Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial.

PURPOSE: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in breast cancer; high expression is associated with an adverse prognosis. Patritumab deruxtecan (HER3-DXd) is an investigational HER3-targeted antibody-drug conjugate that is being evaluated as a novel treatment in HER3-expressing advanced breast cancer in the U31402-A-J101 study. METHODS: Adults with disease progression on previous therapies were eligible. Patients in the dose-escalation, dose-finding, and dose-expansion parts received HER3-DXd 1.6-8.0 mg/kg intravenously once every 3 weeks or one of two alternative dosing regimens. In the dose-escalation part, the primary objectives were to determine the maximum tolerated dose and recommended dose for expansion (RDE). The safety and efficacy of the RDE were assessed during dose expansion. RESULTS: One hundred eighty-two enrolled patients received ≥1 dose of HER3-DXd. Patients had a median of five previous therapies for advanced disease. Efficacy results are reported across clinical subtypes: hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer (n = 113; objective response rate [ORR], 30.1%; median progression-free survival [mPFS], 7.4 months), triple-negative breast cancer (n = 53; ORR, 22.6%; mPFS, 5.5 months), and HER2-positive breast cancer (n = 14; ORR, 42.9%; mPFS, 11.0 months). Objective responses were observed in cancers with HER3-high and HER3-low membrane expression. Dose-limiting toxicities observed during dose selection were decreased platelet count and elevated aminotransferases. In dose expansion, GI and hematologic toxicities were the most common treatment-emergent adverse events (TEAEs) observed. Grade ≥3 TEAEs were observed in 71.4% of patients, and 9.9% discontinued treatment because of TEAEs. Three grade 3 and one grade 5 treatment-related interstitial lung disease events occurred. CONCLUSION: HER3-DXd demonstrated a manageable safety profile and durable efficacy in heavily pretreated patients across clinical subtypes. These data warrant further evaluation of HER3-DXd in patients with HER3-expressing metastatic breast cancer.

[Association of D-dimer Levels with Complications after Subcutaneous Implantable Central Venous Port Placement in Combination Chemotherapy with Bevacizumab for Colorectal Cancer].

Bevacizumab(BV)combination chemotherapy in colorectal cancer under subcutaneously implanted central venous port (CVP)implantation may cause complications after the implantation. Measurement of D-dimer is recommended to predict thromboembolism and other complications, but its relevance to complications after CVP implantation remains unclear. In this study, we investigated the association between D-dimer and complications after CVP implantation in 93 patients with colorectal cancer who received BV combination chemotherapy. Complications after CVP implantation occurred in 26 patients (28%), and those with VTE showed higher D-dimer values at the onset of the complication. The D-dimer values of the patients with VTE displayed a sharp increase at the onset of the disease, while those with an abnormal CVP implantation site showed a more variable course. Measurement of D-dimer levels appeared useful in estimating the incidence of VTE and abnormal CVP implantation sites in post-CVP implantation complications of BV combination chemotherapy for colorectal cancer. Further, monitoring not only the quantitative values but also the fluctuations over time is also important.

Butyrylcholinesterase level as an independent prognostic factor for overall survival in patients on maintenance hemodialysis: a single-center retrospective study.

BACKGROUND: We investigated whether butyrylcholinesterase (BChE) was independently related to the overall survival (OS) of patients on maintenance hemodialysis (MHD). METHODS: Baseline information, serum BChE level, and other laboratory data were collected from 295 patients on MHD in a single HD hospital in 2018. We retrospectively investigated the mortality of these patients after 38 months. We assessed the prognostic markers such as the Geriatric Nutritional Risk Index (GNRI), Erythropoiesis Resistance Index (ERI), and Simplified Creatinine Index (SCI) of each patient. The primary objective was to examine the impact of BChE on OS. The secondary objective included the designation of a risk score in predicting the OS. RESULTS: We evaluated 284 patients. The median value of the serum BChE level was 206 IU/L. Of 284 patients evaluated, eighty-six patients died; all had a higher ERI and a lower serum BChE level, SCI, and GNRI than the surviving patients. The optimal cutoff values of the BChE level, GNRI, ERI, and SCI for OS were 166 IU/L, 90.0, 8.00, and 20.6, respectively. The multivariate Cox regression analysis showed that the age, HD vintage, dialysis dose, GNRI of < 90.0, and serum BChE level of < 166 IU/L (hazard ratio, 2.03; P = 0.003) were the independent prognostic factors. We designed a risk score consisting of the GNRI and serum BChE level. The predictive value of our risk score was superior to that of GNRI alone. CONCLUSION: The serum BChE level could be an independent prognostic factor for patients on MHD.

