Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors

Panzuto, Francesco; Severi, Carola; Cannizzaro, Renato; Falconi, Massimo; Angeletti, Stefano; Pasquali, Alessandra; Corleto, V.D.; Annibale, Bruno; Buonadonna, Angela; Pederzoli, Paolo; Fave, Gianfranco Delle

doi:10.1007/bf03350903

Cited by 97 publications

(65 citation statements)

References 22 publications

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“…The most critical discrepancies were (a) the composition of the case groups, with the strongest difference being represented by the fact that some studies included NEN from all sites (Bernini et al 2001, Donica et al 2010, Molina et al 2011, Korse et al 2012, Marotta et al 2012, Tohmola et al 2014, whereas some others tried to analyze more homogeneous set of patients, mainly selecting gastroenteropancreatic tumors (Tomassetti et al 2001a, Peracchi et al 2003, Nehar et al 2004, Zatelli et al 2007, Belli et al 2009, Modlin et al 2013 (Table 1); (b) the composition of the control groups: although the majority of studies used healthy subjects as controls (Bernini et al 2001, Tomassetti et al 2001b, Peracchi et al 2003, Nehar et al 2004, Campana et al 2007, Zatelli et al 2007, Belli et al 2009, Donica et al 2010, Molina et al 2011, Korse et al 2012, which represents the best approach to assess the diagnostic performance of a marker (Shapiro 1999), some researchers determined the metrics of circulating CgA by comparing NEN with non-NEN tumors (Nobels et al 1998, Panzuto et al 2004 or active versus diseasefree NEN (Bajetta et al 1999, Panzuto et al 2004; (c) the consideration of interfering factors: some authors tried to clean up the control group from those conditions with known effect on CgA levels, thus obtaining a more pristine evaluation of marker specificity (Bernini et al 2001, Tomassetti et al 2001b, Nehar et al 2004, Campana et al 2007…”

Section: Circulating Cga In the Diagnostic Phase Of Nenmentioning

confidence: 99%

“…By contrast, there are some tumors showing CgA elevation where the presence of histological neuroendocrine differentiation has not been reported, such as primary hepatocellular cancer (Spadaro et al 2005) and breast cancer (Giovanella et al 2001). To date, the capability of circulating CgA in discriminating NEN from other malignancies has been evaluated by many studies, which reported controversial results characterized by wide variation of specificity values (Nobels et al 1998, Nehar et al 2004, Panzuto et al 2004, Molina et al 2011, Marotta et al 2012 (Table 3). This was likely due to the heterogeneity of both NEN groups and neoplastic controls, with the latter including different tumor types.…”

Section: Oncological Causes Of Cga Elevationmentioning

confidence: 99%

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Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Marotta

Zatelli

Sciammarella³

et al. 2018

Endocrine-Related Cancer

128

104

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Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects.

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Section: Circulating Cga In the Diagnostic Phase Of Nenmentioning

confidence: 99%

Section: Oncological Causes Of Cga Elevationmentioning

confidence: 99%

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Marotta

Zatelli

Sciammarella³

et al. 2018

Endocrine-Related Cancer

128

104

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“…Furthermore, pheochromocytoma or paraganglioma in the pancreas, to a certain extent, is a type of pancreatic neuroendocrine tumor (pNET), which means that the tumor cells of resected tumors may demonstrate positive reactions for CgA and Syn following immunohistochemical staining (12). With regard to the first two cases presented here, this pathological feature is of significant value for histological diagnosis of pancreatic pheochromocytoma.…”

Section: Discussionmentioning

confidence: 72%

Pheochromocytoma of the pancreas: A report of three cases and a literature review

