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Background: CD44 and CD133 are stem cell markers in colorectal cancer (CRC). CD44 has distinctive isoforms with different oncological properties like total CD44 (CD44T) and variant CD44 (CD44V). Clinical significance of such markers remains elusive., Methods: Sixty colon cancer were examined for CD44T/CD44V and CD133 at mRNA level in a quantitative PCR, and clarified for their association with clinicopathological factors., Results: (1) Both CD44T and CD44V showed higher expression in primary colon tumors than in non-cancerous mucosas (p<0.0001), while CD133 was expressed even in non-cancerous mucosa and rather decreased in the tumors (p = 0.048). (2) CD44V expression was significantly associated with CD44T expression (R = 0.62, p<0.0001), while they were not correlated to CD133 at all in the primary tumors. (3) CD44V/CD44T expressions were significantly higher in right colon cancer than in left colon cancer (p = 0.035/p = 0.012, respectively), while CD133 expression were not (p = 0.20). (4) In primary tumors, unexpectedly, CD44V/CD44T/CD133 mRNA expressions were not correlated with aggressive phenotypes, but CD44V/CD44T rather significantly with less aggressive lymph node metastasis/distant metastasis (p = 0.040/p = 0.039, respectively). Moreover, both CD44V and CD133 expressions were significantly decreased in liver metastasis as compared to primary tumors (p = 0.0005 and p = 0.0006, respectively)., Conclusion: Our transcript expression analysis of cancer stem cell markers did not conclude that their expression could represent aggressive phenotypes of primary and metastatic tumors, and rather represented less demand on stem cell marker-positive cancer cells., Competing Interests: Dr. Naitoh reports financial relationship outside the submitted work: grants and personal fees from Chugai pharm, Taiho pharm, Kaken pharm, Daiichi-Sankyo, and Eli Lilly Japan, personal fees from Takeda pharm, Merck, Bayer, and Boehringer Ingelheim. Dr. Hiki reports financial relationship outside the submitted work: grants and personal fees from Abbott Japan, EA pharm, Johnson&Johnson, Otsuka pharm, Otsuka Pharm Factory Inc., Kaken pharm, Covidien Japan Inc., Takeda Pharm, Daiichi Sankyo, Taiho pharm, Tsumura, Terumo, and Miyarisan pharm, grants from Shionogi pharm, Chugai pharm, Hogy Medical, and Yakult Honsha, personal fees from NHK, Pfizer Japan, AstraZeneca, Nihon pharm, Olympus, Novartis pharm, Intuitive Surgical G.K., Ono pharm, Kaigen pharm, QLife, Sumitomo Dainippon pharm, and Nestle Japan. Dr. Kumamoto reports financial relationship outside the submitted work: grants and personal fees from Taiho pharm, Takeda pharm, and Asahi Kasei pharm, grants from Kaken pharm, Eli Lilly Japan, Chugai pharm, Daiichi Sankyo, Covidien Japan Inc., Yakult Honsha, Nihon pharm, personal fees from Viatris pharm, Ono pharm, AMCO, Novartis pharm, Olympus, Japan Blood Products Organization, and Terumo. Dr.Sangai reports financial relationship outside the submitted work: grants and personal fees from Chugai pharm, Taiho pharm, Eisai, and Kyowa Kirin, grants from Takeda pharm, and Nippon Kayaku, personal fees from Pfizer Japan, AstraZeneca, Novartis pharm, Daiichi Sankyo, Eli Lilly Japan, and Maruho. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Kaida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Through this multi-institutional study, we aimed to retrospectively evaluate the safety and efficacy of repeated stereotactic body radiation therapy (SBRT) for intrahepatic recurrent hepatocellular carcinoma (HCC)., Methods and Materials: Between 2005 and 2017, 709 patients with 835 HCCs underwent SBRT; those treated with repeated SBRT were eligible. The median prescribed dose was 40 Gy in 5 fractions., Results: Eighty-one patients with 189 tumors underwent repeated SBRT (≥ 2 courses [median 2 times; range, 2-5 times]). The median follow-up periods from the first to the second SBRT were 41.5 (range, 12-99) and 20 (range, 1-81) months, respectively. The median interval between the first and second SBRT was 18 (range, 3-74) months. The 5-year local recurrence rate was 6.3% (95% confidence interval [CI], 2.3%-13.4%). The 5-year overall survival (OS) and liver-related death rates from the first SBRT were 60.4% (95% CI, 