Competition between Osmotic Squeezing versus Friction-Driven Swelling of Gels.

Some types of hydro-gels have almost the same equilibrium swelling volume in water and in ethylene glycol (EG), a highly viscous liquid completely miscible with water. Experiments showed that when a gel fully swollen with EG is immersed into a large amount of water, it temporarily swells up and then relaxes to the equilibrium volume in water. The temporary swelling is explained by the friction force exerted on the gel network from the outward EG flux In this paper, we experimentally show that the temporary swelling is suppressed by adding linear PEG (polyethylene glycol) in the outer water. Although the suppression seems to be explained by the osmotic pressure (i.e., by the same mechanism as the conventional osmotic squeezing), our theoretical analysis reveals that the effect of PEG is much stronger than that expected from the equilibrium osmotic pressure, implying that the PEG chains are condensed on the gel surface.

[Exploratory Study of the Risk Factors for Acute Kidney Injury in the Cisplatin Combination Chemotherapy for Solid Cancer].

In the present study, we investigated the rate of cisplatin(CDDP)-induced acute kidney injury(CIA)and examined its association with various clinical factors in the combination therapy with CDDP for solid cancers. A total of 726 cases of solid cancer that had been indicated for the CDDP combination regimen from December 2012 to December 2013 were enrolled. CIA occurred in 48 cases(6.6%). The multivariate analysis revealed that diabetes, the regular use of non-steroidal anti- inflammatory drugs(NSAIDs), first dose of CDDP, and severe hyponatremia(≥Grade 3)within one week after CDDP administration were significantly associated with an increased risk for CIA, whereas magnesium supplementation was associated with a significantly reduced risk for CIA. Particularly, diabetes and cardiovascular disease were identified as risk factors for CIA in patients with esophageal and head and neck cancers. Based on the results of this survey, it is important to formulate preventive measures, evaluate risk factors, and respond rapidly.

Pre-dialysis serum creatinine as an independent predictor of responsiveness to zinc supplementation among patients on hemodialysis.

BACKGROUND: To investigate whether pre-dialysis level of serum creatinine (SCre) could indicate the responsiveness to zinc supplementation of patients on maintenance hemodialysis (MHD). METHODS: We retrospectively reviewed the results of our previous randomized study of 91 patients who had been on MHD and received zinc supplementation with either zinc acetate hydrate (ZAH; zinc, 50 mg/day) or polaprezinc (PPZ; zinc, 34 mg/day). A late response to zinc supplementation was defined as a serum zinc level of < 80 µg/dL three months after the study began. Patients were divided into two groups: late response (serum zinc level < 80 µg/dL) and early response (serum zinc level ≥ 80 µg/dL). Factors independently associated with a late response to zinc supplementation were determined using inverse probability of treatment weighting (IPTW) multivariate logistic analysis. RESULTS: Of 91 patients, 86 continued to receive zinc supplementation after three months. The mean pre-dialysis SCre level was 10.0 mg/dL. The number of patients with a late response and response to zinc supplementation was 32 and 54, respectively. There was a significant negative correlation between the pre-dialysis SCre and the Δserum zinc change for 3 months. (r = - 0.284, P = 0.008). IPTW multivariate analysis showed that a pre-dialysis SCre level ≥ 10.0 mg/dL (odds ratio, 3.71; 95% confidence interval; 1.24-11.1, P = 0.022) was an independent factor associated with a late response to zinc supplementation. CONCLUSIONS: Pre-dialysis SCre level was independently associated with responsiveness to zinc supplementation after three months in patients on MHD.

