Early evaluation of risk stratification and clinical outcomes for patients with advanced breast cancer through combined monitoring of baseline circulating tumor cells and DNA.

PURPOSE: Early evaluation of tumor heterogeneity related to metastasis and outcomes is a major challenge in the management of advanced BCa in the clinic. Here we introduce the value of baseline CTCs and ctDNA to early differentiate clinical stages, tumor heterogeneity, and prognosis. EXPERIMENTAL DESIGN: We enrolled 254 stage IV and 38 stage III BCa patients and examined the baseline levels of CTCs, CTC-clusters, and plasma ctDNA before initiating therapies. Outcome including PFS, and OS were evaluated. RESULTS: The baseline CTCs for stage IV patients were approximately 9.5 times higher than those detected in stage III patients. Baseline CTC counts with a cutoff of 5 were significantly associated with prognosis. Within each stage, patients with <5 CTCs had longer PFS. Stage III patients with no CTCs exhibited the longest survival compared to patients with ≥1 CTC. CTC-clusters were only found in stage IV patients, among whom 15 stage IV patients with ≥5 CTC-clusters had the worst PFS compared to the 239 stage IV patients with <5 CTC-clusters. Similar outcomes were observed in 28 out of 254 stage IV patients who had at least 1 CTC-cluster detected, as these patients had shorter PFS. The major differences in ctDNA mutations between stage III and stage IV BCa were in PIK3CA and ESR1, which were associated with specific organ metastasis and worse outcomes. CONCLUSIONS: Assessing the baseline levels of CTCs, CTC-clusters, and mutational ctDNA profile could reliably aid in differentiation of clinical stage and early prediction of metastasis and outcomes in advanced BCa.

Prostate-specific membrane antigen-targeted surgery in prostate cancer: Accurate identification, real-time diagnosis, and precise resection.

Radical prostatectomy (RP) combined with pelvic lymph node dissection (PLND) is the first step in multimodal treatment of prostate cancer (PCa) without distant metastases. For a long time, the surgical resection range has been highly dependent on the surgeon's visualization and experience with preoperative imaging. With the rapid development of prostate-specific membrane antigen positron emission tomography and single-photon emission computed tomography (PSMA-PET and PSMA-SPECT), PSMA-targeted surgery has been introduced for a more accurate pathological diagnosis and complete resection of positive surgical margins (PSMs) and micro-lymph node metastases (LNMs). We reviewed PSMA-targeted surgeries, including PSMA-PET-guided prostatic biopsy (PSMA-TB), PSMA-targeted radio-guided surgery (PSMA-RGS), PSMA-targeted fluorescence-guided surgery (PSMA-FGS), and multi-modality/multi-targeted PSMA-targeted surgery. We also discuss the strengths and challenges of PSMA-targeted surgery, and propose that PSMA-targeted surgery could be a great addition to existing surgery protocols, thereby improving the accuracy and convenience of surgery for primary and recurrent PCa in the near future.

Efficacy and Safety of Disitamab Vedotin Combined with Programmed Death-1 Inhibitor for Advanced Urothelial Cancer: A Case-Series Study.

INTRODUCTION: Antibody-drug conjugate (ADC) and programmed death-1 (PD-1) inhibitors play crucial roles in the treatment of advanced urothelial cancer (aUC). Increasingly, combination treatment modalities are used in patients with aUC intolerant to platinum-based chemotherapy (PBC). However, clinical evidence on the efficacy and safety of disitamab vedotin plus PD-1 inhibitors for aUC is limited. This case series aims to address this knowledge gap. METHODS: Patients with aUC who were refractory or intolerant to PBC were included. All patients received combined treatment with disitamab vedotin (one of the ADC drugs) and PD-1 inhibitors for at least three cycles. The clinical characteristics of examination, histopathology, outcomes, and adverse events (AEs) were retrospectively collected. RESULTS: Among this case series, eight patients received disitamab vedotin plus PD-1 inhibitors, of which three achieved a complete response (CR) and two had a partial response (PR). The most common AE was peripheral neuropathy (4/8); the remaining AEs were mostly of mild to moderate severity or unknown and were manageable by supportive care. CONCLUSIONS: Disitamab vedotin combined with PD-1 inhibitors exhibits a favorable efficacy and safety profile, but subsequent larger cohort clinical studies are required to provide evidence-based medicine for the universal application of this regimen.

Avoiding unnecessary biopsy: the combination of PRIMARY score with prostate-specific antigen density for prostate biopsy decision.

