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1.
Dig Surg ; 34(1): 60-67, 2017.
Article in English | MEDLINE | ID: mdl-27454870

ABSTRACT

BACKGROUND/AIMS: Although the diagnostic value of fluorine-18 2-fluoro-2-deoxy-D-glucose (F-18-FDG) positron emission tomography/computed tomography (F-18-FDG-PET/CT) in patients with colorectal cancer (CRC) has been reported, the association between the F-18-FDG uptake in metastatic lymph nodes (FDGLN) and clinicopathological variables has not been fully investigated. We evaluated the diagnostic value of F-18-FDG-PET/CT in detecting LN metastasis from CRC, and the relationship between F-18-FDG-PET/CT-detecting LN metastasis and prognosis. METHODS: We retrospectively analyzed the medical records of 370 patients who underwent preoperative F-18-FDG-PET/CT, followed by surgical resection for CRC between January 2007 and December 2010. We analyzed the sensitivity, specificity, and accuracy of F-18-FDG-PET/CT and CT in diagnosing metastatic LNs. Survival was analyzed in 115 patients with stage III CRC. RESULTS: The sensitivity, specificity, and accuracy for detecting metastatic LNs using F-18-FDG-PET/CT were 56.8, 90.3, and 74.2%, and those for contrast-enhanced CT were 38.4, 95.5, and 65.0%, respectively. The accuracy of F-18-FDG-PET/CT was significantly associated with tumor depth and lymphatic involvement. In the survival analysis, cancer-specific survival and the disease-free survival were significantly shorter in patients with stage III CRC with FDGLN than in those without FDGLN. CONCLUSION: F-18-FDG-PET/CT had low sensitivity and high specificity for detecting metastatic LNs from CRC. FDGLN independently predicted poor prognosis in patients with stage III CRC.


Subject(s)
Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Lymph Nodes/diagnostic imaging , Positron Emission Tomography Computed Tomography , Adult , Aged , Aged, 80 and over , Contrast Media , Disease Progression , Disease-Free Survival , Female , Fluorodeoxyglucose F18 , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Radiopharmaceuticals , Retrospective Studies , Survival Rate , Tomography, X-Ray Computed , Young Adult
2.
Surg Today ; 44(11): 2131-7, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24604119

ABSTRACT

PURPOSE: Ghrelin may lead to weight gain by appetite stimulation. This prospective study investigated the association between weight loss and the ghrelin levels in patients after gastrectomy. METHODS: Thirty-three males and eight females were enrolled in the study. The average age was 66 years. Measurements of the serum ghrelin level and an appetite questionnaire were performed preoperatively and at one, three, six and 12 months postoperatively. RESULTS: The preoperative serum total ghrelin level was 51.6 ± 31.9 (fmol/ml ± SD), and that at one, three, six and 12 months postoperatively was 16.9 ± 9.0, 21.2 ± 16.0, 28.0 ± 19.1 and 29.6 ± 20.6 (fmol/ml ± SD), respectively. The appetite score was 2.02 ± 1.09 points at 1 month, and increased significantly to 2.61 ± 1.00 by 12 months. CONCLUSIONS: The ghrelin levels were reduced after gastrectomy and did not recover by 12 months postoperatively. Further studies are needed to evaluate these results as the basis of a therapeutic trial.


Subject(s)
Appetite/genetics , Eating/genetics , Gastrectomy , Ghrelin/blood , Recovery of Function/genetics , Recovery of Function/physiology , Stomach Neoplasms/physiopathology , Stomach Neoplasms/surgery , Aged , Female , Ghrelin/physiology , Humans , Male , Middle Aged , Neoplasm Staging , Perioperative Period , Prospective Studies , Stomach Neoplasms/blood , Stomach Neoplasms/pathology , Surveys and Questionnaires , Time Factors , Weight Gain/genetics , Weight Loss/genetics
3.
Hepatogastroenterology ; 60(127): 1588-91, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23933785

