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Protein kinase C delta (PKCδ) is a leaderless protein generally localized in the cytoplasm and nucleus; however, its extracellular unconventional protein secretion occurs exclusively in hepatocellular carcinoma (HCC) cells (but not in normal and non-cancerous hepatocytes or other gastrointestinal cancer cells) via an autophagy mechanism, despite the lack of a secretory signal. Therefore, PKCδ is detectable in the peripheral blood of HCC patients. Serum PKCδ indicates cancer-related unconventional protein secretion of an inactive form of cytosolic PKCδ and can be a unique biomarker independent of conventional markers. To examine the specificity of serum PKCδ for HCC, its levels and positivity rates were compared between 226 HCC and 108 gastrointestinal cancer patients. Furthermore, we focused on patients with malignant or benign intrahepatic tumors (17 intrahepatic cholangiocarcinoma, 42 liver metastases, and 6 focal nodular hyperplasia). A sandwich enzyme-linked immunosorbent assay was used to measure serum PKCδ levels; the optimal cutoff value was set to 57.7 ng/mL. HCC patients had significantly higher PKCδ levels and positivity rates than gastrointestinal cancer patients (median, 51.1 vs. 34.6 ng/mL; 39.8 % vs. 4.6 %; P < 0.001 for both). Thus, the specificity was 95.4 %. Focusing on intrahepatic tumors, 2 (4.8 %) of 42 gastrointestinal cancer patients with liver metastasis were positive for PKCδ. Notably, all patients with intrahepatic cholangiocarcinoma and focal nodular hyperplasia were negative for PKCδ, irrespective of their intrahepatic tumors being malignant or benign. Serum PKCδ is an extracellularly secreted protein specific for HCC that can be a novel diagnostic biomarker because it distinguishes HCC from other gastrointestinal cancers and intrahepatic non-HCC tumors., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) more...

Objectives: This study aimed to assess the prognostic significance of a novel biomarker, the fibrinogen-C-reactive protein-albumin ratio (F-CAR), in pancreatic cancer patients undergoing pancreatectomy., Method: We retrospectively analyzed 163 patients undergoing pancreatectomy for pancreatic cancer. The relationship between F-CAR, calculated from preoperative serum fibrinogen, albumin, and C-reactive protein levels, and long-term outcomes following pancreatectomy was examined., Results: Multivariate analysis revealed that several factors, including age (P < 0.01), high serum carbohydrate antigen 19-9 (CA19-9) level (P < 0.01), high serum carcinoembryonic antigen level (P = 0.049), pT3 or pT4 (UICC) (P < 0.01), pN1 or pN2 (P < 0.01), and high F-CAR (hazards ratio, 1.51; 95% confidence interval, 1.03-2.22; P = 0.04), were independent and significant predictors of disease-free survival. Moreover, factors such as age (P = 0.02), high serum carcinoembryonic antigen level (P < 0.01), preoperative biliary drainage (P = 0.02), preoperative chemotherapy (P = 0.04), lymph node metastasis (P < 0.01), adjuvant chemotherapy (P = 0.046), and high F-CAR (hazards ratio, 1.55; 95% confidence interval, 1.03-2.35; P = 0.04) were found to be independent and significant predictors of overall survival., Conclusions: F-CAR is a useful prognostic factor for disease-free survival and overall survival after pancreatectomy in pancreatic cancer patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) more...

Osteopenia is a potential prognostic factor in patients with cancer. Occult vertebral fracture, the most common complication of osteopenia, has recently been associated with cancer. The present study aimed to investigate the prognostic value of occult vertebral fracture after gastrectomy in patients with gastric cancer. The current retrospective study included 222 patients who underwent gastrectomy for gastric cancer between October 2013 and February 2023. Occult vertebral fracture was quantitatively evaluated using preoperative sagittal computed tomography images from the 11th thoracic to 5th lumbar vertebrae. Multivariate analysis showed that occult vertebral fracture (P<0.01, P=0.02, respectively), stage II or III (P<0.01, P<0.01, respectively), and R1 or R2 curability (P<0.01, P=0.03, respectively) were independent and significant predictors of disease-free and overall survival rates. Additionally, patients with both occult vertebral fracture and osteopenia had significantly lower disease-free and overall survival rates than those with either osteopenia or occult vertebral fracture (P<0.01, P<0.01, respectively). In conclusion, occult vertebral fracture may be considered a strong predictor of poor clinical outcomes in patients undergoing gastrectomy for gastric cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2025, Spandidos Publications.) more...

Aim: Prognosis of pancreatic cancer is improved by combining postoperative adjuvant chemotherapy and preoperative adjuvant chemotherapy with surgery, while the importance of extended dissection surgery has decreased. To better understand prognostic factors of recurrence, we focused on the timing of postoperative adjuvant chemotherapy in patients with pancreatic cancer., Methods: One hundred patients who underwent pancreatectomy or pancreaticoduodenectomy and chemotherapy for pancreatic cancer were classified into early and late postoperative adjuvant therapy initiation groups. Prognosis was evaluated retrospectively using known prognostic factors., Results: On receiver operating characteristic analysis, optimum cut-off between the early (<52 days; n = 60) and late adjuvant initiation groups (≥52 days; n = 40) was 52 days. The two groups were well-matched, except the early initiation group had more surgeries with D2 lymph node dissection (75 % vs 48 %; p = 0.01); fewer postoperative complications (17 % vs 59 %; p = 0.04), including less postoperative pancreatic fistula (13 % vs 35 %; p = 0.03); and longer disease-free survival (0.7 years v 0.5 years; p = 0.02). On multivariate evaluation, early initiation and completion of adjuvant therapy were associated with increased overall survival, while early initiation was associated with prolonged disease-free survival., Conclusions: Prognosis of patients with pancreatic cancer is improved by earlier rather than later initiation of postoperative adjuvant therapy., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.) more...

Purpose: Inflammatory, nutritional, and immune biomarkers are associated with the prognosis of patients with various tumors. Recently, a comprehensive predictive biomarker, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, was introduced to predict clinical outcomes. We investigated the prognostic impact of preoperative HALP scores in patients who underwent hepatectomy for colorectal liver metastasis (CRLM)., Method: The subjects of this study were 209 patients who underwent hepatectomy for CRLM between February, 2005 and September, 2023. The HALP score was defined as (albumin [mg/dL] × hemoglobin [g/L] × lymphocyte [count/L]) / platelet [count/L]. The cutoff value was calculated according to the receiver operating characteristic curve based on 3-year survival., Results: The cutoff value of the HALP score was 35, and a low HALP score was confirmed in 107 patients (51%). Multivariate analysis of disease-free survival identified lymph node metastasis (HR 1.53, p = 0.03), extrahepatic lesions (HR 2.48, p < 0.01), and a low HALP score (HR 2.0, p < 0.01) as independently poor prognostic factors. Multivariate analysis of overall survival identified extrahepatic lesions (HR 2.98, p < 0.01), a high CEA (HR 1.78, p = 0.02), and a low HALP score (HR 1.92, p = 0.02) as independently poor prognostic factors., Conclusions: The HALP score is a useful prognostic factor for patients undergoing hepatectomy for CRLM., Competing Interests: Declarations. Conflict of interest: We have no conflicts of interest or funding to declare., (© 2025. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.) more...

Background/aim: The aim of this study was to investigate the prognostic impact of the inflammatory burden index (IBI), a novel inflammation-based biomarker, in patients with colorectal liver metastases (CRLM) after hepatic resection., Patients and Methods: One hundred fifty patients with CRLM who underwent hepatectomy were retrospectively analyzed. The IBI was defined as C-reactive protein × neutrophil count/lymphocyte count. The relationship of the IBI with overall survival was investigated by univariate and multivariate analyses., Results: Seventy-three (49%) patients had a high IBI (>3.45). In univariate analysis, overall survival was significantly worse in patients with lymph node metastases ( P = 0.048), high NLR ( P = 0.03), and high IBI ( P < 0.01). In multivariate analysis, high IBI ( P = 0.048) was an independent and significant predictor of overall survival. Patients with a high IBI had more postoperative complications compared with those with a low IBI ( P < 0.01)., Conclusion: The IBI was a strong predictor for both short- and long-term outcomes in patients who underwent hepatic resection for CRLM., 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. more...

