Language：English   Publisher：Surgery Today  

Purposes: Owing to recent advances in induction chemo(radio)therapy, patients with unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) are sometimes indicated for conversion surgery (CS). However, the predictors for proceeding to CS are unclear. We investigated the predictive factors for CS, especially at the early stage of induction therapy, and evaluated the impact of CS on the survival. Methods: We analyzed 49 UR-LA PDAC patients retrospectively and investigated the predictive factors for proceeding to CS, including early tumor shrinkage (ETS). ETS in this study was defined as shrinkage of tumors by ≥ 15% at 8–12 weeks after the induction of treatment. Results: CS was performed in 21 patients (43%). In a multivariate logistic regression analysis, ETS was an independent predictive factor for successfully proceeding to CS (P = 0.046). The median overall survival (OS) was not reached in the CS group but was 17.2 months in the non-CS group (P < 0.0001). A multivariate analysis by the Cox proportional hazard model identified CS as the only significant independent determinant of the OS (hazard ratio: 0.26, 95% confidence interval: 0.07–0.94, P = 0.004). Conclusions: ETS by induction therapy is a significant predictor of proceeding to CS among patients with UR-LA PDAC. CS was the only independent prognostic factor for this population.

DOI： 10.1007/s00595-020-02220-2

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PubMed

Publisher：Journal of Mental Health Training, Education and Practice  

Purpose: Occupational stress-relating overwork among teachers predispose to mental disorders and eventually lead to long leave from work. Although some studies have been conducted to assess these problems among elementary and junior high school teachers, a quantitative investigation has been limited to date. In this study, the authors sought to explore the association between overwork and mental stress among Japanese elementary and junior high school teachers. Design/methodology/approach: An exploratory cross-sectional questionnaire survey was carried out on 294 Japanese elementary and junior high school teachers. The respondents filled a questionnaire on personal data, and occupational stress reaction was evaluated by Japanese version of Brief Job Questionnaire. Multiple linear regression model was used to evaluate the association between overwork information and psychological and physical stress. Findings: Working during holidays was significantly likely to increase psychological and physical stress reactions among elementary school teachers (adjusted mean difference = −1.67, 95% CI: −2.81 to −0.54) and junior high school teachers (adjusted mean difference = −5.24, 95% CI: −9.60 to −0.87). A weakly positive association was found between high risk of psychological and physical stress and marital status (p = 0.005), teacher in charge of class (p = 0.015) among elementary school teachers. Originality/value: This study indicated an association between working during holidays and psychological and physical stress reactions among elementary and junior high school teachers after adjusting for sociodemographic and work-related status. Further study for the confirmation of this finding is warranted.

DOI： 10.1108/JMHTEP-01-2020-0002

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Scopus

Language：English   Publisher：European Journal of Cancer  

Background: Peripheral sensory neuropathy (PSN) caused by oxaliplatin-based adjuvant chemotherapy adversely affects patients' quality of life. This study evaluated the efficacy and safety of capecitabine plus oxaliplatin (CAPOX) with intermittent oxaliplatin use compared with the standard CAPOX in adjuvant therapy for colon cancer. Patients and methods: Patients with curative resection for stage II/III colon cancer were randomly assigned to receive either CAPOX with continuous oxaliplatin (eight cycles of CAPOX) or CAPOX with intermittent oxaliplatin (two cycles of CAPOX, four cycles of capecitabine and two cycles of CAPOX). The primary end-point was the 1-year PSN rate, and the key secondary end-point was disease-free survival (DFS). Results: Two hundred patients were enrolled in the intent-to-treat population. After 4 patients withdrew, 196 patients were included in the safety analysis. The overall treatment completion rate was 65% for continuous vs. 89% for intermittent treatment (p < 0.001). The 1-year PSN rate was 60% (95% confidence interval [CI], 50%–70%) for continuous and 16% (95% CI, 10%–25%) for intermittent treatment (p < 0.001). After a median follow-up of 52 months, 40 events (20%) were observed. The 3-year DFS was 81% (95% CI, 71%–87%) for continuous and 84% (95% CI, 75%–90%) for intermittent treatment (hazard ratio [HR], 0.87; 95% CI, 0.47–1.63). Among patients with high-risk disease (T4 or N2-3), the 3-year DFS was 57% for continuous vs. 74% for intermittent treatment (HR, 0.66). Conclusion: CAPOX with planned intermittent oxaliplatin may be feasible as an adjuvant therapy for colon cancer and substantially reduce the duration of long-lasting PSN. Trial identifier: UMIN000012535.

