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1.
Nihon Shokakibyo Gakkai Zasshi ; 120(7): 610-614, 2023.
Article in Japanese | MEDLINE | ID: mdl-37423732

ABSTRACT

A 79-year-old woman underwent colonoscopy that revealed a 30-mm-sized nodular, mixed-type, lateral spreading tumor-granular in the lower rectum. Endoscopic submucosal dissection was performed, and the pathological findings indicated a mostly adenoma-type tumor with synaptophysin, cluster of differentiation 56-positive, and chromogranin A-negative associated with neuroendocrine carcinoma. Surgical resection was performed owing to vascular invasion, and the lymph node metastasis of the endocrine carcinoma component was observed. Thus, we reported a rare case of the coexistence of adenoma and neuroendocrine carcinoma.


Subject(s)
Adenoma , Carcinoma, Neuroendocrine , Rectal Neoplasms , Aged , Female , Humans , Adenoma/pathology , Adenoma/surgery , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/surgery , Lymphatic Metastasis , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Colonoscopy
2.
Cancer Sci ; 113(3): 1069-1077, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34962016

ABSTRACT

Routinely available clinical samples of all stages of pancreatic cancer are used in the present study to elucidate its molecular mechanisms and identify novel therapeutic targets. We evaluated the use of next-generation sequencing (NGS) of endoscopically obtained pancreatic cancer tissues. We enrolled 147 patients who underwent endoscopic ultrasound-guided fine-needle aspiration or endoscopic biopsy. The quantity and quality of the extracted DNA was assessed. Tissue samples were used for NGS of 78 cancer-related genes, from which gene alterations and microsatellite instability (MSI) were extracted. NGS was successful in 141 out of 147 (96%) cases. Gene alterations were detected in 134 out of 141 (91%) samples, among which eight out of 10 samples with a DNA concentration below the detection limit had some type of gene alteration. Targetable genes were detected in 28 (19.9%) cases. MSI and germline mutations in homologous recombination repair associated genes were detected in 5% and 3% of cases, respectively. Cox regression analysis revealed that metastasis (P < .005; hazard ratio [HR], 3.30) was associated with poor prognosis in all pancreatic cancer patients. In addition, fewer than three mutations (P = .03; HR, 2.48) and serum carcinoembryonic antigen levels >5 ng/mL (P < .005; HR, 3.94) were associated with worse prognosis in cases without and with metastasis, respectively. Targeted sequencing of all stages of pancreatic cancer using available samples from real clinical practice could be used to determine the relationship between gene alterations and prognosis to help determine treatment choices.


Subject(s)
High-Throughput Nucleotide Sequencing , Pancreatic Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Humans , Male , Microsatellite Instability , Middle Aged , Mutation , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Prognosis , Survival Rate
3.
BMC Cancer ; 21(1): 1245, 2021 Nov 19.
Article in English | MEDLINE | ID: mdl-34798839

ABSTRACT

BACKGROUND: The genetic changes underlying carcinogenesis in patients with risk factors of gallbladder carcinoma (GBC) remains controversial, especially in patients with pancreaticobiliary maljunction (PBM). This study aimed to clarify the association between risk factors of GBC and genetic changes using next-generation sequencing (NGS). METHODS: We retrospectively analyzed resected tissues of 64 patients who were diagnosed with GBC (n = 26), PBM [with GBC (n = 8), without GBC (n = 20)], and chronic cholecystitis, used as a control group (n = 10). DNA was extracted from tumors and their surrounding tissues, which were precisely separated by laser-capture microdissection. Gene alterations of 50 cancer-related genes were detected by NGS and compared with clinical information, including PBM status. RESULTS: The most frequent gene alterations in GBC tissues occurred in TP53 (50%), followed by EGFR (20.6%), RB1 (17.6%), and ERBB2 (17.6%). Gene alterations that were targetable by molecular targeted drugs were detected in 20 cases (58.8%). Statistical analysis of gene alterations and risk factors revealed that TP53 alteration rate was higher in GBC patients with PBM than those without PBM (p = 0.038), and the TP53 mutation rates in the epithelium of control patients, epithelium of PBM patients without GBC, peritumoral mucosa of GBC patients with PBM, and tumor tissue of GBC patients with PBM were 10, 10, 38, and 75%, respectively (p <  0.01). CONCLUSIONS: TP53 alteration more than KRAS mutation was revealed to underlie carcinogenesis in patients with PBM.


