P < 0.001). Patients who had surgery had a similar ECOG performance status to the ones who did not (P = 0.1798, two sample t test; P = 0.2449, Wilcoxon rank sum test). Univariate and propensity score analysis confirmed that patients treated with surgery had longer OS than those not treated surgically irrespective of age, race, primary tumor size and location, number of metastatic sites, and genetic background (log-rank P < 0.001).In patients with hormonally active tumors (70.8%), the symptoms of catecholamine excess improved after surgery. However, the tumor burden was a more important determinant of OS than hormonal secretion. Primary tumor resection in patients with metastatic PPG appeared to be

Malignant Perivascular Epithelioid Cell Neoplasm (PEComa) of the Pelvis: A Case Report.

PubMed

D'Andrea, David; Hanspeter, Esther; D'Elia, Carolina; Martini, Thomas; Pycha, Armin

2016-05-01

Perivascular epithelioid cell neoplasms (PEComa) are rare mesenchymal tumors that can occur in any part of the body and have unpredictable pathological behavior. They are usually benign, but may be malignant. We present a case of malignant PEComa of the pelvic retroperitoneum treated with radical surgery.

Preliminary clinical trial of immunotherapy for malignant glioma.

PubMed

Ingram, M; Shelden, C H; Jacques, S; Skillen, R G; Bradley, W G; Techy, G B; Freshwater, D B; Abts, R M; Rand, R W

1987-10-01

An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

Rare malignant pediatric tumors registered in the German Childhood Cancer Registry 2001-2010.

PubMed

Brecht, Ines B; Bremensdorfer, Claudia; Schneider, Dominik T; Frühwald, Michael C; Offenmüller, Sonja; Mertens, Rolf; Vorwerk, Peter; Koscielniak, Ewa; Bielack, Stefan S; Benesch, Martin; Hero, Barbara; Graf, Norbert; von Schweinitz, Dietrich; Kaatsch, Peter

2014-07-01

The German Childhood Cancer Registry (GCCR) annually registers approximately 2,000 children diagnosed with a malignant disease (completeness of registration >95%). While most pediatric cancer patients are diagnosed and treated according to standardized cooperative protocols of the German Society for Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk of not being integrated in the network including trials and reference centers. A retrospective analysis of all rare extracranial solid tumors reported to the GCCR 2001-2010 (age <18 years) was undertaken using a combination of the International Classification of Childhood Cancer (ICCC-3) and the International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting for <0.3% of all malignancies were defined as rare (approx. 6 cases/year and registered malignancy). According to this definition 1,189 rare extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were registered, among these 232 patients (19.5% of rare tumor cases), were not included in preexisting GPOH studies/registries. Within 10 years, the number of registered non-GPOH-trial patients with a rare tumor increased. Though most of the GCCR-registered patients with rare malignant tumors are treated within GPOH trials, there is a considerable number of patients that have been diagnosed and treated outside the structures of the GPOH. These patients should be reported to the recently founded German Pediatric Rare Tumor Registry (STEP). Active data accrual and the development of appropriate structures will allow for better registration and improvement of medical care in these patients. © 2014 Wiley Periodicals, Inc.

[Self-expandable metallic biliary endoprosthesis in malignant obstructive jaundice].

PubMed

Güitrón-Cantú, Alfredo; Adalid-Martínez, Raúl; Gutiérrez-Bermúdez, José A

2005-01-01

Implantation of metallic stents for malignant biliary strictures has been recognized to be effective alternatives. To show our experience in metallic stents for palliation of malignant biliary strictures. Seventy three patients (38 males, 35 females, mean age 64.26) with malignant biliary strictures have been treated by implantation of metallic stents. Causes of obstruction were pancreatic carcinoma (23/73, 31.5%), bile duct carcinoma (31/73, 42.5%), carcinoma of ampula of Vater (11/73, 15%) and Klatskin tumor (3/73, 4.1%). Endoscopic procedure was successful in all cases. Neither procedure-related morbidity nor mortality was observed. Life surviving curve was 9 months and showed significant difference (p < 0.0071) in patients with carcinoma of ampula of Vater. Self-expanding metal endoprosthesis is a recognized method of palliation in malignant biliary obstruction. It efficiently relieves jaundice and generally improves comfort and nutritional status during the patient's remaining lifetime. The metallic stents are advantageous in patients surviving 6 months or less.

Malignant Perivascular Epithelioid Cell Neoplasm (PEComa) of the Pelvis: A Case Report

PubMed Central

D'Andrea, David; Hanspeter, Esther; D'Elia, Carolina; Martini, Thomas; Pycha, Armin

2016-01-01

Perivascular epithelioid cell neoplasms (PEComa) are rare mesenchymal tumors that can occur in any part of the body and have unpredictable pathological behavior. They are usually benign, but may be malignant. We present a case of malignant PEComa of the pelvic retroperitoneum treated with radical surgery. PMID:27169023

Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

PubMed Central

Kaneko, Sadahiro

2016-01-01

Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD. PMID:27429612

Malignant Transformation of Rat Kidney Induced by Environmental Substances and Estrogen

PubMed Central

Alfaro-Lira, Susana; Pizarro-Ortiz, María; Calaf, Gloria M.

2012-01-01

The use of organophosphorous insecticides in agricultural environments and in urban settings has increased significantly. The aim of the present study was to analyze morphological alterations induced by malathion and 17β-estradiol (estrogen) in rat kidney tissues. There were four groups of animals: control, malathion, estrogen and combination of both substances. The animals were injected for five days and sacrificed 30, 124 and 240 days after treatments. Kidney tissues were analyzed for histomorphological and immunocytochemical alterations. Morphometric analysis indicated that malathion plus estrogen-treated animals showed a significantly (p < 0.05) higher grade of glomerular hypertrophy, signs of tubular damage, atypical proliferation in cortical and hilium zone than malathion or estrogen alone-treated and control animals after 240 days. Results indicated that MFG, ER-α, ER-β, PgR, CYP1A1, Neu/ErbB2, PCNA, vimentin and Thrombospondin 1 (THB) protein expression was increased in convoluted tubules of animals treated with combination of malathion and estrogen after 240 days of 5 day treatment. Malignant proliferation was observed in the hilium zone. In summary, the combination of malathion and estrogen induced pathological lesions in glomeruli, convoluted tubules, atypical cell proliferation and malignant proliferation in hilium zone and immunocytochemical alterations in comparison to control animals or animals treated with either substance alone. It can be concluded that an increased risk of kidney malignant transformation can be induced by exposure to environmental and endogenous substances. PMID:22754462

Double stenting with silicone and metallic stents for malignant airway stenosis.

PubMed

Matsumoto, Keitaro; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Kamohara, Ryotaro; Hatachi, Go; Nagayasu, Takeshi

2017-08-01

For severe malignant airway stenosis, there are several types of commercially available airway stents, and each has its own advantages and disadvantages. We herein describe the safety and efficacy of combination stenting with silicone and metallic stents for patients with extended malignant airway stenosis. Seven patients with malignant airway stenosis were treated via combination stenting with a silicone stent and a metallic stent for extended airway stenosis from the central to peripheral airways. Five patients were diagnosed with advanced esophageal cancer, two of whom had tracheoesophageal fistulas. One patient had adenoid cystic carcinoma, and another had mediastinal tumor. There were no specific complications related to the double stenting. Combination stenting with silicone and metallic stents proved to be a safe option for patients with severe, extended, and complicated malignant airway stenosis.

Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor

PubMed Central

Kochenderfer, James N.; Dudley, Mark E.; Kassim, Sadik H.; Somerville, Robert P.T.; Carpenter, Robert O.; Stetler-Stevenson, Maryalice; Yang, James C.; Phan, Giao Q.; Hughes, Marybeth S.; Sherry, Richard M.; Raffeld, Mark; Feldman, Steven; Lu, Lily; Li, Yong F.; Ngo, Lien T.; Goy, Andre; Feldman, Tatyana; Spaner, David E.; Wang, Michael L.; Chen, Clara C.; Kranick, Sarah M.; Nath, Avindra; Nathan, Debbie-Ann N.; Morton, Kathleen E.; Toomey, Mary Ann; Rosenberg, Steven A.

2015-01-01

Purpose T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19+ B-cell malignancies. Patients and Methods We treated 15 patients with advanced B-cell malignancies. Nine patients had diffuse large B-cell lymphoma (DLBCL), two had indolent lymphomas, and four had chronic lymphocytic leukemia. Patients received a conditioning chemotherapy regimen of cyclophosphamide and fludarabine followed by a single infusion of anti-CD19 CAR T cells. Results Of 15 patients, eight achieved complete remissions (CRs), four achieved partial remissions, one had stable lymphoma, and two were not evaluable for response. CRs were obtained by four of seven evaluable patients with chemotherapy-refractory DLBCL; three of these four CRs are ongoing, with durations ranging from 9 to 22 months. Acute toxicities including fever, hypotension, delirium, and other neurologic toxicities occurred in some patients after infusion of anti-CD19 CAR T cells; these toxicities resolved within 3 weeks after cell infusion. One patient died suddenly as a result of an unknown cause 16 days after cell infusion. CAR T cells were detected in the blood of patients at peak levels, ranging from nine to 777 CAR-positive T cells/μL. Conclusion This is the first report to our knowledge of successful treatment of DLBCL with anti-CD19 CAR T cells. These results demonstrate the feasibility and effectiveness of treating chemotherapy-refractory B-cell malignancies with anti-CD19 CAR T cells. The numerous remissions obtained provide strong support for further development of this approach. PMID:25154820

Malignant hyperthermia

MedlinePlus

... about MH: Malignant Hyperthermia Association of the United States -- www.mhaus.org National Organization for Rare Disorders -- rarediseases.org/rare-diseases/malignant-hyperthermia NIH Genetics Home Reference -- ghr.nlm.nih.gov/condition/malignant-hyperthermia

Sequential Stenting for Extensive Malignant Airway Stenosis

PubMed Central

Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Tei, Keiko; Yamamoto, Ryoji

2014-01-01

Purpose: Malignant airway stenosis extending from the bronchial bifurcation to the lower lobar orifice was treated with airway stenting. We herein examine the effectiveness of airway stenting for extensive malignant airway stenosis. Methods: Twelve patients with extensive malignant airway stenosis underwent placement of a silicone Dumon Y stent (Novatech, La Ciotat, France) at the tracheal bifurcation and a metallic Spiral Z-stent (Medico’s Hirata, Osaka, Japan) at either distal side of the Y stent. We retrospectively analyzed the therapeutic efficacy of the sequential placement of these silicone and metallic stents in these 12 patients. Results: The primary disease was lung cancer in eight patients, breast cancer in two patients, tracheal cancer in one patient, and thyroid cancer in one patient. The median survival period after airway stent placement was 46 days. The Hugh–Jones classification and performance status improved in nine patients after airway stenting. One patient had prolonged hemoptysis and died of respiratory tract hemorrhage 15 days after the treatment. Conclusion: Because the initial disease was advanced and aggressive, the prognosis after sequential airway stent placement was significantly poor. However, because respiratory distress decreased after the treatment in most patients, this treatment may be acceptable for selected patients with extensive malignant airway stenosis. PMID:25273272

Clinical and Molecular Features of Renal and Pheochromocytoma/Paraganglioma Tumor Association Syndrome (RAPTAS): Case Series and Literature Review.

PubMed

Casey, Ruth T; Warren, Anne Y; Martin, Jose Ezequiel; Challis, Benjamin G; Rattenberry, Eleanor; Whitworth, James; Andrews, Katrina A; Roberts, Thomas; Clark, Graeme R; West, Hannah; Smith, Philip S; Docquier, France M; Rodger, Fay; Murray, Vicki; Simpson, Helen L; Wallis, Yvonne; Giger, Olivier; Tran, Maxine; Tomkins, Susan; Stewart, Grant D; Park, Soo-Mi; Woodward, Emma R; Maher, Eamonn R

2017-11-01

The co-occurrence of pheochromocytoma (PC) and renal tumors was linked to the inherited familial cancer syndrome von Hippel-Lindau (VHL) disease more than six decades ago. Subsequently, other shared genetic causes of predisposition to renal tumors and to PC, paraganglioma (PGL), or head and neck paraganglioma (HNPGL) have been described, but case series of non-VHL-related cases of renal tumor and pheochromocytoma/paraganglioma tumor association syndrome (RAPTAS) are rare. To determine the clinical and molecular features of non-VHL RAPTAS by literature review and characterization of a case series. A review of the literature was performed and a retrospective study of referrals for investigation of genetic causes of RAPTAS. Literature review revealed evidence of an association, in addition to VHL disease, between germline mutations in SDHB, SDHC, SDHD, TMEM127, and MAX genes and RAPTAS [defined here as the co-occurrence of tumors from both classes (PC/PGL/HNPGL and renal tumors) in the same individual or in first-degree relatives]. In both the literature review and our case series of 22 probands with non-VHL RAPTAS, SDHB mutations were the most frequent cause of non-VHL RAPTAS. A genetic cause was identified in 36.3% (8/22) of kindreds. Renal tumors and PC/PGL/HNPGL tumors share common molecular features and their co-occurrence in an individual or family should prompt genetic investigations. We report a case of MAX-associated renal cell carcinoma and confirm the role of TMEM127 mutations with renal cell carcinoma predisposition. Copyright © 2017 Endocrine Society

Palliative management of malignant upper urinary tract obstruction

PubMed Central

Sountoulides, P; Mykoniatis, I; Dimasis, N

2014-01-01

Malignancies of the genitourinary tract are diagnosed with increased frequency compared to the past. Currently prostate and bladder cancer account for the majority of urological malignancies. While for prostate cancer recent developments in the management of local and metastatic disease are likely to lead the majority of patients to either cure from the disease or to longer survival time, for bladder cancer advanced disease will unfortunately lead to death within months. However, the common clinical scenario in both prostate and bladder cancer includes, in high incidence, upper urinary tract obstruction in the advanced stages of these malignancies. This coupled with the fact that average life expectancy in the western world is increasing, will result in a significant patient population with either advanced, non-curable disease or with problems related to the received therapeutic surgical or medical interventions. There is no doubt that in both circumstances the room and role of palliation therapy is increasing. The care of patients with advanced urologic malignancies requires a multi-disciplinary effort from physicians of many specialties under the guiding role of the treating urologist. This review focuses on currently available palliative therapeutic options for upper urinary tract obstruction in the setting of patients with advanced malignancies of the urinary tract, as recently significant advancements have been witnessed in this field. PMID:26052193

Palliative management of malignant upper urinary tract obstruction.

PubMed

Sountoulides, P; Mykoniatis, I; Dimasis, N

2014-01-01

Malignancies of the genitourinary tract are diagnosed with increased frequency compared to the past. Currently prostate and bladder cancer account for the majority of urological malignancies. While for prostate cancer recent developments in the management of local and metastatic disease are likely to lead the majority of patients to either cure from the disease or to longer survival time, for bladder cancer advanced disease will unfortunately lead to death within months. However, the common clinical scenario in both prostate and bladder cancer includes, in high incidence, upper urinary tract obstruction in the advanced stages of these malignancies. This coupled with the fact that average life expectancy in the western world is increasing, will result in a significant patient population with either advanced, non-curable disease or with problems related to the received therapeutic surgical or medical interventions. There is no doubt that in both circumstances the room and role of palliation therapy is increasing. The care of patients with advanced urologic malignancies requires a multi-disciplinary effort from physicians of many specialties under the guiding role of the treating urologist. This review focuses on currently available palliative therapeutic options for upper urinary tract obstruction in the setting of patients with advanced malignancies of the urinary tract, as recently significant advancements have been witnessed in this field.

18F-FDG avidity of pheochromocytomas and paragangliomas: a new molecular imaging signature?

PubMed

Taïeb, David; Sebag, Frederic; Barlier, Anne; Tessonnier, Laurent; Palazzo, Fausto F; Morange, Isabelle; Niccoli-Sire, Patricia; Fakhry, Nicolas; De Micco, Catherine; Cammilleri, Serge; Enjalbert, Alain; Henry, Jean-François; Mundler, Olivier

2009-05-01

Our objective was to evaluate (18)F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n = 18) and those with metastatic tumors (n = 10). (18)F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. All but 2 patients showed significantly increased (18)F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean +/- SD, 8.2 +/- 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean +/- SD, 9.7 +/- 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P = 0.44), but succinate dehydrogenase-related tumors were notable in being the most (18)F-FDG-avid tumors (SUVmax, 42, 29.3, 21, 17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau-related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome-related tumors (P = 0.02). (18)F-FDG PET was superior to (131)I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, (18)F-FDG PET underestimated the extent of the disease, compared with 6-(18)F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain (18)F-FDG uptake since most tumors were highly avid for (18)F-FDG. (18)F-FDG PET positivity is almost a constant feature of pheochromocytomas

[Adrenal incidentaloma: a clinical problem related to imaging].

PubMed

de Bruijne, E L E; Burgmans, J P J; Krestin, G P; Pols, H A P; van den Meiracker, A H; de Herder, W W

2005-08-13

Two female patients, 68 and 67 years of age, were referred for right abdominal pain and pyelonephritis, respectively. During the diagnostic work-up, an unsuspected adrenal mass was found in both patients. Hormonal evaluation and imaging showed a benign non-hyperactive functioning adenoma in one patient and a pheochromocytoma in the other. Both patients were successfully treated with endoscopic adrenalectomy. Wider application and improvement of abdominal imaging procedures have caused an increase of incidentally detected adrenal masses, posing a common clinical problem. Typically, a diagnosis can be made on the basis of the characteristic radiological image. The exact nature of the defect is often unclear and further evaluation is required to determine functionality and possible malignancy. An algorithm is presented for the management of adrenal incidentalomas.

Analysis of orbital malignancies presenting in a tertiary care hospital in Pakistan

PubMed Central

Khan, Asad Aslam; Sarwar, Suhail; Sadiq, Mohammad Ali A; Ahmad, Imran; Tariq, Nayab; Sibghat-ul-Noor

2017-01-01

Objective: To determine the frequencies of various orbital malignancies amongst orbital lesions in patients presenting in a tertiary care hospital in Pakistan. Methods: A retrospective analysis of 666 orbital cases with an established histopathological diagnosis of malignant tumors treated in Mayo Hospital Lahore from 1996 to 2015 (20 years). Results: About 66% of the malignant tumors were primary, 25% secondary, 8% haematopoietic and 1% metastatic. Almost 50% of the cases were children. Retinoblastoma is the commonest tumor (43% overall and 87% among children). Squamous cell carcinoma is the second commonest (15.6% overall and 31% among adults). These are then followed by Adenoid cystic carcinoma of Lacrimal Gland (9%), Lymphoma/Leukaemia (8%) and Rhabdomyosarcoma (6.3%). Conclusion: Frequencies of various orbital malignancies show geographical variation in both paediatric and adult population. PMID:28367175

[Adrenal incidentaloma and nuclear medicine examination].

PubMed

Tenenbaum, F

2009-03-01

In the setting of adrenal incidentaloma, nuclear medicine evaluation is only indicated after biological and imaging work-up has been completed. MIBG scintigraphy is helpful to characterize pheochromocytomas. In lesions without MIBG uptake, 18F FDG or 18F DOPA PET can be considered to characterize chromaffin cell tumours. To characterize lesions of the adrenal cortex, iodocholesterol scintigraphy is performed to confirm the origin of the adenoma and the benign or malignant nature of the lesion since benign adenomas show tracer uptake and malignant lesions show no tracer uptake. 18F FDG PET only characterizes the lesion as benign or malignant.

A rare case of juvenile hypertension: coexistence of type 2 multiple endocrine neoplasia -related bilateral pheochromocytoma and reninoma in a young patient with ACE gene polymorphism.

PubMed

Paragliola, Rosa Maria; Capoluongo, Ettore; Torino, Francesco; Minucci, Angelo; Canu, Giulia; Prete, Alessandro; Pontecorvi, Alfredo; Corsello, Salvatore Maria

2015-06-18

Pheochromocytoma and reninoma represent two rare diseases causing hypertension. We here reported a rare case of association between type 2 multiple endocrine neoplasia related bilateral pheochromocytoma and reninoma. Moreover, polymorphism of ACE gene, which is known to be related to an increase of cardiovascular risk, has been found in the same patient. A 24 year old Caucasian man came to our attention for severe hypertension, resistant to anti-hypertensive polytherapy. At the age of twenty he had undergone total thyroidectomy with lymphadenectomy for medullary carcinoma. Genetic testing showed a RET mutation of codon 918 (exon 16) not documented in other family members. During the follow-up, a progressive increase of urinary metanephrines and catecholamines was recorded. Our evaluation confirmed the presence of severe hypertension (220/140 mmHg) and a severe increase of urinary catecholamines and metanephrines. Due to the presence of hypokalemia, other causes of hypertension were researched leading to the discovery of hyperreninemia (236 μUI/ml) with mild hyperaldosteronism, and a mild increase of the renal artery resistance at ultrasound. An abdominal MRI showed multiple adrenal masses and a right kidney nodular lesion of about 2 cm. The patient underwent bilateral adrenalectomy and right nephrectomy, and histology confirmed the presence of bilateral pheochromocytoma and right reninoma. The post-surgery laboratory evaluation showed a rapid reduction of the urinary metanephrines while plasma renin level remained low in spite of the bilateral adrenalectomy without any mineralocorticoid supplementation. To further investigate these unusual feature, we performed genetic testing for the ACE gene, which revealed the presence of ACE I/D polymorphism. This unique report describes the association between two rare causes of hypertension in the same patient. Furthermore, the absence of requirement of mineralocorticoid supplementation in spite of bilateral adrenalectomy

Inverse association between brown adipose tissue activation and white adipose tissue accumulation in successfully treated pediatric malignancy1234

PubMed Central

Chalfant, James S; Smith, Michelle L; Hu, Houchun H; Dorey, Fred J; Goodarzian, Fariba; Fu, Cecilia H

2012-01-01

Background: Although the accumulation of white adipose tissue (WAT) is a risk factor for disease, brown adipose tissue (BAT) has been suggested to have a protective role against obesity. Objective: We studied whether changes in BAT were related to changes in the amounts of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in children treated for malignancy. Design: We examined the effect of BAT activity on weight, SAT, and VAT in 32 pediatric patients with cancer whose positron emission tomography–computed tomography (PET-CT) scans at diagnosis showed no BAT activity. Changes in weight, SAT, and VAT from diagnosis to remission for children with metabolically active BAT at disease-free follow-up (BAT+) were compared with those in children without visualized BAT when free of disease (BAT−). Results: Follow-up PET-CT studies (4.7 ± 2.4 mo later) after successful treatment of the cancer showed BAT+ in 19 patients but no active BAT (BAT−) in 13 patients. BAT+ patients, in comparison with BAT− patients, gained significantly less weight (3.3 ± 6.6% compared with 11.0 ± 11.6%; P = 0.02) and had significantly less SAT (18.2 ± 26.5% compared with 67.4 ± 71.7%; P = 0.01) and VAT (22.6 ± 33.5% compared with 131.6 ± 171.8%; P = 0.01) during treatment. Multiple regression analysis indicated that the inverse relations between BAT activation and measures of weight, SAT, and VAT persisted even after age, glucocorticoid treatment, and the season when the PET-CT scans were obtained were accounted for. Conclusion: The activation of BAT in pediatric patients undergoing treatment of malignancy is associated with significantly less adipose accumulation. This trial was registered at clinicaltrials.gov as NCT01517581. PMID:22456659

Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors

PubMed Central

Mastorakos, Panagiotis; Zhang, Clark; Song, Eric; Kim, Young Eun; Park, Hee Won; Berry, Sneha; Choi, Won Kyu; Hanes, Justin; Suk, Jung Soo

2018-01-01

The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5 kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats. Rapid diffusion of these DNA-loaded nanocomplexes observed in fresh tissues ex vivo demonstrated that they avoided adhesive trapping in the brain owing to their dense PEG coating, which was critical to achieving widespread transgene expression throughout orthotopic rat brain tumors in vivo following administration by convection enhanced delivery. Transgene expression with the PBAE/PBAE-PEG blended nanocomplexes (DNA-loaded brain-penetrating nanocomplexes, or DNA-BPN) was uniform throughout the tumor core compared to nanocomplexes composed of DNA with PBAE only (DNA-loaded conventional nanocomplexes, or DNA-CN), and transgene expression reached beyond the tumor edge, where infiltrative cancer cells are found, only for the DNA-BPN formulation. Finally, DNA-BPN loaded with anti-cancer plasmid DNA provided significantly enhanced survival compared to the same plasmid DNA loaded in DNA-CN in two aggressive orthotopic brain tumor models in rats. These findings underscore the importance of achieving widespread delivery of therapeutic nucleic acids within brain tumors and provide a promising new delivery platform for localized gene therapy in the brain. PMID:28694032

Concomitant endometriosis in malignant and borderline ovarian tumours.