DOI： 10.1016/j.ejca.2020.11.007

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PubMed

Language：English   Publisher：In Vivo  

Background/Aim: Hepatocellular carcinoma (HCC) mainly develops in the damaged liver from hepatitis C virus (HCV) or hepatitis B virus (HBV) infection in Japan. On the other hand, the occurrence of HCCs derived from the liver without viral infection has recently been increasing. Our aim was to identify characteristics specific to HCCs with virus-infected liver (HCC-BC) or those with non-B- and non-C-infected liver (HCC-NBNC), Patients and Methods: We collected preoperative serum α-fetoprotein (AFP) and Des-Gamma-Carboxy Prothrombin (DCP), also known as PIVKA-II values from surgically resected HCC cases during 1994-2017 in our department. Results: Preoperative serum AFP values of HCC-BC cases (n=284) were higher compared to HCC-NBNC cases (n=88) (p=0.016), whereas serum DCP values of HCC-NBNC cases were higher compared to HCC-BC cases (p<0.001). Multivariable analyses indicated that abnormal serum AFP [hazard ratio (HR)=1.46, 95% conficdence interval (CI)=1.03-2.07, p=0.035) was one of the significant recurrence-free survival predictors of HCC-BC cases, while abnormal serum DCP (HR=4.99, 95%CI=1.91-13.01, p=0.001) was one of the significant recurrence-free survival predictors of HCC-NBNC cases. Conclusion: HCC-NBNC cases have a different tumor marker profile from HCC-BC cases. Elevated DCP could be both a diagnostic and prognostic marker of HCC-NBNC patients.

DOI： 10.21873/invivo.12434

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PubMed

Language：English   Publisher：Oncologist  

Lessons Learned: A biweekly TAS-102 plus BEV schedule in patients with heavily pretreated mCRC showed equivalent efficacy with less toxicity compared with the current schedule of TAS-102 plus BEV combination. Biweekly TAS-102 plus BEV combination could reduce unnecessary dose reduction of TAS-102, maintain higher doses, and possibly be effective even in cases without chemotherapy-induced neutropenia (CIN). The prespecified subgroup analysis of this study showed an obvious association between CIN within the first two cycles and prognosis of biweekly TAS-102 plus BEV. Background: TAS-102 (trifluridine/tipiracil) plus bevacizumab (BEV) combination therapy has shown promising activity in patients with metastatic colorectal cancer (mCRC). However, the previously reported dose and schedule for the TAS-102 (70 mg/m2/day on days 1–5 and 8–12, every 4 weeks) plus BEV (5 mg/kg on day 1, every 2 weeks) regimen is complicated by severe hematological toxicities and difficult administration schedules. Here, we evaluated the efficacy and safety of a more convenient biweekly TAS-102 plus BEV combination. Methods: Patients with mCRC who were refractory or intolerant to standard chemotherapies were enrolled. Patients received biweekly TAS-102 (twice daily on days 1–5, every 2 weeks) with BEV (5mg/kg on day 1, every 2 weeks). The primary endpoint was progression-free survival rate at 16 weeks (16-w PFS rate). Results: From October 2017 to January 2018, 46 patients were enrolled. The recommended phase II dose was determined to be TAS-102 (70 mg/m2/day). Of the 44 eligible patients, the 16-w PFS rate was 40.9% (95% confidence interval, 26.3%–56.8%), and the null hypothesis was rejected (p <.0001). Median progression-free survival (PFS) and overall survival were 4.29 months and 10.86 months, respectively. Disease control rate was 59.1%. Common grade 3 or higher adverse events were hypertension (40.9%), neutropenia (15.9%), and leucopenia (15.9%). Conclusion: Biweekly TAS-102 plus BEV showed promising antitumor activity with safety.

