Gynecologic Cancer InterGroup (GCIG) Consensus Review for Carcinoid Tumors of the Ovary

AbstractNeuroendocrine tumors (NETs) are a heterogeneous group of neoplasms most commonly occurring in the gastrointestinal tract or the lungs. More frequent are gastrointestinal tumors, but over the past 30 years, there have been a number of small series or anecdotal case reports on ovarian NETs. Neuroendocrine tumors in the gynecologic tract are uncommon and account for about 2% of all gynecologic malignancies but may also be metastatic from other sites. They require a multimodality therapeutic approach determined by the extent of disease and the primary organ of involvement. Pathological diagnosis is critical to guide therapy. Surgery is the cornerstone of treatment for localized disease. There have been many new developments for treatment of advanced NETs including somatostatin analogs, hepatic artery embolization, chemotherapy, interferons, mammalian target of rapamycin inhibitors and radiolabeled somatostatin analogs. Given the rarity and lack of level I evidence, this is by nature more of a guidance and recommendation for management of these rare tumors until we can mount international studies.

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Gastrointestinal neuroendocrine tumors: a role for targeted therapies?

Endocrine Related Cancer ◽

10.1677/erc-06-0061 ◽

2007 ◽

Vol 14 (2) ◽

pp. 207-219 ◽

Cited By ~ 20

Author(s):

Matthew H Kulke

Keyword(s):

Neuroendocrine Tumors ◽

Tumor Regression ◽

Somatostatin Analogs ◽

Mammalian Target Of Rapamycin ◽

Hepatic Metastases ◽

Clinical Results ◽

Interferon Α ◽

Ablative Therapies ◽

Surgical Debulking ◽

Endothelial Growth Factor

Traditional therapies have offered patients with advanced gastrointestinal neuroendocrine tumors limited benefit. Selected patients with hepatic metastases may benefit from surgical debulking, embolization, or other ablative therapies. While somatostatin analogs are highly effective in controlling symptoms of hormonal secretion, they are only rarely associated with tumor regression. The clinical benefit associated with the administration of systemic agents such as interferon-α or cytotoxic chemotherapy is less clear, and the widespread use of such regimens has been limited by their relatively modest anti-tumor activity, as well as concerns regarding their potential toxicity. The mixed clinical results seen with these agents in neuroendocrine tumors have led to great interest in the development of novel treatment approaches for patients with advanced disease. Recent clinical studies of novel agents, particularly those targeting the vascular endothelial growth factor pathway and mammalian target of rapamycin, have demonstrated promising activity in patients with advanced neuroendocrine tumors. Ongoing randomized studies should help better define the role these and other targeted agents will play in the future treatment of patients with this disease.

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Adenomatous Tumors of the Middle Ear: A Literature Review

International Archives of Otorhinolaryngology ◽

10.1055/s-0037-1601400 ◽

2017 ◽

Vol 21 (03) ◽

pp. 308-312 ◽

Cited By ~ 8

Author(s):

Flavia Cardoso ◽

Eduardo Machado Monteiro ◽

Livia Lopes ◽

Marianna Avila ◽

Bernardo Scarioli

Keyword(s):

Middle Ear ◽

Age Of Onset ◽

Case Reports ◽

Preoperative Evaluation ◽

Somatostatin Analogs ◽

Clinical Manifestations ◽

Ossicular Chain ◽

Final Diagnosis ◽

Small Series ◽

Conductive Hearing

Introduction Neuroendocrine adenomas of the middle ear (NAME) are uncommon causes of middle ear masses. Mostly limited to case reports and small series, the literature is poor in providing an overall assessment of these tumors. Objective To review the current literature about all aspects of the disease, including its etiology, clinical manifestations, diagnosis, and treatment. Data Synthesis The pathogenesis of adenomatous tumors of the middle ear is not clear yet. One potential explanation is that an undifferentiated pluripotent endodermal stem cell may still be present in the middle ear mucosal surface, and may be the origin of the tumors. It typically appears as a nonspecific retrotympanic mass. The average age of onset for the disease is the fifth decade, and the most common clinical symptom is conductive hearing loss. Malign behavior is rare. There are numerous differential diagnoses of NAME. The final diagnosis depends on microscopic findings. The preoperative evaluation should include the use of computed tomography and magnetic resonance imaging. The adjunctive therapy of middle ear adenomatous tumors with radiotherapy, chemotherapy or somatostatin analogs is generally not recommended. Conclusion There is still much debate on pathogenesis and classification of NAME. Saliba's classification is currently the most complete and preferable one. Aggressive surgical procedure with ossicular chain excision is the gold standard treatment. Follow-up with physical and radiological exams is mandatory, particularly if the first procedure was conservative, without the removal of the encased ossicles.

