Long-term Outcomes of Hepatic Resection Combined With Intraoperative Ablation Versus Hepatic Resection Alone for Multinodular Hepatocellular Carcinoma: Insights from a Single-center Study.

BACKGROUND/AIM: The efficacy of combining hepatic resection (HR) with ablation therapy in treating multinodular hepatocellular carcinoma (mHCC) remains uncertain. This study aimed to compare the long-term survival outcomes of patients with mHCC undergoing HR combined with intraoperative ablation (HRA) versus those undergoing HR alone. PATIENTS AND METHODS: A retrospective analysis was conducted on 296 patients diagnosed with early-stage [Barcelona Clinic Liver Cancer (BCLC)-A] or intermediate-stage (BCLC-B) mHCC who underwent initial HR. Patients were divided into two groups: those who received HRA (HRA group, n=159) and those who underwent HR alone (HR group, n=137). Propensity score (PS), estimated as the likelihood of undergoing HRA, was applied to adjust for between-group differences in baseline characteristics. Overall survival (OS) and relapse-free survival (RFS) were compared using Cox regression and Kaplan-Meier analyses. RESULTS: There were no significant differences in survival between the HRA and HR groups, with 5-year OS and RFS rates of 47.7% versus 51.9% (p=0.837) and 17.0% versus 25.9% (p=0.094), respectively. After adjusting for PS, the differences remained non-significant (p=0.579 for OS and p=0.410 for RFS). Consistent results were also observed in PS-adjusted subgroup analysis stratified by factors such as BCLC stage, "Up-to-7" criteria, and Child-Pugh class. CONCLUSION: HRA may offer comparable long-term efficacy to HR alone in mHCC, suggesting broader treatment options that challenge the guideline-based monotherapy.

High hand grip strength is a significant risk factor and a useful predictor of postoperative pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most critical complications of pancreaticoduodenectomy (PD). Studies on predictive factors for POPF that can be identified preoperatively are limited. Recent reports have highlighted the association between the preoperative nutritional status, including sarcopenia, and postoperative complications. We examined preoperative risk factors for POPF after PD, focusing on nutritional indicators. METHODS: A total of 153 consecutive patients who underwent PD at our institution were enrolled in this study. Preoperative nutritional parameters, including hand grip strength (HGS) and skeletal muscle mass as components of sarcopenia, were incorporated into the analysis. POPFs were categorized according to the International Study Group of Pancreatic Fistula (ISGPF) definition as biochemical (grade A) or clinically relevant (CR-POPF; grades B and C). RESULTS: Thirty-seven of the 153 patients (24.1%) fulfilled the ISGPF definition of CR-POPF postoperatively. In the univariate analysis, the incidence of CR-POPF was associated with male sex, non-pancreatic tumor diseases, a high body mass index, a high HGS and a high skeletal muscle mass index. In the multivariate analysis, non-pancreatic tumor diseases and an HGS ≥23.0 kg were selected as independent risk factors for CR-POPF (P <0.05). CONCLUSIONS: A high HGS, a screening tool for sarcopenia, was a risk factor for CR-POPF. It can accurately serve as a useful predictor of POPF risk in patients undergoing PD. These results highlight the potential of sarcopenia to reduce the incidence of POPF and highlight the need to clarify the mechanism of POPF occurrence.

Predicting Pathological Response to Preoperative Chemotherapy in Pancreatic Ductal Adenocarcinoma Using Post-Chemotherapy Computed Tomography Radiomics.

INTRODUCTION: Assessing the response to preoperative treatment in pancreatic cancer provides valuable information for guiding subsequent treatment strategies. The present study aims to develop and validate a computed tomography (CT) radiomics-based machine learning (ML) model for predicting pathological response (PR) to preoperative chemotherapy in pancreatic ductal adenocarcinoma (PDAC). METHODS: Retrospective data were analyzed from 86 PDAC patients undergoing neoadjuvant or conversion chemotherapy followed by surgical resection from January 2018 to May 2023. The cohort was randomly divided into training (70%, n = 60) and testing (30%, n = 26) sets. Favorable PR was defined as Evans grade IIb or greater. Radiomic features were extracted from post-chemotherapy CT images, and dimensionality reduction was performed using the least absolute shrinkage and selection operator (LASSO) logistic regression. Four ML classifiers (Light Gradient Boosting Machine (LGBM), Random Forest, AdaBoost, and Quadratic Discriminant Analysis) were evaluated for predicting a favorable PR. Model performance was primarily assessed using the area under the receiver operating characteristic curve (AUC), Brier score, and decision curve analysis. RESULTS: Forty-one (47.7%) patients had a favorable PR. LASSO analysis on the training set identified five radiomic features. The LGBM model demonstrated the best performance, with a training AUC of 0.902 and a testing AUC of 0.923. It also exhibited the lowest Brier scores, both in training (0.136) and testing (0.135). Decision curve analysis further confirmed its clinical potential. CONCLUSION: The CT radiomics-based ML model exhibited promising performance in predicting PR in PDAC after neoadjuvant/conversion chemotherapy. This suggests clinical utility in optimizing surgical candidates and timing of surgery, leading to personalized treatment strategies.

