Long-term urological outcome of cloaca patients with multidisciplinary management.

PURPOSE: Urological management of Cloacal Malformation (CM) focuses on preserving renal function and continence. Study aim was to analyze urinary and intestinal outcomes in CM patients, considering the length of common channel (CC) and presence of occult spinal dysraphism (OSD). METHODS: Retrospective review of CM treated at our institution by a multidisciplinary team from 1999 to 2020. Patients with follow-up < 2.5 years were excluded. Length of CC, renal function, urinary and bowel outcomes, presence of associated anomalies (especially OSD) were evaluated. RESULTS: Twenty patients were included, median age at follow-up: 8 years (4-15). A long CC > 3 cm was described in 11 (55%). Chronic kidney disease was found in 3 patients. Urinary continence was achieved in 8/20 patients, dryness (with intermittent catheterization) in 9/20. Fecal continence was obtained in 3/20, cleanliness in 14 (under bowel regimen). OSD was present in 10 patients (higher prevalence in long-CC, 73%). Among OSD, 1 patient reached fecal continence, 7 were clean; 2 achieved urinary continence, while 6 were dry. CONCLUSIONS: Length of CC and OSD may affect urinary and fecal continence. An early counseling can improve outcome at long-term follow-up. Multidisciplinary management with patient centralization in high grade institutions is recommended to achieve better results.

Recurrence-specific supervised graph clustering for subtyping Hodgkin Lymphoma radiomic phenotypes.

The prediction at baseline of patients at high risk for therapy failure or recurrence would significantly impact on Hodgkin Lymphoma patients treatment, informing clinical practice. Current literature is extensively searching insights in radiomics, a promising framework for high-throughput imaging feature extraction, to derive biomarkers and quantitative prognostic factors from images. However, existing studies are limited by intrinsic radiomic limitations, high dimensionality among others. We propose an exhaustive patient representation and a recurrence-specific multi-view supervised clustering algorithm for estimating patient-to-patient similarity graph and learning recurrence probability. We stratified patients in two risk classes and characterize each group in terms of clinical variables.

Interdisciplinarity: An essential requirement for translation of radiomics research into clinical practice -a systematic review focused on thoracic oncology. / Interdisciplinaridad: un requerimiento esencial para la traslación de investigación en radiómica a la práctica clínica.

BACKGROUND: Recently, evidence has accumulated that demonstrates the potential for future applications of radiomics in many clinical settings, including thoracic oncology. Methodological reasons for the immaturity of image mining (radiomics and artificial intelligence-based) studies have been identified. However, data on the influence of the composition of the research team on the quality of investigations in radiomics are lacking. AIM: This review aims to evaluate the interdisciplinarity within studies on radiomics in thoracic oncology in order to assess its influence on the quality of research (QUADAS-2 score) in the image mining field. METHODS: We considered for inclusion radiomics investigations with objectives relating to clinical practice in thoracic oncology. Subsequently, we interviewed the corresponding authors. The field of expertise and/or educational degree was then used to assess interdisciplinarity. Subsequently, all studies were evaluated applying the QUADAS-2 score and assigned to a research phase from 0 to IV. RESULTS: Overall, 27 studies were included. The study quality according to the QUADAS-2 score was low (score ≤5) in 8, moderate (=6) in 12, and high (≥7) in 7 papers. An interdisciplinary team (at least 3 different expertise categories) was involved in half of the papers without any type of validation and in all papers with independent validation. Clinicians were not involved in phase 0 studies while they contributed to all papers classified as phase I and to 4/5 papers classified as phase II with independent validation. CONCLUSIONS: The composition of the research team influences the quality of investigations in radiomics. Also, growth in interdisciplinarity appears to reflect research development from the early phase to a more mature, clinically oriented stage of investigation.

PET Radiomics in NSCLC: state of the art and a proposal for harmonization of methodology.