DOI： 10.1634/theoncologist.2020-0643

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Language：English   Publisher：Nagoya journal of medical science  

The efficacy of nab-paclitaxel combined with gemcitabine (GnP) and of chemoradiotherapy (CRT) for unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) is still unclear. We previously conducted a phase I study of CRT using GnP and determined the recommended dose and have now designed a phase II trial to evaluate the efficacy of CRT incorporating GnP for UR-LA PDAC. Eligibility criteria are chemotherapy-naïve patients with UR-LA PDAC as defined by the NCCN guidelines version 2. 2016. Study patients will receive 100 mg/m2 nab-paclitaxel and 800 mg/m2 gemcitabine on Days 1, 8, and 15 per 4-week cycle with concurrent radiation therapy (total dose of 50.4 Gy in 28 fractions of 1.8 Gy per day, 5 days per week). Treatment will be continued until disease progression or surgery, which is to be performed only for patients in whom the disease is well-controlled at 8 months from beginning the protocol treatment. Primary endpoint is 2-year overall survival rate and co-primary endpoint is resection rate. Secondary endpoints are overall survival, progression free survival, time to treatment failure, response rate, disease control rate, early tumor shrinkage, depth of response, reduction of SUV-max on PET-CT, serum tumor markers, relative dose intensity, safety, and Quality of life. This study will show the efficacy and safety of chemoradiotherapy combined with GnP.

DOI： 10.18999/nagjms.81.2.233

Open Access

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PubMed

DOI： 10.1200/JCO.2019.37.4_suppl.647

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Language：English   Publisher：Cancer Chemotherapy and Pharmacology  

Purpose: Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted. Methods: This single-arm, open-label multicenter phase II trial recruited patients with KRAS WT mCRC from 16 institutes between January 2012 and October 2014. Panitumumab (6 mg/kg) was intravenously administered every 2 weeks, combined with fluorouracil monotherapy, in 2-week cycles. The primary objective was overall response rate, and secondary endpoints included disease-control rate, progression-free survival, overall survival, toxicity, and blood-test data. Results: Forty patients (male, 65.0%; median age, 74 years; colon cancer, 72.5%) met eligibility criteria and received 7 cycles (median) of fluorouracil chemotherapy combined with panitumumab. There were no treatment-related deaths. Median time to treatment failure was 3.2 months. 23 (57.5%) patients experienced at least one adverse effect ≥ grade 3. The response rate was 10.0% (95% confidence interval 2.8–23.7%). Median progression-free survival and overall survival were 4.3 and 11.3 months, respectively. Total lactase dehydrogenase (LDH) levels and those of LDH-4 and LDH-5, quickly changed with disease reduction or progression. Conclusions: Fluorouracil monotherapy combined with panitumumab was safely administered to patients with KRAS WT mCRC intolerant to oxaliplatin and irinotecan. Serum LDH levels may predict early responses.

DOI： 10.1007/s00280-018-3556-1

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PubMed

Language：English   Publisher：Cancer Chemotherapy and Pharmacology  

Purpose: For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen. Methods: Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined. Patients were classified according to the designated dose levels of chemoradiotherapy using the GnP regimen. After additional 6 cycles of the GnP regimen were administered, surgery was considered if the patients had stable disease and tumor marker levels had normalized. Results: DLT (grade 4 thrombocytopenia) was observed only in 1 of 12 patients, and the RD was set at level 3. Grade 3–4 leukopenia was observed in 9 (75.0%) patients, and neutropenia in 7 (58.3%). The response rate was 41.7%, and the disease control rate was 100%. Conversion surgery was performed in 6 (50%) patients, and curative resection (R0) was performed in all 6 patients (100%). Stratification according to the Evans classification system demonstrated one patient with grade 1b, one with grade 2, two with grade 3, and two with grade 4 disease. Conclusion: The RD for weekly administration was 800 mg/m2 for gemcitabine and 100 mg/m2 for nab-paclitaxel with a 50.4 Gy radiation. The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery, and should be evaluated further in a phase II trial.

DOI： 10.1007/s00280-018-3554-3

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PubMed

DOI： 10.1200/JCO.2018.36.4_suppl.523

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Language：Japanese   Publisher：Japan Pancreas Society  

<p>Resectability criteria for pancreatic cancer have been established by the NCCN guidelines and have been implemented in our clinics, however, these are revised annually and we address certain issues. The 7^th edition of the JPS guidelines was published last year and the tumor extent (T), the lymph node metastasis (N) and stage classification were revised in order to maintain the compatibility with those of the 7^th UICC guidelines. Also, new criteria for histological response and original resectability criteria for Japan are proposed. Based on these new resectability criteria, the survival outcomes in our resected pancreatic cancer patients without neoadjuvant therapy were analyzed. As a result, the definition of borderline resectable pancreatic cancer based on the degree of portal system invasion (abutment/contact) is shown to be valid. Compared to the NCCN guidelines, the new resectability criteria is written much more clearly and concisely, and is very useful for decision-making and use in clinical trials.</p>