ABSTRACT

BACKGROUND/AIMS: Ampulla of Vater carcinoma is a relatively rare digestive tract tumor; postoperative prognostic factors have been well studied. However, any indicator of preoperative prognosis remains poorly identified. This study aims to identify serum tumor markers as preoperative prognostic factors and other variables as postoperative prognostic factors for ampulla of Vater carcinoma. METHODOLOGY: This study retrospectively analyzed data from 26 patients undergoing pancreaticoduodenectomy (PD), including pylorus preserving PD for ampulla of Vater carcinoma between April 1993 and December 2006. The main outcome measures were survival rates of patients with and without high levels of CA19-9 and CEA. RESULTS: Patients with high levels of CA19-9 (n = 12) had significantly higher survival rates than those without (n = 14) (p = 0.0027). High levels of CEA did not influence cumulative survival rates (p = 0.4522). Histopathological classification was an independent predictor of poor survival rates; patients with well differentiated adenocarcinoma (n = 18) had significantly higher survival rates than those with moderate to poorly differentiated tumors (n = 12) (p = 0.0280). Other factors such as tumor size, lymph node metastasis (p = 0.4006), or invasion of pancreas (p = 0.1156), duodenum (p = 0.0.3723), vein (p = 0.4331), and lymph vessel (p = 0.8606), and perineural invasion (p = 0.0.8765) were not an independent indicators of poor survival rate. CONCLUSIONS: The results of our study indicated that high levels of CA19-9 and histopathological classification were significant independent predictors of poor survival rates for the ampulla of Vater carcinoma.


Subject(s)
Adenocarcinoma/blood , Ampulla of Vater , CA-19-9 Antigen/blood , Common Bile Duct Neoplasms/blood , Adenocarcinoma/immunology , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Aged, 80 and over , Ampulla of Vater/pathology , Ampulla of Vater/surgery , Cell Differentiation , Chi-Square Distribution , Common Bile Duct Neoplasms/immunology , Common Bile Duct Neoplasms/mortality , Common Bile Duct Neoplasms/pathology , Common Bile Duct Neoplasms/surgery , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pancreaticoduodenectomy , Predictive Value of Tests , Retrospective Studies , Time Factors , Treatment Outcome , Up-Regulation
4.
Hepatogastroenterology ; 60(127): 1759-65, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24634947

ABSTRACT

BACKGROUND/AIMS: A positive surgical margin is a poor prognosis factor. Resection of the invaded portal vein (PV) may be necessary to achieve a negative surgical margin during pancreaticoduodenectomy (PD). This study clarifies the intraoperative and long-term survival of patients who received PD with PV resection compared to without. METHODOLOGY: Between July 1992 and March 2012, a retrospective analysis of 119 patients undergoing PD with or without PV resection for pancreatic head cancer was performed. Main outcome measures were perioperative mortality and survival rate of PD with and without PV resection. RESULTS: Perioperative mortality was not different between PD (1 of 51 cases: 2.0%) and PD with PV resection (3 of 68 cases: 4.4%) (p = 0.462). Patients without resection had a significantly better prognosis than patients with PV resection (p = 0.0052). Patients on whom >2.1 cm of the PV was resected (n = 34) had a worse cumulative survival rates than patients with a resection of <2.1 cm (n = 19) (p = 0.0380). Patients with no invasion of PV wall (n = 18) had a significantly higher survival rate than positive PV wall invasion (n = 49) (p =0.039). CONCLUSIONS: Patients with PV resection had a significantly worse prognosis than patients without PV resection. Some patients survived more than 5 years post-operation after PD with PV resection. PV resection contributes to attaining complete tumor resection.


Subject(s)
Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Portal Vein/surgery , Vascular Surgical Procedures/methods , Adult , Aged , Aged, 80 and over , Chi-Square Distribution , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Invasiveness , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/mortality , Portal Vein/pathology , Proportional Hazards Models , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Vascular Surgical Procedures/adverse effects , Vascular Surgical Procedures/mortality
5.
Cancer Sci ; 102(3): 630-8, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21199170

ABSTRACT

The development of a new plasma biomarker for early detection would be necessary to improve the overall outcome of colorectal cancer. Here we report the identification and validation of the ninth component of complement (C9) as a novel plasma biomarker for colorectal cancer by cutting-edge proteomic technologies. Plasma proteins were enzymatically digested into a large array of peptides, and the relative quantity of a total of 94,803 peptide peaks was compared between 31 colorectal cancer patients and 59 age/sex-matched healthy controls using 2D image-converted analysis of liquid chromatography and mass spectrometry. The selected biomarker candidates were validated in 345 subjects (115 colorectal cancer patients and 230 age/sex-matched healthy controls) using high-density reverse-phase protein microarrays. Plasma levels of Apo AI and C9 in colorectal cancer patients significantly differed from healthy controls with P values of 7.94×10(-4) and 1.43×10(-12) (Student's t-test), respectively. In particular, C9 was elevated in patients with colorectal cancer, including those with stage-I and -II diseases (P=3.01×10(-3) and P=1.13×10(-5) , respectively). Although the significance of the present study must be validated in an independent clinical study, the increment of plasma C9 may be applicable to the early detection of colorectal cancer.


