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Radioactivity after administration of 123I-sodium iodide was measured in breast milk samples obtained from a patient with postpartum thyroiditis. The breast milk was collected over 93 h during the infant's regular feeding times. The radioactivity in the breast milk was calculated with a 123I capsule of the same lot number as the standard source. 123I was excreted exponentially with an effective half-life of 5.5 h; 2.5% of the total radioactivity administered was excreted in the breast milk over the 93 h, 95% of which was excreted within the first 24 h, and 98.2% within 36 h. The first milk sample collected at 7 h after administration of the radiopharmaceutical contained 48.5% of the total radioactivity excreted. We estimated the potential absorption of radioactivity to an infant's thyroid in uninterrupted breast-feeding to be 30.3 mGy. With a 24-hour interruption, the absorbed radioactivity would be 1.25 mGy; with a 36-hour interruption, it would be 0.24 mGy. According to our calculations, breast feeding should be curtailed for 36 h to reduce the infant's exposure to 123I radioactivity. By using a correction factor based on maximum radioactivity from another 123I capsule of the same lot, we were able to ascertain the appropriate protocol for our patient and establish a measurement method that can be applied in similar clinical situations. [ABSTRACT FROM AUTHOR]

Background: Acquired hemophilia A (AHA) is a rare disease characterized by a prolonged activated partial thromboplastin time (aPTT) and the production of coagulation factor VIII inhibitors. We encountered two cases of AHA in the perioperative period of pancreatoduodenectomy (PD)., Case Presentation: Case 1: A 76-year-old woman with intraductal papillary mucinous carcinoma developed acute cholecystitis 5 days before PD. Despite immediate improvement in her acute cholecystitis with biliary drainage and antibiotics, her aPTT level was prolonged (55.9 s). PD was performed as scheduled. On postoperative day (POD) 2, she developed intra-abdominal hemorrhaging that required reoperation. However, intra-abdominal bleeding and concomitant anemia persisted after reoperation. On POD 13, she was diagnosed with AHA based on the detection of an inhibitor of coagulation factor VIII. Despite hemostatic and immunosuppressive treatment, including massive blood transfusion, her general condition gradually worsened due to continuous bleeding and secondary infections. She ultimately died of multiple organ failure on POD 71. Case 2: An 82-year-old man received PD for distal cholangiocarcinoma. On POD 3, a small amount of blood via abdominal drainage was observed. On POD 4, his aPTT level was prolonged (61.5 s). On POD 8, subcutaneous hemorrhaging of the median wound was observed, and corticosteroids were administered under suspicion of AHA on POD 9. On POD 15, an inhibitor of FVIII was detected, and he was diagnosed with AHA. On POD 17, the aPTT level had normalized, and an inhibitor of FVIII was undetectable. On POD 41, he was discharged without any serious hemorrhagic events., Conclusions: AHA may be more frequent than previously reported. When unexplained prolonged aPTT or bleeding symptoms are observed, it is important to keep AHA in mind during the perioperative period of invasive surgery., (© 2023. The Author(s).)

Roxadustat and other hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have recently been approved for the treatment of chronic renal anemia. In macrophages and monocytes, the activation of HIF-1 by pro-inflammatory cytokines induces iNOS expression and activity through the NF-κB pathway to produce nitric oxide (NO), which causes liver injury when excessively produced. Few studies have reported a relationship between HIF activity and iNOS induction in hepatocytes. We investigated the effect of drug- and hypoxia-induced HIF activations on NO production in primary cultured rat hepatocytes. Roxadustat treatment and hypoxic conditions activated HIF. Contrary to expectations, HIF-PHI treatment and hypoxia inhibited IL-1β-induced NO production. RNA-Seq analysis of mRNA expression in rat hepatocytes showed that roxadustat treatment decreased the expression of genes related to inflammation, and genes in the NF-κB signaling pathway were induced by IL-1β. Moreover, roxadustat suppressed IL-1β-activated signaling pathways in an HIF-dependent manner. GalN/LPS-treated rats were used as in vivo models of hepatic injury, and roxadustat treatment showed a tendency to suppress the death of rats. Therefore, exogenous HIF-1 activation, including HIF-PHI and hypoxia exposures, suppressed IL-1β-induced iNOS mRNA expression and subsequent NO production in hepatocytes, by suppressing the NF-κB signaling pathway. Roxadustat treatment suppresses the expression of pro-inflammatory genes by activating HIF, and thus may exhibit hepatoprotective effects., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pancreatic cancer has an extremely poor prognosis, even after curative resection. Treatment options for pancreatic cancer remain limited, therefore new therapeutic targets are urgently needed. We searched for genes predictive of poor prognosis in pancreatic cancer using a public database and validated the survival impact of the selected gene in a patient cohort., Methods: We used a public database to search for genes associated with early pancreatic cancer recurrence. As a validation cohort, 201 patients who underwent radical resection in our institution were enrolled. Expression of the target gene was evaluated using immunohistochemistry (IHC). We evaluated growth and invasiveness using small interfering RNAs, then performed pathway analysis using gene set enrichment analysis., Results: We extracted ARHGEF2 from GSE21501 as a gene with a high hazard ratio (HR) for early recurrence within 1 year. The high ARHGEF2 expression group had significantly poorer recurrence-free survival (RFS) and poorer overall survival (OS) than the low ARHGEF2 expression group. Multivariate analysis demonstrated that high ARHGEF2 expression was an independent poor prognostic factor for RFS (HR 1.92) and OS (HR 1.63). In vitro, ARHGEF2 suppression resulted in reduced cell growth and invasiveness. Bioinformatic analysis revealed that ARHGEF2 expression was associated with MYC, G2M, E2F, and CDC25A expression, suggesting that c-Myc and cell cycle genes are associated with high ARHGEF2 expression. IHC revealed a positive correlation between ARHGEF2 and c-Myc expression., Conclusions: High ARHGEF2 expression is associated with cell cycle progression, and predicts early recurrence and poor survival in patients with pancreatic cancer.