Background: This study aimed to investigate the effects of changes in clinicopathological factors during preoperative chemotherapy for pancreatic cancer, including skeletal muscle volume, on recurrence and prognosis after pancreatectomy., Methods: Data from 41 patients who underwent resection for pancreatic cancer after preoperative chemotherapy from 2012 to 2021 were retrospectively reviewed. Skeletal muscle volume was substituted for the psoas muscle area (PMA) at the level of the third lumbar vertebra. We investigated the relationship of clinicopathological factors during preoperative chemotherapy with disease-free survival (DFS) and overall survival (OS). The association between clinicopathological factors and a decrease in PMA was investigated., Results: In the multivariate analyses for DFS and OS, the factors associated with recurrence were as follows: decrease in PMA ( P = 0.003) and the absence of adjuvant therapy ( P = 0.03), and the factors associated with poor prognosis were as follows: decrease in PMA ( P = 0.04) and the absence of adjuvant therapy ( P = 0.008), and the resectability of borderline resectable and unresectable-locally advanced tumors ( P = 0.033). All patients with partial response according to the Response Evaluation Criteria in Solid Tumors (version 1.1) had no decrease in PMA ( P = 0.01). The proportion of patients with Evans classification ≥ II was significantly higher in the group without a decrease in PMA ( P = 0.02). The proportion of patients with an average relative dose intensity of adjuvant therapy ≥0.6 was significantly higher in the group without a decrease in PMA ( P = 0.02)., Conclusion: Changes in preoperative skeletal muscle volume during preoperative chemotherapy for pancreatic cancer is a potential predictor of recurrence and prognosis after pancreatectomy., 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. more...

Background: This study aimed to identify postoperative recurrence and prognostic factors, including osteosarcopenia for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer and to examine the impact of postoperative pancreatic enzyme replacement therapy (PERT)., Methods: We retrospectively examined 32 resected patients with BR and UR-LA pancreatic cancer. We investigated independent factors in the disease-free survival and overall survival. The relation of osteosarcopenia with the clinicopathological factors was investigated. Additionally, the association of the administration of a standard dose of pancrelipase, the amount of lipase required for patients with pancreatic exocrine insufficiency, for ≥6 months postoperatively with improvement of sarcopenia, osteopenia, and osteosarcopenia and completion rate of adjuvant chemotherapy was investigated., Results: Multivariate analyses identified osteosarcopenia ( P = 0.049) and lymph node metastasis ( P = 0.01) as independent recurrence predictors, and osteosarcopenia ( P = 0.002), maximum tumor diameter ≥40 mm ( P = 0.006), and no adjuvant therapy ( P = 0.01) as independent prognostic predictors. In the osteosarcopenia group, serum CA19-9 levels were higher ( P = 0.03). The administration of a standard dose of pancrelipase for ≥6 months postoperatively was none in the osteosarcopenia group (0% vs 42.9%, P = 0.01), while significantly improved postoperative sarcopenia (33% vs 0%, P = 0.004), increased number of cycles of adjuvant chemotherapy (n = 6 vs n = 3, P = 0.03), and the completion rate of adjuvant chemotherapy in excluding cases interrupted because of recurrence (86% vs 25%, P = 0.007)., Conclusions: Osteosarcopenia was an independent recurrent and prognostic factor in patients after pancreatectomy for locally advanced pancreatic cancer. Appropriate postoperative PERT may contribute to a better prognosis by improving sarcopenia and increasing the completion rate of adjuvant chemotherapy., 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. more...

Purpose: Atherosclerosis and cancer may progress through common pathological factors. This study was performed to investigate the association between the abdominal aortic calcification (AAC) volume and outcomes following surgical treatment for pancreatic cancer., Methods: The subjects of this retrospective study were 194 patients who underwent pancreatic cancer surgery between 2007 and 2020. The AAC volume was assessed through routine preoperative computed tomography. Univariate and multivariate analyses were performed to evaluate the impact of the AAC volume on oncological outcomes., Results: A higher AAC volume (≥ 312 mm 3 ) was identified in 66 (34%) patients, who were significantly older and had a higher prevalence of diabetes and sarcopenia. Univariate analysis revealed several risk factors for overall survival (OS), including male sex, an AAC volume ≥ 312 mm3, elevated carbohydrate antigen 19-9, prolonged operation time, increased intraoperative bleeding, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy. Multivariate analysis identified an AAC volume ≥ 312 mm3, prolonged operation time, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy as independent OS risk factors. The OS rate was significantly lower in the high AAC group than in the low AAC group., Conclusion: The AAC volume may serve as a preoperative prognostic indicator for patients with pancreatic cancer., Competing Interests: Declarations. Conflict of interest: We have no conflicts of interest to declare for this article. Ethics statement: This study was approved by the Ethics Committee of The Jikei University School of Medicine (no. 27–177)., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.) more...

Background: This study aimed to identify the prognostic factors after pancreatectomy for borderline resectable pancreatic cancer abutting major arteries (BR-A). Methods: We retrospectively investigated relationship between preoperative and intraoperative variables and overall survival (OS) through univariate and multivariate analyses. The cut-off points of preoperative therapy duration and response rates of serum carbohydrate antigen 19-9 (CA19-9) levels after preoperative therapy were determined through a minimum P -value approach using the log-rank test for OS. Overall survival was compared among patients stratified according to the independent prognostic factors and the presence or absence of pancreatectomy. Results: After pretreatment, 17 patients underwent pancreatectomy and four patients continued chemotherapy without surgery. Multivariate analysis in 17 resected BR-A patients demonstrated decreased serum CA19-9 levels and preoperative therapy duration of ≥4 months were the independent prognostic factors [hazard ratio (HR) 0.01; P = 0.002, HR 0.13; P = 0.02]. Patients who underwent surgery with decreased serum CA19-9 levels after preoperative therapy of ≥4 months had a significantly better prognosis than those without one or both of independent prognostic factors and those who did not undergo surgery (median survival time: not estimated, 23.3 months, 10.5 months, and 10.8 months; P = 0.02, P = 0.004, and P = 0.001, respectively). Furthermore, the prognosis did not significantly differ between the patients who underwent surgery without meeting either one or both criteria and those without surgery. Conclusions: Preoperative therapy duration of ≥4 months and decreased serum CA19-9 levels are independent prognostic factors among BR-A patients., 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. more...

Background: Biliary stricture is a common complication after living-donor liver transplantation (LDLT), but its management is challenging. We herein report a case of successful internal drainage achieved through combination of the gun-sight technique and dual hepatic vascular embolization (DHVE)., Case Presentation: A 54-year-old woman with primary biliary cholangitis underwent ABO-incompatible LDLT with the right lobe. Duct-to-duct biliary anastomosis was performed, and V5 and V8 of the graft were reconstructed using a vein graft. However, 5 months after surgery, magnetic resonance cholangiopancreatography revealed stricture of the bile duct anastomosis. Endoscopic stenting could not be attempted because of the sigmoidal bending of the bile duct. Instead, percutaneous transhepatic cholangiographic drainage (PTCD) of the anterior and posterior branches was performed. We attempted to remove the PTCD tube by an endofistulization technique. We performed the gun-sight technique, originally employed for transjugular intrahepatic portosystemic shunt procedures, to create a pathway for internal drainage of the posterior segment. The anterior lobe was abandoned by applying DHVE, resulting in no external drainage tubes., Conclusion: Application of the gun-sight technique with DHVE for sigmoidal refractory biliary stricture after LDLT appears to be a feasible treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kenei Furukawa reports financial support was provided by JSPS KAKENHI. If there are other authors, they 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 Elsevier Inc. All rights reserved.) more...

