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Introduction: Esophagogastroduodenoscopy is the most important tool to detect gastric cancer (GC). In this study, we developed a computer-aided detection (CADe) system to detect GC with white light imaging (WLI) and linked color imaging (LCI) modes and aimed to compare the performance of CADe with that of endoscopists., Methods: The system was developed based on the deep learning framework from 9,021 images in 385 patients between 2017 and 2020. A total of 116 LCI and WLI videos from 110 patients between 2017 and 2023 were used to evaluate per-case sensitivity and per-frame specificity., Results: The per-case sensitivity and per-frame specificity of CADe with a confidence level of 0.5 in detecting GC were 78.6% and 93.4% for WLI and 94.0% and 93.3% for LCI, respectively (p < 0.001). The per-case sensitivities of nonexpert endoscopists for WLI and LCI were 45.8% and 80.4%, whereas those of expert endoscopists were 66.7% and 90.6%, respectively. Regarding detectability between CADe and endoscopists, the per-case sensitivities for WLI and LCI were 78.6% and 94.0% in CADe, respectively, which were significantly higher than those for LCI in experts (90.6%, p = 0.004) and those for WLI and LCI in nonexperts (45.8% and 80.4%, respectively, p < 0.001); however, no significant difference for WLI was observed between CADe and experts (p = 0.134)., Conclusions: Our CADe system showed significantly better sensitivity in detecting GC when used in LCI compared with WLI mode. Moreover, the sensitivity of CADe using LCI is significantly higher than those of expert endoscopists using LCI to detect GC., (© 2024 S. Karger AG, Basel.)

After endoscopic treatment for esophageal cancer, a 65-year-old male underwent surveillance esophagogastroduodenoscopy. A 12-mm discolored flat lesion was noted on the greater curvature of the middle gastric body. Magnifying endoscopy with blue laser imaging demonstrated an irregular papillary surface. Biopsy revealed atypical cells with mucus and irregularly distributed nuclei. The lesion was diagnosed as a gastric-type neoplasm with low atypia. Thereafter, endoscopic submucosal dissection (ESD) was conducted and specimen was sent for biopsy. The ESD specimen suggested a signet-ring cell carcinoma with MUC5AC-positive phenotype and adenocarcinoma of the fundic gland type, with MUC6 positivity and pepsinogen I positivity in the shallow and deeper layers, respectively. Moreover, the cervical region of fundic glands demonstrated a transformation zone of the signet-ring cell carcinoma into an adenocarcinoma of the fundic gland type. Herein, we report this rare case along with a literature review.

Gastric schwannoma is a relatively rare tumor arising from Auerbach plexus in the muscle layer of the gastric wall, and constitutes 0.1% to 0.2% of all gastric tumors and 5% of benign non-epithelium-related gastric tumors. We report the case of a 49-year-old woman in whom upper gastrointestinal endoscopy revealed an approximately 2-cm submucosal tumor on the anterior wall of the fornix of the stomach. Contrast-enhanced computed tomography revealed a homogeneously enhanced lesion (~ 17 mm) in the upper third of the stomach as well as a lesion (~ 25 mm) on the left kidney that was strongly enhanced in the early phase. An 18 F-fluorodeoxyglucose positron emission tomography scan revealed high accumulation that is characteristic of gastric tumors. The possibility of malignancy was not completely excluded, and the gastric tumor was resected by non-exposed endoscopic wall-inversion surgery. The patient was discharged with a good prognosis 5 days after surgery. In conclusion, non-exposed endoscopic wall-inversion surgery is a minimally invasive and effective method for resecting small gastric submucosal tumors (diameters < 3 cm) for which preoperative diagnosis is difficult.

Endoscopic submucosal dissection (ESD) of lesions using expanded indications for early gastric cancer (EGC) has been accepted as an alternative treatment for cases without lymph node metastasis. We herein report a rare case of metastatic lymph node tissue in mixed adenoneuroendocrine carcinoma (MANEC) after curative ESD using the expanded pathological criteria. A 70-year-old man underwent ESD for two EGC lesions. A pathological examination revealed lesions that required curative resection based on the expanded pathological criteria of the Japanese classification of gastric carcinoma. However, lymph node metastasis was detected at 26 months after ESD. Additional surgical resection was performed and MANEC was pathologically diagnosed in the metastatic lymph node. The patient subsequently underwent additional chemotherapy and remains alive at 2 years after surgery. Even though MANEC is a rare tumor, this case suggests that periodic follow-up is important when patients undergo curative resection by ESD based on the expanded indications because of the high malignant potential and the poor prognosis.

We reported a case of early gastric cancer with submucosal heterotopic gastric glands.A 62-year-old woman presented with poor appetite, weight loss, and epigastric pain.Endoscopy examination identified giant gastric folds and a gastric ulcer on the posterior wall of the upper-middle stomach.Biopsy specimen analysis showed adenocarcinoma.We preoperatively diagnosed the lesion as type II c-like advanced cancer and performed a total gastrectomy.Pathologically, the lesion was diagnosed as gastric cancer(non-solid type poorly differentiated adenocarcinoma)located in the mucosal layer and accompanied by submucosal heterotopic gastric glands.Submucosal gastric gland heterotopia is a relatively rare disease, and it is difficult to diagnose the glands before surgery is performed.However, endoscopic ultrasonography helps to demonstrate diffuse cystic lesion preoperatively.It is often associated with multiple gastric cancers.Therefore, we must diagnose and treat the disease with great care.

Objective: The criteria for endoscopic resection for early gastric cancer include absolute and expanded indications. Consensus already exists for the absolute indications. However, the suitability of the expanded indications must be validated by long-term outcome analyses since such lesions have only recently become resectable with the development of endoscopic submucosal dissection. The aim of this study is to clarify the suitability of the expanded indications for the treatment of early gastric cancer with endoscopic submucosal dissection., Materials and Methods: The medical records of 1161 patients with early gastric cancers (1332 lesions) treated by endoscopic submucosal dissection and meeting the criteria for absolute or expanded indications without additional treatment with gastrectomy were divided into absolute indication group or expanded indication group., Results: Complete resection rates were 96.4% and 93.4% in absolute and expanded indication groups, respectively, with no significant differences between the groups. Delayed bleeding rates were significantly higher in the expanded indication group, whereas all cases were successfully managed conservatively. The 5-year overall survival and recurrence-free rates were 93.7%/99.77% and 90.49%/98.90% in the absolute and the expanded indication groups, respectively, with no significant differences between the groups for either measure. Multivariate analyses revealed that affected horizontal margin and tumor location were independent predictive factors for recurrence., Conclusion: The expanded indication group showed excellent post-endoscopic submucosal dissection short-term and long-term outcomes compared with the absolute indications group, demonstrating that expanded indications are suitable for endoscopic submucosal dissection for early gastric cancer.

