Development and Validation of a Preoperative Nomogram for Endoscopic Management Decision Making in Upper Urinary Tract Urothelial Carcinoma.

OBJECTIVE: We aimed to develop and validate a preoperative nomogram that predicts low-grade, non-muscle invasive upper urinary tract urothelial carcinoma (LG-NMI UTUC), thereby aiding in the accurate selection of endoscopic management (EM) candidates. METHODS: This was a retrospective study that included 454 patients who underwent radical surgery (Cohort 1 and Cohort 2), and 26 patients who received EM (Cohort 3). Utilizing a multivariate logistic regression model, a nomogram predicting LG-NMI UTUC was developed based on data from Cohort 1. The nomogram's accuracy was compared with conventional European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) models. External validation was performed using Cohort 2 data, and the nomogram's prognostic value was evaluated via disease progression metrics in Cohort 3. RESULTS: In Cohort 1, multivariate analyses highlighted the absence of invasive disease on imaging (odds ratio [OR] 7.04; p = 0.011), absence of hydronephrosis (OR 2.06; p = 0.027), papillary architecture (OR 24.9; p < 0.001), and lack of high-grade urine cytology (OR 0.22; p < 0.001) as independent predictive factors for LG-NMI disease. The nomogram outperformed the two conventional models in predictive accuracy (0.869 vs. 0.759-0.821) and exhibited a higher net benefit in decision curve analysis. The model's clinical efficacy was corroborated in Cohort 2. Moreover, the nomogram stratified disease progression-free survival rates in Cohort 3. CONCLUSION: Our nomogram ( https://kmur.shinyapps.io/UTUC_URS/ ) accurately predicts LG-NMI UTUC, thereby identifying suitable candidates for EM. Additionally, the model serves as a useful tool for prognostic stratification in patients undergoing EM.

Prognostic impact of combination therapy with gemcitabine and cisplatin plus S-1 and subsequent conversion surgery for initially unresectable upper biliary tract cancers.

PURPOSE AND BACKGROUND: For the past decade, there have been few chemotherapy options for unresectable biliary tract cancer (BTC). Recently, however, combination therapy with gemcitabine and cisplatin plus S-1 (GCS) has been identified as a promising strategy. This retrospective study analyzes the clinical results of GCS therapy and subsequent conversion surgery (CS). METHOD: We analyzed the clinical data of 60 consecutive patients who received GCS therapy for unresectable upper BTC at our university hospital during the 5 years between September, 2018 and December, 2022. RESULTS: All patients received GCS therapy as first-line chemotherapy. The response rate was 33.9% and subsequent CS was performed in 35.0%. Of the patients who underwent CS, 81% required more than bisectionectomy of the liver with extrahepatic bile duct resection. The median overall survival of the patients who received GCS therapy and underwent subsequent CS was significantly longer than that of the patients who received GCS therapy alone (28.0 months vs. 12.4 months, respectively; p < 0.001). A decrease in the CA19-9 level 1 month after chemotherapy and RECIST PR were independent positive predictors of CS, whereas unresectable gallbladder cancer and pretreatment ALBI grade 3 were negative predictors of CS. CONCLUSION: GCS therapy and subsequent CS may contribute to the longer term survival of patients with unresectable upper BTC.

Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

PURPOSE: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. RESULTS: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. CONCLUSION: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation.

Combination therapy with lenvatinib and radiation significantly inhibits thyroid cancer growth by uptake of tyrosine kinase inhibitor.

Although surgical treatment cures >90% of differentiated thyroid cancer (DTC) patients, the remaining patients, including advanced DTC cases, have poor clinical outcomes. These patients with inoperable disease have only two choices of radioactive iodine therapy and tyrosine kinase inhibitors such as lenvatinib, which have a high incidence of treatment-related adverse events and can only prolong progression free survival by approximately 5-15 months. In this study, we investigated the antitumor effects of combination therapy with lenvatinib and radiation (CTLR) for DTC. CTLR synergistically inhibited cell replication and colony formation in vitro and tumor growth in nude mice without apparent toxicities and suppressed the expression of proliferation marker (Ki-67). CTLR also induced apoptosis and G2/M phase cell cycle arrest. Moreover, quantitative analysis of the intracellular uptake of lenvatinib using liquid chromatography and mass spectrometry demonstrated that intracellular uptake of lenvatinib was significantly increased 48 h following irradiation. These data suggest that increased membrane permeability caused by irradiation increases the intracellular concentration of levatinib, contributing to the synergistic effect. This mechanism-based potential of combination therapy suggests a powerful new therapeutic strategy for advanced thyroid cancer with fewer side effects and might be a milestone for developing a regimen in clinical practice.