Background/aim: Lipoprotein(a) (Lp(a)) is a complex protein involved in the transport of insoluble lipids in plasma. Its expression is predominantly genetically determined, with 70% to over 90% influenced by the number of Kringle IV type 2 domains. This study investigated the association between preoperative serum Lp(a) level and development of post-pancreatectomy nonalcoholic fatty liver disease (NAFLD) in patients who underwent pancreatectomy., Patients and Methods: Serum Lp(a) level was measured preoperatively and retrospectively evaluated together with other known risk factors for NAFLD, which was defined using a computed tomography-based Hounsfield unit (HU) value for liver parenchyma below 40 HU at the anteroposterior midpoint., Results: NAFLD developed after pancreatectomy in 40 patients (17.5%) in the high Lp(a)-group, which was significantly lower compared to the 30 patients (53%) in the low Lp(a)-group (p=0.01). There were no other significant background factors related to preoperative Lp (a) level. Multivariate analysis indicated that low Lp(a) level is an independent risk factor for postoperative NAFLD, as well as pancreatic head resection, a small residual pancreatic volume, poor intake of pancrelipase, and postoperative diarrhea., Conclusion: NAFLD after pancreatectomy could be predicted preoperatively to a certain extent by examining serum Lp(a) level., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...

Competing Interests: Disclosures: The authors declare no conflicts of interest.

Background: AT-rich interaction domain 4B (ARID4B) is a transcriptional activator that regulates the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in prostate cancer. However, the role of ARID4B in hepatocellular carcinoma (HCC) has remained unclear., Methods: This study included 162 patients who had undergone primary hepatic resection for HCC between 2008 and 2019. Their HCC samples were immunohistochemically stained for ARID4B, and ARID4B score was calculated from the intensity and percentage of staining. We retrospectively investigated the association of ARID4B score with disease-free and overall survival, and primary recurrence patterns of HCC. Furthermore, human HCC cell lines (HuH-1 and HuH-7) were knocked down for ARID4B using small-interfering RNA (siRNA), and the expression of PI3K/AKT proteins, cell proliferation, migration, and invasion ability were assessed., Results: In multivariate analyses, negative HBs-antigen (p = 0.02), multiple tumors (p < 0.01), microvascular invasion (p = 0.03), and high ARID4B score (p = 0.01) were independent predictors of disease-free survival, while tumor size >5 cm (p = 0.03), microvascular invasion (p < 0.01), and high ARID4B score (p = 0.04) were independent predictors of overall survival. A high ARID4B score was associated with high serum α-fetoprotein (AFP) level (p = 0.04), poor tumor differentiation (p < 0.01), and microvascular invasion (p < 0.01). ARID4B scores were significantly lower in the no recurrence, intrahepatic recurrence, and extrahepatic recurrence groups, in that order. Knockdown of ARID4B using siRNA in human HCC cell lines significantly suppressed the PI3K/AKT pathway, cell proliferation, migration, and invasion., Conclusions: ARID4B may activate the PI3K/AKT signaling pathway in HCC and may be a prognostic factor after hepatic resection for HCC., Competing Interests: Disclosures: Munetoshi Akaoka, Mitsuru Yanagaki, Hoshiho Kubota, Koichiro Haruki, Kenei Furukawa, Tomohiko Taniai, Shinji Onda, Ryoga Hamura, Masashi Tsunematsu, Yoshihiro Shirai, Michinori Matsumoto, Masayuki Shimoda, and Toru Ikegami declare no conflicts of interest that may be relevant to the contents of this study. The authors would like to thank Mr Mitsunobu Arizono and Ms Risako Suzuki (the Jikei University School of Medicine) for their excellent assistance with the in vitro experiments. Ethical Approval: This study protocol was approved by the Ethics Committee of the Jikei University School of Medicine (approval number 27-177). Informed Consent: Individual consent was waived because of the anonymous nature of the data., (© 2025. Society of Surgical Oncology.) more...

Background & Aims: The inhibition of epigenetic regulators activates endogenous retrovirus (ERV) expression, which can stimulate a viral mimicry response in cancer cells. ERV elements are aberrantly expressed in hepatocellular carcinoma (HCC); however, the expression of ERVs regulated by histone modifications and their clinical significance in HCC remain unclear. Here, we identified specific human endogenous retrovirus (HERV) elements epigenetically suppressed by the histone methyltransferase SETDB1 in HCC., Methods: The Cancer Genome Atlas (TCGA) dataset was analyzed to identify HERV elements based on SETDB1 expression levels. SETDB1 knockdown (KD) was performed in mouse and human HCC cells to investigate the resulting biological effects and changes in HERV expression, both in vitro and in vivo ., Results: TCGA analysis revealed an inverse correlation between SETDB1 and retroelements in human HCC (R = -0.723, p  = 2.297 × 10 -40 ), identifying four specific HERV elements in SETDB1 -high expressing HCC cases. Low expression of these four HERVs was associated with poor prognosis, and their combined expression provided additional prognostic insight ( p <0.001). Increased expression of the four HERV elements and decreased H3K9me3 levels at these regions were detected in human HCC cells with SETDB1 -KD. In murine HCC cells, Setdb1 -KD impaired in vivo tumor growth with increasing CD8-positive T-cell infiltration. Moreover, the interferon α response pathway and multiple ERV elements were activated in mouse HCC cells with Setdb1 -KD. The expression of interferon-stimulated genes, as indicators of a viral mimicry response, was elevated in both murine and human SETDB1 -KD HCC cells., Conclusions: The suppression of four novel HERV elements by SETDB1 serves as a prognostic marker in HCC. Activation of these SETDB1-regulated HERVs could represent a promising therapeutic strategy for HCC., Impact and Implications: An inverse relationship between retroelements including human endogenous retrovirus (HERV) elements and SETDB1 expression was observed in human hepatocellular carcinoma (HCC) by The Cancer Genome Atlas data analysis. We identified four HERV elements downregulated by SETDB1-dependent H3K9me3 in HCC cells, with low expression levels of these HERV elements correlating with poor prognosis in patients with HCC. SETDB1 depletion resulted in upregulation of various interferon-stimulated genes associated with viral mimicry in HCC cells. These findings suggest that the four SETDB1-regulated HERVs could serve as prognostic markers and potential therapeutic targets for HCC., Competing Interests: The authors have no conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Author(s).) more...

Purpose: Simultaneous dual hepatic vein embolization (DHVE) has been proposed for safe right-sided hepatectomy, with good results for liver hypertrophy and function. However, the histological and radiological findings of DHVE have not been thoroughly investigated., Methods: This study included 14 patients who underwent DHVE before right-sided major hepatectomy. DHVE was performed if the future liver remnant was < 35% or borderline, but with concomitant vascular resection. The liver function was assessed using the signal intensity on Gd-EOB-DTPA-MRI. A histological evaluation of the area of DHVE and portal vein embolization (PVE) were performed., Results: The median pre- and post-functional liver remnants were 363 ml and 498 ml, respectively (p < 0.001). The median growth rate was 48.6%, and there was no post-hepatectomy liver failure in the patients who underwent DHVE. The signal intensity ratio in the area of DHVE was lower than that in the areas of PVE and the remnant liver (p < 0.01). The degree of congestion and necrosis was greater in the area of DHVE than in the area of PVE alone (p < 0.01 and p = 0.04, respectively)., Conclusions: We observed good liver hypertrophy after DHVE and histological and radiological changes in the area of DHVE. Our findings provide a compelling rationale for further investigation of the mechanism of liver hypertrophy in DHVE., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest in association with the present study. Ethical approval: This study protocol was approved by the ethics committee of Jikei University School of Medicine (No. 32-504). Patients were given the opportunity to opt out of this study through public announcements., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.) more...