BACKGROUND: Avoiding unnecessary biopsies for men with suspected prostate cancer remains a clinical priority. The recently proposed PRIMARY score improves diagnostic accuracy in detecting clinically significant prostate cancer (csPCa). The aim of this study was to determine the best strategy combining PRIMARY score or MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]) with prostate-specific antigen density (PSAD) for prostate biopsy decision making. METHODS: A retrospective analysis of 343 patients who underwent both 68Ga-PSMA PET/CT and MRI before prostate biopsy was performed. PSA was restricted to <20 ng/ml. Different biopsy strategies were developed and compared based on PRIMARY score or PI-RADS with PSAD thresholds. Decision curve analysis (DCA) was plotted to define the optimal biopsy strategy. RESULTS: The prevalence of csPCa was 41.1% (141/343). According to DCA, the strategies of PRIMARY score +PSAD (strategy #1, strategy #2, strategy #6) had a higher net benefit than the strategies of PI-RADS + PSAD at the risk threshold of 8-20%. The best diagnostic strategy was strategy #1 (PRIMARY score 4-5 or PSAD ≥ 0.20), which avoided 38.2% biopsy procedures while missed 9.2% of csPCa cases. From a clinical perspective, strategies with a lower risk of missing csPCa were strategy #2 (PRIMARY score ≥4 or PSAD ≥ 0.15), which avoided 28.6% biopsies while missed 5.7% of csPCa cases, or strategy #6 (PRIMARY score≥3 or PSAD ≥ 0.15), which avoided 20.7% biopsies while missed only 3.5% of csPCa cases. The limitations of the study were the retrospective single-center nature. CONCLUSIONS: The combination of PRIMARY score +PSAD allows individualized decisions to avoid unnecessary biopsy, outperforming the strategies of PI-RADS + PSAD. Further prospective trials are needed to validate these findings.

The PRIMARY Score: Diagnostic Performance and Added Value Compared With MRI in Detecting Clinically Significant Prostate Cancer.

PURPOSE: Multiparametric MRI is the current standard for detecting clinically significant prostate cancer (csPCa). However, men with negative or equivocal MRI often undergo unnecessary biopsies due to concerns about false-negative results. The recently proposed 68 Ga-PSMA PET/CT-based PRIMARY score exhibited good diagnostic performance for csPCa. This study aimed to externally validate the performance of the PRIMARY score and evaluate its added diagnostic value to MRI triage in detecting csPCa. PATIENTS AND METHODS: This retrospective cohort study included 431 men who underwent both 68 Ga-PSMA PET/CT and MRI before biopsy. Performance was assessed using the area under the receiver operating characteristic curve and the decision curve analysis. The PRIMARY score + MRI was considered positive for either PRIMARY score 3-5 or Prostate Imaging Reporting and Data System (PI-RADS) 4/5. RESULTS: The prevalence of csPCa was 51.7% (223/431). The area under the receiver operating characteristic curve of the 5-level PRIMARY score for csPCa was significantly higher than that of MRI (0.873 vs 0.786, P < 0.001). For the entire group, sensitivity, specificity, positive predictive value, and negative predictive value of the PRIMARY score were 90.6%, 61.1%, 71.4%, and 85.8%, respectively, which outperformed 87.9%, 49.0%, 64.9%, and 79.1% of PI-RADS on MRI. The PRIAMRY score + MRI improved sensitivity (96.0% vs 87.9%, P < 0.001) and negative predictive value (91.5% vs 79.1%, P < 0.001) without compromising specificity and positive predictive value compared with MRI alone. This combined approach avoided 24.6% (106/431) of unnecessary biopsies, while missing 4.0% (9/223) of csPCa cases. The addition of the PRIMARY score in men with PI-RADS 1-3 showed a net benefit, but not in men with PI-RADS 4/5. CONCLUSIONS: The PRIMARY score was superior to MRI in detecting csPCa, and its added diagnostic value was in men with negative or equivocal MRI results. The PRIMARY score + MRI improved negative predictive value and sensitivity for csPCa compared with MRI alone. Further prospective trials will validate whether men with clinical suspicion of csPCa but negative PRIMARY score + MRI can safely avoid unnecessary biopsies.

A Prostate-Specific Membrane Antigen PET-Based Approach for Improved Diagnosis of Prostate Cancer in Gleason Grade Group 1: A Multicenter Retrospective Study.