Gel dynamics in the mixture of low and high viscosity solvents: Re-entrant volume change induced by dynamical asymmetry.

When a gel swollen with a certain solvent is placed in the bath of another solvent, the gel swells or de-swells depending on the thermodynamic affinity to the gel. Toyotama et al. [Langmuir 22, 1952 (2006)] reported an unusual volume change of chemical gels that cannot be explained by the affinity difference: when a chemical gel saturated with water is immersed in ethylene glycol (EG), although those solvents have almost the same affinity to the polymer, the gel first shrinks and then re-swells and finally takes the same equilibrium volume as the initial. The re-entrant swelling was attributed to different diffusion rates between water and EG (dynamical asymmetry), but the detailed mechanism was not clarified. In this paper, we experimentally show that the characteristic times for the temporal shrinking and subsequent volume relaxation are proportional to the squared system size. This indicates that the phenomenon is governed by diffusive dynamics. According to this observation, we propose a coupled diffusion model explaining the physical mechanism of the re-entrant volume change.

Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single-center, open-label, prospective randomized study.

The efficacy and safety of zinc acetate hydrate (ZAH) for zinc supplementation in patients on maintenance hemodialysis (MHD) remains unknown. In this prospective, single-center, open-label, parallel-group trial for MHD patients with serum zinc level <70 µg/dL, we compared ZAH (zinc; 50 mg/day) and polaprezinc (PPZ; zinc; 34 mg/day) beyond 6-month administration in a 1:1 randomization manner. The ZAH and PPZ groups had 44 and 47 patients, respectively. At 3 months, the change rate of serum zinc levels in the ZAH group was significantly higher than that in the PPZ group. Three months after the study, serum copper levels significantly decreased in the ZAH group, but not in the PPZ group. No significant differences were noted in anemia management in either group. ZAH was superior to PPZ in increasing serum zinc levels. Clinicians should note the stronger decline in serum copper levels when using ZAH for MHD patients.

[Risk Factors of Thromboembolism in Colorectal Cancer Patients Receiving Combination Chemotherapy with Bevacizumab].

We investigated the incidence of thromboembolism in patients receiving combination chemotherapy with bevacizumab (BV)for colorectal cancer and examined its association with clinical factors. Between July 2007 and April 2014, 250 patients with colorectal cancer received combination chemotherapy with BV. Thromboembolism occurred in 24 cases(9.6%). Five predictive risk factors(platelet count B350,000/µL, hemoglobin <10 g/dL, leukocyte count>11,000/mL, body mass index B25.3 kg/m2, and D-dimer B1.44 µg/mL)were set based on a previous report, and the corresponding number of risk factors for thromboembolism and incidence of thromboembolism were examined. The results of multivariate analysis showed that the occurrence of 3 or more risk factors conferred a significant risk for the incidence of thromboembolism. Due to the increased risk of developing thromboembolism in such patients, special attention during management is required.

[Survey of Cholinergic Symptoms in Patients with Colorectal Cancer Who Were Receiving Irinotecan Hydrochloride Combination Chemotherapy].

We investigated the incidence of cholinergic symptoms related to irinotecan hydrochloride(CPT-11)and examined their association with clinical factors. The subjects were 61 patients with colorectal cancer for whom combination chemotherapy with CPT-11 was indicated between May 2008 and December 2014. The incidence of CPT-11-related cholinergic symptoms was investigated. Cholinergic symptoms were observed in 46 patients(75.4%), of whom 29(47.5%)showed Grade 2 or higher symptoms as follows: nasal discharge(47.5%), lacrimation(39.3%), nausea/vomiting(29.5%), and watery stool (26.2%). The results of the multivariate analysis showed that high-dose CPT-11 administration(150mg/m2)was a significant risk factor for the appearance of cholinergic symptoms and that PS 0 was a significant factor for reducing the onset of symptoms. It is important to adequately manage cholinergic symptoms, considering these clinical factors.

