Comparison of hybrid <Superscript>68</Superscript>Ga-PSMA-PET/CT and <Superscript>99m</Superscript>Tc-DPD-SPECT/CT for the detection of bone metastases in prostate cancer patients: <Emphasis Type="Italic">Additional value of morphologic information from low dose CT</Emphasis>

Purpose

This study compared ⁶⁸Gallium-prostate-specific-membrane-antigen based Positron-emission-tomography (⁶⁸Ga-PSMA-PET) and ^99metastabletechnetium-3,3-diphospho-1,2-propanedicarbonacid (^99mTc-DPD-SPECT) in performing skeletal staging in prostate cancer (PC) patients and evaluated the additional value of the information from low-dose-computed tomography (CT).

Materials and Methods

In this retrospective study, 54 patients who received ⁶⁸Ga-PSMA-PET/CT and ^99mTc-DPD-SPECT/CT within 80 days were extracted from our database. Osseous lesions were classified as benign, malignant or equivocal. Lesion, region and patient based analysis was performed with and without CT fusion. The reference standard was generated by defining a best valuable comparator (BVC) containing information from all available data.

Results

In the patient based analysis, accuracies measured as “area-under-the-curve” (AUC) for ⁶⁸Ga-PSMA-PET, ^99mTc-SPECT, ⁶⁸Ga-PSMA-PET/CT and ^99mTc-SPECT/CT were 0.97-0.96, 0.86-0.83, 1.00 and 0.83, respectively (p<0.05) (ranges = optimistic vs. pessimistic view). Region based analysis resulted in the following sensitivities and specificities: 91.8-97.7%, 100-99.5% (PET); 61.2-70.6%, 99.8-98.3% (SPECT); 97.7%, 100% (PET/CT), 69.4% and 98.3% (SPECT/CT) (p<0.05). The amount of correct classifications of equivocal lesions by CT was significantly higher in PET (100%) compared to SPECT (52.4%) (p<0.05).

Conclusion

⁶⁸Ga-PSMA-PET outperforms ^99mTc-DPD-SPECT in detecting bone metastases in PC patients. Additional information from low-dose-CT resulted in a significant reduction in equivocal lesions in both modalities, however ⁶⁸Ga-PSMA-PET benefited most.

Key Points

? Ga-PSMA-PET outperforms ^99m Tc-DPD-SPECT in skeletal staging in prostate cancer patients ? Proportion of equivocal decisions was significantly reduced by CT-fusion in both modalities ? Ga-PSMA-PET benefits more from CT information, compared to ^99m Tc-DPD-SPECT

     

Targeting glucose transport and the NAD pathway in tumor cells with STF-31: a re-evaluation

Background

Targeting glucose metabolism is a promising way to interfere with tumor cell proliferation and survival. However, controversy exists about the specificity of some glucose metabolism targeting anticancer drugs. Especially the potency of STF-31 has been debated. Here, we aimed to assess the impact of the glucose transporter (GLUT) inhibitors fasentin and WZB117, and the nicotinamide phosphoribosyltransferase (NAMPT) inhibitors GMX1778 and STF-31 on tumor cell proliferation and survival, as well as on glucose uptake.

Methods

Tumor-derived A172 (glioblastoma), BHY (oral squamous cell carcinoma), HeLa (cervix adenocarcinoma), HN (head neck cancer), HT-29 (colon carcinoma) and MG-63 (osteosarcoma) cells were treated with fasentin, WZB117, GMX1778 and STF-31. Proliferation rates and cell viabilities were assessed using XTT, crystal violet and LDH assays. mRNA and protein expression of GLUT1 and NAPRT were assessed using qPCR and Western blotting, respectively. The effects of inhibiting compounds on glucose uptake were measured using [¹⁸F]-fluoro-deoxyglucose uptake experiments.

Results

Stimulation of tumor-derived cells with the different inhibitors tested revealed a complex pattern, whereby proliferation inhibiting and survival reducing concentrations varied in [¹⁸F]-fluoro-deoxyglucose uptake experiments more than one order of magnitude among the different cells tested. We found that the effects of GMX1778 and STF-31 could be partially abolished by (i) nicotinic acid (NA) only in nicotinic acid phosphoribosyltransferase (NAPRT) expressing cells and (ii) nicotinamide mononucleotide (NMN) in all cells tested, supporting the classification of these compounds as NAMPT inhibitors. In short-time [¹⁸F]-fluoro-deoxyglucose uptake experiments the application of WZB-117 was found to lead to an almost complete uptake inhibition in all cells tested, whereas the effect of fasentin was found to be cell type dependent with a maximum value of ~35% in A172, BHY, HeLa and HT-29 cells. We also found that STF-31 inhibited glucose uptake in all cells tested in a range of 25–50%. These data support the classification of STF-31 as a GLUT inhibitor.