The preoperative Gleason grade group (GG) from transrectal ultrasound-guided prostate biopsy is crucial for treatment decisions but may underestimate the postoperative GG and miss clinically significant prostate cancer (csPCa), particularly in patients with biopsy GG1. In such patients, an SUVmax of at least 12 has 100% specificity for detecting csPCa. In patients with an SUVmax of less than 12, we aimed to develop a model to improve the diagnostic accuracy of csPCa. Methods: The study retrospectively included 56 prostate cancer patients with transrectal ultrasound-guided biopsy GG1 and an SUVmax of less than 12 from 2 tertiary hospitals. All [68Ga]Ga-PSMA-HBED-CC PET scans were centrally reviewed in Xijing Hospital. A deep learning model was used to evaluate the overlap of SUVmax (size scale, 3 cm) and the level of Gleason pattern (size scale, 500 µm). A diagnostic model was developed using the PRIMARY score and SUVmax, and its discriminative performance and clinical utility were compared with other methods. The 5-fold cross-validation (repeated 1,000 times) was used for internal validation. Results: In patients with GG1 and an SUVmax of less than 12, significant prostate-specific membrane antigen (PSMA) histochemical score (H-score) H-score overlap occurred among benign gland, Gleason pattern 3, and Gleason pattern 4 lesions, causing SUVmax overlap between csPCa and non-csPCa. The model of 10 × PRIMARY score + 2 × SUVmax exhibited a higher area under the curve (AUC, 0.8359; 95% CI, 0.7233-0.9484) than that found using only the SUVmax (AUC, 0.7353; P = 0.048) or PRIMARY score (AUC, 0.7257; P = 0.009) for the cohort and a higher AUC (0.8364; 95% CI, 0.7114-0.9614) than that found using only the Prostate Imaging Reporting and Data System (PI-RADS) score of 5-4 versus 3-1 (AUC, 0.7036; P = 0.149) and the PI-RADS score of 5-3 versus 2-1 (AUC, 0.6373; P = 0.014) for a subgroup. The model reduced the misdiagnosis of the PI-RADS score of 5-4 versus 3-1 by 78.57% (11/14) and the PI-RADS score of 5-3 versus 2-1 by 77.78% (14/18). The internal validation showed that the mean 5-fold cross-validated AUC was 0.8357 (95% CI, 0.8357-0.8358). Conclusion: We preliminarily suggest that the model of 10 × PRIMARY score + 2 × SUVmax may enhance the diagnostic accuracy of csPCa in patients with biopsy GG1 and an SUVmax of less than 12 by maximizing PSMA information use, reducing the misdiagnosis of the PI-RADS score, and thereby aiding in making appropriate treatment decisions.

Unambiguous radiologic extranodal extension determined by MRI could be a biomarker in predicting metastatic prostate cancer.

OBJECTIVE: To explore the relationship between unambiguous radiologic extranodal extension (rENE) and M1 staging in patients with metastatic PCa. METHODS: A respective analysis of 1073 patients of PCa N1 staging from January 2004 to May 2022 was retrospectively enrolled. They were divided into rENE + and rENE - groups and retrospectively analyzed the M staging with nuclear medicine data. The correlation index between unambiguous rENE and M1b staging was calculated. Logistic regression was used to evaluate the predictive performance of unambiguous rENE in M1b staging. ROC curves were used to investigate the relationship between unambiguous rENE and M staging in patients who underwent 68 Ga-PSMA PET/CT. RESULTS: A total of 1073 patients were included. Seven hundred and eighty patients were classified into the rENE + group (mean age, 69.6 years ± 8.7 [standard deviation]), and 293 were classified into rENE - group (mean age, 66.7 years ± 9.4 [standard deviation]). Relationship between unambiguous rENE and M1b existed (r = 0.58, 95%CI: 0.52-0.64, P < 0.05). Unambiguous rENE could be an independent predictor for M1b (OR = 13.64, 95%CI: 9.23-20.14, P < 0.05). The AUC of unambiguous rENE in predicting M1b and M staging was 0.835 and 0.915, respectively, in patients who underwent 68 Ga-PSMA PET/CT. CONCLUSIONS: Unambiguous rENE could be a strong biomarker to predict M1b and M staging in patients with PCa. When rENE came up, patients should perform nuclear medicine immediately, and a systematic treatment should be considered.

Comparison of prostate volume measured by transabdominal ultrasound and MRI with the radical prostatectomy specimen volume: a retrospective observational study.

