Search

Purpose: Assessment of nutritional status and nutritional interventions is important in gastric cancer patients. We investigated the factors associated with perioperative edema in patients with stage I gastric cancer using a body composition analyzer., Methods: The study included 106 patients with stage I gastric cancer who underwent distal gastrectomy. The body composition of each patient was evaluated by bioelectrical impedance analysis (BIA) using an InBody 720 body composition analyzer. Patients with an extracellular water to total body water ratio of ≥ 0.4 before and 1 week after gastrectomy were considered to have edema, the cause of which was determined retrospectively., Results: Patients with preoperative edema were significantly older, had a significantly higher lymph node metastasis rate and disease stage, and had a significantly poorer Controlling Nutritional Status (CONUT) score, and Prognostic Nutritional Index (PNI) compared with patients without preoperative edema. The group with postoperative edema had significantly higher proportions of elderly and female patients as well as a higher rate of Billroth-II reconstruction compared with the group without postoperative edema. The group with postoperative edema also had significantly lower intracellular water content, total body water content, protein content, skeletal muscle mass, and PNI., Conclusions: Preoperative edema occurs in elderly patients with poor nutritional status, and postoperative edema occurs in elderly patients with a shorter operative time. Perioperative edema status assessed by BIA is thought to be related to perioperative nutritional status.

Background/aim: This study aimed to investigate the effect of preoperative skeletal muscle mass and muscle mass loss after surgery on overall survival in patients with gastric cancer who underwent radical resection. We also examined factors involved in postoperative skeletal muscle loss., Patients and Methods: One hundred fifty gastric cancer patients who underwent radical resection were retrospectively examined. Skeletal muscle index (SMI) was measured using computed tomography before surgery and 1 year after. Degree of muscle reduction (MR) was calculated. Patients were stratified according to preoperative SMI (high/low) and MR (high/low) for analysis. In addition, patients were grouped according to SMI and MR stratification as follows: group A, low SMI/high MR; group B, low SMI/low MR; group C, high SMI/high MR; and group D, high SMI/low MR., Results: In multivariate analysis, preoperative SMI and MR were independent predictors of overall survival. Overall survival significantly differed among groups A, B, C, and D (p<0.0001). The list of groups in order of worsening overall survival was as follows: group D, group C, group B, and group A. In multivariate analysis, patient group according to SMI and MR stratification was an independent predictor of overall survival. MR was affected by operation time (>430 min) and surgical procedure (total gastrectomy)., Conclusion: Preoperative SMI and reduction in skeletal muscle mass after gastric cancer surgery were significantly associated with overall survival. Long-term management of these patients should focus on maintenance of postoperative skeletal muscle mass., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Robotic gastrectomy (RG) is an alternative minimally invasive surgical technique that has gradually come into use for the treatment of gastric cancer (GC). This study aimed to assess the feasibility and safety of RG for the treatment of GC. We retrospectively reviewed the use of RG in 47 patients with GC, and clinicopathological features and surgical outcomes were evaluated. The median age and body mass index of the patients were 68 years and 21.9 kg/m 2 , respectively. Distal gastrectomy, total gastrectomy, and proximal gastrectomy were performed in 39 (83.0%), 5 (10.6%), and 3 (6.4%) patients, respectively. The median operative time was 354 (256- 603) min. None of the operations were converted to open or laparoscopic procedures. The median blood loss was 15 (2-350) ml. None of the patients required blood transfusion. The mean number of resected lymph nodes was 43 (7-93). The median duration of postoperative hospital stay was 13 (9-37) days. Approximately 4.3% and 2.1% of the patients had anastomotic leakage and pancreatic fistula, respectively. One (2.1%) patient had Clavien-Dindo classification grade IIIa surgical complication (anastomotic leakage). No treatment-related deaths were observed. These findings suggest that RG might be a safe and feasible procedure for the treatment of GC.

Background/aim: Peritoneal lavage cytology is widely used to predict peritoneal recurrence after surgery, but cases of peritoneal recurrence are often recognized in patients with peritoneal lavage cytology negativity (CY0) who underwent no residual tumour (R0) surgery. We used peritoneal lavage fluid before and after gastric cancer surgery to detect cytokeratin 20 (KRT20) and carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) mRNA by RT-PCR., Materials and Methods: We collected peritoneal lavage fluid before and after surgery from 58 patients who underwent gastrectomy. RNA was extracted from these samples and RT-PCR was performed. RNA expression was defined as positive and negative in cases with values higher or lower than the median value. We investigated the relationship between mRNA expression and clinicopathological and surgical factors and prognosis., Results: Tumour invasion to the sub-serosa (T3) or penetration of the serosa (T4a), lymph node metastasis, and more than 150 ml intraoperative bleeding were significantly correlated with KRT20 mRNA expression. Multivariate analysis of its relationship with peritoneal recurrence showed that the odds ratio of CEACAM6 mRNA for recurrence was high (odds ratio=24.753; 95%CI=0.883-694.06; p=0.0592). All cases with peritoneal recurrence were CEACAM6-positive at pre- or post-surgery. The prognosis of peritoneal recurrence for both KRT20- and CEACAM6-positive cases was significantly poorer than that of other cases. The recurrence-free survival of the CEACAM6-positive group was significantly poorer than that of the CEACAM6-negative group., Conclusion: Measurement of CEACAM6 mRNA in peritoneal lavage fluid at pre- and post-surgery may be useful as a predictor of peritoneal recurrence., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Robotic distal gastrectomy (RDG) has been increasingly used for the treatment of gastric cancer (GC). However, whether RDG has a clinical advantage over laparoscopic distal gastrectomy (LDG) is yet to be determined. Thus, this study aimed to assess the feasibility and safety of RDG for the treatment of GC as compared with LDG., Methods: In total, 157 patients were enrolled between February 2018 and August 2020 in this retrospective study. We then compared the surgical outcomes between RDG and LDG using propensity score-matching (PSM) analysis to reduce the confounding differences., Results: After PSM, a clinicopathologically well-balanced cohort of 100 patients (50 in each group) was analyzed. The operation time for the RDG group (350.1 ± 58.1 min) was determined to be significantly longer than that for the LDG group (257.5 ± 63.7 min; P < 0.0001). Of interest, there was a decreased incidence of pancreatic fistulas and severe complications after RDG as compared with LDG (P = 0.092 and P = 0.061, respectively). In addition, postoperative hospital stay was statistically slightly shorter in the RDG group as compared with the LDG group (12.0 ± 5.6 vs. 13.0 ± 12.3 days; P = 0.038)., Conclusions: Our study confirmed that RDG is a feasible and safe procedure for GC in terms of short-term surgical outcomes. A surgical robot might reduce postoperative severe complications and length of hospital stay.

