[Show abstract][Hide abstract] ABSTRACT: We report a rare case of multiple hepatocellular adenomas difficulty in ruling out well-differentiated hepatocellular carcinomas prior to resection. A 40s female was admitted to the hospital for examination of multiple liver tumors. CT and Gd-EOB-MRI showed that tumors were located in segment 2 and 5. We conducted a percutaneous tumor biopsy and tumor showed low atypical cells containing fat deposit. As the possibility of multiple hepatocellular carcinomas could not be denied, partial hepatectomy and RFA were done. All resected tumors showed a decreased expression of the liver fatty acid binding protein (L-FABP), and were finally diagnosed as multiple HNF1α-inactivated type hepatocellular adenomas Multiple hepatocellular adenomas are rare tumors, so we report this case with review of the literatures.
[Show abstract][Hide abstract] ABSTRACT: Background
Preoperative chemotherapy is a promising strategy for downstaging advanced gastric cancer before radical resection, although severe adverse events can occur and clinical outcomes are often unsatisfactory. To identify predictive biomarkers of drug sensitivity, we used a well-designed functional apoptosis assay and assessed the correlations between chemosensitivity and clinical outcomes.
Drug sensitivity to docetaxel, cisplatin, and 5-fluorouracil was examined in 11 gastric cancer cell lines. BCL2-homology domain 3 (BH3) profiling was performed and assessed for correlations with drug sensitivity. Immunohistochemical staining of clinical gastric cancer specimens was performed before preoperative chemotherapy, and correlations with histopathological responses and clinical outcomes were assessed.
BIM (BCL2L11)-BH3 profiling results correlated with docetaxel sensitivity and BAK protein expression, whose knockdown caused docetaxel resistance. The BAK expression indexes of 69 gastric cancer specimens before preoperative chemotherapy (including docetaxel treatment) were determined by multiplying numerical values describing the degrees of BAK positivity and staining intensity observed. Patients whose specimens showed good chemotherapeutic histopathological responses had higher BAK indexes than those with poor responses. Patients with BAK index values ≥3 showed improved progression-free survival (HR, 2.664; 95 % CI, 1.352–5.248; P = 0.005) and overall survival (HR, 3.390; 95 % CI, 1.549–7.422; P = 0.002).
BH3 profiling clearly showed that BIM expression, which depends on BAK expression, correlated with docetaxel sensitivity. BAK expression in gastric cancer is thus predictive of chemotherapeutic responses to docetaxel and clinical prognosis in patients treated with preoperative chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: The risks of myelodysplastic syndrome (MDS) and acute leukemia are increased in patients previously treated for other malignancies. Therapy-related MDS (t-MDS) occurs after exposure to certain cytotoxic agents or radiation used for cancer treatment. We report a case of t-MDS following curative chemoradiotherapy (CRT) for esophageal and oropharyngeal cancer. An 80-year-old male diagnosed with double cancers of the esophagus and oropharynx underwent definitive CRT and achieved a complete response. Six years later, he became anemic, and bone marrow examination showed 3.4% blast cells with fine chromatin structures and basophilic cytoplasm. Cytogenetic analysis indicated a complex karyotype that included chromosome 5 and 7 abnormalities. These findings were consistent with t-MDS. Subsequently, he developed acute myeloid leukemia and died 8 months later. This case indicates that long-term surveillance is needed to closely monitor the risk of t-MDS in patients treated with CRT.
No preview · Article · Sep 2015 · Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology
[Show abstract][Hide abstract] ABSTRACT: A 37-year-old woman was found in a medical checkup to have liver dysfunction. Abdominal CT scan im-ages demonstrated multiple liver tumors. She was referred to our hospital for examination and treatment. Ab-dominal enhanced CT scan images showed irregularly spreading hypovascular tumors located in the surface of both hepatic lobes. Needle liver biopsy revealed many atypical cells with positive staining for factor VIII-related-antigen and CD34. The tumor was diagnosed as an hepatic epithelioid hemangioendothelioma (HEHE). She has received intravenous administration of recombinant interleukin-2 (rIL-2) for six years with a reduction in tumor volume. HEHE is a rare tumor which has low malignant potential, also is often unresectable due to multifocal tumors involving both hepatic lobes at the time of diagnosis. There was no generally accepted therapy except surgical resection and liver transplantation. The long-term survival observed in the present case may indicate the effectiveness of rIL-2 for HEHE.
