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Biomedical subjects

Mitsuru Sasako

Publications and source records attributed to Mitsuru Sasako.

At least 19 recordsLinked to original sources
PubMed2007

Favorable indications for hepatectomy in patients with liver metastasis from gastric cancer.

BACKGROUND: The prognosis of patients with liver metastasis from gastric cancer (LMGC) is dismal. The purpose of this study was to review our recent outcomes of hepatectomy for LMGC and to determine the suitable candidates for surgery. STUDY DESIGN: The outcomes of 37 patients with LMGC who underwent hepatectomy between 1990 and 2005 were assessed. No extrahepatic distant metastasis and feasibility of macroscopic curative resection were requisite indications for surgery. The prognostic values of clinicopathological factors were assessed by univariate and multivariate analyses. RESULTS: There was no in-hospital mortality. The median survival time and overall 5-year survival rate after hepatectomy of the patients with LMGC were 31 months and 11%, respectively. Intrahepatic recurrence following hepatectomy was found in 23 patients (62%). Variables independently associated with poor survival were bilobar metastasis (P = 0.002, CI = 1.9-16.3) and a maximum tumor diameter of >or= 4 cm (P = 0.006, CI = 1.4-7.7). The depth of the primary tumor and the timing of metastasis were not associated with survival. CONCLUSIONS: Surgical resection for LMGC may be indicated in patients with unilobar metastasis and/or tumors less than 4 cm in diameter. Synchronous metastasis is not a contraindication for hepatectomy.

Adenocarcinoma↗
PubMed2006

Influence of overweight on surgical complications for gastric cancer: results from a randomized control trial comparing D2 and extended para-aortic D3 lymphadenectomy (JCOG9501).

BACKGROUND: The impact of overweight on the outcome of gastrectomy with lymphadenectomy is controversial, and data from a well-controlled, randomized study are needed to identify a possible relationship. METHODS: We used data from 523 patients registered for a prospective randomized trial comparing D2 and extended para-aortic D3 lymphadenectomy to compare the effects of body mass index (BMI) and the extent of lymphadenectomy for the development of general or major surgical complications (anastomotic leakage, abdominal abscess, and pancreatic fistula). RESULTS: Seventy-seven patients were classified as overweight with BMI >or= 25, and 38 and 39 of these patients underwent a D2 or D3 lymphadenectomy, respectively. Among the 446 patients classified as nonoverweight with BMI < 25, 225 received D2 and 221 received D3 lymphadenectomy. Surgical complications, operation time, and blood loss were statistically significantly associated with BMI, and logistic regression analysis revealed that overweight directly affected the occurrence of surgical complications even after considering operation time and blood loss as intermediate factors instead of outcome variables. Among patients undergoing D2 lymphadenectomy, being overweight increased the risk for surgical complications and blood loss, whereas overweight was associated with only blood loss and operation time among patients receiving D3 lymphadenectomy. CONCLUSIONS: Overweight increased the risk of surgical complications in patients undergoing gastrectomy both directly and indirectly through operation time and blood loss. The impact of overweight on surgical complications was more evident in patients undergoing a D2 dissection.

Aged↗
PubMed2006

Follow-up of gastric cancer: a review.

Although there is broad agreement in the staging, classification, and surgery for gastric cancer, there is no consensus regarding follow-up after gastrectomy. Follow-up varies from investigations on clinical suspicion of relapse to intensive investigations to detect recurrences early, assuming that this improves survival and quality of life. Advanced gastric cancers recur mainly by locoregional recurrence or distant metastasis. Local recurrences detected at endoscopy or on computed tomography (CT) are invariably incurable. For early gastric cancers, endoscopy can detect new primaries, but the incidence of these tumors is low, and many thousands of procedures are required to detect each operable case. CT is much better at detecting liver metastasis and, although these are usually multiple and unresectable, there are several reports of good survival following liver resection for isolated metastasis. Tumor markers have been used with some success to detect subclinical recurrences and could be used to target more invasive or expensive procedures. In chemotherapy, many newer agents are promising significantly improved survival, but again, the evidence for greater benefit when administered prior to the patient becoming symptomatic is lacking. Overall, it appears that follow-up policy is as much decided by the wealth and facilities of the institution as by any significant evidence base. Although the early detection of recurrent cancer is an emotive issue for both patients and surgeons, considering the amount of time and money invested in follow-up, and the lack of evidence of efficacy, a randomized controlled trial of intensive follow-up is required.

Follow-Up Studies↗
PubMed2006

Left thoracoabdominal approach versus abdominal-transhiatal approach for gastric cancer of the cardia or subcardia: a randomised controlled trial.