BACKGROUND: Few studies have compared the use of transabdominal ultrasound (TAUS) and magnetic resonance imaging (MRI) to measure prostate volume (PV). In this study, we evaluate the accuracy and reliability of PV measured by TAUS and MRI. METHODS: A total of 106 patients who underwent TAUS and MRI prior to radical prostatectomy were retrospectively analyzed. The TAUS-based and MRI-based PV were calculated using the ellipsoid formula. The specimen volume measured by the water-displacement method was used as a reference standard. Correlation analysis and intraclass correlation coefficients (ICC) were performed to compare different measurement methods and Bland Altman plots were drawn to assess the agreement. RESULTS: There was a high degree of correlation and agreement between the specimen volume and PV measured with TAUS (r = 0.838, p < 0.01; ICC = 0.83) and MRI (r = 0.914, p < 0.01; ICC = 0.90). TAUS overestimated specimen volume by 2.4ml, but the difference was independent of specimen volume (p = 0.19). MRI underestimated specimen volume by 1.7ml, the direction and magnitude of the difference varied with specimen volume (p < 0.01). The percentage error of PV measured by TAUS and MRI was within ± 20% in 65/106(61%) and 87/106(82%), respectively. In patients with PV greater than 50 ml, MRI volume still correlated strongly with specimen volume (r = 0.837, p < 0.01), while TAUS volume showed only moderate correlation with specimen (r = 0.665, p < 0.01) or MRI volume (r = 0.678, p < 0.01). CONCLUSIONS: This study demonstrated that PV measured by MRI and TAUS is highly correlated and reliable with the specimen volume. MRI might be a more appropriate choice for measuring the large prostate.

Alternation of the gut microbiota in irritable bowel syndrome: an integrated analysis based on multicenter amplicon sequencing data.

BACKGROUND: Gut dysbacteriosis has been reported as one of the etiologies for irritable bowel syndrome (IBS). However, the association between gut microbiota and IBS is still inconclusive. METHOD: A paired-sample study was designed by retrieving original multicenter 16 s-rRNA data of IBS patients and healthy controls from the GMrepo database. The propensity score matching (PSM) algorithm was applied to reduce confounding bias. The differential analysis of microbiota composition was performed at different taxonomic levels. The co-occurrence network was established. Subgroup analysis was performed to identify specific microbial compositions in different IBS subtypes. RESULTS: A total of 1522 amplicon samples were initially enrolled. After PSM, 708 individuals (354 IBS and 354 healthy controls) were eligible for further analysis. A total of 1,160 genera were identified. We identified significantly changed taxa in IBS groups (IBS-enriched: the families Enterobacteriaceae, Moraxellaceae and Sphingobacteriaceae; the genera Streptococcus, Bacillus, Enterocloster, Sphingobacterium, Holdemania and Acinetobacter. IBS-depleted: the phyla Firmicutes, Euryarchaeota, Cyanobacteria, Acidobacteria and Lentisphaerae; the families Bifidobacteriaceae, Ruminococcaceae, Methanobacteriaceae and the other 25 families; the genera Faecalibacterium, Bifidobacterium and other 68 genera). The co-occurrence network identified three hub genera and six hub species (including Faecalibacterium prausnitzii) that may be involved in IBS pathophysiology. Strong positive interactions were identified among the Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium adolescentis in the Bifidobacterium community. CONCLUSION: This study provides quantitative analysis and visualization of the interaction between the gut microbiota and IBS. The identification of key species should be further validated to evaluate their causal relationships with the pathogenesis of IBS.

Metagenomic analysis of the interaction between the gut microbiota and colorectal cancer: a paired-sample study based on the GMrepo database.

BACKGROUND: Previous evidence has shown that the gut microbiota plays a role in the development and progression of colorectal cancer (CRC). This study aimed to provide quantitative analysis and visualization of the interaction between the gut microbiota and CRC in order to establish a more precise microbiota panel for CRC diagnosis. METHOD: A paired-sample study was designed by retrieving original metagenomic data from the GMrepo database. The differences in the distribution of the gut microbiota between CRCs and controls were analysed at the species level. A co-occurrence network was established, and the microbial interactions with environmental factors were assessed. Random forest models were used to determine significant biomarkers for differentiating CRC and control samples. RESULTS: A total of 709 metagenomic samples from 6 projects were identified. After matching, 86 CRC patients and 86 matched healthy controls from six countries were enrolled. A total of 484 microbial species and 166 related genera were analysed. In addition to previously recognized associations between Fusobacterium nucleatum and species belonging to the genera Peptostreptococcus, Porphyromonas, and Prevotella and CRC, we found new associations with the novel species of Parvimonas micra and Collinsella tanakaei. In CRC patients, Bacteroides uniformis and Collinsella tanakaei were positively correlated with age, whereas Dorea longicatena, Adlercreutzia equolifaciens, and Eubacterium hallii had positive associations with body mass index (BMI). Finally, a random forest model was established by integrating different numbers of species with the highest model-building importance and lowest inner subcategory bias. The median value of the area under the receiver operating characteristic curve (AUC) was 0.812 in the training cohort and 0.790 in the validation set. CONCLUSIONS: Our study provides a novel bioinformatics approach for investigating the interaction between the gut microbiota and CRC using an online free database. The identification of key species and their associated genes should be further emphasized to determine the relative causality of microbial organisms in the development of CRC.

