The prevention of adverse pregnancy outcomes by periodontal treatment during pregnancy (PROBE) intervention study-A controlled intervention study: Protocol paper.

INTRODUCTION: Pregnancy increases the risk of periodontitis due to the increase in progesterone and estrogen. Moreover, periodontitis during pregnancy is associated with development of pregnancy and birth related complications. The aim of this study is to determine, whether periodontal treatment during pregnancy can reduce systemic inflammation and lower the risk of adverse pregnancy and birth related outcomes. METHODS AND ANALYSIS: The PROBE study is a non-randomized controlled intervention study conducted among 600 pregnant women with periodontitis. The women will be recruited among all pregnant women at two Danish hospitals in Region Zealand during their nuchal translucency scan and will subsequently be screened for periodontitis. The intervention group includes 300 pregnant women, who will be offered state-of-the-art periodontal treatment during pregnancy. The control group includes additional 300 pregnant women, who will be offered periodontal treatment after giving birth. Outcome measures include periodontal measures, inflammatory, hormonal and glycaemic markers as well as the prevalence of preterm birth risk, low birth weight and risk markers of gestational diabetes mellitus (GDM) and preeclampsia that will be collected from all screened women and further during pregnancy week 20 and pregnancy week 35 for women enrolled in the intervention. ETHICS AND DISSEMINATION: The study's findings will be published in peer reviewed journals and disseminated at national and international conferences and through social media. The PROBE study is designed to provide important new knowledge as to whether periodontal treatment during pregnancy can reduce the prevalence of complications related to pregnancy and birth. CLINICAL TRIALS REGISTRATION: The study was registered on clinicaltrials.gov (NCT06110143).

Preoperative localization of water clear cell giant parathyroid adenoma: A case report.

Primary hyperparathyroidism commonly results from a solitary parathyroid adenoma. A water clear cell parathyroid adenoma represents a rare histological variant. This report presents the challenges of preoperative detection of a giant parathyroid adenoma, which was of the water clear cell variant. A case of severe hypercalcemia in a patient without clinical symptoms and equivocal findings on standard imaging modalities, in which the use of [11C]C-Methionine PET/CT facilitated the preoperative detection of a giant parathyroid adenoma. Histopathological examination confirmed the diagnosis of a water clear cell giant parathyroid adenoma following surgical excision. These findings highlight the significance of advanced imaging techniques in the detection and management of a rare form of parathyroid adenoma.

Loneliness and the risk of type 2 diabetes.

INTRODUCTION: The incidence of type 2 diabetes is increasing globally. Recent research suggests that loneliness could be a potential risk factor for the development of type 2 diabetes. We aimed to investigate the association between loneliness and type 2 diabetes and the modifying effect of mental disorders. RESEARCH DESIGN AND METHODS: We conducted a prospective study including 465 290 adults (aged ≥16 years) who participated in either the Danish Health and Morbidity Survey or the Danish National Health Survey between 2000 and 2017. Loneliness was based on self-report, while type 2 diabetes was measured using an algorithm combining several health registers including type 2 diabetes patients treated both within the hospital sector and general practice. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During a mean follow-up time of 6.3 years, 13 771 individuals (3%) developed type 2 diabetes. Feeling lonely once in a while was associated with a 14% increased risk of type 2 diabetes (95% CI 1.09 to 1.20), while feeling lonely often was associated with a 24% increased risk (95% CI 1.14 to 1.34), independent of sociodemographic factors and body mass index. The association was stronger among individuals without a mental disorder (HR 1.21, 95% CI 1.10 to 1.34 among those feeling lonely often) compared with those with a mental disorder (HR 1.07, 95% CI 0.93 to 1.23). CONCLUSIONS: Loneliness independently increased the risk of type 2 diabetes. The effect was more pronounced in individuals without a mental disorder, as having a mental disorder itself likely increases the risk of type 2 diabetes. These findings emphasize the importance of addressing loneliness as a modifiable risk factor in preventing type 2 diabetes.

The Fusion Clinic: Integrating the care of people with severe mental illness and diabetes.