Low serum butyrylcholinesterase is independently related to low fetuin-A in patients on hemodialysis: a cross-sectional study.

PURPOSE: Fetuin-A, which plays a protective role against the atherosclerosis and progression of vascular calcification, is decreased in patients on hemodialysis (HD). Fetuin-A and serum butyrylcholinesterase (BChE) levels decrease during malnutrition. We explored whether BChE was independently related to fetuin-A in patients on HD. METHODS: Laboratory data including BChE and serum fetuin-A were acquired from 230 patients on HD between August 2017 and April 2018. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). Abdominal aortic calcification index (ACI) was measured using computed tomography. Patients were stratified into two groups: low fetuin-A (< lowest quartile) and non-low fetuin-A (≥ lowest quartile) groups. Patient background, medication, and laboratory data were compared. The receiver operating characteristic analysis was conducted to determine the optimal cutoff values of BChE and GNRI for lower fetuin-A level. Factors independently related with lower fetuin-A levels were determined using multivariate logistic regression analysis. RESULTS: The lowest quartile value of fetuin-A and optimal cutoff values of BChE and GNRI were 0.213 g/L, 200 IU/L, and 92.6, respectively. The study included 57 and 173 patients in the low fetuin-A and non-low fetuin-A groups, respectively. Significant between-group differences were observed for age, C-reactive protein (CRP), history of cardiovascular disease, serum albumin, GNRI, and BChE. Multivariate analysis showed that BChE of < 200 IU/L [odds ratio (OR) 3.05], CRP (OR 2.49), and GNRI of < 92.6 (OR 2.34) were independent factors for lower fetuin-A level after adjusting for confounders. CONCLUSIONS: BChE was a significant independent marker for fetuin-A levels in patients on HD, in addition to GNRI.

Proton pump inhibitor as an independent factor of progression of abdominal aortic calcification in patients on maintenance hemodialysis.

BACKGROUNDS: Proton pump inhibitors (PPIs) can be associated with vascular calcification in patients undergoing dialysis through hypomagnesemia. However, only few studies have demonstrated the influence of PPIs on vascular calcification in patients on maintenance hemodialysis (HD). This study aimed to investigate whether the use of PPIs accelerates vascular calcification in patients on HD. MATERIALS AND METHODS: We retrospectively evaluated 200 HD patients who underwent regular blood tests and computed tomography (CT) between 2016 and 2017. The abdominal aortic calcification index (ACI) was measured using abdominal CT. The difference in the ACI values between 2016 and 2017 was evaluated as ΔACI. Patients were divided into PPI and non-PPI groups, and variables, such as patient background, medication, laboratory data, and ΔACI were compared. Factors independently associated with higher ΔACI progression (≥ third tertile value of ΔACI in this study) were determined using multivariate logistic regression analysis. RESULTS: The PPI and non-PPI groups had 112 (56%) and 88 (44%) patients, respectively. Median and third tertile value of ΔACIs were 4.2% and 5.8%, respectively. Serum magnesium was significantly lower in the PPI (2.1 mg/dL) than in the non-PPI (2.3 mg/dL) group (P <0.001). Median ΔACI was significantly higher in the PPI (5.0%) than in the non-PPI (3.8%) group (P = 0.009). A total of 77 (39%) patients had a higher ΔACI. Multivariate analysis revealed that PPIs (odds ratio = 2.23; 95% confidence interval = 1.11-4.49), annual mean calcium phosphorus product, ACI in 2016, baseline serum magnesium levels, and HD vintage were independent factors associated with higher ΔACI progression after adjusting for confounders. CONCLUSION: PPI use may accelerate vascular calcification in patients on HD. Further studies are necessary to elucidate their influence on vascular calcification.