Purposes: The optimal surgical technique and perioperative management to prevent postoperative pancreatic fistula (POPF) formation after pancreaticoduodenectomy have not yet been established. This study examined the perioperative outcomes of pancreaticogastrostomy with endoscopic transgastric drainage., Methods: We performed a retrospective analysis of 191 patients who underwent pancreaticoduodenectomy between 2016 and 2023. They were divided into two groups: pancreaticojejunostomy group (n = 135) and pancreaticogastrostomy group (n = 56). We compared preoperative factors and postoperative outcomes. We performed endoscopic drainage only in the pancreaticogastrostomy group., Results: Preoperative factors were similar between the two groups. Operative time [480 (404-542) vs. 382 (346-458) minutes], blood loss [505 (270-850) vs. 315 (145-535) g], pseudoaneurysm formation (7 % vs. 0 %), and postoperative hospital stay [28 (22-38) vs. 19 (17-24) days] were significantly lower in the pancreaticogastrostomy group. In the analysis of 41 patients with POPF, postoperative hospital stay [40 (23-108) vs. 27 (18-54) days] and hospital stay after POPF diagnosis [30 (10-99) vs. 15 (5-35) days] were significantly shorter in the pancreaticogastrostomy group. Endoscopic transgastric drainage was performed in 77 % of patients in the pancreaticogastrostomy group, and drainage was successfully completed in all patients., Conclusion: Pancreaticogastrostomy with endoscopic transgastric drainage could be effective for the safe management of pancreaticoduodenectomy., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...

Background: The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index is a novel immune nutrition scoring system associated with cancer prognosis. This study investigated the association between the CALLY index and the long-term outcomes of patients with gastric cancer., Methods: We included 175 patients with gastric cancer who underwent curative gastrectomies at the Department of Surgery, International University of Health and Welfare Hospital between January 2011 and October 2019. The CALLY index was calculated based on the levels of serum albumin, serum CRP, and peripheral lymphocyte count. Utilizing both univariate and multivariate analyses, the prognostic value of the CALLY index was investigated., Results: In the multivariate analyses, disease stage (hazard ratio [HR], 7.85; 95% confidence interval [CI], 3.31-18.6; P < .01), microvascular invasion (HR, 2.88; 95% CI, 1.30-6.36; P < .01), and low CALLY index (HR, 2.18; 95% CI, 1.00-4.76; P = .05) were independent and significant predictors of disease-free survival. Low body mass index (HR, 4.15; 95% CI, 1.63-10.6; P < .01), advanced disease stage (HR, 8.22; 95% CI, 3.47-19.5; P < .01), and low CALLY index (HR, 3.00; 95% CI, 1.3-6.93; P = .01) were independent and significant predictors of overall survival. The low CALLY index group had a lower body mass index ( P < .01), advanced disease stage ( P < .01), and a higher Glasgow prognostic score ( P < .01)., Conclusions: The CALLY index may be associated with a poor prognosis for gastric cancer, highlighting the utility of a comprehensive assessment using inflammatory, nutritional, and immunological statuses., 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. more...

Background/aim: The study aimed to investigate the efficacy of radiotherapy or chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer., Patients and Methods: Twenty-eight patients who had isolated locoregional recurrence after pancreatectomy for pancreatic cancer between 2007 and 2021 were retrospectively analyzed. We investigated the effect of the treatment method [radiotherapy or chemoradiotherapy (radiotherapy with concurrent chemotherapy)] on progression-free survival (PFS) and post-recurrence survival (PRS)., Results: The median disease-free survival was 16.1 months (range=4.7-47.1 months). Five patients received radiotherapy and 21 patients received chemoradiotherapy [radiotherapy concurrent with gemcitabine (GEM) or S-1] for locoregional recurrence. All patients except one patient with interstitial pneumonia were treated with salvage chemotherapy after irradiation. The median PFS rates of the radiotherapy group and the chemoradiotherapy group were 2.8 months (range=1.5-5.4 months) and 16.8 months (range=2.7-42.8 months), respectively. The median PRS rates were 23.7 months (range=8.1-26.4 months) for the radiotherapy group and 26.2 months (range=6.0-64.7 months) for the chemoradiotherapy group. Multivariate analysis identified radiotherapy [hazard ratio (HR)=12.2, 95% confidence interval (CI)=3.29-45.6, p<0.001] and serum DUPAN-2 >150 U/ml (HR=2.90, 95%CI=1.22-6.93, p=0.02) as independent predictors of PFS, and UICC TNM Stage ≥III (HR=3.23, 95%CI=1.17-8.96, p=0.02) and modified Glasgow prognostic score before the treatment for the recurrence 1 or 2 (HR=3.05, 95%CI=1.15-8.08, p=0.03) as independent predictors of PRS., Conclusion: Chemoradiotherapy for isolated locoregional recurrence after pancreatectomy for pancreatic cancer could suppress re-recurrence more effectively than radiotherapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...

Background/aim: No studies have investigated the advantage of laparoscopic hepatectomy (LH) compared with open hepatectomy (OH) from a nutritional perspective. This study aimed to compare the postoperative nutritional status between LH and OH., Patients and Methods: A total of 186 patients who underwent partial hepatic resection for liver tumors were analyzed retrospectively. We compared perioperative variables between LH and OH. The nutritional status was assessed using serum albumin (Alb) and rapid turnover protein concentrations. We investigated risk factors for postoperative malnutrition using univariate and multivariate analyses., Results: The LH group, compared with the OH group, had a significantly shorter operative time (239 vs. 344 min, p<0.03), less intraoperative blood loss (100 vs. 343 g, p<0.01), and a shorter length of postoperative stay (8 vs. 11 days, p<0.01). Postoperative serum Alb and prealbumin concentrations in the LH group were significantly higher than those in the OH group (3.4 vs. 3.2 g/dl, p<0.01; 15.0 vs. 12.0 mg/dl, p=0.02, respectively). The multivariate analysis showed that OH (p=0.02) and hepatocellular carcinoma (p<0.01) were significant and independent risk factors for postoperative malnutrition., Conclusion: LH may be superior to OH in terms of the postoperative nutritional status, intraoperative blood loss, and length of postoperative stay., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...

Purpose: Abdominal aortic calcification (AAC), an indicator of systemic arteriosclerosis, is associated with short- and long-term outcomes in malignancies. We investigated the prognostic impact of AAC in patients who underwent hepatectomy for intrahepatic cholangiocarcinoma (IHCC)., Methods: The study cohort comprised 46 patients who underwent hepatectomy for IHCC between January 2008 and September 2020. The AAC volume measured by preoperative computed tomography was used to construct a model of the calcified segment from the renal artery to the common iliac artery bifurcation. We investigated the relationship between AAC and the long-term outcomes. The AAC volume cutoff value was calculated from a receiver-operating characteristic curve based on the three-year survival., Results: According to our cutoff AAC volume of 3,700 mm 3 , 11 patients (24%) had high AAC volumes. The high-AAC group was significantly older than the low-AAC group (73 vs. 62 years old, p < 0.01). A multivariate analysis of the cancer-specific survival showed that a high serum carbohydrate antigen 19-9 concentration (hazard ratio [HR] 5.57, p = 0.01), high AAC volume (HR 3.03, p = 0.04), and [high?] T3 or T4 levels (HR 9.05, p < 0.01) were independently associated with a poor prognosis., Conclusion: AAC is a useful predictor of the oncological prognosis in patients undergoing hepatectomy for IHCC., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.) more...

Background/aim: This study evaluated the prognostic impact of vertebral fractures (VFs) on the survival of patients with colorectal cancer (CRC)., Patients and Methods: We included 299 patients with stage I-III CRC who had undergone elective surgery. The patients were divided into the VF group (n=94) and non-VF group (n=205). VFs were assessed using sagittal computed tomography image reconstruction (Th11-L5) performed preoperatively. Disease-free survival (DFS) and overall survival (OS) rates were analyzed., Results: The VF group had lower 5-year DFS and OS rates compared to the non-VF group (both, p<0.001). The independent predictors of DFS were carbohydrate antigen 19-9 (CA19-9) ≥37.0 ng/ml, T3/T4 disease, stage III CRC, osteopenia, and VF; for OS, CA19-9 ≥37.0 ng/ml, stage III, osteopenia, and VF. VF, compared with osteopenia, was a more significant prognostic factor for DFS and OS in patients with stage I+ II CRC (both, p<0.001)., Conclusion: Preoperative VF was associated with worse DFS and OS following CRC resection., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...