PubMed

Oral, Engin; Aydin, Ovgu; Kumbak, Banu Aygun; İlvan, Sennur; Yilmaz, Handan; Tustas, Esra; Bese, Tugan; Demirkiran, Fuat; Arvas, Macit

2018-06-08

ovarian tumours and the endometriosis-associated malignant ovarian tumours were mostly early stage. What are the implications of these findings for clinical practice and/or further research? Additional studies need to be conducted to develop screening approaches for malignant transformation or an association in women with endometriosis. Till that time, a change of current clinical practices cannot be justified. However, counselling and treating women with endometriosis who are at high risk for cancer coexistence or conversion is encouraged.

Indium In 111 Pentetreotide in Treating Patients With Refractory Cancer

ClinicalTrials.gov

2014-07-01

Brain and Central Nervous System Tumors; Childhood Langerhans Cell Histiocytosis; Gastrointestinal Carcinoid Tumor; Head and Neck Cancer; Intraocular Melanoma; Islet Cell Tumor; Kidney Cancer; Lung Cancer; Melanoma (Skin); Neoplastic Syndrome; Neuroendocrine Carcinoma of the Skin; Pheochromocytoma

Current update of adoptive immunotherapy using cytokine-induced killer cells to eliminate malignant gliomas.

PubMed

Ryu, Je Il; Han, Myung Hoon; Cheong, Jin Hwan; Kim, Jae Min; Kim, Choong Hyun

2017-03-01

The therapeutic outcome for those with malignant glioma is poor, even though diverse therapeutic modalities have been developed. Immunotherapy has emerged as a therapeutic approach for malignant gliomas, making it possible to selectively treat tumors while sparing normal tissue. Here, we review clinical trials of adoptive immunotherapy approaches for malignant gliomas. We also describe a clinical trial that examined the efficacy and safety of autologous cytokine-induced killer (CIK) cells along with concomitant chemoradiotherapy for newly diagnosed glioblastoma. These CIK cells identify and kill autologous tumor cells. This review focuses on the use of adoptive immunotherapy for malignant gliomas and reviews the current literature on the concept of antitumor activity mediated by CIK cells.

Predicted Rate of Secondary Malignancies Following Adjuvant Proton Versus Photon Radiation Therapy for Thymoma.

PubMed

Vogel, J; Lin, L; Litzky, L A; Berman, A T; Simone, C B

2017-10-01

Thymic malignancies are the most common tumors of the anterior mediastinum. The benefit of adjuvant radiation therapy for stage II disease remains controversial, and patients treated with adjuvant radiation therapy are at risk of late complications, including radiation-induced secondary malignant neoplasms (SMNs), that may reduce the overall benefit of treatment. We assess the risk of predicted SMNs following adjuvant proton radiation therapy compared with photon radiation therapy after resection of stage II thymic malignancies to determine whether proton therapy improves the risk-benefit ratio. Ten consecutive patients treated with double-scattered proton beam radiation therapy (DS-PBT) were prospectively enrolled in an institutional review board-approved proton registry study. All patients were treated with DS-PBT. Intensity modulated radiation therapy (IMRT) plans for comparison were generated. SMN risk was calculated based on organ equivalent dose. Patients had a median age of 65 years (range, 25-77 years), and 60% were men. All patients had stage II disease, and many had close or positive margins (60%). The median dose was 50.4 Gy (range, 50.4-54.0 Gy) in 1.8-Gy relative biological effectiveness daily fractions. No differences in target coverage were seen with DS-PBT compared with IMRT plans. Significant reductions were seen in mean and volumetric lung, heart, and esophageal doses with DS-PBT compared with IMRT plans (all P≤.01). Significant reductions in SMNs in the lung, breast, esophagus, skin, and stomach were seen with DS-PBT compared with IMRT. For patients with thymoma diagnosed at the median national age, 5 excess secondary malignancies per 100 patients would be avoided by treating them with protons instead of photons. Treatment with proton therapy can achieve comparable target coverage but significantly reduced doses to critical normal structures, which can lead to fewer predicted SMNs compared with IMRT. By decreasing expected late

Systemic malignancies presenting as primary osteolytic lesion.

PubMed

Sirelkhatim, A; Kaiserova, E; Kolenova, A; Puskacova, J; Subova, Z; Petrzalkova, D; Banikova, K; Suvada, J; Sejnova, D

2009-01-01

The tumor formation may be the earliest manifestation preceeding other symptoms, signs and bone marrow evidence of systemic malignancy - leukemia/lymphoma. Here we present three cases of systemic malignancy in which bone lesions were the first manifested signs of the disease. All three cases were thought to be orthopedic cases and had been treated as so without genuing improvement. We would like to draw an attention to children who present with multifocal musculoskeletal pain and the importance of whole-body scaning. We describe interesting cases of diffuse large cell lymphoma and leukemia that initially presented as primary osteolytic bone lesion and discuss the differential diagnosis, literature review of non-Hodgkin's lymphoma arising in bone as the primary site (Tab. 1, Fig. 3, Ref. 18). Full Text (Free, PDF) www.bmj.sk.

Pseudoprogression in boron neutron capture therapy for malignant gliomas and meningiomas

PubMed Central

Miyatake, Shin-Ichi; Kawabata, Shinji; Nonoguchi, Naosuke; Yokoyama, Kunio; Kuroiwa, Toshihiko; Matsui, Hideki; Ono, Koji

2009-01-01

Pseudoprogression has been recognized and widely accepted in the treatment of malignant gliomas, as transient increases in the volume of the enhanced area just after chemoradiotherapy, especially using temozolomide. We experienced a similar phenomenon in the treatment of malignant gliomas and meningiomas using boron neutron capture therapy (BNCT), a cell-selective form of particle radiation. Here, we introduce representative cases and analyze the pathogenesis. Fifty-two cases of malignant glioma and 13 cases of malignant meningioma who were treated by BNCT were reviewed retrospectively mainly via MR images. Eleven of 52 malignant gliomas and 3 of 13 malignant meningiomas showed transient increases of enhanced volume in MR images within 3 months after BNCT. Among these cases, five patients with glioma underwent surgery because of suspicion of relapse. In histology, most of the specimens showed necrosis with small amounts of residual tumor cells. Ki-67 labeling showed decreased positivity compared with previous samples from the individuals. Fluoride-labeled boronophenylalanine PET was applied in four and two cases of malignant gliomas and meningiomas, respectively, at the time of transient increase of lesions. These PET scans showed decreased lesion:normal brain ratios in all cases compared with scans obtained prior to BNCT. With or without surgery, all lesions were decreased or stable in size during observation. Transient increases in enhanced volume in malignant gliomas and meningiomas immediately after BNCT seemed to be pseudoprogression. This pathogenesis was considered as treatment-related intratumoral necrosis in the subacute phase after BNCT. PMID:19289492

Familial association of specific histologic types of ovarian malignancy with other malignancies.

PubMed

Lorenzo Bermejo, Justo; Rawal, Rajesh; Hemminki, Kari

2004-04-01

Population-based data on the familial association of specific histologic types of ovarian malignancy with other malignancies are limited. Such data may help to elucidate etiologic differences among histologic types of ovarian malignancy. The nationwide Swedish Family-Cancer Database, which includes 10.3 million individuals and 20,974 ovarian carcinomas, was used to calculate standardized incidence ratios and 95% confidence intervals for age- and histology-specific ovarian malignancies in women whose parents or siblings were affected with malignancies at the most common disease sites. Ovarian malignancy was found to be associated with ovarian, laryngeal, breast, endometrial, liver, and colon carcinoma, as well as myeloma; epithelial ovarian malignancy was found to be associated with ovarian, endometrial, and skin malignancies and with melanoma and myeloma; papillary serous cystadenocarcinoma was found to be associated with ovarian and skin malignancies and with myeloma; and endometrioid carcinoma was found to be associated with endometrial, ovarian, and prostate malignancies and with melanoma. For younger women (ages 40-45 years) whose mothers were affected with endometrial malignancies, the risk of developing endometrioid carcinoma was slightly greater than the risk of developing papillary serous cystadenocarcinoma. Specific types of ovarian malignancy may be associated with specific familial disease sites, with such associations depending on age at diagnosis; the strength of the observed associations varied according to histology. Associations were found between endometrioid carcinoma and endometrial malignancy and between serous carcinoma and Hodgkin disease. Copyright 2004 American Cancer Society.

Bevacizumab Plus Irinotecan in Recurrent WHO Grade 3 Malignant Gliomas

PubMed Central

Desjardins, Annick; Reardon, David A.; Herndon, James E.; Marcello, Jennifer; Quinn, Jennifer A.; Rich, Jeremy N.; Sathornsumetee, Sith; Gururangan, Sridharan; Sampson, John; Bailey, Leighann; Bigner, Darell D.; Friedman, Allan H.; Friedman, Henry S.; Vredenburgh, James J.

2013-01-01

Purpose Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma, salvage therapies following recurrence offer essentially palliative benefit. We did a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan for patients with recurrent grade 3 malignant glioma. Experimental Design Upon documentation of adequate safety among an initial cohort of nine patients treated with bevacizumab (10 mg/kg) and irinotecan every 14 days, a second cohort (n = 24) was treated with bevacizumab (15 mg/kg) every 3 weeks with irinotecan on days 1, 8, 22, and 29 of each 42-day cycle. For both cohorts, the dose of irinotecan was 340 mg/m2 for patients on enzyme-inducing antiepileptic drugs (EIAED) and 125 mg/m2 for patients not on EIAEDs. After each 6-week cycle, patients were evaluated with a physical examination and magnetic resonance imaging. Results The 6-month progression-free survival was 55% (95% confidence interval, 36–70%). The 6-month overall survival was 79% (95% confidence interval, 61–89%). Twenty patients (61%) had at least a partial response. Outcome did not differ between the two treatment cohorts. Significant adverse events were infrequent and included a central nervous system hemorrhage in one patient, and one patient who developed thrombotic thrombocytopenic purpura. Conclusion Bevacizumab and irinotecan is an active regimen with acceptable toxicity for patients with recurrent WHO grade 3 malignant glioma. PMID:18981004

Accuracy of recommended sampling and assay methods for the determination of plasma-free and urinary fractionated metanephrines in the diagnosis of pheochromocytoma and paraganglioma: a systematic review.

PubMed

Därr, Roland; Kuhn, Matthias; Bode, Christoph; Bornstein, Stefan R; Pacak, Karel; Lenders, Jacques W M; Eisenhofer, Graeme

2017-06-01

To determine the accuracy of biochemical tests for the diagnosis of pheochromocytoma and paraganglioma. A search of the PubMed database was conducted for English-language articles published between October 1958 and December 2016 on the biochemical diagnosis of pheochromocytoma and paraganglioma using immunoassay methods or high-performance liquid chromatography with coulometric/electrochemical or tandem mass spectrometric detection for measurement of fractionated metanephrines in 24-h urine collections or plasma-free metanephrines obtained under seated or supine blood sampling conditions. Application of the Standards for Reporting of Diagnostic Studies Accuracy Group criteria yielded 23 suitable articles. Summary receiver operating characteristic analysis revealed sensitivities/specificities of 94/93% and 91/93% for measurement of plasma-free metanephrines and urinary fractionated metanephrines using high-performance liquid chromatography or immunoassay methods, respectively. Partial areas under the curve were 0.947 vs. 0.911. Irrespective of the analytical method, sensitivity was significantly higher for supine compared with seated sampling, 95 vs. 89% (p < 0.02), while specificity was significantly higher for supine sampling compared with 24-h urine, 95 vs. 90% (p < 0.03). Partial areas under the curve were 0.942, 0.913, and 0.932 for supine sampling, seated sampling, and urine. Test accuracy increased linearly from 90 to 93% for 24-h urine at prevalence rates of 0.0-1.0, decreased linearly from 94 to 89% for seated sampling and was constant at 95% for supine conditions. Current tests for the biochemical diagnosis of pheochromocytoma and paraganglioma show excellent diagnostic accuracy. Supine sampling conditions and measurement of plasma-free metanephrines using high-performance liquid chromatography with coulometric/electrochemical or tandem mass spectrometric detection provides the highest accuracy at all prevalence rates.

Risk of radiation-induced malignancy with heterotopic ossification prophylaxis: a case-control analysis.

PubMed

Sheybani, Arshin; TenNapel, Mindi J; Lack, William D; Clerkin, Patrick; Hyer, Daniel E; Sun, Wenqing; Jacobson, Geraldine M

2014-07-01

To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). A matched case-control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not develop a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not. Copyright © 2014 Elsevier Inc. All rights reserved.

Risk of Radiation-Induced Malignancy With Heterotopic Ossification Prophylaxis: A Case–Control Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheybani, Arshin, E-mail: arshin-sheybani@uiowa.edu; TenNapel, Mindi J.; Lack, William D.

2014-07-01

Purpose: To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). Methods and Materials: A matched case–control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not developmore » a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. Results: A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. Conclusion: We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not.« less

Development of venetoclax for therapy of lymphoid malignancies.

PubMed

Zhu, Huayuan; Almasan, Alexandru

2017-01-01

B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients. Also, unlike the other targeted agents, it is effective against tumor cells that reside in the blood marrow. Despite its promising outcome in CLL, preclinical data have already uncovered mechanistic insights underlying venetoclax resistance, such as upregulation of MCL-1 or BCL-xL expression and protective signaling from the microenvironment. In this review, we describe the role of the BCL-2 family in the pathogenesis of B-cell lymphoid malignancies, the development of venetoclax, and its current clinical outcome in CLL and other B-cell malignancies. We also discuss the resistance mechanisms that develop following venetoclax therapy, potential strategies to overcome them, and how this knowledge can be translated into clinical applications.

Development of venetoclax for therapy of lymphoid malignancies

PubMed Central

Zhu, Huayuan; Almasan, Alexandru

2017-01-01

B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients. Also, unlike the other targeted agents, it is effective against tumor cells that reside in the blood marrow. Despite its promising outcome in CLL, preclinical data have already uncovered mechanistic insights underlying venetoclax resistance, such as upregulation of MCL-1 or BCL-xL expression and protective signaling from the microenvironment. In this review, we describe the role of the BCL-2 family in the pathogenesis of B-cell lymphoid malignancies, the development of venetoclax, and its current clinical outcome in CLL and other B-cell malignancies. We also discuss the resistance mechanisms that develop following venetoclax therapy, potential strategies to overcome them, and how this knowledge can be translated into clinical applications. PMID:28331288

An unusual combination of extra-adrenal pheochromocytoma and arteriovenous malformation of the ureter in a young adult.

PubMed

Khawaja, Ali; Aziz, Wajahat; Nazim, Syed Muhammad; Abbas, Farhat

2013-04-23

We present a case of a 24-year-old gentleman who presented with painless pan haematuria for 2 weeks. During the workup, he was diagnosed to have a retrocaval mass after a CT scan while cystoscopy revealed a polypoidal pulsating lesion in the left ureter. After surgical manipulation of the retrocaval mass, the blood pressure of the patient raised to 260/130 mm Hg. It was completely resected and diagnosed as extra-adrenal pheochromocytoma (paraganglioma) after histopathology. The lesion in the ureter was completely excised and fulgurated and diagnosed as an arteriovenous malformation. To the best of our knowledge, this is the first patient to be presented in the literature with this unusual combination.

Clinical studies of photodynamic therapy for malignant brain tumors: Karnofsky score and neurological score in patients with recurrent gloms treated with Photofrin PDT

NASA Astrophysics Data System (ADS)

Muller, Paul J.; Wilson, Brian C.; Lilge, Lothar D.; Yang, Victor X.; Varma, Abhay; Bogaards, Arjen; Hetzel, Fred W.; Chen, Qun; Fullagar, Tim; Fenstermaker, Robert; Selker, Robert; Abrams, Judith

2002-06-01

In our previous phase II studies we treated 112 patients with malignant brain tumors with 2-mg/kg Photofrin i.v. and intra-operative cavitary PDT. We concluded that PDT was safe in patients with newly diagnosed or recurrent supratentorial malignant gliomas. Pathology, performance grade and light dose were significantly related to survival time. In selected patients when an adequate light dose was used survival time improved. The surgical mortality rate was less than 3%. [spie 2000] We have initiated two randomized prospective trials - the first, to determine if the addition of PDT to standard therapy [surgery, radiation and/or chemotherapy] prolongs the survival of patients with newly diagnosed malignant astrocytic tumors; and the second, to determine whether high light dose PDT [120 J/cm2] is superior to low light dose PDT [40 J/cm2] in patients with recurrent malignant astrocytic tumors. To date, 158 patients have been recruited - 72 to the newly diagnosed malignant glioma study and 86 to the recurrent glioma study. In the recurrent glioma study we compared the pre-operative KS and elements of the neurological examination [speech function, visual fields, cognitive function, sensory examination and gait] to the post-operative examinations at hospital discharge. The means were compared by paired student-t test. The KS in 86 of 88 patients with recurrent gliomas were assessable. The mean [s.d.] preoperative and post-operative KS were 82+/- 14 and 79+/- 17, respectively [p=0.003]. The mean decline in KS, although statistically significant, was small and of no clinical importance. The median Karnofsky score changed from 90 to 80. The KS improved in 8 patients; their post-operative average length of stay (alos) was =9.7 days. There was no change in 47 [alos=8.3], a decline of 10 points in 24 [aloc=13.4] and declined by more than 10 points in 7 [alos=23.3]. Three of these 7 patients who had a decline of >10 points improved in follow-up but did not reach their

The skin as a window to the blood: Cutaneous manifestations of myeloid malignancies.

PubMed

Li, Alvin W; Yin, Emily S; Stahl, Maximilian; Kim, Tae Kon; Panse, Gauri; Zeidan, Amer M; Leventhal, Jonathan S

2017-11-01

Cutaneous manifestations of myeloid malignancies are common and have a broad range of presentations. These skin findings are classified as specific, due to direct infiltration by malignant hematopoietic cells, or non-specific. Early recognition and diagnosis can have significant clinical implications, as skin manifestations may be the first indication of underlying hematologic malignancy, can reflect the immune status and stage of disease, and cutaneous reactions may occur from conventional and targeted agents used to treat myeloid disease. In addition, infections with cutaneous involvement are common in immunocompromised patients with myeloid disease. Given the varying presentations, dermatologic findings associated with myeloid malignancies can pose diagnostic challenges for hematologists and dermatologists. In this clinical review intended for the practicing hematologist/oncologist, we discuss the presentation, diagnosis, treatment, and prognostic value of the most common cutaneous manifestations associated with myeloid malignancies using illustrative macro- and microscopic figures and with a special emphasis on practical considerations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Malignant hypertension

MedlinePlus

... Nephrosclerosis - arteriolar; Hypertension - malignant; High blood pressure - malignant Images Hypertensive kidney References Archbold A, Naish J. The cardiovascular system. In: Naish J, Court DS, ...

Extracorporeal irradiation for malignant bone tumors.

PubMed

Hong, A; Stevens, G; Stalley, P; Pendlebury, S; Ahern, V; Ralston, A; Estoesta, E; Barrett, I

2001-06-01

Extracorporeal irradiation (ECI) has been used selectively in the management of primary malignant bone tumors since 1996. We report our techniques for ECI and the short-term oncologic and orthopedic outcomes. Sixteen patients with primary malignant bone tumors were treated with ECI from 1996 to 2000. The median age was 14 years. The histologic diagnoses were Ewing's sarcoma (11), osteosarcoma (4) and chondrosarcoma (1). The treated sites were femur (7), tibia (4), humerus (2), ilium (2), and sacrum (1). Following induction chemotherapy in Ewing's sarcomas and osteosarcoma, en bloc resection of the tumor and tumor-bearing bone was performed. A single dose of 50 Gy was delivered to the bone extracorporeally using either a linear accelerator (9 cases) or a blood product irradiator (7 cases). The orthopedic outcome was recorded using a standard functional scale. At a median follow-up of 19.5 months, there were no cases of local recurrence or graft failure. One patient required amputation due to chronic osteomyelitis. For the 10 patients with follow-up greater than 18 months, the functional outcomes were graded good to excellent. The short-term oncologic and orthopedic results are encouraging and suggest that ECI provides a good alternative for reconstruction in limb conservative surgery in selected patients. This technique should only be used in a multidisciplinary setting, where careful follow-up is available to assess the long-term outcomes.

Malignant glaucoma after cataract surgery.

PubMed

Varma, Devesh K; Belovay, Graham W; Tam, Diamond Y; Ahmed, Iqbal Ike K

2014-11-01

To report a series of eyes that developed malignant glaucoma after cataract surgery. Private academic practice, Toronto, Ontario, Canada. Retrospective case series. Eyes that developed malignant glaucoma after cataract surgery were treated with medical therapy. This was followed by laser iridozonulohyaloidotomy, anterior chamber reformation and intraocular lens (IOL) pushback, and finally with surgical iridozonulohyaloidovitrectomy if all other measures were unsuccessful. Refraction, intraocular pressure (IOP), gonioscopy, and anterior chamber depth (ACD) by anterior segment optical coherence tomography were analyzed before treatment and after treatment. The study evaluated 20 eyes of 18 female patients aged 44 to 86 years. Preoperatively, the mean refraction was +3.11 diopters (D) ± 2.89 (SD), the mean axial length was 21.30 ± 1.40 mm, and all eyes had narrow or closed angles. Malignant glaucoma was diagnosed a mean of 5.8 ± 7.1 weeks postoperatively. At diagnosis, the mean refraction was -2.15 ± 2.95 D; the mean ACD, 2.49 ± 0.72 mm; and the mean IOP, 28.3 ± 10.8 mm Hg on a mean of 1.3 ± 1.6 medications. Two eyes responded to cycloplegia, 7 to laser iridozonulohyaloidotomy, and 6 to anterior chamber reformation-IOL pushback; 5 eyes required vitrectomy. Posttreatment, the mean refraction was -0.56 ± 1.07 D; the mean ACD, 3.30 ± 0.50 mm; and the mean IOP, 14.4 ± 4.60 mm Hg on a mean of 1.2 ± 1.4 medications. Cycloplegia was discontinued in 17 eyes. Malignant glaucoma can occur after phacoemulsification and presents with myopic surprise, anterior chamber shallowing and, possibly, elevated IOP. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Malignant pleural mesothelioma: a phase II trial with docetaxel.

PubMed

Vorobiof, D A; Rapoport, B L; Chasen, M R; Abratt, R P; Cronje, N; Fourie, L; McMichael, G; Hacking, D

2002-03-01

Current cytotoxic therapy has been of limited benefit to patients with malignant pleural mesothelioma. Single agent chemotherapy has been extensively evaluated in small series of phase II clinical trials, with disappointing responses. Docetaxel, an effective taxane in the treatment of advanced breast cancer and non-small-cell lung cancer, was administered intravenously at a dose of 100 mg/m2 every 3 weeks to 30 chemotherapy naive patients with malignant pleural mesothelioma in a prospective multi-institutional phase II clinical trial. An objective response rate (partial responses) of 10% was documented. Additionally, 21% of the patients had minor responses (intention-to-treat analysis). Three patients died within 2 weeks post-first cycle of therapy, although only one patient's death was directly attributed to the investigational drug, whilst in the majority of the patients, manageable and treatable toxicities were encountered. In this phase II clinical trial, docetaxel proved to be mildly effective in the treatment of patients with malignant pleural mesothelioma.

THE DIFFERENTIAL ALGORITHM BETWEEN RHEUMATOLOGIC AND MALIGN DISEASES

PubMed Central

Këpuska, Arbnore Batalli; Spahiju, Lidvana; Bejiq, Ramush; Manqestena, Rufadije; Stavileci, Valbona; Ibraimi, Zana

2016-01-01

Objective: The aim of this study is to determine the differential algorithm between rheumatism and malignant diseases. For every pediatrician, to be warned when attending joint pain and child arthralgia and prevent and treat within time malignant diseases. Methods: Our case presented in Pediatric Clinic, was referred by Regional Hospital of Ferizaj with suspected diagnose of Febris Rheumatica and Arthralgia. The main complaint was joint pain. Initially the patient was admitted at Cardiology and Rheumatology department. Then after examinations was referred to Hemato-Oncology department. Hospitalized during the period from 12.12.2014 to 18.01.2015. Results: Bone marrow biopsy as terminal diagnostic tool reviled severe malignant hematologic disease, which was masked by clinical and lab findings as Febris Rheumatica. Conclusion: Arthralgia as one of child’s often complain, should have a special attention paid to, as it might be a warning sign for a lot of diseases. Steroid treatment should not be used before final diagnose of the disease and before rolling out hematologic etiology with peripheral blood smear. PMID:27147926

Febuxostat as a Prophylaxis for Tumor Lysis Syndrome in Children with Hematological Malignancies.

