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Biomedical subjects

Masazumi Takahashi

Publications and source records attributed to Masazumi Takahashi.

13 recordsLinked to original sources

Lymph node status in patients with submucosal gastric cancer.

BACKGROUND: The aim of this study was to clarify the lymph node status in patients with submucosal gastric cancer. METHODS: Between April 1994 and December 1999, 615 patients with histologically proven submucosal gastric cancer who underwent curative resection were included in this study. The results of the surgery and predictive factors for lymph node metastasis were evaluated by univariate and multivariate analyses. The accuracy of the predictive factors was assessed in a second population of a further 186 patients. RESULTS: Lymph node metastasis was observed in 119 patients (19.3%). Multivariate analysis showed that pathologic tumor diameter (> or = 20 mm) and lymphatic invasion were independent predictive factors for lymph node metastasis. The incidence of lymph node metastasis without these 2 predictive factors was 1.8% (2 of 113), and it was 51.2% (85 of 166) with the 2 predictive factors, 9.5% (14 of 148) in tumors < 20 mm in diameter, and 5.3% (22 of 414) in tumors without lymphatic invasion. Among patients with a tumor < 20 mm in diameter, the incidence of lymph node metastasis was significantly reduced in those with a differentiated tumor: 4.2% (4 of 95). These results were almost identical to those observed in the second population. CONCLUSIONS: Lymph node status can be accurately predicted on the basis of pathologic tumor diameter < 20 mm, lymphatic invasion (absence), and histological type (differentiated) in patients with submucosal gastric cancer. Less extensive surgery for these patients might be reconsidered after confirmation of the reproducibility of the results of this study by an appropriately designed prospective clinical trial.

Adenocarcinoma↗

Comparison of surgical results of D2 versus D3 gastrectomy (para-aortic lymph node dissection) for advanced gastric carcinoma: a multi-institutional study.

BACKGROUND: Curative gastrectomy is a promising approach for the treatment of gastric cancer; however, the optimal extent of lymph node dissection for advanced cancer remains controversial. The aim of this multi-institutional study was to evaluate the feasibility of D3 gastrectomy (para-aortic lymph node dissection) for advanced gastric cancer. The surgical results of D2 and D3 gastrectomy (para-aortic lymph node dissection) were retrospectively compared. METHODS: A series of 580 advanced gastric cancer patients were registered between 1992 and 2000. Of these, 430 underwent D2 gastrectomy and 150 underwent D3 gastrectomy. Survival time, prognostic factors, postoperative morbidity/mortality, and pattern of recurrence were compared. RESULTS: There was no significant difference in survival time between D2 and D3 patients. However, the survival times of D3 patients with tumor diameters measuring 50 to 100 mm or with pN1 disease were significantly longer than those of the corresponding D2 patients. Analysis of the survival of patients with tumor diameters measuring 50 to 100 mm revealed that D3 gastrectomy conferred a survival advantage only to patients with pN2 disease. The incidence of lymphatic recurrence was lower in D3 patients with 50- to 100-mm tumors than in the corresponding D2 patients. CONCLUSIONS: D3 gastrectomy might be beneficial in patients with advanced pN2 gastric cancer within the group with tumors measuring 50 to 100 mm. A randomized controlled trial of patients with 50- to 100-mm tumors should be performed to test the validity of this preliminary result.

Aged↗

Significance of long-term follow-up of early gastric cancer.

BACKGROUND: Therapeutic outcomes for most patients with early gastric cancer are favorable. However, mortality among these patients remains a concern. Improvements in therapeutic outcomes are being sought by studying the timing and causes of death. Here, the results of surgery were evaluated to assess the appropriate treatment and follow-up schedule for early gastric cancer. METHODS: A total of 1169 patients with early gastric cancer underwent curative gastrectomy between 1992 and 1999. Survival time, prognostic factors, cause of death, and time of death were evaluated retrospectively. RESULTS: Multivariate analysis of disease-specific survival identified lymph node metastasis as an independent prognostic factor. The anatomical extent of lymph node metastasis and the number of metastatic lymph nodes influenced the rate of recurrence. Multivariate analysis of overall survival identified age as a prognostic factor. A total of 91 patients (7.8%) from the study group died: 56 from comorbid diseases, 21 from gastric cancer, and 14 from other second primary cancers. Death from gastric cancer was frequently observed within 5 years of surgical resection, whereas death from other diseases usually occurred after 5 years. Patients who died as a result of diseases other than gastric cancer tended to be older. CONCLUSIONS: Appropriate lymph node dissection is necessary for patients with early gastric cancer, particularly those with risk factors associated with lymph node metastasis. Meticulous follow-up protocols that can detect second primary cancers, together with the development of treatments for comorbid diseases, are required to improve survival.

