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Biomedical subjects

Shinji Tanaka

Publications and source records attributed to Shinji Tanaka.

At least 19 recordsLinked to original sources

Lymphatic vessel density at the site of deepest penetration as a predictor of lymph node metastasis in submucosal colorectal cancer.

PURPOSE: Lymph node metastasis is an important factor that influences curability after endoscopic treatment of submucosal colorectal cancer. This study was designed to determine the usefulness of identification of lymphatic vessels by immunohistochemistry in predicting lymph node metastasis of submucosal colorectal cancer. METHODS: Lymphatic involvement was assessed by hematoxylin and eosin staining and podoplanin immunostaining on samples resected from 268 patients with submucosal colorectal cancer. Lymphatic vessel density was estimated by two investigators by average count of three fields (x200) in the area of greatest number of podoplanin-positive capillaries at the site of deepest submucosal penetration. Relations with other clinicopathologic parameters also were investigated. RESULTS: Lesions with high lymphatic vessel density (> or =9 vessels per field) showed a significantly greater incidence of lymph node metastasis than did those with low lymphatic vessel density (<9 vessels per field; 23.3 vs. 8.4 percent). By multivariate analysis, lymphatic vessel density was determined to be an independent risk factor for lymph node metastasis of submucosal colorectal cancer (P = 0.0044). Lymphatic vessel density also correlated with tumor budding and the degree of inflammation at the invasive front. CONCLUSIONS: Identification of lymphatic vessels by podoplanin immunostaining provides objective and accurate evaluation of lymphatic involvement. Lymphatic vessel density at the site of deepest penetration is a useful predictor of lymph node metastasis of submucosal colorectal cancer.

Colorectal Neoplasms↗

Defensive medicine practices among gastroenterologists in Japan.

AIM: To clarify the prevalence of defensive medicine and the specific defensive medicine practices among gastroenterologists in Japan. METHODS: A survey of gastroenterologists in Hiroshima, Japan, was conducted by mail in March 2006. The number of gastroenterologists reporting defensive medicine behaviors or changes in their scope of practice and the reported defensive medicine practices, i.e., assurance and avoidance behaviors, were examined. RESULTS: A total of 131 (77%) out of 171 gastroenterologists completed the survey. Three (2%) respondents were sued, and most respondents (96%) had liability insurance. Nearly all respondents (98%) reported practicing defensive medicine. Avoidance behaviors, such as avoiding certain procedures or interventions and avoiding caring for high-risk patients, were very common (96%). Seventy-five percent of respondents reported often avoiding certain procedures or interventions. However, seasoned gastroenterologists (those in practice for more than 20 years) adopted avoidance behaviors significantly less often than those in practice for less than 10 years. Assurance behaviors, i.e., supplying additional services of marginal or no medical value, were also widespread (91%). Sixty-eight percent of respondents reported that they sometimes or often referred patients to other specialists unnecessarily. CONCLUSION: Defensive medicine may be highly prevalent among gastroenterologists throughout Japan, with potentially serious implications regarding costs, access, and both technical and interpersonal quality of care.

Defensive Medicine↗

Evaluation of clinical prognosis and activities of daily living using functional independence measure in patients with hip fractures.

BACKGROUND: The functional independence measure (FIM) is an evaluation method of activities of daily living (ADL) that assesses motor functions and cognitive functions in the Uniform Data System. The FIM has recently been used to assess disability. The purpose of this study was to standardize criteria using the FIM for determining when and to where patients can be discharged following surgery for hip fracture. METHODS: Patients with hip fracture (n=68) aged>or=65 years who underwent surgery at our hospital were classified by their residence at the time of injury (their own home, a hospital, or an elderly care facility) and by postoperative residence after discharge from hospital. We investigated the FIM of these patients before injury and at the time of discharge and retrospectively compared the results with the Japan Orthopaedic Association (JOA) hip score at the time of discharge. RESULTS: Patients who entered a facility after discharge following surgery demonstrated a reduction in motor function score on the FIM. Cognitive function scores in each group were not reduced postoperatively in the short term. The average reduction in scores on the FIM for patients who were discharged from hospital to their own home was 15.9 points, and it was 25.9 points for those who were injured in their own home and transferred to a facility after discharge. There was a significant correlation between the FIM and the JOA hip score at the time of discharge. CONCLUSIONS: The FIM cannot determine whether such patients should be discharged to their home or transferred to a care facility. However, the motor function scores on the FIM are valid for assessing hip fracture patients and may be suitable as a standardized procedure for determining their postdischarge residence.