AIM: People with coexisting severe mental illness (SMI) and type 2 diabetes have a shorter life expectancy and poorer diabetes outcomes than those without SMI. This is partly explained by the separate treatment of diabetes and SMI, which occurs in parallel silos in many healthcare systems. The Steno Diabetes Center Sjaelland and Region Zealand established the Fusion Clinic to offer combined psychiatric and diabetes care delivered by both diabetes and mental healthcare professionals. This study describes how the clinic was established and the initial diabetes outcomes. METHODS: The Fusion Clinic was co-designed by people with diabetes and SMI and healthcare professionals to improve the care of adults with diabetes and SMI. The clinic approach utilised the F-ACT model. The 63 people referred to the Fusion Clinic between 01.02.2020 and 01.01.2022 who attended the clinic for more than 6 months were included in this study. Diabetes outcomes were recorded in the electronic medical records (Sundhedsplatformen EPIC). RESULTS: There was a high prevalence of diabetes complications at baseline. Furthermore, 70% had one or more additional concomitant diseases, as well as SMI and diabetes. Assessment of diabetes complications and measurements of HbA1c and lipid profile improved after referral to the clinic. HbA1c declined during the first 6 months of attendance at the clinic. CONCLUSIONS: This model of service delivery has the potential to improve the quality of care for people with SMI and type 2 diabetes.

Diabetic complications and risk of depression and anxiety among adults with type 2 diabetes.

AIMS: To investigate if diabetic complications increase the risk of depression and/or anxiety among adults with type 2 diabetes. METHODS: This register-based, prospective study included 265,799 adult individuals diagnosed with type 2 diabetes between 1997 and 2017 without a recent history of depression or anxiety. Diabetic complications included cardiovascular disease, amputation of lower extremities, neuropathy, nephropathy and retinopathy. Both diabetic complications and depression and anxiety were defined by hospital contacts and prescription-based medication. All individuals were followed from the date of type 2 diabetes diagnosis until the date of incident depression or anxiety, emigration, death or 31 December 2018, whichever occurred first. RESULTS: The total risk time was 1,915,390 person-years. The incidence rate of depression and/or anxiety was 3368 per 100,000 person-years among individuals with diabetic complications and 1929 per 100,000 person-years among those without. Having or developing any diabetic complication was associated with an increased risk of depression and/or anxiety (HR 1.77, 95% CI 1.73-1.80). The risk for depression and/or anxiety was increased for all types of diabetic complications. The strongest association was found for amputation of lower extremities (HR 2.16, 95% CI 2.01-2.31) and the weakest for retinopathy (HR 1.13, 95% CI 1.09-1.17). CONCLUSION: Individuals with type 2 diabetes and diabetic complications are at increased risk of depression and anxiety. This points towards the importance of an increased clinical focus on mental well-being among individuals with type 2 diabetes and complications.

[18F]FDOPA PET/CT is superior to [68Ga]DOTATOC PET/CT in diagnostic imaging of pheochromocytoma.

BACKGROUND: Both [18F]FDOPA (FDOPA) and [68Ga]DOTATOC PET/CT (DOTATOC) are widely used for detection of pheochromocytomas/paraganglioma (PPGL). However, direct comparisons of the performance of the two tracers are only available in small series. We conducted a retrospective comparative analysis of FDOPA and DOTATOC to assess their sensitivity and accuracy in detecting PPGL when administered based on suspicion of PPGL. We consecutively included patients referred on suspicion of PPGL or PPGL recurrence who were scanned with both FDOPA and DOTATOC. Both scans were reviewed retrospectively by two experienced observers, who were blinded to the final diagnosis. The assessment was made both visually and quantitatively. The final diagnosis was primarily based on pathology. RESULTS: In total, 113 patients were included (97 suspected of primary PPGL and 16 suspected of recurrence). Of the 97 patients, 51 had pheochromocytomas (PCC) (in total 55 lesions) and 6 had paragangliomas (PGL) (in total 7 lesions). FDOPA detected and correctly localized all 55 PCC, while DOTATOC only detected 25 (sensitivity 100% vs. 49%, p < 0.0001; specificity 95% vs. 98%, p = 1.00). The negative predictive value (100% vs. 63%, p < 0.001) and diagnostic accuracy (98% vs. 70%, p < 0.01) were higher for FDOPA compared to DOTATOC. FDOPA identified 6 of 6 patients with hormone producing PGL, of which one was negative on DOTATOC. Diagnostic performances of FDOPA and DOTATOC were similar in the 16 patients with previous PPGL suspected of recurrence. CONCLUSIONS: FDOPA is superior to DOTATOC for localization of PCC. In contrast to DOTATOC, FDOPA also identified all PGL but with a limited number of patient cases.

