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1.
Case Rep Gastroenterol ; 18(1): 279-285, 2024.
Article in English | MEDLINE | ID: mdl-39015521

ABSTRACT

Introduction: The peribiliary gland is an accessory bile duct gland. Hyperplasia of these tissues may lead to elevation of the mucosa in the bile ducts and bile duct stenosis. We herein report a case of peribiliary gland hyperplasia that required preoperative differentiation from bile duct cancer, with a discussion of the literature. Case Presentation: The patient had an adenomatous lesion in the ascending colon that was difficult to treat endoscopically; therefore, surgery was planned. Preoperative abdominal ultrasonography revealed a bile duct tumor, and endoscopic ultrasonography revealed a mass lesion around the confluence of the cystic duct. Computed tomography revealed localized wall thickening in the middle bile duct, and the upstream bile ducts were slightly dilated. In addition, continuous thickening of the bile duct wall from the gallbladder to the confluence of the cystic duct was observed. No distant metastases, such as liver metastases, or nearby enlarged lymph nodes were observed. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography revealed a papillary-like elevated lesion in the bile duct near the confluence of the cystic duct, and a biopsy and bile cytology from the same area showed no malignant findings. As a result, the possibility that the patient had gallbladder or bile duct cancer could not be ruled out; therefore, a policy of surgery together with the ascending colon tumor was decided after receiving sufficient informed consent. During surgery, the patient underwent extrahepatic bile duct resection, reconstruction of the biliary tract using the Roux-en-Y method, and right hemicolectomy. Both duodenal and hilar bile duct transects were subjected to a fast frozen section analysis during surgery, and the results were negative for cancer. A histopathological examination of the resected specimen revealed no malignant findings in the bile duct lesions, and a diagnosis of peribiliary gland hyperplasia with chronic inflammatory cell infiltration and fibrosis of the extrahepatic bile duct wall was made. Conclusions: We encountered a case of peribiliary gland hyperplasia that was difficult to distinguish from bile duct cancer.

2.
J Surg Case Rep ; 2024(7): rjae457, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39005639

ABSTRACT

This study presents a case of a 72-year-old man diagnosed with non-small cell lung cancer (cT4N0M0) referred to our hospital for possible surgical treatment of a solitary nodule detected in the mesorectum. The patient had received combined chemoradiotherapy and achieved a complete response 13 months before the presentation. On examination, the mesorectal nodule was incidentally detected during surveillance computed tomography, and the maximum standardized uptake value of the nodule was 10.3. Because of the potential malignancy and need for en-bloc resection of the nodule, we performed laparoscopically assisted high anterior resection of the rectum. The postoperative course was uneventful. Notably, while pathological examination revealed that the mesorectal nodule comprised an intravenous organized thromboembolism, malignancy was not observed. These findings suggest that although positron emission tomography/computed tomography with 18F-fluorodeoxyglucose is useful for the diagnosis of malignant diseases, surgical resection might be the most reliable option for complex cases such as ours.

3.
DEN Open ; 3(1): e228, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36998349

ABSTRACT

Intraductal papillary neoplasms of the bile duct (IPNB) are a tumor derived from bile duct epithelium that tends to spread laterally and non-invasively. Surgery is the first-choice treatment for IPNB. It is extremely important to accurately diagnose the extent of lateral tumor extension. Although peroral cholangioscopy (POCS) is a potentially useful modality for detecting tumor range with direct observation, poor image quality is a limitation of POCS. Recently, a new-generation endoscopy system (EVIS X1) was equipped with functions such as red dichromatic imaging to improve image quality. A 75-year-old man with cholangitis was referred to our department. Various imaging studies showed a mass in the middle to lower bile duct and dilatation of the common bile duct and the intrahepatic bile duct. Endoscopic retrograde cholangiopancreatography was performed. A biopsy of the main tumor in the lower common bile duct revealed IPNB. It was difficult to determine the extent of superficial tumor extension with modalities such as contrast-enhanced computed tomography, magnetic resonance imaging, and endoscopic ultrasonography but the detailed evaluation was possible using POCS with red dichromatic imaging 3. The patient underwent hepatopancreatoduodenectomy. This case suggests the usefulness of direct observation using POCS with red dichromatic imaging 3 to determine the range of IPNB.