Background: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis even after curative-intent hepatic resection due to a high recurrence rate. The aim of this study was to investigate preoperative risk factors for early recurrence after surgery for ICC, which may help to identify patients who need preoperative chemotherapy., Methods: We retrospectively analyzed 51 patients who had undergone primary surgery for ICC. We investigated the association of preoperative clinical variables with recurrence within 1 year after resection for ICC. We then created a high-risk ICC score using the identified preoperative factors and investigated the association of the score with disease-free and overall survival., Results: Recurrence within 1 year after surgery for ICC was significantly associated with poor overall survival ( P < .01). In the multivariate analysis, preoperative tumor size > 5 cm ( P = .03) and elevated C-reactive protein-to-albumin ratio (CAR) ( P = .04) were significantly associated with recurrence within 1 year after surgery. A high-risk ICC score of 2 was associated with poor disease-free survival ( P < .01) and overall survival ( P = .02) compared with a score of 0 or 1., Conclusions: Our high-risk ICC score, combining preoperative tumor size and CAR, can be an indicator of early recurrence and poor survival in patients after hepatic resection for ICC. Our findings may provide better preoperative risk stratification of patients with ICC, and the high-risk ICC patients may benefit from preoperative therapy., 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. more...

Background/aim: With the aging of the population, there is a rising proportion of elderly patients undergoing liver resection. However, the safety and efficacy of laparoscopic liver resection (LLR) in the elderly have not yet been established. In this study, we compared the short-term results of LLR and open liver resection (OLR) in elderly patients using propensity score matched (PSM) analysis., Patients and Methods: The study comprised 237 elderly patients aged 65 years and older who had undergone liver resection between 2015 to 2021, excluding biliary and vascular reconstruction and simultaneous surgeries other than liver resection. We conducted PSM analysis for baseline characteristics (age, sex, BMI, ASA-PS, disease, procedure, tumor size, and number of tumors) to eliminate potential selection bias. We then compared short-term postoperative outcomes between LLR and OLR groups in patients selected by PSM analysis., Results: Applying PSM analysis, 90 cases each were selected for the LLR and OLR groups. The LLR group had a significantly lower complication rate (Clavien-Dindo: CD ≥II) (19% vs. 33%, p=0.03), especially bile leakage (CD ≥II) (0% vs. 6.7%, p=0.03) compared with those in the OLR group. In addition, a shorter operation time (244 min vs. 351 min, p<0.01), less blood loss (150 ml vs. 335 ml, p<0.01), and shorter hospital stay (8 days vs. 12 days, p<0.01) were observed in the LLR group. No operative or in-hospital deaths were observed in both groups., Conclusion: LLR can be safely performed in elderly patients and offers better short-term outcomes., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...

Background: Owing to advances in the multidisciplinary treatment of hepatocellular carcinoma (HCC), a conceptualization and definition for borderline resectable (BR) HCC, which carries a high risk of recurrence, is warranted. In this study, we aimed to define BR-HCC using a prognosis-oriented approach., Study Design: The study included an original cohort of 221 patients and an independent validation cohort of 181 patients who had undergone primary hepatic resection for HCC. To define biological BR-HCC, we evaluated the risk factors for early recurrence beyond the Milan criteria within 1 year after hepatic resection using multivariable logistic regression models. Subsequently, we developed high-risk scores using the identified risk factors and defined BR-HCC. The utility of high-risk score was validated in the validation cohort., Results: In the original cohort (hepatitis B virus:hepatitis C virus = 20%:29%), recurrence beyond the Milan criteria within 1 year was observed in 28 patients (13%), with a 5-year survival rate of 25%. Multivariable analysis identified risk factors for recurrence beyond the Milan criteria within 1 year, including serum alpha-fetoprotein levels of 12 ng/mL or more (p = 0.02), tumor diameters less than 5 cm (p = 0.02), tumor number 3 or more (p = 0.001), and macrovascular invasion (p = 0.04). BR-HCC was defined as a tumor with 2 or more identified risk factors, and 42 patients (19%) were diagnosed with BR-HCC, with a 5-year survival rate of 51%. In the validation cohort, 45 (25%) patients had BR-HCC, with a 5-year survival rate of 42%., Conclusions: The prognosis-oriented definition of BR-HCC enabled us to identify patients who are susceptible to early unresectable recurrence and have poor survival after hepatic resection for HCC. For patients with BR-HCC, preoperative systemic therapy may be a viable option to improve postresection outcomes., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.) more...

Purposes: End-stage liver and kidney disease is an indication for simultaneous liver and kidney transplantation. However, in countries where deceased donor transplantation is not well established, living donor liver transplantation (LDLT) is a realistic option for patients on hemodialysis (HD). We investigated the outcomes of LDLT for patients on HD., Methods: We conducted a retrospective multicenter survey of patients on chronic HD who underwent LDLT in East Asian countries. The characteristics of donors and recipients and the short and long-term outcomes were analyzed., Results: Between 2001 and 2021, 45 patients on HD underwent LDLT and 11 of these patients also underwent kidney transplantation (KT). The overall survival rate at 5 years of the 34 patients who underwent only LDLT was 44.5%. Multivariate analysis identified a low graft recipient weight ratio (< 1%) (p = 0.048) and long HD duration (≥ 10 years) (p = 0.046) as independent predictors of poor overall survival. The major complication was posttransplant bleeding, which occurred in12 patients (35%)., Conclusion: It is important to establish the indications for LDLT, taking into consideration graft size and HD duration in candidate patients on HD., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.) more...

Purpose: This study examined the impact of osteosarcopenia on recurrence and the prognosis after resection for extrahepatic biliary tract cancer (EBTC)., Methods: We retrospectively analyzed 138 patients after resection for perihilar cholangiocarcinoma (11), distal cholangiocarcinoma (54), gallbladder carcinoma (30), or ampullary carcinoma (43). Osteosarcopenia is defined as the concomitant occurrence of osteopenia and sarcopenia. We investigated the relationship between osteosarcopenia and the overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses., Results: Osteosarcopenia was identified in 38 patients (27.5%) before propensity score (PS) matching. In the multivariate analysis, the independent recurrence factors were the prognostic nutrition index (p = 0.015), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.004), perineural invasion (p = 0.002), and non-curability (p = 0.008), whereas the independent prognostic factors were prognostic nutrition index (p = 0.030), osteosarcopenia (p < 0.001), poorly differentiated adenocarcinoma (p = 0.007), lymphatic invasion (p = 0.018), and non-curability (p = 0.004). After PS matching, there was no significant difference in the variables between the patients with and without osteosarcopenia (n = 34 each). The 5-year DFS and OS after PS matching in patients with osteosarcopenia were significantly worse than in patients without osteosarcopenia (17.6% vs. 38.8%, p = 0.013 and 20.6% vs. 57.4%, p = 0.0005, respectively)., Conclusions: Preoperative osteosarcopenia could predict the DFS and OS of patients after resection for EBTC., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.) more...

Background/aim: Laparoscopic hepatic resection is currently used for ruptured hepatocellular carcinoma (HCC); however, it is technically challenging. We developed and implemented surgical strategies for emergency laparoscopic partial liver resection in selected patients with peripheral lesions who were hemodynamically stable and without severe liver dysfunction., Patients and Methods: The surgical techniques used were as follows. First, the Pringle maneuver was performed to control hepatic blood inflow (step 1). Next, strong hemostatic agents were applied at the rupture point of the tumor (step 2). The hanging tape was positioned along the dorsal side of the resection line to control the partial blood inflow and outflow of the tumor, as well as to expose the surgical plane (step 3). The liver parenchyma was dissected along the hanging tape (step 4). We performed emergency laparoscopic partial liver resection in three patients who were in a pre-shock status., Results: The tumors were located in segments 6 (cases 1 and 2) and 2 (case 3). The tumor diameters were 90, 62, and 80 mm. The Preoperative Child-Pugh scores were B7, B9, and B8. The hemostatic products performed well and controlled bleeding from the ruptured HCC. The hanging tape facilitated the dissection of the liver parenchyma. The operative time and intraoperative blood loss were 135 min and 400 ml, 266 min and 200 ml, and 191 min and 495 ml for cases 1, 2, and 3 respectively. There were no in-hospital deaths., Conclusion: Emergency laparoscopic partial liver resection could be an option for patients with ruptured HCC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...

