- Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases. [Journal Article]
- OOncotarget 2018 Jun 05; 9(43):27027-27038
- CONCLUSIONS: SuPAR represents a promising novel biomarker in CRLM patients that might help to guide preoperative treatment decisions regarding patients' outcome and to identify patients particularly susceptible to AKI.
- Effects of linker modification on tumor-to-kidney contrast of 68Ga-labeled PSMA-targeted imaging probes. [Journal Article]
- MPMol Pharm 2018 Jun 19
- 68Ga-PSMA-11 is currently the most popular prostate-specific membrane antigen (PSMA) radioligand used in the clinic to detect prostate cancer and metastases. However, the high uptake of 68Ga-PSMA-11 ...
68Ga-PSMA-11 is currently the most popular prostate-specific membrane antigen (PSMA) radioligand used in the clinic to detect prostate cancer and metastases. However, the high uptake of 68Ga-PSMA-11 in kidneys can create halo-artifacts resulting in lower detection sensitivity for lesions adjacent to the kidneys. In this study, we developed two 68Ga-labeled PSMA-targeted tracers, 68Ga-HTK01166 and 68Ga-HTK01167, based on 68Ga-PSMA-617 with the goal of improving tumor-to-kidney ratio compared to 68Ga-PSMA-11. The 2-naphthylalanine (2-Nal) in PSMA-617 was replaced with 2-indanylglycine (Igl) or 3,3-diphenylalanine (Dip) to synthesize HTK01166 and HTK01167, respectively. Binding affinities (Ki) of Ga-PSMA-11, Ga-PSMA-617, Ga-HTK01166 and Ga-HTK01167 to PSMA were 3.13 ± 0.40, 1.23 ± 0.08, 5.74 ± 2.48 and 25.7 ± 9.84 nM, respectively, as determined by in vitro competition binding assays. 68Ga labeling was performed in HEPES buffer with microwave heating, and 68Ga-labeled PSMA-11, PSMA-617, HTK01166 and HTK01167 were obtained in 46 - 69% average decay-corrected radiochemical yield with >99% radiochemical purity and 62.9 - 152 GBq/μmol average specific activity. PET imaging and biodistribution studies were performed in mice bearing PSMA-expressing LNCap prostate cancer xenografts. All tracers enabled clear visualization of tumors in PET images with excellent tumor-to-background contrast. The uptake values (%ID/g) for tumor and kidneys at 1 h post-injection were 8.91 ± 0.86 and 204 ± 70.6 for 68Ga-PSMA-11, 16.7 ± 2.30 and 29.2 ± 5.14 for 68Ga-PSMA-617, 14.1 ± 4.40 and 147 ± 59.6 for 68Ga-HTK01166, and 7.79 ± 1.65 and 4.30 ± 1.80 for 68Ga-HTK01167. The tumor-to-kidney ratios for 68Ga-labeled PSMA-11, PSMA-617, HTK01166 and HTK01167 were 0.05 ± 0.02, 0.63 ± 0.10, 0.10 ± 0.02 and 1.98 ± 0.63, respectively. Compared with 68Ga-PSMA-617, 68Ga-HTK01166 showed comparable tumor uptake, and almost 5-fold higher kidney uptake; whereas 68Ga-HTK01167 exhibited lower tumor and kidney uptake. Compared with 68Ga-PSMA-11, 68Ga-HTK01167 had similar tumor uptake and tumor-to-blood contrast ratio (23.8 ± 6.71 vs 20.4 ± 4.98) but higher tumor-to-background contrast ratios for other background organs especially for kidneys. Our data indicate that substitution of 2-Nal in PSMA-617 with other lipophilic amino acid can modulate PSMA binding affinity and their pharmacokinetics in vivo.
- Biomarkers of aggressiveness in genitourinary tumors with emphasis on kidney, bladder and prostate cancer. [Journal Article]
- ERExpert Rev Mol Diagn 2018 Jun 18
- Over the last decade, the improvement in molecular techniques and the acquisition of genomic information has transformed and increased the quality of patient care and our knowledge of diseases. Areas...
Over the last decade, the improvement in molecular techniques and the acquisition of genomic information has transformed and increased the quality of patient care and our knowledge of diseases. Areas covered: Protein expression levels in immunohistochemistry and molecular biomarkers are reported for their ability to predict recurrence, progression, development of metastases, or patient survival. In particular, for renal cell carcinoma, we take into consideration the biomarkers applicable to immunohistochemistry and with molecular and genetic analyses. In urothelial carcinoma, there is great interest in the possibility of distinguishing the basal vs. luminal subtypes and to acquire deeper insight into the tumour biology through examining exosomes in urine and biomarkers in the serum. In prostate cancer, single gene expression and multiple gene expression classifiers are reviewed as a tool to distinguish indolent vs. aggressive disease. Expert commentary: The genomic information along with the application of ancillary techniques allow the definition of a neoplasia not only by its morphology but also by its biological signature. This continuous increase in knowledge will result in a better comprehension of oncogenesis, development of targeted therapies and optimizing decision-making processes related to patient care.
