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Purpose: Chyle leakage (CL) is a common complication in pancreatic surgery. Lymphangiography is a therapeutic option for CL in cases of conservative treatment failure. This study investigated the effect of lymphangiography on the healing time of CL., Methods: We retrospectively evaluated 283 patients who underwent pancreatic resection between January 2016 and June 2022. The risk factors for CL and the treatment period were evaluated according to whether or not lymphangiography was performed., Results: Of the 29 patients (10.2%) that had CL, lymphangiography was performed in 6. Malignant disease, the number of harvested lymph nodes, and drain fluid volume on postoperative day 2 were identified as independent risk factors for CL. Lymphangiography was associated with the cumulative healing rate of CL, and patients who underwent lymphangiography had a significantly shorter treatment period. No lymphangiography-related adverse events were observed., Conclusion: Lymphangiography is a feasible and safe treatment option for CL. The CL treatment period after pancreatic surgery was significantly shorter in patients who underwent lymphangiography than in those who did not. Our results suggest that lymphangiography may contribute to early improvement of persistent CL., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Glomus tumors (GT) generally occur in the skin. However, esophageal GT, an extremely rare condition, has no established standardized treatment guidelines. Herein, we report the case of an esophageal GT successfully removed by thoracoscopic enucleation in the prone position using intra-esophageal balloon compression., Case Presentation: A 45-year-old man underwent an annual endoscopic examination and was found to have a submucosal tumor in the lower esophagus. Endoscopic ultrasound (EUS) revealed a hyperechoic mass originating from the muscular layer. Contrast-enhanced computed tomography identified a 2 cm mass lesion with high contrast enhancement in the right side of the lower esophagus. Pathologic findings of EUS-guided fine needle aspiration biopsy (EUS-FNA) revealed round to spindle shaped atypical cells without mitotic activity. Immunohistochemically, the tumor was positive for alpha-smooth muscle actin, but negative for CD34, desmin, keratin 18, S-100 protein, melan A, c-kit, and STAT6. He was diagnosed with an esophageal GT and a thoracoscopic approach to tumor resection was planned. Under general anesthesia, a Sengstaken-Blakemore (SB) tube was inserted into the esophagus. The patient was placed in the prone position and a right thoracoscopic approach was achieved. The esophagus around the tumor was mobilized and the SB tube balloon inflated to compress the tumor toward the thoracic cavity. The muscle layer was divided and the tumor was successfully enucleated without mucosal penetration. Oral intake was initiated on postoperative day (POD) 3 and the patient discharged on POD 9. No surgical complications or tumor metastasis were observed during the 1-year postoperative follow-up., Conclusions: As malignancy criteria for esophageal GT are not yet established, the least invasive procedure for complete resection should be selected on a case-by-case basis. Thoracoscopic enucleation in the prone position using intra-esophageal balloon compression is useful to treat esophageal GT on the right side of the esophagus., (© 2024. The Author(s).)

Aims: This study aimed to determine the value of the drainage fluid volume and direct bilirubin level for predicting significant bile leakage (BL) after hepatectomy and establish novel criteria for early drain removal., Methods: Data from 351 patients who underwent hepatic resection at Gunma University in Japan between October 2018 and March 2022 were retrospectively analyzed. Clinical characteristics and surgical outcomes of patients with and without significant BL were compared. Criteria for early drain removal were determined and verified., Results: Bile leakage occurred in 27 (7.1%) patients; 8 (2.3%) had grade A leakage and 19 (5.4%) had grade B leakage. The optimal cut-off value for the drainage fluid direct bilirubin level on postoperative day (POD) 2 was 0.16 mg/dL, which had the highest area under the curve and negative predictive value (NPV). Patients with BL had significantly larger drainage volumes on POD 2. The best cut-off value was 125 mL because it had the greatest NPV. Patients in both the primary and validation (n = 90) cohorts with bilirubin levels less than 0.16 mg/dL and drainage volumes less than 125 mL did not experience leakage., Conclusions: A drainage fluid volume less than 125 mL and direct bilirubin level less than 0.16 mg/dL on POD 2 are criteria for safe early drain removal after hepatectomy., (© 2024 Japan Society of Hepatology.)

Pancreatic cancer (PC) is a challenging malignancy to treat. Mac-2-binding protein glycan isomer (M2BPGi) is a novel serum marker of liver fibrosis and hepatocellular carcinoma and is secreted by hepatic stellate and stroma cells. Serum M2BPGi levels are upregulated in PC patients. We measured the expression of M2BPGi in the serum of 27 PC patients and determined whether M2BPGi affects the malignant potential of PC cells in vitro. We also examined the effect of M2BP on PC tumor growth and gemcitabine sensitivity in vivo. Serum M2BPGi levels in PC patients were higher compared with those of healthy subjects. M2BPGi extraction in cancer-associated fibroblasts (CAFs) was higher compared with that of PC cells. M2BPGi treatment promoted the proliferation and invasion of PC cells. The suppression of galectin-3, which binds to M2BPGi, did not affect the proliferation-promoting effect of M2BPGi in PC cells. The suppression of M2BP reduced tumor growth and enhanced gemcitabine sensitivity in PC-bearing xenograft mice. CAF-derived M2BPGi promotes the proliferation and invasion of PC cells. Targeting M2BPGi may represent a new therapeutic strategy to circumvent refractory PC., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. As reported in previous studies, the loss of skeletal muscle mass is associated with poor liver regeneration after hepatectomy. It is considered important to clarify the effect of sarcopenia on liver regeneration; however, there are no reports about model animals for sarcopenia. We focused on the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) transgenic mice that overexpressed PGC-1α, specifically for skeletal muscle, and showed significant atrophy of type 2B fiber-rich muscles like sarcopenia., Methods: We performed 70% hepatectomy using PGC-1α transgenic mice and examined the liver regeneration rate and the effects of branched-chain amino acids (BCAA) after hepatectomy., Results: Liver regeneration after 70% hepatectomy was significantly suppressed in the PGC-1α transgenic mice. In addition, a decrease in the blood BCAA concentration and a decrease in the liver glycogen content after 70% hepatectomy were observed in the PGC-1α transgenic mice. By administering BCAA before and after surgery, it was clarified that a significant increase in the blood BCAA concentration was observed and the liver regeneration rate was improved in the PGC-1α transgenic mice., Conclusions: BCAA administration may improve the suppression of liver regeneration in patients with sarcopenia., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Fibrolamellar hepatocellular carcinoma (HCC) (FL-HCC) is rare in Japan. FL-HCC develops in young patients with no history of cirrhosis and tends to manifest lymphatic metastasis with clinical features similar to those of HCC. We present a case of FL-HCC in a young male patient., Case Presentation: A 14-year-old male patient underwent abdominal computed tomography (CT) to diagnose appendicitis, wherein a hepatic tumor was detected. Dynamic enhanced CT revealed a 35-mm solid tumor, which contrasted at the early phase of dynamic enhanced study of the right hepatic segments, with occlusion of the right portal vein. We performed right hepatectomy for these lesions. The patient experienced a single lymphatic recurrence on the hepatoduodenal ligament 12 months after the initial surgery. We performed lymphadenectomy for the recurrent tumor. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing of the resected specimens (primary tumor, lymphatic metastasis, and normal liver). RNA-seq detected DNAJB1-PRKACA in both primary and metastatic lesions as previously reported. Furthermore, The Cancer Genome Atlas (TCGA) database was used to compare other gene expressions in this case with those of previously reported cases of FL-HCC and HCC in young patients. Principal component analysis of differentially expressed genes in the top 10% revealed that the gene expression in our case was similar to that of previous FL-HCC cases but was a different cluster from that in HCC cases in young patients. Mutational analysis did not detect any somatic mutations associated with carcinogenesis, including previously reported mutations (Kastenhuber et al. in Proc Natl Acad Sci USA 114: 13076-84, 2017)., Conclusion: We encountered a case of FL-HCC, a rare hepatic tumor in an adolescent patient, and evaluated the genetic background. Our findings could contribute to the elucidation of the mechanisms underlying carcinogenesis and progression in patients with FL-HCC and thereby contribute to the development of new therapeutic strategies in the future that may improve patient prognosis., (© 2023. Japan Surgical Society.)