Background: Hepatocellular carcinoma has a high recurrence rate even after curative surgery, and hepatocellular carcinoma risk-predictive biomarkers will enable identification of patients who most need close monitoring and cancer-preventive intervention. Hepatocellular carcinoma has 2 different recurrence patterns-a multicentric recurrence and an intrahepatic metastasis. We have reported that the molecular gene signature from the gene expression of adjacent liver can be used to predict multicentric recurrence of hepatocellular carcinoma, but the signature to predict recurrence from intrahepatic metastasis has not been established. We aimed to identify the recurrence from intrahepatic metastasis gene signature from the gene expression of tumor to predict recurrence from intrahepatic metastasis., Methods: The intrahepatic metastasis-risk signature was created based on the exhaustive analysis using a microarray transcriptome database of hepatocellular carcinoma. The intrahepatic metastasis-risk signature was measured in a cohort of 80 hepatocellular carcinoma patients, and the correlation with hepatocellular carcinoma recurrence and overall survival and each gene signature were analyzed and validated., Results: The gene signature assay classified the patients into high- (n = 20), intermediate- (n = 40), and low-risk (n = 20) groups. The high-risk prediction was independently associated with higher early hepatocellular carcinoma recurrence (hazard ratio = 3.7, P = .03) in multivariable modeling adjusted by tumor size, tumor number, and microvascular invasion. Gene set enrichment analysis demonstrates that the gene sets associated with "cell cycle" or "histone modulation" are highly enriched in the high intrahepatic metastasis gene signature group CONCLUSION: The intrahepatic metastasis gene signature predicts early recurrence and is associated with malignant potential related to the promoted cell cycle., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A 46-year-old woman with metastatic breast cancer developed dyspnea that progressed relatively rapidly during chemotherapy. Chest-abdominal CT revealed wedge-shaped infiltration shadow, and cardiac catheterization revealed elevated pulmonary artery pressure. Aspiration cytology of pulmonary arterial blood was performed and malignant cells were confirmed. Chemotherapy was difficult to continue because of deterioration in general condition, and she died 7 days after diagnosis. This time, we report a case of PTTM for which pulmonary arterial blood cytology was useful for diagnosis.

Introduction: The objective of this study was to describe the surgical techniques for a thoracoscopic approach to treat hepatocellular carcinoma in the hepatic dome. Also, safety, feasibility, and long-term outcomes were evaluated., Methods: Surgical procedures were selected based on liver function, the extent and location of the tumor, and each patient's general condition. Thoracoscopic hepatic resection was performed under direct vision through a diaphragmatic incision. Thoracoscopic radiofrequency ablation (TRFA) was performed either with a transdiaphragmatic puncture for deeply located tumors or under direct vision through a diaphragmatic incision for subcapsular tumors., Results: Thoracoscopic surgery was indicated for 107 patients with hepatocellular carcinoma in the hepatic dome. Among these patients, 5 underwent hepatectomy and 102 underwent radiofrequency ablation, which was more frequently employed in patients with impaired liver function. Of the patients who underwent radiofrequency ablation, 43 (42.2%) required a diaphragmatic incision. In the thoracoscopic hepatic resection group and TRFA group, the median operating time was 350 and 197 minutes, the median blood loss was 200 and 5 mL, and the complication rate was 12.7% and 20.0%, respectively. The 5-year overall and disease-free survival rates were 100% and 50.0% in the thoracoscopic hepatic resection group, respectively, and 60.7% and 18.1% in the TRFA group, respectively. Local recurrence after TRFA was observed in 10 patients (9.8%)., Conclusion: The thoracoscopic approach is safe and feasible, with promising short- and long-term outcomes. It could serve as a treatment option for hepatocellular carcinoma in the hepatic dome., (© 2019 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

We present the case of an 88-year-old woman who had undergone breast conserving surgery for left breast cancer 8 years ago.She received postoperative radiotherapy(total dose of 60 G/30 Fr)to the residual breast together with endocrine therapy.She underwent skin biopsy after having had a red skin tumor in the left breast.Angiosarcoma was diagnosed and chemotherapy and radiotherapy were initiated.The patient is alive without recurrence 8 months after chemotherapy.

Patients with cholangiocarcinoma sometimes show very slow progression and thereby exhibit long-term survival under treatment of the disease. A 72-year-old male with hilar cholangiocarcinoma underwent extended-right hemi-hepatectomy and caudate lobectomy. Pathological finding revealed a well differentiated tumor and carcinoma in situ at the bile duct margin. Routine imaging follow-up was continued for 5 years. Ten years after the surgery, the patient noticed a right-hand chest wall mass formation of 5 cm without any symptoms, and the tumor was diagnosed metastatic cholangiocarcinoma by needle biopsy. Radical resection of the metastatic tumor was performed. The pathological findings of the primary tumor and the metastatic tumor were similar. Three months later, recurrent multiple lesions were identified in the chest wall and the liver. The patient received chemotherapy. We here report a rare case of metastatic cholangiocarcinoma 10 years after hepatectomy with positive ductal margin of carcinoma in situ, implying that rare event of very late recurrence of patients with hilar cholangiocarcinoma should be taken into consideration., Competing Interests: Conflict of interestThe authors have no conflicts of interest., (© The Japan Society of Clinical Oncology 2020.)

