Prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is unsatisfactory. Tumor, host, and treatment factors including hepatic arterial infusion chemotherapy (HAIC) are intricately involved ...in the progression of ICC. We aimed to identify profiles associated with disease control rate (DCR) and the prognosis of patients with unresectable ICC by decision tree analysis. We analyzed 31 consecutive patients with unresectable ICC (median age, 71 years; the male ratio was 58.1%). Stage IVB occupied 51.6% of patients, and 38.7% and 58.1% of patients were treated with gemcitabine plus cisplatin combination therapy and HAIC, respectively. Profiles associated with prognosis as well as DCR were investigated by decision tree analysis. The median survival time (MST) of the patients was 11.6 months, and the DCR was 70.9%. Multivariate correlation analysis showed that albumin levels and WBC levels were significantly correlated with survival time (albumin, ρ = 0.3572,
= 0.0485; WBC, ρ = -0.4008,
= 0.0280). In decision tree analysis, WBC level was selected as the initial split variable, and subjects with WBC levels of 6800/μL or less (45.1%) showed a long survival time (MST 476 days). We also demonstrated that the profile associated with the highest DCR was "less than 4.46 mg/dL of CRP levels and treatment with HAIC". We demonstrated a new prognostic profile for ICC patients, which consisted of WBC and CRP levels. Moreover, we demonstrated that HAIC was associated with better disease control in ICC patients with low CPR levels. Thus, these new profiles may be useful for the management of ICC patients.
We report on a 62-year-old man with chronic hepatitis C who developed rapidly growing hepatocellular carcinoma (HCC) after achieving sustained virological response at post-treatment week 24 (SVR 24) ...by direct-acting antiviral (DAA) treatment. In 2008, he failed interferon therapy at 56 years of age. He received daclatasvir plus asunaprevir for 24 weeks after confirmation of no liver tumor by abdominal ultrasonography. He had no advanced liver fibrosis. Three months after initiation of DAA treatment, a liver tumor measuring 6 mm in diameter was detected by ultrasonography and confirmed with magnetic resonance imaging. After achieving SVR 24, the tumor increased in size to 16 mm. Two months later, a tumor biopsy was performed, and histology revealed moderately to poorly differentiated HCC. The patient’s alpha-fetoprotein (AFP) level was within the normal range, but the Lens culinaris agglutinin-reactive fraction of AFP level was elevated. The diameter of the tumor increased to 32 mm at 2 months after diagnosis. Lymph node metastasis in porta hepatis was found by positron emission tomography at 4 months after diagnosis. The patient received hepatic arterial infusion chemotherapy and radiation therapy, but died later. Careful monitoring is required during and after DAA treatment because HCC can grow fast even in patients with normal AFP and no advanced liver fibrosis.
Background/Aims: C‐reactive protein (CRP) was recently identified as a prognostic factor for patients with hepatocellular carcinoma (HCC) after surgical resection. We investigated the relationship ...between the serum levels of high sensitivity CRP (H‐CRP) and the prognosis of HCC patients.
Method: We conducted a cohort study of 90 HCC patients enrolled from 1997 to 1998. All patients were treated and followed for a mean period of 3.2 years. Clinical variables were compared between patients positive for H‐CRP (serum H‐CRP levels ≥3.0 mg/L, n=47) and those negative for H‐CRP (serum H‐CRP levels <3.0 mg/L, n=43). We also determined the relationship between serum H‐CRP and prognosis in HCC patients.
Results: The survival rate of patients of the H‐CRP‐positive group was lower than that of H‐CRP‐negative patients. Tumour stage (stages 3 or 4), total bilirubin ≥1.2 mg/dL, albumin (Alb) <3.5 g/dL, des‐γ‐carboxy prothrombin ≥40 mAU/mL, positive H‐CRP and initial treatment (transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy or best supportive care) were identified as significant poor prognostic factors by univariate analysis, while positive H‐CRP hazard ratio (HR), 1.58; P=0.048, Alb<3.5 g/dL (HR, 2.10; P=0.004), tumour stage (stages 3 or 4; HR, 3.05; P=0.001) and initial treatment (HR, 1.88; P=0.029) were considered to be significant determinants of poor prognosis by multivariate Cox proportional hazards analysis.
Conclusions: The prognosis of H‐CRP‐positive patients was poorer compared with H‐CRP‐negative patients. This study confirmed that H‐CRP, like CRP, is a marker of poor prognosis in HCC patients.
Background: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only ...upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients. Aim: To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC. Discussion: Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.