Men's Experiences With Managing Type 2 Diabetes and Their Encounters With Health Professionals: A Scoping Review.

Type 2 diabetes is on the rise globally, and previous research has identified gender as one known risk factor for developing this disease. Gender has also been reported to affect patients' experiences of managing type 2 diabetes. However, little is known of men's specific experiences with type 2 diabetes, as research with a gendered focus has concentrated more on women's experiences with the disease. This scoping review explores how research has addressed men's experiences of managing type 2 diabetes and their encounters with health professionals. The review consists of an iterative process, involving six steps: identification of the research questions, identification of relevant studies, study selection, charting the data, collating and summarizing results, and consultation with external stakeholders. Through the process, 28 publications were identified, which indicate a gap in research on patients' experiences with type 2 diabetes. The majority of the identified studies focuses on men from an ethnic minority due to their poorer health outcomes. However, a knowledge gap regarding men belonging to an ethnic or racial majority warrants further attention, as studies indicate that men who share similar social economic status face similar barriers to improving the management of type 2 diabetes. There is little discussion of how the gendered dynamics in encounters between patients and health professionals affect the management of type 2 diabetes. This review suggests a need for further research that explores how practices of masculinities, that is, the normative practices guiding men's behavior, intersect with men's experiences with type 2 diabetes in a broader perspective.

Early acquisition of [18F]FDOPA PET/CT imaging in patients with recurrent or residual medullary thyroid cancer is safe-and slightly better!

PURPOSE: The aim of this study was to compare early (15 min) and late (60 min) [18F]FDOPA PET/CT acquisition times in the detection of recurrence/residual disease in medullary thyroid cancer (MTC) patients. MATERIALS AND METHODS: Thirty-two dual-phase [18F]FDOPA PET scans were retrospectively reviewed. Scan indications were (1) suspected recurrence of MTC, (2) treatment monitoring, or (3) restaging. In four scans, no final verification could be obtained, and one scan was excluded due to non-consistency with the acquisition protocol. Images were analyzed visually and semiquantitatively (using SUVmax). On both per-scan and per-lesion basis, early (median time 15 min) and late (median time 60 min) acquisition were compared by number and SUVmax of detected MTC lesions, and a washout rate between the two acquisitions was calculated. Sensitivity and specificity of early and late acquisition were also compared. RESULTS: Out of the 27 eligible PET scans, twenty were classified as PET positive and 7 as PET negative. By subsequent histology and/or combination of imaging and clinical data during follow-up, the MTC diagnosis was verified, showing a scan-based sensitivity and specificity of 100% and 87.5%, respectively, for the early acquisition, and for the late acquisition both were 100%. However, there were no statistically significant difference in detection rate between the two acquisitions. Lesions on the early acquisition were significantly more intense compared to lesions on the late acquisition (median washout rate of - 33% (- 57 to + 50%)). CONCLUSION: Our study confirms that it is safe to omit the late [18F]FDOPA PET/CT acquisition in the detection of recurrent/residual MTC.

What do persons with diabetes want from community pharmacies? A qualitative study.