Photodynamic therapy for prostate cancer: Recent advances, challenges and opportunities.

Over the past two decades, there has been a tendency toward early diagnosis of prostate cancer due to raised awareness among the general public and professionals, as well as the promotion of prostate-specific antigen (PSA) screening. As a result, patients with prostate cancer are detected at an earlier stage. Due to the risks of urine incontinence, erectile dysfunction, etc., surgery is not advised because the tumor is so small at this early stage. Doctors typically only advise active surveillance. However, it will bring negative psychological effects on patients, such as anxiety. And there is a higher chance of cancer progression. Focal therapy has received increasing attention as an alternative option between active monitoring and radical therapy. Due to its minimally invasive, oncological safety, low toxicity, minimal effects on functional outcomes and support by level 1 evidence from the only RCT within the focal therapy literature, photodynamic treatment (PDT) holds significant promise as the focal therapy of choice over other modalities for men with localized prostate cancer. However, there are still numerous obstacles that prevent further advancement. The review that follows provides an overview of the preclinical and clinical published research on PDT for prostate cancer from 1999 to the present. It focuses on clinical applications of PDT and innovative techniques and technologies that address current problems, especially the use of nanoparticle photosensitizers in PDT of prostate cancer.

Prostate specific membrane antigen positron emission tomography in primary prostate cancer diagnosis: First-line imaging is afoot.

Prostate specific membrane antigen positron emission tomography (PSMA PET) is an excellent molecular imaging technique for prostate cancer. Currently, PSMA PET for patients with primary prostate cancer is supplementary to conventional imaging techniques, according to guidelines. This supplementary function of PSMA PET is due to a lack of systematic review of its strengths, limitations, and potential development direction. Thus, we review PSMA ligands, detection, T, N, and M staging, treatment management, and false results of PSMA PET in clinical studies. We also discuss the strengths and challenges of PSMA PET. PSMA PET can greatly increase the detection rate of prostate cancer and accuracy of T/N/M staging, which facilitates more appropriate treatment for primary prostate cancer. Lastly, we propose that PSMA PET could become the first-line imaging modality for primary prostate cancer, and we describe its potential expanded application.

Prognostic value and underlying mechanism of autophagy-related genes in bladder cancer.

Bladder cancer (BLCA) is the most common malignancy whose early diagnosis can ensure a better prognosis. However, the predictive accuracy of commonly used predictors, including patients' general condition, histological grade, and pathological stage, is insufficient to identify the patients who need invasive treatment. Autophagy is regarded as a vital factor in maintaining mitochondrial function and energy homeostasis in cancer cells. Whether autophagy-related genes (ARGs) can predict the prognosis of BLCA patients deserves to be investigated. Based on BLCA data retrieved from the Cancer Genome Atlas and ARGs list obtained from the Human Autophagy Database website, we identified prognosis-related differentially expressed ARGs (PDEARGs) through Wilcox text and constructed a PDEARGs-based prognostic model through multivariate Cox regression analysis. The predictive accuracy, independent forecasting capability, and the correlation between present model and clinical variables or tumor microenvironment were evaluated through R software. Enrichment analysis of PDEARGs was performed to explore the underlying mechanism, and a systematic prognostic signature with nomogram was constructed by integrating clinical variables and the aforementioned PDEARGs-based model. We found that the risk score generated by PDEARGs-based model could effectively reflect deteriorated clinical variables and tumor-promoting microenvironment. Additionally, several immune-related gene ontology terms were significantly enriched by PDEARGs, which might provide insights for present model and propose potential therapeutic targets for BLCA patients. Finally, a systematic prognostic signature with promoted clinical utility and predictive accuracy was constructed to assist clinician decision. PDEARGs are valuable prognostic predictors and potential therapeutic targets for BLCA patients.

Galectin-9 expression predicts poor prognosis in hepatitis B virus-associated hepatocellular carcinoma.

