Crystal-Phase- and B-Content-Dependent Electrochemical Behavior of Pd─B Nanocrystals toward Oxygen Reduction Reaction.

The manipulation of crystal phases in metal-nonmetal interstitial alloy nanostructures has attracted considerable attention due to the formation of unique electronic structures and surface atomic arrangements, resulting in unprecedented catalytic performances. However, achieving simultaneous control over crystal phase and nonmetal elements in metal-nonmetal interstitial alloy nanostructures has remained a formidable challenge. Here, a novel synthesis approach is presented for Pd─B interstitial alloy nanocrystals (NCs) that allows investigation of the crystal-phase- and B-content-dependent catalytic performance. Through comparison of the oxygen reduction reaction (ORR) properties of Pd─BX interstitial alloy NCs with different crystal phases and B contents, achieved by precise control of reaction temperature and time, the influences of crystal phase and B contents in the Pd─BX interstitial alloy NCs on ORR are precisely investigated. The hexagonal closed packed (hcp) PdB0.5 NCs exhibit superior catalytic activity, with mass activities reaching 2.58 A mg-1, surpassing Pd/C by 10.3 times, attributed to synergistic effects by the hcp crystal phase and relatively high B contents. This study not only provides a novel approach to fabricate interstitial alloy nanostructures with unconventional crystal phases and finely controlled nonmetal elements but also elucidates the importance of crystal phase and nonmetal element content in optimizing electrocatalytic efficiency.

Clinical Application of Multimodal Sentinel Lymph Node Mapping Method in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy: An Interim Analysis.

BACKGROUND: After neoadjuvant chemotherapy (NAC), the SLN identification rate is lower and has a higher false-negative rate than that at upfront surgery. This clinical trial aimed to confirm the effectiveness of sentinel lymph node (SLN) surgery by determining the lymph node identification rate using multimodal SLN marker methods in patients with advanced breast cancer undergoing NAC. PATIENTS AND METHODS: This clinical study is a prospective single-center randomized controlled trial involving patients with breast cancer receiving NAC. Patients are randomized (1:1:1) into arm A that involves the use of radioisotope (RI) plus indocyanine green fluorescence (ICG-F); arm B, RI plus vital dye; and, arm C, ICG-F plus vital dye. A total of 348 patients are needed. An interim analysis was performed on 50% of the patients enrolled. The primary outcome of this trial was the SLN identification rate. RESULTS: Among the 164 total patients (median age 51 years), T2 and N1 were the most common clinical stages. The identification rate of SLN was 95% in arm A, 92% in arm B, and 79% in arm C. To assess superior efficacy, the one-sided endpoint was set at α < 0.0056. Arms A and C showed a difference of 0.1597 in the detection rate (p = 0.0055). CONCLUSIONS: The use of ICG-F plus vital dye for SLNB was the least effective. The results show that the choice of tracer should be radioisotope in combination with one of the other tracers to have the highest SLN identification rate when SLNB cannot be implemented conventionally due to the circumstances of each institution.

The Efficacy and Safety of an Indocyanine Green-Macroaggregated Albumin-Hyaluronic Acid Mixture (LuminoMark™) for Surgical Localization of Recurrent Thyroid Cancer.

BACKGROUND: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer. METHODS: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated. RESULTS: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively. CONCLUSION: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control.

FDG metabolic parameter-based models for predicting recurrence after upfront surgery in synchronous colorectal cancer liver metastasis.