Subject(s)
Biomarkers, Tumor/blood , Colorectal Neoplasms/diagnosis , Complement C9/analysis , Protein Array Analysis/methods , Tandem Mass Spectrometry/methods , Aged , Apolipoprotein A-I/blood , Area Under Curve , Colorectal Neoplasms/blood , Female , Humans , Male , Middle Aged , Proteomics
6.
J Biol Chem ; 284(42): 29041-9, 2009 Oct 16.
Article in English | MEDLINE | ID: mdl-19696023

ABSTRACT

Plasma proteome analysis requires sufficient power to compare numerous samples and detect changes in protein modification, because the protein content of human samples varies significantly among individuals, and many plasma proteins undergo changes in the bloodstream. A label-free proteomics platform developed in our laboratory, termed "Two-Dimensional Image Converted Analysis of Liquid chromatography and mass spectrometry (2DICAL)," is capable of these tasks. Here, we describe successful detection of novel prolyl hydroxylation of alpha-fibrinogen using 2DICAL, based on comparison of plasma samples of 38 pancreatic cancer patients and 39 healthy subjects. Using a newly generated monoclonal antibody 11A5, we confirmed the increase in prolyl-hydroxylated alpha-fibrinogen plasma levels and identified prolyl 4-hydroxylase A1 as a key enzyme for the modification. Competitive enzyme-linked immunosorbent assay of 685 blood samples revealed dynamic changes in prolyl-hydroxylated alpha-fibrinogen plasma level depending on clinical status. Prolyl-hydroxylated alpha-fibrinogen is presumably controlled by multiple biological mechanisms, which remain to be clarified in future studies.


Subject(s)
Blood Proteins/chemistry , Fibrinogen/chemistry , Procollagen-Proline Dioxygenase/chemistry , Proteomics/methods , Adenocarcinoma/blood , Case-Control Studies , Cell Line, Tumor , Chromatography, Liquid/methods , Enzyme-Linked Immunosorbent Assay/methods , Humans , Image Processing, Computer-Assisted , Mass Spectrometry/methods , Pancreatic Neoplasms/blood , Proteome , RNA Interference
7.
Cancer Sci ; 101(1): 60-4, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19793350

ABSTRACT

To identify novel cancer-promoting genes in biliary tract cancer (BTC), we constructed a retroviral cDNA expression library from a clinical specimen of BTC with anomalous pancreaticobiliary duct junction (APBDJ), and used the library for a focus formation assay with 3T3 fibroblasts. One of the cDNAs rescued from transformed foci was found to encode Indian hedgehog homolog (IHH). The oncogenic potential of IHH was confirmed both in vitro with the focus formation assay and in vivo with a tumorigenicity assay in nude mice. The isolated IHH cDNA had no sequence alterations, suggesting that upregulation of IHH expression may contribute to malignant transformation. Quantitation of IHH mRNA among clinical specimens has revealed that the expression level of IHH in BTC with APBDJ is higher than that in BTC without APBDJ and than in non-cancerous biliary tissues. Our data thus implicate a direct role of IHH in the carcinogenesis of BTC with APBDJ.


Subject(s)
Biliary Tract Neoplasms/etiology , Cell Transformation, Neoplastic , Hedgehog Proteins/physiology , Retroviridae/genetics , 3T3 Cells , Animals , Bile Ducts/abnormalities , Hedgehog Proteins/analysis , Hedgehog Proteins/genetics , Humans , Immunohistochemistry , Mice , Pancreatic Ducts/abnormalities
8.
Cancer Sci ; 101(1): 54-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19780758

ABSTRACT

Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer-promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein-coupled receptor for short-chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT-PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short-chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract.


Subject(s)
Cell Transformation, Neoplastic , Gallbladder Neoplasms/etiology , Receptors, Cell Surface/physiology , Receptors, G-Protein-Coupled/physiology , Retroviridae/genetics , 3T3 Cells , Animals , Base Sequence , Humans , Male , Mice , Mice, Inbred BALB C , Middle Aged , Molecular Sequence Data , Receptors, Cell Surface/analysis , Receptors, Cell Surface/genetics , Receptors, G-Protein-Coupled/analysis , Receptors, G-Protein-Coupled/genetics
9.
Int J Clin Oncol ; 15(2): 166-71, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20195683

