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ABSTRACT: Control of liver metastasis is an important issue in the treatment of colorectal cancer (CRC). Micro RNAs (miRNA) have been shown to be involved in the development of many cancers, but little is known about their role in the process of colorectal liver metastasis. We compared miRNA expression between primary colorectal tumors and liver metastasis to identify those involved in the process of metastasis. Cancer cells were isolated from formalin-fixed paraffin-embedded primary CRC samples and their corresponding metastatic liver tumors in six patients using laser capture microdissection, and miRNA expression was analyzed using TaqMan miRNA arrays. miR-122 was the most abundant miRNA in liver metastasis compared with primary tumors. Immunohistochemical analysis revealed that the expression levels of cationic amino acid transporter 1 (CAT1), a negative target gene of miR-122, were lower in liver metastases than primary tumors (P<0.001). Expression levels of CAT1 in 132 primary tumors were negatively correlated with the existence of synchronous liver metastasis (P=0.0333) and tumor stage (P<0.0001). In an analysis of 121 colon cancer patients without synchronous liver metastasis, patients with CAT1-low colon cancer had significantly shorter liver metastasis-free survival (P=0.0258) but not overall survival or disease-free survival. Overexpression of miR-122 and concomitant suppression of CAT1 in the primary tumor appears to play important roles in the development of colorectal liver metastasis. CAT1 expression in the primary CRC has the potential to be a novel biomarker to predict the risk of postoperative liver metastasis of CRC patients.
Cancer Science 02/2013; · 3.33 Impact Factor
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ABSTRACT: A 46-year-old woman was admitted to our hospital for an evaluation of progressive renal insufficiency and elevated liver enzymes. A renal biopsy revealed chronic granulomatous interstitial nephritis. Her laboratory findings indicated primary biliary cirrhosis (PBC), which was confirmed with a liver biopsy. CD4(+) T cells and CD8(+) T cells with granuloma formation were the predominant cells infiltrating into the interstitium of the kidneys and liver. The etiology of tubulointerstitial nephritis in the present patient was not clear; however, it might have shared the same pathogenesis as PBC due to the relatively close onset, the similar profiles of infiltrating cells and the presence of granulomas.
Internal Medicine 01/2013; 52(4):467-71. · 0.94 Impact Factor
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Keisuke Inaba,
Takanori Sakaguchi,
Kiyotaka Kurachi,
Hiroki Mori,
Hong Tao,
Toshio Nakamura,
Yasuo Takehara, Satoshi Baba,
Masato Maekawa,
Haruhiko Sugimura,
Hiroyuki Konno
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ABSTRACT: Hepatocellular adenoma (HCA) is a benign liver tumor that most frequently occurs in young women using oral contraceptives. We report a rare case of HCA in a 29 years old female with familial adenomatous polyposis (FAP). The first proband was her sister, who underwent a total colectomy and was genetically diagnosed as FAP. A tumor, 3.0 cm in diameter, was detected in the right lobe of the liver during a screening study for FAP. A colonoscopy and gastroendoscopy revealed numerous adenomatous polyps without carcinoma. The patient underwent a total colectomy and ileo-anal anastomosis and hepatic posterior sectoriectomy. The pathological findings of the liver tumor were compatible with HCA. The resected specimen of the colon revealed multiple colonic adenomatous polyps. Examination of genetic alteration revealed a germ-line mutation of the adenomatous polyposis coli (APC) gene. Inactivation of the second APC allele was not found. Other genetic alterations in the hepatocyte nuclear factor 1 alpha and β-catenin gene, which are reported to be associated with HCA, were not detected. Although FAP is reported to be complicated with various neoplasias in extracolic organs, only six cases of HCA associated with FAP, including the present case, have been reported. Additional reports will establish the precise mechanisms of HCA development in FAP patients.
World journal of hepatology. 11/2012; 4(11):322-6.