The relationship between poor nutritional status and progression of aortic calcification in patients on maintenance hemodialysis.

BACKGROUND: Although aortic calcification has a significant negative impact on prognosis in patients on hemodialysis (HD), risk factors for aortic calcification progression remain unclear. The aim of this study was to investigate the relationship between malnutrition and aortic calcification progression in patients on HD. METHODS: Between April 2015 and October 2016, we treated 232 patients on HD. Of those, we retrospectively evaluated data from 184 patients who had had regular blood tests and computed tomography (CT) scans. The abdominal aortic calcification index (ACI) was quantitatively measured by abdominal CT. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). A normalized treatment ratio of functional urea clearance was evaluated by Kt/V. The difference in ACI values between 2015 and 2016 was evaluated as a ΔACI, and patients were stratified into two groups according to ΔACI value: high (≥75th percentile, ΔACI-high group) and low (<75th percentile, ΔACI-low group). Variables such as age, sex, comorbidities, dialysis vintage, serum data, and GNRI were compared between ΔACI-high and ΔACI-low patients. Factors independently associated with a higher ΔACI progression (ΔACI ≥75th percentile) were determined using multivariate logistic analysis. RESULTS: Median values of ACIs in 2015 and 2016 were 40.8 and 44.6%, respectively. Of 184 patients, 125 (68%) patients experienced ACI progression for 1 year. The median ΔACI and 75th percentile of ΔACI were 2.5% and 5.8%, respectively. The number of patients in the ΔACI-low and ΔACI-high groups were 128 (70%) and 56 (30%), respectively. There were significant differences in sex, presence of diabetic nephropathy, HD vintage, serum albumin, serum phosphate, C-reactive protein, intact parathyroid hormone, Kt/V, and GNRI. Multivariate logistic regression analysis revealed that independent factors associated with a higher ΔACI progression were male sex, serum phosphate levels, HD vintage, and GNRI of < 90. CONCLUSIONS: Our results suggest that poor nutritional status is an independent risk factor for the progression of aortic calcification. Nutrition management may have the potential to improve progression of aortic calcification in patients on HD. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000028050 .

Butyrylcholinesterase level as an independent factor of erythropoiesis-stimulating agent resistance in patients on maintenance hemodialysis: a single-center cross-sectional study.

BACKGROUND: Erythropoiesis-stimulating agent (ESA) responsiveness is related to the nutritional status of patients on hemodialysis (HD). Serum butyrylcholinesterase (BChE), an alpha-glycoprotein, may decrease in case of malnutrition. We investigated whether BChE was independently related to ESA resistance in patients on HD. METHODS: The laboratory data and ESA resistance index (ERI), defined as ESA dosage per week divided by dry weight and hemoglobin, were investigated in 215 patients on HD between July and September 2017. Malnutrition was defined as Geriatric Nutritional Risk Index (GNRI) of < 91.2. The patients were stratified into two groups: ERI-high (ERI ≥ 9.44) and ERI-low (ERI < 9.44) groups. Variables such as patient's background, medication, and laboratory data were compared between the two groups. The optimal cutoff value of BChE for higher ERI was determined using receiver operating characteristic analysis. Factors independently associated with higher ERI were determined using multivariate logistic regression analysis. RESULTS: The median and optimal cutoff values of ERI and BChE were 6.51 and 200 IU/L, respectively. The study included 71 (33%) and 144 (67%) patients in the ERI-high and ERI-low groups, respectively. Significant between-group differences were observed concerning age, hemoglobin, ESA dose, lipid profiles, serum albumin, body mass index, GNRI, iron metabolism markers, ferric medicines, and BChE. Multivariate analysis showed that BChE < 200 IU/L (odds ratio 3.67; 95% confidence interval 1.73-7.77) continued to be an independent factor associated with higher ERI after adjusting for potential confounders, which was a similar odds ratio as GNRI < 91.2. CONCLUSION: BChE may be an independent indicator of ESA resistance.

