Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/bjs/znaf049

Open Access

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：日本臨床外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: Gemcitabine and nab-paclitaxel combination therapy (GnP) is a standard treatment for unresectable or recurrent pancreatic cancer. However, fatigue and malaise are frequent adverse effects. Recently, Kampo medicine containing ginsenoside has been reported to relieve cancer-related fatigue. Therefore, in this randomized trial, we used red ginseng powder (Koujin, TJ-3020), which contains ginsenoside, to evaluate its effect on unresectable or recurrent pancreatic cancer treatment. MATERIALS AND METHODS: From December 2017 to December 2020, we enrolled 40 pancreatic cancer patients. The patients underwent 2 cycles of GnP for unresectable cancer or postoperative recurrence. The patients were randomized into group A (red ginseng powder administration) or group B (no red ginseng). In group A, 0.67 g of red ginseng powder was taken orally 3 times a day before each meal for 56 days of the planned chemotherapy period. The Cancer Fatigue Scale evaluated physical, mental, cognitive, and comprehensive fatigue over time. RESULTS: The patients' backgrounds, including age, sex, pancreatic cancer status, and relative dose intensity of the GnP chemotherapy, did not differ between groups A and B. Cases with abnormal CA19-9 were frequently assigned to group A. None of the Cancer Fatigue Scale fatigue scores differed significantly between the groups. Mental fatigue score was significantly higher in patients aged ≥70 years (odds ratio: 4.57; P  = 0.033), and recurrent pancreatic cancer status tended to influence all fatigue scores. However, no other critical factor significantly affected each score. CONCLUSIONS: In this phase II randomized trial, oral administration of red ginseng powder at 2.0 g per day did not reduce pancreatic cancer patients' fatigue or malaise induced by GnP combination chemotherapy.

DOI： 10.1097/MPA.0000000000002446

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Multimodal treatment is now the primary strategy for managing pancreatic cancer. Blood-based protein markers are sometimes useless for evaluating the real-time disease condition to determine treatment strategies. This study focused on detecting novel exosomal lipid biomarkers, as exosomes contain several biological mediators. MATERIALS AND METHODS: Lipidomic analysis was conducted by liquid chromatography-mass spectrometry (LC-MS) using serum exosome-derived lipid samples from four pancreatic ductal adenocarcinoma (PDAC) patients and four healthy controls. Some candidates were ascertained using multiple time-point blood samples from four additional PDAC patients. Furthermore, we validated them using an additional twelve multimodal-treated PDAC patient cohort. RESULTS: Nontarget LC-MS analysis revealed that lysophosphatidylcholine (LPC) expression levels were significantly decreased in PDAC patients compared to healthy controls. Multiple time-point blood samples demonstrated that LPC (16:0) and LPC (18:1) consistently showed lower levels in relapsed cases than in non-relapsed cases over time. In the validation cohort, a low LPC level before initial treatment was associated with histological lymphatic invasion (p=0.04) and was linked to progressive-free survival (PFS) (p=0.04). CONCLUSION: PDAC patients with initially low LPC levels in the blood exosomes demonstrated an unfavorable PFS. Exosomal lipid markers may serve as potential indicators for disease monitoring in pancreatic cancer patients undergoing multimodal treatment.