Background: Chemotherapy for colorectal liver metastasis (CRLM) has improved dramatically over the past few decades. However, sinusoidal obstruction syndrome (SOS) induced by oxaliplatin leads to increased severe morbidity after hepatectomy for CRLM. Autotaxin is a novel liver fibrosis marker known to be taken up and metabolized by sinusoidal endothelial cells. This study aimed to evaluate whether autotaxin levels could be a novel surrogate marker of SOS for CRLM., Methods: We retrospectively evaluated 73 consecutive patients who underwent hepatectomy for CRLM, and assessed the relationship between their preoperative autotaxin levels and SOS., Results: Median autotaxin level was 0.750 mg/L. Preoperative oxaliplatin-based chemotherapy for CRLM was administered to 51 patients, and SOS was histologically observed in 45 patients. Patients who received the oxaliplatin-based chemotherapy had significantly higher autotaxin levels than those who did not (p = 0.038). Furthermore, autotaxin levels were higher in patients with SOS than in those without (p = 0.011). Univariate and multivariate analyses revealed that autotaxin level can be an independent predictive factor for SOS preoperatively (p = 0.001)., Conclusions: Autotaxin level is a noninvasive and promising surrogate marker for predicting SOS before surgical resection for CRLM., (© 2023 Japan Society of Hepatology.)

