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Background Although total tumour volume (TTV) may have prognostic value for hepatic resection in certain solid cancers, its importance in colorectal liver metastases (CRLM) remains unexplored. This study investigated its prognostic value in patients with resectable CRLM. Method This was a retrospective review of patients who underwent hepatic resection for CRLM between 2008 and 2017 in a single institution. TTV was measured from CT images using three‐dimensional construction software; cut‐off values were determined using receiver operating characteristic (ROC) curve analyses. Potential prognostic factors, overall survival (OS) and recurrence‐free survival (RFS) were determined using multivariable and Kaplan–Meier analyses. Results Some 94 patients were included. TTV cut‐off values for OS and RFS were 100 and 10 ml respectively. Right colonic primary tumours, primary lymph node metastasis and bilobar liver metastasis were included in the multivariable analysis of OS; a TTV of 100 ml or above was independently associated with poorer OS (hazard ratio (HR) 6·34, 95 per cent c.i. 2·08 to 17·90; P = 0·002). Right colonic primary tumours and primary lymph node metastasis were included in the RFS analysis; a TTV of 10 ml or more independently predicted poorer RFS (HR 1·90, 1·12 to 3·57; P = 0·017). The 5‐year OS rate for a TTV of 100 ml or more was 41 per cent, compared with 67 per cent for a TTV below 100 ml (P = 0·006). Corresponding RFS rates with TTV of 10 ml or more, or less than 10 ml, were 14 and 58 per cent respectively (P = 0·009). A TTV of at least 100 ml conferred a higher rate of unresectable initial recurrences (12 of 15, 80 per cent) after initial hepatic resection. Conclusion TTV was associated with RFS and OS after initial hepatic resection for CRLM; TTV of 100 ml or above was associated with a higher rate of unresectable recurrence.

The rough lemon pathotype of Alternaria alternata produces host-selective ACR-toxin and causes Alternaria leaf spot disease of rough lemon (Citrus jambhiri). The structure of ACR-toxin I (MW = 496) consists of a polyketide with an α-dihydropyrone ring in a 19-carbon polyalcohol. Genes responsible for toxin production were localized to a 1.5-Mb chromosome in the genome of the rough lemon pathotype. Sequence analysis of this chromosome revealed an 8,338-bp open reading frame, ACRTS2, that was present only in the genomes of ACR-toxin-producing isolates. ACRTS2 is predicted to encode a putative polyketide synthase of 2,513 amino acids and belongs to the fungal reducing type I polyketide synthases. Typical polyketide functional domains were identified in the predicted amino acid sequence, including β-ketoacyl synthase, acyl transferase, methyl transferase, dehydratase, β-ketoreductase, and phosphopantetheine attachment site domains. Combined use of homologous recombination-mediated gene disruption and RNA silencing allowed examination of the functional role of multiple paralogs in ACR-toxin production. ACRTS2 was found to be essential for ACR-toxin production and pathogenicity of the rough lemon pathotype of A. alternata.

The tangerine pathotype of Alternaria alternata produces host-selective ACT-toxin and causes Alternaria brown spot disease of tangerine and tangerine hybrids. Sequence analysis of a genomic BAC clone identified part of the ACT-toxin TOX (ACTT) gene cluster, and knockout experiments have implicated several open reading frames (ORF) contained within the cluster in the biosynthesis of ACT-toxin. One of the ORF, designated ACTTS3, encoding a putative polyketide synthase, was isolated by rapid amplification of cDNA ends and genomic/reverse transcription-polymerase chain reactions using the specific primers designed from the BAC sequences. The 7,374-bp ORF encodes a polyketide synthase with putative β-ketoacyl synthase, acyltransferase, methyltransferase, β-ketoacyl reductase, and phosphopantetheine attachment site domains. Genomic Southern blots demonstrated that ACTTS3 is present on the smallest chromosome in the tangerine pathotype of A. alternata, and the presence of ACTTS3 is highly correlated with ACT-toxin production and pathogenicity. Targeted gene disruption of two copies of ACTTS3 led to a complete loss of ACT-toxin production and pathogenicity. These results indicate that ACTTS3 is an essential gene for ACT-toxin biosynthesis in the tangerine pathotype of A. alternata and is required for pathogenicity of this fungus.

Alternaria brown spot, caused by the tangerine pathotype of Alternaria alternata, is a serious disease of commercially important tangerines and their hybrids. The pathogen produces host-selective ACT toxin, and several genes (named ACTT) responsible for ACT-toxin biosynthesis have been identified. These genes have many paralogs, which are clustered on a small, conditionally dispensable chromosome, making it difficult to disrupt entire functional copies of ACTT genes using homologous recombination-mediated gene disruption. To overcome this problem, we attempted to use RNA silencing, which has never been employed in Alternaria spp., to knock down the functional copies of one ACTT gene with a single silencing event. ACTT2, which encodes a putative hydrolase and is present in multiple copies in the genome, was silenced by transforming the fungus with a plasmid construct expressing hairpin ACTT2 RNAs. The ACTT2 RNA-silenced transformant (S-7-24-2) completely lost ACTT2 transcripts and ACT-toxin production as well as pathogenicity. These results indicated that RNA silencing may be a useful technique for studying the role of ACTT genes responsible for host-selective toxin biosynthesis in A. alternata. Further, this technique may be broadly applicable to the analysis of many genes present in multiple copies in fungal genomes that are difficult to analyze using recombination-mediated knockdowns.