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ABSTRACT: Hemangiopericytoma (HPC) preferentially developing in soft tissues and the meninges has been gradually recognized to be an aggressive, highly metastatic tumor. We herein report the case of a 65-year-old male with pancreatic metastases of cerebellar HPC that developed following two resections of intracranial local recurrent foci, 24 years after the initial craniotomy and 7 years after resection of metastases to the lungs and kidneys. Follow-up abdominal computed tomography scanning and magnetic resonance imaging revealed a solitary tumor in the pancreatic body. Since no other recurrent foci were detectable, distal pancreatectomy was performed. Another metastasis was incidentally found in the resected pancreas. Both foci were pathologically proven to be metastases of HPC. Among the 12 reported cases of pancreatic metastases of HPC, including ours, this case showed the longest duration between initial onset and the development of pancreatic metastases, suggesting that providing long-term follow-up is necessary for HPC patients.
Surgery Today 11/2012; · 1.22 Impact Factor
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Hatsuko Nasu,
Akiko Ikeda,
Hiroyuki Ogura,
Chikako Teruya,
Kei Koizumi,
Mana Kinoshita,
Takashi Tsuchida, Satoshi Baba,
Katsutoshi Miura,
Yasuo Takehara,
Harumi Sakahara
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ABSTRACT: Diabetic mastopathy is a rare benign condition associated with long-standing diabetes mellitus and presents with breast lumps. This report describes two cases in which diffusion-weighted images (DWI) on magnetic resonance imaging were quite different from each other. In case 1, there were hyperintense lesions on DWI, and surgically removed specimens revealed ductitis with marked lymphocytic infiltration. In case 2, no abnormal intensity was depicted on DWI, and biopsy specimens showed dense stromal fibrosis with mild perivascular lymphocytic infiltration that corresponded to previous reports. Although it is reported that diabetic mastopathy is composed of dense fibrous tissue with low cellularity that results in no hyperintense lesion on DWI, in cases with marked lymphocytic infiltration, strong hyperintensity can be seen on DWI mimicking malignant breast tumors.
Breast Cancer 09/2012; · 1.36 Impact Factor
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Yoshifumi Arai,
Takashi Tsuchida,
Isao Kosugi,
Hideya Kawasaki,
Shiori Meguro,
Mana Kinoshita, Satoshi Baba,
Matsuyoshi Maeda,
Yuichiro Shinmura,
Yoshihiro Tsutsui,
Toshihide Iwashita
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ABSTRACT: Pulmonary cytomegalovirus (CMV) infection causes fatal CMV pneumonia (CMVp) in immunocompromised patients; however, the mechanisms underlying CMV-infection-induced pulmonary lesion development remain largely unknown. We examined the relationship between CMVp patterns and intrapulmonary viral tropism, including expression of inflammatory cytokines and related molecules. Double immunohistochemistry of CMV antigen and cellular markers showed that epithelial tropism was associated with a diffuse alveolar damage (DAD) pattern (CMVp-DAD) while stromal tropism was associated with a predominantly interstitial inflammation/fibrosis (IIF) (CMVp-IIF) or a combination of DAD and IIF (CMVp-complex). Transforming growth factor (TGF)-β1 expression was relevant to CMV-induced tissue injury, and its expression was higher in CMVp-complex and CMVp-IIF than in CMVp-DAD. Expression of integrin β6 (ITGB6), an adhesion molecule and important activator of TGF-β1 in interstitial pneumonia, was lost in CMV-infected pneumocytes, especially CMVp-DAD, whereas CMV-negative pneumocytes in CMVp-complex and CMVp-IIF showed overexpression. Diffuse interleukin (IL)-8 up-regulation and strong expression were present in both CMV-infected pneumocytes and stromal cells only in CMVp-IIF cases with marked interstitial neutrophilic infiltration. On the basis of viral tropism and the expression of TGF-β1, ITGB6, and IL-8, we conclude that CMV-infected pulmonary cells play an important role in the development of diverse CMVp patterns.