4.
BMC Surg ; 22(1): 213, 2022 Jun 03.
Article in English | MEDLINE | ID: mdl-35655198

ABSTRACT

BACKGROUND: Our aim of was to compare importance of the tumor markers (TMs) serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in prediction of recurrence after curative gastrectomy for gastric cancer. METHODS: We reviewed retrospectively the clinical records of 149 patients who underwent curative gastrectomy for stage I-III gastric cancer and whose CEA and CA19-9 levels were determined once preoperatively and for more than 3 years postoperatively. We investigated whether the clinicopathological characteristics of patients including age, sex, pathological disease stage, operative approach, type of gastrectomy, and degree of lymph node dissection as well as preoperative positivity of CEA and CA19-9 were risk factors for recurrence in univariate and multivariate analyses. Rate of recurrence was compared between patients positive and negative for postoperative CEA or CA19-9. We also calculated sensitivity, specificity, positive and negative predictable values of postoperative positivity of CEA and CA19-9 for recurrence. The lead time was compared between CEA and CA19-9 that was defined as the time of the first detection of increases in tumor markers and confirmation of recurrence on imaging modalities. RESULTS: The number of patients positive for preoperative CEA was 25 (17%) and for CA19-9 was 11 (7%). Recurrence was confirmed in 29 (19%) patients. Stage III disease, preoperative positivity for CA19-9 but not CEA, and total gastrectomy were risk factors for recurrence in univariate analysis, but stage III disease was the only risk factor for recurrence in multivariate analysis. Forty and 15 patients were positive for postoperative CEA and CA19-9, respectively. The recurrence rate of 47% (7/15) in patients positive for postoperative CA19-9 was greater than that in negative patients (22/134 = 16%), but it did not differ between patients who were positive or negative for postoperative CEA. Specificity for CA19-9 was greater than that for CEA (P < 0.05). The lead time of CEA (3.9 ± 4.7 months) was not different from that of CA19-9 (6.1 ± 7.1 months). CONCLUSIONS: These results indicate that CA19-9 rather than CEA is likely to be more useful for the detection of recurrence after curative gastrectomy for gastric cancer.


Subject(s)
CA-19-9 Antigen , Stomach Neoplasms , Biomarkers, Tumor , Carcinoembryonic Antigen , Gastrectomy , Humans , Neoplasm Recurrence, Local/surgery , Retrospective Studies , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
5.
Case Rep Gastroenterol ; 15(2): 578-586, 2021.
Article in English | MEDLINE | ID: mdl-34616259

ABSTRACT

Schwannomas are benign tumors originating from Schwann cells, which are the main component of the neural sheath. Biliary schwannomas are extremely rare. We report the case of a 78-year-old man who presented with no abdominal symptoms or jaundice. CT imaging showed a hyperdense mass extending along the extrahepatic bile duct, and the upstream bile ducts were dilated. We performed extrahepatic bile duct resection under a preoperative diagnosis of the extrahepatic bile duct cancer. A histopathological examination of the resected specimen revealed that the tumor consisted of spindle cells which exhibited a palisading arrangement. Immunohistochemical staining was positive for protein S-100 and vimentin. Based on these pathological findings, we diagnosed the patient with schwannoma of the extrahepatic bile duct. Our search of the relevant literature revealed 19 case studies of biliary schwannomas. In our case, the surgical findings showed that the tumor was noninvasive and mobile. During surgery, a fast frozen section analysis was performed, and no malignant findings were observed. These results enabled us to avoid extrahepatic bile duct resection with major hepatectomy. We experienced a case of biliary schwannoma that was difficult to distinguish from bile duct cancer.

7.
Sci Rep ; 10(1): 21592, 2020 12 09.
Article in English | MEDLINE | ID: mdl-33299012

ABSTRACT

Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274low fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274low cells, and that BEX2 knockdown decreased the tumorigenicity and G0 phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G0 phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma.


