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Objectives A reappraisal of the validity of the conclusions of systematic reviews (SRs) related to nirmatrelvir/ritonavir for the treatment of COVID-19. Methods An overview of SRs (umbrella review). The methodological quality of the SRs was assessed using the AMSTAR 2 checklist; quality of the evidence from the trials included in each SR was appraised following the GRADE approach. Results Sixteen SRs with meta-analysis published between 2020 and 2023 were included in this overview. The SRs reported data from 108 overlapping reports, based on 43 individual primary studies [3 randomized clinical trials (RCTs), 40 non-RCTs]. In outpatient settings the use of nirmatrelvir/ritonavir reduced overall mortality, hospital admission and progression of disease compared with controls (from moderate to low certainty of evidence); nirmatrelvir/ritonavir reduced mortality, hospital admission and progression of disease in both immunized and non-immunized patients. No differences in the occurrence of any adverse events between groups were observed in the large majority of SRs; serious adverse events, including adverse events requiring discontinuation of treatment, were reported with lower prevalence in nirmatrelvir recipients compared with controls (from low to moderate certainty of evidence). Conclusions There is low to moderate certainty of evidence from SRs that nirmatrelvir/ritonavir reduces mortality, clinical progression and hospitalization rate in COVID-19 patients compared with controls, without increasing the occurrence of overall and serious adverse events. Based on the overall methodological assessment, on average we can have high confidence in the quality of results generated by the SRs. [ABSTRACT FROM AUTHOR]

Somatostatin receptor scintigraphy (SRS) is an essential examination for the diagnosis of neuroendocrine tumors (NETs). This study developed a method to individually optimize the display of whole-body SRS images using a deep convolutional neural network (DCNN) reconstructed by transfer learning of a DCNN constructed using Gallium-67 (67Ga) images. The initial DCNN was constructed using U-Net to optimize the display of 67Ga images (493 cases/986 images), and a DCNN with transposed weight coefficients was reconstructed for the optimization of whole-body SRS images (133 cases/266 images). A DCNN was constructed for each observer using reference display conditions estimated in advance. Furthermore, to eliminate information loss in the original image, a grayscale linear process is performed based on the DCNN output image to obtain the final linearly corrected DCNN (LcDCNN) image. To verify the usefulness of the proposed method, an observer study using a paired-comparison method was conducted on the original, reference, and LcDCNN images of 15 cases with 30 images. The paired comparison method showed that in most cases (29/30), the LcDCNN images were significantly superior to the original images in terms of display conditions. When comparing the LcDCNN and reference images, the number of LcDCNN and reference images that were superior to each other in the display condition was 17 and 13, respectively, and in both cases, 6 of these images showed statistically significant differences. The optimized SRS images obtained using the proposed method, while reflecting the observer's preference, were superior to the conventional manually adjusted images. [ABSTRACT FROM AUTHOR]

We report a 58-year-old male with a histopathologically proven grade 2 (G2) pancreatic neuroendocrine neoplasm and multiple abdominal node metastases by use of a laparoscopic pancreatic body and tail resection procedure, plus abdominal lymph node dissection. A primary pancreatic tail neuroendocrine tumor sized 20 × 25 mm was detected by contrast-enhanced computed tomography, somatostatin receptor scintigraphy (SRS), and fluorodeoxyglucose positron emission tomography (FDG-PET) examinations and pathologically diagnosed as a pancreatic neuroendocrine tumor (PNET, G2) based on positive immunostaining for somatostatin receptor (SSTR) type 2. Of three metastatic histopathological lymph nodes, two measured 18 × 21 and 10 × 12 mm, respectively, with whole strong SSTR immunostaining showing moderate uptake in SRS findings, whereas the other node, sized 8 × 10 mm, had strong SSTR immunostaining only in a small 6 × 6-mm-sized portion and showed no uptake in SRS findings, likely because of the limited spatial resolution of scintigraphy. On the other hand, only the largest node (18 × 21 mm) was visualized by FDG-PET. SRS may be useful for metastatic lymph node diagnosis based on SSTR immunostaining, though a disadvantage is the spatial resolution limitation.