The expression of membrane antigens on rat hepatocytes transplanted syngeneically and heterotopically was analyzed immunohistochemically using monoclonal antibodies against rat hepatocytes. Isolated adult and fetal hepatocytes were able to survive in the spleen, salivary gland, thymus, or subcapsular region of the kidney for various periods after transplantation. Fairly clear expression of HAM2, 4, and 8 antigens was observed on hepatocytes transplanted into syngeneic spleen, suggesting that the cells might be functionally equivalent to hepatocytes in situ. HAM4 antigen was localized specifically on the newly formed bile-canalicular faces of hepatocytes. The expression of HAM2 (MHC class I) antigen on the transplanted hepatocytes appeared much stronger on the side facing lymphoid tissues, than on the other faces, suggesting that some immunological reactions may take place between hepatocytes and lymphoid tissue. HAM8 antigen, which is localized on gap junctions between neighboring hepatocytes in rat liver, was also recognized between transplanted hepatocytes. In salivary glands where hepatocytes were transplanted, bile-canaliculus-like structures were observed not only between neighboring hepatocytes but also between hepatocytes and salivary acinar cells, suggesting good interaction between the two different epithelial cell types. Hepatocytes transplanted into thymus appeared viable, but most showed fatty degeneration. Some healthy hepatocytes survived in the interlobular connective tissue and the thymic cortical tissue. When fetal hepatocytes were transplanted heterotopically, they formed a mass consisting of hepatocytes and bile duct-like structures 7 wk after transplantation. The inoculated hepatocytes possessed HAM4 antigen, which was not recognized on fetal hepatocytes at day 14 of gestation. These results suggest that transplanted hepatocytes can grow in any syngeneic tissues, and that a common feature on such hepatocytes is a rich reticulin fiber network, visualized by silver staining. To judge the state of transplanted hepatocytes, monoclonal antibodies against rat hepatocyte surface antigens might therefore be a useful tool.

Competing Interests: Declaration of Competing Interest The authors declare no competing interests.

Background: Proanthocyanidins (PACs) from black soybean seed coat have antioxidant and anti-tumorigenic properties. We investigated the anti-tumor properties and mechanisms of action of PACs on colorectal cancer (CRC)., Methods: We fed the APC min/+ mice, which are highly susceptible to spontaneous intestinal adenoma formation, diets supplemented with or without PACs for 7 weeks and assessed adverse effects, the number and size of intestinal polyps, and the expression of pro- and anti-proliferative proteins in the intestine. The mouse gut microbiome composition was analyzed, and the concentrations of gut short-chain fatty acids (SCFAs) were quantified. We also compared CRC incidence in Tamba in Japan, where black soybean is consumed frequently, with that in the rest of Japan., Results: The number and size of intestinal polyps notably decreased in the PAC-fed mice. Compared with control mice, the PAC-fed mice showed lower expression of proliferation markers proliferating cell nuclear antigen and β catenin and a higher expression of the anti-inflammatory protein oligomeric mucus gel-forming. PAC supplementation increased the prevalence and concentrations of beneficial gut microbes and SCFAs, respectively., Conclusions: Diet supplemented with black soybean-derived PACs could prevent CRC development in mice through gut microbiome remodeling. Regions consuming black soybeans have low CRC incidence. Notably, the incidence of CRC, breast cancer, and liver cancer was significantly lower in Tamba than in the rest of Hyogo Prefecture or Japan. Future studies should delineate the mechanisms underlying the CRC-protective effects of PACs. Nevertheless, our results demonstrate the potential of including PACs in dietary recommendations for cancer prevention.

Competing Interests: Disclosure There are no conflict of interest.

Schwannomas consist of both high-cellularity regions (Antoni A area) and hypocellular regions (Antoni B area) in histopathological findings. Neurofibromas characteristically consist of CD34 positive spindle cells with thin, wavy, nuclei and wavy collagen bands. Previous reports have described segments of schwannomas with neurofibroma features as hybrid tumors, although hybrid tumors were diagnosed based on partial CD34 positivity in many previous reports. On the other hand, the Antoni B area of some schwannomas was reported to be positive for CD34. Therefore, the definition of a hybrid tumor has not been clear. The objective of this study was to determine whether only CD34 positive findings in schwannomas could be used to define a hybrid tumor. In the analysis of our patient with schwannomatosis caused by a novel LZTR1 germline mutation, part of the tumor had CD34 positive hypocellular regions. These regions contained no thin, wavy, nuclei, indicating an Antoni B area. Laser microdissection was used to investigate the genetic background and differences in molecular mechanisms between CD34 positive and CD34 negative regions. All mutations identified in CD34 positive regions were also found in CD34 negative regions. Our data could not clear the genetic background of Antoni B which was CD34 positive area. We then reviewed the pathologies of 66 sporadic schwannomas. Histopathological examinations of all schwannomas revealed the absence of thin, wavy, nuclei and wavy collagen bands, and no hybrid tumors were found in any of the cases. Ten of 66 patients were randomly selected for CD34 immunostaining and positivity was found in all cases. Our data suggest that it is difficult to distinguish schwannomas by staining for CD34 alone, as Antoni B areas can also be positive for CD34. Therefore, CD34 staining alone should not be used to diagnose hybrid tumors in patients with schwannomas., (© 2024 Japanese Dermatological Association.)