Background: Pancreatic cancer has an extremely poor prognosis and is one of the most chemoresistant cancers. Targeting cancer cell transcriptional complexes may enhance chemotherapy effectiveness. RNA-polymerase I (Pol-I)-mediated transcription is an essential initial step for ribosome biogenesis and is related to cancer cell proliferation. RRN3 is a Pol-I-specific transcription initiation factor. In this study, we aimed to elucidate the function and clinical significance of RRN3 in pancreatic cancer., Methods: We performed immunohistochemical staining to detect RRN3 protein expression in 96 pancreatic cancer tissues and analyzed the relationship between RRN3 protein expression, clinicopathological factors, and cancer patient prognosis. Moreover, we evaluated RRN3 function in vitro and in vivo using proliferation, invasion, and chemosensitivity assays in PANC-1 and SW1990 cell lines, with/without depleting RRN3 expression., Results: RRN3 was mainly expressed in cancer cell nuclei. High levels of RRN3 expression were associated with Ki-67 expression and shorter overall survival. Additionally, proliferation and invasion ability were decreased when RRN3 was silenced with siRNA, compared to non-targeting siRNA-transfected cells. Chemosensitivity analysis showed that inhibition of RRN3 enhanced the sensitivity of pancreatic cancer cell lines to gemcitabine and paclitaxel. RRN3 siRNA-transfected PANC-1 tumors showed significantly reduced tumor volumes and high gemcitabine sensitivity compared to the control in a mouse xenograft model., Conclusion: High levels of RRN3 expression are associated with poor prognosis and cancer malignancy, such as proliferation, invasion ability, and chemosensitivity in pancreatic cancer. RRN3 targeting with anticancer drugs may be a promising therapeutic strategy to overcome refractory pancreatic cancer., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background/aim: Theoretically, laparoscopic procedures reduce the incidence of surgical site infection (SSI) compared with open surgery. This study aimed to investigate whether laparoscopic liver resection (LLR) attenuates organ-space SSI compared with open liver resection (OLR) using propensity score-matched (PSM) analysis., Patients and Methods: This study included 530 patients who underwent liver resection as the original cohort. PSM was conducted to adjust for confounding factors between OLR and LLR. Two groups were compared regarding the incidence of postoperative complications, including organ-space SSI. We also evaluated risk factors for organ-space SSI using univariate and multivariate analyses., Results: In the original cohort, incidence of bile leakage (p<0.001) and organ-space SSI (p<0.001) were significantly lower in the LLR group than those in the OLR group. A pair of 105 patients were selected for the PSM analysis. After matching, LLR was significantly associated with lower blood loss (p<0.001), longer Pringle clamp time (p<0.001), lower incidence of bile leakage (p=0.035), organ-space SSI (p=0.035), Clavien-Dindo grade ≥III complications (p=0.005), and longer length of hospital stay (p<0.001) than OLR. In multivariate analysis, OLR (p=0.045) was an independent risk factor for organ-space SSI., Conclusion: LLR has potential to reduce the risk of organ-space SSI caused by intra-abdominal abscess and bile leakage more than OLR., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: This study aimed to evaluate the usefulness of the serum creatinine/cystatin C (Cr/CysC) ratio as a prognostic factor after pancreatic surgery in patients with pancreatic cancer., Methods: We retrospectively analyzed the data of 88 patients with pancreatic ductal carcinoma who underwent pancreatic surgery from January 2017 to December 2020. CysC measured from frozen serum samples and circulating Cr levels were used to calculate the Cr/CysC ratio. The cutoff value of the Cr/CysC ratio was determined using receiver operating characteristic curves. Cox proportional hazards model analysis and survival curves were applied to identify the prognostic factors., Results: The optimal cutoff value of the Cr/CysC ratio for predicting mortality after surgery was 1.05. This study included 20 (22.7%) and 68 (77.3%) patients with high and low Cr/CysC ratios, respectively. The low Cr/CysC ratio was significantly associated with female sex ( p  = 0.020) and higher levels of C-reactive protein ( p  = 0.020). The postoperative length of stay was significantly longer in patients with low Cr/CysC rates ( p  = 0.044). Patients with low Cr/CysC ratio showed poorer prognosis in relapse-free survival (hazard ratio [HR] = 3.33; 95% confidence interval [CI]: 1.54-4.20; p  = 0.002) and overall survival (HR = 2.52, 95% CI: 1.04-6.10, p  = 0.041), respectively, which were significantly worse than in those with high Cr/CysC ratios ( p  = 0.003 and 0.049, respectively)., Conclusion: The Cr/CysC ratio could be a useful screening tool for predicting the prognosis of patients with pancreatic ductal carcinoma undergoing pancreatic surgery., Competing Interests: Author Ken Shirabe is an editorial board member of Annals of Gastroenterological Surgery. The other authors declare no conflict of interest for this article. The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Purpose: Curative surgical treatment of biliary tract cancer is highly invasive and involves postoperative complications. Abdominal aortic calcification is a parameter that is reportedly linked to systemic arteriosclerosis. We measured the abdominal aortic calcification volume (AACV), assessed the correlation between AACV and postoperative complications, and evaluated the clinical utility of AACV., Methods: We retrospectively evaluated 97 patients (ampullary carcinoma, n = 21; distal bile duct cancer, n = 43; hilar bile duct cancer, n = 33). We assessed the calcification volume of the abdominal aorta from the renal artery ramification to the common iliac artery bifurcation. The correlation between AACV, clinical factors, and postoperative complications was evaluated., Results: The average AACV was 5.02 cm 3 , and the median AACV was 3.74 (range 0-27.4) cm 3 . The AACV was significantly related to age (P = 0.009), Brinkman index (P = 0.007), and history of cardiovascular disease (P = 0.015). The AACV was strongly correlated with postoperative complications (P < 0.001) and Clavien-Dindo grade > III postoperative complications (P < 0.001). The AACV was also correlated with pancreatic fistula in pancreatectomy cases (P < 0.001). A multivariate analysis revealed that the AACV was an independent predictor of postoperative complications., Conclusion: The AACV was significantly associated with postoperative complications. The AACV could be used for the preoperative assessment of surgical risk., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background/aim: The relationship between body composition including skeletal muscle and liver hypertrophy initiated by portal vein embolization (PVE) for major hepatectomy has not been clarified. This study aimed to investigate the effects of skeletal muscle, body adipose, and nutritional indicators on liver hypertrophy., Patients and Methods: Fifty-nine patients who underwent PVE scheduled for major right-sided hepatectomy were included. The skeletal muscle area of L3 as skeletal muscle index was calculated. The relationship between skeletal muscle loss and clinical variables was assessed. We also evaluated the relationship between >30% liver growth or >12% liver growth/week after PVE., Results: Skeletal muscle loss was observed in 39 patients (66.1%) and associated with zinc deficiency, visceral adipose index, liver growth rate, and liver growth rate/week. Multivariate analysis indicated that future liver volume and skeletal muscle index were associated with >30% liver growth, and functional future liver volume and skeletal muscle index were associated with >12% liver growth/week., Conclusion: Loss of skeletal muscle, and a small future remnant liver volume, attenuates liver hypertrophy initiated by PVE. Strength building and nutritional supplementation may have positive effects on liver hypertrophy after PVE., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to identify the potential risk for postoperative pancreatic fistula (POPF), a major complication of pancreaticoduodenectomy., Patients and Methods: This retrospective study included 124 patients with biliary and pancreatic disorders who underwent pancreaticoduodenectomy between 2015 and 2020. Bone marrow density (BMD) was determined in the 11th thoracic vertebra using preoperative computed tomographic images. Delta BMD (dBMD=measured BMD - standard BMD) was calculated using standard BMD determined on the basis of age and sex, and dBMD <0 was defined as osteopenia. The relationship between clinicopathological factors and dBMD was investigated., Results: The average BMD level was 140 Hounsfield units. BMD was significantly lower in women than in men (p<0.01) and in older patients than in younger patients (p<0.01). POPF was significantly correlated with low dBMD (p=0.032). Osteopenia was a risk factor for POPF in patients with soft pancreas (p=0.016)., Conclusion: Osteopenia was an independent risk factor for POPF after pancreaticoduodenectomy in patients with soft pancreas. Preoperative osteopenia assessment may be useful for the prediction of POPF, and preoperative vitamin D supplementation might be considered in patients with osteopenia., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Factor V (FV) deficiency is an extremely rare disease, with an incidence of 1 in 1 million. The bleeding symptoms are mild, and the prognosis is good; however, the safety of surgical treatment is unclear, because there are few available reports. Herein, we report a case of hepatocellular carcinoma with congenital FV deficiency in a patient who safely underwent laparoscopic hepatectomy., Case Presentation: A 79-year-old man, diagnosed with hepatocellular carcinoma of liver segment 5, with type C cirrhosis and sustained virological response visited our hospital. He had congenital FV deficiency, and blood tests showed coagulation deficiencies with an FV activity of < 2.6%, prothrombin time activity of 11%, and activated partial thromboplastin time of 100.3 s. Surgery and radiofrequency ablation were considered for treatment. Since the tumor was in contact with the Glissonean pedicle 5 + 6, surgery was judged to be superior from the viewpoint of safety and curability. After discussing the safety of the surgery with a hematologist, it was determined that the operation could be performed safely by transfusing sufficient fresh frozen plasma (FFP). Laparoscopic hepatic segment 5 + 6 subsegmental resection was performed with FFP transfusion, fluid restriction, airway pressure control, and central venous pressure reduction to control the bleeding. Bleeding was minimized during the transection of the liver parenchyma and no bleeding tendency was observed. The operative time was 445 min, and the amount of intraoperative bleeding was 171 mL. No complications, such as postoperative bleeding, were observed, and the patient was discharged on the eighth postoperative day., Conclusions: Liver surgery can be performed safely in FV-deficient patients with strict coagulation capacity monitoring and appropriate transfusion of FFP. Preoperative evaluation of cardiac function to determine tolerance to high doses of FFP and ingenuity of surgery and intraoperative management to minimize blood loss are important., (© 2022. The Author(s).)

Purpose: To evaluate the effect of morphine or morphine equivalents on the risk of bile leakage (BL) after hepatectomy., Methods: The subjects of this retrospective study were 379 patients who underwent hepatectomy without biliary reconstruction and biliary decompression tube insertion at Gunma University between 2016 and 2020. Clinical BL was defined as International Study Group of Liver Surgery post-hepatectomy bile leakage Grade B or C., Results: Intra- and post-operative analgesia comprised intravenous patient-controlled analgesia (IV-PCA) with fentanyl (n = 58), epidural analgesia with fentanyl (n = 157), epidural analgesia with morphine (n = 151), and epidural analgesia with ropivacaine or levobupivacaine (n = 13). Clinical BL was diagnosed in 14 of the 379 (3.7%) patients. The significant risk factors for clinical BL were hepatocellular carcinoma (HCC), elevated serum total bilirubin, high indocyanine green retention at 15 min, elevated Mac-2-binding protein glycosylated isomer, prolonged duration of surgery, and a large volume of blood loss. There was no significant correlation of clinical BL with intra- and post-operative analgesia and total oral morphine equivalents., Conclusion: Intra- and post-operative IV-PCA and epidural analgesia were not related to clinical BL after hepatectomy. Based on our data, fentanyl and morphine can be administered safely as epidural or intravenous analgesic agents., (© 2021. Springer Nature Singapore Pte Ltd.)

