The role of Ga68 PSMA PET/CT imaging in Lu177 PSMA treatment planning in metastatic castration-resistant prostate cancer.

OBJECTIVE: Lutetium-177 (Lu177) prostate-specific membrane antigen (Lu177 PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (CRPC). The purpose of the study was to determine the molecular volumetric Gallium-68 (Ga68) PSMA PET/CT parameters that can predict patients who will respond to treatment. METHODS: These single-center retrospective data were obtained from metastatic CRPC patients receiving intravenous 6.0-8.5 GBq Lu177 PSMA treatment every 6-8 weeks for a maximum of 3-8 cycles, with baseline Ga68 PSMA PET/CT scan, clinical data, and information on treatment responses. All lesions were divided into two groups according to the increase and decrease in PSMA expression levels of 600 bone lesions and 85 lymph nodes that were compatible with metastasis of 23 patients after the treatment. The primary endpoint of our study was the evaluation of the relation between the baseline SUVmax, PSMA TV, TL PSMA values, and the treatment response of the two groups. The threshold values were determined for the parameters that had significant relations. In the present study, the prostate-specific antigen (PSA) response and treatment-induced toxicities were also evaluated as the secondary endpoint. RESULTS: It was found that SUVmax, PSMA TV, and TL PSMA values in bone metastases showed significant differences between the groups with decreased and increased PSMA expression levels after the treatment. The AUC value for SUVmax was significant (AUC = 0.677; p < 0.001). The cutoff value was > 10.50 (sensitivity = 91.8%, Specificity = 41.5%) for SUVmax, > 1.50 cm3 (sensitivity = 49.1%, specificity = 70%) for PSMA TV and > 8.50 g (sensitivity = %60.9, specificity = %72.2) for TL PSMA. The median SUVmax value before the treatment in all metastatic lymph nodes was found to be 7.1 (5.4-12.4), and the median SUVmax after the treatment was 2.5 (1.6-12.1) (p < 0.001). CONCLUSION: It was shown in the present study that Lu177 PSMA treatment response may be higher in CRPC patients with metastatic bone lesion with high baseline PSMA expression level, and better treatment response may be achieved in patients with lymph node metastases than in bone metastases.

Prognostic value of metabolic tumor volume and total lesion glycolysis assessed by 18F-FDG PET/CT in endometrial cancer.

OBJECTIVE: Surgical staging is the most confidential method for prognosis prediction. However, in which stage the surgery is needed and the treatment management of these patients is controversial. Presentation of new determinant factors with imaging methods for prediction of poor prognosis can provide better disease management. The aim of our study was to demonstrate the ability of metabolic tumor volume and total lesion glycolysis as a prognostic factor to predict the disease-free survival time, necessity of adjuvant radiotherapy-chemotherapy, and the association of these parameters with the clinicopathological features. METHODS: Forty-four endometrial cancer diagnosed patients whose PET/CT scans were performed for treatment planning were included in our study. Metabolic parameters (SUVmax, metabolic tumor volume, total lesion glycolysis) of the primary tumor were calculated. Abdominal hysterectomy was performed for all patients. Histopathologic findings were noted. Patients were followed for 31.4 ± 14.8 months. RESULTS: Metabolic tumor volume and total lesion glycolysis were significant prognostic factors for disease-free survival, whereas SUVmax did not effect disease-free survival. According to regression analysis, only metabolic tumor volume was found significant for radiotherapy planning (cutoff metabolic tumor volume; 26.30 ml). There was significant association between metabolic tumor volume, total lesion glycolysis and early-stage, myometrial invasion, and lymph node positivity. We observed only weak association between SUVmax and myometrial invasion. ROC curve calculated metabolic tumor volume and total lesion glycolysis cutoff values as 19.6 ml and 90 g for early-stage, 14.3 ml and 173.4 g for myometrial invasion, and 29.7 ml and 283.1 g for lymph node positivity, respectively. CONCLUSION: Metabolic tumor volume and total lesion glycolysis may be used as prognostic factors for endometrial cancer. The association between SUVmax and clinical findings, disease-free survival, histopathological features are weak. Further studies are needed for demonstrating the prognostic value of metabolic volumetric parameters.