Ding¹,

Min²,

He³

et al. 2016

Oncology Letters

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Abstract. Pheochromocytoma is primarily derived from the adrenal medulla. The majority of extra-adrenal pheochromocytoma cases occur in the superior para-aortic region and para-adrenal area. However, pheochromocytoma originating from the pancreas is rare. The present study reports the cases of three patients who had no history of hypertension but were post-operatively diagnosed with pheochromocytoma located in the pancreas. Of the three patients, two were admitted to hospital due to abdominal pain, and imaging examinations revealed a soft-tissue lesion in the head of pancreas. Local resection of the pancreatic tumor was successfully performed and a diagnosis of pheochromocytoma derived from the pancreas was subsequently made by pathologists. The third patient was admitted to hospital for surgical treatment due to the identification of a continuously growing lesion in the tail of pancreas during physical examinations. Distal resection of the pancreas was stopped during surgery when the patient's blood pressure and heart rate suddenly increased to 180/110 mmHg and 140 beats/min, respectively. Due to a marked rise in noradrenaline and adrenaline levels in the blood subsequent to surgery, the patient was diagnosed with pancreatic pheochromocytoma. The present study additionally reviewed the associated literature concerning pheochromocytoma in order to improve the understanding of this rare clinical phenomenon. The aim of the present study is to highlight to surgeons that although patients may not present with typical clinical manifestations due to the non-functional status of the tumor, undiagnosed pheochromocytoma of the pancreas should be considered when surgeons observe an unexpected hypertensive crisis during pancreatic tumor surgery. IntroductionPheochromocytoma is a catecholamine-secreting tumor that originates from chromaffin cells. The majority of these tumors arise in the adrenal medulla (1), and when they occur outside the adrenal gland they are known as an extra-adrenal pheochromocytoma or a paraganglioma (2). Pheochromocytoma is primarily sporadic, but may additionally be associated with multiple endocrine neoplasia syndrome (3) and mutations of mitochondrial complex 2 succinate dehydrogenase enzymes (4).Extra-adrenal pheochromocytoma has been previously reported to account for ~10% of all pheochromocytoma cases during adulthood and for 30-40% of cases in children (5). These tumors may occur in the superior para-aortic region, the para-adrenal area and the inferior para-aortic region, as well as the organ of Zuckerkandl and the urinary bladder (6-8). Pancreatic localization of extra-adrenal pheochromocytoma is rare, and to the best of our knowledge, only one case has been previously reported in the Chinese literature (9). In the present study, the cases of three patients (Table I) with pheochromocytoma involving the pancreas are presented. To the best of our knowledge, the present report is the first to present three definite and comprehensive cases of this rare clinical phenomenon. In addition, the rele...

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“…• Chromogranin A (CgA) 67-93% [8] 85-88% [8] • Chromogranin B (CgB) 57% [19] 100% [19] Neuronspecifi kus enoláz (NSE) 100% [9] 32,9% [9] Pancreaspolipeptid (PP) 54-57% [33] 81% [33] …”

Section: Chromograninokmentioning

confidence: 99%

Significance of biochemical markers in the diagnosis of neuroendocrine tumours and in the follow-up of patients

et al. 2014

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A vérben keringő, illetve a vizelettel ürülő neuroendokrin tumormarkerek vizsgálata kiemelt fontosságú diagnosztikai eszköz a neuroendokrin daganatok kórisméjének felállításában. Az általános neuroendokrin tumormarkerek olyan biológiailag aktív fehérjék, amelyek szintézisére minden neuroendokrin differenciálódást mutató sejt képes, ezért vizsgálatuk megfelelően érzékeny módszernek bizonyult e daganatok felismeréséhez. Az általános neuroendokrin tumormarkerek közül a legszélesebb körben a chromogranin A vizsgálata terjedt el. A legújabb eredmények szerint a chromogranin A szérumkoncentrációjának vizsgálata a kórjóslat megállapításában, a daganatellenes terápia haté-konyságának előrejelzésében, továbbá a daganatkiújulás észlelésében is fontos eszközként szolgál. Az általános tumormarker mellett a sejtspecifi kus markerek is komoly jelentőséggel bírnak. Jelen közleményben a szerzők áttekintik a neuroendokrin tumormarkerek szerepét a daganatok diagnosztikájában, illetve a betegek kezelése és utánkövetése során. Orv. Hetil., 2014, 155(45), 1775-1782

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Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors

Abstract: The combined assessment of PP and CgA leads to a significant increase in sensitivity in the diagnosis of GEP tumors, particularly in pancreatic NF.

Cited by 97 publications

References 22 publications

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Pheochromocytoma of the pancreas: A report of three cases and a literature review

Significance of biochemical markers in the diagnosis of neuroendocrine tumours and in the follow-up of patients

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