Germ cell migration: Unexpected role of juvenile hormone before juvenile stages.

Juvenile hormone is best known for its role in maintaining juvenile-stage insects in their immature states during postembryonic development. A new study finds an unexpected role for this signaling lipid in guiding primordial germ cell migration during embryogenesis - possibly an ancestral function of isoprenoid signaling molecules.

Machine learning approach to predict postpancreatectomy hemorrhage following pancreaticoduodenectomy: a retrospective study.

BACKGROUND: Postpancreatectomy hemorrhage (PPH) is a rare yet dreaded complication following pancreaticoduodenectomy (PD). This retrospective study aimed to explore a machine learning (ML) model for predicting PPH in PD patients. METHODS: A total of 284 patients who underwent open PD at our institute were included in the analysis. To address the issue of imbalanced data, the adaptive synthetic sampling (ADASYN) technique was employed. The best-performing ML model was selected using the PyCaret library in Python and evaluated based on recall, precision, and F1 score metrics. In addition to assessing the model's performance on the test data, bootstrap validation (n = 1000) with the original dataset was conducted. RESULTS: PPH occurred in 11 patients (3.9%), with a median onset time of 22 days postoperatively. These minority cases were oversampled to 85 using ADASYN. The extra trees classifier demonstrated superior performance with recall, precision, and F1 score of 0.967, 0.914, and 0.937, respectively. Both validation using the test data and bootstrap resampling consistently demonstrated recall, precision, and F1 score exceeding 0.9. The model identified the peak value of C-reactive protein during the first 7 postoperative days as the most significant feature, followed by the preoperative neutrophil-to-lymphocyte ratio. CONCLUSIONS: This study highlights the potential of the ML approach to predict PPH occurrence following PD. Vigilance and early interventions guided by such model predictions could positively impact outcomes for high-risk patients.

Laparoscopic Projection Mapping of the Liver Portal Segment, Based on Augmented Reality Combined With Artificial Intelligence, for Laparoscopic Anatomical Liver Resection.

Hepatocellular carcinoma causes intrahepatic metastasis via the trans-portal vein. Thus, appropriate mapping of portal segments is necessary for laparoscopic anatomical liver resection. However, because of the difficulty in identifying tactile sensations and the limited surgical view of laparoscopy, augmented reality (AR) has recently been utilized in laparoscopic liver surgery to identify the tumor, vessels, and portal segments. Moreover, artificial intelligence (AI) has been employed to identify landmarks in two-dimensional (2D) images because of concerns regarding the accuracy of superimposing a three-dimensional (3D) model onto a 2D laparoscopic image. In this study, we report an AR-based projection mapping method of portal segments superimposing preoperative 3D models assisted by AI in laparoscopic surgery. The liver silhouette in laparoscopic images should be detected to superimpose 3D models. Labeled liver silhouettes were obtained from 380 images in surgical videos as learning images to implement AI-based silhouette detection. To implement this technique, we used Detectron2, a PyTorch-based object detection library by Facebook AI Research (Now, Meta AI, Menlo Park, California, United States). In the videos, the liver edges were displayed as green outlines according to AI. Additionally, 3D liver models with segmental mapping were generated using the open-source software 3D Slicer from computed tomography images. For AR display, we utilized the model target function of Vuforia SDK (PTC, Inc., Boston, Massachusetts, United States), an industrial AR library with silhouette-based AR display. Lastly, we merged the AI output video with a 3D model in Unity (Unity Software Inc., San Francisco, California, United States) to establish the projection mapping of the portal segment on 2D surgical images. The accuracy was assessed by measuring the maximum error between the liver edges of laparoscopic images and 3D liver silhouettes in five surgical videos. The maximum error between liver edges and 3D model silhouettes ranged from 4 mm to 22 mm in the AI-based approach and 12 mm to 55 mm in the non-AI-based approach. Meanwhile, the mean error was 14.5 and 31.2 mm in the AI-based and non-AI-based approaches, respectively. Despite camera movement, 3D AR displays were maintained. Thus, our AI-assisted projection mapping of the portal segment could offer a new approach for laparoscopic anatomical liver resection.