Purpose: Surgeons' adaptability to robotic manipulation remains underexplored. This study evaluated the participants' first-touch robotic training skills using the hinotori surgical robot system and its simulator (hi-Sim) to assess adaptability., Methods: We enrolled 11 robotic surgeons (RS), 13 laparoscopic surgeons (LS), and 15 novices (N). After tutorial and training, participants performed pegboard tasks, camera and clutch operations, energizing operations, and suture sponge tasks on hi-Sim. They also completed a suture ligation task using the hinotori surgical robot system on a suture simulator. Median scores and task completion times were compared., Results: Pegboard task scores were 95.0%, 92.0%, and 91.5% for the RS, LS, and N groups, respectively, with differences between the RS group and LS and N groups. Camera and clutch operation scores were 93.1%, 49.7%, and 89.1%, respectively, showing differences between the RS group and LS and N groups. Energizing operation scores were 90.9%, 85.2%, and 95.0%, respectively, with a significant difference between the LS and N groups. Suture sponge task scores were 90.6%, 43.1%, and 46.2%, respectively, with differences between the RS group and LS and N groups. For the suture ligation task, completion times were 368 s, 666 s, and 1095 s, respectively, indicating differences among groups. Suture scores were 12, 10, and 7 points, respectively, with differences between the RS and N groups., Conclusion: First-touch simulator-based robotic skills were partially influenced by prior robotic surgical experience, while suturing skills were affected by overall surgical experience. Thus, robotic training programs should be tailored to individual adaptability., (© 2024. The Author(s).)

Background: Preoperative recognition of the anatomy of caudate biliary branches is important for the safe and complete resection of perihilar cholangiocarcinoma (PHC). In the present study, we identified these branches using an endoscopic nasobiliary drainage tube (ENBD)., Methods: Between January 2012 and October 2022, 89 patients with suspected PHC underwent computed tomographic (CT) cholangiography through ENBD and caudate biliary branching patterns were examined. Multidetector raw CT (MDCT) scans on 85 patients with PHC without biliary drainage were also investigated. The caudate biliary branches detected by each modality were evaluated., Results: ENBD-CT cholangiography detected 206 caudate branches (2.44 branches/patient), while MDCT identified 62 branches (0.78 branches/patient). ENBD-CT cholangiography showed that 89 caudate branches drained into the left hepatic duct (LHD), 87 into the posterior hepatic duct (Bpost), and 30 into the right hepatic duct. LHD and Bpost were the common roots of the caudate branches. Some branches (20%) joined the contralateral hepatic duct across the left-right border, but not the anterior hepatic duct or infraportal-type Bpost., Conclusions: ENBD-CT cholangiography clearly showed the caudate biliary branches in patients with PHC after biliary drainage., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS , GNAS , APC , BRAF , CTNNB1 , SMAD4 , TP53 , or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Maintaining physical activity and the development of physical and cognitive functions are essential especially in vulnerable populations such as children. Considering the substantial impact of the COVID-19 epidemic on preschool children and the lack of research focusing on this age group, this study examined the duration of physical activity among preschool-aged children on weekend days and its relationship with the environment. This study was conducted between October and November 2021, with the cooperation of 357 parents of preschoolers attending kindergartens, nurseries, and childcare centers. Physical activity was assessed using a 24h physical activity record. A questionnaire was used to collect basic data on the neighborhood environment. Stepwise multiple regression analysis was used to analyze the relationship between the five physical activity measures (sedentary time, screen time, indoor playing time, outdoor playing time, and going out time) and the questionnaire data. Our findings revealed a relationship between physical activity and the neighborhood environment; however, the R2 values were low. Despite low prediction accuracy, the results of this study were similar to those of previous studies, indicating a positive correlation of physical activity with the absence of undulating roads, a crime-free environment, and safety around the home. Overall, these findings emphasize the need for providing children with opportunities for outdoor physical activity and play in the context of the COVID-19 recovery phase for adherence to the relevant guidelines., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 YAMAGUCHI et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Particle therapy (PT) as an initial hepatocellular carcinoma (HCC) treatment has been reported to be effective; however, its efficacy for the treatment of recurrent HCC remains unclear., Objective: This study aimed to evaluate the efficacy of PT compared with repeat liver resection for treating recurrent HCC after initial LR, with a focus on prognostic outcomes., Methods: Between 2005 and 2019, 89 and 49 patients underwent repeat LR and PT for recurrent HCC after initial LR, respectively. The 5-year overall survival (OS) and recurrence-free survival (RFS) were evaluated using propensity score matching. Treatment-related complications were scored using the National Institute Common Terminology Criteria for Adverse Events (CTCAE) and were compared between the repeat LR and PT groups., Results: In the entire cohort, the 5-year OS was significantly better in the repeat LR group than in the PT group (75% vs. 48%; p = 0.0003), and the 5-year RFS was comparable in both groups (22% vs. 13%; p = 0.088). Propensity score matching created 34 pairs of patients; no significant differences in the 5-year OS (65% vs. 48%; p = 0.310) and RFS (21% vs. 8%; p = 0.271) were observed between the repeat LR and PT groups. The proportion of CTCAE grade ≥3 complications was 8.8% and 5.9% in the repeat LR and PT groups, respectively (p = 0.641)., Conclusions: After initial LR, the prognosis and treatment-related complications in patients with recurrent HCC were comparable between the repeat LR and PT groups in the matched cohort; therefore, PT may remain one of the multidisciplinary treatment options for recurrent HCC., (© 2024. Society of Surgical Oncology.)