DOI： 10.21873/anticanres.17520

Open Access

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：金原出版  

DOI： 10.18888/op.0000004309

CiNii Research

Language：English  

DOI： 10.1200/JCO.2025.43.4_suppl.798

Open Access

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: The severe malignancy of pancreatic ductal adenocarcinoma (PDAC) is mainly due to frequent local invasiveness and distant metastasis. As for local invasiveness, we previously reported that cancer-specific molecular alterations detected on resected PDAC specimen surfaces, so-called molecular surgical margin (MSM) positiveness, were significantly associated with postoperative locoregional recurrence and distant metastasis. However, due to anatomical limitations, achieving adequate surgical margins during pancreatic cancer resection is often challenging. Therefore, predicting local invasiveness based on the primary tumor's gene profile is crucial to avoid positive MSM. MATERIALS AND METHODS: Genome-wide miRNA expression profiles were examined and compared between MSM-positive and negative cases. Candidate miRNAs were evaluated in another validation cohort, and their clinicopathological characteristics were examined. Mimic or inhibitor constructs of the candidate miRNA were transfected to PDAC cell lines to evaluate the miRNA function in the pancreatic cancer cell lines and detect the downstream targets. RESULTS: Among some candidates with highly expressed miRNAs in MSM-positive cases by miRNA expression array, recurrence-free survival (RFS) was significantly shorter in the miR-210-3p high expression group (p=0.015). High miR-210-3p was significantly associated with large tumor diameter (p=0.001), anterior invasion positive (p=0.010), and positive lymph node metastasis (p<0.001). miR-210-3p inhibition in PDAC cell lines resulted in decreased proliferation and invasiveness. The iron-sulfur cluster assembly enzyme (ISCU) gene was identified as a target of miR-210-3p. ISCU reduction was significantly observed in PDAC primary tumors with high levels of miR-210-3p, leading to mitochondrial dysfunction in miR-210-3p-overexpressing PDAC cell lines, as demonstrated by glycolysis stress tests. CONCLUSION: Highly expressed hypoxia-inducible miR-210-3p in primary PDAC tissues induces locally invasive characteristics through mitochondrial dysfunction by suppressing ISCU expression, which may result in poor postoperative RFS outcomes.

DOI： 10.21873/anticanres.17297

Open Access

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：(株)篠原出版新社  

Web of Science

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407214706

CiNii Research

Language：English   Publisher：Surgery Today  

Purposes: The purpose of this study was to compare the financial burden of surgery for retroperitoneal sarcoma (RPS) and gastric cancer (GC). Methods: All patients who underwent surgery for GC or RPS between 2020 and 2021 at Nagoya University Hospital were included. The clinical characteristics, surgical fees per surgeon, and surgical fees per hour were compared between the two groups. Results: The GC and RPS groups included 35 and 63 patients, respectively. In the latter group, 37 patients (59%) underwent tumor resection combined with organ resection; the most common organ was the intestine (n = 23, 37%), followed by the kidney (n = 16, 25%). The mean operative time (248 vs. 417 min, p < 0.001) and intraoperative blood loss (423 vs. 1123 ml, p < 0.001) were significantly greater in the RPS group than in the GC group. The mean surgical fee per surgeon was USD 1667 in the GC group and USD 1022 in the RPS group (p < 0.001) and USD 1388 and USD 777 per hour, respectively (p < 0.001). Conclusions: The financial burden of surgical treatment for RPS is unexpectedly higher than that for GC.

DOI： 10.1007/s00595-024-02831-z

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Organs of the digestive system are frequent sites of cancer development, and digestive tract cancers are the leading causes of death worldwide, including in Japan. Most of these cancers are associated with smoking or drinking habits. This study focused on the clinical and genomic characteristics of patients with these cancers using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which comprises a large volume of data on Japanese patients who have undergone tumor profiling gene panel tests. PATIENTS AND METHODS: The genomic and clinical data from patients with digestive tract cancers registered in C-CAT between 2019 and 2023 were retrospectively reviewed. The data were derived from 412 patients with esophageal squamous cell carcinoma, 558 with gastric adenocarcinoma, 3,368 with colorectal adenocarcinoma, 139 with hepatocellular carcinoma, 2,050 with cholangiocarcinoma, and 2,552 with pancreatic ductal adenocarcinoma. RESULTS: CDKN2A, CDKN2B, and MTAP mutations were associated with both smoking and drinking history, and patients with these mutations had a worse prognosis. Almost all gene alterations in CDKN2B and MTAP were deletions, often accompanied by CDKN2A deletion. CDKN2A mutation emerged as the most decisive prognostic factor among these mutations. Although CDKN2A mutations were frequently seen in esophageal squamous cell carcinoma, cholangiocarcinoma, and pancreatic ductal adenocarcinoma, statistically significant differences in survival outcomes were only identified in the latter two. CONCLUSION: CDKN2A mutations were associated with smoking and drinking in digestive cancers. This mutation was prevalent among patients with cholangiocarcinoma and pancreatic ductal adenocarcinoma, for whom they could serve as prognostic factors.