Background: The cachexia index (CXI), which consists of skeletal muscle, inflammation, and nutritional status, has been associated with prognosis in patients with hepatocellular carcinoma (HCC). We hypothesized that dynamic changes in CXI might be associated with long-term outcomes in HCC., Methods: This study comprised 131 patients who had undergone primary hepatic resection for HCC between 2008 and 2019. Preoperative CXI (pre-CXI) and postoperative CXI (post-CXI) were calculated by the following formula: skeletal muscle index x serum albumin level / neutrophil-to-lymphocyte ratio. Pre- and post-CXI were classified into two groups (high vs. low). We retrospectively investigated the association of perioperative dynamic changes in CXI with disease-free and overall survival., Results: In multivariate analyses, negative HBs-antigen ( p  = 0.02), high serum PIVKA-II level ( p  < 0.01), poor tumor differentiation ( p  = 0.02), multiple tumors ( p  < 0.01), microvascular invasion ( p  < 0.01), partial resection ( p  < 0.01), postoperative complications ( p  < 0.01), and low-pre-CXI ( p  < 0.01) were significant predictors of disease-free survival, while high ICG R15 ( p  = 0.01), poor tumor differentiation ( p  < 0.01), multiple tumors ( p  = 0.01), postoperative complications ( p  < 0.01), low-pre-CXI ( p  < 0.01), and low-post-CXI ( p  < 0.01) were significant predictors of overall survival. Low-post-CXI was associated with older age ( p  = 0.045), larger tumor ( p  < 0.01), longer operation time ( p  = 0.047), greater intraoperative bleeding ( p  < 0.01), and intraoperative blood transfusion ( p  < 0.01). Moreover, dynamic changes in CXI were associated with overall survival in each subgroup of patients with low-pre-CXI ( p  = 0.02) or high-pre-CXI ( p  = 0.03)., Conclusions: Not only post-CXI but also dynamic changes in CXI from pre- to post-hepatectomy can be a prognostic indicator of HCC, providing a compelling rationale for aggressive perioperative nutritional and physical interventions to improve long-term outcomes., Competing Interests: The authors declare no conflict of interests for this article., (© 2024 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.) more...

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of Kras G12D -driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism., (© 2024. The Author(s).) more...

Background/aim: This study aimed to identify the risk factors for early recurrence (ER) after pancreatic ductal adenocarcinoma (PDAC) resection to create a novel scoring system for ER and analyze their effect on the recurrence pattern., Patients and Methods: Sixty patients with PDAC who underwent pancreatectomy were included. The predicted risk factors for ER were analyzed. A new score defining ER was created and analyzed for recurrence pattern and prognosis., Results: Independent predictors included high CA 19-9 (≥147 U/ml), high lymph node ratio (LNR of ≥0.1277), and no adjuvant chemotherapy (AC). The 5-year overall survival rates with a score of 0, 1, and 2 were 55.8%, 11.0%, and 0%, respectively. In the moderate- risk score group, prognosis was improved by induction of AC within 58 days., Conclusion: Preoperative high CA19-9, high LNR, and no AC could be ER predictors. Induction of postoperative chemotherapy within 58 days may improve prognosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...

Objectives: Signal intensity ratio of pancreas to spleen (SI ratio p/s ) on fat-suppressed T1-weighted images of magnetic resonance imaging has been associated with pancreatic exocrine function. We here investigated the predictive value of the SI ratio p/s for the development of nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD)., Materials and Methods: This study comprised 208 patients who underwent PD. NAFLD was defined as a liver-to-spleen attenuation ratio of <0.9 calculated by a computed tomography 1 year after surgery. SI ratio p/s was calculated by dividing the average pancreas SI by the spleen SI. We retrospectively investigated the association of clinical variables including the SI ratio p/s and NAFLD by univariate and multivariate analyses., Results: NAFLD after 1 year was developed in 27 patients (13%). In multivariate analysis, the SI ratio p/s < 1 ( P < 0.001) was an independent predictor of incidence of NAFLD. The SI ratio p/s < 1 was associated with low amylase level of the pancreatic juice ( P < 0.001) and progressed pancreatic fibrosis ( P = 0.017). According to the receiver operating characteristics curve, the SI ratio p/s had better prognostic ability of NAFLD than the remnant pancreas volume., Conclusions: The SI ratio p/s is useful to predict NAFLD development after PD. Moreover, the SI ratio p/s can be a surrogate marker, which represents exocrine function of the pancreas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) more...

Aim: To study the effect of preoperative osteosarcopenia (OSP) on the prognosis of treatment (surgery or radiofrequency ablation (RFA)) in patients with Barcelona Cancer Liver Classification stage A hepatocellular carcinoma (BCLC A HCC)., Methods: This study enrolled 102 patients with BCLC A HCC who underwent surgical resection (n = 45) and RFA (n = 57); the patients were divided into two groups: OSP (n = 33) and non-OSP (n = 69). Overall survival (OS) and disease-free survival (DFS) curves for both the groups and treatment methods (surgery and RFA) were generated using the Kaplan-Meier method and compared using the log-rank test. Univariate analyses for OS and DFS were performed using log-rank test. Multivariate analyses were performed for factors that were significant at univariate analysis by Cox proportional hazard model., Results: Multivariate analysis showed that OSP (HR 2.44; 95 % CI 1.30-4.55; p < 0.01) and treatment (HR 0.57; 95 % CI 0.31-0.99; p = 0.05) were significant independent predictors of DFS; and treatment (HR, 0.30; 95 % CI 0.10-0.85; p = 0.03) was a significant independent predictor of OS in the non-OSP group, in which the OS rate was significantly lower in patients treated with RFA than in those treated by resection (p = 0.01)., Conclusions: OSP is a prognostic factor for BCLC A HCC treatment. Surgical approach was associated with a significantly better prognosis in patients without OSP compared to those who underwent RFA., Competing Interests: Declaration of competing interest The authors declare no Conflicts of Interest for this article., (Copyright © 2024. Published by Elsevier Ltd.) more...

Background/aim: This study aimed to investigate the relationship between prechemotherapy blood eicosapentaenoic acid (EPA) levels, sarcopenia, and overall survival in patients with pancreatic and biliary tract cancer undergoing chemotherapy., Patients and Methods: Forty-five patients with recurrent, non-resected pancreatic or biliary tract cancer undergoing chemotherapy were retrospectively analyzed. The skeletal muscle mass was measured at the third lumbar vertebra. Sarcopenia cut-off values were based on the Japanese Society of Hepatology sarcopenia assessment criteria. Two months after starting chemotherapy, the patients received enteral nutrition containing omega-3 fatty acids., Results: Patients with pancreatic and biliary tract cancers with low pre-treatment blood EPA levels had significantly more intense sarcopenia than those with high EPA levels (p=0.023). Patients with sarcopenia before chemotherapy had significantly lower overall survival than those without sarcopenia. Multivariate analysis revealed blood EPA concentration as an independent prognostic factor (p<0.01). Lumbar muscle volume, a marker of sarcopenia, showed a clear positive correlation with prechemotherapy EPA concentration (p=0.008). In patients administered with enteral nutrition containing omega-3 fatty acids, both EPA concentration and lumbar muscle volume were significantly higher than those prior to intervention, indicating sarcopenia improvement due to the intervention., Conclusion: In patients with recurrent non-resected pancreatic and biliary tract cancer, low blood EPA levels before chemotherapy are associated with sarcopenia and poor prognosis., Competing Interests: The Authors declare no conflicts of interest in relation to this study., (Copyright 2024, International Institute of Anticancer Research.) more...