Presurgical axitinib therapy increases fibrotic reactions within tumor thrombus in renal cell carcinoma with thrombus extending to the inferior vena cava.

BACKGROUND: Clinical benefits of presurgical axitinib therapy for renal cell carcinoma (RCC) extending into the inferior vena cava (IVC) remain unclear. We aimed to investigate surgical benefits and pathological antitumor effects of presurgical axitinib therapy for RCC with IVC thrombus. METHODS: Of 56 consecutive RCC patients with IVC thrombus between January 1994 and December 2016, 41 patients who underwent radical nephrectomy (RN) were categorized as upfront RN (Upfront group) or presurgical axitinib followed by RN (Presurgical group). We retrospectively evaluated safety, radiologic tumor responses, and Ki-67 proliferation index before and after axitinib administration in the Presurgical group. Surgical outcomes, postoperative complications, and fibrosis within the IVC thrombus were compared between the Upfront and Presurgical groups. RESULTS: The number of patients in the Upfront and Presurgical groups was 31 and 10, respectively. Major presurgical axitinib-related adverse events were grade 2 or 3 hypertension (50%). The median radiological tumor response in the renal tumor, IVC thrombus length, and IVC thrombus volume were -19%, -21 mm, and -54%, respectively. The fibrosis within the IVC thrombus was significantly higher in the Presurgical group (10%) than in the Upfront group (3.4%). The Ki-67 proliferation index was significantly decreased in RN specimens (7.3%) versus needle biopsy specimens (23%) in the Presurgical group. Blood loss and operative duration were significantly lower and shorter, respectively, in the Presurgical group than in the Upfront group. CONCLUSIONS: Presurgical axitinib therapy enhanced tumor reduction accompanied by fibrosis and may contribute to surgical risk reduction for selected patients.

Opacity of big toenail predicts poor prognosis in patients with end-stage renal disease on hemodialysis.

BACKGROUND: The impact of nail abnormalities on prognosis in hemodialysis patients is unknown. This study investigated whether toenail opacity as a readout of nail abnormalities predicted prognosis in hemodialysis patients. METHODS: In this observational study, 494 eligible hemodialysis patients who received hemodialysis at Oyokyo Kidney Research Institute between September 2010 and December 2015 were included. The presence of nail abnormalities was objectively evaluated by big toenail opacity ratio measurement. Primary endpoint was overall survival, and secondary endpoints were lower limb amputation and determination of risk factors for poor prognosis among patient demographics, comorbidities, blood tests, and big toenail opacity. Overall survival and lower limb survival were evaluated using the Kaplan-Meier method with log-rank test. Multivariate Cox regression analyses assessed predictors for poor prognosis. RESULTS: Big toenail opacity was found in 259 (52%) patients. Patients with big toenail opacity were significantly older, had shorter duration of dialysis, higher prevalence rates of diabetes mellitus (DM), cardiovascular disease (CVD), and higher mortality rates than those without opacity. Presence of big toenail opacity predicted poor prognosis for both overall and lower limb survival. Multivariate Cox regression analyses revealed serum albumin, the presence of DM and big toenail opacity were independent risk factors for both poor overall and lower limb survivals. CONCLUSION: The prevalence of big toenail opacity was high in hemodialysis patients. Despite the short observation period, our findings indicated that big toenail opacity had significant predictive power for poor overall and lower limb survival.

The influence of serum uric acid on renal function in patients with calcium or uric acid stone: A population-based analysis.