Pathology International 09/2012; 62(9):628-39. · 1.62 Impact Factor
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ABSTRACT: Extranodal natural killer (NK)/T-cell lymphoma, nasal type, exhibits aggressive tumor behavior and carries a poor prognosis. Recently, lymphomatoid gastropathy with NK/T cell infiltration into gastric mucosa has been recognized as a pseudo-malignant disease which regresses without treatment. Because the conventional immunohistochemical criteria of lymphomatoid gastropathy is similar to that of extranodal NK/T-cell lymphoma nasal type, it is difficult to distinguish between the two conditions by histopathological evaluation only. Here, we report a rare case of lymphomatoid gastropathy in a 57-year-old female. Gastroendoscopy on routine check-up revealed elevated reddish lesions < 1 cm in diameter in the gastric fornix and body. Although repeat endoscopies at 1 and 6 mo later revealed no gastric lesions at any locations without any treatments, at 12 mo later gastric lymphomatoid lesions recurred at gastric fornix and body. Histological examination of endoscopic biopsy specimens at 12 mo showed atypical NK cell infiltration with CD3⁺, CD4⁻, CD5⁻, CD7⁺, CD8⁻, CD20⁻, CD30⁻, CD56⁺, CD79a⁻ and T-cell-restricted intracellular antigen-1⁺ into gastric mucosa. After treatment for Helicobacter pylori (H. pylori) eradication, the lesions disappeared in all locations of the gastric fornix and body over the subsequent 12 mo. Here, we report a case of H. pylori-positive lymphomatoid gastropathy with massive NK-cell proliferation, and also review the literature concerning newly identified lymphomatoid gastropathy based on comparison of extra nodal NK/T-cell lymphoma nasal type. In any case, these lesions are evaluated with biopsy specimens, the possibility of this benign entity should be considered, and excessive treatment should be carefully avoided. Close follow-up for this case of lymphomatoid gastropathy is necessary to exclude any underlying malignancy.
World Journal of Gastroenterology 05/2012; 18(17):2140-4. · 2.47 Impact Factor
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Yoshifumi Morita,
Takanori Sakaguchi,
Naoki Unno,
Yasushi Shibasaki,
Atsushi Suzuki,
Kazuhiko Fukumoto,
Keisuke Inaba, Satoshi Baba,
Yasuo Takehara,
Shohachi Suzuki,
Hiroyuki Konno
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ABSTRACT: BACKGROUND: Indocyanine green (ICG), an agent for measuring liver function, becomes fluorescent under near-infrared (NIR) light after binding to serum proteins. Hepatocellular carcinoma (HCC) with a deposit of preoperatively administered ICG becomes clearly detectable under ICG fluorography; however, it remains unclear whether this detection method is always reliable. This case series study was designed to clarify the reliability of this method. METHODS: ICG (0.5 mg/kg) was injected from the 3rd to 28th preoperative day to evaluate hepatic function in 58 patients with HCCs. Preoperative imaging modalities identified 76 HCC foci. The operative fields and resected specimens were observed with an NIR camera system. Preoperatively detected lesions and lesions newly detected by the ICG fluorography were histologically investigated. RESULTS: ICG fluorography identified 73 of 76 preoperatively diagnosed HCC lesions. Intraoperative ICG fluorography visualized 47 lesions in 40 patients. The other 26 lesions showing emission were found in the sectioned specimens under NIR observation. Other than preoperatively diagnosed foci, ICG fluorography visualized 35 new lesions, including 6 HCCs, 2 dysplastic nodules and 27 non-neoplastic lesions, such as bile plugs and cysts. The sensitivity of ICG fluorography for HCCs was 96% and its positive predictive value was 71.5%. CONCLUSIONS: Indocyanine green fluorography is useful to detect HCCs; however, attention should be paid to the fact that HCCs may be occasionally overlooked by this imaging method and that lesions detected by this method are not always neoplastic lesions.
International Journal of Clinical Oncology 12/2011; · 1.41 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 08/2011; 69 Suppl 6:93-8.