Imaging with positron emission tomography (PET)/computed tomography (CT) is crucial in the management of cancer because of its value in tumor staging, response assessment, restaging, prognosis and treatment responsiveness prediction. In the last years, interest has grown in texture analysis which provides an "in-vivo" lesion characterization, and predictive information in several malignances including NSCLC; however several drawbacks and limitations affect these studies, especially because of lack of standardization in features calculation, definitions and methodology reporting. The present paper provides a comprehensive review of literature describing the state-of-the-art of FDG-PET/CT texture analysis in NSCLC, suggesting a proposal for harmonization of methodology.

[18F]FDG-PET/CT texture analysis in thyroid incidentalomas: preliminary results.

BACKGROUND: significance of incidental thyroid 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans remains controversial. We aimed to evaluate the ability of [18F]FDG-PET/CT texture analysis to predict final diagnosis in thyroid incidentaloma. METHODS: We retrospectively evaluated medical records of all patients who performed a [18F]FDG-PET/CT from January 2012 to October 2016. Those patients who presented a thyroid incidentaloma described in the medical records and performed a fine needle aspiration in our institution were considered for the analysis. Cytological and/or histological results were used as reference standard to define the final diagnosis. In case of negative cytology, the nodule was considered benign. In case of non-diagnostic or inconclusive results ultrasound, follow-up and further cytology/histology were used as final diagnosis. For suspected or positive cytological result, histology was used as reference standard. PET images were segmented using a General Electric AW workstation running PET VCAR software (GE Healthcare, Waukesha, WI, USA) settled with a threshold of 40% SUVmax. LifeX software (http://www.lifexsoft.org) was used to perform texture analysis. Statistical analysis was performed with R package (https://www.r-project.org). RESULTS: We identified 55 patients with incidental thyroid [18F]FDG uptake. Five patients were excluded from the analysis because a final diagnosis was not available. Thirty-two out of 50 patients had benign nodules while in 18/50 cases a malignancy (primary thyroid cancer = 15, metastases = 3) was diagnosed. Conventional PET parameters and histogram-based features were calculated for all 50 patients, while other matrices-based features were available for 28/50 patients. SUVmax and skewness resulted significantly different in benign and malignant nodules (p = 0.01 and = 0.02, respectively). Using ROC analysis, seven features were identified as potential predictors. Among all the textural features tested, skewness showed the best area under the curve (= 0.66). SUV-based parameters resulted in the highest specificity while MTV, TLG, skewness and kurtosis, as well as correlationGLCM resulted better in sensitivity. CONCLUSIONS: [18F]FDG-PET/CT texture analysis seems to be a promising approach to stratify the patients with thyroid incidentaloma identified on PET scans, with respect to the risk of the diagnosis of a malignant thyroid nodule and thus, could refine the selection of the patients to be referred for cytology.

Somatostatin receptor positron emission tomography/computed tomography imaging in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon aggressive primary cutaneous carcinoma with neuroendocrine differentiation. However, literature data about the use of somatostatin receptor positron emission tomography/computed tomography (PET/CT) imaging in MCC are limited and its role is not clearly stated. OBJECTIVE: To investigate the role of PET/CT using somatostatin analogues radiolabelled with gallium-68 in patients with MCC. METHODS: All patients affected by MCC who performed a somatostatin receptor PET/CT imaging from October 2007 to May 2014 were retrospectively analysed. The diagnostic performances of PET/CT were evaluated on a patient-based analysis and compared to final diagnosis (histology = 3 or clinical/radiological follow-up = 20). RESULTS: We evaluated 23 consecutive MCC patients [18 men; median age 71 years (range 47-87)]. Primary tumour was located in ear (1/23), cheek (3/23), arm (2/23), hand (1/23), back (1/23), anal canal (1/23), gluteus (4/23), thigh (3/23) and popliteal fossa (1/23). In 6/23 patients, the site of primary tumour was unknown. PET/CT was performed to detect primary tumour site (4/23) or to stage (8/23) or re-stage (11/23) patients. PET/CT resulted positive in 14/23 patients and according to the final diagnosis was defined true positive, true negative, false positive (FP) and false negative in 11/23, 8/23, 3/23 and 1/23 cases respectively. FP PET/CT results were due to unspecific liver uptake, post-surgical inflammation and pancreatic neuroendocrine tumour. PET/CT was unable to detect primary tumour site in all patients with unknown primary MCC. Sensitivity, specificity and diagnostic accuracy of PET/CT were 92%, 73% and 83% respectively. CONCLUSIONS: In our experience, somatostatin receptor PET/CT imaging resulted useful in patients with MCC and presented high diagnostic performances with a significant impact in disease management although in patients with unknown primary MCC, it was unable to identify the primary tumour site.