Background: Lentinan (LNT) is a purified β-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer., Patients and Methods: Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment., Results: One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group., Conclusions: OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer., Clinical Trial Registration Id Number: UMIN 000000574., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: The kidney is a dose-limiting organ for upper abdominal radiotherapy. In this study, radiation-induced kidney injury represented by changes of creatinine clearance (Ccr) and renal parenchymal volume measured by computed tomography (CT) were evaluated by analysing dose-volume histograms (DVHs) in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL) treated with chemoradiotherapy., Materials and Methods: Thirty-eight PGDLBCL patients (seventy-six kidneys) treated with chemoradiotherapy were included in this study. At least 4 years of follow-up was required for eligibility. Patients underwent (immuno-) chemotherapy followed by radiotherapy with approximately 40Gy to the whole stomach and perigastric lymph nodes. Ccr and CT were obtained at least annually. Changes of Ccr and renal parenchymal volume before and 4years after radiotherapy were compared using DVH parameters., Results: Mean Ccr decreased significantly from 82.7mL/min (range, 39-124mL/min) before radiotherapy to 70.4mL/min (range, 35-109mL/min) (p=0.01) 4years after radiotherapy. Mean reduction of bilateral renal parenchymal volume was 12% (range, -5-37%) in the same time period. Ccr and renal parenchymal volume tended to lower over time more than 4years after radiotherapy. Concerning DVH analysis, V20Gy⩾26.6% and D30%⩾19Gy had a significant risk of bilateral renal atrophy of ⩾14% and reduction of the Ccr⩾20mL/min., Conclusion: This study revealed that there was a definite relationship between DVH, renal atrophy and Ccr reduction. V20Gy<26.6% and D30%<19Gy appeared to be safe dose constraints for a Ccr reduction of <20mL/min 4years after radiotherapy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Situs inversus totalis (SIT) is a rare congenital anomaly in which the positions of the abdominal and thoracic cavity structures are reversed. The reported incidence of SIT is one in 10,000 to 50,000 live births. There are few reports of gastric cancer in individuals with SIT or of the potential complications of surgical intervention in such cases. We report the case of a 79-year-old woman with SIT who underwent surgical treatment for advanced gastric cancer at our hospital and review the pertinent literature. Prior to surgery, abdominal computed topography angiography with 3-dimensional reconstruction was performed to uncover any variations and to verify the exact structures and locations of vessels. Total gastrectomy with D2 lymphadenectomy and cholecystectomy were performed safely and with careful consideration of the mirror-image anatomy.