Background: Diabetes is a demanding disease with a complex treatment regimen. Many persons with diabetes have difficulty managing their disease and taking medication as prescribed, possibly because they lack knowledge and sometimes misinterpret medical benefits. Community pharmacies continuously provide professional counselling to persons with diabetes. Objective: This study aimed to explore 1) which services adults with type 1 and type 2 diabetes want from community pharmacies and 2) how pharmacies can meet these wishes. Methods: A qualitative, explorative study design using focus group interviews was chosen. Informants were recruited from Region Zealand in Denmark. Data were digitally recorded, transcribed verbatim and analyzed by means of thematic analysis. Results: Thirteen adults (11 female) with the mean age of 66.2 years (range 49-81 years) participated in one physical (n=6) or one online (n=7) focus group interview. Ten had type 2 diabetes, three had type 1 diabetes. The average duration of participants' diabetes was 13.4 years (range 2.3-33.0 years). The analysis revealed three overall themes of the functions which the informants would like community pharmacies to fulfil: 1) raise awareness of pharmacies' counselling service and competences; 2) act as a dialogue partner; 3) be a source of information and guidance about local activities and support. Conclusion: The informants did not regard community pharmacies as a natural part of the healthcare system or as a place where they would expect counselling. They would like the community pharmacy to make their medical competences and services obvious and the community pharmacy staff to act as a dialogue partner and provide competent counselling. The informants would like to have a contact person with diabetes competences with whom they can book an appointment to complement over-the-counter counselling. They experience a gap in their care between routine visits in the healthcare system and suggest that community pharmacies counselling services become a natural supplement and that healthcare professionals in the primary and secondary sectors inform patients about the services - especially for patients newly diagnosed with diabetes. Finally, they would like a formal collaboration between diabetes associations and community pharmacies to make their competences, services and information visible.

What do persons with diabetes want from community pharmacies? A qualitative study

Background: Diabetes is a demanding disease with a complex treatment regimen. Many persons with diabetes have difficulty managing their disease and taking medication as prescribed, possibly because they lack knowledge and sometimes misinterpret medical benefits. Community pharmacies continuously provide professional counselling to persons with diabetes. Objective: This study aimed to explore 1) which services adults with type 1 and type 2 diabetes want from community pharmacies and 2) how pharmacies can meet these wishes. Methods: A qualitative, explorative study design using focus group interviews was chosen. Informants were recruited from Region Zealand in Denmark. Data were digitally recorded, transcribed verbatim and analyzed by means of thematic analysis. Results: Thirteen adults (11 female) with the mean age of 66.2 years (range 49–81 years) participated in one physical (n=6) or one online (n=7) focus group interview. Ten had type 2 diabetes, three had type 1 diabetes. The average duration of participants’ diabetes was 13.4 years (range 2.3–33.0 years). The analysis revealed three overall themes of the functions which the informants would like community pharmacies to fulfil: 1) raise awareness of pharmacies’ counselling service and competences; 2) act as a dialogue partner; 3) be a source of information and guidance about local activities and support. (AU)

PSMA-Positive Low Malignant Gastrointestinal Stromal Tumor in the Stomach on F-18-PSMA-1007 PET/CT.

A 76-year-old man with newly diagnosed high-risk prostate cancer was referred for primary staging with F-18-PSMA-1007 PET/CT. The PET/CT scan showed no lymph node or bone metastases, only localized disease within the prostate gland. Additionally, the F-18-PSMA PET/CT scan showed a PSMA-positive lesion correlating to a polyp located in the body of the stomach on the greater curvature. A prior F-18-FDG PET/CT showed low FDG uptake in the polyp, but this was not reported initially in the written report. The patient had no upper gastrointestinal symptoms. A gastroscopy with biopsies was performed, and the histopathology results showed chronic unspecific inflammation with no granulomas, dysplastic or malignant changes in three out of three biopsies. A repeated gastroscopy with biopsy showed an epithelioid variant of a gastrointestinal stromal tumor (Ki-67 index 2%). A laparoscopic tumor extirpation was planned after radiation treatment in combination with endocrine therapy of the localized prostate cancer. To our knowledge, this is one of very few reported cases of a PSMA-positive gastrointestinal stromal tumor (GIST), and can be added to the list of malignant pitfalls of PSMA PET/CT in prostate cancer patients.

