Value of Surgical Cytoreduction in Patients with Small Intestinal Neuroendocrine Tumors Metastatic to the Liver and Peritoneum.

BACKGROUND: Cytoreductive hepatectomy can improve survival and symptoms of hormonal excess in patients with small intestinal neuroendocrine tumor (siNET) liver metastases, but whether to proceed when peritoneal metastases are encountered at the time of planned cytoreductive hepatectomy is controversial. METHODS: This was a retrospective review of patients who underwent surgical management of metastatic siNETs at Mayo Clinic between 2000 and 2020. Patients who underwent cytoreductive operation for isolated liver metastases or both liver and peritoneal metastases were compared. RESULTS: Of 261 patients who underwent cytoreductive operation for siNETs, 211 had isolated liver metastases and 50 had liver and peritoneal metastases. Complete cytoreduction was achieved in 78% of patients with isolated liver metastases and 56% of those with liver and peritoneal metastases (p = 0.002). After complete cytoreduction, median overall survival (OS) was 11.5 years for isolated liver metastases and 11.2 years for liver and peritoneal metastases (p = 0.10), and relief of carcinoid syndrome was ≥ 97% in both groups. After incomplete cytoreduction with debulking of > 90% of hepatic disease and/or closing Lyon score of 1-2, median OS was 6.4 years for isolated liver metastases and 7.1 years for liver and peritoneal metastases (p = 0.12). CONCLUSIONS: Patients with siNETs metastatic to both the liver and peritoneum have favorable outcomes after aggressive surgical cytoreduction, with the best outcomes observed after complete cytoreduction. Therefore, the presence of peritoneal metastases should not by itself preclude surgical cytoreduction in this population.

Paget Disease of Bone Harboring Bone Metastatic Neuroendocrine Cancer: A Case Report.

In this case report, we describe an uncommon case of neuroendocrine cancer of unknown origin began with cauda equina syndrome in a patient affected by Paget disease of bone (PDB). A 76-year-old man with diagnosis of PDB, without history of pain or bone deformity, developed sudden severe low back pain. Bone alkaline phosphatase was increased and MRI and whole-body scintigraphy confirmed the localization of the disease at the third vertebra of the lumbar spine. Treatment with Neridronic Acid was started, but after only 2 weeks of therapy anuria and bowel occlusion occurred together with lower limb weakness and walking impairment. Cauda equina syndrome consequent to spinal stenosis at the level of L2-L3 was diagnosed after admission to Emergency Department and the patient underwent neurosurgery for spinal medulla decompression. The histologic results showed a complete subversion of bone structure in neoplastic tissue, consistent with metastatic neuroendocrine carcinoma of unknown origin. In conclusion, low back pain in the elderly may require deep investigation to individuate rare diseases. In asymptomatic patients with apparently stable PDB, the sudden appearance of pain or neurologic symptoms may alert the clinician for the possibility of other superimposing diseases, like bone metastases.

Al18F-NOTA-Octreotide outperforms 18F-FDG in identifying rare renal metastases from pancreatic neuroendocrine tumor.

We presented a case involving a 56-year-old man who had been experiencing shoulder and back pain for over a year, with extensive bone metastases revealed by a bone scan. To identify the primary source of these issues, the patients underwent a fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scan, which indicated moderate uptake in the right renal soft mass and low uptake in multiple osteolytic lesions. Pathological examination and immunohistochemical staining of the renal mass supported the diagnosis of neuroendocrine tumors. Subsequently, a novel somatostatin receptor imaging agent, Al18F-NOTA-octreotide (18F-OC), was performed to further investigate the source of metastatic lesions and to stage the tumor. The 18F-OC scan revealed a high-uptake lesion in the pancreatic head, as well as additional lymph node and bone metastases lesions. Compared to 18F-FDG, the 18F-OC demonstrated superior imaging capabilities and a significantly higher tumor-to-background ratio in neuroendocrine neoplasms, which contributed to improving the staging and treatment management.

[Systemic treatment of patients with metastatic neuroendocrine Neoplasia]. / Systemtherapie von neuroendokrinen Neoplasien.

Due to the complexity and heterogeneity of metastatic NEN an interdisciplinary expert team should be involved in an individualized treatment strategy. SSA is the mainstay of antisecretory treatment in most functioning tumors. In antiproliferative intention SSA are first line treatment in receptor positive low proliferative NET. In intestinal metastatic disease PRRT is best established second line treatment. Further options are Everolimus (labeled) and tyrosine kinase inhibitors (off-label). Everolimus is the only approved drug for antiproliferative treatment in patients with metastatic lung NET, whereas in pancreatic NET more therapeutic options are available (SSA, chemotherapy, PRRT, Sunitinib, Everolimus) without a standard of best sequence. In patients with metastatic NEC standard first line treatment (platinum + etoposide) has not changed for decades and new treatment options for this fatal disease are urgently needed. Benefit of immunotherapy is limited to a small subset of patients - new combinations are under investigation. This review summarizes the standard of care, criteria of treatment selection and new developments for systemic therapy in patients with metastatic NEN.