Aim: Few reported studies examine the relationship between zinc (Zn) deficiency and short- and long-term outcomes in patients with hepatocellular carcinoma undergoing hepatic resection., Methods: We retrospectively reviewed data from 179 consecutive patients who had undergone curative hepatic resection for hepatocellular carcinoma in our institute between January 2016 and May 2019. Zn deficiency was defined in accordance with the Japanese Society of Clinical Nutrition guidelines. We allocated the participants into two groups according to Zn deficiency status, and analyzed the clinicopathological and short- and long-term outcomes., Results: In this series, 32 patients (17.8%) had Zn deficiency. Zn deficiency was significantly associated with older age, lower serum albumin, higher aspartate aminotransferase, lower hemoglobin, higher creatinine, lower prognostic nutritional index, higher liver fibrosis markers, albumin-bilirubin 2, portal hypertension, larger amount of estimated blood loss, larger amount of maximum ascites, longer hospital stay, postoperative complications, and liver-related complications. Concentrations of liver fibrosis markers were negatively correlated with serum Zn concentrations. Zn deficiency, albumin-bilirubin 2, and non-laparoscopic approach were identified as independent predictors of postoperative complications. Multivariate analyses revealed that the overall survival rate decreased in parallel with decreasing Zn concentrations., Conclusions: In this study, Zn deficiency was significantly associated with poorer liver function, more severe liver fibrosis, higher incidence of postoperative complications, and worse overall survival according to multivariate analysis. Serum Zn status could serve as a new surrogate marker for predicting short- and long-term outcomes in patients undergoing hepatic resection for hepatocellular carcinoma., (© 2021 The Japan Society of Hepatology.)

Background: Mac-2 binding protein (M2BP) glycosylated isomer (M2BPGi) is a serum marker of liver fibrosis; M2BPGi is a glycosylated form of M2BP. Hepatocytes and hepatic stellate cells (HSCs) have been studied to determine the source of M2BP. This study proposes to identify the origin of M2BP in fibrotic liver., Methods: Using liver fibrosis tissue specimens from 15 patients with liver cancer, M2BP mRNA and M2BP were detected by in situ hybridization and immunohistochemistry, respectively. The expression levels of M2BP mRNA were evaluated with scores of 3, 2, and 1. Fluorescent in situ hybridization was carried out to evaluate the distribution of M2BP mRNA and the activated-HSC marker αSMA mRNA; multicolor fluorescent immunohistochemistry was used for protein localization of M2BP, αSMA, and CD68. The Kruskal-Wallis test analyzed the relationship between M2BP mRNA expression and existing serum fibrosis markers., Results: M2BP mRNA was expressed in spindle-shaped cells along the fibrous septa and in the perisinusoidal area of the fibrotic liver. The HSC markers αSMA mRNA and M2BP mRNA were colocalized in the spindle-shaped cells; on the protein level, M2BP was expressed in Kupffer cells. M2BP mRNA expression was positively correlated with serum M2BPGi levels. Aspartate transaminase-to-platelet ratio index, Fibrosis-4, hyaluronic acid, and the 15-minute indocyanine green retention rate were significantly correlated with M2BP mRNA expression., Conclusions: M2BP mRNA transcription in fibrotic liver was primarily observed in HSCs but not at the M2BP level, which suggests that HSCs might produce and introduce M2BP to Kupffer cells and serum., (© 2021 The Japan Society of Hepatology.)

Background: Sarcopenia is closely associated with morbidity after pancreatic surgery. We investigated the impact of preoperative nutritional support and rehabilitation on patients undergoing pancreaticoduodenectomy., Methods: This was a retrospective analysis of 101 patients who underwent pancreaticoduodenectomy. Skeletal muscle (SM) loss was defined using the SM index (cutoff level: 42 cm 2 /m 2 in men and 38 cm 2 /m 2 in women). A total of 33 and 30 patients received preoperative nutrition and prehabilitation, respectively. The neutrophil-to-lymphocyte ratio (NLR), Prognostic Nutritional Index (PNI), and modified Glasgow Prognostic Score (mGPS) values were calculated during the first visit and immediately before surgery., Results: SM loss was present in 65 of 101 patients and was significantly correlated with female sex, older age, lower body mass index, and low PNI. Preoperative nutritional support and prehabilitation prevented the decrease in PNI values in patients with SM loss. The NLR significantly improved in patients with SM loss who received nutritional support and prehabilitation. In patients with SM loss, the lack of preoperative nutrition and prehabilitation was an independent risk factor for postoperative pancreatic fistula., Conclusions: Preoperative nutritional support and prehabilitation may reduce the incidence of pancreatic fistula in patients with SM loss and improve the surgical outcomes of patients undergoing pancreaticoduodenectomy., (© 2021. Japan Society of Clinical Oncology.)

The efficacy and prognosis of adjuvant chemotherapy for resected pancreatic cancer remain unclear. We investigated the utility and risk factors of S-1 adjuvant chemotherapy in patients with pancreatic cancer undergoing pancreatectomy. This study comprised 80 patients, including 58 patients who received S-1 adjuvant chemotherapy. Skeletal muscle loss was defined using cutoff values of skeletal muscle mass index. In total, 16 (20%) octogenarian patients underwent pancreatectomy. Skeletal muscle loss was present in 56 (70%) patients. The entire course of S-1 adjuvant chemotherapy for 6 months was completed in 33 patients (41%). S-1 adjuvant chemotherapy <6 months was an independent prognostic indicator of poor overall survival. Patients who completed S-1 adjuvant chemotherapy exhibited significantly longer overall and relapse-free survival rates than those did not complete the chemotherapy ( p < 0.0001 and p = 0.0003, respectively). Being an octogenarian and skeletal muscle loss were independent variables associated with the discontinuation of S-1 adjuvant chemotherapy. Finally, the S-1 adjuvant chemotherapy rates were 6.3% (1/16) and 28.6% (16/56) in octogenarian patients and those with skeletal muscle loss, respectively. S-1 adjuvant chemotherapy completion was associated with improved prognosis in patients with pancreatic cancer. Skeletal muscle loss and octogenarian status predicted the failure of S-1 adjuvant chemotherapy completion.

CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) maintains membrane PD-L1 expression by controlling its endosomal recycling. However, in patients with hepatocellular carcinoma (HCC), the correlation among CMTM6, B7 family ligands, and CD8-positive cytotoxic T lymphocytes (CTLs), and the molecular function of CMTM6 in HCC have not been established. We performed immunohistochemistry to evaluate the relationships among CMTM6 expression, clinicopathological factors, B7 family ligands expression, and CTL infiltration in HCC samples. Moreover, we established CMTM6-knockout human HCC cell lines to evaluate the function of human CMTM6 in immune regulation and tumor viability. CMTM6 expression was positively associated with membrane B7 family ligands expression and CTL infiltration in HCC samples. High CMTM6 expression in HCC tissues was associated with the expression of the proliferation marker Ki-67 and shorter recurrence-free survival. In vitro analysis showed the downregulation of membrane B7 family ligands and proliferation potency in the CMTM6-knockout human HCC cell line. High membrane CMTM6 expression was associated with tumor recurrence and proliferation via the regulation of membranous B7 family ligands expression. Thus, CMTM6 might be a biomarker to predict the risk of HCC recurrence and a therapeutic target to suppress tumor growth and increase CTL activity., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Treatment of hepatocellular carcinoma (HCC) is currently challenging. Cancer-associated fibroblasts (CAFs) promote the malignancy of HCC cells via production of cytokines. Conophylline (CnP), a vinca alkaloid obtained from Ervatamia microphylla leaves, has been reported to suppress activation of hepatic stellate cells and liver fibrosis in rats. We examined the efficacy of CnP in suppressing tumor growth in HCC. Specifically, we investigated whether CnP could inhibit CAFs, which were derived from HCC tissues in vitro and in vivo Same as previous reports, CAFs promoted proliferative and invasive ability of HCC cells. CnP suppressed α-smooth muscle actin expression of CAFs, and inhibited their cancer-promoting effects. CnP significantly suppressed CAFs producting cytokines such as IL6, IL8, C-C motif chemokine ligand 2, angiogenin, and osteopontin (OPN). Combined therapy with sorafenib and CnP against HCC cells and CAFs in vivo showed to inhibit tumor growth the most compared with controls and single treatment with CnP or sorafenib. Transcriptome analysis revealed that GPR68 in CAFs was strongly suppressed by CnP. The cancer-promoting effects of cytokines were eliminated by knockdown of GPR68 in CAFs. CnP inhibited the HCC-promoting effects of CAFs by suppressing several HCC-promoting cytokines secreted by CAFs expressing GPR68. Combination therapy with CnP and existing anticancer agents may be a promising strategy for treating refractory HCC associated with activated CAFs., (©2021 American Association for Cancer Research.)

Background: Hepatocellular adenoma (HCA) subtypes are considered as risk factors for malignant transformation; thus, an accurate diagnosis is important. We report a case of resected HCA previously diagnosed as unclassified HCA using immunohistochemistry, subsequently discovered to harbor a mutation in exon 3 of the beta (β)-catenin gene using deoxyribonucleic acid (DNA) sequencing., Case Presentation: The patient was a 26-year-old woman who was referred to our hospital because of a 150-mm tumor in the right lobe of the liver. Considering the possibility of malignancy, we performed right lobe hepatectomy. Based on the histopathological and immunohistochemical findings, the tumor was diagnosed as an unclassified HCA. Next, we performed sequencing of DNA isolated from the tumor and identified a mutation in exon 3 of β-catenin, suggesting that the tumor contained an activating mutation of the β-catenin gene., Conclusion: β-Catenin mutations in HCA cannot be detected by immunohistochemistry alone, and molecular analysis is required to accurately diagnose and evaluate its prognosis.

Purpose: This study aimed to elucidate the association between postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) and clinicopathological factors and intraoperative and postoperative epidural or intravenous patient-controlled analgesia (IV-PCA)., Methods: We reviewed data of 116 patients who underwent distal pancreatectomy at Gunma University Hospital from October 2000 to October 2019. Clinical POPF was defined as the International Study Group of Pancreatic Fistula grade B or C., Results: Intraoperative and postoperative analgesia included fentanyl-mediated IV-PCA (n = 37, 32%), fentanyl-mediated epidural analgesia (n = 39, 34%), and morphine-mediated epidural analgesia (n = 40, 34%). All patients had received analgesia. Clinical POPF occurred in 34 of the 116 (29%) DP cases. Male sex (P = 0.035) and the length of operation time (P = 0.0070) were significant risk factors of clinical POPF. Furthermore, a thick pancreas was more likely to cause clinical POPF than a thin one (P = 0.052). No statistically significant difference was found between other factors, including intraoperative and postoperative analgesia (P = 0.95), total median oral morphine equivalents (P = 0.23), and clinical POPF., Conclusion: Intraoperative and postoperative epidural analgesia and IV-PCA are not associated with clinical POPF after DP. Our results suggest that morphine and fentanyl can be used as IV-PCA or epidural analgesia.

Objectives: The aim of this study was to identify whether diffusion-weighted magnetic resonance imaging (DW-MRI) can predict the malignant behavior of preoperative well-differentiated pancreatic neuroendocrine tumors (PanNETs)., Method: Forty patients with PanNETs who underwent pancreatectomy were enrolled in this study. The apparent diffusion coefficient (ADC) values were measured. Clinicopathological factors were compared in patients with high ADC and low ADC values and in patients with and without lymph node metastasis (LNM)., Result: The low ADC group was significantly associated with higher Ki-67 index, higher mitotic count, larger tumor size, higher rate of LNM, and venous invasion. In patients with low ADC values, the incidence of LNMs was 33.3%. In patients with high ADC values, there were no patients with LNM being 0%. A significant negative correlation was found between the mean ADC values and the Ki-67 index and between the mean ADC values and the mitotic count. In multivariate analysis, neural invasion and mean ADC values ≤ 1458 were independent predictors of LNM., Conclusion: ADC values obtained using DW-MRI in the preoperative assessment of patients with PanNETs might be a useful predictor of malignant potential, especially LNM.

Background: We retrospectively investigated factors predictive for ascites after hepatic resection to treat hepatocellular carcinoma (HCC)., Patients and Methods: The data of 114 patients with HCC who underwent curative hepatic resection were reviewed. The patients were assigned to two groups according to the presence or not of postoperative ascites., Results: Ascites occurred in 16 patients (14.0%), and refractory ascites in four (3.5%). A MAC2-binding protein glycosylation isomer (M2BPGi) cutoff index of 1.61 [sensitivity=75.0%, specificity 67.9%, area under the curve (AUC)=0.745] and virtual touch tissue quantification (VTQ) of 2.62 (sensitivity=68.8%, specificity=89.8%, AUC=0.827) were the best cut-off values. Patients with ascites had lower serum albumin levels, higher serum creatinine levels, higher albumin-bilirubin (ALBI) grade, higher M2BPGi, higher VTQ, and longer operative time. ALBI grade 2 and both M2BPGi>1.61 and VTQ>2.62 were independent predictors of postoperative ascites., Conclusion: We demonstrated retrospectively that ALBI grade 2 and both high M2BPGi and VTQ were independent predictors of postoperative ascites in patients undergoing hepatic resection for HCC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: We investigated the predictors of bile leakage after hepatic resection., Methods: The data of 270 consecutive patients who underwent curative hepatic resection in our institute between January, 2016 and April, 2019 were reviewed retrospectively. The patients were assigned to one of two groups according to the presence of bile leakage and the clinicopathological and surgical outcomes were analyzed. Bile leakage was defined by the International Study Group of Liver Surgery (ISGLS) grade., Results: There were no hospital deaths. The median intraoperative blood loss volume was 167 ml. Bile leakage occurred in 12 patients (4.4%), as ISGLS grade A leakage in 1 and as ISGLS grade B leakage in 11. The mean hospital stay was significantly longer for patients with bile leakage. High-risk procedures, hepatocellular carcinoma, and Albumin-Indocyanine Green Evaluation (ALICE) grade 3 were independent predictors of ISGLS grade B or C postoperative bile leakage. In patients with three high-risk factors, the incidence of bile leakage was 53.9%., Conclusions: Based on this retrospective analysis, high-risk procedures, hepatocellular carcinoma, and ALICE grade 3 were independent predictors of bile leakage in patients undergoing hepatic resection. Thus, special care must be taken during surgery to prevent bile leakage in patients with these risk factors.