- An interdisciplinary consensus on the management of bone metastases from renal cell carcinoma. [Review]
- NRNat Rev Urol 2018 Jun 14
- Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease ...
Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease stages. The prognosis of these patients is generally poor and the treatment is, therefore, aimed at palliation. However, RCC-associated bone metastases can be curable in select patients. Current data support a multimodal management strategy that includes wide resection of lesions, radiotherapy, systemic therapy, and other local treatment options, which can improve quality of life and survival. Nevertheless, the optimal approach for metastatic bone disease in RCC has not yet been defined and practical recommendations are rare. To improve the management and outcomes of patients with RCC and bone metastases, the International Kidney Cancer Coalition and the interdisciplinary working group on renal tumours of the German Cancer Society convened a meeting of experts with a global perspective to perform an unstructured review and elaborate on current treatment strategies on the basis of published data and expertise. The panel formulated recommendations for the diagnosis and treatment of patients with RCC and metastasis to the bone. Furthermore, the experts summarized current challenges and unmet patient needs that should be addressed in the future.
- Robotic treatment of oligometastatic kidney tumor with synchronous pancreatic metastasis: case report and review of the literature. [Journal Article]
- BSBMC Surg 2018 Jun 13; 18(1):40
- CONCLUSIONS: The rationale for surgical removal of disseminated tumor, followed by immunotherapy, includes improving prognosis and enhancing the potential of an immune-mediated response to systemic treatment. A spleen-sparing procedure can adequately preserve post-operative immunologic capabilities. In our experience, the correct assessment of pre-operative imaging data and surgeon skills in robotic surgery seem to play a key role in the success of these procedures. Robotic surgery seems to enhance the possibility to control multiple vessels encountered during dissection. Such a conservative approach may be helpful in future research aimed at uncovering biological features, and also leading to better targeted preventive interventions and more individualized and effective treatments.
- A Preliminary Study on the Estimation of the Number of Cancer Patients Eligible for Hadron Therapy in Iran and Fars Province. [Journal Article]
- IJIran J Med Sci 2018; 43(3):313-317
- Hadron therapy (HT) with protons and carbon ions is an advanced radiotherapy technique. As the first report addressing this topic, the present study aimed to estimate the number of patients eligible ...
Hadron therapy (HT) with protons and carbon ions is an advanced radiotherapy technique. As the first report addressing this topic, the present study aimed to estimate the number of patients eligible for HT in Fars province and the whole of Iran. The data were collected through direct inspection of medical records of the patients treated at the Radiotherapy Department, Namazi Hospital, Shiraz, Iran in 2014. The patients who were treated with external-beam radiotherapy and declared to be a resident of Fars province were extracted from the medical records. After classification based on appropriate indications and factors, the number of eligible patients in Iran was calculated by scaling (Iran: Fars population). Of the 2,932 medical records, 1,943 patients were treated with external-beam radiotherapy, among which 1,536 were from Fars. The total number of patients eligible for HT in Fars was >351 cases/year (22.9% of the treated patients). The cancer site distribution of the eligible Fars residents was central nervous system primary tumors (n=31), brain metastases (n=64), eye (n=7), head and neck (n=28); thyroid (n=4), lung (n=17), breast (n=56), esophagus (n=5); pancreas (n=5), gastric (n=32), liver and bile duct (n=0), rectum and anus (n=26); prostate (n=27), bladder (n=8), cervix (n=6), soft tissue (n=17); kidney (n=1), Hodgkin lymphoma (n=9), non-Hodgkin lymphoma (n=4), and bone metastases (n=4). A total number of 5,756 cases/year was estimated for the entire country. Considering the experiences of other countries, these results suggest that establishing at least two HT centers (covering the northern and southern parts of Iran) is justified based on the total number of patients. Further accurate estimations and cost evaluations are recommended.
- Basic Parameters of Blood Count, Serum Sodium, and Creatinine as Prognostic Factors for Renal Cell Carcinoma at Five-Year Follow-Up. [Journal Article]
- MSMed Sci Monit 2018 Jun 09; 24:3895-3902
- CONCLUSIONS: Preoperative PLT, serum sodium, and tumor staging were independent risk factors for local recurrence. Blood PLT, serum sodium, creatinine, and tumor staging were useful indicators for estimating 5-year cancer specific survival.
- Metastasizing pleomorphic adenoma in the multiple organs: A case report on FDG-PET/CT imaging. [Journal Article]
- MMedicine (Baltimore) 2018; 97(23):e11077
- CONCLUSIONS: Metastases of pleomorphic adenomas may occur years after the initial disease in association with local recurrences. Careful observation with whole-body imaging such as FDG-PET/CT is necessary.
- In Vivo Evaluation of [225Ac]Ac-DOTAZOL for α-Therapy of Bone Metastases. [Journal Article]
- CRCurr Radiopharm 2018 Jun 03
- Background Conjugates of bisphosphonates with macrocyclic chelators possess high potential in bone targeted radionuclide imaging and therapy. DOTAZOL, zoledronic acid conjugated to DOTA (1,4,7,10-tet...
