The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy.

BACKGROUND: While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. METHOD: We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. RESULT: A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). CONCLUSION: The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.

VCAN Hypomethylation and Expression as Predictive Biomarkers of Drug Sensitivity in Upper Urinary Tract Urothelial Carcinoma.

Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial cancer (UTUC) is not well understood. In this study, we collected tissues from 10 patients with UTUC, including 6 with and 4 without lymphovascular invasion (LVI), a pathological feature that plays a significant role in determining metastasis. Results from RNA sequencing revealed that the most differentially expressed genes were involved in extracellular matrix organization. Using the TCGA database for clinical correlation, VCAN was identified as a target for study. A chromosome methylation assay showed that VCAN was hypomethylated in tumors with LVI. In our patient samples, VCAN expression was also found to be high in UTUC tumors with LVI. In vitro analysis showed that knocking down VCAN inhibited cell migration but not proliferation. A heatmap analysis also confirmed a significant correlation between VCAN and migration genes. Additionally, silencing VCAN increased the effectiveness of cisplatin, gemcitabine and epirubicin, thus providing potential opportunities for clinical application.

Case 296: Phlebosclerotic Colitis.

History A 55-year-old woman without systemic underlying disease, such as diabetes mellitus, inflammatory bowel disease, autoimmune disease, or chronic kidney disease, presented with generalized dull abdominal pain of 1-week duration. She had ingested herbal medicine for physical conditioning for several years. Laboratory findings, including biochemistry, electrolyte levels, and complete blood count, were all within normal limits, except for elevated serum C-reactive protein level (7.719 mg/dL; normal range, <1 mg/dL). The patient underwent initial evaluation with conventional abdominal radiography. She underwent subsequent evaluation with noncontrast CT of the abdomen and colonoscopy.

Case 296.

History A 55-year-old woman without systemic underlying disease, such as diabetes mellitus, inflammatory bowel disease, autoimmune disease, or chronic kidney disease, presented with generalized dull abdominal pain of 1-week duration. She had ingested herbal medicine for physical conditioning for several years. Laboratory findings, including biochemistry, electrolyte levels, and complete blood count, were all within normal limits, except for elevated serum C-reactive protein level (7.719 mg/dL; normal range,<1 mg/dL). The patient underwent initial evaluation with conventional abdominal radiography (Fig 1). She underwent subsequent evaluation with noncontrast CT of the abdomen (Figs 2, 3) and colonoscopy (Fig 4).

Hypomethylated RRBP1 Potentiates Tumor Malignancy and Chemoresistance in Upper Tract Urothelial Carcinoma.

Ribosome-binding protein 1 (RRBP1) is a potential oncogene in several cancer types. However, the correlation between RRBP1 expression and the prognosis of patients with upper tract urothelial carcinoma (UTUC) remains unclear. In this study, we identified that RRBP1 is associated with carcinogenesis and metastasis in UTUC using a methylation profiling microarray. High correlations between RRBP1 and cancer stages, nodal metastasis status, molecular subtypes, and prognosis in bladder urothelial cancer (BLCA) were found. Aberrant DNA methylation in the gene body region of RRBP1 was determined in UTUC tissues by methylation-specific PCR. RRBP1 expression was significantly increased in UTUC tissues and cell lines, as determined by real-time PCR and immunohistochemistry. RRBP1 depletion significantly reduced BFTC909 cell growth induced by specific shRNA. On the other hand, molecular subtype analysis showed that the expression of RRBP1 was associated with genes related to cell proliferation, epithelial-mesenchymal transition, and basal markers. A patient-derived organoid model was established to analyze patients' responses to different drugs. The expression of RRBP1 was related to chemoresistance. Taken together, these results provide the first evidence that RRBP1 gene body hypomethylation predicts RRBP1 high expression in UTUC. The data highlight the importance of RRBP1 in UTUC malignancy and chemotherapeutic tolerance.

Comparative Study of the Safety and Efficacy of First-Line Cisplatin and Carboplatin Chemotherapy in Elderly Patients with Metastatic Urothelial Carcinoma.

