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Biomedical subjects

Katsuyoshi Hatakeyama

Publications and source records attributed to Katsuyoshi Hatakeyama.

At least 19 recordsLinked to original sources

Curative resection performed twice for circular-staple-line recurrence after colorectal carcinoma surgery: report of a case.

Staple-line recurrence is an important pattern of recurrence after colorectal carcinoma surgery, occurring in approximately 1% of patients. We report the case of a 44-year-old woman who underwent resection of carcinoma recurrence in a circular-staple-line twice within 34 months. Initially, she underwent sigmoidectomy for carcinoma of the sigmoid colon, followed by end-to-end anastomosis, done using a circular stapler. Subsequently, she underwent an anterior resection, then a low anterior resection, 12 and 34 months after the initial operation, respectively, both to treat a circular-staple-line recurrence of the tumor. Histological examination of all resected specimens revealed moderately differentiated adenocarcinoma with clear surgical margins and no lymph node metastasis. The patient remains well with no evidence of disease 48 months after her initial operation. To our knowledge, this is the first reported case of curative surgical resection being performed twice for circular-staple-line recurrence of colorectal carcinoma. Based on our experience and our review of the literature, early detection by follow-up colonoscopy and surgical resection may improve the prognosis of patients with a staple-line recurrence after the resection of colorectal carcinoma.

Adenocarcinoma↗

Prognostic groups in colorectal carcinoma patients based on tumor cell proliferation and classification and regression tree (CART) survival analysis.

BACKGROUND: In this study, an alternative analytical method was used to model colorectal cancer (CRC) patients' long-term survival by assessing the prognostic value of the Ki-67 protein as a marker of tumor cell proliferation, and to illustrate the interaction between standard clinicopathologic variables and the proliferation marker in relation to their impact on survival. METHODS: A cohort of 106 surgically treated CRC patients was used for analysis. The expression of the cell-cycle-related Ki-67 protein in tumor samples was evaluated by immunohistochemistry. A score was assigned as the percentage of positive tumor cell staining, denoted as proliferation index (PI), and was used in a multivariate analysis using a recursive partitioning algorithm referred to as classification and regression tree (CART) to characterize the long-term survival after surgery. RESULTS: Of the covariates selected for their prognostic value, PI contributed most to the classification of survival status of patients. However, CART analysis selected the presence of distant metastasis as the best first split-up factor for predicting 5-year survival. CART then selected the following covariates for building up subgroups at risk for death: (1) PI; (2) pathological lymph node metastasis; (3) tumor size. Seven terminal subgroups were formed, with an overall misclassification rate of 16%. CONCLUSIONS: These analyses demonstrated that a Ki-67-protein-based tumor proliferation index appeared as an independent prognostic variable that was consistently applied by the CART algorithm to classify patients into groups with similar clinical features and survival.

Adult↗

Successful treatment for esophageal carcinoma with lung metastasis by induction chemotherapy followed by salvage esophagectomy: report of a case.

We here report a case of a 51-year-old man with lung metastasis from esophageal carcinoma that was initially treated by combination chemotherapy consisting of fluorouracil and nedaplatin. Because metastatic disease disappeared, salvage esophagectomy was performed. Although chest wall recurrence developed at the thoracotomy wound, prolonged survival of 48 mo was achieved by local tumor resection and additional chemotherapy. This combination chemotherapy is regarded as a promising and considerable treatment for metastatic esophageal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

Chronic oral exposure to inorganic arsenate interferes with methylation status of p16INK4a and RASSF1A and induces lung cancer in A/J mice.

