Somatostatin Receptor Scintigraphy Research Articles

PULMONARY NODULE IN A PATIENT WITH REMOTE HISTORY OF BREAST CANCER: AMBIGUOUS IMAGING AND HISTOLOGY CAN LEAD YOU ASTRAY

SESSION TITLE: Lung Pathology 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: When a pulmonary nodule is seen on surveillance imaging of a patient with a remote history of breast cancer, it can be tempting to assume that the lung nodule is pulmonary metastasis. We herein describe a case of right middle lobe (RML) typical carcinoid and simultaneous recurrence of breast cancer (ER positive, PR positive, HER2 negative) involving the right supraclavicular lymph node that was challenging to determine a treatment regimen due to ambiguous imaging and histology results. CASE PRESENTATION: We present a 63-year-old woman, who was diagnosed with Stage II-B (T2N1M0) breast carcinoma in 2003. She underwent right mastectomy, radiation to the right chest wall, and tamoxifen therapy. Annual surveillance in 2016 revealed an increase in tumor markers. Computed Tomography (CT) revealed a 1.5-cm RML nodule near the hilum, with a standardized uptake value of 2.8 on subsequent Positron Emission Tomography (PET) scan. The patient underwent navigation bronchoscopy with biopsy of the RML nodule. Pathology of the RML nodule revealed uniform tumor cells with minimal atypia expressing chromogranin, synaptophysin and TTF1-Napsin but not ER, mammaglobin or GATA3. Octreotide scan was performed, which oddly demonstrated increased activity in a small lymph node in the right supraclavicular fossa. After thoracic tumor board discussion, she underwent excisional biopsy of the 1.3-cm lymph node, which revealed metastatic breast cancer. DISCUSSION: Carcinoid tumors are expected to be positive on Octreotide scan and negative on PET, whereas breast cancer metastasis should be positive on PET and negative on Octreotide scan. However, it is important to note that these findings are not always guaranteed. In one large study, Octreotide scan localized only 86% of carcinoids (Krenning et al, 1993). Additionally, the specificity of PET scan for neuroendocrine tumors (NETs) is dependent on the level of malignancy of the tumor; with PET scans, high grade NETs are more likely to be localized, whereas low grade NETs (typical carcinoid), are more likely to be missed (Maxwell et al, 2015). Given that imaging findings differed from what was expected, the case was discussed with a multidisciplinary tumor board and investigated further with histopathology before determining a treatment course. During the tumor board meeting, neuroendocrine differentiation of breast cancer was discussed, however, it was determined that the pathology and immunohistochemistry of the RML nodule was suggestive of typical carcinoid despite the imaging findings. CONCLUSIONS: In the setting where tumor imaging findings are different from what is expected, it is important to discuss the case in a multidisciplinary tumor board and investigate further with histopathology before determining a treatment course. When imaging and histopathology results conflict with one another, treatment should be based on histopathology findings rather than imaging. Reference #1: Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur. J. Nucl. Med. 1993;20(8):716–731. Reference #2: Maxwell, Jessica E, and James R Howe. “Imaging in Neuroendocrine Tumors: an Update for the Clinician.” International Journal of Endocrine Oncology, vol. 2, no. 2, 2015, pp. 159–168., https://doi.org/10.2217/ije.14.40. DISCLOSURES: No relevant relationships by Matthew Gerling, source=Web Response No relevant relationships by Ali Saeed, source=Web Response No relevant relationships by Jessica Zimmerberg-Helms, source=Web Response

A Case of Simultaneous Small Cell Neuroendocrine Carcinoma of the Esophagus and Barrettʼs Adenocarcinoma

Introduction: Neuroendocrine carcinoma (NEC) is a very rare and aggressive disease that accounts for 0.4-2.0% of all esophageal malignancies with the coexistence of a second primary esophageal cancer being an even rarer event. We present a case of an elderly male with an atypical presentation of right upper quadrant (RUQ) abdominal pain and found to have two primary malignancies of the esophagus, small cell NEC and adenocarcinoma.Case: An 86 year-old male presented with persistent RUQ abdominal pain that radiated to the epigastric region. Two weeks prior, he was diagnosed with acute on chronic cholecystitis and had a percutaneous cholecystostomy tube placed. Labs were unremarkable and a noncontrasted CT abdomen showed cholelithiasis with a malpositioned indwelling catheter.Interventional radiology replaced the percutaneous cholecystostomy tube but with minimal pain relief. Over the next 72 hours, he was in continued pain and unable to tolerate a diet. Given the mystery of his pain, a repeat CT abdomen was performed, but this time with contrast, which exhibited a duodenal ulcer and multiple lytic lesions of the right eighth rib, concerning for metastasis. Gastroenterology consult was placed and subsequent esophagogastroduodenoscopy (EGD) portrayed long-segment Barrett's esophagus, a fungating mass in the middle-third of the esophagus, multiple 3-5 mm nodules in the lower-third of the esophagus, and a non-bleeding duodenal ulcer. Biopsies revealed high-grade small cell NEC of the mid-esophagus and invasive adenocarcinoma of the lower esophagus.Oncology was consulted and patient was started on chemotherapy. He was discharged after a 13-day hospitalization with close follow-up. Discussion: NEC is a rare diagnosis, while the concomitant presence of a second primary cancer being an uncommon occurrence. NEC is usually found in older men with specific factors such as alcohol and smoking playing a key role. The initial diagnosis is usually made by somatostatin receptor scintigraphy (SRI), which is followed by endoscopic biopsy for histologic evaluation. However, our patient's lesion was first discovered on endoscopy without prior SRI. These tumors can usually be found in the mid to lower esophagus with dysphagia as the most common presentation, while its presence in the upper and middle third of the esophagus does not frequently cause dysphagia. The prognosis of NEC is very poor which makes developing an effective therapeutic strategy very difficult.1772_A Figure 1. Esophagogastroduodenoscopy (EGD) reveals a medium-sized fungating mass in the middle third of the esophagus.1772_B Figure 2. Biopsy of fungating mid-esophageal mass staining positively for synaptophysin.