ABSTRACT

BACKGROUND: In patients with adverse events of S-1, the dose is generally reduced or the treatment cycle is shortened. Whether the therapeutic effectiveness of modified regimens is similar to that of the standard dosage remains unclear. METHODS: We retrospectively studied patients with gastric cancer who received S-1 on alternate days. RESULTS: A total of 266 patients received S-1 on alternate days. In 116 patients, S-1 was initially given at the standard dosage but was switched to alternate-day treatment because of toxicity within 28 days on average. The other 150 patients initially received alternate-day treatment because of poor general condition. In the adjuvant chemotherapy group (n = 96), the 3-year survival rate was 88% in patients with stage II, 73% in stage IIIA, and 67% in stage IIIB who underwent D2 lymph-node dissection. In the palliative surgery group (n = 96), the response rate was 13%, with a median survival time (MST) of 624 days. In patients with unresectable/recurrent disease (n = 74), the response rate was 25%, with an MST of 338 days. Among the 116 patients who initially received treatment on consecutive days, 100% had grade 1, 53% had grade 2, and 5.2% had grade 3 adverse events. When S-1 was switched to alternate-day treatment, toxicity decreased in all patients. In the 266 patients who received alternate-day treatment, 8% had grade 1, 6% had grade 2, and 0% had grade 3 adverse events. CONCLUSION: Alternate-day treatment with S-1 may have milder adverse events without compromising therapeutic effectiveness.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Oxonic Acid/administration & dosage , Stomach Neoplasms/drug therapy , Tegafur/administration & dosage , Adult , Aged , Antimetabolites, Antineoplastic/adverse effects , Chemotherapy, Adjuvant , Disease-Free Survival , Drug Administration Schedule , Drug Combinations , Female , Gastrectomy , Humans , Kaplan-Meier Estimate , Lymph Node Excision , Male , Middle Aged , Oxonic Acid/adverse effects , Palliative Care , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/surgery , Tegafur/adverse effects , Time Factors , Treatment Outcome
10.
J Hepatobiliary Pancreat Surg ; 16(4): 485-92, 2009.
Article in English | MEDLINE | ID: mdl-19333537

ABSTRACT

BACKGROUND: Pancreatic carcinoma causes more than 20,000 deaths every year in Japan. The role of (neo-) adjuvant chemotherapy for pancreatic carcinoma is still controversial. METHODS: At the 34th Annual Meeting of the Japanese Society of Pancreatic Surgery in 2007, questionnaires were distributed regarding the use of (neo-) adjuvant chemo(radio)therapy for pancreatic carcinoma between 2001 and 2005. RESULTS: Sixty of the 146 member institutions responded to the questionnaires. There were a total of 1,846 cases of resected pancreatic carcinoma between 2001 and 2005. The study population had a greater proportion of males, and a mean age of 65.3 years (range 34-90 years). The lesion was located in the head of the pancreas in 1,204 cases (71.7%), in the body in 353 cases (21.0%), and in the tail in 111 cases (6.6%). Overall survival rates were 67.3% at 1 year, 36.0% at 2 years, and 23.9% at 3 years, respectively. Adjuvant chemotherapy (usually involving gemcitabine) was used in 66.0% of cases. The use of adjuvant chemotherapy was found to improve the overall survival rate. Interestingly, adjuvant chemotherapy only improved survival in late-stage (UICC stages IIB, III, and IV) but not early stage (IA, IB, and IIA) patients. Survival was treatment duration-dependent, with patients who received more than 12 months of therapy having a 3-year survival rate of 51.2%. CONCLUSION: This high volume retrospective data indicated the promising effect of gemcitabine-based adjuvant chemotherapy and the rational duration of adjuvant chemotherapy should be determined in the future prospective studies.


Subject(s)
Pancreatic Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/therapeutic use , Chemotherapy, Adjuvant , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Female , Health Surveys , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Pancreatic Neoplasms/pathology , Pancreaticoduodenectomy , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies , Survival Analysis , Gemcitabine
11.
Abdom Imaging ; 34(1): 113-20, 2009.
Article in English | MEDLINE | ID: mdl-18253779