Aim: The preoperative prediction of lymph node metastasis of well‐differentiated rectal neuroendocrine tumours is highly desirable and useful in defining surgical indication more accurately. We aimed to evaluate lymph node metastasis in rectal neuroendocrine neoplasms using multiple imaging modalities. Methods: The clinical records and radiological images of 70 patients with well‐differentiated rectal neuroendocrine tumours who received treatment at the University of Tokyo Hospital between 2010 and 2022 were retrospectively analysed. The relationship between evaluation by multiple imaging modalities and pathological lymph node metastasis was analysed. Results: The receiver operating characteristic curves showed that a maximum lymph node diameter ≥4 mm on computed tomography and ≥8 mm on magnetic resonance imaging were the optimal predictive factors for lymph node metastasis. Accumulation in the lymph nodes on somatostatin receptor scintigraphy (P = 0.058) and Delle's findings on colonoscopy (P = 0.014) were also significant predictors of pathological lymph node positivity, and combination of multiple modalities was useful. Pathologically, lymphatic (P = 0.0030)/venous (P = 0.0007) invasion were risk factors for lymph node metastasis. Conclusions: In addition to pathological risk factors, a combination of multiple radiological imaging modalities is useful for predicting lymph node metastasis in well‐differentiated rectal neuroendocrine tumours. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumor (NET) is a rare tumor commonly found in the gastrointestinal tract and lungs and rarely originates from and metastasizes to the kidney. We report a case of a 66-year-old man with metastatic rectal NET to the kidney, pancreas and bone following the resection of renal tumor with robot-assisted partial nephrectomy (RAPN). A rectal tumor of 10mm in diameter had been endoscopically resected and diagnosed NET with positive surgical margin 9 years before RAPN. Somatostatin receptor (SSR) scintigraphy revealed the other two metastases postoperatively, therefore is an effective tool to detect primary and metastatic sites of NETs.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.

Simple Summary: Determining the most sensitive imaging technique to evaluate neuroendocrine tumors spread may have an impact on therapeutic management. The aim of this multicentric study was to prospectively assess 68Ga-DOTANOC PET/CT sensitivity compared to the combination of multiphasic CT, somatostatin receptor scintigraphy and MRI to evaluate whether this imaging modality results in therapeutic modifications. We confirm in a homogenous population of 105 grade 1 or 2 gastroenteropancreatic neuroendocrine tumors the higher sensitivity of 68Ga-DOTANOC PET/CT in per-patient and per-region analysis, as well as in the detection of primary tumor and small lesions such as peritoneal carcinomatosis and bone lesions leading to an impact on therapeutic management of almost half of the patients. The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p < 0.001) analyses, in the detection of the primary (97.9% vs. 78.7%; p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p < 0.001), and bone metastases (100% vs. 33.3%, p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs. [ABSTRACT FROM AUTHOR]

We report a 58-year-old male with a histopathologically proven grade 2 (G2) pancreatic neuroendocrine neoplasm and multiple abdominal node metastases by use of a laparoscopic pancreatic body and tail resection procedure, plus abdominal lymph node dissection. A primary pancreatic tail neuroendocrine tumor sized 20 × 25 mm was detected by contrast-enhanced computed tomography, somatostatin receptor scintigraphy (SRS), and fluorodeoxyglucose positron emission tomography (FDG-PET) examinations and pathologically diagnosed as a pancreatic neuroendocrine tumor (PNET, G2) based on positive immunostaining for somatostatin receptor (SSTR) type 2. Of three metastatic histopathological lymph nodes, two measured 18 × 21 and 10 × 12 mm, respectively, with whole strong SSTR immunostaining showing moderate uptake in SRS findings, whereas the other node, sized 8 × 10 mm, had strong SSTR immunostaining only in a small 6 × 6-mm-sized portion and showed no uptake in SRS findings, likely because of the limited spatial resolution of scintigraphy. On the other hand, only the largest node (18 × 21 mm) was visualized by FDG-PET. SRS may be useful for metastatic lymph node diagnosis based on SSTR immunostaining, though a disadvantage is the spatial resolution limitation. [ABSTRACT FROM AUTHOR]

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Introduction: Negative radioiodine (131I) whole-body scan with elevated serum thyroglobulin (Tg) level are found in 20% of patients with differentiated thyroid cancer (DTC), which can be a diagnostic challenge. We evaluated the efficacy of Technetium-99m-Hydrazinonicotinyl-Tyr3-Octreotide ([99mTc]Tc-HYNIC-TOC) somatostatin receptor scintigraphy (SRS) for detection of non-iodine-avid metastases and its impact on staging and management of these patients. Methods: The study population consisted of 35 DTC patients (25 females; PTC = 88.2%, FTC = 11.8%) who had elevated serum Tg levels despite negative post-ablation radioiodine whole-body scan. All patients underwent whole body SRS 3-4 hours after intravenous injection of 20mCi (740 MBq) of [99mTc]Tc-HYNIC-TOC. Sites of suspected radiotracer accumulation were confirmed with anatomic imaging. Ultimately, corresponding changes in the staging and management were recorded. Results: SRS was positive in 27 (77.1%) cases. Patients with positive scan had significantly higher Tg levels at the time of scan, compared to those with negative scans (154.5±188.6 vs. 28.2±32.7 ng/mL, p-value = 0.005). Interestingly, previous history of neck external beam radiation therapy (EBRT) was significantly correlated with [99mTc]Tc-HYNIC-TOC avidity (Likelihood ratio = 11.2, p = 0.005). Addition of SSTR scintigraphy changed overall staging and management in 11% and 32.4% of the patients, respectively. Conclusion: SRS can be a useful diagnostic adjunct in DTC patients with highly elevated Tg and negative radioiodine wholebody scan. The likelihood of positive findings on [99mTc]Tc-HYNIC-TOC was higher in cases with previous history of EBRT or high Tg levels (i.e. suppressed-Tg >80 ng/mL) at the time of scan. [ABSTRACT FROM AUTHOR]