Subject(s)
Gallbladder Neoplasms/genetics , Genes, p53/genetics , Mutation , Pancreaticobiliary Maljunction/genetics , Adult , Aged , Case-Control Studies , Cholecystitis/genetics , Female , Gene Expression Profiling , Genes, Retinoblastoma , Genes, erbB-1 , Genes, erbB-2 , Genes, ras , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mutation Accumulation , Retrospective Studies , Risk Factors
4.
Int J Mol Sci ; 22(6)2021 Mar 22.
Article in English | MEDLINE | ID: mdl-33809988

ABSTRACT

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.


Subject(s)
Adenocarcinoma, Mucinous/genetics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Papillary/genetics , Membrane Glycoproteins/genetics , Pancreatic Juice/metabolism , Receptors, Immunologic/genetics , Adenocarcinoma, Mucinous/diagnosis , Aged , Aged, 80 and over , Biomarkers, Tumor , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Papillary/diagnosis , Computational Biology/methods , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , High-Throughput Nucleotide Sequencing , Humans , Male , MicroRNAs/genetics , Middle Aged , Prognosis
5.
Int J Mol Sci ; 21(9)2020 May 07.
Article in English | MEDLINE | ID: mdl-32392821

ABSTRACT

We aimed to evaluate a newly developed peroral cholangioscopy (POCS) classification system by comparing classified lesions with histological and genetic findings. We analyzed 30 biopsied specimens from 11 patients with biliary tract cancer (BTC) who underwent POCS. An original classification of POCS findings was made based on the biliary surface's form (F factor, 4 grades) and vessel structure (V-factor, 3 grades). Findings were then compared with those of corresponding biopsy specimens analyzed histologically and by next-generation sequencing to identify somatic mutations. In addition, the histology of postoperative surgical stumps and preoperative POCS findings were compared. Histological malignancy rate in biopsied specimens increased with increasing F- and V-factor scores (F1, 0%; F1, 25%; F3, 50%; F4, 62.5%; p = 0.0015; V1, 0%; V2, 20%; V3, 70%; p < 0.001). Furthermore, we observed a statistically significant increase of the mutant allele frequency of mutated genes with increasing F- and V-factor scores (F factor, p = 0.0050; V-factor, p < 0.001). All surgical stumps were accurately diagnosed using POCS findings. The F-V classification of POCS findings is both histologically and genetically valid and will contribute to the methods of diagnosing the superficial spread of BTC tumors.


Subject(s)
Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/pathology , Endoscopy, Digestive System/methods , Mutation , Aged , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/surgery , Biopsy , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Pilot Projects , Sequence Analysis, DNA
6.
BMC Gastroenterol ; 17(1): 105, 2017 Oct 11.
Article in English | MEDLINE | ID: mdl-29020933

ABSTRACT

BACKGROUND: Self-expandable metal stents (SEMSs) are widely used for malignant biliary obstructions. Nitinol-covered SEMSs have been developed to improve stent patency. Currently, SEMSs may be uncovered, partially covered, or fully covered; however, there is no consensus on the best stent type for the management of malignant distal biliary obstruction (MDBO). METHODS: Patients with unresectable MDBO receiving SEMS (Wallflex™) were retrospectively analyzed. Time to recurrent biliary obstruction (TRBO) and survival time were compared among the three types of SEMSs. Univariate and multivariate analyses were performed to identify risk factors for stent dysfunction. RESULTS: In total, 101 patients received SEMSs for unresectable MDBO (44 uncovered, 28 partially covered, and 29 fully covered SEMSs). Median survival time was 200, 168, and 276 days in the uncovered, partially covered, and fully covered SEMSs groups, respectively. There were no differences in survival among the three groups. Median TRBO was 199, 444, and 194 days in the uncovered, partially covered, and fully covered SEMSs groups, respectively. Partially covered SEMSs had longer TRBO than uncovered (p = 0.013) and fully covered (p = 0.010) SEMSs. Tumor ingrowth occurred only with uncovered SEMSs and stent migration occurred only with fully covered SEMSs. Multivariate analyses confirmed that partially covered SEMSs have lower risk of dysfunction. CONCLUSIONS: Partially covered SEMSs with a proximal uncovered flared end have longer patency than uncovered and fully covered SEMSs by preventing tumor ingrowth and stent migration.