[Show abstract][Hide abstract] ABSTRACT: A60s -year-old woman with metastatic colorectal cancer was treated using mFOLFOX6 plus bevacizumab. Zoledronic acid was also administered owing to the presence of bone metastasis. The patient was admitted to our hospital with progressive hypokalemia, hypocalcemia, hypophosphatemia, and proximal renal tubular dysfunction. Adiagnosis of Fanconi syndrome was made, and was believed to be induced by zoledronic acid treatment. This treatment was discontinued, and the patient's renal tubular function recovered. Denosumab was subsequently administered to treat the bone metastasis, and no renal tubular dysfunction occurred. It was possible to continue chemotherapy, and a complete response was obtained. Fanconi syndrome induced by zoledronic acid is rare, but it may hinder chemotherapy. Therefore, monitoring renal tubular function is recommended during therapy with zoledronic acid.
No preview · Article · Jul 2015 · Gan to kagaku ryoho. Cancer & chemotherapy
[Show abstract][Hide abstract] ABSTRACT: Oxidative stress has been investigated in the context of alcoholic liver injury for many years and shown to be a causal factor of chronic hepatitis C (CHC), nonalcoholic steatohepatitis (NASH), drug-induced liver injury, Wilson's disease, and hemochromatosis. In CHC, it has been demonstrated that oxidative stress plays an important role in hepatocarcinogenesis. In cases with persistent hepatitis due to failure of hepatitis C virus eradication, or chronic liver disease, such as NASH, the treatment of which remains unestablished, it is important to reduce serum alanine aminotransferase levels and prevent liver fibrosis and development of hepatocellular carcinoma. This also suggests the importance of antioxidant therapy. Among treatment options where it would be expected that anti-inflammatory activity plays a role in their confirmed efficacy for chronic hepatitis, iron depletion therapy, glycyrrhizin, ursodeoxycholic acid, Sho-Saiko-To, and vitamin E can all be considered antioxidant therapies. To date, however, the ability of these treatments to prevent cancer has been confirmed only in CHC. Nevertheless, anti-inflammatory and anti-fibrotic effects have been demonstrated in other liver diseases and these therapies may potentially be effective for cancer prevention.
No preview · Article · Mar 2015 · World Journal of Hepatology
[Show abstract][Hide abstract] ABSTRACT: S-1 and gemcitabine (GS) combination therapy is a promising treatment for advanced biliary tract cancer (BTC). However, systemic administration of GS is associated with a high rate of grade 3 and 4 neutropenia. Hepatic arterial infusion (HAI) of gemcitabine may overcome this problem. We conducted a prospective phase 1 trial to determine the maximum tolerated dose (MTD) of S-1 and rates of dose-limiting toxicities (DLTs) associated with HAI of gemcitabine in patients with unresectable BTC.
BTC patients were treated with 21-day cycles of HAI of gemcitabine (1000 mg/m(2) on days 1 and 8) and oral S-1 (60, 70, or 80 mg/m(2) on days 1-14) until disease progression occurred.
Fifteen patients were enrolled in the study. Grade 3 and 4 neutropenia occurred in five of 15 (33 %) patients. Among six patients who were treated with 60 mg/m(2) S-1, one developed grade 4 neutropenia. DLTs (grade 4 neutropenia and bladder infection) occurred in two of six patients who were treated with 70 mg/m(2) S-1. Two of the three patients who were treated with 80 mg/m(2) S-1 experienced DLTs (grade 4 leukopenia and neutropenia and grade 3 febrile neutropenia). Thus, 80 mg/m(2) was defined as the MTD of S-1.
The MTD of oral S-1 in GS therapy is 80 mg/m(2). Furthermore, HAI of gemcitabine may reduce the rate of grade 3 and 4 neutropenia in BTC patients receiving GS therapy.
Full-text · Article · Feb 2015 · Cancer Chemotherapy and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the recommended dose (RD) of a triweekly capecitabine, oxaliplatin, irinotecan, and bevacizumab (XELOXIRI/bevacizumab) regimen that was easier to administer than FOLFOXIRI/bevacizumab, using capecitabine instead of 5-fuorouracil (5-FU), in patients with metastatic colorectal cancer (mCRC).
Patients received oxaliplatin (100 mg/m(2), day 1), capecitabine (1,700 mg/m(2) per day from day 2 to 15), irinotecan (100, 120, 150 mg/m(2) for dose levels 1, 2, 3, day 1), and bevacizumab (7.5 mg/kg, day 1), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first two cycles to determine the maximum tolerated dose (MTD).
Twelve patients received a median of 6.5 cycles of therapy (range 2-12). The DLT was grade 4 neutropenia, observed in one of six patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m(2). The most common grade ≥3 toxicities were neutropenia (41 %), anemia (17 %), diarrhea (8 %), and febrile neutropenia (8 %). The response rate and median progression-free survival were 83 % and 15 months, respectively.