DOI： 10.21873/anticanres.17077

Open Access

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：(一社)日本外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Proximal gastrectomy (PG) is a therapy for early-stage proximal gastric cancer and offers advantages such as the preservation of food storage capacity and less body weight loss (BWL). Nevertheless, significant BWL following PG may occur, affecting the patient's well-being and survival. In this study, we aimed to identify the relevant factors for BWL following PG by analyzing an institutional database of patients. PATIENTS AND METHODS: We enrolled 58 consecutive patients who underwent PG for gastric or esophagogastric junction cancer at our institution between April 2004 and March 2021. Based on BWL at 12 months postoperatively, we retrospectively compared and examined patient characteristics, surgical details, and nutritional markers. RESULTS: The mean BWL of the 58 patients included in this analysis was 14.0±7.2%. When the patients were divided into BWL-moderate (n=29) and BWL-severe (n=29) groups using a cutoff value of 15.7%, the latter experienced early BWL within 1 month postoperatively, primarily due to body fat mass reduction, with no recovery during the 60 months of follow up. In contrast, gradual recovery was observed among patients in the BWL-moderate group after experiencing the lowest body weight 24 months postoperatively. A greater decrease in body fat mass than in muscle mass was observed in both groups. Blood hemoglobin levels did not recover in the BWL-severe group. CONCLUSION: The BWL-severe group after proximal gastrectomy demonstrated significantly greater early postoperative BWL, primarily attributed to a reduction in body fat mass, with hardly any recovery. Early postoperative nutritional intervention might be proposed to prevent long-term BWL.

DOI： 10.21873/anticanres.16963

Open Access

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：The Japanese Society of Gastroenterological Surgery  

<p>The patient was a 63-year-old woman who was diagnosed with a pancreatic tumor in an abdominal ultrasound examination. CT showed a 33-mm low density mass anterior to the tail of the pancreas. The lesion showed incremental and heterogeneous contrast. MRI showed a low intensity signal on T1WI, a low intensity signal in the center and a mildly high intensity signal in the margins on T2WI, and a high intensity signal in the margins and a low intensity signal in the center on DWI. Based on these findings, solid pseudopapillary neoplasm (SPN) or desmoid tumor was suspected as the differential diagnosis. Considering the risk of seeding, we decided not to conduct a biopsy and to perform laparoscopic pancreatectomy. Intraoperative findings suggested invasion of the gastric wall. Therefore, distal pancreatectomy with partial resection of the stomach wall and splenectomy was performed. The pathological diagnosis was desmoid tumor. Reports of laparoscopic pancreatic resection for intra-abdominal desmoid tumor are rare, and we report our findings including a literature review.</p>

DOI： 10.5833/jjgs.2022.0100

Open Access

Scopus

CiNii Research

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407214373

CiNii Research

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞ポイント ◆オペ記事の作成は遅くとも当日中に,オペに関する記憶が残っている間に行う.◆手術内容(切離した動静脈や臓器の切除範囲,リンパ節郭清範囲,再建方法など)をもれなく記載する.