BACKGROUND: Because of the inaccessibility of mediastinal nodal metastases, the left thoracoabdominal approach (LTA) has often been used to treat gastric cancer of the cardia or subcardia. In a randomised phase III study, we aimed to compare LTA with the abdominal-transhiatal approach (TH) in the treatment of these tumours. METHODS: Between July, 1995, and December, 2003, 167 patients were enrolled from 27 Japanese hospitals and randomly assigned to TH (n=82) or LTA (n=85). The primary endpoint was overall survival, and secondary endpoints were disease-free survival, postoperative morbidity and hospital mortality, and postoperative symptoms and change of respiratory function. The projected sample size was 302. After the first interim analysis, the predicted probability of LTA having a significantly better overall survival than TH at the final analysis was only 3.65%, and the trial was closed immediately. Analysis was by intention to treat. This study is registered with , number NCT00149266. FINDINGS: 5-year overall survival was 52.3% (95% CI 40.4-64.1) in the TH group and 37.9% (26.1-49.6) in the LTA group. The hazard ratio of death for LTA compared with TH was 1.36 (0.89-2.08, p=0.92). Three patients died in hospital after LTA but none after TH. Morbidity was worse after LTA than after TH. INTERPRETATION: Because LTA does not improve survival after TH and leads to increased morbidity in patients with cancer of the cardia or subcardia, LTA cannot be justified to treat these tumours.

Adult↗
PubMed2006

Usefulness and clinical significance of quantitative real-time RT-PCR to detect isolated tumor cells in the peripheral blood and tumor drainage blood of patients with colorectal cancer.

The clinical significance of isolated tumor cells (ITC) circulating in the blood of patients with colorectal cancer is unclear. In this study, we investigated the relationship between the presence of ITC that express carcinoembryonic antigen (CEA) and/or cytokeratin 20 (CK20) transcripts in the blood and the clinicopathological findings and prognosis using the quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. We studied peripheral blood and tumor drainage blood from 167 patients with colorectal cancer. Quantitative real-time RT-PCR assay was able to detect one tumor cell in 3x10(6) peripheral blood mononuclear cells. Applying a cut-off value, CEA and/or CK20 (CEA/CK20) were detected in 10.2% (17/167) of the patients' preoperative peripheral blood samples and 34.1% (57/167) of the patients' tumor drainage blood samples. In the relationship between the CEA/CK20 of the blood and the clinicopathological factors, a significant correlation was demonstrated between the positivity of marker genes and the depth of invasion, venous invasion, lymph node metastasis, liver metastasis or stage. The disease-free and overall survival of patients with CEA/CK20-positive peripheral or tumor drainage blood was significantly shorter than that of marker gene-negative patients. CEA/CK20 transcripts in tumor drainage blood were independent factors for prognosis in disease-free survival and overall survival. These results suggest that detecting CEA/CK20 mRNA in tumor drainage blood by real-time RT-PCR has prognostic value in patients with colorectal cancer. Large scale and long-term clinical studies are needed to confirm the prognostic value of genetically detecting ITC in the peripheral blood.

Adult↗
PubMed2006

[Adjuvant chemotherapy using S-1 for curatively resected gastric cancer-the nationwide clinical trial].

Actually there has been no established adjuvant therapy for curable gastric cancer. Thus it is strongly recommended in the guidelines to actively carry out clinical trials. A large scale clinical trial on adjuvant chemotherapy for gastric cancer using S-1 (ACTS-GC) started in 2001. This was the first large trial having the surgery alone as control after 1980. The target population was Stage II, IIIA, IIIB, and the expected hazard ratio was less than 0.70. Between October 2001 and December 2004, for 3 years and 2 months, 1,056 patients were enrolled. Thus it was proven that we should carry out a pivotal study instead of making meta-analysis in the field of gastric cancer. Certainly, the results of this trial will strongly affect the clinical practice in Japan. If the results are negative, the use of adjuvant chemotherapy in practice and in social insurance might be restricted.

Antimetabolites, Antineoplastic↗
PubMed2005

Distribution of the deepest penetrating point of minute submucosal gastric cancer.

