Expression of MMP-7 and MT1-MMP in peritoneal dissemination of gastric cancer.

BACKGROUND/AIMS: In this study, we examined the expression of MMP-2, MMP-7, and MT1-MMP in peritoneal dissemination of gastric cancer, so as to clarify a possible role of these MMPs in developing peritoneal dissemination, using culture cells and an animal model with peritoneal dissemination. METHODOLOGY: Total RNA was extracted from tumor tissues of disseminated foci from 7 patients with gastric cancer and human gastric cancer cell lines of STSA, STKM-1, MKN-28, MKN-45, and KATOIII. Expressions of mRNA for MMP-2, MMP-7, and MT1-MMP were analyzed by reverse transcriptase-polymerase chain reaction. To examine relationships between the expression of these mRNAs and the ability to establish peritoneal dissemination, nude mice were injected into the intraperitoneal cavity with 106 cultured cells of those 5 gastric cancer cell lines. RESULTS: MMP-7 was expressed in 6 of 7 tissues (85.7%) and MT1-MMP in 2 of 7 tissues (28.6%), while MMP-2 was not detected in any of 7 tumor tissues. All 7 tumors had either MMP-7 or MT1-MMP. MMP-7 was recognized in 4 of 5 cells (80%) and MT1-MMP in 2 of 5 cells (40%), while MMP-2 was not found at all. All 5 cancer cells expressed at least one MMP mRNA. In the animal experiments, nude mice inoculated with STKM-1 or MKN-45 cells developed peritoneal dissemination, while those with other cell lines did not. MMP-7 was found both in STSA and MKN-28 (dissemination negative), and in STKM-1 and MKN-45 (dissemination positive). MT1-MMP mRNA was detected in one of two dissemination positive cell lines and in one of three dissemination negative ones. CONCLUSIONS: Our results suggested the importance of MMP-7 and MT1-MMP in the peritoneal metastases of gastric cancer, however, it has to be further dissected what role these MMPs might play in detaching of cancer cells from the gastric wall and establishing peritoneal disseminating foci.

Brief psychotic disorder mimicking the symptoms of cerebrovascular attack evoked by symptoms that symbolized death in a patient with terminal stage stomach cancer: case report and review of the literature.

OBJECTIVE: We report here a terminally ill patient with stomach cancer who developed a brief psychotic disorder mimicking cerebrovascular attack after a short episode of nasal bleeding. Close examination of the patient revealed that nasal bleeding was an event that symbolized deterioration of the general condition leading to death for the patient. METHODS: A 77-year-old male, who was diagnosed as having stomach cancer and was receiving palliative care, presented with tremor and insomnia just after a short episode of nasal bleeding and showed reduced response to stimuli mimicking cerebrovascular attack. Laboratory data were unremarkable. The next day, catatonic behavior developed. He had no history of psychiatric illness or drug or alcohol abuse. After receiving haloperidol, psychiatric symptoms disappeared and he returned to the previous level of functioning within 3 days. The patient explained that he had seen a patient whose general condition deteriorated after nasal bleeding and regarded nasal bleeding as a symptom of deteriorating general condition leading to death and thereafter became afraid of the nasal bleeding. RESULTS AND SIGNIFICANCE OF RESULTS: Although, nasal bleeding is common and usually not severe in medical settings, for the patient, it was an event that symbolized deterioration of the general condition leading to death. Brief psychotic disorder in cancer patients is rare in the literature, although patients receiving terminal care share various kinds of psychological burden. Medical staff in the palliative care unit should be aware of the psychological distress experienced by each patient and consider brief psychotic disorder as part of the differential diagnosis when patients show unexplained neurological-like and/or psychiatric symptoms.

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

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

Protein levels of tissue inhibitor of metalloproteinase-1 in tumor extracts as a marker for prognosis and recurrence in patients with gastric cancer.

BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) correlates with tumor progression in patients with gastric cancer; however, the clinical significance of TIMP-1 as a marker for prognosis and recurrence has not been fully clarified. METHODS: TIMP-1 protein was measured by an enzyme-linked immunosorbent assay in tumor samples from 86 patients who had undergone surgical resection. An intratumoral TIMP-1 value of 10.0 ng/mg protein or more was defined as positive. Patients were followed up for more than 5 years prospectively. RESULTS: Thirty-one of the 86 patients (36.0%) were positive for TIMP-1. Kaplan-Meier curves for overall survival were significantly different between patients who were positive and those who were negative for TIMP-1. Univariate analysis of factors affecting overall survival showed that depth of tumor invasion; lymph node metastasis; peritoneal dissemination; lymphatic invasion; venous invasion; Lauren classification of histology; curability; and TIMP-1 were statistically significant. Stepwise multivariate analysis for overall survival demonstrated that depth of tumor invasion, nodal metastasis, peritoneal dissemination, and TIMP-1 remained independent prognostic factors. Kaplan-Meier curves for disease-free survival were significantly different between patients who were positive and those who were negative for TIMP-1. The incidence of recurrence was significantly higher in patients positive for TIMP-1 than in those who were negative for TIMP-1. The frequency at each site of recurrence was higher in patients positive for TIMP-1. CONCLUSION: These results suggested that the protein concentration of TIMP-1 in the tumor extracts was a useful marker for overall survival, disease-free survival, and disease recurrence in patients with gastric cancer. Thus, tumor TIMP-1 may serve to identify a high-risk group, for whom optimal surgical and medical treatment can be given.

Feasibility study of biweekly CPT-11 plus CDDP for S-1- and paclitaxel-refractory, metastatic gastric cancer.

BACKGROUND: To confirm the feasibility and efficacy of biweekly irinotecan (CPT-11) plus cisplatin (CDDP) as third-line chemotherapy, the response rate (RR), overall survival and toxicity were evaluated in patients who had been treated with S-1 as a first-line and paclitaxel as a second-line chemotherapy for metastatic gastric cancer. PATIENTS AND METHODS: The eligibility criteria of our study were: i) pathologically-confirmed adenocarcinoma of the stomach, ii) primary non-resectable or recurrent tumors, iii) Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or less, iv) age less than 75 years, v) adequate hepatic, renal and bone marrow functions and vi) patients had received S-1 as a first-line and paclitaxel as a second-line chemotherapy and both regimens had failed. The treatment consisted of CPT-11 (60 mg/m2) and CDDP (30 mg/m2) on day 1 and day 15, repeated every 4 weeks. RESULTS: Twenty-six patients were enrolled in this study. All the treatment was administered at the out-patient clinic except the first course for the initial 4 patients. The overall RR was 23.1% in all and 30.0% in the patients with target tumors (6 partial response, 11 stable disease, 7 progressive disease, 2 non-evaluable). Overall grade 3/4 toxicity was observed in 5 patients (19.2%) including pancytopenia, neutropenia, anemia, anorexia and elevation of AST/ALT. The time-to-treatment failure and the median survival time were 95 and 299 days, respectively. CONCLUSION: Biweekly CPT-11 plus CDDP was feasible for S-1- and paclitaxel-refractory metastatic gastric cancer, with moderate activity and favorable toxicity. This regimen was safely performed at the out-patient clinic as third-line chemotherapy.

The efficacy of gastrectomy for large gastric cancer.

BACKGROUND: Large gastric cancer (LGC) is frequently associated with extended disease, and the role of surgical resection has been debated. We investigated the efficacy of surgical treatment for LGC. METHODS: The size of LGC was defined as 8 cm or greater. Four hundred and fifteen patients with LGC who underwent gastrectomy were included. The clinicopathological features, the status of the residual tumor, the incidence and patterns of relapse, and the survival were analyzed. RESULTS: Macroscopically, diffuse-type tumors were dominant (60%). The numbers of patients with tumors of T3 or greater, lymph node involvement, and peritoneal metastases were 356 (86%), 359 (87%), and 126 (30%), respectively. One hundred and eighty-eight patients (45%) underwent incomplete tumor resection (R2). The R2/R0 (no residual tumor) ratio was greater than 1 in patients with type 4 tumors and N1 or greater metastasis and in those with type 3 tumors and N2 or greater metastasis. In contrast, T2, type 2, and type 5 tumors were more likely to be completely resected. The 5-year survival for all 415 patients was 26%. The survival rates were inversely related to the tumor type, size, and lymph node metastasis. In the 216 patients with R0, the 5-year survivals of those with pN (International Union Against Cancer [UICC] classification) 0, 1, 2, and 3 were 66%, 56%, 36%, and 5%, respectively (P = 0.001). In 96 of these 216 patients (44%) the tumor recurred, and peritoneal metastasis was the most frequent mode of recurrence (48%). By Cox's proportional hazard model, the tumor size was an independent prognostic factor. CONCLUSION: The chance of achieving R0 resection for LGC is low, except for T2, type 2, or type 5 tumors. Primary resection should be avoided for other types of LGC.