OBJECTIVES: The aim of this study was to explore the expression of Galectin-9 in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), evaluate its clinicopathological significance, and investigate whether Galecin-9 expression has prognostic value in HBV-associated HCC. METHODS: Immunohistochemistry staining was performed to examine the expression of Galectin-9 in paraffin-embedded tissues from 140 cases of HBV-associated HCC specimens. The association between Gal-9 expression, clinicopathological features and prognosis was analyzed by Kaplan-Meier method, log-rank test and Cox regression analysis. Dual immunofluorescence (IF) staining was performed to identify the cell types that have positive Gal-9 expression. RESULTS: Among the 140 cases of HBV-associated HCC, 39 (27.9%) cases showed high Gal-9 expression (score≥6), 21 (15%) cases showed moderate Gal-9 expression (6>score≥3), 33 (23.6%) cases showed weak Gal-9 expression (3>score>0), and 47 (33.6%) cases had no detectable Gal-9 expression (score=0). Positive Gal-9 expression (score>0) was associated with lymph node metastasis (P=0.029), Ki-67 proliferation index (P=0.009) and poor prognosis. Univariate and multivariate analyses showed that Gal-9 expression could be used as an independent prognostic marker for HBV-associated HCC. Dual IF staining indicated that Gal-9 was mainly expressed in CD68+CD163+ Kupffer cells (KCs) in HBV-associated HCC. CONCLUSIONS: Gal-9 was specifically expressed in certain HBV-associated HCC. Positive Gal-9 expression was significantly associated with poor prognosis, and Gal-9 could be used as a prognostic marker in HBV-associated HCC. Specific expression of Gal-9 on KCs indicated it may have immunosuppressive function in HBV-associated HCC.

Case reports of robot-assisted laparoscopic radical nephrectomy and inferior vena cava tumor thrombectomy: A retrospective analysis.

ABSTRACT: Renal cell carcinoma is one common type of urologic cancers. It has tendencies to invade into the inferior vena cava (IVC) and usually requires an open surgery procedure. High rates of operative complications and mortality are usually associated with an open surgery procedure. The recently emerged robot-assisted laparoscopic radical nephrectomy (RAL-RN) and IVC tumor thrombectomy have shown to reduce operative related complications in patients with renal cell carcinoma.This case series study aimed to summarize technical utilization, perioperative outcomes, and efficacies of RAL-RN and IVC tumor thrombectomy in our hospital. A retrospective analysis was performed on clinical data from 20 patients who underwent RAL-RN and IVC tumor thrombectomy from January 2017 to December 2019 in our department.Patients had a median age of 59 years (interquartile range [IQR], 46-68). Four patients had renal neoplasm on left side and 16 on right side. Nineteen patients underwent RAL-RN (level 0: n = 2) or RAL-RN with IVC thrombectomy (n = 17) (level I: n = 3; level II: n = 12; and level III: n = 3) and 1 patient was converted into an open surgery. The median operative time was 328 minutes (IQR, 221-453). The estimated median blood loss was 500 mL (IQR, 200-1200). The median size of removed renal carcinoma was 67 cm2 (IQR, 40-91); the length of IVC tumor thrombus was 5 cm (IQR, 3-7). The postsurgery hospital length of stay was 6 days (IQR, 5-7). The complications included intestinal obstruction (n = 1), lymphatic fistula (n = 1), heart failure (n = 1), and low hemoglobin level (n = 1). The outcomes for patients after 16 months (IQR, 11-21) follow-up were tumor-free (n = 10), tumor progression (n = 4), loss of contact (n = 1), and death (n = 5).We concluded that RAL-RN and IVC thrombectomy renders good safety profiles including minimal invasiveness, low estimated median blood loss, short hospitalization, low morbidity, and quick renal function recovery. The long-term efficacy needs a further investigation.

Establishment and prospective validation of an SUVmax cutoff value to discriminate clinically significant prostate cancer from benign prostate diseases in patients with suspected prostate cancer by 68Ga-PSMA PET/CT: a real-world study.

