Use of Molecular Profiling to Guide Treatment Decisions in Patients with Neuroendocrine Tumors: Preliminary Results

This case series demonstrates the potential of molecular profiling to improve selection of anti-tumor therapies in the treatment of patients with neuroendocrine and carcinoid tumors. Carcinoid tumors resected at one institution over a 3-year period were sent for molecular profiling to guide choice of treatment. Potentially beneficial therapies were identified based on the measured expression of 20 proteins and oncogenes and a comprehensive review of the chemotherapy response literature. The clinical charts of 41 patients were reviewed retrospectively, and 12 were selected as representatives of the range of effects molecular profiling has on carcinoid treatment. Their presentation, molecular profile results, treatment, and disease progression is reviewed in the following case series. A total of nine patients were treated with drugs identified as potentially beneficial by molecular profile reports. These include capecitabine, 5-fluorouracil, temozolomide, oxaliplatin, and gemcitabine. Based on clinical symptoms, serum markers of disease, and radio-graphic evidence five of nine patients responded to treatment, two had mixed responses, and two did not respond to treatment. At this early juncture, our critique of molecular profiling for neuroendocrine tumors is favorable, as a significant number of our patients responded to drugs identified by molecular profiling as potentially beneficial.

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Investigating the clinical, pathological and molecular profile of oncocytic adrenocortical neoplasms

Endocrine Oncology ◽

10.1530/eo-21-0011 ◽

2021 ◽

Author(s):

Eleanor Fewings ◽

Serena Khoo Sert Kim ◽

Alexey Larionov ◽

Alison Marker ◽

Olivier Giger ◽

...

Keyword(s):

Treatment Strategies ◽

Case Series ◽

Missense Variant ◽

Molecular Profiling ◽

The Cancer Genome Atlas ◽

Biological Behavior ◽

Molecular Profile ◽

Mutation Burden ◽

Rare Tumours ◽

Paired Tumour

Background: Malignant oncocytic adrenocortical neoplasms (OANs) are rare tumours with a distinctive biological behavior compared to conventional adrenocortical carcinoma (ACC). The current prognostic systems overestimate the malignant potential of these tumours and guidance for surveillance and treatment strategies are lacking. Aim: To evaluate the utility of clinical, pathological and molecular markers in predicting the biological behavior and outcomes of malignant OANs. Methods: A retrospective clinicopathological review of ten histologically confirmed OANs was carried out. Whole exome sequencing (WES) of germline and paired tumour samples was performed for four of the ten OAN cases and compared to WES data from five cases of conventional ACC and data from The Cancer Genome Atlas (TCGA). We reviewed all cases of malignant OAN reported in the literature and compared to our case series. Results: Eight (80%) tumours were classified as malignant, one borderline and one benign (Lin-Weiss-Bisceglia criteria: LWB). The malignant OAN were larger tumours and had higher MIB index and Helsinki scores. Molecular profiling identified a pathogenic germline variant in MSH6 in an individual in the OAN group. The OAN samples had a lower mutation burden compared to the ACC samples. Somatic driver variants were identified in OAN and ACC samples including a pathogenic missense variant in CTNNB1. Conclusion: In this study, the LWB classification demonstrated sensitivity for the differentiation of benign from malignant OAN. Molecular profiling identified dysregulation in DNA repair and Wnt signaling pathways in both OAN and ACC samples, suggesting a molecular overlap between OAN and conventional ACC.

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Die Rolle der131J-Metajod-benzylguanidin-(MIBG-) Szintigraphie in der Diagnostik der intestinalen Karzinoide

Nuklearmedizin ◽

10.1055/s-0038-1628901 ◽

1987 ◽

Vol 26 (06) ◽

pp. 263-267

Author(s):

M. L. Sautter-Bihl ◽

K. R. Wilhelm ◽

B. Kimmig ◽

H. Bihl

Keyword(s):

Neuroendocrine Tumors ◽

False Positive ◽

Clinical Symptoms ◽

Cell System ◽

Carcinoid Tumors ◽

Mibg Scintigraphy ◽

Mibg Uptake ◽

131I Mibg

lodine-131 metaiodobenzylguanidine (131I-MIBG) is concentrated in a variety of neuroendocrine tumors, such as pheochromocytoma and neuroblastoma. Other neuroendocrine tumors from the APUD-cell system such as carcinoid tumors, may posses this uptake capability as well. We investigated 11 patients suffering from intestinal carcinoid with 131I-MIBG in order to determine the value of MIBG scintigraphy in these tumors. MIBG scans were positive in 5 out of 11 patients (45%). False-positive MIBG-scans did not occur. No correlation between MIBG uptake, clinical symptoms and urinary 5-HIAA level could be found.