The patient was a 48-year-old woman who was diagnosed with early gastric cancer during a long-term follow-up period for Gardner syndrome. Subtotal colectomy for colon leiomyoma was performed when the patient was 22 years old. Partial resection of the ileum was performed for ileum leiomyoma at the age of 27. Total resection of the remaining colon with ileostomy was performed for a pelvic desmoid tumor at the age of 40. In addition, resection of a desmoid tumor of the abdominal wall was performed 8 times in the 25 years since the first operation. During the follow-up for gastric polyps associated with Gardner syndrome, gastric cancer was detected from biopsy specimens of a wide range of the fundus polyps. Endoscopic resection was considered not to be applicable because of the extensive nature of the lesion. Total gastrectomy was also considered not to be applicable because of concerns about short bowel syndrome due to intestinal reconstruction. Therefore, proximal gastrectomy with esophagogastric anastomosis was performed. The pathological diagnosis was 0-IIa, 70 × 44 mm, tub1, m, ly0, v0, n0, PM (-), DM (-), stageIA. The postoperative course was uneventful, and the patient was discharged on postoperative day (POD) 16. We speculate that long-term survival of patients with Gardner syndrome without severe short bowel syndrome might result in carcinogenesis of gastric polyps.

Background: Endoscopic resection (ER) causes inflammation, edema, fibrosis of the stomach, and severe adhesions around the surrounding tissue. However, little is known about the clinical influence of ER on subsequent laparoscopic gastrectomy (LG) for gastric cancer., Patients and Methods: Between October 2007 and April 2011, 202 consecutive patients underwent curative LG for gastric cancer. Out of these, 30 (15%) LG cases had previously undergone ER and further LG to achieve a cure. The remaining 172 patients (85%) had no history of ER. We reviewed their hospital records retrospectively., Results: Intraperitoneal adhesions were detected in all patients after ER. However, there were no significant differences in clinical outcome, such as surgical duration, blood loss, number of dissected lymph nodes, complications, or hospital stay, between LG cases with and those without previous ER. Of the 30 cases of LG with previous ER, 15 treated within two months after ER had greater blood loss (p<0.005) and a longer surgical duration (p=0.06). LG cases with major or minor perforation during ER also had slightly greater blood loss (p=0.07) than those without. However, the number of dissected lymph nodes associated with surgical curability and postoperative complications were not significantly different in patients with and those without these clinical factors., Conclusion: LG can be performed curatively and safely even after ER. Perforation during ER and shorter time to LG after ER may be potential risks of surgical difficulty in subsequent LG.

Purpose: The clinical impact of the directionality of lymph node (LN) metastasis was assessed in comparison with the staging by the Japanese Classification of Gastric Carcinoma (JCGC), a numerical LN staging system., Methods: Two hundred forty-one gastric cancer patients who were diagnosed pathologically to have LN metastasis, and 54 patients who underwent preoperative multidetector-row computed tomography (MDCT) with an image thickness of 1 mm were classified into three groups (unidirectional [Uni-], bidirectional [Bi-], and tridirectional [Tri-] groups) depending on the directionality of their LN metastasis., Results: The prognosis of the Uni-group was better than that of the Bi- or the Tri-group when assessed on the basis of the pathological findings of metastatic LN and also the preoperative MDCT findings. The exact preoperative evaluation was 70.2 % for the directionality system and 61.7 % for the JCGC system, respectively. The stages were less frequently underestimated by the directionality system than the JCGC system (P < 0.02, 19.1 vs. 34.0 %), and the staging could be more precisely performed by both systems in combination., Conclusions: More precise preoperative evaluation of disease stage could be obtained by the directionality system and the JCGC system in combination.

Background: Precise staging of gastric cancer is essential when selecting for the appropriate treatment approach. 5-Aminolevulinic acid (5-ALA) is metabolized and accumulated as protoporphyrin IX (PpIX), which is a photosensitizer. In this study, we evaluated the diagnostic usefulness of 5-ALA for demonstrating peritoneal dissemination in patients with gastric cancer., Materials and Methods: Fluorescence laparoscopy (FL) was performed in 13 patients with gastric cancer. All patients received preoperative oral administration of 5-ALA. Fluorescence-light laparoscopies were sequentially performed intraoperatively., Results: In four out of the 13 patients, primary tumors were detected by FL and demonstrated serosal invasion on histological examination. Five out of the 13 patients demonstrated peritoneal metastases, and one patient demonstrated superficial liver micrometastases, by FL. All of these lesions were diagnosed as metastatic lesions by hematoxylin and eosin staining., Conclusion: These findings show that FL diagnosis with 5-ALA is accurate and suitable for the detection of peritoneal metastases and of superficial liver micrometastases in patients with gastric cancer.

Background and Purpose: Recent imaging modalities such as multi-detector computed tomography, fluorodeoxyglucose positron emission tomography/computed tomography, and magnetic resonance imaging have emerged as promising diagnostic and staging methods in various cancers. However, these modalities lack the diagnostic ability to evaluate tissue elasticity, which could instead be easily estimated by a surgeon through palpitation. To add tissue elasticity to future diagnostic methods, this study was designed to evaluate the ability of surgeons to estimate elasticity by direct inspection and palpitation during intra-operative nodal staging of gastric cancer., Patients and Methods: Between 2008 and 2009, 57 consecutive patients with gastric cancer underwent curative gastrectomy and all their regional lymph nodes showing metastatic involvement were intra-operatively counted using direct inspection and palpitation by surgeons., Results: The overall sensitivity, specificity, and accuracy were 63.1%, 86.8%, and 82.8%, respectively. The sensitivity was higher in D1 lymph nodes such as No.6, No.5, No.7, and No.3. The specificity and accuracy were higher in D2 lymph nodes such as No.9, No.11p and No.8a., Conclusions: Nodal diagnosis through direct inspection and palpitation by surgeons could be a reliable and accurate method in gastric cancer, comparable to other recent modalities. These data imply that tissue elasticity could be applied as a new modality in the nodal diagnosis of gastric cancer.

Despite recent perioperative technological advances in gastric cancer treatment, duodenal stump leakage and intractable duodenal fistula are still major critical complications following gastrectomy that should be specifically targeted in order to improve postoperative outcomes. Here, we provide a preliminary report of a case of intractable duodenal fistula successfully treated with Trafermin containing basic fibroblast growth factor. A 70-year-old man underwent distal gastrectomy with radical lymphadenectomy for early distal gastric cancer (pT1bN0M0). After surgery, duodenal fistula occurred and persisted for 1 year and 2 months despite surgery and several conservative treatments. After obtaining informed consent, we started injection of Trafermin at 50 μg/day through a drainage tube into the dehiscence of the duodenum. Consequently, the duodenal fistula was successfully closed within 4 weeks. Our novel treatment technique is simple, rapid, and cost effective. If informed consent is obtained from patients with a low risk of recurrence, this technique should be recommended as one of the treatment choices for intractable duodenal fistula following curative gastrectomy for gastric cancer.

Background: An aging population and advances in diagnostic technology have led to an increase in the incidence of double or multiple primary cancers(DMPC) in patients with gastric cancer(GC). This study was designed to evaluate the clinical influence of DMPC on the prognosis of patients with GC., Methods: Between 1997 and 2009, 1,086 patients underwent curative gastrectomy for GC in our hospital., Results: 1) 1,086 patients were analyzed, and of these 166 patients (15%) had DMPC and the remaining 920 patients had no DMPC. GC patients with DMPC had a significantly higher age (p <0.0001) and higher incidence of differentiated cancer(p=0.0045) than those without DMPC. 2) Multivariate analysis showed the presence of DMPC was an independent prognostic factor for overall survival. It was particularly noteworthy that the prognosis of GC patients with hematological cancer, hepato-biliary pancreatic cancer and esophageal cancer was extremely poor. In contrast, those with colorectal cancer and urological cancer had a comparatively better prognosis. The number of DMPC had little influence on the prognosis of GC patients. 3) In a survival associated with GC, the presence of DMPC had no influence on the prognosis of GC patients., Conclusions: The types of DMPC had more clinical influence on the prognosis of GC patients than the number of DMPC with respect to overall survival.