XELOXIRI/bevacizumab is a feasible regimen for patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150 mg/m(2). The response rate observed is very promising and warrants further investigation.
Full-text · Article · Jan 2015 · Cancer Chemotherapy and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Adult T cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm. Humanized anti-CC chemokine receptor 4 monoclonal antibody (mogamulizumab) has been shown to be effective for relapsed/refractory ATLL. However, the effects of mogamulizumab application before allogeneic stem cell transplantation are uncertain. Here, we present an ATLL patient who was administered mogamulizumab and suffered from refractory acute graft-versus-host disease (GVHD) following umbilical cord blood transplantation (UCBT). This was accompanied by delayed reconstitution and a long-lasting reduction of regulatory T cells (Tregs). We suggest that this attenuation of Tregs influenced the clinical course of the severe/refractory GVHD following UCBT in a patient pretreated with mogamulizumab therapy.
[Show abstract][Hide abstract] ABSTRACT: ST6GalNAc I is a sialyltransferase controlling the expression of sialyl-Tn antigen (STn), which is overexpressed in several epithelial cancers, including gastric cancer, and is highly correlated with cancer metastasis. However, the functional contribution of ST6GalNAc I to development or progression of gastric cancer remains unclear. In this study, we investigated the effects of suppression of ST6GalNAc I on gastric cancer in vitro and in vivo.
Gastric cancer cell lines were transfected with ST6GalNAc I siRNA and were examined by cell proliferation, migration, and invasion assays. We also evaluated the effect of ST6GalNAc I siRNA treatment in a peritoneal dissemination mouse model. The differences in mRNA levels of selected signaling molecules were analyzed by polymerase chain reaction (PCR) arrays associated with tumor metastasis in MKN45 cells. The signal transducer and activator of transcription 5b (STAT5b) signaling pathways that reportedly regulate the insulin-like growth factor-1 (IGF-1) were analyzed by Western blot.
ST6GalNAc I siRNA inhibited gastric cancer cell growth, migration, and invasion in vitro. Furthermore, intraperitoneal administration of ST6GalNAc I siRNA- liposome significantly inhibited peritoneal dissemination and prolonged the survival of xenograft model mice with peritoneal dissemination of gastric cancer. PCR array confirmed that suppression of ST6GalNAc I caused a significant reduction in expression of IGF-1 mRNA. Decreased IGF-1 expression in MKN45 cells treated with ST6GalNAc I siRNA was accompanied by reduced phosphorylation of STAT5b.
ST6GalNAc I may regulate the gene expression of IGF-1 through STAT5b activation in gastric cancer cells and may be a potential target for treatment of metastasizing gastric cancer.
[Show abstract][Hide abstract] ABSTRACT: Branched‑chain amino acids (BCAAs) and trace element deficiencies are associated with poor prognosis in hepatitis C virus (HCV)‑infected patients. The aim of this study was to investigate the effects of BCAA and zinc‑enriched supplementation on prognostic factors in HCV‑infected patients. Fifty‑three HCV‑infected patients were enrolled in this multicenter randomized controlled trial. The patients were assigned to either the placebo (n=27) or supplement group (n=26; 6,400 mg/day BCAAs and 10 mg/day zinc) and were followed up for 60 days. Primary outcomes were prognostic factors for chronic liver disease, including the serum BCAA‑to‑tyrosine ratio (BTR), zinc levels and α‑fetoprotein (AFP) levels. There were no significant differences in any of the prognostic factors between the placebo and supplement groups at baseline. In the supplement group, the BTR and zinc levels were significantly increased compared with the placebo group (BTR: 5.14±1.59 vs. 4.23±1.14, P=0.0290; zinc: 76±11 vs. 68±11 µg/dl, P=0.0497). No significant differences were observed in AFP levels between the groups in the whole analysis. However, a stratification analysis showed a significant reduction in ΔAFP levels in the supplement group, with elevated AFP levels compared with the other groups (‑2.72±3.45 ng/ml, P=0.0079). It was demonstrated that BCAA and zinc‑enriched supplementation increased the BTR and zinc levels in the HCV‑infected patients. Furthermore, the supplementation reduced the serum AFP levels in patients who had elevated serum AFP levels at baseline. Thus, BCAA and zinc‑enriched supplementation may prolong the survival of HCV‑infected patients by improving amino acid imbalance and zinc deficiency, and by partly downregulating AFP.
