[Traumatic Intercostal Lung Hernia Repaired by Video-assisted Thoracoscopic Surgery;Report of a Case].

The 40-year-old male patient was raced to our hospital complaining respiratory difficulty after hitting his left chest at a handle when falling down from a bicycle. Fracture of 5th left rib and partial lung prolapsed intercostally out of the thorax was observed by computed tomography (CT). Due to exacerbated pneumothorax and pneumoderma recognized 12 hours later by CT with the lung remained incarcerated, a surgery was conducted. Camera port was placed from 8th intercostal part at left midaxillary line. The left lung was partially incarcerated from ruptured intercostal part of fractured 5th rib. Adding a working port from 7th intercostal part at the posterior axillary line, the incarcerated lung was thoracoscopically reduced. The thoracoscopic surgery was completed by fixing the rib outside the thoracic wall with 2-0 nylon suture without partial resection of the lung. The patient was discharged on day 7 with satisfactory progress. Thoracoscopic approach is effective for traumatic intercostal lung hernia.

[A Case of Cecum Cancer with Synchronous Adrenal Solitary Metastasis].

We herein report a case of cecum cancer with synchronous adrenal solitary metastasis. A 62-year-old woman who had been treated for other disease complained of weight loss. Lower endoscopy revealed cecum cancer, and computed tomography( CT)demonstrated a solitary left adrenal tumor; thus, she was diagnosed with a metastatic tumor. We concluded that the patient was a possible candidate for surgical resection because she did not present with local metastasis other than in the adrenal glands. Ileocecal resection and left adrenalectomy were performed. The histological findings indicated moderately differentiated adenocarcinoma, which was compatible with cecum cancer. The patient was administered chemotherapy containing mFOLFOX6, and no recurrence has been detected 4 years after the surgery. Some patients who develop solitary adrenal metastasis from colonic cancer appear to be good candidates for surgery in anticipation of a good prognosis.

Precordial skin burns after endoscopic submucosal dissection for gastric tube cancer.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is useful as a minimally invasive treatment option for early gastric cancer. ESD is also used in the management of postoperative remnant gastric cancers in the stomach and gastric tube cancers. Perforation and delayed bleeding have been the main complications of ESD reported in the management of gastric tube cancer. However, in the current literature, there is no description of precordial skin burns caused by electrical coagulation. METHODS: While we treated 22 patients with gastric tube cancers by ESD from 2005 to 2014, we experienced five skin burns in four patients after ESD. We retrospectively analyzed clinical characteristics of precordial skin burn as a complication of ESD. RESULTS: All skin burns occurred in patients reconstructed using a presternal route, whose incidence of precordial skin burn was 55.6%. In all cases, lesions were located in the upper or middle third of gastric tubes irrespective of their direction. Skin burn developed on postoperative day (POD) 1 or POD 2, taking 4-7 days to heal and was accompanied by high fever in 60% of cases. CONCLUSION: The present study suggests that when carrying out ESD for gastric tube cancer using the presternal route, it is necessary to consider the occurrence of a precordial skin burn as a possible complication.

[Neoadjuvant chemotherapy with combined S-1 plus weekly low-dose cisplatin followed by surgical resection for advanced gastric cancer].

We retrospectively examined patients with advanced gastric cancer who underwent gastrectomy following neoadjuvant chemotherapy (NAC) with S-1 plus weekly low-dose cisplatin (CDDP). Between 2007 and 2009, 27 patients with advanced gastric cancer not amenable to curative surgery were enrolled. One course of NAC comprised S-1 (80 mg/m2/day) for 21 consecutive days and CDDP (20 mg/m2) on days 1, 8, and 15; this was followed by a 2-week rest after the end of S-1 administration. Grade 3 side effects were observed in 5 patients: 3 experienced neutropenia and 2 experienced digestive symptoms. The outpatient completion rate was 81.5% (22/27); there was no incidence of renal dysfunction. During pretherapy diagnosis, depth of invasion was classified as T4 in all cases. Postoperative pathologic results showed that the depth of invasion was T3 or lower in 4 patients. In addition, the number of patients with N0 and M0 classification increased and downstaging was observed in 12 patients (44.4%). A comprehensive assessment revealed that a partial response (PR) was observed in 13 patients and stable disease (SD) was observed in 12 patients, resulting in a response rate of 48.1%. The median survival time was 580 days, and the 1-year survival rate was 72%. NAC with S-1 plus weekly low-dose CDDP can also be administered on an outpatient basis, and it is a potential regimen for the treatment of advanced gastric cancer associated with a poor prognosis.