Sarcoidosis is an idiopathic systemic disease with non-caseating granuloma that is reported to occur concomitantly with various malignant tumors. We report here a case of advanced gastric cancer with sarcoidosis, for which precise preoperative diagnosis was difficult. A 69-year-old woman was diagnosed with a far-advanced gastric cancer because multiple intra-abdominal and intra-thoracic lymph node swellings and a tumorous lesion in the spleen were detected by multidetector computed tomography and fluorodeoxyglucose positron emission tomography. However, these multiple changes might be derived from sarcoidosis, because the multiple lymph node swellings were nonspecific changes for gastric cancer. With appropriate informed consent, surgery was selected in order to accurately confirm the stage of progression. Consequently, these changes were shown to not be metastatic, and curative surgery was performed. In conclusion, careful examination and a reasonable treatment strategy are important for avoiding the risk of overdiagnosis in gastric cancer patients with sarcoidosis.

Recent technological advances in optical and surgical devices have resulted in laparoscopic surgery for gastric and colorectal cancer, gaining wider acceptance and becoming more common. Simultaneous laparoscopic surgery for gastric and colorectal cancer has many potential advantages, including a small incision, good cosmetic result, less postoperative pain, and less mobility. However, some problems have to be resolved. To clarify the anastomotic problem of combined abdominal minilaparotomy, we present here 2 typical cases of simultaneous laparoscopic surgery for gastric and colorectal cancer. Case 1: The anastomoses after laparoscopic right hemicolectomy and distal gastrectomy were easily performed by combined upper abdominal minilaparotomy. Case 2: The anastomosis after laparoscopic right hemicolectomy was easily performed by upper abdominal minilaparotomy. However, the ensuing esophago-jejuno anastomosis after laparoscopic total gastrectomy resulted in failure during combined upper abdominal minilaparotomy because the anastomotic angle was incomplete. In conclusion, the choice of abdominal mini-incision site is crucial during simultaneous laparoscopic surgery for gastric and colorectal cancer. Surgeons should not hesitate to perform an additional mini-incision or change other anastomotic procedures if the operation is difficult, requires a long time to complete, and is likely to cause intraoperative complications.

Background: Thin-slice multidetector row computed tomography (MDCT) has emerged as a promising diagnostic modality in various cancers. This study was designed to evaluate the utility of metastatic nodal counts on MDCT as a surrogate maker for surgical curability in gastric cancer., Methods: Between 2005 and 2007, a total of 92 patients with gastric cancer underwent preoperative MDCT at a slice thickness of 1.0 mm at our hospital. All regional lymph nodes showing metastatic involvement were preoperatively counted., Results: Although the total counts of metastatic lymph nodes on MDCT were significantly smaller than those found by histopathology (P = 0.00001), there was a significant correlation between nodal counts on MDCT and histopathology by Spearman's analysis [P < 0.0001, pathologic counts = 1.63x (counts on MDCT) + 2.5]. Nodal counts on MDCT of ≥4 were analyzed as putative pathologic nodal counts of ≥8 by the equation, and pathologic metastatic nodal counts of ≥8 were most significantly correlated with noncurative resection (P < 0.0001). According to the logistic regression analysis, nodal counts on MDCT of ≥4 were a significant independent variable for noncurative resection (P = 0.0052, odds ratio 26.68). Nodal counts on MDCT of ≥4 could distinguish noncurative patients from curative patients with 94.4% sensitivity and 71.6% specificity., Conclusions: Nodal counts on MDCT could be a reliable surrogate maker for surgical curability of gastric cancer. This marker might enable us to select prospective candidates for additional or alternative treatments in gastric cancer.

Background: This study was designed to evaluate the clinical significance of undifferentiated component in differentiated T1/T2 gastric adenocarcinoma., Methods: Two hundred thirty-one patients who underwent curative gastrectomy were diagnosed pathologically as differentiated type T1/T2 gastric cancer according to Japanese Classification of Gastric Carcinoma (JCGC). The patients were divided into subgroups, pure differentiated type (pure D group, 181 patients) and differentiated-predominant mixed type (D > U group, 51 patients). The clinicopathological features of D > U group were compared with those of pure D group, and also those of undifferentiated-predominant type (U > D group)., Results: Patients in D > U group were more likely to have larger and deeper tumors with lymphatic invasion and metastases than pure D group. However, there was no significant difference in clinicopathological factors between D > U and U > D groups, except for depth of tumor invasion. The postoperative 5-year survival rate of D > U group was significantly poorer than that of pure D group (88% and 98%, P = 0.011). Multivariate analysis revealed the presence of undifferentiated component was an independent prognostic factor., Conclusions: The presence of undifferentiated component in differentiated T1/T2 gastric cancer is associated with tumor progression. Therefore, the decision criterion of histological mixed type in TNM classification is better suited than JCGC in T1/T2 gastric cancer., (Copyright © 2012 Wiley Periodicals, Inc.)

Aim: To re-evaluate the recent clinicopathological features of remnant gastric cancer (RGC) and to develop desirable surveillance programs., Methods: Between 1997 and 2008, 1149 patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Japan. Of these, 33 patients underwent gastrectomy with lymphadenectomy for RGC. Regarding the initial gastric disease, there were 19 patients with benign disease and 14 patients with gastric cancer. The hospital records of these patients were reviewed retrospectively., Results: Concerning the initial gastric disease, the RGC group following gastric cancer had a shorter interval [P < 0.05; gastric cancer vs benign disease: 12 (2-22) vs 30 (4-51) years] and were more frequently reconstructed by Billroth-I procedure than those following benign lesions (P < 0.001). Regarding reconstruction, RGC following Billroth-II reconstruction showed a longer interval between surgical procedures [P < 0.001; Billroth-II vs Billroth-I: 32 (5-51) vs 12 (2-36) years] and tumors were more frequently associated with benign disease (P < 0.001) than those following Billroth-I reconstruction. In tumor location of RGC, after Billroth-I reconstruction, RGC occurred more frequently near the suture line and remnant gastric wall. After Billroth-II reconstruction, RGC occurred more frequently at the anastomotic site. The duration of follow-up was significantly associated with the stage of RGC (P < 0.05). Patients diagnosed with early stage RGC such as stage I-II tended to have been followed up almost every second year., Conclusion: Meticulous follow-up examination and early detection of RGC might lead to a better prognosis. Based on the initial gastric disease and the procedure of reconstruction, an appropriate follow-up interval and programs might enable early detection of RGC.