Theranostics is a term coined by combining the words "therapeutics" and "diagnostics," referring to single chemical entities developed to deliver therapy and diagnosis simultaneously. Neuroendocrine tumors are rare cancers that occur in various organs of the body, and they express neuroendocrine factors such as chromogranin A and somatostatin receptor. Somatostatin analogs bind to somatostatin receptor, and when combined with diagnostic radionuclides, such as gamma‐emitters, are utilized for diagnosis of neuroendocrine tumor. Somatostatin receptor scintigraphy when combined with therapeutic radionuclides, such as beta‐emitters, are effective in treating neuroendocrine tumor as peptide receptor radionuclide therapy. Somatostatin receptor scintigraphy and peptide receptor radionuclide therapy are some of the most frequently used and successful theranostics for neuroendocrine tumor. In Japan, radiopharmaceuticals are regulated under a complex law system, creating a significant drug lag, which is a major public concern. It took nearly 10 years to obtain the approval for somatostatin receptor scintigraphy and peptide receptor radionuclide therapy use by the Japanese government. In 2021, 111Lu‐DOTATATE (Lutathera), a drug for peptide receptor radionuclide therapy, was covered by insurance in Japan. In this review, we summarize the history of the development of neuroendocrine tumor theranostics and theranostics in general, as therapeutic treatment for cancer in the future. Furthermore, we briefly address the Japanese point of view regarding the development of new radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Treatment-related neuroendocrine-differentiated prostate cancer (NEPC) is a rare tumor entity that transdifferentiates from adenocarcinoma as an adaptive response to androgen receptor pathway inhibition. We report a 79-year-old male with treatment-related NEPC, presenting as rectal bleeding after hormonal therapy. MRI showed a 51 × 52 × 65 mm tumor occupying almost the whole prostate gland and invading the seminal vesicle and rectum as moderately heterogeneous hypointensity on T2-weighted image, restricted diffusion on apparent diffusion coefficient map and diffusion-weighted imaging, and heterogeneous enhancement on Gd-enhanced T1-weighted image. FDG-PET/CT showed strong FDG uptake of the prostate tumor, and somatostatin receptor scintigraphy (SRS) showed mild uptake of the prostate tumor. The surgically resected specimen revealed NEPC. If prostate cancer worsens despite conventional therapy, treatment-related NEPC should be considered, and the benefit of imaging examinations including prostate MRI, FDG-PET/CT, and SRS is in localizing lesions with neuroendocrine differentiation.

Purpose: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET.Methods: Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of 177Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs.Results: Six Japanese patients (three men and three women; mean age 61.5 years; range 50-70 years) with SRS-positive unresectable NETs were recruited. 177Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%-69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of 177Lu-DOTATATE was 16.8 Gy (range 12.0-21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2-21.5 Gy). Administration of 177Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease.Conclusion: PRRT with 177Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, 177Lu-DOTA0-Tyr3-octreotate . [ABSTRACT FROM AUTHOR]

Abstract Background A majority of gastrinomas causing Zollinger–Ellison syndrome are located in the duodenum or pancreas. Primary hepatic gastrinomas are rare and difficult to diagnose. We report a rare case of primary hepatic gastrinoma, which could be diagnosed preoperatively. Case presentation A 29-year-old man with a 55-mm tumor in segments 5 and 6 (S 5/6) of the liver was admitted to our hospital. After thorough investigations, he was treated for a suspected inflammatory pseudotumor and advised to undergo routine follow-up. Two years later, he revisited our hospital with a complaint of abdominal pain, vomiting, and diarrhea. Upper gastrointestinal endoscopy revealed multiple duodenal ulcers. His serum gastrin level was 2350 pg/mL (normal: 37–172 pg/mL), suggesting Zollinger–Ellison syndrome. Abdominal computed tomography showed a 78-mm hypervascular tumor with cystic degeneration in the S 5/6 region of the liver, with a potential to increase over time. The tumor showed hypointensity on T2-weighted and hyperintensity on diffusion-weighted abdominal contrast-enhanced magnetic resonance imaging. Somatostatin receptor scintigraphy (SRS) only detected a hepatic tumor. No tumors in the gastrinoma triangle were detected by endoscopic ultrasonography. Hence, selective arterial calcium injection (SACI) test was performed to determine the location of the gastrinoma. The serum gastrin concentration increased from 4620 pg/mL to 23,600 pg/mL at 20 s after calcium gluconate injection into the proper hepatic artery. Conversely, no effect on serum gastrin level was observed after the injection into any other arteries. Extended right hepatic lobectomy and cholecystectomy were performed after percutaneous transhepatic portal vein embolization. A histopathological examination of the liver tumor revealed a gastrinoma. The patient’s serum gastrin concentration on postoperative day 1 decreased to 65 pg/mL. Conclusion We report a surgical case of primary hepatic gastrinoma correctly diagnosed preoperatively. The patient underwent extended right hepatic lobectomy, resulting in a histological definitive diagnosis of primary hepatic gastrinoma.

