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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.)

Endothelial dysfunction may trigger coronary spastic angina (CSA). However, the risk factors for CSA in young patients remain unclear. This study aimed to investigate the age-dependent role of serum uric acid levels in patients with CSA. We enrolled 423 patients who underwent an ergonovine tolerance test during coronary angiography for the CSA evaluation. We categorized the patients as (1) young (age ≤ 65 years) CSA-positive (n = 33), (2) young CSA-negative (n = 138), (3) elderly (age > 66 years) CSA-positive (n = 42), and (4) elderly CSA-negative (n = 210) groups. In the young groups, the smoker proportion (57.6 vs. 38.4%, p = 0.04) and serum uric acid levels (6.3 ± 1.4 vs. 5.4 ± 1.5 mg/dl, p = 0.006) were significantly higher in the CSA-positive compared with the CSA-negative group. Conversely, in the elderly group, the male proportion (66.6 vs. 47.1%, p = 0.02) and alcohol consumption level (40.5 vs. 21.0%, p = 0.01) were significantly higher in the CSA-positive compared with the CSA-negative group. The multivariate analysis in young groups revealed the independent association between the serum uric acid level (p = 0.02) and the presence of CSA. Our results indicate that elevated serum uric acid levels may affect CSA development in young patients., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Teratoma is a germ cell tumor composed of 2 or 3 germ cell layers, and it can occur in various parts of the human body. However, teratomas of the renal hilum are particularly rare, and those complicated by carcinoids are even more uncommon. Herein, we report the example of an asymptomatic 49-year-old woman in whom a tumor in the right renal hilum was unexpectedly discovered on imaging. Histological examination revealed a carcinoid tumor arising from a simple cyst composed of teratomatous tissue. Although the tumor was located in the renal hilum and touched the renal parenchyma, it appeared independent of the kidney and urinary tract. This report highlights the rare occurrence of teratomas with carcinoids and provides insights into their origins., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.)

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: Focal pancreatic parenchymal atrophy (FPPA) and upstream pancreatic atrophy (UPA) may indicate the presence of early pancreatic cancer. In early pancreatic cancer, the tumor occasionally spreads laterally along the main pancreatic duct, presenting challenges in determining the extent of surgical resection. This study aimed to investigate the association of pancreatic atrophy pattern and intraductal cancer extension., Methods: Thirty-two patients with early-stage pancreatic cancer who underwent surgery at five participating centers were enrolled. Pancreatic atrophy was defined as the narrowing of parenchyma compared to the surrounding parenchyma and was classified as either FPPA (partial atrophy surrounding the pancreatic duct stenosis) or UPA (global atrophy caudal to the site of duct stenosis). Intraductal cancer extension was defined as an extension exceeding 10 mm., Results: Preoperative computed tomography revealed FPPA, UPA, and no parenchymal atrophy in 13, 13, and 6 patients. Cases with FPPA or UPA showed significantly longer cancer extensions than those without atrophy (P = 0.005 and P = 0.03, respectively). Intraductal cancer extension was present in all but one case of FPPA. 69% (9/13) of the cases with UPA showed intraductal cancer extension, whereas cases without atrophy showed no intraductal cancer extension. Importantly, two patients with FPPA or UPA showed positive resection margins during surgery and three patients with FPPA or UPA showed recurrence in the remnant pancreas., Conclusions: The presence of FPPA and UPA indicates lateral cancer extension in early-stage pancreatic cancer. Preoperative assessment of the pancreatic parenchyma may provide valuable insights for determining the extent of surgical resection., (© 2024. The Author(s).)

Co-infection, caused by multiple pathogen attacks on an organism, can lead to disease development or immunity. This complex interaction can be synergetic, co-existing, or antagonistic, ultimately influencing disease severity. The interaction between fungus, bacterium, and virus (three kingdom pathogens) is most prevalent. However, the underlying mechanisms of co-infection need to be explored further. In this study, we investigated the co-infection phenomenon in rice plants exposed to multiple pathogen species, specifically Rice necrosis mosaic virus (RNMV) and rice blast fungus (Magnaporthe oryzae, MO), bacterial leaf blight (Xanthomonas oryzae pv. oryzae, XO) or Cucumber mosaic virus (CMV). Our research showed that RNMV interacts synergistically with MO, XO, or CMV, increasing pathogen growth and lesion size. These findings suggest positive synergy in RNMV co-infections with three kingdom pathogens, increasing accumulation and symptoms. Additionally, to investigate the role of RNAi in pathogen synergism, we analyzed rice mutant lines deficient in RNA-dependent RNA polymerase 1 (OsRDR1) or 6 (OsRDR6). Notably, we observed the loss of synergy in each mutant line, highlighting the crucial role of OsRDR1 and OsRDR6 in maintaining the positive interaction between RNMV and three kingdom pathogens. Hence, our study emphasized the role of the RNA silencing pathway in the intricate landscape of pathogen interactions; the study's outcome could be applied to understand the plant defense response to improve crop yields., Competing Interests: Declaration of Competing Interest All the authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A synthetic method of tertiary alcohols was developed based on the formal umpolung addition of aryl ketones with electrophiles utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis. The addition reaction of α-hydroxyphosphonates, derived from alkyl aryl- and diaryl ketones, with electrophiles such as phenyl vinyl sulfone, afforded phosphates having a tertiary alkyl group, which were readily convertible to the corresponding tertiary benzylic alcohols. This operationally simple protocol provides efficient complementary access to tertiary alcohols that are difficult to synthesize by conventional methods., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal-dominant disorder caused by a heterozygous germline mutation in the fumarate hydratase ( FH ) gene. HLRCC is clinically characterized by the development of three tumors: uterine leiomyomata, cutaneous leiomyomata, and renal cell carcinoma (RCC). HLRCC-associated RCC is aggressive and diagnosed at a much earlier age than sporadic RCC. It is essential for carriers of HLRCC to undergo annual renal screening by magnetic resonance imaging to detect early stage RCCs. Metastatic HLRCC-associated RCC must be treated by systemic therapy; however, it is unclear which medicines are most effective in treating this cancer owing to its low incidence rate. Immune checkpoint inhibitor (ICI) combinations or ICIs plus tyrosine kinase inhibitors are administered as systemic therapy for clear cell RCC. Here, we report a patient with HLRCC-associated RCC treated with sequential therapy, including ipilimumab plus nivolumab combination and cabozantinib, after diagnosis of HLRCC-associated RCC using FoundationOne Liquid CDx and single-site analysis. We also investigated familial FH mutations and describe a new family pedigree for HLRCC., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press.)