OBJECTIVE: This study aimed to develop and validate post- and preoperative models for predicting recurrence after curative-intent surgery using an FDG PET-CT metabolic parameter to improve the prognosis of patients with synchronous colorectal cancer liver metastasis (SCLM). METHODS: In this retrospective multicenter study, consecutive patients with resectable SCLM underwent upfront surgery between 2006 and 2015 (development cohort) and between 2006 and 2017 (validation cohort). In the development cohort, we developed and internally validated the post- and preoperative models using multivariable Cox regression with an FDG metabolic parameter (metastasis-to-primary-tumor uptake ratio [M/P ratio]) and clinicopathological variables as predictors. In the validation cohort, the models were externally validated for discrimination, calibration, and clinical usefulness. Model performance was compared with that of Fong's clinical risk score (FCRS). RESULTS: A total of 374 patients (59.1 ± 10.5 years, 254 men) belonged in the development cohort and 151 (60.3 ± 12.0 years, 94 men) in the validation cohort. The M/P ratio and nine clinicopathological predictors were included in the models. Both postoperative and preoperative models showed significantly higher discrimination than FCRS (p < .05) in the external validation (time-dependent AUC = 0.76 [95% CI 0.68-0.84] and 0.76 [0.68-0.84] vs. 0.65 [0.57-0.74], respectively). Calibration plots and decision curve analysis demonstrated that both models were well calibrated and clinically useful. The developed models are presented as a web-based calculator ( https://cpmodel.shinyapps.io/SCLM/ ) and nomograms. CONCLUSIONS: FDG metabolic parameter-based prognostic models are well-calibrated recurrence prediction models with good discriminative power. They can be used for accurate risk stratification in patients with SCLM. KEY POINTS: • In this multicenter study, we developed and validated prediction models for recurrence in patients with resectable synchronous colorectal cancer liver metastasis using a metabolic parameter from FDG PET-CT. • The developed models showed good predictive performance on external validation, significantly exceeding that of a pre-existing model. • The models may be utilized for accurate patient risk stratification, thereby aiding in therapeutic decision-making.

Ergonomic effects of medical augmented reality glasses in video-assisted surgery.

BACKGROUND: The aim of this study was to objectively compare medical augmented reality glasses (ARG) and conventional monitors in video-assisted surgery and to systematically analyze its ergonomic benefits. METHODS: Three surgeons (thoracic, laparoscopic, and thyroid surgeons) participated in the study. Six thoracoscopic metastasectomies, six subtotal laparoscopic gastrectomies, and six thyroidectomies were performed with and without ARG. The subjective experience was evaluated using a questionnaire-based NASA-Task Load Index (NASA-TLX). Postures during surgeries were recorded. The risk of musculoskeletal disorders associated with video-assisted surgery was assessed using rapid entire body assessment (REBA). Surface electromyography (EMG) was recorded. Muscle fatigue was objectively measured. RESULTS: NASA-TLX scores of three surgeons were lower when ARG was used compared to those with conventional monitor (66.4 versus 82.7). Less workload during surgery was reported with ARG. The laparoscopic surgeon exhibited a substantial decrease in mental and physical demand [- 21.1 and 12.5%)] and the thyroid surgeon did (- 40.0 and - 66.7%).Total REBA scores decreased with ARG (8 to 3.6). The risk of musculoskeletal disorders was improved in regions of the neck and shoulders. Root mean square (RMS) of the EMG signal decreased from 0.347 ± 0.150 to 0.286 ± 0.130 (p = 0.010) with usage of ARG; a decrease was observed in all surgeons. The greatest RMS decrease was observed in trapezius and sternocleidomastoid muscles. The decrease in brachioradialis muscle was small. CONCLUSION: ARG assisted with correction of bad posture in surgeons during video-assisted surgery and reduced muscular fatigue of the upper body. This study highlights the superior ergonomic efficiency of ARG in video-assisted surgery.

The Sentinel Lymph Node Biopsy Using Indocyanine Green Fluorescence Plus Radioisotope Method Compared With the Radioisotope-Only Method for Breast Cancer Patients After Neoadjuvant Chemotherapy: A Prospective, Randomized, Open-Label, Single-Center Phase 2 Trial.

BACKGROUND: This study aimed to compare the sentinel lymph node (SLN) identification rates for breast cancer patients after neoadjuvant chemotherapy (NAC) between the dual method (DM) of indocyanine green fluorescence (ICG-F) plus a radioisotope (RI) and RI alone. METHODS: This randomized study enrolled 130 patients who received NAC for breast cancer and 122 patients who received SLN biopsy (SLNB) using either DM (n = 58) or RI only (n = 64). The study compared the identification rate, number of SLNs, and detection time of SLNB. RESULTS: Among the 122 patients, 113 (92.6%) were clinically node-positive before NAC. The SLN identification rate was 98.3% in the DM group and 93.8% in the RI group (p = 0.14). The DM group and the RI group were similar in the average number of SLNs (2.2 ± 1.13 vs. 1.9 ± 1.33; p = 0.26) and the time to detection of the first SLN (8.7 ± 4.98 vs. 8.3 ± 4.31 min; p = 0.30). In the DM group, transcutaneous lymphatic drainage was visualized by fluorescence imaging for 65.5% (38 of 58) of the patients. The SLN identification rate was 94.7% using ICG-F and 93% using RI (p = 0.79). During and after the operation, no complications, including allergic reactions or skin necrosis, occurred. CONCLUSIONS: This study is the first randomized trial to use ICG-F for SLNB in breast cancer patients after NAC. The DM including ICG-F could be a feasible and safe method for SLNB in initially node-positive breast cancer patients with NAC.