The aim of investigation was to assess the role of somatostatin receptor scintigraphy in diagnosis and follow-up of pancreatic neuroendocrine neoplasms. Somatostatin receptor scintigraphy was performed with 740 MBq 99mTc-EDDA/HYNIC TOC for diagnosis of primary tumors and follow-up after the therapy. There were 63 true positive, 24 true negative, 4 false positive, and 6 false negative findings. Sensitivity was 91.3 %, specificity 85.7 %, positive predictive value 94.0 %, negative predictive value 80.0 %, accuracy 89.7 %. The SPECT contributed diagnosis in 28 true positive findings. In 32 patients (33 %) somatostatin receptor scintigraphy significantly changed the management of the patients (10 had surgery, in 17 somatostatin analogues, and in 5 peptide receptor radionuclide therapy was introduced). Mean Ki-67 index in true positive patients was 13.8 ±5.0 % while in true negative 7.1 ± 3.4% which is significantly lower at p < 0.05. There was significantly (p < 0.01) higher number of increased chromogranin A values in true positive than in true negative patients (p = 0.000857). Our results confirmed the value of SRS in the diagnosis and follow-up of the patients with pancreatic neuroendocrine neoplasms PanNEN if primary tumors, recurrences or metastases are suspected, as well as for appropriate choice of the therapy.

Neuroendocrine carcinomas (NECs) are rare and highly malignant tumors with a generally poor prognosis. Carcinoembryonic antigen (CEA) is often associated with adenocarcinoma, but its significant elevation in NEC cases is unusual. A 69-year-old man was admitted to our hospital in January 2016 due to syncope induced by anemia. The patient had a hemoglobin level of 8.0 g/dL and an ileocecal mass causing small bowel obstruction on computed tomography. His CEA level was markedly elevated at 3625.4 ng/mL. A colonoscopy revealed a neoplastic lesion in the terminal ileum, leading to an emergency ileocecal resection. Pathology confirmed a NEC, positive for synaptophysin and CEA, with a Ki-67 index of 30%. The patient was diagnosed with stage IIIb NEC (pT3N2M0). A postoperative increase in CEA to 4124.6 ng/mL and metastases in the right lung and multiple lymph nodes were detected. Initial chemotherapy with irinotecan, cisplatin (IP), and octreotide acetate proved ineffective. Subsequent octreoscans showed disease progression. Switching to everolimus as second-line therapy temporarily decreased CEA levels and tumor size, but the disease progressed with cervical lymph node involvement. The patient underwent palliative radiotherapy but succumbed to disease progression in May 2018, with a final CEA level of 36,643 ng/mL. Necropsy of the cervical lymph nodes was consistent with the original surgical findings. This case highlights the aggressive nature and challenging management of NEC with significantly elevated CEA levels., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sugimoto et al.)

Introduction: In the neuroendocrine tumors management, the accurate monitoring of the radiotracer biodistribution and tumors dimensions are vital. We have created a visual functional grading scale, which could better classify the pathological uptakes in possibly different grades. Material and method: We conducted a retrospective, bi-centric study, for a period of 18 months on 65 patients, with different types of NETs. Somatostatin receptor scintigraphy was performed using a radiolabeled somatostatin analogue. Using the Regions of Interest (ROI) technique, we defined and used a visual functional grading scale, in three degrees, qualitatively evaluating the intensity of the physiological and pathological uptake of the tracer. Results: Applying our proposed visual functional grading scale, positive 99mTc-TOC NETs lesions were identified, in all analyzed patients: 31 G1 primary NET, corrected ROI tumor values of 1.16-4.75, 19 G2 primary NETs, corrected ROI tumor values between 5-14.9 and 7 G3 primary NETs, corrected ROI tumor values between 15.65-243.79. Conclusion: Our proposed evaluation scale was useful for the interpretation of SRS for NET precision medicine and could be applicable in the evaluation of other neoplastic pathologies images. [ABSTRACT FROM AUTHOR]