Efficacy of Combination Therapy with Lenvatinib and Radioactive Iodine in Thyroid Cancer Preclinical Model.

Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and 131I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, 131I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after 131I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.

Evaluation of an aspiration-type semiautomatic cutting biopsy needle.

PURPOSE: The purpose of this study was to evaluate an aspiration-type semiautomatic cutting biopsy needle for biopsy of bovine tissue. MATERIAL AND METHODS: Aspiration-type semiautomatic cutting biopsy needles (18 gauge × 160 mm) with aspiration (Group A), aspiration-type semiautomatic biopsy needles without aspiration (Group Wo), or normal-type semiautomatic biopsy needles (18 gauge × 150 mm) (Group N) were used in 10 biopsies each of bovine liver or lung. The specimens were weighed with an electronic balance. RESULTS: Mean (standard deviation) weights for bovine liver specimens in Groups A, Wo, and N were 6.80 (0.615) mg, 5.62 (0.843) mg, and 4.19 (0.140) mg, respectively. Mean weights of bovine lung specimens from Groups A, Wo, and N were 2.98 (0.828) mg, 2.67 (0.832) mg, and 1.94 (0.864) mg, respectively. A significant difference was seen between the 3 groups for bovine liver. However, a significant difference was only seen between Groups A and N for bovine lung. CONCLUSION: Bovine liver and lung specimens obtained using the aspiration-type semiautomatic cutting biopsy needle were heavier than those obtained using the normal-type semiautomatic biopsy needle.

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis].

BACKGROUND: Dexmedetomidine (Precedex®)is an agonist of a2-adrenergic receptors in certain parts of the brain. It was approved for "procedural sedation in the non-intubation in under local anesthesia" in June 2013 in Japan. However, because of metabolism delay, dexmedetomidine has to be administered carefully to patients with liver dysfunction. PURPOSE: To evaluate the feasibility and safety of sedation using dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction. METHODS: Thirty consecutive cases of percutaneous arterial chemoembolization for hepatocellular carcinoma with hepatitis C-related cirrhosis(male, 23; female, 7; age, 74±5.9; weight, 62.7±12.3 kg; Child-Pugh A, 23; Child-Pugh B, 7)were analyzed retrospectively. Dexmedetomidine was administered at 3 mg/kg/h for 15 minutes as the initial loading dose and at 0.4 mg/kg/h as the maintenance dose. The sedation level was evaluated using the Ramsay sedation scale. RESULTS: In 30 of 30 cases, percutaneous arterial chemoembolization therapy could be performed with dexme- detomidine sedation. In 27 of 30 cases, the procedure was completed with the maintenance dose of 0.4 mg/kg/h. In 3 of 30 cases, the maintenance dose was increased to 0.6 mg/kg/h because of patient body motion. The mean administration time of dexmedetomidine was 82±30 minutes. The level of sedation measured with the Ramsay sedation scale at the end of the procedure was 3 points in 29 cases and 5 points in one case. Adverse events occurred in 3 of 30 cases. Intravenous drip leakage occurred in one case, vertigo occurred in one case, and vomiting occurred in one case. There were no adverse events requiring treatment. CONCLUSION: Sedation with dexmedetomidine in percutaneous arterial chemoembolization for hepatocellular carcinoma with liver dysfunction was feasible and safe.

Radiation dose of nurses during IR procedures: a controlled trial evaluating operator alerts before nursing tasks.

PURPOSE: To compare radiation exposure of nurses when performing nursing tasks associated with interventional procedures depending on whether or not the nurses called out to the operator before approaching the patient. MATERIALS AND METHODS: In a prospective study, 93 interventional radiology procedures were randomly divided into a call group and a no-call group; there were 50 procedures in the call group and 43 procedures in the no-call group. Two monitoring badges were used to calculate effective dose of nurses. In the call group, the nurse first told the operator she was going to approach the patient each time she was about to do so. In the no-call group, the nurse did not say anything to the operator when she was about to approach the patient. RESULTS: In all the nursing tasks, the equivalent dose at the umbilical level inside the lead apron was below the detectable limit. The equivalent dose at the sternal level outside the lead apron was 0.16 µSv ± 0.41 per procedure in the call group and 0.51 µSv ± 1.17 per procedure in the no-call group. The effective dose was 0.018 µSv ± 0.04 per procedure in the call group and 0.056 µSv ± 0.129 per procedure in the no-call group. The call group had a significantly lower radiation dose (P = .034). CONCLUSIONS: Radiation doses of nurses were lower in the group in which the nurse called to the operator before she approached the patient.

Portopulmonary venous anastomosis in balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices.