Expression of p27Kip1 protein in gastric carcinoma.

BACKGROUND/AIMS: p27 protein resulted in the accumulation of cyclin E/cyclin dependent kinase 2/p27 ternary complexes inhibits gap1 to synthesis phase transition. Here, we have investigated the correlations, if any, between the expressions of p27 and p53, and proliferation cell nuclear antigen. METHODOLOGY: A retrospective study was performed on 75 cases of gastric cancer that had undergone surgical resection. Immunohistochemical staining was performed using the avidin-biotin-peroxidase complex technique method, with anti-p27 antibody, anti-p53 antibody and anti-proliferation cell nuclear antigen antibody. RESULTS: The rate of lymph node metastasis in the p27 negative cases was significantly higher than that in the p27 positive cases.The rate of tumor limited to the gastric wall in the p27 positive cases was significantly higher than-that in the p27 negative cases.The mean proliferation cell nuclear antigen index of the p27 negative cases was significantly higher than that of the p27 positive cases. The survival rate of the p27 positive cases was significantly higher than that of the p27 negative cases. In Stage III cases, the survival rate of the p53 negative p27 positive or p53 negative p27 negative cases was significantly higher than that of p53 positive p27 negative cases. CONCLUSIONS: p27 was correlated with lymph node metastasis, depth of invasion, and proliferative activity of gastric cancer. Immunoreactivity of combination of p53 and p27 was a useful predictive marker of prognosis of gastric cancer.

Cronkhite-Canada syndrome complicated with multiple gastric cancers and multiple colon adenomas.

BACKGROUND: We experienced a case in which Cronkhite-Canada Syndrome presented with complications of multiple gastric cancers and multiple colon adenomas. CASE REPORT: Our case is a 64-year-old male who visited a nearby hospital with diarrhea and weight loss. The patient was anemic and hypoproteinemic, with multiple polyps in the stomach, duodenum, and large intestine. He also presented with alopecia, onychatrophia, cutaneous pigmentation, and dysgeusia, and was diagnosed with Cronkhite-Canada Syndrome. Follow-up examinations found multiple gastric cancers and colon adenomas. We performed a total gastrectomy and a polypectomy of the large intestine lesions, revealing 4 well-differentiated adenocarcinomas in the resected stomach, and tubular adenomas in the large intestine lesions. Intraoperative findings included scattered melanoid pigmentation on the mesentery and the small intestinal wall. Tumor cells were positive for p53 and Ki67 and partially positive for MUC5AC and MUC2. Cronkhite-Canada Syndrome polyps are generally classified as juvenile type polyps, and these polyps rarely become cancerous. However, of the 383 cases of Cronkhite-Canada Syndrome reported in Japan, complications of gastric cancer were found in 39 cases (10.2%), and only 8 cases with multiple gastric cancer were reported in Japan. including the cases we have personally experienced. There were only two English literatures on Cronkhite-Canada Syndrome complicated with gastric cancer. So it is necessary to notify this information of Cronkhite-Canada Syndrome to the world. CONCLUSIONS: Close gastrointestinal examination and strict follow-up are believed to be essential for Cronkhite-Canada Syndrome patients.

Characteristics and prognosis of gastric cancer in young patients.