ABSTRACT

BACKGROUND: Retroperitoneal endoscopic adrenalectomy (EA) is recognized as a principal procedure for benign adrenal tumors. However, a limited visual field and a narrow working space make this approach difficult, particularly in cases of obese patients or small tumors. Using multidetector row CT (MD-CT), this study investigated the use of preoperative virtual simulation (PVS) to identify tumor and central vein locations for EA, and verified these findings during EA surgery. PATIENTS AND METHODS: The study enrolled 11 cases comprising 10 adrenal adenomas and one ACTH-independent macronodular adrenal hyperplasia admitted to Jichi Medical University Hospital, Tochigi, Japan, between November 2003 and October 2006. Patients were evaluated in a lateral bending position using MD-CT. 3D PVS images of ribs, vertebrae, kidneys, and adrenal tumors were generated and compared with real images obtained during EA. RESULTS: The PVS images clearly showed the relative locations of the adrenal tumor, kidney, and adjacent anatomical structures. These locations were verified during EA. The central vein was identified in the PVS images in all cases. Information derived from the PVS images assisted in the performance of EA surgery. CONCLUSIONS: Preoperative 3D-simulation images using MD-CT contributed to the safety and efficiency of performing EAs.


Subject(s)
Adrenal Gland Neoplasms/diagnostic imaging , Adrenocortical Adenoma/diagnostic imaging , Imaging, Three-Dimensional/methods , Tomography, X-Ray Computed/methods , Adolescent , Adrenal Gland Neoplasms/pathology , Adrenal Gland Neoplasms/surgery , Adrenalectomy , Adrenocortical Adenoma/pathology , Adrenocortical Adenoma/surgery , Adult , Aged , Female , Humans , Laparoscopy , Male , Middle Aged , Radiographic Image Interpretation, Computer-Assisted , User-Computer Interface
12.
Nihon Shokakibyo Gakkai Zasshi ; 106(5): 668-73, 2009 May.
Article in Japanese | MEDLINE | ID: mdl-19420871

ABSTRACT

A 34-year-old woman was referred to our hospital with ileus. She had undergone surgical resection following chemotherapy for yolk sac tumor at the age of 12 years, and had received additional surgery and radiation therapy for a local recurrence at age 13. Following evaluation, a sigmoid colon tumor was detected and was surgically resected. Histology proved well differentiated adenocarcinoma with chronic irradiation colitis, suggesting that irradiation may have induced the colon cancer.


Subject(s)
Adenocarcinoma/etiology , Endodermal Sinus Tumor/radiotherapy , Ovarian Neoplasms/radiotherapy , Radiotherapy/adverse effects , Sigmoid Neoplasms/etiology , Adenocarcinoma/pathology , Adult , Chemotherapy, Adjuvant , Chronic Disease , Colitis/etiology , Female , Humans , Neoplasm Recurrence, Local , Ovariectomy , Sigmoid Neoplasms/pathology , Time Factors
13.
Cancer Sci ; 99(9): 1835-40, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18564138

ABSTRACT

Colorectal carcinoma (CRC) remains the major cause of cancer death in humans. Although chromosomal structural anomaly is presumed to play an important role in the carcinogenesis of CRC, chromosomal copy number alterations (CNA) and loss of heterozygosity (LOH) have not yet been analyzed extensively at high resolution in CRC. Here we aim to identify recurrent CNA and LOH in human CRC with the use of single nucleotide polymorphism-typing microarrays, and to reveal their relevance to clinical outcome. Surgically resected CRC specimens and paired normal mucosa were obtained from a consecutive series of 94 patients with CRC, and both of them were subjected to genotyping with Affymetrix Mapping 50K arrays. CNA and LOH were inferred computationally on every single nucleotide polymorphism site by integrating the array data for paired specimens. Our large dataset reveals recurrent CNA in CRC at chromosomes 7, 8, 13, 18, and 20, and recurrent LOH at chromosomes 1p, 4q, 5q, 8p, 11q, 14q, 15q, 17p, 18, and 22. Frequent uniparental disomy was also identified in chromosomes 8p, 17p, and 18q. Very common CNA and LOH were present at narrow loci of <1 Mbp containing only a few genes. In addition, we revealed a number of novel CNA and LOH that were linked statistically to the prognosis of the patients. The precise and large-scale measurement of CNA and LOH in the CRC genome is efficient for pinpointing prognosis-related genome regions as well as providing a list of unknown genes that are likely to be involved in CRC development.