Background: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs is an innovative treatment for advanced somatostatin‐positive neuroendocrine tumors (NETs). PRRT cannot be performed in Japan because there is no approval or insurance cover so far. Methods: We relied on foreign institutions to perform PRRT for Japanese patients with NETs. We retrospectively evaluated the safety and efficacy of PRRT. The inclusion criteria were pathologically confirmed well‐differentiated NET and visible tumor uptake on pre‐therapeutic somatostatin receptor scintigraphy. 177Lu‐DOTA‐TOC was used as the standard treatment, and patients received three infusions every 8 weeks. Until the end of 2017, combination treatment with 90Y and 177Lu‐DOTA‐TOC was performed using the same protocol. Results: Thirty‐five patients were evaluated, and the primary lesions were pancreas, rectum, small intestine, stomach, and other locations. The partial response rate was 42.9%. Progression‐free survival (PFS) was 12.8 months and overall survival was 42.8 months. There was no significant difference in PFS between front‐line and late‐line PRRT (11.0 months vs 28.0 months; P =.383). Severe adverse events included lymphocytopenia (20.0%) and thrombocytopenia (5.7%). Myelodysplastic syndrome occurred in one case. Conclusion: PRRT was effective and safe for Japanese patients with advanced NETs. PRRT was equally effective as front‐line and late‐line treatment. [ABSTRACT FROM AUTHOR]

We report a case of myocarditis imaged with technetium-99m octreotide cardiac single-photon emission computed tomography which showed diffuse uptake in the myocardium, indicating inflammatory reaction to myocardial damage. Somatostatin receptor scintigraphy of the heart could be considered in patients with suspected cardiac inflammation. This could facilitate early diagnosis and guide appropriate treatment. [ABSTRACT FROM AUTHOR]

Treatment-related neuroendocrine-differentiated prostate cancer (NEPC) is a rare tumor entity that transdifferentiates from adenocarcinoma as an adaptive response to androgen receptor pathway inhibition. We report a 79-year-old male with treatment-related NEPC, presenting as rectal bleeding after hormonal therapy. MRI showed a 51 × 52 × 65 mm tumor occupying almost the whole prostate gland and invading the seminal vesicle and rectum as moderately heterogeneous hypointensity on T2-weighted image, restricted diffusion on apparent diffusion coefficient map and diffusion-weighted imaging, and heterogeneous enhancement on Gd-enhanced T1-weighted image. FDG-PET/CT showed strong FDG uptake of the prostate tumor, and somatostatin receptor scintigraphy (SRS) showed mild uptake of the prostate tumor. The surgically resected specimen revealed NEPC. If prostate cancer worsens despite conventional therapy, treatment-related NEPC should be considered, and the benefit of imaging examinations including prostate MRI, FDG-PET/CT, and SRS is in localizing lesions with neuroendocrine differentiation. [ABSTRACT FROM AUTHOR]

Gastrin-secreting tumors, hypergastrinemia and severe ulcer disease form the trademarks of Zollinger-Ellison syndrome (ZES). We report a case of gastrinoma, in a patient who was misdiagnosed for almost five years. The case emphsizes the the special role of functional imaging in the personalized approach to the patient with suggestive symptomatology for NETs. Taking into account that in 80 to 100% of cases of gastroenteropancreatic (GEP) NETs are expressing somatostatin receptors, the functional imaging with radiolabeled somatostatin analogues can be used in order to improve its diagnosis, respectively the treatment of GEP NETs. In the approach to the patient with tremendous digestive symptomatology, physicians from different specialties should evaluate NETs specific markers and then insist on structural-functional complementarity, avoiding the waste of time and high cost of repeated structural investigations. The conclusion of our study is that functional imaging is mandatory in the diagnostic algorithm of gastrinoma. [ABSTRACT FROM AUTHOR]

The number of patients with the extremely rare disease gastroenteropancreatic (GEP) neuroendocrine tumor (NET) has increased rapidly in recent years. 111In-pentetreotide SPECT in somatostatin receptor scintigraphy has been used for the assessment of GEP NET patients. To diagnose GEP NET, appropriate selection of image correction parameters is critical. Correction methods may improve the 111In-pentetreotide SPECT image quality, but there is currently no standard technique. The purpose of this study was to determine the optimal correction parameter settings for 111In-pentetreotide SPECT. Methods: A phantom study produced images with a tumor-to-background ratio of as high as 16:1. A triple energy window was used for scatter correction (SC), and attenuation correction (AC) was CT-based. Correlation analysis was performed in 4 groups: no correction (NC), SC, AC, and combined SC with AC (CC). The 111In-pentetreotide SPECT results for 20 randomly selected patients (13 men and 7 women; age range, 37-81 y) with confirmed GEP NET were analyzed using data collected 4 h after injection of 111 MBq of 111In-pentetreotide. Emission data were reconstructed using ordered-subset expectation maximization (OSEM) with different settings. Different combinations of the correction parameters were used to analyze the contrast-to-noise ratios (CNRs) obtained with the phantom. In the clinical study, 20 GEP NET patients were used to evaluate the GEP NET lesion CNR by 4 different image correction methods obtained from 111In-pentetreotide SPECT images: NC, SC, AC, and CC. NC was used as a reference method. Results: The phantom study revealed that the optimal energy window in the photopeak for somatostatin receptor scintigraphy was 171 keV ± 10% and 245 keV ± 7.5%, and the optimal OSEM reconstruction conditions were 8 subsets and 6 iterations. Among the OSEM collection conditions, CC produced a significantly higher CNR than NC or SC (P < 0.05). In the clinical study, CC was found to increase the CNR (P < 0.05). Conclusion: CC improves the correction in 111In-pentetreotide SPECT studies, compared with NC, providing better contrast and sharper outlines of lesions and organs. [ABSTRACT FROM AUTHOR]