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ABSTRACT: We present the first case report of the use of sorafenib and S-1 for the treatment of renal cell carcinoma (RCC) producing granulocyte colony-stimulating factor (G-CSF). This entity is clinically rare and has a poor outcome. A 78-year-old Japanese man presented with macrohematuria, left flank pain, and a palpable mass. Laboratory data showed marked leukocytosis with increased serum and urinary G-CSF. The histopathological diagnosis was unclassified RCC. New combination therapy with sorafenib and S-1 exerted a therapeutic effect and apparently decreased serum and urinary G-CSF levels, although the patient died of gastrointestinal perforation. The use of combined sorafenib and S-1 may be worthy of consideration in the treatment of RCC producing G-CSF.
International Journal of Clinical Oncology 06/2011; 16(3):275-8. · 1.41 Impact Factor
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ABSTRACT: We report a case of pancreatic metastasis from breast cancer during multimodality therapy. A 53-year-old woman received right breast-conserving surgery for invasive ductal carcinoma and then chemo-radiotherapy for liver, brain, bone, neck and axillary lymphnodes, mediastinum, pleural, and spinal cord metastasis. Although she then survived in a tumor-free condition, a blood examination performed 4 years after the surgery showed an elevated serum amylase level. Abdominal CT and US revealed swelling of the pancreas head and body with main pancreatic duct dilatation of the pancreatic tail. ERCP showed diffuse stenosis of the extrahepatic bile duct and the main pancreatic duct of the pancreatic head and body. Immunohistochemical staining of the biopsy specimen from the pancreatic head confirmed pancreatic metastasis from breast cancer. Despite the intensive chemotherapy including trastuzumab, she died 2 years after the onset of pancreatic metastasis. Metastatic breast cancer to the pancreas is very rare. However, considering the recent advances of multimodality therapy for breast cancer, this clinical state may become more common.
Gan to kagaku ryoho. Cancer & chemotherapy 02/2011; 38(2):301-3.
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ABSTRACT: A 56-year-old man with chief complaints of dry cough and dyspnea was admitted. He had severe hypoxemia, and his chest radiographs showed enhancement of pulmonary artery opacities with multiple defects on pulmonary blood flow scintigraphy. Enhanced computed tomography (CT) revealed swelling of the mediastinum and hilar lymph nodes, but no apparent thrombi in the pulmonary arteries was seen. A biopsy specimen of a left neck lymph node showed poorly differentiated adenocarcinoma, including signet-ring cell carcinoma components, but the origin was unclear. Despite receiving chemotherapy, his respiratory condition worsened, and he died 3 days after admission. Routine autopsy failed to clarify the tumor origin, but a detailed dissection of specimens confirmed early gastric cancer. Additionally, pathology of the pulmonary arteries was compatible with pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is a rare condition characterized by the presence of diffuse thrombotic microthrombi and fibrocellular intimal proliferation in the pulmonary vasculature. Accompanied with early gastric cancer, this is an extremely rare but important case of PTTM.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 02/2011; 49(2):122-7.
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Yoshifumi Morita,
Takanori Sakaguchi,
Yasushi Shibasaki,
Kosuke Oishi,
Atsushi Suzuki,
Kazuhiko Fukumoto,
Keisuke Inaba, Satoshi Baba,
Yasuo Takehara,
Shohachi Suzuki,
Takashi Okai,
Hiroyuki Konno
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ABSTRACT: We report a case of primary hepatic actinomycosis showing elevation of serum protein induced by vitamin K absence or antagonist II (PIVKA-II). A 68-year-old man visited an affiliated hospital with a complaint of high fever and body weight loss. Hematological examination revealed severe inflammatory reactions and liver dysfunction. Abdominal CT showed a heterogeneous low density area composed of cystic and solid part. We suspected the cystic part with band-like enhancement to be a hepatic abscess and performed percutaneous transhepatic abscess drainage. Although inflammatory reactions decreased after the drainage, the solid part did not shrink and blood chemistry revealed elevation of PIVKA-II. Since we could not rule out the possibility of hepatoma, right hepatectomy was performed. Histological examination revealed actinomycetes. Although primary hepatic actinomycosis is a rare disease, it must be kept in mind in the differential diagnosis of the liver tumor.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2011; 108(10):1735-42.
