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Biomedical subjects

H Katai

Publications and source records attributed to H Katai.

At least 37 records · Page 2Linked to original sources

Absence of germline CHK2 mutations in familial gastric cancer.

Recently, the CHK2 gene was identified as being a candidate gene responsible for Li-Fraumeni syndrome (LFS). Gastric cancer is often clustered in families with LFS, so it is possible that germline CHK2 mutation is also present in familial gastric cancer (FGC). We therefore defined the genomic structure of the CHK2 gene, designed intronic primers, and searched for germline CHK2 mutations in 25 FGC cases by polymerase chain reaction-single strand conformational polymorphism analysis of the entire coding region. In all of the 25 cases, at least two siblings had histories of gastric cancer. There were no FGC cases that showed germline CHK2 mutations. Thus, it was indicated that germline CHK2 mutations do not contribute to the familial clustering of gastric cancer.

Aged↗

[Current status and problem of adjuvant chemotherapy for curatively resected gastric cancer].

Randomized controlled trials (RCT) on adjuvant chemotherapy for gastric cancer published in the West and Japan were reviewed. Although several small trials showed positive data, adjuvant chemotherapy for curatively resected gastric cancer has been thought to be ineffective in western countries. Results of Japanese RCTs also have not become evidence of its benefit. Despite this, suggestive data by non-predefined subset analyses of old RCTs have been misread as definitive evidence of benefit because of less understanding of clinical statistics in Japan. As a result most Japanese patients have received postoperative adjuvant chemoimmunotherapy. Recently understanding of clinical trial has spread gradually and well designed RCTs with sufficient sample size have been reported. First of all we have to determine the efficacy of adjuvant chemotherapy by carefully designed RCT using surgery alone arm as control.

Antineoplastic Combined Chemotherapy Protocols↗

Can sentinel node biopsy indicate rational extent of lymphadenectomy in gastric cancer surgery? Fundamental and new information on lymph-node dissection.

Lymph-node dissection has been regarded as an effective surgical treatment for gastric cancer in Japan. It reduces local recurrence and improves survival rate. Japanese-style systematic D2 lymphadenectomy is now being introduced in western countries for treatment of gastric cancer. This surgical procedure, however, is not simple and should be performed by experienced surgeons. And it is too early to apply sentinel node biopsy for reducing extent of lymphadenectomy because of so complicated lymphatic streams from the stomach and frequent skip- and micrometastases.

Humans↗

[Practice guidelines in western countries].

The concept of clinical practice guidelines was established in the 1960's to reduce medical costs that had been increasing dramatically in the US. To reduce medical expenses without lowering the quality of medical care, thorough control of medical practices was undertaken by rationalization of these practices. Guidelines were started initially for social and economical reasons, but were eventually accepted widely by society for several reasons. First, the concept of patients' autonomy was widely accepted after 1970, which supported full disclosure of information to patients. Second, there was too much information, necessitating ranking by scientific certainty. Third, the risk of litigation for doctors in the USA increased dramatically during these years. Whether a medical practice follows the guidelines or not has become one of the most important issues in medical lawsuits. Fourth, there is a constant demand for the effective use of social resources. Methods for developing clinical practice guidelines are already established in many societies. The first step is an intensive review of relevant articles to generate evidence-based recommendations (EBR). Then, to formulate practice guidelines, these EBR are ratified and modified by clinicians to whom they apply. They are then reviewed by independent experts. After final adjustment of the EBR or guidelines for administrative reasons, they are adopted with a future expiry date. Practice guidelines are not actually adopted in European countries. However, the concept of guidelines is well appreciated and medical practice is based on scientific evidence. In socialistic European countries like Sweden, Denmark or the Netherlands, there is huge pressure to control limited social resources, leading to aggressive efforts to reduce unexplained and inappropriate variations in medical practice.

Evidence-Based Medicine↗

Surgical resection of pulmonary metastases from gastric cancer.

