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Background: Although outcomes of operations for advanced gastric cancer in the upper third of the stomach are said to be poorer, outcomes of operations for early gastric cancer in the upper third of the stomach have been less well studied. The aim of this study is to analyze and establish a therapeutic strategy for early tumors in the upper third of the stomach., Study Design: Patients (n = 673; 79 patients were located in the upper third of the stomach and 594 in more distal sites) with early gastric cancer who underwent curative gastrectomy were included in this study. Clinicopathologic characteristics and results of operations for early tumors were compared between the two groups. Prognostic factors were evaluated with uni- and multivariate analyses., Results: Tumors in the upper third of the stomach were more often protruded, differentiated, submucosa invasive, and located at the posterior wall, and more often involved venous invasion and adjacent metastatic lymph nodes. Lymph node metastasis, but not tumor location, was an independent prognostic factor in all registered patients. Results of operations were not different between the two groups., Conclusions: Early proximal tumors show distinct features, but prognosis after curative operation is as good as that of distal two-third tumors.

Background: Gastric cancer is the fourth most common malignancy worldwide. Adenoviral vectors (Ads) have been applied for gene therapy of various cancers because of their high transduction efficiency. However, the infectivity of gastrointestinal cancer cells is poor due to the limited expression of the Coxsackie-adenovirus receptor (CAR). In addition, few tumor-specific promoters (TSPs) have been characterized for this type of cancer. To overcome these problems, we proposed TSP-driven conditionally replicating adenoviruses (CRAds) with fiber modification for virotherapy of gastric cancer., Methods: We assessed the expression profile of eight TSPs in gastric cancer cell lines and evaluated promising candidates in the context of CRAd cytocidal effect. Next, infectivity enhancement by fiber modifications was analyzed in the gastric cancer cell lines. Finally, we combined the TSP-driven CRAds of choice with the fiber modifications to augment the killing effect., Results: Out of the eight TSPs, the midkine (MK) and cyclooxygenase-2 (Cox-2M and Cox-2L) promoters showed high transcriptional activity in gastric cancer cells. When these promoters were used in a CRAd context, Cox-2 CRAds elicited the strongest cytocidal effect. The greatest infectivity enhancement was observed with adenoviral vectors displaying 5/3 chimeric fibers. Likewise, Cox-2 CRAds with 5/3 chimeric fibers showed the strongest cytocidal effect in gastric cancer cell lines. Therefore, Cox-2 CRAds with 5/3 chimeric fiber modification showed good selectivity and infectivity in gastric cancer cells to yield enhanced oncolysis., Conclusions: Cox-2 CRAds with 5/3 chimeric fiber modification are promising for virotherapy of gastric cancer.

Background/aims: As no appropriate therapeutic strategy has yet been established in scirrhous type gastric cancer, we retrospectively analyzed the therapeutic outcomes in patients with this type of cancer., Methodology: A total of 183 patients with scirrhous type gastric cancer were enrolled in the study. 127 of them underwent resection; 61 potentially curative gastrectomy; 66 palliative resection; and 56 had no surgery., Results: Univariate analysis revealed that the number of metastatic lymph nodes and the depth of invasion influenced prognosis in curatively resected cases, whereas no factor did so after palliative resection. Multivariate analysis showed that prognosis was affected independently by peritoneal metastasis and non-regional lymph node metastasis in all resected cases, but by the number of metastatic lymph nodes in curatively resected cases. There was no significant difference in survival between patients undergoing and those not undergoing palliative gastrectomy. Prophylactic (6) and therapeutic CHPP (12) had no efficacy on peritoneal metastasis. Furthermore, left upper abdominal evisceration (LUAE) (9) did not improve long-term results in curatively resected cases., Conclusions: In scirrhous type gastric cancer, gastrectomy including extended lymph node dissection is justified only in patients with limited lymph node metastasis, and palliative gastrectomy should be not performed because it has no efficacy on survival.

The authors attempted to clarify the feasibility and safety of thoracoscopic esophagectomy with a voice-controlled robot, the AESOP system (3000 HR), and further determine whether innovative surgical equipment could allow the performance of complex thoracoscopic esophagectomy. Thoracoscopic surgery with a voice-controlled robot system has already been used in single-surgeon lung resection. Intra-operative and postoperative outcomes were compared between patients receiving hand-assisted laparoscopic surgery (HALS) and video-assisted thoracoscopic surgery (VATS) with the AESOP system (n = 15) and patients receiving open surgery (n = 30). In the AESOP group, the volume of blood loss was significantly less, but the total operation time was longer than in the open group. There were no significant differences in postoperative outcomes or the incidences of morbidity and mortality between the two groups. The surgeon using the AESOP system could obtain a stable, close-up, and long-lasting operative view. Laparoscopic and thoracoscopic surgery with the AESOP system has the potential to enable a single surgeon to perform a complex surgical procedure like esophagectomy.