Background and Aims: The aims of this study were to establish a maximum standardized uptake value (SUVmax) cutoff to discriminate clinically significant prostate cancer (csPCa) from benign prostate disease (BPD) by 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) in patients with suspected prostate cancer (PCa), and to perform a prospective real-world validation of this cutoff value. Methods: The study included a training cohort to identify an SUVmax cutoff value and a prospective real-world cohort to validate it. A retrospective analysis assessed 135 patients with suspected PCa in a large tertiary care hospital in China who underwent 68Ga-PSMA-11 PET/CT. All patients were suspected of having PCa based on symptoms, digital rectal examination (DRE), total prostate-specific antigen (tPSA) level, and multiparameter magnetic resonance imaging (mpMRI). The 68Ga-PSMA PET/CT results were evaluated using histopathological results from transrectal ultrasound-guided 12-core biopsy with necessary targeted biopsy as references. Patients with Gleason scores (GS) ≥7 from the biopsy results were diagnosed with csPCa, and patients with negative biopsy and follow-up results were diagnosed with BPD. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal SUVmax cutoff value. The cutoff value was prospectively validated in 58 patients with suspected PCa. The diagnostic benefits of the cutoff value for clinical decision making were also evaluated. Results: According to ROC curve analysis, the most appropriate SUVmax cutoff value for discriminating csPCa from BPD was 5.30 (sensitivity, 85.85%; specificity, 86.21%; area under the curve [AUC], 0.893). The cutoff achieved a sensitivity of 83.33%, a specificity of 81.25%, a positive predictive value (PPV) of 92.11%, a negative predictive value (NPV) of 65.00%, and an accuracy of 82.76% in the prospective validation cohort. Metastases were used as an indicator to reduce false negative results in patients with SUVmax ≤ 5.30. In patients without metastases, an SUVmax value of 5.30 was also the best cutoff to diagnose localized csPCa (sensitivity, 80.43%; specificity, 86.21%; AUC, 0.852). The cutoff discriminated localized csPCa from BPD with a sensitivity of 76.19%, a specificity of 81.25%, a PPV of 84.21%, an NPV of 72.22%, and an accuracy of 78.38% in the prospective validation cohort. The cutoff, combined with metastases, achieved an accuracy of 89.12% in all patients, increasing accuracy by 8.29% and reducing equivocal results compared with manual reading. There was a strong correlation between SUVmax and PSMA expression (rs = 0.831, P < 0.001) and a moderate correlation between SUVmax and GS (rs = 0.509, P < 0.001). The PSMA expression and SUVmax values of patients with csPCa were significantly higher than those of patients with BPD (P < 0.001). Conclusion: We established and prospectively validated the best SUVmax cutoff value (5.30) for discriminating csPCa from BPD with high accuracy in patients with suspected PCa. 5.30 is an effective cutoff to discriminate csPCa patients with or without metastases. The cutoff may provide a potential tool for the precise identification of csPCa by 68Ga-PSMA PET/CT, ensuring high accuracy and reducing equivocal results.

The Establishment of New Thresholds for PLND-Validated Clinical Nomograms to Predict Non-Regional Lymph Node Metastases: Using 68Ga-PSMA PET/CT as References.

PURPOSE: PLND (pelvic lymph node dissection)-validated nomograms are widely accepted clinical tools to determine the necessity of PLND by predicting the metastasis of lymph nodes (LNMs) in pelvic region. However, these nomograms are in lacking of a threshold to predict the metastasis of extrareolar lymph nodes beyond pelvic region, which is not suitable for PLND. The aim of this study is to evaluate a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases beyond pelvic region in high-risk prostate cancer patients, by using 68Ga-PSMA PET/CT as a reference to determine LN metastases (LNMs). EXPERIMENTAL DESIGN: We performed a retrospective analysis of 57 high-risk treatment-naïve PC patients in a large tertiary care hospital in China who underwent 68Ga-PSMA-617 PET/CT imaging. LNMs was detected by 68Ga-PSMA-617 PET/CT and further determined by imaging follow-up after anti-androgen therapy. The pattern of LN metastatic spread of PC patients were evaluated and analyzed. The impact of 68Ga-PSMA PET/CT on clinical decisions based on three clinical PLND-validated nomograms (Briganti, Memorial Sloan Kettering Cancer Center, Winter) were evaluated by a multidisciplinary prostate cancer therapy team. The diagnostic performance and the threshold of these nomograms in predicting extrareolar LNMs metastasis were evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: LNMs were observed in 49.1% of the patients by 68Ga-PSMA PET/CT, among which 65.5% of LNMs were pelvic-regional and 34.5% of LNMs were observed in extrareolar sites (52.1% of these were located above the diaphragm). The Briganti, MSKCC and Winter nomograms showed that 70.2%-71.9% of the patients in this study need to receive ePLND according to the EAU and NCCN guidelines. The LN staging information obtained from 68Ga-PSMA PET/CT would have led to changes of planned management in 70.2% of these patients, including therapy modality changes in 21.1% of the patients, which were mainly due to newly detected non-regional LNMs. The thresholds of nomograms to predict non-regional LNMs were between 64% and 75%. The PC patients with a score >64% in Briganti nomogram, a score >75% in MSKCC nomogram and a score >67% in Winter nomogram were more likely to have non-regional LNMs. The AUCs (Area under curves) of the clinical nomograms (Briganti, MSKCC and Winter) in predicting non-regional LNMs were 0.816, 0.830 and 0.793, respectively. CONCLUSIONS: By using 68Ga-PSMA PET/CT as reference of LNM, the PLND-validated clinical nomograms can not only predict regional LNMs, but also predict non-regional LNMs. The additional information from 68Ga-PSMA PET/CT may provide added benefit to nomograms-based clinical decision-making in more than two-thirds of patients for reducing unnecessary PLND. We focused on that a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases with an AUC accuracy of about 80% after optimizing the simple nomograms which may help to improve the efficiency for PC therapy significantly in clinical practice.