Subject(s)
Bile Duct Neoplasms/metabolism , Cholangiocarcinoma/metabolism , Gene Expression Regulation, Neoplastic , Mitochondria/metabolism , Neoplastic Stem Cells/metabolism , Nerve Tissue Proteins/metabolism , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/pathology , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Cullin Proteins/genetics , Cullin Proteins/metabolism , Humans , Mitochondria/genetics , Mitochondria/pathology , Nerve Tissue Proteins/genetics , Oxygen Consumption/physiology
8.
Pancreatology ; 20(3): 493-500, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32007357

ABSTRACT

BACKGROUND: Accumulating evidence indicates that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is highly expressed in human epithelial carcinomas of multiple organs including the pancreas, but its functional role in carcinoma development has not yet been fully clarified. The aim of this study was to investigate the role of CD109 in the malignancy of pancreatic ductal adenocarcinoma (PDAC). METHODS: PDAC specimens of 145 cases were immunostained for CD109, and correlations between CD109 expression and clinicopathological conditions were analyzed. CD109 expression in PANC-1 cells, a PDAC-derived cell line, was decreased by siRNA or shRNA and its effect on the malignancy of PANC-1 cells was examined. RESULTS: Suppression of CD109 expression in PANC-1 cells resulted in reduction of in vitro cell motility and tumorigenicity in xenografts. Based on these results, we investigated the relationship between CD109 expression and metastasis of PDAC using tumor tissue specimens. Among 106 recurrent cases of 145 PDAC, there was a tendency for CD109-positive cases to be accompanied by distant metastasis. CONCLUSIONS: CD109 plays a critical role in the promotion of tumorigenic ability and cellular motility relating to metastasis of PDAC cells.


Subject(s)
Antigens, CD/genetics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Neoplasm Proteins/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Animals , Cell Line, Tumor , Cell Movement/genetics , Female , GPI-Linked Proteins/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Mice , Middle Aged , Neoplasm Metastasis/genetics , Neoplasm Metastasis/pathology , RNA, Small Interfering/pharmacology , Wound Healing , Xenograft Model Antitumor Assays
9.
BMC Surg ; 19(1): 106, 2019 Aug 08.
Article in English | MEDLINE | ID: mdl-31395044

ABSTRACT

BACKGROUND: The aim of this study was to investigate the influence of patients' age on postoperative morbidities including pneumonia. METHODS: We reviewed the clinical records of 211 patients with stages I - III gastric cancer undergoing curative distal gastrectomy (DG) or total gastrectomy (TG). Patients were classified into an elderly (≧80 y.o.) or a control (< 80 y.o.) group. We compared patient characteristics (sex ratio, disease stage, degree of lymph node dissection, number of retrieved lymph nodes, and type of reconstruction) and early postoperative outcomes (operation time, intra-operative blood loss, and postoperative morbidity including pneumonia, and mortality) between the two groups separately in DG and TG. RESULTS: There were 134 and 77 patients who underwent DG and TG, respectively. The numbers of patients in the elderly and control groups were 25 and 109 in DG and 12 and 65 in TG. The percentage of female patients in the elderly group was greater than that in the control group in both DG and TG. The extent of lymph node dissection did not differ between two groups in TG; in contrast in DG, the rate of a D1 dissection was greater in the elderly group than in the control group. There were no differences between the two groups in distribution of disease stage, number of retrieved lymph nodes, operation time, and blood loss in DG and in TG. Overall postoperative morbidity did not differ between two groups after DG and after TG. The rate of infectious complications in the elderly group was not different from that in the control group after DG and after TG. The incidence of pneumonia was more frequent in the elderly group compared to the control group after DG (8% vs. 1%, P < 0.05) but not after TG (17% vs. 5%). When patients were compared between the elderly and the control groups regardless of type of gastrectomy, the incidence of pneumonia in the elderly group (4/37 (11%)) was greater than that in the control group (4/174 (2%), P < 0.05). CONCLUSIONS: These results suggest that pneumonia is increased in patients older than 80 years after DG.