DOI： 10.11477/mf.1407214373

Language：English   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Background: Staging laparoscopy (SL) has been advocated for pancreatic cancer, mainly to evaluate the peritoneal washing cytology (CY) status, which seems to impact the prognosis of pancreatic cancer. To establish an optimal treatment strategy for CY positive (CY+) pancreatic cancer cases, real-world clinical data about CY status-depending surgical outcomes should be accumulated. Methods: Peritoneal washing samples were collected from 183 consecutive patients who could be classified as either resectable or borderline resectable (BR) pancreatic cancer between January 2012 and December 2020. Correlations between the CY status and other clinicopathological parameters with the recurrence patterns and survival outcomes were examined. In addition, we analyzed several risk factors for the CY+ status and attempted to identify the patient population that may benefit most from SL. Results: A total of 24 of the 183 patients were CY+. Peritoneal recurrence occurred more frequently in CY+ cases than in CY− cases (29% vs. 6%, p <.001) and median survival time after surgery was significantly shorter in CY+ cases than in CY− cases (28.5 months vs. 67.5 months; p <.001). In detail, almost all CY+ patients among curative resection-intended cases had either elevated preoperative serum CA19-9 levels (≥250 U/mL) or DUPAN-2 levels (≥150 U/mL). Significant predictive factors of CY positivity were BR status (p =.028) and serum CA19-9 level exceeding 250 U/mL (p =.008). Conclusion: CY status was identified as an independent prognostic factor, and SL examination should be recommended, especially for patients with risk factors for CY positivity, such as BR cancer and elevated serum CA19-9 levels.

DOI： 10.1002/jhbp.1373

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIM: Pancreatic cancer cells release certain tissue factors into the bloodstream. It is well known that pancreatic cancer progresses with thrombus formation. Because we routinely measure serum D-dimer levels in preoperative patients as a screening marker of deep venous thrombosis, we examined its association with high serum D-dimer in our cohort of pancreatic cancer resected cases. PATIENTS AND METHODS: We examined 315 patients with pancreatic ductal adenocarcinoma who underwent surgical resection in our department from January 2012 to July 2021. All cases were divided into high D-dimer cases (n=118) and low D-dimer cases (n=197) using the cut-off value of 1.0 μg/ml, an institutional upper limit. Clinicohistological characteristics and postoperative survival outcomes were evaluated. RESULTS: Preoperative high D-dimer cases showed significantly worse progression-free survival (PFS) (p=0.021) and overall survival (OS) (p=0.027) than low D-dimer cases; median PFS was 13.9 months versus 21.4 months, and that of OS was 33.4 months versus 68.0 months. Clinicohistological characteristics of high D-dimer cases were age over 70 years (p<0.001), pathological portal vein invasion (p=0.003), and initially borderline resectable or unresectable cases (p=0.027). Multivariate analysis indicated that preoperative high D-dimer was a significant prognostic factor of PFS (hazard ratio=1.42, p=0.025) and OS (hazard ratio=1.51, p=0.036). CONCLUSION: Preoperative high serum D-dimer over 1.0 μg/ml was associated with pathological portal vein invasion and could be an unfavorable prognostic marker of PFS and OS after surgery, typically due to distant metastasis.

DOI： 10.21873/anticanres.16491

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The pretreatment albumin-globulin ratio (AGR) is a frequently used inflammation-associated factor that has been reported to have associations with the survival outcomes of various malignancies. METHODS: We retrospectively analyzed 162 patients with pancreatic cancer who underwent preoperative treatment followed by curative surgery at Nagoya University Hospital between April 2010 and December 2020. Representative nutritional status indicators of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and albumin-globulin ratio (AGR) were calculated for each case. RESULTS: Among pretreatment blood examination parameters, only AGR (cutoff: 1.33) showed a significant difference in overall survival time (OS) and progression-free survival time (PFS) from the beginning of the preoperative treatment. Median PFS was 22.3 mo, in high AGR cases and 17.1 mo, in low AGR cases (P = 0.019). Median OS was 48.7 mo, in high AGR cases and 32.9 mo, in low AGR cases (P = 0.043). CONCLUSION: High pretreatment AGR may be a favorable prognostic factor for pancreatic cancer patients who received preoperative multimodal therapy followed by curative cancer resection. It may imply that nutritional status and inflammation control before the multimodal treatment affect the survival outcomes of pancreatic cancer cases and needs to be optimized.