The clinicopathological features of gastric cancer (GC) differ between younger and older patients, and it is thought that younger patients have a worse prognosis than older patients due to delayed diagnosis and more aggressive tumor behavior. These characteristics, however, remain controversial. A total of 3,818 patients with pathologically confirmed primary gastric adenocarcinoma were treated at our institution. We analyzed the difference in demographic and clinicopathological characteristics between 169 young [≤40 years of age, younger group (YG)] and 3,649 older [>40 years of age, older group (OG)] GC patients. There was a significantly higher proportion of females in the YG compared with the OG (53.3 and 31.0%, respectively; P<0.0001). The 5-year overall survival of the YG was significantly lower compared to that of the OG (59.7 and 65.9%, respectively; P=0.049). However, YG patients with curative resection had a similar 5-year survival rate to OG patients with curative resection (88.0 and 85.8%, respectively; P=0.547). Female patients in the YG showed a significantly lower survival rate than males in the YG (44.3 and 73.1%, respectively; P=0.0002). Multivariate analyses revealed that macroscopic type, depth of invasion, peritoneal metastasis, distant metastasis and curative resection were independent prognostic factors for the YG with GC. Young GC patients who undergo curative resection do not have a worse prognosis than older patients. Early diagnosis is important in successfully carrying out a curative resection and offering a better prognosis, particularly in females.

Molecular targeting therapy using bevacizumab for peritoneal metastasis from gastric cancer.

AIM: To clarify the significance of vascular endothelial growth factor (VEGF) in peritoneal metastasis from gastric cancer, using the gastric cancer cell line MKN-45 compared with the high potential peritoneal dissemination gastric cancer cell line MKN-45P. METHODS: The supernatant of culture medium of MKN-45 cells or MKN-45P cells was collected and the concentrations were measured of various cytokines, matrix metalloproteinases, growth factor and angiogenic factors, including VEGF. We performed an initial pilot study to explore whether bevacizumab, a humanized monoclonal antibody against VEGF, had any suppressive effect on the peritoneal dissemination from gastric cancer in an experimental nude mouse model of peritoneal metastasis. RESULTS: The concentrations of interleukin-6 (IL-6), IL-8, VEGF and matrix metalloproteinase-2 protein in the culture supernatant were each significantly higher than each of those for MKN-45. In the in vivo study, the volume of ascites and the mitotic index were significantly lower in the therapy group than in the non-therapy group. The survival curve of the therapy group was significantly higher than that of the non-therapy group. These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer. CONCLUSION: Findings suggested that bevacizumab for inhibiting VEGF could suppress peritoneal dissemination from gastric cancer.

Surgical procedures, complications, and prognosis for gastric cancer in the very elderly (>85): a retrospective study.

Many elderly individuals suffer from reduced functioning of major organs with cardiovascular and respiratory system comorbidity. Consequently, surgical stress and postoperative complications can be fatal. We investigated whether gastrectomy can safely improve the prognosis in very elderly (>85 years) patients with gastric cancer. We compared the clinical and pathological features of patients 85 years and older (Group A) with those 80- to 84-year-old (Group B) who underwent gastrectomy. We also compared the survival rates of Group A and Group B, and investigated the prognostic factors. Group A had a high incidence of patients with 3 or more comorbidities, but these did not influence postoperative complications or survival rate. Patients at stage I or II had a significantly higher survival rate than those who did not undergo surgery. However, there was no statistical difference in survival rate at stage III or IV. Our study results revealed that in the early stages (I and II) of well-differentiated gastric cancer with low risk of lymph node metastasis, surgery should consist of minimal lymphadenectomy and be minimally invasive. Further, treatments other than gastrectomy should be considered for patients in whom complete resection via reduction surgery is not possible.

Comparison between the gastric cancer cell line MKN-45 and the high-potential peritoneal dissemination gastric cancer cell line MKN-45P.