PubMed

Kishimoto, Kenji; Kobayashi, Ryoji; Hori, Daiki; Sano, Hirozumi; Suzuki, Daisuke; Kobayashi, Kunihiko

2017-10-01

The aim of the present study was to determine if febuxostat could prevent tumor lysis syndrome (TLS) in children who received induction chemotherapy for hematologic malignancies. A retrospective analysis was performed in 45 pediatric patients with hematological malignancies who received febuxostat (10 mg daily, n=20) or allopurinol (300 mg/m 2 daily, n=25) as a prophylaxis for TLS. A significant decrease of serum uric acid (UA) level was observed in patients with febuxostat over the first 2 days (6.6±3.8 mg/dl vs. 4.5±2.8 mg/dl, p<0.001). The febuxostat group also showed significant reduction of urinary UA/creatinine ratios during the first two days of treatment (0.98±0.85 vs. 0.51±0.26, p=0.010). No significant differences were observed between febuxostat-treated and allopurinol-treated patients regarding the percent change in serum UA level. Febuxostat had a notable effect in reducing serum UA level in children with hematological malignancies. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells

PubMed Central

Halder, Babli; Singh, Shruti; Thakur, Suman S.

2015-01-01

In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells. PMID:26334881

Malignant biliary disease: percutaneous interventions.

PubMed

Morgan, R A; Adam, A N

2001-09-01

Interventional radiologists have an important role in the management of patients with malignant biliary obstruction. This article describes the techniques for percutaneous biliary drainage, insertion of biliary endoprostheses, and the management of occluded biliary endoprostheses. Most procedures are performed by using fluoroscopic guidance alone. Ultrasound is also a useful modality for guiding biliary drainage, particularly drainage of the left biliary ducts. Patients should be treated by internal drainage if possible. Metallic endoprostheses can be inserted at the time of the initial biliary drainage procedure. Plastic tubes should be inserted a few days after biliary drainage because of their relatively large size compared with metallic stents. Occluded plastic stents should be replaced. Blocked metallic stents should be treated either by placement of additional overlapping metallic stents or by placement of plastic stents within the metallic stent lumen. Copyright 2001 by W.B. Saunders Company

Branding to treat jaundice in India.

PubMed

John, Selva Inita; Balekuduru, Ainash; Zachariah, Uday; Eapen, C E; Chandy, George

2009-01-01

Jaundice is regarded as a mysterious disease rather than a symptom of disease in several parts of India. We describe 8 cases that underwent branding to treat jaundice and subsequently presented to our centre. The causes for jaundice in these patients included a variety of benign and malignant disorders. Our report suggests that despite being literate, strong cultural beliefs lead people to seek potentially harmful procedures like branding to treat jaundice in parts of India.

Boron neutron capture therapy for malignant melanoma: first clinical case report in China

PubMed Central

Yong, Zhong; Song, Zewen; Zhou, Yongmao; Liu, Tong; Zhang, Zizhu; Zhao, Yanzhong; Chen, Yang; Jin, Congjun; Chen, Xiang; Lu, Jianyun; Han, Rui; Li, Pengzhou; Sun, Xulong; Wang, Guohui; Shi, Guangqing; Zhu, Shaihong

2016-01-01

A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals. PMID:28174492

Photodynamic therapy of advanced malignant tumors

NASA Astrophysics Data System (ADS)

Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

1993-03-01

Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

[An unusual risk of liposuction: liposuction of a malignant tumor. About 2 patients].

PubMed

Voulliaume, D; Vasseur, C; Delaporte, T; Delay, E

2003-06-01

Liposuction is a simple and elegant way to treat fatty excess; it has been even used for the treatment of lipomas and some gynecomasties. The goal of this article is to present 2 patients with an unusual complication of this use: the liposuction of a malignant tumor. The first patient consulted following the liposuction of a "gynecomasty", which was in fact a breast cancer. The second was treated by liposuction for an ankle "lipoma"; it proved to be a liposarcoma. In order to avoid liposuction and dissemination of a malignant tumor, the pre-operative investigations have to search clinical peculiarities evoking the diagnosis: an unilateral "gynecomasty", irregular, hard or painless, in a 50-years-old patient, must incite the surgeon to perform a classical excision, just as a recurrent "lipoma", deeply located, voluminous or quickly extensive, situated on the limbs or in the humeroscapular area. Paraclinic investigations may be indicated; doubtful cases must be right away rejected for liposuction, and treated by a surgical excision with strict safety margins and complete anatomopathologic examination of the lesion. Liposuction has become a very useful technique for the plastic surgeon; however, we must not forget, despite of its many advantages the risk for dissemination of an unknown malignant tumor. Every surgeon must keep it in mind and prefer a surgical removal in atypical cases.

The treatment of pseudoaneurysms with flow diverters after malignant otitis externa.

PubMed

Németh, Tamás; Szakács, László; Bella, Zsolt; Majoros, Valéria; Barzó, Pál; Vörös, Erika

2017-12-01

Background We report a case of bilateral malignant otitis externa complicated with bilateral petrous internal carotid artery pseudoaneurysms and their successful treatment with a flow diverter. Case report A 68-year-old woman with serious complications of type II diabetes mellitus had malignant otitis externa on the right side. She was treated with combined antibiotic therapy and underwent mastoidectomy for mastoiditis. She presented at our hospital with acute hemorrhage from the right external auditory canal. The emergency computed tomography (CT) angiography revealed a multiobulated pseudoaneurysm at the petrous segment of the right internal carotid artery. The pseudoaneurysm was treated with a 5 × 40-mm Surpass flow diverter. Three months later, she developed a malignant external otitis on the left side. As the infection progressed, a left-sided mastoiditis, a brain abscess, and a pseudoaneurysm at the petrous segment of the left internal carotid artery developed. The pseudoaneurysm caused bleeding from the left ear, and was treated with a 5 × 50-mm Surpass flow diverter. No recurrent bleeding was observed. Four months later, a follow-up angiography showed complete occlusion of the pseudoaneurysm on the left side, but a residual aneurysm could be detected on the right side. One year after the first intervention, the follow-up CT and magnetic resonance angiography revealed the complete occlusion of the aneurysms bilaterally. Conclusion The use of a flow diverter appears to be an efficient and safe method to occlude carotid pseudoaneurysms even in an inflammatory milieu.

Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies

PubMed Central

Firor, Amelia E.; Pinz, Kevin G.; Jares, Alexander; Liu, Hua; Salman, Huda; Golightly, Marc; Lan, Fengshuo; Jiang, Xun; Ma, Yupo

2016-01-01

Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to treat, very aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and dismal patient outlook. Despite the fact that PTCLs comprise the majority of T-cell malignancies, the standard of care is poorly established. Chimeric antigen receptor (CAR) immunotherapy has shown in B-cell malignancies to be an effective curative option and this extends promise into treating T-cell malignancies. Because PTCLS frequently develop from mature T-cells, CD3 is similarly strongly and uniformly expressed in many PTCL malignancies, with expression specific to the hematological compartment thus making it an attractive target for CAR design. We engineered a robust 3rd generation anti-CD3 CAR construct (CD3CAR) into an NK cell line (NK-92). We found that CD3CAR NK-92 cells specifically and potently lysed diverse CD3+ human PTCL primary samples as well as T-cell leukemia cells lines ex vivo. Furthermore, CD3CAR NK-92 cells effectively controlled and suppressed Jurkat tumor cell growth in vivo and significantly prolonged survival. In this study, we present the CAR directed targeting of a novel target - CD3 using CAR modified NK-92 cells with an emphasis on efficacy, specificity, and potential for new therapeutic approaches that could improve the current standard of care for PTCLs. PMID:27494836

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

PubMed Central

Law, Man Fai; Ho, Rita; Cheung, Carmen K M; Tam, Lydia H P; Ma, Karen; So, Kent C Y; Ip, Bonaventure; So, Jacqueline; Lai, Jennifer; Ng, Joyce; Tam, Tommy H C

2016-01-01

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although

Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

PubMed Central

Dénes, Judit; Swords, Francesca; Rattenberry, Eleanor; Stals, Karen; Owens, Martina; Cranston, Treena; Xekouki, Paraskevi; Moran, Linda; Kumar, Ajith; Wassif, Christopher; Fersht, Naomi; Baldeweg, Stephanie E.; Morris, Damian; Lightman, Stafford; Agha, Amar; Rees, Aled; Grieve, Joan; Powell, Michael; Boguszewski, Cesar Luiz; Dutta, Pinaki; Thakker, Rajesh V.; Srirangalingam, Umasuthan; Thompson, Chris J.; Druce, Maralyn; Higham, Claire; Davis, Julian; Eeles, Rosalind; Stevenson, Mark; O'Sullivan, Brendan; Taniere, Phillipe; Skordilis, Kassiani; Gabrovska, Plamena; Barlier, Anne; Webb, Susan M.; Aulinas, Anna; Drake, William M.; Bevan, John S.; Preda, Cristina; Dalantaeva, Nadezhda; Ribeiro-Oliveira, Antônio; Garcia, Isabel Tena; Yordanova, Galina; Iotova, Violeta; Evanson, Jane; Grossman, Ashley B.; Trouillas, Jacqueline; Ellard, Sian; Stratakis, Constantine A.; Maher, Eamonn R.; Roncaroli, Federico

2015-01-01

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma. PMID:25494863

Cutaneous malignant melanoma in children and adolescents treated in pediatric oncology units.

PubMed

Réguerre, Yves; Vittaz, Marie; Orbach, Daniel; Robert, Caroline; Bodemer, Christine; Mateus, Christina; Plantaz, Dominique; Plouvier, Emmanuel; Lutz, Patrick; Rakotonjanahary, Josue; Fraitag, Sylvie; Martin, Ludovic

2016-11-01

Recent progress in the understanding of tumor biology and new targeted therapies has led to improved survival in adults with malignant melanoma (MM). MM is rare in children, especially before puberty. We report here our experience with pediatric patients with MM, describe the clinical presentation, treatment and evolution, and compare prepubescent and postpubescent disease. A retrospective, descriptive, national multicenter study was undertaken of 52 cases of MM in children and adolescents. Demographic, histopathology, treatment evolution data, and survival distributions are described. Median age was 15 years (5-18). The tumors were often amelanotic (45%) and raised (83%), and Breslow thickness was greater than 4 mm in 35% of cases. Histological examination showed superficial spreading (n = 16) or spitzoid (n = 16) or nodular (n = 9) pattern. Twelve children (23%) were less than 10 years of age. The spitzoid histotype was more frequent in prepubescent children (seven of 12). Seventeen patients relapsed, of whom four had skin lesions initially diagnosed as benign. Ten patients died after relapse. Five-year event-free survival and overall survival were 62.7% (95% confidence interval [CI]: 45.3-76) and 75.5% (95% CI: 56.8-87.1), respectively. MM appears to be different in prepubescent children, of whom most had a spitzoid histotype. Diagnosis can be difficult, leading to delay in treatment. New biological tools to identify targets for treatment in MM and to differentiate spitzoid melanomas from Spitz nevi now exist. As effective targeted therapies are now available, we recommend requesting biological examination of all melanocyte-derived skin lesions in children that could be malignant. © 2016 Wiley Periodicals, Inc.

Correlation between fertility drugs use and malignant melanoma incidence: the state of the art.

PubMed

Tomao, Federica; Papa, Anselmo; Lo Russo, Giuseppe; Zuber, Sara; Spinelli, Gian Paolo; Rossi, Luigi; Caruso, Davide; Prinzi, Natalie; Stati, Valeria; Benedetti Panici, Pierluigi; Tomao, Silverio

2014-09-01

The relationship between fertility, reproductive hormones, and risk of malignant melanoma has acquired much interest in recent years. Melanocytes are hormonally responsive cells, and some in vitro studies demonstrated that estrogen hormones stimulate the growth of melanocytes. Moreover, estrogen receptors have been identified in melanoma cells, as well as in melanocytic nevi and in normal skin. Some evidences suggest a possible link between fertility treatments and the increased risk of malignant melanoma. This article addresses this association through a scrupulous search of the literature published thus far. The aim of this review is to determine the incidence of malignant melanoma in women treated with fertility drugs and to examine if the exposure to fertility treatments really increases the risk of malignant melanoma. In particular, our analysis focused on the different types of drugs and different treatment schedules used. Finally, this study provides additional insights regarding the long-term relationships between fertility drugs and the risk of malignant melanoma.

Update on the management of unusual neuroendocrine tumors: pheochromocytoma and paraganglioma, medullary thyroid cancer and adrenocortical carcinoma.

PubMed

Strosberg, Jonathan R

2013-02-01

Pheochromocytomas, paragangliomas, and medullary thyroid carcinomas (MTCs) originate in cells that share a common neuroectodermal origin. Like other neuroendocrine neoplasms, they are characterized by a propensity to secrete amines (epinephrine and norepinephrine) and peptide hormones (calcitonin). Improved understanding of underlying molecular pathways, such as mutations of the RET (rearranged during transfection) proto-oncogene, has led to new rational targeted therapies. Adrenocortical carcinomas (ACCs) originate in the steroid hormone-producing adrenal cortex. While tumors of the adrenal cortex are not, strictly speaking, part the "diffuse neuroendocrine system," they are often included in neuroendocrine tumor guidelines due to their orphan status. In this update on management of unusual neuroendocrine tumors, we review the biology and treatment of these rare neoplasms. Copyright © 2013 Elsevier Inc. All rights reserved.

Concurrent Chemotherapy of Malignant Glioma in Rats by Using Multidrug-Loaded Biodegradable Nanofibrous Membranes

NASA Astrophysics Data System (ADS)

Tseng, Yuan-Yun; Huang, Yin-Chen; Yang, Tao-Chieh; Yang, Shun-Tai; Liu, Shou-Cheng; Chang, Tzu-Min; Kau, Yi-Chuan; Liu, Shih-Jung

2016-07-01

Glioblastoma multiforme has a poor prognosis and is highly chemoresistant. In this study, we implanted biodegradable 1,3-bis[2-chloroethyl]-1-nitroso-urea-, irinotecan-, and cisplatin-eluting poly[(d,l)-lactide-co-glycolide] (BIC/PLGA) and virgin nanofibrous membranes on the brain surface of C6 glioma-bearing rats in concurrent and virgin groups, respectively. The concentrations of all applied drugs were significantly higher in the brain than in the blood for more than 8 weeks in all studied rats. Tumor growth was more rapid in the vehicle-treated group, and tumor volumes were significantly higher in the vehicle-treated group. Moreover, the average survival time was significantly shorter in the vehicle-treated group (P = 0.026), and the BIC/PLGA nanofibrous membranes significantly reduced the risk of mortality (P < 0.001). Furthermore, the results suggested that the BIC/PLGA nanofibers reduced the malignancy of C6 glioma. The experimental findings indicate that the multianticancer drug (i.e., BIC)-eluting PLGA nanofibers are favorable candidates for treating malignant glioma.

Concurrent Chemotherapy of Malignant Glioma in Rats by Using Multidrug-Loaded Biodegradable Nanofibrous Membranes

PubMed Central

Tseng, Yuan-Yun; Huang, Yin-Chen; Yang, Tao-Chieh; Yang, Shun-Tai; Liu, Shou-Cheng; Chang, Tzu-Min; Kau, Yi-Chuan; Liu, Shih-Jung

2016-01-01

Glioblastoma multiforme has a poor prognosis and is highly chemoresistant. In this study, we implanted biodegradable 1,3-bis[2-chloroethyl]-1-nitroso-urea-, irinotecan-, and cisplatin-eluting poly[(d,l)-lactide-co-glycolide] (BIC/PLGA) and virgin nanofibrous membranes on the brain surface of C6 glioma-bearing rats in concurrent and virgin groups, respectively. The concentrations of all applied drugs were significantly higher in the brain than in the blood for more than 8 weeks in all studied rats. Tumor growth was more rapid in the vehicle-treated group, and tumor volumes were significantly higher in the vehicle-treated group. Moreover, the average survival time was significantly shorter in the vehicle-treated group (P = 0.026), and the BIC/PLGA nanofibrous membranes significantly reduced the risk of mortality (P < 0.001). Furthermore, the results suggested that the BIC/PLGA nanofibers reduced the malignancy of C6 glioma. The experimental findings indicate that the multianticancer drug (i.e., BIC)-eluting PLGA nanofibers are favorable candidates for treating malignant glioma. PMID:27471070

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

ClinicalTrials.gov

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

The treatment of malignant glaucoma in nanophthalmos: a case report.

PubMed

Wang, Jie; Du, Ergang; Tang, Jinfei

2018-02-23

The management of eyes with nanophthalmos is a dilemma for ophthalmologists due to various complications, especial the eye with malignant glaucoma. We report a case of effective treatment for malignant glaucoma in nanophthalmos. An 82-year-old man was performed phacoemulsification in the right eye with normal ocular pressure and nanophthalmos. The surgery was uneventful: an intraocular lens (IOL) was placed and centered in the capsular bag. 2 months later, the patient presented with malignant glaucoma, and the intraocular pressure fluctuated between 18.6 mmHg and 30.8 mmHg with antiglaucoma medications. The patient did not respond to surgical peripheral iridotomy and goniosynechialysis. Then a single treatment with laser peripheral lens posterior capsulotomy and vitreous anterior membranectomy was performed. The intraocular pressure normalized, and the anterior chamber deepened within 24 h. The patient's condition remained stable for 9 months with no further treatment, and his Snellen corrected distance visual acuity was 20/50. The left eye of this patient was treated by combined surgery including phacoemulsification, IOL implantation, anterior vitrectomy, surgical peripheral iridotomy (PI), and goniosynechialysis. No intraoperative or postoperative complications were observed. This case suggests that it is essential to choose a suitable treatment for nanophthalmos patients to deal with malignant glaucoma and to reduce the incidence of malignant glaucoma.

HIV-Associated Urogenital Malignancies.

PubMed

Hentrich, Marcus; Pfister, David

2017-01-01

Non-AIDS-defining malignancies (NADM) are a leading cause of morbidity and mortality for HIV-infected subjects. The risk of testicular germ cell cancer (GCC) and renal cell cancer is slightly increased in the setting of HIV, whereas there is a slightly decreased risk of prostate cancer and bladder cancer. As in industrialized countries the majority of people living with HIV are men, and people aged 55 and older now account for more than a quarter of persons living with HIV, both testis and prostate cancer are assumed to occur with increased frequency in HIV-infected subjects. Overall, treatments should be the same as in HIV-negative patients with urogenital malignancies. Since the introduction of combination antiretroviral therapy (cART) the outcome appears to have improved due to a decrease in HIV-related deaths. HIV-infected men who are treated with standard therapies for GCC now have a similar cancer-free survival compared with their HIV-negative counterparts. Screening and treatment for prostate cancer should follow recommendations established for HIV-negative men. During radio- or chemotherapy patients should receive concurrent cART but the drug-drug interaction potential must be taken into account. © 2017 S. Karger GmbH, Freiburg.

Adoptive immunotherapy for B-cell malignancies with autologous chimeric antigen receptor modified tumor targeted T cells.

PubMed

Park, Jae H; Brentjens, Renier J

2010-04-01

Chemotherapy-resistant B-cell hematologic malignancies may be cured with allogeneic hematopoietic stem cell transplantation (HSCT), demonstrating the potential susceptibility of these tumors to donor T-cell mediated immune responses. However, high rates of transplant-related morbidity and mortality limit this approach. For this reason, there is an urgent need for less-toxic forms of immune-based cellular therapy to treat these malignancies. Adoptive transfer of autologous T cells genetically modified to express chimeric antigen receptors (CARs) targeted to specific tumor-associated antigens represents an attractive means of overcoming the limitations of conventional HSCT. To this end, investigators have generated CARs targeted to various antigens expressed by B-cell malignancies, optimized the design of these CARs to enhance receptor mediated T cell signaling, and demonstrated significant anti-tumor efficacy of the resulting CAR modified T cells both in vitro and in vivo mouse tumor models. These encouraging preclinical data have justified the translation of this approach to the clinical setting with currently 12 open clinical trials and one completed clinical trial treating various B-cell malignancies utilizing CAR modified T cells targeted to either the CD19 or CD20 B-cell specific antigens.

Second malignancies after multiple myeloma: from 1960s to 2010s

PubMed Central

Thomas, Anish; Mailankody, Sham; Korde, Neha; Kristinsson, Sigurdur Y.; Turesson, Ingemar

2012-01-01

Based on small numbers, recent reports from 3 randomized trials have consistently demonstrated more hematologic malignancies in patients treated with lenalidomide as maintenance (vs placebo). This fact has prompted concern and highlighted the association between multiple myeloma and second malignancies. Furthermore, an excess of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after multiple myeloma has been known for over 4 decades. Most prior studies have been restricted because of small numbers of patients, inadequate follow-up, and limitations of ascertainment of second malignancies. Although the underlying biologic mechanisms of AML/MDS after multiple myeloma are unknown, treatment-related factors are presumed to be responsible. Recently, an excess risk of AML/MDS was found among 5652 patients with IgG/IgA (but not IgM) monoclonal gammopathy of undetermined significance, supporting a role for disease-related factors. Furthermore, there is evidence to suggest that polymorphisms in germline genes may contribute to a person's susceptibility to subsequent cancers, whereas the potential influence of environmental and behavioral factors remains poorly understood. This review discusses current knowledge regarding second malignancies after multiple myeloma and gives future directions for efforts designed to characterize underlying biologic mechanisms, with the goal to maximize survival and minimize the risk for second malignancies for individual patients. PMID:22310913

Immunotherapy Approaches for Malignant Glioma From 2007 to 2009

PubMed Central

Sampson, John H.

2012-01-01

Malignant glioma is a deadly disease for which there have been few therapeutic advances over the past century. Although previous treatments were largely unsuccessful, glioma may be an ideal target for immune-based therapy. Recently, translational research led to several clinical trials based on tumor immunotherapy to treat patients with malignant glioma. Here we review 17 recent glioma immunotherapy clinical trials, published over the past 3 years. Various approaches were used, including passive transfer of naked and radiolabeled antibodies, tumor antigen-specific peptide immunization, and the use of patient tumor cells with or without dendritic cells as vaccines. We compare and discuss the current state of the art of clinical immunotherapy treatment, as well as its limited successes, pitfalls, and future potential. PMID:20424975

The role of CCN family genes in haematological malignancies.

PubMed

Wells, J E; Howlett, M; Cheung, L C; Kees, Ursula R

2015-09-01

Haematological malignancies, although a broad range of specific disease types, continue to show considerable overlap in classification, and patients are treated using similar chemotherapy regimes. In this review we look at the role of the CCN family of matricellular proteins and indicate their role in nine haematological malignancies including both myeloid and lymphoid neoplasms. The potential for further haematological neoplasms with CCN family associations is argued by summarising the demonstrated role of CCN family genes in the differentiation of haematopoietic stem cells (HSC) and mesenchymal stem cells. The expanding field of knowledge encompassing CCN family genes and cancers of the HSC-lineage highlights the importance of extracellular matrix-interactions in both normal physiology and tumorigenesis of the blood, bone marrow and lymph nodes.

Giant hidradenocarcinoma: a report of malignant transformation from nodular hidradenoma.

PubMed

Lim, S C; Lee, M J; Lee, M S; Kee, K H; Suh, C H

1998-10-01

A giant hidradenocarcinoma presented by a 75-year-old female is reported. The patient had a malignant transformation within a nodular hidradenoma involving the right postauricular area, which was treated by mass removal and a right radical neck dissection with a free-flap covering. Malignant hidradenocarcinoma is the least common adnexal tumor of uncertain origin. They are usually malignant from their inception, but some develop from a benign counterpart. To the authors' knowledge, only three cases have been reported previously. Two histologically distinct components were seen in this tumor: (i) typical nodular hidradenoma, which constituted a small part of the tumor; and (ii) carcinoma with areas of transition. The secretory cells of hidradenocarcinoma showed decapitation secretion on light and electron microscopic observations, which is evidence of apocrine differentiation. Histologically, this case was concluded as a hidradenocarcinoma arising from a long-standing nodular hidradenoma. A literature review is presented and the histological, immunohistochemical and ultrastructural features are described.

Passive antibody-mediated immunotherapy for the treatment of malignant gliomas.

PubMed

Mitra, Siddhartha; Li, Gordon; Harsh, Griffith R

2010-01-01

Despite advances in understanding the molecular mechanisms of brain cancer, the outcome of patients with malignant gliomas treated according to the current standard of care remains poor. Novel therapies are needed, and immunotherapy has emerged with great promise. The diffuse infiltration of malignant gliomas is a major challenge to effective treatment; immunotherapy has the advantage of accessing the entire brain with specificity for tumor cells. Therapeutic immune approaches include cytokine therapy, passive immunotherapy, and active immunotherapy. Cytokine therapy involves the administration of immunomodulatory cytokines to activate the immune system. Active immunotherapy is the generation or augmentation of an immune response, typically by vaccination against tumor antigens. Passive immunotherapy connotes either adoptive therapy, in which tumor-specific immune cells are expanded ex vivo and reintroduced into the patient, or passive antibody-mediated therapy. In this article, the authors discuss the preclinical and clinical studies that have used passive antibody-mediated immunotherapy, otherwise known as serotherapy, for the treatment of malignant gliomas.