Subject(s)
Cholestasis/surgery , Prosthesis Design , Prosthesis Failure , Self Expandable Metallic Stents , Aged , Aged, 80 and over , Biliary Tract Neoplasms/complications , Biliary Tract Neoplasms/mortality , Cholestasis/etiology , Cholestasis/mortality , Female , Humans , Male , Middle Aged , Palliative Care , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/mortality , Recurrence , Retrospective Studies , Risk Factors , Self Expandable Metallic Stents/adverse effects , Survival Analysis , Time Factors
7.
Nihon Shokakibyo Gakkai Zasshi ; 111(4): 765-72, 2014 Apr.
Article in Japanese | MEDLINE | ID: mdl-24769466

ABSTRACT

A 72-year-old male was admitted because of hearing impairment, blurred vision, right hemifacial numbness, and difficulty walking. Brain magnetic resonance imaging revealed two enhancing lesions with infiltration around the cranial nerves indicating either metastatic brain tumors or meningeal carcinomatosis. Cytological examination of the cerebrospinal fluid revealed malignant cells with keratotic changes. Upper gastrointestinal endoscopy was performed, which revealed type 1 squamous cell carcinoma of the esophagus;this led to the diagnosis of leptomeningeal carcinomatosis. In this report, we present a rare case of esophageal carcinoma accompanied by meningeal carcinomatosis diagnosed on the basis of neurological symptoms.


Subject(s)
Carcinoma, Squamous Cell/complications , Esophageal Neoplasms/complications , Meningeal Carcinomatosis/etiology , Nervous System Diseases/etiology , Aged , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/radiotherapy , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/radiotherapy , Fatal Outcome , Humans , Magnetic Resonance Imaging , Male , Meningeal Carcinomatosis/diagnosis , Meningeal Carcinomatosis/radiotherapy , Positron-Emission Tomography , Tomography, X-Ray Computed
8.
Hepatology ; 56(5): 1611-21, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22577043

ABSTRACT

UNLABELLED: To comprehensively characterize the contribution of virological factors as well as interleukin-28B (IL28B) single-nucleotide polymorphisms (SNPs) in determining treatment responses in pegylated-interferon plus ribavirin (Peg-IFN/RBV) therapy for chronic hepatitis C virus (HCV)-1b infection, we undertook a retrospective cohort analysis for the pretreatment dominant complete HCV open reading frame (ORF) amino-acid (aa) sequence study in 103 consecutive HCV-1b Japanese patients. The dominant HCV sequences classified by the response were subjected to systematic sliding-window comparison analysis to characterize response-specific viral sequences, along with IL28B SNP analyses (rs8099917). In each comparison of the patients between with and without rapid viral response (RVR), nonearly viral response (nEVR), sustained virological response (SVR), or relapse, the following regions were extracted as most significantly associated with the different responses respectively: nonstructural protein 5A (NS5A) aa.2224-2248 (P = 1.2E-07); core aa.70 (P = 4E-04); NS5A aa.2340-2382 (P = 7.0E-08); and NS5A aa.2360-2377 (P = 1.1E-05). Those NS5A regions nearly coincided with the interferon (IFN) sensitivity-determining region (NS5A aa.2209-2248) and the IFN/RBV resistance-determining region (NS5A aa.2339-2379). In a multivariate analysis, the IL28B SNP (odds ratio [OR] = 16.8; P = 0.009) and NS5A aa.2340-2382 (OR = 13.8; P = 0.0003) were extracted as the two most-significant independent variables contributing to the final outcome. CONCLUSION: In Peg-IFN/RBV therapy, polymorphisms in IL28B, NS5A aa.2224-2248, core aa.70, and, most important, NS5A aa.2340-2382 have a tremendous influence on treatment response in association with viral kinetics, resulting in significantly different outcomes in chronic HCV-1b infection.