Peritoneal metastasis is the most common form of recurrence in gastric cancer, and is associated with a poor prognosis. It is clear that many agents are involved at the various stages of this process, however, many aspects of the progression remain unclear. In the present study we compared the gastric cancer cell line MKN-45 with the high-potential peritoneal dissemination gastric cancer cell line MKN-45P, established from MKN-45. The supernatant of culture medium of MKN-45 cells or MKN-45P cells was collected, and the concentrations of interleukin-1ß (IL-1ß), IL-6, IL-8, hepatocyte growth factor (HGF), Transforming growth factor beta-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) proteins were measured using an enzyme-linked immuno sorbent assay (ELISA) method. Invasion, wound healing and adhesion assays were performed in vitro to examine interstitial invasion, migration and adhesion in the gastric cancer cell lines. Moreover, Western blotting was performed to determine the expression of cyclooxygenase-1 (COX-1) and COX-2 proteins in the culture media of the cell lines. The concentrations of IL-6, IL-8, VEGF and MMP-2 protein in the culture supernatant of MKN-45P were significantly higher than those of MKN-45. Percent adhesion of MKN-45P was significantly higher than that of MKN-45 in the fibronectin-coated group. There was no significant difference in invasion or migration between MKN-45 and MKN-45P. COX-1 and COX-2 proteins were observed in both cell lines. These results suggested that secretion of IL-6, IL-8, VEGF and MMP-2 from cancer cells, and adhesion of cancer cells to fibronectin, were related to the establishment of peritoneal dissemination.

Prognosis of metastatic splenic hilum lymph node in patients with gastric cancer after total gastrectomy and splenectomy.

AIM: To clarify the significance of combined resection of the spleen to dissect the No. 10 lymph node (LN). METHODS: We studied 191 patients who had undergone total gastrectomy with splenectomy, excluding non-curative cases, resection of multiple gastric cancer, and those with remnant stomach cancer. Various clinicopathological factors were evaluated for any independent contributions to No. 10 LN metastasis, using χ(2) test. Significant factors were extracted for further analysis, carried out using a logistic regression method. Furthermore, lymph node metastasis was evaluated for any independent contribution to No. 10 LN metastasis, using the same methods. The cumulative survival rate was calculated using the Kaplan-Meier method. The significance of any difference between the survival curves was determined using the Cox-Mantel test, and any difference was considered significant at the 5% level. RESULTS: From the variables considered to be potentially associated with No. 10 LN metastasis, age, depth, invasion of lymph vessel, N factor, the number of lymph node metastasis, Stage, the number of sites, and location were found to differ significantly between those with metastasis (the Positive Group) and those without (the Negative Group). A logistic regression analysis showed that the localization and Stage were significant parameters for No. 10 LN metastasis. There was no case located on the lesser curvature in the Positive Group. The numbers of No. 2, No. 3, No. 4sa, No. 4sb, No. 4d, No. 7, and No. 11 LN metastasis were each found to differ significantly between the Positive Group and the Negative Group. A logistic regression analysis showed that No. 4sa, No. 4sb, and No. 11 LN metastasis were each a significant parameter for No. 10 LN metastasis. There was no significant difference in survival curves between the Positive Group and the Negative Group. CONCLUSION: Splenectomy should be performed to dissect No. 10 LN for cases which have No. 4sa, No. 4sb or No. 11 LN metastasis. However, in cases where the tumor is located on the lesser curvature, splenectomy can be omitted.

Suppressive effect of bevacizumab on peritoneal dissemination from gastric cancer in a peritoneal metastasis model.

PURPOSE: Vascular endothelial growth factor (VEGF) has been reported to enhance vascular permeability and angiogenesis in the abdominal wall, thereby contributing to peritoneal dissemination with malignant ascites. We conducted this experimental study to find out if bevacizumab, a humanized monoclonal antibody against VEGF, had a suppressive effect on peritoneal dissemination from gastric cancer, in an experimental nude mouse model of peritoneal metastasis. METHODS: Each mouse was treated with a single intraperitoneal (i.p.) injection of bevacizumab. Five mice were killed, and we measured their body weight, the mean number of tumor nodules, and the volume of ascites. We also extracted retroperitoneal tissues for histological examination, to count the frequency of mitosis, and to calculate the mitotic index. Another five mice were monitored until death, and their mean survival duration was calculated. RESULTS: The volume of ascites and the mitotic index were significantly lower in the therapy group than in the nontherapy group (P = 0.042 and P < 0.01, respectively). The survival curve of the therapy group was significantly higher than that of the nontherapy group (P = 0.005). CONCLUSION: Bevacizumab may suppress peritoneal dissemination from gastric cancer.