Fucoidan attenuates radioiodine-induced salivary gland dysfunction in mice.

BACKGROUND: Radioiodine (RI) treatments can destroy the cellular components of salivary glands (SG) and disrupt their function. This study investigated whether fucoidan could attenuate radioiodine-induced SG dysfunction in a mouse model. METHODS: Female C57BL/6 mice (n = 36) were classified into three groups; i) a normal (control) group, ii) an RI-treated group (0.2 mCi/20 g mouse, administered orally), and iii) a fucoidan and RI-treated group. Mice in each group were classified into three subgroups and sacrificed at 2, 4, and 12 weeks after RI treatment. The measurements of salivary flow rates and lag times and histomorphologic examinations were performed, and apoptotic assays were conducted. Changes in salivary 99mTechnetium (Tc)-pertechnetate parameters using single-photon emission computed tomography were followed. RESULTS: Salivary flow rates and lag times in the fucoidan group were improved compared to the RI-treated group. Histologic examinations of SGs in the fucoidan group showed mucin-rich parenchymal areas and reduced periductal fibrosis as compared to the RI-treated group. Moreover, compared with the RI-treated group, fucoidan-treated groups showed evidence of cytoprotection, with a greater number of salivary epithelial cells and myoepithelial cells being observed. Fewer apoptotic cells were observed in the fucoidan group as compared to the RI group. The extent of 99mTc pertechnetate excretion in the fucoidan group was similar to that of the control group. CONCLUSION: Our results demonstrate that fucoidan administration before RI treatment could attenuate RI-induced SG damage and provides a possible candidate for preventing SG damage induced by RI.

Current status and challenges in sentinel node navigation surgery for early gastric cancer.

Although a number of feasibility studies for sentinel node (SN) concepts in gastric cancer have been conducted since 2000, there remains a debate regarding detailed detection techniques and oncological safety. Two important multicenter phase II clinical trials were performed in Japan that used different methods and reached different conclusions; one confirmed acceptable results with a false-negative rate of 7%, and the other showed an unacceptably high false-negative rate of 46.4%. The Sentinel Node Oriented Tailored Approach (SENORITA) trial is a multicenter randomized controlled phase III trial being performed in Korea. Patient enrollment is now complete and the long-term results are currently awaited. Recently, an image-guided SN mapping technique using infrared ray/fluorescence was introduced. This method might be a promising technology because it allows the clear visualization of SNs. With regard to the primary tumor, the non-exposed endoscopic wall-inversion surgery technique and non-exposure endolaparoscopic full-thickness resection with simple suturing technique have been reported. These methods prevent abdominal infection and tumor seeding and can be good alternatives to conventional laparoscopic gastric wedge resection. For indications, SN navigation surgery can be extended to patients who underwent non-curative endoscopic resection. Although a few studies have been performed on these patients, sentinel concepts may be beneficial to patients as they omit the need for additional gastrectomy. SN navigation surgery can lead to actual organ-preserving surgery and plays a key role in improving the quality of life of patients with early gastric cancer in the future.

A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival.

BACKGROUND: We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association between CYP2A6 genotype and outcome. METHODS: Patients with LAGC [clinical stage III-IV (M0) by the Japanese staging system] received three cycles of pre- and postoperative chemotherapy (S-1 40 mg/m(2) twice daily on days 1-14; intravenous docetaxel 35 mg/m(2) on days 1 and 8, every 3 weeks) followed by gastrectomy with D2 dissection. We also performed a pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1. RESULTS: From October 2006 to June 2008, 44 patients entered the study. 43 eligible patients completed preoperative chemotherapy and 40 completed postoperative chemotherapy. The most common G3/4 toxicities during pre- and postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The clinical response rate by RECIST was 74.4 % (95 % CI, 61.4-87.4 %), and the R0 resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of patients. The 3-year progression-free survival (PFS) rate was 62.8 % and 5-year overall survival (OS) rate was 69.6 %. PFS and OS differed significantly according to clinical response, clinical downstaging, and CYP2A6 genotype. Patients with CYP2A6 variant/variant genotypes had a higher tegafur C max and worse survival than those with wild/wild or wild/variant genotypes. CONCLUSION: Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging, and CYP2A6 genotype may predict efficacy.