A Liver-First Approach Using Ablation for Oligometastatic Pancreatic Cancer: A Report of a Successful Case.

Pancreatic cancer (PC) is a highly aggressive malignancy, often accompanied by liver metastases as a common manifestation. While palliative chemotherapy remains the mainstay treatment for liver metastatic PC, local treatment approaches have gained attention, especially for patients with oligometastasis who exhibit a positive response to chemotherapy. This case report illustrates the successful application of a liver-first strategy in a 79-year-old male diagnosed with liver oligometastatic PC, originating in the pancreatic tail. The strategy encompassed percutaneous microwave ablation for liver metastases, followed by FOLFIRINOX (5-fluorouracil, folic acid, irinotecan, and oxaliplatin) chemotherapy, and subsequent primary tumor resection. The patient has remained disease-free for over a year post-surgery. This multidisciplinary approach may hold promise for selected patients with liver oligometastatic PC, although further research and case studies are needed for comprehensive evaluation.

Optimal Dosage of Indocyanine Green Fluorescence for Intraoperative Positive Staining in Laparoscopic Anatomical Liver Resection.

Introduction Fluorescence imaging technology, specifically utilizing indocyanine green (ICG), has emerged as a valuable tool in laparoscopic hepatectomy. In particular, laparoscopic anatomical liver resection (ALR) has benefited from the implementation of both positive and negative staining methods. A case series study reported a success rate of 53% for the positive staining method, citing potential issues regarding the proper ICG dosage needed for accurate fluorescence. Thus, it is crucial to conduct research to investigate the optimal dosage for ICG-positive staining in clinical practice to maximize the benefits of this technique. Materials and methods This retrospective study was conducted at a single center, Meiwa Hospital, and received approval from the hospital's ethics committee in accordance with the Helsinki Declaration. We reviewed the records of 264 patients who underwent open and laparoscopic hepatectomies for benign and malignant liver diseases from January 2019 to January 2023. Of these, 18 patients who underwent laparoscopic ALR with the ICG-positive staining method were evaluated. Fluorescence-emitting segmental borders were assessed immediately after puncture (first stage) and during parenchymal dissection (second stage). In the first stage, we evaluated the intensity of fluorescence emission, categorizing it as "strong" or "weak." The absence of visible fluorescence emission was considered a puncture failure. During the second stage of evaluation, from parenchymal resection to completion, we assessed the sustainability of fluorescence emission, defining it as "clear" or "contaminated." Both evaluations were subjectively judged by three surgeons at our center. The ICG quantity per targeted portal vein-bearing liver volume (mg/100 mL) was calculated for each patient, and the optimal dosage was determined using receiver operating characteristic (ROC) curve analysis. To ascertain the minimum value for adequate fluorescence emission intensity, ROC curve analysis was performed to discriminate between binary outcomes of "strong" or "weak" emission. Furthermore, to establish the maximum value for maintaining a clear fluorescence border, ROC curve analysis was conducted to discriminate between "clear" and "contaminated" during the second evaluation. Results Among the 18 successful puncture cases, the first-stage evaluation of fluorescence intensity revealed 14 punctures with "strong" intensity and four punctures with "weak" intensity. In the second-stage evaluation, 13 cases demonstrated "clear" borders, while five cases exhibited "contaminated" borders. ROC curve analysis was performed to determine the optimal ICG dose for adequate fluorescence intensity and preservation of clear borders during dissection. The analysis indicated that the appropriate ICG dose for achieving optimal intensity was 0.028 mg/100 mL (area under the curve [AUC]: 0.893), while the dose that prevented contamination of fluorescence in non-target areas until after dissection was 0.083 mg/100 mL (AUC: 0.723). Conclusions Laparoscopic anatomical resection using the positive staining method requires an optimal ICG dosage of 0.028-0.083 mg per 100 mL of liver volume. By employing this methodology, more precise and safer laparoscopic anatomical resections can be conducted, thereby enhancing the safety of the surgical procedure for patients.