No preview · Article · Nov 2014 · Molecular Medicine Reports
[Show abstract][Hide abstract] ABSTRACT: The combination of glutamine, fiber and oligosaccharides (GFO) is thought to be beneficial for alleviating gastrointestinal mucosal damage caused by chemotherapy. A commercial enteral supplementation product (GFO) enriched with these 3 components is available in Japan. We performed a retrospective study to test whether oral GFO decreased the severity of mucosal injury following hematopoietic stem cell transplantation (HSCT). Of 44 HSCT patients, 22 received GFO and 22 did not. Severity of diarrhea/mucositis, overall survival, weight loss, febrile illness/documented infection, intravenous hyperalimentation days/hospital days, engraftment, acute and chronic GVHD, and cumulative incidence of relapse were studied. Sex, age, performance status, diagnosis, disease status, and treatment variables were similar in both groups. There were fewer days of diarrhea grade 3-4 in patients receiving GFO than in those who did not (0.86 vs. 3.27 days); the same was true for days of mucositis grade 3-4 (3.86 vs. 6.00 days). Survival at day 100 was 100% in the GFO group, but only 77.3% for the patients not receiving GFO (p = 0.0091, log-rank test). Weight loss and the number of days of intravenous hyperalimentation were better in the GFO group (p < 0.001 and p = 0.0014, respectively). Although not significant, less gut bacterial translocation with Enterococcus species developed in the GFO group (p = 0.0728) than in the non-GFO group. Other outcomes were not affected. To the best of our knowledge, this is the first comparative clinical study of GFO supplementation to alleviate mucosal injury after allo-HSCT. We conclude that glutamine, fiber and oligosaccharide supplementation is an effective supportive therapy to decrease the severity of mucosal damage in HSCT.
Full-text · Article · Oct 2014 · Case Reports in Oncology
[Show abstract][Hide abstract] ABSTRACT: Reactivation of hepatitis B virus (HBV) has recently been reported as a fatal complication in patients undergoing cytotoxic chemotherapy. We herein describe a case of reactivation in a 76-year-old man who had undergone pelvic exenteration for colorectal cancer (CRC). He was treated with a modified FOLFOX6 chemotherapy regimen after the operation. Thirteen months later, his laboratory data showed severe liver dysfunction. His hepatitis B surface antigen (HBsAg) test was positive, and his HBV-DNA level was elevated. We diagnosed the patient with HBV reactivation as his HBsAg test was negative before starting chemotherapy. His liver dysfunction improved after administration of entecavir. This is the first report describing HBV reactivation following chemotherapy for an HBsAg-negative CRC patient.
Full-text · Article · Aug 2014 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Aim:
To investigate the effectiveness of phenol for the relief of cancer pain by endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN).
Twenty-two patients referred to our hospital with cancer pain from August 2009 to July 2011 for EUS-CPN were enrolled in this study. Phenol was used for 6 patients with alcohol intolerance and ethanol was used for 16 patients without alcohol intolerance. The primary endpoint was the positive response rate (pain score decreased to ≤ 3) on postoperative day 7. Secondary endpoints included the time to onset of pain relief, duration of pain relief, and complication rates.
There was no significant difference in the positive response rate on day 7. The rates were 83% and 69% in the phenol and ethanol groups, respectively. Regarding the time to onset of pain relief, in the phenol group, the median pre-treatment pain score was 5, whereas the post-treatment scores decreased to 1.5, 1.5, and 1.5 at 2, 8, and 24 h, respectively (P < 0.05). In the ethanol group, the median pre-treatment pain score was 5.5, whereas the post-treatment scores significantly decreased to 2.5, 2.5, and 2.5 at 2, 8, and 24 h, respectively (P < 0.01). There was no significant difference in the duration of pain relief between the phenol and ethanol groups. No significant difference was found in the rate of complications between the 2 groups; however, burning pain and inebriation occurred only in the ethanol group.
Phenol had similar pain-relieving effects to ethanol in EUS-CPN. Comparing the incidences of inebriation and burning pain, phenol may be superior to ethanol in EUS-CPN procedures.
Full-text · Article · Aug 2014 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Pazopanib, an oral tyrosine kinase inhibitor, is the first molecular-targeted agent approved for the treatment of advanced soft tissue sarcoma(STS). Rhabdomyosarcoma in adults is rare, accounting for less than 3%of all adult STS cases. A 57-yearold woman presented with cervical lymphadenopathy. Computed tomography revealed a heterogeneous mass in the retroperitoneum, replacing the entire right kidney. On the basis of the above findings, the patient was diagnosed with alveolar rhabdomyosarcoma. She was first treated with 4 courses of vincristine, actinomycin D, and cyclophosphamide(VAC), which resulted in a partial response. Dose reduction and delay occurred owing to hematological toxicity and febrile neutropenia. As second-line chemotherapy, the patient was administered a single daily dose of 800 mg of pazopanib. Because of an episode of hand-foot syndrome and hepatic impairment, the 800-mg daily dose of pazopanibwas reduced to a daily dose of 600 mg, which had to be further reduced to a daily dose of 400 mg owing to fatigue and anorexia. The patient maintained a partial response for a total of 4.3 months when treated with pazopanib. Therefore, this drug may be a new treatment option for patients showing metastatic STS after previous chemotherapy.
