Biomedical subjects
Publications and source records attributed to Hiroyuki Katoh.
Vertebroplasty for pseudoartrosis of vertebral fracture using PMMA (polymethylmetacrylate) or CPC (calcium phosphate cement) is a new less invasive surgical method providing sufficient pain relief and correction of kyphosis.
Several reports on immunotherapy using dendritic cells-based vaccine have been published. We investigated findings using fusion cells (FCs) generated from rat dendritic cells and a syngeneic hepatic cancer cell line with regard to inducing anti-tumor immunity. Vaccination of rats using FCs protected against growth of the subcutaneously implanted tumor in vivo and induced infiltration of CD8(+) T cells into the tumor. At the site of CD8(+) T cell infiltration, there were apoptotic tumor cells. T cells from spleen of FCs-vaccinated rats with protective ability against tumor growth included tumor specific cytotoxic CD8(+) T cells restricted to major histocompatibility complex Class I. In addition, adaptive transfer of in vitro re-stimulated splenic T cells with FCs was effective in preventing tumor growth and in vivo vaccinations of rats with FCs after resection of the subcutaneous implanted tumor inhibited local tumor recurrences. Immunotherapy using FCs appears to be an effective method if used in combination with surgical or other anti-cancer therapies.
BACKGROUND: Locally advanced cancer of the pancreatic body involving the celiac and/or common hepatic arteries is often considered unresectable. Radical distal pancreatectomy with en bloc resection of these arteries without reconstruction was recently introduced to treat these tumors. However, experience is still limited. This study reviewed the safety and utility of the operation. PATIENTS AND METHODS: We retrospectively studied the charts of 13 patients who underwent radical distal pancreatectomy. RESULTS: Unplanned arterial reconstruction was required in three patients due to accidental injury. The postoperative mortality rate was 0% despite a morbidity rate of 62%. Patient's intractable abdominal and/or back pain was completely relieved immediately after surgery. Contrary to expectations, postoperative diarrhea was mild. The surgical margins, including the retroperitoneum, were clear histologically (R0 resection) in all patients. The 1- and 2-year survival rates were 51% and 14%, respectively, and median survival was 12.2 months. The site of recurrence was the liver in six patients and retroperitoneum in one. CONCLUSIONS: Distal pancreatectomy with en bloc resection of the celiac artery is feasible and safe, offers a high resectability rate, and has dramatic analgesic effect. Local control of disease is excellent despite frequent hepatic recurrence.
The purpose of this study is to clarify the roles of immune cell types, both individually and synergistically, in esophageal squamous cell carcinoma (ESCC). One hundred and twenty-two patients (105 males and 17 females; mean age, 62.3 years) with primary ESCC underwent surgical tumor resection at the Department of Surgical Oncology, School of Medicine, Hokkaido University and two affiliated hospitals between 1989 and 1999. Immunohistochemical analyses were performed for CD4, CD8, and CD57 (surface markers for natural killer cells). Patient prognosis was found to correlate with the number of CD4(+) and CD8(+) T cells in the stroma and the number of CD8(+) T cells within the cancer cell nest. Furthermore, the number of CD8(+) T cells in the stroma and within the cancer cell nest was found to be correlated [correlation coefficient (r) = 0.790; P < 0.0001). However, no correlation was observed between the number of natural killer cells and patient prognosis. Patients were classified into the following four groups based on CD4(+) and CD8(+) T-cell count: CD4/8(+/+), CD4/8(+/-), CD4/8(-/+), CD4/8(-/-). For the general patient pool, as well as for selected p-stage III and IV cases (n = 48), the survival rate for CD4/8(+/+) patients was significantly higher than that for the other three groups (log-rank test, P = 0.0012 and 0.0088, respectively). Multivariate analysis identified CD4/8(+/+) status, T classification, and N classification as independent prognostic factors. In conclusion, cooperation between CD4(+) and CD8(+) T cells correlates strongly with ESCC patient prognosis.
BACKGROUND: The caudate lobe of the liver is divided into three subsegments based on the portal blood supply: the Spiegel lobe, the paracaval portion (S1r), and the caudate process. An isolated paracaval (S1r) subsegmentectomy is indicated for a small hepatocellular carcinoma localized within S1r. Because this challenging procedure has not been described, we report the details of successful surgical technique. METHODS: The portal pedicle isolation technique provides easy access to the S1r portal pedicle. A tape is passed along the midline of the anterior surface of the vena cava and its lower end is passed through the caudate parenchyma dorsoventrally to establish a landmark for the left border of S1r. A liver-splitting anterior approach is used to open the interlobar plane widely to the precaval tape. As exposing the vena cava and the root of the right hepatic vein, parenchymal dissection is advanced to the right and then, upward. RESULTS: The procedure was performed successfully in a 51-year-old man with hepatitis B who had a 2-cm hepatocellular carcinoma in S1r. Blood loss was 645 ml. CONCLUSIONS: An isolated paracaval subsegmentectomy of the caudate lobe can be performed successfully, although it is likely to remain an uncommonly used procedure.