Conclusions

Our data reveal a dual mode of action of STF-31, serving either as a NAMPT or as a GLUT inhibitor, whereby the latter seems to be apparent only at higher STF-31 concentrations. The molecular basis of such a dual function and its appearance in compounds previously designated as NAMPT-specific inhibitors requires further investigation.

     

Another fatal case related to the recreational abuse of U-47700

The abuse of synthetic opioids has become a major threat in recent years. Several clinical reports and fatal case reports exist discussing life-threatening hypoventilation and fatal respiratory depression following the abuse of trans-3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide (U-47700). The reported concentration of U-47700 in peripheral blood varies between 0.01 μg/mL and 1.46 μg/mL. These values depend on the mode of administration and whether the drug was used in combination with other drugs and/or pharmaceuticals. In the past, U-47700 was predominantly insufflated and not injected. The current study presents a non-targeted liquid chromatography/mass spectrometry (LC/MS)-based screening approach of urine and cerebrospinal fluid samples after intravenous injection of U-47700. Furthermore, quantitative values on U-47700 as obtained by liquid chromatography coupled to a linear ion trap (LC/ESI-QTRAPMS) are presented concerning femoral blood (0.29 μg/mL), urine (0.24 μg/mL), gastric contents (0.57 μg/mL), bile fluid (2.3 μg/mL), heart blood (1.25 μg/mL), liver (9.9 μg/g), cerebrospinal fluid (0.4 μg/mL), and hair (0.14 ng/mg). Thereof, concentrations in hair, gastric contents, bile fluid and cerebrospinal fluid have never been reported before. Drug paraphernalia were also analyzed by liquid chromatography coupled to a diode array detector (LC/DAD) and nuclear magnetic resonance spectrometer (NMR). The analyses show that the powder had a relatively high purity and was adulterated to a low degree. This is the first case report which lists concentration distributions of various specimens after intravenous injection. These findings as well as the U-47700 concentration are important to evaluate autopsy cases of U-47700 intoxication in the future.     

Tumor cell implantation after colonoscopy with biopsies in a patient with rectal cancer

PURPOSE: Colonoscopy with biopsy(ies) is performed in patients with colorectal cancer for diagnosis and screening of synchronous lesions. There is some fear of spreading the disease related to implantation of tumor cells at sites of mucosal damage or to hematogenous or lymphatic spread as a result of tumor manipulation. METHODS: A total colonoscopy including biopsies, performed in a patient because of anal blood loss and tenesmus, revealed a circular, polypoid, ulcerated mass from 1.5 to 12 cm above the anal verge. After preoperative radiotherapy, the patient was subjected to surgical intervention. RESULTS: Histopathology revealed a poorly differentiated rectum adenocarcinoma, staged pT4N1Mx. At approximately 12 cm proximally from the tumor, a biopsy taken through a minute irregularity of the mucosa revealed some granulation tissue with adjacent normal colon mucosa. The basis of this granulation tissue, corresponding to submucosa, contained poorly differentiated tumor elements. CONCLUSIONS: This tiny lesion might have been caused by implantation of exfoliated cancer cells in a biopsy site. It may not be without risk to create excessive biopsy lesions in the presence of a manifestly malignant tumor because of the possibility of tumor cell implantation.     

A prospective,multicentre study on the use of epidermal grafts to optimise outpatient wound management