BACKGROUND: Accurate assessment of depth of invasion is critical in decision-making for additional surgery after endoscopic resection of early gastric cancer (EGC). Although this depth of invasion is determined at the deepest point of submucosal invasion (DPSI), there is no literature describing the distribution of deepest invasion point. OBJECTIVE: To describe the location of the DPSI, and to determine whether it is possible to predict this point by clinicopathological features before treatment. METHODS: One hundred and ninety-five lesions of EGC with minute submucosal invasion, which had been resected en bloc between 1991 and 2003, were reviewed. For each lesion, we recorded the location of the DPSI as being in one of three areas demarcated by three concentric equal distance rings. We also examined the correlation between the location of the deepest penetration and the clinicopathological characteristics. RESULTS: The DPSI was located most often (53%) in the central, less often (31%) in the middle and least often (16%) in the outermost area. There was no significant correlation between the distribution of the deepest point and any clinicopathological features. CONCLUSIONS: The DPSI was not always in the central area, and it was impossible to predict its location by clinicopathological features alone. To obtain an accurate measure of depth of tumor invasion, we must histologically assess the entire lesion by thin sections.

Adenocarcinoma↗
PubMed2005

Pancreaticoduodenectomy for advanced gastric cancer.

BACKGROUND: Although pancreaticoduodenectomy has been rarely performed for gastric cancer because of frequent morbidity and mortality, some favorable results after this procedure have been reported recently. Our objective was to present our data that might aid in the selection of patients to undergo this procedure. METHODS: Between 1970 and 2001, 23 patients who had pancreaticoduodenectomy for gastric cancer with tumor invading the pancreatic head were identified, and they were the subjects of this study. Clinical, operative, and pathological data, and morbidity and mortality rates were collected and analyzed. Survival outcome was also calculated and analyzed. RESULTS: Five patients underwent this procedure for disease in the gastric remnant, 18 undergoing the procedure for primary tumors. Median operating time was 8 h (range, 6-13 h), and median blood loss was 1600 ml (range, 700-16,000 ml). Regarding extent of gastrectomy, all patients with primary cancer (n = 18) underwent a distal gastrectomy and patients with disease in the gastric remnant (n = 5) underwent a completion gastrectomy. Incurable factors, including paraaortic lymph node metastasis, positive lavage cytology, or peritoneal dissemination were found in 8 patients. The postoperative morbidity rate was 73.9%; however, operation-related death was zero. The overall 5-year survival rate was 34.3%. The 5-year survival rate of the 8 patients with incurable factors was 0%, while that of the 15 patients without incurable factors was 47.4%. CONCLUSION: If an R0 resection can be achieved by pancreaticoduodenectomy, this procedure should be performed for patients with tumor invading the pancreatic head. Patients with incurable factors should not be considered for pancreaticoduodenectomy.

Adult↗
PubMed2005

Increasing body mass index in Japanese patients with gastric cancer.

We studied the body mass index (BMI) of 986 patients who underwent potentially curative gastrectomy for gastric cancer at the National Cancer Center Hospital, Tokyo, in 1971, 1981, 1991, and 2001. The median BMI increased from 20.8 kg/m(2) in 1971 to 22.6 kg/m(2) in 2001 (P, 0.01). The increase was significant in both early and advanced gastric cancers, and in males, but not in females. The proportion of overweight patients (BMI > or = 25.0 kg/m(2)) increased from 9.2% in 1971 to 24.0% in 2001. Obese patients (BMI > or = 30.0 kg/m(2)) were rare. In conclusion, surgeons at the National Cancer Center Hospital, Tokyo, are increasingly having to operate on fat patients, but obese patients are still uncommon compared to the West.

Adult↗
PubMed2005

Risk factors for pancreas-related abscess after total gastrectomy.

BACKGROUND: European clinical trials of gastrectomy have shown that pancreas-related complications are the major cause of mortality. The aim of this study was to determine the risk factors for pancreas-related abscess after gastrectomy and to evaluate the effects of the abscess on postoperative mortality. METHODS: Between 1992 and 1999, 663 consecutive patients with gastric carcinoma underwent total gastrectomy. Data from these patients were analyzed, to identify the predictors of pancreas-related abscess caused by pancreatic juice leakage, by a multiple logistic regression model. RESULTS: On multivariate analysis, increasing age (P = 0.018) and body mass index (P = 0.006) were independent preoperative risk factors. Dissection along the distal splenic artery was an intraoperative risk factor. The hazard ratios were increased 9.13-fold (P = 0.000) with a pancreas-preserving operation and 16.72-fold (P = 0.000) by distal pancreatectomy. Patients with the abscess had a higher postoperative mortality rate (P = 0.008), and a higher re-operation rate (P < 0.001) than patients without the abscess. CONCLUSION: Pancreas-related abscess is more likely to occur in older, obese patients undergoing node dissection along the distal splenic artery. Abscess formation is associated with a higher mortality and re-operation rate. Spleen preservation should be evaluated in Japan.

Abscess↗
PubMed2005

Clinical trials of surgical treatment of malignant diseases.