Subject(s)
Aneuploidy , Chromosome Aberrations , Colorectal Neoplasms/genetics , Loss of Heterozygosity , Colorectal Neoplasms/diagnosis , Female , Genetic Testing , Genome , Genotype , Humans , Male , Mass Screening , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide , Prognosis
14.
J Histochem Cytochem ; 56(8): 753-64, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18443362

ABSTRACT

Periostin is a unique extracellular matrix protein, deposition of which is enhanced by mechanical stress and the tissue repair process. Its significance in normal and neoplastic colon has not been fully clarified yet. Using immunohistochemistry and immunoelectron microscopy with a highly specific monoclonal antibody, periostin deposition was observed in close proximity to pericryptal fibroblasts of colonic crypts. The pericryptal pattern of periostin deposition was decreased in adenoma and adenocarcinoma, preceding the decrease of the number of pericryptal fibroblasts. Periostin immunoreactivity appeared again at the invasive front of the carcinoma and increased along the appearance of cancer-associated fibroblasts. ISH showed periostin signals in cancer-associated fibroblasts but not in cancer cells. Ki-67-positive epithelial cells were significantly decreased in the colonic crypts of periostin-/- mice (approximately 0.6-fold) compared with periostin+/+ mice. In three-dimensional co-culture within type I collagen gel, both colony size and number of human colon cancer cell line HCT116 cells were significantly larger ( approximately 1.5-fold) when cultured with fibroblasts derived from periostin+/+ mice or periostin-transfected NIH3T3 cells than with those from periostin-/- mice or periostin-non-producing NIH3T3 cells, respectively. Periostin is secreted by pericryptal and cancer-associated fibroblasts in the colon, both of which support the growth of epithelial components.


Subject(s)
Adenocarcinoma/metabolism , Adenoma/metabolism , Cell Adhesion Molecules/biosynthesis , Colon/metabolism , Colonic Neoplasms/metabolism , Fibroblasts/metabolism , Adenocarcinoma/pathology , Adenoma/pathology , Animals , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Cell Proliferation , Cells, Cultured , Coculture Techniques , Collagen Type I , Colon/pathology , Colonic Neoplasms/pathology , Gels , Humans , Immunohistochemistry , In Situ Hybridization , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Lung/cytology , Mice , Mice, Inbred ICR , Microscopy, Immunoelectron , Reverse Transcriptase Polymerase Chain Reaction
15.
Dis Colon Rectum ; 51(10): 1529-34, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18592315

ABSTRACT

PURPOSE: This study was designed to identify colonoscopic stigmata, indicating substantial invasion into the submucosa by T1 colorectal cancer with sessile morphology, including both flat and protruded types. METHODS: A total of 111 Tis or T1 colorectal cancers were studied retrospectively. The lesions were divided into two groups: Group A (n = 83), Tis or T1 cancers with <1 mm submucosal invasion; and Group B (n = 28), T1 cancers with a >/=1 mm submucosal invasion. Printed photographs of the lesions were reviewed by five experienced colonoscopists who were blinded to histology. Deep depression, irregular surface, ulceration or erosion, fold convergence, and spontaneous bleeding were independently evaluated. Findings considered present by three or more reviewers were defined as positive. Kappa analysis was used to measure inter/intraobserver variability. RESULTS: Positive rates of four findings but not fold convergence were significantly higher in Group B than in Group A. Irregular surface and spontaneous bleeding were significant independent predictors of >/=1 mm submucosal invasion, with diagnostic accuracies of 85.6 and 76.6 percent, respectively. Kappa analysis demonstrated fair-to-good inter/intraobserver agreement for spontaneous bleeding and fair-to-good intraobserver agreement for irregular surface. CONCLUSIONS: Irregular surface and spontaneous bleeding were colonoscopic stigmata, indicating >/=1 mm submucosal invasion in T1 colorectal cancer.


Subject(s)
Colonoscopy , Colorectal Neoplasms/pathology , Aged , Female , Humans , Logistic Models , Male , Neoplasm Invasiveness , Neoplasm Staging , Retrospective Studies
16.
Diabetes ; 55(12): 3486-93, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17130496

ABSTRACT

The gastric hormone ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), are expressed in pancreas. Here, we report that ghrelin is released from pancreatic islets to regulate glucose-induced insulin release. Plasma concentrations of ghrelin, as well as insulin, were higher in pancreatic veins than in arteries. GHSR antagonist and immunoneutralization of endogenous ghrelin enhanced glucose-induced insulin release from perfused pancreas, whereas exogenous ghrelin suppressed it. GHSR antagonist increased plasma insulin levels in gastrectomized and normal rats to a similar extent. Ghrelin knockout mice displayed enhanced glucose-induced insulin release from isolated islets, whereas islet density, size, insulin content, and insulin mRNA levels were unaltered. Glucose tolerance tests (GTTs) in ghrelin knockout mice showed increased insulin and decreased glucose responses. Treatment with high-fat diet produced glucose intolerance in GTTs in wild-type mice. In ghrelin knockout mice, the high-fat diet-induced glucose intolerance was largely prevented, whereas insulin responses to GTTs were markedly enhanced. These findings demonstrate that ghrelin originating from pancreatic islets is a physiological regulator of glucose-induced insulin release. Antagonism of the ghrelin function can enhance insulin release to meet increased demand for insulin in high-fat diet-induced obesity and thereby normalize glycemic control, which may provide a potential therapeutic application to counteract the progression of type 2 diabetes.