Background: Although remnant gastric cancer (RGC) following distal gastrectomy is located in the proximal stomach, little is known about the differences of the lymphatic distribution and surgical outcomes between RGC and primary proximal gastric cancer (PGC)., Methods: Between 1997 and 2008, 1,149 patients underwent gastrectomy for gastric cancer. Of these, 33 (2.9%) RGC patients and 207 (18.5%) PGC patients were treated at our department. We reviewed their hospital records retrospectively., Results: Compared with the PGC patients, those with RGC had a slightly higher age at onset (p=0.09), higher incidence of undifferentiated cancer (p=0.06), higher incidence of vascular invasion (p=0.09), and higher incidence of T4 (p=0.07). Gastrectomy for RGC involved greater blood loss (p<0.005), longer surgical duration (p=0.01), combined resection, and high incidence of complications. However, the survival rate for RGC patients was similar to that for PGC patients (p=0.67). 2) Patients with RGC had a different pattern of lymph node metastasis compared with that in PGC. Particularly in advanced RGC with pT2-T4 tumors, RGC frequently demonstrated jejunal mesentery lymph node metastases (RGC vs. PGC, 35% vs. 0%) and splenic hilar lymph node metastases (RGC vs. PGC, 17% vs. 10%). The jejunal mesentery lymph node metastases were detected only following Billroth II reconstruction (Billroth I vs. Billroth II, 0% vs. 67%)., Conclusion: Although the clinical behaviors of the two gastric cancers were different, the survival rates were similar. The pattern of metastasis indicates that the jejunal mesentery and splenic hilar lymph nodes should be specifically targeted for en bloc resection during complete gastrectomy in RGC.

Advances in diagnostic and surgical techniques have improved the prognosis of esophageal cancer, but there is growing concern about gastric tube cancer after esophagectomy. Gastric carcinoma arising in tubes that were reconstructed retrosternally is usually resected through a median sternotomy; however, this is invasive and carries a risk of osteomyelitis after suture-line failure. We performed video-assisted gastric tube resection, eliminating the need for sternotomy by using a sternal lifting method, on a 71-year-old man who had previously undergone esophagectomy and reconstruction retrosternally. The tumor was a Borrmann type 1 advanced cancer located near the esophagogastric anastomosis. Neck collar and upper abdominal incisions were made, and the sternum was lifted using a Kent retractor to extend the retrosternal space. Under videoscope assistance, we stripped the adhesions around the gastric tube carefully and performed total gastric tube resection. For the reconstruction, the ileocolon was lifted through the retrosternal space, and an ileoesophagostomy and Roux-en-Y reconstruction were performed. Despite leakage from an esophago-ileoanastomosis on postoperative day 6, the patient recovered well without mediastinitis or osteomyelitis of the sternum. Thus, our surgical procedure provides a good surgical view, decreases surgical stress, and reduces the risk of fatal postoperative complications.

Recently, laparoscopic and endoscopic cooperative surgery (LECS) for submucosal gastric tumor has been developed to avoid an excessive surgical resection of gastric wall, which causes a deformity of the stomach and reduced oral intake. We report here a case of failed LECS for gastric submucosal tumor, and discuss the cause of failure. An 89-year-old woman underwent LECS for an intraluminal type submucosal tumor involving the upper and posterior gastric wall. Specifically, two sites of the gastric wall were fixed with subumbilical and left latero-abdominal wall approaches and two trocars with balloons were introduced into the stomach. Endoscopic submucosal resection was performed circumferentially around the tumor. Then, we tried to lift the tumor using an Endo-loop®. However, the amount of lifting was not sufficient for a safe surgical resection because the surgical field was extremely narrow. Therefore, we converted LECS to open surgery. In conclusion, it is important to consider clinical factors such as body size, tumor size and tumor location when planning LECS. Particularly, the intraabdominal suturing technique instead of using a linear stapler is desirable for a tumor involving the posterior wall.

Background/aims: The most critical problem of the numerical lymph node staging system is difficulty in evaluating preoperative staging. We investigated the directionality of metastatic lymph nodes as an alternative prognostic indicator of gastric cancer., Methodology: One hundred and seventy two patients who had undergone curative gastrectomy were examined. We divided the stations of lymph nodes into three zones according to the anatomical site. Then patients were classified into two groups according to the number of positive zones, unidirectional or multidirectional lymphatic spreading., Results: Seventy-five patients showed unidirectional lymphatic spreading, whereas 97 patients showed multidirectional. Logistic regression analysis showed that directionality correlated with the number of metastatic nodes. Directionality was found to be a significant prognostic factor on univariate analysis, but not on multivariate analysis., Conclusions: The directionality could be a surrogate marker of total number of metastatic lymph nodes as a prognostic factor in patients with gastric cancer.

Despite recent perioperative technological advances in gastric cancer, intractable pancreatic fistula is still a major critical complication following gastrectomy and should be specifically targeted in the effort to improve postoperative outcomes. We preliminary report here a successfully treated case with intractable pancreatic fistula using Trafermin® consisting of basic fibroblast growth factor (bFGF). A 67-year-old man underwent laparoscopic proximal gastrectomy with radical lymphadenectomy for early proximal gastric cancer (pT1bN0M0). After surgery, pancreatic fistula was occurred. Pancreatic fistula persisted for three months despite of surgical and several conservative treatments. After obtaining informed consent, we started to inject 50 μg/day of Trafermin® through a drainage tube into the dehiscence of pancreas. Consequently, pancreatic fistula was successfully closed within three weeks. Our novel treatment technique is simple, rapid and not costly. If informed consent was obtained from patients with low risk of recurrences, this technique should be recommended as one of the treatment choices for intractable pancreatic fistula following curative gastrectomy for gastric cancer.

Thymidylate synthase (TS) plays a major role in the response to 5-fluorouracil (5-FU) by binding directly to the 5-FU metabolite, 5-fluoro-dUMP (FdUMP). The change in the TS expression levels after 5-FU administration was examined in parallel to 5-FU responsiveness in six human gastric adenocarcinoma cell lines to elucidate the source of variability of 5-FU sensitivity. MKN-1, SH-10-TC and MKN-74 cells were more resistant to 5-FU than MKN-28, KATO III and MKN-45 cells. Western blotting analysis revealed that the 5-FU sensitivity of these cells did not correlate with the basal TS expression levels but did correlate with rapid detection of the TS-FdUMP complex after exposure to 5-FU. In 5-FU-resistant cells, very low levels of the TS-FdUMP complex early after 5-FU exposure were elevated by pretreatment with calpain inhibitors such as benzyloxycarbonyl-leucyl-leucinal (ZLLH), benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLH) and ALLN, but not by other protease inhibitors. In contrast, ONO-3403, which causes calpain activation, stimulated downregulation of the TS-FdUMP complex in 5-FU-sensitive cells. The expression levels of calpastatin, an endogenous calpain inhibitor, were higher in 5-FU-sensitive cells than in 5-FU-resistant cells. ZLLH increased the 5-FU sensitivity of 5-FU-resistant cells, whereas ONO-3403 decreased the sensitivity of 5-FU-sensitive cells. In addition, knockdown of m-calpain by siRNA increased the 5-FU sensitivity in 5-FU-resistant cells, while knockdown of calpastatin reduced the sensitivity in 5-FU-sensitive cells. These results suggest that calpain might reduce the chemosensitivity of human gastric cancer cells to 5-FU possibly by rapid degradation of the TS-FdUMP complex, a finding that is considered to have novel therapeutic implications., (© 2011 Japanese Cancer Association.)