C-11 methionine positron emission tomography scans improve the preoperative localization of pathologic parathyroid glands in primary hyperparathyroidism.

BACKGROUND AND OBJECTIVE: Preoperative localization of pathologic parathyroid glands is essential in the preparation of a parathyroidectomy. We evaluated the use of a C-11 methionine positron emission tomography/computed tomography scan in a 7-year period in selected patients with primary hyperparathyroidism. The indications to perform a C-11 methionine positron emission tomography/computed tomography were either persistent primary hyperparathyroidism after parathyroidectomy or inconclusive preoperative localization on ultrasound and sestaMIBI. METHODS: A group of 36 patients was referred for a C-11 methionine positron emission tomography/computed tomography. Biochemical data, pathology, and results of sestaMIBI were collected retrospectively. The primary hyperparathyroidism patients were divided into two groups. In group 1 (N = 17), the C-11 methionine positron emission tomography/computed tomography was performed before parathyroidectomy. In group 2 (N = 19), the C-11 methionine positron emission tomography/computed tomography was performed after unsuccessful parathyroidectomy and before a reoperation. RESULTS: Overall, in 30 of the 36 patients (83%), C-11 methionine positron emission tomography/computed tomography identified a true-positive pathologic parathyroid gland confirmed by an experienced pathologist, consistent with a positive predictive value of 91%. In group 1, 94% of the patients (N = 16) had pathologic parathyroid tissue identified by C-11 methionine positron emission tomography/computed tomography. This resulted in a clinical benefit in 13 patients (76%). In group 2, the benefit was slightly lower, as 74% of the patients (N = 14) had a true-positive C-11 methionine positron emission tomography/computed tomography scan resulting in a clinical benefit in nine patients (47%). CONCLUSIONS: In two selected groups of patients planned for an initial operation or reoperation of primary hyperparathyroidism and inconclusive conventional imaging, we found C-11 methionine positron emission tomography/computed tomography to give parathyroid surgeons a clinical benefit in the majority of cases, electing the patients for unilateral surgery.

A Randomized, Factorial Phase II Study to Determine the Optimal Dosing Regimen for 68Ga-Satoreotide Trizoxetan as an Imaging Agent in Patients with Gastroenteropancreatic Neuroendocrine Tumors.

68Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist associated with high sensitivity and reproducibility in neuroendocrine tumor (NET) detection and localization. However, the optimal peptide mass and radioactivity ranges for 68Ga-satoreotide trizoxetan have not yet been established. We therefore aimed to determine its optimal dosing regimen in patients with metastatic gastroenteropancreatic NETs in a prospective, randomized, 2 × 3 factorial, multicenter phase II study. Methods: Patients received 68Ga-satoreotide trizoxetan at a peptide mass of 5-20 µg on day 1 of the study and of 30-45 µg on days 16-22, at 1 of 3 68Ga radioactivity ranges (40-80, 100-140, or 160-200 MBq). Whole-body PET/CT imaging was performed 50-70 min after each injection. The primary endpoint was the detection rate of NET lesions imaged by 68Ga-satoreotide trizoxetan relative to contrast-enhanced CT (for each of the 6 peptide mass and radioactivity range combinations). Results: Twenty-four patients were evaluated in the per-protocol analysis. The median number of lesions detected by 68Ga-satoreotide trizoxetan PET/CT or PET alone was at least twice as high as the number detected by contrast-enhanced CT across the 6 studied peptide mass and radioactivity range combinations. There were no differences between the 2 peptide mass ranges or between the 3 radioactivity ranges in the number of identified lesions. However, a trend toward a lower relative lesion count was noted in the liver for the 40- to 80-MBq range. No relationship was observed between the radioactivity range per patient's body weight (MBq/kg) and the number of lesions detected by 68Ga-satoreotide trizoxetan. The median diagnostic sensitivity of 68Ga-satoreotide trizoxetan PET/CT, based on the number of lesions per patient, ranged from 85% to 87% across the different peptide mass and radioactivity ranges. Almost all reported adverse events were mild and self-limiting. Conclusion: A radioactivity of 100-200 MBq with a peptide mass of up to 50 µg was confirmed as the optimal dosing regimen for 68Ga-satoreotide trizoxetan to be used in future phase III studies.