During radiotherapy for gastric lymphoma, it is difficult to protect the liver and kidneys in cases where there is considerable overlap between these organs and the target volume. This study was conducted to compare the three radiotherapy planning techniques of four-fields 3D conformal radiotherapy (3DCRT), half-field radiotherapy (the half-beam method) and intensity-modulated radiotherapy (IMRT) used to treat primary gastric lymphoma in which the planning target volume (PTV) had a large overlap with the left kidney. A total of 17 patients with gastric diffuse large B-cell lymphoma (DLBCL) were included. In DLBCL, immunochemotherapy (Rituximab + CHOP) was followed by radiotherapy of 40 Gy to the whole stomach and peri-gastric lymph nodes. 3DCRT, the half-field method, and IMRT were compared with respect to the dose-volume histogram (DVH) parameters and generalized equivalent uniform dose (gEUD) to the kidneys, liver and PTV. The mean dose and gEUD for 3DCRT was higher than for IMRT and the half-beam method in the left kidney and both kidneys. The mean dose and gEUD of the left kidney was 2117 cGy and 2224 cGy for 3DCRT, 1520 cGy and 1637 cGy for IMRT, and 1100 cGy and 1357 cGy for the half-beam method, respectively. The mean dose and gEUD of both kidneys was 1335 cGy and 1559 cGy for 3DCRT, 1184 cGy and 1311 cGy for IMRT, and 700 cGy and 937 cGy for the half-beam method, respectively. Dose-volume histograms (DVHs) of the liver revealed a larger volume was irradiated in the dose range <25 Gy with 3DCRT, while the half-beam method irradiated a larger volume of liver with the higher dose range (>25 Gy). IMRT and the half-beam method had the advantages of dose reduction for the kidneys and liver., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Proximal gastrectomy (PG) is a widely accepted, efficient treatment for upper-third early gastric cancer. However, it is associated with reduced quality of life (QOL) following surgery, and cancer recurrence in the remaining stomach. Various reconstruction methods have been proposed, but the optimal method has yet to be determined. We investigated the clinicopathological characteristics, reconstruction methods, and postoperative complications in 101 cases of PG, and additionally compared 93 cases of early gastric cancer treated by PG, and 38 cases treated by total gastrectomy (TG). We found that esophagogastrostomy was superior in terms of operation time, intraoperative blood loss, and postoperative hospital stay, while no significant differences were observed in postoperative complications compared with jejunal interposition or jejunal pouch interposition. We found more cases of multiple gastric cancers and advanced-stage cancer in the TG group than in the PG group. The TG group also had a significantly higher proportion of cases with large tumor diameters, low degrees of differentiation, many lymph node metastases, and advanced-stage disease. There were no differences in the recurrence rate or survival rate between the PG and TG groups. The PG group also showed significantly better results in operating time, intraoperative blood loss, and postoperative complications, with a tendency toward shorter hospital stays. In conclusion, PG is a curative but less invasive treatment for upper-third early gastric cancer, and esophagogastrostomy can be considered the most satisfactory reconstruction method following PG.

Aim: To assess the clinicopathologic characteristics, risk factors, and prognosis for synchronous multiple early gastric cancer (SMGC)., Methods: A total of 146 patients with SMGC and 1194 patients with single gastric cancer who had undergone gastrectomy between 1989 and 2008 were retrospectively analyzed to determine their clinicopathologic characteristics and postoperative survival. Tumors were classified into groups on the basis of location and histology. Smoking habits were evaluated using the Brinkman index. Clinical and pathological factors were compared using either Fisher's exact test or Pearson's χ(2) test. Logistic regression analysis was performed to identify independent risk factors. Survival rate was calculated using the Kaplan-Meier method., Results: SMGCs accounted for 10.9% of gastric cancer cases and occurred predominantly in elderly male patients with a family history of gastric cancer who were both smokers and drinkers. These tumors were typically macroscopically elevated and histologically differentiated. There were no significant differences between SMGC and single gastric cancer patients with respect to tumor location, tumor size, lymph node metastasis, the number of metastatic lymph nodes, venous invasion, or tumor stage (P = 0.052, P = 0.347, P = 0.595, P = 0.805, P = 0.559, and P = 0.408, respectively). Further, there was no significant difference in postoperative survival between the patient groups (P = 0.200). Of the 146 SMGC patients, a single patient had remnant cancer., Conclusion: A careful preoperative endoscopy is necessary for patients who are at high risk of SMGC, and minimally invasive treatment may be indicated in some cases.

Background: There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma., Methods: The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population., Results: There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma., Conclusion: There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma, especially of diffuse large B-cell lymphoma.

Purpose: Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique., Patients and Methods: Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines., Results: Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure., Conclusion: The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.

A 47-year-old woman was diagnosed as advanced gastric cancer of cardia(poorly-differentiated adenocarcionoma), with multiple para-aortic lymph node and liver metastasis, in March, 2005. We attempted neo-adjuvant chemotherapy with docetaxel(DOC), cisplatin(CDDP), and S-1(DCS). After 3 courses of DCS, we confirmed that the para-aortic lymph nodes and liver metastasis became small. Then, we were able to perform total gastrectomy, splenectomy, and D2 lymph node dissection. Additionally, we performed an intraoperative radiofrequency ablation to the scar of the liver metastasis. Histopathologically, we identified lymph node metastases in #1 and #16b1 pre. S-1 and DOC were administered as adjuvant chemotherapy. At seven years since the operation, the patient has shown no signs of recurrence. Combined modality therapy for advanced gastric cancer diagnosed with stage IV can be an effective treatment, so we hope that it will be established as a standard therapy.

In May, 2009, a man in his 30s presented to the department of outpatient palliative care of this hospital. His chief complaints were of severe nausea and abdominal fullness associated with cancerous peritonitis following surgery for gastric cancer. Abdominal fullness was reduced after the initiation of a continued subcutaneous administration of octreotide acetate, but combination therapy with metoclopramide and domperidone did not relieve nausea. The administration of olanzapine orally disintegrating tables (OLZ-ODT) at a dose of 10 mg twice daily was associated with the tendency to reduce nausea. As the symptoms were relieved, palliative care at his home was initiated. The patient's self-discontinuation of OLZ-ODT because the nausea was relieved resulted in its aggravation, but it was relieved again when the administration was resumed. Subsequently, home care was possible for approximately two and half a months without aggravation. Maintaining nausea control well leads to higher-quality care. OLZ-ODT appears to not only be effective for relieving nausea associated with cancerous peritonitis, but is also important for disseminating palliative care at home.