A PROMISING PREDICTIVE FACTOR OF MORTALITY IN INTERSTITIAL LUNG DISEASE

SESSION TITLE: Diffuse Lung Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 pm - 02:00 pm PURPOSE: Many predictive risk factors of idiopathic pulmonary fibrosis (IPF/ UIP) such as FVC, DLCO, and 6-MWT showed low accuracy in recent clinical trials... Aims: to evaluate the prognostic value of the New York Heart Association index (NYHA) compared to high resolution CT, somatostatin receptor scintigraphy (octreoscan), and echocardiography METHODS: A prospective study population of 128 patients, IPF = 59, NSIP = 19, granulomatous diseases, such as sarcoidosis, Wegener granulomatosis, alveolitis, = 50 were enrolled respectively. The diagnosis of all patients was confirmed histologically. RESULTS: Median survival was 89.3 months (7.4 years) and 79.4 percent of patients were alive at 3 years after diagnosis with a poorer survival rate among UIP patients. Strong correlation was found with age (p<0.001), CT-score, octreoscan between all UIP patients with respect to NSIP and granulomatous diseases. No deaths were observed among patients with NYHA index and prognosis was progressively worse with increased index (LRT p-value <0.001). Among patients with UIP, NYHA was confirmed to be a performing prognostic factor, as survival of patients with moderate levels was lower than that observed in lower NYHA levels (p<0.01) Indeed, age and NYHA were independent prognostic factors (LLR test p-value <0.001) . CONCLUSIONS: The NYHA index is confirmed to be a reliable and important prognostic factor when observing the significant difference in survival rates among the different NYHA levels, and when confirming for the histological pattern of UIP. CLINICAL IMPLICATIONS: Following our findings we strongly recommend the use of NYHA as prognostic factor of IPF including graulomatous lung diseases. DISCLOSURES: no disclosure on file for Giovanni Bottino; No relevant relationships by Roberto CARBONE, source=Web Response no disclosure on file for Assaf Monselise; no disclosure on file for Paolo Paredi

Liver Mass: When in Doubt Think Carcinoid or Islet Cell Carcinoma

Few differentials for liver lesions include hepatocellular carcinoma, cholangiocarcinoma, hepatic adenoma, hepatic hemangioma, hepatic cysts and metastases. Carcinoids and islet cell carcinomas are normally not in the differential due to their rarity in comparison to the other conditions. Since these tumors are slow growing, the liver has time to adapt; hence patients present with minimal symptoms and large masses on imaging. It is imperative to have both carcinoid and islet cell carcinoma on top of the list for differentials when an incidental asymptomatic liver lesion is seen. 66-year-old male previously treated with ABVD for Hodgkin's lymphoma in 1999 presented with back pain. He denied flushing, chills, fever, diarrhea and lightheadedness. Physical exam was benign. Pertinent laboratory data revealed creatinine of 3.1, potassium of 5.3 and mildly elevated alkaline phosphatase. Three-phase CT of the abdomenshowed two masses in the liver (Figure 1): a 22 cm mass in the right lobe and a 2.5 cm mass in the left lobe. There was also a 4 cm mass in the right kidney. Initially, the liver lesions were thought to be metastases from the kidney. However, biopsy of the kidney mass revealed renal cell carcinoma while biopsy of the largest liver lesion was consistent with neuroendocrine carcinoma. To classify the etiology of the neuroendocrine carcinoma, whole body imaging with SPECT and octreotide scan was performed. A large 19 cm mass and two small lesions were noted in the right lobe of the liver. Lymph node adjacent to the third portion of the duodenum demonstrated abnormal uptake and it was presumed that the duodenum was the primary source of the neuroendocrine carcinoma. Lesions in the liver were likely metastases. The patient was treated with an ablation for renal cell carcinoma and started on somatostatin for neuroendocrine carcinoma of the duodenum. Differentiating carcinoids and islet cell carcinomas poses a diagnostic challenge for pathologists as both entities share the same histology and often immune staining can yield mixed results. It is very important as specialists to have both these diseases in the differential and make the correct diagnosis by taking into consideration the primary site involved along with the presence of 5-HIAA. Even with risk factors for other etiologies, a biopsy should be performed with further testing as indicated to make the correct diagnosis. Identifying the correct diagnosis further helps optimize treatment.2368 Figure 1. Aymptomatic Liver Lesion