Results of treatment of choroidal malignant melanoma with high-dose-rate strontium-90 brachytherapy. A retrospective study of 46 patients treated between 1983 and 1995.

PubMed

Missotten, L; Dirven, W; Van der Schueren, A; Leys, A; De Meester, G; Van Limbergen, E

1998-03-01

We review the results of treatment of small to medium-sized choroidal malignant melanomas after high-dose-rate brachytherapy with a strontium-90 applicator. The applicator is positioned against the sclera using an afterloading technique. Brachytherapy is completed in a single session lasting 2-4 h with the patient under local anaesthesia. From September 1983 until March 1995, 46 eyes were treated in this way. Most tumours were 7-11 mm in diameter (range from 4.5-15 mm) with a mean height of approximately 3 mm (range from 1.5-7 mm). Follow-up ranged from 6 months to 12 years (mean 49 months). Thirty of the 46 eyes had at the final evaluation a nonevolutive scar (20 of these after a single application, the others with some additional treatment). In 13 eyes the tumours were in involution but their complete destruction was not yet certain, and 3 eyes were enucleated for local recurrence. Three patients developed systemic metastases. No radiogenic complications were noticed. Strontium-90 brachytherapy is a valuable and safe treatment technique for small to medium-sized choroidal malignant melanomas. In addition the use of a strontium-90 applicator is inexpensive thanks to this element's long half-life and the short application time.

Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

ClinicalTrials.gov

2018-05-23

Lymphoma; Metastatic Malignant Solid Neoplasm; Metastatic Melanoma; Metastatic Renal Cell Cancer; Recurrent Bladder Carcinoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Renal Cell Carcinoma; Stage III Bladder Cancer; Stage III Lymphoma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Renal Cell Cancer; Stage III Skin Melanoma; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Lymphoma; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IVA Bladder Cancer; Stage IVB Bladder Cancer; Unresectable Head and Neck Squamous Cell Carcinoma; Unresectable Solid Neoplasm

Second malignant neoplasms in childhood cancer survivors in a tertiary paediatric oncology centre in Hong Kong, China.

PubMed

Sun, Wai-Fun; Cheng, Frankie Wai-Tsoi; Lee, Vincent; Leung, Wing-Kwan; Shing, Ming-Kong; Yuen, Patrick Man-Pan; Li, Chi-Kong

2011-11-01

Childhood cancer survivors were at risk of development of second malignant neoplasms. The aim of this study is to evaluate the incidence, risk factors and outcome of second malignant neoplasms in childhood cancer survivors in a tertiary paediatric oncology centre in Hong Kong, China. We performed a retrospective review of patients with childhood cancer treated in Children's Cancer Centre in Prince of Wales Hospital, Hong Kong, China between May 1984 and June 2009. Case records of patients who developed second malignant neoplasms were reviewed. Totally 1374 new cases aged less than 21-year old were treated in our centre in this 25-year study period. Twelve cases developed second malignant neoplasms with 10-year and 20-year cumulative incidence of 1.3% (95% confidence interval 0.3% - 2.3%) and 2.9% (95% confidence interval 1.1% - 4.7%) respectively. Another 4 cases were referred to us from other centres for the management of second malignant neoplasms. In this cohort of 16 children with second malignant neoplasms, the most frequent second malignant neoplasms were acute leukemia or myelodysplastic syndrome (n = 6) and central nervous system tumor (n = 4). Median interval between diagnosis of primary and second malignant neoplasms was 7.4 years (range 2.1 - 13.3 years). Eight patients developed second solid tumor within the previous irradiated field. Radiotherapy significantly increased the risk of development of second solid tumor in patients with acute lymphoblastic leukemia (P = 0.027). Seven out of 16 patients who developed second malignant neoplasms had a family history of cancer among the first or second-degree relatives. Nine patients died of progression of second malignant neoplasms, mainly resulted from second central nervous system tumor and osteosarcoma. Cumulative incidence of second cancer in our centre was comparable to western countries. Radiotherapy was associated with second solid tumour among patients with acute lymphoblastic leukemia. Patients who

Malignant Gastroduodenal Obstruction: Treatment with Self-Expanding Uncovered Wallstent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gutzeit, Andreas, E-mail: Andreas.Gutzeit@ksw.ch; Binkert, Christoph A.; Schoch, Eric

2009-01-15

Purpose: To retrospectively evaluate the clinical effectiveness of a self-expanding uncovered Wallstent in patients with malignant gastroduodenal obstruction. Materials and Methods: Under combined endoscopic and fluoroscopic guidance, 29 patients with a malignant gastroduodenal stenosis were treated with a self-expanding uncovered metallic Wallstent. A dysphagia score was assessed before and after the intervention to measure the success of this palliative therapy. The dysphagia score ranged between grade 0 to grade 4: grade 0 = able to tolerate solid food, grade 1 = able to tolerate soft food, grade 2 = able to tolerate thick liquids, grade 3 = able to toleratemore » water or clear fluids, and grade 4 = unable to tolerate anything perorally. Stent patency and patients survival rates were calculated. Results: The insertion of the gastroduodenal stent was technically successful in 28 patients (96.5%). After stenting, 25 patients (86.2%) showed clinical improvement by at least one score point. During follow-up, 22 (78.5%) of 28 patients showed no stent occlusion until death and did not have to undergo any further intervention. In six patients (20.6%), all of whom were treated with secondary stent insertions, occlusion with tumor ingrowth and/or overgrowth was observed after the intervention. The median period of primary stent patency in our study was 240 days. Conclusion: Placement of an uncovered Wallstent is clinically effective in patients with malignant gastroduodenal obstruction. Stent placement is associated with high technical success, good palliation effect, and high durability of stent function.« less

Hypofractionated stereotactic radiotherapy in combination with bevacizumab or fotemustine for patients with progressive malignant gliomas.

PubMed

Minniti, Giuseppe; Agolli, Linda; Falco, Teresa; Scaringi, Claudia; Lanzetta, Gaetano; Caporello, Paola; Osti, Mattia Falchetto; Esposito, Vincenzo; Enrici, Riccardo Maurizi

2015-05-01

To evaluate the efficacy of hypofractionated stereotactic radiotherapy performed as reirradiation in combination with fotemustine or bevacizumab as salvage treatment in patients with recurrent malignant glioma. Between May 2006 and December 2013, 54 patients with recurrent malignant glioma received hypofractionated stereotactic radiotherapy (HSRT, 25 Gy in 5-Gy fractions) plus either fotemustine or bevacizumab at University of Rome Sapienza, Sant'Andrea Hospital. All patients had Karnofsky performance score (KPS) ≥ 60 and were previously treated with standard chemoradiotherapy. Forty-two patients had a GBM and 12 patients had an anaplastic astrocytoma (AA). The median overall survival (OS) time and 12-month OS rates after HSRT was 11 months and 30 % for patients treated with HSRT plus bevacizumab and 8.3 months and 5 % for those treated with HSRT plus fotemustine (p = 0.01). Median PFS times were 4 and 6 months for patients treated with HSRT plus fotemustine or bevacizumab, respectively (p = 0.01). KPS > 70 (p = 0.04), AA histology, and the treatment with bevacizumab were independent favourable prognostic factors for OS. In general, both treatments were well tolerated with relatively low treatment-related toxicity. HSRT combined with bevacizumab or fotemustine may represent a feasible treatment option for patients with progressive malignant gliomas, although most of the tumors recur in a few months. Efficacy of bevacizumab or alkylating agents in combination with different radiation schedules needs to be evaluated in prospective studies.

Palliative Management of Malignant Bowel Obstruction in Terminally Ill Patient

PubMed Central

Thaker, Darshit A; Stafford, Bruce C; Gaffney, Luke S

2010-01-01

Mr. P was a 57-year-old man who presented with symptoms of bowel obstruction in the setting of a known metastatic pancreatic cancer. Diagnosis of malignant bowel obstruction was made clinically and radiologically and he was treated conservatively (non-operatively)with octreotide, metoclopromide and dexamethasone, which provided good control over symptoms and allowed him to have quality time with family until he died few weeks later with liver failure. Bowel obstruction in patients with abdominal malignancy requires careful assessment. The patient and family should always be involved in decision making. The ultimate goals of palliative care (symptom management, quality of life and dignity of death) should never be forgotten during decision making for any patient. PMID:21811356

Application of a protocol for magnetic resonance spectroscopy of adrenal glands: an experiment with over 100 cases.

PubMed

Melo, Homero José de Farias E; Goldman, Suzan M; Szejnfeld, Jacob; Faria, Juliano F; Huayllas, Martha K P; Andreoni, Cássio; Kater, Cláudio E

2014-01-01

To evaluate a protocol for two-dimensional (2D) hydrogen proton (1H) magnetic resonance spectroscopy (MRS) (Siemens Medical Systems; Erlangen, Germany) in the detection of adrenal nodules and differentiation between benign and malignant masses (adenomas, pheochromocytomas, carcinomas and metastases). A total of 118 patients (36 men; 82 women) (mean age: 57.3 ± 13.3 years) presenting with 138 adrenal nodules/masses were prospectively assessed. A multivoxel system was utilized with a 2D point-resolved spectroscopy/chemical shift imaging sequence. The following ratios were calculated: choline (Cho)/creatine (Cr), 4.0-4.3/Cr, lipid (Lip)/Cr, Cho/Lip and lactate (Lac)/Cr. 2D-1H-MRS was successful in 123 (89.13%) lesions. Sensitivity and specificity values observed for the ratios and cutoff points were the following: Cho/Cr ≥ 1.2, 100% sensitivity, 98.2% specificity (differences between adenomas/pheochromocytomas and carcinomas/ metastases); 4.0-4.3 ppm/Cr ≥ 1.5, 92.3% sensitivity, 96.9% specificity (differences between carcinomas/pheochromocytomas and adenomas/metastases); Lac/Cr ≤ -7.449, 90.9% sensitivity and 77.8% specificity (differences between pheochromocytomas and carcinomas/adenomas). Information provided by 2D-1H-MRS were effective and allowed for the differentiation between adrenal masses and nodules in most cases of lesions with > 1.0 cm in diameter.

Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beadle, Beth M.; Guadagnolo, B. Ashleigh; Ballo, Matthew T.

2009-04-01

Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) hadmore » sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.« less

Subsequent malignancies associated with carcinoma of the uterine cervix: including an analysis of the effect of patient and treatment parameters on incidence and sites of metachronous malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kapp, D.S.; Fischer, D.; Grady, K.J.

1982-02-01

The incidence and sites of metachronous malignancies were retrospectively determined from the records of 763 patients seen at Yale University Medical Center and affiliated hospitals with previously untreated, invasive carcinoma of the uterine cervix from 1953-1972. These patients were treated predominantly with radiation therapy; follow-up status was known for periods of 5-25 years or until time of death in over 96% of the patients. Forty-four patients had second malignancies noted at least 6 months after the initial cervical cancer was diagnosed. The expected incidence of second malignancies was determined from the Connecticut State Tumor Registry data controlling for year ofmore » diagnosis of the cervical cancer, patient age, sex, and time at risk (person-years exposure). To correct for any error in estimation of second malignancies introduced by the existence of a latency period for the development of a second cancer, the expected incidence of malignancies was also computed for 5-year time intervals following the cervical cancer. No significant increase in second malignancies was found (observed/expected-44/36) for the entire follow-up period nor for any individual 5-year interval. However, a statistically significant increase in lung cancer and vulva-vaginal cancer was noted and a significant decrease in breast cancer was observed. Cox regression analyses were performed to study the effect of total radium exposure and total external beam treatment, adjusting for other factors. No statistically significant increased risks were found.« less

Abdominal aortic aneurysm with periaortic malignant lymphoma differentiated from aneurysmal rupture by clinical presentation and magnetic resonance imaging.

PubMed

Kamata, Sokichi; Itou, Yoshito; Idoguchi, Koji; Imakita, Masami; Funatsu, Toshihiro; Yagihara, Toshikatsu

2018-06-01

Abdominal aortic aneurysm (AAA) associated with periaortic malignant lymphoma is difficult to differentiate from aneurysmal rupture because of similarities in their clinical presentation and appearance on computed tomography images. We here report a case of AAA associated with periaortic malignant lymphoma diagnosed preoperatively with an absence of typical symptoms, showing that AAA in periaortic malignant lymphoma can present without any clinical correlates. Magnetic resonance imaging was used to confirm the diagnosis. The patient was treated by endovascular repair, which may be safer and more effective than open surgery for AAA associated with malignant lymphoma because of the tight adhesion between the aneurysm and the lymphoid tissue.

A Somatic HIF2α Mutation-Induced Multiple and Recurrent Pheochromocytoma/Paraganglioma with Polycythemia: Clinical Study with Literature Review.

PubMed

Liu, Qiuli; Wang, Yan; Tong, Dali; Liu, Gaolei; Yuan, Wenqiang; Zhang, Jun; Ye, Jin; Zhang, Yao; Yuan, Gang; Feng, Qingxing; Zhang, Dianzheng; Jiang, Jun

2017-03-01

A syndrome known as pheochromocytomas (PCC)/paragangliomas (PGL) and polycythemia resulted from gain-of-function mutation of hypoxia-inducible factor 2α (HIF2α) has been reported recently. However, clinical features of this syndrome vary from patient to patient. In our study, we described the clinical features of the patient within 15-year follow-up with a literature review. The patient presented with "red face" since childhood and was diagnosed with polycythemia and pheochromocytoma in 2000, and then, tumor was removed at his age of 27 (year 2000). However, 13 years later (2013), he was diagnosed with multiple paragangliomas. Moreover, 2 years later (2015), another two paragangaliomas were also confirmed. Genetic analysis of hereditary PCC/PGL-related genes was conducted. A somatic heterozygous missense mutation of HIF2α (c.1589C>T) was identified at exon 12, which is responsible for the elevated levels of HIF2α and erythropoietin (EPO) and subsequent development of paragangaliomas. However, this mutation was only found in the tumors from three different areas, not in the blood. So far, 13 cases of PCC/PGL with polycythemia have been reported. Among them, somatic mutations of HIF2α at exon 12 are responsible for 12 cases, and only 1 case was caused by germline mutation of HIF2α at exon 9. The HIF2α mutation-induced polycythemia with PCC/PGL is a rare syndrome with no treatment for cure. Comprehensive therapies for this disease include removal of the tumors and intermittent phlebotomies; administration of medications to control blood pressure and to prevent complications or death resulted from high concentration of red blood cell (RBC). Genetic test is strongly recommended for patients with early onset of polycythemia and multiple/recurrent PCC/PGL.

p.Arg82Leu von Hippel-Lindau (VHL) Gene Mutation among Three Members of a Family with Familial Bilateral Pheochromocytoma in India: Molecular Analysis and In Silico Characterization

PubMed Central

John, Anulekha Mary; C, George Priya Doss; Ebenazer, Andrew; Seshadri, Mandalam Subramaniam; Nair, Aravindan; Rajaratnam, Simon; Pai, Rekha

2013-01-01

Various missense mutations in the VHL gene have been reported among patients with familial bilateral pheochromocytoma. However, the p.Arg82Leu mutation in the VHL gene described here among patients with familial bilateral pheochromocytoma, has never been reported previously in a germline configuration. Interestingly, long-term follow-up of these patients indicated that the mutation might have had little impact on the normal function of the VHL gene, since all of them have remained asymptomatic. We further attempted to correlate this information with the results obtained by in silico analysis of this mutation using SIFT, PhD-SNP SVM profile, MutPred, PolyPhen2, and SNPs&GO prediction tools. To gain, new mechanistic insight into the structural effect, we mapped the mutation on to 3D structure (PDB ID 1LM8). Further, we analyzed the structural level changes in time scale level with respect to native and mutant protein complexes by using 12 ns molecular dynamics simulation method. Though these methods predict the mutation to have a pathogenic potential, it remains to be seen if these patients will eventually develop symptomatic disease. PMID:23626751

Do patients have any special medical or rehabilitation difficulties after a craniectomy for malignant cerebral infarction during their hospitalization in a physical medicine and rehabilitation department?

PubMed

Mandon, L; Bradaï, N; Guettard, E; Bonan, I; Vahedi, K; Bousser, M G; Yelnik, A

2010-03-01

To observe whether medical complications, the evolution of neurological disorders and dependence and/or the discharge destinations are different for patients treated by craniectomy for malignant cerebral infarction in the middle cerebral artery compared to patients treated medically for severe or malignant cerebral infarction in the same cerebral territory, during their hospitalization in a physical medicine and rehabilitation department. This retrospective study compared patients treated by craniectomy for malignant cerebral infarction in the middle cerebral artery and patients treated medically for severe or malignant cerebral infarction in the same cerebral territory. Patients were paired according to age, lesion side and hospitalization period. Twelve patients treated by craniectomy (age 43+/-10.44) were paired with 12 patients treated medically (age 49+/-7.66). The two groups were comparable in terms of general undesirable medical events. The medical events related to craniectomy are described. The evolution of patient deficiencies, the length of the hospital stay (194+/-118.93 days vs 152+/-94.64 days), the Functional Independence Measure at discharge (87+/-21.28 vs 95+/-22.19) and the number of direct home discharges (7 vs 9) did not significantly differ between groups. No more medical problems were observed in the patients treated by craniectomy than in the patients treated medically, except for the medical events specifically related to craniectomy, which extended the hospital stay but had no major repercussions. 2010 Elsevier Masson SAS. All rights reserved.

Malignant disease and dentistry.

PubMed

Walton, Graham; Seymour, Robin A

2009-11-01

Reports of an ageing population, increasing incidence of malignancy and improved treatments mean that dentists may have an increasing number of patients with, or who have recovered from, a malignancy. Dental professionals are expected to have an understanding of this important disease group so that appropriate dental care can be provided safely. In this first of three articles, we shall describe the important epidemiological and clinical features of the commonest malignancies in the United Kingdom. Dentists should understand the clinical implications of a patient with, or recovering from, a malignancy. This article gives a summary of the relevant features of the commonest malignancies.

AKT Axis, miR-21, and RECK Play Pivotal Roles in Dihydroartemisinin Killing Malignant Glioma Cells

PubMed Central

Shao, Ying-Ying; Zhang, Tao-Lan; Wu, Lan-Xiang; Zou, He-Cun; Li, Shuang; Huang, Jin; Zhou, Hong-Hao

2017-01-01

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is known to play important roles in inhibiting proliferation rate, inducing apoptosis, as well as hindering the metastasis and invasion of glioma cells, but the underlying mechanisms are still unclear so far. In this study, methyl thiazolyl tetrazolium (MTT), colony-forming, wound healing, invasion, and apoptosis assays were performed to investigate the effect of DHA on malignant glioma cells. Results showed that DHA induced apoptosis of malignant glioma cells through Protein Kinase B (AKT) axis, induced death of malignant glioma cells by downregulating miR-21, and inhibited the invasion of malignant glioma cells corresponding with up-regulation of the reversion-inducing-cysteine-rich protein with kazal motifs (RECK). These results revealed that AKT axis, miR-21, and RECK play pivotal roles in DHA killing malignant glioma cells, suggesting that DHA is a potential agent for treating glioma. PMID:28208619

Intracranial solitary fibrous tumors/hemangiopericytomas: first report of malignant progression.

PubMed

Apra, Caroline; Mokhtari, Karima; Cornu, Philippe; Peyre, Matthieu; Kalamarides, Michel

2018-06-01

OBJECTIVE Meningeal solitary fibrous tumors/hemangiopericytomas (MSFTs/HPCs) are rare intracranial tumors resembling meningiomas. Their classification was redefined in 2016 by the World Health Organization (WHO) as benign Grade I fibrohyaline type, intermediate Grade II hypercellular type, and malignant highly mitotic Grade III. This grouping is based on common histological features and identification of a common NAB2-STAT6 fusion. METHODS The authors retrospectively identified 49 cases of MSFT/HPC. Clinical data were obtained from the medical records, and all cases were analyzed according to this new 2016 WHO grading classification in order to identify malignant transformations. RESULTS Recurrent surgery was performed in 18 (37%) of 49 patients. Malignant progression was identified in 5 (28%) of these 18 cases, with 3 Grade I and 2 Grade II tumors progressing to Grade III, 3-13 years after the initial surgery. Of 31 Grade III tumors treated in this case series, 16% (5/31) were proved to be malignant progressions from lower-grade tumors. CONCLUSIONS Low-grade MSFTs/HPCs can transform into higher grades as shown in this first report of such progression. This is a decisive argument in favor of a common identity for MSFT and meningeal HPC. High-grade MSFTs/HPCs tend to recur more often and be associated with reduced overall survival. Malignant progression could be one mechanism explaining some recurrences or metastases, and justifying long-term follow-up, even for patients with Grade I tumors.

Therapeutic radiation and the potential risk of second malignancies.

PubMed

Kamran, Sophia C; Berrington de Gonzalez, Amy; Ng, Andrea; Haas-Kogan, Daphne; Viswanathan, Akila N

2016-06-15

Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. © 2016 American Cancer Society. © 2016 American Cancer Society.

Targeted cellular ablation based on the morphology of malignant cells

NASA Astrophysics Data System (ADS)

Ivey, Jill W.; Latouche, Eduardo L.; Sano, Michael B.; Rossmeisl, John H.; Davalos, Rafael V.; Verbridge, Scott S.

2015-11-01

Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100 μs) is enhanced for larger cells, short pulses (~1 μs) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors.

Endoscopic transnasal management of sinonasal malignancies – our initial experience

PubMed Central

Osuch-Wójcikiewicz, Ewa; Held-Ziółkowska, Marta; Kużmińska, Magdalena; Niemczyk, Kazimierz

2014-01-01

Introduction Malignant tumors of the paranasal sinuses are traditionally managed through external approaches. Advances in endoscopic transnasal surgery have allowed for the endoscopic treatment of some of these tumors. Aim To present the results of treatment of a series of patients with paranasal sinus malignancies treated with an endoscopic approach at a single institution. Material and methods The data on tumor type, operative technique, perioperative complications and postoperative course were analyzed. Results Eleven patients meeting the inclusion criteria were identified. The histopathology was as follows: malignant melanoma in 3 patients, squamous cell carcinoma in 2, adenocarcinoma in 2, poorly differentiated carcinoma in 1, hemangiopericytoma in 1, adenoid cystic carcinoma in 1 and fibrosarcoma in 1. There were no severe perioperative complications with the exception of 1 case of cerebrospinal fluid leak, which was successfully closed. The mean observation period was 13.5 months. One of the patients died of disease, another was lost to follow-up, and one was reoperated on due to recurrence. The remaining 8 patients are alive with no signs of recurrence. Conclusions Our initial experience seems to confirm results obtained by other authors indicating that in selected cases endoscopic surgery of sinonasal malignancies is similarly effective as external approach surgery. PMID:25097677

Targeted cellular ablation based on the morphology of malignant cells

PubMed Central

Ivey, Jill W.; Latouche, Eduardo L.; Sano, Michael B.; Rossmeisl, John H.; Davalos, Rafael V.; Verbridge, Scott S.

2015-01-01

Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100 μs) is enhanced for larger cells, short pulses (~1 μs) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors. PMID:26596248

A rare case of malignant pediatric ectomesenchymoma arising from the cerebrum.

PubMed

Kun, Yao; Duan, Zejun; Mei, Xi; Xu, Ying; Li, Jiuzhou; Li, Shouwei; Qi, Xueling

2015-01-01

Malignant ectomesenchymoma is a rare tumor that contains both ectodermal and mesenchymal elements. So far, only 7 patients with a manifestation in the cerebrum (with confirmed clinicopathological data) have been reported. A 4-year-old girl was present at our hospital with a 3-week history of intermittent sudden dizzy with no apparent cause. MRI showed an irregular enhanced lesion in the left frontal-parietal lobe and lateral ventricle with peripheral gadolinium-enhancement with a significant surrounding edema. Total removal of the tumor was performed. Histological examination of the resected tumor revealed a mixed astrocytoma and anaplastic ependymoma component with undifferentiated mesenchymal spindle cell component. Generally speaking, the main malignant part in most cases of malignant ectomesenchymoma (MEM) is the mesenchymal component. In the present case, the malignant component was both in the mesenchymal and ectodermal part. In particular, the mesenchymal part was mainly composed of spindle cells, and the ectodermal part primarily consisted of gliomatous component and anaplastic ependymoma component. The patient was then treated with chemotherapy and as regard to the prognosis, there was no evidence of tumor recurrence at the 5 months' follow-up. The long term follow-up is still in progress.

Incident cancers and late mortality in Australian children treated by allogeneic stem cell transplantation for non-malignant diseases.