Abstract: Dermatofibrosarcoma protuberans (DFSP) is a neoplasm of intermediate malignancy with high local recurrence rates. The sclerosing variant is characterized by the presence of sclerotic areas in more than 50% of tumors and is rarely reported. In this report, we describe a case of sclerosing DFSP with areas histopathologically resembling sclerotic fibroma, where the initial biopsy tissue presented a diagnostic challenge. A 77-year-old man presented with a 2-cm firm, erythematous nodule on the chest. A punch biopsy revealed plywood-like sclerosis and spindle cells with a vaguely storiform pattern. The tumor cells were positive for CD34. Sclerotic fibroma and DFSP were considered differential diagnoses. Subsequent excisional biopsy revealed that the tumor comprised 3 different histopathological areas: classic DFSP, sclerotic fibroma-like, and giant cell fibroblastoma-like. This report highlights the importance of reevaluating the clinical context and excision for further characterization., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, a taxane (genotoxic drug), although it has a limited effect owing to chemoresistance to prolonged treatment. In this study, we examine an alternative angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We find that the chemotherapeutic drugs cisplatin and paclitaxel efficiently induce senescence in angiosarcoma cells. Subsequent treatment with the senolytic agent ABT-263 eliminates senescent cells by activating the apoptotic pathway. In addition, expression analysis indicates that senescence-associated secretory phenotype genes are activated in senescent angiosarcoma cells and that ABT-263 treatment downregulates IFN-I pathway genes in senescent cells. Moreover, we show that cisplatin treatment alone requires high doses to remove angiosarcoma cells. In contrast, lower doses of cisplatin are sufficient to induce senescence, followed by the elimination of senescent cells by the senolytic treatment. This study sheds light on a potential therapeutic strategy against angiosarcoma by combining a relatively low dose of cisplatin with the ABT-263 senolytic agent, which can help ease the deleterious side effects of chemotherapy., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Robot-assisted surgery is widely performed for renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombi. Although many chemotherapeutic options are available for the treatment of unresectable RCC, there are very few reports on robot-assisted radical nephrectomy (RARN) with inferior vena cava thrombectomy (IVCT) after presurgical treatment with immune checkpoint inhibitors and tyrosine kinase inhibitors. We believe that pre-surgical treatment can provide minimally invasive surgical benefits to high-risk patients during the perioperative period., Case Description: A 77-year-old male with right RCC that invaded the IVC (cT3bN0M0, Mayo classification level III) underwent pembrolizumab and axitinib combination therapy because he had high surgical risk due to angina pectoris. The level of the tumor thrombus decreased from level III to II, and RARN with IVCT was then performed. Surgery was performed without complications, and the patient was discharged on postoperative day seven. The pathological diagnosis was clear cell RCC (ypT3b, G2). Adjuvant chemotherapy using pembrolizumab monotherapy is still ongoing., Conclusions: In this report, the inferior vena cave tumor thrombus level was down staged from level III to level II by treatment with pembrolizumab and axitinib. RARN with IVCT was safely performed without complication completely under robotic assistance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1547/coif). The series “Current Status of Robotic Surgery for Genitourinary Diseases in Japan” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: Systemic inflammation and altered metabolism are essential hallmarks of cancer. We hypothesized that the rapid turnover protein transthyretin (TTR) (half-life: 2-3 days), compared with the conventional marker albumin (21 days), better reflects the inflammatory/metabolic dynamics of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and is a useful prognostic marker., Methods: Serum TTR and albumin levels were measured in 104 consecutive post-NAT PDAC patients before curative resection. The associations of preoperative TTR and albumin levels with overall survival (OS) after pancreatectomy were retrospectively analyzed., Results: The mean (SD) TTR and albumin levels were 21.6 (6.4) mg/dL (normal range: ≥22.0 mg/dL) and 3.9 (0.55) g/dL. A low (<22.0 mg/dL) post-NAT TTR level was associated with an advanced tumor stage and higher CEA and CRP levels. Patients with low TTR levels showed significantly worse OS compared with normal levels (3-year OS 39 % vs. 54 %, P = 0.037), although albumin levels did not. We modified prognostic biomarkers of systemic inflammation/metabolism, such as GPS, PNI, and CONUT scores, using the serum TTR instead of albumin level and successfully showed that modified scores were better associated with OS compared with original scores using serum albumin level., Conclusions: Our data suggest that the TTR level is a promising prognostic biomarker for PDAC patients after NAT., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: Xeroderma pigmentosum (XP) is characterized by photosensitivity that causes pigmentary disorder and predisposition to skin cancers on sunlight-exposed areas due to DNA repair deficiency. Patients with XP group A (XP-A) develop freckle-like pigmented maculae and depigmented maculae within a year unless strict sun-protection is enforced. Although it is crucial to study pigment cells (melanocytes: MCs) as disease target cells, establishing MCs in primary cultures is challenging., Objective: Elucidation of the disease pathogenesis by comparison between MCs differentiated from XP-A induced pluripotent stem cells (iPSCs) and healthy control iPSCs on the response to UV irradiation., Methods: iPSCs were established from a XP-A fibroblasts and differentiated into MCs. Differences in gene expression profiles between XP-A-iPSC-derived melanocytes (XP-A-iMCs) and Healthy control iPSC-derived MCs (HC-iMCs) were analyzed 4 and 12 h after irradiation with 30 or 150 J/m 2 of UV-B using microarray analysis., Results: XP-A-iMCs expressed SOX10, MITF, and TYR, and showed melanin synthesis. Further, XP-A-iMCs showed reduced DNA repair ability. Gene expression profile between XP-A-iMCs and HC-iMCs revealed that, numerous gene probes that were specifically upregulated or downregulated in XP-A-iMCs after 150-J/m 2 of UV-B irradiation did not return to basal levels. Of note that apoptotic pathways were highly upregulated at 150 J/m 2 UV exposure in XP-A-iMCs, and cytokine-related pathways were upregulated even at 30 J/m 2 UV exposure., Conclusion: We revealed for the first time that cytokine-related pathways were upregulated even at low-dose UV exposure in XP-A-iMCs. Disease-specific iPSCs are useful to elucidate the disease pathogenesis and develop treatment strategies of XP., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background Pancreatic duct (PD) disruption can occasionally be attributed to pancreatic cancer. Therapeutic interventions for PD disruption due to pancreatic cancer and their influence on pancreatic cancer prognosis remain unclear. This study investigated the therapeutic modalities and prognostic implications of PD disruption in pancreatic cancer. Methods This retrospective study included 15 patients with PD disruption concomitant with pancreatic cancer between April 2011 and March 2023. As an endoscopic intervention for PD disruption, endoscopic pancreatic stenting (EPS) or endoscopic ultrasonography-guided pancreatic fluid collection drainage (EUS-PFD) was performed. Technical success was defined as stent placement and clinical success was defined as an improvement in PD disruption. Results Of the 15 cases of PD disruption, two involved only pancreatic juice leakage without symptoms, four involved pancreatic pseudocyst (PPC) without infection, and nine involved PPC with infection. Four patients underwent EPS, nine underwent EUS-PFD, and two underwent lumen-apposing metal stent placement. All patients achieved both technical and clinical success without complications. The clinical stage of pancreatic cancer ranged from carcinoma in situ to the metastatic phase. For the treatment of pancreatic cancer, five patients underwent surgical resection, and eight underwent chemotherapy. There was no obvious recurrence of peritoneal sowing. The median overall survival from the diagnosis of pancreatic cancer in the resected and non-resected cases was 74 and 9.6 months, respectively. Conclusion Endoscopic intervention was effective in all cases of PD disruption due to pancreatic cancer. Furthermore, even in cases of pancreatic cancer after PD disruption, survival rates were similar to those in cases without PD disruption and were achieved through surgical resection or chemotherapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Kobe University School of Medicine Ethics Committee issued approval B232030. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Oka et al.)