OBJECTIVES: Platinum-based chemotherapy is the standard treatment for metastatic urothelial carcinoma (mUC). However, considering elderly patients often experience comorbidities and frailty, the utility of cisplatin-based chemotherapy for elderly patients is still debatable. We conducted this study to compare the safety and efficacy of carboplatin and cisplatin in elderly patients with mUC. METHODS: This retrospective study enrolled elderly patients with mUC (defined as aged ≥70 years) who underwent first-line platinum-based chemotherapy between September 2001 and October 2018. The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death. The secondary outcomes were overall survival (OS) and progression-free survival calculated by Kaplan-Meier analysis. RESULTS: In total, 108 elderly patients with mUC were enrolled and allocated into the cisplatin or carboplatin group. Patients treated with carboplatin-based chemotherapy had a significantly higher incidence of all grade ≥3 AEs (78.8 vs. 50.0%, p = 0.008) than those on cisplatin. AE-related hospitalization (47.5 vs. 19.1%, p = 0.002) and treatment-related death (17.5 vs. 4.4%, p = 0.02) were significantly increased in the carboplatin group. In the univariate analysis, the median OS in the cisplatin group was significantly increased compared with the carboplatin group (13.6 vs. 7.2 months, p = 0.045). The Cox multivariate regression model indicated that leukocytosis (HR 3.17, 95% CI 1.84-5.46, p < 0.001) and anemia (HR 2.02, 95% CI 1.11-3.65, p = 0.02) were independent prognostic factors. CONCLUSION: Elderly patients with mUC treated with cisplatin-based chemotherapy had better survival and safety profiles than those treated with carboplatin. Age itself was not a crucial factor in determining cisplatin eligibility.

Effects of the Glutamine Administration on T Helper Cell Regulation and Inflammatory Response in Obese Mice Complicated with Polymicrobial Sepsis.

This study investigated the impacts of GLN on inflammation and T cell dysregulation in obese mice complicated with sepsis. Mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat and was administered for 10 weeks to induce obesity. Mice fed with a high-fat diet were then assigned to sham (SH) and sepsis with saline (SS) or GLN (SG) groups. The SH group was subjected to laparotomy, while the sepsis group underwent cecal ligation and puncture (CLP). The SS group was intravenously injected with saline. The SG group was intravenously administered GLN after CLP. Mice were sacrificed at 12, 24, or 48 h post-CLP, respectively. Results demonstrated that in the presence of obesity, sepsis drove CD4+ T cells toward the helper T (Th)2 and Th17 lineages. Also, expressions of inflammatory cytokines and macrophage infiltration markers in adipose tissues and lungs were elevated. Treatment of obese mice with GLN after sepsis reversed Th polarization and downregulated macrophage infiltration and inflammatory cytokine, whereas the tight junction-associated protein expression increased in the lungs. These findings suggest that the intravenous administration of GLN to obese mice after sepsis modulated a more balanced Th cell lineage, alleviated inflammation, and attenuated lung injury.

Proteomics Analysis of Tangeretin-Induced Apoptosis through Mitochondrial Dysfunction in Bladder Cancer Cells.

Tangeretin is one of the most abundant compounds in citrus peel, and studies have shown that it possesses anti-oxidant and anti-cancer properties. However, no study has been conducted on bladder cancer cells. Bladder cancer has the second highest mortality rate among urological cancers and is the fifth most common malignancy in the world. Currently, combination chemotherapy is the most common approach by which to treat patients with bladder cancer, and thus identifying more effective chemotherapeutic agents that can be safely administered to patients is a very important research issue. Therefore, this study investigated whether tangeretin can induce apoptosis and identified the signaling pathways of tangeretin-induced apoptosis in human bladder cancer cells using two-dimensional gel electrophoresis (2DGE). The results of the study demonstrated that 60 µM tangeretin reduced the cell survival of a BFTC-905 bladder carcinoma cell line by 42%, and induced early and late apoptosis in the cells. In this study 2DGE proteomics technology identified 41 proteins that were differentially-expressed in tangeretin-treated cells, and subsequently LC⁻MS/MS analysis was performed to identify the proteins. Based on the functions of the differentially-expressed proteins, the results suggested that tangeretin caused mitochondrial dysfunction and further induced apoptosis in bladder cancer cells. Moreover, western blotting analysis demonstrated that tangeretin treatment disturbed calcium homeostasis in the mitochondria, triggered cytochrome C release, and activated caspase-3 and caspase-9, which led to apoptosis. In conclusion, our results showed that tangeretin-induced apoptosis in human bladder cancer cells is mediated by mitochondrial inactivation, suggesting that tangeretin has the potential to be developed as a new drug for the treatment of bladder cancer.

Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma.

Advanced upper urinary tract urothelial carcinoma (UTUC) is often associated with poor oncologic outcomes. The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) protein, belongs to the SPARC-related family of matricellular proteins. Much literature has been published describing the role of SPARCL1 in the prognosis many cancers. In this study, methylated promoter regions in high-grade and high-stage upper urinary urothelial tumours compared with normal urothelium were analyzed and revealed that SPARCL1 was the most significantly hypermethylated gene in UTUC tissues. Then we prospectively collected UTUC samples and adjacent normal urothelium for pyrosequencing validation, identifying significant CpG site methylation in UTUC tissues. In addition, SPARCL1 RNA levels were significantly lower in UTUC samples. Multivariate Cox regression analysis from 78 patients with solitary renal pelvic or ureteral pT3N0M0 urothelial carcinomas revealed that only negative SPARCL1 expression and nonpapillary tumour architecture were independently associated with systemic recurrence (p = 0.011 and 0.008, respectively). In vitro studies revealed that the behaviour of BFTC-909 cells was less aggressive and more sensitive to radiation or chemotherapy after SPARCL1 overexpression. Thus, SPARCL1 could be considered as a prognostic marker and help decision-making in clinical practice.

Aristolochic Acid Affects Upper Tract Urothelial Cancer Behavior through the MAPK Pathway.

The prevalence of upper tract urothelial carcinoma (UTUC) in Taiwan is relatively higher than thatin Western countries. Aristolochic acid (AA), which is widely used in traditional Chinese herbology, is now recognized to be one of the carcinogens for UTUC. Numerous UTUC patients have chronic kidney diseases or end-stage renal diseases; however, little literature hasreported on theoncogenic pathway of AA-related UTUC. The aim of our study was to identify the potential target treatment for AA-related UTUC. Here, we established an AA pre-exposure followed bya 3-methylcholanthrene (MCA) stimulus tumorigenic cell model. We not only demonstrated that AA pre-exposure MCA stimulus tumorigenic cells have more behaviors of cell migration and invasion by enhancing the metalloproteinases (MMP) activity, which is compatible with clinical findings of AA-related UTUC, but we also validated that AA pre-exposure MCA stimulus tumorigeniccells could be activated through the mitogen-activated protein kinases (MAPK) pathway. We further dissected the route of the MAPK pathway and found that the p38 and extracellular signal regulated kinases (ERK) sub-pathways might play essential roles in AA pre-exposure urothelial cancer cell lines. This consequence was also corroborated with a tissue study in AA-exposed patients.

The diagnostic performance of ultrasonography and computerized tomography in differentiating superficial from deep lobe parotid tumours.