47.0%-73.8%) and 32.9% (95% CI, 20.3%-46.0%), respectively, and the 3-year rates from the second SBRT were 61.0% (95% CI, 49.9%-75.2%) and 34.5% (95% CI, 20.6%-48.9%), respectively. The frequency of grade 3 toxicity was not significantly different between the first and second SBRT (first: 11% [95% CI, 5.2%-20%]; second: 15% [95% CI, 7.9%-24%]; P = .48). Among 39 patients with no intrahepatic recurrence for 1 year after the first and second SBRT, the deterioration in liver function after the first and second SBRT was not significantly different; the albumin-bilirubin score increased 1 year after the first versus second SBRT (first, 0.143 ± 0.23; second, 0.195 ± 0.38; P = .48). Multivariate analysis revealed that the intrahepatic recurrence-free interval was the only significant factor for OS., Conclusions: Repeated SBRT for intrahepatic recurrent HCC resulted in high local control with safety and a satisfactory OS comparable with that of other curative local treatments for patients with well-preserved liver function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aim: Sarcopenia is a prognostic factor in hepatocellular carcinoma (HCC) patients. HCC patients who underwent transcatheter arterial chemoembolization (TACE) are at a risk of muscle atrophy. We aimed to investigate the effects of in-hospital exercise on muscle mass and factors associated with muscle hypertrophy in HCC patients who underwent TACE., Methods: We enrolled 209 HCC patients who underwent TACE. Patients were classified into either an exercise (n = 102) or control (n = 107) group. In the exercise group, patients were treated with in-hospital exercise (median 2.5 metabolic equivalents/20-40 min/day). The effects of exercise on muscle mass were evaluated by changes in skeletal muscle index (ΔSMI) between before and after TACE. Factors associated with an increase in SMI were analyzed by logistic regression and decision-tree analyses., Results: There was no significant difference in serum albumin and bilirubin levels between the two groups. ΔSMI was significantly higher in the exercise group than in the control group (0.28 cm 2 /m 2 vs -1.11 cm 2 /m 2 , P = 0.0029). In the logistic regression analysis, exercise was an independent factor for an increase in SMI (hazard ratio 2.13; 95% confidence interval 1.215-3.846; P = 0.0085). Moreover, the decision-tree analysis showed that exercise was the initial divergence variable for an increase in SMI (the ratio of increased SMI: 53% in the exercise group vs 36% in the control group)., Conclusions: In-hospital exercises increased muscle mass in HCC patients who underwent TACE. In addition, exercise was an independent factor for muscle hypertrophy. Thus, in-hospital exercise may prevent sarcopenia in HCC patients who underwent TACE., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The patient was a 52-year-old man who had a positive fecal occult-blood test on a medical check-upi n April 2015 and was referred to our hospital in June. Detailed preoperative examinations resulted in a diagnosis of cancer of the lower rectum, multiple liver metastases, and clinical Stage IV . A biopsy showed moderately differentiated tubular adenocarcinoma. All-RAS was wild type, and the patient was asymptomatic. Unresectable advanced rectal cancer was diagnosed, and the patient was scheduled to receive systemic chemotherapy. The patient received a total of 16 courses of combination chemotherapy with 5- fluorouracil, Leucovorin, and oxaliplatin(FOLFOX)plus panitumumab, starting in October 2015. In July 2016, Colonoscopy showed scar findings at the site of the primary rectal cancer lesion. A biopsy revealed no cancer cells. It was difficult to identify the primary lesion on computed tomography, and there was no evidence of clinically significant lymphadenopathy. Positronemission tomography and computed tomography showed shrinkage of the liver metastases, with no accumulation of tracer in the primary lesion or lymph nodes. The primary lesion had a clinical complete response(CR), and the metastatic lesions had a clinical partial response(PR). In October 2016, laparoscopic partial hepatectomy was performed to treat the liver metastases. Histologic examination showed that the liver metastases were from rectal cancer. It is currently under observation.