A genetic variant in the gene encoding the stress70 protein chaperone family member STCH is associated with gastric cancer in the Japanese population.

Association analysis, based on linkage disequilibrium between specific alleles in the candidate loci and nearby genetic markers, has been proposed to identify genes conferring susceptibility to multifactorial diseases. Using the affected sib-pair method, we previously mapped four candidate chromosomal regions, 1p32, 2q33-q35, 11p13-p14, and 21q21, for gastric cancer by linkage analysis. To identify genes involved in the disease, we performed a gene-based association analysis of 66 genes, located on 21p11-21q22, using 126 single nucleotide polymorphisms (SNPs) as genetic markers in 373 patients with 250 controls. We found a significant association of five SNPs in the stress70 protein chaperon family member STCH gene with gastric cancer, especially with the non-cardia localization subgroup (P=0.0005-0.02, odds ratio=1.44-1.72). Comparisons of haplotype frequency showed significant association between TTGGC haplotype and gastric cancer (P=0.0001, odds ratio=1.59). These results suggest that, in the Japanese population, STCH might be a new candidate for conferring susceptibility to this disease.

Induction of lymphokine-activated cytotoxic T lymphocytes stimulated by dendritic cells and autologous tumor from a patient with gastric cancer and their effects in vitro.

BACKGROUND/AIMS: The purpose of the study was to generate lymphokine-activated cytotoxic T lymphocytes stimulated by dendritic cells (DC) and autologous tumor from a patient with gastric cancer and to clarify their cytotoxic effects in vitro. METHODOLOGY: DC was induced by interleukin-4 (IL-4) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) from the peripheral blood mononuclear cells (PBMC). Then, PBMC was incubated with mitomycin C-treated tumor cells and DC, and following that was activated with IL-2 and anti-CD3. Induction of DC and cytotoxic T cells (CTL) were confirmed by the analyses of the cell surface antigens, killing activities, and blocking tests. RESULTS: Induction of DC and cytotoxic T cells (CTL) was confirmed by the analyses of the cell surface antigens, killing activities, and blocking tests. In vitro study demonstrated that lymphokine-activated lymphocytes pulsed by DCs and autologous tumor contained the largest population of CTLs, the greatest production of IFN-gamma, and the greatest ATK activity. CONCLUSIONS: Those results indicated that CTLs could be generated in vitro from a patient with gastric cancer more successfully by this method than by conventional methods, suggesting the possibility of a new immunotherapy for the treatment of gastric cancer.

Victims of physical abuse among patients with cancer referred to psychiatric clinic in a cancer center hospital: a pilot study.

OBJECTIVE: Physical abuse is one of the most important public health problems, but little is known about physical abuse of cancer patients. The objects of this study are (1) to identify whether cancer patients have sustained physical abuse; (2) to explore clinical characteristics of the abused patients. METHODS: We reviewed 584 cancer patients referred to our psychiatry clinic by a cancer center hospital and investigated whether there were victims of physical abuse among these patients. We also investigated psychiatric characteristics of the abused patients. RESULTS: Of these 584 patients, three patients were recognized as victims of physical abuse at the time of referral. The perpetrator of physical abuse was their husband (domestic violence) in all three cases. All three patients had sustained physical abuse from their husbands for years before being diagnosed with cancer. In addition to physical abuse, all three patients had sustained emotional abuse (e.g., threat or intimidation) from their husbands. Psychiatric diagnoses of all three patients fulfilled the DSM-IV criteria for post-traumatic stress disorder (PTSD) and the traumatic event was mainly physical abuse by their husbands. SIGNIFICANCE OF RESULTS: Oncologists and psychiatrists should pay greater attention to the psychosocial and environmental problems of cancer patients and inquire about the presence of physical abuse in suspected cases. Medical staff should also know that early multidisciplinary interventions in addition to cancer treatments are needed for victims of physical abuse among cancer patients and that these interventions are necessary to improve compliance with treatment and proper decision making.