1828P - Role of SPECT-CT somatostatin-receptor scintigraphy in the management of medullary thyroid cancer (MTC)

Background: The MTC arises from the parafollicular, calcitonin-secreting malignant transformed thyroid C-cells who express on the surface somatostatin SSTR receptors. The most of aggressive locally advanced/metastatic MTC tumors, found to be positive for RET proto-oncogene mutation, are treated with Vandetanib. SPECT-CT somatostatin-receptor scintigraphy with 99mTc-Tektrotyd should be considered for MTC imaging before and after therapy for exact staging and follow-up of the disease due to its highly sensitivity and specificity for detection of neuroendocrine tumors, expressed SSTR. The aim of this study was to evaluate clinical role of SPECT-CT scintigraphy with 99mTc-Tektrotyd in the management of patients with MTC. Methods: 25pts (7M;18F) with MTC were studied; whole body somatostatin scintigraphy followed by target SPECT-CT studies were performed 2-4 hrs post i.v.inj. of 740 MBq 99mTc-Tektrotyd (Polatom). SPECT-CT camera Symbia T2, Siemens was used. Three of them were studied for initial pre-operative N/M-staging, 17 were follow-up after surgery. In 5 patients with metastatic disease SPECT-CT with 99mTc-Tektrotyd were performed before and after target therapy with Caprelsa (Vandetanib), 300mg/d orally. Results: Initial pre-operative staging showed 3 positive results for the primary tumor and metastatic lymph nodes and 2 false negative imaging of small 1-4 mm lung metastases. True negative results were obtained in 5 cases after thyroidectomy. True positive results were obtained in 17 cases with local recurrence in the thyroid bed, lymphadenopathy, osteolytic bone metastases, lung and subcutaneous lesions. False positive result was in 1 case with benign ovary cyst. Plasma levels of calcitonin vary from 94 to 5496 pg/ml in all 17 patients with local recurrence and/or metastatic lesions. In 5/17 cases SPECT-CT studies were used to evaluate effect of target therapy, respectively: partial response – in 2 cases, stable disease – in 2 cases and progressive disease – in 1 cases. Conclusions: SPECT-CT somatostatin-receptor scintigraphy with 99mTc-Tektrotyd is very useful functional imaging modality in patients with MTC in order to determinate personalized therapeutic disease approach. Legal entity responsible for the study: Sonya Sergieva. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Gastrointestinal Occurrence of a Glomus Tumor

Glomus tumors are benign subepithelial mesenchymal neoplasms generally found in the fingers. It is rare to find a glomus tumor in the gastrointestinal tract. This is a case of a gastric glomus tumor (GGT). It is important to understand the difference betwen a glomus tumor and a gastrointestinal stromal tumor (GIST), which is far more common. The patient is a 26 year old Caucasian female who, for the past one year, had been visiting the gastroenterology clinic with complaints of epigastric abdominal pain, constipation, diarrhea, and heartburn. She was a moderately built individual with no abnormal vitals or notable findings on physical examination. We decided to do an EGD, and a mass in the body of the stomach was discovered. CT abdomen revealed a high density nodular lesion. EUS showed a 2.5cm x 2.2cm submucosal mass with mixed echogenicity and cystic spaces, arising from the muscularis propria of the stomach wall. The biopsy was consistent with a neuroendocrine lesion. Neuroendocrine markers were negative. However, smooth muscle actin and vimentin were strongly immunoreactive. Serotonin levels were normal, and octreotide scan revealed a faint glow in the tumor. Surgery was consulted and laparoscopic partial gastrectomy was performed. Pathology of the wedge resection revealed a gastric glomus tumor 1.8cm in diameter with well-defined margins and no evidence of malignancy. Subepithelial tumors of the gastrointestinal tract include carcinoid tumors, lymphomas, glomus tumors, and GIST. GIST, being the most common, are thought to arise from the interstitial cells of Cajal of the autonomic nervous system of the intestine. Glomus tumors arise from the glomus body in the intramuscular layer, typically in the antrum of the stomach. Both appear on CT as well-circumscribed homogenous masses, and on EUS as hypoechoic masses. However, GGT can be distinguished from GIST based on immunohistochemisty. GIST is typically positive for c-kit (CD117), whereas GGT may test positive for smooth muscle actin, laminin, collagen type IV, desmin, and vimentin.2680_A Figure 1. MR Abdomen, showing a 2.2cm homogenously-enhancing subepithelial gastric antral wall mass.2680_B Figure 2. Microscopic examination, showing multiple blood vessels surrounded by round glomus cells.Even though EUS-FNA differentiates GTs from more aggressive gastric tumors with a 95.6% accuracy, surgery is still preferred. According to the National Comprehensive Cancer Network, if the GIST is >2cm it should be surgically resected. Even if there were any doubt between a GT or GIST, wedge resection is the therapeutic management of choice. This rare case taught us how to diagnose and treat a gastrointestinal glomus tumor.