Background: The clinical significance of programmed death 1 and its ligand (PD-L1) as therapeutic targets has been reported previously. This study aimed to investigate the clinical impact of PD-L1 expression in cancer and stroma cells in cholangiocarcinoma (CCA)., Methods: The study enrolled 177 consecutive CCA patients who underwent curative resection between 2005 and 2014. Expression of PD-L1 in CCA and stroma cells was assayed by immunohistochemistry, and their relationships with patient clinicopathologic characteristics and prognoses were evaluated. Tumor-infiltrating immune cells (CD66b + neutrophils [TANs] and CD163 + M2 macrophages [TAMs]) also were assayed by immunohistochemistry, and their relationship with PD-L1 expression in cancer and stroma cells was evaluated., Results: Among the 177 analyzed CCA cases, PD-L1 expression was identified in cancer cells in 54 cases (30.5%) and in stroma cells in 77 cases (43.5%). The patients with positive PD-L1 expression in cancer and stroma cells had worse overall survival rates than those negative for PD-L1 (cancer cells: hazard ratio [HR] 2.08; P = 0.0004; stroma cells: HR 1.84; P = 0.003). Moreover, the patients with PD-L1-positive cancer cells had higher rates of PD-L1 expression in stroma cells (P < 0.0001) and higher numbers of TANs (P = 0.0003) and TAMs (P = 0.004) than those with low PD-L1 expression. In the multivariate analysis, PD-L1 expression in both cancer and stroma cells (HR 2.20; P = 0.002) was an independent predictor of poor overall survival., Conclusions: The study showed PD-L1 expressed in both CCA and stromal cells and demonstrated that its expression may affect numbers of TANs and TAMs and play a pivotal role in CCA outcomes.

The demand for breast reconstruction is expected to increase with the currently observed increase in the number of breast cancer patients. Among the 70 patients included in the study, 59 received tissue expanders, 1 received implant, and 10 received deep inferior epigastric perforator flaps. Complications were noted in is 11 patients who received tissue expanders. In this study, age>50 years and smoking were associated with higher rates of complication. Choosing an appropriate method for breast reconstruction is important. In addition with plastic surgery, an approach to reduce complications will be necessary in future.

Purposes: This study aimed to clarify the impact of postoperative nonalcoholic fatty liver disease (NAFLD) on the clinical course of patients with pancreatic ductal adenocarcinoma (PDAC)., Methods: One hundred and eight patients with pancreatic cancer undergoing pancreaticoduodenectomy (PD) with curative intent in between 2005 and 2016 were enrolled in this study. Post-PD NAFLD was assessed by computed tomography (CT), which was routinely performed at 3 months, 6 months, and 1 year after surgery. The clinical impact of post-PD NAFLD was examined from an oncological perspective., Results: There were 50 (46.2%) post-PD NAFLD patients. The NAFLD group showed significantly lower CT values at 3 months, 6 months, and 1 year after surgery than those without NAFLD. Patients with NAFLD showed significant body weight loss and a decrease in serum albumin level after surgery compared with those without NAFLD. Consequently, the 70% completion rate of adjuvant chemotherapy with gemcitabine, but not S1, was significantly lower in the NAFLD group than in the non-NAFLD group. The 5-year overall survival and disease-free survival rates were comparable between the two groups., Conclusion: Post-PD NAFLD was associated with malnutrition in patients with PDAC, reducing their tolerance to gemcitabine-based adjuvant chemotherapy. Post-PD NAFLD needs to be emphasized and requires special nutritional intervention in patients with PDAC.

Nipple discharge is a common symptom and frequently results from benign tumors. However, there is a 5-30% risk of malignancy. A 65-year-old woman presented at the hospital because of bloody nipple discharge in her right breast. She had noticed an abnormal nipple discharge for several months. Mammography showed focal asymmetric densities without calcification in the middle outer quadrant of her right breast. Ultrasonography indicated a 1.5×1.1 cm sized cyst with fluid-fluid level. Breast MRI showed a simple cyst with a benign contrast enhancement pattern. No malignant cells were observed by fine-needle aspiration. Considering the low sensitivity of mammography and breast MRI to DCIS, we performed an excisional biopsy. Histological examination revealed that the lesion was DCIS. The patient underwent right total mastectomy and was diagnosed with low grade DCIS(ER-positive, PgR-positive, HER2-negative). She continues endocrine therapy with an aromatase inhibitor.