CpG island promoter methylation of tumor suppressor genes is one of the most characteristic abnormalities in EBV-associated gastric carcinoma (GC). Aberrant promoter methylation and expression loss of PTEN were evaluated in cancer tissues of GC by methylation-specific PCR and immunohistochemistry, respectively, showing that both abnormalities occurred concurrently in EBV-associated GC. PTEN abnormalities were reiterated in GC cell lines MKN-1 and MKN-7 infected with recombinant EBV, and DNA methyltransferase 1 (DNMT1) was commonly overexpressed in both cell lines. Stable and transient transfection systems in MKN-1 similarly showed that viral latent membrane protein 2A (LMP2A) up-regulated DNMT1, leading to an increase in methylation of the PTEN promoter. Importantly, the level of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased in the nuclei of LMP2A-expressing GC cells, and knockdown of STAT3 counteracted LMP2A-mediated DNMT1 overexpression. Immunohistochemistry for both pSTAT3 and DNMT1 showed diffuse labeling in the nuclei of the cancer cells in GC tissues, especially in EBV-associated GC. Taken together, LMP2A induces the phosphorylation of STAT3, which activates DNMT1 transcription and causes PTEN expression loss through CpG island methylation of the PTEN promoter in EBV-associated GC. LMP2A plays an essential role in the epigenetic abnormalities in host stomach cells and in the development and maintenance of EBV-associated cancer.

We examined 198 cases of primary scirrhous type 4 gastric cancer at our department from 1984 to 2003. Of these, 139 cases underwent gastrectomy. The essential cause of inoperability was peritoneal dissemination with malignant abdominal abscises. The incidence of peritoneal dissemination was 48.2% of all resected cases. The 5-year survival rate of all resected cases was 12% and that of non-resectable cases was 0%. One of the 59 nonresectable cases who responded remarkably to treatment by TS-1/paclitaxel combination chemotherapy obtained survival of 12 months. Six cases with peritoneal dissemination were treated by chemotherapy with cisplatin and etoposide infused intra-peritoneally and 2 of them were diagnosed as P 0 after 4 weeks. One case with type 4 gastric cancer who had right hydronephrosis and malignant abdominal ascites underwent curative resection after successful treatment with TS-1. We have selected the way of conventional chemotherapy for inoperable type 4 gastric cancers, but the prognosis is still poor. It is thought necessary to improve survival by newly developed anticancer agents such as TS-1, etoposide and taxanes. Immuno-cellular therapy with autologous tumor cell stimulated lymphocyte may be examined as a neo-adjuvant therapy as well as chemotherapy.

The aim of the present study was to examine the significance of the p21 expression in gastric cancer. We examined the expression of p53, p21, TGF beta 1 and PCNA in 75 cases of gastric cancer using immunohistochemical examinations and the expression of p21 RNA by in situ hybridization (ISH). The combination of p53 and p21 expression was related to depth of invasion, lymph node metastasis, and stage grouping. The survival curves of the p53 negative-Group and the p21-positive Group were significantly higher than those of the p53-positive and the p21-negative Group, the p53-and-p21-both-positive Group, and the p53-and-p21-both-negative Group (each p < 0.01). The average PCNA Labelling Index (LI) of the p53-negative-and-p21-positive Group was significantly lower than that of either the p53-positive-and-p21-negative Group or the p53-and-p21-both-positive Group or the p53-and-p21-both-negative Group (p < 0.01, p < 0.05, p < 0.05, respectively). All of the p53-and-p21-both-positive cases were TGF beta 1 positive, and the rate of the TGF beta 1 positive cases in the p53-and-p21-both-positive Group was significantly higher than that of the p53-positive-and-p21-negative Group, and than the rate in the p53-and-p21-both-negative Group (each p < 0.01). The survival curves of the cases with expression of p21 RNA were higher than that of cases without p21 RNA (p < 0.05). Many of the p53-positive-and-p21-negative cases were advanced cancer with very poor prognosis, but many of the p53-negative-and-p21-positive cases were early cancer with good prognosis. These results suggest that p21 suppressed synthesis of DNA via PCNA, and TGF beta 1 is a regulation factor for the expression of p21, and that the combination of p53 and p21 expression is concluded to be a useful prognostic marker of gastric carcinoma.

A 54-year-old man suffering from Borrmann type 4 advanced gastric cancer with pancreatic invasion and paraaortic lymph node metastases underwent a total gastrectomy, which was a radical C operation. From postoperative month 4, he visited our hospital with multiple liver metastases and increased lymph node metastases. After chemotherapy with CDDP and 5-FU, CDDP and UFT was administered on an outpatient basis. The effect of this therapy was PD, therefore, docetaxel and 5'-DFUR combination chemotherapy was performed as second line therapy. After 2 courses of this therapy, the size of liver and lymph node metastases was reduced and the effect of this therapy was PR. The patient has undergone 4 courses of this therapy and is maintaining a clinical PR. It is conceivable that docetaxel and 5'-DFUR combination chemotherapy is useful for patients with advanced and recurrent gastric cancer, even if they had been treated with 5-FU administration as first line therapy.