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Tomohiko Setoguchi,
Hirotoshi Kikuchi,
Masayoshi Yamamoto,
Megumi Baba,
Manabu Ohta,
Kinji Kamiya,
Tatsuo Tanaka, Satoshi Baba,
Naoko Goto-Inoue,
Mitsutoshi Setou,
Takeshi Sasaki,
Hiroki Mori,
Haruhiko Sugimura,
Hiroyuki Konno
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ABSTRACT: Although the main cause of gastrointestinal stromal tumor (GIST) is gain-of-function mutations in the c-kit gene in the interstitial cells of Cajal, concomitant genetic or epigenetic changes other than c-kit appear to occur in the development of metastasis. We sought to identify the genes involved in the metastatic process of gastric GIST. Microarray analysis was performed to compare gene expressions between three gastric GIST and four metastatic liver GIST. Expression levels were higher for 165 genes and lower for 146 genes in metastatic liver GIST. The upregulation of five oncogenes and downregulation of four tumor suppressor genes including versican and CD9 were confirmed by quantitative reverse transcriptional PCR. Immunohistochemistry in 117 GIST revealed that protein levels of versican and CD9 were higher and lower, respectively, in metastatic GIST. High expression of versican and low expression of CD9 in 104 primary gastric GIST correlated with poor disease-free survival (P = 0.0078 and P = 0.0018). In addition to the c-kit gene mutation, genetic or epigenetic changes other than c-kit play important roles in the metastatic process. In particular, versican and CD9 are potential prognostic markers in gastric GIST.
Cancer Science 01/2011; 102(4):883-9. · 3.33 Impact Factor
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ABSTRACT: This report presents a case of pancreatic neuroendocrine cell carcinoma with multiple liver metastases secreting gastrin and parathyroid hormone-related protein (PTHrP) related to lumbar bone fracture and hypercalcemia. A 58-year-old woman visited an affiliated hospital with a chief complaint of lumbago without any evidence of trauma. She was diagnosed with hepatic dysfunction and hypercalcemia as well as multiple lumbar compression fractures without osteolytic lesions. Abdominal computed tomography (CT) showed a hypervascular mass in the pancreatic tail and multiple liver tumors. Duodenal ulcers were found with gastrointestinal endoscopy. There was a marked increase in the serum gastrin level. She was diagnosed as gastrinoma with multiple liver metastases and was admitted to the hospital. She had an increase in serum PTHrP level without the elevation of intact parathyroid hormone at the time of admission. She underwent an extended right hepatectomy in addition to a distal pancreatectomy with a regional lymphadenectomy and splenectomy. The postoperative course was uneventful, and serum gastrin and PTHrP activities reduced to normal levels. She remained symptom-free, and serum calcium, gastrin, and PTHrP levels remain within the normal ranges 19 months after surgery without adjuvant therapy.
Surgery Today 12/2010; 40(12):1192-6. · 1.22 Impact Factor
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ABSTRACT: The case was a man in his 60s with no past history of heart and lung. Chest tightness was felt during the first course of cetuximab therapy for recurrent colon cancer. He was diagnosed as having vasospastic angina, and administration of vasodilatation agents was done. After the therapy, no chest pain attack was seen. Chemotherapy was continued. After 3 courses, fever elevation, chest tightness and dyspnea were seen. Chest X-ray and CT revealed diffuse interstitial pneumonia in bilateral lung. Although steroid pulse therapy and intensive therapy with mandatory ventilation were performed, he died of respiratory failure. Pathological findings of autopsy revealed remarkable metastasis of cancer cells to the bilateral lungs accompanied chiefly with carcinomatous lymphangiosis. Furthermore, acute and subacute interstitial pneumonia with diffuse alveolar damage were seen in the background of the lungs. Cardiopulmonary disorder as well as skin disorder should be considered as possible adverse events of cetuximab therapy.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(11):2193-8.