Background: Reports of clinicopathological characteristics and prognosis in patients with signet ring cell carcinoma (SRC) of the stomach are conflicting., Methods: A retrospective review was undertaken of 1450 patients with gastric cancer who had undergone gastrectomy. Of 1113 patients who underwent a curative gastrectomy, 174 had SRC (early, 120; advanced, 54) and 939 had other types of gastric carcinoma. Clinicopathological features, prognostic factors and surgical outcome in patients with SRC and non-SRC were compared., Results: In patients with early gastric cancer, age, histological type, and number and anatomical extent of lymph node metastases independently affected prognosis. Patients with SRC had a significantly better survival rate than those with non-SRC, although there was no difference in the extent or number of lymph node metastases. Mucosal tumours with a diameter of 40 mm or less and submucosal lesions with a diameter of 20 mm or less were not associated with lymph node metastasis. SRC in advanced disease was frequently poorly differentiated or scirrhous, but macroscopic appearance was not an independent prognostic factor., Conclusion: Early SRC of the stomach is associated with a better prognosis than non-SRC. Conversely, in advanced gastric cancer histological type cannot be used to establish a definitive therapeutic strategy., (Copyright (c) 2004 British Journal of Surgery Society Ltd)

The purpose of the present study was to clarify prognostic factors and to investigate appropriate therapeutic strategies for T2 gastric carcinoma. A total of 297 consecutive patients with T2 gastric carcinoma (T2a; 130, T2b; 167) were enrolled in this study. The overall 5-year survival rate was 75.3%. There was a significant difference in survival between T2a and T2b tumor. Multivariate analysis showed that age, depth of invasion and lymph node metastasis independently influenced prognosis. Peritoneal recurrence was frequently observed in 37 patients. Multivariate analysis revealed that lymph node metastasis was an independent predictive factor for peritoneal recurrence. Furthermore, the quantity of the stroma was an independent prognostic factor for hematogenous metastasis, and lymph node metastasis for lmphatic metastasis. Prophylactic therapeutic strategy should be advised for patients with many metastatic lymph nodes, for peritoneal or lymphatic recurrence and in patients with "medullary" stroma for hematogenous recurrence.

Background/aims: Despite the advances in surgical treatment and the improvements in perioperative care for esophageal cancer, the long-term prognosis of this disease is poor. To improve long-term survival, it is essential to identify prognostic factors. This paper deals with the prognostic factors in esophageal cancer after potentially curative resection. Furthermore, correlation of the genetic alteration obtained from biopsy specimens with the prognostic factor was determined., Methodology: A total of 102 patients, who underwent transthoracic esophagectomy, were retrospectively analyzed. In 18 recent patients, the genetic alteration of E-cadherin, cyclin D1, and p16INK4 were evaluated in the biopsy specimens., Results: Univariate analysis revealed that the number of metastatic lymph nodes and the tumor diameter significantly influenced prognosis. A Cox proportional regression hazard model showed that only the number of metastatic lymph nodes significantly affected prognosis. Overexpression of E-cadherin and amplification of cyclin D1 was correlated with the number of metastatic lymph nodes but not with p16INK4., Conclusions: Preoperative genetic assessment of biopsy specimens obtained endoscopically provides useful information concerning selection of treatment modalities.

Background/aims: In cases of incurable stage IV gastric cancer with distant metastases, surgical treatment has usually consisted merely of palliation. The effect of palliative resection in these highly advanced cases remains controversial. Palliative resection may be prohibited by the potential disadvantages of surgical stress., Methodology: Over the past 23 years, 382 stage IV incurable gastric cancer patients with distant metastases were classified into a resection group (group R) whose subjects underwent a palliative resection of the primary tumor and the non-resection group (group N) who were treated without resection of primary tumor. In order to exclude patients with very poor prognosis due to irresectability even if trying to resect, we restricted the subjects to patients who survived more than 30 and 60 days and some months and estimated the mean survival. Cumulative survival rates were calculated by using the Kaplan-Meier method, and the mean survivals of groups R and N were compared., Results: A significantly longer mean survival was observed in group R than in group N (381 vs. 181 days, P<0.0001). Restricting the subjects to patients who survived more than 30 and 60 days, there is also a significant difference between the mean survival of group R and that of group N. However, restricting the subjects to patients who survived more than 300 days, no significant difference was seen between the two groups. The rate of hospital death was higher in group N than in group R (15.9% vs. 3.4%), Conclusions: Palliative resection of the primary tumor in stage IV gastric cancer is meaningful in view of hospital stay, long-term survival, and satisfaction with the treatment. We should resect the primary tumor in cases in which it is resectable.

Background: There are many reports suggesting predictive factors for respiratory complications after esophagectomy, but few studies have focused on this problem from the aspect of immunonutrition., Methods: A series of 45 esophageal cancer patients who underwent potentially curative resection between April 1996 and March 2001 was enrolled in this study. Preoperative and intraoperative variables were analyzed for a correlation between risk factors and respiratory complications. In this study, immunonutrition variables as assessed by ultrasonography and indirect calorimetry were used. Uni- and multivariate analyses were performed to determine the predictive factors., Results: Of 45 patients, nine patients (20%) developed respiratory complications. In univariate analysis, forced expiratory volume in 1 s per body surface area (m(2)) in preoperative respiratory parameters, respiratory quotient, and caloric contributions of fat (percentage) and carbohydrate according to indirect calorimetry, and serum CH50 level significantly influenced the occurrence of postoperative respiratory complications. In multivariate analysis, the caloric contribution of fat (percentage) by indirect calorimetry and serum alpha(1)-antitrypsin (serine protease inhibitor) independently affected the occurrence of respiratory complications., Conclusions: Preoperative excessive fat oxidation (potential starvation) and alpha(1)-antitrypsin were independent predictive factors for postoperative complications. Nutrition support such as enteral feeding to improve this malnourished state would reduce the incidence of postoperative respiratory complications.