Subject(s)
Antiviral Agents/therapeutic use , Drug Resistance, Viral/genetics , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/genetics , Interleukins/genetics , Viral Nonstructural Proteins/genetics , Adolescent , Adult , Aged , Alleles , Female , Genotype , Humans , Interferons/therapeutic use , Japan , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Open Reading Frames , Polyethylene Glycols/therapeutic use , Polymorphism, Single Nucleotide , Recurrence , Retrospective Studies , Ribavirin/therapeutic use , Treatment Outcome
9.
Hepatol Res ; 43(8): 865-75, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23279319

ABSTRACT

AIM: Prediction of treatment responses to pegylated interferon (PEG IFN) plus ribavirin (RBV) therapy is uncertain for genotype 1b chronic hepatitis C. METHODS: In this study, 96 patients were investigated for the correlation between 36 pretreatment serum chemokine/cytokine levels and PEG IFN/RBV treatment efficacy by a sandwich enzyme-linked immunoassay (ELISA) and a bead array. RESULTS: First, chemokines/cytokines were measured semiquantitatively by sandwich ELISA in 31 randomly-selected patients and the serum regulated on activation normal T-cell expressed and secreted (RANTES) level was found to be significantly higher in the sustained virological response (SVR) group than the non-SVR group (P = 0.048). Precise RANTES measurement in all 96 patients using a bead array confirmed this correlation (P = 0.002). However, the genetic RANTES haplotype was not significantly related to the serum level. The serum RANTES level was extracted by multivariate analysis (odds ratio = 4.09, 95% confidence interval = 1.02-16.5, P = 0.048) as an independent variable contributing to SVR. CONCLUSION: The serum RANTES level is an important determinant influencing the virological response to PEG IFN/RBV therapy in chronic hepatitis C.

10.
DEN Open ; 3(1): e169, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36247313

ABSTRACT

Background: The present study aimed to examine the correlation between preoperative carcinoembryonic antigen levels in pancreatic juice (PJ-CEA) and the histological subtype of intraductal papillary mucinous neoplasm (IPMN). Methods: We enrolled IPMN patients who underwent endoscopic retrograde pancreatography between March 2002 and March 2018. Clinical factors associated with IPMN histological subtypes of 67 patients who underwent surgery were analyzed. Furthermore, the relationship between CEA immunohistochemistry findings and histological subtypes was investigated. Results: Median PJ-CEA were 15 ng/ml in the gastric type, 150 ng/ml in the intestinal type, and 175 ng/ml in the pancreatobiliary type. Both intestinal and pancreatobiliary types had significantly higher PJ-CEA than the gastric type (p = 0.001). In the analysis of histological subtype predictors, high PJ-CEA (≥63 ng/ml) only showed a significant difference in multivariate analyses (95% confidence interval 4.8-70.2; p < 0.001). Immunohistochemistry findings revealed significantly higher CEA expression in the non-gastric type than in the gastric type (p < 0.001). The non-gastric type showed a significantly worse prognosis than the gastric type (p = 0.017). Conclusion: PJ-CEA was an independent predictor of IPMN histological subtypes in a preoperative setting. High PJ-CEA predict the non-gastric type, while low PJ-CEA predict the gastric type.