Activities of Daily Living↗

Outcomes and recurrence of initially resectable hepatocellular carcinoma meeting milan criteria: Rationale for partial hepatectomy as first strategy.

BACKGROUND: Partial hepatectomy and liver transplantation are considered curative treatments for small hepatocellular carcinoma (HCC) meeting the Milan criteria (solitary tumor <5 cm or up to 3 nodules <3 cm). This study was designed to clarify whether partial hepatectomy can be the first option in patients eligible for both treatments. STUDY DESIGN: All patients (n = 152) underwent curative surgical operation for primary HCC during 2000 to 2005 at our hospital. Eighty-seven patients met Milan criteria and the remaining 65 did not. Outcomes were examined according to Milan criteria. RESULTS: After partial hepatectomy, 3-year survival rate was 89.6% for the group that met Milan criteria, compared with 60.8% for the group that did not (p = 0.0044). Among patients with HCC who initially met the criteria, tumor recurrences were observed in 30 patients; 23 patients met criteria and 7 patients exceeded the criteria at first diagnosis of recurrence. Patients with recurrence within the criteria showed a higher 3-year survival rate compared with patients with recurrence exceeding the criteria (100% versus 19.8%; p < 0.0001). Analysis of clinicopathologic variables to predict mode of recurrence revealed tumor size (p < 0.0001) and lower histologic differentiation (p = 0.0326) as positive factors for recurrence exceeding Milan criteria. CONCLUSIONS: Our results suggest that it is an appropriate strategy to treat HCC patients who meet Milan criteria with partial hepatectomy. It should be noted that approximately one-tenth of patients who initially met Milan criteria experienced postoperative recurrence that exceeded the criteria.

Adult↗

Medical malpractice litigation related to gastrointestinal endoscopy in Japan: a two-decade review of civil court cases.

AIM: To examine the allegations in malpractice litigations related to gastrointestinal endoscopy in Japan. METHODS: A retrospective review of cases tried in the civil court system during the 21-year period from 1985 to 2005, identified in a computerized legal database, was undertaken. RESULTS: Eighteen malpractice litigations and a total of 30 allegations were identified. Of the 18 (44%) malpractice litigations, 8 (44%) were related to esophagogastroduodenoscopy, 4 (22%) to colonoscopy, 4 (22%) to endoscopic sphincterotomy, and 2 (11%) to endoscopic retrograde cholangiopancreatography. Seventeen (94%) cases pertained to complications, and the remaining (6%) case pertained to misdiagnosis. In 10 cases, the patient died of the complications. Allegations were categorized as: (1) performance error during the endoscopic procedure (n = 12, 40%); (2) lack of informed consent (n = 9, 30%); (3) performance error during the treatment after the endoscopic procedure (n = 4, 13%); (4) premedication error (n = 3, 10%); (5) diagnostic error (n = 1, 3%); and (6) indication error for the endoscopic procedure (n = 1, 3%). CONCLUSION: These data may aid in the design of risk prevention strategies to be used by gastrointestinal endoscopists.

Endoscopy, Gastrointestinal↗

Advantage of endoscopic submucosal dissection compared with EMR for early gastric cancer.