Subject(s)
Dietary Fats , Glucose Intolerance/prevention & control , Insulin/metabolism , Islets of Langerhans/metabolism , Peptide Hormones/antagonists & inhibitors , Peptide Hormones/metabolism , Animals , Blood Glucose/metabolism , Ghrelin , Insulin/blood , Insulin/genetics , Insulin Secretion , Male , Mice , Mice, Knockout , Peptide Hormones/deficiency , Peptide Hormones/genetics , RNA, Messenger/genetics , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction
17.
J Gastroenterol ; 42 Suppl 17: 131-4, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17238042

ABSTRACT

Alcoholic chronic pancreatitis (CP) is not usually diagnosed until the end stage of the disease, and hence enormous medical and social resources are consumed in the treatment of established alcoholic CP. With the aim of early diagnosis and prevention of alcoholic CP, we here propose "alcoholic pancreatopathy" as a new category of pancreatic disorder induced by alcohol intake. In addition to a history of excessive alcohol intake (>80 g/day), the presence of at least one of the following conditions establishes the diagnosis of alcoholic pancreatopathy: 1. History of alcoholic acute pancreatitis. 2. Recurrent abdominal pain or gastrointestinal symptoms induced by alcohol intake. 3. Hyperamylasemia or a high serum level of any other pancreatic enzymes. 4. Abnormal findings in the pancreas by routine abdominal ultrasonography. Alcoholic pancreatopathy is a comprehensive concept that includes the early stage of pancreatic injury induced by alcohol, and is useful for detecting the preclinical stage of pancreatic injury induced by alcohol and hence for treating the early stage of the disease. Further assessments and well-designed studies for investigating the early stage of alcoholic CP are necessary, in which alcoholic pancreatopathy could play a key role.


Subject(s)
Pancreatitis, Alcoholic/classification , Pancreatitis, Alcoholic/diagnosis , Abdominal Pain/etiology , Early Diagnosis , Humans , Hyperamylasemia/etiology , Pancreatitis, Alcoholic/complications , Risk Factors , Severity of Illness Index
18.
Clin Cancer Res ; 12(10): 2995-3002, 2006 May 15.
Article in English | MEDLINE | ID: mdl-16707594

ABSTRACT

PURPOSE: EBV-associated gastric carcinoma shows global CpG island methylation of the promoter region of various cancer-related genes. To further clarify the significance of CpG island methylator phenotype (CIMP) status in gastric carcinoma, we investigated methylation profile and clinicopathologic features including overall survival in four subgroups defined by EBV infection and CIMP status: EBV-associated gastric carcinoma and EBV-negative/CIMP-high (H), EBV-intermediate (I), and EBV-negative (N) gastric carcinoma. EXPERIMENTAL DESIGN: Methylation-specific PCR was applied to 106 gastric carcinoma cases. CIMP-N, CIMP-I, and CIMP-H status was determined by the number (0, 1-3, and 4-5, respectively) of methylated marker genes (LOX, HRASLS, FLNc, HAND1, and TM), that were newly identified as highly methylated in gastric cancer cell lines. The methylation status of 10 other cancer-related genes (p14, p15, p16, p73, TIMP-3, E-cadherin, DAPK, GSTP1, hMLH1, and MGMT) was also evaluated. RESULTS: Nearly all (14 of 15) of EBV-associated gastric carcinoma exhibited CIMP-H, constituting a homogenous group (14%). EBV-negative gastric carcinoma consisted of CIMP-H (24%), CIMP-I (38%), and CIMP-N (24%). EBV-associated gastric carcinoma showed significantly higher frequencies of methylation of cancer-related genes (mean number +/- SD = 6.9 +/- 1.5) even if compared with EBV-negative/CIMP-H gastric carcinoma (3.5 +/- 1.8). Among EBV-negative gastric carcinoma subgroups, CIMP-H gastric carcinoma showed comparatively higher frequency of methylation than CIMP-I or CIMP-N, especially of p16 and hMLH1. CIMP-N gastric carcinoma predominantly consisted of advanced carcinoma with significantly higher frequency of lymph node metastasis. The prognosis of the patients of CIMP-N was significantly worse compared with other groups overall by univariate analysis (P = 0.0313). CONCLUSION: The methylation profile of five representative genes is useful to stratify gastric carcinomas into biologically different subgroups. EBV-associated gastric carcinoma showed global CpG island methylation, comprising a pathogenetically distinct subgroup in CIMP-H gastric carcinoma.