Background: The conventional markers for hepatocellular carcinoma (HCC), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), have several limitations; both have low sensitivity in patients with early-stage HCC; low sensitivity for AFP with HCC after eliminating hepatitis C virus (HCV); low specificity for DCP in patients with non-viral HCC, which is increasing worldwide; low specificity for AFP in patients with liver injury; and low specificity for DCP in patients treated with warfarin. To overcome these issues, the identification of novel biomarkers is an unmet need., Objective: This study aimed to assess the usefulness of serum protein kinase C delta (PKCδ) for detecting these HCCs., Methods: PKCδ levels were measured using a sandwich enzyme-linked immunosorbent assay in 363 chronic liver disease (CLD) patients with and without HCC., Results: In both viral and non-viral CLD, PKCδ can detect HCCs with high sensitivity and specificity, particularly in the very early stages. Notably, the value and sensitivity of PKCδ were not modified by HCV elimination status. Liver injury and warfarin administration, which are known to cause false-positive results for conventional markers, did not modify PKCδ levels., Conclusions: PKCδ is an enhanced biomarker for the diagnosis of HCC that compensates for the drawbacks of conventional markers. more...

Purpose: The preoperative platelet-to-lymphocyte ratio (PLR) has been reported as an important prognostic index for pancreatic ductal adenocarcinoma (PDAC); however, the significance of the postoperative (post-op) PLR for this disease has not been elucidated., Methods: We analyzed data on 118 patients who underwent pancreaticoduodenectomy for pancreatic head PDAC, collected from a prospectively maintained database. The post-op PLR was obtained by dividing the platelet count after surgery by the lymphocyte count on post-op day (POD) 14. The patients were divided into two groups according to a post-op PLR of < 310 or ≥ 310. Survival data were analyzed., Results: A high post-op PLR was identified as a significant prognostic index on univariate analysis for disease-free survival (DFS) and overall survival (OS). The post-op PLR remained significant, along with tumor differentiation and adjuvant chemotherapy, on multivariate analysis for OS (hazard ratio = 2.077, 95% confidence interval: 1.220-3.537; p = 0.007). The post-op PLR was a significant independent prognostic index for poor DFS, along with tumor differentiation and lymphatic invasion, on multivariate analysis (hazard ratio = 1.678, 95% confidence interval: 1.056-2.667; p = 0.028)., Conclusions: The post-op PLR in patients with pancreatic head PDAC was an independent predictor of DFS and OS after elective resection., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.) more...

Objective: The prognostic impact of occult vertebral fracture (OVF) in patients with malignancies is a new cutting edge in cancer research. This study was performed to analyze the prognostic impact of OVF after surgery for pancreatic cancer., Methods: This study involved 200 patients who underwent surgical treatment of pancreatic ductal adenocarcinoma. OVF was diagnosed by quantitative measurement using preoperative sagittal computed tomography image reconstruction from the 11th thoracic vertebra to the 5th lumbar vertebra., Results: OVF was diagnosed in 65 (32.5 %) patients. The multivariate analyses showed that male sex (p = 0.01), osteopenia (p < 0.01), OVF (p < 0.01), a carbohydrate antigen 19-9 level of ≥400 U/mL (p < 0.01), advanced stage of cancer (p < 0.01), and non-adjuvant chemotherapy (p = 0.02) were independent risk factors for overall survival. An age of ≥74 years (p < 0.01) and obstructive jaundice (p = 0.03) were independent risk factors for OVF. Furthermore, the combination of OVF and osteopenia further worsened disease-free survival and overall survival compared with osteopenia or OVF alone (p < 0.01; respectively)., Conclusion: Evaluation of preoperative OVF might be a useful prognostic indicator for patients with pancreatic ductal adenocarcinoma., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.) more...

Aim: Pancreatic ductal adenocarcinoma treatment is mainly based on the anatomical resectability classification. However, prognosis-based classification may be more reasonable. In this study, we stratified resectable pancreatic ductal adenocarcinoma according to preoperative factors and reconsidered treatment strategies., Methods: We retrospectively evaluated 131 patients who underwent upfront surgery for resectable pancreatic ductal adenocarcinoma between 2007 and 2019. Recurrence within 1 year after surgery was defined as early recurrence, and the risk factors for early recurrence were identified using preoperative factors. Subsequently, we calculated the scores and stratified the participant groups., Results: Fifty-five (42 %) patients who relapsed within 1 year showed significantly poorer survival than those without recurrence (median overall survival, 14.0 vs. 80.6 months; p < 0.01). Multivariate analysis revealed that a tumor diameter of ≥24 mm (p < 0.01) and preoperative serum carbohydrate antigen 19-9 level of ≥380 U/mL (p = 0.04) were the independent risk factors for early recurrence. Early recurrence score was created using these factors, stratifying the participant group into three groups of 0-2 points, and the prognosis was significantly different (median overall survival, 49.3 vs. 31.2 vs. 16.0 months; p < 0.01)., Conclusion: We stratified the upfront surgical cases of resectable pancreatic ductal adenocarcinoma. The group with a score of 0 had a good prognosis, and upfront surgery was possibly not futile on patients in poor general condition. The group with a score of 2 had a poor prognosis and may require stronger preoperative treatment., (Copyright © 2024. Published by Elsevier Ltd.) more...

Background: Pancreatic cancer in contact with the superior mesenteric vein/portal vein is classified as resectable pancreatic cancer; however, the biological malignancy and treatment strategy have not been clarified., Methods: Data from 186 patients who underwent pancreatectomy for pancreatic cancer were evaluated using a prospectively maintained database. The patients were classified as having resectable tumors without superior mesenteric vein/portal vein contact and with superior mesenteric vein/portal vein contact of ≤180°. Disease-free survival, overall survival, and prognostic factors were analyzed., Results: In the univariate analysis, superior mesenteric vein/portal vein contact in resectable pancreatic cancer was a significant prognostic index for disease-free survival and overall survival. In the multivariate analysis for poor disease-free survival, the superior mesenteric vein/portal vein contact remained significant (hazard ratio = 2.13, 95% confidence interval: 1.29-3.51; p < 0.01). In the multivariate analysis, superior mesenteric vein/portal vein contact was a significant independent prognostic index for overall survival (hazard ratio = 2.17, 95% confidence interval: 1.27-3.70; p < 0.01), along with sex, tumor differentiation, nodal involvement, and adjuvant chemotherapy. Portal vein resection for superior mesenteric vein/portal vein contact did not improve the overall survival (p = 0.86)., Conclusions: Superior mesenteric vein/portal vein contact in resectable pancreatic cancer was found to be an independent predictor of disease-free survival and overall survival after elective resection. Thus, pancreatic cancer in contact with the superior mesenteric vein/portal vein may be considered as borderline resectable pancreatic cancer., 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 © 2023 Elsevier Ltd. All rights reserved.) more...

Purpose: Anamorelin, a selective ghrelin receptor agonist, has been approved for pancreatic cancer treatment in Japan. We aimed to investigate whether systemic inflammation, represented by the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein (CRP)-albumin ratio (CAR), could predict the effect of anamorelin in patients with advanced pancreatic cancer., Methods: This study included 31 patients who had received anamorelin for advanced pancreatic cancer between 2021 and 2023. Patients' NLR, PLR, LMR, and CAR were evaluated before anamorelin administration. The patients were classified as responders and non-responders based on whether they gained body weight after 3 months of anamorelin administration. We investigated the association between systemic inflammation and anamorelin efficacy using a univariate analysis., Results: Twelve (39%) patients were non-responders. A high serum CRP level (p = 0.007) and high CAR (p = 0.013) was associated with non-response to anamorelin. According to the receiver operating characteristics analysis, the CAR cutoff value was 0.06, and CAR ≥ 0.06 was a risk factor (odds ratio, 5.6 [95% confidence interval 1.2-27.1], p = 0.032) for non-response to anamorelin., Conclusion: CAR can be a predictor of non-response to anamorelin in patients with advanced pancreatic cancer, suggesting the importance of a comprehensive assessment of the inflammatory status., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...