DOI： 10.1080/01635581.2023.2191384

Open Access

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407213928

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1245/s10434-022-12084-0

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The axon guidance gene family, SLIT/ROBO pathway, controls neural network formation, which correlates with the development of several cancers. METHODS: We found through analysis of the public database that ROBO4, one of the axon guidance molecules among the SLIT/ROBO family, is significantly downregulated in primary pancreatic cancer tissues compared with adjacent normal tissues. We carried out transfection experiments using three pancreatic cancer cell lines (MiaPaCa-2, BxPC-3, and SW1990) and one pancreatic duct epithelial cell line (HPDE6c7). A total of 51 clinical samples were then examined by immunohistochemical staining to find an association between ROBO4 expression at the protein level, clinical characteristics, and surgical outcomes. RESULTS: ROBO4 overexpression suppressed the invasion and migration abilities in MiaPaCa-2 and BxPC-3, while ROBO4 siRNA transfection to SW1990 and HPDE6c7 enhanced those activities. PCR-based profiling detected MMP-9 as a candidate downstream target of ROBO4, which was validated by decreased MMP-9 activity after the ROBO4 overexpression assay. High ROBO4 expression clinical samples had significantly better overall survival rather than low ROBO4 cases (P = 0.048). CONCLUSION: These findings suggest that decreased ROBO4 expression activates malignant phenotypes in cancer cells and is correlated with poor survival outcomes in pancreatic cancer.

DOI： 10.1245/s10434-022-12039-5

Web of Science

Scopus

PubMed

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1407213835

CiNii Research

Language：English   Publisher：Anticancer Research  

Background/Aim: The regimen of nanoliposomal irinotecan plus 5-fluorouracil and leucovorin (Nal-IRI/FL) was approved in Japan as second-line chemotherapy after gemcitabine-based treatment for pancreatic ductal adenocarcinoma (PDAC) in 2020. We examined the difference in outcome between patients treated with second-line folinic acid, fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX) and those treated with nal-IRI/FL after first-line gemcitabine and nab-paclitaxel (GnP). Patients and Methods: The outcomes of 34 patients with PDAC who received second-line FOLFIRINOX (n=21) or nal-IRI/FL (n=13) after GnP at our Department from January 2016 to June 2021 were reviewed retrospectively. Results: Patient backgrounds did not differ between the groups. Dose reduction was more frequently required for treatment with FOLFIRINOX than with nal-IRI/FL (86% vs. 46%, p=0.022). Pegfilgrastim and aprepitant were used more frequently in the FOLFIRINOX group (both p<0.01). Progression-free survival (5.9 vs. 8.3 months) and overall survival (9.1 vs. 11.2 months) did not differ significantly between the groups. The frequency of grade 3 (Common Terminology Criteria for Adverse Events) or higher adverse events was similar between the groups. All-grade peripheral neuropathy was more common in the FOLFIRINOX group (100% vs. 77%, p=0.048). Conclusion: FOLFIRINOX and nal-IRI/FL as second-line therapy after GnP provided similar prognoses, although supportive treatment and dose reduction were more frequently required for FOLFIRINOX.

DOI： 10.21873/anticanres.15882

Web of Science

Scopus

PubMed

Language：English   Publisher：Journal of Hepato-Biliary-Pancreatic Sciences  

Patients with pancreatic ductal adenocarcinoma (PDAC) with peritoneal dissemination have a dismal prognosis because discontinuation of systemic chemotherapy is required for massive ascites or poor performance status. The natural history, diagnosis and treatment of PDAC with peritoneal dissemination have not been fully investigated. We systematically reviewed published information on the clinical diagnosis and treatment of PDAC with peritoneal dissemination using the PubMed database (2000-2020) and provided recommendations in response to clinical questions. This guideline was created according to the "Minds Clinical Practice Guideline Development Guide 2017". The literature quality and body of evidence were evaluated with the GRADE System and classified into four levels (“strong”, “medium”, “weak”, “very weak”). The strength of each final recommendation was decided by a vote of committee members based on the GRADE Grid method. These guidelines address three subjects: diagnostic, chemotherapeutic, and surgical approaches. They include nine clinical questions and statements with recommendation strengths, evidence levels, and agreement rates, in addition to one “column”. This is the English synopsis of the 2021 Japanese clinical practice guideline for PDAC with peritoneal dissemination. It summarizes the clinical evidence for the diagnosis and treatment of PDAC with peritoneal dissemination and provides future perspectives.