Hepatocellular carcinoma (HCC) has high recurrence rates even after curative hepatectomy. Drug therapy for recurrence of HCC is still limited; therefore, identifying new therapeutic targets is urgently needed. We searched for genes that would predict HCC recurrence from intrahepatic metastasis in an exhaustive DNA microarray database by searching genes associated with high early recurrence rate and having higher expression in the tumor area compared to background liver. We detected lysyl oxidase (LOX) and validated the clinical significance of LOX in 358 patients who underwent hepatectomy. Expression of LOX was evaluated by qRT- PCR, and immunohistochemical (IHC) staining. High LOX expression group had a significantly higher recurrence rate than the low LOX expression group (2-year recurrence rate was 64.0% vs 24.2%, P < .0001 for IHC) and poorer survival rate (5-year rate was 60.1% vs 86.2%, P < .0001 for IHC). Multivariate analysis showed that high LOX expression was an independent risk factor for early recurrence (IHC: HR, 2.52; P < .0001). Bioinformatic analysis showed that LOX expression was associated with hypoxia-inducible factor-1α (HIF-1α) and the hypoxia cascade, suggesting that HIF-1α or hypoxia regulates LOX expression and induces epithelial-mesenchymal transition (EMT). In vitro, LOX and HIF-1α were involved in migration and invasion capability. High LOX expression is associated with EMT markers and predicts early recurrence and poor survival in patients with HCC. These findings indicate that lysyl oxidase could be a potential therapeutic target for early recurrence of HCC., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background/aim: Prognoses of patients with cancer can be predicted on the basis of preoperative nutrition- or inflammation-based scores; however, predicting the prognostic impact of undergoing surgery remains challenging. In this study, we investigated the usefulness of the perioperative C-reactive protein/albumin (CRP/Alb) ratio in patients with intrahepatic cholangiocarcinoma (ICC)., Patients and Methods: We retrospectively investigated 80 patients who had undergone curative resection of primary ICC between April 2002 and December 2017. We identified the time at which perioperative CRP/Alb ratio most influences the prognosis, and investigated the correlations among the perioperative CRP/Alb ratio, clinicopathological features and patient outcomes., Results: The only perioperative CRP/Alb ratios significantly associated with shorter overall survival (OS) was a high CRP/Alb ratio on POD14. High CRP/Alb ratio on POD 14 was significantly associated with older age, male sex, and the presence of postoperative complications. Finally, a high CRP/Alb ratio at POD 14 was an independent prognostic factor for poor OS., Conclusion: CRP/Alb ratio on POD 14 may be a useful prognostic factor in patients with ICC who have undergone curative resections., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of this study was to verify the significance of high Lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3) in patients with hepatocellular carcinoma (HCC) with low AFP., Materials and Methods: There were 283 patients with low AFP who underwent initial hepatic resection with or without radiofrequency ablation for HCC. Patients were divided into two groups based on AFP-L3 values: >10%: high AFP-L3 (n=24); and ≤10%: low AFP-L3 (n=259). Overall survival (OS) and 2-year recurrence rates were compared, and independent prognostic factors were identified., Results: The OS and 2-year recurrence rates of the high AFP-L3 group were significantly worse than those of the low AFP-L3 group. The independent prognostic factors for poor OS were des-gamma-carboxy prothrombin (DCP) of >40 mAU/ml, microvascular invasion, and invasive growth, and those for 2-year recurrence were 99m Tc-galactosyl human serum albumin uptake ratio of <0.90, DCP of >40 mAU/ml, multiple tumors, microvascular invasion, and poor differentiation. DCP levels increased with AFP-L3, and cases with high DCP and AFP-L3 had worse prognoses and higher 2-year recurrence rates compared to those with elevation of only one of these., Conclusion: Patients with high AFP-L3 but low AFP have poor prognosis and high 2-year recurrence rates. DCP strongly reflects HCC malignancy in patients with low AFP., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Neuroendocrine tumors usually develop in the gastrointestinal tract, pancreas, and lung. Therefore, a neuroendocrine tumor of the bile duct is quite rare. We present a 59-year-old-male patient whose preoperative diagnosis was hilar cholangiocarcinoma. One month after embolization of the left branch and anterior branch of the portal vein, he underwent left hepatic trisegmentectomy and extrahepatic bile duct resection. Pathological examination revealed the neuroendocrine tumor in the submucosal layer of the hilar bile duct. Because there was no neuroendocrine tumor in other organs, the tumor was considered a primary neuroendocrine tumor of the hilar bile duct, rather than a liver metastasis from other organs. We also present a review of the English literature regarding neuroendocrine tumors of the bile duct., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Carcinosarcoma is a rare tumor that includes both carcinoma and sarcoma components. It develops commonly in the female reproductive tract, most often in the uterus. However, as there are a small number of similar cases in the English literature, we would like to present a rare case of a carcinosarcoma in Vater's papilla., Case Presentation: A 76-year-old female patient was preoperatively diagnosed with a papillary adenocarcinoma in Vater's papilla by endoscopic biopsy. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy, and postoperative pathological examination diagnosed the carcinosarcoma. The patient received adjuvant chemotherapy with gemcitabine, but multiple liver metastases were found 3 months after the operation. Though chemotherapy with gemcitabine and cisplatin was introduced, she died owing to tumor progression 7 months after the operation., Conclusion: Because carcinosarcoma of Vater's papilla is a rare disease, a suitable treatment strategy has been unclear. We also present a review of the English literature regarding carcinosarcoma of Vater's papilla.

Immunotherapy using anti-PD-1/PD-L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD-L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD-L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)-α upregulated PD-L1 expression in PDAC cells through NF-κB signaling. The induction of PD-L1 expression was also caused by co-culture with activated macrophages, and the upregulation was inhibited by neutralization with anti-TNF-α antibody after co-culture with activated macrophages. PD-L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD-L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8-positive T-cell infiltration. These findings indicate that tumor-infiltrating macrophage-derived TNF-α could be a potential therapeutic target for PDAC., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Several reported complications associated with radiofrequency ablation for liver tumors are due to thermal damage of neighboring organs. We herein report a first case of esophageal perforation due to thermal injury of laparoscopic radiofrequency ablation (RFA)., Case Presentation: A 75-year-old woman was treated repeatedly with RFA (percutaneous and laparoscopic) and transcatheter arterial chemoembolization for hepatocellular carcinoma. One week after laparoscopic RFA for recurrent HCC located in segment 2 of the liver, dysphagia and thoracic pain occurred. Upper gastrointestinal endoscopy revealed a perforated esophageal ulcer at the esophago-gastric junction. Inflammation was localized because of severe intra-abdominal adhesion due to repeat surgery, so we decided to treat the patient conservatively. The perforation of the esophagus gradually scarred, and exacerbation did not occur after restarting oral intake., Conclusions: When patients with a history of abdominal surgery or intra-abdominal inflammation undergo thermal ablation therapy, caution is required, as there is a possibility of thermal injury of unexpected organs.

Objectives: The prognostic value of the prognostic nutrition index (PNI) in pancreatic ductal adenocarcinoma (PDAC) is still controversial. This study aimed to assess the correlation between PNI and the outcome for PDAC patients and to generate a new score from PNI and serum markers., Methods: This study investigated 151 patients who underwent pancreatic resection for PDAC between April 2002 and June 2012. Disease-free survival (DFS), overall survival, and clinicopathological parameters were analyzed according to the PNI value., Results: The low PNI patients had poorer 5-year DFS rate than high-PNI patients (10.7% and 34.8%, respectively). Multivariate analyses revealed that independent risk factors for poor DFS were high carcinoembryonic antigen (hazard ratio [HR], 1.53; P = 0.038), high carbohydrate antigen 19-9 (HR, 1.67; P = 0.017), positive lymph node metastasis (HR, 1.98; P = 0.017), R1 or 2 resection (HR, 3.50; P < 0.001), and low PNI (HR, 0.37 [high/low]; P = 0.029]. Scoring based on the formula -0.49 × (PNI) + 0.41 × (carcinoembryonic antigen) + 0.67 × (carbohydrate antigen 19-9) was significantly associated with poor DFS (P < 0.001) and overall survival (P = 0.0019)., Conclusions: Low PNI and serum marker score are significantly associated with poor DFS.