Subject(s)
Carcinoma/genetics , Carcinoma/virology , CpG Islands/genetics , DNA Methylation , Epstein-Barr Virus Infections , Stomach Neoplasms/genetics , Stomach Neoplasms/virology , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Case-Control Studies , Female , Genes, Neoplasm , Genetic Markers , Humans , Male , Middle Aged , Neoplasm Metastasis , Phenotype , Polymerase Chain Reaction , Prognosis , Promoter Regions, Genetic , Stomach Neoplasms/pathology , Survival Analysis , Tumor Cells, Cultured
19.
Surg Endosc ; 21(5): 782-4, 2007 May.
Article in English | MEDLINE | ID: mdl-17177080

ABSTRACT

BACKGROUND: Using a conventional Doppler probe, it is difficult to identify blood vessels precisely in lymph node dissection during laparoscopic surgery. METHODS: For 26 patients undergoing laparoscopic colectomy and 26 patients undergoing laparoscopic subtotal gastrectomy, we used conventional and vertical scanning Doppler probes to compare their ability to identify invisible blood vessels through differences in power output voltage. RESULTS: The vertical scanning Doppler probe was 100% successful in identifying the target blood vessels regardless of the patient's body mass index (BMI), and also was superior to the conventional Doppler probe in detection sensitivity. The vertical scanning Doppler probe was useful for image training of recently qualified surgeons through real-time monitoring of the probe position and response on the monitor. Furthermore, findings showed that the vertical scanning Doppler probe was applicable to lymph node dissection as a forceps for laparoscopic usage. CONCLUSION: The vertical scanning Doppler could identify the target blood vessels regardless of the patient's BMI. It was verified to be useful as a surgical assistive device apart from being a sensor and may serve in the education of recently qualified surgeons.


Subject(s)
Blood Vessels/diagnostic imaging , Colectomy , Gastrectomy , Laparoscopy , Ultrasonography, Doppler/instrumentation , Arteries/diagnostic imaging , Body Mass Index , Education, Medical, Graduate , Educational Technology/instrumentation , Equipment Design , General Surgery/education , Humans , Lymph Node Excision , Mesenteric Artery, Inferior/diagnostic imaging , Sensitivity and Specificity , Stomach/blood supply
20.
JOP ; 8(1): 44-9, 2007 Jan 09.
Article in English | MEDLINE | ID: mdl-17228133

ABSTRACT

CONTEXT: Primary pancreatic lymphoma is a rare form of extranodal lymphoma originating in the pancreas. The present report describes a case of follicular lymphoma of the pancreas with unique CT and MRI findings. CASE REPORT: A 58-year-old male complained of sudden abdominal pain, and routine ultrasonography detected an 8 cm hypoechoic tumor in the head of the pancreas. The 3D image generated using multi-cholangiography and virtual duodenography provided the information necessary for a laparotomy. The tumor was enucleated for diagnosis. Follicular lymphoma is quite rare in the pancreas and gastrointestinal tract. A considerable number of pancreatic lymphoma subtypes have been reported. The expression "pancreatic lymphoma" has been used to describe both primary lymphoid neoplasms originating in the pancreatic parenchyma and tumors invading from a peri-pancreatic lymphadenopathy. The present case belongs to the latter, which might explain the unique imaging findings and histological type. These subtypes display different imaging findings and different clinical characteristics. In the future, primary pancreatic lymphoma should be discussed separately depending on the subtype. CONCLUSION: We propose a new subtype of primary pancreatic lymphoma. Multi-cholangiography and virtual duodenography provided the information necessary for a laparotomy in the present case. Enucleation is indicated for benign and low-grade malignant tumors of the pancreas, even if the tumor is located in the head of the pancreas.


Subject(s)
Lymphoma, Follicular/diagnosis , Pancreas/pathology , Pancreatic Neoplasms/diagnosis , Cholangiography/methods , Humans , Lymphoma, Follicular/pathology , Lymphoma, Follicular/surgery , Male , Middle Aged , Pancreas/surgery , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Tomography, X-Ray Computed/methods
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