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Mitsuru Sasako

Publications and source records attributed to Mitsuru Sasako.

At least 37 records · Page 2Linked to original sources
PubMed2004

TNM and Japanese staging systems for gastric cancer: how do they coexist?

Two staging systems for gastric cancer, International Union Against Cancer (UICC)/TNM and the Japanese classification, have been used widely for clinical practice and research. The two systems started independently in the 1960s, and underwent several revisions and amendments in order to approach each other, but have become more divergent in the latest editions because of characteristics based on different philosophies. The TNM system adopted a number-based system for N-staging that provides easy and accurate prognostic stratification. Comparative studies have shown that the TNM system has greater prognostic power than the Japanese classification. It contains, however, no treatment guidance and should primarily be used as a guide to prognosis. In contrast, the Japanese classification has been designed as a comprehensive guide to treatment, originally for surgeons and pathologists, and today for oncologists and endoscopists as well. Its anatomical-based N-staging was established based on analysis of lymphadenectomy effectiveness, and naturally provides direct surgical guidance. Clinicians should understand the roles of each system and must not mix the systems or terminology when they report their study results.

Humans↗
PubMed2004

Role of surgery in multidisciplinary treatment for solid cancers.

In the evolution of solid cancer, there are four steps: noninvasive tumor, local invasive cancer without metastasis, local invasive cancer with lymph node metastasis, and eventually systemic disease. For the first three phases, local treatment, including lymph node dissection, may cure the disease. The choice of local treatment depends on the tumor characteristics, but surgery remains important in many of these cancers. Gastric cancer is one of the typical tumors which remain locally invasive, with or without nodal metastasis, but without systemic metastasis for a rather long period. Metastasis to lymph nodes occurs, frequently even in T1 tumors, but seldom to other sites until the late stage. Thus, the target of local control is the regional lymph nodes. The Intergroup study IT-0116 proved the effect of chemoradiotherapy (CRT) for curable gastric cancer, and thus proved the insufficiency of limited surgery (D0/1). The conventional method of local control for gastric cancer is surgery, including regional lymph node dissection (D2). However, the superiority of D2 has not been proven by randomized controlled trials (RCTs). But all RCTs so far have a crucial problem in the quality of treatment given in the D2 arm. D2 is not a dangerous procedure if done by specialists in large-volume hospitals. D0/1 plus CRT is better than D0/1 alone, but it may be worse than D2 alone. The survival benefit of CRT after D2 is an open question. Establishing standard adjuvant chemotherapy after D2 is a more urgent clinical issue, and there is no reason to abandon D2 gastrectomy for curable gastric cancer in Japan.

Chemotherapy, Adjuvant↗
PubMed2004

Gastric cancer surgery in the elderly without operative mortality.

BACKGROUND: Surgeons are increasingly being faced with the problem of treating elder gastric carcinoma patients. Recent improvements in the techniques for preoperative diagnosis and perioperative management have been made. The purpose of this study was to elucidate whether these improvements have produced a decrease in postoperative complications and mortality and resulted in a better clinical outcome. METHODS: Between 1993 and 2003, 141 elderly patients (aged 80 years or above) with gastric cancer underwent operation under the care of dedicated staff surgeons. The results of treatment were analysed. RESULTS: 52 (36.9%) patients had a diagnosis of gastric cancer during a health-check. Only 19 patients (13.5%) had no preoperative risk factors. The ASA score was II in 80%. Approximately 35% of the patients had early gastric cancer. Nodal metastasis was observed in 56% of the patients. The proportion of stage I patients was 40%. Resection rate was 95.7%. Reduced nodal dissection (<D2) was common (47%). The surgery-related complication rate was as low as 8% and the number of operation-related deaths was zero. The 3 (5) year survival rates were 59.0 (48.2-69.8), 48.8 (36.0-61.6) % overall, and 70.0 (58.3-81.7), 56.6 (41.4-71.8) % after curative resection. The 3 (5) year survival rate was 80.3 (63.9-96.7), 73.6 (54.0-93.2) % for early gastric cancer. CONCLUSIONS: Gastrectomy for elder patients can be carried out very safely by specialists with an excellent patient prognosis.

Adenocarcinoma↗
PubMed2004

Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers.