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Treatment and therapeutic strategies for pituitary apoplexy in pregnancy: a case series

Journal of Medical Case Reports ◽

10.1186/s13256-021-02892-5 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Yuya Kato ◽

Yoshikazu Ogawa ◽

Teiji Tominaga

Keyword(s):

Pituitary Apoplexy ◽

Clinical Symptoms ◽

Case Series ◽

Optimal Timing ◽

Presenting Symptoms ◽

Pathological Evaluation ◽

Mother And Child ◽

Life Threatening ◽

In Pregnancy

Abstract Background Pregnancy is a known risk factor for pituitary apoplexy, which is life threatening for both mother and child. However, very few clinical interventions have been proposed for managing pituitary apoplexy in pregnancy. Case presentation We describe the management of three cases of pituitary apoplexy during pregnancy and review available literature. Presenting symptoms in our case series were headache and/or visual disturbances, and the etiology in all cases was hemorrhage. Conservative therapy was followed until 34 weeks of gestation, after which babies were delivered by cesarean section with prophylactic bolus hydrocortisone supplementation. Tumor removal was only electively performed after delivery using the transsphenoidal approach. All three patients and their babies had a good clinical course, and postoperative pathological evaluation revealed that all tumors were functional and that they secreted prolactin. Conclusions Although the mechanism of pituitary apoplexy occurrence remains unknown, the most important treatment strategy for pituitary apoplexy in pregnancy remains adequate hydrocortisone supplementation and frequent hormonal investigation. Radiological follow-up should be performed only if clinical symptoms deteriorate, and optimal timing for surgical resection should be discussed by a multidisciplinary team that includes obstetricians and neonatologists.

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Acute Pancreatitis as a Complication of Antiepileptic Treatment: Case Series and Review of the Literature

Pediatric Reports ◽

10.3390/pediatric13010014 ◽

2021 ◽

Vol 13 (1) ◽

pp. 98-103

Author(s):

Agnieszka Pawłowska-Kamieniak ◽

Paulina Krawiec ◽

Elżbieta Pac-Kożuchowska

Keyword(s):

Valproic Acid ◽

Acute Pancreatitis ◽

Metabolic Disorders ◽

Genetic Factors ◽

Clinical Symptoms ◽

Gallstone Disease ◽

Young Patients ◽

Case Series ◽

Review Of The Literature ◽

Acid Therapy

Acute pancreatitis (AP) appears to be rare disease in childhood. In children, it has a different aetiology and course, and requires different management than in adult patients. The diagnosis of AP is based on at least two of the three criteria, which include typical clinical symptoms, abnormalities in laboratory tests and/or imaging studies of the pancreas. There are many known causes leading to AP in children including infections, blunt abdominal trauma, genetic factors, gallstone disease, metabolic disorders, anatomical defects of the pancreas, systemic diseases, as well as drugs, including antiepileptic drugs, and especially preparations of valproic acid. In our study, we present four cases of young patients diagnosed with acute pancreatitis as a complication of valproic acid therapy and we present a review of the literature. We believe that the activity of pancreatic enzymes should be monitored in children treated with valproate preparations in the case of clinical symptoms suggesting AP.

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Ultrasound and surgical inspection of plantaris tendon involvement in chronic painful insertional Achilles tendinopathy: a case series

BMJ Open Sport & Exercise Medicine ◽

10.1136/bmjsem-2020-000979 ◽

2021 ◽

Vol 7 (1) ◽

pp. e000979

Author(s):

Håkan Alfredson ◽

Lorenzo Masci ◽

Christoph Spang

Keyword(s):