PubMed

Nelson, Adam S; Vajdic, Claire M; Ashton, Lesley J; Le Marsney, Renate E; Nivison-Smith, Ian; Wilcox, Leonie; Dodds, Anthony J; O'Brien, Tracey A

2017-01-01

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for children with a variety of non-malignant conditions. However, these children face an increased risk of late death and incident cancers after HSCT, which may occur many years after their initial HSCT. We examined cancer occurrence and late mortality in a population-based cohort of 318 Australian children who underwent allogeneic HSCT for non-malignant disease. Standardized incident ratios (SIRs) and standardized mortality ratios (SMRs) were calculated and compared with population controls. We identified six (1.9%) cancers at a median 9.2 years post-HSCT. Cancer occurred 15 times more frequently than in the general population (SIR 15.4, 95% CI = 6.9-34.2). Of the 198 patients who survived for at least 2 years post-HSCT, 11 (5.6%) died at a median 7.5 years post-HSCT. The mortality rate was 17 times higher than in the general population (SMR 17.5, 95% CI = 9.7-31.2). Children transplanted for non-malignant conditions require evidence-based survivorship programs to reduce excess morbidity and mortality. © 2016 Wiley Periodicals, Inc.

Evidence That High Catecholamine Levels Produced by Pheochromocytoma May be Responsible for Tako-Tsubo Cardiomyopathy.

PubMed

Sharkey, Scott W; McAllister, Nancy; Dassenko, David; Lin, David; Han, Kelly; Maron, Barry J

2015-06-01

Tako-tsubo cardiomyopathy (TC) is a novel form of acute heart failure, characterized by regional left ventricular dysfunction without coronary artery obstruction, and usually triggered by a stressful event. Excessive circulating catecholamines have been implicated in the pathophysiology of this condition. This report documents the unusual occurrence of acute TC events in 2 male subjects of disparate ages, 16 and 66 years, for whom subsequent investigation in both led to the unexpected discovery of catecholamine-producing pheochromocytoma. Marked elevation of plasma catecholamines (epinephrine, norepinephrine, and dopamine) was present in both subjects and were remarkably similar to those previously reported in female patients with TC triggered by emotional stress. These observations show a common link between TC occurrence and elevated catecholamine levels in both male and female patients and, therefore, support the hypothesis that excessive levels of catecholamines may be involved in the pathophysiology of TC independent of age or gender. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of infection between internal-external and external percutaneous transhepatic biliary drainage in treating patients with malignant obstructive jaundice.

PubMed

Xu, Chuan; Huang, Xin-En; Wang, Shu-Xiang; Lv, Peng-Hua; Sun, Ling; Wang, Fu-An

2015-01-01

Percutaneous transhepatic biliary drainage (PTBD) is a form of palliative care for patients with malignant obstructive jaundice. We here compared the infection incidence between internal-external and external drainage for patients with malignant obstructive jaundice. Patients with malignant obstructive jaundice without infection before surgery receiving internal-external or external drainage from January 2008 to July 2014 were recruited. According to percutaneous transhepatic cholangiography (PTC), if the guide wire could pass through the occlusion and enter the duodenum, we recommended internal-external drainage, and external drainage biliary drainage was set up if the occlusion was not crossed. All patients with infection after procedure received a cultivation of blood and a bile bacteriological test. Among 110 patients with malignant obstructive jaundice, 22 (52.4%) were diagnosed with infection after the procedure in the internal-external drainage group, whereas 19 (27.9%) patients were so affected in the external drainage group, the difference being significant (p<0.05). In 8 patients (36.3%) in the internal-external group infection was controlled, as compared to 12 (63.1%) in the external group (p<0.05). The mortality rate for patients with infection not controlled in internal-external group in one month was 42.8%, while this rate in external group was 28.6% (p<0.05). External drainage is a good choice, which could significantly reduce the chance of biliary infection caused by bacteria, and decrease the mortality rate at one month and improve the long-term prognosis.

Early Non Invasive Ventilation and Hematological Malignancies

ClinicalTrials.gov

2018-01-03

Hematological Malignancies; Chronic Hypoxemic Respiratory Failure; Blood And Marrow Transplantation; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

Interstitial therapy of perineal and gynecological malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez, A.; Herstein, P.; Portnuff, J.

1983-03-01

Thirty-five patients, 38 to 88 years of age, were treated with 125-Iodine or 192-Iridium interstitial implants at Stanford University Medical Center between July 1974, and December, 1978. There were 25 primary epithelial malignancies, eight extensions from intrapelvic organs and two metastatic tumors (hypernephroma and Hodgkin's disease). The involved sites were: urethra (6 patients); vulva (9 patients); vagina (8 patients); anus (7 patients); cervix (5 patients). Implantation was usually performed to treat evident or microscopic disease in conjunction with external beam pelvic treatment with or without local excision. Computerized implant preplanning was used.125-Iodine seeds were inserted either directly or within absorbablemore » suture Polyglactin 910; 192-Iridium in nylon carriers was placed by suture or transperineal template. Two patients were lost to follow-up leaving 33 patients, 27 of whom are alive and free of local disease from 37 to 76 months. The overall local control rate was 88%, or 29/33 patients. All four local recurrences appeared before 24 months. Minor complications included: 10 patients with transient mucositis, four with superficial ulcers, and one patient with infection at the implanted site. Two major complications occurred: a necrotic rectal ulcer requiring a colostomy and a contracted, painful bladder necessitating a urinary diversion. It is concluded that in selected cases interstitial irradiation provides good local control of perineal and gynecological malignancies with low morbidity in this elderly and quite often fragile group of patients.« less

Malignant perivascular epithelioid cell tumor of the mesentery: a case report and literature review.

PubMed

Lai, Chien-Liang; Hsu, Kuo-Feng; Yu, Jyh-Cherng; Chen, Cheng-Jueng; Hsieh, Chung-Bao; Chan, De-Chuan; Li, Heng-Sheng; Hsu, Hung-Ming

2012-01-01

Perivascular epithelioid cell tumors (PEComas) are very rare mesenchymal neoplasms, and have been found in various organs such as the liver, kidney, falciform ligament, uterus, uterine cervix, and both the small and large bowel. However, only 3 cases of mesenteric PEComa have been described in the literature so far. The treatment and prognosis of malignant mesenteric PEComas are discussed. We report the case of a 59-year-old man diagnosed with PEComa. He underwent segmental resection of the jejunum and tumor resection. Malignant mesenteric PEComa was confirmed on the basis of clinicopathological features. Tumor resection was followed by concurrent chemoradiotherapy. Besides surgery, no effective treatment for malignant PEComa has been established thus far because of the rarity of this tumor. Here, we report our experience of treating a malignant mesenteric PEComa using surgery and subsequent adjuvant therapy, which effectively controlled disease progression and prevented local recurrence. Copyright © 2012 S. Karger AG, Basel.

Interventional bronchoscopy in malignant central airway obstruction by extra-pulmonary malignancy.

PubMed

Shin, Beomsu; Chang, Boksoon; Kim, Hojoong; Jeong, Byeong-Ho

2018-03-13

Interventional bronchoscopy is considered an effective treatment option for malignant central airway obstruction (MCAO). However, there are few reports of interventional bronchoscopy in patients with MCAOs due to extra-pulmonary malignancy. Therefore, the objective of this study was to investigate treatment outcomes and prognostic factors for bronchoscopic intervention in patients with MCAO due to extra-pulmonary malignancy. We retrospectively analyzed consecutive 98 patients with MCAO due to extra-pulmonary malignancy who underwent interventional bronchoscopy between 2004 and 2014 at Samsung Medical Center (Seoul, Korea). The most common primary site of malignancy was esophageal cancer (37.9%), followed by thyroid cancer (16.3%) and head & neck cancer (10.2%). Bronchoscopic interventions were usually performed using a combination of mechanical debulking (84.7%), stent insertion (70.4%), and laser cauterization (37.8%). Of 98 patients, 76 (77.6%) patients had MCAO due to progression of malignancy, and 42 (42.9%) patients had exhausted all other anti-cancer treatment at the time of bronchoscopic intervention. Technical success was achieved in 89.9% of patients, and acute complications and procedure-related deaths occurred in 20.4% and 3.1% of patients, respectively. Reduced survival was associated with MCAO due to cancer other than thyroid cancer or lymphoma, mixed lesions, and not receiving adjuvant treatment after bronchoscopic intervention. Bronchoscopic intervention could be a safe and effective procedure for MCAO due to end-stage extra-pulmonary malignancies. In addition, we identified possible prognostic factors for poor survival after intervention, which could guide clinicians select candidates that will benefit from bronchoscopic intervention.

Second Malignancies After Adjuvant Radiation Therapy for Early Stage Breast Cancer: Is There Increased Risk With Addition of Regional Radiation to Local Radiation?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, Sarah Nicole; Department of Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, British Columbia; Tyldesley, Scott, E-mail: styldesl@bccancer.bc.ca

2015-04-01

Purpose: This study was undertaken to determine whether there was an increased risk of second malignancies (SM), particularly lung cancer, in early stage breast cancer patients treated with the addition of nodal fields to breast and/or chest wall radiation therapy (RT). Materials and Methods: Subjects were stage I/II female breast cancer patients 20 to 79 years of age, diagnosed between 1989 and 2005 and treated with adjuvant RT at our institution. Patients were included if they survived and did not have SM within 3 years of diagnosis. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to compare SM incidencemore » to cancer incidence in the general sex- and age-matched populations. Secondary malignancy risks in patients treated with local RT (LRT) to the breast/chest wall were compared to those in patients treated with locoregional RT (LRRT) to the breast/chest wall and regional nodes, using multivariate regression analysis (MVA) to account for covariates. Results: The cohort included 12,836 patients with a median follow-up of 8.4 years. LRRT was used in 18% of patients. The SIR comparing patients treated with LRT to the general population was 1.29 (CI: 1.21-1.38). No statistically significant increased incidence of in-field malignancies (SIR, 1.04; CI: 0.87-1.23) and lung cancers (SIR, 1.06; CI: 0.88-1.26) was detected. The SIR comparing patients treated with LRRT to the general population was 1.39 (CI: 1.17-1.64). No statistically significant increased incidence of in-field malignancies (SIR, 1.26; CI: 0.77-1.94) and lung cancers (SIR, 1.27; CI: 0.76-1.98) was detected. On MVA comparing LRRT to LRT, the adjusted hazard ratio was 1.20 for in-field malignancies (CI: 0.68-2.16) and 1.26 for lung cancer (CI: 0.67-2.36). The excess attributable risk (EAR) to regional RT was 3.1 per 10,000 person years (CI: −8.7 to 9.9). Conclusions: No statistically significant increased risk of second malignancy was detected after LRRT

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

PubMed

Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

2016-06-01

Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

ACCURACY OF PLASMA FREE METANEPHRINES IN THE DIAGNOSIS OF PHEOCHROMOCYTOMA AND PARAGANGLIOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PubMed

Chen, Yan; Xiao, Huangmeng; Zhou, Xieda; Huang, Xiaoyu; Li, Yanbing; Xiao, Haipeng; Cao, Xiaopei

2017-10-01

Various studies have validated plasma free metanephrines (MNs) as biomarkers for pheochromocytoma and paraganglioma (PPGL). This meta-analysis aimed to estimate the overall diagnostic accuracy of this biochemical test for PPGL. We searched the PubMed, the Cochrane Library, Web of Science, Embase, Scopus, OvidSP, and ProQuest Dissertations & Theses databases from January 1, 1995 to December 2, 2016 and selected studies written in English that assessed plasma free MNs in the diagnosis of PPGL. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate the quality of the included studies. We calculated pooled sensitivities, specificities, positive and negative likelihood ratios, diagnostic odds ratios (DORs) and areas under curve (AUCs) with their 95% confidence intervals (95% CIs). Heterogeneity was assessed by I 2 . To identify the source of heterogeneity, we evaluated the threshold effect and performed a meta-regression. Deeks' funnel plot was selected for investigating any potential publication bias. Although the combination of metanephrine (MN) and normetanephrine (NMN) carried lower specificity (0.94, 95% CI 0.90-0.97) than NMN (0.97, 95% CI 0.92-0.99), NMN was generally more accurate than individual tests, with the highest AUC (0.99, 95% CI 0.97-0.99), DOR (443.35, 95% CI 216.9-906.23), and pooled sensitivity (0.97, 95% CI 0.94-0.98) values. Threshold effect and meta-regression analyses showed that different cut-offs, blood sampling positions, study types and test methods contributed to heterogeneity. This meta-analysis suggested an effective value for combined plasma free MNs for the diagnosis of PPGL, but testing for MNs requires more standardization using tightly regulated studies. AUC = area under curve; CI = confidence interval; DOR = diagnostic odds ratio; EIA = enzyme immunoassay; LC-ECD = liquid chromatography-electrochemical detection; LC-MS/MS = liquid chromatography-tandem mass spectrometry; MN = metanephrine; NMN

Outcome of stenting in biliary and pancreatic benign and malignant diseases: A comprehensive review

PubMed Central

Mangiavillano, Benedetto; Pagano, Nico; Baron, Todd H; Luigiano, Carmelo

2015-01-01

Endoscopic stenting has become a widely method for the management of various malignant and benign pancreatico-biliary disorders. Biliary and pancreatic stents are devices made of plastic or metal used primarily to establish patency of an obstructed bile or pancreatic duct and may also be used to treat biliary or pancreatic leaks, pancreatic fluid collections and to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis. In this review, relevant literature search and expert opinions have been used to evaluate the outcome of stenting in biliary and pancreatic benign and malignant diseases. PMID:26290631

Immunotherapy for recurrent malignant glioma: an interim report on survival.

PubMed

Ingram, M; Buckwalter, J G; Jacques, D B; Freshwater, D B; Abts, R M; Techy, G B; Miyagi, K; Shelden, C H; Rand, R W; English, L W

1990-12-01

We present interim survival data for a group of 83 adult patients with recurrent malignant glioma treated by implanting stimulated autologous lymphocytes into the tumour bed following surgical debulking. The patients were treated 6 months or more prior to data analysis. Fifty-nine patients were male and 24 female. The mean age for the entire group was 48.4 years and the mean Karnofsky rating (KR) was 67.2. Eight of the patients had grade II tumours, 33 had grade III tumours and 42 had grade IV tumours. Statistical analysis focuses on tumour grade, KR and patient age, factors that have been shown to affect survival in previous studies. Multifactorial analyses are employed to identify interrelationships among factors related to survival. Seven patients (8%) did not respond to immunotherapy, 76 (92%) had a good initial response. Twenty-five patients (30.1%) are living and 18 (22%) have shown no evidence of recurrence. Results are evaluated in the light of those obtained in trials of other experimental therapies for recurrent malignant gliomas. It is concluded that the present protocol offers a safe and comparatively effective treatment option.

Salvage immunotherapy of malignant glioma.

PubMed

Ingram, M; Jacques, S; Freshwater, D B; Techy, G B; Shelden, C H; Helsper, J T

1987-12-01

We present the preliminary results of a phase I trial of adoptive immunotherapy for recurrent or residual malignant glioma. The protocol is based on surgical debulking followed by implantation into the tumor bed of autologous lymphocytes that have been stimulated with phytohemagglutinin-P and then cultured in vitro in the presence of interleukin 2. Fifty-five patients with a mean Karnofsky rating of 64 were treated between February 1985 and March 1987. No significant toxicity was associated with the immunotherapy. Fifty patients had a positive initial response to therapy, nine patients had early recurrence (two to four months after treatment), and 22 patients died. We comment on major differences between the protocol described and other immunotherapy protocols.

Malignant Pleural Mesothelioma

PubMed Central

Tsao, Anne S.; Wistuba, Ignacio; Roth, Jack A.; Kindler, Hedy Lee

2009-01-01

Malignant pleural mesothelioma (MPM) is a deadly disease that occurs in 2,000 to 3,000 people each year in the United States. Although MPM is an extremely difficult disease to treat, with the median overall survival ranging between 9 and 17 months regardless of stage, there has been significant progress over the last few years that has reshaped the clinical landscape. This article will provide a comprehensive discussion of the latest developments in the treatment of MPM. We will provide an update of the major clinical trials that impact mesothelioma treatment in the resectable and unresectable settings, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. In addition, there are controversial issues, such as the role of extrapleural pneumonectomy, adjuvant radiotherapy, and use of intensity-modulated radiotherapy versus hemithoracic therapy that will also be addressed in this manuscript. PMID:19255316

Preauricular infratemporal fossa approach for advanced malignant parotid tumors.

PubMed

Leonetti, John P; Benscoter, Brent J; Marzo, Sam J; Borrowdale, Richard W; Pontikis, George C

2012-09-01

The aims of this study were to demonstrate the surgical technique involved in the preauricular infratemporal fossa (ITF) approach, outline the clinical indications for use of this technique, and present the results in using this approach in 159 patients with malignant parotid tumors. At the conclusion of this article, the reader should be able to understand the utility of the preauricular infratemporal fossa approach in the management of patients with advanced malignant parotid tumors. This was a retrospective chart review of 159 patients treated at a tertiary care academic medical center following institutional review board approval. A comprehensive medical records review was performed for all patients with malignant parotid tumors who underwent a preauricular ITF approach between July 1988 and July 2010. The most common presenting symptoms were pain and trismus, whereas the presence of a parotid mass and facial paralysis were the most common clinical signs. Mucoepidermoid and adenoid cystic carcinoma accounted for 63% of the tumors, and perineural invasion was found in nearly 71% of the patients. Despite negative surgical margins in 92% of the patients, local or regional tumor recurrence was found in 17% of the cases. The mean follow-up time was 12.8 years. The preauricular ITF approach should be used in the surgical extirpation of advanced malignant parotid neoplasms. This technique provides proximal facial nerve identification, internal carotid artery protection, and negative tumor margins at the skull base. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

First report of bilateral pheochromocytoma in the clinical spectrum of HIF2A-related polycythemia-paraganglioma syndrome.

PubMed

Taïeb, David; Yang, Chunzhang; Delenne, Blandine; Zhuang, Zhengping; Barlier, Anne; Sebag, Fréderic; Pacak, Karel

2013-05-01

Molecular genetic research has so far resulted in the identification of 10 well-characterized susceptibility genes for hereditary pheochromocytoma (PHEO) or paraganglioma (PGL). Recently, a new syndrome characterized by multiple PGLs and somatostatinomas associated with congenital polycythemia due to somatic mutations in HIF2A has been reported. The aim of the study was to define the genetic defect in a new case of bilateral PHEO and multiple PGLs associated with congenital polycythemia. A female patient presented with neonatal polycythemia (treated by phlebotomies, 1 session approximately every 4 mo), mildly enlarged cerebral ventricles, and bilateral PHEO and multiple PGLs. There was no family history of any neuroendocrine tumor or polycythemia. Surgical removal of the tumors only temporarily normalized plasma erythropoietin (Epo) levels and discontinued phlebotomies. No germline mutations were initially detected in the SDHB, SDHC, SDHD, VHL, and PHD2 genes, known to be associated with polycythemia. The PHEOs presented with a typical noradrenergic biochemical phenotype. A heterozygous missense mutation (c.1589C>T) was identified in exon 12 of HIF2A, resulting in an alanine 530 substitution in the HIF-2α protein with valine (A530V). This somatic mutation was detected in the tissue from 1 PHEO and 1 PGL, with no HIF2A germline mutation found. This mutation led to stabilization of HIF-2α and hence a gain-of-function phenotype, as in previously published studies. This case represents the first association of a somatic HIF2A gain-of-function mutation with PHEO and congenital polycythemia, and it alerts physicians to perform proper genetic screening in patients presenting with multiple norepinephrine-producing PHEOs and polycythemia. This report also extends the previous findings of a new syndrome of only multiple PGLs, somatostatinomas, and polycythemia to multiple PHEOs.

Radiotherapy for non-malignant disorders: state of the art and update of the evidence-based practice guidelines

PubMed Central

Micke, O; Muecke, R

2015-01-01

Every year in Germany about 50,000 patients are referred and treated by radiotherapy (RT) for “non-malignant disorders”. This highly successful treatment is applied only for specific indications such as preservation or recovery of the quality of life by means of pain reduction or resolution and/or an improvement of formerly impaired physical body function owing to specific disease-related symptoms. Since 1995, German radiation oncologists have treated non-malignant disorders according to national consensus guidelines; these guidelines were updated and further developed over 3 years by implementation of a systematic consensus process to achieve national upgraded and accepted S2e clinical practice guidelines. Throughout this process, international standards of evaluation were implemented. This review summarizes most of the generally accepted indications for the application of RT for non-malignant diseases and presents the special treatment concepts. The following disease groups are addressed: painful degenerative skeletal disorders, hyperproliferative disorders and symptomatic functional disorders. These state of the art guidelines may serve as a platform for daily clinical work; they provide a new starting point for quality assessment, future clinical research, including the design of prospective clinical trials, and outcome research in the underrepresented and less appreciated field of RT for non-malignant disorders. PMID:25955230

Clinical Outcomes of Self-Expandable Metal Stents for Malignant Rectal Obstruction.

PubMed

Lee, Hyun Jung; Hong, Sung Pil; Cheon, Jae Hee; Kim, Tae Il; Kim, Won Ho; Park, Soo Jung

2018-01-01

Self-expandable metal stents are widely used to treat malignant colorectal obstruction. However, data on clinical outcomes of stent placement for rectal obstruction specifically are lacking. We aimed to investigate the clinical outcomes of self-expandable metal stents in malignant rectal obstruction in comparison with those in left colonic obstruction and to identify factors associated with clinical failure and complication. This was a retrospective study. The study was conducted at a tertiary care center. Between January 2005 and December 2013, medical charts of patients who underwent stent placement for malignant rectal or left colonic obstruction were reviewed retrospectively. Study intervention included self-expandable metal stent placement. Technical success, clinical success, and complications were measured. Technical success rates for the 2 study groups (rectum vs left colon, 93.5% vs 93.1%; p = 0.86) did not differ significantly; however, the clinical success rate was lower in patients with rectal obstruction (85.4% vs 92.1%; p = 0.02). In addition, the complication rate was higher in patients with rectal obstruction (37.4% vs 25.1%; p = 0.01). Patients with rectal obstruction showed higher rates of obstruction because of extracolonic malignancy (33.8% vs 15.8%; p < 0.001) and stent use for palliation (78.6% vs 56.3%; p < 0.001). Multivariate analysis indicated obstruction attributed to extracolonic malignancy and covered stent usage to be independent risk factors for clinical failure. Factors predictive of complications in the palliative group were total obstruction, obstruction because of extracolonic malignancy, and covered stent usage. This was a retrospective, single-center study. The efficacy and safety of stent placement for malignant rectal obstruction were comparable with those for left colonic obstruction. However, obstruction attributed to extracolonic malignancy, use of covered stents, and total obstruction negatively impacted clinical outcomes

[Malignant tumors of the female genital track in the elderly].

PubMed

Gottwald, Leszek; Akoel, Kindah Mo; Wójcik-Krowiranda, Katarzyna; Bieńkiewicz, Andrzej

2003-09-01

In senium the increase in the incidence of most malignant neoplasms, as well as gynecological cancers is found. In this period of life the vast number of women do not apply for the preventive and follow-up examinations, which increases the number of malignant diseases diagnosed at advanced clinical stages. The coexisting another diseases often limits the possibility of the operative treatment in those cases. To assess the profile of malignant tumors of the genital tract and their treatment in women above 70 year old. 61 women aged from 71 yrs. to 88 yrs. treated operatively between 1997-2001 due to gynecological cancers were included into the study. The structure and detectability of the neoplasms, as well as the type of performed surgical procedures were analysed. 30 endometrial cancers (49.2%), 16 ovarian cancers (26.2%), 14 vulvar cancers (22.9%) and 1 cervical cancer were diagnosed and surgically treated. The endometrial cancer stage I was detected in 18 cases, stage II in 4 cases and stage III in 8 cases. In each case the radical operation was done (total hysterectomy, lymphadenectomy and appendectomy). The ovarian cancer stage I was detected in 3 cases, stage II in 2 cases, stage III in 5 cases, and stage IV in 6 cases. Only in 5 cases out of this group the radical surgery was performed (total hysterectomy, omentectomy and appendectomy). The vulvar cancer stage I was detected in 2 cases, stage II in 11 cases, and FIGO stage III in 4 cases. In each of these women the vulva and bilateral inguinal lymph nodes were resected, and in 2 cases additionally at the same time the Miles operation was performed. The cervical cancer clinical stage I was detected, and the Wertheim operation was performed. The most often diagnosed malignant neoplasm in women above 70 yrs. was the endometrial cancer. The worst first-time diagnosis structure was observed in the ovarian cancer, what significantly decreased the ability of surgical treatment in this group.