[Radiologically guided interventional therapies for the treatment of neuroendocrine tumors]. / Radiologisch-interventionelle Möglichkeiten zur Behandlung von neuroendokrinen Tumoren.

BACKGROUND: The majority of patients with neuroendocrine tumors (NET) develop liver metastases during the course of the disease, significantly impacting prognosis and quality of life. CLINICAL ISSUE: Radiologically guided interventional therapies, such as thermal ablation, transarterial embolization (TAE)/chemoembolization (TACE), and selective internal radiotherapy (TARE), can play a crucial role in the treatment of metastatic NET. DATA: Due to the rarity of the disease, the majority of evidence is based on retrospective studies. For thermal ablation, the complete response rates ranging from 31.6 to 95.3% depending on the study. No significant differences in outcomes were found between TAE, TACE, and TARE. In several studies, all intra-arterial procedures led to a reduction of tumor-related symptoms and achieved disease control. CONCLUSION: Thermal ablation can be used as a curative therapy in oligometastatic patients with nonresectable liver metastases from NETs. In cases of disseminated liver metastases, intra-arterial therapy using TAE, TACE, or TARE can be employed.

Non-cirrhotic hyperammonaemic encephalopathy secondary to metastatic pancreatic neuroendocrine tumour treated with peptide receptor radio nucleotide therapy and transarterial chemoembolisation.

Neuroendocrine tumours (NETs) are rare cancers which often carry significant morbidity and mortality, frequently related to burden of liver metastases. Hyperammonaemia and subsequent hepatic encephalopathy carries a poor prognosis and has been described in these patients. We discuss a case of a woman in her 50s with hyperammonaemic encephalopathy and a new diagnosis of pancreatic NET with hepatic metastases. She presented with a reduced conscious state a few days post commencing chemotherapy. This was considered to have a multifactorial pathophysiology: the primary driver being large volume hepatic metastases and contributed by portosystemic microshunting, sepsis, severe weight loss and malnutrition. We describe how each of these exacerbating factors was addressed and highlight the effective multimodal treatment approach consisting of sequential transarterial chemoembolisation followed by peptide receptor radio nucleotide therapy, resulting in the resolution of hyperammonaemic encephalopathy and radiological partial metabolic response.

A Case Series of Choroidal and Orbital Neuroendocrine Tumors: Metastasis: Two Patients Treated With Peptide Radionuclide Therapy.

ABSTRACT: Neuroendocrine tumors (NETs) are rare cancers with heterogeneous histologies, response to treatments, and prognoses. Majority of these cancers originate in the gastrointestinal tract and metastasize to the liver. We report the cases of 5 patients with low-grade NET disease with rare metastases to the choroids. Two of the patients were treated with peptide receptor radionuclide therapy (lutetium 177 [ 177 Lu]). This is the first report confirming peptide radionuclide therapy safety in patients with low-grade NET with ocular metastases.

[Imaging of pancreatic neuroendocrine tumors]. / Bildgebung von neuroendokrinen Tumoren des Pankreas.

BACKGROUND: Neuroendocrine tumors of the pancreas have a broad biological spectrum. The treatment decision is based on an optimal diagnosis with regard to the local findings and possible locoregional and distant metastases. In addition to purely morphologic imaging procedures, functional parameters are playing an increasingly important role in imaging. OBJECTIVES: Prerequisites for optimal imaging of the pancreas, technical principles are provided, and the advantages and disadvantages of common cross-sectional imaging techniques as well as clinical indications for these special imaging methods are discussed. MATERIALS AND METHODS: Guidelines, basic and review papers will be analyzed. RESULTS: Neuroendocrine tumors of the pancreas have a broad imaging spectrum. Therefore, there is a need for multimodality imaging in which morphologic and functional techniques support each other. While positron emission tomography/computed tomography (PET/CT) can determine the presence of one or more lesions and its/their functional status of the tumor, magnetic resonance imaging (MRI) efficiently identifies the location, relationship to the main duct and the presence of liver metastases. CT allows a better vascular evaluation, even in the presence of anatomical variants as well as sensitive detection of lung metastases. CONCLUSIONS: Knowledge of the optimal combination of imaging modalities including clinical and histopathologic results and dedicated imaging techniques is essential to achieve an accurate diagnosis to optimize treatment decision-making and to assess therapy response.