OBJECTIVES: To validate and compare ultrasound (US) versus computerized tomography (CT) criteria in the localisation of superficial/deep lobe tumours of the parotid gland. DESIGN AND SETTING: This was a retrospective study of diagnostic tests performed from January 2008 to June 2017. PARTICIPANTS: We included adult patients who were referred for a neck ultrasonography examination due to parotid tumours, and who subsequently underwent parotid surgery. MAIN OUTCOME MEASURES: We assessed the location of parotid tumours, comparing the minimum fascia-tumour distance (MFTD) criterion on an US with eight CT criteria. We analysed receiver operating characteristic (ROC) curves of the MFTD for malignant, benign, and all parotid tumours, and compared the accuracy, sensitivity, and specificity of the optimal MFTD with those of CT anatomical criteria. RESULTS: A total of 166 parotid tumours were included. The mean (SD) MFTD in superficial lobe tumours was significantly shorter than that of deep lobe tumours (1.2 [0.7] vs 2.8 [1.9] mm, effect size: 1.84; 95% CI, 1.27-2.41). The areas under the ROC curve were 0.63 for malignant tumours and 0.88 for benign tumours. The optimal MFTD cut point was 2.4 mm for the 154 benign parotid tumours, and the accuracy, sensitivity and specificity were 90%, 80% and 91%, respectively. For the 136 benign parotid tumours that underwent CT examination, three criteria had an accuracy of over 90% (FNline, tMasseter and Conn's arc), but the sensitivities were all below 50%. CONCLUSIONS: Minimum fascia-tumour distance is more feasible for benign tumours than for malignant tumours for the localisation of parotid tumours. For benign parotid tumours, US is enough to guide operations.

TRIP-1 in the extracellular matrix promotes nucleation of calcium phosphate polymorphs.

In search for bone and dentin extracellular matrix (ECM) proteins, transforming growth factor beta receptor II interacting protein 1 (TRIP-1) was identified as a novel protein synthesized by osteoblasts and odontoblasts and exported to the ECM. TRIP-1 is a WD-40 (WD is Tryptophan-Aspartic acid dipeptide) protein that has been well recognized for its physiological role in the endoplasmic reticulum (ER). In the ER, TRIP-1 functions as an essential subunit of eukaryotic elongation initiation factor 3 and is involved in the protein translational machinery. Recently, we reported that TRIP-1 is localized in the ECM of bone and dentin. In this study, we demonstrate that varying concentrations of TRIP-1 can participate in the nucleation of calcium phosphate polymorphs. Nucleation studies performed with high calcium and phosphate concentration demonstrated that recombinant TRIP-1 could orchestrate the formation of hydroxyapatite crystals. Nucleation experiments performed on demineralized and deproteinized dentin wafer under physiological conditions and subsequent transmission electron microscope analysis of the deposits at the end of 7 and 14 days showed that TRIP-1 promoted the deposition of calcium phosphate mineral aggregates in the gap-overlap region of type I collagen. Taken together, we provide mechanistic insight into the role of this intracellular protein in matrix mineralization.

Graft calcification caused by a torsion of the hepatic vein after a living-related donor liver transplantation.

 The torsion of vessels after liver transplantation rarely occurs. Likewise, calcification of a liver graft has seldom been reported. This report details a case which had torsion of the left hepatic vein on the seventh day after living-related donor liver transplantation. The torsion was reduced soon after re-exploration; however, congestion with partial necrosis of the graft occurred. On the follow-up imaging studies, some resolution of necrosis and graft regeneration were found, yet geographic calcification of the liver graft appeared.The patient died of pneumonia after 13 weeks, post-operation. The avoidance such torsion of vessels is necessary and important.

Multicomponent Strategy for the Synthesis of Prostaglandin E2 Methyl Ester under Anion Relay Chelation Control.

Starting with four components, the enantioselective synthesis of prostaglandin E2 methyl ester has been achieved through a highly stereoselective heteroatom-directed conjugate addition reaction and cyclopentanone ring cyclization as the key steps. This asymmetric strategy includes (i) an asymmetric Reformatsky reaction; (ii) conjugate addition of a chiral vinyllithium reagent; (iii) cyclization to form a sulfonylated cyclopentanone in one-pot; followed by (iv) allylation of the side chain. Four carbon-carbon bond-forming processes and three stereogenic centers were established, with the steps from (ii) to (iii) being achieved in a one-pot process.

Patient Cranial Angle and Intrafractional Stability in CyberKnife Robotic Radiosurgery: A Retrospective Analysis.