Subject(s)
Gastrectomy , Pneumonia/etiology , Postoperative Complications/etiology , Stomach Neoplasms/surgery , Adult , Age Factors , Aged , Aged, 80 and over , Case-Control Studies , Female , Gastrectomy/methods , Humans , Incidence , Male , Middle Aged , Pneumonia/epidemiology , Postoperative Complications/epidemiology , Retrospective Studies , Risk Factors
10.
Int J Oncol ; 52(3): 881-891, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29393401

ABSTRACT

The majority of cancer cells maintain a high glycolytic activity and an increased lactate production, even in a well oxygenated environment. This phenomenon is known as the Warburg effect. Previous studies have revealed that various types of cancer selectively express the pyruvate kinase M2 isoform (PKM2), and that PKM2 plays a pivotal role in the Warburg effect. Although elevated PKM2 levels have been observed in pancreatic cancer and other types of cancer, little is known about the biological function of PKM2. In this study, in order to examine the expression and role of PKM2 in pancreatic ductal adenocarcinoma (PDAC), we knocked down PKM2 in PDAC cells by introducing small interfering and short hairpin RNAs, and examined the gene expression profiles in the cells by microarray analysis. We analyzed the energy-producing pathways in the cells by XFe Extracellular Flux Analyzers, and detected intracellular metabolites by capillary electrophoresis time-of-flight mass spectrometry. We found that the RNAi-mediated knockdown of PKM2 diminished the proliferative, migratory and tumorigenic ability of the PDAC cell-lines. PKM2 knockdown also resulted in lower glycolytic activities and decreased levels of some intracellular metabolites, such as pyruvate and polyamine; however, it led to elevated levels of reactive oxygen species. Microarray analysis revealed the functional association between PKM2 and the expression of genes that drive the cell cycle. On the whole, the findings of this study demonstrate that PKM2 plays an important role in metabolic activities, as well as in the malignancy of PDAC cells.


Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Carrier Proteins/metabolism , Gene Expression Regulation, Neoplastic , Membrane Proteins/metabolism , Pancreatic Neoplasms/pathology , Reactive Oxygen Species/metabolism , Thyroid Hormones/metabolism , Animals , Carcinogenesis/genetics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/surgery , Carrier Proteins/genetics , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Profiling/methods , Gene Knockdown Techniques , Glycolysis/genetics , Humans , Isoenzymes/metabolism , Membrane Proteins/genetics , Metabolomics/methods , Mice, SCID , Pancreas/pathology , Pancreas/surgery , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/surgery , RNA, Small Interfering/metabolism , Thyroid Hormones/genetics , Xenograft Model Antitumor Assays , Thyroid Hormone-Binding Proteins
11.
Expert Opin Drug Deliv ; 14(12): 1355-1366, 2017 12.
Article in English | MEDLINE | ID: mdl-28379040

ABSTRACT

INTRODUCTION: Sixty years since its introduction, 5-FU still forms the core of chemotherapy regimens for many types of malignancies. 5-FU is a time-dependent drug but is rapidly degraded in plasma by dihydropyrimidine dehydrogenase (DPD). Although originally developed in an intravenous form, 5-FU oral prodrugs were developed with the goal of improving efficacy and minimizing toxicity as well as to capitalize on the advantages of oral drug administration. The inactive 5-FU prodrug is gradually converted into the active form in the systemic circulation. UFT, S-1, and capecitabine are oral 5-FU prodrugs currently in clinical use. However, the efficacy of 5-FU can be further improved by its combination with DPD inhibitors and biochemical modulators, such as uracil and leucovorin, in addition to modifying administration schedules. Areas covered: We focused on the drug delivery of oral 5-FU prodrugs, their pharmacokinetics, and the development of DPD inhibitors. Since oral 5-FU prodrugs have been formulated into combination drugs, we also discussed the regulatory approval of combination drugs. Expert opinion: Many regimens that include intravenously administered 5-FU can be replaced by oral 5-FU prodrugs. Patients would benefit from development of combination 5-FU oral prodrug formulations and its associated path through the combination drug regulatory approval process.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents/administration & dosage , Drug Delivery Systems/methods , Fluorouracil/administration & dosage , Neoplasms/drug therapy , Administration, Intravenous , Administration, Oral , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Dihydrouracil Dehydrogenase (NADP)/antagonists & inhibitors , Enzyme Inhibitors/administration & dosage , Fluorouracil/therapeutic use , Humans , Prodrugs/administration & dosage , Pyrimidines
12.
Hepatogastroenterology ; 62(138): 303-8, 2015.
Article in English | MEDLINE | ID: mdl-25916054