Background/aims: Multidetector row computed tomography (MDCT) has emerged as a new diagnostic technology in various cancers. The aim was to evaluate its clinical compatibility with the 13th Japanese Classification of Gastric Carcinoma (JCGC), the 6th TNM and the new 14th JCGC/ 7th TNM systems in preoperative nodal staging (N-stage) of gastric cancer., Methodology: Between January 2005 and December 2007, 92 consecutive patients with gastric cancer underwent preoperative MDCT at a slice thickness of 1.0 mm., Results: The 13th JCGC N-stage on MDCT demonstrated the potential correlation with pathological findings (p=0.057). However, preoperative 6th TNM and the new 14th JCGC/7th TNM N-stage on MDCT from N1 to N3 did not significant correlate with pathological findings (p=0.979, 0.847) because the number of metastatic lymph nodes detected preoperatively on MDCT was significantly smaller than that detected on pathological diagnosis (p<0.0001)., Conclusions: Nodal staging in the 13th JCGC staging system correlates with histological examination better than the 6th TNM and 14th JCGC/7th TNM staging systems. The optimal preoperative nodal staging using the current 14th JCGC/7th TNM staging system on MDCT needs further investigation.

Background/aims: Although routine postoperative follow-up is generally performed for early detection of recurrences, there is no evidence that the periodic follow-up improves survival in patients with gastric cancers. This study aimed to assess the prognostic impact of cancer-related symptomatic status during postoperative followup in gastric cancer patients., Methodology: A total of 81 gastric cancer patients, who developed recurrences after curative surgery, were retrospectively evaluated for clinicopathological findings with regard to the relationship to cancer-related symptoms at the time recurrences were diagnosed., Results: Undifferentiated tumor type, advanced T-stage (T3/4) and peritoneal recurrence were more common in symptomatic patients groups, whereas differentiated tumor type and both locoregional and hematogenous recurrences were more common in asymptomatic patients (p = 0.02, 0.03 and 0.03, respectively). Disease-free survival showed that there were no significant differences between the asymptomatic and symptomatic patient group. However, the post-recurrence survival in patient with symptoms was significantly worse than that in those without symptoms (p < 0.01)., Conclusions: Cancer-related symptomatic status at the time recurrences are diagnosed might provide prognostic information predicting post-recurrence survival. However, we have to conclude that even intensive follow-up did not contribute to the early detection of recurrences in patients with gastric cancers.

A randomized controlled trial of adjuvant chemotherapy with S-1 for gastric cancer (ACTS-GC) demonstrated that the chemotherapy with S-1 improved the relapse-free survival and overall survival rates of patients with locally advanced gastric cancer. We examined retrospectively 47 patients with locally advanced gastric cancer, who received adjuvant chemotherapy with S-1 after curative gastrectomy. Patients who received more than 50% of the total scheduled dose of S-1 during the first 1 year after starting the chemotherapy showed a tendency to favorable outcome in terms of relapse-free survival compared with patients who received less than 50% of the dose, although no statistical significance was detected. Age did not show a significant correlation with tolerability. The number of elderly people with gastric cancer will increase in the next decade. They should be candidates for adjuvant chemotherapy on the basis of a geriatric assessment.

Background/aims: This study investigated outcomes of standardized laparoscopy-assisted distal gastrectomy (sLADG)., Methodology: Although laparoscopic surgery was performed in patients with early gastric cancers in our hospital, a number of staff surgeons performed individualized variations of the procedure. We introduced sLADG to our hospital, and the short-term outcomes of these patients were examined., Results: The mean surgical duration was significantly reduced (299 min. vs. 358 min, p < 0.01), and the amount of blood loss was also significantly decreased (98 ml vs. 207 ml, p < 0.05) in the standardized procedures in comparison with the previous procedures. However, there was no significant difference in the total number of retrieved lymph nodes among open procedure, conventional and standardized LADG series. Postoperative hospital stay and the occurrence of complications were significantly shorter and less frequent in the sLADG group., Conclusions: Performance of sLADG by experienced surgeons is expected to promote a safe procedure without reducing surgical curability.

In gastric cancer, several tumor suppressor and tumor-related genes are silenced by aberrant methylation. Previously, we demonstrated that BCL2L10, which belongs to the pro-apoptotic Bcl-2 family, was transcriptionally repressed by promoter hypermethylation and that its overexpression caused apoptosis and growth inhibition of gastric cancer cells. In this study, we investigated the methylation status of BCL2L10 and its expression in 21 gastric cancer tissues and corresponding non-neoplastic mucosae along with the methylation status of p16, RUNX3, and hMLH1 genes by using methylation specific PCR. In addition, we examined the association between the methylation status of each gene and the expression of EZH2, which was associated with DNA methylation of its target genes. As a result, aberrant methylation of BCL2L10 was detected in 38% of gastric cancer and in 24% of corresponding non-neoplastic mucosae and correlated with low expression of BCL2L10. Methylation of p16, RUNX3, and hMLH1 was found in gastric cancer and in corresponding non-neoplastic mucosae at almost similar frequencies as previous reports. Expression of EZH2 was detected more frequently in tumors (48%) as compared to corresponding non-neoplastic mucosae (10%) (p=0.006), however, no significant difference was found between expression of EZH2 and the methylation frequency of each gene. In conclusion, our data suggest that silencing of BCL2L10 by aberrant methylation is a common feature in gastric cancer and its inactivation may be involved in the early steps of gastric carcinogenesis.

Background: The depth of wall invasion is one of the most important prognostic factors in patients with gastric cancers. We hypothesized that the horizontal width of spread of the neoplasm in the subserosal layer correlated with frequency of latent tumor exposure to the subserosal surface in subserosal (ss) gastric cancer., Methods: We compared retrospectively the relationship between the horizontal width of ss invasion and other clinicopathologic factors in 124 patients with ss cancer confirmed carefully to have T2 and not T3 neoplasms. Selected clinicopathologic parameters of these ss patients were compared to 134 patients with serosal penetration (se) by gastric cancer, and 78 patients with invasion of the muscularis propria only (mp)., Results: The width of ss invasion was found to be an important prognostic factor on both univariate (P < .001) and multivariate analyses (P = .006). The prognosis of ss-cancer with narrow-width invasion (less than 20 mm) was similar to that of mp-cancer, while the prognosis of ss-cancer with wide width (more than 20 mm) was similar to that of se-cancer., Conclusion: Our findings showed that narrow-width ss-cancer (<20 mm) behaved very similar to mp-cancers, while wide ss-cancers (> or =20 mm) behaved very similar to se-cancers. These findings demonstrated the prognostic impact of the width of cancer invasion in subserosal layer in patients with ss-cancer. Intensive chemotherapy and close follow-up should be recommended for ss-cancer patients with greater than 20 mm involvement of the subserosal layer., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: Laparoscopy-assisted distal gastrectomy (LADG) has recently been accepted as a preferred surgical procedure for patient with early gastric cancer. The Billroth-I method has been performed widely because of physiologic advantages and technical simplicity., Methods: Since September 2007, we performed standardized LADG for 35 patients with early gastric cancer. Of these 35 patients, 27 patients were reconstructed by Billroth-I anastomosis. Gastroduodenostomy was performed under direct vision for 11 patients (extracorporeal) and remaining 16 patients were anastomosed under laparoscopic vision facilitated by abdominal wall lifting with a right angle retractor (intracorporeal)., Results: The mean duration of the anastomosis procedure was 17 and 20 minutes in extracorporeal and intracorporeal patients, respectively. The abdominal lifting method with a right angle retractor provided a good visual field without reestablishing pneumoperitoneum. The laparoscopic fine view could prevent surrounding fatty tissues and organs from intervening between the anastomosis planes and consequently guided an accurate and safe anastomosis. Neither anastomotic-related nor pancreatic-related complication was observed in this series., Conclusions: This anastomotic technique should be useful as an easy and safe reconstruction method in LADG and is especially recommendable for less-experienced laparoscopic gastric surgeons.