Purpose: The aim of this study was to investigate whether variations in cranial angles and treatment accuracy during CyberKnife robotic radiosurgery necessitate adjustment of the margins of the planning target volume. Patients and Methods: Data from 66 patients receiving CyberKnife treatment for brain tumors were retrospectively analyzed. Patients were immobilized using a thermoplastic mask and headrest. The cranial angle was measured on planning CT and patients were divided into 2 groups: ≤10° (Group A) and >10° (Group B). Intrafractional motion was recorded using the CyberKnife tracking system over 50 min. Translational and rotational errors were compared between groups, and planning target volume margins were calculated. Results: In Group A, significant translational error differences were found along with the X-axis over time (P < .02). In Group B, significant differences occurred along with the Z-axis (P < .03). No significant rotational or 3-dimensional vector differences were found in either group. Group A had significantly lower Y-axis (P < .045) and roll axis (P < .005) errors compared to Group B. Estimated planning target volume margins in Group A were 0.56 mm (X), 0.46 mm (Y), and 0.47 mm (Z). In Group B, margins were 0.62 mm (X), 0.48 mm (Y), and 0.46 mm (Z). Margins covering 95% of intrafraction motion were 0.49 to 0.50 mm (X, Y, Z) and 0.69 mm (3-dimensional vector) for Group A, and 0.48 to 0.60 mm and 0.79 mm for Group B. With a 1-mm margin, complete coverage was achieved in Group A while 2.1% of vectors in Group B exceeded 1 mm. Conclusion: Adjusting cranial angle to ≤10° during thermoplastic mask molding provided better or similar intrafractional stability compared to >10°.

Evaluation of nanoscale versus hybrid micro/nano surface topographies for endosseous implants.

We examined the effect of a nanoscale titanium surface topography (D) versus two hybrid micro/nanoscale topographies (B and OS) on adherent mesenchymal stem cells (MSCs) and bone marrow derived macrophages (BMMs) function in cell culture and in vivo. In the in vitro study, compared to OS and B surfaces, D surface induced earlier and greater cell spreading, and earlier and profound mRNA expression of RUNX2, Osterix and BMP2 in MSCs. D surface induced earlier and higher expression of RUNX2 and BMP2 and lower expression of inflammatory genes in implant adherent cells in vivo. Measurement of osteogenesis at implant surfaces showed greater bone-to-implant contact at D versus OS surfaces after 21 days. We explored the cell population on the D and OS implant surfaces 24 h after placement using single-cell RNA sequencing and identified distinct cell clusters including macrophages, neutrophils and B cells. D surface induced lower expression and earlier reduction of inflammatory genes expression in BMMs in vitro. BMMs on D, B and OS surfaces demonstrated a marked increase of BMP2 expression after 1 and 3 days, and this increase was significantly higher on D surface at day 3. Our data implicates a dynamic process that may be influenced by nanotopography at multiple stages of osseointegration including initial immunomodulation, recruitment of MSCs and later osteoblastic differentiation leading to bone matrix production and mineralization. The results suggest that a nanoscale topography (D) favorably modulates adherent macrophage polarization toward anti-inflammatory and regenerative phenotypes and promotes the osteoinductive phenotype of adherent mesenchymal stem cells. STATEMENT OF SIGNIFICANCE: Our manuscript contains original data developed to define effects of a novel nanotopography on the process of osseointegration at the cell and tissue level.  Few studies have compared the effects of a nanoscale surface versus the more typical hybrid micro/nano-scale surfaces used today. We have utilized single-cell RNA sequencing for the first time to identify earliest cell populations on implant surfaces in vivo. We provide data indicating that the nanoscale surface acts upon both osteoprogenitor and immune cell (macrophages) to alter the process of bone formation in a surface-specific manner. This work represents new observations regarding osseointegration and immunomodulation.

Association between Statin Use and Clinical Outcomes in Patients with De Novo Metastatic Prostate Cancer: A Propensity Score-weighted Analysis.

PURPOSE: Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. MATERIALS AND METHODS: We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. RESULTS: The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. CONCLUSIONS: Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.

The impact of body mass index on survival endpoints among patients with metastatic urothelial carcinoma undergoing treatment with immune checkpoint inhibitors: A real-world multicenter analysis.