Background: The TNM and Japanese classifications of regional lymph node spread (N categories) for gastric cancer differ, whereas the classifications of local extent (T categories) are identical. This study was designed to compare these staging systems and devise a more rational system for gastric carcinoma., Methods: A series of 1244 patients with gastric cancer were enrolled in the study. Survival rates were evaluated to clarify which aspects of each staging system (feasibility, reproducibility, and accuracy of prognostic stratification) were superior., Results: The TNM and Japanese classification systems differ in their categorizations of lymph node spread. A significant difference in survival rate was observed in lymph node metastasis classified as N1 and N2 by the Japanese classification and then subclassified by the TNM classification, although there was no significant difference in the survival in cases of lymph node metastasis classified by TNM into pN1 and pN2 and then subclassified by the Japanese classification. Among patients with M1 metastasis (number 16 a2 and b1 in Japanese classification) in the TNM classification, there was a significant difference in survival. A new classification that included the para-aortic lymph nodes (number 16 a2 and b1) as regional lymph nodes within the TNM classification provided homogeneity and an improvement in staging., Conclusions: TNM classification was more rational and homogenous than Japanese classification. New classification could lead to worldwide uniformity in the description of patients and make possible uniform interinstitutional comparisons of surgical results.

Background: Prognostic factors in gastric cancer may alter with time after surgery. Ascertaining prognostic factors appropriate for each post-operative year should contribute to the establishment of better therapeutic strategies and ultimately to the improvement of their long-term results., Patients and Methods: In the present study, in order to elucidate whether prognostic factors would alter annually, cause of death, recurrence patterns and prognostic factors of gastric cancer by uni- and multivariate analysis were evaluated retrospectively in 833 consecutive patients who underwent potentially curative gastrectomy., Results: During the first 2 years, the prognostic factors were age, T3-4, pN3, tumor diameter and number of metastatic lymph nodes. During the 3rd and 4th years, they were age, pN2 and number of metastatic lymph nodes; for the fourth year, age and number of metastatic lymph nodes; for the fifth year, age alone. Peritoneal recurrence was predominant throughout the post-operative period, but its incidence decreased gradually with time. The incidence of hematogenous recurrence increased while that of lymphatic recurrence did not change with time., Conclusion: As prognostic factors change over time, appropriate alterations to therapeutic strategy should be established for each successive period. Particularly, effective therapeutic strategy for peritoneal metastasis should be established in patients with a high number of metastatic lymph nodes during the first five years. Moreover, the treatment of concomitant disease and the evaluation of other malignant disease should be continued after the 5th year.

Background: What extent of lymph node dissection for advanced gastric cancer is appropriate is a matter of controversy., Patients and Methods: Three hundred and ninety-nine gastric cancer patients underwent potentially curative D2 gastrectomy and 125 underwent D3 gastrectomy between 1985 and 1998., Results: Our study revealed that pN3, but not D3 gastrectomy, significantly influenced prognosis. There was no significant difference in the 5-year survival rate and mean survival time between D2 and D3 patients: but the survival in D3 patients with tumor diameters measuring 50-100 mm or with pN1 was significantly longer than that in D2 patients with the same tumors. Analysis of survival of patients with tumor diameters measuring 50-100 mm revealed that there was a significant difference only in pN1. The incidence of lymphatic recurrence was significantly lower in D3 patients with pN1 tumor or a tumor measuring 50-100 mm than in D2 patients., Conclusion: Patients with advanced gastric cancer measuring 50-100 mm and pN1 may benefit from para-aortic lymph node dissection.

To identify adequate surgical strategies for patients with incurable gastric cancer, long-term results in 228 patients with peritoneal metastasis were analyzed. There was a significant difference in survival between the 141 palliatively gastrectomized and the 87 non-gastrectomized patients. The prognostic factor both in all patients and in gastrectomized patients was the degree of peritoneal metastasis (hazard ratio 1.9073/1.2530) but none was selected in those not gastrectomized. In patients with slight peritoneal metastases (POCY1, P1), the prognostic factors were resection (hazard ratio 5.8631) and a tumor diameter less than 100 mm (hazard ratio 1.7762), but there were non where severe peritoneal metastases were present (P2, P3). Morbidity was frequent in palliation. Palliative gastrectomy is indicated in POCY1 or P1 cases with tumor diameters less than 100 mm. In such gastrectomy, lymph node dissection is limited to a little more than D1, which eradicates only macroscopically identifiable metastatic lymph nodes near the stomach.