Structural colouration observed in antimony phosphate nanosheet suspensions has been known for two decades, but the stability of their inner structures has not been a topic in colloidal nanosheet systems. In this study, we investigate the time evolution of structures in suspension using UV-visible spectrometry and small-angle X-ray scattering. Here, we report that antimony phosphate nanosheet systems re-organise their inner structures, especially at lower concentrations (isotropic or biphasic region), and that the basal spacing decreases with time after sample preparation, although the evolution speed depends on the sample concentration. The stability of the inner structure of the suspension is essential for their application as structural colour materials in sensors and colourants.

Space-making particle therapy, which consists of surgical placement of a spacer followed by particle therapy, has become a solution to the problem of normal organs being exposed to a high radiation dose. A bioabsorbable spacer is particularly suitable for this purpose, but is not widely used. Surgical placement of a spacer is performed mostly to protect the digestive tract, but can also be used to protect the kidneys. Therefore, we have been interested in the use of space-making particle therapy to preserve renal function. A 14 month-old boy with intermediate-risk retroperitoneal rhabdomyosarcoma underwent surgery with placement of a bioabsorbable spacer following neoadjuvant chemotherapy and then received proton beam therapy of 41.4 Gy (relative biological effectiveness) in 23 fractions. In the 41 months since PBT, he has survived without local recurrence or signs of renal impairment. This report describes the first-ever case of surgical placement of a bioabsorbable spacer with the aim of preserving renal function during proton beam therapy. Space-making particle therapy is an innovative solution for peritoneal tumors adjacent to the kidneys., Competing Interests: Conflict of interestRyohei Sasaki received research funding from Alfresa Pharma Corporation; Takumi Fukumoto received patent licensing fees from Alfresa Pharma Corporation and research funding from Alfresa Pharma Corporation, Kanai Juyo Kogyo Co.,Ltd, and Kureha Corporation., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear., Methods: We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023., Results: Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences., Conclusion: The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss., The Trial Registration Number: B230165 (approved at December 26, 2023)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Briganti nomogram (cut-off value 5%) is commonly used to determine the indications for pelvic lymph node dissection (PLND) in patients with prostate cancer. We retrospectively analyzed the potential oncological benefit of PLND based on the 5% cut-off value on the Briganti nomogram. We obtained the data from the Medical Investigation Cancer Network (MICAN) Study, which included 3,463 patients who underwent a radical prostatectomy (RP) at nine institutions in Japan between 2010 and 2020. We included patients with Briganti scores ≥ 5% and a follow-up period ≥6 months and excluded patients categorized in the very high-risk group (based on NCCN categories); a final total of the cases of 1,068 patients were analyzed. The biochemical recurrence (BCR)-free survival was significantly worse in the patients who underwent PLND compared to those who did not (p=0.019). A multivariate analysis showed that high prostate-specific antigen (PSA) levels (p<0.001) and an advanced T-stage (p=0.018) were significant prognostic factors for BCR, whereas PLND had no effect on BCR (p=0.059). Thus, PLND in patients with prostate cancer whose Briganti score was 5% did not provide any oncological benefit. Further research is necessary to determine the indication criteria for conducting PLND., Competing Interests: No potential conflict of interest relevant to this article was reported.