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Finding the Appropriate Therapeutic Strategy in Patients with Neuroendocrine Tumors of the Pancreas: Guideline Recommendations Meet the Clinical Reality

Journal of Clinical Medicine ◽

10.3390/jcm10143023 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3023

Author(s):

Sebastian Krug ◽

Marko Damm ◽

Jakob Garbe ◽

Senta König ◽

Rosa Lynn Schmitz ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Case Reports ◽

Somatostatin Analogs ◽

Current Data ◽

Controlled Trials ◽

Second Line ◽

Pancreatic Neuroendocrine Tumors ◽

Ki 67 ◽

Therapy Algorithm ◽

Nccn Guidelines

The systemic treatment of patients with pancreatic neuroendocrine tumors is based on placebo-controlled trials and long-established chemotherapy approaches. In addition, peptide receptor radionuclide therapy (PRRT) was approved as a parallel approach for pancreatic neuroendocrine tumors (NET), in addition to small bowel NET, after the NETTER-1 trial. The current ESMO and NCCN guidelines attempted to describe treatment algorithms for pancreatic NET based on the current data. In our survey, we recorded therapy decisions for the first- until the third-line of therapy in German-speaking countries (Germany, Austria, and Switzerland) using fictional case reports and discussed these in the context of the current ESMO guidelines. Compared with the recommendations of the guidelines, PRRT was used more frequently and earlier. In patients with NET G1/G2 Ki-67 < 10%, the therapy algorithm consisting of somatostatin analogs (SSA)-PRRT-targeted therapy is a relevant approach. In clinical situations where chemotherapy is primarily used (remission pressure, Ki-67 > 10%), second-line PRRT was found acceptance and was often considered prior to targeted therapies. Despite the lack of prospective controlled trials, our study demonstrated the pivotal impact of PRRT. Therefore, further studies should compare PRRT with chemotherapy in pancreatic NETs in different clinical settings in first- and second-line approaches.

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Small Cell Carcinoma of the Uterine Cervix in a Pregnant Patient Diagnosed with Liquid Based Cytology and Cell Block Immunocytochemistry

Case Reports in Pathology ◽

10.1155/2014/971464 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Mawuli F. Attipoe ◽

Charles D. Sturgis

Keyword(s):

Cell Carcinoma ◽

Small Cell Carcinoma ◽

Uterine Cervix ◽

Case Reports ◽

Pregnant Patient ◽

Small Cell ◽

Tumor Type ◽

Cell Block ◽

Current Case ◽

Small Series

Definitive cytomorphologic diagnosis of small cell carcinoma of the uterine cervix is possible but can be challenging in routine cervicovaginal cancer screening specimens. Several small series of reported cases of cervical small cell carcinoma have shown this uncommon malignancy to represent fewer than 2% of all invasive cervical cancers. This tumor type is associated with poor prognosis and rapid disease progression and can develop to an advanced stage in the interval between screening visits. Only rare case reports of small cell carcinoma arising in gravid cervices are known. In the current case a 29-year-old, gravida 6, para 2, pregnant (10-week gestation) female presented with postcoital bleeding. A definitive diagnosis of small cell carcinoma of the cervix was made possible by liquid based Pap testing with ancillary cell block preparation allowing for immunocytochemical characterization of the lesional cell population.