Achilles Tendon ◽

Clinical Symptoms ◽

Fatty Infiltration ◽

Case Series ◽

Achilles Tendinopathy ◽

Level Of Evidence ◽

Plantaris Tendon ◽

Medial Pain ◽

Tendon Insertion ◽

Insertional Achilles Tendinopathy

ObjectivesChronic painful insertional Achilles tendinopathy is known to be difficult to manage. The diagnosis is not always easy because multiple different tissues can be involved. The plantaris tendon has recently been described to frequently be involved in chronic painful mid-portion Achilles tendinopathy. This study aimed to evaluate possible plantaris tendon involvement in patients with chronic painful insertional Achilles tendinopathy.MethodsNinety-nine consecutive patients (74 males, 25 females) with a mean age of 40 years (range 24–64) who were surgically treated for insertional Achilles tendinopathy, were included. Clinical examination, ultrasound (US)+Doppler examination, and surgical findings were used to evaluate plantaris tendon involvement.ResultsIn 48/99 patients, there were clinical symptoms of plantaris tendon involvement with pain and tenderness located medially at the Achilles tendon insertion. In all these cases, surgical findings showed a thick and wide plantaris tendon together with a richly vascularised fatty infiltration between the plantaris and Achilles tendon. US examination suspected plantaris involvement in 32/48 patients.ConclusionPlantaris tendon involvement can potentially be part of the pathology in chronic painful insertional Achilles tendinopathy and should be considered for diagnosis and treatment when there is distinct and focal medial pain and tenderness.Level of evidenceIV case series.

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Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling

BMC Neurology ◽

10.1186/s12883-021-02233-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Christopher Dardis ◽

David Donner ◽

Nader Sanai ◽

Joanne Xiu ◽

Sandeep Mittal ◽

...

Keyword(s):

Copy Number ◽

Epithelial To Mesenchymal Transition ◽

Clinical Care ◽

Case Series ◽

Molecular Profiling ◽

Retrospective Case ◽

Who Grade ◽

Exact Test ◽

Mesenchymal Transition ◽

Dna And Rna

Abstract Background Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level. Methods Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS. Results Potentially meaningful associations (p<0.1, Fisher’s exact test (FET)) were found for 14 of these tests in GS vs. GB. A novel finding was higher levels of proteins mediating immuno-evasion (PD-1, PD-L1) in GS. All of the differences we observed have been associated with epithelial-to-mesenchymal transition (EMT) in other tumor types. Many of the changes we saw in GS are novel in the setting of glial tumors, including copy number amplification in LYL1 and mutations in PTPN11. Conclusions GS shows certain characteristics of EMT, by contrast with GB. Treatments targeting immuno-evasion may be of greater therapeutic value in GS relative to GB.

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Explore the Rare—Molecular Identification and Wine Evaluation of Two Autochthonous Greek Varieties: “Karnachalades” and “Bogialamades”

Plants ◽

10.3390/plants10081556 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1556

Author(s):

Dimitrios Evangelos Miliordos ◽

Georgios Merkouropoulos ◽

Charikleia Kogkou ◽

Spyridon Arseniou ◽

Anastasios Alatzas ◽

...

Keyword(s):

Molecular Data ◽

Molecular Profiling ◽

Scientific Data ◽

Financial Impact ◽

Molecular Profile ◽

Red Wines ◽

Grape Berries ◽

Quality Aspects ◽

Commercial Vineyard ◽

Of Greece

Wines produced from autochthonous Vitis vinifera varieties have an essential financial impact on the national economy of Greece. However, scientific data regarding characteristics and quality aspects of these wines is extremely limited. The aim of the current study is to define the molecular profile and to describe chemical and sensory characteristics of the wines produced by two autochthonous red grapevine varieties—“Karnachalades” and “Bogialamades”—grown in the wider area of Soufli (Thrace, Greece). We used seven microsatellites to define the molecular profile of the two varieties, and then we compared their profile to similar molecular data from other autochthonous as well as international varieties. Grape berries were harvested at optimum technological maturity from a commercial vineyard for two consecutive vintages (2017–2018) and vilification was performed using a common vinification protocol: the 2017 vintage provided wines, from both varieties, with greater rates of phenolics and anthocyanins than 2018, whereas regarding the sensory analysis, “Bogialamades” wine provided a richer profile than “Karnachalades”. To our knowledge, this is the first study that couples both molecular profiling and exploration of the enological potential of the rare Greek varieties “Karnachalades” and “Bogialamades”; they represent two promising varieties for the production of red wines in the historic region of Thrace.

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Trans-hiatal herniation following esophagectomy or gastrectomy: retrospective single-center experiences with a potential surgical emergency

Hernia ◽

10.1007/s10029-021-02380-1 ◽

2021 ◽

Author(s):

P. U. Oppelt ◽

I. Askevold ◽

R. Hörbelt ◽

F. C. Roller ◽

W. Padberg ◽

...