DOI： 10.1002/jhbp.1085

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Pancreatic cancer is one of the lethal cancers among solid malignancies. Pathological diagnosis of surgical margins is sometimes unreliable due to tissue shrinkage, invisible field cancerization and skipped lesions like tumor budding. As a result, tumor recurrences sometimes occur even from the pathologically negative surgical margins. METHODS: We applied molecular surgical margin (MSM) analysis by tissue imprinting procedure to improve the detection sensitivity of tiny cancerous cells on the surgical specimen surface after pancreatoduodenectomy. Surgical specimens were collected from 45 pancreatic cancer cases who received subtotal stomach preserving pancreatoduodenectomy at Nagoya University Hospital during 2017-2019. Quantitative methylation-specific PCR (QMSP) of the original methylation marker panel (CD1D, KCNK12, PAX5) were performed and analyzed with postoperative survival outcomes. RESULTS: Among 45 tumors, 26 cases (58%) were QMSP-positive for CD1D, 25 (56%) for KCNK12 and 27 (60%) for PAX5. Among the 38 tumors in which at least one of the three markers was positive, CD1D-positive cancer cells, KCNK12-positive cancer cells, and PAX5-positive cancer cells were detected at the surgical margin in 8 cases, 7 cases and 10 cases, respectively. Consequently, a total of 17 patients had at least one marker detected at the surgical margin by QMSP, and these patients were defined as MSM-positive. They were associated with significantly poor recurrence-free survival (p = 0.002) and overall survival (p = 0.005) than MSM-negative patients. Multivariable analysis showed that MSM-positive was the only significant independent factor for worse recurrence-free survival (hazard ratio: 3.522, 95% confidence interval: 1.352-9.179, p = 0.010). On the other hand, a significant proportion of MSM-negative cases were found to have received neoadjuvant chemotherapy (p = 0.019). CONCLUSION: Pancreatic cancer-specific methylation marker panel was established to perform MSM analysis. MSM-positive status might represent microscopically undetectable cancer cells on the surgical margin and might influence the postoperative long-term outcomes.

DOI： 10.1186/s13148-021-01165-8

Open Access

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Reports show miR-23b to be a cancer-related biomarker in various cancer types. Interestingly, it has a dual role of oncogenic and tumor-suppressive functions, depending on the cancer type. This study focused on the unknown association of miR-23b-3p with hepatocellular carcinoma (HCC). METHODS: Expression of miR-23b-3p was measured in nine HCC cell lines and 125 resected human HCC samples by TaqMan microRNA assays. To detect its downstream target, miR-23b-3p mimic and inhibitor constructs were transfected and analyzed. RESULTS: HepG2, a high miR-23b-3p-expressing cell line, was transfected with a miR-23b-3p inhibitor construct, whereas SK-Hep1, a low miR-23b-3p-expressing cell line, was transfected with a mimic construct. Proliferation of HCC cells was activated by miR-23b-3p overexpression and diminished by its knockdown. Then, 125 clinical HCC samples were examined to measure miR-23b-3p expression. Tumor expression of miR-23b-3p was upregulated in 48 cases (38%) and downregulated in 77 cases (62%). The upregulated cases were correlated with elderly patients (P = 0.015). These patients also showed significantly poor overall survival [hazard ratio (HR), 3.10; 95% conflidence interval (CI), 1.57-6.29; P = 0.001] in a multivariate analysis. Furthermore, mitochondrial metabolism-related genes (MICU3 and AUH) were detected as specific binding targets. CONCLUSION: The study showed that miR-23b-3p functions as an oncogenic microRNA in HCC cell lines. Its overexpression in resected HCC tissues was a significant prognostic factor of overall survival. Both MICU3 and AUH may be candidate gene targets of miR-23b-3p.