11.
J Med Virol ; 84(9): 1360-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22825814

ABSTRACT

The emergence of amino acid or nucleotide substitutions leads to lamivudine resistance in hepatitis B virus (HBV) infected patients. The aim of this study was to investigate whether viral sequences help predict the emergence of lamivudine resistance. The study subjects comprised 59 consecutive patients infected with HBV treated with daily therapy of 100 mg lamivudine. Among those, 32 patients with adequate pretreatment serum preservation were investigated for the correlation between viral amino acid substitutions and the appearance of lamivudine resistance with consideration of clinical background by determining dominant HBV full open reading frames. Viral resistance to lamivudine emerged in 28 of 59 patients (47%) in a median period of 2.45 years. Sequence comparisons of HBV genomes between patients who later developed lamivudine resistance and patients who did not revealed the existence of significant differences between the two groups in the pre-S1 84 (P = 0.042), pre-S2 1 (P = 0.017) and 22 (P = 0.015), and polymerase tp 95 (P = 0.046), judged by a log-rank test. Viral sequence analyses revealed the presence of amino acid substitutions in HBV pre-S1 and pre-S2 that may be associated with the emergence of lamivudine resistance during chronic HBV infection.


Subject(s)
Drug Resistance, Viral/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Lamivudine/pharmacology , Reverse Transcriptase Inhibitors/pharmacology , Adult , Aged , Alanine Transaminase/blood , Amino Acid Sequence , Amino Acid Substitution , DNA, Viral/blood , DNA, Viral/genetics , Female , Gene Products, pol/genetics , Genes, Viral , Hepatitis B virus/enzymology , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/enzymology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Molecular Sequence Data , Multivariate Analysis , Open Reading Frames , Sequence Analysis, DNA , Statistics, Nonparametric
12.
JMA J ; 5(4): 512-519, 2022 Oct 17.
Article in English | MEDLINE | ID: mdl-36407075

ABSTRACT

Introduction: The usefulness of various prognostic factors for advanced pancreatic cancer (APC) has been reported, but the number of elderly patients in these studies is disproportionately fewer than those in general practice. This study aimed to examine the prognostic factors for elderly patients with APC receiving gemcitabine plus nab-paclitaxel (GnP) considering the G8 geriatric assessment tool. Methods: We retrospectively analyzed 77 elderly (≥65 years old) patients with APC who received GnP as first-line chemotherapy at our hospital. We used the receiver operating characteristic curve to set the optimal cutoff value for G8. Univariate and multivariate Cox regression models were applied to study independent prognostic factors. Results: The progression-free survival was 5.5 months, and the overall survival (OS) was 12.0 months in all patients. The most optimal cutoff of G8 was 10.5. OS of G8 ≥10.5 patients was superior to that of G8 <10.5 patients (18.5 versus 8.0 months). Multivariate analysis showed that Eastern Cooperative Oncology Group performance status 1 (hazard ratio [HR] 3.00, p = 0.02), neutrophil-lymphocyte ratio ≥3.9 (HR 2.73, p = 0.03), and G8 geriatric assessment <10.5 (HR 5.38, p < 0.001) were independent negative prognostic factors. Conclusions: G8 is useful for predicting prognoses in elderly patients with APC receiving GnP.

13.
J Clin Med ; 11(14)2022 Jul 19.
Article in English | MEDLINE | ID: mdl-35887953

ABSTRACT

The diagnosis of autoimmune pancreatitis (AIP) and immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) may require a somewhat invasive pathological examination and steroid responsiveness. This retrospective study assessed the complemental diagnosis of AIP and IgG4-SC using submandibular gland (SG) ultrasonography (US) in 69 patients, including 54 patients with AIP, 2 patients with IgG4-SC, and 13 patients with both AIP and IgG4-SC. The data from the physical examination and US of SGs to diagnose AIP (n = 67) and IgG4-SC (n = 15) were analyzed. The steroid therapy efficacy in resolving hypoechoic lesions in SGs was evaluated in 36 cases. The presence of IgG4-related pancreaticobiliary disease with multiple hypoechoic lesions in SGs was reduced from 31 to 11 cases after steroid therapy, suggesting that multiple hypoechoic lesions in SGs are strongly associated with IgG4-positive cell infiltrations. Multiple hypoechoic lesions in SGs were observed in 53 cases, whereas submandibular swelling on palpation was observed in 21 cases of IgG4-related pancreaticobiliary diseases. A complemental diagnosis of IgG4-related pancreaticobiliary diseases without a histological diagnosis and steroid therapy was achieved in 57 and 68 cases without and with multiple hypoechoic lesions in SGs, respectively. In conclusion, multiple hypoechoic lesions in SGs are useful for the complemental diagnosis of IgG4-related pancreaticobiliary diseases.