Prognostic value of geriatric nutritional risk index for patients with biliary tract cancer undergoing surgical resection - a single-institution retrospective cohort study.

Introduction: The geriatric nutritional risk index (GNRI) is an index of nutritional status associated with clinical outcomes in various cancers; however, its prognostic value in biliary tract cancer (BTC) remains to be elucidated. This retrospective study aimed to investigate the association between preoperative GNRI and long-term prognosis of patients with BTC undergoing surgical resection. Material and methods: A total of 213 patients were included. The relationships between GNRI and clinicopathological variables, including inflammatory markers such as C-reactive protein (CRP) and neutrophil-to-lympho-cyte ratio, were analysed. The impact of GNRI on overall survival (OS) and relapse-free survival (RFS) was investigated by Kaplan-Meier curves and Cox proportional hazards models. Results: Applying a GNRI cut-off of 98, the low-GNRI group comprised 135 patients (63%). The low-GNRI group had elevated carbohydrate antigen 19-9 and CRP levels, high rates of preoperative biliary stenting, lymph node metastases, and perineural invasion, and a lower rate of R0 resection than the high-GNRI group. Both OS and RFS in the low-GNRI group were significantly lower. In multivariate analysis, low GNRI was a significant predictor of poor OS (hazard ratio [HR], 1.731; 95% CI: 1.111-2.696; p = 0.015) and RFS (HR, 1.900; 95% CI: 1.231-2.931; p = 0.004), independently of inflammatory and tumour markers, as well as of pathological features. Conclusions: Preoperative GNRI may be an easily accessible predictor of poor prognosis in patients with BTC undergoing surgical resection.

Steroid hormone signaling: What we can learn from insect models.

Ecdysteroids are a group of steroid hormones in arthropods with pleiotropic functions throughout their life history. Ecdysteroid research in insects has made a significant contribution to our current understanding of steroid hormone signaling in metazoans, but how far can we extrapolate our findings in insects to other systems, such as mammals? In this chapter, we compare steroid hormone signaling in insects and mammals from multiple perspectives and discuss similarities and differences between the two lineages. We also highlight a few understudied areas and remaining questions of steroid hormone biology in metazoans and propose potential future research directions.

Establishment and Internal Validation of a Prognostic Score for Post-hepatectomy Liver Failure Based on Functional Liver Parameters Estimated via TC-99m GSA.

Background The 99mTc-galactosyl human serum albumin (Tc-99m GSA) scintigraphy evaluates the future remnant liver function, which is an important prognostic factor for post-hepatectomy liver failure (PHLF). This study aimed to establish a new prognostic score for PHLF, including the functional liver parameters evaluated by Tc-99m GSA scintigraphy. Materials and methods This study reviewed a single-center, retrospective 368-patient database of those who underwent open and laparoscopic hepatectomy in Meiwa Hospital from January 2016 to October 2021. Moreover, 102 patients who underwent Tc-99m GSA scintigraphy following hepatectomy were analyzed. The index of blood clearance of the tracer was calculated from the uptake ratio of heart at 15 minutes to that at 3 minutes (HH15) and the index of hepatic accumulation was calculated from the uptake ratio of liver to liver plus heart at 15 minutes after the injection (LHL15) were calculated for the general functional parameters. The maximal removal rate of Tc-99m GSA (GSARmax) was also calculated, then the GSARmax of the remnant liver (GSARmax-RL) was estimated as the future remnant liver function depending on the hepatectomy. Multivariate analysis was conducted to identify the PHLF predictor, and then a risk-scoring system was established with the 1,000-times bootstrapped validation. Results PHLF (grade ≥ B) was observed in 13 of 102 patients. Multivariate analysis revealed that PHLF was independently predicted by GSARmax-RL (<0.26 mg/min) and LHL15 (<0.89). The risk score was assigned to each item and then classified into four subgroups, with a predicted PHLF of 3.7%, 14.4%, 42.8%, and 76.8%. Receiver operating characteristic (ROC) curve analysis demonstrated good discrimination (adjusted area under the curve (AUC) after bootstrapped validation, 0.779). The ROC curve analysis compared with other prognostic scores showed that the new model had the highest AUC values for accuracy. Conclusions The new prognostic score based on Tc-99m GSA scintigraphy could recognize patients with a high risk of progressing to PHLF and be helpful in planning therapeutic strategies.