A novel endoscopic fluorescent band ligation method for tumor localization.

BACKGROUND: Accurate tumor localization is essential for minimally invasive surgery. This study describes the development of a novel endoscopic fluorescent band ligation method for the rapid and accurate identification of tumor sites during surgery. METHODS AND MATERIALS: The method utilized a fluorescent rubber band, made of indocyanine green (ICG) and a liquid rubber solution mixture, as well as a near-infrared fluorescence laparoscopic system with a dual light source using a high-powered light-emitting diode (LED) and a 785-nm laser diode. The fluorescent rubber bands were endoscopically placed on the mucosae of porcine stomachs and colons. During subsequent conventional laparoscopic stomach and colon surgery, the fluorescent bands were assayed using the near-infrared fluorescence laparoscopy system. RESULTS: The locations of the fluorescent clips were clearly identified on the fluorescence images in real time. The system was able to distinguish the two or three bands marked on the mucosal surfaces of the stomach and colon. Resection margins around the fluorescent bands were sufficient in the resected specimens obtained during stomach and colon surgery. CONCLUSION: These novel endoscopic fluorescent bands could be rapidly and accurately localized during stomach and colon surgery. Use of these bands may make possible the excision of exact target sites during minimally invasive gastrointestinal surgery.

Risk factors for recurrence after therapeutic lateral neck dissection for primary papillary thyroid cancer.

BACKGROUND: Lateral lymph node metastasis is an important prognostic factor and is predictive of tumor recurrence and cause-specific survival in patients with papillary thyroid cancer (PTC). However, the factors predicting recurrence and clinical outcomes after therapeutic lateral neck dissection are not well established. The aims of this study were to evaluate the incidence, pattern, and factors predictive of PTC recurrence after therapeutic lateral neck dissection. MATERIALS AND METHODS: The records of 126 consecutive patients who underwent total thyroidectomy with therapeutic lateral neck dissection for primary PTC at the National Cancer Center were retrospectively reviewed. The factors predictive of recurrence were determined using both univariate and multivariate analyses considering several clinicopathologic variables. RESULTS: The median follow-up period was 61.2 months, during which 22 patients (17.5 %) experienced recurrence with 1 death (0.8 %) due to disease. Locoregional recurrence and distant metastasis were found in 20 cases (15.9 %) and 2 cases (1.6 %), respectively. Male gender, aggressive histology, number of lymph node metastases, initial level of T4-off Tg per ng/mL, and ATA risk categories (high risk) were independent risk factors for recurrence. Of note, initial T4-off Tg levels greater than 4.2 ng/mL showed highest sensitivity and specificity in predicting recurrence. CONCLUSIONS: These results provide useful information regarding the clinical outcomes after therapeutic lateral neck dissection for primary PTC and can be used to identify at-risk patients who need aggressive treatment and intensive surveillance for postoperative recurrence.

Comparison of sentinel lymph node biopsy guided by the multimodal method of indocyanine green fluorescence, radioisotope, and blue dye versus the radioisotope method in breast cancer: a randomized controlled trial.

PURPOSE: This study aimed to evaluate the identification rate and surgery time of sentinel lymph node biopsy (SLNB) by a multimodal method (MMM) using a mixture of indocyanine green (ICG), radioisotope (RI), and blue dye (BD) compared with the RI alone. METHODS: In this phase II randomized study, 86 patients with clinically node-negative breast cancer were enrolled and received SLNB with either MMM or RI. We compared the identification rate, number of sentinel lymph nodes (SLNs), and detection time of SLNB and evaluated the safety. RESULTS: The mean age of the MMM group and RI group was 48.2 and 51.0 years (p = 0.12), respectively. There were no differences in histopathologic factors, including tumor size, node positivity, and hormone receptor positivity between groups. SLNs were identified in all patients of both groups (100 % in the MMM group and 100 % in the RI group). The average number of SLNs in the MMM group was more than that in the RI group (3.4 ± 1.37 vs. 2.3 ± 1.04, respectively; p < 0.001). The time to detect the first sentinel lymph node was similar in each group (6.5 ± 5.16 vs. 8.0 ± 4.35 min; p = 0.13). In the MMM group, percutaneous lymphatic drainage was visualized by fluorescent imaging in 90.7 % (39 of 43 patients). During and after the operation, there were no complications, including allergic reactions, skin staining, or necrosis. CONCLUSIONS: This study is the first randomized trial that compared MMM using ICG, RI, and BD and the conventional RI method for SLNB. MMM is a feasible and safe method for SLNB.