Clinical diagnosis of metastatic gastric tumors: clinicopathologic findings and prognosis of nine patients in a single cancer center.

The clinical features of metastatic gastric tumors (MGTs) have not been well documented. We present a clinical series of nine patients with MGTs. Among 2579 patients with gastric tumors seen between 1992 and 2001, we studied 9 (0.3%) patients with MGT according to a prospective database. The MGTs were diagnosed based on findings in the surgical or endoscopic specimen, and patients with malignant lymphoma or direct invasion from adjacent organs were excluded from the study. MGTs were detected simultaneously with the primary tumors in three and afterward in six patients at 14 to 74 months. The primary tumors included one each of squamous cell carcinoma of the esophagus, signet-ring cell carcinoma of the breast, large-cell or small-cell carcinoma of the lung, renal cell carcinoma, hepatocellular carcinoma, squamous cell or epidermoid carcinoma of the uterus, and melanoma. Multiple organ metastases were present simultaneously in six patients. Although six patients underwent gastrectomy, macroscopic eradication of gastric metastatic disease was accomplished in only four, in whom a UICC R0 resection was possible in only two. Five patients were treated by chemotherapy with no apparent survival benefit. A median survival after MGT diagnosis was 170 days (range 16-892 days) for all cases, 384 days for those who underwent gastrectomy (n = 6), and 27 days for those without active treatment (n = 3) (p = 0.002). The cause of death was multiple organ metastases in most cases. Because multiple metastases are common, the prognosis of MGT is poor even after curative resection. MGT is likely to be a preterminal event, and surgical resection may be useful only for palliation.

Is bursectomy necessary for patients with gastric cancer invading the serosa?

BACKGROUND/AIMS: To confirm the impact of bursectomy on survival, we reviewed the clinical records of patients who underwent radical total gastrectomy with bursectomy for gastric cancer invading the serosa, with special reference to the location of tumor invasion. METHODOLOGY: From the records, patients were selected for this retrospective cohort study according to the following criteria: (a) Invasion beyond the serosal surface, (b) No metastases to liver, peritoneum, or distant organs, (c) Negative for peritoneal lavage cytology, and (d) Patients underwent curative D2 total gastrectomy with complete omental bursectomy. A total of 134 patients were eligible. These patients were divided into a group I which included patients with tumors that invaded only the posterior wall and a group II which included those with others. Survival was examined by uni- and multivariate analyses. RESULTS: Survival rates at 3 and 5 years were 67.3% and 53.0% for group I and 68.8% and 53.8% for group II. There was no significant difference in the survival between the two groups (p=0.969), even if survival was stratified by various clinicopathological factors. Multivariate analyses demonstrated that the significant independent factors for the survival were macroscopic type and lymph node metastasis. Location of the invasion was not a significant factor. CONCLUSIONS: These results suggested that bursectomy did not inhibit the spreading of tumor cells into the retro-stomach space. There might be no survival benefit of bursectomy in patients with gastric cancer.

Effects of TS-1 on peritoneal dissemination of gastric cancer in nude mice.

BACKGROUND/AIMS: We investigated the effects of TS-1 on the survival of nude mice developing peritoneal dissemination of gastric cancer. METHODOLOGY: MKN-45 cells were injected into the peritoneal cavity of nude mice and a model of peritoneal dissemination was developed. TS-1 was administered orally every day from day 1 to day 10 or day 10 to day 19. RESULTS: Survival time of these treatment groups was significantly longer than untreated controls. In a pharmacokinetic study, TS-1 was administered on day 10 and the 5-fluorouracil levels were retained and maintained for a longer time, in the ascites and tumor than in plasma. The area under the concentration curve for 5-FU in the tumor was higher, than in plasma or ascites. CONCLUSIONS: TS-1 could be effective in treating peritoneal dissemination of gastric cancer, due to the supply of 5-fluorouracil in the tumor by systemic and intraperitoneal circulation.

Route from the paraaortic lymphatic system to the tracheobronchial lymph nodes evidenced on lymphangiogram in a patient with gastric cancer.