Although inorganic arsenate (iAs(V)) or arsenite (iAs(III)) is clearly a human carcinogen, it has been difficult to produce tumors in rodents. In the present study, we orally administered iAs(V) to A/J mice to examine arsenic carcinogenicity in rodent. A/J mice (male, n = 120) assigned to four groups were given drinking water containing 0, 1, 10, and 100 ppm iAs(V) for 18 months. At the end of experiment, the complete lungs were removed and used for examining histopathology and extracting RNA and DNA. Epigenetic effects of iAs(V) on DNA methylation patterns of p16INK4a and RASSF1A genes were determined by methylation-specific polymerase chain reaction. Changes of p16INK4a and RASSF1A at mRNA and protein levels were examined by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Arsenic was accumulated dose dependently in the lung tissues of iAs(V)-exposed mice. Increase in lung tumor number and lung tumor size was observed in iAs(V)-exposed mice compared to the control. Histopathological examination showed that the rate of poorly differentiated lung adenocarcinoma was much higher in iAs(V)-exposed mice than in the control. Methylation rates appeared to be higher in a dose-related tendency in lung tumors from iAs(V)-exposed mice compared to the control. Lower or loss of p16INK4a and RASSF1A expression was found in lung tumors from iAs(V)-exposed mice, compared to that in nontumor lung tissues from both control and iAs(V)-exposed mice, and this reduced or lost expression was in accordance with hypermethylation of the genes. In conclusion, iAs(V) exposure increased lung tumor incidence and multiplicity in A/J mice. Epigenetic changes of tumor suppressor genes such as p16INK4a and RASSF1A are involved in the iAs(V)-induced lung carcinogenesis.

Adenocarcinoma↗

Anergic lymphocytes generated by blocking CD28 and ICOS pathways in vitro prolong rat cardiac graft survival.

Regulatory cells may play a pivotal role in inducing and maintaining transplantation tolerance. We investigated the mechanism of anergic lymphocytes with regulatory cell potential generated in vitro by ICOS and CD 28 co-stimulatory blockades as a source of cellular therapy for treating allograft rejection. Anergic lymphocytes were generated by a mixed lymphocyte reaction consisting of DA splenocytes as the stimulator and Lewis splenocytes as the responder in the presence of anti-ICOS mAb and rCTLA-4I g. Immunoregulatory effects of these lymphocytes were evaluated by secondary MLR and using other various stimulations. DA heart was transplanted into 7.5 Gy-irradiated Lewis rat after intravenous administration of these cells and/or Lewis spleen lymphocytes. We observed that these lymphocytes were not only anergic to alloantigen and polyclonal stimulations but also exhibited regulative activity to inhibit the alloreactive T-cell response. Our adoptive transfer studies revealed that irradiated recipients that received both anergic lymphocytes and naIve Lewis lymphocytes had significantly prolonged DA cardiac graft survival (mean 17.5 days) compared with a group that received Lewis lymphocytes alone (mean 10.8 days). Furthermore, some of the recipients accepted the graft indefinitely after receiving anergic lymphocytes alone (>100 days). These results demonstrated that anergic lymphocytes with regulatory activities can be generated through blocking co-stimulatory signals, CD 28 and ICOS, simultaneously in vitro, and may advance a new immunomodulatory strategy for preventing allorejection in organ transplantation.

Abatacept↗

An inguinal hernia sac tumor of extrahepatic cholangiocarcinoma origin.

BACKGROUND: Metastatic hernia sac tumor from biliary malignancy is extremely rare with only one such case previously reported. We herein report an additional case of extrahepatic cholangiocarcinoma presenting as a hernia sac tumor. CASE PRESENTATION: A 78-year-old man presented with an irreducible right inguinal hernia associated with a firm tumor, 2.0 cm in diameter. A computed tomography scan demonstrated a soft tissue density mass with heterogeneous enhancement within the right inguinal canal. The patient underwent a hernia repair and the hernia sac tumor was resected. Histological examination of the tumor revealed a metastatic adenocarcinoma suggesting the tumor was of pancreato-biliary origin. Further investigation using imaging studies disclosed a primary tumor in the upper bile duct. The patient died of the disease nine months after the resection. CONCLUSION: Hernia sac tumors should be considered when an irreducible, growing mass appears within an inguinal hernia. Computed tomography may be useful for the early detection of hernia sac tumors from undiagnosed intra-abdominal malignancies.

Journal Article↗

Shear stress induces hepatocyte PAI-1 gene expression through cooperative Sp1/Ets-1 activation of transcription.