Owing to the high objective response rate of atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC), the concept of sequential conversion to local treatment has recently become mainstream. The conversion concept is mainly applied to Barcelona Clinic for Liver Cancer (BCLC) stage B cases, and radiotherapy is rarely considered as a conversion local treatment. We herein report three patients who were treated with the novel concept of "sequential particle radiotherapy," consisting of Atez/Bev therapy followed by particle radiotherapy (PRT) for HCC with advanced portal vein tumor thrombus (Vp3/4 PVTT). All patients achieved partial response radiologically and were switched to PRT. All patients were recurrence free at 1 year after the introduction of Atez/Bev therapy without any additional treatment. This upcoming combination strategy includes the advocacy of sequential concepts for BCLC stage C cases and the introduction of PRT as a local treatment after Atez/Bev., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Aim: The IMbrave150 trial revealed that atezolizumab plus bevacizumab (AtezoBv) showed a higher objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC). Although conversion therapy after AtezoBv has been recently reported, markers predictive of its efficacy, particularly radiological imaging markers, have not yet been identified. The present study focused on tumor morphological appearance on radiological imaging and evaluated whether it could be associated with AtezoBv efficacy., Methods: Ninety-five intrahepatic lesions in 74 patients who were given AtezoBv for advanced HCC were recruited for evaluation. The lesions were divided into two groups, simple nodular (SN group) and non-simple nodular (non-SN group), based on the gross morphology on pretreatment imaging, and retrospectively evaluated for treatment response and other relevant clinical outcomes., Results: Assessing the size of individual tumors after treatment, waterfall plots showed that tumor shrinkage in the non-SN group including 56 lesions was higher than that in the SN group comprising 39 lesions. The ORR was significantly higher in the non-SN group (39.3% vs. 15.4%, p = 0.012). Additionally, the median time to nodular progression was longer in the non-SN group (21.0 months vs. 8.1 months, p = 0.119) compared to the SN group. Six patients with non-SN lesions underwent sequential local therapy., Conclusions: Atezolizumab plus bevacizumab may show increased therapeutic efficacy in patients with tumors with a higher potential for aggressive oncological behavior, such as non-SN lesions. Treatment strategies focusing on conversion therapy may be crucial in patients with non-SN lesions., (© 2024 Japan Society of Hepatology.)