ABSTRACT

BACKGROUND/AIMS: This multicenter and single arm phase II clinical trial was performed to examine the safety and efficacy of modified FOLFOX6 (mFOLFOX6) as adjuvant treatment after resection of liver metastases from colorectal cancer. METHODOLOGY: Patients who had undergone R0-1 resection of liver metastases were assigned to 12 cycles of mFOLFOX6. The primary end point was disease-free survival (DFS). RESULTS: We enrolled 49 cases and analyzed adverse events in 48 cases, since in one patient cancer recurred before starting treatment. As to the relative dose intensity, 5-FU was 78.8%, and oxaliplatin was 75.9%. Adverse events of Grade 3 and above includ- ed 18 cases of neutropenia (37.5%), 4 cases of sensory neuropathy (8.3%), 4 cases of thrombocytopenia (8.3%) and 4 cases of allergy (8.3%), and there were no cases of fatality caused by adverse events. The most difference of adverse event compared with MOSAIC trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer) was thrombocytopenia. The 2-year DFS was 59.2% (95% CI: 36.7-78.4) in the 49 enrolled cases. CONCLUSION: mFOLFOX6 after hepatectomy was tolerable. And mFOLFOX6 also seemed to improve DFS. mFOLFOX is one of the options for such patients and appears promising as an adjuvant treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/pathology , Hepatectomy , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Adjuvant , Colorectal Neoplasms/mortality , Disease-Free Survival , Drug Administration Schedule , Feasibility Studies , Female , Fluorouracil/administration & dosage , Hepatectomy/adverse effects , Hepatectomy/mortality , Humans , Japan , Leucovorin/administration & dosage , Liver Neoplasms/mortality , Male , Middle Aged , Neoplasm Recurrence, Local , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Time Factors , Treatment Outcome
13.
Expert Opin Drug Discov ; 10(4): 411-26, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25724579

ABSTRACT

INTRODUCTION: Natural products (NPs) are evolutionarily designed and contain more complex and challenging structures than synthetic compounds. Since the 1980s, the pharmaceutical industry has gradually shifted to a strategy of developing targeted agents by screening libraries of synthetic compounds. However, NPs have recently received renewed focus as a rich repository for drug discovery. Irinotecan was developed as a derivative of camptothecin and was applied in standard regimens for metastatic colorectal cancer (CRC) worldwide. Additionally, polysaccharide K is approved for CRC in Japan and Taiwan in combination with cytotoxic agents. However, after the approval of irinotecan in 1996, no anti-cancer agents derived from NPs have been approved for CRC. AREAS COVERED: This review discusses NPs that are currently under investigation for the treatment of CRC. In addition, other NPs derived as purified ingredients and crude extracts are listed and also discussed. EXPERT OPINION: The use of NPs for the discovery of anti-cancer agents has not been fully investigated. New technologies that are currently applied for synthetic compounds may be utilized for anti-cancer drug discovery including NPs for CRC.