The mainstay of treatment for metastatic colorectal cancer is surgery. Therefore, colorectal cancer metastasis is distinctive, compared to other cancer types in which chemotherapy is the main treatment. Initially, Japan experienced medical druglag compared with western countries. However, the use of oxaliplatin for unresectable recurrent metastatic colorectal cancer became available in Japan, as well as in western countries, in 2005. We have since shifted chemotherapeutic regimens from monotherapy to combination therapy with molecular targeted agents. The combination therapy has rapidly become a standard therapy for unresectable metastatic colorectal cancer, and prognosis has dramatically increased for patients with this condition. Herein, we describe the treatment of liver metastasis of colorectal cancer, and surgery and adjuvant or neoadjuvant therapy options for resectable cancer. Furthermore, we focus on conversion therapy for unresectable cancer.

Purpose: CT during hepatic arteriography (CTHA) of cone-beam computed tomography (CBCT) provides valid information in performing transcatheter arterial chemo-embolization (TACE). The usefulness of CTHA with the diluted contrast medium has been reported in some medical conferences. However, the operation becomes somehow complicated for the medical institutions that have angiography injectors with a single head. In this study, we aimed to investigate the clinical equivalence of low-rate injection method and diluted injection method., Methods: The relationship between the injection rate and transit time of contrast medium was tested. Then, we measured the signal values of CBCT and CT values both in varying injection rates and in the case of doubling dilution., Results: The transit time of contrast medium became delayed with decreasing injection rate. The signal values of CBCT in the case of doubling dilution showed almost the same as those at a half of injection rate without dilution. We also obtained the same finding from the comparative investigation of CT values. ROC analysis of digital subtraction angiography (DSA) and CBCT was carried out, and the area under the curve (AUC) of CBCT showed a significantly higher value., Conclusion: It is suggested that CTHA with low-rate injection method offers diagnostic image similar in some degree to the diluted injection method.

A 65-year-old man was diagnosed with small cell lung cancer with multiple liver metastases. Three days after initiating chemotherapy, he experienced abdominal discomfort with hypotension. Computed tomography revealed a ruptured liver metastasis and the presence of hemorrhagic ascites. Transcatheter arterial embolization to the appropriate hepatic artery in concomitant with supportive therapies successfully stabilized his condition. Unlike with hepatocellular carcinoma, the rupture of a liver metastasis and associated hemoperitoneum is very rare in patients with lung cancer. We comprehensively reviewed the literature and found 10 similar cases with this serious condition. Physicians should therefore be aware of the risk of hemoperitoneum caused by ruptured liver metastases in patients with lung cancer.

We report the case of a 12-year-old boy with a huge liver tumour 20 cm in diameter with multiple lung metastases. Six months after systemic chemotherapy was initiated, all tumours had disappeared with the exception of the liver tumour and a tiny lung tumour 2.5 mm in diameter. Fluoroscopy-assisted thoracoscopic resection of the pulmonary nodule was performed to evaluate whether viable tumour tissue remained in the lung lesion. Before moving the patient to the operating room, the nodule was marked by Lipiodol under CT fluoroscopic guidance with the patient under local anaesthesia. This procedure allowed correct visualisation of the area that should be resected., (© 2011 The Authors. Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists.)

We describe a 71-year-old woman with a hepatocellular carcinoma who underwent percutaneous radiofrequency ablation (RF) with a single internally cooled electrode under computed tomography (CT) fluoroscopic guidance. Nine months after the procedure, CT images showed herniation of the large intestine into the right pleural cavity. To our knowledge this complication of RF performed with a single internally cooled electrode under CT guidance has not been previously reported.