Bortezomib sensitizes human esophageal squamous cell carcinoma cells to TRAIL-mediated apoptosis via activation of both extrinsic and intrinsic apoptosis pathways.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive human cancers, and novel treatment modalities are required. We investigated the therapeutic potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) in combination with the proteasome inhibitor bortezomib (Velcade) on human ESCC cell lines. Bortezomib enhanced the susceptibility to TRAIL in 12 of the 15 ESCC cell lines tested, although most showed low sensitivity to TRAIL as a single agent. The enhancement of TRAIL-induced apoptosis by bortezomib was caspase dependent. Increased processing of caspase-8 often accompanied enhancement of TRAIL-induced apoptosis by bortezomib. However, the increased cell surface expression of death receptors observed on bortezomib treatment did not seem to be crucial for this effect. For some ESCC, bortezomib treatment resulted in a more efficient recruitment of caspase-8 and the Fas-associated death domain to the death-inducing signaling complex. Additional downregulation of the cellular FLICE-inhibitory protein long isoform [c-FLIP(L)] could cooperate in the activation of the extrinsic pathway in some cases. For other ESCC, the crucial effect of bortezomib treatment seemed to be increased signaling via the intrinsic apoptotic pathway on subsequent exposure to TRAIL. Thus, bortezomib could sensitize ESCC to TRAIL apoptosis by multiple molecular mechanisms of action. Therefore, the combination of bortezomib and TRAIL might be a novel therapeutic strategy for ESCC patients who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway.

Malignant potential of gastrointestinal stromal tumor of the stomach.

Here, we report the Ki-67 Labeling Index, the expression of c-kit, p53, bcl-2, and apoptosis in 11 gastrointestinal stromal tumors (GISTs). The Ki-67 Labeling Index in the malignant GIST group was higher than that in the benign group. The Ki-67 Labeling Index in the p53-positive cases was higher than that in the p53-negative cases. The Ki-67 Labeling Index in the C-kit-positive group was higher than that in the C-kit-negative group. The bcl-2 expression was not correlated with potential malignancy. The apoptotic count in the bcl-2-positive cases was higher than that in the bcl-2-negative cases. The Ki-67 Labeling Index, the p53 overexpression, and the C-kit expression were useful in predicting the potential malignancy.

[Therapeutic experience of S-1 plus other drug combination therapy for synchronia multiple liver metastases of gastric cancer].

A treatment of multiple liver metastases of gastric cancer is very hard and its prognosis is extremely poor. At this time, we reviewed an efficacy of the therapeutic experience case with a new anticancer agent. The treatment was performed on nine cases of synchronia multiple liver metastases of gastric cancer since the new anticancer agent was introduced to the treatment. All of the 9 gastric cancer cases were diagnosed as being resectable other than ones with metastases to the liver, or a primary tumor resection was performed on the cases. The 1st line chemotherapy regimen was a combination of S-1+CDDP intra-arterial injection. The 2nd line chemotherapy regimen was S-1+CPT-11 intra-arterial injection. Furthermore, the 3rd line chemotherapy regimen was an administration of paclitaxel. There were no adverse events, such as hematotoxicity and non-hematotoxicity, that were greater than grade 3 during the duration of chemotherapy. Hence, we could continue the treatment regimen on all of the cases. The tumor responses for all of the cases were judged to be stable disease (SD). The best overall responses for all of the cases were judged to be progressive disease (PD). A median survival time (MST) of the treatment was 16 months, and that was significantly improved from 5.5 months, the regimen without a new anticancer agent (p=0.002). An ambulatory treatment was capable with the QOL in all of the cases. In conclusion, the tumor response did not show on the imaging, but it could be evaluable when there was an efficacy in the treatment that would support a daily life of patient.

The TIMP-1 gene transferred through adenovirus mediation shows a suppressive effect on peritoneal metastases from gastric cancer.