Partial hepatectomy causes hemodynamic changes that increase portal blood flow in the remaining lobe, where the expression of immediate-early genes, including plasminogen activator inhibitor-1 (PAI-1), is induced. We hypothesized that a hyperdynamic circulatory state occurring in the remaining lobe induces immediate-early gene expression. In this study, we investigated whether the mechanical force generated by flowing blood, shear stress, induces PAI-1 expression in hepatocytes. When cultured rat hepatocytes were exposed to flow, PAI-1 mRNA levels began to increase within 3 h, peaked at levels significantly higher than the static control levels, and then gradually decreased. The flow-induced PAI-1 expression was shear stress dependent rather than shear rate dependent and accompanied by increased hepatocyte production of PAI-1 protein. Shear stress increased PAI-1 transcription but did not affect PAI-1 mRNA stability. Functional analysis of the 2.1-kb PAI-1 5'-promoter indicated that a 278-bp segment containing transcription factor Sp1 and Ets-1 consensus sequences was critical to the shear stress-dependent increase of PAI-1 transcription. Mutations of both the Sp1 and Ets-1 consensus sequences, but not of either one alone, markedly prevented basal PAI-1 transcription and abolished the response of the PAI-1 promoter to shear stress. EMSA and chromatin immunoprecipitation assays showed binding of Sp1 and Ets-1 to each consensus sequence under static conditions, which increased in response to shear stress. In conclusion, hepatocyte PAI-1 expression is flow sensitive and transcriptionally regulated by shear stress via cooperative interactions between Sp1 and Ets-1.

Animals↗

Long-term outcomes of hepatectomy vs percutaneous ablation for treatment of hepatocellular carcinoma < or =4 cm.

AIM: To determine which treatment modality--hepatectomy or percutaneous ablation--is more beneficial for patients with small hepatocellular carcinoma (HCC) (< or =4 cm) in terms of long-term outcomes. METHODS: A retrospective analysis of 149 patients with HCC < or =4 cm was conducted. Eighty-five patients underwent partial hepatectomy (anatomic in 47 and non-anatomic in 38) and 64 underwent percutaneous ablation (percutaneous ethanol injection in 37, radiofrequency ablation in 21, and microwave coagulation in 6). The median follow-up period was 69 mo. RESULTS: Hepatectomy was associated with larger tumor size (P<0.001), whereas percutaneous ablation was significantly associated with impaired hepatic functional reserve. Local recurrence was less frequent following hepatectomy (P<0.0001). Survival was better following hepatectomy (median survival time: 122 mo) than following percutaneous ablation (median survival time: 66 mo; P=0.0123). When tumor size was divided into < or =2 cm vs >2 cm, the favorable effects of hepatectomy on long-term survival was seen only in patients with tumors>2 cm (P=0.0001). The Cox proportional hazards regression model revealed that hepatectomy (P=0.006) and tumors < or =2 cm (P=0.017) were independently associated with better survival. CONCLUSION: Hepatectomy provides both better local control and better long-term survival for patients with HCC < or =4 cm compared with percutaneous ablation. Of the patients with HCC < or =4 cm, those with tumors >2 cm are good candidates for hepatectomy, provided that the hepatic functional reserve of the patient permits resection.

Adult↗

Heterogeneous expression of GAGE, NY-ESO-1, MAGE-A and SSX proteins in esophageal cancer: Implications for immunotherapy.

Cancer/testis antigens (CTAs) elicit immune response in cancer patients and are therefore targets of immunotherapy. Current information on CTA expression is primarily based on mRNA assays and little is known about their expression at the protein level. The objectives of our study are to analyze GAGE, NY-ESO-1, MAGE-A and SSX protein expression in esophageal cancer and to correlate their expression patterns with clinicopathologic parameters and survival. We examined CTA protein expression in 213 patients with esophageal cancer by immunohistochemistry. Antigen-positive tumors were evaluated once and antigen-negative tumors were evaluated 3 times by examining different parts of the cancer specimen. GAGE, NY-ESO-1 and MAGE-A were heterogeneously expressed in 42 (20%), 44 (21%) and 111 (52%) tumors, respectively, whereas SSX expression was not detected. Of the 126 (59%) patients expressing CTAs, 70 (33%) expressed 1, 41 (19%) expressed 2 and 15 (7%) expressed 3 antigens. The expression of MAGE-A was correlated with those of GAGE (p = 0.001) and NY-ESO-1 (p = 0.002), and the expression of GAGE was correlated with that of NY-ESO-1 (p = 0.002). One hundred fifty-six (79%) sections were positively stained in the first evaluation, whereas 37 (19%) and 4 (2%) positive sections were identified in the second and third evaluations, respectively. Particularly, MAGE and GAGE expression showed overlaps. GAGE, NY-ESO-1 and MAGE-A protein expression was not correlated with the disease progression, TNM factors or survival. The detection of immunonegative cells in every specimen suggests addition of other drugs such as 5-aza-2'-deoxycytidine to increase the therapeutic effect of CTA-specific cancer vaccines.