Gallbladder neuroendocrine carcinoma (NEC) is a rare gallbladder tumor. The current report is a case of a patient preoperatively diagnosed with gallbladder NEC using somatostatin receptor scintigraphy (SRS). A 63-year-old man was admitted to our hospital by a family doctor after abdominal ultrasonography revealed thickened walls of the neck of his gallbladder. At Kagoshima University Hospital, CT and MRI of the abdomen and endoscopic ultrasonography confirmed the thickening of the walls of the neck of the gallbladder. However, it did not resemble a typical gallbladder cancer or tumor, such as a neuroendocrine tumor or malignant lymphoma. Positron emission tomography and SRS showed abnormal accumulation at the tumor site. Endoscopic retrograde cholangiopancreatography was performed, adenocarcinoma was suspected based on intra-gallbladder bile cytology, and a cholecystectomy with lymphadenectomy was performed. The postoperative pathological diagnosis was small cell NEC (pT3a, N0, M0, stage II). Immunohistochemistry indicated that the gallbladder tumor cells were positive for synaptophysin, chromogranin A, and cluster of differentiation (CD) 56, and negative for somatostatin receptors (SSTR) 2 and 5. Gene expression assays revealed the expression of all SSTR subtypes (SSTR1-5) in the tumor. Generally, NECs exhibit poor accumulation in SRS, however, the results of the current case suggest that SRS may be useful in the preoperative diagnosis of NEC. [ABSTRACT FROM AUTHOR]

Aim: To determine whether whole-body magnetic resonance imaging is valuable in staging of neuroendocrine tumors by comparison with the conventional imaging defined by the combination of computed tomography and somatostatin receptor scintigraphy. Methods: This study concerned the patients included in the multicenter prospective study NCT02786303 with the following inclusion criteria: well-differentiated gastroenteropancreatic neuroendocrine tumors or of unknown primary, and computed tomography, whole-body magnetic resonance imaging and somatostatin receptor scintigraphy performed within 6 weeks. Results of the conventional imaging were compared with those of magnetic resonance imaging. Discrepancies between the conventional imaging and magnetic resonance imaging were evaluated by reviewing medical records. Results: Thirty-one patients (17 men and 14 women) were prospectively included. Complete concordance between the magnetic resonance imaging and the conventional imaging results was observed in 25 patients and discrepancies in 6. Whole-body magnetic resonance imaging detected more liver lesions than the conventional imaging did but standard imaging set was more effective in the detection of bone and peritoneum lesions than magnetic resonance imaging. Detecting more lesions had no impact on therapeutic management. Conclusions: Whole-body magnetic resonance imaging including diffusion weighted may be a valuable alternative to computed tomography and somatostatin receptor scintigraphy. Further studies should compare whole-body MRI to the 68Ga PET/CT. [ABSTRACT FROM AUTHOR]

Abstract Background Primary hepatic gastrinoma causing severe ulcerogenic syndrome is extremely rare. Herein, we report a case of primary hepatic gastrinoma accompanied by hyperplasia of multi-nodular Brunner’s glands in a patient who instead, preoperatively, was suspected of having multiple duodenal gastrinomas and hepatic metastasis. Case presentation A 57-year-old woman consulted a clinic complaining of melena, intermittent abdominal pain, diarrhea, and vomiting which had persisted for about 3 years. Six months before her presentation, she underwent segmental resection of the jejunum for acute peritonitis due to the spontaneous jejunal perforation. A blood test revealed that her serum immunoreactive gastrin (IRG) level was 12,037 pg/mL. Subsequently, she was transferred to our hospital. On computed tomography (CT), a hypervascular tumor of 23 mm in the segment 5 (S5) region of the liver was visualized. A selective arterial secretagogue injection test (SASI test) was performed twice. The first SASI test revealed that the hepatic tumor was a gastrinoma, and there was no gastrinoma in the duodeno-pancreatic region. Additionally, somatostatin receptor scintigraphy only visualized the tumor in the liver. However, the second SASI test, which was performed during the administration of a proton pump inhibitor and a somatostatin analog (octreotide acetate), revealed that there may have been gastrinomas existing not only in the liver but also in the upper part of the duodenum or the head of the pancreas. Duodenal endoscopy revealed multiple submucosal tumors in the first and the second portion of the duodenum, although a pathological examination of biopsied specimens obtained from the duodenal lesions was negative for malignant cells. Multiple endocrine neoplasia type 1 (MEN1) was excluded from her family history, and serum levels of both intact parathyroid hormone (iPTH) and calcium were within normal ranges. An anterior segmentectomy of the liver and pancreas-preserving total duodenectomy were performed on September 9, 2013. Postoperatively, her serum immunoreactive gastrin level decreased to less than 50 pg/mL. Pathological study of the resected specimens revealed a gastrinoma in the liver, but no gastrinoma in the duodenum. Interestingly, the duodenal submucosal tumor-like lesions were hyperplastic Brunner’s glands. Postoperatively, she has been well without recurrence of hypergastrinemia for 4 years. Conclusion We report a case of primary hepatic gastrinoma in a patient who has been cured for 4 years postoperatively. The diagnosis was somewhat difficult due to the coexisting, multiple hyperplastic Brunner’s glands of the duodenum mimicking the submucosal neuroendocrine tumors, which might have developed due to long-term hypergastrinemia.