A Rare Case of Gastric Neuroendocrine Tumor in a Patient with History of Familial Adenomatous Polyposis - Is There an Association?

Familial adenomatous polyposis (FAP), is one of the genetic colorectal cancer syndromes. It is an autosomal dominant inherited disease caused by a somatic mutation in the APC tumor suppressor gene on the chromosome 5q21 with an estimated prevalence of this syndrome between 1 per 5,000-7,000. Adenomatous polyps of the upper intestinal tract (gastric, duodenal, periampullary, and ileal adenomas) are also commonly found in familial adenomatous polyposis (FAP). Gastric neuroendocrine tumors (GNETs) are a rare disease with a reported incidence of 1 to 2 cases/1,000,000 persons per year, comprising 8.7% of gastrointestinal neuroendocrine tumors. Rarely have GNETs been associated with FAP. We present a rare case of gastric neuroendocrine tumor in a patient with FAP. A 56-year-old woman with a past medical history of hypertension, hyperlipidemia, type 2 diabetes, hypothyroidism and FAP with a history of colectomy performed in 1989. As part of her surveillance for extracolonic manifestations of FAP, an Upper endoscopy was performed. Upper endoscopy revealed few 2-3mm gastric body and antral polyps, and multiple 2-3 mm polyps in the duodenal bulb.(Figure 1) Duodenal biopsy showed tubular adenomas. Biopsy of the gastric polyps revealed tubular adenomas with low-grade dysplasia and a low-grade neuroendocrine neoplasm. The tumor cells were positive for pancytokeratin (AE1/AE3), synaptophysin and chromogranin staining and were negative for CD3, CD20, and CD138, consistent with a diagnosis of neuroendocrine tumor. (Figure 2).The patient is undergoing further workup including a magnetic resonance imaging of abdomen and pelvis, and an octreotide scan to stage her disease.2663_A Figure 1. Endoscopic view of gastric and duodenal polyps2663_B Figure 2. Synaptophysin Positive, 400x, confirming presence of carcinoid tumor cells.Gastrointestinal neuroendocrine tumors may be found in association with neurofibromatosis (periampullary carcinoids), Zollinger-Ellison, and multiple endocrine neoplasia syndromes and have rarely been reported in association with FAP. Patients with FAP have dysregulation of the Wnt/b-catenin signaling pathway. Recent findings of b-catenin mutations in neuroendocrine tumors suggest that Wnt/b-catenin alterations may be the common pathway for both tumors. The presence of these two rare entities in the same patient might suggest an association and further research is indicated to determine this association.

Hidden Figures: Occult Intra-Cardiac Metastases in Asymptomatic Neuroendocrine Tumor Patients.

Carcinoid heart disease is a devastating paraneoplastic consequence of unchecked hormone production from neuroendocrine tumors (NET) and often results in right-sided heart failure. While it occurs frequently in NET patients with carcinoid syndrome, cardiac metastases occur much less often and are usually only incidentally found. Gallium-68 dotatate (ga-68) is an imaging tracer which binds to somatostatin receptor 2 with greater avidity than Indium-111, the tracer used commonly in octreotide scans. Ga-68 PET/CT is the most sensitive study for detecting occult NET metastases and has emerged as the current imaging gold standard. We describe two cases from Vanderbilt University Medical Center and Stanford University Medical Center where asymptomatic patients with well-differentiated midgut NET were diagnosed with intra-cardiac metastases using ga-68 PET/CT. Management of these patients was altered based on the findings as they underwent extensive cardiac evaluation and initiation of therapy with octreotide. Fortunately, they have not suffered life-threatening cardiac complications seen in some NET patients, from other published series, such as bradycardia, heart block, syncope and arrhythmias. These possibilities suggest early cardiology evaluation and consideration of other therapies beyond octreotide, such as surgery or PRRT, may be essential for all NET patients found to have intra-cardiac metastases.