14.
JMA J ; 4(2): 141-147, 2021 Apr 15.
Article in English | MEDLINE | ID: mdl-33997448

ABSTRACT

Introduction: Common bile duct stones (CBDS) are a common disease that can cause biliary complications, including cholangitis, obstructive jaundice, and biliary pancreatitis. Regardless of the presence or absence of symptoms, endoscopic removal of CBDS is generally recommended, but endoscopic retrograde cholangiopancreatography (ERCP) is a high-risk procedure with complications, such as post-ERCP pancreatitis (PEP). As few reports have addressed the risk of PEP by focusing on asymptomatic CBDS, the purpose of this study is to examine the incidence of PEP for asymptomatic CBDS. Methods: This retrospective study included data from 302 patients with naive papilla who underwent therapeutic ERCP for CBDS between January 2012 and December 2019 at our hospital. Univariate and multivariate logistic regression models were used to investigate independent risk factors for PEP. Results: Of the 302 patients, 32 were asymptomatic, and the remaining 270 were symptomatic. Five asymptomatic patients (15.6%) suffered from mild PEP, whereas 10 (3.7%) symptomatic patients suffered from PEP (9 were mild, and 1 was severe). Univariate analysis identified deep cannulation time more than 10 min, endoscopic papillary balloon dilation (EPBD), and asymptomatic CBDS as risk factors for PEP, whereas multivariate analysis revealed deep cannulation time more than 10 min (odds ratio (OR), 6.67; p < 0.001), EPBD (HR, 5.70; p < 0.001), and asymptomatic CBDS (HR, 5.49; p < 0.001) as independent risk factors for PEP. Conclusions: A wait-and-see approach may be an option for the management of asymptomatic CBDS. EPBD may be avoided, especially in case of asymptomatic or if difficult for bile duct cannulation.

15.
Intern Med ; 60(10): 1525-1528, 2021 May 15.
Article in English | MEDLINE | ID: mdl-33250468

ABSTRACT

Duodenal stenting has gradually been established as the first-line treatment for malignant gastric outlet obstruction (GOO). We encountered a case of duodenal stent fracture in a 76-year-old woman with gastric cancer and GOO. She underwent self-expandable metallic stent (SEMS) placement. The SEMS was found to be fractured 4 weeks after its placement. We removed the broken part of the stent and placed a second SEMS. SEMS fracture is a rare and - to the best of our knowledge - unreported complication; hence, clinicians and their patients should be aware of this possibility.


Subject(s)
Gastric Outlet Obstruction , Self Expandable Metallic Stents , Stomach Neoplasms , Aged , Female , Gastric Outlet Obstruction/etiology , Gastric Outlet Obstruction/surgery , Humans , Palliative Care , Retrospective Studies , Self Expandable Metallic Stents/adverse effects , Stents/adverse effects , Stomach Neoplasms/complications , Treatment Outcome
16.
JGH Open ; 5(4): 508-516, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33860102

ABSTRACT

BACKGROUND AND AIM: The clinical applicability of digital next-generation sequencing (dNGS), which eliminates polymerase chain reaction (PCR) and sequencing error-derived noise by using molecular barcodes (MBs), has not been fully evaluated. We evaluated the utility of dNGS of cell-free DNA (cfDNA) in liquid biopsies obtained from patients with pancreatic cancer. METHODS: Fifty-eight patients with pancreatic cancer undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) were included. Samples were subjected to sequencing of 50 cancer-related genes using next-generation sequencing (NGS). The results were used as reference gene alterations. NGS of cfDNA from plasma was performed for patients with a mutant allele frequency (MAF) >1% and an absolute mutant number > 10 copies/plasma mL in KRAS or GNAS by digital PCR. Sequence readings with and without MBs were compared with reference to EUS-FNA-derived gene alterations. RESULTS: The concordance rate between dNGS of cfDNA and EUS-FNA-derived gene alterations was higher with than without MBs (p = 0.039), and MAF cut-off values in dNGS could be decreased to 0.2%. dNGS using MBs eliminated PCR and sequencing error by 74% and 68% for TP53 and all genes, respectively. Overall, dNGS detected mutations in KRAS (45%) and TP53 (26%) and copy number alterations in CCND2, CCND3, CDK4, FGFR1, and MYC, which are targets of molecular-targeted drugs. CONCLUSIONS: dNGS of cfDNA using MBs is useful for accurate detection of gene alterations even with low levels of MAFs. These results may be used to inform the development of diagnostics and therapeutics that can improve the prognosis of pancreatic cancer.