Laparoscopic approach to gastrointestinal malignancies: Toward the future with caution

PubMed Central

Bencini, Lapo; Bernini, Marco; Farsi, Marco

2014-01-01

After the rapid acceptance of laparoscopy to manage multiple benign diseases arising from gastrointestinal districts, some surgeons started to treat malignancies by the same way. However, if the limits of laparoscopy for benign diseases are mainly represented by technical issues, oncologic outcomes remain the foundation of any procedures to cure malignancies. Cancerous patients represent an important group with peculiar aspects including reduced survival expectancy, worsened quality of life due to surgery itself and adjuvant therapies, and challenging psychological impact. All these issues could, potentially, receive a better management with a laparoscopic surgical approach. In order to confirm such aspects, similarly to testing the newest weapons (surgical or pharmacologic) against cancer, long-term follow-up is always recommendable to assess the real benefits in terms of overall survival, cancer-free survival and quality of life. Furthermore, it seems of crucial importance that surgeons will be correctly trained in specific oncologic principles of surgical oncology as well as in modern miniinvasive technologies. Therefore, laparoscopic treatment of gastrointestinal malignancies requires more caution and deep analysis of published evidences, as compared to those achieved for inflammatory bowel diseases, gastroesophageal reflux disease or diverticular disease. This review tries to examine the evidence available to date for the use of laparoscopy and robotics in malignancies arising from the gastrointestinal district. PMID:24587655

Evolving adoptive cellular therapies in urological malignancies.

PubMed

Wong, Yien Ning Sophia; Joshi, Kroopa; Pule, Martin; Peggs, Karl S; Swanton, Charles; Quezada, Sergio A; Linch, Mark

2017-06-01

Immunotherapies have long been used to treat urological cancers but rarely lead to cure. In the past 5 years, success of immune checkpoint inhibition has led to a resurgence of enthusiasm for immunotherapy in the treatment of solid tumours. Increased understanding of tumour immune biology, technological advancements of gene transfer and cell culture, and improved clinical infrastructures for routine delivery of cell products, has made cell-based immunotherapeutics a real prospect for cancer therapy. These scientific and clinical activities, attempting to exploit the innate and adaptive immune systems for therapeutic gain, are well exemplified by the urological malignancies of renal, bladder, prostate, and penile cancer, a group of anatomically localised diseases, each with a distinct biology and different immunotherapeutic challenges. In this Review, we present the results of clinical studies investigating autologous cellular therapies in urological malignancies. Specifically, we discuss the rationale for upcoming studies, and how novel therapies and adoptive cell combinations can be used for personalised cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Management of malignant obstructive jaundice at The Middlesex Hospital.

PubMed

Leung, J W; Emery, R; Cotton, P B; Russell, R C; Vallon, A G; Mason, R R

1983-10-01

A total of 180 patients with malignant obstructive jaundice have been treated by 5 different methods: surgical resection; surgical by-pass; percutaneous prosthesis; endoscopic prosthesis; and endoscopic sphincterotomy (for papillary tumours). The spectrum of patients is unusual, because many elderly and ill patients were referred for nonoperative management. Operative by-pass, percutaneous and endoscopic prostheses gave similar overall results, with a mean survival of about 6 months. Patients with tumours of the papilla of Vater treated by endoscopy or surgery fared well; 11 of 18 were alive at follow-up. Median survival after resection of other tumours was 17 months. These results underline the need for randomized clinical trials, which are now in progress.

Chest wall toxicity after hypofractionated proton beam therapy for liver malignancies.

PubMed

Yeung, Rosanna; Bowen, Stephen R; Chapman, Tobias R; MacLennan, Grayden T; Apisarnthanarax, Smith

2017-12-24

Normal liver-sparing with proton beam therapy (PBT) allows for dose escalation in the treatment of liver malignancies, but it may result in high doses to the chest wall (CW). CW toxicity (CWT) data after PBT for liver malignancies are limited, with most published reports describing toxicity after a combination of hypofractionated proton and photon radiation therapy. We examined the incidence and associated factors for CWT after hypofractionated PBT for liver malignancies. We retrospectively reviewed the charts of 37 consecutive patients with liver malignancies (30 hepatocellular carcinoma, 6 intrahepatic cholangiocarcinoma, and 1 metastasis) treated with hypofractionated PBT. CWT was scored using Common Terminology Criteria for Adverse Events, version 4. Receiver-operating characteristic curves were used to identify patient and dosimetric factors associated with CWT and to determine optimal dose-volume histogram parameters/cutoffs. Cox regression univariate analysis was used to associate factors to time-dependent onset of CWT. Thirty-nine liver lesions were treated with a median dose of 60 GyE (range, 35-67.5) in 15 fractions (range, 13-20). Median follow-up was 11 months (range, 2-44). Grade ≥2 and 3 CW pain occurred in 7 (19%) and 4 (11%) patients, respectively. Median time to onset of pain was 6 months (range, 1-14). No patients had radiographic rib fracture. On univariate analysis, CW equivalent 2 Gy dose with an α/β = 3 Gy (EQD2 α/β=3 ), V57 >20 cm 3 (hazard ratio [HR], 2.7; P = .004), V63 >17 cm 3 (HR, 2.7; P = .003), and V78 >8 cm 3 (HR, 2.6; P = .003) had the strongest association with grade ≥2 CW pain, as did tumor dose of >75 Gy EQD2 α/β=10 (HR, 8.7; P = .03). No other patient factors were associated with CWT. CWT after hypofractionated PBT for liver malignancies is clinically relevant. For a 15-fraction regimen, V47 >20 cm 3 , V50 >17 cm 3 , and V58 >8 cm 3 were associated with higher rates of CWT. Further investigation of PBT techniques to

Palliation double stenting for malignant biliary and duodenal obstruction

PubMed Central

ZHAO, LIANG; XU, HAITAO; ZHANG, YUBAO

2016-01-01

The surgical management of patients with malignant biliary and duodenal obstruction is complex. Tumor excision is no longer possible in the majority of patients with malignant obstructive jaundice and duodenal obstruction. The aim of the present study was to evaluate the effectiveness of intraluminal dual stent placement in malignant biliary and duodenal obstruction. In total, 20 patients with malignant obstructive jaundice and duodenal obstruction, including 6 with pancreatic carcinoma, 11 with cholangiocarcinoma, 1 with duodenal carcinoma and 2 with abdominal lymph node metastasis, were treated with intraluminal stent placement. Bile duct obstruction with late occurrence of duodenal obstruction was observed in 16 cases, and duodenal obstruction followed by a late occurrence of bile duct obstruction was observed in 3 cases, while, in 1 case, bile duct obstruction and duodenal obstruction occurred simultaneously. After X-ray fluoroscopy revealed obstruction in the bile duct and duodenum, stents were placed into the respective lumens. Percutaneous transhepatic placement was employed for the biliary stent, while the duodenal stent was placed perioraly. The clinical outcomes, including complications associated with the procedures and patency of the stents, were evaluated. The biliary and duodenal stents were successfully implanted in 18 patients and the technical success rate was 90% (18/20). A total of 39 stents were implanted in 20 patients. In 2 cases, duodenal stent placement failed following biliary stent placement. Duodenal obstruction remitted in 15 patients, and 1 patient succumbed to aspiration pneumonia 5 days after the procedure. No severe complications were observed in any other patient. The survival time of the 18 patients was 5–21 months (median, 9.6 months), and 6 of those patients survived for >12 months. The present study suggests that X-ray fluoroscopy-guided intraluminal stent implantation is an effective procedure for the treatment of malignant

[Risk factors for malignant evolution of gastrointestinal stromal tumors].

PubMed

Andrei, S; Andrei, Adriana; Tonea, A; Andronesi, D; Becheanu, G; Dumbravă, Mona; Pechianu, C; Herlea, V; Popescu, I

2007-01-01

Gastrointestinal stromal tumors are the most frequent non-epithelial digestive tumors, being classified in the group of primitive mesenchymal tumors of the digestive tract. These tumors have a non predictable evolution and where stratified regarding the risk for malignant behavior in 4 categories: very low risk, low risk, intermediate risk and high risk. We performed a retrospective non randomised study including the patients with gastrointestinal stromal tumors treated in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute in the period January 2002 - June 2007, to define the epidemiological, clinico-paraclinical, histological and especially evolutive features of the gastrointestinal stromal tumors from this group, with a special regard to the risk factors for their malignant behavior. The most important risk factors in gastrointestinal stromal tumors are the tumor size and the mitotic index, based on them being realised the classification of Fletcher in the 4 risk categories mentioned above. In our group all the local advanced or metastatic gastrointestinal stromal tumors, regardless of their location, were classified in the group of high risk for the malignant behavior. The gastric location and the epithelioid type were positive prognostic factors, and the complete resection of the tumor, an other important positive prognostic feature, was possible in about 80% of the cases, probably because the gastrointestinal stromal tumors in our study were diagnosed in less advanced evolutive situations, only about one third being metastatic and about 14% being locally advanced at the time of diagnose. The association with other neoplasias was in our cases insignificant, only 5% of the patients presenting concomitant malignant digestive tumors and 7.6% intraabdominal benign tumors. Gastrointestinal stromal tumors remain a challenge for the medical staff, regarding their diagnose and therapeutical management, the stratification of the

Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer.

PubMed

Molenaar, Remco J; Sidana, Surbhi; Radivoyevitch, Tomas; Advani, Anjali S; Gerds, Aaron T; Carraway, Hetty E; Angelini, Dana; Kalaycio, Matt; Nazha, Aziz; Adelstein, David J; Nasr, Christian; Maciejewski, Jaroslaw P; Majhail, Navneet S; Sekeres, Mikkael A; Mukherjee, Sudipto

2017-12-18

Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

Is there an increased rate of additional malignancies in patients with mantle cell lymphoma?

PubMed

Barista, I; Cabanillas, F; Romaguera, J E; Khouri, I F; Yang, Y; Smith, T L; Strom, S S; Medeiros, L J; Hagemeister, F B

2002-02-01

To examine the frequency of additional neoplasms preceding and following the diagnosis of mantle cell lymphoma (MCL). A total of 156 patients with MCL treated on the hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternated with methotrexate and cytosine arabinoside (Hyper-CVAD/M-A) program with or without rituximab from 1994 to 2000 were the subjects of this report. These patients were followed for a median time of 26 months, and a total of 32 (21%) additional neoplasms were diagnosed, 21 preceding the diagnosis of MCL and 11 following MCL. After excluding certain types of non-invasive neoplasms, including basal cell carcinoma, meningioma and cervical intraepithelial neoplasia, we observed seven second malignancies after the diagnosis of MCL, and the 5-year cumulative incidence rate of second malignancy was 11%. The observed-to-expected (O/E) ratio was 7/0.07 = 100 [95% confidence interval (CI) 49.3 to 186.6; P <0.0001]. Of the 21 malignancies diagnosed prior to MCL, 16 were invasive and five non-invasive. There were a total of 10 urologic malignancies occurring before or after the diagnosis of MCL was established. Our findings suggest that there is an increased incidence of second malignancies in patients with MCL. In addition, the high number of cases with urinary tract cancer in our series may substantiate prior reports describing a possible association between lymphoma and urologic malignancies.

Malignancy Rate in Thyroid Nodules Classified as Bethesda Category III (AUS/FLUS)

PubMed Central

Ho, Allen S.; Sarti, Evan E.; Jain, Kunal S.; Wang, Hangjun; Nixon, Iain J.; Shaha, Ashok R.; Shah, Jatin P.; Kraus, Dennis H.; Ghossein, Ronald; Fish, Stephanie A.; Wong, Richard J.; Lin, Oscar

2014-01-01

Background: The Bethesda System for Reporting Thyroid Cytopathology is the standard for interpreting fine needle aspiration (FNA) specimens. The “atypia of undetermined significance/follicular lesion of undetermined significance” (AUS/FLUS) category, known as Bethesda Category III, has been ascribed a malignancy risk of 5–15%, but the probability of malignancy in AUS/FLUS specimens remains unclear. Our objective was to determine the risk of malignancy in thyroid FNAs categorized as AUS/FLUS at a comprehensive cancer center. Methods: The management of 541 AUS/FLUS thyroid nodule patients treated at Memorial Sloan–Kettering Cancer Center between 2008 and 2011 was analyzed. Clinical and radiologic features were examined as predictors for surgery. Target AUS/FLUS nodules were correlated with surgical pathology. Results: Of patients with an FNA initially categorized as AUS/FLUS, 64.7% (350/541) underwent immediate surgery, 17.7% (96/541) had repeat FNA, and 17.6% (95/541) were observed. Repeat FNA cytology was unsatisfactory in 5.2% (5/96), benign in 42.7% (41/96), AUS/FLUS in 38.5% (37/96), suspicious for follicular neoplasm in 5.2% (5/96), suspicious for malignancy in 4.2% (4/96), and malignant in 4.2% (4/96). Of nodules with two consecutive AUS/FLUS diagnoses that were resected, 26.3% (5/19) were malignant. Among all index AUS/FLUS nodules (triaged to surgery, repeat FNA, or observation), malignancy was confirmed on surgical pathology in 26.6% [CI 22.4–31.3]. Among AUS/FLUS nodules triaged to surgery, the malignancy rate was 37.8% [CI 33.1–42.8]. Incidental cancers were found in 22.3% of patients. On univariate logistic regression analysis, factors associated with triage to surgery were younger patient age (p<0.0001), increasing nodule size (p<0.0001), and nodule hypervascularity (p=0.032). Conclusions: In patients presenting to a comprehensive cancer center, malignancy rates in nodules with AUS/FLUS cytology are higher than previously estimated, with 26

The Possible Role of Infertility Drugs in Later Malignancy: A Review.

PubMed

Schaffer, Moshe; Schaffer, Pamela Manuela; Kassem, Riad; Shlomo, Izhar Ben

2016-01-01

Some 15% of all couples in the industrialized world suffer from infertility. Accordingly, any possible life-long morbidity that may result from treatments for infertility presents a significant concern to public health. The use of medications for infertility is specifically relevant to their possible effects on the classical target tissues for hormones involved in the sex axes, i.e., uterus, ovaries, and breast, but may have an effect on other organs, which harbor receptors for some of the hormones involved in reproduction. When one deals with the effect of treatment for infertility on the occurrence of malignant conditions, there is no doubt that certain malignancies tend to occur more frequently in women who suffered from and/or were treated for infertility. To review the accumulated data on the association of treatments for infertility with subsequent malignancies both in the classical target organs of sex steroids and in non-target organs. Systematic compilation of the relevant literature. Contrary to popular believes, treatment for infertility is associated with very little increase in malignacies.

Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience.

PubMed

Madajewicz, S; Karakousis, C; West, C R; Caracandas, J; Avellanosa, A M

1984-06-01

One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion.

Myxoid malignant fibrous histiocytoma presenting as a midline nasal mass.

PubMed

DeRosa, Jaimie; Smit, Jeffrey R

2012-04-01

Myxoid malignant fibrous histiocytoma is a rare type of pediatric non-rhabdomyosarcoma soft-tissue sarcoma. The case of a 5-year-old girl is presented, highlighting the potential for multiple pitfalls and aberrant differential diagnoses that need to be identified for successful treatment of pediatric myxofibrosarcomas. An awareness of these tumors and a call for standardized postsurgical treatment protocols is necessary in order to successfully treat children with this disease.

Pleural malignancies.

PubMed

Vargas, F S; Teixeira, L R

1996-07-01

Carcinoma of the lung, metastatic breast carcinoma, and lymphoma are responsible for approximately 75% of all malignant pleural effusions. The presence of malignant cells in the pleural fluid or in the parietal pleura confirms the diagnosis. Recently, several authors have proposed the combination of morphometric procedures and quantitative analysis of nucleolar organizer regions stained by silver nitrate. Videothoracoscopy is recommended for patients suspected of having a malignant pleural effusion in whom the diagnosis is not established after two cytologic studies of the fluid and one needle biopsy. The standard treatment is the intrapleural instillation of a chemical agent to produce a pleurodesis. The recommended sclerosant is talc, a tetracycline derivative, or Corynebacterium parvum where it is available. When a patient is not an ideal candidate for chemical pleurodesis, the options include symptomatic treatment, serial thoracentesis, implantation of a pleuroperitoneal shunt, and pleurectomy.

Pediatric Salivary Gland Malignancies.

PubMed

Ord, Robert A; Carlson, Eric R

2016-02-01

Pediatric malignant salivary gland tumors are extremely rare. The percentage of malignant tumors is higher than that seen in adults, although the outcomes in terms of survival are better in pediatric patients. The mainstay of treatment is surgical excision with negative margins. This article reviews current concepts in demographics, etiology, management, and outcomes of malignant salivary tumors in children. Copyright © 2016 Elsevier Inc. All rights reserved.

Pheochromocytoma and Paraganglioma in Cyanotic Congenital Heart Disease

PubMed Central

Moko, Lilamarie E.; Ginns, Jonathan; Rosenbaum, Marlon; Greutmann, Matthias; Aboulhosn, Jamil; Hageman, Abbie; Kim, Yuli; Deng, Lisa X.; Grewal, Jasmine; Zaidi, Ali N.; Almansoori, Ghadeera; Oechslin, Erwin; Earing, Michael; Landzberg, Michael J.; Singh, Michael N.; Wu, Fred

2015-01-01

Context: Aberrant cellular oxygen sensing is a leading theory for development of pheochromocytoma (PHEO) and paraganglioma (PGL). Objective: The objective of the study was to test the hypothesis that chronic hypoxia in patients with cyanotic congenital heart disease (CCHD) increases the risk for PHEO-PGL. Design/Setting/Participants: We investigated the association between CCHD and PHEO-PGL with two complementary studies: study 1) an international consortium was established to identify congenital heart disease (CHD) patients with a PHEO-PGL diagnosis confirmed by pathology or biochemistry and imaging; study 2) the 2000–2009 Nationwide Inpatient Survey, a nationally representative discharge database, was used to determine population-based cross-sectional PHEO-PGL frequency in hospitalized CCHD patients compared with noncyanotic CHD and those without CHD using multivariable logistic regression adjusted for age, sex, and genetic PHEO-PGL syndromes. Results: In study 1, we identified 20 PHEO-PGL cases, of which 18 had CCHD. Most presented with cardiovascular or psychiatric symptoms. Median cyanosis duration for the CCHD PHEO-PGL cases was 20 years (range 1–57 y). Cases were young at diagnosis (median 31.5 y, range 15–57 y) and 7 of 18 had multiple tumors (two bilateral PHEO; six multifocal or recurrent PGL), whereas 11 had single tumors (seven PHEO; four PGL). PGLs were abdominal (13 of 17) or head/neck (4 of 17). Cases displayed a noradrenergic biochemical phenotype similar to reported hypoxia-related PHEO-PGL genetic syndromes but without clinical signs of such syndromes. In study 2, hospitalized CCHD patients had an increased likelihood of PHEO-PGL (adjusted odds ratio 6.0, 95% confidence interval 2.6–13.7, P < .0001) compared with those without CHD; patients with noncyanotic CHD had no increased risk (odds ratio 0.9, P = .48). Conclusions: There is a strong link between CCHD and PHEO-PGL. Whether these rare diseases coassociate due to hypoxic stress, common

Risk of malignant neoplasms in acromegaly: a case-control study.

PubMed

Wolinski, K; Stangierski, A; Dyrda, K; Nowicka, K; Pelka, M; Iqbal, A; Car, A; Lazizi, M; Bednarek, N; Czarnywojtek, A; Gurgul, E; Ruchala, M

2017-03-01

Acromegaly is a chronic disease resulting from pathological oversecretion of growth hormone and subsequently insulin growth factor-1. Several complications of the disease have been reported, including cardiovascular diseases, respiratory disorders but also increased risk of benign and malignant neoplasms. The aim of the study was to evaluate the risk of malignant neoplasms in the patients with acromegaly in comparison with the control group. Medical documentation of acromegalic patients treated in one medical center between 2005 and 2016 has been analyzed. Results were compared with sex- and age-matched group of subjects with prolactinomas and hormonally inactive pituitary lesions hospitalized in the same department. Two hundred patients with acromegaly were included. Control group was composed of 145 patients. Any malignant neoplasm in anamnesis was present in 27 (13.5 %) patients with acromegaly and six (4.1 %) subjects from control group (p = 0.003). Thyroid cancer was present in 14 (7.0 %) patients with acromegaly and two (1.4 %) in control group (p = 0.02). Breast cancer was present in seven women (5.4 % of women) in acromegaly group but none of subjects in control group (p = 0.02). Colon cancer-4 (2.0 %) patients in acromegaly group and 0 in control group (p = 0.14). Malignant neoplasms are significantly more common in patients with acromegaly. Particularly, risk of thyroid cancer was increased over fivefold. Systematic screening for neoplastic diseases should be important part of follow-up in these patients. Further case-control studies are strongly indicated to evaluate which neoplasms are more common in acromegalic patients and what is the exact risk of malignancy.

Meeting the challenge of hematologic malignancies in sub-Saharan Africa

PubMed Central

Wood, William A.; Lee, Stephanie J.; Shea, Thomas C.; Naresh, Kikkeri N.; Kazembe, Peter N.; Casper, Corey; Hesseling, Peter B.; Mitsuyasu, Ronald T.

2012-01-01

Cancer is a leading cause of death and disability in sub-Saharan Africa and will eclipse infectious diseases within the next several decades if current trends continue. Hematologic malignancies, including non-Hodgkin lymphoma, leukemia, Hodgkin lymphoma, and multiple myeloma, account for nearly 10% of the overall cancer burden in the region, and the incidence of non-Hodgkin lymphoma and Hodgkin lymphoma is rapidly increasing as a result of HIV. Despite an increasing burden, mechanisms for diagnosing, treating, and palliating malignant hematologic disorders are inadequate. In this review, we describe the scope of the problem, including the impact of endemic infections, such as HIV, Epstein-Barr virus, malaria, and Kaposi sarcoma–associated herpesvirus. We additionally describe current limitations in hematopathology, chemotherapy, radiotherapy, hematopoietic stem cell transplantation, and supportive care and palliation. We review contemporary treatment and outcomes of hematologic malignancies in the region and outline a clinical service and research agenda, which builds on recent global health successes combating HIV and other infectious diseases. Achieving similar progress against hematologic cancers in sub-Saharan Africa will require the sustained collaboration and advocacy of the entire global cancer community. PMID:22461494

Intraoperative intracavitary hyperthermic chemotherapy for malignant pleural mesothelioma

PubMed Central

2017-01-01

Malignant pleural mesothelioma (MPM) is a dreadful disease with a poor prognosis. Multimodality therapy including surgical macroscopic complete resection is performed to treat operable MPM. Intraoperative intracavitary hyperthermic chemotherapy for MPM was reviewed. Appropriate papers published between 2006 and present were extracted by the PubMed advanced search by MPM (Title/Abstract), chemotherapy (Title/Abstract), and hyperthermia (All fields). Among the selected papers, those written in English, and treated more than ten MPM patients were reviewed. The intraoperative intracavitary hyperthermic chemotherapy has been performed following extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) for MPM. Cisplatin was mainly used for perfusion, and the morbidity and mortality was acceptable. In conclusion, the intraoperative intracavitary hyperthermic chemotherapy following EPP or P/D for MPM might enhance local control in the chest cavity. PMID:28706901

Malignant Transformation Potentials of Human Umbilical Cord Mesenchymal Stem Cells Both Spontaneously and via 3-Methycholanthrene Induction

PubMed Central

Lai, Xiulan; Liu, Sizheng; Chen, Yezeng; Zheng, Zexin; Xie, Qingdong; Maldonado, Martin; Cai, Zhiwei; Qin, Shan; Ho, Guyu; Ma, Lian

2013-01-01

Human umbilical cord mesenchymal stem cells (HUMSCs) are highly proliferative and can be induced to differentiate into advanced derivatives of all three germ layers. Thus, HUMSCs are considered to be a promising source for cell-targeted therapies and tissue engineering. However there are reports on spontaneous transformation of mesenchymal stem cells (MSCs) derived from human bone marrows. The capacity for HUMSCs to undergo malignant transform spontaneously or via induction by chemical carcinogens is presently unknown. Therefore, we isolated HUMSCs from 10 donors and assessed their transformation potential either spontaneously or by treating them with 3-methycholanthrene (3-MCA), a DNA-damaging carcinogen. The malignant transformation of HUMSCs in vitro was evaluated by morphological changes, proliferation rates, ability to enter cell senescence, the telomerase activity, chromosomal abnormality, and the ability to form tumors in vivo. Our studies showed that HUMSCs from all 10 donors ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUMSCs from two of the 10 donors treated with 3-MCA displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. When these cells (tHUMSCs) were injected into immunodeficient mice, they gave rise to sarcoma-like or poorly differentiated tumors. Moreover, in contrast to HUMSCs, tHUMSCs showed a positive expression of human telomerase reverse transcriptase (hTERT) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro. Our studies demonstrate that HUMSCs are not susceptible to spontaneous malignant transformation. However, the malignant transformation could be induced by chemical carcinogen 3-MCA. PMID:24339974

Additional value of hybrid SPECT/CT systems in neuroendocrine tumors, adrenal tumors, pheochromocytomas and paragangliomas.