BACKGROUND AND AIM: Several reports have described portopulmonary venous anastomosis (PPVA). However, in balloon-occluded retrograde transvenous obliteration (BRTO), attention has not been paid to paradoxical embolism. The objective of this study was to investigate the existence of a right-left shunt due to PPVA when the drainage vein is occluded by a balloon during BRTO. METHODS: The subjects were 19 patients who underwent BRTO. Whether PPVA was present was confirmed on balloon-occluded retrograde transvenous venography (BRTV). After BRTV, a retrograde bolus injection of 20 mL of carbon dioxide (CO2 ) via the balloon catheter was performed under balloon occlusion, and the flow of bubbles into both ventricles was observed with four-chamber view echocardiography. During the same balloon occlusion, bolus injection of CO2 into the inferior vena cava was performed, followed by echocardiography. RESULTS: PPVA was confirmed on BRTV in four patients (21.1%). On echocardiography with retrograde CO2 injection, bubbles were confirmed in the left ventricle in six patients (31.6%). On echocardiography with CO2 injection into the inferior vena cava, bubbles were not confirmed in the left ventricle in any cases. CONCLUSIONS: When the draining vein was occluded with a balloon and blood flow in a gastrorenal or gastrocaval shunt was stopped during BRTO, PPVA was confirmed in 21.1% of cases on retrograde angiography, and a right-left shunt was confirmed in 31.6% of cases on echocardiography.

HPLC-fluorescence determination of thiol compounds in the serum of human male and female subjects using HILIC-mode column.

High-performance liquid chromatography-fluorescence detection using a hydrophilic interaction chromatography-mode column (ZIC®-HILIC) was used to determine four kinds of thiol compounds in human serum. Sera were obtained from 34 subjects for this study (17 male subjects aged 22-38 years and 17 female subjects aged 18-38 years). Serum cysteine, cysteinylglycine, glutathione, and γ-glutamylcysteine, derivatized with ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate, were separated on the ZIC®-HILIC column and quantified. The serum concentrations of cysteine, cysteinylglycine, glutathione and γ-glutamylcysteine were 226 ± 4.7, 23.4 ± 1.3, 3.7 ± 0.2 and 3.2 ± 0.1 µm, respectively. In addition, the concentrations of serum thiol compounds from male subjects were significantly higher than those of the female subjects (p < 0.05).

Direct puncture embolization using N-butyl cyanoacrylate for a hepatic artery pseudoaneurysm.

Massive hemobilia caused by hepatic artery pseudoaneurysm is an uncommon but potentially fatal complication that can occur after biliary intervention. Previous intervention or surgery, atherosclerotic disease, inflammation and even anatomic variants may make the pseudoaneurysm inaccessible to transcatheter approach, therefore it is not always feasible. The present report describes a case of successful embolization of a hepatic artery pseudoaneurysm with N-butyl cyanoacrylate via direct puncture as an alternative approach. The case presentation is followed by the technical points and the properties of N-butyl cyanoacrylate that are particularly advantageous for use in direct puncture procedures.

Comparison of Tc-99m GSA scintigraphy and CT volumetry for evaluation in portal vein embolization.

PURPOSE: To determine the correlation of the rate of change of each future remnant liver (FRL) before and after portal vein embolization (PVE), by CT volumetry and Tc-99m galactosyl human serum albumin scintigraphy (GSA scintigraphy). MATERIAL AND METHODS: From December 2007 to July 2012, ten patients underwent PVE before hepatic resection. CT volumetry and GSA scintigraphy were performed before and after PVE. The FRL was divided at Cantlie's line for CT volumetry, and volume change rates before and after PVE were calculated. The maximum removal rate (Rmax) was calculated using a radiopharmacokinetic model in GSA scintigraphy. The FRL Rmax change rates before and after PVE were calculated. The correlation between the volume change rates and the Rmax change rates was analyzed. RESULTS: The FRL volume change rate was 1.28 ± 0.26 (mean ± SD); the FRL hypertrophied in all patients significantly (p = 0.005). The FRL Rmax change rate was 1.66 ± 0.75; excluding one patient, there was significant FRL Rmax increase (p = 0.022). Although both increased significantly, no correlation between the volume change rate and the Rmax change rate was observed. CONCLUSION: No correlation was observed between the FRL volume rate and the Rmax rate.

Intra-arterial infusion of thrombin: animal experiments.