Background: Various treatments for hepatocellular carcinoma (HCC) beneath the diaphragm have been reported. Transpulmonary radiofrequency (TPRF) ablation for HCC beneath the diaphragm has been developed as a safe treatment, but pneumothorax has been reported as the most common complication of TPRF ablation., Purpose: To evaluate the relationship between the incidence of pneumothorax and various variables after TPRF ablation., Material and Methods: Seventy-six TPRF ablation sessions for unresectable HCC were performed in 66 patients (19 women, 47 men; mean age 69.6 years) under computed tomography (CT)-fluoroscopic guidance between November 2005 and April 2009. All patients had HCC beneath the diaphragm, not visible by ultrasonography. In 62 of the 76 sessions, the number of transpulmonary approaches was one as adequate, while multiple transpulmonary approaches were performed in 14 of the 76 sessions. The rate of pneumothorax and risk factors for pneumothorax were investigated., Results: Among the 76 sessions, pneumothorax was detected in 51 sessions (67.1%). Among the 14 sessions with multiple transpulmonary passages, pneumothorax was detected in 13 (92.9%), while in the 62 sessions with a single transpulmonary passage, pneumothorax occurred in 38 sessions (61.3%). Hence, the number of transpulmonary approaches was a significant factor (P=0.0232). Among 13 variables investigated for the 62 sessions with a single transpulmonary approach, the only significant factor correlated with the occurrence of pneumothorax was the length of the needle trajectory through the aerated lung (P=0.0014). The incidence of chest tube placement was 7.9%., Conclusion: Pneumothorax occurred frequently after TPRF ablation for HCC. The main risk factors for pneumothorax after TPRF ablation for HCC were increased length of needle trajectory through the aerated lung and multiple transpulmonary approaches in one session. Even if pneumothorax occurred, pneumothorax disappeared spontaneously or with simple treatment such as manual aspiration in most cases.

We used a retrospective non-randomised study to investigate the clinical effect of selective embolisation of the right gastric artery before hepatic arterial infusion chemotherapy (HAIC) using a port-catheter system. We evaluated whether the hepatic artery or the left gastric artery is the better approach for selecting the right gastric artery. A total of 367 patients (244 men and 123 women; mean age, 64.1 years) with unresectable advanced liver cancer underwent percutaneous implantation of a port-catheter system. In 294 of these patients, right gastric arterial embolisation with microcoils was attempted before placement of the port-catheter system to prevent gastric mucosal lesions. Approach was either through the hepatic artery (175 patients) or through the left gastric artery (119 patients), with success rates in catheterising the right gastric artery of 78.3% and 77.3%, respectively. If the attempt was unsuccessful, the catheter was redirected to the alternative approach, which increased the final success rate to 96.3%. Only seven patients experienced gastroduodenal mucosal lesions acutely after HAIC, as revealed by endoscopy. Embolisation of the right gastric artery is a feasible procedure that can reduce the incidence of gastric mucosal lesions associated with HAIC. Approach through either the hepatic artery or the left gastric artery is equally acceptable.

Hepatocellular carcinoma (HCC) is usually known to develop in patients with underlying high-risk liver diseases such as viral hepatitis, cirrhosis and alcohol abuse, whereas reports dealing with HCC in Crohn's disease (CD) are limited. We present a case of HCC, which developed sequentially within a short period in a 52-year-old Japanese man with a 36-year history of CD without risky conditions for HCC. He also had not taken immunosuppressants such as azathioprine. Although the definitive etiological factors contributing to hepatocarcinogenesis in the present case could not be elucidated, further close surveillance is required.