PubMed

Wong, K K; Chondrogiannis, S; Fuster, D; Ruiz, C; Marzola, M C; Giammarile, F; Colletti, P M; Rubello, D

The aim of this review was to evaluate the potential advantages of SPECT/CT hybrid imaging in the management of neuroendocrine tumors, adrenal tumors, pheochromocytomas and paragangliomas. From the collected data, the superiority of fused images was observed as providing both functional/molecular and morphological imaging compared to planar imaging. This provided an improvement in diagnostic imaging, with significant advantages as regards: (1) precise locating of the lesions; (2) an improvement in characterization of the findings, resulting higher specificity, improved sensitivity, and overall greater accuracy, (3) additional anatomical information derived from the CT component; (4) CT-based attenuation correction and potential for volumetric dosimetry calculations, and (5) improvement on the impact on patient management (e.g. in better defining treatment plans, in shortening surgical operating times). It can be concluded that SPECT/CT hybrid imaging provides the nuclear medicine physician with a powerful imaging modality in comparison to planar imaging, providing essential information about the location of lesions, and high quality homogeneous images. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Malignant central airway obstruction

PubMed Central

Mudambi, Lakshmi; Miller, Russell

2017-01-01

This review comprehensively describes recent advances in the management of malignant central airway obstruction (CAO). Malignant CAO can be a dramatic and devastating manifestation of primary lung cancer or metastatic disease. A variety of diagnostic modalities are available to provide valuable information to plan a therapeutic intervention. Clinical heterogeneity in the presentation of malignant CAO provides opportunities to adapt and utilize endoscopic technology and tools in many ways. Mechanical debulking, thermal tools, cryotherapy and airway stents are methods and instruments used to rapidly restore airway patency. Delayed bronchoscopic methods, such as photodynamic therapy (PDT) and brachytherapy can also be utilized in specific non-emergent situations to establish airway patency. Although data regarding the success and complications of therapeutic interventions are retrospective and characterized by clinical and outcome measure variability, the symptoms of malignant CAO can often be successfully palliated. Assessment of risks and benefits of interventions in each individual patient during the decision-making process forms the critical foundation of the management of malignant CAO. PMID:29214067

[Arsenical keratosis treated by dermatome shaving].

PubMed

Kjerkegaard, Ulrik Knap; Heje, Jens Martin; Vestergaard, Christian; Stausbøl-Grøn, Birgitte; Stolle, Lars Bjørn

2014-05-05

Cutaneous malignancy in association with arsenic exposure is a rare but well-documented phenomenon. Signs of chronic arsenic exposure are very rare in Denmark today. However, arsenic was used in the medical treatment of psoriasis vulgaris up till the 1980's and several patients suffer from this arsenic treatment today. This case report shows that arsenical keratosis can be treated by dermatome shaving, a superficial destructive therapy.

Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

ClinicalTrials.gov

2016-05-16

Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme

PubMed Central

Curtis, Jeffrey R; Lee, Eun Bong; Kaplan, Irina V; Kwok, Kenneth; Geier, Jamie; Benda, Birgitta; Soma, Koshika; Wang, Lisy; Riese, Richard

2016-01-01

Objectives Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To further assess the potential role of Janus kinase inhibition in the development of malignancies, we performed an integrated analysis of data from the tofacitinib RA clinical development programme. Methods Malignancy data (up to 10 April 2013) were pooled from six phase II, six Phase III and two long-term extension (LTE) studies involving tofacitinib. In the phase II and III studies, patients with moderate-to-severe RA were randomised to various tofacitinib doses as monotherapy or with background non-biological disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate. The LTE studies (tofacitinib 5 or 10 mg twice daily) enrolled patients from qualifying prior phase I, II and III index studies. Results Of 5671 tofacitinib-treated patients, 107 developed malignancies (excluding non-melanoma skin cancer (NMSC)). The most common malignancy was lung cancer (n=24) followed by breast cancer (n=19), lymphoma (n=10) and gastric cancer (n=6). The rate of malignancies by 6-month intervals of tofacitinib exposure indicates rates remained stable over time. Standardised incidence ratios (comparison with Surveillance, Epidemiology and End Results) for all malignancies (excluding NMSC) and selected malignancies (lung, breast, lymphoma, NMSC) were within the expected range of patients with moderate-to-severe RA. Conclusions The overall rates and types of malignancies observed in the tofacitinib clinical programme remained stable over time with increasing tofacitinib exposure. PMID:25902789

Fertility-sparing surgery in advanced stage malignant ovarian germ cell tumor: a case report.

PubMed

Ghalleb, Montassar; Bouzaiene, Hatem; Slim, Skander; Hadiji, Achraf; Hechiche, Monia; Ben Hassouna, Jamel; Rahal, Khaled

2017-12-17

Malignant ovarian germ cell tumor is a rare type of disease, which generally has a good prognosis due to the high chemosensitivity of this type of tumor. Fertility preservation is an important issue because malignant ovarian germ cell tumor commonly affects young women. Although conservation is the standard for early stage, it becomes more debatable as the disease progresses to more advanced stages. Report the case of a patient with an International Federation of Gynecology and Obstetrics Stage IIIc malignant ovarian germ cell tumor, who had conservative surgery and chemotherapy with a good fertility outcome. A 23-year-old North African woman with a left malignant ovarian germ cell tumor stage IIIc was treated by left adnexectomy and omentectomy followed by chemotherapy. A 15-year follow-up showed no signs of relapse, and she completed three full-term natural pregnancies. Malignant ovarian germ cell tumor is a rare ovarian tumor with a good prognosis. It is usually associated with a good fertility outcome in early stages. However, due to the rarity of the disease in advanced stages, the fertility outcome for this group of patients is not clear. This lack of data surrounding advanced stages points to the need for a meta-analysis of all published cases.

Reduced Intensity Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

ClinicalTrials.gov

2018-05-10

Acute Myeloid Leukemia; Acute Myeloid Leukemia in Remission; Aplastic Anemia; Chronic Myelomonocytic Leukemia; Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Malignant Neoplasm; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

[Case of neuroleptic malignant syndrome following open heart surgery for thoracic aortic aneurysm with parkinson's disease].

PubMed

Shinoda, Maiko; Sakamoto, Mik; Shindo, Yuki; Ando, Yumi; Tateda, Takeshi

2013-12-01

An 80-year-old woman with Parkinson's disease was scheduled for open heart surgery to repair thoracic aortic aneurysm. Parkinson's symptoms were normally treated using oral levodopa (200 mg), selegiline-hydrochloride (5 mg), bromocriptine-mesilate (2 mg), and amantadine-hydrochloride (200 mg) daily. On the day before surgery, levodopa 50mg was infused intravenously. Another 25 mg of levodopa was infused immediately after surgery. Twenty hours later, the patient developed tremors, heyperventilation, but no obvious muscle rigidity. Two days after surgery, the patient exhibited high fever, hydropoiesis, elevated creatine kinase, and a rise in blood leukocytes. She was diagnosed with neuroleptic malignant syndrome. She was intubated, and received dantrolene sodium. Symptoms of neuroleptic malignant syndrome disappeared on the fourth postoperative day. The stress of open heart surgery, specifically extracorporeal circulation and concomitant dilution of levodopa, triggered neuroleptic malignant syndrome in this patient. Parkinson's patients require higher doses of levodopa prior to surgery to compensate and prevent neuroleptic malignant syndrome after surgery.

Successful palliation of malignant ascites from peritoneal mesothelioma by laparoscopic intraperitoneal hyperthermic chemotherapy.

PubMed

Patriti, Alberto; Cavazzoni, Emanuel; Graziosi, Luigina; Pisciaroli, Antonio; Luzi, Debora; Gullà, Nino; Donini, Annibale

2008-08-01

A variety of options have been proposed to treat malignant ascites but most of them have failed to reach a significant impact in terms of palliation. Laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC) could represent a good therapeutic tool for patients in whom medical therapies have failed and peritoneovenous shunting is contraindicated. Here we present a case of a 49-year-old woman with malignant ascites secondary to peritoneal spreading of a right pleural mesothelioma. After failure of medical therapy, the patient underwent LHIPEC with Cisplatin 25 mg/m/L and Doxorubicin 7 mg/m/L. A dramatic reduction of ascites was documented in the postoperative period and the patient experienced complete abdominal symptom relief. Ascites did not recur during a follow-up period of 6 months. LHIPEC could be a good therapeutic option to palliate malignant ascites from mesothelioma in cases not eligible for a radical treatment. Further studies are needed to standardize dosage and perfusion parameters.

Chronic myeloid leukemia among patients with a history of prior malignancies: A tale of dual survivorship.

PubMed

Koller, Paul B; Kantarjian, Hagop M; Nogueras-Gonzalez, Graciela M; Jabbour, Elias; Verstovsek, Srdan; Borthakur, Gautam; Estrov, Zeev; Wierda, William G; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Ravandi, Farhad; O'Brien, Susan M; Cortes, Jorge E

2017-02-15

Some patients with chronic myeloid leukemia (CML) have a history of previous malignancies. To the authors' knowledge, outcomes for CML diagnosed in these patients have not been well described. The current study was conducted to determine the outcome of patients with CML and a history of prior malignancies. The current study included patients who were enrolled in clinical trials of tyrosine kinase inhibitors as initial therapy for CML in chronic phase from July 2000 to January 2014. Of the 630 patients with CML who were treated with frontline tyrosine kinase inhibitors, 626 had a known prior malignancy status. Of these, 45 patients (7%) had a prior malignancy other than nonmelanoma skin cancer whereas 17 patients (3%) had a history of nonmelanoma skin cancers alone. Characteristics of CML were similar between the patients with no prior malignancy, those with a prior malignancy, and those with nonmelanoma skin cancer. Patients with a prior malignancy were found to have an older median age compared with the other 2 groups. The most common prior malignancies were nonmelanoma skin cancer in 20 patients, breast cancer in 11 patients, melanoma in 7 patients, prostate cancer in 6 patients, and colorectal cancer in 5 patients. With regard to CML, the event-free survival, transformation-free survival, and failure-free survival rates were found to be similar between the groups. There was a statistically significantly decreased survival in the group with a prior malignancy versus the group with no prior malignancy versus the group with nonmelanoma skin cancer. In a multivariate analysis, advanced age and an elevated creatinine level were found to be associated with worse survival after a diagnosis of CML. Patients with CML with a history of prior malignancies appear to have the same excellent outcome as patients with no prior malignancies. In the few instances in which concomitant therapy for other malignancies was required during therapy with tyrosine kinase inhibitors, this

Long-Term Experience With World Health Organization Grade III (Malignant) Meningiomas at a Single Institution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenberg, Lewis A.; Case Western Reserve University School of Medicine, Cleveland, OH; Prayson, Richard A.

2009-06-01

Purpose: To evaluate the outcomes for patients with Grade III meningiomas as defined by the 2007 World Health Organization standards. Methods and Materials: The slides from patients who had been treated at the Cleveland Clinic for malignant meningiomas were reviewed by a single neuropathologist. The data from 13 patients treated between 1984 and 2006 satisfied the World Health Organization 2007 definition of Grade III meningioma. A total of 24 surgeries were performed, including 13 primary, 7 salvage, and 4 second salvage. Also, 14 courses of radiotherapy (RT) were administered, including fractionated RT in 3 patients after primary surgery, fractionated RTmore » in 4 patients after salvage surgery, salvage stereotactic radiosurgery to six separate areas in 3 patients, and salvage intensity-modulated RT in 1 patient. Results: From the primary surgery, the median survival was 3.4 years, the 5-year survival rate was 47.2%, and the 8-year survival rate was 12.2%. The median time to recurrence was 9.6 months. A trend was seen toward longer survival for patients who had received adjuvant RT after initial surgery compared with those treated with surgery alone. Two patients developed radiation necrosis, and three had surgical complications. Conclusion: This is one of the few studies reporting the outcomes for malignant meningioma patients according to recent definitions. Our results are consistent with existing reports of the overall poor outcomes for atypical and malignant meningioma patients. From the available data, surgical resection followed by RT and salvage therapy can lead to extended survival.« less

SDHB-related pheochromocytoma and paraganglioma penetrance and genotype-phenotype correlations.

PubMed

Jochmanova, Ivana; Wolf, Katherine I; King, Kathryn S; Nambuba, Joan; Wesley, Robert; Martucci, Victoria; Raygada, Margarita; Adams, Karen T; Prodanov, Tamara; Fojo, Antonio Tito; Lazurova, Ivica; Pacak, Karel

2017-08-01

Succinate dehydrogenase subunit B (SDHB) gene mutations are associated with an aggressive clinical disease course of pheochromocytoma/paraganglioma (PHEO/PGL). Limited information is available concerning PHEO/PGL penetrance among SDHB mutation carriers with regards to primary tumor location, specific mutation type, and gender. We assessed PHEO/PGL penetrance in SDHB mutation carriers and described the clinical presentation and disease course. Asymptomatic relatives (N = 611) of 103 index patients were tested for SDHB mutations. Mutation carriers (N = 328) were offered PHEO/PGL screening, of which 241 participated and were included in penetrance analysis. For additional disease outcome analysis, the 103 index patients and 40 screened individuals who developed PHEO/PGL were included. Clinical data were collected between October 2004 and June 2016. Forty (16.60%) of the 241 screened individuals developed PHEO/PGL during the study. The penetrance estimate in this population was 49.80% (95% CI 29-74.9) at 85 years. A significantly higher age-related penetrance of disease was observed in males compared to females, with 50% penetrance achieved at age 74 vs. not reached. Age-related penetrance analysis demonstrated 4 mutations (Ile127Ser, IVS1+1G>T, Exon 1 deletion, Arg90X) presenting with a slower rate of disease development (50% penetrance ages, respectively: not achieved, 70, 63, 61 years) compared to Arg46X and Val140Phe mutations (50% penetrance at 38 years). Here, we found a higher estimated penetrance compared to several other studies, and a striking difference in age-related penetrance between male and female SDHB mutation carriers with no association between mutation and gender or tumor location.

First case report of locally advanced malignant nodular hidradenoma of the scrotum.

PubMed

Shah, Binay K; Qamruzzaman, Yusuf; Serban, Karina; Hire, Ervin; Ying, Shan-Ching

2010-01-01

Malignant nodular hidradenoma (MNH) is a malignant tumor of the eccrine glands, and most commonly involves the head, trunk, and extremities. To the best of our knowledge, MNH of the scrotum has not yet been described in the English literature. Despite the use of surgery, chemotherapy, radiotherapy, and hormonal therapy, optimal treatment of MNH is unclear. We describe the case of a 30-year-old African American man who was diagnosed with locally advanced MNH of the scrotum and treated with surgery. More than 2 years after surgery, the patient is without evidence of disease. This is the first case report of MNH of the scrotum. Surgery alone may be sufficient for the treatment of localized or locally advanced MNH. Copyright © 2010 S. Karger AG, Basel.

Endoscopic stenting versus operative gastrojejunostomy for malignant gastric outlet obstruction.

PubMed

Chandrasegaram, Manju D; Eslick, Guy D; Mansfield, Clare O; Liem, Han; Richardson, Mark; Ahmed, Sulman; Cox, Michael R

2012-02-01

Malignant gastric outlet obstruction represents a terminal stage in pancreatic cancer. Between 5% and 25% of patients with pancreatic cancer ultimately experience malignant gastric outlet obstruction. The aim in palliating patients with malignant gastric outlet obstruction is to reestablish an oral intake by restoring gastrointestinal continuity. This ultimately improves their quality of life in the advanced stages of cancer. The main drawback to operative bypass is the high incidence of delayed gastric emptying, particularly in this group of patients with symptomatic obstruction. This study aimed to compare surgical gastrojejunostomy and endoscopic stenting in palliation of malignant gastric outlet obstruction, acknowledging the diversity and heterogeneity of patients with this presentation. This retrospective study investigated patients treated for malignant gastric outlet obstruction from December 1998 to November 2008 at Nepean Hospital, Sydney, Australia. Endoscopic duodenal stenting was performed under fluoroscopic guidance for placement of the stent. The operative patients underwent open surgical gastrojejunostomy. The outcomes assessed included time to diet, hospital length of stay (LOS), biliary drainage procedures, morbidity, and mortality. Of the 45 participants in this study, 26 underwent duodenal stenting and 19 had operative bypass. Comparing the stenting and operative patients, the median time to fluid intake was respectively 0 vs. 7 days (P < 0.001), and the time to intake of solids was 2 vs. 9 days (P = 0.004). The median total LOS was shorter in the stenting group (11 vs. 25 days; P < 0.001), as was the median postprocedure LOS (5 vs. 10 days; P = 0.07). Endoscopic stenting is preferable to operative gastrojejunostomy in terms of shorter LOS, faster return to fluids and solids, and reduced morbidity and in-hospital mortality for patients with a limited life span.

[Non-Hodgkin's malignant lymphoma with cervicofacial expression. Modulation of the radiotherapy-chemotherapy combination according to the cytological class].

PubMed

Bolla, M; Sotto, J J; Sotto, M F; Junien Lavillauroy, C; Bryon, J P; Vrousos, C; Holland, D

1984-01-01

An analysis was conducted in March 1983, after a mean follow up of 40 months, of cases of cervicofacial stages I and II non-Hodgkins malignant lymphoma in 3 children and 41 adults (mean age: 51 years, range: 6-90 years) treated between 1969 and March 1981. According to the Working Formulation malignancy was low in 4 cases, intermediate in 24 and high in 13; 3 cases could not ne classified retrospectively. Cytologic classification showed 13 of class 1 of low malignancy, 7 of class 2 of high malignancy with leukemic potential, and 16 of class 3 of high malignancy with a course leading to tumor formation. The cavum was involved in 10 cases, the tonsils in 9, the parotids in 1, the uvula in 1, isolated cervical adenopathies in 14, multiple unilateral adenopathies in 3 and bilateral cervical adenopathies in 5 cases. Therapy varied according to the series: in the first series (1969-1975) the 23 cases were treated by radiotherapy alone (40-55 Gy). In the second series (1976-1981) of 21 cases, chemotherapy was given as a function of the cytologic class: prophylactic chemotherapy for 6 months after radiation for classes 1 and 2, initial chemotherapy for 6 weeks, cerebral radiation and methotrexate intrathecally, and maintenance chemotherapy for 3 months in class 3. The failure rate for radiated zones was identical in the 2 series (less than 10%). Adjusted 5-year survival rate was 60% for series 1 against 70% for series 2 (p = 0.9), and adjusted remission rate was 43% against 64% (p = 0.8).

Malignant melanoma of the nose.

PubMed

Souza, S D; Sujata, G

2001-04-01

Invasive tumors containing abnormal melanocvtes are termed ax malignant melanomas. Primary malignant melanomas of the nasal and paranasal cavities are extremely rare. A 65 years old female presented with bleeding from the nose and a gradually increasing mass in the left nostril. Histopathological examination of the specimen showed "poorly differentiated carcinoma" like features. But S-100 staining proved it to be a malignant melanoma. This case is reported here for its rarity. The literature on malignant melanoma is reviewed and the aetiology pathology, diagnostic and therapeutic problems are also discussed.

[Consensus statement on the clinical management of non-AIDS defining malignancies. GeSIDA expert panel].

PubMed

Santos, Jesús; Valencia, Eulalia

2014-10-01

This consensus document has been prepared by a panel of experts appointed by GeSIDA. This paper reviews the recommendations on the most important non-AIDS defining malignancies that can affect patients living with AIDS. Lung cancer, hepatocellular carcinoma, anal carcinoma and other less frequent malignancies such as breast, prostate, vagina or colon cancers are reviewed. The aim of the recommendations is to make clinicians who attend to this patients aware of how to prevent, diagnose and treat this diseases. The recommendations for the use of antiretroviral therapy when the patient develops a malignancy are also presented. In support of the recommendations we have used the modified criteria of the Infectious Diseases Society of America. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies

PubMed Central

Tai, Yu-Hsiao; Tai, Yi-Jou; Hsu, Heng-Cheng; Lee, Shu-Ping; Chen, Yun-Yuan; Chiang, Ying-Cheng; Chen, Yu-Li; Chen, Chi-An; Cheng, Wen-Fang

2017-01-01

We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease (P < 0.001, Kruskal-Wallis test), serous and mixed histological types (P = 0.003, Kruskal-Wallis test), malignant ascites (P = 0.009, chi-square test), and history of other drug allergy (P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t-test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t-test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications. PMID:29163180

Malignant fibrous histiocytoma of the head and neck: a case series.

PubMed

Hardison, Scott Allen; Davis, Paul Lawson; Browne, J Dale

2013-01-01

The study objective is to evaluate the clinical features and outcomes of patients treated for head and neck malignant fibrous histiocytoma at a tertiary care medical facility. This is a retrospective case series of 17 adult subjects with malignant fibrous histiocytoma of the head and neck who were treated between January 1, 1965, and December 31, 2010. This study was conducted using patient charts at a tertiary medical center. Subject selection was conducted using Current Procedural Terminology numbers; International Classification of Diseases, Ninth Revision, codes; and a search of the tumor registry. Chart review of the 17 identified subjects revealed an overwhelming male predominance (88%) with an overall mean age of 69 years(52-87 years). Thirteen patients (78%) underwent some form of surgical resection, 6 patients (35%) received radiation therapy, and 6 (35%) were given chemotherapy over the course of treatment. Nine tumors (53%) had a cutaneous origin, whereas 8 lesions (47.1%) were found in the soft tissue of the head and neck region. The local recurrence rate following a single resection was 46%. Overall median survival following diagnosis was found to be 65 months, with a 5-year survival rate of 52%. Median disease-free survival was 20 months, with a 5-year disease-free survival rate of 37%. Overall median and 5-year survival rates were found to increase with clear surgical margins, as was 5-year survival. Aggressive surgical management to achieve clear margins is central to the effective treatment of malignant fibrous histiocytoma of the head and neck. Metastatic disease portends a dismal prognosis. Copyright © 2013 Elsevier Inc. All rights reserved.

Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.

PubMed

Tai, Yu-Hsiao; Tai, Yi-Jou; Hsu, Heng-Cheng; Lee, Shu-Ping; Chen, Yun-Yuan; Chiang, Ying-Cheng; Chen, Yu-Li; Chen, Chi-An; Cheng, Wen-Fang

2017-01-01

We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease ( P < 0.001, Kruskal-Wallis test), serous and mixed histological types ( P = 0.003, Kruskal-Wallis test), malignant ascites ( P = 0.009, chi-square test), and history of other drug allergy ( P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t -test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t -test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

Long-term follow-up of endocrine function among young children with newly diagnosed malignant central nervous system tumors treated with irradiation-avoiding regimens.

PubMed

Cochrane, Anne M; Cheung, Clement; Rangan, Kasey; Freyer, David; Nahata, Leena; Dhall, Girish; Finlay, Jonathan L

2017-11-01

The adverse effects of irradiation on endocrine function among patients with pediatric brain tumor are well documented. Intensive induction chemotherapy followed by marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) without central nervous system (CNS) irradiation has demonstrated efficacy in a proportion of very young children with some malignant CNS tumors. This study assessed the long-term endocrine function of young children following chemotherapy-only treatment regimens. A retrospective chart review was performed on 99 patients under 6 years of age with malignant brain tumors newly diagnosed between May 1991 and October 2010 treated with irradiation-avoiding strategies. Thirty patients survived post-AuHCR without cranial irradiation for a mean of 8.1 years (range 3.0-22.25 years). The patient cohort included 18 males and 12 females (mean age at AuHCR of 2.5 years, range 0.8-5.1 years). All 30 surviving patients had documented normal age-related thyroid function, insulin-like growth factor binding protein 3 (IGF-BP3), prolactin, testosterone, and estradiol levels. Insulin-like growth factor 1 age-related levels were abnormal in one child with normal height. Ninety-seven percent of patients had normal cortisol levels, while follicle-stimulating hormone and LH levels among females were normal in 83% and 92%, respectively, and in 100% of males. Growth charts demonstrated age-associated growth within 2 standard deviations of the mean in 67% of patients. Of 10 patients (33%) with short stature, 6 had proportional diminutions in both height and weight. These findings demonstrate that the use of relatively brief, intensive chemotherapy regimens including marrow-ablative chemotherapy with AuHCR results in fewer endocrine sequelae than treatment schemes utilizing CNS irradiation. © 2017 Wiley Periodicals, Inc.

Evaluation of T1/T2 ratios in a pilot study as a potential biomarker of biopsy: proven benign and malignant breast lesions in correlation with histopathological disease stage.

PubMed

Malikova, Marina A; Tkacz, Jaroslaw N; Slanetz, Priscilla J; Guo, Chao-Yu; Aakil, Adam; Jara, Hernan

2017-08-01

Early breast cancer detection is important for intervention and prognosis. Advances in treatment and outcome require diagnostic tools with highly positive predictive value. To study the potential role of quantitative MRI (qMRI) using T1/T2 ratios to differentiate benign from malignant breast lesions. A cross-sectional study of 69 women with 69 known or suspicious breast lesions were scanned with mixed-turbo spin echo pulse sequence. Patients were grouped according to histopathological assessment of disease stage: untreated malignant tumor, treated malignancy and benign disease. Elevated T1/T2 means were observed for biopsy-proven malignant lesions and for malignant lesions treated prior to qMRI with chemotherapy and/or radiation, as compared with benign lesions. The qMRI-obtained T1/T2 ratios correlated with histopathology. Analysis revealed correlation between elevated T1/T2 ratio and disease stage. This could provide valuable complementary information on tissue properties as an additional diagnostic tool.