Background: Liver cirrhosis occurs in approximately 80-90% of patients with hepatocellular carcinoma (HCC), and hepatic resection may be dangerous because of well-documented liver cirrhosis, which may be accompanied by portal hypertension (PH). Here we report a patient with advanced HCC with gastric varices and PH who experienced a good clinical course after undergoing balloon-occluded retrograde transvenous obliteration (BRTO), percutaneous transhepatic portal vein embolization (PTPE), hand-assisted laparoscopic (HALS) splenectomy, and right lobectomy of the liver., Case Presentation: A 72-year-old man had two HCCs with gastric varices. CT revealed one tumor (4.5 cm) located in segment 7, involving the right hepatic vein, adjacent to the middle hepatic vein. Another tumor (2.7 cm) was located in segment 6. He first underwent BRTO for gastric varices and PTPE for planned right lobectomy of the liver. To reduce PH, HALS splenectomy was performed, and uncomplicated right lobectomy of the liver was performed 10 weeks after the first visit. He has remained free of recurrence for at least 1 year., Conclusions: Our patient underwent uncomplicated BRTO, PTPE, HALS splenectomy, and right lobectomy of the liver for advanced HCC with PH. Controlling portal pressure is important when hepatic resection is required to treat HCC with PH.

Background: Hepatocellular adenoma (HCA) is conventionally considered a rare benign liver tumor, but advanced studies have revealed that HCA is heterogeneous, and may include a type that is prone to malignant transformations. Differentiation between well-differentiated hepatocellular carcinoma and focal nodular hyperplasia is necessary to diagnose hepatocellular adenoma through imaging; however, the tumor marker of hepatocellular carcinoma, protein induced by vitamin K absence, or antagonist II (PIVKA-II), is rarely positive in hepatocellular adenoma., Case Presentation: A 44-year-old woman presented to our hospital with complaints of loss of appetite and weight loss. Multidetector row computed tomography revealed a liver tumor (diameter, 80 mm) that was enhanced in the arterial phase. Her serum PIVKA-II level was very high (3327 mAU/mL). Based on the enlargement of the mass and the results of the diagnostic imaging, hepatocellular adenoma or hepatocellular carcinoma was suspected, and we considered the possibility of a malignant transformation due to the high level of serum PIVKA-II; thus, we performed hepatectomy. Histological examination showed brown pigment deposition in the hepatocytes, which was determined to be lipofuscin granules. Based on immunohistochemical findings, the diagnosis was unclassified hepatocellular adenoma. Immunohistochemical examinations revealed that the adenoma cells in the tumor were positive for PIVKA-II. Her serum PIVKA-II level returned to normal after the resection., Conclusions: We present a case of unclassified hepatocellular adenoma with brown pigment deposition and elevation of serum PIVKA-II level. For the differentiation of liver tumors with high levels of PIVKA-II and hypervascular mass, hepatocellular adenoma should be considered.

Background: Intrahepatic cholangiocarcinoma (ICC) is a malignancy that is challenging to treat. Fibroblasts in ICC tissues have been identified as cancer-associated fibroblasts (CAFs) that promote the malignant behaviour of ICC cells. An antifibrotic drug nintedanib has been reported to suppress activated hepatic stellate cells in liver fibrosis., Methods: We investigated whether nintedanib could suppress the cancer-promoting effect of CAFs derived from ICC tissues in vitro and in vivo., Results: CAFs promoted the proliferation and invasion of ICC cells. Nintedanib suppressed activated CAFs expressing α-smooth muscle actin (α-SMA) and inhibited the ICC-promoting effects of CAFs. Nintedanib greatly reduced the levels of cancer-promoting cytokines, such as interleukin (IL)-6 (IL-6) and IL-8, secreted by CAFs. An in vivo study demonstrated that nintedanib reduced xenografted ICC growth and activated CAFs expressing α-SMA, and that combination therapy with nintedanib and gemcitabine against CAFs and ICC cells showed the strongest inhibition of tumour growth compared with the control and single-treatment groups., Conclusions: Nintedanib inhibited the cancer-promoting effect of CAFs via the suppression of CAF activation and secretion of cancer-promoting cytokines. Our findings suggest that therapeutic strategies combining conventional cytotoxic agents with nintedanib targeting CAFs are promising for overcoming refractory ICC with activated CAFs.

Background: Pancreatic cancer tissue contains abundant stromal components, including extracellular matrix proteins such as tenascin C (TNC), which exists as large (TNC-L) and non-large splice variants. Here, we examined human pancreatic cancer specimens for the expression of total TNC (TNC-ALL) and TNC-L in the stroma and annexin A2 (ANXA2), a cell surface receptor for TNC, and evaluated their significance as prognostic markers for pancreatic cancer., Methods: Expression of ANXA2, TNC-ALL, and TNC-L was examined in 106 pancreatic cancer tissues from patients who underwent curative resection and who had not received prior therapy or surgery. Protein expression was measured by immunohistochemistry and scored on a semi-quantitative scale. The relationships between protein expression, clinicopathological factors, and prognosis were evaluated by Cox proportional hazards analysis., Results: TNC-ALL and TNC-L were detected mainly in the stroma, whereas ANXA2 was predominantly expressed in cancer cell membranes. TNC-ALL was also expressed in non-tumor pancreatic tissue. High levels of stromal TNC-L and membranous ANXA2, but not stromal TNC-ALL, were independently associated with cancer progression and poor prognosis. Moreover, high co-expression of stromal TNC-L and membranous ANXA2 was a superior indicator of poor prognosis compared with detection of TNC-ALL, TNC-L, or ANXA2 alone., Conclusions: Our data suggest that co-expression of stromal TNC-L and membranous ANXA2 is a poor prognostic marker compared with detection of TNC-L or ANXA2 alone for pancreatic cancer patients. Additionally, targeting of crosstalk between stromal TNC and cancer cell ANXA2 could be a promising therapeutic strategy to overcome refractory pancreatic cancer.