Aged↗

Surgical outcomes in patients with T4 gastric carcinoma.

BACKGROUND: There is controversy about the best therapeutic surgical approach for treatment of patients with T4 gastric cancer. STUDY DESIGN: We used univariate and multivariate analyses to review the surgical outcomes and prognostic factors of 117 patients who underwent surgery for T4 gastric carcinoma. RESULTS: Curative resection was performed in 38 (32.4%) patients, with the pancreas being the most frequently resected organ. The 5-year survival rate was 16.0% and the median survival time (MST) was 11 months for all 117 registered patients. The 5-year survival rates and MSTs in patients after curative and noncurative resection were 32.2% versus 9.5% and 20 months versus 8 months, respectively. These values differed considerably between the two groups (p < 0.0001). Curability was an independent prognostic factor among all registered patients, including those who underwent noncurative resection. A relatively small tumor diameter (< 100 mm) and few lymph node metastases (six or fewer metastatic lymph nodes) were independent prognostic factors when curative resection could be performed. Postoperative morbidity and mortality were acceptable after curative combined resection. CONCLUSIONS: We recommend the use of aggressive combined resection of adjacent organs, with extended lymph node dissection, for patients with T4 gastric carcinoma in whom curative resection can be used; that is, those with few metastatic lymph nodes (six or less) and a relatively small tumor diameter (100 mm). But noncurative resection should be avoided in patients with T4 gastric cancer.

Adenocarcinoma↗

Automated identification of single nucleotide polymorphisms from sequencing data.

The single nucleotide polymorphism (SNP) is the difference of the DNA sequence between individuals and provides abundant information about genetic variation. Large scale discovery of high frequency SNPs is being undertaken using various methods. However, the publicly available SNP data sometimes need to be verified. If only a particular gene locus is concerned, locus-specific polymerase chain reaction amplification may be useful. Problem of this method is that the secondary peak has to be measured. We have analyzed trace data from conventional sequencing equipment and found an applicable rule to discern SNPs from noise. The rule is applied to multiply aligned sequences with a trace and the peak height of the traces are compared between samples. We have developed software that integrates this function to automatically identify SNPs. The software works accurately for high quality sequences and also can detect SNPs in low quality sequences. Further, it can determine allele frequency, display this information as a bar graph and assign corresponding nucleotide combinations. It is also designed for a person to verify and edit sequences easily on the screen. It is very useful for identifying de novo SNPs in a DNA fragment of interest.

Algorithms↗

Lack of efficacy of prophylactic continuous hyperthermic peritoneal perfusion on subsequent peritoneal recurrence and survival in patients with advanced gastric cancer.

BACKGROUND: Peritoneal recurrence is a major cause of death in advanced gastric cancer. Although many kinds of chemotherapy intended to prevent peritoneal recurrence of gastric cancer have been evaluated, few have been successful. Few studies have assessed the clinical significance of continuous hyperthermic peritoneal perfusion in peritoneal recurrence. METHODS: From 1992 to 1999, a total of 124 patients with advanced gastric cancer with tumors invading deeper than the serosa but with no peritoneal metastasis underwent potentially curative gastrectomy and were enrolled in this study. Prophylactic continuous hyperthermic peritoneal perfusion (P-CHPP) was performed in 45 patients younger than 65 years old and without comorbidity who gave informed consent. Seventy-nine patients who did not meet the inclusion criteria represented the control group. After reconstruction of the alimentary tract, P-CHPP was carried out for 40 minutes with 150 mg cisplatin, 15 mg mitomycin C, and 150 mg etoposide in 5 to 6 L physiologic saline maintained at 42 degrees C to 43 degrees C. The surgical results, recurrent pattern, and postoperative morbidity were assessed by univariate and multivariate analysis. RESULTS: When compared with patients not undergoing P-CHPP, patients treated by P-CHPP had higher incidences of respiratory failure (73% vs 19%; P <.0001) and renal failure (7% vs 0%; P <.03). Neither 5-year survival (49% vs 56%) nor the patterns of recurrence (peritoneal, hematogenous, and lymphatic) were affected by P-CHPP. CONCLUSIONS: P-CHPP by our methods had no efficacy as prophylactic treatment for peritoneal recurrence induced by gastric cancer. New therapeutic strategies, such as chemosensitivity assessment, are necessary to obtain good therapeutic results with CHPP.