Background: We have investigated the correlations among the expression of proliferating cell nuclear antigen (PCNA), p53, p21, and the prognosis of primary gastric lymphoma, and we have investigated apoptosis by using transferase-mediated deoxyuridine triphosphate nick-end labeling staining., Methods: A retrospective study was performed on 33 cases of primary gastric lymphoma that were surgically resected. Histopathologic examination was undertaken according to the Working Formulation classification. Immunohistochemical staining was performed by using the avidin-biotin-peroxidase complex method, with anti-PCNA antibody, anti-p53 antibody, and anti-p21 antibody. Apoptosis was quantified in situ from paraffin-embedded specimens by using an in situ apoptosis detection kit., Results: On histologic grade, the survival rate of high-grade type was significantly lower than that of low-grade type and than that of intermediate-grade type. The PCNA index of low-grade type was significantly lower than that of intermediate-grade type and than that of high-grade type. Those patients who experienced recurrence were both p53(+) and p21(-). Two of these patients were receiving postoperative chemotherapy but nevertheless experienced recurrence at 18 months and at 5 months after surgery. The PCNA index of p53(+) p21(-) cases was significantly higher than that of p53(-) p21(+) cases. The apoptotic count of p53(-) p21(+) cases was significantly higher than that of p53(+) p21(-) cases., Conclusions: The Working Formulation classification and the PCNA index were each significant factors predicting the prognosis of primary gastric lymphoma. The prognosis of p53(+) p21(-) cases was poor, and the apoptotic count of p53(+) p21(-) cases was low. Accordingly, the effect of combined chemotherapy for those cases was thought to be poor.

We have reported a successful case of curative partial liver resection of metachronous liver metastasis from advanced gastric cancer. The patient was 56 years old and has undergone total gastrectomy with D2 lymph node dissection (2 type, well-differentiated adenocarcinoma, H0P0n0se, Stage 2). At 18 months later, follow-up ultrasound detected liver metastasis in the right posterior segment. Together with other imaging modalities, it was diagnosed as a solitary lesion without any other recurrence, and we performed partial resection of the right posterior segment. During the operation, there was no sign of any other recurrence (no peritoneal dissemination, no lymph node metastasis, and no other liver metastasis). Two Mitomycin-C (MMC) intravenous injections were given as postoperative chemotherapy. Usually, surgery for liver metastasis from gastric cancer is very rare as a curative therapy, because it is difficult to predict the effectiveness of the operation. In the present case, we decided on the operation since there was no sign of any other recurrence. It has now been 13 years to date since the partial liver resection and the patient remains free from recurrence.

We have experienced a case of early gastric carcinoma associated with amyloidosis. The patient was a 63-year-old woman diagnosed as having early gastric cancer type 0 Ila at the anterior wall on the greater curvature of the antrum, and multiple polypoid lesions on the antrum to the body of the stomach. We performed total gastrectomy, and rho-Roux-en-Y reconstruction. The tumor lesion was recognized at the anterior wall of the prepylorus, and the multiple polypoid lesions which were composed of amyloid masses were recognized on the whole stomach. The histological findings of the biopsy specimens from the rectum and the skin showed no amyloid-deposit. The urine examination was negative for a Bence-Jones protein reaction. This was a rare case of early gastric carcinoma associated with stomach amyloidosis, apparently confined to the stomach.

We have experienced a case of long-term survival after treatment with low dosage 5-fluorouracil (5-FU) and cisplatin (FP regimen). The patient was a 60-year-old man diagnosed as having advanced gastric cancer type 3 with numerous large lymph node metastases. After treatment with 2 courses of FP regimen, the primary tumor and para-aortic lymph nodes were decreased in size by 41% and 92%, respectively, and the serum level of alpha-fetoprotein was decreased to normal. We then recommended surgery, but the patient did not consent. Therefore, he was treated with a third course of FP regimen. He died at 3 years later. These results suggested that the FP regimen was an effective treatment for advanced gastric cancer which was difficult for curative resection because of the numerous large lymph node metastases.

The objective of this study was to show that hepatocyte growth factor (HGF) and HGF receptor (c-met protein) play an important role in the cancer growth and infiltration in scirrhous gastric cancer. The expression level of c-met protein was examined in 90 cases of advanced gastric cancer using anti-c-met antibody. Co-cultivation of each of four gastric cancer cell lines with gastric fibroblasts was performed using a double chamber method. The expression rate of c-met was 79.5% in type 4 tumors, significantly higher than in other types. The expression rates were 63.6% in undifferentiated-type cancer and 36.3% in differentiated-type cancer. Co-cultivation of undifferentiated-type cancer with fibroblasts showed a significantly higher HGF concentration than fibroblasts cultured alone. The growth in three undifferentiated-type cancers was accelerated by an addition of rhHGF and by co-cultivation with fibroblasts and was inhibited by anti-HGF antibody. Moreover rhHGF stimulated the invasion activity of undifferentiated cancer cell lines. These findings suggested that gastric fibroblasts in scirrhous cancer stimulate tumor growth and invasion through activation of the HGF/c-met system.

We measured pyrimidine nucleoside phosphorylase (PyNPase), a known angiogenetic factor, and dihydropyrimidine dehydrogenase (DPD) in advanced gastric cancers. PyNPase was expressed in cytoplasm of the cancer cells and surrounding interstitial cells. The levels of PyNPase and DPD were significantly higher in cancer tissue. With respect to tumor factors, the level of PyNPase was significantly higher in cases positive for venous invasion. We divided patients into two groups, with high and low activities of IAP and MMP-9. The level of PyNPase was significantly higher in the high IAP activity group. A correlation was suggested between the level of PyNPase and the activity of IAP. 5'-Deoxy-5-fluorouridine (5'-DFUR) is transformed into 5-FU by PyNPase and manifests antitumor effects. DPD is a rate-limiting enzyme in the process of degradation of 5-FU. In the present study, the level of PyNPase/DPD was significantly higher in cancer tissue. PyNPase/DPD suggests not only the malignant potential of the tumor but also the efficiency of chemotherapy using 5-FU, especially 5'-DFUR.

The expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), transforming growth factor alpha (TGF alpha), and of c-erbB-2 was immunohistochemically investigated in resected gastric carcinoma (in 39 cases of superspreading type and in 11 cases of penetrating type), to understand the differential biological features of these two types of gastric carcinoma. EGF, EGFR and c-erbB-2 positive cases were preferentially found in penetrating type rather than in superspreading type (p < 0.05, p < 0.01, and p < 0.05, respectively). The positive rates of EGFR and c-erbB-2 were significantly higher in submucosal gastric carcinoma than in intramucosal gastric carcinoma (p < 0.01, p < 0.05, respectively). These results suggested that the autocrine mechanism of the growth factors and the expression of c-erbB-2 were correlated to the degree of gastric wall invasion.

We have experienced a case of advanced gastric cancer with para-aortic lymph node metastasis effectively treated by neoadjuvant continuous low dosage 5-fluorouracil and cisplatin (FP regimen). The patient was a 67-year-old man diagnosed as having advanced gastric cancer type 4 with para-aortic lymph node metastasis. This patient was treated by continuous infusion of 5-fluorouracil (5-FU) 500 mg/day, for 28 days, and infusion of cisplatin 10 mg/day over 1 hr on days 1-5, 8-12, 15-19, and 22-26. At 4 weeks later, a CT revealed that swelling in the para-aortic lymph node had disappeared, and the thickening in the stomach wall had diminished. This patient underwent a curative operation, and both the serum level of carcinoembryonal antigen (CEA) and carbohydrate antigen (CA 19-9) decreased to normal. These results suggested that the FP regimen was an effective neoadjuvant treatment for advanced gastric cancer with para-aortic lymph node metastasis.

We have experienced two cases of long-term survival after surgery for gastric cancer case with liver metastasis. One case was of a 66-year-old male patient diagnosed as having type 1 advanced gastric cancer located in the posterior wall of the lower body with liver metastasis. The stage of this case was P0H1N1T2M0 stage IV. This patient underwent distal gastrectomy with D2 lymph node resection, partial hepatectomy of the S3 region including the metastatic liver tumor and coagulation of metastatic liver tumors in the S6 and S7 regions. This patient was treated by intra-hepatic arterial infusion of 5-FU, CDDP and peroral administration of UFT after surgery. This patient has died at 3 years and 7 months after surgery. The other case was of a 55-year-old male patient diagnosed as having type 2 advanced gastric cancer located in the lesser curvature of the cardia with liver metastasis. The stage of this case was P0H1N1T3 M0 stage IV. This patient underwent total gastrectomy with D2 lymph node dissection, wedge resection of the S8 region including the metastatic liver tumor and coagulation of a metastatic liver tumor in the S4 region. This patient was treated by obstruction of the hepatic artery using coils, peroral administration of UFT, lentinan, MMC, and continuous low-dosage 5-FU and CDDP after surgery. This patient has died at 3 years and 6 months after surgery. These results suggest that for long-term survival in cases of gastric cancer with liver metastasis, hepatectomy or coagulation of the metastatic tumor with postoperative chemotherapy are indicated in cases that have no non-curative factors and only a few metastatic tumors.

We have experienced two cases of unresectable advanced gastric cancer effectively treated by chemo-immunotherapy. One case was of a 68-year-old male patient diagnosed as having inoperable advanced gastric cancer with liver and lung metastasis. This patient was treated by combined chemo-immunotherapy of MMC 10 mg/M, 5'-DFUR 800 mg/day and OK-432 5 KE/2W. At 6 months later, a computed tomography (CT) scan and upper gastrointestinal (GI) series revealed that the metastatic liver tumors and stomach lesion were remarkably decreased in size, and endoscopic biopsy confirmed no cancer cells in the stomach lesion. Moreover, the metastatic lung tumor had disappeared on chest X-ray. The other case was of a 68-year-old female patient with unresectable advanced gastric cancer treated by combined administration of MMC 10 mg/M, 5-FU 200 mg/day and OK-432 5 KE/2W. At 2 months after commencing the treatment, there was a reduction in the serum carcinoembryonal antigen (CEA) level. At 6 months later, the CEA had decreased to normal, the primary and metastatic sites had completely disappeared on CT, and endoscopic biopsy confirmed no cancer cells in the stomach lesion. This patient has survived to date for 5 years and 6 months after commencing the treatment. These results suggested that combined chemo-immunotherapy of MMC, antimetabolite, and OK-432 was an effective treatment for unresectable advanced gastric cancer.