DOI： 10.2958/suizo.33.12

CiNii Research

Language：English   Publisher：BMC Cancer  

Background: The aim of this study was to evaluate the efficacy and safety of CapeOX plus bevacizumab with a planned oxaliplatin stop-and-go strategy in Japanese patients with metastatic colorectal cancer (mCRC). Methods: Patients with untreated mCRC were treated with 4 cycles of CapeOX plus bevacizumab therapy, followed by capecitabine plus bevacizumab maintenance therapy. Reintroduction of oxaliplatin was scheduled after 8 cycles of maintenance therapy or upon tumor progression. The primary endpoint was progression-free survival (PFS), and secondary end points included overall survival (OS), objective response rate to each treatment, reintroduction rate of oxaliplatin, frequency of peripheral sensory neuropathy (PSN), and safety. Results: The 52 patients who received the protocol treatment were included in the evaluation of efficacy and safety. Median PFS and OS were 12.4 months (95% confidence interval [CI], 10.0-14.8) and 30.6 months (95% CI, 27.6-33.5), respectively. The objective response rates were 55.8% for the initial CapeOX plus bevacizumab therapy, 17.8% for capecitabine plus bevacizumab maintenance therapy, and 31.0% for reintroduced CapeOX plus bevacizumab therapy. The frequency of PSN was 63.5%, including 3.8% of patients with grade 3 PSN. No patients required treatment discontinuation because of PSN during the induction or maintenance therapy. Conclusions: CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy is a feasible first-line treatment for Japanese patients with mCRC. Trial registration: This trial is registered with the University Hospital Medical Information Network in 15 March 2010 ( UMIN000006478 ).

DOI： 10.1186/s12885-017-3245-1

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PubMed

DOI： 10.1200/JCO.2017.35.4_suppl.259

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DOI： 10.1200/JCO.2017.35.4_suppl.390

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Language：English   Publisher：Annals of Surgical Oncology  

Background: Advantages of neoadjuvant chemotherapy combined with monoclonal antibodies for treating patients with resectable colorectal cancer liver metastasis (CLM) have not been established. The purpose of this study was to evaluate the efficacy and safety of oxaliplatin-based regimen (FOLFOX or XELOX) plus monoclonal antibodies (cetuximab or bevacizumab) treatment in patients with resectable CLM. Methods: A single-arm, open-label, multicenter, phase II trial was conducted for patients aged ≥ 20 years with resectable and untreated CLM. Patients received preoperative FOLFOX (6 cycles) or XELOX (4 cycles). Cetuximab or bevacizumab was administered to patients with wild-type or mutated KRAS codons 12 and 13, respectively. The primary endpoint was progression-free survival (PFS). Results: Between January 2010 and June 2012, 47 patients were enrolled from 12 institutions. Wild-type or mutant KRAS sequences were examined in 32 and 15 patients, respectively. Twenty-one (45 %) patients experienced Grades 3/4 adverse events, and 55 % of all patients responded to therapy. The sizes of tumors of patients in the wild-type KRAS group were significantly reduced compared with those of the mutant KRAS group. The overall rates of liver resection and postoperative morbidity were 83 and 14 %, respectively, and the median PFS was 15.6 months. The median PFS times of the KRAS wild-type and mutant groups were 22.5 months and 10.5 months, respectively. Conclusions: Neoadjuvant therapy using FOLFOX/XELOX combined with monoclonal antibodies did not improve PFS, although it was administered safely and had less adverse effects after liver resection.

DOI： 10.1245/s10434-016-5557-9

Open Access

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PubMed

Language：English   Publisher：Epigenetics  

Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments of individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001–2013 were examined. PAX5, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identified as an extremely tumor-specific event in squamous cell carcinogenesis of head and neck. PAX5 methylation status was evaluated by quantitative MSP (QMSP) assays. Mean QMSP value was 15.7 (0–136.3) in ESCCs and 0.3 (0–8.6) in adjacent normal tissues (P < 0.001). The 78 cases were divided into high QMSP value (high QMSP, n = 26) and low QMSP value (low QMSP, n = 52). High QMSP cases were significantly associated with downregulated PAX5 expression (P = 0.040), and showed significantly poor recurrence-free survival [Hazard Ratio (HR) = 2.84; P = 0.005; 95% Confidence Interval (CI): 1.39–5.81] and overall survival (HR = 3.23; P = 0.002; 95%CI: 1.52–7.01) in multivariable analyses with histopathological factors. PAX5-knockdown cells exhibited significantly increased cell proliferation and cisplatin resistance. PAX5 gene methylation can predict poor survival outcomes and cisplatin sensitivity in ESCCs and could be a useful diagnostic tool for cancer therapy selection.