We evaluated the significance of aberrant DNA methyltransferase 1 (DNMT1) protein expression during gastric carcinogenesis. The protein expression of DNMT1, Muc2, human gastric mucin, E-cadherin, and proliferating cell nuclear antigen was examined immunohistochemically in gastric cancers and corresponding noncancerous mucosae from 134 patients. The DNA methylation status of the CpG islands of the p16, human MutL homologue 1 (hMLH1), E-cadherin, and thrombospondin-1 (THBS-1) genes and the methylated in tumor (MINT)-1, -2, -12, and -31 clones was examined by methylation-specific polymerase chain reaction and combined bisulfite restriction enzyme analysis. Epstein-Barr virus (EBV) infection was detected by in situ hybridization. Nuclear immunoreactivity for DNMT1 was not detected in any of the noncancerous epithelia, except in proliferative zones (positive internal control), but was found in 97 (72%) of the gastric cancers. DNMT1 overexpression correlated significantly with poorer tumor differentiation (P < 0.001), but not with the phenotype (gastric type versus intestinal type) of the cancer cells. It also correlated significantly with DNA hypermethylation of the CpG islands of the hMLH1 (P = 0.024) and THBS-1 genes (P = 0.043), and with the CpG island methylator phenotype in the gastric cancers (P = 0.007). Reduced E-cadherin expression correlated significantly with poorer tumor differentiation (P = 0.002), DNA hypermethylation of the E-cadherin gene (P < 0.001) and DNMT1 overexpression (P = 0.014). DNMT1 overexpression was also associated with EBV infection (a potential etiological factor in gastric carcinogenesis) but not with the proliferative activity of the cancer cells as indicated by the proliferating cell nuclear antigen-labeling index. These results suggest that DNMT1 overexpression may not be just a secondary effect of increased cancer cell proliferative activity, but may be associated with EBV infection and other etiological factors during gastric carcinogenesis. Furthermore, DNMT1 may play a significant role in the development of poorly differentiated gastric cancers by inducing frequent DNA hypermethylation of multiple CpG islands.

Adult↗
PubMed2004

Update on surgery of gastric cancer: new procedures versus standard technique.

D2 lymphadenectomy has been the mainstay of treatment for every stage of gastric cancer including early gastric cancer in Japan. However, the use of conventional D2 nodal dissection is being challenged. There was a recent improvement in techniques for preoperative diagnosis and perioperative diagnosis. Less extensive surgeries to maintain patients' quality of life have been introduced as standard treatment for some forms of early gastric cancer in the Gastric Cancer Treatment Guidelines 2001 (The Japanese Gastric Cancer Association). Superextended dissection (more than D2) for non-early gastric cancer is set at investigational treatment. Japanese surgeons are now aiming at wide variations of surgical treatment according to the stage of disease based on new procedures. Further evaluations are proceeding to prove superior to standard techniques.

Digestive System Surgical Procedures↗
PubMed2003

Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1.

PURPOSE: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients (excluding patients who were T1N0), we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated. PATIENTS AND METHODS: From January 1993 to December 1994, 252 patients were enrolled into the study and allocated randomly to adjuvant chemotherapy or surgery alone. The chemotherapy comprised intravenous mitomycin 1.33 mg/m2, fluorouracil (FU) 166.7 mg/m2, and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery, and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2. The primary end point was relapse-free survival. Overall survival and the site of recurrence were secondary end points. RESULTS: Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection. There were no treatment-related deaths and few serious adverse events. There was no significant difference in relapse-free and overall survival between the arms (5-year relapse-free survival 88.8% chemotherapy v 83.7% surgery alone; P =.14 and 5-year survival 91.2% chemotherapy v 86.1% surgery alone; P =.13, respectively). Nine patients (7.1%) in the chemotherapy arm and 17 patients (13.8%) in the surgery-alone arm had cancer recurrence. CONCLUSION: There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection, and there was no statistical difference between the two arms relating to the types of cancer recurrence. We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice.

Administration, Oral↗
PubMed2002

Endoscopic evaluation of the remnant stomach after gastrectomy: proposal for a new classification.