Practical kidney dosimetry in peptide receptor radionuclide therapy using [177Lu]Lu-DOTATOC and [177Lu]Lu-DOTATATE with focus on uncertainty estimates.

BACKGROUND: Kidney dosimetry after peptide receptor radionuclide therapy using 177Lu-labelled somatostatin analogues is a procedure with multiple steps. We present the SPECT/CT-based implementation at Aarhus University Hospital and evaluate the uncertainty of the various steps in order to estimate the total uncertainty and to identify the major sources of uncertainty. Absorbed dose data from 115 treatment fractions are reported. RESULTS: The total absorbed dose with uncertainty is presented for 59 treatments with [177Lu]Lu-DOTATOC and 56 treatments with [177Lu]Lu-DOTATATE. For [177Lu]Lu-DOTATOC the mean and median specific absorbed dose (dose per injected activity) is 0.37 Gy/GBq and 0.38 Gy/GBq, respectively, while for [177Lu]Lu-DOTATATE the median and mean are 0.47 Gy/GBq and 0.46 Gy/GBq, respectively. The uncertainty of the procedure is estimated to be about 13% for a single treatment fraction, where the absorbed dose calculation is based on three SPECT/CT scans 1, 4 and 7 days post-injection, while it increases to about 19% if only a single SPECT/CT scan is performed 1 day post-injection. CONCLUSIONS: The specific absorbed dose values obtained with the described procedure are comparable to those from other treatment sites for both [177Lu]Lu-DOTATOC and [177Lu]Lu-DOTATATE, but towards the lower end of the range of reported values. The estimated uncertainty is also comparable to that from other reports and judged acceptable for clinical and research use, thus proving the kidney dosimetry procedure a useful tool. The greatest reduction in uncertainty can be obtained by improved activity determination, partial volume correction and additional SPECT/CT scans.

A novel read methodology to evaluate the optimal dose of 68Ga-satoreotide trizoxetan as a PET imaging agent in patients with gastroenteropancreatic neuroendocrine tumours: a phase II clinical trial.

BACKGROUND: 68Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist exhibiting higher tumour-to-background ratios and sensitivity compared to 68Ga-DOTATOC. This randomised, 2 × 3 factorial, phase II study aimed to confirm the optimal peptide mass and radioactivity ranges for 68Ga-satoreotide trizoxetan, using binary visual reading. To that end, 24 patients with metastatic gastroenteropancreatic neuroendocrine tumours received 5-20 µg of 68Ga-satoreotide trizoxetan on day 1 of the study and 30-45 µg on day 16-22, with one of three gallium-68  radioactivity ranges (40-80, 100-140, or 160-200 MBq) per visit. Two 68Ga-satoreotide trizoxetan PET/CT scans were acquired from each patient post-injection, and were scored by experienced independent blinded readers using a binary system (0 for non-optimal image quality and 1 for optimal image quality). For each patient pair of 68Ga-satoreotide trizoxetan scans, one or both images could score 1. RESULTS: Total image quality score for 68Ga-satoreotide trizoxetan PET scans was lower in the 40-80 MBq radioactivity range (56.3%) compared to 100-140 MBq (90.6%) and 160-200 MBq (81.3%). Both qualitative and semi-quantitative analysis showed that peptide mass (5-20 or 30-45 µg) did not influence 68Ga-satoreotide trizoxetan imaging. There was only one reading where readers diverged on scoring; one reader preferred one image because of higher lesion conspicuity, and the other reader preferred the alternative image because of the ability to identify more lesions. CONCLUSIONS: Binary visual reading, which was associated with a low inter-reader variability, has further supported that the optimal administered radioactivity of 68Ga-satoreotide trizoxetan was 100-200 MBq with a peptide mass up to 50 µg. Trial registration ClinicalTrials.gov, NCT03220217. Registered 18 July 2017, https://clinicaltrials.gov/ct2/show/NCT03220217.