17.
Cancer Med ; 10(4): 1264-1274, 2021 02.
Article in English | MEDLINE | ID: mdl-33455072

ABSTRACT

Although comprehensive gene analyses of pancreatic cancer provide new knowledge on molecular mechanisms, the usefulness and possibility of the analyses in routinely available clinical samples remain unclear. We assessed the possibility and utility of target sequencing of endoscopically obtained pancreatic cancer samples. Fifty-eight pancreatic cancer patients who underwent EUS-FNA or endoscopic biopsy were enrolled. The extracted DNA quantity was assessed and used for next-generation sequencing (NGS) of 50 cancer-related genes from which gene mutations, copy number alterations, and microsatellite instability (MSI) were extracted via secondary analysis. A median of 19.2 ng (3.8-228) of DNA was extracted from formalin-fixed paraffin-embedded samples. Gene alterations were detected in 55 of 58 samples (94.8%), including all samples with a DNA concentration below the detection limit (n = 11). Four frequently altered genes were KRAS (83%), TP53 (66%), SMAD4 (26%), and PTEN (17%), and molecular targetable genes were detected in 13 cases (22.4%). Five samples (8.6%) had many mutations and suspected MSI with impaired mismatch repair genes. A Cox regression analysis revealed that metastasis (p < 0.005, hazard ratio [HR] 10.1), serum CEA >5 ng/ml (p = 0.01, HR 2.86), ≤10 detected hotspot mutations (p = 0.03, HR 9.86), and intact Ras signaling (p < 0.005, HR 5.57) were associated with a poor pancreatic cancer prognosis. We performed small, targeted sequencing of pancreatic cancer using available samples from real clinical practice and determined the relationship between gene alterations and prognosis to help determine treatment choices.


Subject(s)
Mutation , Pancreatic Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biopsy/methods , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Female , High-Throughput Nucleotide Sequencing/methods , Humans , Male , Middle Aged , Molecular Targeted Therapy , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology
18.
J Gastroenterol ; 56(3): 250-260, 2021 03.
Article in English | MEDLINE | ID: mdl-33106918

ABSTRACT

BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) rearrangement is expected to be a novel therapeutic target in advanced/recurrent biliary tract cancer (BTC). However, efficient detection and the exact frequency of FGFR2 rearrangements among patients with advanced/recurrent BTC have not been determined, and the clinical characteristics of FGFR2 rearrangement-positive patients have not been fully elucidated. We aimed to determine the frequency of FGFR2 rearrangement-positive patients among those with advanced/recurrent BTC and elucidate their clinicopathological characteristics. METHODS: Paraffin-embedded tumor samples from formalin-fixed surgical or biopsy specimens of patients with advanced/recurrent BTC were analyzed for positivity of FGFR2 rearrangement by fluorescent in situ hybridization (FISH). RNA sequencing was performed on samples from all FISH-positive and part of FISH-negative patients. RESULTS: A total of 445 patients were enrolled. FISH was performed on 423 patients (272 patients with intrahepatic cholangiocarcinoma (ICC), 83 patients with perihilar cholangiocarcinoma (PCC), and 68 patients with other BTC). Twenty-one patients with ICC and four patients with PCC were diagnosed as FGFR2-FISH positive. Twenty-three of the 25 FISH-positive patients (20 ICC and 3 PCC) were recognized as FGFR2 rearrangement positive by targeted RNA sequencing. Younger age (≤ 65 years; p = 0.018) and HCV Ab- and/or HBs Ag-positivity (p = 0.037) were significantly associated with the presence of FGFR2 rearrangement (logistic regression). CONCLUSIONS: FGFR2 rearrangement was identified in ICC and PCC patients, and was associated with younger age and history of hepatitis viral infection.