BACKGROUND: It has become clear in recent years that peritoneal metastasis takes place as the result of a multistep process involving attachment, invasion, proliferation, and angiogenesis. The aim of the present study was to evaluate the suppressive effect of tissue inhibitor of metalloproteinase-1 (TIMP-1) gene transfer on peritoneal dissemination. METHODS: We established a high-potential peritoneal metastasis cell line (MKN-45P), using the gastric cancer cell line MKN-45, and developed a peritoneal metastasis model in nude mice. The TIMP-1 gene was transferred to MKN-45 or MKN-45P by adenoviral transfection, and we performed an in vitro invasion assay and an in vivo study, using the peritoneal metastasis model. The TIMP-1 transfected group was compared with a non-virus group and a Lac-Z transfected group. RESULTS: The in vitro invasion assay showed that the number of invasive cells was significantly reduced in the TIMP-1 transfected group compared with that in the non-virus group and the Lac-Z transfected group, Moreover, the in vivo studies showed that the number and the weight of the peritoneal nodes in the TIMP-1 transfected group were significantly less than those in the Lac-Z transfected group, and less than those in the non-viral group. No bloody ascites was recognized in the TIMP-1 transfected group. The mean number of tumor vessels in the non-virus group and the Lac-Z group was significantly higher than that in the TIMP-1 group. CONCLUSION: TIMP-1 demonstrated an inhibitory effect on angiogenesis, and may be worthwhile investigating for use as a future therapy for peritoneal dissemination.

[A resected case of advanced gastric cancer after treatment with low-dosage TS-1].

We report a case of advanced gastric cancer that responded well to low-dosage TS-1. A 72-year-old woman was diagnosed as having unresectable advanced gastric cancer with ascites and hydronephrosis in the right kidney. She was treated with chemotherapy using a low-dosage of TS-1 (80 mg/body/day) administered perorally for 4 weeks followed by a drug-free 2 weeks, in six-week cycles. However, she developed weight loss, appetite loss, and stomatitis. We therefore reduced the dosage of TS-1 from 80 mg/body/day to 60 mg/body/day. The ascites and hydronephrosis gradually improved during the following 3 months, whereupon she could undergo total gastrectomy. The postoperative findings showed no ascites and no peritoneal dissemination. The postoperative pathological findings showed that the cancer cells were localized to within the mucosa, and there were no cancer cells in the greater and lesser omentum. Three weeks after the operation, TS-1 was resumed at 60 mg/body/day. However, 3 months later,ascites and metastasis to the abdominal skin developed, and she died 9 months after the operation.

Clinical examination of the water-soluble vitamin levels in blood during peripheral parenteral nutrition.

The water-soluble vitamin (included vitamin B1, B6, B12 and C) preparations are not always replenished when peripheral parenteral nutrition (PPN) is used in Japan. We evaluated the need for administration of vitamins preparation during PPN, and involved analysis of the blood levels of water-soluble vitamins in patients receiving perioperative PPN before and after gastrectomy. Patients were examined as two set of groups as follows; 18 patients who did not receive water-soluble vitamin preparations during PPN, the Unsupplemented Group, and 22 patients who received such preparations during PPN, the Supplemented Group. Consequently, in the Unsupplemented Group, the blood vitamin B1 level during the early postoperative period was significantly lower than the preoperative level, but in the Supplemented Group, it was significantly higher than the preoperative level. In the Supplemented Group, the blood vitamin B12 level during the early postoperative period was markedly higher than the preoperative level. And in both groups, the blood vitamin C level remained below the lower limit of the criterion range throughout the perioperative period. These results suggested that administration of water-soluble vitamins during PPN was needed to avoid potential vitamin deficiencies after surgery and to prevent a potential onset of severe metabolic complications from any deficiencies.

VEGF significance in peritoneal recurrence from gastric cancer.