Adult↗

Clinical significance of lymph node micrometastasis in ampullary carcinoma.

BACKGROUND: This study aimed to clarify the clinical significance of lymph node micrometastasis in ampullary carcinoma. MATERIALS AND METHODS: Pancreaticoduodenectomy with regional lymphadenectomy was performed for 50 consecutive patients with ampullary carcinoma. A total of 1,283 regional lymph nodes (median, 25 per patient) were examined histologically for metastases. Overt metastasis was defined as metastasis detected during routine histologic examination with hematoxylin and eosin. Micrometastasis was defined as metastasis first detected by immunohistochemistry with an antibody against cytokeratins 7 and 8. The median follow-up period was 119 months after resection. RESULTS: Overt metastasis was positive in 90 lymph nodes from 27 patients. Micrometastasis was positive in 33 lymph nodes from 12 patients, all of whom also had overt nodal metastases. Patients with nodal micrometastasis had a larger number of lymph nodes with overt metastasis (median, 3.5) than those without (median, 0; P<0.001). Overt metastasis to distant nodes (superior mesenteric nodes, para-aortic nodes) was more frequent (P=0.001 and P=0.038, respectively) in patients with nodal micrometastasis. Nodal micrometastasis was found to be a strong independent prognostic factor on univariate (P<0.0001) and multivariate (relative risk, 5.085; P=0.007) analyses. From among the 27 patients with overt nodal metastasis, the outcome after resection was significantly worse in the patients with nodal micrometastasis (median survival time of 11 months) than in those without (median survival time of 63 months; P=0.0009). CONCLUSIONS: Immunohistochemically detected lymph node micrometastasis indicates intensive lymphatic spread, and thus adversely affects the survival of patients with ampullary carcinoma.

Adult↗

Management of major portosystemic shunting in small-for-size adult living-related donor liver transplantation with a left-sided graft liver.

PURPOSE: We investigated the mechanisms of small-for-size graft syndrome by time-lag ligation, a novel approach to treating major portosystemic shunts in small-for-size adult living-related donor liver transplantation (LRDLT) using left-sided graft liver. METHODS: Five patients with end-stage liver failure and major splenorenal shunting underwent LRDLT using left lobe grafts. The average graft volume to recipient body weight (GV/RBW) ratio was 0.68 +/- 0.14. Two patients underwent time-lag ligation of their splenorenal (SR) shunts on postoperative days (PODs) 8 and 14, respectively. The shunts of the other three patients were untreated. RESULTS: The portal pressures in the first patient who underwent time-lag ligation rose above 300 mmH(2)O and remained there for 2 weeks. Thus, we ligated the SR shunt in the second patient on POD 14, resulting in an increase from 177 mmH(2)O to 258 mmH(2)O, but it decreased again thereafter. In the other three patients, the SR shunt was not ligated because portal blood flow volumes remained sufficient. Total bilirubin levels in the first time-lag ligation patient rose to 16 mg/dl, paralleling the rise in portal pressures. Although they increased after ligation in the second patient, they did not exceed 10 mg/dl. CONCLUSIONS: We recommend time-lag ligation if portal venous blood flow decreases in the early post-transplant period, but not until at least 2 weeks after transplantation. If the portal venous blood flow does not decrease, early postoperative ligation is unnecessary. If there are no major portosystemic shunts, making a portosystemic shunt might decompress excessive portal hypertension. With donor safety priority in LRDLT, novel approaches must be developed to enable the use of smaller donor grafts. We describe a potential means of using left lobe grafts in adult LRDLT.

Age Factors↗

Clinical and diagnostic significance of preoperative computed tomography findings of ascites in patients with advanced gastric cancer.