BACKGROUND AND OBJECTIVES: There are no reports concerning surgical treatment on pulmonary metastases from gastric cancer. The aims of this study were to characterize patients with pulmonary metastasis from gastric cancer and to determine the efficacy of surgical therapy. METHODS: Between 1977 and 1993, 3,076 patients underwent curative resection for gastric cancer. Among them, four patients (0.1%) with pulmonary metastases from gastric cancer underwent pulmonary resection. RESULTS: All four patients had advanced gastric cancers involving regional lymph nodes far from the primary gastric lesion. The median tumor-free interval after the initial gastrectomy was 32.0 months (range: 19-48 months). All patients underwent a lobectomy for a solitary pulmonary lesion. Although transthoracic fine-needle aspiration cytology revealed adenocarcinoma in all cases, none of them were definitely diagnosed as metastasis from gastric cancer preoperatively. The diagnosis was obtained after pulmonary resection. All patients received postoperative chemotherapy or radiotherapy, or both. However, they all subsequently developed systematic metastases. The time interval to recurrence after pulmonary resection ranged from 6 to 36 months and they were all dead at a median follow-up of 24.3 months after the pulmonary resection. CONCLUSIONS: An aggressive surgical approach was not warranted in patients with isolated resectable pulmonary metastases from gastric cancer. However, the possibility of surgical treatment could not be eliminated because surgery is the only diagnostic method for a solitary pulmonary nodule when there is some doubt about the diagnosis of primary or secondary lung cancer in patients with gastric cancer.

Adenocarcinoma↗

The outcome of surgical treatment for gastric carcinoma in the elderly.

Surgeons are increasingly being faced with the problem of treating elderly gastric carcinoma patients. The purpose of this study was to elucidate the feasibility of surgical treatment for these patients. Among 4740 gastric carcinoma patients treated from 1971 to 1990, 112 (2.4%) were aged 80 or over. The results of treatment in this elderly group were compared retrospectively with those in 2664 younger gastric carcinoma patients (aged 50-69, control group, 56.2%). The TNM stage distribution and the curative resection rates (75.9 vs 81.4%) were similar between the groups. Reduced nodal dissection was more common in the elderly group. The elderly had a higher incidence of preoperative risk factors (76.8 vs 53.1%) and 90-day mortality (10.7 vs 3.9%). However, the postoperative complication rates were similar between the groups. The 90-day mortality rates in the elderly group were higher in the subgroups undergoing total gastrectomy or D2 dissection. In the patients without pre-existing morbidity, the 30-day mortality, 90-day mortality and postoperative complications were similar between the groups. The 5-year survival rate after curative resection of the elderly group was significantly lower than that of the control group (44.4 vs 74.0%). This difference lost significance when non-cancer death was excluded (62.5 vs 79.9%). We believe that, although gastrectomy can be carried out safely in elderly patients, extended surgery should be limited to those without preoperative morbidity.

Aged↗

Cloning and characterization of the promoter region of monkey thymidylate synthase gene.

Thymidylate synthase (TS) catalyzes the conversion of deoxyuridylate to thymidylate. Promoter regions of the TS gene from three vertebrates, human, mouse and rat, have been analyzed so far. A unique inverted repeat was present in the promoter region of the human, but not in the mouse and rat, TS genes, and the feature of the promoter region is considerably different between the human TS gene and the two rodent TS genes. To examine whether the characteristics of the human TS gene promoter is intrinsic to human or primate, we cloned a DNA fragment containing the promoter region of the monkey TS gene and determined the nucleotide sequence in this region. The nucleotide sequence in the promoter region of the monkey TS gene was revealed to have 88% homology with that in the corresponding region of the human TS gene. The unique repeated structure mentioned above was also found in the monkey TS gene. Furthermore, the Sp1-binding motif and the CACCC box were found to be conserved in the monkey TS gene. The result of chloramphenicol acetyltransferase assay suggested that the Sp1-binding motif and the CACCC box are essential for the promoter activity of the monkey TS gene, as in the case of the human TS gene.