Background: Metronomic chemotherapy involves frequent, regular administration of cytotoxic drugs at nontoxic doses, usually without prolonged breaks. We investigated the therapeutic efficacies of ...metronomic S-1, an oral 5-fluorouracil prodrug, and vandetanib, an epidermal growth factor receptor and vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, in models of hepatocellular carcinoma (HCC). Methods: We compared anti-HCC effects and toxicity in the six treatment groups: control (untreated), maximum tolerated dose (MTD) S-1, metronomic S-1, vandetanib, MTD S-1 with vandetanib, and metronomic S-1 with vandetanib. Tumor microvessel density (MVD) and tumor apoptosis were evaluated by immunohistochemistry. The expression of VEGF and thrombospondin-1, an endogenous inhibitor of angiogenesis, was analyzed by Western blot. Results: Metronomic S-1 significantly inhibited tumor growth, which was enhanced by combination with vandetanib. With respect to toxicities, MTD S-1 caused severe body weight loss and myelosuppression, whereas metronomic S-1 did not cause any overt toxicities. Moreover, metronomic S-1 or metronomic S-1 with vandetanib prolonged survival, the latter treatment providing the greatest benefit. Metronomic S-1 and metronomic S-1 with vandetanib decreased MVDs and increased apoptosis in tumor tissues. The expression of VEGF in tumor tissues was upregulated by vandetanib and metronomic S-1 with vandetanib, whereas the expression of thrombospondin-1 was upregulated by metronomic S-1 and metronomic S-1 with vandetanib. Conclusion: Metronomic S-1 with an antiangiogenic agent seems to be an effective and safe therapeutic strategy for HCC.
Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) progresses with a highly multicentric occurrence (MO) even after radical hepatectomy. Despite several efforts to clarify the ...pathogenesis of MO, the underlying molecular mechanism remains elusive. The aim of this study was to evaluate alterations in DNA methylation in noncancerous liver tissues in the MO of HCC.
A total of 203 patients with HCV-related HCC who underwent radical hepatectomy at our hospital between January 2008 and January 2012 were recruited. We defined a group of nonearly recurrence of HCC (NR) for ≥3 years after radical hepatectomy and a group of early recurrence of HCC (ER) with MO within 2 years after radical hepatectomy.
Three patients each were selected in the NR and ER groups in the first set, and 13 patients in the NR group and 17 patients in the ER group were selected in the second set. Genome-wide DNA methylation profiles were obtained from noncancerous liver tissues using a Human Methylation 450 BeadChip, and the differences between the groups were analyzed for each set. After excluding single nucleotide polymorphism-associated methylation sites and low-call sites, 401,282 sites were assessed using a generalized linear model without any adjustments. Nine gene regions, APBB1P, CLSTN3, DLG5, IRX5, OAS1, SOX12, SNX19, TENM2, and TRIM54, exhibiting a significant difference (P < .001) in DNA methylation levels were identified in the common direction between the 2 analysis sets.
Alterations in DNA methylation of 9 genes in noncancerous liver tissues appear to be involved in MO after radical hepatectomy for HCV-related HCC.
Lymphangioleiomyomatosis (LAM) is a rare and progressive neoplastic disease of young woman, characterized by the proliferation of abnormal smooth muscle-like cells (LAM cells) in the lungs and axial ...lymphatics. A 44-year-old woman was referred to our hospital because pleural effusion was detected during a health checkup. She had chylothorax, chylous ascites, and chyluria, and her computed tomography scan showed a solid tumor in the pelvis. Surgical biopsy was performed; she was diagnosed as having LAM. We could not control the fluid collection and chyluria using standard medical treatments. Therefore, we chose to administer sirolimus, and her symptoms dramatically improved. The mechanism of chyluria presumably involved LAM cell infiltrates in the ureter via the lymphatic vessel flow, which causes LAM to develop because of ureter wall exposure.
Aim: This study explored recent improvements in the management of hepatocellular carcinoma (HCC) diagnosed during surveillance.
Methods: The subjects were 1074 patients with HCC, subdivided into ...three groups. Group A comprised 211 patients for whom HCC was detected during periodic follow‐up examinations at Kurume University School of Medicine, Group B comprised 544 patients diagnosed with HCC during periodic follow‐up examinations at other institutions, and, Group C comprised 319 patients with HCC detected incidentally or because of symptoms.
Results: In 1995–2000 and 2001–2006, 91% and 91% of group A, 68% and 70% of group B, and 27% and 26% of group C patients with HCC, respectively, met the Milan criteria. For groups A and B, the proportions of patients with Child–Pugh class A and use of promising treatment increased in the later periods compared to those diagnosed during the earlier periods (group A, Child–Pugh class A, 72% vs 58% P = 0.040, receiving treatment, 90% vs 70% P < 0.0001; group B, Child–Pugh class A, 71% vs 62% P = 0.031; receiving treatment, 72% vs 52% P < 0.0001, respectively). The cumulative survival rates of the 405 patients with HCC detected in the latter 6 years tended to be better than those for patients diagnosed in the former 6 years (350 patients) (4 years, 58% vs 50% P = 0.0349).
Conclusion: The use of promising treatment and prognosis have improved in the last 6 years for patients with HCC diagnosed through surveillance relative to those identified in 1995–2000.
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