Subject(s)
Antineoplastic Agents/therapeutic use , Biological Products/therapeutic use , Colorectal Neoplasms/drug therapy , Animals , Colorectal Neoplasms/pathology , Drug Design , Drug Discovery/methods , Humans
14.
Expert Opin Drug Discov ; 9(9): 1087-101, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24896071

ABSTRACT

INTRODUCTION: The RAS-RAF-MEK-ERK pathway is one of the best characterized kinase cascades. During the exploration of small molecules that inhibit RAF1 kinase, regorafenib (BAY 73-4506) was discovered as a multikinase inhibitor which demonstrated anti-cancer, anti-angiogenic, and apoptotic activities in metastatic colorectal cancer. This was not the first multikinase inhibitor discovered for the disease; indeed, before regorafenib was approved by FDA as a multikinase inhibitor for metastatic colorectal cancer in 2012, sorafenib (BAY 43-9006) had already been developed to be the first in the world as a multikinase inhibitor for malignancy. Indeed, the only difference between the two compounds is fluorine bound to its proximal phenyl ring although the end result is a considerably different profile, both as a kinase inhibitor as well as in its clinical application. AREAS COVERED: In this drug discovery case history, the authors review the design, discovery, and development of both regorafenib and sorafenib from back in the 1990s. Furthermore, the authors highlight the drug's anti-cancer and anti-angiogenic properties as well as its efficacy, safety pharmacology and toxicology based on FDA documents. EXPERT OPINION: In order to better predict the efficacy of kinase inhibitors and to utilize them more efficiently, our understanding of drug discovery, the approaches for kinase profiling, and technologies needed for their development are paramount. Indeed, the authors believe that the field should better explore the use of predictive biomarkers that might be able to better assess these therapeutics. Pharmaceutical scientists must also consider the cost effectiveness of the targeted agents developed as a number of the drugs developed are very expensive.


Subject(s)
Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Phenylurea Compounds/therapeutic use , Pyridines/therapeutic use , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacology , Colorectal Neoplasms/pathology , Drug Design , Drug Discovery , Drug Evaluation, Preclinical , Humans , Niacinamide/analogs & derivatives , Niacinamide/pharmacology , Niacinamide/therapeutic use , Phenylurea Compounds/adverse effects , Phenylurea Compounds/pharmacology , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pyridines/adverse effects , Pyridines/pharmacology , Sorafenib
15.
Anticancer Res ; 32(8): 3069-75, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22843875

ABSTRACT

Aromatase is one of the key estrogen-producing enzymes and is regarded as one of the therapeutic targets in estrogen receptor-positive breast cancer patients. Human colon carcinoma has also been recently proposed as being an estrogen-responsive malignancy, but the detailed status of aromatase has not yet been reported. Therefore, in this study, we evaluated the aromatase expression in colon carcinoma using immunohistochemistry and real-time polymerase chain reaction. Aromatase mRNA was significantly higher (p=0.03) in colon carcinoma than in the corresponding non-neoplastic mucosa (n=31). Aromatase immunoreactivity tended to be positively associated with the intratumoral concentration of estrogens (n=53), and in particular, the concentration of estradiol was significantly higher (p=0.02) in aromatase-positive cases in men. Aromatase immunoreactivity was detected in the cytoplasm of the carcinoma cells in 217/328 (65%) examined colon carcinoma cases. Aromatase immunoreactivity was significantly positively correlated with tubular differentiation, and inversely correlated with Ki-67 labeling index, although not necessarily correlated with the clinical outcome of the patients. All these results demonstrate that colon carcinoma expresses functional aromatase, and that estrogens are locally synthesized in the tumor tissues. The findings reported here could contribute to a better understanding of the actions of estrogen in colon carcinoma.


Subject(s)
Aromatase/metabolism , Colonic Neoplasms/enzymology , Adult , Aged , Aged, 80 and over , Aromatase/genetics , Chromatography, Liquid , Female , Humans , Immunohistochemistry , Male , Middle Aged , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Spectrometry, Mass, Electrospray Ionization
16.
Hepatogastroenterology ; 59(115): 691-5, 2012 May.
Article in English | MEDLINE | ID: mdl-22469710