Self-assembled materials and supramolecular chemistry within microfluidic environments: from common thermodynamic states to non-equilibrium structures.

Self-assembly is a crucial component in the bottom-up fabrication of hierarchical supramolecular structures and advanced functional materials. Control has traditionally relied on the use of encoded building blocks bearing suitable moieties for recognition and interaction, with targeting of the thermodynamic equilibrium state. On the other hand, nature leverages the control of reaction-diffusion processes to create hierarchically organized materials with surprisingly complex biological functions. Indeed, under non-equilibrium conditions (kinetic control), the spatio-temporal command of chemical gradients and reactant mixing during self-assembly (the creation of non-uniform chemical environments for example) can strongly affect the outcome of the self-assembly process. This directly enables a precise control over material properties and functions. In this tutorial review, we show how the unique physical conditions offered by microfluidic technologies can be advantageously used to control the self-assembly of materials and of supramolecular aggregates in solution, making possible the isolation of intermediate states and unprecedented non-equilibrium structures, as well as the emergence of novel functions. Selected examples from the literature will be used to confirm that microfluidic devices are an invaluable toolbox technology for unveiling, understanding and steering self-assembly pathways to desired structures, properties and functions, as well as advanced processing tools for device fabrication and integration.

Intra-observer and inter-observer reliability of leg circumference measurement among six observers: a single blinded randomized trial.

Hypothesis: Circumference measurement of extremities that was reported to be a reliable method as long as being standardized is commonly used both in clinical and home settings by clinicians or caregivers due to its cheapness and easy use. Objectives: The aims of this study were to determine the inter-observer and intra-observer reliability of manual circumference measurement among different observers and various measurement points. Methods and Results: A total of 58 lower limbs were included in the study. Both lower limbs of each subject were assessed by 6 observers randomly using circumference measurement method from 9 reference points specified with a Leg-O-Meter. All observers performed the measurements and they were blind to each other's measurements. Results: Measurement results from reference points were statistically significant between good to perfect (ICC 0.65-0.99, p<0.001). Interrater reliability of all observers' first and second measurements showed perfect reliability for both measurements (ICC: 0.92-0.99, p<0.001). Conclusions: This study demonstrated that the lower extremity manual circumference measurement is a reliable method for clinical practice. Abbreviations: BMI = Body Mass Index, ICC = Intraclass Correlation Coefficient, Metatarsal heads (cA), Ankle-heel (cY), Ankle (cB), Distal beginning point of gastrocnemius (cB1), The widest point for gastrocnemius (cC), Head of fibula (cD), Midline of knee (cE), Midline of thigh (cF), Groin level (cG).

Granulosa cell tumor and concurrent endometrial cancer with (18)F-FDG uptake.

The findings and the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for the diagnosis of ovarian granulosa cell tumor (OG) are described. We present the pre-operative findings of (18)F-FDG PET/CT scan of a case of OG concurrent with endometrium cancer and endometrial hyperplasia, which revealed a 48mm mass demonstrating mild increased metabolic activity on the right ovary. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. Frozen and paraffin-enbeded sections showed an encapsulated OG. There were few mitoses. There was concurrent atypical endometrial hyperplasia. In conclusion, we reported a case of an encapsulated OG, which showed mild uptake of the (18)F-FDG with concurrent endometrial cancer. There has been only one report of (18)F-FDG findings in primary ovarian granulosa cell tumor, similar to ours.

Efficacy of preincisional levobupivacaine for adult tonsillectomy patients.

PROBLEM/OBJECTIVE: We compared the effects of preincisional peritonsillar infiltration of 5 ml levobupivacaine hydrochloride (50 mg/10 ml) on bleeding during surgery and pain after tonsillectomy in patients aged 16 years or older. METHODOLOGY: The study was conducted in 44 adult patients who underwent tonsillectomy. These patients were randomized to either the study group (SG) who received levobupivacaine infiltration to the peritonsillary fossae prior to surgery, or a control group (CG) treated with 0.9% sodium chloride infiltration to the peritonsillary fossae prior to incision. The volume of intraoperative bleeding was recorded. Pain was evaluated using a visual analogue scale (VAS). The first pain score was assessed immediately after arriving in the postoperative care unit. VAS scores were subsequently re-assessed 2, 4, 8, 12, and 24 hours postoperatively. The first analgesic requirement was assessed 24 hours postoperatively. RESULTS: The pain relieving effect in the levobupivacaine group was statistically significant 2, 4, 12, and 24 hours postoperatively (p ≤ 0.05), but there was no difference in VAS scores between groups at the first and 8-hour postoperative assessments. There were no differences between the two groups regarding analgesic requirements. The difference between the mean intraoperative blood loss in the SG and CG was statistically significant (p ≤ 0.05). No serious complications were observed in either group. CONCLUSION: Preincisional levobupivacaine infiltration seems to be a safe and easily applied medication for postoperative pain control, and decreased the volume of intraoperative blood loss in adult patients after tonsillectomy.