PURPOSE: Thrombin inhibits cadherin on vascular endothelial cells, rapidly and reversibly increasing endothelial permeability. The purpose of this study was to evaluate the feasibility of trans-arterial infusion with thrombin. MATERIAL AND METHODS: Ten rabbits with right thigh tumor were randomly divided into two groups: A thrombin group and a control group. In the thrombin group, a suspension of thrombin (300 IU), cisplatin (3 mg), lipiodol (0.3 ml) and iopamidol (0.3 ml) was infused into the right femoral artery. In the control group, a suspension of cisplatin, lipiodol and iopamidol was infused. Platinum concentrations in plasma were measured five and ten minutes after administration. Platinum concentrations were also measured in tumor specimens excised 30 minutes after infusion. RESULTS: At both five and ten minutes after infusion, platinum concentrations in plasma were significantly lower for the thrombin group than for the control group. Platinum concentration in tumor tissue was significantly higher for the thrombin group than for the control group. CONCLUSION: The present results suggest that transarterial infusion with thrombin may offer a number of pharmacological advantages.

Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

Self-organizing map improves understanding on the hydrochemical processes in aquifer systems.

The holistic understanding of hydrochemical features is a crucial task for management and protection of water resources. However, it is challenging for a complex region, where multiple factors can cause hydrochemical changes in studied catchment. We collected 208 groundwater samples from such region in Kumamoto, southern Japan to explicitly characterize these processes by applying machine learning technique. The analyzed groundwater chemistry data like major cations and anions were fed to the self-organizing map (SOM) and the results were compared with classical classification approaches like Stiff diagram, standalone cluster analysis and score plots of principal component analysis (PCA). The SOM with integrated application of clustering divided the data into 11 clusters in this complex region. We confirmed that the results provide much greater details for the associated hydrochemical and contamination processes than the traditional approaches, which show quite good correspondence with the recent high resolution hydrological simulation model and aspects from geochemical modeling. However, the careful application of the SOM is necessary for obtaining accurate results. This study tested different normalization approaches for selecting the best SOM map and found that the topographic error (TE) was more important over the quantization error (QE). For instance, the lower QE obtained from min-max and log normalizations showed problems after clustering the SOM map, since the QE did not confirm the topological preservation. In contrast, the lowest TE obtained from Z-transformation data showed better spatial matching of the clusters with relevant hydrochemical characteristics. The results from this study clearly demonstrated that the SOM is a helpful approach for explicit understanding of the hydrochemical processes on reginal scale that may capably facilitate better groundwater resource management.

Carcinoma of Unknown Original Identified as Renal Cell Carcinoma by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Scan: A Report of Two Cases.

Imaging is useful in identifying the primary site of an unknown primary cancer, and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is an excellent imaging modality for identifying the primary lesion. However, a potential limitation is that 18F-FDG is physiologically excreted from the kidneys, thus masking renal lesions. In this report, we describe two cases of cancer of unknown origin that were detected as originating from renal cancer on 18F-FDG PET/CT. Both cases showed abnormal nodular accumulation of 18F-FDG in the kidney, which can be distinguished from the physiological excretion of 18F-FDG in the urinary tract. It is clinically crucial to be able to confirm the possibility of renal cancer, and careful observation of the urinary tract with 18F-FDG PET/CT can be useful.

Two cases of 18F-FDG-PET/CT positive Schloffer tumor following curative surgery of colon cancer.

We report two cases of Schloffer tumor that required resection after radical colon cancer surgery because of suspected lymph node recurrence on contrast-enhanced (CE) CT and 18F-FDG-PET/CT. Case1 is a 69-year-old man with sigmoid colon cancer pStage IIA, and case2 is a 61-year-old man with descending colon cancer pStage IIIB.

Estimation of the degree of surgical difficulty anticipated for pancreatoduodenectomy: Preoperative and intraoperative factors.

BACKGROUND: Pancreatoduodenectomy (PD) is a technically complex procedure. Preoperative anticipation of the degree of difficulty could contribute to patient safety during trainee surgical education. METHODS: We prospectively administered a questionnaire to the chief surgeon after each PD performed between 2016 and 2018 at our institution (99 consecutive patients). The surgeon rated the difficulty of the procedure; we then analyzed this information against perioperative data. RESULTS: The difficulty of PD was ranked as simple (29.3%), moderate (40.4%), or difficult (30.3%). The difficult procedures required an operative time of 2 h longer than the simple procedures and involved an additional 800 mL of intraoperative blood loss. Postoperative complications were similar in all groups. Multivariate analysis revealed that an unrecognized tissue plane for dissection was an independent determinant of a difficult PD (odds ratio [OR]: 89.2, 95% confidence interval [CI]: 9.2-861.2; P < .001). Independent predictors of a difficult PD were a pretreatment status of borderline resectable or unresectable (OR: 21.9, CI: 5.3-90.6; P < .001) and cholangitis during the preoperative period (OR: 4.1, CI: 1.3-13.0; P = .017). CONCLUSIONS: Surgeons deem the PD procedure to be difficult when the proper tissue plane for dissection is unrecognized. Preoperative assessment of the anticipated difficulty could contribute to better operative management.