Aim: The impact of occult vertebral fracture (OVF) on oncological outcomes after surgery has not been investigated, although its significance in orthopedics has been much debated recently. We evaluated the prognostic significance of OVF on the long-term outcomes of patients with colorectal liver metastases (CRLM) after hepatectomy., Methods: We included 140 patients with CRLM who underwent hepatectomy. OVF was identified using quantitative measurement and preoperative sagittal computed tomography image reconstruction from the 11th thoracic vertebra to the 5th lumber vertebra., Results: OVF was identified in 48 (34%) of the patients. In multivariate analysis, lymph node metastases ( p < 0.01), multiple tumors ( p = 0.02), extrahepatic lesions ( p < 0.01), OVF ( p < 0.01), intraoperative bleeding ( p = 0.04), and curability 1 or 2 ( p < 0.01) were independent and significant predictors of disease-free survival and extrahepatic lesions ( p < 0.01), osteosarcopenia ( p = 0.02), and OVF ( p < 0.01) were independent and significant predictors of overall survival. A higher age, adjuvant chemotherapy for a primary lesion before metachronous liver metastases, osteopenia, and hypoalbuminemia were independent risk factors for OVF., Conclusions: The evaluation of preoperative OVF is a useful prognostic factor for risk stratification and clinical decision-making for patients with CRLM. more...

Introduction: The aim of the present study was to evaluate the prognostic value of the ratio of serum fibrinogen to prognostic nutritional index (PNI; Fbg/PNI) in patients undergoing resection for pancreatic ductal adenocarcinoma., Methods: A total of 140 patients who had undergone resection for pancreatic cancer were included. Patients were divided into two groups according to a Fbg/PNI ≥8.8 or <8.8. Survival data were analyzed using the log-rank test for univariate analysis and Cox proportional hazards for multivariate analysis., Results: Fbg/PNI was a significant prognostic indicator in univariate analysis for overall survival (OS) and disease-free survival (DFS). Fbg/PNI retained significance in multivariate analysis for OS (hazard ratio, 1.81; 95% confidence interval, 1.19-2.77; P < .01) in addition to tumor differentiation and nodal involvement. Fbg/PNI was a significant independent prognostic indicator of poor DFS on multivariate analysis (hazard ratio, 1.54; 95% confidence interval, 1.05-2.26; P = .03)., Conclusion: Preoperative Fbg/PNI is a novel significant independent prognostic indicator for OS and DFS following resection of pancreatic cancer with curative intent., 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. more...

Background/aim: The prognostic outcome of the controlling nutritional status (CONUT) score in patients with colorectal liver metastases (CRLM) who underwent hepatectomy has not been investigated. The aim of this study was to investigate the prognostic value of preoperative CONUT score and other systemic inflammation-related biomarkers in patients who underwent hepatectomy for CRLM., Patients and Methods: The subjects included 145 patients with CRLM who underwent hepatectomy and retrospectively investigated the association of preoperative CONUT score with disease-free survival (DFS), surgical failure-free survival (SFS), and overall survival (OS) using univariate and multivariate analyses., Results: In this study, the cut-off of the CONUT score was 4. In the univariate analysis, the high CONUT score was associated with worse SFS and OS (p=0.01, 0.01). The multivariate analysis showed significant and independent predictors of OS were lymph node metastases (p=0.03) and a high CONUT score (p=0.04). In patients with a high CONUT score, postoperative complications due to infections were significantly more than in those with a low CONUT score (27% vs. 9%, p=0.04)., Conclusion: The CONUT score can be useful for predicting not only short-term but also long-term outcomes in patients with CRLM after hepatectomy., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...

Background: Laparoscopic hepatectomy after esophageal cancer surgery is a technically challenging procedure as it is difficult to control hepatic inflow due to adhesion 1. Ann Hepatobiliary Pancreat Surg. 22:344-349; 2. Dis Esophagus. 28:483-487; 3. Surg Endosc. 35:5375-5380; 4. Surg Laparosc Endosc Percutan Tech. 23:e103-105. Thus, we introduce our technique for hepatic inflow control using an endovascular clip., Methods: After the confirmation of space between the right and dorsal side of the hepatoduodenal ligament and the inferior vena cava, an endovascular clip was introduced laterally from the right side of the hepatoduodenal ligament to control hepatic inflow. The control of hepatic inflow was confirmed using intraoperative Doppler ultrasound and then a hepatic parenchymal transection was performed. The video demonstrates our technique using an endovascular clip for hepatic inflow control to perform safe open or laparoscopic hepatectomy after esophageal cancer surgery. Patient 1 was an 82-year-old woman with a history of laparoscopic assisted esophagectomy for esophageal neuroendocrine cancer. She underwent open anatomical resection of segment 3 for a 38-mm liver tumor. Patient 2 was a 71-year-old man with a history of laparoscopic esophagectomy for esophageal cancer. He underwent laparoscopic partial resection of segment 6 for a 24-mm liver tumor., Results: The operation times were 105 and 123 min, and the estimated blood loss was 30 g and 10 g, respectively. The patients' postoperative courses were uneventful and the patients were discharged on postoperative days 9 and 8, respectively., Conclusion: Right-lateral Pringle maneuver using an endovascular clip may be a safe and feasible technique in both open and laparoscopic hepatectomy after esophagectomy., (© 2023. Society of Surgical Oncology.) more...

Antibody-mediated rejection (AMR) after liver transplantation is uncommon but sometimes has a grave prognosis. We herein describe a 40-year-old man who developed simultaneous acute cellular rejection and acute AMR due to de novo donor-specific anti-human leukocyte antigen antibodies after living donor liver transplantation. He underwent living donor liver transplantation with his brother-in-law as the donor. Hepatic function deteriorated on postoperative day 6, and a liver biopsy revealed histologic findings of typical acute cellular rejection. However, steroid pulse therapy and thymoglobulin did not produce a clinical response, and his liver function dramatically deteriorated on postoperative day 13 (aspartate aminotransferase, 2787 IU/L; total bilirubin, 14.1 mg/dL). We diagnosed acute AMR based on positive immunohistochemical staining for C4d in portal areas and added plasma exchange and high-dose intravenous immunoglobulin after rituximab. The patient's clinical state improved and ultimately resolved. To our knowledge, this is the first report of dual antibody treatment for simultaneous acute cellular rejection and acute AMR induced by de novo donor-specific anti-human leukocyte antigen antibodies. Despite his fulminant clinical course, we successfully rescued the recipient with immediate anti-humoral therapy. The rapid treatment decision and adequate understanding of the mechanisms of anti-humoral therapy were crucial to overcoming acute AMR in this case., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.) more...

Background/aim: This study aimed to identify the optimal duration of pretreatment for unresectable locally advanced (UR-LA) pancreatic cancer and analyze its effect on the prognosis., Patients and Methods: This retrospective study included 39 patients with UR-LA pancreatic cancer after pancreatectomy. The cutoff period of preoperative therapy was determined using a receiver operating characteristic curve. We investigated the relationship between preoperative and intraoperative clinical variables and overall survival (OS) in univariate and multivariate analyses. The relationship between the preoperative therapy duration and the clinicopathological variables was investigated. OS was compared according to preoperative therapy duration and the presence or absence of adjuvant surgery., Results: After pretreatment, 15 patients underwent adjuvant surgery and 24 patients continued on chemotherapy without surgery. The multivariate analysis demonstrated preoperative therapy duration ≥6 months was an independent prognostic factor [hazard ratio (HR)=0.10, p=0.04]. No significant difference in the clinicopathological variables was observed between the two groups according to preoperative therapy duration. The OS was significantly better in patients who underwent adjuvant surgery after preoperative therapy duration ≥6 months than in those after preoperative therapy duration <6 months and in those without adjuvant surgery (5-year OS rates: 80% vs. 0%; p=0.01 and 5-year OS rates: 80% vs. 0%; p=0.004, respectively). The OS was not significantly better in patients with adjuvant surgery after preoperative therapy duration <6 months than in those without adjuvant surgery (2-year OS rates: 45.7% vs. 38.1%; p=0.98)., Conclusion: Preoperative therapy for UR-LA pancreatic cancer for ≥6 months is necessary to improve prognosis after adjuvant surgery., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...