DOI： 10.1080/15592294.2017.1365207

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Language：English  

DOI： 10.1186/s40792-016-0166-1

Open Access

PubMed

Language：English   Publisher：Annals of Surgical Oncology  

Akinobu Kondo’s first name is incorrect in the original article. It is corrected as shown in this erratum. Also, the following Acknowledgment was inadvertently omitted: Acknowledgment This study was supported, in part, by the nonprofit organization Epidemiological and Clinical Research Information Network (ECRIN).

DOI： 10.1245/s10434-016-5593-5

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PubMed

Language：English   Publisher：Journal of Surgical Research  

Background Hepatocellular carcinoma (HCC) is one of the top five causes of cancer-related deaths worldwide. We developed a novel technique to identify cancer-related genes of HCC as follows: triple-combination array analysis, which combines gene expression profiles, single nucleotide polymorphism arrays, and methylation arrays. Materials and methods Triple-combination array analysis was performed on one HCC sample from a 68-y-old female patient, and one candidate cancer-related gene was selected. Subsequently, we analyzed the identified gene by quantitative real-time reverse-transcriptase polymerase chain reaction (PCR) and methylation-specific PCR in nine HCC cell lines and in samples from 48 HCC patients. Additionally, we evaluated gene expression by immunohistochemistry and Western blotting. Results Using this method, protein tyrosine kinase 7 (PTK7) was detected as a candidate cancer-related gene. PTK7 was revealed to be hypermethylated (methylation value 0.826, range 0-1.0) in cancer tissue, compared with that of adjacent noncancerous tissues (0.047) by methylation array. Of the 48 clinical samples, 30 HCC samples (62.5%) showed PTK7 promoter hypermethylation. Downregulation of PTK7 (expressions in tumor tissues decreased by ≥50% compared with the noncancerous tissues) was significantly associated with age >60 y (P = 0.030) and elevation in serum protein induced by vitamin K absence or antagonists-II (P = 0.033). Moreover, patients with downregulation were significantly inferior in overall survival (P < 0.001) than the others. Conclusions Our data imply that PTK7 acts as a cancer-related gene and may be a potent prognostic marker for HCC. Triple-combination array analysis was once again found to be useful in identifying cancer-related genes.

DOI： 10.1016/j.jss.2014.12.045

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PubMed

Language：English   Publisher：International Journal of Oncology  

Hepatocellular carcinoma (HCC) has a high likelihood of recurrence and a poor prognosis. To detect cancer-related genes of HCC, we developed a new technique: triple combination array analysis, consisting of a methylation array, a gene expression array and a single nucleotide polymorphism array. A surgical specimen obtained from a 68-year-old female HCC patient was analyzed using triple combination array, which identified cyclin J (CCNJ) as a candidate cancer-related gene of HCC. Subsequently, samples from 85 HCC patients were evaluated for CCNJ promoter hypermethylation and expression status using methylation-specific PCR (MSP) and quantitative reverse transcriptase RT-PCR, respectively. CCNJ was found to be hypermethylated (methylation value, 0.906; range, 0-1.0) in cancer tissue, compared with adjacent non-cancerous tissue (0.112) using a methylation array. MSP revealed that CCNJ was hypermethylated in 67 (78.8%) of the tumor samples. CCNJ expression was significantly decreased in cases with hypermethylation (P<0.0001). Furthermore, cases with both promoter hypermethylation and decreased expression of CCNJ in the tumor tissue had a worse overall survival than the other cases (P=0.0383). In conclusion, our results indicated that CCNJ could be a novel prognostic marker of HCC, and this study indicated that triple combination array analysis was effective in detecting new tumor-related genes and their mechanisms.