Animals↗

[TNM classification: cancer of the stomach].

The 5th edition of TNM Classification was published by the UICC (International Union Against Cancer) in 1997. In the classification of gastric cancer, anatomical subsites and N category were newly published. The new classification and role of the Japanese TNM Joint Committee were described in this paper. The Japanese committee had strongly advocated to continue "the anatomical N classification", because the hazard ratios were more significant for prognosis of patients with gastric cancer, and had many reasonable and scientific advantages. However, the UICC introduced "a new N classification by number of metastatic lymph nodes" because of the difficulty in studying nodes by anatomical classification. The new TNM can not be considered an improved classification, and so we are looking for a more scientific, practical, and internationally acceptable classification.

Humans↗

Surgical treatment for gastric leiomyosarcoma.

BACKGROUND: Gastric leiomyosarcoma is an uncommon disease, and the optimal treatment has not been established. In order to better define the optimal surgical treatment, we retrospectively analyzed our experience with these tumors. METHODS: Records of 103 patients, who underwent surgery between 1972 and 1997 were reviewed. RESULTS: The upper third of stomach was the most frequent site of disease (66 cases). Seventy one tumors were smaller than 50 mm. Forty patients had ulcerated tumors. Twenty nine of 33 tumors had an inhomogeneous pattern on endoscopic ultrasonography. Nodal involvement was not observed in our series. The most common surgery was wedge resection, performed in 68 patients. The 5-year disease-specific survival rate after curative resection was 93.0% overall, 87.5% after gastrectomy, and 95.0% after wedge resection. 5 year survival rate was worse in patients with ulcer than those without ulcer (87.1% vs. 96.3%, p < 0.01). No patient with a tumor smaller than 3 cm died from the disease. The dominant mode of recurrence was liver and peritoneal metastasis. No lymph node recurrence was observed. CONCLUSIONS: Surgery is indicated for tumors larger than 3 cm, with rapid growth, with inhomogeneous US pattern, or with ulceration. Wedge resection is the preferred treatment.

Disease-Free Survival↗

Total gastrectomy for primary gastric lymphoma at stages IE and IIE: a prospective study of fifty cases.

BACKGROUND: Treatment of primary gastric lymphoma at Ann Arbor stage IE or IIE is controversial. Randomized trials to compare various modalities are not feasible because of the rarity of this disease. We have prospectively treated patients by means of primary surgery to achieve complete local control and accurate staging. METHODS: Between 1987 and 1995, 50 patients with stage IE or IIE gastric lymphoma were prospectively treated by total gastrectomy with systematic lymphadenectomy. When nodal metastases were histologically confirmed or the resection was noncurative, chemotherapy was added. Intragastric tumor spread, lymph node metastasis, and treatment results were examined. RESULTS: Resection was potentially curative in 48 cases. There were no operative deaths. Histologically, the middle third of the stomach was most frequently involved. Either the proximal two thirds or the entire stomach was involved in 62% of all patients. Lymph node metastasis was demonstrated in 25 patients. The deeper the tumor invasion in the gastric wall, the more frequent and distant the nodal involvement. The 5-year survival rate was 85.6%, excluding one death caused by heart disease. CONCLUSIONS: Primary surgery followed by chemotherapy in selected cases is an appropriate strategy for primary gastric lymphoma in patients in whom this regimen can be safely carried out.

Adult↗

A prospective study of surgery and adjuvant chemotherapy for primary gastric lymphoma stage II.