Ovarian neuroendocrine tumor metastases can induce estrogen production in postmenopausal patients.

Neuroendocrine tumors (NETs) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations. An extensive workup was performed for 2 index patients with ovarian metastases of small bowel neuroendocrine tumors and symptoms of postmenopausal vaginal bleeding. Clinically significant ovarian estrogen production was demonstrated by a combination of ovarian vein sampling and normalization of circulating estrogen levels after oophorectomy. Immunohistochemical analyses revealed marked aromatase immunoactivity in the ovarian NET cells, while CYP17A1 and SF-1 were detected in the adjacent ovarian stromal cells but not the NET cells. Ex vivo and in vivo endocrine tests were unable to identify a paracrine mechanism of ovarian estradiol overproduction by NET cells. A retrospective search of electronic medical records revealed that 21% (14/66) of postmenopausal patients with an ovarian NET localization reported symptoms of vaginal blood loss. Together, these findings support the presence of a novel NET-associated hormonal syndrome.

Neuroendocrine tumors: An epidemiological study of 250 cases at a tertiary hospital / Tumores neuroendócrinos: estudo epidemiológico de 250 casos em um hospital terciário

Summary Objective: To compare the frequency of neuroendocrine tumors in our service with that reported in the literature considering age, gender, location, degree of differentiation and increase in incidence by means of a retrospective study. Method: Search of variables from a database of neuroendocrine tumor cases diagnosed at the Department of Pathological Sciences, Hospital da Santa Casa de São Paulo over the past 10 years, relating them to epidemiological data such as gender, age, distribution across organs, most-used immunohistochemical markers and presence or absence of either lymph node or distant metastases. Results: In all, 250 cases were reviewed, 133 involving females, predominantly in the 61-70 age range. The lung was the most frequent site, followed by the stomach. CD56, synaptophysin and chromogranin were the immunohistochemical markers used most often and to a lesser extent Ki67, a marker of cell proliferation that indicates a higher or lower degree of histological malignancy. Metastases, either in lymph nodes and/or distant sites, were found in 44 cases (17.6%). Conclusion: The results were largely consistent with those in the literature, including age group, gender and location. Most metastases originated from high-grade tumors, with high Ki67 levels and greater impairment of the liver. However, only 36.4% of the cases had Ki67 index. Reevaluation of the Ki67 proliferative index using image analysis in doubtful cases will allow for a correlation between progression and prognosis.

Resumo Objetivo: Comparar a frequência de tumores neuroendócrinos em nosso serviço com a literatura em relação idade, sexo, localização, grau de diferenciação e aumento da incidência por meio de um estudo retrospectivo. Método: Levantamento em banco de dados de casos de tumores neuroendócrinos diagnosticados no Serviço de Anatomia Patológica do Hospital da Santa Casa de São Paulo nos últimos 10 anos, relacionando com os dados epidemiológicos, como sexo, idade, distribuição pelos diversos órgãos, marcadores imuno-histoquímicos mais utilizados e presença ou não de metástase em linfonodos ou a distância. Resultados: Foram revistos 250 casos, 133 femininos, com faixa etária predominante entre 61 e 70 anos. O pulmão foi o local com maior frequência, seguido do estômago. Os marcadores imuno-histoquímicos mais utilizados foram CD56, sinaptofisina e cromogranina, às vezes complementados pelo Ki67, que permite avaliar o grau de proliferação celular, indicativo de maior ou menor grau de malignidade histológica. Metástases em linfonodos e/ou a distância foram constatadas em 44 casos (17,6%). Conclusão: Os resultados foram em grande parte concordantes com os dados da literatura, como idade, sexo e localização. A maioria das metástases se originou de neoplasias de alto grau, com alto índice do Ki67, com maior comprometimento do fígado. No entanto, o índice proliferativo do Ki67 foi feito em apenas 36,4% dos casos. A reavaliação dos índices proliferativos do Ki67 por meio de análise de imagem, de casos duvidosos, permitirão relacionar com a evolução e o prognóstico dos pacientes.

Eritema necrolítico migratorio: presentación de un caso y revisión de la literatura / Necrolytic migratory erythema: case and literature review

El eritema necrolítico migratorio es una erupción cutánea característica, con hallazgos histopatológicos específicos que se relacionan frecuentemente con un tumor pancreático, el glucagonoma. Los pacientes con este síndrome son generalmente mal diagnosticados. Se presenta un paciente de 54 años de edad con una erupción cutánea recurrente, pérdida de peso, glositis e hiperglucemia de cuatro meses de duración. Esta importante, pero rara enfermedad, puede ser diagnosticada tempranamente, basándonos en el cuadro cutáneo