Background: The prognosis in gastric cancer is usually defined at the time of presentation. Prognosis, however, is a variable that alters with time. Once a patient has survived for 1 year, the prognosis will change. This study examines this variable in patients who have survived from 1 to 5 years after operation., Methods: Of 1468 patients with gastric cancer, the next 5-year survival (5YS) of patients who already survived for 1, 2, 3, 4, and 5 years after the initial operation was examined, ie, for patients who have survived 1 year, the 5YS (the 6-year survival from operation) was calculated. Similar survival was determined for patients who had survived more than 2, 3, 4, or 5 years and reported according to stage., Results: In patients who survived 2 years, the next 5YS from that time of patients in stage III a stage was similar to that in stage II, and was similar to the 5YS of patients in stage II at the time of diagnosis. In patients who survived 3, 4, or 5 years, the next 5YS from that time of patients in stage III b and stage III a was similar to that of stage II, and subsequently improved. Similarly, the relationship between stage and survival was disordered subsequently with the passage of time. Similar improvement in survival such that 5YS from the 3rd, 4th, and 5th postoperative year approximated that of the survival of patients at an earlier stage at the time of diagnosis., Conclusions: Survival is not only stage-dependent at the time of diagnosis but dependent on the length of survival from the initial operation. Progressive improvement in subsequent 5YS appears to approximate survival of lower-stage disease with the passage of time.

A 51-year-old man was admitted to our hospital with a tumor in the right anterior region of his neck. Aspiration biopsy revealed squamous cell carcinoma (SCC). Further investigations, including upper gastro-intestinal series and endoscopy, showed two flush lesions in the middle and lower thoracic esophagus. An endoscopic biopsy was done and the pathological findings indicated poorly differentiated SCC. He underwent esophagectomy with three-field lymph node dissection, including the neck tumor. Histological findings revealed that the tumor in the middle thoracic esophagus was moderately differentiated SCC, and that the other tumor below it was basaloid cell carcinoma (BCC). The depths of invasion were to the lamina propria mucosae for the former and to the submucosal layer for the latter. There was no lymphatic invasion, venous invasion, or lymph node metastasis. A diagnosis of poorly differentiated SCC of unknown origin was made for the neck tumor. Postoperative recombinant chemotherapy with cisplatin and 5-fluorouracil was given for the unknown primary site, which we still have not identified. No recurrence of the esophageal cancer has been detected.

Background/aims: The long-term survival of patients with gastric cancer is governed by various factors, such as the clinical stage of the cancer, the patient's nutritional state, and the treatment and may be governed by the volume of intraperitoneal adipose tissue. The aim of this study is to clarify the relationship between the degree of the patients' body mass index and their long-term survival., Methodology: Gastric cancer patients who had undergone a gastrectomy with D2-lymphadenectomy and with resection A and B according to the criteria of the Japanese Research Society for Gastric Cancer Rules were subgrouped into those patients with a body mass index < 0.185 (the lower body mass index group) and those patients with a body mass index > 0.210 (the higher body mass index group). The patient's morbidity and long-term survival rate was retrospectively compared between the 2 groups., Results: A significantly longer mean survival rate was observed for the lower body mass index group in stage 2 (1667 vs. 1322 days, P = 0.0240). Also, a significantly longer mean survival rate was observed for the higher BMI group in stage 3a (1431 vs. 943, P = 0.0071)., Conclusions: The body mass index is one of the prognostic factors of stage 2 and stage 3a gastric cancer. However, it does not appear to be useful for determining the prognosis of stage 1a, 1b, 3b, and 4a gastric cancers.

We investigated the effectiveness of continuous hyperthermic peritoneal perfusion (CHPP) for the peritoneal dissemination of gastric cancer. A total 124 patients with advanced gastric cancer were enrolled in this study. Prophylactic CHPP (P-CHPP) was performed in 45 patients who had macroscopic serosal invasion without peritoneal dissemination, and 79 patients without CHPP were a control group. Therapeutic CHPP (T-CHPP) was performed in 21 patients with peritoneal dissemination, and 52 patients without CHPP were a control group. There was no significant difference in 5 year survival between patients treated and not treated with P-CHPP. Univariate analysis showed that location of tumor, tumor diameter, and lymph node metastasis influenced prognosis, but there was no prognostic factor in the Cox proportional regression hazard model. There was no significant difference in 5-year survival between patients treated and not treated with T-CHPP. Univariate analysis showed that degree of peritoneal dissemination and adjuvant chemotherapy influenced prognosis, and the Cox proportional regression hazard model showed that the macroscopic types and degree of peritoneal dissemination affected prognosis. In the patients with CHPP, the incidences of respiratory failure and renal failure were each statistically greater than in the patients undergoing CHPP.

A 64-year-old man who had type IIc-like advanced gastric cancer with multiple liver metastases was admitted to our hospital. He underwent combined hepatic arterial and aortic infusion chemotherapy with cisplatinum (CDDP), 5-fluorouracil (5-FU), and levofolinate calcium (l-LV). After 4 weeks (2 courses) of chemotherapy, a partial response was achieved for the hepatic metastasis. Therefore, distal gastrectomy, right hepatectomy combined with caudate lobectomy, partial resection of the hepatic right lobe, and microwave coagulation therapy of the residual tumor of the hepatic right lobe were performed. With this operation, all tumor cells were removed or killed. Histopathologically, almost all of the primary tumor was fibrous tissue, and only a few sections of moderately differentiated adenocarcinoma observed in the subserosal layer. In the periphery of the metastatic lesion, residual well to moderately differentiated adenocarcinomas were observed, and in the center, only necrotic tissue was seen. The postoperative course was uneventful. Now, one year and seven months after the operation, he is followed as an outpatient. Combined hepatic arterial and aortic infusion chemotherapy with CDDP, 5-FU, and l-LV is thought to be an effective regimen for advanced gastric cancer with multiple liver metastases.