(18)F-FDG PET/CT versus bone scintigraphy in the follow-up of gastric cancer.

A 53-year-old patient underwent a positron emission tomography/computed tomography with 2-fluoro-2-deoxy-d-glucose ((18)F-FDG PET/CT) in the suspicious of gastric tumor recurrence (mediastinal and abdominal lymph nodes). PET/CT identified only an area of (18)F-FDGuptake in the twelfth thoracic vertebrae. Unexpectedly, a bone scintigraphy revealed many "hot" spots changing the diagnosis (single metastasis versus plurimetastatic disease) and impacting on patient's management.

New approaches for imaging and therapy of solid cancer.

Radionuclide therapy is a systemic treatment that aims to deliver cytotoxic radiation to cancer cells. Due to their properties, antibodies have been considered as suitable agent for the delivery of therapeutic radioisotopes, radioimmunotherapy (RIT). This article gives an overview of new approaches for imaging and therapy of solid cancer with particular attention to strategies to enhance treatment success. Examples of increased antibody uptake by targeting stromal constituent of tumor microenvironment such as fibronectin (FN) an important tumor-associated angiogenesis targeting agent, with specifically designed antibody format will be provided. Strategies oriented to identify patients most likely to benefit from RIT including identification of radiosensitivity profiles, in vivo target identification by teragnostic approach and better prediction of dosimetric estimates would be presents. Combination regimens such as with chemo-radiotherapy and immunotherapy would be also discussed as an approach to enhance RIT success.

Applications of PET imaging with radiolabelled choline (11C/18F-choline).

The use of radiopharmaceuticals is the distinguishing characteristics of nuclear medicine. Among the panel of available radiopharmaceuticals in many PET centers around the world, choline is well represented, being widely used to image prostate cancer. Carbon-11 labelled choline can only be produced in centres with a cyclotron available, but the 18F-labelled radiopharmaceutical is distributed and licensed in several countries in Europe. Besides prostate cancer, other possible uses of choline are related to its ability to indirectly evaluate the cell proliferation as a measure of the synthesis of lipids required for cell membrane. In particular, the radiopharmaceutical can be successfully used in those districts where 18F-FDG has a high uptake, like the brain. Moreover, slow growing tumors, not always taking up 18F-FDG, like hepatocellular carcinoma, can also be imaged. We will evaluate possibly uses of this molecule in patients affected by prostate cancer, brain tumors and hepatocellular carcinoma.

Radiolabelled leucocyte scintigraphy versus conventional radiological imaging for the management of late, low-grade vascular prosthesis infections.