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Structural brain injury in sports-related concussion

Neurosurgical FOCUS ◽

10.3171/2012.10.focus12279 ◽

2012 ◽

Vol 33 (6) ◽

pp. E6 ◽

Cited By ~ 13

Author(s):

Scott L. Zuckerman ◽

Andrew Kuhn ◽

Michael C. Dewan ◽

Peter J. Morone ◽

Jonathan A. Forbes ◽

...

Keyword(s):

Brain Injury ◽

Literature Review ◽

Brain Injuries ◽

Case Reports ◽

Head Injuries ◽

Health Concern ◽

Prevalence Data ◽

Small Series ◽

Structural Brain

Object Sports-related concussions (SRCs) represent a significant and growing public health concern. The vast majority of SRCs produce mild symptoms that resolve within 1–2 weeks and are not associated with imaging-documented changes. On occasion, however, structural brain injury occurs, and neurosurgical management and intervention is appropriate. Methods A literature review was performed to address the epidemiology of SRC with a targeted focus on structural brain injury in the last half decade. MEDLINE and PubMed databases were searched to identify all studies pertaining to structural head injury in sports-related head injuries. Results The literature review yielded a variety of case reports, several small series, and no prospective cohort studies. Conclusions The authors conclude that reliable incidence and prevalence data related to structural brain injuries in SRC cannot be offered at present. A prospective registry collecting incidence, management, and follow-up data after structural brain injuries in the setting of SRC would be of great benefit to the neurosurgical community.

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Mammalian target of rapamycin signaling activation patterns in neuroendocrine tumors of the lung

Endocrine Related Cancer ◽

10.1677/erc-10-0157 ◽

2010 ◽

Vol 17 (4) ◽

pp. 977-987 ◽

Cited By ~ 64

Author(s):

Luisella Righi ◽

Marco Volante ◽

Ida Rapa ◽

Veronica Tavaglione ◽

Frediano Inzani ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Mammalian Target Of Rapamycin ◽

Mtor Pathway ◽

Differential Sensitivity ◽

Initiation Factor ◽

Target Of Rapamycin ◽

Low Grade ◽

Mtor Inhibition ◽

Signaling Activation ◽

Activation Status

Among alternative therapeutic strategies in clinically aggressive neuroendocrine tumors (NETs) of the lung, promising results have been obtained in experimental clinical trials with mammalian target of rapamycin (mTOR) inhibitors, though in the absence of a proven mTOR signaling activation status. This study analyzed the expression of phosphorylated mTOR (p-mTOR) and its major targets, the ribosomal p70S6-kinase (S6K) and the eukaryotic initiation factor 4E-binding protein 1 (4EBP1) in a large series of 218 surgically resected, malignant lung NETs, including 24 metastasizing typical carcinoids, 73 atypical carcinoids, 60 large cell neuroendocrine carcinomas (LCNECs), and 61 small cell carcinomas (SCLCs). By immunohistochemistry, low-to-intermediate-grade tumors as compared with high-grade tumors showed higher levels of p-mTOR and phosphorylated S6K (p-S6K) (P<0.001), at variance with phosphorylated 4EBP1 (p-4EBP1), which was mainly expressed in LCNECs and SCLCs (P<0.001). The activated status of mTOR pathway was proved by the strong correlation of p-mTOR with p-S6K and somatostatin receptor(s). Western blot analysis of NET tumor samples confirmed such findings, and differential sensitivity to mTOR inhibition according to mTOR pathway activation characteristics was determined in two lung carcinoid cell lines in vitro. None of the investigated molecules had an impact on survival. However, in low-grade tumors, low p-mTOR expression correlated with lymph node metastases (P=0.016), recurrent disease, and survival (P=0.005). In conclusion, these data demonstrate a differential mTOR activation status in the spectrum of pulmonary NETs, possibly suggesting that mTOR pathway profiling might play a predictive role in candidate patients for mTOR-targeted therapies.

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Neuroendocrine Testicular Tumors: A Systematic Review and Meta-Analysis

Current Urology ◽

10.1159/000447146 ◽

2016 ◽

Vol 10 (1) ◽

pp. 15-25 ◽

Cited By ~ 7

Author(s):

Mseddi M. Amine ◽

Bouzguenda Mohamed ◽

Hadjslimane Mourad ◽

Hamza Majed ◽

Charfi Slim ◽

...