BACKGROUND: In Japan, approximately half of gastric cancers are diagnosed in the early stage. Longer survival has been provided for patients with early gastric cancer (EGC). Several new surgical procedures have been employed for some EGCs. To compare the functional results of these techniques with those of classic distal gastrectomy, it is important to evaluate the remnant stomach in relation to quality of life (QOL) and secondary cancers. We propose a new endoscopic classification, regarding several aspects of the remnant stomach, which enables common understanding and description of the condition. METHODS: Of 651 patients who underwent a distal gastrectomy or pylorus-preserving gastrectomy (PPG), 324 had at least one upper gastrointestinal (GI) endoscopy during the follow-up period. Ninety-three of the 324 patients underwent a Roux-en-Y reconstruction (RY); 175, Billroth type 1 (B1); and 56, PPG. Endoscopic findings regarding residual food, gastritis, and bile reflux in the gastric stump were investigated for these patients. We classified the amount of residual food into five grades, the degree and the extent of gastritis into five grades, and bile reflux into two grades. First, we evaluated the consistency of diagnosis between two endoscopists, in the first 200 patients, and then we applied the classification to all 324 patients to examine the usefulness of this classification. RESULTS: Consistency of diagnosis was obtained between two endoscopists who classified the patients independently. The agreement rate was 98.5% for residual food, 93% for gastritis, and 100% for bile reflux. Residual food was observed in 14.0% of the RY group, 22.3% of the B1 group, and 37.5% of the PPG group. These differences were significant (RY versus B1; P < 0.05 and RY versus PPG; P < 0.01). The remnant stomach after B1 showed significantly more severe and extensive gastritis than that after RY and PPG ( P < 0.01). As for bile reflux, there was no significant difference among the three groups. CONCLUSION: The classification (RGB classification: Residue, Gastritis, Bile) can be used easily and is practical. The results suggest some important differences among methods of reconstruction. This classification seems to be useful to describe these findings and to further evaluate these reconstructive methods.

Endoscopy, Gastrointestinal↗
PubMed2002

Determining prognostic factors for gastric cancer using the regression tree method.

BACKGROUND: The regression tree method is a useful statistical technique that has been little used in the analysis of prognosis. METHODS: The prognostic factors of gastric cancer were investigated, using the regression tree method, in 555 patients who had undergone curative resection for serosa-negative gastric cancer and who were enrolled in a randomized controlled trial of postoperative adjuvant chemotherapy (JCOG [Japan Clinical Oncology Group] 8801 study). RESULTS: By the regression tree method, the first divided prognostic factor (the most important factor) was lymph node metastasis; in particular, extent of lymphatic spread had the greatest impact on prognosis. In addition, age, tumor size, depth of invasion, and individual dose intensity were found to be significant prognostic factors, whereas sex, tumor location, macroscopic tumor type, and extent of lymph node dissection were not. The resulting tree structure consisted of nine terminal nodes with different prognostic factors, and four clusters were obtained by the merging of terminal nodes that showed a similar prognosis. The cluster which showed the best survival rate (5-year survival rate, 0.986) consisted of two terminal nodes: node 12, which contained N0T1 patients who were younger than 62 years and had a tumor size of less than 7.5 cm, and node 14, which contained N1 patients who were younger than 46 years. CONCLUSION: In serosa-negative gastric cancer, lymph node metastasis was the most important prognostic factor. Utilization of the regression tree method enabled visual interpretation of the results of statistical analyses through the graphic representation of prognostic factors. It allowed the identification of the optimal combination of these prognostic factors that defined several groups of patients with distinct prognoses and may serve as a useful reference for the individualization of treatment strategy.

Adult↗
PubMed2002

Randomized controlled trial to evaluate splenectomy in total gastrectomy for proximal gastric carcinoma: Japan clinical oncology group study JCOG 0110-MF.

A randomized controlled trial has started in Japan to evaluate the role of splenectomy in the surgical management of gastric cancer. Patients with T2 or deeper carcinoma in the proximal third of the stomach are intra-operatively randomized to either splenectomy or spleen preservation. Tumors invading the greater curvature of the stomach or those with apparent nodal involvement in the splenic hilum are excluded. Surgeons in 29 specialized institutions will recruit 500 patients. Endpoints are overall survival, operative morbidity, operative time and blood loss.

Adenocarcinoma↗
PubMed2002

Appendectomy in rabbits with extended unilateral anesthesia.

Thoracic paravertebral anesthesia was not believed to accompany numbness in the lumbar nerve region. However, we recently discovered that thoracic paravertebral anesthesia could produce analgesia in the lumbar region. We called this block extended unilateral anesthesia. In this study, appendectomy was attempted in rabbits with extended unilateral anesthesia. After a catheter was inserted into the endothoracic fascia in the paravertebral region on the right side at the level of the 11th thoracic vertebra, a 3-ml dose of 2% mepivacaine was injected repeatedly through the catheter. After an injection of the local anesthetic we could observe motor and sensory paralysis unilaterally from the chest down to the lower limb in all the rabbits, the extended unilateral anesthesia. With this anesthesia, we could accomplish appendectomy. This is the initial report of extended unilateral anesthesia applied to appendectomy in rabbits. We think that this anesthesia could be beneficial in future medical and veterinary use.

Analgesia↗
PubMed2000

Decreasing complication rates with stapled esophagojejunostomy following a learning curve.