DOI： 10.3892/ijo.2015.2892

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PubMed

Language：English   Publisher：Oncology Reports  

When assessing hepatocellular carcinoma (HCC), it is important to examine prognostic factors in the background normal liver tissue and consider malignant aspects of the primary lesion. Candidate genes were extracted from the background normal liver samples via multiarray analysis. Control samples, termed supernormal (SN) liver, were obtained from 11 cases of metastatic liver cancer. Corresponding normal (CN) liver tissue was surgically obtained from a typical HCC patient with chronic hepatitis C background for comparison. Expression profile and methylation array demonstrated that Janus kinase 2 (JAK2) gene expression was increased by 2.378-fold in the CN tissue. Methylation array reported a lower value for CN (0.125) than SN tissues (0.748). We then investigated JAK2 expression by real-time quantitative reverse transcription-polymerase chain reaction in 100 consecutive resected HCC cases. The average expression level of JAK2 (normalized to GAPDH) was significantly lower in CN (9.24±6.43, n=100) than in SN (35.21±21.38, n=11) tissues (P<0.001). As such a result was contrary to our expectation, the case used for array analysis seemed to be a rare incidence. One hundred HCC cases were subsequently divided into two groups based on JAK2 expression in the adjacent normal tissue: one consisting of the upper 70% of cases (n=70) and the other of the remaining 30% (n=30). Higher JAK2 expression in the adjacent tissue demonstrated significant correlation with worse survival (P=0.022). Furthermore, multivariate analysis identified higher JAK2 expression in the background normal liver tissue of HCC as an independent prognostic factor (P=0.032). Our findings suggest that higher JAK2 expression in the background normal liver tissue of HCC may be a good prognostic biomarker for resected HCC.

DOI： 10.3892/or.2014.3621

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DOI： 10.1200/jco.2015.33.3_suppl.539

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DOI： 10.1200/jco.2015.33.3_suppl.761

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Language：Japanese   Publisher：Japan Surgical Association  

Herein, we report a case of a leiomyosarcoma arising from the left ovarian vein, which is extremely rare. A 65-year-old woman was referred to our hospital because of a palpable mass in her left lower abdomen. The pre-operative diagnosis was left ovarian cancer or leiomyosarcoma of the ovarian vein. The operative findings revealed that the ovary was obviously normal and the left ovarian vein was involved by the mass. We resected the mass and the left ovary. Histopathological findings revealed that the tumor was connected to the left ovarian vein, and immunohistochemical staining demonstrated that the tumor cells expressed smooth muscle cell antigens, such as smooth muscle actin and desmin, but they showed no staining for S-100, CD34, or c-kit. As a result, a diagnosis of leiomyosarcoma was made. The postoperative course was uneventful and the patient has had no recurrence after 6 months.

DOI： 10.3919/jjsa.76.396

Open Access

CiNii Research

DOI： 10.1158/1538-7445.AM2014-3816

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DOI： 10.1158/1538-7445.AM2014-4717

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DOI： 10.1158/1538-7445.AM2014-3822

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DOI： 10.1158/1538-7445.AM2014-2870

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Language：English   Publisher：Annals of Surgical Oncology  

Background. Hepatocellular carcinoma (HCC) often recurs and multicentric occurrence is more common than intrahepatic metastases after surgery. Prognostic prediction is insufficient when considering only factors in resected primary tumor. Methods. Control samples, termed supernormal (SN) liver, were taken from 11 cases of metastatic secondary malignancies of the liver. We selected adjacent nonneoplastic liver tissue from a patient with HCC and liver cirrhosis by hepatitis C (CN) for comparison. Results. Expression profiling and methylation arrays were performed. We identified genes showing differences in both arrays. Prognosis was predicted for 179 cases of HCC based on gene expression. Expression profiling showed that expression of thimet oligopeptidase (THOP1) gene was decreased 4.119-fold in CN. Methylation array showed a higher value for CN (0.869) than SN (0.488). We studied THOP1 gene expression by real-time reverse transcriptase polymerase chain reaction. The average expression level of THOP1 (THOP1 value × 103/GAPDH) decreased in matching normal tissue (14.53 ± 10.14) relative to SN (78.14 ± 44.50). The group with higher than average THOP1 expression (n = 74) showed significant correlations with prolonged survival (P = 0.0383). Strongly reduced THOP1 expression (<3.0, n = 50) was shown to be an independent prognostic factor by multivariate analysis (P = 0.0024). Conclusions. Expression of the THOP1 gene in the background liver of HCC is likely to be a good biomarker for risk of HCC development. When assessing HCC, it is important to extract prognostic factors from background liver tissue as well as considering malignant factors of the primary cancer lesion. © 2014 Society of Surgical Oncology.