Objective: The purpose of our study was to evaluate the usefulness of N-butyl cyanoacrylate (NBCA) in addition to microcoils in the percutaneous implantation of a port-catheter system for repeated hepatic arterial infusion chemotherapy with the fixed-catheter-tip method., Materials and Methods: We retrospectively studied 166 consecutive patients with unresectable advanced liver cancer for whom a port-catheter system was percutaneously implanted with its tip fixed at the gastroduodenal artery with microcoils. In 107 patients, NBCA was also used for catheter tip fixation. We compared this group with a control cohort of 59 patients who did not receive NBCA. Outcomes, including rate of success in implantation, details of embolic agents for fixation, and occurrence of complications related to catheter placement that would prohibit continuation of chemotherapy if not corrected, were compared., Results: In all, port-catheter placement was successful. However, 38 complications occurred in 32 patients. Catheter dislocation occurred in nine. Hepatic artery obstruction or severe stenosis was seen in 10. Recanalization of a once-embolized gastroduodenal artery was found in two patients. The rate of dislocation did not differ significantly between patients in whom NBCA was and those in whom it was not used. However, hepatic artery obstruction appeared at a significantly higher rate, and recanalization of a gastroduodenal artery at a significantly lower rate, in patients in whom the catheter tip was fixed with NBCA., Conclusion: The use of NBCA correlated with a higher rate of hepatic artery obstruction. The use of NBCA should not always be required in port-catheter implantation with the fixed-catheter-tip method.

A 54-year-old man had undergone transcatheter arterial embolization (TAE) three times to treat hepatitis B virus-related hepatocellular carcinoma (HCC), but recurrence was found in June 2005. A large tumor in the left lateral portion of the liver showed extrahepatic growth and was attached to the gastric wall. TAE was performed a forth time. In September 2005, the patient was admitted with worsening anemia. Computed tomography and upper gastrointestinal endoscopy revealed that the HCC had directly invaded the stomach and caused gastrointestinal hemorrhage. Endoscopic hemostasis was effective, but the patient died because of worsening hepatic failure.

In this study, we examined the antitumor activities of isoprenoid derivatives conjugated with substrates of energy metabolism in human hepatoma-bearing athymic mice. Among these compounds, N-geranylpyruvic amide, N-geranyl-p-pyruvaminobenzoic amide, N,N'-digeranylmalic diamide and N,N'-digeranyl-O-acetylmalic diamide had strong antitumor effects. These geranylamine derivatives also inhibited in vitro cell growth. Sugar conjugates of geranylamine, geranic acid and mevalonic acid did not show any antitumor effect in vivo or in vitro. Although the geranylamine derivatives had no impact on the cell cycle distribution at 24 h, a sub-G1 (apoptotic) peak of varying magnitude was seen in DNA histograms of cells treated with the derivatives for 48 h. However, the geranylamine derivatives did not inhibit protein isoprenylation, which has been reported in cancer cells treated with several natural isoprenoids. These results suggest that the geranylamine derivatives conjugated with malic acid and pyruvic acid have a different mechanism of antitumor activity from that of natural isoprenoids.

A 66-year-old man with hepatocellular carcinoma (HCC) showed marked thrombocytosis (110.7 x 10(4)/microl). Bone marrow (BM) aspirates demonstrated an increase of mature megakaryocytes (MgK). The serum thrombopoietin (TPO) level was increased to about 100-fold that of the normal level in the terminal stage. However, the platelet count gradually decreased to 13.5 x 10(4)/microl. The autopsy specimen revealed normoplastic BM with decreased MgK, mainly consisting of the immature type, and it was negative for tumor cells. Liver specimen showed markedly fatty metamorphosis. Immunohistochemical staining of TPO demonstrated that hepatocytes were weakly stained and HCC cells strongly stained, suggesting TPO-producing HCC.

We report a case of advanced rectal cancer accompanied by unresectable liver metastasis in which remission has been achieved for 7 years. The patient was a 64-year-old woman, and her chief complaints were a feeling of abdominal distention and melena. After low anterior resection (D3), oral administration of 600 mg/day of UFT-E and chemotherapy against the liver metastasis by hepatic arterial injection via a reservoir were started. Since the arterial injection via a reservoir became impossible due to infection, her clinical course was observed solely with oral administration of UFT-E. As a result, complete remission was achieved 7 months postoperatively, and the patient is still alive in good health without recurrences at present (7 years postoperatively). The reason why a favorable outcome has been achieved is probably that, although the initial operation resulted is non-curative resection, measures sufficient to enable the patient to lead an ordinary social life were taken at the beginning, and efforts to achieve a long-term survival were made while respecting the quality of life of the patient so that the patient would be able to coexist with the cancer.