BACKGROUND: In EMR of early gastric cancer (EGC), en bloc resection reduces the risk of residual cancer. Endoscopic submucosal dissection (ESD) now allows en bloc resection of large EGCs. OBJECTIVE: To retrospectively determine whether ESD is more advantageous than EMR for EGCs. DESIGN: EMR (825 lesions, 711 patients) or ESD (195 lesions, 185 patients) was performed. The en bloc resection rate, histologically complete resection rate, operation time, complications, and local recurrence rate were studied in relation to ulceration. SETTING: Hiroshima University Hospital. PATIENTS: Subjects comprised 896 patients in whom 1020 EGCs were resected endoscopically from 1990 to 2004. RESULTS: In cases without ulceration, en bloc and histologically complete resection rates were significantly higher with ESD than with EMR, regardless of tumor size. The frequency of ulceration did not differ significantly between groups. Average operation time was significantly longer for ESD than for EMR, regardless of tumor size. Also, regardless of ulceration, the incidence of intraoperative bleeding was significantly higher with ESD (22.6%) than with EMR (7.6%). Delayed bleeding did not differ. In cases with ulceration, the incidence of perforation was significantly higher with ESD (53.8%) than with EMR (2.9%). Local recurrences were treated by incomplete EMR (en bloc, 2.9%; piecemeal, 4.4%). No patient experienced recurrence after ESD. CONCLUSIONS: ESD increased en bloc and histologically complete resection rates and may reduce the local recurrence rate. Increased operation time and complication risks with ESD in comparison with EMR remain problematic. Special measures are necessary for ESD of ulcerated lesions to reduce the rates of perforation and incomplete resection.

Biopsy↗

Catalytic removal of N-allyloxycarbonyl groups using the [CpRu(IV)(pi-C3H5)(2-quinolinecarboxylato)]PF6 complex. A new efficient deprotecting method in peptide synthesis.

A variety of amines including even sterically less demanding and highly nucleophilic secondary amines have been efficiently deprotected without decarboxylative N-allylation from the corresponding N-allyloxycarbonyl (N-AOC) compounds by using a catalytic amount of [CpRu(IV)(pi-C3H5)(2-quinolinecarboxylato)]PF6 in the presence of 1 molar amount of trifluoromethanesulfonic acid, the general utility of which has been demonstrated by the efficient synthesis of a collagen protein unit tripeptide, Pro-Pro-Gly.

Amines↗

Helicobacter pylori infection is the major risk factor for gastric inflammation in the cardia.

We attempted to clarify the pathogenesis of gastric inflammation in the cardia. Eighty Japanese participated in this study. Biopsy specimens of the gastric antrum, corpus, and cardia (1 cm from the squamocolumnar junction) were obtained, and histological gastritis was evaluated. Cardiac inflammation was also evaluated using magnifying gastroscopy. We examined Helicobacter pylori infection, gastric juice pH/bile acid (BA), serum pepsinogen and gastrin levels, gastroesophageal reflux disease (GERD), and habitual smoking and assessed the relations between these factors and cardiac inflammation. The prevalence of H. pylori infection was statistically higher in patients with cardiac inflammation than in those without inflammation (P < 0.05). The relationship was also demonstrated by magnifying gastroscopy. Cardiac inflammation was linked to low acid output but not linked to the BA concentration or habitual smoking. Cardiac inflammation was more pronounced in patients without GERD. These results suggest that H. pylori is a major risk factor for cardiac inflammation in the Japanese.

Adult↗

Specific peptide ligand for Grb7 signal transduction protein and pancreatic cancer metastasis.

BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies, with high rates of invasion and metastasis and with generally poor prognosis. We previously found that metastasis was strongly associated with the expression of growth factor receptor-bound protein 7 (Grb7), which contains a Src homology 2 (SH2) domain. In this study, we evaluated Grb7 protein as a molecular target of therapy for metastatic pancreatic cancer. METHODS: Grb7 protein expression was measured by immunohistochemistry in 36 human pancreatic cancer specimens and adjacent normal pancreatic tissue. We synthesized a nonphosphorylated peptide inhibitor that binds specifically to the SH2 domain of Grb7. Intracellular signaling was assessed by immunoprecipitation and immunoblot assays in cultured human pancreatic cancer cells. Cell migration was measured with a modified Boyden chamber method. Peritoneal metastasis of the pancreatic cancer cells was measured with a mouse model. All statistical tests were two-sided. RESULTS: We found that 22 (61%) of 36 pancreatic cancer specimens had higher levels of Grb7 protein than their corresponding normal pancreatic tissue specimens. Grb7 expression was statistically significantly different between specimens from patients without lymph node metastasis (stage N0; two of the 10 patients) and patients with lymph node metastasis (stages N1 + N2; 20 of the 26 patients) (P = .006). The Grb7 peptide inhibitor selectively blocked the interaction between Grb7 and focal adhesion kinase and blocked the phosphorylation of Grb7 protein. In vivo Grb7 peptide inhibitor statistically significantly attenuated cell migration (for control peptide, 87.5 cells migrated, 95% confidence interval [CI] = 82.6 to 92.4 cells; for Grb7 peptide, 5.7 cells migrated, 95% CI = 2.3 to 9.0 cells; P < .001) and peritoneal metastasis of the pancreatic cancer cells in a mouse model, as assessed by the number of nodules (control = 72.6 nodules, 95% CI = 55.8 to 89.4 nodules; and for Grb7 peptide = 3.2 nodules, 95% CI = 1.6 to 4.8 nodules; P < .001, t test) and their weight (control = 4.13 g, 95% CI = 3.40 to 4.86 g; Grb7 peptide = 0.19 g, 95% CI = 0.06 to 0.32 g; P < .001, t test). CONCLUSIONS: The Grb7 peptide inhibitor appears to be a promising molecularly targeted therapeutic agent against metastatic pancreatic cancer.

Adenocarcinoma↗

Development of a novel method to detect Helicobacter pylori cagA genotype from paraffin-embedded materials: comparison between patients with duodenal ulcer and gastric cancer in young Japanese.

BACKGROUND/AIM: cagA gene polymorphism of Helicobacter pylori contributes to clinical outcome of patients. We investigated the implication of the cagA polymorphism in young Japanese patients using paraffin-embedded sections. METHODS: We studied 71 young patients with gastric cancer or with duodenal ulcer. H. pylori infection was confirmed by sections with Giemsa staining and immunohistochemical staining and the degree of gastritis was evaluated. DNA was extracted from paraffin-embedded sections of 20 patients both from the gastric corpus and the antrum. A portion of cagA gene was amplified with polymerase chain reaction, followed by direct sequencing of the fragment. RESULTS: We established a novel method to determine the cagA subtype using paraffin-embedded sections. We found that all the samples possessed East-Asian type cagA both in the corpus and the antrum, not only in patients with gastric cancer but also with duodenal ulcer. Although the cagA gene sequence was completely identical between the gastric corpus and the antrum in all patients, the corpus gastritis was more prominent in patients with gastric cancer than those with duodenal ulcer. CONCLUSIONS: cagA polymorphism can be evaluated with the use of paraffin-embedded sections. The degree of corpus gastritis may not be regulated by cagA diversity only.

Adult↗

Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis.

Many epidemiological reports indicate that Helicobacter pylori (H pylori) infection plays an important role in gastric carcinogenesis. Several genetic and epigenetic alterations contribute to the initiation, promotion, and progression of the cancer cells in a multi-step manner. H pylori is known to induce chronic inflammation in the gastric mucosa. Its products, including superoxides, participate in the DNA damage followed by initiation, and the inflammation-derived cytokines and growth factors contribute to the promotion of gastric carcinogenesis. By eradicating H pylori, gastric inflammation can be cured; the therapy diminishes the levels not only of inflammatory cell infiltration, but also atrophy/intestinal metaplasia in part. A randomized controlled trial revealed that the eradication therapy diminished the gastric cancer prevalence in cases without pre-cancerous conditions. In addition, recent epidemiological studies from Japanese groups demonstrated that the development of gastric cancer, especially of the intestinal type, was decreased by successful eradication therapy, although these were designed in a non-randomized manner. However, it should be mentioned that endoscopic detection is the only way to evaluate the degree of gastric carcinogenesis. We have reported that the endoscopic and histological morphologies could be modified by eradication therapy and it might contribute to the prevalence of gastric cancer development. Considering the biological nature of cancer cell proliferation, it is considered that a sufficiently long-term follow-up would be essential to discuss the anticancer effect of eradication therapy.