DOI： 10.1245/s10434-014-3581-1

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Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：Japanese   Publisher：一般社団法人日本外科学会  

CiNii Research

Language：English   Publisher：Oncology Reports  

Patients with hepatocellular carcinoma (HCC) have a poor prognosis, and novel molecular targets for treating recurrence and progression of the disease along with associated biomarkers are urgently required. In the present study, expression and the regulatory mechanism of TUSC1 (tumor suppressor candidate 1) were investigated to determine if it is a candidate tumor suppressor gene for HCC, which shows repressed transcription that involves aberrant DNA methylation. TUSC1 mRNA expression levels in HCC cell lines and 94 pairs of surgical specimens were determined using quantitative real-time reverse transcription polymerase chain reaction assay. Methylation status of HCC cell lines and clinical samples were analyzed to investigate the regulatory mechanism of TUSC1 transcription and the relationship between the methylation status of the TUSC1 gene and clinicopathological factors. The expression and distribution of the TUSC1 protein in liver tissues were determined using immunohistochemistry. A majority of HCC cell lines (89%) and surgical specimens (84%) demonstrated reduced expression levels of TUSC1 mRNA compared with paired non-cancerous liver tissues. The mean mRNA expression level in HCC was significantly lower than in corresponding non-cancerous liver. In contrast, no significant difference was found in TUSC1 mRNA expression level between adjacent normal and cirrhotic liver tissue from HCC patients. The TUSC1 protein expression pattern in HCC and liver tissues was consistent with TUSC1 mRNA expression. Twenty-nine (31%) of 94 patients showed intragenic hypermethylation of the TUSC1 gene in HCC, and hypermethylation was significantly associated with advanced pathological stage. Subsequently, patients with hypermethylation of the TUSC1 gene had a significantly poorer prognosis than patients without hypermethylation. Our results suggest that TUSC1 is a candidate tumor suppressor gene and intragenic hypermethylation is one of the suppressive mechanisms that regulate TUSC1 transcription in HCC. Intragenic methylation of the TUSC1 gene may serve as a novel prognostic marker of HCC.

DOI： 10.3892/or.2013.2939

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Publisher：Hepato-Gastroenterology  

We performed total pancreatectomy with segmental duodenectomy preserving the gastrocolic trunk and right gastroepiploic vein, to prevent gastric venous congestion, for treatment of pancreatic tumor. This is believed to be the first report of such a procedure. The patient was a 58-year-old man with high serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen. He was examined by abdominal ultrasonography and computed tomography, and diagnosed with cancer of the pancreatic body. No distant metastasis was found. We decided to perform distal pancreatectomy. After surgery, the cut edge of the distal pancreas was subjected to frozen section examination, and there was carcinoma in situ in the stump of the main pancreatic duct. Therefore, we cut the pancreatic head partially, twice, but carcinoma in situ remained. We additionally performed pancreatic head resection with segmental duodenectomy, with preservation of the gastroduodenal artery, right gastroepiploic artery, gastrocolic trunk and right gastroepiploic vein to prevent gastric venous congestion. The postoperative course was uneventful and the patient remains in good condition. This surgical technique is considered feasible and safe for prevention of gastric venous congestion. © H.G.E. Update Medical Publishing S.A.

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PubMed

Web of Science

Language：Japanese   Publisher：Japan Surgical Association  

The prognosis of adrenocortical cancer is poor, and there is not established treatment for progressive and recurrent adrenocortical cancer. We report a case of adrenocortical cancer successfully treated with chemotherapy.<BR>The patient was a 29-year-old woman. She had been treated for malignant lymphoma with chemotherapy at the age of 17. When she was 27 years old, she was referred to the hospital because of a retroperitoneal tumor detected by a CT scan performed for persistent fever. No definite diagnosis was made and thus laparotomy was performed. The tumor was diagnosed as anaplastic carcinoma by an intraoperative rapid histopathological study. We did not perform surgical resection, and started chemotherapy (Etopside+CDDP). But the final histopathological diagnosis was adrenocortical cancer. We thus performed surgical resection after three courses of the chemotherapy. One year four months after the surgery, peritoneum recurrence was detected and the same chemotherapy (Etopside+CDDP) was performed. The tumor of the peritoneum reduced after eight courses of the chemotherapy.

DOI： 10.3919/jjsa.69.671

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