The Dutch Gastric Cancer Study Group Trial was the first clinical phase III trial to be carried out in the field of cancer surgery. In spite of the excellent quality of the trial, it was heavily criticized for the poor quality of the treatment itself. Actually, the hospital mortality after the new surgical treatment (D2 lymph node dissection for gastric cancer) was unacceptably high. In surgical trials, special attention should be paid to quality issues specific to surgery. The first and the most important issue is the quality of treatment given. Reproducibility, homogeneity, and verifiability are the greatest problems in surgical trials. There are also some patient factors. If the patient is old, or fragile, or obese, the results of the surgical treatment can easily be affected by these factors. The surgeon can also be a prognostic factor, especially in complicated procedures or those requiring experience and training. Experience, including postoperative care, and dexterity affect the results. If surgeons do not know how to manage complications, mortality becomes very high. Because blinding is impossible in surgical trials, the treatment may easily be affected by personal preference or prejudice. To minimize the influence of these hampering factors, the procedures should be defined in as detailed a way as possible. If pretrial training or a feasibility study (phase II) is needed, it should be carried out properly for the patients' sake. An excellent design and excellent statistical analysis cannot lead to meaningful results if the quality of treatment is poor. Nonsense in, nonsense out.

Clinical Trials, Phase III as Topic↗
PubMed2005

Treatment of early gastric cancer in the elderly patient: results of EMR and gastrectomy at a national referral center in Japan.

BACKGROUND: The Japanese population is rapidly aging, and the actual number of elderly patients with gastric cancer, including early cancer, has been increasing, even though the standardized incidence of gastric cancer in the population is decreasing. The optimal treatment for these patients remains a challenge to the surgeon. The aim of this retrospective analysis was to describe the results of gastrectomy and EMR for early gastric cancer in elderly patients (80 years of age and over). METHODS: This is a retrospective review of 93 elderly patients who had undergone gastrectomy or EMR at the National Cancer Center Hospital for early gastric cancer. EMR was performed aiming en bloc local resection with a clear curative margin (R0). The clinicopathologic characteristics, comorbidity, postoperative mortality, and outcome were recorded. RESULTS: Gastrectomy was performed in 44 patients (surgery group) and EMR in 49 patients (EMR group). There were significant differences in mean tumor size (p < 0.05), histologic type (p < 0.05), and depth of tumor invasion (p < 0.05) between the two groups. There was no significant difference in comorbidity between the two groups. No operative death was reported in either group. In the EMR group, 7 patients were reported to have recurrence of local disease and two patients died of advanced disease. There were no significant differences in the overall 3-year survival rate or the 5-year survival rate between the surgery group and EMR group (73.5% vs. 82.5% and 55.0% vs. 62.5%, respectively). CONCLUSIONS: EMR (R0) resection was performed safely in the elderly, and the overall results were excellent, the same as the results with gastrectomy. Gastrectomy can still be performed if EMR is unsuccessful.

Aged↗
PubMed2005

Overview of adjuvant therapy for resected gastric cancer: differences in Japan and the United States.

Survival in adjuvant chemotherapy following resected gastric cancer has been studied by both Japanese and Western investigators using varied chemotherapy regimens in different target patients. Gastrectomy with D2 lymphadenectomy is the standard in Japan, and trials of adjuvant therapy in these patients have shown no survival advantages over surgery alone. In the United States, where 5-year survival rates in patients with gastric cancer are much lower following potentially curative surgery, adjuvant therapy has shown a survival benefit. The differences observed in these trials may result from the additional experience that Japanese surgeons have gained because of the higher incidence of gastric cancer there, or because of this increased incidence, there are more stringent screening guidelines in place and these cancers are possibly being diagnosed at an earlier stage. The Japanese viewpoint on the use of adjuvant therapy in patients with gastric cancer following potentially curative resection is that the quality of surgery, including diagnostic and pathologic procedures, is a more important prognostic factor than adjuvant chemotherapy. Also, they have determined from previously conducted clinical trials that patients with stage 1-2 tumors should be excluded from the target populations of randomized trials. Until the results of INT-0116 became available, there had been no improvement, or only marginal improvement, in overall or disease-free survival for patients receiving adjuvant chemotherapy following gastric cancer resection in the United States and Europe.

Adenocarcinoma↗
PubMed2005

[Recent changes in informed consent for cancer treatment].

"Truth telling" which was focused on just telling patients they have cancer, is gradually developing into "informed consent (IC)" which is focused on patients' understanding of their disease after careful explanation by their doctors. The major goal of IC is to respect the patients' self-determination and self-selection of the therapies they will receive and to establish close relationships between patients and doctors. Although truth telling about patients' prognosis is not yet fully established, providing such information to patients is basically unavoidable to obtain true IC. In delivering the bad news and obtaining IC as part of patient medical care, it is very important for doctors to brush up their communication skills with patients.