Since it is reported that adrenomedullin (AM) upregulated by hypoxia inhibits hypoxic cell death, we examined the effects of AM antagonist (AM C-terminal fragment; AM(22-52)) on the growth of pancreatic cancer cells. We, for the first time, demonstrated that AM antagonist significantly reduced the in vivo growth of the pancreatic cancer cell line. Immunohistochemical analysis demonstrated that the mean diameter of blood vessels was significantly smaller in the tumor tissues treated with AM antagonist than in those treated with AM N-terminal fragment (AM(1-25)), and that the PCNA-labeling index was lower in the former than in the latter. Then we demonstrated that AM antagonist showed no effect on the in vitro growth of the pancreatic cancer cell line. These results showed that AM played an important role in the growth of pancreatic cancer cells in vivo, suggesting that AM antagonist might be a useful tool for treating pancreatic cancers.
The retinoblastoma protein (pRB) and its homologues, p107 and p130, prevent cell cycle progression from G(0)/G(1) to S phase by forming complexes with E2F transcription factors. Upon phosphorylation by G(1) cyclin-cyclin-dependent kinase (Cdk) complexes such as cyclin D1-Cdk4/6 and cyclin E-Cdk2, they lose the ability to bind E2F, and cells are thereby allowed to progress into S phase. Functional loss of one or more of the pRB family members, as a result of genetic mutation or deregulated phosphorylation, is considered to be an essential prerequisite for cellular transformation. In this study, we found that pRB family proteins have the ability to stimulate cyclin D1 transcription by activation of the NF-kappaB transcription factor. The cyclin D1-inducing activity of pRB is abolished by adenovirus E1A oncoprotein but not by the deletion of the A-box, the B-box, or the C-terminal region of the pocket, indicating that multiple pocket sequences are independently involved in cyclin D1 activation. Intriguingly, tumor-derived pRB pocket mutants retain the cyclin D1-inducing activity. Our results reveal a novel role of pRB family proteins as potential activators of NF-kappaB and inducers of G(1) cyclin. Certain pRB pocket mutants may give rise to a cellular situation in which deregulated E2F and cyclin D1 cooperatively promote abnormal cell proliferation.
BACKGROUND AND OBJECTIVES: Tumor-infiltrating lymphocytes form an important aspect of the host defense against an expanding neoplasm. CD8+ T cells have been identified as a prognostic factor in several cancers. Here, we investigate that the influence of CD8+ T cells on extrahepatic bile duct carcinoma (EBDC) patient survival. METHODS: CD8+ T cell immunoreactivity in 58 surgically resected EBDC specimens was investigated. The relationship between CD8+ T cell immunoreactivity and clinical and histopathologic features was analyzed. RESULTS: Thirty-two tumors (55%) possessed intratumoral CD8+ T cells. The degree of intratumoral CD8+ T cell immunoreactivity demonstrated a significant relationship to lower numbers of lymph node metastasis, reduced venous invasion, decreased perineural invasion, and better pTNM staging. Intratumoral CD8- T cells were also associated with increased patient survival. Multivariate analysis indicated that the presence of intratumoral CD8+ T cells was an independent prognostic factors. CONCLUSIONS: The infiltration of a cancer cell nest by CD8+ T cells is a reliable marker predicting increased survival of patients with EBDC.
Effective treatment has not yet been established for intestinal pseudo-obstruction, a rare complication of malignant pheochromocytoma. We report the case of a 41-year-old man who presented with malignant pheochromocytoma associated with pseudo-obstruction of the colon. His serum catecholamine level was markedly elevated, and his large intestine was distended with gas and lodged stool. Laxatives and enemas were not effective in relieving his symptoms. We subsequently performed an ileostomy, after which the patient had good bowel movement and was able to resume oral food intake.