BACKGROUND: The relationship between ascites, as detected by preoperative computed tomography (CT), and peritoneal metastasis of gastric cancer requires clarification because of its likely significance for clinical outcome. METHODS: A retrospective analysis of 293 patients with advanced gastric cancer investigated the association between preoperative CT findings of ascites and surgical findings of peritoneal washing cytology and peritoneal metastasis. RESULTS: Forty-five of 293 patients (15%) presented with ascites on preoperative CT. Positive ascites on CT predicted the presence of free tumor cells with 40% sensitivity and 97% specificity, and peritoneal metastasis with 51% sensitivity and 97% specificity. Ascites on CT was an independent prognostic factor by univariate (P < .001) and multivariate (relative risk, 2.03; 95% confidence interval, 1.39-2.96; P < .001) analyses. The median survival time was 6.0 months in patients with positive ascites on CT. CONCLUSIONS: The presence of ascites on CT suggests the presence of peritoneal metastasis and indicates a poor prognosis. The presence of peritoneal metastasis should be confirmed by diagnostic laparoscopy in gastric cancer patients with ascites.

Adenocarcinoma↗

Arsenic trioxide inhibits DNA methyltransferase and restores methylation-silenced genes in human liver cancer cells.

In the present study, we investigated methylation status of the CpG islands of some major tumor suppressor genes both in human hepatocellular carcinoma and liver cancer cell lines and examined whether demethylation by arsenic trioxide (As2O3) could restore their expression in the cell lines. HepG2 and Huh-7 cells were treated with 2 to 10 micromol/L of AS2O3 and/or 1 micromol/L of 5-aza-2'-deoxycytidine for 24, 48, and 72 hours. The methylation status of the CpG island around the promoter regions of p161NK4a, RASSF1A, E cadherin, and GSTP1 was detected by a methylation-specific polymerase chain reaction (MSP). The messenger RNA (mRNA) and protein levels of these genes were determined by quantitative real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical analyses. The DNA methyltransferase (DNMT) mRNA levels and enzyme activity were also examined. The hypermethylated status of the promoter regions of p16INK4a, RASSF1A, E cadherin, and GSTP1 was observed in 10 (40%), 14 (56%), 6 (24%), and 12 (48%) of 25 patients with hepatocellular carcinoma, respectively. CpG methylation of the p16INK4a, RASSF1A, E cadherin, and GSTP1 genes was correlated to the reduction of mRNA levels in the cell lines, and mRNA expression of these 4 genes were indeed restored by low concentrations (2-6 micromol/L) of As2O3 through demethylation, as well as 1 micromol/L of 5-aza-2'-deoxycytidine. Western blot and immunohistochemical analyses confirmed that each protein was markedly enhanced after treatment with a low concentration of As2O3. In contrast, As2O3 at a high concentration (10 micromol/L) damaged cell membranes and remarkably suppressed these 4 protein levels. As2O3 decreased the mRNA expression of DNMT 1 and also dose-dependently inhibited DNMT activity. In conclusion, a low concentration of As2O3 induces CpG island demethylation of tumor suppressor genes by inhibition of DNMT and reactivates the partially/fully silenced genes in liver cancer cells.

Aged↗

An 11-year-old male patient demonstrating cholangiocarcinoma associated with congenital biliary dilatation.

We herein report an 11-year-old male patient demonstrating advanced cholangiocarcinoma associated with congenital biliary dilatation (CBD). This Japanese boy presented with abdominal pain lasting a few days, and a diagnosis of type IV-A CBD was made based on the findings of imaging studies using ultrasonography, computed tomography, and magnetic resonance imaging. These studies also revealed a wide flat lesion associated with a few small round masses in the dilated choledochus. Intraoperative cholangiography revealed the presence of pancreaticobiliary maljunction of CP type. Malignant cells were found in biopsy specimens from both the flat and polypoid lesions. Because the distal stump of choledochus at anomalous confluent to the pancreatic duct also showed malignant cells, a pyloric preserved pancreaticoduodenectomy with lymph node dissection was thus performed. Lymph node metastasis was found in one of the mesenteric lymph nodes, and vascular invasion was also found in the main tumor lesions of the dilated bile duct. The postoperative course was uneventful, and the patient has been followed with chemotherapy as an outpatient without any evidence of recurrence. To our knowledge, this report is the youngest case of cholangiocarcinoma associated with CBD.