Aim: Postoperative ascites is one of the most common complications after hepatic resection and is related to liver fibrosis. Mac-2 binding protein glycosylation isomer (M2BPGi) is a reliable and non-invasive marker for assessing liver fibrosis. This study aimed to evaluate whether preoperative M2BPGi level can predict postoperative refractory ascites in patients with curative hepatic resection for hepatocellular carcinoma., Methods: The present study retrospectively evaluated 59 patients between January 2016 and June 2018. We assessed the relationship between preoperative M2BPGi levels, expressed as the cut-off index, and postoperative ascites., Results: The median M2BPGi level was 1.36 (range 0.34-11.56). Postoperative ascites occurred in seven patients (11.9%). Among them, refractory ascites, defined as diuretic-resistant ascites, occurred in four patients (6.8%). Uni- and multivariate analysis showed that preoperative M2BPGi level was the only independent risk factor of postoperative ascites (odds ratio 3.28, P = 0.033). The cut-off values of M2BPGi for postoperative ascites and refractory ascites were 2.41 and 3.10, respectively. Remarkably, there were no patients with postoperative ascites and refractory ascites when the preoperative M2BPGi levels were less than each cut-off value., Conclusion: Our results suggest that M2BPGi level is a reliable and non-invasive surrogate marker for predicting postoperative ascites before curative resection for hepatocellular carcinoma., (© 2019 The Japan Society of Hepatology.)

Background: Recent studies have shown that the systemic inflammatory response induced by cancer leads to cancer progression. Neutrophil-to-lymphocyte ratio (NLR) is the most reliable marker to detect systemic inflammation. In this study, we investigated the significance of NLR in patients with well-differentiated pancreatic neuroendocrine tumors (PanNETs) according to the World Health Organization 2017 classification., Methods: We retrospectively collected data for patients with PanNET who underwent pancreatic resection with curative intent between January 2008 and December 2017 at six institutions. Clinicopathological factors, recurrence, and immunohistochemical staining of tumor-associated macrophages (TAMs) were analyzed in a total of 55 patients in this study., Results: High NLR (>3.41) in patients was significantly associated with higher white blood cell count, higher Ki-67 index, higher mitotic count, higher grade, higher incidence of lymph node metastasis, higher incidence of lymphatic and neural invasion, massive blood loss, and a large number of CD163-expressing TAMs. Recurrence-free survival of patients with high NLR was significantly poorer than that of patients with low NLR. Multivariate analysis identified high NLR, NET Grade 2 (G2) or Grade 3 (G3), and synchronous hepatic resection as independent risk factors for recurrence after curative resection., Conclusions: NLR is a promising predictor of recurrence after pancreatectomy that needs to be further investigated and that accumulation of TAMs in the tumor could be one of the causes of NLR elevation., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: Understanding the effect of lymph node metastasis (LNM) on prognosis in pancreatic neuroendocrine neoplasm is helpful for surgery and follow-up. In this study, we investigated the significance of LNM in well-differentiated pancreatic neuroendocrine tumors (PanNETs) according to the World Health Organization 2017 classification., Methods: We retrospectively collected data for 95 consecutive patients with PanNET who underwent pancreatic resection with curative intent between January 2008 and December 2017 at 6 institutions. The clinicopathological factors were compared in patients with and without LNM, and prognostic factors were analyzed., Results: Lymph node metastasis was significantly associated with malignant potential of PanNET, such as larger tumor size, higher Ki-67 index, higher tumor grade, and higher incidence of lymphatic, vessel, and neural invasion. Lymph node metastasis was also associated with disease-free but not overall survival. Multivariate analysis identified NET grade 2 (G2) and G3 as independent risk factors for recurrence after curative resection., Conclusions: World Health Organization 2017 classification was the most independent prognostic factor in patients with resectable well-differentiated PanNETs. Patients with G2 and higher-grade tumors require lymph node dissection to improve prognosis.

Background: Pleomorphic leiomyosarcomas (PLMSs) are extremely rare tumors. We present the first case of hepatic primary PLMS after surgery for gastric gastrointestinal stromal tumor (GIST)., Case Presentation: The patient was a 62-year-old man who was referred to our hospital for resection of a hepatic tumor arising after gastric GIST surgery that was resistant to imatinib and sunitinib. A 40-mm tumor in the left lobe of the liver and three small nodules in the right lobe were detected. We performed hepatic left lobectomy and partial resections for three lesions. According to the histopathological and immunohistochemical findings and c-kit gene mutations analysis, the main tumor was diagnosed as a PLMS., Conclusion: It is necessary to consider the possibility that imatinib-resistant GIST recurrence lesions are a different kind of soft-tissue sarcoma. Accurate diagnosis is required to not miss the opportunity for radical excision of PLMS.

Background: Patients with idiopathic thrombocytopenic purpura (ITP) have low platelet counts and an increased risk of complications. Therefore, these patients generally require high-dose immunoglobulin therapy and platelet transfusion. However, thrombopoietin receptor agonists (TPO-RAs) have recently become available for use in the preoperative treatment strategy for intractable ITP. Recent studies have also reported radiofrequency ablation (RFA) or tissue biopsy as perioperative management for thrombocytopenia using TPO-RA. However, no report has described the use of TPO-RA in a case of hepatectomy., Case Presentation: A 76-year-old man presented with intrahepatic cholangiocarcinoma (IHCC) complicated with ITP. His platelet count was 3.5 × 10 4 /μL. To increase platelet levels prior to surgery, romiplostim was administered subcutaneously (70 μg per week for 3 weeks) and eltrombopag was administered orally (25 mg per day for 23 days), as TPO-RA. His platelet count increased to 14.1 × 10 4 /μL. The patient was successfully and safely treated with left hemi-hepatectomy and TPO-RA as preoperative platelet management., Conclusions: This case suggests that TPO-RA can be effective, and could serve as a new treatment option in the preoperative management of ITP.