The efficiency of new anti-cancer drugs such as the S-1 system was demonstrated in a controlled study comparing treatment and non-treatment groups. We encountered a patient with gastric cancer demonstrating peritoneal dissemination, who was successfully treated by combination therapy using S-1 and docetaxel. A 62-year-old woman was admitted to the hospital due to appetite loss and nausea. Upper GI endoscopy demonstrated a type 3 gastric cancer extending from the upper to lower body of the stomach. In the pelvic cavity, an abdominal CT scan demonstrated massive ascites. An abnormally high CA72-4 (143.8 U/mL) level was detected in serum. Treatment with S-1 and docetaxel was started with the following regimen: daily oral administration of 80 mg/body S-1 for 14 days, followed by a 7-day rest and infusion of 40 mg/m2 docetaxel on day 1. After 4 courses, the sites of dissemination had disappeared, and the serum CA72-4 value returned to normal. The patient clinically achieved good QOL by this method, which was very effective for non-resected gastric cancer with peritoneal dissemination.

Background and Objectives: This study investigated the prognostic impact of lymphatic invasion on the outcome of patients with node-negative gastric cancer., Methods: A total of 828 patients with node-negative gastric cancer who underwent curative gastrectomy were reviewed retrospectively. The clinicopathological features and prognoses of patients with lymphatic invasion were compared to those of patients without such invasion., Results: The total rate of lymphatic invasion was 18.2% in node-negative gastric cancers, with a significant difference between early gastric cancers (9.8%) and advanced gastric cancers (49.2%). The presence of lymphatic invasion correlated significantly with tumor location, size and depth of tumor (P < 0.01). Lymphatic invasion was significantly associated with a poorer overall survival in node-negative gastric cancer patients on univariate analysis (P < 0.001) as well as multivariate analysis (P < 0.01)., Conclusions: Lymphatic invasion provides additional useful information that could be applied to identify patients at high risk for recurrence who might be candidates for adjuvant therapies in patients with node-negative gastric cancers.

Peritoneal dissemination of gastric cancer is a refractory disease. This paper focuses on the efficacy of actin-binding marine macrolide latrunculin A, which quickly inhibits actin polymerization and disrupts the function of the actin cytoskeleton. The effects of latrunculin A on cell viability in vitro were evaluated by treatment of MKN45 or NUGC-4 cell cultures. An in vitro viability assay demonstrated an anticancer effect of latrunculin A in a dose-dependent manner. Latrunculin A induced acute cell injury and programmed cell death through activating the caspase-3/7 pathway. In vivo, MKN45 or NUGC-4 cells were intraperitoneally inoculated into nude mice, as a model of peritoneal dissemination. Intraperitoneal (i.p.) injection of latrunculin A significantly improved survival rate in mice without any major side-effects. Data indicated that latrunculin A has strong anticancer effects, and it may be a new candidate i.p. drug against peritoneal dissemination of gastric cancer in humans.

We report a case of gastric cancer with simultaneous multiple liver metastasis that was successfully treated by paclitaxel and UFT-E. A 54-year-old man with gastric cancer was admitted to our hospital for further examination and treatment. A type III gastric cancer was located in the lower to middle part of the gastric body. Abdominal CT revealed multiple liver metastases and lymph node metastases. Then, we performed distal gastrectomy and cholecystectomy. Postoperative pathological diagnosis was stage IV(a type 3 tumor( 78x65 mm), pT3, por 2, INF g, ly3, v0, pN2(+)(26/ 28), H1(bilobular multiple metastases), CY0, P0). Postoperatively, he was treated with S-1 po at 100 mg/body/day as first-line chemotherapy. Thirteen days after S-1 initiation, he was readmitted due to grade 3 diarrhea, and S-1 was immediately stopped. After his general condition was improved, paclitaxel was administered biweekly at a dose of 80 mg/m2. He was discharged after twice administration, and the regimen was continued at an outpatient clinic. Four months after the operation, abdominal computed tomography(CT)showed a remarkable reduction of the multiple liver metastases, and the serum levels of tumor markers(CEA, CA19-9)were reduced. Five months after the operation, the serum levels of tumor markers elevated again. Then, additional administration of UFT-E po(300 mg/body daily) was started. Seven months after the operation, abdominal CT showed a complete regression of the multiple liver metastasis, and the serum levels of tumor markers were also reduced within the normal range. During chemotherapy at an outpatient clinic, critical adverse effects did not appear. Paclitaxel or paclitaxel combined with UFT-E might be an effective regimen as second- or third-line chemotherapy for the liver metastases of gastric cancer.

A 30-year-old man was diagnosed to have a large intra-abdominal tumor in 1999. A histological examination of a resected liver specimen from an operation in 2002 revealed a gastrointestinal stromal tumor (GIST), diagnosed based on positive immunostaining for CD34 and c-kit. Two years after the operation, new lesions developed in the residual liver and the lesser curvature of the stomach. An immunohistological examination of both specimens showed the features of a GIST, thus matching those of the first histological examination of the liver GIST. While there were no mutations at exon 11 of c-kit in the liver GISTs resected in 2002 and 2004, the gastric lesion had a mutation at P577L (CCT to CTT) at exon 11. Therefore, the liver GIST and the gastric lesion were diagnosed to be independent. The patient already has survived for more than 9 years after receiving surgery three times and with administration of imatinib.

Background/aims: Extended lymphadenectomy with gastrectomy is widely performed for patients with advanced gastric carcinoma. However, the therapeutic value of prophylactic extensive lymphadenectomy in patients with node-negative advanced gastric cancer is controversial., Methodology: We retrospectively analyzed 221 patients who underwent curative gastrectomy for advanced gastric carcinoma without lymph node metastasis to evaluate the effect of prophylactic extended lymphadenectomy on postoperative survival. The postoperative survival rate of patients who underwent extended lymphadenectomy was compared with that of patients who underwent limited lymphadenectomy. Predictive risk factors for tumor recurrence and recurrent patterns also were analyzed., Results: Extended lymphadenectomy improved the postoperative survival rate of patients with advanced tumors even when lymph node spread was absent. Whether or not prophylactic extended lymphadenectomy was performed significantly affected tumor recurrence in patients with node-negative advanced gastric carcinoma., Conclusions: Extensive lymphadenectomy with gastrectomy prolongs survival of patients with node-negative advanced tumors.