Background/aim: Neskeep ® , an absorbable polyglycolic acid spacer, has been developed as the optimal material for spacer placement surgery. However, preventing its severe adhesion is a crucial concern. Therefore, we aimed to identify an effective anti-adhesion agent for Neskeep ® using rat models., Materials and Methods: Animal experiments were performed using 60 rats, which underwent Neskeep ® placement on the abdominal wall. Three types of anti-adhesion agents were employed, establishing four subgroups: Seprafilm ® , INTERCEED ® , AdSpray ® , and only Neskeep ® (control) groups. Rats were sacrificed on postoperative days 7, 14, and 28 to assess adhesion levels around the Neskeep ® Macroscopic visual assessment with the Lauder score and histopathological evaluation were performed to assess the degree of adhesion., Results: There were no significant differences in the proportion of Lauder scores on days 7 and 14 between the four groups. Histological evaluation revealed no significant differences between groups at any observation time. However, the mean Lauder scores at day 28 were 5.0, 1.6, 4.0, and 4.8 in the Neskeep ® , Seprafilm ® , INTERCEED ® , and AdSpray ® groups, respectively. The proportion of milder Lauder score was significantly higher in the Seprafilm ® group on day 28., Conclusion: Seprafilm ® may exhibit an anti-adhesive effect when used with Neskeep ® ., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Context: Adrenal incidentalomas, including nonfunctioning adrenal incidentalomas (NFAI), are associated with a high prevalence of diabetes mellitus (DM). While NFAI is diagnosed by exclusion when no hormone excess exists, subtle cortisol secretion may exist and contribute to DM development. However, it alone cannot explain the increased risk, and whether other steroid metabolites are involved remains unclear., Purpose: To investigate steroid metabolites associated with DM in patients with NFAI using plasma steroid profiles., Methods: Using liquid chromatography-tandem mass spectrometry, 22 plasma steroid metabolites were measured in 68 patients with NFAI (31 men and 37 women). Data were adjusted for age before normalization., Results: Discriminant analysis showed that plasma steroid profiles discriminated between patients with and without DM in men (n = 10 and = 21, respectively) but not women: 11β-hydroxytestosterone, an adrenal-derived 11-oxygenated androgen, contributed most to this discrimination and was higher in patients with DM than in those without DM (false discovery rate = .002). 11β-hydroxytestosterone was correlated positively with fasting plasma glucose (r = .507) and hemoglobin A1c (HbA1c) (r = .553) but negatively with homeostatic model assessment of β-cell function (HOMA2-B) (r = -.410). These correlations remained significant after adjusting for confounders, including serum cortisol after the 1-mg dexamethasone suppression test. Bayesian kernel machine regression analysis verified the association of 11β-hydroxytestosterone with HbA1c and HOMA2-B in men., Main Conclusion: Plasma steroid profiles differed between those with and without DM in men with NFAI. 11β-hydroxytestosterone was associated with hyperglycemia and indicators related to pancreatic β-cell dysfunction, independently of cortisol., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: The impact of postoperative bile leak on the prognosis of patients with hepatocellular carcinoma who underwent liver resection is controversial. This study aimed to investigate the prognostic impact of bile leak for patients with hepatocellular carcinoma who underwent liver resection., Methods: Patients with hepatocellular carcinoma who underwent liver resection between 2009 and 2019 at Kobe University Hospital and Hyogo Cancer Center were included. After propensity score matching between the bile leak and no bile leak groups, differences in 5-year recurrence-free and overall survival rates were evaluated using the Kaplan-Meier method., Results: A total of 781 patients, including 43 with postoperative bile leak, were analyzed. In the matched cohort, 40 patients were included in each group. The 5-year recurrence-free survival rates after liver resection were 35% and 32% for the bile leak and no bile leak groups, respectively (P = 0.857). The 5-year overall survival rates were 44% and 54% for the bile leak and no bile leak groups, respectively (P = 0.216)., Conclusion: Overall, bile leak may not have a profound negative impact on the prognosis of patients with hepatocellular carcinoma who have undergone liver resection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan., Methods: A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients)., Results: The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis., Conclusions: The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set., Methods: The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model., Results: Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors., Conclusion: This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background/aim: Sorafenib and lenvatinib have long been used as a first-line treatment for advanced hepatocellular carcinoma (HCC). Along with the development of systemic chemotherapy for HCC, the concept of conversion hepatectomy has recently become widespread. The present study aimed to assess the clinical outcomes of sorafenib and lenvatinib for HCC regarding the possibility of conversion hepatectomy in clinical practice., Patients and Methods: A total of 295 patients with advanced HCC receiving sorafenib and lenvatinib, accounting for 306 treatments (sorafenib, n=157; lenvatinib, n=149, 11 patients received lenvatinib after sorafenib treatment) at five different institutions were enrolled. Patients were assessed for their clinical characteristics and therapeutic response using both Response Evaluation Criteria in Solid Tumors criteria (RECIST) and modified RECIST (mRECIST) criteria. Additionally, an indication of surgery after tyrosine kinase inhibitor administration was determined based on the tumor status of patients., Results: The median survival times of patients treated with sorafenib and lenvatinib were 12.8 and 16.4 months, respectively, without significant difference (p=0.1645). The objective response rates (ORR) of sorafenib based on mRECIST and RECIST were 10.1% and 5.9%, respectively, and those of lenvatinib were 38.1% and 19.0%, respectively. Among the 306 treatments, two cases (sorafenib and lenvatinib, one each) underwent hepatectomy after systemic chemotherapy., Conclusion: Few cases with unresectable HCC were amenable to conversion hepatectomy after sorafenib and lenvatinib treatments due to the limited ORR by RECIST. Cautious approach must be taken when administering neoadjuvant chemotherapy aimed at conversion hepatectomy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Novel adhesives for biological tissues offer an advanced surgical approach. Here, the authors report the development and application of solid-state adhesives consisting of porous hydroxyapatite (HAp) biocompatible ceramics as novel internal organ retractors. The operational principles of the porous solid-state adhesives are experimentally established in terms of water migration from biological soft tissues into the pores of the adhesives, and their performance is evaluated on several soft tissues with different hydration states. As an example of practical medical utility, HAp adhesive devices demonstrate the holding ability of porcine livers and on-demand detachability in vivo, showing great potential as internal organ retractors in laparoscopic surgery., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Riehl's melanosis is a pigmented dermatitis that manifests as brown-gray facial pigmentation with pigment incontinence and infiltration of cells in the upper dermis. The associated inflammation is induced by a variety of products such as drugs and cosmetics. Henna, commonly referred to as a hypoallergenic cosmetic, has been reported to cause Riehl's melanosis in some cases. Although skin depigmenting agents have been occasionally used, satisfactory results have not been obtained and no established therapeutic strategies exist to treat Riehl's melanosis. Meanwhile, picosecond lasers effectively treat other hyperpigmentation disorders. In this study, we report safe and effective treatment of henna induced-atypical Riehl's melanosis using a 755-nm picosecond Alexandrite laser. Immunohistochemical analyses revealed a potential role of CD8-positive lymphocytes in henna-induced inflammation and hyperpigmentation of the basal layer, and a role of melanophages in the pigmented dermis of Riehl's melanosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kishimoto, Iwayama, Horita and Fukumoto.)

Objective: The human adrenal cortex comprises three functionally and structurally distinct layers that produce layer-specific steroid hormones. With aging, the human adrenal cortex undergoes functional and structural alteration or "adrenal aging", leading to the unbalanced production of steroid hormones. Given the marked species differences in adrenal biology, the underlying mechanisms of human adrenal aging have not been sufficiently studied. This study was designed to elucidate the mechanisms linking the functional and structural alterations of the human adrenal cortex., Methods: We conducted single-cell RNA sequencing and spatial transcriptomics analysis of the aged human adrenal cortex., Results: The data of this study suggest that the layer-specific alterations of multiple signaling pathways underlie the abnormal layered structure and layer-specific changes in steroidogenic cells. We also highlighted that macrophages mediate age-related adrenocortical cell inflammation and senescence., Conclusions: This study is the first detailed analysis of the aged human adrenal cortex at single-cell resolution and helps to elucidate the mechanism of human adrenal aging, thereby leading to a better understanding of the pathophysiology of age-related disorders associated with adrenal aging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Introduction: Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC., Methods: We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis., Results: After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P = .04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR: .57, 95% CI: .33-.97, P = .03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0., Discussion: S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Spontaneous rupture of a primary hepatocellular carcinoma (HCC) is a frequently observed and fatal complication. However, the rupture of lymph node (LN) metastases from HCC is rare. A 79 year-old male with hepatitis B underwent three liver resections for HCC. Two years and 6 months after the last liver resection, enhanced computed tomography (CT) revealed a nodule with a diameter of 3 cm in the lower pole of the spleen. Splenic metastasis of HCC was suspected, and splenectomy was scheduled. During our hospital stay for a urinary tract infection before the scheduled operation, he complained of acute left-sided abdominal pain, and CT showed intra-abdominal hemorrhage due to rupture of the splenic tumor. Emergency splenectomy was performed, and the postoperative course was uneventful. Histopathological examination revealed a poorly differentiated HCC in the lower splenic pole lesion, which contained LN structures. The ruptured lesion was diagnosed as splenic hilar LN metastasis of HCC. Although laparoscopic partial liver resection was performed for intrahepatic recurrence, and atezolizumab plus bevacizumab therapy was administered for peritoneal metastases, the patient was alive 25 months after the splenectomy. Our case suggests that emergency surgery for LN metastatic rupture can achieve hemostasis and lead to improved survival outcomes., (© 2024. Japanese Society of Gastroenterology.)