The standard management of primary gastric lymphoma (PGL) (stage II) has not been established despite the use of various treatment modalities. The present prospective trial of combined surgery and chemotherapy for the treatment of PGL (stage II) included 25 consecutive patients treated between July 1978 and December 1993. Twenty-one patients were treated with total gastrectomy and four with partial gastrectomy; this was followed by post-operative chemotherapy with m-VEPA (vincristine, cyclophosphamide, prednisolone and doxorubicin), followed by consolidation chemotherapy with VEMP (vindesine, cyclophosphamide, methotrexate and prednisolone) or VQEP (vindesine, carbazilquinone, cyclophosphamide and prednisolone). Twenty-one of the 25 patients who completed post-operative chemotherapy were free of relapse 26-203 (median 94) months after the gastrectomy. Of the four patients who did not complete the projected chemotherapy, two relapsed and died of lymphoma. Another patient with recurrent lymphoma died in an accident, and the fourth patient was in remission at 54 months after surgery. The post-operative overall and disease-free survival rates at 10 years for the 25 evaluable patients were 81.6% and 92.0% respectively. Major surgical complications and treatment-related death after chemotherapy were not observed. PGL (stage II) appears to be curable when treated with gastrectomy and adjuvant chemotherapy.

Adult↗

Amylase concentration of drainage fluid after total gastrectomy.

BACKGROUND: Pancreatic fistula is a serious complication of total gastrectomy with splenectomy. The amylase content of drainage fluid was examined and its usefulness for predicting pancreatic complications after gastrectomy was evaluated. METHODS: The amylase concentration of the fluid in the peripancreatic drain was determined prospectively in 102 patients who underwent total gastrectomy in 1995. RESULTS: Pancreatic fistula developed in 13 patients, whose drainage fluid amylase levels on the first postoperative morning were significantly higher than those of patients without fistula formation. Among 27 patients with amylase levels exceeding 4000 units, eight later developed pancreatic fistula, while only five (7 per cent) of 68 with amylase levels below 4000 units did so. All complications were successfully managed and there were no deaths. CONCLUSION: Determination of drainage fluid amylase levels is a simple and useful method for the prediction of pancreatic fistula formation and may help to plan appropriate management.

Adult↗

Microsatellite instability in gastric cancer prone families.

We examined for germ-line p53 mutations and microsatellite instability in three gastric cancer patients who had family histories of gastric cancer aggregation. Although no germ-line p53 mutation was detected in these three cases, the replication error (RER) phenotype was observed in two of them. One base deletion in the sequence of ten repeating adenines of the type II transforming growth factor-beta receptor gene was detected in one of these two cases. Furthermore, there were young patients of 50 years and downward in their families. Therefore, it is possible that inherited disorders in mismatch repair systems contribute to high susceptibility to gastric cancers in these families.

Adult↗

Gastric carcinoma in young adults.

Among 4608 patients with gastric carcinoma treated during a 20-year period from 1971 to 1990, 328 (7.1%) were less than 40 years of age. The clinicopathologic features and treatment results in this young group were compared with those for older gastric carcinoma patients (40-79 years of age, control group). In the young group, the male/female ratio and the prevalence of tumors in the lower third of the stomach were both lower than in the control group, and undifferentiated-type adenocarcinomas with diffusely infiltrative growth predominated. The TNM stage distribution and the proportion of curative resections were similar in the two groups. The overall cumulative 5-year survival rates were also similar, although that of patients who underwent curative resection was higher in the young group, due probably to the low rate of death from other causes. There was no difference in the recurrence rates after curative resection between the two groups. Contrary to widely held belief, the prognosis of young patients with gastric carcinoma is not poorer than that of older patients if the disease is diagnosed at a reasonably early stage.

Adult↗

A case of bone marrow recurrence from gastric carcinoma after a nine-year disease-free interval.

We present a case of very late and unusual recurrence of gastric cancer. Nine years following total gastrectomy for gastric carcinoma, a 57-year-old man presented with disseminated intravascular coagulation associated with bone marrow recurrence. The primary tumor was a signet ring cell carcinoma invading the subserosal layer with lymph node metastasis. The patient was treated with sequential administration of methotrexate and 5-fluorouracil and went into remission. After treatment, he survived 10 months. Autopsy revealed diffuse bone marrow infiltration and distant lymph node metastasis with signet ring carcinoma cells.

Antineoplastic Combined Chemotherapy Protocols↗