Keyword(s):

Hernia Repair ◽

Hiatal Hernia ◽

Surgical Repair ◽

Clinical Symptoms ◽

Gastrointestinal Symptoms ◽

Case Series ◽

Gastric Surgery ◽

Hiatal Hernia Repair ◽

Single Center ◽

Asymptomatic Patients

Abstract Purpose Trans-hiatal herniation after esophago-gastric surgery is a potentially severe complication due to the risk of bowel incarceration and cardiac or respiratory complaints. However, measures for prevention and treatment options are based on a single surgeon´s experiences and small case series in the literature. Methods Retrospective single-center analysis on patients who underwent surgical repair of trans-hiatal hernia following gastrectomy or esophagectomy from 01/2003 to 07/2020 regarding clinical symptoms, hernia characteristics, pre-operative imaging, hernia repair technique and perioperative outcome. Results Trans-hiatal hernia repair was performed in 9 patients following abdomino-thoracic esophagectomy (40.9%), in 8 patients following trans-hiatal esophagectomy (36.4%) and in 5 patients following conventional gastrectomy (22.7%). Gastrointestinal symptoms with bowel obstruction and pain were mostly prevalent (63.6 and 59.1%, respectively), two patients were asymptomatic. Transverse colon (54.5%) and small intestine (77.3%) most frequently prolapsed into the left chest after esophagectomy (88.2%) and into the dorsal mediastinum after gastrectomy (60.0%). Half of the patients had signs of incarceration in pre-operative imaging, 10 patients underwent emergency surgery. However, bowel resection was only necessary in one patient. Hernia repair was performed by suture cruroplasty without (n = 12) or with mesh reinforcement (n = 5) or tension-free mesh interposition (n = 5). Postoperative pleural complications were most frequently observed, especially in patients who underwent any kind of mesh repair. Three patients developed recurrency, of whom two underwent again surgical repair. Conclusion Trans-hiatal herniation after esophago-gastric surgery is rare but relevant. The role of surgical repair in asymptomatic patients is disputed. However, early hernia repair prevents patients from severe complications. Measures for prevention and adequate closure techniques are not yet defined.

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The Clinical Clues of Pulmonary Alveolar Proteinosis: A Report of 11 Cases and Literature Review

Canadian Respiratory Journal ◽

10.1155/2016/4021928 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Qiongya Mo ◽

Bingbin Wang ◽

Nian Dong ◽

Lianmin Bao ◽

Xiaoqiong Su ◽

...

Keyword(s):

Bronchoalveolar Lavage Fluid ◽

Clinical Symptoms ◽

Pulmonary Alveolar Proteinosis ◽

Relevant Literature ◽

Neuron Specific Enolase ◽

Lavage Fluid ◽

Lung Lavage ◽

Serum Markers ◽

Open Lung Biopsy ◽

Alveolar Proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease characterized by the abnormal alveolar accumulation of surfactant components. The diagnosis of PAP can be easily missed since it is rare and lacks specific clinical symptoms. It is of great importance to have a better understanding of the crucial clue to clinically diagnose PAP and take PAP into consideration in the differential diagnosis of interstitial pulmonary diseases or other diseases with similar manifestations. Here, we analyze the clinical characteristics of 11 cases of PAP patients in local hospital and review the relevant literature in order to provide more information in diagnosis and management of PAP. In our observation, cyfra21-1 and neuron-specific enolase (NSE) known as tumor markers probably can be useful serum markers for diagnosis of PAP. As for the method of pathologic diagnosis, open-lung biopsy was the gold standard but now it is less required because findings on examination of bronchoalveolar lavage fluid (BALF) can help to make the diagnosis. We also have deep experience about when and how to carry out lung lavage.

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Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?

Endocrine Pathology ◽

10.1007/s12022-021-09668-z ◽

2021 ◽

Vol 32 (1) ◽

pp. 154-168 ◽

Cited By ~ 1

Author(s):

Marco Volante ◽

Ozgur Mete ◽

Giuseppe Pelosi ◽

Anja C. Roden ◽

Ernst Jan M. Speel ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Young Patients ◽

Carcinoid Tumors ◽

Neuroendocrine Neoplasms ◽

Grey Zone ◽

Cell Hyperplasia ◽

Ki 67 ◽

Familial Form ◽

Well Differentiated ◽

Neuroendocrine Carcinomas

AbstractThoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered.

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