Background: Peritoneal recurrence is a major cause of death in advanced gastric cancer. Although many kinds of chemotherapy intended to prevent peritoneal recurrence of gastric cancer have been evaluated, few have been successful. Few studies have assessed the clinical significance of continuous hyperthermic peritoneal perfusion in peritoneal recurrence., Methods: From 1992 to 1999, a total of 124 patients with advanced gastric cancer with tumors invading deeper than the serosa but with no peritoneal metastasis underwent potentially curative gastrectomy and were enrolled in this study. Prophylactic continuous hyperthermic peritoneal perfusion (P-CHPP) was performed in 45 patients younger than 65 years old and without comorbidity who gave informed consent. Seventy-nine patients who did not meet the inclusion criteria represented the control group. After reconstruction of the alimentary tract, P-CHPP was carried out for 40 minutes with 150 mg cisplatin, 15 mg mitomycin C, and 150 mg etoposide in 5 to 6 L physiologic saline maintained at 42 degrees C to 43 degrees C. The surgical results, recurrent pattern, and postoperative morbidity were assessed by univariate and multivariate analysis., Results: When compared with patients not undergoing P-CHPP, patients treated by P-CHPP had higher incidences of respiratory failure (73% vs 19%; P <.0001) and renal failure (7% vs 0%; P <.03). Neither 5-year survival (49% vs 56%) nor the patterns of recurrence (peritoneal, hematogenous, and lymphatic) were affected by P-CHPP., Conclusions: P-CHPP by our methods had no efficacy as prophylactic treatment for peritoneal recurrence induced by gastric cancer. New therapeutic strategies, such as chemosensitivity assessment, are necessary to obtain good therapeutic results with CHPP.

Endotoxin (ETX) primes polymorphonuclear cells (PMNs) for the subsequent release of reactive oxygen species (ROS) in response to various stimulants such as phorbol myristate acetate (PMA). Although PMNs contribute to oxidative stress after stimulation by standard stimulants and after priming by many humoral factors, it is unknown whether the PMNs from patients at different postoperative times exhibit the same response to the same standard stimulant. We examined the response of PMA-induced production of ROS from PMNs at various intervals after major abdominal surgery in response to ETX priming. This study was a prospective clinical and laboratory study conducted over a 7-day period that involved 25 patients who were referred for elective major abdominal surgery (8 for gastric cancer, 9 for colonic cancer, 8 for rectal cancer). Blood was sampled on the day before operation and on postoperative days (PODs) 1, 3, and 7. For each sample we measured luminol-dependent chemiluminescence (CL), the time to peak counts (Tmax) of PMNs stimulated by PMA, and the serum ETX level. We studied the correlation between CL and ETX in samples from PODs 1 and 3. We also studied the CL of PMNs on PODs 1 and 3 preincubated (primed) with various concentrations of ETX (0, 20, 40, 60, and 100 pg/ml). We found that CL decreased on POD 1 compared with the preoperative level (p <0.05) because of the decreased Tmax. The level of CL per 1 ml of whole blood, however, was higher on PODs 1 and 3 than preoperatively. During this time, leukocytosis should compensate for the impaired production of ROS by an individual PMN. The serum ETX level was increased on POD 1 (p <0.05). There was a negative correlation between CL and ETX on POD 1 (correlation coefficient ?0.62, p < 0.01) and a positive correlation on POD 3 (0.61, p <0.01). CL on POD 3 was accelerated by ETX priming, but the CL on POD 1 was depressed by the priming using a low concentration of ETX. The mode of the response of PMNs to ETX priming differed between PODs 1 and 3. On POD 1 the responses of PMNs to environmental stimulants is suppressed, but by POD 3 these responses had increased.

Background/aims: Lymphatic flow and the incidence of lymph node metastasis in remnant stomach cancer after distal gastrectomy are obscure. There is consequent controversy about appropriate lymph node dissection in such cases., Methodology: Thirty-three consecutive patients with remnant stomach cancer and 44 consecutive patients primary gastric cancer in the upper third of the stomach were investigated retrospectively about lymphatic flow by injection of activated carbon particles, and about the incidence of lymph node metastasis., Results: Lymphatic flow and the incidence of lymph node metastasis in remnant stomach cancer after distal gastrectomy without lymph node dissection were the same as those in primary gastric cancer in the upper third of the stomach. Lymphatic flow after distal gastrectomy with lymph node dissection frequently streamed toward the para-aortic lymph nodes through the lymph nodes along the greater curvature and the suprapancreatic lymph nodes. Lymphatic flow toward the jejunal and colonic mesentery was observed regardless of the method of reconstruction. This lymphogenesis was clearly observed, especially in patients with tumors invading the anastomosis site of Billroth-II reconstruction. Station Nos. 110 (lower paraesophageal) and 111 (supradiaphragmatic) lymph nodes were also stained, despite being considered sites of distant metastasis irrespective of the method of reconstruction., Conclusions: On the basis of the evidence of altered lymphatic flow and the incidence of lymph node metastases in remnant stomach cancer, left upper abdominal evisceration with para-aortic lymph node dissection should be performed in advanced remnant stomach cancer.