Surgical targeting of recurrent thyroid cancer using a novel mixture of 99m-technetium macroaggregated albumin and indocyanine green.

BACKGROUND: Precise targeting has played a pivotal role in the success of surgery for recurrent differentiated thyroid cancers (DTCs). To improve on current targeting methods, we developed a novel technique using (99m)Tc-macroaggregated human serum albumin and indocyanine green (TIGMA), with which surgeons effectively target lesions in real time by radiofluorescence dual guidance. METHODS: Seven patients with 10 recurrent DTC lesions were retrospectively enrolled in the study. Prior to the operation, we injected TIGMA into the target lesion under the guidance of ultrasonography. Resection was concurrently monitored using a gamma probe and a specially designed near infrared fluorescence camera. Outcomes were evaluated using imaging, surgical, and pathological records. RESULTS: In all enrolled cases, both injection of TIGMA and radiofluorescence dual guidance were well tolerated and easy to implement. The technical success rates were 100%, confirmed by final pathological examination, postoperative ultrasonography, and I-131 scan clearance. Complications such as temporary postoperative neck pain (n = 2) were minimal. CONCLUSIONS: TIGMA using radiofluorescence dual guidance facilitated the precise targeting of recurrent lesions. The entire procedure was feasible, safe, and successful. This method would help enhance surgical outcomes for recurrent DTCs.

Sn-Doped Zinc Oxide as an Electron Transporting Layer for Enhanced Performance in PbS Quantum Dot Solar Cells.

Colloidal PbS quantum dot solar cells (QDSCs) have been primarily demonstrated in n-i-p structures by incorporating a solution-processed ZnO electron transporting layer (ETL). Nevertheless, the inherent energy barrier for the electron extraction at the ZnO/PbS junction along with the defective nature significantly diminishes the performance of the PbS QDSCs. In this study, by employing Sn-doped ZnO (ZTO) ETL, we have tuned the conduction band offset at the junction from spike-type to cliff-type so that the electron extraction barrier can be eliminated and the overall photovoltaic parameters can be enhanced (open-circuit voltage of 0.7 V, fill factor over 70%, and efficiency of 11.3%) as compared with the counterpart with the undoped ZnO ETL. The X-ray photoelectron spectroscopy (XPS) analysis revealed a mitigation of oxygen vacancies in the ZTO ETL of our PbS QDSCs. Our work signifies the importance of Sn doping into the conventional ZnO ETL for the superior electron extraction in PbS QDSCs.

(18)F-FDG-PET/CT predicts early tumor recurrence in living donor liver transplantation for hepatocellular carcinoma.

The prognosis including (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) for the early recurrence for hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) was not well established. Consecutive patients who underwent (18)F-FDG-PET/CT and subsequent LDLT for HCC from March 2005 to June 2011 were enrolled. The 191 patients with a median follow-up of 26.1 months were evaluated. There were 20 patients (10.5%) with early recurrence (≤6 months), 18 patients (9.4%) with late recurrence (>6 months), and 153 patients (80.1%) with no recurrence. Fifty-five patients (28.8%) displayed increased PET/CT tumor uptake. Three-year overall and disease-free survival for PET/CT-positive patients were 65.5% and 57.1%, respectively, while PET/CT-negative patients showed respective values of 89.8% and 86.8% (P = 0.001 vs. P < 0.001). Tumor variables associated with PET/CT-positive finding were preoperative AFP level, Milan, UCSF criteria, maximum tumor size, total tumor size, differentiation, vascular invasion, and serosal invasion. PET/CT-positive status was identified as an independent prognostic factor for disease-free survival influencing early recurrence in multivariable analysis (HR 3.945, 95% CI 1.196-13.016, P = 0.024). (18)F-FDG-PET/CT is an independent and significant predictor of early tumor recurrence in LDLT for HCC.

Predictive value of (18)FDG PET-CT for tumour response in patients with locally advanced rectal cancer treated by preoperative chemoradiotherapy.