Cyclin D1 and E have been found to be deregulated and overexpressed in various types of cancers. In order to study the cell cycle regulatory mechanisms in gastric cancer, we have analyzed the protein expression of cyclin D1 and cyclin E in 76 tumor specimens from patients with primary gastric cancer, using immunohistochemistry. Overexpression of cyclin D1 was observed in 38 cases (50.0%). Overexpression of cyclin E was observed in 40 cases (52.6%). There was no significant difference between the expression of cyclin D1 and any clinicopathological factor. Cyclin E overexpression was correlated with a high incidence of lymph node metastasis, a low incidence of T1, and with Stage I. There was no significant difference in survival curves between cyclin D1 (+) and cyclin D1 (-). The survival curves of cyclin E (-) were significantly higher than those of cyclin E (+). These results suggested that in gastric carcinoma, cyclin E overexpression was useful as a prognostic indicator, but cyclin D1 was not.

We have recently encountered two patients with early gastric cancer in the remnant stomach which resulted from gastritis cystica polyposa at the anastomosis site. The remnant stomach, which had been reconstructed with the Billroth II method, contained an elevated sessile lesion at the anastomosis site. One patient was a 73-year-old woman who had undergone gastrectomy for a gastric ulcer at 30 years earlier, cancer type I + IIa of the remnant stomach was diagnosed, and total remnant gastrectomy was performed. The other patient was a 59-year-old man who had undergone gastrectomy for a duodenal ulcer at 31 years earlier, cancer type I + IIa of the remnant stomach was diagnosed, and subtotal remnant gastrectomy was performed. Histological examination in each case showed that moderately differentiated adenocarcinoma had developed from gastritis cystica polyposa. These results suggested that this cancer has a close relationship with gastritis cystica polyposa.

A retrospective study of 25 patients treated for primary gastric lymphoma was made to investigate a number of problems related to treatments and report the factors influencing prognosis. In the 5-year-survival rate according to Working Formulation classification, either survival rate of low-grade type or intermediate-grade type was higher than that of high-grade type. Both the 5-year-survival rate of cases without lymph node metastasis and that of cases that involved perigastric lymph nodes were higher than that of cases that involved distant gastric lymph nodes. Those surviving five years after perigastric lymph node metastasis had received D3 or D4 dissection and postoperative multicombined chemotherapy. Tumors invading only to the submucosal layer had received D2 dissection and were not treated by postoperative multicombined chemotherapy, and recurrence was not recognized in these cases. Of 9 cases infiltrating into the musclaris propria or serosa without lymph node metastasis, 8 cases were treated by postoperative multicombined chemotherapy and were alive without recurrence, but one case without postoperative multicombined chemotherapy died by recurrence. Therefore, adequate therapy for gastric lymphoma with infiltrating into submucosal layer is gastrectomy with D2 lymph node dissection, and postoperative multicombined chemotherapy is not necessary. The cases with perigastric lymph node metastasis, or the cases with invading from muscularis propria to serosa require D3 or D4 lymph node dissection with postoperative multicombined chemotherapy. But the cases with distant gastric lymph node metastasis or invading adjacent structure or high-grade type histologically (WF classification) require preoperative chemotherapy.

We have experienced a case of the stomach with hypergastrinemia and type A gastritis with multiple carcinoids in a 37-year-old woman. An upper gastrointestinal series revealed multiple minute polyps in the upper body of the stomach. All polyps were diagnosed as carcinoid using endoscopic biopsies. She had neither symptom or signs of typical carcinoid disease. The serum gastrin level was as high as 725 pg/ml. Total gastrectomy was performed, and the diagnosis of multiple gastric carcinoids (sm, no) with type A gastritis was histologically confirmed. After the operation, the serum gastrin level returned to normal, and the patient has been doing well and is disease-free to date at 7 years after the operation. This case suggested that multiple gastric carcinoid lesions may be precipitated by chronic atrophic gastritis accompanying hypergastrinemia. In the treatment of multiple gastric carcinoids with type A gastritis, total gastrectomy with lymph node dissection should be standard operative procedure, in order to resect the fundic gland area completely which could be the origin of carcinoids and endocrine cell micronest.

We have experienced a case of advanced gastric cancer with liver metastasis effectively treated by intra-hepatic arterial infusion of 5-fluorouracil (5-FU), mitomycin C (MMC) and peroral administration of 5-FU. The patient was a 48-year-old male diagnosed as having advanced gastric cancer with multiple liver metastasis in the bilateral lobes of the liver. This patient was treated by intra-hepatic arterial infusion of 5-FU (250 mg/2 days x 8 doses), MMC (20 mg x 1 dose, 6 mg/2 weeks x 6 doses) and peroral administration of 5-FU (200 mg/day). At 14 weeks later, a CT revealed that the metastatic liver tumors had disappeared. However, at 7 months after the therapy, the patient eventually died of liver and brain metastasis. These results suggested that intra-hepatic arterial infusion of 5-FU and MMC was an effective therapy for metastatic tumors in the liver, but we need to perform intra-hepatic arterial infusion using a new prolonged regimen to treat the liver metastasis.

We have reviewed the clinicopathological features of submucosal gastric cancer with lymph node metastasis. The degree of vertical submucosal infiltration was classified into three stages as sm1, sm2 or sm3. The number of cases with lymph node metastasis of sm3 was significantly more than that of sm1 or sm2. We found no correlation between the tumor size and the rate of lymph node metastasis from submucosal invasive cancer. Accordingly, we concluded that the vertical submucosal infiltration was a more important factor for lymph node metastasis than horizontal infiltration. Minimal invasive surgery was recommended for a tumor measuring 1 cm or less in size with vertical submucosal invasion of sm1 or sm2.