ABSTRACT

BACKGROUND/AIMS: Gemcitabine is widely used as a first-line therapy for biliary tract cancer (BTC). However, few studies have been conducted to analyze second- line therapies. METHODOLOGY: From 33 patients who had been administered gemcitabine following resection between May 2005 and August 2007, we retrospectively analyzed the safety and efficacy of S-1 in 11 cases who received S-1 as second-line therapy due to recurrence or relapse of the primary disease. RESULTS: Among the adverse events (AEs) observed during S-1 administration, the most common was a decrease in the concentration of hemoglobin, followed by thrombocytopenia. No Grade 4 AEs or worse were detected. In addition, the AEs and their respective severity strongly resembled those of gemcitabine used as a first-line therapy. There were 7 cases that could be evaluated according to RECIST criteria, of which 1 was considered in the partial response and 3 as stable disease. The medians of time to progression after S-1 administration and survival after S-1 administration were 5.6 months and 31 months, respectively. CONCLUSIONS: S-1 could be taken safely as a second-line therapy without provoking severe AEs. By preventing the cessation of S-1 administration due to its AEs, more continued S-1 administration could lead to a better prognosis for BTC.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Biliary Tract Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Drug Resistance, Neoplasm , Neoplasm Recurrence, Local , Oxonic Acid/therapeutic use , Tegafur/therapeutic use , Aged , Antimetabolites, Antineoplastic/adverse effects , Biliary Tract Neoplasms/diagnostic imaging , Biliary Tract Neoplasms/pathology , Biliary Tract Neoplasms/surgery , Biliary Tract Surgical Procedures , Chemotherapy, Adjuvant , Deoxycytidine/therapeutic use , Disease Progression , Drug Combinations , Female , Humans , Japan , Male , Middle Aged , Oxonic Acid/adverse effects , Retrospective Studies , Tegafur/adverse effects , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Gemcitabine
17.
Hepatogastroenterology ; 59(118): 1758-60, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22366495

ABSTRACT

BACKGROUND/AIMS: The rate and site of bone metastasis from cholangiocarcinoma as well as the prognosis are unclear. Therefore, we intend to make a comparative review of the background to bone metastasis, examine a high-risk group for bone metastasis and use the data towards the improvement in quality of life. METHODOLOGY: We studied 200 cases of cholangiocarcinoma resected in our division from January 2003 to April 2010. RESULTS: Bone metastasis was confirmed in four cases (2.0%). The survival period after the diagnosis of bone metastasis ranged from 2.9 months to 21.6 months and the average was 6.7 months. We studied histopathological findings of bone metastasis, lymph node metastasis, lymphatic invasion, blood vessel invasion and perineural invasion (ly, v and pn) and found that all of four bone metastasis cases were positive for lymph node metastasis which was a statistically significant factor affecting bone metastasis. CONCLUSIONS: Since the number of cases we studied is small, it is difficult to determine whether lymph node metastasis is a risk factor for bone metastasis; however, we think it is necessary to take the probability of bone metastasis into consideration when we provide medical care to patients positive for lymph node metastasis.


Subject(s)
Bile Duct Neoplasms/pathology , Bile Ducts, Extrahepatic/pathology , Bone Neoplasms/secondary , Cholangiocarcinoma/secondary , Lymph Nodes/pathology , Aged , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/surgery , Bile Ducts, Extrahepatic/surgery , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/mortality , Bone Neoplasms/therapy , Chi-Square Distribution , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/mortality , Cholangiocarcinoma/therapy , Female , Humans , Japan , Lymphatic Metastasis , Male , Middle Aged , Multimodal Imaging , Neoplasm Invasiveness , Positron-Emission Tomography , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors , Survival Analysis , Time Factors , Tomography, X-Ray Computed
18.
Gan To Kagaku Ryoho ; 39(1): 135-7, 2012 Jan.
Article in Japanese | MEDLINE | ID: mdl-22241369

ABSTRACT

A 68-year-old man with locally advanced pancreatic body cancer invading the celiac axis(CA, including common hepatic artery)and in contact with the superior mesenteric artery(SMA)underwent 2 courses of neoadjuvant chemotherapy(NAC); gemcitabine hydrochloride(GEM 1,000 mg/m / / 2, on day 1 and 15)and S-1(100mg/m2day, 2-weeks of continuous administration followed by 1-week rest). The tumor volume and the contact area to SMA were greatly diminished. All tumor markers were reduced. He underwent R0 resection by distal pancreatectomy with en bloc celiac axis resection(DP-CAR). After the surgery, he could continue adjuvant chemotherapy; (GEM 1,000 mg/m2)only twice because of malnutrition. Nine months later CT revealed local recurrence and multiple lung metastases. The patient died 371 days after surgery. Appropriate NAC can contribute to R0 resection in locally advanced pancreatic cancer.