Catatonic Symptoms Appearing before Autonomic Symptoms Help Distinguish Neuroleptic Malignant Syndrome from Malignant Catatonia.

PubMed

Komatsu, Takayuki; Nomura, Tomohisa; Takami, Hiroki; Sakamoto, So; Mizuno, Keiko; Sekii, Hajime; Hatta, Kotaro; Sugita, Manabu

A 42-year-old Japanese woman with a 10-year history of schizophrenia was admitted due to a disturbance in consciousness that met the diagnostic criteria for both neuroleptic malignant syndrome (NMS) and malignant catatonia. Despite systemic supportive treatments, the catatonic symptoms preceding autonomic symptoms persisted. The symptoms improved after lorazepam administration, leading to a retrospective diagnosis of malignant catatonia. Catatonia is thought to be caused by a dysfunction of ganmma-aminobutyric acid type A receptors in the cortico-cortical networks of the frontal lobes, which causes hypoactivity of the dopaminergic transmission in the subcortical areas. Identifying the catatonic symptoms preceding autonomic symptoms could aid in distinguishing malignant catatonia from NMS.

Antral localization worsens the efficacy of enteral stents in malignant digestive tumors.

PubMed

Dolz, Carlos; Vilella, Àngels; González Carro, Pedro; González Huix, Ferran; Espinós, Juan Carlos; Santolaria, Santos; Pérez Roldán, Francisco; Figa, Montserrat; Loras, Carmen; Andreu, Hernán

2011-02-01

Malignant gastric outlet obstruction can be treated by means of enteral stenting or surgical gastrojejunalanatomosis. We evaluated in a prospective and multicentre study the efficacy of the enteral stent on food intake, the quality of life impact, and the relationship between efficacy and determined clinical and technical parameters. Seventy one patients affected by symptoms arising from gastroduodenal obstruction due to malignant tumors, with criteria of irresecability, metastatic disease or very high surgical risk, were treated by means of self expanding metal stents. We used the GOOSS index to evaluate efficacy, and the Euro Qol-5D index to evaluate quality of life. Before stenting patients with GOOSS 0 and 1 were 68 (98.5%). After stenting patients with GOOSS 2 and 3 (semisolid and solid food) were 58 (84,1%) (P<.0001). The Euro Qol-5D index measured before and a month after stenting were 10.17 and 10.04 respectively (P=.6). The median survival was 91 days (9-552). The enteral stents for localised tumors in the duodenum and the gastrojejunalanastomosis were effective in 26 patients (70.2%) and 13 patients respectively (86.6%), while the enteral stents of tumors in the antrum were effective in only 5 patients (29.4%). The palliative treatment of malignant gastric outlet obstruction with a uncovered metal stent produces a significant improvement of oral food intake and maintains the overall quality of life index. The antral localization is associated with a lower efficacy of the procedure. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Epigenetic regulation of HIV, AIDS, and AIDS-related malignancies.

PubMed

Verma, Mukesh

2015-01-01

Although epigenetics is not a new field, its implications for acquired immunodeficiency syndrome (AIDS) research have not been explored fully. To develop therapeutic and preventive approaches against the human immunodeficiency virus (HIV) and AIDS, it is essential to understand the mechanisms of interaction between the virus and the host, involvement of genetic and epigenetic mechanisms, characterization of viral reservoirs, and factors influencing the latency of the virus. Both methylation of viral genes and histone modifications contribute to initiating and maintaining latency and, depending on the context, triggering viral gene repression or expression. This chapter discusses progress made at the National Institutes of Health (NIH), recommendations from the International AIDS Society Scientific Working Group on HIV Cure, and underlying epigenetic regulation. A number of epigenetic inhibitors have shown potential in treating AIDS-related malignancies. Epigenetic drugs approved by the US Food and Drug Administration and their implications for the eradication of HIV/AIDS and AIDS-related malignancies also are discussed.Past and current progress in developing treatments and understanding the molecular mechanisms of AIDS and HIV infection has greatly improved patient survival. However, increased survival has been coupled with the development of cancer at higher rates than those observed among the HIV/AIDS-negative population. During the early days of the AIDS epidemic, the most frequent AIDS-defining malignancies were Kaposi's sarcoma and non-Hodgkin lymphoma (NHL). Now, with increased survival as the result of widespread use in the developed world of highly active antiretroviral therapy (HAART), non-AIDS defining cancers (i.e., anal, skin, and lung cancers, and Hodgkin disease) are on the increase in HIV-infected populations. The current status of AIDS-related malignancies also is discussed.

The role of chemotherapy in the treatment of malignant astrocytomas.

PubMed

Mathieu, David; Fortin, David

2006-05-01

Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is now used on patients as initial therapy when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide has taken the front seat recently, with recent data demonstrating increased survival when this agent is used concurrently with radiation therapy in newly diagnosed glioblastoma patients. A new class of agents, refered to as biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimens offering promise. In addition, recent advances with biological modifiers are also discussed.

Malignant Mesothelioma—Patient Version

Cancer.gov

Malignant mesothelioma is a cancer of the thin tissue (mesothelium) that lines the lung, chest wall, and abdomen. The major risk factor for mesothelioma is asbestos exposure. Start here to find information on malignant mesothelioma treatment.

Azacitidine and Sonidegib or Decitabine in Treating Patients With Myeloid Malignancies

ClinicalTrials.gov

2018-02-05

Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Polycythemia Vera; Previously Treated Myelodysplastic Syndrome; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Exosomes isolated from cancer patients' sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells.

PubMed

Abdouh, Mohamed; Hamam, Dana; Gao, Zu-Hua; Arena, Vincenzo; Arena, Manuel; Arena, Goffredo Orazio

2017-08-30

Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients' sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients' sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena. We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients' sera or cancer patients' sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts' membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes. Cells treated with exosomes isolated from cancer patients' sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression

Biophotonic markers of malignancy: Discriminating cancers using wavelength-specific biophotons.

PubMed

Murugan, Nirosha J; Rouleau, Nicolas; Karbowski, Lukasz M; Persinger, Michael A

2018-03-01

Early detection is a critically important factor when successfully diagnosing and treating cancer. Whereas contemporary molecular techniques are capable of identifying biomarkers associated with cancer, surgical interventions are required to biopsy tissue. The common imaging alternative, positron-emission tomography (PET), involves the use of nuclear material which poses some risks. Novel, non-invasive techniques to assess the degree to which tissues express malignant properties are now needed. Recent developments in biophoton research have made it possible to discriminate cancerous cells from normal cells both in vitro and in vivo. The current study expands upon a growing body of literature where we classified and characterized malignant and non-malignant cell types according to their biophotonic activity. Using wavelength-exclusion filters, we demonstrate that ratios between infrared and ultraviolet photon emissions differentiate cancer and non-cancer cell types. Further, we identified photon sources associated with three filters (420-nm, 620-nm., and 950-nm) which classified cancer and non-cancer cell types. The temporal increases in biophoton emission within these wavelength bandwidths is shown to be coupled with intrisitic biomolecular events using Cosic's resonant recognition model. Together, the findings suggest that the use of wavelength-exclusion filters in biophotonic measurement can be employed to detect cancer in vitro.

Y-shaped bilateral self-expandable metallic stent placement for malignant hilar biliary obstruction: data from a referral center for palliative care.

PubMed

Di Mitri, R; Mocciaro, F

2014-01-01

Malignant hilar strictures are a clinical challenge because of the current therapeutic approach and the poor prognosis. In recent years, self-expandable metallic stents have proven more effective than plastic stents for palliation of malignant hilar strictures, with the bilateral stent-in-stent technique registering a high success rate. We report our experience with Y-shaped endoscopic self-expandable metallic stents placement for treatment of advanced malignant hilar strictures. From April 2009 to August 2012, we prospectively collected data on patients treated with Y-shaped SEMS placement for advanced malignant hilar carcinoma. Data on technical success, clinical success, and complications were collected. Twenty patients (9 males) were treated (mean age 64.2 ± 15.3 years). The grade of malignant hilar strictures according to the Bismuth classification was II in 5 patients (25%), IIIa in 1 (5%), and IV in 14 (70%). The mean bilirubin level was 14.7 ± 4.9 mg/dL. Technical success was achieved in all patients, with a significant reduction in bilirubin levels (2.9 ± 1.7 mg/dL). One patient experienced cholangitis as early complication, while in 2 patients stent ingrowth was observed. No stents migration was recorded. There was no procedure-related mortality. At the end of the follow-up (7.1 ± 3.1 months), 13 of the 20 patients (65%) had died. Our experience confirms endoscopic bilateral self-expandable metallic stents placement with stent-in-stent technique (Y-shaped configuration) as a feasible, effective, and safe procedure for palliation of unresectable malignant hilar strictures.

Histopathology of malignant salivary gland tumours.

PubMed

Seifert, G

1992-07-01

This report is based upon the Salivary Gland Register in Hamburg and on the second revised edition of the WHO Histological Typing of Salivary Gland Tumours. The group of malignant salivary gland tumours contains carcinomas, malignant non-epithelial tumours, malignant lymphomas and secondary tumours. The various carcinomas are classified in a continuous separate listing because the different types are distinguished not only by histopathology, but also by differences in prognosis and treatment. The term "tumour" is replaced by "carcinoma" in two entities: acinic cell carcinoma and mucoepidermoid carcinoma. New entities are: polymorphous low-grade adenocarcinoma, basal cell adenocarcinoma, salivary duct carcinoma and malignant myoepithelioma. Carcinoma in pleomorphic adenoma can be distinguished as non-invasive and invasive carcinoma, and carcinosarcoma. Malignant non-epithelial tumours are mostly malignant fibrous histiocytoma, malignant schwannoma and rhabdomyosarcoma. The large majority of malignant lymphomas are non-Hodgkin-lymphomas with high differentiation. Many lymphomas are associated with chronic immunosialadenitis (Sjögren's syndrome). Secondary tumours are mostly metastases from primary squamous cell carcinomas or from melanomas of the skin (head and neck area). Haematogeneous metastases are very rare (mainly from lung, kidney or breast).

TAK228 With Carbo and Taxol in Advanced Malignancies

ClinicalTrials.gov

2018-03-12

Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

Cirrhosis related chylous ascites successfully treated with TIPS.

PubMed

de Vries, G J; Ryan, B M; de Bièvre, M; Driessen, A; Stockbrugger, R W; Koek, G H

2005-04-01

We describe a patient with chylous ascites, who was extensively investigated for the cause. No malignant or lymphatic disease could be found, but a liver biopsy revealed liver cirrhosis. The chylous ascites was unsuccessfully treated with a sodium restriction diet, diuretics and a medium chain triglyceride diet. After the placement of a transjugular intrahepatic portosystemic shunt the ascites disappeared.

Catatonic Symptoms Appearing before Autonomic Symptoms Help Distinguish Neuroleptic Malignant Syndrome from Malignant Catatonia

PubMed Central

Komatsu, Takayuki; Nomura, Tomohisa; Takami, Hiroki; Sakamoto, So; Mizuno, Keiko; Sekii, Hajime; Hatta, Kotaro; Sugita, Manabu

2016-01-01

A 42-year-old Japanese woman with a 10-year history of schizophrenia was admitted due to a disturbance in consciousness that met the diagnostic criteria for both neuroleptic malignant syndrome (NMS) and malignant catatonia. Despite systemic supportive treatments, the catatonic symptoms preceding autonomic symptoms persisted. The symptoms improved after lorazepam administration, leading to a retrospective diagnosis of malignant catatonia. Catatonia is thought to be caused by a dysfunction of ganmma-aminobutyric acid type A receptors in the cortico-cortical networks of the frontal lobes, which causes hypoactivity of the dopaminergic transmission in the subcortical areas. Identifying the catatonic symptoms preceding autonomic symptoms could aid in distinguishing malignant catatonia from NMS. PMID:27725556

P16.29 Malignant craniopharyngioma

PubMed Central

Unal, E.; Kilic, K.; Ozdemir, N.; Gunver, F.; Isik, S.; Can, S.

2017-01-01

Abstract Introduction: Malignant transformation of craniopharyngioma has rarely been described. In this article, we report a case of 28th malignant craniopharyngioma ever mentioned in English literature. Materials and Methods: We performed a PUBMED, HUBMED, BAU Library Database and Ovid search on malignant craniopharyngiomas and identified 27 reported cases. CASE DESCRIPTION: 44 years old female patient was diagnosed with craniopharyngioma two years ago and underwent surgical resection of a typical craniopharyngioma, the histopathological result was adamantinomatous craniopharyngioma of Grade I. There was no malignancy. One year ago cavernous sinus invasion has been detected and gamma knife irradiation has been made. At admission she was blind in the right eye for the last six months and the vision was diminished in the left eye for a month. The MRI showed that nasal cavity was full of tumor, that the clivus was almost completely destructed and that orbita and maxillary sinus were also invaded. Firstly the ENT surgeons debulked the tumor via transmaxillary route and then the transcranial approach allowed only a subtotal removal due to a profuse bleeding. The histopatological examination showed malignant tumoral infiltration rich in cells with many mitoses. The patient died two years later. CONCLUSION: The relevant literature of malignant craniopharyngioma is reviewed and discussed. The surgeon must be aware that total removal of a malignant craniopharyngioma can be hazardous because of intractable bleedings occurring during surgery.

Malignant adenomyoepithelioma of breast masquerading as soft tissue lytic lesion of right iliac bone: a rare entity.

PubMed

R, Kalyani; Murthy V, Srinivas

2014-09-01

Adenomyoepithelioma (AME) of breast is a low grade malignant biphasic tumour, usually seen in elderly women as a firm, well circumscribed tumour having both glandular and myoepithelial cells. The cells may show atypical features. The tumour may harbour foci of carcinoma which may be epithelial type, myoepithelial type, both or of metaplastic cells. The behaviour is hard to predict as it can be treated by local excision, recurrence is known or it can present with distant metastasis and hence the prognosis. We present a case of 50-year-old women who presented with right iliac bone lytic lesion diagnosed as metastatic deposits. Past history revealed that patient was diagnosed and treated for AME of right breast seven years back. The metastatic deposits also showed features of adenomyoepithelioma. Hence, a diagnosis of malignant AME deposits in right iliac bone was made.

Impact of Radiofrequency Ablation on Malignant Biliary Strictures: Results of a Collaborative Registry.

PubMed

Sharaiha, Reem Z; Sethi, Amrita; Weaver, Kristen R; Gonda, Tamas A; Shah, Raj J; Fukami, Norio; Kedia, Prashant; Kumta, Nikhil A; Clavo, Carlos M Rondon; Saunders, Michael D; Cerecedo-Rodriguez, Jorge; Barojas, Paola Figueroa; Widmer, Jessica L; Gaidhane, Monica; Brugge, William R; Kahaleh, Michel

2015-07-01

Radiofrequency ablation of malignant biliary strictures has been offered for the last 3 years, but only limited data have been published. To assess the safety, efficacy, and survival outcomes of patients receiving endoscopic radiofrequency ablation. Between April 2010 and December 2013, 69 patients with unresectable neoplastic lesions and malignant biliary obstruction underwent 98 radiofrequency ablation sessions with stenting. A total of 69 patients (22 male, aged 66.1 ± 13.3) were included in the registry. The etiology of malignant biliary stricture included unresectable cholangiocarcinoma (n = 45), pancreatic cancer (n = 19), gallbladder cancer (n = 2), gastric cancer (n = 1), and liver metastasis from colon cancer (n = 3). Seventy-eight percentage of patients had prior chemotherapy. All strictures were stented post-radiofrequency ablation with either plastic stents or metal stents. The mean stricture length treated was 14.3 mm. There was a statistically significant improvement in stricture diameter post-ablation (p < 0.0001). The likelihood of stricture improvement was significantly greater in pancreatic cancer-associated strictures [RR 1.8 (95 % 1.03-5.38)]. Seven patients (10 %) had adverse events, not linked directly to radiofrequency ablation. Median survival was 11.46 months (6.2-25 months). Radiofrequency ablation is effective and safe in malignant biliary obstruction and seems to be associated with improved survival.

Management of occluded self-expanding biliary metal stents in malignant biliary disease.

PubMed

Nennstiel, Simon; Tschurtschenthaler, Isolde; Neu, Bruno; Algül, Hana; Bajbouj, Monther; Schmid, Roland M; von Delius, Stefan; Weber, Andreas

2018-02-01

Occlusion of self-expanding metal stents (SEMS) in malignant biliary obstruction occurs in up to 40% of patients. This study aimed to compare the different techniques to resolve stent occlusion in our collective of patients. Patients with malignant biliary obstruction and occlusion of biliary metal stent at a tertiary referral endoscopic center were retrospectively identified between April 1, 1994 and May 31, 2014. The clinical records were further analyzed regarding the characteristics of patients, malignant strictures, SEMS, management strategies, stent patency, subsequent interventions, survival time and case charges. A total of 108 patients with biliary metal stent occlusion were identified. Seventy-nine of these patients were eligible for further analysis. Favored management was plastic stent insertion in 73.4% patients. Second SEMS were inserted in 12.7% patients. Percutaneous transhepatic biliary drainage and mechanical cleansing were conducted in a minority of patients. Further analysis showed no statistically significant difference in median overall secondary stent patency (88 vs. 143 days, P = 0.069), median survival time (95 vs. 192 days, P = 0.116), median subsequent intervention rate (53.4% vs. 40.0%, P = 0.501) and median case charge (€5145 vs. €3473, P = 0.803) for the treatment with a second metal stent insertion compared to plastic stent insertion. In patients with survival time of more than three months, significantly more patients treated with plastic stents needed re-interventions than patients treated with second SEMS (93.3% vs. 57.1%, P = 0.037). In malignant biliary strictures, both plastic and metal stent insertions are feasible strategies for the treatment of occluded SEMS. Our data suggest that in palliative biliary stenting, patients especially those with longer expected survival might benefit from second SEMS insertion. Careful patient selection is important to ensure a proper decision for either management

Percutaneous stent placement for the treatment of malignant biliary obstruction: nitinol versus elgiloy stents.

PubMed

Zurstrassen, Charles Edouard; Bitencourt, Almir Galvão Vieira; Guimaraes, Marcos Duarte; Cavalcante, Aline Cristine Barbosa Santos; Tyng, Chiang Jeng; Amoedo, Mauricio Kauark; Matsushita Junior, João Paulo Kawaoka; Szklaruk, Janio; Marchiori, Edson; Chojniak, Rubens

2017-01-01

This study aimed to compare two self-expanding stents, a nitinol stent and an elgiloy stent, both placed percutaneously, in terms of their efficacy in palliating inoperable malignant biliary obstruction. We retrospectively investigated 99 patients with unresectable malignant biliary obstruction treated with percutaneous placement of a self-expanding metallic stent at our institution between May 2007 and January 2010. Serum bilirubin and liver enzyme levels were measured before and 30 days after stenting. For all procedures using elgiloy or nitinol stents, stent occlusion and patient survival rates were calculated using Kaplan-Meyer analysis. All of the patients showed clinical improvement after stent placement, with no difference between the two groups. In both groups, the occlusion-free survival rate was 67% at 30 days, 37% at 90 days, 25% at 180 days, and 10% at 360 days, with no significant difference in relation to the type of stent. The two stents evaluated showed comparable efficacy for the percutaneous treatment of unresectable biliary malignancy, with good clinical results.

188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas

PubMed Central

Allard, Emilie; Hindré, François; Passirani, Catherine; Lemaire, Laurent; Lepareur, Nicolas; Noiret, Nicolas; Menei, Philippe; Benoit, Jean-Pierre

2008-01-01

Purpose Lipid nanocapsules (LNC) entrapping lipophilic complexes of 188Re (188Re(S3CPh)2(S2CPh) [188Re-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intracerebral administration of 188Re-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model. Methods Female Fischer rats with 9L glioma were treated with a single injection of 188Re-SSS LNC by CED 6 days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8, and 3 Gy in comparison with blank LNC, perrhenate solution (4Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring 188Re elimination in faeces and urine over 72h after the CED injection. The therapeutic effect of 188Re-SSS LNC was assessed based on animal survival. Results CED of 188Re perrhenate solution resulted in rapid drug clearance with a brain T1/2 of 7h. In contrast, when administered in LNC, 188Re tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72h. Rat median survival was significantly improved for the group treated with 8Gy 188Re-SSS LNC compared to the control group and blank-LNC treated animals. The increase in the median survival time (ISTmedian) was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8Gy proved to be a very effective dose, between toxic (10–12Gy) and ineffective (3–4Gy) doses. Conclusions These findings show that CED of Rhenium-188-loaded lipid nanocapsules is a safe and potent antitumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of Rhenium-188 internal radiotherapy for the treatment of brain malignancy. PMID:18465130

A potential individual cell malignancy indicator: focal length

NASA Astrophysics Data System (ADS)

Wang, Weina; Lear, Kevin L.

2011-03-01

The label-free technique of optofluidic intracavity spectroscopy (OFIS) utilizes the optical transmission spectrum of a cell in a microfluidic Fabry-Pérot (F-P) cavity to distinguish cells from cancerous cell lines and baseline normal blood cells. The classification between canine hemangiosarcoma (HSA) cancer cells and monocytes in canine normal peripheral blood mononuclear cells (PBMCs) had been demonstrated with 95% sensitivity and 98% specificity. Now with a new optical model that treats the cell settled at the bottom of the cavity as a thin lens, the focal length of cells was extracted and used as an individual cell malignancy indicator.

Changing presentation of cutaneous malignant melanoma.

PubMed

Klit, Anders; Lassen, Cecilie Brandt; Olsen, Caroline Holkmann; Lock-Andersen, Jørgen

2015-10-01

The incidence of cutaneous malignant melanoma is rapidly increasing in Denmark like in other Northern and Western European countries. Our objective was to investigate the characteristics of current patients suffering from cutaneous malignant melanoma. We evaluated patient and tumour characteristics in a cross-sectional study based on data from the Danish Melanoma Register. We included all patients diagnosed with cutaneous malignant melanoma in Healthcare Region Zealand in 2012 and 2013. We identified 520 patients with invasive cutaneous malignant melanoma. More females than males suffered from cutaneous malignant melanoma. Furthermore, females were younger than males, and the anatomical distribution of malignant melanoma varied between the genders. Outcome of sentinel lymph node biopsy was associated with tumour thickness. When comparing findings in our study with earlier Danish studies, we see a trend towards an increase in age at diagnosis. Furthermore, tumour thickness is decreasing and the topical distribution of cutaneous malignant melanoma in females changes towards a male pattern. none. The study has been approved by the Danish National Data Protection Agency.

18F-FDOPA PET/CT imaging of MAX-related pheochromocytoma.

PubMed

Taïeb, David; Jha, Abhishek; Guerin, Carole; Pang, Ying; Adams, Karen T; Chen, Clara C; Romanet, Pauline; Roche, Philippe; Essamet, Wassim; Ling, Alexander; Quezado, Martha M; Castinetti, Frédéric; Sebag, Fréderic; Pacak, Karel

2018-03-08

MYC associated factor X (MAX) has been recently described as a new susceptibility pheochromocytoma (PHEO) gene with a total of approximately 40 reported cases. At present, no study has specifically described the functional imaging phenotype of MAX-related PHEO. The objective of this study was to present our experience with contrast-enhanced CT and 18F-FDOPA PET/CT imaging in 6 consecutive patients (4 at initial diagnosis and 2 at follow-up evaluation) with rare but clinically important MAX-related PHEOs. In 5 patients, 18F-FDOPA was also compared to other radiopharmaceuticals. Patients had 5 different mutations in the MAX gene that caused disruption of Max/Myc interaction and/or abolished interaction with DNA based on in-silico analyses. All but one patient developed bilateral PHEOs during their lifetime. In all cases, 18F-FDOPA PET/CT accurately visualized PHEOs that were often multiple within the same gland or bilateral and detected more adrenal and extradrenal lesions than CT (per lesion sensitivity 90.5% vs 52.4% for CT/MRI). The 2 missed PHEO on 18F-FDOPA PET/CT were <1cm, corresponding to nodular adrenomedullary hyperplasia. 68Ga-DOTATATE PET/CT detected fewer lesions than 18F-FDOPA PET/CT in 1/3 patients and 18F-FDG PET/CT was only faintly positive in 2/4 patients with underestimation of extraadrenal lesions in 1 patient. MAX-related PHEO exihibit a marked 18F-FDOPA uptake, a finding that illustrates the common well-differentiated chromaffin pattern of PHEO associated with activation of kinase signaling pathways. 18F-FDOPA PET/CT should be considered as the first-line functional imaging modality for diagnostic or follow-up evaluation in these patients.