OBJECTIVES: To determine the influence of serum uric acid (UA) levels on renal impairment in patients with UA stone. MATERIALS AND METHODS: We retrospectively analyzed 463 patients with calcium oxalate and/or calcium phosphate stones (CaOx/CaP), and 139 patients with UA stones. The subjects were divided into the serum UA-high (UA ≥ 7.0 mg/dL) or the UA-low group (UA < 7.0 mg/dL). The control group comprised 3082 community-dwelling individuals that were pair-matched according to age, sex, body mass index, comorbidities, hemoglobin, serum albumin, and serum UA using propensity score matching. We compared renal function between controls and patients with UA stone (analysis 1), and between patients with CaOx/CaP and with UA stone (analysis 2). Logistic regression analysis was used to evaluate the impact of the hyperuricemia on the development of stage 3 and 3B chronic kidney disease (CKD) (analysis 3). RESULTS: The renal function was significantly associated with serum UA levels in the controls and patients with CaOx/CaP and UA stones. In pair-matched subgroups, patients with UA stone had significantly lower renal function than the control subjects (analysis 1) and patients with CaOx/CaP stones (analysis 2) regardless of hyperuricemia. Multivariate logistic regression analysis revealed that patients with UA stone, CaOx/CaP, hyperuricemia, presence of cardiovascular disease, higher body mass index, older age and lower hemoglobin had significantly higher risk of stage 3 and 3B CKD (analysis 3). CONCLUSION: Patients with UA stones had significantly worse renal function than controls and CaOx/CaP patients regardless of hyperuricemia. Urolithiasis (CaOx/CaP and UA stone) and hyperuricemia had an association with impaired renal function. Our findings encourage clinicians to initiate intensive treatment and education approaches in patients with urolithiasis and/or hyperuricemia in order to prevent the progression of renal impairment.

Overall survival of high-risk prostate cancer patients who received neoadjuvant chemohormonal therapy followed by radical prostatectomy at a single institution.

BACKGROUND: The optimal treatment for high-risk prostate cancer (PCa) remains to be established. We previously reported favorable, biochemical recurrence-free survival in high-risk PCa patients treated with a neoadjuvant gonadotropin-releasing hormone agonist or antagonist and estramustine phosphate (EMP) (chemohormonal therapy; CHT) followed by radical prostatectomy (RP). We conducted a retrospective study to elucidate the clinical benefit of neoadjuvant CHT for high-risk PCa patients. METHODS: We reviewed the clinical and pathological records of 1254 PCa patients who underwent RP and bilateral pelvic lymphadenectomy between July 1996 and April 2016 at Hirosaki University. According to the D'Amico risk classification, we focused on 613 patients in the high-risk group. The high-risk PCa patients were further divided into two groups based on whether the patients received neoadjuvant CHT before RP (EMP group) or not (non-EMP group). The endpoint was overall survival (OS) after surgery. RESULTS: The 5- and 10-year OS rates were 98.5 and 92.6%, respectively. The 10-year OS rate in the EMP group was significantly higher compared to the non-EMP group (P = 0.021). In multivariate analysis, administration of neoadjuvant CHT, lymph node involvement, and castration-resistant PCa status were significantly associated with OS. CONCLUSIONS: RP with neoadjuvant CHT using EMP for high-risk PCa patients provided excellent long-term OS.

Contrast media enhancement reduction predicts tumor response to presurgical molecular-targeting therapy in patients with advanced renal cell carcinoma.

BACKGROUND AND OBJECTIVE: A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy. RESULTS: Of 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were -19%, -24%, and -49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST. MATERIALS AND METHODS: Between March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis. CONCLUSIONS: CMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy.

Stretching an Elastic Loop: Crease, Helicoid, and Pop Out.

Under geometric constraints, a thin structure can respond to an external loading in an unexpected way. A paper strip that is looped and pulled can be used for simple experimentation of such a process. Here, we study this seemingly very simple phenomenon in detail by combing experiments and theory. We identify the three types of shape transitions, i.e., crease, helicoid, and pop out, from a stretched loop, and classify them in terms of parameters characterizing a ribbon geometry. We establish a transition-type diagram by compiling our extensive experimental data. Numerical simulations based on the Kirchhoff rod theory and scaling argument reveal that the pop-out transition is governed by a single characteristic length ξ∼b^{2}/h, where b and h are the ribbon's width and thickness, respectively. We also reveal the key roles of other physical effects such as the anisotropy of the bending elasticity and plastic deformations upon the shape selection mechanisms of a constraint ribbon.