Pulmonary nocardiosis mimicking small cell lung cancer in ectopic ACTH syndrome associated with transformation of olfactory neuroblastoma: a case report

BackgroundPulmonary nocardiosis frequently develops as an opportunistic infection in cell-mediated immunosuppressive patients, and sometimes requires differentiation from pulmonary malignancy. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a neoplastic disorder which leads to impaired cell-mediated immunity, and is commonly associated with small cell lung cancer (SCLC). Because pulmonary infection and causative malignancy can appear as pulmonary lesions with EAS, differentiation of these diseases remains a critical issue for physicians.Case presentationA 52-year-old woman with progressive lower limb paralysis and general fatigue was referred to us. She had been diagnosed with olfactory neuroblastoma (ONB) and treated with surgery and radiation therapy 10 years before the referral and had required stereotactic radiosurgery and chemotherapy 4 years later for a relapse of the ONB. On referral, she presented with Cushing’s syndrome with elevated cortisol and ACTH levels. Potassium supplement improved her symptoms; however, a month later, she was urgently hospitalized due to acute pleuritic chest pain on inspiration. Chest computed tomography revealed left lower lobular consolidations and a contralateral nodule in the right middle lobe. The clinical history and laboratory work-up suggested that her Cushing’s syndrome had most likely arisen from EAS. Additionally, the lungs were suspected as the ACTH source due to high levels of progastrin-releasing peptide and progressive pulmonary consolidation with a contralateral nodule, suggesting SCLC. However, histological examination from bronchoscopy revealed no evidence of malignancy, and Nocardia cyriacigeorgica was isolated from bronchoalveolar lavage fluid. Sulfamethoxazole/trimethoprim improved her pulmonary lesions. Somatostatin receptor scintigraphy revealed strong tracer uptake in the ONB lesions, indicating that the origin of the EAS was the olfactory tumor. However, histological examination of ONB specimens resected 10 years earlier showed no intracytoplasmic immunopositivity for ACTH.ConclusionsWe highlight a rare case of pulmonary nocardiosis, which was associated with EAS mimicking SCLC, and was related to ONB transformation. Nocardiosis has to be considered even though anamnestic, clinical, and radiological aspects suggest the presence of metastasis. Additionally, physicians should carefully monitor patients with ONB for the development of Cushing’s symptoms because the tumor can transform into an ACTH-producing form, even after long-term follow-up.

The Successful Use of Somatostatin Receptor Scintigraphy to Determine the Treatment Strategy for Lung Typical Carcinoid

The Successful Use of Somatostatin Receptor Scintigraphy to Determine the Treatment Strategy for Lung Typical Carcinoid

Better way to image and manage Neuroendocrine Tumours: Role of 68Gallium DOTA-Peptide PET-CT scan

&lt;p&gt;Neuroendocrine tumours (NETs) are special entity of neoplasms arising from nervous and endocrine systems and involving variety of organs. Over expression of somatostatin receptors is an unique characteristic of these tumours. This allows molecular imaging to play a significant role in evaluation of NETs using somatostatin analogues. &lt;sup&gt;111&lt;/sup&gt; In Pentetreotide scintigraphy has been playing a significant role as molecular imaging of choice to locate the primary tumor, evaluate extent of disease and plan for surgical management. Recently &lt;sup&gt;68 &lt;/sup&gt;Ga labelled peptides have emerged as promising PET tracers for scintigraphy of these tumours. Several recent studies have demonstrated the superiority of &lt;sup&gt;68&lt;/sup&gt;Ga DOTA- Peptide PET-CT scan with a number of advantages over conventional somatostatin receptor scintigraphy.&lt;/p&gt;&lt;p&gt;Bangladesh J. Nuclear Med. 20(2): 136-142, July 2017&lt;/p&gt;

Oncogenic Osteomalacia: The Search, Treatment, and Cure of a Debilitating Tumor

Objective: To present a rare case of oncogenic osteomalacia, describe the breadth of potential clinical symptoms, and review the underlying pathophysiology of this disorder. Methods: We report a case of oncogenic osteomalacia cured by surgical resection of a mesenchymal tumor. Results: A 48-year-old, wheelchair-dependent man presented to a tertiary care academic hospital with progressive back pain and diffuse weakness. Biochemical evaluation revealed elevated alkaline phosphatase, marked hypophosphatemia, phosphaturia, vitamin D deficiency, and elevated fibroblast growth factor 23, results that are concerning for oncogenic osteomalacia. Subsequent imaging showed extensive loss of vertebral height, numerous fractures, and ultimately identified an area suspicious for tumor in the right mandible, with concurrent uptake on octreotide scan. Segmental resection of the right mandible revealed a calcifying mesenchymal tumor. Following surgery there was a normalization of biochemistries and dramatic improvement in...

Prospective evaluation of 68 Ga-DOTATATE PET/CT in limited disease neuroendocrine tumours and/or elevated serum neuroendocrine biomarkers.