Background Conjugates of bisphosphonates with macrocyclic chelators possess high potential in bone targeted radionuclide imaging and therapy. DOTAZOL, zoledronic acid conjugated to DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), demonstrated promising results in vivo in small animals as well as in first patient applications using 68Ga for diagnosis via PET and the low-energy β-emitter 177Lu for therapy of painful bone metastases. In consideration of the fact that targeted α-therapy probably offers various advantages over the use of β--emitters, the 225Ac-labelled derivative [225Ac]Ac-DOTAZOL was synthesized and evaluated in vivo. Here we report on radiolabelling and biodistribution of [225Ac]Ac-DOTAZOL in healthy Wistar rats. Methods Methods DOTAZOL was labelled with 225Ac and injected without further purification into the tail vein with activities of 404 ± 47 kBq per animal. Ex vivo biodistribution studies were performed in healthy Wistar rats at 1 hour, 24 hours, 5 days and 10 days post injection. The accumulation of [225Ac]Ac-DOTAZOL on healthy bone and soft tissue organs was determined in terms of SUV. The results were compared to those of other radiolabelled bisphosphonates such as [68Ga]Ga-DOTAZOL and [177Lu]Lu-DOTAZOL. A group of 7 animals was observed over a period of 3 month after application of 394 kBq ± 10 kBq of [225Ac]Ac-DOTAZOL for signs of toxicity. After 3 month kidneys were microscopically analysed for signs of chronic kidney damage. Results Radiolabelling of DOTAZOL with 225Ac at 98 °C provided radiochemical yields ≥98 % within 30 minutes. [225Ac]Ac-DOTAZOL showed high femur uptake (SUVfemur = 4.99 ± 0.97, 10 d p.i.), which was comparable to that of other Me(III)-DOTAZOL derivatives. Ratios between bone uptake and blood pool activity reached levels of 5, 940, 2181 and 2409 at 1 hour, 24 hours, 5 days and 10 days post injection. During the observation period of the first two month no toxicity was observed clinically. Histopathology of kidneys after 3 month revealed significant tubular damage in most of the animals. Conclusion [225Ac]Ac-DOTAZOL repeats the well-known pharmacology of DOTAZOL derivatives in preclinical evaluations. It thus may be considered for translational application together with strategies to reduce renal toxicity.
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- Acquired Cystic Disease-associated Renal Cell Carcinoma (ACD-RCC): A Multiinstitutional Study of 40 Cases With Clinical Follow-up. [Journal Article]
- AJAm J Surg Pathol 2018 May 30
- The incidence of renal cell carcinoma (RCC) is known to be higher in patients with end-stage renal disease, including those with acquired cystic kidney disease due to dialysis. Acquired cystic diseas...
The incidence of renal cell carcinoma (RCC) is known to be higher in patients with end-stage renal disease, including those with acquired cystic kidney disease due to dialysis. Acquired cystic disease (ACD)-associated RCC was recently incorporated into the 2016 WHO Classification of Tumors of the Urinary System and Male Genital Tract as a distinct entity and is reportedly the most common RCC arising in end-stage renal disease. In this study, we sought to further describe clinicopathologic findings in a large series of ACD-RCC, emphasizing histologic features, immunophenotype, clinical outcome, and patterns of disease spread. We collected 40 previously unpublished cases of ACD-RCC with mean clinical follow-up of 27 months (median, 19 mo; range, 1 to 126 mo). Mean tumor size was 2.7 cm (median, 2.4 cm), and 32 tumors (80%) were confined to the kidney (pT stage less than pT3a). International Society of Urological Pathology grade was 3 in 37 cases (92.5%), grade 2 in 1 case (2.5%), and grade 4 in 2 cases (5%). Architectural variability among ACD-RCC was common, as 39 cases (98%) showed varying combinations of tubular, cystic, solid, and/or papillary growth. ACD-RCC frequently occurred in association with other renal tumor subtypes within the same kidney, including papillary RCC (14 patients), papillary adenomas (7 cases), clear cell papillary RCC (5 cases), clear cell RCC (1 case), and RCC, unclassified type (1 case). A previously undescribed pattern of perinephric and renal sinus adipose tissue involvement by dilated epithelial cysts with minimal or absent intervening capsule or renal parenchyma was identified in 20 cases (50%); these cysts were part of the tumor itself in 5 cases (25%) and were part of the non-neoplastic acquired cystic change in the background kidney in the remaining 15 cases (75%). Of the 24 cases (60%) with tissue available for immunohistochemical stains, 19 (79%) were positive for PAX8, 20 (83%) showed negative to patchy expression of cytokeratin 7, and 24 (100%) were both positive for AMACR and negative for CD117. Fumarate hydratase expression was retained in all tumors, including those with nuclear features resembling fumarate hydratase-deficient RCCs. Of the 36 patients (90%) with available follow-up information, 4 (11%) experienced adverse events: 2 patients developed a local recurrence, 1 patient experienced multiple visceral metastases and subsequently died of disease, and 1 patient developed metastases to regional lymph nodes only. One local recurrence and the lymph node only metastasis both had an unusual, exclusively cystic pattern of growth. In summary, we present the largest clinicopathologic series of ACD-RCC to date and describe previously unreported cystic patterns of local soft tissue involvement and recurrence/metastases.