A 75-year-old woman presented with a pulsatile, movable mass, about 5 cm in diameter, in her lower abdomen. Abdominal ultrasonography revealed a circular mass with a variable hypo- and isoechoic border and a hypoechoic center. Color Doppler echography showed blood flow in the hypoechoic center, which was strongly enhanced on contrast-enhanced computed tomography. Based on these findings, we diagnosed a splanchnic artery aneurysm; however, celiac arteriography, performed twice, could not definitively identify it. An operation was performed under the tentative diagnosis of an aneurysm of the superior mesenteric artery or the gastroepiploic artery. On laparoscopic exploration, a globe-shaped mass, about 5 cm in diameter, was found in the right side of the greater omentum, which was diagnosed as an aneurysm of the right gastroepiploic artery. We resected the aneurysm laparoscopically and the patient had an uneventful postoperative course. Thus, laparoscopic surgery was effective for this patient who required no vascular reconstruction.
Primary small cell carcinoma of the hepatobiliary tract is rare. Most cases occur in the gallbladder or in the ampulla of Vater, and such cases in the common bile duct (CBD) are extremely rare. We herein report a case of small cell carcinoma arising in the CBD. In this case, neoadjuvant chemotherapy followed by pylorus-preserving pancreaticoduodenectomy showed an excellent response. To our knowledge, this is the first reported case of small cell carcinoma of the CBD in which a radical resection was performed after successful neoadjuvant chemotherapy.
Radical esophagectomy is a highly invasive operation for esophageal cancer, and improved techniques are being sought to reduce the invasiveness of this procedure. We devised a method in which an assistant inserts their left hand into the thoracic cavity, and the operator inserts their left hand into the abdominal cavity through a small incision in the upper quadrant during an endoscopic procedure. Between 1996 and 1999, we performed endoscopic esophagectomy on 18 patients. The median number of mediastinal lymph nodes removed by thoracoscopic surgery was 20.1 +/- 9.4 and the median number of abdominal lymph nodes removed by laparoscopic surgery was 11.1 +/- 5.6. The number of nodes dissected by endoscopic surgery did not differ significantly from the number of nodes dissected by conventional thoracotomy with laparotomy. Our experience shows that endoscopic esophagectomy with reconstruction of the esophagus assisted by inserting the hand into the thoracic and abdominal cavity, for safety and certainty, is an effective technique that is much less invasive than radical esophagectomy performed by conventional thoracotomy with laparotomy.
In human genetics and molecular oncology, mutation research is necessary not only to identify mutations in nucleic acid sequences, but also to analyze the loss of function caused by mutant proteins. We reconstructed a protein-protein network system of human beta-catenin and TCF4, in Saccharomyces cerevisiae. beta-Catenin and TCF4 proteins form a complex and transactivate reporter genes. Co-expressed wild-type APC with beta-catenin and TCF4 inhibit the transcriptional activity of the beta-catenin/TCF4 complex in yeast, as well as in mammals. This unique method in which the beta-catenin/TCF4 signaling pathway is reconstructed in vivo may prove useful for the functional evaluation of APC mutants, including a type of APC truncated and missense mutants influenced to the ability of binding to beta-catenin.
In the tumor cells exposed to hypoxia, hypoxia-inducible factor-1 (HIF-1)-mediated adaptation responses such as angiogenesis and anaerobic metabolism are induced for their survival. We have recently reported that the constitutive expression of HIF-1 alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and glucose deprivation. We then established dominant-negative HIF-1 alpha (dnHIF-1 alpha) transfectants and examined their susceptibility to apoptosis and growth inhibition induced by hypoxia and glucose deprivation in vitro and their tumorigenicity in SCID mice. We further examined the expressions of aldolase A and Glut-1 in vitro and Glut-1 expression and glucose uptake in the tumor tissues and microvessel counts in the tumor tissues. As a result, dnHIF-1 alpha rendered the pancreatic cancer cells sensitive to apoptosis and growth inhibition induced by hypoxia and glucose deprivation. Also it abrogated the enhanced expression of Glut-1 and aldolase A mRNAs under hypoxia and reduced the expression of Glut-1 and the glucose uptake in the tumor tissues and consequently in vivo tumorigenicity. We found no significant difference in the microvessel counts among the tumor tissues. From these results, we suggest that the disruption of the HIF-1 pathway might be effective in the treatment of pancreatic cancers.