The 68 Ga-labelled somatostatin analogues (68 Ga-DOTA-SSAs) is becoming popular as an important diagnostic tool in neuroendocrine tumours as evidenced by a growing number of reports detailing institutional experience with various DOTA peptides. However, only few prospective studies have compared 68 Ga-DOTA-SSAs and somatostatin receptor scintigraphy (SRS) in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) and pulmonary neuroendocrine tumours. The aim of our prospective study was to perform head-to-head comparison between 68 Ga-DOTATATE PET/CT and standard imaging work-up (SI) that included multiphasic CT, liver MRI and SRS using single photon emission computed tomography. In this prospective study, the patients were enrolled only if they met any of the following inclusion criteria: (i) initial staging of a NETs without distant metastases on SI or neuroendocrine tumour with unknown primary on SI; (ii) restaging of NETs that could be treated by focused therapeutic interventions; (iii) elevated serum neuroendocrine hormones or peptides. The exclusion criteria was grade 3 GEP-NETs. Thirty-two patients were enrolled in the study. Eleven patients (6 pancreas, 4 ileum, 1 duodenal) were included for initial evaluation and staging of NETs, 8 patients (5 pancreas, 1 ileal, 1 lung, 1 duodenal gastrinoma) for restaging, and 13 patients for elevated serum neuroendocrine biomarkers (5 ectopic Cushing's syndrome, 5 organic hypoglycaemia, 1 patient each with elevated vasoactive inhibitory peptide, chromogranin A and neuron-specific enolase). 68 Ga-DOTATATE PET/CT detected more primary tumours than SRS (15/18 vs 10/18: P=.074). The missed tumours on 68 Ga-DOTATATE PET/CT were located in the lung in two cases and duodenum in one case. For other anatomical regions (nodal and distant metastasis), no statistical difference was observed between imaging modalities using 68 Ga-DOTATATE PET/CT and SRS. Overall, 68 Ga-DOTATATE PET/CT+CT+MRI detected 31/33 of the involved regions (including primaries) (29 and 22 for 68 Ga-DOTATATE and SRS, respectively). Our study shows that 68 Ga-DOTATATE PET/CT detected similar number of sites than combination of SRS, liver MRI and thoraco-abdominopelvic CT on region-based analysis. 68 Ga-DOTATATE PET/CT missed half of primary lung carcinoids with ectopic Cushing's syndrome.

Imaging Somatostatin Receptor Activity in Neuroendocrine-differentiated Prostate Cancer

Neuroendocrine-differentiated prostate cancer (NEPC) is a rare pathophysiology. We herein report a patient diagnosed with conventional prostate adenocarcinoma before hormone therapy, which was later diagnosed as NEPC. The nadir of prostate-specific antigen (PSA) was achieved once. However, adenocarcinoma changed to NEPC in recurrence, and the serum progastrin-releasing peptide (Pro-GRP) and neuron-specific enolase (NSE) values increased. A prostate needle biopsy revealed neuroendocrine differentiation. The chemotherapy regimen was changed, and somatostatin receptor scintigraphy (SRS) helped to determine the distribution and features of lesions as well as the effects of therapy. When prostate cancer worsens despite conventional therapy, NEPC should be considered.

Оценка эффективности сцинтиграфии рецепторов соматостатина с 111In-октреотидом в диагностике нейроэндокринных опухолей

Purpose: Exploring methods to improve diagnosis of neuroendocrine tumors (NET) in different locations using somatostatin receptors scintigraphy with 111In-octreotide. Material and methods: The study included 125 patients with NET in different locations. Activity of injected 111In-octreotide was 200–250 MBq (effective dose – 0.054 mSv/MBq), which allows to carry out a planar study as and single photon emission computed tomography. The study was performed after 24 hours on intravenous injection of indicator on the combined SPECT/CT machine Symbia T2 (Siemens, Germany). Results: In the sample of patients, NET distribution by localization is indicated in Fig. 1. The results of the study with 111In-octreotide are presented in the form of scintigrams in the whole body scanning mode and in the form of single-photon emission computer tomograms combined with CT. To determine the effectiveness of scintigraphy with 111In-octreotide, after a visual evaluation of the scintigrams obtained, the number of positive and negative results of the study was calculated. A comparison was made with the data of other methods and the number of TP, TN, FP, and FN results was determined. Further, the characteristic parameters of the method studied were calculated to determine its effectiveness. The study of values of characteristic parameters showed that the sensitivity was 73 % (95 % CI: 63–83 %), specificity – 97 % (95 % CI: 88–100 %) accuracy is 79 % (95 % CI: 71–87 %). The value of the positive predictive value of 99 % (95 % CI: 94–100 %), the predictive value of negative results – 55 % (95 % CI: 40–70 %). While the study shows a high frequency of TP results, while the frequencies of the TN and FN results are not significantly different (the average frequency of the FN results falls within the confidence interval for the frequency of the TN results). The method has a high value of the prognostic value of the positive result, which gives the right to assert about the high probability of the presence of a neuroendocrine neoplasm in obtaining a positive result. In the present study, no FP results were obtained due to the presence of concomitant diseases, in which accumulation of used radiopharmaceutical is possible, since the data on the presence of such diseases were taken into account in the analysis of scintigrams. The data obtained in this paper are in good agreement with the data obtained by other authors, as well as early Russian publications. It is worth noting that the data of domestic authors were obtained on a small sample, without specifying confidence intervals; the injected activity was less than in this study. In addition, the possibility of obtaining more information than using classical imaging methods (for SPECT/CT, the tissue with the pathological accumulation of 111In-octreotide appeared to be intact on CT), allows us to recommend the method as a method of choice in the diagnosis of NET of different localization. Conclusions: The method of somatostatin receptors scintigraphy using domestic analogue of somatostatin in the diagnosis of NET has a high efficiency (efficiency of the method, calculated as the average value of the parameters of sensitivity and specificity of 85 % (95 % CI: 66–100 %).