Animals↗

Current status and perspective of antiangiogenic therapy for cancer: hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is well known as a typical angiogenic tumor, especially in the moderately to poorly differentiated type. Such clinicopathological characteristics are not only useful for imaging diagnosis but are also applicable to the treatment of HCC. In addition, recent molecular studies have revealed that angiogenesis is closely related to hepatocarcinogenesis. In this review, the molecular mechanism of HCC angiogenesis and the antiangiogenic prevention of HCC are reviewed to introduce the latest trends in antiangiogenic treatment of cancers, including HCC.

Angiogenesis Inhibitors↗

Double-balloon enteroscopy in patients with GI bleeding of obscure origin.

BACKGROUND: Small-bowel bleeding is difficult to treat and diagnose. The recent introduction of wireless capsule endoscopy permits examination of the entire small intestine, but this method lacks tissue sampling and therapeutic capabilities. Recently, Yamamoto et al established a double-balloon insertion method for enteroscopy that allows examination of the entire small bowel and interventional options. OBJECTIVE: To evaluate double-balloon enteroscopy in patients with obscure GI bleeding. SETTING: Single-center prospective study. PATIENTS: Thirty-one consecutive patients with obscure GI bleeding (13 females, 18 males; mean age 56.4 +/- 3.2 years). Criteria for inclusion in the study were documented iron deficiency anemia (hemoglobin level <10 g/dL or a decrease of >2 g/dL over > or =2 months); upper endoscopy not revealing a site/cause of blood loss; and similarly uninformative lower endoscopy including examination of the terminal ileum. INTERVENTIONS: Endoscopic biopsy or therapy was performed as clinically indicated. MAIN OUTCOME MEASUREMENTS: Diagnostic yield for patients with obscure GI bleeding and patient follow-up. RESULTS: Double-balloon enteroscopy was completed without complications in all patients. Bleeding points were identified in 23 patients (74.2%). In 21 (91.3%) of these 23 patients the cause of blood loss was identified and treated with no further bleeding at 8.5 +/- 0.6 months of follow-up. LIMITATIONS: Small number of patients. CONCLUSIONS: These data suggest that double-balloon enteroscopy is useful for evaluation and treatment of patients with GI bleeding of obscure origin.

Adolescent↗

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↗

Biological diagnosis for neuroblastoma using the combination of highly sensitive analysis of prognostic factors.

BACKGROUND/PURPOSE: To select the optimal treatment according to the degree of malignancy of neuroblastoma, it is essential to accurately and rapidly identify any genetic abnormalities associated with the prognosis. This study aims to assess the correlation between the combination of prognostic factors and the biologic findings of neuroblastoma using a highly sensitive analysis of prognostic factors. METHODS: In 44 neuroblastoma primary samples, we determined the gene dosages of MYCN and Survivin (as the target of 17q gain) and the expression levels of MYCN, Survivin, and BIN1 using highly sensitive analysis (the quantitative polymerase chain reaction method); furthermore, we assessed the correlation between the combination of their prognostic factors and the biology of neuroblastoma. RESULTS: The gene dosage of MYCN or Survivin was significantly associated with all known prognostic factors. The expression level of MYCN or Survivin was not significantly associated with any prognostic factors, whereas the expression level of BIN1 was significantly associated with 5 of 6 prognostic factors. Regarding the combination of MYCN amplification and 17q gain (the gene dosage of Survivin), and the low expression of BIN1, the rates of advanced stages (stage III or IV) were 100% for the cases with 3 factors, 63% for the cases with 2 factors, 42% for the cases with 1 factor, and 0% for the cases with null factor. Furthermore, the survival rates were 20% for the cases with 3 factors, 50% for the cases with 2 factors, 100% for the cases with 1 factor, and 100% for the cases with null factor. CONCLUSION: The combination of gene dosages of MYCN and Survivin and the expression level of BIN1 using the quantitative polymerase chain reaction method was significantly correlated with the clinical stage and the patients' outcome. This combination of biologic factors may enhance the accuracy to the conventional criteria, but this would have to be shown in a much larger study that is adequately powered to detect such an advantage.

Adaptor Proteins, Signal Transducing↗

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↗