Quicker, deeper and stronger imaging: A review of tumor-targeted, near-infrared fluorescent dyes for fluorescence guided surgery in the preclinical and clinical stages.

Cancer is a public health problem and the main cause of human mortality and morbidity worldwide. Complete removal of tumors and metastatic lymph nodes in surgery is significantly beneficial for the prognosis of patients. Tumor-targeted, near-infrared fluorescent (NIRF) imaging is an emerging field of real-time intraoperative cancer imaging based on tumor-targeted NIRF dyes. Targeted NIRF dyes contain NIRF fluorophores and specific binding ligands such as antibodies, peptides and small molecules. The present article reviews recently updated tumor-targeted NIRF dyes for the molecular imaging of malignant tumors in the preclinical stage and clinical trials. The strengths and challenges of NIRF agents with tumor-targeting ability are also summarized. Smaller ligands, near infrared II dyes, dual-modality dyes and activatable dyes may contribute to quicker, deeper, stronger imaging in the nearest future. In this review, we highlighted tumor-targeted NIRF dyes for fluorescence-guided surgery and their potential clinical translation.

Diaminopyrene modified reduced graphene oxide as a novel electrode material for excellent performance supercapacitors.

In this paper, novel reduced graphene oxide (rGO) composites (DAPrGOs) modified by diaminopyrene (DAP) were successfully synthesized via a facile solvothermal reaction method and used for supercapacitors. Compared with the pristine rGO, the DAPrGO1 electrode showed distinctly better performance (397.63 F g-1 vs. 80.29 F g-1 of pristine rGO at 0.5 A g-1) with small charge transfer resistance. When a symmetric device was fabricated using DAPrGO1 as the active material, it also exhibited a high capacitance of 82.70 F g-1 at 0.5 A g-1 with an energy density of 25.84 W h kg-1 at a power density of 375 W kg-1, and even offered a high power density of 7500 W kg-1 (18.71 W h kg-1) at 10 A g-1. Moreover, the device possessed good electrochemical stability up to 20 000 cycles, implying promising applications in energy storage fields.

Establishment of a nested-ASP-PCR method to determine the clarithromycin resistance of Helicobacter pylori.

AIM: To investigate clarithromycin resistance positions 2142, 2143 and 2144 of the 23SrRNA gene in Helicobacter pylori (H. pylori) by nested-allele specific primer-polymerase chain reaction (nested-ASP-PCR). METHODS: The gastric tissue and saliva samples from 99 patients with positive results of the rapid urease test (RUT) were collected. The nested-ASP-PCR method was carried out with the external primers and inner allele-specific primers corresponding to the reference strain and clinical strains. Thirty gastric tissue and saliva samples were tested to determine the sensitivity of nested-ASP-PCR and ASP-PCR methods. Then, clarithromycin resistance was detected for 99 clinical samples by using different methods, including nested-ASP-PCR, bacterial culture and disk diffusion. RESULTS: The nested-ASP-PCR method was successfully established to test the resistance mutation points 2142, 2143 and 2144 of the 23SrRNA gene of H. pylori. Among 30 samples of gastric tissue and saliva, the H. pylori detection rate of nested-ASP-PCR was 90% and 83.33%, while the detection rate of ASP-PCR was just 63% and 56.67%. Especially in the saliva samples, nested-ASP-PCR showed much higher sensitivity in H. pylori detection and resistance mutation rates than ASP-PCR. In the 99 RUT-positive gastric tissue and saliva samples, the H. pylori-positive detection rate by nested-ASP-PCR was 87 (87.88%) and 67 (67.68%), in which there were 30 wild-type and 57 mutated strains in gastric tissue and 22 wild-type and 45 mutated strains in saliva. Genotype analysis showed that three-points mixed mutations were quite common, but different resistant strains were present in gastric mucosa and saliva. Compared to the high sensitivity shown by nested-ASP-PCR, the positive detection of bacterial culture with gastric tissue samples was 50 cases, in which only 26 drug-resistant strains were found through analyzing minimum inhibitory zone of clarithromycin. CONCLUSION: The nested-ASP-PCR assay showed higher detection sensitivity than ASP-PCR and drug sensitivity testing, which could be performed to evaluate clarithromycin resistance of H. pylori.