BACKGROUND: Neuroendocrine neoplasms of the pancreas (p-NEN) are common gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). The aim of this retrospective study was to review the value of Somatostatin Receptor Scintigraphy (SRS) in initial detection of p-NEN, evaluation of tumour extent and as imaging follow-up after radical surgery in patients with confirmed well (NETG1) or moderately (NETG2) differentiated p-NEN based on pathological WHO 2017 classification. MATERIAL AND METHODS: Overall 281 patients with confirmed p-NEN were enrolled. The SRS was performed to evaluate primary p-NEN, to assess clinical stage of disease, based on current World Health Organization (WHO) classification and during clinical follow-up. A total of 829 examinations were performed over time in these 281 patients using 99mTc HYNICTOC. Images were acquired between 1-3 h after i.v. injection of radiotracer. Initially whole body WB-SPECT and then WB-SPECT/CT with standard iterative reconstruction were used. RESULTS: There were 159 patients with NETG1 (57%) and 122 subjects with NETG2 (43%). The female to male ratio was 1.1:1. In 68 patients (22%) with NETG1/G2 eighty-seven SRSs (10%) were performed to confirm initial diagnosis. SRS results were as follow: true positive (TP) = 84 (97%), false negative (FN) = 3 (3%), no true negative (TN) or false positive (FP) results of SRS examination (sensitivity of SRS per patient was 96%). In 198 subjects (66%) SRS was used in evaluation and re-evaluation of the clinical stage. A total of 661 (80%) examinations were carried out in these patients. There were TP = 514 (77%), TN = 136 (21%), FN = 7 (1%) and FP = 4 (1%) results. The sensitivity and specificity per patient were: 96% and 95%. The sensitivity and specificity per study were: 98% and 97%. In 35 patients (12%) SRS was used as imaging follow-up after radical surgery; there were overall 81 examinations (10%) performed. There were 76 (91%) TN results of SRS examinations and in 4 patients we identified recurrence (TP). In total, which consists of initial diagnosis/staging and patient follow-up, the sensitivity of SRS was 96% and specificity 97% per patient and per study sensitivity and specificity was 98%. CONCLUSIONS: SRS using 99mTc HYNICTOC acquired in WB-SPECT or WB-SPECT/CT techniques is an excellent imaging modality in detection of primary NETG1/G2 p-NEN. Our study confirms that SRS has high sensitivity and specificity, as a result has tremendous value as an examination method to assess clinical stage of disease and as an imaging follow-up after radical treatment. [ABSTRACT FROM AUTHOR]

This article is the review of issues of the literature for the past 10 years and is dedicated to the analysis of the radiopharmaceuticals and efficacy of the novel nuclear medicine technologies for the diagnosis, staging and prognosis of neuroendocrine tumors. Diagnostic efficacy of a scintigraphy and a positron emission tomography for detection of gastroenteropancreatic and lung carcinoid, medullary thyroid cancer, pheochromocytoma and haraganglioma and choice of radiopharmaceuticals were demonstrated by the results of the clinical studies. The causes of false positive and falce negative results were specified.

Background/Objective This study was conducted to explore authorship characteristics and publication trends of all orthodontic randomized controlled trials (RCTs), systematic reviews (SRs), and meta-analyses (MAs) published in non-orthodontic journals with impact factor (IF). Materials and methods Appropriate research strategies were developed to search for all articles published until December 2015, without restrictions regarding language or publication status. The initial search generated 4524 results, but after application of the inclusion criteria, the final number of articles was reduced to 274 (SRs: 152; MAs: 36; and RCTs: 86). Various authorship characteristics were recorded for each article. Frequency distributions for all parameters were explored with Pearson chi-square for independence at the 0.05 level of significance. Results More than half of the included publications were SRs (55.5 per cent), followed by RCTs (31.4 per cent) and MAs (13.1 per cent); one hundred seventy-eight (65 per cent) appeared in dental journals and 96 (35 per cent) were published in non-dental journals. The last decade was significantly more productive than the period before 2006, with 236 (86.1 per cent) articles published between 2006 and 2015. European countries produced 51.5 per cent of the total number of publications, followed by Asia (18.6 per cent) and North America (USA and Canada; 16.8 per cent). Limitations Studies published in journals without IF were not included. Conclusions/Implications Level-1 evidence orthodontic literature published in non-orthodontic journals has significantly increased during 2006–15. This indicates a larger interest of other specialty journals in orthodontic related studies and a trend for orthodontic authors to publish their work in journals with impact in broader fields of dentistry and medicine. [ABSTRACT FROM AUTHOR]