The quantity and quality of circulating DNA fragments was analyzed by quantitative real-time polymerase chain reactions (qPCR) in plasma from patients with esophageal and gastric cancer, in order to assess their diagnostic value. Plasma was collected preoperatively from 24 patients with esophageal cancer 53 patients with gastric cancer and from 21 healthy controls. qPCR was performed using two primer sets for the BETA-actin gene, amplifying short (102 bp) and long (253 bp) segments. The DNA concentrations in both the short and long segment assays of both cancer patients were significantly higher than the controls. The difference of concentrations between disease group and controls was more significant in esophageal cancer patients. The area under the receiver-operating characteristic curve was 0.83 (short) and 0.91 (long) for esophageal cancer patients, and 0.75 (short) and 0.67 (long) for gastric cancer versus the controls. There was also a significant difference in DNA integrity (short/long) between esophageal cancer patients and the control group (p = 0.001). qPCR assays for plasma DNA concentrations and their integrity can serve as new diagnostic markers for screening and monitoring patients with esophageal and gastric cancer.

Background/aims: We previously reported that aberrant methylation of p16 and/or E-cadherin genes in serum DNA could serve together as a tumor marker in gastric cancer. We presently investigated whether sensitivity could be increased by consideration of a third gene, which encodes retinoic acid receptor-1 (RARbeta)., Methodology: We performed a methylation-specific polymerase chain reaction (MSP) in serum DNA to detect aberrant methylation of RARbeta from 109 preoperative gastric cancer patients, in which the first two genes had been characterized. We also examined all three genes in sera from 10 outpatients during postgastrectomy follow-up., Results: Aberrant methylation of RARbeta was demonstrated in 26 preoperative patients (24%). Considering this with previous results, 52 patients (48%) of the 109 preoperative showed hypermethylation of at least one gene (p16, E-cadherin, and/or RARbeta). No aberrant methylation was detected in control sera. In the follow-up group, aberrant methylation was demonstrated in 2 of the 3 patients who had definite radiologic evidence of recurrences. One of the patients showing promoter hypermethylation without definite findings of recurrence at the time of analysis developed peritoneal recurrence 6 months later., Conclusions: Including the MSP assay in conventional follow-up could facilitate early detection of recurrent disease in gastric cancer patients.

Background/aims: Tumor size requires more investigation as a factor in determining extent of regional lymph node dissection in early gastric carcinoma. We retrospectively investigated 573 patients with such tumors to identify predictors of lymph node metastasis., Methodology: Postoperative survival was examined for groups of patients defined by tumor size under 2 cm, between 2 and 4cm, and over than 4cm. Factors predicting tumor recurrence and regional lymph node metastasis also were determined., Results: Postoperative survival of patients with tumors larger than 4 cm was significantly worsethan that of patients with tumors smaller than 2 cm. Multivariate analysis identified lymph node metastasis as a significant risk factor for recurrence of early gastric carcinoma, while identifying primary tumor size and lymphatic vessel involvement as significant risk factors for lymph node metastasis., Conclusions: Lymph node metastasis, which increased risk of postoperative recurrence in early gastric carcinoma, was related to tumor size.

Background: The diagnostic value of circulating mRNA for the early detection of primary and recurrent gastric cancer was evaluated., Patients and Methods: Circulating hTERT and MUC1 mRNA were amplified in the plasma from 52 gastric cancer patients (40 preoperative and 12 postoperative patients) and 20 healthy controls. The results were compared with those of a circulating cancer cell assay and methylation-specific polymerase chain reaction assay., Results: Cell-free mRNA of the analyzed genes was detected in 6 (15%) preoperative gastric cancer patients (hTERT: 3 and MUC1: 4 patients) and 2 follow-up patients. These mRNAs were not detected in the plasma from healthy volunteers. There was no correlation between the results of the cell-free mRNA and the other assays., Conclusion: Detection of circulating cell-free mRNA might serve as a new complementary tumor marker for gastric cancer.

Tailor-made surgeries for patients with solid malignancies have been under consideration on the basis of the development of new approaches for minor metastatic foci of malignant tumors. Accurate and reliable methods to detect metastases in biopsy specimens with certain rapidity are essential for the performance of these surgeries. The aim of this study was to develop a rapid and practical method to detect metastasis in specimens from patients with gastric carcinoma with the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) reaction, a novel technique for detecting mRNA expressions of targeted sequences with high sensitivity, specificity and rapidity under isothermal conditions. RT-LAMP primers to detect cytokeratin19 (CK19) mRNA were generated and 92 lymph nodes (LNs) obtained from 9 patients with gastric cancer were tested for tumor metastases with this technique. Among 92 LNs, 15 were metastasis-positive by routine histopathological examination. RT-LAMP reaction detected CK19 expression in all of the pathologically positive LNs and in 16 of 77 negative LNs. Nested RT-PCR assay for CK19 expression was also performed on 2 of the 9 cases including 32 LNs. The agreement rate of CK19 expression detection by RT-LAMP and RT-PCR analysis was 31/32 (97%). The RT-LAMP technique showed similar sensitivity to detect metastases as nested RT-PCR assay, with a rapidity comparable to that of intraoperative histopathological examination with frozen sectioning and hematoxylin and eosin staining. This method is expected to play an essential role in the performance of tailor-made surgeries in the near future., (Copyright 2006 Wiley-Liss, Inc.)

Several molecular approaches, using peripheral blood of patients with cancers, have been assessed recently for ability to detect various primary and recurrent cancers at an early stage. One is the reverse transcriptase polymerase chain reaction (RT-PCR) analysis, which can detect a small number of circulating cancer cells. Another is the methylation-specific polymerase chain reaction (MSP), which detects tumor-specific alterations of cell-free serum DNA released from tumor into the circulation by necrosis and/or apoptosis. In the present study, we set out to assess the diagnostic value of the RT-PCR assay and the MSP assay for an early detection of recurrent diseases in patients after curative gastrectomy. Two of the 25 patients (8%) exhibited a CEA specific signal in their peripheral blood. On the other hand, seven patients (28%) showed aberrant methylation of the promoter region of at least one gene (3 patients for p16, 3 for E-cadherin, 3 for RARbeta genes, and 1 for CDH4 respectively). No abnormal signal was detected in sera from volunteers who served as controls. Of 10 patients who developed recurrences, a CEA-specific signal and aberrant methylation was demonstrated in plasma samples of 1 and 4 patients, respectively. One patient, without definite findings of recurrence at the time of analysis, developed recurrences 6 months later. Both assays can serve as markers that allow selection of those cases requiring more intensive screening and aggressive postoperative treatment.

Mono-(adenosine 5'-diphosphate) (ADP)-ribosylation, which transfers an ADP-ribose from nicotinamide adenine dinucleotide (NAD) to an acceptor protein, is an important post-translational modification of cellular proteins. Several bacterial toxins are known to possess the mono-ADP-ribosyltransferase activity to catalyze this reaction as a possible pathogenic factor. Therefore, the aim of this study was to examine whether H. pylori may also induce mono-ADP-ribosylation in a human gastric mucosal protein in association with gastric cancer development. Tumorous and adjacent non-tumorous mucosal tissue specimens were obtained from the surgically removed stomachs of 5 patients with gastric adenocarcinoma, and then were homogenized into cytosolic and membranous fractions. Each homogenate or an H. pylori extract was assayed for mono-ADP-ribosylation with [adenylate-(32)P]-NAD and 3-aminobenzamide, a potent inhibitor of poly-ADP-ribosylation. The radiolabeled proteins were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis followed by radio-image analysis. In the extracts from H. pylori, a strain-dependent, endogenous radiolabeling of 70-kDa protein was detected. An assay of the membranous fractions from 5 gastric adenocarcinomas with the extract of OMH4, a clinical H. pylori isolate, revealed notable radiolabelings of 55- and 45-kDa proteins, which were not found without the OMH4 extract. In contrast, the radiolabelings were minimal in the membranous fractions from respective non-tumorous mucosae, and they were not detected in any of the examined cytosolic fractions. All three radiolabelings of 70-, 55-, and 45-kDa proteins were dependent on NAD, but not on ADP-ribose. Snake venom phosphodiesterase digestion of the 3 radiolabeled proteins released only AMP. We thus found that H. pylori had an enzymatic mono-ADP-ribosyltransferase activity which enabled it to modify the 55- and 45-kDa membranous proteins of human gastric adenocarcinoma, as well as the 70-kDa protein of H. pylori itself. The possible roles underlying our observations on carcinogenesis or development of human gastric carcinoma are yet to be elucidated.