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.)

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.)

A 49-year-old man underwent an open cholecystectomy for advanced gallbladder cancer in 2021. Three months after surgery, the patient underwent an additional resection, which showed no malignant findings, but 12 months after surgery, contrast-enhanced CT and MRI showed a new mass lesion in segment 8 of the liver, and the patient was diagnosed with postoperative hepatic metastatic recurrence of gallbladder cancer. After referral to our institution, he received 1 course of gemcitabine+cisplatin(GC)therapy and 8 courses of gemcitabine+cisplatin+durvalumab(GCD)therapy. Contrast- enhanced CT and MRI showed that the metastases had shrunk, and PET scan showed no FDG accumulation. Two months after completion of chemotherapy, there was no evidence of metastatic enlargement and new metastasis including distant metastasis, and the patient was referred to our department. Since curative resection was expected, a laparoscopic partial hepatectomy of segment 8 of the liver was performed. Pathological diagnosis revealed no residual tumor. If the metastases could be well controlled by systemic chemotherapy, hepatectomy for hepatic metastases of biliary tract cancer could be a treatment option.

A 54-year-old woman developed new-onset heart failure and was diagnosed with cardiac sarcoidosis. An implantable cardioverter-defibrillator with biventricular pacing was implanted before immunosuppressive therapy to prevent sudden death. The patient refused oral steroids because she disliked their specific side effects and potential adverse events with long-term use; therefore, methotrexate was chosen as an alternative first-line drug. Nine months after starting oral therapy, 18 F-fluorodeoxyglucose-positron emission tomography revealed remission of sarcoidosis, disappearance of heart failure symptoms, marked improvement in cardiac contractility, and a reduced frequency of ventricular arrhythmias.

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.)

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.)

Mantle xenoliths usually represent fragments derived from the depleted and degassed lithospheric mantle with 3 He/ 4 He isotope ratios (6 ± 1 R A ) lower than those of mid-ocean ridge basalts (8 ± 1 R A ). Otherwise, basalts from oceanic islands related to hotspots often have high 3 He/ 4 He ratios (>10 R A ), suggesting a deep and pristine undegassed mantle source. Here we present a striking high- 3 He/ 4 He component (up to 27.68 R A ) recorded by spinel-facies mantle xenoliths from Patagonia. Remarkably, the highest ratios were found in a long-lived trans-lithospheric suture zone related to the Carboniferous-Permian collision of two continental blocks: the Deseado and the North Patagonian massifs. The mantle xenoliths with notably high- 3 He/ 4 He ratios are inferred to be fragments of the shallow asthenosphere rising through the eroded and rejuvenated thin lithosphere. The pristine helium component is derived from the western margin of the Karoo mantle plume, related to the initial stages of the Gondwana fragmentation., (© 2024. The Author(s).)

Epicardial adipose tissue (EAT) have been shown to be associated with several heart disease, including coronary artery disease (CAD), atrial fibrillation (AF), and heart failure (HF). It is reported that the quality of EAT, represented by fat attenuation determined using computed tomography (CT) imaging, can detect the histologically-assessed remodeled EAT. We tested the hypothesis that quality of EAT would predict major adverse cerebral and cardiovascular events (MACCE) following transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis (AS). A total of 125 consecutive severe AS patients who underwent TAVI were enrolled (39 male, mean 85.4 ± 4.0 years). Using CT imaging before TAVI, we measured the average CT fat attenuation of EAT (EAT attenuation) and investigated the association with MACCE. During the mean follow up period of 567 ± 371 days, 21 cases of MACCE were observed. Patients with MACCE had greater levels of EAT attenuation compared to those without (- 74 ± 3.7 Hounsfield Units (HU) vs - 77 ± 5.5 HU, p = 0.010). Based on the ROC curves, the high EAT attenuation was defined as > - 74.3 HU. According to this cut-off index, 44 patients were classified into the high EAT attenuation group (28 female, mean age 87 ± 3.6 years), whereas 81 patients were classified into the low EAT attenuation group (13 female, 85 ± 4.1 years). Kaplan-Meier survival curve demonstrated that the patients in the high EAT attenuation group showed greater prevalence of MACCE (log-rank 6.64, p = 0.010). Cox proportional hazards regression analysis revealed that EAT attenuation and Logistic EuroSCORE were independently associated with the incidence of MACCE. Our results suggest that quality of EAT, assessed by EAT attenuation detected by CT imaging, can predict the cerebral and cardiovascular events after TAVI in patients with AS., (© 2024. Springer Nature Japan KK, part of Springer Nature.)