Epidermal growth factor (EGF) induced the disruption and scattering of colonies of TMK-1, a cell line derived from a human gastric carcinoma. A stimulatory action of EGF on cell migration was also observed as determined by a wound assay. However, these actions of EGF were inhibited if the cells were pretreated with dexamethasone, a synthetic glucocorticoid. Dexamethasone increased cell adhesion to collagen type IV and laminin, but not to poly-L-lysine and fibronectin. In contrast, EGF did not affect cell adhesion to these extracellular matrices whether dexamethasone was present or not. Dexamethasone enhanced the protein levels of both alpha1 and beta1 integrin subunits, and that of the alpha1 beta1 heterodimer. Further, flow cytometric analysis revealed that dexamethasone increased the expression of beta1 and alpha1 integrin subunits at the cell surface, whereas EGF increased expression of beta1 and alpha2 subunits at the cell surface. Antibodies against alpha1 and beta1 integrin subunits inhibited the increased cell adhesion seen in the presence of dexamethasone. An immunofluorescence study indicated that dexamethasone increased the formation of focal adhesions along the entire edges of cell colonies. In contrast, EGF led to the formation of focal adhesions preferentially at the cell front, and this EGF-induced preferential formation was not observed if the cells were pretreated with dexamethasone. These results suggest that glucocorticoid increased cell adhesion to the extracellular matrix via alpha1 beta1 integrin, and thereby antagonized EGF-induced cell migration.

Method and Materials: To suggest improved guidelines for treating lymphatic spread and to understand the results of extended lymphadenectomy. A total of 141 cases of cardia carcinoma admitted to our hospital during 1980 to 1993 were analyzed., Results: 123 of 141 cases underwent resection. The incidence of mediastinal lymph node involvement rose from 8.7% in cases with 1-2 cm invasion to 52.9% in cases with more than 4 cm invasion into the esophagus. The incidence of abdominal lymph node involvement also rose with increasing esophageal invasion. Paraaortic lymph node metastasis was frequently observed in cases of more than 1 cm esophageal invasion. D4 lymphadenectomy (extended lymphadenectomy) revealed better results for the cases with lymph node involvement (P<0.05). There was no difference in the incidence of postoperative complication or in operative death, between the abdominal approach and the thoracoabdominal approach, or between the D4 lymphadenectomy and D2 lymphadenectomy., Conclusion: Sufficient mediastinal and abdominal lymphadenectomy under a clear wide surgical field achieved through the thoracoabdominal approach appeared to bring better results.

We examined the expression of p53, p21, cyclin D1, E, and PCNA in 75 cases of gastric cancer by immunohistochemical study and the expression of p21 RNA in cases by in situ hybridization. The rate of stage III, IV cases of p53(+) p21(-) group was significantly higher than that of any other groups. The apportinately 3-year survival rate of p53(+) p21(-) group was significantly lower than either that of p21(+) p53(-) or p53(-) p21(-) group. The 3-year survival rates of positive cases were significantly lower than those of negative cases on both cyclin D1 and E. The positive rate of cyclin E of the p53(-) p21(+) group was significantly lower than that of the p53(+) p21(-) group. The average PCNA Labeling. Index (LI) of the p53(+) p21(-) group was significantly higher than that of the p53(-) p21(+) group. The 3-year survival rate of cases with expression of p21 RNA was higher than that of cases without p21 RNA. Average PCNA L1 of cases with expression of mutant-type p53 was high and the number of poor prognostic cases in cases with expression of mutant-type p53 was large. In contrast, the average PCNA LI of cases with expression of p21 was low and the number of good prognostic cases with expression of p21 was large. These results suggest that p21 suppresses synthesis of DNA via cyclin E and PCNA.

We administered preoperatively 5'-deoxy-5-fluorouridine (5'-DFUR) for treatment of advanced gastric and colonic cancers, and measured pyrimidine nucleoside phosphorylase (PyNPase) in the excised tumor sample and serum immunosuppressive acidic protein (serum IAP), which is an index of the immunity of host-bearing cancer, while studying its direct antitumor effect and improved immunity. Patients with 24 advanced gastric cancers and 36 colonic cancers were randomly divided into a preoperatively administered group and a non-administered group. In the preoperatively administered group, 5'-DFUR (1,200 mg/day) was orally administered on preoperative days 7 approximately 14. After collecting samples (about 0.5 g) from adjacent normal tissues with tumor within 30 minutes after extirpation of tumor and freezing those less than -20 degrees C, the PyNPase level was measured as soon as possible. Moreever, serum IAP levels at pre-administration in the administered group and on admission in the non-administered group were measured. Those in the administered group were measured again on the operative day. No decreasing tendency of PyNPase was generally found in cases with gastric colonic cancers, and no significant difference in stage-II was not either. However, a decreasing tendency in tumor activity was found by pre-administration. Moreover, there was significant improvement in the serum IAP level in cases with gastric and colonic cancers by pre-operative administration of 5'-DFUR. This tendency was also found in advanced colonic cancer with Dukes-C by Dukes's classification. In conclusion, it was suggested that the pre-operative administration of 5'-DFUR for treatment of advanced gastric and colonic cancers has a favorable influence for prognosis because the tumor region was retarded by the high PyNPase activity according to the severity of tumors and elevating tendency of the immune response in host.