Background/aims: Angiogenesis is critical for the development and progression of solid tumors. The purpose of this study was to evaluate the possible role of vascular endothelial growth factor (which is considered to be one of the most important factors involved in tumor-associated angiogenesis), in human hepatocellular carcinoma., Methods: Vascular endothelial growth factor gene and protein expression were analyzed by means of Northern hybridization and immunohistochemical methods in 5 hepatocellular carcinoma cell lines. Secretion of vascular endothelial growth factor was evaluated by immunoblotting of conditioned medium of these hepatocellular carcinoma cells. Further, we compared the level of vascular endothelial growth factor expression in hepatocellular carcinoma tissues along with that in surrounding tumor-free tissues obtained from 20 patients. We also analyzed mRNA expression of Flt-1, one of the vascular endothelial growth factor specific high-affinity receptors, in hepatocellular carcinoma cell lines., Results: Northern hybridization analysis and immunohistochemistry revealed that all cultured hepatocellular carcinoma cells exhibited a high level of vascular endothelial growth factor mRNA. In addition, vascular endothelial growth factor secretion by Hep G2, one of the hepatocellular carcinoma cell lines, was shown by Western blot. In vivo, we observed vascular endothelial growth factor expression in both hepatocellular carcinoma and non-hepatocellular carcinoma tissues. However, in 12 of 20 cases, vascular endothelial growth factor mRNA levels were significantly up-regulated in hepatocellular carcinoma tissues. In the majority of cases (10 out of 12 cases) with abundant tumor vascularity, vascular endothelial growth factor mRNA up-regulation in hepatocellular carcinoma tissues was observed. We failed to detect Flt-1 mRNA expression in hepatocellular carcinoma cells., Conclusions: This study suggests that the possibility that hepatocellular carcinoma cells overexpress the vascular endothelial growth factor gene and protein. These findings support the hypothesis that vascular endothelial growth factor is one of the important factors involved in the angiogenesis of hepatocellular carcinoma, and may even be involved in the development and/or progression of hepatocellular carcinoma itself.

A case of hepatocellular carcinoma producing carcinoembryonic antigen and carbohydrate antigen 19-9 is reported. The serum level of carcinoembryonic antigen was 26,800 ng/ml and carbohydrate antigen 19-9, 5,500 U/ml on the final day. Immunohistochemical study revealed positive monoclonal antibodies for these two antigens within the cytoplasm of the hepatocellular carcinoma cells.

The experimental and pharmacological characteristics of various formulations of an anticancer agent (epirubicin, EPI) and lipiodol were evaluated in vitro and in vivo. Three forms of EPI-lipiodol, i.e., an oil-in-water type of emulsion (O/W type), a water-in-oil type of emulsion (W/O type), and a suspension (S type), were prepared and investigated for their stability. An O/W-type emulsion using a stock solution of Iopamidol as the solvent for EPI was the most stable form in the stationary state in vitro. In 16 patients with malignant liver tumors (14 hepatocellular carcinomas and 2 liver metastases), the three forms of EPI-lipiodol were injected into the proper hepatic artery. The plasma EPI level was monitored periodically and analyzed pharmacokinetically. No significant difference in the pharmacokinetics of EPI was detected among the O/W, W/O, and S types.

We have assayed both estrogen and androgen receptors in hepatocellular carcinomas, in the surrounding noncancerous liver tissue, and in normal liver tissue. Estrogen receptors (ERs) were detected in 5 out of 22 HCC tissues, 14 out of 22 surrounding noncancerous tissues, and in 5 out of 6 normal liver tissues. Androgen receptors (Ars) were detected in 4 out of 21 HCC tissues, in 7 out of 21 surrounding noncancerous tissues, and in 2 out of 5 normal liver tissues. These results suggest that the pathogenesis of some HCC may be dependent on estrogen or androgen. Hence, it may be beneficial to provide hormonal therapy for HCC, especially in cases that show high concentrations of ER and/or AR.