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

What is the risk of prostate cancer mortality following negative systematic TRUS-guided biopsies? A systematic review.

OBJECTIVE: To investigate the risk of prostate cancer-specific mortality (PCSM) following initial negative systematic transrectal ultrasound-guided (TRUS) prostate biopsies. DESIGN: Systematic review. DATA SOURCES: PubMed and Embase were searched using a string combination with keywords/Medical Subject Headings terms and free text in the search builder. Date of search was 13 April 2020. STUDY SELECTION: Studies addressing PCSM following initial negative TRUS biopsies. Randomised controlled trials and population-based studies including men with initial negative TRUS biopsies reported in English from 1990 until present were included. DATA EXTRACTION: Data extraction was done using a predefined form by two authors independently and compared with confirm data; risk of bias was assessed using the Newcastle-Ottawa Scale for cohort studies when applicable. RESULTS: Four eligible studies were identified. Outcomes were reported differently in the studies as both cumulative incidence and Kaplan-Meier estimates have been used. Regardless of the study differences, all studies reported low estimated incidence of PCSM of 1.8%-5.2% in men with negative TRUS biopsies during the following 10-20 years. Main limitation in all studies was limited follow-up. CONCLUSION: Only a few studies have investigated the risk of PCSM following initial negative biopsies and all studies included patients before the era of MRI of the prostate. However, the studies point to the fact that the risk of PCSM is low following initial negative TRUS biopsies, and that the level of prostate-specific antigen before biopsies holds prognostic information. This may be considered when advising patients about the need for further diagnostic evaluation. PROSPERO REGISTRATION NUMBER: CRD42019134548.

Extravasation of [177Lu]Lu-DOTATOC: case report and discussion.

BACKGROUND: In the case of extravasation of radioactive drugs used in peptide-receptor radionuclide therapy of neuroendocrine tumors, or in radionuclide therapy in general, rapid action is important to reduce or avoid complications. The literature on extravasation of drugs for radionuclide therapy is sparse. Based on the present case, we discuss handling and consequences of extravasation. Further, we demonstrate that dosimetry can aid in judging if the treatment of neuroendocrine tumors is satisfactory even after extravasation. CASE PRESENTATION: A case of extravasation of [177Lu]Lu-DOTATOC with a treatment strategy involving exercise and elevation of the affected arm and application of a compression bandage and heating is reported. Redistribution of the drug is verified and quantified by whole-body imaging and quantitative SPECT/CT and measurements of the dose rate at contact with the injection site. [177Lu]Lu-DOTATOC was redistributed to tumors and organs within 1 day. The patient did not report any discomfort during or after hospitalization, and no side effects related to extravasation were observed. Quantitative SPECT/CT scans at the subsequent treatment cycle of the same patient were analyzed for a comparison between the treatments. Dosimetry showed the treatments were similar with respect to the kidney and tumor absorbed doses. The radiation dose to the epidermal basal layer near the injection site was estimated and found to be consistent with the lack of side effects. CONCLUSIONS: The treatment of extravasation was successful, and the redistribution of the drug can be easily verified through measurement of the dose rate at contact with the skin. From the results of dosimetry, it was assessed that no change of the treatment course was necessary to compensate for a possibly incomplete treatment as a result of the extravasation.

68Ga-Prostate-Specific Membrane Antigen Uptake in a Pancreatic Neuroendocrine Tumor.

We present a 60-year-old man with known prostate cancer treated with robot-assisted radical prostatectomy. Prostate-specific antigen levels did not decline accordingly, and a second Ga-PSMA PET/CT demonstrated a new focus with high Ga-PSMA uptake in the pancreatic tail. A subsequent CT scan did not display the lesion as a typical pancreatic tumor, and a spleen scintigraphy was also negative excluding an ectopic intrapancreatic accessory spleen. Ga-DOTATOC PET/CT showed uptake in the same area of the pancreatic tail consistent with a neuroendocrine tumor. This case illustrates that neuroendocrine tumors can be important pitfalls in Ga-PSMA PET/CT performed in prostate cancer patients.