We made an intracellular single-chain variable fragment (sFv) from the C219 monoclonal antibody that recognized the intracellular domain of the multidrug resistance (MDR) gene product, P-glycoprotein (P-gp). Immuno-cytochemistry using the FITC conjugated anti-C-myc tag antibody showed that the sFv protein was expressed in the cytoplasm of the cells. Although transfection of the sFv did not result in the down-regulation of P-gp expression in P-gp positive MDR cells as determined by flow cytometry analysis, Adriamycin (ADM) uptake and Rhodamine123 (Rh123) retention were increased by the C219 intra-cellular sFv transfection. The transfected cells exhibited a higher sensitivity to ADM using a 10-day colony formation assay. The conventional 3-day MTT assay showed the drug resistant tendency in C219 sFv transfected cell we tested. The growth rate of C219 sFv transfected cells was delayed in all non-MDR and MDR cells that might be the reason why C219 transfected cells exhibited the drug resistant tendency in the MTT assay. Despite this unexpected effect of C219 sFv on growth rate, our data suggest that the intra-cellular sFv technique could knockout MDR functionally and may offer a means of increasing the effectiveness of tumor chemotherapy., (Copyright 2001 Wiley-Liss, Inc.)

Purpose: Few data are available on factors encouraging continued caregiving at home, especially in relation to positive perceptions of caregiving and the care burden. This study was conducted to explore this question., Methods: We collected data from forty caregivers using Visiting nursing station, with structured interviews conducted at home., Results: 1. Sixty-five percent of caregivers had positive perceptions of the worth and enjoyment of their work in caregiving. 2. Encouraging continued caregiving was associated with positive perceptions and these are relatively independent of the care burden. 3. Caregivers who had high encouraging continued caregiving were spouses or children of the clients. They had positive attitude to caregiving, an intention to use social services and satisfaction in caregiving. 4. Events from which caregivers felt worth and enjoyment in their work were improvement of client's health conditions, gratitude in client response, learning of care skills and strengthening bonds of family relationship., Conclusion: The findings suggest it is important to approach caregivers for the positive perceptions, rather than simply by decreasing burden.

Background: Lymph node dissection in patients with early gastric cancer is controversial because lymph node metastases are much less common than in advanced cancer. Therefore, routine extensive lymph node dissection with wide resection of the stomach may be excessive, and an appropriate lymph node dissection procedure in patients with early gastric cancer should be established., Methods: Retrospectively, 588 consecutive patients with early gastric cancer were analyzed by univariate and multivariate analysis to predict lymph node metastases with clinicopathologic variables. The sites and rates of lymph node metastases for each tumor location were mapped., Results: In early gastric cancer, depth of invasion was an independent predictive factor of lymph node metastases. In cancer confined to the mucosa, however, tumor diameter was the only predictive factor. In contrast, tumor diameter, macroscopic appearance, and histologic type were not predictive factors in early gastric cancers invading the submucosa. In mucosal cancer, metastasis to lymph nodes was confined to the paragastric lymph nodes on the same side of the stomach as the tumor. In submucosal cancer, the incidence of lymph node metastasis was 2% to 17% in group 1 and 1% to 3% in group 2 lymph nodes., Conclusions: In mucosal cancer, lymph node dissection is unnecessary for tumors measuring less than 30 mm, and limited lymph node dissection with local gastrectomy is appropriate when tumor diameters are 30 mm or greater. In submucosal cancer, gastrectomy with dissection of group 1 and some group 2 lymph nodes should be sufficient to remove all nodal metastases.

To determine whether the expression of p53, p21, bcl-2 or Ki-67 in cancer cells is predictive of chemosensitivity, immunohistochemical examination of these factors and chemosensitivity assays were performed on colon and gastric cancer specimens. Chemosensitivity tests were performed using CDDP, 5-FU, MMC, or ADR and inhibition rate (IR) was calculated by MTT assay. Before exposure to anticancer drugs, the samples were investigated immunohistochemically for expression of the above factors and after anticancer drug exposure by TUNNEL staining, for the presence of apoptotic cells. With 5-FU and MMC, the apoptotic index was well correlated with IR, so their effects were related to apoptosis. Moreover, with these two agents, the p53 labeling index (LI) was inversely correlated with IR and p21-LI showed a good correlation with IR. We therefore concluded that immunohistochemical studies for p53 and p21 were useful for predicting the chemosensitivities of colon and gastric cancer to MMC and 5-FU.

Background/aims: D2 gastrectomy has been regarded as an inconvenient procedure with high morbidity and no survival benefit in the West. Recent western studies, however, especially from specialist centers, have shown a survival benefit and the safety of D2 gastrectomy. The aim of this study is to clarify the safety of D2 gastrectomy (defined by the Japanese Research Society for the Study of Gastric Cancer), even if carried out by a junior surgeon, and to show that it is not a particularly difficult or special procedure., Methods: Patients who underwent a typical distal gastrectomy (DG) with D2 resection (n = 344) and total gastrectomy (TG) with D2 resection (n = 111) were analyzed. The subjects were divided into 3 groups according to the postgraduate year of the operator (group I = the surgeon's postgraduate experience was less than 5 years; group II = surgeons with more than 5 years and less than 10 years postgraduate experience; group III = surgeons with more than 10 years postgraduate experience). The rate of postoperative complications and the 5-year survival rate were compared among the 3 groups., Results: The overall operative mortality rate, hospital death rate and the overall rate of postoperative complications were 1.2, 2.0 and 10.2% in DG patients, and 14.4, 0 and 1.8% in TG patients, respectively. There was no significant difference in the operative blood loss, the rate of operative mortality, hospital death rate and postoperative complications among the 3 groups. There was no significant difference in the 5-year survival rate among the 3 groups in each stage., Conclusion: The postoperative mortality rate, morbidity rate and 5-year survival rate after a typical D2 gastrectomy were independent of the experience of the operator. It is considered to be a safe and useful procedure in view of the rate of postoperative complications and the long-term survival rate, even if performed by a junior trainee under the supervision of experienced surgeons in a nonspecialized hospital., (Copyright 2001 S. Karger AG, Basel)