Somatostatin receptor expression in non-classical locations - clinical relevance?

In-111 pentetreotide (Octreoscan) is a radiolabeled somatostatin analog with high binding affinity to somatostatin receptors (SSTR) used in somatostatin receptor scintigraphy (SRS). Pentetreotide labelled with In-111 is widely used due to its high affinity to SSTR 2 and 5. SSTR are expressed on neuroendocrine cells as well as several non-neural and non-endocrine cells with varying levels of density. We retrospectively reviewed articles and publications related to octreoscan accumulation in sites that classically do not have high concentrations of SSTR as well as in organs and tissues from diseases which are not usually diagnosed by octreoscan. The significance of a positive uptake as assessed by octreoscan in non-somatostatin receptor related diseases is not fully understood yet. Localization of octreotide in non-oncological disease states such as inflammation is due to presence of SSTR in activated immunological cells, over-expression by activated cells in the respective tissue and SSTR expression by blood vessels. In granulomatous diseases, over-expression of SSTR2 preferential binding sites were detected in epitheloid and giant cells. The purpose of the current study is to identify octreoscan localization in non-somatostatin receptor related disease sites to better understand the mechanism of this nonspecific accumulation which may help expand the clinical utilization of functional imaging utilizing somatostatin receptor scintigraphy in diagnosis and perhaps therapy.

Is endoscopic ultrasonography more sensitive than magnetic resonance imaging in detecting and localizing pancreatic neuroendocrine tumors?

To compare endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) in terms of their sensitivities to localize pancreatic neuroendocrine tumors (pNET) preoperatively. Systematic analysis of the literature; sensitivity of EUS and MRI in insulinomas and pancreaticoduodenal NETs in multiple endocrine neoplasia type 1 (MEN1) in series of at least 20 subjects referring to tumors confirmed by surgery and histopathology. Other imaging methods reported were also assessed. Eighteen publications on insulinomas (782 cases) could be analyzed, no study in MEN1 fulfilled the inclusion criteria and compared EUS to MRI. Data quality was moderate: all publications referred to case series. Mean correct detection / localization rates (sensitivity) were calculated: EUS 80%, MRI 66%, computed tomography 63%, angiography 52%, somatostatin receptor scintigraphy 42%, ultrasonography 23%; arterial calcium stimulation with hepatic venous sampling regionalized correctly in 80%. EUS seems to be more sensitive than MRI in localizing pancreatic neuroendocrine tumors. If a specialized endosonographist is available, EUS is the preferable imaging procedure. Otherwise, MRI is a suitable alternative.

Perioperative treatment of patients with pheochromocytoma/paraganglioma combined catecholamine cardiomyopathy

Objective To discuss the diagnosis, perioperative treatment, cardiac function changing of pheochromocytoma/paraganglioma (PHEO/PGL)patients with catecholamine cardiomyopathy. Methods Fifteen PHEO/PGL patients with catecholamine cardiomyopathy were included in our hospital from Jan 2008 to Mar 2018. There were 8 males and 7 females with an average age of 32.8 years, ranging 13-64 years old.4 cases were found left PHEO. 4 cases were found right PHEO and 3 cases were bilateral PHEO, including 2 cases of VHL. One case was jugular PGL. 2 cases were lift PGL and 1 case was right PGL. The tumors diameter ranged from 2.3 to 7.2 cm. 14 patients were diagnosed as PHEO/PGL with catecholamine cardiomyopathy with typical clinical manifestations of PHEO/PGL, such as headache, palpitation and perspiration. Their 24 hours of urine catecholamines showed an average of 24.87 μg/24 h in epinephrine and 551.70 μg/24 h in norepinephrine. Their average value of dopamine was 395.41 μg/24 h. Among 7 cases, the octreotide scan and Iodine-131-meta-iodobenzylguanidine(131I-MIBG)s scan were positive in 6 and 1 case, respectively. Enhanced CT showed significantly heterogeneous enhancement tumors in adrenal or retroperitoneal area. Ischemia and necrosis area were found inside tumors. The blood flow of some tumors were extremely rich and irregular vascular network with a racemose distribution around the tumors could be observed. Echocardiography showed that the left ventricular ejection fraction (LVEF) ranged from 32% to 54%, mean (42.0±7.1) % during catecholamine cardiomyopathy. 5 cases were mild abnormal, which the LVEF ranged from 45% to 54%. 9 cases were moderate abnormal, which the LVEF ranged from 30% to 44%.Their catecholamine cardiomyopathy performance including left ventricular hypertrophy, myocardial echo enhancement and left ventricular enlargement.9 cases combined with acute left ventricular failure manifested as pulmonary edema and pink foamy phlegm. Sensitive antibiotics were given to suspected pulmonary infection patients. 14 cases accepted regular alpha blockers, beta blockers and calcium antagonists treatment for 1 to 3 months and underwent surgery after a significant improvement in cardiac function.1 non-functional PHEO patient was lack of typical clinical and imaging changing. Both of her 24 hours of urine catecholamines and octreotide scan were negative. Echocardiography showed that LVEF was 73% before operation. She was misdiagnosed as an adrenal non-functional adenoma. All patients underwent surgical treatment, including 13 laparoscopic surgery.One case switched to open surgery. 2 PGL patients all accepted open surgery. Rusults All cases accepted complete resection of the tumors. 1 case of non-functional PHEO had severe fluctuations in blood pressure during operation. Her BP were 190/130 to 80/50 mmHg (1 mmHg=0.133 kPa) and heart rate raised to 150 bpm. Catecholamine cardiomyopathy appeared in ICU ward after operation. Echocardiography showed that LVEF was 37%. The left ventricular enlargement and myocardial systolic function decreased. Fibrous bronchoscopy showed pink foamy phlegm in both sides of lungs. Chest X ray showed bilateral pulmonary edema which predominant in left side. The diagnosis was catecholamine cardiomyopathy of this patient. The LVEF was (55.9±7.6)% after treatment in 14 PHEO/PGL patients with catecholamine cardiomyopathy, and there was statistically significant difference between before and after treatment (P=0.041). The LVEF was (66.1±8.5)% postoperation, and there was statistically significant difference between postoperation and after treatment (P=0.013). The non-functional PHEO case occurred severe catecholamin cardiomyopathy after operation and cardiac function recovered after treatment. 15 cases were followed up from 1 months to 10 years without recurrence. Conclusions PHEO/PGL patients with catecholamine cardiomyopathy should have adequate medication. The abnormal cardiac function of patients would be reversed after surgical treatment. Cardiac function failure would be recovered after active treatment. Non-functional pheochromocytoma patients were extremely dangerous. Adequate medication should be given to any suspected non-functional pheochromocytoma patients. Key words: Pheochromocytoma; Paraganglioma; Catecholamines; Cardiomypathies; Nonfunctioning