Subject(s)
Pancreatectomy , Pancreatic Neoplasms/surgery , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Drug Combinations , Fatal Outcome , Humans , Male , Neoadjuvant Therapy , Neoplasm Invasiveness , Oxonic Acid/administration & dosage , Oxonic Acid/therapeutic use , Pancreatic Neoplasms/blood supply , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Tegafur/administration & dosage , Tegafur/therapeutic use , Tomography, X-Ray Computed , Gemcitabine
19.
Clin J Gastroenterol ; 4(6): 391-5, 2011 Dec.
Article in English | MEDLINE | ID: mdl-26189742

ABSTRACT

We report a case of severe hepatic failure caused by gemcitabine hydrochloride (GEM) monotherapy after pancreaticoduodenectomy for advanced pancreatic cancer. A 73-year-old woman received GEM as an adjuvant chemotherapy. She suffered from progressive edema, fatigue, and jaundice after the third GEM administration. Severe liver dysfunction and elevation of bilirubin was observed. A computed tomography scan and magnetic resonance imaging showed diffuse liver swelling suggesting severe hepatic edema with fat accumulation. Needle biopsy of the liver revealed remarkable cholestasis and fat deposition with mild damage of hepatocytes. Drug-induced liver failure was suspected. GEM-stimulated lymphocyte test was negative, but antinuclear antibody was elevated with a marked inflammatory response. She improved to an almost normal condition by steroid and liver protective therapies within a week. Although the frequency of liver failure induced by GEM monotherapy is very rare, it could be fatal. It is important to distinguish it from other causes of liver dysfunction following pancreaticoduodenectomy. Early detection and appropriate drug therapy can improve the prognosis.

20.
J Gastrointest Surg ; 15(3): 525-32, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21181561

ABSTRACT

UNLABELLED: BACKGROUNS/AIMS: There are few studies about the assessment of pancreatic function using computed tomography (CT) volumetry. In this study, we examined the correlation between CT volumetry and endocrine parameters (blood glucose and HbA1c) of the pancreas. METHODS: A total of 68 patients underwent enhanced CT for pancreatic disease from January to December in 2008. In particular, we analyzed the correlation of diabetic status and pancreatic CT parameters at 1 year after pancreatoduodenectomy in 32 patients. CT parameters including volume, volume/body weight, arterial phase density, the arterial phase to portal phase density ratio (A/P ratio) of the pancreas, and size of pancreatic duct were also analyzed. Correlation between CT parameters and diabetic status was analyzed preoperatively and postoperatively by ANOVA test. RESULTS: The preoperative diabetic status and parameters correlated well with arterial phase density (p = 0.004), A/P ratio, and pancreatic duct size (p < 0.0001). In the patients who underwent pancreatectomy, two out of 25 patients without preoperative diabetes mellitus (DM) had DM, and two out of seven patients with preoperative DM recovered from DM. Postoperative CT parameters correlated with the DM status 1 year after pancreatectomy. CONCLUSION: CT is a useful modality for evaluation of the pancreatic endocrine function and could be used for the prediction of postoperative diabetic outcome.


Subject(s)
Diabetes Mellitus/diagnostic imaging , Imaging, Three-Dimensional , Pancreas/diagnostic imaging , Tomography, X-Ray Computed , Analysis of Variance , Blood Glucose/metabolism , Body Weight , Diabetes Mellitus/blood , Diabetes Mellitus/etiology , Glycated Hemoglobin/metabolism , Humans , Organ Size , Pancreas/metabolism , Pancreas/surgery , Pancreaticoduodenectomy/adverse effects , Preoperative Period , ROC Curve
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