Background/aims: Opportunities of observing patients with recurrent early gastric cancer are rare. Assessment of prognostic factors for the recurrence of early gastric cancer is important for determining adequate strategies for managing early gastric cancer., Methodology: Clinicopathologic variables were compared in 8 patients with and 453 without recurrence who were followed for over 5 years after curative resection. Expression of mutant p53 and Ki-67 was evaluated in 16 patients with n2 or above., Results: Eight patients died of gastric cancer with recurrence. There were no inter-group differences in mean diameter, histologic classification, patterns of infiltrating growth, or cancer-stroma relationship; but macroscopic appearance, depth of invasion, lymphatic invasion, venous invasion and lymph node metastases were significantly more frequent on univariate analysis in those with recurrence. Lymph node metastases was an independent prognostic factor by the Cox proportional hazards regression model. In patients with n2 or above, mutant p53 expression was higher in recurrent than in nonrecurrent cases., Conclusions: Lymph node metastasis was the only independent prognostic factor for the recurrence of early gastric cancer. The expression of mutant p53 may be an indicator of recurrence in patients with n2 or above.

Background/aims: Portal vein embolization is becoming more common as a method of preventing hepatic failure after an extended hepatectomy but its mechanism is not well understood. This clinicopathological study focused on its mechanism., Methodology: Thirty patients who underwent extended hepatectomy after portal vein embolization were evaluated. Liver volume was measured before and after portal vein embolization, and histological studies were performed to examine morphological changes, morphometric parameters and apoptosis of hepatocytes., Results: The mean volume of the non-embolized lobe grew significantly from 392 to 462 mL after portal vein embolization (P < 0.0001). The hypertrophy ratio of the non-embolized lobe (100 x volume change during portal vein embolization/volume before portal vein embolization, %) was correlated closely with the volume of the non-embolized lobe before portal vein embolization (r = -0.65, P < 0.0001). Histological study showed the embolized lobe hepatocytes to be atrophic, partly necrotic and apoptotic. In the non-embolized lobe, the mean hepatocyte volume was 8686 micron 3 (control: 6544 micron 3) and the mean hepatocyte count was 109 x 10(6)/mL (control: 122 x 10(6)/mL)., Conclusions: The enlargement of the non-embolized lobe was caused by hypertrophy rather than hyperplasia suggesting hyperfunction. The resection of the atrophic embolized lobe, leaving the hypertrophic non-embolized lobe was thought to be less surgically stressful than hepatectomy without portal vein embolization.

We investigated the antiemetic effect, safety and usefulness of granisetron hydrochloride tablets on nausea and vomiting induced by oral anticancer drugs used in chemotherapy for gastric cancer and colorectal cancer. In the present trial, oral administration of granisetron hydrochloride was performed during 5 days after nausea or vomiting. 1) Clinically, the effective rate of granisetron hydrochloride (the percentage of cases in which the drug was assessed as "Remarkably effective" or "Effective") was more than 75% on each day of administration. There were no adverse events or abnormal laboratory tests. 2) In terms of usefulness, granisetron hydrochloride was rated "Extremely useful" or "Useful" in 17 out of 23 cases (78.2%). The above results have shown that granisetron hydrochloride tablets, administrated orally once daily at a dose of 2 mg, have an excellent antiemetic effect, and that this is a safe and useful drug.

Background/aims: The surgical results for stage IVb gastric cancer remain very poor. The purpose of the current study is to reveal indications for paraaortic lymph node dissection in stage IVb gastric cancer patients with paraaortic lymph node involvement by analyzing prognostic factors for 3-year survival of stage IVb gastric cancer patients followed by curative B resection., Methodology: The 3-year survival in clinicopathologic variables were compared by univariate analysis. Using Cox proportional hazards regression model, independent prognostic factors were identified from 11 variables., Results: Overall 5-year survival in stage IVb was 26.5%; mean survival was 19 months. Using univariate analysis, p53 expression significantly influenced 3-year survival. Using Cox proportional hazards regression model, the number of total positive lymph nodes, the number of positive paraaortic lymph nodes, and p53 expression were independent prognostic factors., Conclusions: In stage IVb, paraaortic lymph node dissection should be indicated in patients with < or = 10 total positive lymph nodes, and < or = 3 positive paraaortic lymph nodes or p53 expression < or = 50%. This indication can be applied according to the preoperative imaging, the staining of p53 by endoscopic biopsy specimens and the intraoperative microscopic evaluation of dissected lymph nodes.