Perioperative Fluid Balance and the Risk of Postoperative Pancreatic Fistula After Pancreaticoduodenectomy: A Propensity Score-adjusted Analysis.

BACKGROUND/AIM: The impact of perioperative fluid management on postoperative morbidity after pancreaticoduodenectomy (PD) remains uncertain. This study aimed to investigate the independent association between perioperative fluid balance (FB) and clinically relevant postoperative pancreatic fistula (POPF) in PD patients. PATIENTS AND METHODS: A total of 243 consecutive open PD patients were included. Intra- and postoperative FB until postoperative day 3 were calculated, and their predictive performance for POPF was assessed using receiver operating characteristic (ROC) analysis. Propensity score (PS) was estimated as the probability of having higher FB, and factors associated with POPF were identified using crude and PS-adjusted logistic regression models. RESULTS: POPF occurred in 60 patients (24.7%). ROC analysis showed the highest predictive value for total FB on postoperative days 1 and 2, with a cut-off value of 1,585 ml (area under the ROC curve=0.74). Patients with FB ≥1,585 ml had a significantly higher POPF rate (48.3%) compared to those with lower FB (11.0%, PS-adjusted p<0.001). Male sex, body mass index ≥25 kg/m2, non-pancreatic ductal adenocarcinoma, biliary drainage, main pancreatic duct diameter <3 mm, and higher FB showed significant associations with POPF in crude univariate analysis. Higher FB remained a significant factor in both crude multivariate and PS-adjusted analysis [crude multivariate: odds ratio (OR)=8.0; PS-adjusted univariate: OR=4.2; PS-adjusted multivariate: OR=6.1, all p<0.001]. CONCLUSION: Higher early postoperative FB, a potentially modifiable factor, may be independently associated with increased risk of POPF in PD patients.

Genetic Mapping of Seven Kinds of Locus for Resistance to Asian Soybean Rust.

Asian soybean rust (ASR), caused by Phakopsora pachyrhizi, is one of the most serious soybean (Glycine max) diseases in tropical and subtropical regions. To facilitate the development of resistant varieties using gene pyramiding, DNA markers closely linked to seven resistance genes, namely, Rpp1, Rpp1-b, Rpp2, Rpp3, Rpp4, Rpp5, and Rpp6, were identified. Linkage analysis of resistance-related traits and marker genotypes using 13 segregating populations of ASR resistance, including eight previously published by our group and five newly developed populations, identified the resistance loci with markers at intervals of less than 2.0 cM for all seven resistance genes. Inoculation was conducted of the same population with two P. pachyrhizi isolates of different virulence, and two resistant varieties, 'Kinoshita' and 'Shiranui,' previously thought to only harbor Rpp5, was found to also harbor Rpp3. Markers closely linked to the resistance loci identified in this study will be used for ASR-resistance breeding and the identification of the genes responsible for resistance.

Preoperative Psoas Muscle Thickness to Height Ratio Predicts Poor Survival After Resection of Biliary Tract Cancer.

BACKGROUND/AIM: Accumulating evidence suggests that muscle mass depletion (sarcopenia) has a negative impact on survival in several malignancies, including biliary tract cancer (BTC). Computed tomography (CT)-measured psoas muscle thickness to height ratio (PMTH) has been reported as a surrogate measure for muscle mass that does not require specialized equipment or software. The aim of this retrospective study was to investigate whether preoperative PMTH predicts oncological outcomes of patients undergoing surgical resection for BTC. PATIENTS AND METHODS: PMTH was assessed in 211 patients by analyzing axial CT images at the level of the umbilicus. The most predictive cutoff of PMTH was determined by survival classification and regression tree analysis. Propensity score-based inverse probability weighting (IPW) was used to balance characteristics between the low and high PMTH groups. RESULTS: Applying a PMTH cutoff of 17.5 mm/m, the low PMTH group comprised 114 patients (54%). Low PMTH was associated with female sex, non-obesity, CA19-9 elevation, and lymph node metastasis. After IPW adjustment, the low PMTH group had a significantly shorter disease-specific survival (p<0.001) and relapse-free survival (p<0.001) than the high PMTH group. IPW-adjusted regression analysis revealed that a low PMTH was independently associated with worse disease-specific survival (hazard ratio=2.98, p<0.001) and relapse-free survival (hazard ratio=2.49, p<0.001), in addition to other factors such as tumor differentiation, perineural invasion, and resection margin status. CONCLUSION: Preoperative PMTH may be a simple and feasible index of sarcopenia for predicting poor survival after resection of BTC.