Current wound management through the use of a split‐thickness skin graft often requires hospital admission, a period of immobility, attentive donor site wound care and pain management. This study evaluates the feasibility of using a novel epidermal graft‐harvesting device (CelluTome) that allows pain‐free epidermal skin grafting in the outpatient clinic setting. A prospective series of 35 patients was performed in 2 centres, involving 10 acute and 25 chronic wounds. All patients were subjected to epidermal grafting in the outpatient specialist clinic, without the use of anaesthesia, and allowed to return home after the procedure. Completely healed wounds were noted in 22 patients (62·9%). The overall mean time for 50% and 100% reduction in wound size was 3·31 ± 2·33 and 5·91 ± 3·48 weeks, respectively. There was no significant difference in healing times between the acute and chronic wounds (50% reduction in wound size; acute 2·20 ± 0·91 weeks versus chronic 3·73 ± 2·63 weeks, P = 0·171. Hundred percent reduction in wound size; acute 4·80 ± 1·61 weeks versus chronic 6·83 ± 4·47 weeks, P = 0·183). The mean time for donor site healing was 5·49 ± 1·48 days. The mean pain score during graft harvest was 1·42 ± 0·95, and the donor site Vancouver Scar Scale was 0 for all cases at 6 weeks. This automated device offers autologous skin harvesting in the outpatient setting with minimal or no pain and a scar free donor site, equally benefiting both the acute and chronic wounds. It has the potential to save NHS resources by eliminating the need for theatre space and a hospital bed while at the same time benefiting patient care.     

If you could see what we see,would it bother you?

Objective

The purpose of our study was to determine whether the anatomic threshold for pelvic organ prolapse (POP) diagnosis and surgical success remains valid when the patient sees what we see on exam.

Methods

Two hundred participants were assigned, by computer-generated block randomization, to see one of four videos. Each video contained the same six clips representative of various degrees of anterior vaginal wall support. Participants were asked questions immediately after each clip. They were asked: “In your opinion, does this patient have a bulge or something falling out that she can see or feel in the vaginal area?” Similarly, they were asked to give their opinion on surgical outcome on a 4-point Likert scale.

Results

The proportion of participants who identified the presence of a vaginal bulge increased substantially at the level of early stage 2 prolapse (1 cm above the hymen), with 67 % answering yes to the question regarding bulge. The proportion of participants who felt that surgical outcome was less desirable also increased substantially at early stage 2 prolapse (1 cm above the hymen), with 52 % describing that outcome as “not at all” or “somewhat” successful.

Conclusion

Early stage 2 POP (1 cm above the hymen) is the anatomic threshold at which women identify both a vaginal bulge and a less desirable surgical outcome when they see what we see on examination.

     

A Novel Approach for Streamlining Delivery of Brief Motivational Interventions to Mandated College Students: Using Group and Individual Sessions Matched to Level of Risk

Background: Mandated college students (those in violation of a campus alcohol policy) are heterogenous with respect to alcohol consumption. Thus, when universities consider required treatment for mandated students, one promising option is to match treatment intensity according to level of alcohol involvement. The present study evaluates such an approach with minimal resources. Methods: Mandated students (N = 285) were required to complete a baseline assessment. Participants identified as high-risk (5+ past month alcohol problems AND 2+ past month heavy drinking episodes) received a one session individual Brief Motivational Intervention (I-BMI) whereas those identified as low-risk (all others) received a one session group Brief Motivational Intervention (G-BMI). I-BMI and G-BMI sessions were delivered by doctoral students in Clinical Psychology. Follow-up assessments were collected 1 month post-intervention (response rate = 73%). Results: The vast majority of students complied with their requirement. Participants assigned to I-BMI reported an 82% reduction in drinks per week, a 58% reduction in heavy episodic drinking, and a 74% reduction in alcohol-related problems at a 1 month follow-up. Participants assigned to G-BMI reported a 61% reduction in drinks per week and a 42% reduction in alcohol-related problems at follow-up relative to baseline. Conclusion/Importance: We demonstrate that matching intervention intensity on baseline alcohol involvement with mandated students is feasible and associated with short-term reductions in alcohol use and consequences. Universities may wish to consider the procedure outlined here as a way of allocating more resources to those who drink at problematic levels.     

Sensitivity ranking for freshwater invertebrates towards hydrocarbon contaminants

Hydrocarbons have an utmost economical importance but may also cause substantial ecological impacts due to accidents or inadequate transportation and use. Currently, freshwater biomonitoring methods lack an indicator that can unequivocally reflect the impacts caused by hydrocarbons while being independent from effects of other stressors. The aim of the present study was to develop a sensitivity ranking for freshwater invertebrates towards hydrocarbon contaminants, which can be used in hydrocarbon-specific bioindicators. We employed the Relative Sensitivity method and developed the sensitivity ranking S _hydrocarbons based on literature ecotoxicological data supplemented with rapid and mesocosm test results. A first validation of the sensitivity ranking based on an earlier field study has been conducted and revealed the S _hydrocarbons ranking to be promising for application in sensitivity based indicators. Thus, the first results indicate that the ranking can serve as the core component of future hydrocarbon-specific and sensitivity trait based bioindicators.