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ABSTRACT: Acinar cell carcinoma is a relatively rare malignant neoplasm, which represents 1%-2% of all pancreatic exocrine tumors. Its prognosis is thought to be poor, especially when it metastasizes to the liver. This report concerns a case of a long-term survivor of metastatic acinar cell carcinoma who was successfully treated with repetitive surgery. A 62-year-old man underwent a distal pancreatectomy for a pancreatic tumor, which was histologically diagnosed as an acinar cell carcinoma. The tumor recurred in the liver three times within 41 months. At the first recurrence, four hepatic lesions appeared 7 months after the initial pancreatectomy and were managed with an extended left hepatic lobectomy and partial liver resection. Thereafter, a solitary nodule in Segment 6 was identified 21 months after the second surgery and was treated with a partial liver resection. A solitary lesion in Segment 8/5 appeared 11 months after the third surgery and was also managed by a partial liver resection. The patient has remained disease-free for 22 months since the last surgery and has survived 65 months since the initial diagnosis. Although no consensus has been reached on surgery for metastatic acinar cell carcinoma, the current case has important implications for establishing an appropriate treatment strategy.
Surgery Today 07/2010; 40(7):679-83. · 1.22 Impact Factor
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ABSTRACT: Microscopic pulmonary tumor embolism is difficult to diagnose. Herein is presented the case of a patient who suffered from acute dyspnea and breast cancer on the right side. Two weeks after the breast cancer diagnosis the patient began to experience dyspnea. After 2 weeks of dyspnea, the patient died without an accurate diagnosis of dyspnea. Autopsy indicated massive microscopic pulmonary emboli of the breast cancer. Immunohistochemistry showed that most of the cancer cells in the primary site were negative for estrogen receptors, progesterone receptors Her2/neu oncogene (triple negative), and stem cell-like markers (OCT3/4, NANOG2, CD44, CD24, aldehyde dehydrogenase 1 (ALDH1)). The breast cancer cells in the lung (the metastasized site), however, were triple negative, but were enriched in stem cell-like markers (OCT3/4(+), NANOG2(+), CD44(+)/CD24(-/low), ALDH1(+)). This is a significant case report indicating that vascular emboli themselves contain the essential molecular signature of 'stemness' independent of the origin.
Pathology International 03/2010; 60(3):228-34. · 1.62 Impact Factor
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ABSTRACT: A 95-year-old woman who presented with ischemic heart disease was admitted due to a sensation of chest compression. Endoscopy was performed due to anemia which showed an irregular ulcerative lesion in the duodenal bulb which a biopsy revealed to be high-grade neuroendocrine carcinoma. Distant metastasis was found and the patient died from the original disease 3 months after the first medical examination. The result of autopsy was neuroendocrine carcinoma of duodenum and invasion and metastases to multiple organs. We report a case of neuroendocrine carcinoma originating from the duodenum excluding the papilla which is extremely rare in Japan.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2010; 107(1):84-92.
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Naoko Nakayama,
Yoshihide Fujigaki,
Takayuki Tsuji,
Masanori Sakakima,
Hideo Yasuda,
Akashi Togawa,
Hiroyuki Suzuki,
Tomoyuki Fujikura,
Akihiko Kato, Satoshi Baba,
Satoru Takahashi,
Akira Hishida
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ABSTRACT: Here we report a 75-year-old man with multiple myeloma who developed acute deterioration of renal function. Systemic AL amyloid deposition was found in the stomach, duodenum and brachial artery. A small amount of proteinuria without significant abnormal urinary sediments, increased excretion of urinary low-molecular-weight proteins and Bence Jones protein were observed. Significant renal Ga-67 uptake suggested acute tubulointerstitial lesions. Renal necropsy after sudden death 40 days after introduction of hemodialysis revealed mesangial expansion with glomerular basement membrane thickening, tubular basement membrane thickening with or without tubular atrophy and massive tubulointerstitial fibrosis. Slight amyloid depositions in the mesangium and vessels, and massive granular electron-dense deposits and deposition of monoclonal light chain lambda in renal basement membranes and vessels were found, indicating the rare condition of coexistence of amyloidosis and light chain deposition disease(LCDD). The rapid progression of renal failure may have been caused by massive deposition of monoclonal light chains in our patient.
Clinical and Experimental Nephrology 09/2009; 13(6):671-6. · 1.37 Impact Factor