Understanding Phakopsora pachyrhizi in soybean: comprehensive insights, threats, and interventions from the Asian perspective.

Soybean (Glycine max L.) is an important crop in Asia, accounting for 17% of global soybean cultivation. However, this crop faces formidable challenges from the devastating foliar disease, Asian Soybean Rust (ASR), caused by Phakopsora pachyrhizi, a biotrophic fungus with a broad host range, causing substantial yield losses (10-100%) in Asia. This comprehensive review consolidates knowledge on ASR, encompassing its impact, historical perspectives, genetic diversity, epidemic drivers, early detection, risk assessment, and sustainable management strategies of ASR in the region. ASR has expanded globally from Asia, reaching Africa and Americas, driven by wind-dispersed urediniospores. Genetic diversity studies reveal the complexity of P. pachyrhizi, with distinct populations exhibiting varying virulence patterns. Factors affecting ASR epidemics in Asia include host susceptibility, landscape connectivity, climate, and environmental conditions. Understanding the interplay of these factors is essential for early intervention and control of ASR in soybean fields. Effectively managing ASR can exploit the utilization of diverse intervention strategies, encompassing disease forecasting, automated early detection, disease resistance, fungicide application, and biological control. A pivotal aspect of successful, sustainable disease management lies in reducing the ASR pathogen virulence and preventing it from developing fungicide resistance, while the highpoint of effectiveness in disease control is attained through a synergistic approach, integrating various strategies. In summary, this comprehensive review provides insights into multifaceted approaches that contribute to the development of sustainable and economically impactful soybean production in the face of the persistent threat of ASR in Asia.

Internal sensory neurons regulate stage-specific growth in Drosophila.

Animals control their developmental schedule in accordance with internal states and external environments. In Drosophila larvae, it is well established that nutrient status is sensed by different internal organs, which in turn regulate production of insulin-like peptides and thereby control growth. In contrast, the impact of the chemosensory system on larval development remains largely unclear. Here, we performed a genetic screen to identify gustatory receptor (Gr) neurons regulating growth and development, and found that Gr28a-expressing neurons are required for proper progression of larval growth. Gr28a is expressed in a subset of peripheral internal sensory neurons, which directly extend their axons to insulin-producing cells (IPCs) in the central nervous system. Silencing of Gr28a-expressing neurons blocked insulin-like peptide release from IPCs and suppressed larval growth during the mid-larval period. These results indicate that Gr28a-expressing neurons promote larval development by directly regulating growth-promoting endocrine signaling in a stage-specific manner.

Neoadjuvant Modified Short-course Radiotherapy for Stage IV Rectal Cancer.

BACKGROUND/AIM: This study aimed to assess the clinical outcomes of neoadjuvant modified short-course radiotherapy (mSC-RT) for rectal metastatic adenocarcinoma. PATIENTS AND METHODS: Data from 14 patients who underwent mSC-RT followed by surgery for primary tumors were retrospectively analyzed. Twelve patients received systemic chemotherapy for 18 weeks. A 2.5 Gy dose twice daily, up to a total dose of 25 Gy in 10 fractions, over 5 consecutive days was administered through mSC-RT. Surgery for primary tumor was performed five weeks (range=3-7 weeks) after mSC-RT. Nine patients underwent adjuvant chemotherapy. The median follow-up was 38.5 months. RESULTS: No patients developed grade ≥3 toxicities before surgery. Three patients developed local failures and 10 died during the follow-up period. The 1-, and 3-year local control rates were 91.7% and 71.3%, respectively. The median overall survival (OS) was 45.1 months. The 1-, and 3-year OS rates were 85.7% and 56.3%, respectively. Patients with stage IVA showed significantly better OS than those with stage IVB disease. CONCLUSION: mSC-RT followed by delayed surgery was well-tolerated and led to good local control in patients with rectal metastatic adenocarcinoma. mSC-RT could be a treatment option for patients with rectal metastatic adenocarcinoma as it is less likely to lead to cessation of systemic chemotherapy.

Preoperative Alkaline Phosphatase-adjusted CA19-9 as a Superior Prognosticator for Extrahepatic Biliary Tract Cancer With Jaundice.