Different findings in Tc-99m MDP bone scintigraphy of patients with sickle cell disease: report of three cases.

OBJECTIVE: Sickle cell anemia is an inherited disorder caused by abnormal hemoglobin, the S hemoglobin. Although vaso-occlusive crises can occur virtually in any organ, they are particularly common in the bony skeleton of affected patients. Bone marrow necrosis, bone infarcts, osteomyelitis, and aseptic necrosis are common complications in patients with sickle cell disease. Beside these abnormalities of the skeletal system, diffuse micro or macro calcification resulting from both splenic infarction and repeated vaso-occlusive episodes in the kidneys can be shown by technetium-99m methylenediphosphonate (Tc-99m MDP) bone scintigraphy. We present here the different osseous and extraosseous abnormalities noted on bone scintigraphies of three patients with sickle cell anemia. METHODS: Whole-body bone scan was performed after injecting 740 MBq of Tc-99m MDP in three patients with sickle cell disease. RESULTS: Tc-99m MDP whole-body image of the first patient showed non-uniform uptake in the anterior and posterior aspects of multiple ribs and bilateral femurs and tibias that was attributed to repetitive infarcts. Additionally, increased activity in shoulders, right elbow, and right knee was consistent with arthritis. Tc-99m MDP image of the second patient demonstrated avascular necrosis of the left femoral head and diffuse activity in the enlarged kidneys. Increased activity in the spleen that was attributed to repetitive infarcts was visualized in bone scan of the third patient. CONCLUSIONS: In light of the findings in these cases, bone scintigraphy is a reliable imaging method in detecting both osseous and extraosseous abnormalities of sickle cell disease and may be used initially.

Long-term effectiveness of steroid injections and splinting in mild and moderate carpal tunnel syndrome.

To evaluate the long-term efficacy of non-surgical treatment methods for mild and moderate carpal tunnel syndrome, 120 patients with clinical symptoms and electrophysiologic evidence were included in a prospective, randomized and blinded trial: 60 patients were instructed to wear splints every night, 30 received injections of betamethasone 4 cm proximal to the carpal tunnel, and 30 received injections distal to the carpal tunnel. After approximately 1 year (mean, 11 months; range, 9-14), 108 patients were available for final evaluation. We assessed clinical symptom severity and performed detailed electrophysiologic examinations before and after treatment. Splinting provided symptomatic relief and improved sensory and motor nerve conduction velocities at the long-term follow-up when the splints were worn almost every night. Proximal and distal injections of steroids were ineffective on the basis of both clinical symptoms and electrophysiologic findings.

Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey.

BACKGROUND AND OBJECTIVES: Restless legs syndrome (RLS) is an important and common cause of insomnia, and previous studies indicate that psychiatric wellbeing may be impaired among RLS patients. We aimed to investigate the interaction between anxiety/depression and RLS in a population based survey. METHODS: Data were drawn from the Mersin University Neuro-Epidemiology Project, a representative community sample of adults aged over 17 years residing in Mersin (n = 3234). Subjects found to be positive for RLS (n = 103) were evaluated for symptoms of anxiety and depression using the Hamilton Anxiety and Depression Scales and compared with the same number of contemporaneous control subjects. RESULTS: Significantly greater anxiety and depression symptoms were observed among patients with RLS than in the control subjects. Our data also seem to provide initial evidence of a correlation between the severity of RLS and of anxiety and depression symptoms (r = 0.21, p = 0.03 and r = 0.201, p = 0.04 respectively). CONCLUSIONS: Assessment of psychiatric status of RLS patients can be helpful and sometimes necessary to determine additional features and treatment strategies of this bothering condition. Further studies are needed to replicate our findings using longitudinal data.