DOI： 10.1245/s10434-020-09283-y

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

Circular RNA (circRNA) is a type of non-coding RNA known to affect cancer-related micro RNAs and various transcription factors. circRNA has promise as a cancer-related biomarker because its circular structure affords high stability. We found using high-throughput sequencing that seven candidate circRNAs (hsa_circ_0041150, hsa_circ_0025624, hsa_circ_0001020, hsa_circ_0028129, hsa_circ_0008558, hsa_circ_0036683, hsa_circ_0058087) were downregulated in HCC. The expression of these circRNAs was examined by quantitative PCR in 233 sets of HCC and matched background normal liver tissues, and correlations between candidate circRNA expression and prognosis were evaluated. The results of quantitative PCR showed that expression of hsa_circ_0041150, hsa_circ_0001020 and hsa_circ_0008558 was significantly lower in HCC than in background normal liver tissues. Kaplan-Meier analysis revealed that low expression of hsa_circ_0001020, hsa_circ_0036683, and hsa_circ_0058087 was associated with poor recurrence-free (RFS) and overall survival (OS) in HCC. Additionally, multivariate analysis revealed that low hsa_circ_0036683 expression was a significant prognostic factor, independent from other clinicopathological features, for inferior RFS and OS. There was no significant association between the expression of these circRNAs and hepatitis B/C status or cirrhosis. This study therefore identified circRNAs as potential prognostic markers for patients who undergo curative surgery for HCC and highlighted hsa_circ_0036683 as the most useful biomarker.

DOI： 10.1038/s41598-021-85237-y

Open Access

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: In this study, we retrospectively assessed the feasibility and prognostic efficacy of perioperative chemo(radio)therapy for pancreatic cancer (PC) patients according to age. METHODS: A total of 556 consecutive patients who underwent curative-intent pancreatectomy for PC between 2000 and 2018 were enrolled. RESULTS: Of the 556 patients who underwent resection, 95 (17%) were elderly (age, ≥75 years). Postoperative complications did not significantly differ between the 2 age groups, and postoperative prognoses were also similar (recurrence-free survival [RFS], P = 0.68; overall survival [OS], P = 0.28). In this cohort, 103 patients (19%) underwent preoperative chemo(radio)therapy, and 417 (77%) underwent postoperative chemotherapy. Perioperative therapy was found to be significantly beneficial for younger patients (preoperative therapy: RFS, P = 0.006; OS, P < 0.001; postoperative therapy: RFS, P < 0.001; OS, P < 0.001). Conversely, no significant survival benefit of perioperative therapy was found for the elderly (preoperative therapy: RFS, P = 0.28; OS, P = 0.44; postoperative therapy: RFS, P = 0.77; OS, P = 0.08). CONCLUSIONS: This study demonstrated that, although perioperative therapy is feasible for selected elderly patients with PC, this approach might not be as beneficial as it is for younger PC patients.

DOI： 10.1097/MPA.0000000000001712

Web of Science

Scopus

PubMed

Language：Japanese  

Web of Science

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(一社)日本消化器外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本外科学会  

Language：Japanese   Publisher：(一社)日本膵臓学会  

Language：Japanese   Publisher：日本消化器病学会-東海支部  

Language：English   Publisher：(一社)日本癌治療学会  

Language：English  

DOI： 10.1186/s12967-018-1762-6

Open Access

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS INC  

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 &lt; 0.001). The 78 cases were divided into high QMSP value (high QMSP, n D 26) and low QMSP value (low QMSP, n D 52). High QMSP cases were significantly associated with downregulated PAX5 expression (P D 0.040), and showed significantly poor recurrencefree survival [Hazard Ratio (HR) D 2.84; P D 0.005; 95% Confidence Interval (CI): 1.39-5.81] and overall survival (HR D 3.23; P D 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

Web of Science

Scopus

PubMed

Event date： 2023.6 - 2023.7

Language：English   Presentation type：Symposium, workshop panel (public)