BACKGROUND/AIM: The major limitation of carbohydrate antigen (CA)19-9 as a tumor marker is the high incidence of false-positive results during cholestasis. We evaluated preoperative CA19-9 and its adjusted values [ratios of CA19-9 to total-bilirubin (TB), direct-bilirubin (DB), and alkaline phosphatase (ALP)] to investigate the most suitable prognostic parameter in extrahepatic biliary tract cancer (eBTC) patients with or without jaundice. PATIENTS AND METHODS: eBTC patients (n=140) who underwent resection were divided based on the absence (TB <2.0 mg/dl, n=90) or presence (TB ≥2.0 mg/dl, n=50) of preoperative jaundice. Within each group, the associations with overall survival (OS) were assessed for CA19-9, CA19-9/TB, CA19-9/DB and CA19-9/ALP ratios using Cox regression, receiver operating characteristic (ROC) analyses, and area under the curve (AUC) estimates. RESULTS: In univariate analysis in the group without jaundice, both high CA19-9 and high CA19-9/TB ratio were associated with poor OS, whereas other parameters were not. ROC-AUC for OS prediction was greater in CA19-9 than in the CA19-9/TB ratio, and CA19-9 was identified as an independent prognosticator in multivariate analysis. In the group with jaundice, CA19-9 was not significant; however, CA19-9/TB, CA19-9/DB, and CA19-9/ALP ratios were all associated with poor OS. In ROC-AUC analysis, CA19-9/ALP ratio showed the highest predictive value; furthermore, it was an independent prognosticator in multivariate analysis. CONCLUSION: Adjustment of the CA19-9 value was less useful as a predictor in the absence of jaundice. On the other hand, the CA19-9/ALP ratio showed superior prognostic value in jaundiced patients with eBTC.

Surgery versus Radiofrequency Ablation for Small Hepatocellular Carcinoma: A Randomized Controlled Trial (SURF Trial).

Introduction: It remains unclear which surgery or radiofrequency ablation (RFA) is the more effective treatment for small hepatocellular carcinoma (HCC). We aimed to compare survival between patients undergoing surgery (surgery group) and patients undergoing RFA (RFA group). Methods: We conducted a randomized controlled trial involving 49 institutions in Japan. Patients with Child-Pugh scores ≤7, largest HCC diameter ≤3 cm, and ≤3 HCC nodules were considered eligible. The co-primary endpoints were recurrence-free survival (RFS) and overall survival (OS). The current study reports the final result of RFS, and the follow-up of OS is still ongoing. Results: During 2009-2015, 308 patients were registered. After excluding ineligible patients, the surgery and RFA groups included 150 and 151 patients, respectively. Baseline factors did not differ significantly between the groups. In both groups, 90% of patients had solitary HCC. The median largest HCC diameter was 1.8 cm (interquartile range [IQR], 1.5-2.2 cm) in the surgery group and 1.8 cm (IQR, 1.5-2.3 cm) in the RFA group. The median procedure duration (274 vs. 40 min, p < 0.01) and the median duration of hospital stay (17 days vs. 10 days, p < 0.01) were longer in the surgery group than in the RFA group. RFS did not differ significantly between the groups as the median RFS was 3.5 (95% confidence interval [CI], 2.6-5.1) years in the surgery group and 3.0 (95% CI, 2.4-5.6) years in the RFA group (hazard ratio, 0.92; 95% CI, 0.67-1.25; p = 0.58). Discussion/Conclusion: Our study did not show which surgery or RFA is the better treatment option for small HCC.

Essential functions of mosquito ecdysone importers in development and reproduction.

The primary insect steroid hormone ecdysone requires a membrane transporter to enter its target cells. Although an organic anion-transporting polypeptide (OATP) named Ecdysone Importer (EcI) serves this role in the fruit fly Drosophila melanogaster and most likely in other arthropod species, this highly conserved transporter is apparently missing in mosquitoes. Here we report three additional OATPs that facilitate cellular incorporation of ecdysone in Drosophila and the yellow fever mosquito Aedes aegypti. These additional ecdysone importers (EcI-2, -3, and -4) are dispensable for development and reproduction in Drosophila, consistent with the predominant role of EcI. In contrast, in Aedes, EcI-2 is indispensable for ecdysone-mediated development, whereas EcI-4 is critical for vitellogenesis induced by ecdysone in adult females. Altogether, our results indicate unique and essential functions of these additional ecdysone importers in mosquito development and reproduction, making them attractive molecular targets for species- and stage-specific control of ecdysone signaling in mosquitoes.