During the cell cycle of the yeast Saccharomyces cerevisiae, the actin cytoskeleton and the growth of cell surface are polarized, mediating bud emergence, bud growth, and cytokinesis. We identified CDC50 as a multicopy suppressor of the myo3 myo5-360 temperature-sensitive mutant, which is defective in organization of cortical actin patches. The cdc50 null mutant showed cold-sensitive cell cycle arrest with a small bud as reported previously. Cortical actin patches and Myo5p, which are normally localized to polarization sites, were depolarized in the cdc50 mutant. Furthermore, actin cables disappeared, and Bni1p and Gic1p, effectors of the Cdc42p small GTPase, were mislocalized in the cdc50 mutant. As predicted by its amino acid sequence, Cdc50p appears to be a transmembrane protein because it was solubilized from the membranes by detergent treatment. Cdc50p colocalized with Vps21p in endosomal compartments and was also localized to the class E compartment in the vps27 mutant. The cdc50 mutant showed defects in a late stage of endocytosis but not in the internalization step. It showed, however, only modest defects in vacuolar protein sorting. Our results indicate that Cdc50p is a novel endosomal protein that regulates polarized cell growth.
INTRODUCTION: The mouse pancreas exhibits distinct atrophy of the exocrine tissue following pancreatic duct ligation. AIM: To investigate changes of innervation in the whole pancreas after pancreatic duct ligation. METHODOLOGY: The mouse pancreatic duct was ligated at 6 weeks of age. Pancreatic tissues were removed 7 days and 14 days after the ligation, fixed by perfusion and immersion with Zamboni solution, and embedded in gelatin. The whole organ was serially sectioned at a thickness of 100 microm, histochemically stained for cholinesterase, and observed by light microscopy. The number and volume of intrapancreatic ganglia, number of ganglion cells, and volume of each ganglion cell in the whole pancreas were quantitated. Some sections were analyzed using transmission electron microscopy after histochemically staining for cholinesterase. RESULTS: In the normal pancreas, ganglia were often situated on the outer surface of the islets of Langerhans. Thick nerve bundles ran along the arteries and emanated thin nerve fibers that surrounded the arterioles. In the atrophied pancreas following pancreatic duct ligation, ganglia remained on the islets of Langerhans as in normal mice, while the nerve fibers appeared dense, bending and curling in a more complex manner. The thin nerves also crossed each other in a complex network. Using morphometry in the pancreas following pancreatic duct ligation, the total ganglion cell number was found to decrease from normal levels. The mean ganglion cell volume in the ligated pancreas was significantly smaller than that in normal mice. As observed by transmission electron microscopy, some ganglion cells in the ligated pancreas were negative for cholinesterase activity but were surrounded by positive staining around the surface. CONCLUSIONS: These results suggest that the function of pancreatic ganglion cells changes with organ atrophy after pancreatic duct ligation.
A 65-yr-old man who underwent pancreaticoduodenectomy with portal vein resection for pancreatic cancer is alive 8 yr after surgery. Originally, computed tomography (CT) revealed an 8-cm tumor in the pancreatic head. The tumor had infiltrated the portal vein, but grew expansively, so there was neither biliary obstruction nor jaundice. Pancreaticoduodenectomy with resection of the portal vein was performed for pancreatic cancer. Many tumor-infiltrating lymphocytes were seen within cancer cell nests on routine histopathology. We performed immunostaining for CD8, and found that a large number of the lymphocytes were CD8+ T cells. The patient's prognosis was considered poor because the tumor was large and had infiltrated the portal vein. We suspect that long-term survival may be related to the response of CD8+ T cells to the cancer.
BACKGROUND: Although pancreatic endocrine tumor can produce a variety of hormones, few pancreatic tumors produce a high systemic calcitonin concentration. Furthermore, calcitonin-producing pancreatic tumors rarely produce elevations of VIP in addition. METHODS: We evaluated and treated a 50-yr-old woman with the WDHA syndrome. Abdominal computed tomography (CT) detected a tumor in the tail of the pancreas. Peripheral plasma calcitonin and VIP concentrations were markedly increased to 2000 pg/mL (normal, <74 pg/mL) and 7200 pg/mL (normal, <100 pg/mL), respectively. We diagnosed a calcitonin- and VIP-producing pancreatic endocrine tumor, which was removed by distal pancreatectomy including splenectomy. RESULTS: Plasma calcitonin and VIP were determined in blood from the vein draining the tumor and splenic vein, sampled at operation. These secreted concentrations were extremely high: 4640 and 3610 pg/mL for calcitonin; 24700 and 13500 pg/mL for VIP. Calcitonin and VIP were also highly elevated in the resected tumor. Plasma calcitonin and VIP rapidly decreased after tumor resection. The patient has been well without recurrence for over 20 yr. CONCLUSION: An unusual pancreatic tumor secreting vasoactive intestinal peptide (VIP) caused WDHA syndrome (watery diarrhea, hypokalemia, and achlorhydria/hypochlorhydria) and also hypercalcemia. The latter was only partially offset by a large excess of calcitonin also secreted by the tumor.