BACKGROUND: In gastric cancer, the management of peritoneal dissemination in the Peritoneal cavity is extremely important; however, peritoneal dissemination in the final stage of gastric cancer remains untreatable. Peritoneal dissemination involves several steps, including tumor-cell attachment, invasion, and growth in the peritoneum. Many cytokines, growth factors, matrix metalloproteinases (MMPs), and angiogenic factors play important roles in these steps. So far, few studies have investigated the correlation, if any, between peritoneal dissemination and the angiogenic factor, vascular endothelial growth factor (VEGF). METHODS: Immunohistochemical staining, using the avidin-biotin peroxidase complex method, was performed on slides of surgical specimens from 40 patients with stage II gastric cancer with serosal invasion, who underwent surgery at our hospital between 1990 and 2000. Anti-human VEGF rabbit polyclonal IgG was used as the primary antibody. VEGF expression was classified in one of four categories depending on the percentage of tumor-cell staining (P). VEGF expression was also classified in one of three categories depending on the staining intensity (I). The VEGF expression score was calculated as P x I. RESULTS: There were ten patients with peritoneal recurrence. Of these, seven had macroscopic type-4 scirrhous-type gastric carcinoma. In the immunohistochemical study, the VEGF score of patients with peritoneal recurrence was 9.40 +/- 2.46; on the other hand, that of patients without peritoneal recurrence was 3.47 +/- 2.36. The VEGF score of patients with peritoneal recurrence was significantly higher than that of patients without peritoneal recurrence. In patients with macroscopic type 4, the VEGF score of those with peritoneal recurrence was 9.14 +/- 2.19, while on the other hand, that of the patients without peritoneal recurrence was 3.80 +/- 3.03. The VEGF score of these patients with peritoneal recurrence was significantly higher than that of those without peritoneal recurrence. The survival rate in the VEGF low-expression group was significantly higher than that in the VEGF high-expression group. Multivariate analysis showed that the VEGF score was a significant parameter of peritoneal recurrence. CONCLUSION: These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer, and that VEGF was a useful indicator of peritoneal recurrence.

Surgery and clinicopathological features of gastric adenocarcinoma involving the esophago-gastric junction.

To clarify the optimal operative procedure for gastric adenocarcinoma involving the esophago-gastric junction (EGJ), we investigated 49 cases with an upper gastric cancer invading the esophagus who underwent surgical treatment in our department during the period from 1991 to 2000. According to Siewert's classification, there were 21 cases with a type II tumor, and 28 cases with a type III tumor. Twenty-five cases underwent surgery through an abdominal approach only. The remaining 24 cases were operated on via a left thoraco-abdominal approach. Eight (33%) of 24 cases who underwent extended lymphadenectomy through a left thoraco-abdominal approach had lower mediastinal lymph node metastasis. Metastasis was observed in cases with cancer invasion more than 2 cm from the EGJ. There were 6 cases with a T1 tumor, 6 with a T2 tumor, 27 with a T3 tumor, and 10 with a T4 tumor. Incidences of lymph node metastasis were 0% for T1, 67% for T2, 81% for T3, and 80% for T4. Proximal gastrectomy was performed in 6 cases at the early stage and in 10 cases at the advanced stage with distant metastasis (M1). Total gastrectomy was done in 33 cases at the advanced stage, and 3 of these 33 cases had metastasis to the parapyloric lymph nodes. We performed combined resection of the body and tail of the pancreas and the spleen in 7 cases. One of these 7 cases had direct invasion to the pancreas and 6 cases had remarkable metastasis to the lymph nodes along the splenic artery. Splenectomy preserving the pancreas was done in 24 cases. The incidences of metastasis of the lymph nodes along the splenic artery and the splenic hilum were 25% and 17%, respectively. We performed partial resection of the diaphragm surrounding the esophageal hiatus in 15 cases through a left thoraco-abdominal approach. Six cases had metastasis to the diaphragm and nine cases had direct invasion to the diaphragm. Tumors were stage I in 8 cases, II in 5 cases, III in 13 cases and IV in 23 cases, and the curability was categorized as A in 8 cases, B in 20 and C in 21. The overall 5-year-survival rate was 25%, and the rates according to cancer stage were 86% for stage I, 40% for stage II , 21% for stage III and 0% for stage IV. The 5-year survival rates of cases at stage II and III were 33% for cases using the left thoraco-abdominal approach and 28% for cases with the abdominal approach. Based on these results, we recommend distal esophagectomy with total gastrectomy, and occasional combined resection of the spleen and the diaphragm through a left thoraco-abdominal approach for advanced gastric adenocarcinoma involving the EGJ.