Background Aims: Tacrolimus (TAC) plus short-term methotrexate (stMTX) is used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). TAC blood concentrations are frequently adjusted to enhance the graft-versus-leukemia/lymphoma effect or attenuate severe GVHD. Limited information is available on the clinical impact of these adjustments and the optimal time to perform them in order to achieve good clinical outcomes., Methods: We retrospectively analyzed 211 patients who underwent allo-HSCT at our institutes., Results: Higher TAC concentrations in week 3 correlated with a significantly higher cumulative incidence of relapse (CIR) (P = 0.03) and lower nonrelapse mortality (P = 0.04). The clinical impact of high TAC concentrations in week 3 on CIR was detected in the refined disease risk index: low/intermediate (P = 0.04) and high (P < 0.01), and conditioning regimens other than cyclophosphamide/total body irradiation and busulfan/cyclophosphamide (P = 0.07). Higher TAC concentrations in week 1 correlated with a lower grade 2-4 acute GVHD rate (P = 0.01). Higher TAC concentrations in weeks 2 and 3 correlated with slightly lower (P = 0.05) and significantly lower (P = 0.02) grade 3-4 acute GVHD rates, respectively. Higher TAC concentrations in weeks 1 and 3 were beneficial for severe acute GVHD in patients with a human leukocyte antigen-matched donor (P = 0.03 and P < 0.01, respectively), not treated with anti-thymocyte globulin (P = 0.02 and P = 0.02, respectively), and receiving three stMTX doses (P = 0.03 and P = 0.02, respectively)., Conclusions: The clinical impact of TAC concentrations varied according to patient characteristics, including disease malignancy, conditioning regimens, donor sources, and GVHD prophylaxis. These results suggest that TAC management needs to be based on patient profiles., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background/aim: This study aimed to evaluate the utility of the albumin-bilirubin grade for predicting the prognosis after repeat liver resection for patients with recurrent hepatocellular carcinoma., Patients and Methods: Ninety patients with intrahepatic recurrent hepatocellular carcinoma who underwent repeat liver resection at our institution between 2005 and 2019 were retrospectively analyzed. Cox proportional-hazards regression models evaluated independent preoperative prognostic factors, including the albumin-bilirubin grade. Prognosis differences between patients with albumin-bilirubin grades 1 and 2 were analyzed using the Kaplan-Meier method., Results: Cox proportional-hazards regression analysis revealed that albumin-bilirubin grade 2 (p=0.003) and early recurrence within one year from the initial surgery (p=0.001) were independently associated with poor recurrence-free survival, and albumin-bilirubin grade 2 (p=0.020) was independently associated with poor overall survival. The five-year recurrence-free (31% and 17%, respectively) and overall (86% and 60%, respectively) survival rates after repeat liver resection for patients with albumin-bilirubin grades 1 and 2 were significantly different between groups (both p=0.003)., Conclusion: The albumin-bilirubin grade is useful for preoperatively predicting favorable survival rates after repeat liver resection for patients with recurrent hepatocellular carcinoma. Patients with an albumin-bilirubin grade 1 are better candidates for surgical treatment of recurrent hepatocellular carcinoma., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The treatment algorithm for systemic therapies for advanced hepatocellular carcinoma (HCC) has changed dramatically; however, the therapeutic landscape for sequential second-line or later-line treatments, including ramucirumab, remains controversial. This study aimed to investigate the role of ramucirumab for treating HCC., Patients and Methods: We retrospectively analyzed data from 17 patients with advanced HCC who received ramucirumab, and 8 of them who received lenvatinib re-administration after ramucirumab treatment failure., Results: The median overall survival of 17 patients treated with ramucirumab was 11.5 months. The median ratios of the 1-month post-treatment α-fetoprotein (AFP) levels and albumin-bilirubin (ALBI) scores to the pre-treatment AFP levels and ALBI scores following ramucirumab treatment were 0.880 and 0.965, respectively. The median ratios of the 1-month post-treatment AFP and ALBI levels to the pre-treatment levels were 1.587 and 0.970 for mALBI grade 1/2a, and 1.313 and 0.936 for mALBI grade 2b/3, respectively. Six of the eight patients who received lenvatinib rechallenge treatment exhibited a decrease in AFP levels one month post-lenvatinib treatment. Deterioration of liver function 3 months post-lenvatinib treatment was noted in five of the eight patients who received lenvatinib rechallenge treatment after ramucirumab., Conclusion: Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)