Keyword(s):

Survival Rate ◽

Neuroendocrine Tumors ◽

Carcinoid Syndrome ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Palpable Mass ◽

Pubmed Database ◽

Evolutionary Features ◽

Radical Orchiectomy

Purpose: The purpose of this study is to study the main epidemiological, clinical, para clinical, pathological, therapeutic, and evolutionary features of patients with testicular neuroendocrine tumors (TNET). Materials and Methods: Nine case series and sixteen case reports were identified by searching PubMed database and qualified for inclusion in this study. We added the data of one case treated in the department of urology in Habib Bourguiba Hospital in Sfax, to the published cases. Results: A total of 132 cases were collected. Median age at diagnosis was 39 years old (range 10- 83 years). The most common presenting symptom was either a testicular mass or a swelling in 38.46% of cases. Carcinoid syndrome was documented in 10.60% of patients. The clinical examination revealed a palpable mass in 44.70% of patients. This mass was painless and firm in most cases. Serum tumor markers (β-gonadotrophine chorionique humaine, α-feto protein, and lactate dehydrogenase) were within normal limits in all patients except in one case. Most testicular neuroendocrine tumors (76.52%) were primary and pure. The tumors were positive for chromogranin (100%), synaptophysin (100%) and cytokeratin (93.10%). Metastases were detected at time of diagnosis in eight cases (6.06%). The main treatment was radical orchiectomy performed in 127 patients (96.21%). The 5-year overall survival rate was 78.70% and the 5-year specific survival rate was 84.30%. Conclusion: The diagnosis of testicular carcinoids is based on the immunohistochemistry study. The treatment of choice for these tumors is radical orchiectomy. Somatostatin analogues were reported to be effective in patients with carcinoid syndrome.

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Myositis-associated Interstitial Lung Disease: Predictors of Failure of Conventional Treatment and Response to Tacrolimus in a US Cohort

The Journal of Rheumatology ◽

10.3899/jrheum.161217 ◽

2017 ◽

Vol 44 (11) ◽

pp. 1612-1618 ◽

Cited By ~ 15

Author(s):

Niharika Sharma ◽

Michael S. Putman ◽

Rekha Vij ◽

Mary E. Strek ◽

Anisha Dua

Keyword(s):

Interstitial Lung Disease ◽

Lung Disease ◽

Clinical Characteristics ◽

Conventional Treatment ◽

Case Reports ◽

Response To Therapy ◽

Disease Modifying Antirheumatic Drugs ◽

Antirheumatic Drugs ◽

Small Series ◽

The Mean

Objective.Patients with myositis-associated interstitial lung disease (MA-ILD) are often refractory to conventional treatment, and predicting their response to therapy is challenging. Recent case reports and small series suggest that tacrolimus may be useful in refractory cases.Methods.A retrospective cohort study of patients with MA-ILD comparing clinical characteristics between those who responded to or failed conventional treatment. In those who failed conventional treatment and received adjunctive tacrolimus, response to tacrolimus was measured by the improvement in myositis, ILD, and change in the dose of glucocorticoids.Results.Thirty-one of 54 patients (57%) responded to conventional treatment based on the predefined variables of improvement in myositis and/or ILD. Patients with polymyositis (PM)-ILD were more likely to respond to conventional treatment than those with dermatomyositis (DM)-ILD (67% vs 35%, p = 0.013). Twenty-three patients failed conventional treatment, 18 of whom subsequently received adjunctive tacrolimus. Ninety-four percent had improvements in ILD and 72% showed improvement in both myositis and ILD. The mean doses of prednisone decreased from baseline by 65% at 3–6 months (p = 0.002) and 81% at 1 year (p < 0.001).Conclusion.Patients with PM-ILD were more likely to respond to conventional treatment than patients with DM-ILD, but clinical characteristics and serology did not otherwise predict response to therapy. A majority of patients with MA-ILD refractory to conventional therapy improved while receiving tacrolimus and were able to decrease their dose of both glucocorticoids and other disease-modifying antirheumatic drugs.

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