PURPOSE: Although (18)fluorine-2-deoxy-D-glucose positron emission tomography-computed tomography ((18)FDG PET-CT) is considered a reliable modality for determining tumour response after neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC), the role of (18)FDG PET-CT for predicting pathologic complete response (pCR) remains unclear. The aim of this study was to evaluate whether (18)FDG PET-CT can predict tumour response after CRT in patients with LARC, in terms of downstaging and pCR. METHODS: Between March 2009 and February 2012, 151 patients with LARC treated with neoadjuvant CRT followed by radical surgery were reviewed retrospectively. Pre-CRT SUVmax (maximum standardized uptake value), post-CRT SUVmax, ΔSUVmax (difference between pre- and post-CRT SUVmax), and RI-SUV (response index) were measured before and after CRT. Univariate and multivariate analyses were used to analyse the association of PET-CT-related parameters and clinical variables, to assess downstaging and pCR. RESULTS: Downstaging occurred in 48 patients (31.7 %) and pCR in 19 patients (12.5 %). Univariate and multivariate analysis revealed post-CRT SUVmax as a significant factor for prediction of downstaging, with sensitivity of 60.4 %, specificity of 65.0 %, and accuracy of 55.9 %, for a cutoff value of 3.70. Regarding pCR, post-CRT SUVmax was again found as a significant parameter by univariate and multivariate analysis, with sensitivity of 73.7 %, specificity of 63.7 %, and accuracy of 64.9 %, for a cutoff value of 3.55. CONCLUSIONS: The results indicate that post-CRT SUVmax independently predicts downstaging and pCR. However, the predictive values of post-CRT SUVmax for tumour response after neoadjuvant CRT are too low in sensitivity and specificity to change the treatment plan for LARC.

Unexpected longevity, intergenerational policies, and fertility.

This paper studies the dynamic effects of longevity on intergenerational policies and fertility, distinguishing between effects of expected and unexpected longevity gains. Old agents become poorer from unexpected longevity gains than from expected gains, as they cannot prepare (save) for the former in advance. In an overlapping-generations model with means-tested pay-as-you-go social security, we show that young agents reduce their fertility when longevity increases because they need to save more for their old age ("life-cycle effect"), and in the unexpected case, they also need to pay taxes to support the impoverished elderly ("policy effect"). Using cross-country panel data on mortality rates and social expenditure, we find that an unexpected increase in life expectancy at age 65 lowers total fertility rate growth and government family-related spending growth while raising government old-age spending growth. Supplementary information: The online version contains supplementary material available at 10.1007/s00148-023-00943-3.

Synergistic effects of concurrent photodynamic therapy with indocyanine green and chemotherapy in hepatocellular carcinoma cell lines and mouse models.

BACKGROUND: Photodynamic therapy (PDT) using an 808 nm laser irradiation with indocyanine green (ICG) has shown tumoricidal effects in a hepatocellular (HCC) orthotopic xenograft model. Recently, combining PDT with concurrent chemotherapy has shown synergistic outcomes and a better therapeutic effect for cancer treatment. In the present study, we utilized a combination of chemotherapy drugs and PDT using ICG in vitro and in vivo in a patient-derived orthotopic xenograft (PDoX) model. METHOD: We independently performed PDT and chemotherapy with sorafenib or doxorubicin in the Huh-7 and Hep3b cell lines by increasing the sorafenib or doxorubicin concentration and increasing the total energy of 808 nm light. Subsequently, we combined the two treatments to confirm the effects on cell viability. The combination index (CI) was evaluated in vitro, and thereafter, in the HCC PDoX mouse model, 808 nm laser irradiation with intravenously injected ICG and chemotherapy using doxorubicin were performed for twelve days. RESULT: The viability of the Huh-7 and Hep3B cell lines decreased rapidly as the concentration of sorafenib or doxorubicin increased and as the total energy of 808 nm light increased. The cell viability of the Huh-7 and Hep3b cell lines with combined PDT and chemotherapy was less than that with PDT or chemotherapy alone. The CI was <1 in the sorafenib- or doxorubicin-treated Huh-7 and Hep3b cell lines. In the HCC PDoX mouse model, tumor size was markedly decreased, and complete remission achieved compared to that of the single chemotherapy or PDT and control groups. CONCLUSION: The synergistic effect of concurrent PDT and chemotherapy in the HCC cell line and PDoX model was confirmed with no definite adverse effect. Concurrent PDT and chemotherapy could be applied in further preclinical studies.