Adult↗

Spontaneous muscle action potentials fail to develop without fetal-type acetylcholine receptors.

In mammals, two combinations of muscle nicotinic acetylcholine receptors (AChRs) are used: alpha2betagammadelta (gamma-AChR) or alpha2betaepsilondelta (epsilon-AChR). After birth, gamma-AChRs are replaced by epsilon-AChRs (gamma/epsilon-switch). The two receptors have different conductances and open times. During perinatal period, the long open time gamma-AChRs generate random myofiber action potentials from uniquantal miniature end-plate potentials (mEPPs). epsilon-AChRs are suitable for strong adult muscle activities. Since the effect of the gamma/epsilon-switch on neuromuscular development was unclear, despite the many differences in channel characteristics, we carried out this study to generate gamma-subunit-deficient mice. Homozygotes born alive survived for 2 days in a stable condition, and were able to move their forelimbs. Endplate AChRs included epsilon-subunits, and muscle fibers had multiple neuromuscular junctions. Both pre- and postsynapses were abnormal and spontaneous action potentials generated from mEPPs were totally absent. Results suggest a requirement for gamma-AChRs in mediating synaptically-induced action potential activity critical for neuromuscular development.

Action Potentials↗

Automated identification of single nucleotide polymorphisms from sequencing data.

Single nucleotide polymorphisms (SNPs) provide abundant information about genetic variation. Large scale discovery of high frequency SNPs is being undertaken using various methods. However, the publicly available SNP data are not always accurate, and therefore should be verified. If only a particular gene locus is concerned,locus-specific polymerase chain reaction amplification may be useful. Problem of this method is that the secondary peak has to be measured. We have analyzed trace data from conventional sequencing equipment and found an applicable rule to discern SNPs from noise. We have developed software that integrates this function to automatically identify SNPs. The software works accurately for high quality sequences and also can detect SNPs in low quality sequences. Further, it can determine allele frequency, display this information as a bar graph and assign corresponding nucleotide combinations. It is very useful for identifying de novo SNPs in a DNA fragment of interest.

Algorithms↗

Surgical outcome of para-aortic lymph node dissection preserving neural tissue based on anatomical evaluations.

The anatomical distribution of the para-aortic lymph nodes was studied to establish an effective operative procedure that preserves neural tissue for patients with advanced gastric cancer. Para-aortic lesions were anatomically examined in 31 cadavers, and histologic preparations of 14 cadavers were used to evaluate the relationship between para-aortic lymph nodes and surrounding neural tissue. Surgical results were analyzed in patients with D3 gastrectomy based on anatomical findings (n = 33). Anatomically, the splanchnic nerves merged into the celiac ganglion, which consisted of either one ganglion (type I) or several ganglia (type II). The average number of lymph nodes were 17.4 in the area superior to the superior mesenteric artery (SMA) and 13.3 in the area inferior to the SMA. According to the number of metastatic lymph nodes (< or = 3, > or = 4), the median survival time was 14.7 and 9.7 months, respectively (P < 0.02). Patients either with or without metastatic lymph nodes behind the neural tissue had a median survival time of 14.7 and 9.7 months, respectively (P < 0.02). We conclude that para-aortic lymph node dissection preserving neural tissue is useful in patients with three or fewer para-aortic metastatic lymph nodes that are in front of the neural tissue.

Aorta, Abdominal↗

Clinicopathological features of gastric carcinoma in younger and middle-aged patients: a comparative study.

Gastric carcinoma is relatively rare in patients under the age of 40. This study was undertaken to clarify the clinicopathological characteristics and surgical outcomes of gastric carcinoma in younger patients compared with those of middle-aged patients. The surgical results from 131 younger patients (aged < or = 40 years) and 918 middle-aged patients (aged 55-65 years) were compared retrospectively. Female gender, undifferentiated tumor type and lymphatic invasion were significantly more common in the younger patients. Survival time did not differ between the two groups. The depth of tumor invasion was the only prognostic factor in younger patients, whereas macroscopic appearance, tumor diameter, depth of invasion, lymph node metastasis, and venous invasion were all significant prognostic factors in middle-aged patients. Peritoneal recurrence was significantly more common in younger patients. A family history of gastric adenocarcinoma was observed in 25.9% of younger patients, but this did not affect survival outcomes. As depth of invasion affects prognosis independently, and peritoneal metastasis is the predominant pattern of recurrence, it is essential to establish an optimal prophylactic treatment for peritoneal metastasis to improve surgical outcomes in younger patients with advanced gastric cancer.