Age of Onset↗

Treatment of a case with right-sided diaphragmatic hernia associated with an abnormal vessel communication between a herniated liver and the right lung.

We herein report a rare case of a newborn girl with a right-sided congenital diaphragmatic hernia where a herniated liver had an abnormal vessel communication with the right lung. A surgical repair was initially attempted through a thoracic approach at 4 days of age where only a plication of the hernia capsule was performed without a prominent improvement in the respiratory condition. At 1 year of age, an angiographic examination was performed, which revealed pulmonary hypertension and abnormal vessel communications where the right pulmonary flow returned to the herniated liver and the right lung also received an arterial supply from the liver. During the second surgical repair performed at 1 year and 1 month of age, an abdominal approach through a right subcostal incision was selected. The aberrant vessels between the lung and the liver were carefully identified and ligated. Because the right lobe of the liver was completely herniated, a hepatic segmentectomy of S6 and S7 was performed. The patient has been doing well for 21 months without any mechanical ventilation since 2 months after undergoing the radical second operation. When performing surgery on a right-sided diaphragmatic hernia, the potential presence of such a vessel anomaly should be carefully taken into consideration.

Female↗

Squamous cell carcinoma-antigen messenger RNA level in peripheral blood predicts recurrence after resection in patients with esophageal squamous cell carcinoma.

BACKGROUND: The aim of this study was to clarify whether preoperative squamous cell carcinoma-antigen messenger RNA (SCC-Ag mRNA) level in peripheral blood can be used to predict tumor recurrence after curative resection for esophageal squamous cell carcinoma. METHODS: A prospective analysis was conducted for 46 consecutive patients who underwent curative esophagectomy and who had no residual tumor. The SCC-Ag mRNA level in the peripheral blood of each patient was measured preoperatively by using quantitative reverse transcriptase-polymerase chain reaction. Median follow-up period was 34 months. RESULTS: Receiver operating characteristic analysis demonstrated that the optimal cutoff level of SCC-Ag mRNA was 40. Patients were divided into the high SCC-Ag mRNA level group (n = 14) and the low SCC-Ag mRNA level group (n = 32). The cumulative probabilities of tumor recurrence were higher in the high SCC-Ag mRNA level group (probability of recurrence was 71% at 2 years) than in the low group (22% at 2 years; P = .0005). SCC-Ag mRNA level (relative risk, 3.00; 95% confidence interval, 1.05-8.54; P = .040) was the strongest independent predictor of recurrence by multivariate analysis. CONCLUSIONS: Preoperative SCC-Ag mRNA levels in the peripheral blood are the best predictive factor for recurrence in patients with esophageal squamous cell carcinoma who undergo curative resection (R0).

Aged↗

Video-assisted living donor hemihepatectomy through a 12-cm incision for adult-to-adult liver transplantation.

OBJECTIVES: There has been remarkable progress in recent technical innovations for laparoscopic hepatectomy. However, a laparoscopic procedure rarely has been indicated for donation of the liver in living-related liver transplantation (LRLT). Here, we described the technique and the outcome of video-assisted donor hepatectomy (VADH) for adult-to-adult LRLT. METHODS: For 13 donors in adult-to-adult LRLT, 3 types of major hepatectomy--right hemihepatectomy (3), and left hemihepatectomy, with or without the caudate lobe (10)--were performed through video-assisted procedures; surgical manipulation via ports or via a 12-cm incision and viewing through a laparoscope or through incision were combined and used. RESULTS: VADH was completed in 13 donors, with a median operation time of 363 +/- 33 minutes and a median blood loss of 302 +/- 191 mL. No complications specific to video-assisted procedures, postoperative bile leak, or bleeding were observed. The restoration of the liver function was smooth, and the use of an analgesic (median: 1.2 times) was reduced, compared with the historical control (median: 3.8 times) that underwent a standard donation of the liver. Currently, all donors are healthy and have returned to their previous activities. The grafts have been functioning well, excluding 3 recipients who succumbed to serious complications unrelated to the video-assisted procedure. CONCLUSION: We have shown a new method of VADH through a 12-cm laparotomy for adult-to-adult LRLT. This technique is as feasible as standard open donor hepatectomy, with less pain and with improved postoperative symptoms.

Adult↗