Background/aims: Since surgical results in advanced gastric cancer remain poor and para-aortic lymph node dissection may contribute to survival, it is useful to determine the significance of para-aortic lymph node dissection., Methodology: Para-aortic lymph node dissection was provisionally indicated for patients with invasion depth deeper than the subserosal layer. Clinicopathologic variables were retrospectively analyzed using univariate analysis and multivariate analysis to predict para-aortic lymph node metastasis. Similarly, they were analyzed using univariate analysis and the Cox's proportional hazards regression model to estimate the prognostic factor in 120 patients who underwent para-aortic lymph node dissection. Surgical results and post-operative complications were compared between para-aortic lymph node dissection and D2 dissection., Results: Univariate analysis revealed that the mean diameter, the degree of lymph node metastasis, and the invasion depth were significant predictors of para-aortic lymph node metastasis. Multivariate analysis showed that n2 was the only independent predictive factor as to para-aortic lymph node metastasis. Univariate analysis revealed tumor site, tumor diameter, lymph node metastasis, number of positive lymph nodes, INF, and stage were significantly associated with 5-year survival. The Cox's proportional hazards regression model showed that the number of positive lymph nodes and the number of positive para-aortic lymph nodes were independent prognostic factors. Patients with < or = 10 positive lymph nodes in any stage or < or = 3 positive para-aortic lymph nodes in stage IVb had significantly better surgical results. Surgical results for patients who underwent para-aortic lymph node dissection with n2 or invasion depth deeper than the exposed serosa were significantly higher than those in D2. As to post-operative complications, pancreatic fistula and respiratory complications were significantly frequent after para-aortic lymph node dissection., Conclusions: n2 is helpful in predicting para-aortic lymph node metastasis. Whereas, post-operative morbidity such as pancreatic fistula and respiratory complications after para-aortic lymph node dissection were significantly higher, they were controllable. Para-aortic lymph node dissection should be indicated in advanced gastric cancer patients in which lymph node metastasis is over n2 or invasion depth is deeper than the exposed serosa. But the number of positive para-aortic lymph nodes must be less than three.

To elucidate the pathogenesis of acute gastric mucosal lesion (AGML), burn stress was loaded in rats with and without obstructive jaundice. The activation of gastric mucosal glycosidases (beta-N-acetyl-D-glucosaminidase (NAG), beta-glucuronidase (BG)), which were released into the cytoplasm as a results of instability of the lysosomal membrane, was studied biochemically, enzymatically and histochemically after burn stress with and without obstructive jaundice. The latent enzyme activity calculated by NAG or BG, which represented the stability of lysosomal membrane, was lowest at 2-3 hour after burn stress in both groups. In other words, the degree of activation of the glycosidases was highest at 2-3 hour after burn stress. The latent enzyme activity calculated by NAG decreased significantly (p < 0.05) at 1 hour after burn stress in obstructive jaundice group compared with the non-obstructive jaundice group. The staining of NAG before burn stress was observed in mucus neck cell and surface epithelial cell in granular shape and it was observed diffusely after burn stress, especially in obstructive jaundice group. The changes in staining of BG was similar to NAG. Before activation of glycosidases, the thiobarbituric acid reactants, which are considered products of lipid peroxidation, increased promptly at 30 min after burn stress in both groups. Ulcer index increased gradually after burn stress and the significance was found between in the obstructive jaundice group and in non-obstructive jaundice group at 3 hour after burn stress. It's concluded that obstructive jaundice accelerated the fragility of lysosomal membrane after burn stress and these change were considered to be the reasons of frequent occurrence of AGML.

The effects of intragastric administration of teprenone on acute gastric mucosal lesions induced by cold-restraint stress was investigated using a model of obstructive jaundice. Rats received teprenone 200 mg/kg/day for a week before stress; nontreated rats served as controls. Teprenone suppressed stress-induced depressions in defensive factors (blood flow, transmucosal potential difference, hexosamine content and lectin staining of carbohydrate residues) and suppressed increases in lesion-enhancing factors (gastric mucosal lysosomal enzyme activity and thiobarbituric acid reactants showing lipid peroxidation). Intragastric pH did not change significantly with teprenone but the ulcer index decreased. These results showed that teprenone protects gastric mucosa against stress, even in the presence of obstructive jaundice.

hEGF (GMG111) given i. v. significantly and dose-dependently suppressed the reduction in gastric mucosal potential-difference (PD) induced by 30% ethanol in rats. Pretreatment with indomethacin did not affect its effect, thereby suggesting that endogenous prostaglandins will not be involved in the mechanism of action of MG111. These results indicate that MG111 protects the weakening of "gastric mucosal barrier". The PD was significantly reduced when MG111 was given i. v. at 20 micrograms/kg. This reduction caused by MG111 was not affected by pretreatment with atropine, hexamethonium, propranolol, and phentolamine.

A rare case of primary signet ring cell carcinoma of the breast is reported. The patient was a 54-year-old unmarried female (G 0, P 0, AB 0) with a several months' history of inflammatory reactions, such as infection, erosion, and a swelling of her entire left breast. She died of this disease in 6 months despite an operation and combined chemotherapy (CMF). Her serum CEA level had well reflected the course of her treatment. Histopathologically, a primary lesion and axillary lymph nodes were found to be filled with typical signet ring cells, whose cytoplasm showed positive staining for PAS and Alcian blue stains as well as CEA. This case, both clinically and histopathologically, displayed the peculiar characteristics of signet ring cell carcinoma, which differs from other types of breast cancer.