Background: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and regulates tumor malignancy by gene silencing via histone methylation. In this study we investigate the role of EZH2 in angiogenesis of intrahepatic cholangiocarcinoma (ICC)., Methods: The influence of EZH2 on tumor angiogenesis was examined by bioinformatics analysis of a public database. We also assessed the correlation between EZH2 and vasohibin 1 (VASH1) expression in 47 patients with ICC by immunohistochemical (IHC) staining and in vitro gene silencing assays. The prognostic significance of EZH2 and VASH1 expression by IHC was also examined in the ICC cohort., Results: Bioinformatics analysis showed that EZH2 was associated with several angiogenesis gene sets in the public database. EZH2 suppressed VASH1 expression in in vitro assays and IHC studies. EZH2-high/VASH1-low status was independently associated with poor disease-free survival (P = 0.019) and poor overall survival (P = 0.0055)., Conclusion: The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: To establish if the number of pancreatic acinar cells at the pancreatic cut end is a predictor of postoperative pancreatic fistula (POPF)., Methods: The number of acinar cells was assessed histologically in 121 consecutive patients who underwent pancreaticoduodenectomy (PD) between April, 2012 and July, 2016., Results: POPF developed in 23 of the 121 patients. Univariate analysis revealed that male sex, long operating time, high volume of blood loss, soft remnant pancreas, large pancreatic duct, and the number of pancreatic acinar cells were significantly associated with POPF. Multivariate analysis revealed that male sex (p = 0.022) and the number of pancreatic acinar cells (p < 0.0001) were independently associated with POPF. In the receiver operating characteristic (ROC) curve analysis, the area under curve was 0.83895 when the cut off value of the number of pancreatic acinar cells to predict POPF was 890. Sensitivity and specificity of the number of pancreatic acinar cells were 82.6 and 77.6%, respectively., Conclusions: A large number of pancreatic acinar cells at the cut end of the stump is predictive of POPF after PD. Although POPF is associated with multiple factors and the number of acinar cells is only one of these, our study is the first to confirm this common intuition of surgeons, which has not been assessed definitively before.

Background: Patients' prognoses have been predicted by the preoperative inflammation-based score, but predicting a patient's risk for operative load remains challenging. This study investigates the usefulness of the postoperative C-reactive protein/albumin (CRP/Alb) ratio in patients with pancreatic ductal adenocarcinoma (PDAC)., Methods: This study retrospectively assessed 142 patients who underwent pancreatic resection for PDAC between 2004 and 2014. The time at which perioperative CRP/Alb ratio most influences the prognosis was identified, and the correlations among the perioperative CRP/Alb ratio, clinicopathological factors, and patient outcomes were investigated., Results: Among the perioperative CRP/Alb ratios, only a high CRP/Alb ratio at postoperative day 14 (POD14) was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS). High CRP/Alb ratio at POD 14 was related to high BMI, large amount of intraoperative bleeding, and the presence of complications. Finally, high CRP/Alb at POD14 was an independent prognostic factor of poor OS and RFS., Conclusions: The CRP/Alb ratio at POD14 is a useful predictive marker of surgical invasion, biological reaction, and prognosis in PDAC patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The methylation level of long interspersed nucleotide element-1 (LINE-1) is a good surrogate marker of the global DNA methylation level. The relationship between LINE-1 methylation level and prognosis in primary liver cancer (PLC) patients remains unclear., Results: LINE-1 methylation levels were significantly lower in HCC and cHCC-CC tissues, but not in ICC tissues, than those in noncancerous liver parenchyma (HCC: p < 0.0001; cHCC-CC: p < 0.001; and ICC: p = 0.053). HCC cases with hypomethylated LINE-1 had significantly shorter relapse-free survival (RFS) (log-rank, p = 0.008); however, this was not observed for the cHCC-CC or ICC cases. Multivariate Cox regression analysis revealed a significantly higher HCC recurrence rate in the group with hypomethylated LINE-1 (hazard ratio, 1.62; 95% confidence interval, 1.06-2.58; p = 0.025)., Conclusions: The genome-wide DNA hypomethylation status estimated via LINE-1 methylation levels might be indicative of poor RFS in patients with HCC but not ICC or cHCC-CC., Methods: We evaluated the level of LINE-1 methylation in 321 cases of curatively resected PLC {231 hepatocellular carcinoma (HCC), 19 combined hepatocellular and cholangiocarcinoma (cHCC-CC) and 71 intrahepatic cholangiocarcinoma (ICC)} via pyrosequencing of formalin-fixed paraffin-embedded (FFPE) tissues and examined its prognostic value., Competing Interests: CONFLICTS OF INTEREST None.

Gastrointestinal tract metastasis from pancreatic cancer is quite rare. We present the case of a 58-year-old male patient who underwent distal pancreatectomy for pancreatic body cancer 5 years prior. Four years after the initial operation, a 15-mm cystic submucosal tumor was found in the antrum of the stomach. Because the tumor had grown to 25 mm and the level of carcinoembryonic antigen in the cystic fluid derived by ultrasound-guided fine-needle aspiration biopsy was high, partial resection of the stomach was performed 5 years after the distal pancreatectomy. Pathological diagnosis was gastric metastasis of pancreatic cancer. The patient has been alive without recurrence for 13 months after the resection of the cystic tumor. We are not aware of any similar cases of cystic gastric metastasis from pancreatic cancer published in the English literature.