Subject(s)
Biliary Tract Neoplasms/genetics , Genetic Diseases, Inborn/complications , Receptor, Fibroblast Growth Factor, Type 2/genetics , Adult , Aged , Biliary Tract Neoplasms/physiopathology , Female , Humans , Japan , Male , Middle Aged , Prospective Studies , Recurrence
19.
J Gastrointest Cancer ; 51(2): 515-519, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31256333

ABSTRACT

PURPOSE: For patients receiving palliative care, information about prognosis is important to help them set priorities and expectations for care and to assist clinicians in decision-making. The purpose of this study was to investigate prognostic models applicable to the terminal stage of gastrointestinal cancer, especially in terms of accuracy of prediction regarding 3-week survival. METHODS: We validated retrospectively the accuracy of a prognosis prediction model for 354 end-stage gastrointestinal cancer patients who underwent palliative care at our hospital. Using receiver operating characteristic analysis and the area under the curve (AUC), we selected the cut-off value for 3-week survival and evaluated the predictive ability using sensitivity, specificity, positive predictive value, negative predictive value, and accurate diagnosis rate. RESULTS: In our analysis of various models, Palliative Prognostic Index (PPI) and Biological Prognostic Score (BPS) version 3 showed excellent predictive performance with AUCs of 0.85 and 0.83, respectively, and accurate diagnosis rates of 80.0 and 79.0, respectively. BPS version 2 showed fair predictive performance with an AUC of 0.76 and an accurate diagnosis rate of 72.0. Using these models, stratification of prognostic prediction was possible. CONCLUSIONS: PPI and BPS were found to be accurate prediction models for short-term survival of terminal gastrointestinal cancer patients.


Subject(s)
Gastrointestinal Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis
20.
Sci Rep ; 10(1): 10795, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32612273

ABSTRACT

Sarcopenia is an important prognostic factor in patients with gastrointestinal and chronic liver diseases. Computed tomography and bioelectrical impedance analysis are the gold standards for measuring skeletal muscle mass for the diagnosis of decreased muscle mass, but there are some institutions where BIA and CT cannot be carried out. We evaluated the utility of simplified methods for measuring muscle mass; the psoas muscle mass index (PMI) method, simple PMI method, and arm muscle area (AMA) method. This retrospective study included 331 patients with gastrointestinal diseases and 81 patients with chronic liver diseases who were admitted from June 2018 to December 2019 at Municipal Hospital of Kofu. The skeletal muscle mass was measured using the PMI via the volume analyzer SYNAPSE VINCENT ver3.0, simple PMI based on CT imaging, and AMA method. Positive correlations were found between muscle mass measured by PMI and simple PMI, PMI and AMA, and simple PMI and AMA in patients with gastrointestinal diseases (correlation coefficients = 0.76, 0.57, 0.47, respectively, p < 0.001). Positive correlations were observed between muscle mass measured by PMI and simple PMI, PMI and AMA, and simple PMI and AMA in chronic liver diseases (correlation coefficients = 0.77, 0.53, 0.45, respectively, p < 0.001). Measurement of muscle mass by the AMA method showed some correlation with the PMI method. Measurement of muscle mass by the simple PMI method showed correlation with the PMI method. These simplified methods can be alternative methods of evaluating muscle mass in patients with gastrointestinal and chronic liver disease.


Subject(s)
Gastrointestinal Diseases , Liver Diseases , Muscle, Skeletal , Sarcopenia , Aged , Aged, 80 and over , Female , Gastrointestinal Diseases/pathology , Gastrointestinal Diseases/physiopathology , Humans , Liver Diseases/pathology , Liver Diseases/physiopathology , Male , Middle Aged , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Sarcopenia/pathology , Sarcopenia/physiopathology
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