Adenocarcinoma↗

Implication of extended lymph node dissection stratified for advanced gastric cancer.

BACKGROUND: What extent of lymph node dissection for advanced gastric cancer is appropriate is a matter of controversy. PATIENTS AND METHODS: Three hundred and ninety-nine gastric cancer patients underwent potentially curative D2 gastrectomy and 125 underwent D3 gastrectomy between 1985 and 1998. RESULTS: Our study revealed that pN3, but not D3 gastrectomy, significantly influenced prognosis. There was no significant difference in the 5-year survival rate and mean survival time between D2 and D3 patients: but the survival in D3 patients with tumor diameters measuring 50-100 mm or with pN1 was significantly longer than that in D2 patients with the same tumors. Analysis of survival of patients with tumor diameters measuring 50-100 mm revealed that there was a significant difference only in pN1. The incidence of lymphatic recurrence was significantly lower in D3 patients with pN1 tumor or a tumor measuring 50-100 mm than in D2 patients. CONCLUSION: Patients with advanced gastric cancer measuring 50-100 mm and pN1 may benefit from para-aortic lymph node dissection.

Female↗

Clinicopathological properties of poorly-differentiated adenocarcinoma of the stomach: comparison of solid- and non-solid-types.

BACKGROUND: The purpose of this study was to clarify the clinicopathological and biological properties of the poorly-differentiated types of gastric carcinoma (solid-type and non-solid-type). PATIENTS AND METHODS: A total of 1,558 patients with primary gastric adenocarcinomas were enrolled in this study. The surgical results were compared. RESULTS: Patients with non-solid-type tumors tended to be younger females with peritoneal or lymph node metastases and lymphatic invasion, and with tumors that were ill-defined, of larger diameter and deeper. Those patients with differentiated tumors tended to have the opposite characteristics of those patients with non-solid-type tumors. Patients with solid-type tumors had intermediate characteristics. The survival in patients with non-solid-type tumors was poor compared to those with differentiated or solid-type tumors. There was a significant difference in the survival of stage III tumors with either solid- or non-solid-type tumors (p=0.0480). CONCLUSION: Therapeutic strategies should be based on the histological type of the tumor in patients with poorly-differentiated gastric adenocarcinoma.

Adenocarcinoma↗

Therapeutic outcomes of continuous hyperthermic peritoneal perfusion against advanced gastric cancer with peritoneal carcinomatosis.

BACKGROUND/AIMS: To clarify the efficacy of therapeutic continuous hyperthermic peritoneal perfusion in peritoneal carcinomatosis of gastric cancer. METHODOLOGY: The subjects of this study were 73 advanced gastric cancer patients who underwent palliative surgery between 1992 and 1999. Therapeutic continuous hyperthermic peritoneal perfusion (T-CHPP) was performed in 21 patients, who had macroscopic peritoneal carcinomatosis or positive lavage cytology, were under 65 years old, had no concomitant disease, and gave informed consent. Fifty-two patients who did not meet the inclusion criteria formed the control group. After reconstruction of the alimentary tract, T-CHPP was carried out for 40 min with 300 mg of Cisplatin, 30 mg of mitomycin C, and 300 mg of etoposide in 5-6 L of physiological saline maintained at 42 degrees C to 43 degrees C. RESULTS: The survival of patients who had CY1, P1, P2, P3 was not affected by T-CHPP. Univariate analysis revealed that the degree of peritoneal carcinomatosis and adjuvant chemotherapy were prognostic factors. Furthermore, ill-defined macroscopic appearance and P3 independently affected prognosis, according to multivariate analysis. Patients treated by T-CHPP had higher incidences of respiratory failure (76.2% vs. 17.3%; p < 0.0001) and renal failure (14.3% vs. 0%; p < 0.0054) than those undergoing T-CHPP. CONCLUSIONS: As T-CHPP had no efficacy, a new therapeutic strategy such as chemosensitivity assessment or a well-structured randomized controlled trial is necessary to obtain good therapeutic results with T-CHPP.

Antineoplastic Agents↗