Background: Radiofrequency ablation (RFA) is an alternative to hepatic resection and one of the major therapeutic options for hepatocellular carcinoma (HCC). Here, we investigated the long-term outcomes of RFA as an initial treatment for HCC., Patients and Methods: From January 2000 to December 2014, we treated 1,043 patients with RFA for HCC at the Kumamoto University Hospital; 327 of these patients (31.4%) were treated for primary HCC. After exclusion of 75 patients who underwent combined therapy, data for 252 patients were examined. We retrospectively analyzed the long-term outcomes of RFA and identified factors of poor prognosis., Results: The median platelet count, prothrombin activity and indocyanine green retention rate at 15 min were 9.1×10 4 /μl, 83% and 26%, respectively. The 5-year overall survival (OS) rate was 69% and the median survival time was 7.0 years. The 5-year recurrence-free survival (RFS) rate was 17%, and the median RFS was 2.0 years. A multivariate analysis revealed that age >80 years [hazard ratio (HR)=7.76, p=0.011], tumor diameter >2 cm (HR=1.68, p=0.047) and multiple tumors (HR=1.87, p=0.014) were independent prognostic factors for poor OS. For RFS, des-γ-carboxy prothrombin (DCP) ≥40 mAU/ml (HR=1.47, p=0.038) and multiple tumors (HR=1.63, p=0.0056) were independent prognostic factors. Local recurrence at the ablated site occurred in 33/252 patients (13%), and in 33/372 tumors (8.9%)., Conclusion: Although our cohort included patients with relatively worse liver function, a favorable 5-year survival rate 69% was obtained by RFA. DCP ≥40 mAU/ml and multiple HCCs contribute to a higher risk of recurrence. Patients with these factors should therefore be followed-up intensively., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: The prognostic value of lymphocyte infiltration into hepatocellular carcinoma (HCC) is still controversial, and it has not been reported in hepatitis B virus (HBV)-positive or non-B non-C (NBNC) HCC. The aim of this study is to assess the prognostic significance of lymphocyte infiltrate in tumor for HBV-positive and NBNC HCC patients., Methods: This study investigated 145 HBV-positive or NBNC patients who underwent hepatectomy for HCC between January 2001 and May 2009. Cumulative recurrence rate, overall survival (OS), and clinicopathological parameters were analyzed according to lymphocyte infiltration in tumor., Results: In patients with low lymphocyte infiltration, the 5-year recurrence rate was higher and OS was poor (86.4 and 44.1%, respectively) than that of the patients with high lymphocyte infiltration (55.3 and 83.7%, respectively). Multivariate analyses revealed that independent risk factors for recurrence were low albumin value (hazard ratio [HR] 2.33, P = 0.009), high American Joint Committee on Cancer (AJCC) T stage (HR 2.31, P < 0.0001), high α-fetoprotein (AFP) value (HR 2.06, P = 0.005), and low lymphocyte infiltration (HR 2.50, P = 0.0001). The independent risk factors for OS were low albumin value (HR 3.69, P = 0.003), high AJCC T stage (HR 2.10, P = 0.049), high AFP value (HR 3.98, P < 0.001), and low lymphocyte infiltration (HR 3.47, P = 0.001)., Conclusions: Lymphocyte infiltrate in tumor is significantly associated high recurrence rate and poor overall survival. Evaluation of the infiltrating lymphocyte could improve the prediction of prognosis in HCC patients after curative resection., (© 2017 The Japan Society of Hepatology.)

Skeletal muscle metastasis from pancreatic cancer is rare. We present a 72-year-old female patient with unresectable pancreatic tail cancer. Fifteen months after the introduction of the chemoradiotherapy, an 18-mm elastic hard tumor was found in her right chest wall and resected after confirmation of no other metastatic lesions. Postoperative pathological examination diagnosed it as a muscle metastasis from the pancreatic cancer, and the patient has since been continuing chemotherapy for 10 months. A review of the literature regarding skeletal muscle metastasis from pancreatic cancer is also presented.

Background: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC)., Methods: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b + neutrophils (TANs; tumour associated neutrophils), CD163 + M2 macrophages (TAMs; tumour associated macrophages), CD8 + T cells, and FOXP3 + regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated., Results: Tumour associated neutrophils were inversely correlated with CD8 + T cells (P=0.0001) and positively correlated with Tregs (P=0.001). High TANs (P=0.01), low CD8 + T cells (P=0.02), and high Tregs (P=0.04) were significantly associated with poor overall survival (OS). A high-risk signature, derived from integration of intratumoural inflammatory and immune cells, was significantly associated with poor recurrence-free survival (P=0.01) and OS (P=0.0008). A high-risk signature was correlated with postoperative distant metastases. Furthermore, a high-risk signature was related to the resistance to gemcitabine-based chemotherapy used after recurrence., Conclusions: Our data showed that tumour infiltrating inflammatory and immune cells may play a pivotal role in ECC progression and a high-risk signature predicted poor prognosis in ECC patients.

Background/aim: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma, and has a poor prognosis. Surgical resection is the only option for a cure of ICC. Here we attempted to define the cure rate after hepatic resection for ICC and to identify the predictors for a cure., Patients and Methods: Among the 96 patients who underwent R0 resections for primary ICC between 1990 and 2011 at the Kumamoto University Hospital and Kyushu University Hospital, those who were followed for ≥5 years after surgery were enrolled. "Cure" was defined as recurrence-free survival (RFS) of ≥5 years after surgery., Results: A total of 81 patients were eligible. A cure was achieved in 37 patients (45.7%). The 5-year overall survival and RFS rates were 55.0% and 41.7%, respectively. A multivariate logistic regression analysis identified the absence of lymph node metastasis (relative risk (RR) 7.5, p=0.011) and the absence of microvascular invasion (RR 5.5, p=0.0137) as the independent predictors of achieving a cure., Conclusion: R0 resections achieved a cure in 45.7% of this series of ICC patients. The predictors of a cure identified here, i.e., absence of lymph node metastasis and absence of microvascular invasion, could contribute to the selection of patients who are not candidates for adjuvant chemotherapy., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Although hilar cholangiocarcinoma (HCCA) has a very poor prognosis, there are cases in which long-term survival is rarely obtained by multidisciplinary treatment., Case Presentation: A 61-year-old man diagnosed with HCCA was referred to our hospital. We performed an extended left hemi-hepatectomy and caudate lobectomy with extrahepatic bile duct resection. The tumor stage was T2aN0M0, stage II, based on the TNM classification, seventh edition. R0 resection was successfully performed. Adjuvant chemotherapy was not administered. After 38 months, computed tomography revealed peritoneal dissemination. The patient received chemotherapy with tegafur-gimeracil-oteracil-potassium (S-1) and gemcitabine. The peritoneal dissemination was successfully controlled for more than 50 months. During the treatment, levels of CEA and CA19-9 kept rising slowly, which was followed by bowel obstruction due to peritoneal dissemination of HCCA. The patient underwent resection of transverse colon with tumor nodules, and the tumor was pathologically diagnosed as metastasis of HCCA. Tumor markers decreased to normal levels, and the patient has been free from tumor relapse for 6 months., Conclusions: We here report a rare case of HCCA patient with recurrent peritoneal dissemination 3 years after R0 surgery which was sensitive to chemotherapy. The patient successfully received resection of peritoneal dissemination 50 months after the induction of chemotherapy and survived for 10 years.