Communication↗
PubMed2004

Gastric cancer surgery: morbidity and mortality results from a prospective randomized controlled trial comparing D2 and extended para-aortic lymphadenectomy--Japan Clinical Oncology Group study 9501.

PURPOSE: Radical gastrectomy with regional lymphadenectomy is the only curative treatment option for gastric cancer. The extent of lymphadenectomy, however, is controversial. The two European randomized trials only reported an increase in operative morbidity and mortality, but failed to show survival benefit, in the D2 lymphadenectomy group. We conducted a randomized controlled trial to compare the Japanese standard D2 and D2 + para-aortic nodal dissection. PATIENTS AND METHODS: Only experienced surgeons in both procedures from 24 Japanese institutions participated in the study. Patients with potentially curable gastric adenocarcinoma (T2-subserosa, T3, or T4) who were surgically fit were intraoperatively randomized. Postoperative morbidity and hospital mortality were recorded prospectively in a fixed format and were compared between the two groups in this study. RESULTS: A total of 523 patients were randomized between July 1995 and April 2001. Postoperative complications were reported in 24.5% of all patients. Although the morbidity for the extended surgery group (28.1%) was slightly higher than the standard group (20.9%), there was no difference in the incidence of four major complications (anastomotic leak, pancreatic fistula, abdominal abscess, pneumonia) between the two groups. Hospital mortality was reported at 0.80%: one patient in each group died of operative complications, while one from each group died of rapid progressive cancer while inpatient. CONCLUSION: Specialized surgeons could safely perform gastrectomy with D2 lymphadenectomy in patients with low operative risks. Para-aortic lymphadenectomy could be added without increasing major surgical complications in this setting.

Adenocarcinoma↗
PubMed2004

Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings.

Peritoneal wash cytology plays a pivotal role in the decision for gastric cancer treatment because advanced gastric cancer often turns out incurable with peritoneal metastasis. Molecular detection of minimal cancer cells from peritoneal washings may overcome the sensitivity boundary of conventional cytology and contribute to the prediction of the disease outcome. To select marker candidates out of ten thousands of genes, we performed microarray analyses in 12 gastric cell lines and 8 peritoneal washings of early stage cases. With 40 candidates selected by the above expression profiling, RT-PCR in 16 representative peritoneal wash samples was performed to identify genes specific to cytology positive samples. The finally selected five genes, CK20, FABP1, MUC2, TFF1, and TFF2, were then evaluated for their utility as a marker for minimal residual disease in 99 peritoneal wash samples. Nested RT-PCR using the five genes showed positive results highly specific to incurable cases (91-100%). With a high specificity, the combination of these five genes succeeded in identifying 6 out of 20 (30%) additional patients with all types of early recurrence that could not be predicted by the conventional method. The six newly identified recurrences included four non-peritoneal ones, showing that RT-PCR using the five genes without a real-time quantitative PCR technique contributes to the detection of minimal residual disease.

Ascitic Fluid↗
PubMed2004

Feasibility study of adjuvant chemotherapy with S-1 (TS-1; tegafur, gimeracil, oteracil potassium) for gastric cancer.

BACKGROUND: We conducted a feasibility study using S-1, a novel oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy for curatively resected gastric cancer patients. METHODS: Adjuvant chemotherapy consisted of eight courses (4-week administration and 2-week withdrawal) of S-1, at 80-120 mg/body per day. Forty-one patients from 11 institutions were enrolled in this pilot study, from November 1999 to October 2000. RESULTS: Thirty-five patients were eligible. In 7 patients, S-1 administration was discontinued due to recurrence. Among the 28 patients without recurrence, the planned eight courses of S-1 were administered to 17 patients (60.7%). In 4 patients, S-1 administration was discontinued due to subjective symptoms, such as anorexia, in the first course. Adverse reactions such as neutropenia, leukopenia, elevated total bilirubin, anorexia, general fatigue, diarrhea, nausea, and stomatitis were seen in more than half of the patients. Although grade 3 neutropenia (29.3%), leukopenia (9.8%), and diarrhea (9.8%) were observed, no grade 4 adverse effects appeared. Compared with the treatment of unresectable or recurrent gastric cancer with S-1, the incidence of adverse reactions in the adjuvant setting was slightly higher, probably due to the influence of gastrectomy. CONCLUSION: Except for the early development of anorexia, most likely due to adverse effects of surgery, postoperative administration of S-1 for 1 year seems feasible as adjuvant chemotherapy for gastric cancer.

Adenocarcinoma↗