Lung metastasis from gastric or colonic cancer, without liver metastasis, is seldom seen. However, its metastatic pathway has not been delineated on imaging. We present and discuss such a lymphatic route in a patient with gastric cancer. The appearance of the mediastinum on a lymphangiogram is discussed. To the best of our knowledge, the lymphangiographic demonstration of the route from the paraaortic lymphatics to the tracheobronchial lymph nodes has been not reported. Lymphatics running from the paraaortic to the tracheobronchial lymph nodes through the diaphragm may play an important part in direct metastasizing to lung or tracheobronchial lymph nodes in certain patients.

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

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

A combination immunochemotherapy of 5-fluorouracil, cisplatin, leucovorin, and OK-432 for advanced and recurrent gastric carcinoma.

BACKGROUND/AIMS: Based on theories of biochemical modulation and immunotherapy, a novel regimen consisting of 5-fluorouracil, cisplatin, leucovorin, and OK-432 (FLPO therapy) was devised for the treatment of patients with advanced and recurrent gastric carcinoma. METHODOLOGY: The 14-day combination therapy consisted of continuous infusion of 5-fluorouracil (250 mg/m2/day), a bolus injection of 10 mg cisplatin and 30 mg leucovorin every other day, and a subcutaneous injection or per oral administration of OK-432 (3KE or 5KE) every other day. Thirty patients completed 59 courses of treatment consisting of 2 weeks of therapy followed by at least 2 weeks rest. RESULTS: The overall response rate was 40%, with 1 complete response and 11 partial responses observed. All twelve patients responded after 1 course of treatment. The response rate differed depending upon tumor location, 22.2% at the primary site, 60.0% in the lymph nodes, 45.5% with peritoneal dissemination, 44.4% with liver metastases, 50.0% in the lung, and 100.0% with skin metastases. The most frequently observed toxicity was stomatitis (53.3%). The overall incidence of toxicities of grade 3 or greater was 6.6%, including diarrhea (3.3%) and stomatitis (3.3%). One patient required treatment interruption because of the grade 3 toxicity of diarrhea. The median survival time was 198 days overall, 242 days for responders and 125 days for non-responders. CONCLUSIONS: FLPO therapy seemed to be an effective regimen for the treatment of advanced and recurrent gastric carcinoma.

Should gastric cancer with peritoneal metastasis be treated surgically?

BACKGROUND/AIMS: This study was attempted to elucidate the role of surgery in patients with gastric carcinoma and peritoneal dissemination. METHODOLOGY: A database of 128 patients was retrospectively examined with univariate and multivariate analyses after selecting 4 treatment factors, 7 tumor factors evaluated preoperatively, 2 tumor factors evaluated intraoperatively, and 2 patient factors. RESULTS: The overall median survival time was 188 days. Median survival time was 259 days for patients who underwent resection, 173 days for those who underwent bypass operation, and 108 days for those who underwent laparotomy alone. Multivariate analysis revealed only four significant factors for prognosis including computed tomography findings of metastases to the lymph nodes of groups 2 and 3, distant metastasis, ascites, and postoperative status of the patients. Among these factors, the patient status was the most important factor for survival. In 70 patients with a preoperative bad status, the clinical factors affecting survival were analyzed by multivariate analysis exclusive of the postoperative patient status; ascites, resection, bypass operation, and postoperative chemotherapy were significant independent factors. There was no significant difference in safety, efficacy, or prognosis, between the procedures of resection and bypass. CONCLUSIONS: Surgical treatment is not recommended for patients with gastric cancer and peritoneal dissemination when their preoperative status is good. Palliative surgery should be selected when their status is bad. The primary tumor should be resected only when the patient has anemia due to bleeding from the primary tumor.

Indications of limited surgery for gastric cancer with submucosal invasion--analysis of 715 cases with special reference to site of the tumor and level 2 lymph nodes.