Background: Gastric carcinogenesis is thought to involve multiple genetic and epigenetic changes. The relationships between the promoter methylation status of relevant genes in the serum and outcomes in patients undergoing curative gastrectomy for cancer were investigated., Materials and Methods: Pre-operative serum samples obtained from 97 gastric cancer patients, who underwent radical gastrectomy, were subjected to methylation-specific polymerase chain reaction (MSP) assays for the p16, E-cadherin and retinoic acid receptor beta (RARbeta) genes., Results: Promoter hypermethylation of p16, E-cadherin and the RARbeta gene was detected in sera from 18 (19%), 24 (25%) and 24 patients (25%), respectively. Altogether, 47 patients (48%) showed hypermethylation of at least one gene analyzed. Survival curves differed significantly between groups defined by the methylation status of E-cadherin (p<0.05), but not those defined by p16 or RARbeta (p =0. 77 and 0. 19, respectively)., Conclusion: Serum MSP assays can provide not only diagnostic, but also prognostic information in gastric cancer.

The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated in a total of 12 cases - nine in which partial gastrectomy was performed and three in which total gastrectomy was performed. A single oral dose of S-1, 50 mg as tegafur, was administered, serial peripheral blood samples were collected, and the concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) were measured. The pre-operative S-1 dose was administered about 7 days before surgery and the post-operative dose was administered around post-operative hospital day 14. In the partial gastrectomy cases the maximum post-operative blood concentration (Cmax) of 5-FU and CDHP tended to be lower than before surgery, and the difference in 5-FU concentrations was significant. The area under the blood concentration-time curve (AUC0-8 h) for CDHP was significantly smaller post- than pre-operatively, but no significant difference was observed with regard to 5-FU. In the total gastrectomy cases the post-operative tmax of both 5-FU and CDHP was shorter than the pre-operative tmax, and no significant differences were observed between the pre- and post-operative AUC0-8 h values. Thus, the results of the present study showed that around post-operative hospital day 14, when total oral feeding had become possible after surgery for gastric cancer, the AUC0-8 h values of 5-FU and CDHP after S-1 administration were almost the same as before surgery and that gastrectomy had hardly any effect on the pharmacokinetics of S-1.

We report herein a case with stage IV gastric cancer previously treated with TS-1 completely responding to second-line chemotherapy with weekly paclitaxel therapy. A 65-year-old female was diagnosed as having type 3 gastric cancer with para-aortic lymph node metastases. She underwent total gastrectomy with extended lymph node dissection on March 2003. Histopathological examination revealed that the tumor was poorly-differentiated adenocarcinoma with para-aortic lymph nodes metastases and completely resected. After the operation,she was treated by adjuvant chemotherapy with TS-1. In March of 2004, she suffered from hematuria, and a CT scan revealed para-aortic lymph nodes metastases and left kidney metastasis. Then, she was treated by a weekly infusion of paclitaxel as second-line chemotherapy. After 3 courses, the tumor disappeared and efficacy was judged as CR. Moreover, CR was maintained after 7 courses. At this writing in January of 2005, she is well and has been treated with paclitaxel without any severe adverse events. Therefore, weekly paclitaxel therapy was considered to be one of the promising second-line chemotherapies for advanced or recurrent gastric cancer previously treated by TS-1.

Orotate phosphoribosyl transferase (OPRT) is an essential nucleotide metabolic enzyme for cell proliferation and also a key enzyme for conversion of 5-FU to its active form in tumor tissue. The association between tumor OPRT activity and pathophysiological status, including lymph node metastasis [pN+], and the impact of OPRT for predicting pN+ were investigated in gastric cancer. The lymph node status of 73 resectable gastric cancer patients was analyzed preoperatively by computed tomography (CT), ultrasonography and magnetic resonance, and the OPRT activity of collected tumor tissue was measured. Then these data were compared with pathological observation of a surgical lymph node specimen. OPRT activity in the tumor tissue decreased as the depth of invasion increased. An OPRT test demonstrated superior sensitivity and comparable accuracy and sensitivity for predicting pN+, against current imaging diagnoses. Furthermore, the analysis of node negative patients by CT revealed that 80% of false negative patients were retrieved by this OPRT test. Thus, OPRT activity in tumor tissue was a powerful predictor of pN+ in resectable gastric cancer, and the preoperative OPRT test, when it becomes possible, would provide a basis for accurate evaluation of disease status, which is indispensable for the planning of personalized therapy.

Background: Laparoscopy-assisted surgery with extraperigastric lymph node dissection for gastric cancers has been described, but the clinical benefits of these surgeries still are unclear. Short-term clinical outcomes were compared between laparoscopy-assisted distal gastrectomy (LADG) and conventional open distal gastrectomy (ODG) for early gastric cancer in a prospective randomized fashion., Methods: For this study, 28 patients with early gastric cancers in the lower half of the stomach were randomly assigned to either LADG (n = 4) or ODG (n = 14). Postoperative pain, levels of acute inflammatory responses, and pathologic evaluation of the operative specimens were compared., Results: The LADG group required a significantly shorter period of postoperative epidural anesthesia, showed significantly lower levels of serum interleukin-6 and C-reactive protein, and had no major postsurgery complications. Pathologic examinations showed that surgery was equally radical in the two groups., Conclusion: The findings show that LADG with extraperigastric lymph node dissection is a safe and less invasive alternative to the open procedure.

We herein present a case of resected pancreatic metachronous metastasis arising from alpha-fetoprotein-producing gastric cancer. A 75-year-old man underwent distal gastrectomy for alpha-fetoprotein-producing gastric cancer in November 1999. The staging group of TNM classification was Stage IIIA. The serum AFP level normalized after surgical resection. During the follow-up period, it increased to 42ng/mL in January 2002, and up to 550ng/mL in July 2002: Abdominal computed tomography disclosed a 4-cm mass in the tail of the pancreas and under the diagnosis of pancreas metastasis, distal pancreatectomy with splenectomy was performed. Following this, serum alpha-fetoprotein declined to 61ng/mL, and the postoperative course was uneventful. But it elevated again to 200ng/mL in August, and to 3500ng/mL in September 2002. Computed tomography revealed multiple liver metastases. He was treated with TS-1, but hepatic lesions continued to grow and he died in March 2003. To our knowledge, this case is the first report of resection of solitary pancreas metastasis of alpha-fetoprotein-producing gastric cancer.