Unexpectedly low prevalence and unusual characteristics of RLS in Mersin, Turkey.

OBJECTIVE: To determine the prevalence, risk factors, and clinical presentation of restless legs syndrome (RLS) in a Turkish population. METHODS: A face-to-face, population-based epidemiologic survey was conducted. Multistep, stratified, cluster, and systematic samplings were used. A total of 3,234 adults were interviewed. RESULTS: Of the 3,234 participants, 103 (3.19%) experienced RLS. This prevalence rate is lower than those of other epidemiologic studies conducted among European and North American populations. RLS was found to be more common among women, cigarette smokers, and individuals residing in high altitudes. The self-reported mental and general health status of patients was worse than in the control subjects. The prevalence of RLS did not differ by age or body mass index. CONCLUSION: The discrepancy in RLS prevalence studies (including the authors') suggests that prevalence varies among different races, thus supporting a genetic predisposition.

Prevalence of essential tremor: door-to-door neurologic exams in Mersin Province, Turkey.

Estimates of the prevalence of essential tremor (ET) are probably low because screening questionnaires have been used. The authors estimated the prevalence of ET in Mersin Province, Turkey, in 2,253 individuals aged >or=40 years, all of whom were examined by study neurologists. There were 89 ET cases (prevalence = 4.0%, 95% CI = 3.2 to 4.8%). The prevalence of ET may be higher than previously estimated. This is important when defining the extent of the health care problem.

The brainstem auditory evoked potential abnormalities in severe chronic obstructive pulmonary disease.

OBJECTIVE: The aim of the study was to investigate the abnormalities of brainstem auditory evoked potentials (BAEP) in patients with severe chronic obstructive pulmonary disease (COPD). METHODOLOGY: Twenty-one patients with severe COPD (16 men, five women; mean age: 64 +/- 6.5 years), in whom other causes of BAEP abnormalities had been excluded, were studied. Age-matched, non-smoking, healthy subjects acted as a control group. We performed pulmonary function tests, arterial blood gas analysis and bilateral BAEP measurements in COPD patients and control groups. RESULTS: Brainstem auditory evoked potentials were abnormal in 16 (76.1%) of the 21 COPD patients. Most prominent BAEP abnormalities were prolonged wave I peak latencies (42.8%), V wave peak latencies (38.1%), and III-V interpeak latencies (IPL) (38.1%). In five patients, a prolonged central transmission time (I-V IPL) was observed. No significant correlation was evident between the BAEP parameters and pH, PaO2, PaCO2, FEV1%, FEV1/FVC, haematocrit, duration of disease or cigarette consumption. CONCLUSION: The functions of the eighth cranial nerve and brainstem were highly impaired in severe COPD. These pathological BAEP alterations in severe COPD might be due to the chronic hypoxic-hypercapnic status occurring in the brainstem.

Subclinical peripheral neuropathy associated with chronic obstructive pulmonary disease.

Peripheral nervous system disorders in COPD (chronic obstructive pulmonary disease) have been found more frequently than usual neurologic practice. We planned this prospective clinical and electrophysiological study to determine the incidence and characteristics of neuropathy in patients with COPD. We studied 49 patients with COPD in whom other causes of polyneuropathy had been excluded. COPD patients were divided into two groups: 21 hypoxemic and 28 normoxemic. Age and sex matched, nonsmoker, 21 healthy subjects were included as the control group. We investigated the results of clinical (neurological symptom score-NSS, neurological disability score-NDS and vibration perception thresholds- VPT) and neurophysiological evaluations in COPD patients and the control group. A value over the mean +/- 2.5 SD of control group were accepted pathologic. NSS results were pathologic in 34% of COPD patients, NDS in 42% and VPT in 94%. Carpal tunnel syndrome was found in 24% of the patients, neuropathy in 55%, and polyneuropathy in 44.8%. In conclusion, the incidence of neuropathy was more than expected, the rate of axonal neuropathy was significantly higher in the hypoxemic group than normoxemic group and the severity of neuropathy was correlated with the degree of hypoxemia.