PURPOSE: In this study we evaluated the diagnostic performance of (99m)Tc-HMPAO-leucocyte ((99m)Tc-HMPAO-WBC) scintigraphy in a consecutive series of 55 patients (46 men and 9 women, mean age 71 ± 9 years, range 50 - 88 years) with a suspected late or a low-grade late vascular prosthesis infection (VPI), also comparing the diagnostic accuracy of WBC with that of other radiological imaging methods. METHODS: All patients suspected of having VPI underwent clinical examination, blood tests, microbiology, US and CT, and were classified according to the Fitzgerald criteria. A final diagnosis of VPI was established in 47 of the 55 patients, with microbiological confirmation after surgical removal of the prosthesis in 36 of the 47. In the 11 patients with major contraindications to surgery, the final diagnosis was based on microbiology and clinical follow-up of at least 18 months. RESULTS: (99m)Tc-HMPAO-WBC planar, SPECT and SPECT/CT imaging identified VPI in 43 of 47 patients (20 of these also showed infection at extra-prosthetic sites). In the remaining eight patients without VPI, different sites of infections were found. The use of SPECT/CT images led to a significant reduction in the number of false-positive findings in 37% of patients (sensitivity and specificity 100 %, versus 85.1% and 62.5% for stand-alone SPECT). Sensitivity and specificity were 34% and 75% for US, 48.9% and 83.3% for CT, and 68.1% and 62.5% for the FitzGerald classification. Perioperative mortality was 5.5%, mid-term mortality 12%, and long-term mortality 27%. Survival rates were similar in patients treated with surgery and antimicrobial therapy compared to patients treated with antimicrobial therapy alone (61% versus 63%, respectively), while infection eradication at 12 months was significantly higher following surgery (83.3% versus 45.5%). CONCLUSION: (99m)Tc-HMPAO-WBC SPECT/CT is useful for detecting, localizing and defining the extent of graft infection in patients with late and low-grade late VPI with inconclusive radiological findings. (99m)Tc-HMPAO-WBC SPECT/CT might be used to optimize patient management.

Dosimetry for nonuniform activity distributions: a method for the calculation of 3D absorbed-dose distribution without the use of voxel S-values, point kernels, or Monte Carlo simulations.

PURPOSE: Nonuniform activity within the target lesions and the critical organs constitutes an important limitation for dosimetric estimates in patients treated with tumor-seeking radiopharmaceuticals. The tumor control probability and the normal tissue complication probability are affected by the distribution of the radionuclide in the treated organ/tissue. In this paper, a straightforward method for calculating the absorbed dose at the voxel level is described. This new method takes into account a nonuniform activity distribution in the target/organ. METHODS: The new method is based on the macroscopic S-values (i.e., the S-values calculated for the various organs, as defined in the MIRD approach), on the definition of the number of voxels, and on the raw-count 3D array, corrected for attenuation, scatter, and collimator resolution, in the lesion/organ considered. Starting from these parameters, the only mathematical operation required is to multiply the 3D array by a scalar value, thus avoiding all the complex operations involving the 3D arrays. RESULTS: A comparison with the MIRD approach, fully described in the MIRD Pamphlet No. 17, using S-values at the voxel level, showed a good agreement between the two methods for (131)I and for (90)Y. CONCLUSIONS: Voxel dosimetry is becoming more and more important when performing therapy with tumor-seeking radiopharmaceuticals. The method presented here does not require calculating the S-values at the voxel level, and thus bypasses the mathematical problems linked to the convolution of 3D arrays and to the voxel size. In the paper, the results obtained with this new simplified method as well as the possibility of using it for other radionuclides commonly employed in therapy are discussed. The possibility of using the correct density value of the tissue/organs involved is also discussed.

Radiolabeled somatostatin analogues therapy in advanced neuroendocrine tumors: a single centre experience.

The aim of this study was to assess the efficacy of PRRT in patients with advanced neuroendocrine tumors (NETs). Patients and Methods. From January 2007 to August 2011, we enrolled 65 patients (m/f 38/27; mean age 65 years, range 33-83) with advanced NETs having enhanced SSTR expression, treated with PRRT. The enhanced expression of SSTR was assessed using (68)Ga-DOTATOC/DOTATATE PET/CT. Among all the enrolled patients, 6 of them were excluded from the present analysis since they voluntarily interrupted treatment. Mean activity/cycle of 2.6 GBq ((90)Y-DOTATOC/DOTATATE) or 6.0 GBq ((177)Lu-DOTATOC/DOTATATE) was administrated intravenously (max 9 cycles). Results. Complete response (CR) was found in 1/59 (2%) patients, partial remission (PR) in 24/59 (40.5%) patients, stable disease (SD) in 24/59 (40.5%), and progression (PD) in 10/59 (17%) patients. The overall tumor response rate (CR + PR) was 42.5%. In 40.5% of patients, the disease could be stabilized. Overall, 49 out of 59 patients had no tumor progression (83%). Twelve patients out of 59 (20%) had grade 2-3 hematological side effects including anemia, thrombocytopenia, and leukopenia. Long-term nephrotoxicity was observed in 3 patients (2 moderate, 1 severe). Conclusions. PRRT is a promising perspective for patients with advanced NETs.