Although common side effects of regorafenib include hand-and-foot syndrome and diarrhoea, the incidence of gastrointestinal perforation is reportedly unknown. We describe our experience with the case of a 65-year-old woman treated with regorafenib as a third-line therapy for progressive caecal cancer with multiple hepatic metastases after 4 and 6 courses of systemic mFOLFOX6 + bevacizumab (BV) and FOLFIRI + BV chemotherapy, respectively. The patient used regorafenib for 32 days but visited our hospital with abdominal pain during the second course. She was diagnosed with acute appendicitis and treated conservatively with antibiotics. The abdominal findings did not improve, and a computed tomography evaluation on day 4 of hospitalization revealed free air lateral to the caecal tumour, liver surface, and epigastric region. The patient underwent same-day emergency surgery based on a diagnosis of gastrointestinal perforation with generalized peritonitis. Upon observing digestive fluid leakage into the peri-ileocaecal area and a 5-mm perforation in the appendix, the patient was diagnosed with peritonitis due to gastrointestinal perforation. Ileocaecal resection with D2 debridement was performed, and a colostomy was opened into the ileum and ascending colon. We conclude that our patient developed gastrointestinal perforation during regorafenib therapy and note that clinicians should be aware of this possible complication in patients with a history of prior treatment with BV.

Background: The postoperative complication is one of an indicator of poor prognosis in patients with several gastroenterological cancers after curative operations. We, herein, examined prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations., Methods: We retrospectively analyzed 60 patients with intrahepatic cholangiocarcinoma who underwent primary curative operations from June 2002 to February 2016. Prognostic impacts of postoperative complications were analyzed using log-rank test and Cox proportional hazard model., Results: Postoperative complications (Clavien-Dindo classification grade 3 or more) occurred in 13 patients (21.7%). Overall survival of patients without postoperative complications was significantly better than that of patients with postoperative complications (p = 0.025). Postoperative complications are independent prognostic factor of overall survival (hazard ratio 3.02; p = 0.030). In addition, bile duct resection and reconstruction (Odds ratio 59.1; p = 0.002) and hepatitis C virus antibody positive (Odds ratio 7.14; p= 0.022), and lymph node dissection (Odds ratio 6.28; p = 0.040) were independent predictors of postoperative complications., Conclusion: Postoperative complications may be an independent predictor of poorer survival in patients with intrahepatic cholangiocarcinoma after curative operations. Lymph node dissection and bile duct resection and reconstruction were risk factors for postoperative complications, therefore we should pay attentions to perform lymph node dissections, bile duct resection and reconstruction in patients with intrahepatic cholangiocarcinoma.

Background/aim: The prognostic effect of lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC) remains unclear. The aim of this study was to reveal the clinical benefits of LND in patients with ICC after curative hepatic resections., Patients and Methods: We retrospectively analyzed 64 patients with ICC who underwent primary curative resections between June 2002 and February 2016 and evaluated the survival benefits of LND., Results: We performed LND on patients suspected to have LN metastasis before operation (23/64 cases; 35.9%). There was no significant difference in prognosis between the LND(+) group (n=22) and the LND(-) group (n=41); relapse-free survival (RFS): p=0.635 and overall survival (OS): p=0.347. Among the groups, pN0 (n=17), pN1 (n=7) and pNX (without LND or LN sampling; n=39), the survival curves of pN0 and pNX groups were similar (p=0.568)., Conclusion: Special attention should be given to the indication of LND and the practice of secure operation., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: /Objectives: Enoxaparin is low-molecular-weight heparin that is used for postoperative thromboprophylaxis. The purpose of this study was to evaluate the efficacy and safety of enoxaparin after pancreatic resection. We additionally carried out a literature review regarding venous thromboembolism (VTE) and postoperative bleeding mainly after hepatobiliary-pancreatic surgery., Methods: This was a prospective, single-arm study. Patients aged 20-79 years who planned to undergo pancreatic resection followed by postoperative anticoagulation therapy with enoxaparin were enrolled from 2013 to 2016. The exclusion criteria were low renal function, active bleeding, clinical signs of VTE at screening, or evidence of thromboembolic disease before surgery. The primary endpoint was the incidence of postoperative VTE. The secondary endpoint was the incidence of postoperative complications. For the literature review, PubMed was searched for relevant articles and the PRISMA guidelines were used., Results: In total, 103 patients were analyzed. Two patients (1.9%) developed asymptomatic VTE, and no patients developed symptomatic VTE. No in-hospital mortality occurred. Morbidities (Clavien-Dindo grade ≥ IIIa) occurred in 29 patients (28.1%). Three patients (2.9%) developed intra-abdominal hemorrhage due to pseudoaneurysm formation after pancreaticoduodenectomy or distal pancreatectomy. The literature review included nine articles, and all indicated that the results of this study were feasible., Conclusion: This is the first prospective trial to focus on pharmacologic prophylaxis with enoxaparin after pancreatic surgery. Postoperative anticoagulant therapy with enoxaparin was used in patients who underwent pancreatic surgery with a low incidence of VTE and no increase in postoperative bleeding events compared with existing evidence., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The incidence of postoperative pancreatic fistula (POPF) remains high at approximately 30% of cases with distal pancreatectomy (DP) and is associated with higher incidence of life-threatening complications. However, the most appropriate closure technique for the pancreatic stump during DP remains controversial. We, herein, present details of the use of a linear stapling device with pre-attached bioabsorbable polyglycolic acid (PGA) felt for pancreatic stump closure during DP. Grade B or C POPF occurred in only one case (5%) among 22 consecutive patients., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: There is no consensus on the need for adjuvant chemotherapy for patients with pathological residual invasive breast cancer (non-pCR) after neoadjuvant chemotherapy (NAC). We evaluated the tolerability and safety of tegafur-uracil (UFT) as adjuvant chemotherapy for patients with human epidermal growth factor receptor 2-negative breast cancer that resulted in non-pCR after NAC., Patients and Methods: We treated patients with 270 mg/m 2 UFT per day for 2 years after definitive surgery and radiotherapy, if necessary. In cases with hormone-sensitive cancer, patients received concurrent endocrine therapy. The primary end-point was the rate of completion of scheduled UFT therapy. Secondary end-points included safety and disease-free survival., Results: Twenty-one out of 29 patients (72%) completed the scheduled therapy. Eight patients discontinued the study treatment because of disease recurrence, toxicities, and patients' wish. Excluding liver dysfunction, adverse events were quite mild., Conclusion: Adjuvant UFT therapy after NAC was feasible and safe., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The purpose of this study was to retrospectively analyze the feasibility of outpatient management without initial assessment for febrile patients undergoing adjuvant chemotherapy for breast cancer. A total of 131 consecutive patients with breast cancer treated with adjuvant or neoadjuvant chemotherapy from 2011 to 2013 at Osaka Medical College Hospital (Osaka, Japan) were retrospectively reviewed. In the case of developing a fever (body temperature, ≥38°C), the outpatients had been instructed to take previously prescribed oral antibiotics for 3 days without any initial assessment, and if no improvement had occurred by then, they were required to visit the hospital for examination and to undergo treatment based on the results of a risk assessment for complications. The primary aim of the present study was to assess the outcome of febrile episodes, while the secondary aim was to assess the incidence of febrile episodes, hospitalizations, and the type of chemotherapy. The 131 patients received 840 chemotherapy administrations. Fifty-five patients (42.0%) had a total of 75 febrile episodes after 840 chemotherapy administrations (8.9%). Treatment failure occurred in 12 of the 75 episodes (16.0%) in 11 of the 55 patients (20.0%). Only four episodes required hospitalization. Treatment success was achieved in 63 episodes (84.0%). In conclusion, the feasibility of outpatient management without initial assessment was evaluated in the present study for febrile patients undergoing adjuvant chemotherapy for breast cancer, and the outpatient strategy regimen may be safe and convenient for these patients.