Background: The number of Europeans aged over 65 will double between 2010 and 2060, reaching 30% of the European population. Nutrition is emerging as a key element of healthy life since both obesity and malnutrition are established risk factors for morbidity and disability. The aim of this umbrella review (UR) is to summarize the findings of all current systematic reviews (SRs) and meta-analyzes (MAs) on the effectiveness of nutritional intervention designed to promote healthy aging in older individuals. Methods: Eligible articles published in English or Italian between January 2000 and May 2016 were identified in six databases. Only studies that analyzed nutritional interventions in the population of 65years and over, or papers specifically targeting older adults were deemed eligible. Results: Twenty-eight papers, out of which twenty-five SRs and three MAs, met the inclusion criteria and were included in this umbrella SR. Supplementation with vitamin D and other kind of products was highly effective in preventing falls and fractures. Furthermore, several interventions, ranging from the prescription of supplements to environmental and organizational programs, resulted in an improvement in energy and protein intake, as well as positive weight outcomes. Positive findings were also found for the elderly at risk of malnutrition and for older patients with dementia. Conclusions: The findings of this UR indicate that the use of a wide range of supplements and environmental and organizational intervention improve a number of anthropometric, nutritional and functional indices in the elderly. [ABSTRACT FROM AUTHOR]

Aim: Presentation of an atypical pattern on somatostatin receptor scintigraphy with a risk of false positive interpretation. Case report: 42y-old patient was sent to our department for somatostatin receptor scintigraphy due to a suspicion to neuroendocrine tumor. He experienced a long lasting chronic diarrhea with abdominal pain. He underwent several abdominal surgeries, he had an accident with the liver and spleen laceration with afollowingsplenectomy 13yearsago. Irregularly increased accumulation of a radiopharmaceutical (111In-pen- tetreotide) in the left mesogastrium anteriorly except of physiological accumulation in the liver and kidneys was detected on somatostatin receptor scintigraphy. Small nodules were visible on SPECT/CT images at this location. This patient was evaluated in our department with denaturated erythrocytes due to multiple nodules detected on CT image in the left mesogastrium two months ago; splenic tissue was confirmed in these nodules. Comparing these images with somatostatin receptor scintigraphy, we concluded that atypical location of somatostatin receptors at the left mesogastrium is caused by accumulation of radiopharmaceutical in the splenic tissue in patient after splenectomy with autotransplantation. Conclusion: We present a case of a detection of a splenosis on somatostatin receptor scintigraphy performed in patient evaluated for a suspicion of neuroendocrine tumor. Our case report alerts to a risk of false positive interpretation and points out the necessity of a careful history including a record of splenosis into the medical documentation in a patient with a splenic injury in the past. This can spare such patient unnecessary and potentially riskfuture invasive examination. [ABSTRACT FROM AUTHOR]

ObjectiveThe objective of this study was to evaluate the diagnostic efficacy of Pixon-based reconstruction method on planar somatostatin receptor scintigraphy (SRS).MethodsAll patients with neuroendocrine tumors (NETs) disease who were referred for SRS to our department during 1-year period from January to December 2015 were consecutively included. Three nuclear physicians independently reviewed all the data sets of images which included conventional images (CI; 15 min/view) and processed images (PI) obtained by reconstructing the first 450 s extracted data using Oncoflash® software package. Image analysis using a 3-point rating scale for abnormal uptake of 111 Indium-DTPA-Phe-octreotide in any lesion or organ was interpreted as positive, uncertain, or negative for the evidence of NET disease. A maximum grade uptake of the radiotracer in the lesion was assessed by the Krenning scale method. The results of image interpretation by the two methods were considered significantly discordant when the difference in organ involvement assessment was negative vs. positive or in lesion uptake was ≥2 grades. Agreement between the results of two methods and by different scan observers was evaluated using Cohen κ coefficients.ResultsThere was no significant (p = 0.403) correlation between data acquisition protocol and quality image. The rates of significant discrepancies for exam interpretation and organs involvement assessment were 2.8 and 2.6%, respectively. Mean κ values revealed a good agreement for concordance between CI and PI interpretation without difference of agreement for inter/intra-observer analysis.ConclusionOur results suggest the feasibility to use a Pixon-based reconstruction method for SRS planar images allowing a twofold reduction of acquisition time and without significant alteration of image quality or on image interpretation.