Charybdotoxin-sensitive small conductance K(Ca) channel activated by bradykinin and substance P in endothelial cells.

1 In cultured porcine coronary artery endothelial cells, we have recently shown that substance P and bradykinin stimulated different types of Ca(2+)-dependent K(+) (K(Ca)) current. A large part of this current was insensitive to iberiotoxin and apamin. The aim of the present study was to characterize the K(Ca) channel responsible for this current. 2 In cell-attached configuration and asymmetrical K(+) concentration, 100 nM bradykinin or substance P activated a 10 pS K(+) channel. In inside-out configuration, the channel was half-maximally activated by 795 nM free Ca(2+). 3 Apamin (1 micro M) added to the pipette solution failed to inhibit the channel activity while charybdotoxin (50 nM), completely blocked it. Perfusion at the intracellular face of the cell, of an opener of intermediate conductance K(Ca) channel, 500 micro M 1-ethyl-benzimidazolinone (1-EBIO) increased the channel activity by about 4.5 fold. 4 In whole-cell mode, bradykinin and substance P stimulated an outward K(+) current of similar amplitude. Charybdotoxin inhibited by 75% the bradykinin-induced current and by 80% the substance P-induced current. Charybdotoxin plus iberiotoxin (50 nM each) inhibited by 97% the bradykinin-response. Charybdotoxin plus apamin did not increase the inhibition of the substance P-response obtained in the presence of charybdotoxin alone. 5 1-EBIO activated a transient outward K(+) current and hyperpolarized the membrane potential by about 13 mV. Charybdotoxin reduced the hyperpolarization to about 3 mV. 6 Taken together these results show that bradykinin and substance P activate a 10 pS K(Ca) channel, which largely contributes to the total K(+) current activated by these agonists. Despite its small conductance, this channel shares pharmacological characteristics with intermediate conductance K(Ca) channels.

Substance P and bradykinin activate different types of KCa currents to hyperpolarize cultured porcine coronary artery endothelial cells.

1. Substance P and bradykinin, endothelium-dependent vasodilators of pig coronary artery, trigger in endothelial cells a rise in cytosolic Ca2+ concentration ([Ca2+]i) and membrane hyperpolarization. The aim of the present study was to determine the type of Ca2+-dependent K+ (KCa) currents underlying the endothelial cell hyperpolarization. 2. The substance P-induced increase in [Ca2+]i was 30 % smaller than that induced by bradykinin, although the two peptides triggered a membrane hyperpolarization of the same amplitude. The two agonists evoked a large outward K+ current of the same conductance at maximal stimulation. Agonists applied together produced the same maximal current amplitude as either one applied alone. 3. Iberiotoxin (50 nM) reduced by about 40 % the K+ current activated by bradykinin without modifying the substance P response. Conversely, apamin (1 microM) inhibited the substance P-induced K+ current by about 65 %, without affecting the bradykinin response. Similar results were obtained on peptide-induced membrane hyperpolarization. 4. Bradykinin-induced, but not substance P-induced, endothelium-dependent relaxation resistant to NG-nitro-L-arginine and indomethacin was partly inhibited by 3 microM 17-octadecynoic acid (17-ODYA), an inhibitor of cytochrome P450 epoxygenase. Similarly, the bradykinin-induced K+ current was reduced by 17-ODYA. 5. Our results show that responses to substance P and bradykinin result in a hyperpolarization due to activation of different KCa currents. A current consistent with the activation of large conductance (BKCa) channels was activated only by bradykinin, whereas a current consistent with the activation of small conductance (SKCa) channels was stimulated only by substance P. The observation that a similar electrical response is produced by different pools of channels implies distinct intracellular pathways leading to KCa current activation.