BACKGROUND: Studies on the correlation between high body mass index (BMI) and extended survival among patients receiving immune checkpoint inhibitors (ICIs) have been made, although findings have shown variability. Our research explored the phenomenon of the "obesity paradox" in patients with metastatic urothelial carcinoma (mUC) undergoing treatment with ICIs. MATERIALS AND METHODS: We conducted a retrospective analysis of patients diagnosed with mUC who received a minimum of one cycle of ICI treatment at two medical centers in Taiwan from September 2015 to January 2023. Features of patients' clinicopathologic factors, including age, sex, primary or metastatic location, treatment line, and BMI were examined. The primary outcome were overall survival (OS) and progression-free survival (PFS), which were assessed utilizing the Kaplan-Meier method. We employed the Cox-regression model to adjust for multiple covariates. RESULTS: A total of 215 patients were included, with 128 (59.5%) being male, and the median age was 70 years. In the obese group (BMI ≥25 kg/m2 ), patients demonstrated significantly better median OS compared to the non-obese group (BMI <25 kg/m2 ) (21.9 vs. 8.3 months; p = 0.021). However, there was no significant difference in median PFS between the high and low BMI groups (4.7 vs. 2.8 months; p = 0.16). Post-hoc subgroup revealed a survival benefit from ICI treatment in male patients within the BMI ≥25 kg/m2 group (HR 0.49, 95% CI 0.30-0.81, p = 0.005). CONCLUSION: Based on real-world data from the Asia-Pacific region, there appears to be a correlation between obesity and prolonged OS in patients receiving ICI treatment for mUC.

A compact optical pickup head in blue wavelength with high horizontal stability for laser thermal lithography.

A compact optical pickup head in blue wavelength with a single-axial actuator i.e. focusing, for laser thermal lithography was designed, fabricated, and tested. The numerical aperture of the objective lens was 0.85. The linear range of the focus error signal was 3 µm. A planar spring structure for improving the horizontal stability was designed and incorporated into the actuator. We applied a modified push-pull method together with a static Blu-ray re-writable disc to test the horizontal stability of the pickup head. We found that the in-plane jitter of the pickup head in two orthogonal directions were 0.34 nm and 1.59 nm, respectively. We demonstrated an example of applying the pickup head to write an inorganic photo-resist GeSbSnO film, and well-defined pattern was obtained with ~220 nm spot size.

A pilot study of hepatic arterial infusion of chemotherapy for patients with advanced hepatocellular carcinoma who have failed anti-angiogenic therapy.

BACKGROUND & AIMS: For patients with advanced hepatocellular carcinoma (HCC) who have failed first-line anti-angiogenic therapy, there is no salvage treatment. Hepatic arterial infusion of chemotherapy (HAIC) has been reported to achieve substantial treatment responses in HCC patients. We aimed to explore the feasibility of using HAIC as second-line therapy for advanced HCC. METHODS: We retrospectively reviewed all consecutive patients who received HAIC for advanced HCC after failure of first-line anti-angiogenic therapy at a single institute. Patients received HAIC with 60 mg/m(2) cisplatin on Day 2, and 500 mg/m(2) /d dose of 5-fluorouracil on Days 1-3. The treatment was repeated every 21 days and continued until disease progression or the occurrence of intolerable toxicities. Tumour assessment was performed after every 3 cycles of HAIC following RECIST criteria, version 1.0. RESULTS: A total of 23 patients were included. Eleven (48%) patients had main portal vein thrombosis. Liver reserve was classified as Child-Pugh A in 19 (83%) patients and B in 4 (17%) patients. No complete response was observed, although 6 (26%) patients showed partial responses. The median progression-free survival was 4.4 months, and the median overall survival was 7.5 months. Common toxicities included bone marrow suppression, elevated transaminase levels, neutropenia, nausea and malaise. Only 7 (30%) patients experienced grade 3 or 4 toxicities, and no patients withdrew from the therapy because of intolerable or life-threatening toxicities. CONCLUSION: HAIC is a feasible second-line therapy for patients with advanced HCC who have failed anti-angiogenic therapy.