BACKGROUND/AIMS: There is controversy as to whether limited or extended lymph node dissection should be performed for gastric cancer with submucosal invasion. METHODOLOGY: To clarify the indications of limited surgery for gastric cancer invading the submucosa, we retrospectively examined the incidence of lymph node metastases with regard to the location of the tumor and distant lymph node station in 715 patients who underwent curative gastrectomy with D2 lymphadenectomy for gastric cancer with submucosal invasion. We classified the level 2 lymph nodes into four groups as follows: group 1 was defined as perigastric lymph nodes far from the primary tumors, group 2 as nodes around the left gastric and the common hepatic arteries, group 3 as nodes around the celiac axis, and group 4 as nodes along the splenic artery. RESULTS: The occurrence of the metastases to level 1 nodes was 14.5% (104 of 715) and that to level 2 nodes was 4.5% (32 of 715). Among the latter, metastases to group 1 lymph nodes were detected in 6 only in the lower third (2.1%) and that to group 2 in 5 in the upper third (6.2%), 9 in the middle third (2.6%), and 12 in the lower third of the stomach (4.1%). Metastases to groups 3 and 4 were only recognized in 2 in the middle third of the stomach (0.3%). Tumors less than 8 mm did not metastasize to lymph nodes and those less than 12 mm did not metastasize to distant ones. CONCLUSIONS: These results suggested that in gastric cancer invading the submucosa, it would be sufficient to dissect group 2 lymph nodes for tumors located at the upper third or the middle third of the stomach, and for tumors located in the lower third of the stomach nodes of groups 1 and 2 should be dissected. For tumors less than 8 mm in the diameter partial resection alone could do and for those less than 12 mm D1 dissection is recommended.

Peritoneal cytology in patients with gastric cancer exposed to the serosa--a proposed new classification based on the local and distant cytology.

BACKGROUND/AIMS: The clinical impact of the cytology of intraperitoneal samples taken from the local and distant sites was examined in patients with gastric carcinoma. METHODOLOGY: Intraoperative peritoneal cytology was evaluated in 149 patients with gastric cancer invading the serosa but no metastasis to the peritoneum (macroscopic P0), the liver (H0), or distant organs (M0). Lavage samples were collected from the Douglas pouch and the left subphrenium (distant sites). Both lavage and smear samples were taken from the serosal surface invaded by the tumor (local). RESULTS: Positive peritoneal cytology was found in 33 of 149 patients (22.1%). All patients were categorized into three groups: Group I had negative cytology (n = 116, 77.9%), Group II had positive local cytology (n = 14, 9.4%), and Group III had positive distant cytology irrespective local status (n = 19, 12.8%). By multivariate analysis, peritoneal cytology was the only significant independent factor affecting survival. Median survival was significantly shorter in Group III (400 +/- 177 days) than in Group I (2228 +/- 599 days). The peritoneal recurrence-free interval was significantly shorter in Group II than in Group I. CONCLUSIONS: The extent of peritoneal seeding was variable and appeared to have a significant impact on prognosis. Peritoneal cytology should be evaluated not only at a distant site, but also locally to identify the subset of patients with limited peritoneal dissemination.

Longterm control of advanced and recurrent gastric cancer (ARGC) by S-1.

BACKGROUND: An oral tegafur compound, S-1 (TS-1), was developed to potentiate antitumor activity and to reduce gastrointestinal toxicities for patients with gastric cancer. It has achieved a high response rate against advanced and recurrent gastric cancer (ARGC) in Japan; however, the efficacy and adverse reactions of longterm administration of S-1 remain to be elucidated. METHODS: Sixty-nine patients with ARGC treated with S-1 were studied; 58 patients had measurable lesions, while 11 patients did not. S-1 was orally administered at doses of between 40 and 60 mg/body twice daily for 28 days, followed by 14 days' rest, as one course. RESULTS: The overall response rate was 38% (complete response [CR], 2/58; partial response [PR], 25/58; stable disease [SD], 9/58 progressive disease [PD] 23/58). Response rate by target organ was 40% for the primary lesion, 45% for lymph node metastasis, 38% for peritoneal metastasis, and 25% for liver metastasis. When S-1 was administered as second-line chemotherapy (n = 25), the response rate was 36%. Of the 69 patients, 14 received S-1 for more than a year. The median survival time (MST) after S-1 administration in these 14 patients, including 3 patients with stable disease, was 918 days (range, 536 to 1107 days). There were no grade 3 to 4 toxicities in these 14 patients receiving longterm therapy with S-1. CONCLUSION: S-1 therapy was performed with a high response rate, irrespective of the target organ or the presence of prior chemotherapy. Longterm administration of S-1 may benefit patients with ARGC, providing prolonged disease control with acceptable toxicities.