Squamous cell carcinoma(SCC)of the breast is a rare disease. We encountered a case of SCC of the breast that relapsed in the early postoperative period and rapidly progressed thereafter. A 38-year-old woman visited our hospital presenting with a tumor in the left breast consisting of a 5-cm mass with an irregularly sharped wall. Fine needle biopsy examination showed squamous cell carcinoma. A modified radical mastectomy by Auchincloss's method was performed on the left breast. SCC was confirmed by histological examination. Two months later, local recurrence on the chest wall was found during adjuvant chemotherapy. Thereafter, the disease rapidly progressed, and finally, the patient died of respiratory failure caused by lung metastasis. The prognosis of SCC of the breast is recognized as being more unfavorable than that of invasive ductal carcinoma. We should develop an effective chemotherapeutic strategy for this disease.

Background: Depletion of skeletal muscle mass (sarcopenia) indicates a poor prognosis for patients with several kinds of cancer, but it remains unclear whether esophageal squamous cell carcinoma (ESCC) is among these cancers. The aim of this study was to clarify the relationship between sarcopenia and postoperative outcome in patients with ESCC treated by esophagectomy., Methods: Skeletal muscle mass was assessed in 138 patients who underwent esophagectomy from August 2009 to May 2014. A multifrequency bioelectrical impedance analysis (InBody 720; Biospace, Tokyo, Japan) was used to assess skeletal muscle mass just before surgery. Postoperative complications were graded according to the Clavien-Dindo classification, and univariate and multivariate analyses were performed for postoperative respiratory complications., Results: Sarcopenia was determined in 61 patients (44.2 %). Preoperative pulmonary function was significantly lower and the rate of respiratory complications significantly higher in the sarcopenia group than in the non-sarcopenia group (p < 0.01). For other complications, the differences were not significant. Multivariate analysis showed that sarcopenia [odds ratio (OR) 5.82; p = 0.0001] and longer operation time (OR 3.09; p = 0.04) were risk factors for the occurrence of respiratory complications., Conclusions: Sarcopenia may be a predictor of pulmonary complications after esophagectomy. Further analysis is needed to clarify whether nutritional intervention improves skeletal muscle mass and thus contributes to reducing postoperative respiratory complications in sarcopenic patients.

The temporal image subtraction technique was applied to bone scintigraphy, using Photoshop (commercially available image processing software) and Morpher (public domain warping software). For the temporal subtraction images, 81 subtraction images (19 cases) were prepared by a method used to subtract the previous images from the current ones. Registration of the current and previous images was performed by manual operation using Photoshop, and warping was done using the warping function of Morpher. In addition, difference images prepared after correcting the distributions of radioactive isotopes of the current and previous images using the count of the pelvic region were also examined. Compared with manual operation, alignment of images by warping improved registration and reduced the generation of pseudo-images of subtraction images. The rate of identification of abnormal accumulation-enhanced regions and subjective evaluation by doctors was improved for warping more than for manual operation. Furthermore, abnormal hot regions, which are difficult to find in film images, could be found in three subtraction images. In addition, it was confirmed that abnormal hot regions become more visible in many cases by preparing subtraction images after correcting the count between images using the count of the pelvic region. Thus, it is suggested that the temporal image subtraction technique in bone scintigraphy enables more accurate observation of enhancement of or changes in abnormal hot regions, which will support diagnostic reading. It is considered that enhancement of or changes in abnormal hot regions will be more accurately understood through further detailed discussion in the future.