BACKGROUND: Recently, two reports of clinical trials on gastric cancer surgery have reported high mortality following extended lymph node dissection. In these reports, anastomotic leakage at the esophagojejunostomy was observed in approximately 10% of patients, with high mortality. These data highlight the importance of avoiding this complication. In this article, we report the use of a stapler to achieve a safe anastomosis, with low incidences of leakage and postoperative stenosis. METHODS: From January 1985 to December 1997, we performed 1234 esophagojejunal anastomoses at the National Cancer Center Hospital. Records of the 1234 patients were reviewed to evaluate changes in anastomotic techniques and changes in the incidence of anastomotic leakage. In this series, 588 stapled anastomoses were carried out between 1992 and 1997. These were evaluated to calculate the incidence of leakage and stenosis, with special reference to the use of supplementary sutures around the stapled anastomosis. Statistical analysis was performed by the chi2 test. RESULTS: This series showed an overall increase in the use of staplers to form the esophagojejunal anastomosis, and a decrease in the incidence of leakage. In 1995, all anastomoses were stapled, with a leakage rate of less than 1.0%. In the last 6 years of the series (1992-1997), the leakage rate was 1.0% and the incidence of postoperative stenosis was 1.2%. The results were not improved by supplementary sutures around the stapled anastomosis. CONCLUSION: These data show that a stapled esophagojejunal anastomosis without supplementary sutures is a safe way to create a esophagojejunal anastomosis, with results superior to those with hand suturing. We believe the stapled anastomosis should become the "gold standard" for esophagojejunal anastomosis.

Journal Article↗
PubMed2000

Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers.

BACKGROUND: The presence of lymph node metastasis (LNM) is the most important prognostic factor for patients with early gastric cancer (EGC). A D2 gastrectomy has been the gold standard treatment. Strict criteria for endoscopic mucosal resection have been widely accepted in Japan. There are some trials aimed at expanding the indications for local treatment, although there has not been a comprehensive review of the risk of LNM with the lesions of EGC.METHODS: We investigated 5265 patients who had undergone gastrectomy with lymph node dissection for EGC at the National Cancer Center Hospital and the Cancer Institute Hospital. Nine clinicopathological factors were assessed for their possible association with LNM.RESULTS: None of the 1230 well differentiated intramucosal cancers of less than 30 mm diameter regardless of ulceration findings, were associated with metastases (95% confidence interval [CI], 0-0.3%). None of the 929 lesions without ulceration were associated with nodal metastases (95% CI, 0-0.4%) regardless of tumor size. Similarly to findings for intramucosal cancers, for submucosal lesions, there was a significant correlation between tumor size larger than 30 mm and lymphatic-vascular involvement with an increased risk of LNM. None of the 145 differentiated adenocarcinomas of less than 30-mm-diameter without lymphatic or venous permeation were associated with LNM, provided that the lesion had invaded less than 500 &mgr;m into the submucosa (95% CI, 0-2.5%).CONCLUSION: Based on our large series of cases, we have been able to clarify the risks associated with EGC and to propose expansion of the criteria for local treatment. However, accurate histological evaluation of the resected specimens is essential to avoid recurrence for such EGCs that should be cured.

Journal Article↗
PubMed1998

Incidence of nodal metastasis around the superior border of the pancreas based on number of metastatic perigastric nodes.

Lymph nodes along the superior border of the pancreas are not usually dissected in Western countries. The purpose of this study was to determine whether the number of metastatic perigastric nodes is predictive of supra-pancreatic nodal disease. Supra-pancreatic nodes are the nodes along the left gastric, common hepatic, celiac, or splenic arteries, including the splenic hilum. In 1230 gastric carcinoma patients treated from 1985 through 1991 at the National Cancer Center Hospital, Tokyo, by D2 or more extensive dissection, 475 had nodal metastasis. Nodal involvement was limited to the perigastric nodes alone in 240 patients, while supra-pancreatic node metastasis was observed in 235 patients. We examined the nodal status of supra-pancreatic nodes in relation to the number of metastatic perigastric nodes. When the number of metastatic perigastric nodes was 3-6, 7-9, and 10 and more, the incidence of metastasis in nodes along the superior border of pancreas exceeded 30%, 50%, and 80%, respectively. When lymph nodes outside the perigastric area are not dissected, the likelihood of residual nodal disease can be predicted based on the number of involved perigastric lymph nodes. The 5-year survival rate in patients with supra-pancreatic node metastasis was high, at 39.2 % after systematic node dissection. If the number of perigastric metastatic nodes exceeds three, supra-pancreatic nodal dissection should be considered.

Journal Article↗