No preview · Article · Aug 2014 · Gan to kagaku ryoho. Cancer & chemotherapy
[Show abstract][Hide abstract] ABSTRACT: Background and study aims: The clinical utility of computed virtual chromoendoscopy with flexible spectral imaging color enhancement (FICE) in capsule endoscopy (CE) remains controversial. To clarify the clinical utility of FICE-enhanced CE in evaluating small bowel lesions, we quantitatively assessed white light (WL), FICE, and blue mode (BM) images and examined the sensitivity of these 3 imaging modes of small-bowel lesions from patients who underwent CE.
Methods: The CIELAB color difference (∆E) and visual analogue scales (VAS) were measured in 261 CE images (3 different lesion categories) using WL and FICE set 1, 2, and 3, and BM images, respectively. Three endoscopists reviewed CE videos with WL, 3 FICE mode settings, and BM, and compared the sensitivity and detectability for small intestinal diseases from 50 patients who underwent CE.
Results: In the assessment of visibility in the 152 vascular lesion images, the ∆E and VAS of FICE set 1, 2, and BM images were significantly higher than that of WL images. In 88 erosion/ulceration images, the ∆E and VAS of FICE set 1 and 2 images were significantly higher than that of WL images. In 21 tumor images, there were no significant differences in ∆E among these modalities. When analyzed on a per-patient basis, FICE settings 1 and 2 had the highest sensitivity (100 %) and specificity (97.3 – 100 %) for vascular lesions. As for erosive/ulcerative lesions, FICE setting 2 had the highest sensitivity (100 %) and specificity (97.2 %). For tumors or polyps, WL had the highest sensitivity (90.9 %) and specificity (87.1 %). In per-lesion analysis, FICE settings 1 and 2 showed significantly superior detection ability over WL for vascular lesions. In the detection of erosive/ulcerative lesions, FICE setting 2 was significantly superior to WL. In tumor images, there was no significant improvement with any of the settings relative to WL images.
Conclusions: FICE is most useful for improving CE image quality and detection in cases of angioectasia and erosion/ulceration of the small intestine.
[Show abstract][Hide abstract] ABSTRACT: The clinical utility of computed virtual chromoendoscopy with flexible spectral imaging color enhancement (FICE) in capsule endoscopy (CE) remains controversial. To clarify the clinical utility of FICE-enhanced CE in evaluating small bowel lesions, we quantitatively assessed white light (WL), FICE, and blue mode (BM) images and examined the sensitivity of these 3 imaging modes of small-bowel lesions from patients who underwent CE.
The CIELAB color difference (∆E) and visual analogue scales (VAS) were measured in 261 CE images (3 different lesion categories) using WL and FICE set 1, 2, and 3, and BM images, respectively. Three endoscopists reviewed CE videos with WL, 3 FICE mode settings, and BM, and compared the sensitivity and detectability for small intestinal diseases from 50 patients who underwent CE.
In the assessment of visibility in the 152 vascular lesion images, the ∆E and VAS of FICE set 1, 2, and BM images were significantly higher than that of WL images. In 88 erosion/ulceration images, the ∆E and VAS of FICE set 1 and 2 images were significantly higher than that of WL images. In 21 tumor images, there were no significant differences in ∆E among these modalities. When analyzed on a per-patient basis, FICE settings 1 and 2 had the highest sensitivity (100 %) and specificity (97.3 - 100 %) for vascular lesions. As for erosive/ulcerative lesions, FICE setting 2 had the highest sensitivity (100 %) and specificity (97.2 %). For tumors or polyps, WL had the highest sensitivity (90.9 %) and specificity (87.1 %). In per-lesion analysis, FICE settings 1 and 2 showed significantly superior detection ability over WL for vascular lesions. In the detection of erosive/ulcerative lesions, FICE setting 2 was significantly superior to WL. In tumor images, there was no significant improvement with any of the settings relative to WL images.
FICE is most useful for improving CE image quality and detection in cases of angioectasia and erosion/ulceration of the small intestine.
Full-text · Article · May 2014 · Gastrointestinal Endoscopy