Maxillary tumour-induced osteomalacia

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic form of renal phosphate wasting that results in severe hypophosphatemia, defective vitamin D metabolism, and osteomalacia. In the case reported here, maxillary TIO was not diagnosed for 6years, although initial complaints were reported when the patient was 12years old. Meanwhile she suffered from profound growth limitation, pain, weakness, and spontaneous multiple bone fractures, culminating in complete loss of ambulatory ability and severe limitation in daily activities. At age 18years, she finally received an accurate diagnosis and definitive treatment was administered. She underwent a partial maxillectomy with complete removal of the tumour, resulting in a full cure. Shortly afterwards the patient regained the ability to walk, no longer needing the wheelchair to which she had been confined. This definitive diagnosis was based on three modalities: (1) fibroblast growth factor 23 analysis (high levels of the secreted hormone were found on the left side of the maxilla in the facial vein and pterygoid plexus, pinpointing the tumour location), (2) octreotide scan, and (3) 68Ga-DOTA-NOC-PET/CT. TIO removal via partial maxillectomy led to a complete reversal of this patient’s health condition, restoring her ability to walk and function. The importance of prompt employment of these diagnostic modalities and the high level of clinical suspicion required in such cases are clear.

Hepatic neuroendocrine tumors without an identifiable extrahepatic primary

Background: Hepatic neuroendocrine tumors without an identifiable primary represent either primary tumors or metastases from occult primaries. Primary hepatic neuroendocrine tumors (NET) are very rare. The natural history of patients with liver only disease is poorly defined. Methods: Patients with resected hepatic neuroendocrine tumors were identified for the years 1998–2017. Clinicopathologic variables were abstracted by chart review and immunohistochemistry reviewed for all specimens. Results: Thirteen patients with hepatic NET, without any evidence of non-hepatic primary disease were identified. Extrahepatic primary disease was not identified during a median follow-up of 38 months (1–164 months). The mean age at diagnosis was 54.7 years, 62% female. Pre-operative evaluation to rule out a primary source included CT enterography (n = 1), EUS/ERCP (n = 8), and octreotide scan (n = 11). Six patients had a solitary lesion, while 7 had multifocal disease. Operations performed were right hepatectomy (n = 4), left hepatectomy (n = 4), central hepatectomy (n = 1) and others had a combination of wedge resections and radiofrequency ablation. Six patients had Grade I disease, 6 were Grade 2 and one patient was classified as Grade 3. Two patients died 20 and 33 months after surgery secondary to disease progression (progressive liver disease and solitary brain metastases), both of which were grade 2 with a Ki-67 of 5-10%. The overall survival was 54.1 months (1–164 months) and recurrence free survival was 25.8 months (1–82 months). Conclusion: Primary hepatic NETs are rare, as are liver metastases without an identifiable primary. The natural history of these tumors is in keeping with other neuroendocrine tumors and is generally favorable, especially for low grade disease.