Antigen (Ag)-specific activated CD8 + T cells are critical for tumor elimination but become exhausted, and thus, dysfunctional during immune response against the tumor due to chronic antigen stimulation. The signaling of immune checkpoint receptors is known to be a critical component in this exhaustion; however, the fate of these exhausted CD8 + T cells remains unclear. Therefore, to elucidate this, we followed the fate of Ag-specific CD8 + T cells by directly visualizing them using MHC class I tetramers coupled with ovoalubumin 257-264 in C57BL/6 mice inoculated with EG.7. We found that the number of generated Ag-specific activated CD8 + T cells decreased via apoptosis during a prolonged tumor immune response. However, the number of Ag-specific CD8 + T cells was significantly higher in Fas ligand (FasL)-dysfunctional gld mice than in control mice, resulting in suppressed tumor growth. In contrast, the enforced expression of Bcl-2 failed to rescue apoptosis of the exhausted CD8 + T cells following EG.7 inoculation. These results suggest that Fas/FasL signaling is critical for the survival of exhausted CD8 + T cells during the tumor immune response., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to identify the prognostic impact of metabolic parameters of 18 F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) in patients with intrahepatic cholangiocarcinoma (IHCC) undergoing hepatic resection., Patients and Methods: Twenty-four patients with IHCC who underwent surgical resection were enrolled and 18 F-FDG PET parameters maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured, as well as overall and recurrence-free survival., Results: High TLG was significantly associated with large tumor size and high carbohydrate antigen 19-9 level. Patients with high SUVmax, high MTV or high TLG had a significantly worse prognosis regarding both overall and recurrence-free survival than those with low SUVmax, low MTV and low TLG, respectively. Multivariate Cox proportional hazards analysis identified that high TLG significantly influenced both overall and recurrence-free survival., Conclusion: Preoperative assessment of TLG by 18 F-FDG PET might be a useful prognostic predictor after hepatic resection in patients with IHCC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background : Systemic chemotherapy can drastically downsize metastatic liver tumors and these small liver lesions could sometimes be difficult for surgeons to detect during hepatectomy. We assessed the usefulness of intraoperative real-time virtual sonography (RVS) with contrast-enhanced ultrasonography (CEUS) using 'Sonazoid' contrast agent (RVS-CEUS). Methods : We performed the intraoperative RVS-CEUS technique on 10 tumor lesions in six cases, which were scheduled for hepatic resection of < 10 mm in diameter in our liver metastases series. These lesions were preoperatively diagnosed by contrast enhanced-computed tomography (CE-CT) or Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI). We assessed the detectability of a tumor with RVS-CEUS during surgery and compared it with that of preoperative CE-CT or EOB-MRI. Results : Detectability of RVS-CEUS for 10 small lesions was 90% (n = 9/10) and that of other preoperative modalities were 50% (n = 5/10, CE-CT) and 100% (n = 10/10, EOB-MRI). Minimum tumor size detected was 3.0 mm in diameter, and maximum depth of detection with RVS-CEUS was 43.5 mm ; these results could be an advantage when compared with other intraoperative diagnostic modalities. Conclusion : Intraoperative RVS-CEUS was useful for detecting small metastatic liver lesions after chemotherapy and could be an effective intraoperative diagnostic technique for hepatic resection of a size < 10 mm. J. Med. Invest. 66 : 319-323, August, 2019.

Background: Intracholecystic papillary neoplasm (ICPN) is defined as papillary tumors detected macroscopically in the gallbladder. We report a case of ICPN which exhibited the atypical form like a submucosal tumor., Case Presentation: A 70-year-old man was admitted to our hospital because of hepatic disorder. Computed tomography and magnetic resonance imaging showed irregular thickening of the wall within the gallbladder fundus. Because the lesion might have been malignant, we performed laparoscopic cholecystectomy and liver bed resection. Macroscopic findings showed the mucosal surface of the tumor was smooth, and its form was similar to that of a submucosal tumor. Histopathological examination revealed papillary tumors within the mass with low-grade dysplasia; therefore, we diagnosed ICPN., Conclusion: In the present case, ICPN was resembling a submucosal tumor macroscopically because the tumors arose into the Rokitansky-Aschoff sinus and the adenomyomatous hyperplasia was merged with the ICPN. It is necessary to consider the possibility of tumor lesions within adenomyomatous hyperplasia.

Background/aim: Recently, skeletal muscle quality was important in patients with malignant tumors to predict the surgical outcome. The relationship between postoperative complications of Clavien-Dindo grade III or more and prognosis in patients who have undergone hepatic resection for hepatic malignancies were investigated., Patients and Methods: Patient data were retrospectively collected for 146 consecutive patients who underwent curative hepatic resection in the Department of Hepatobiliary and Pancreatic Surgery, Gunma University, Japan, for hepatic malignancy. The patients were assigned to two groups according to the presence of postoperative complications. The clinicopathological and surgical outcomes were analyzed. Skeletal muscle area (SMA) and intramuscular adipose tissue content (IMAC) were also evaluated., Results: No hospital deaths occurred. Postoperative complications were identified in 12 patients (8.2%). Univariate and multivariate analyses revealed that the independent risk factors for postoperative complications were hemodialysis, psychiatric disorder, high CONUT (controlling nutritional status) score and patients both with low SMA and high IMAC., Conclusion: Intensive surgical care is necessary for high-risk patients with hemodialysis, psychiatric disorder, high CONUT count and/or low skeletal muscle quality to reduce postoperative complication., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The right gastroepiploic artery is commonly used in coronary artery bypass grafting. Appropriate strategies are required when performing upper abdominal surgeries after the right gastroepiploic artery has been used in coronary artery bypass grafting because compressing or injuring the graft may cause myocardial ischemia and fatal arrhythmias. To our knowledge, this is the first reported case of surgery for achalasia performed after coronary artery bypass grafting using the right gastroepiploic artery. We have discussed the surgical procedure and particular intraoperative considerations., Case Presentation: A 62-year-old man who had undergone coronary artery bypass grafting using the right gastroepiploic artery presented with achalasia. Because medication and balloon dilation had been ineffective and he was having difficulty ingesting food, we performed a Heller-Dor procedure via laparotomy. The right gastroepiploic artery was not damaged during this surgery, and there were no perioperative cardiovascular complications. Adequate control of symptoms was achieved., Conclusions: When performing upper abdominal surgeries after coronary artery bypass grafting with the right gastroepiploic artery, it is necessary to investigate the patient carefully preoperatively and adapt the intraoperative procedure to minimize risk of injury to the graft and consequent cardiovascular complications.

Background: Chronic granulomatous disease (CGD), a rare inherited disorder, is characterized by impaired ability of phagocytic cells to kill certain bacteria and fungi. Although liver abscess is a common manifestation of CGD, its optimal management in these patients is unknown. Here, we present a case of successful hepatectomy for hepatic abscess in a patient with CGD., Case Presentation: An adolescent patient with previously diagnosed CGD presented to the pediatrics department of our institution with fever. Blood tests showed high concentrations of inflammatory markers. A computed tomography (CT) scan showed a multilocular mass measuring 52 mm × 34 mm in hepatic segment 4 (S4). Blood cultures were negative. Despite administration of antibiotics and γ-globulin, his fever and high concentrations of inflammatory markers persisted and the mass did not change on CT scan images. Because the medications had proved ineffective and percutaneous drainage would have been difficult because of the honeycombing in the abscess, we performed hepatic S4a + S5 anatomic resection and cholecystectomy. Culture of the excised specimen was negative. The patient's postoperative course was uneventful. On day 62, CT showed no abscess around the resection stump. On day 81, he was transferred to undergo bone marrow transplantation., Conclusions: Surgical treatment for hepatic abscess can be effective when medical treatment has failed.